Hepatitis B learning needs assessment of family medicine trainees in Canada: Results of a nationwide survey

PubMed Central

Sam, Justina J; Heathcote, E Jenny; Wong, David KH; Wooster, Douglas L; Shah, Hemant

2011-01-01

BACKGROUND: An estimated 350 million people worldwide have chronic hepatitis B (CHB), which is a major cause of cirrhosis and hepatocellular carcinoma. OBJECTIVE: To assess the level of knowledge among family medicine trainees regarding the identification and management of CHB. METHODS: A questionnaire to assess knowledge regarding screening and management of patients with CHB and cirrhosis was developed. The questionnaire was pilot tested among primary care physicians, subsequently revised and distributed to family medicine trainees across Canada through an online survey program (QuestionPro). RESULTS: A total of 158 trainees completed the questionnaire. Of these, 54% to 56% routinely offered vaccination against hepatitis A or hepatitis B virus (HBV), and 42% regularly screened patients for HBV risk factors. The percentage who recognized the need to screen high-risk populations for CHB, ie, individuals from an HBV-endemic country, men who have sex with men, or intravenous drug users was 73%, 66% and 74%, respectively. While less than 50% of respondents used the appropriate HBV screening tests, 86% to 91% correctly interpreted various HBV serological patterns. Only 3% recognized cirrhosis in our case scenario. Almost 80% of respondents inappropriately preferred prescribing a narcotic or nonsteroidal anti-inflammatory drug over acetaminophen (4%) for pain control in a patient with cirrhosis. While less than 60% recognized HBeAg negative CHB as an indication for referral and treatment, 90% would have referred a patient in the immune-tolerant phase, even though treatment is not indicated. CONCLUSIONS: Knowledge gaps regarding CHB among family medicine trainees in the areas of primary prevention, disease recognition and management of cirrhosis were identified. Results suggest that opportunities to prevent potentially life-threatening complications are being missed. PMID:21499576

Long-term treatment with tenofovir in Asian-American chronic hepatitis B patients is associated with abnormal renal phosphate handling.

PubMed

Tien, Connie; Xu, Jason J; Chan, Linda S; Chang, Mimi; Lim, Carolina; Lee, Sue; Huh, Brian; Shinada, Shuntaro; Bae, Ho S; Fong, Tse-Ling

2015-02-01

Increased risk of defective urinary phosphate reabsorption and osteoporosis has been reported in HIV and chronic hepatitis B (CHB) patients treated with tenofovir disoproxil fumarate (TDF). Goals of this study were to evaluate the prevalence of renal phosphate wasting and abnormal bone mineral density in CHB patients taking TDF compared to CHB patients treated with entecavir (ETV) and untreated CHB patients. This is a cross-sectional study of 146 consecutive Asian-American CHB patients who were treatment naïve (n = 60) or treated with either TDF (n = 42) or ETV (n = 44). Proximal tubular handling of phosphate was assessed by the maximal rate of tubular reabsorption of phosphate (TmPO4) divided by glomerular filtration rate (GFR) (TmPO4/GFR). Bone mineral density (BMD) was measured using dual X-ray absorptiometry. TmPO4/GFR was similar among CHB patients treated with TDF compared to untreated patients and patients taking ETV. However, among patients treated with ≥18 months of TDF or ETV, prevalence of abnormal TmPO4/GFR was higher among patients treated with TDF compared to ETV (48.5 % (16/33) vs. 12.5 % (3/24), p = 0.005). Overall prevalence of osteoporosis in this cohort of CHB patients was 14 %, with no significant difference between the three groups. Renal phosphate handling did not correlate with osteoporosis. Chronic hepatitis B patients treated with ≥18 months of TDF experienced an increased risk of proximal tubular dysfunction. TDF did not increase the risk of osteoporosis. Longitudinal studies are needed to confirm these findings.

Recognition of Core- and Polymerase-derived immunogenic peptides included in novel therapeutic vaccine by T cells from Chinese chronic hepatitis B patients.

PubMed

Huang, D; Sansas, B; Jiang, J H; Gong, Q M; Jin, G D; Calais, V; Yu, D M; Zhu, M Y; Wei, D; Zhang, D H; Inchauspé, G; Zhang, X X; Zhu, R

2017-11-01

Chronic hepatitis B (CHB) is one of the major public health challenges in the world. Due to a strong interplay between specific T-cell immunity and elimination of hepatitis B virus (HBV), efforts to develop novel immunotherapeutics are gaining attention. TG1050, a novel immunotherapy, has shown efficacy in an animal study. To support the clinical development of TG1050 in China, specific immunity to the fusion antigens of TG1050 was assessed in Chinese patients. One hundred and thirty subjects were divided into three groups as CHB patients, HBV spontaneous resolvers, and CHB patients with HBsAg loss after antiviral treatment. HBV-specific T-cell responses to pools of HBV Core or Polymerase genotype D peptides included in TG1050 were evaluated. HBV Core- or Polymerase-specific cells were detected in peripheral blood mononuclear cells (PBMCs) from the different cohorts. The frequencies and intensities of HBV Core-specific immune responses were significantly lower in CHB patients than in HBsAg loss subjects. In CHB patients, a dominant pool derived from Polymerase (Pol1) was the most immunogenic. CHB patients with low viral loads (<10 6 IU/mL) were more likely to have a positive response specific to the Core peptide pool. Overall, genotype D-derived peptides included in TG1050 could raise broad and functional T-cell responses in PBMCs from Chinese CHB patients infected with genotype B/C isolates. Core-specific immunogenic domains appeared as "hot spots" with the capacity to differentiate between CHB vs HBsAg loss subjects. These observations support the extended application and associated immune monitoring of TG1050 in China. © 2017 The Authors. Journal of Viral Hepatitis Published by John Wiley & Sons Ltd.

Serum from Chronic Hepatitis B Patients Promotes Growth and Proliferation via the IGF-II/IGF-IR/MEK/ERK Signaling Pathway in Hepatocellular Carcinoma Cells.

PubMed

Ji, Yuanyuan; Wang, Zhidong; Chen, Haiyan; Zhang, Lei; Zhuo, Fei; Yang, Qingqing

2018-05-09

Chronic hepatitis B virus (HBV) infection (CHB) plays a central role in the etiology of hepatocellular carcinoma (HCC). Emerging evidence implicates insulin-like growth factor (IGF)-II as a major risk factor for the growth and development of HCC. However, the relationship between HBV infection and IGF-II functions remains to be elucidated. Levels of circulating IGF-II and IGF-I receptor (IGF-IR) in healthy donors (HDs) and CHB patients were tested by ELISA. Human HCC cell lines (HepG-2, SMMC-7721, MHCC97-H) were incubated with serum from HDs and CHB patients at various concentrations for 24, 48, and 72 h. MTT and plate colony formation assays, BrdU ELISA, ELISA, small-interfering RNA (siRNA) transfection, quantitative real-time PCR, and western blot were applied to assess the functional and molecular mechanisms in HCC cell lines. Serum levels of IGF-II and IGF-IR were significantly higher in CHB patients than in HDs. Additionally, serum from CHB patients directly induced cell growth, proliferation, IGF-II secretion, and HDGF-related protein-2 (HRP-2) and nuclear protein 1 (NUPR1) mRNA and protein expression in HCC cells. Moreover, serum from CHB patients increased IGF-II-induced cell growth, proliferation, and HRP-2 and NUPR1 mRNA and protein expression in HCC cells. Blockade of IGF-IR clearly inhibited the above effects. Most importantly, interference with IGF-II function markedly repressed the cell proliferation and HRP-2 and NUPR1 mRNA and protein expression induced by serum from CHB patients. Furthermore, serum from CHB patients induced ERK phosphorylation via IGF-IR, with the MEK inhibitor PD98059 significantly decreasing CHB patient serum-induced IGF-II secretion, cell proliferation, and HRP-2 and NUPR1 mRNA and protein expression. Serum from CHB patients increases cell growth and proliferation and enhances HRP-2 and NUPR1 expression in HCC cells via the IGF-II/IGF-IR/MEK/ERK signaling pathway. These findings help to explain the molecular mechanisms underlying HBV-related HCC and may lead to the development of effective therapies. © 2018 The Author(s). Published by S. Karger AG, Basel.

Toll like receptor7 polymorphisms in relation to disease susceptibility and progression in Chinese patients with chronic HBV infection.

PubMed

Zhu, Junping; Zhang, Tong; Cao, Lina; Li, Aixin; Zheng, Kai; Zhang, Nan; Su, Bin; Chen, Zhiyun; Chen, Ning; Wu, Hao; He, Qiushui

2017-09-29

Toll-like receptors (TLRs) play a key role in innate and adaptive immunity, protecting the host from viral pathogens. We studied the effect of TLR7 polymorphisms on disease susceptibility and progression of chronic hepatitis B (CHB) infection in Chinese adults. Blood samples were taken from 612 patients with confirmed CHB, hepatitis B virus (HBV)-related liver cirrhosis (LC) or hepatocellular carcinoma (HCC) and 293 controls. TLR7 polymorphisms (rs179010-C > T, rs2074109-T > C, and rs179009-A > G) were analyzed by PCR-based sequencing. A significantly higher frequency of TLR7 rs179010 C allele was found in male CHB patients than in controls (74.8% vs 59.5%, P = 0.002). The frequency of rs179009 G allele was markedly increased with disease progression when male patients with CHB, LC and HCC were compared (P = 0.012). The haplotype CTA was significantly associated with an increased susceptibility to CHB among male patients (P = 0.000). Frequency of the haplotype CTG was higher in male patients with HCC than CHB (P = 0.005). No such differences in these allele frequencies were found between female patients and controls. Our results indicated that TLR7 polymorphisms play an important role in disease susceptibility and the progression of CHB infections in Chinese adults, and may partly explain the high incidence of HBV related diseases in Chinese men.

Prevalence of steatosis and insulin resistance in patients with chronic hepatitis B compared with chronic hepatitis C and non-alcoholic fatty liver disease.

PubMed

Pais, Raluca; Rusu, Elena; Zilisteanu, Diana; Circiumaru, Alexandra; Micu, Laurentiu; Voiculescu, Mihai; Poynard, Thierry; Ratziu, Vlad

2015-01-01

The association of NAFLD with chronic hepatitis C (CHC) has been extensively studied but little is known about its coexistence with chronic hepatitis B (CHB). To investigate the prevalence and determinants of steatosis and insulin resistance (IR) in CHB and its consequences on liver injury compared with CHC and NAFLD. Patients with CHB (N=110), CHC (N=111) and NAFLD (N=136) were evaluated by biomarkers of steatosis (SteatoTest>0.38 as a surrogate for steatosis >5%), IR (HOMA-IR>2.7 as a surrogate for IR) and fibrosis (FibroTest>0.48 as a surrogate for significant fibrosis, ≥F2). HOMA-IR gradually increased in CHB, CHC and NAFLD: 2.3±1.8; 3±2.6 and 3.8±2.7 (p<0.001). The prevalence of steatosis >5% was 21% (CHB), 43% (CHC) and 82% (NAFLD), (p<0.001). The prevalence of fibrosis≥F2 was 10% (CHB), 42% (CHC) and 21% (NAFLD), p<0.001. In CHB, IR was related to host and not viral factors. CHB patients with steatosis had higher BMI (29±5.7kg/m(2) vs. 24±4kg/m(2), p<0.001), waist circumference (96±14cm vs. 84±11cm, p=0.001) and HOMA-IR (3.9±2.6 vs. 1.8±1.2, p<0.001) than those without steatosis. HOMA-IR independently predicted steatosis in CHB (OR=1.9, 95% CI, 1.09-3.27, p<0.05) and CHC (OR=1.38; 95% CI, 1.07-1.78, p<0.02). In CHB, metabolic risk factors and HOMA-IR were not associated with significant fibrosis. HOMA-IR was an independent predictor of fibrosis in CHC. Steatosis may co-exist in CHB patients but with a lower prevalence than in CHC and NAFLD. In CHB steatosis is related to host and not viral factors, and is not associated with the severity of fibrosis. Copyright © 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Clinical implications of hepatitis B surface antigen quantitation in the natural history of chronic hepatitis B virus infection.

PubMed

Tan, Zhaoxia; Li, Maoshi; Kuang, Xuemei; Tang, Yu; Fan, Yi; Deng, Guohong; Wang, Yuming; He, Dengming

2014-04-01

HBsAg quantitation may be useful for managing patients with hepatitis B virus (HBV) infection. We explored the clinical implications of HBsAg quantitation for patients with HBsAg levels >250IU/ml (Abbott Diagnostics). Two hundred and thirty-three HBV-infected patients comprising 29 immune tolerance cases, 49 treatment-naïve HBeAg-positive chronic hepatitis B (CHB) cases, 91 inactive HBV carrier cases, and 64 treatment-naïve HBeAg-negative CHB cases were analyzed. HBsAg was quantified by the Architect HBsAg assay (Abbott Diagnostics) after a 1:500 automated dilution. HBsAg (log10IU/ml) was established for immune tolerance (4.50±0.43), HBeAg-positive CHB (4.17±0.66), inactive HBV carrier (3.32±0.44), and HBeAg-negative CHB (3.23±0.40); (p=4.92×10(-35)). No significant difference was observed between inactive HBV carrier and HBeAg-negative CHB (p=0.247). The proportions of HBsAg <2000IU/ml for inactive HBV carrier and HBeAg-negative CHB were 51.6% and 59.3%, respectively (p=0.341). Positive correlations between HBsAg and HBV DNA were observed for immune tolerance (p=1.23×10(-4)) and HBeAg-positive CHB (p=0.003), but not for HBeAg-negative CHB (p=0.432). A negative correlation between HBsAg and age was observed for immune tolerance (p=0.030), HBeAg-positive CHB (p=0.016), and inactive HBV carrier (p=0.001), but not in HBeAg-negative CHB (p=0.249). No significant differences between HBsAg and ALT for HBeAg-positive (p=0.338) or HBeAg-negative CHB (p=0.564) were observed. For patients with HBsAg quantitation >250IU/ml, HBsAg may reflect HBV DNA replication for HBeAg-positive cases. HBsAg is not a suitable marker for evaluating hepatitis activity and distinguishing between cases of HBeAg-negative CHB and inactive HBV carrier state. Copyright © 2014 Elsevier B.V. All rights reserved.

Associations between prescribed Chinese herbal medicine and risk of hepatocellular carcinoma in patients with chronic hepatitis B: a nationwide population-based cohort study

PubMed Central

Tsai, Tzung-Yi; Livneh, Hanoch; Hung, Tsung-Hsing; Lin, I -Hsin; Lu, Ming-Chi; Yeh, Chia-Chou

2017-01-01

Objective Patients with chronic hepatitis B (CHB) are reported to exhibit higher risk of subsequent hepatocellular carcinoma (HCC). However, it remains unclear if Chinese herbal medicine (CHM), an important category of traditional Chinese medicine (TCM), may lower HCC risk in this population. So this study aimed to investigate the effects of CHM on HCC risk among patients with CHB. Methods This cohort study used the Taiwanese National Health Insurance Research Database to identify 21 020 newly diagnosed patients with CHB from 1998 to 2007. Among them, 8640 received CHM products after CHB onset (CHM users), and the remaining 12 380 patients were designated as a control group (non-CHM users). All enrolees were followed until the end of 2012 to measure the incidence rate and HR of HCC. Results During 15 years of follow-up, 371 CHM users and 958 non-CHM users developed HCC, representing an incidence rate of 5.28% and 10.18% per 1000 person-years, respectively. CHM users had significantly lower HCC risk compared with non-CHM users (adjusted HR=0.63, 95% CI 0.56 to 0.72). The predominant effect was observed in those receiving CHM products for more than 180 days (adjusted HR=0.52). Some CHM products, such as Hedyotis diffusa, Scutellaria barbata, Rehmannia glutinosa, Isatis tinctoria, Yi Guan Jian, Xiao Chai Hu Tang, Wu Ling San and Gan Lu Yin, were significantly associated with lower risk of HCC. Conclusions The use of CHM was associated with a significantly reduced HCC risk in patients with CHB, which supports the integration of TCM with CHM into clinical practice to influence a favourable prognosis. PMID:28122837

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Ji Hoon; Park, Joong-Won; Kim, Tae Hyun

Purpose: To investigate whether three-dimensional conformal radiotherapy (3D-CRT) influences hepatitis B virus (HBV) reactivation and chronic hepatitis B (CHB) exacerbation in patients with HBV-related hepatocellular carcinoma (HCC). Methods and Materials: Of the 48 HCC patients with HBV who underwent 3D-CRT to the liver, 16 underwent lamivudine therapy before and during 3D-CRT (Group 1) and 32 did not receive antiviral therapy before 3D-CRT (Group 2). To analyze spontaneous HBV reactivation, we included a control group of 43 HCC patients who did not receive any specific treatment for HCC or CHB. Results: The cumulative rate of radiation-induced liver disease for Groups 1more » and 2 was 12.5% (2 of 16) and 21.8% (7 of 32), respectively (p > 0.05). The cumulative rate of HBV reactivation was significantly greater in Group 2 (21.8%, 7 of 32) than in Group 1 (0%, 0/16) or the control group (2.3%, 1 of 43; p < 0.05 each). The cumulative rate of CHB exacerbation, however, did not differ significantly between Groups 2 (12.5%, 4 of 32) and 1 (0%, 0 of 16) or the control group (2.3%, 1 of 43; p > 0.05 each). The CHB exacerbations in the 4 Group 2 patients had radiation-induced liver disease features but were differentiated by serum HBV DNA changes. Two of these patients required antiviral therapy and effectively recovered with lamivudine therapy. Conclusions: In patients with HBV-related HCC undergoing 3D-CRT, HBV reactivation and consequent CHB exacerbation should be considered in the differential diagnosis of radiation-induced liver disease, and antiviral therapy might be considered for the prevention of liver function deterioration after RT.« less

Association of neutrophil-lymphocyte ratio and T lymphocytes with the pathogenesis and progression of HBV-associated primary liver cancer

PubMed Central

Han, Junyan; Wang, Lijia; Li, Mengge; Jiang, Yuyong; Wang, Xianbo; Yang, Zhiyun

2017-01-01

Background The neutrophil–lymphocyte ratio (NLR) is a new prognostic predictor for patients with liver cancer. The association of NLR and T lymphocytes with the pathogenesis and progression of liver cancer is poorly understood. Methods Seventy-three patients with hepatitis B virus (HBV)-associated primary liver cancer (HBV-PLC), 50 patients with HBV-associated liver cirrhosis (HBV-LC) and 37 patients with chronic HBV infection (CHB) were prospectively enrolled from July 1, 2013 to February 28, 2014 in Beijing Ditan Hospital, Capital Medical University (Beijing, China). The NLR, proportions and concentrations of neutrophils and lymphocytes, concentration of subpopulations of lymphocytes, and the expression of CD31 (index for recent thymic output) and HLA-DR (index for activation of T lymphocytes) of T cells in the peripheral blood samples of the patients were assessed and statistically compared between different groups. Results The NLR was significantly increased from patients with CHB, those with HBV-LC to those with HBV-PLC (P<0.05), along with significant increase of neutrophils and decrease of lymphocytes in the same way (P<0.05). The concentrations of T lymphocytes, natural killer cells, B cells, CD4+ T cells and CD8+ T cells were decreased from patients with CHB, those with HBV-LC to those with HBV-PLC, and were significantly reduced in patients with HBV-PLC compared with those in patients with CHB (P<0.05). The CD31 and HLA-DR expression of naive CD4+ and CD8+ T cells was significantly decreased and increased, respectively in patients with HBV-PLC compared with that in patients with CHB. Conclusions Elevated NLR, resulted from the increase of neutrophils and decrease of lymphocytes, is positively associated with the pathogenesis and progression of HBV-PLC. The reduced thymic output and hyperactivation of T lymphocytes may contribute to the decrease of T lymphocytes, which could be also related to the pathogenesis of HBV-PLC. PMID:28231294

Gamma-Glutamyl Transpeptidase-to-Platelet Ratio Predicts Significant Liver Fibrosis of Chronic Hepatitis B Patients in China

PubMed Central

Ren, Tianyi; Wang, Huan; Wu, Ruihong

2017-01-01

Background and Aims We want to investigate whether a novel noninvasive marker is suitable for Chinese CHB patients. Methods A total of 160 treatment-naïve CHB patients who underwent liver biopsy were enrolled in our study, and we assessed the diagnostic accuracies of GPR, aspartate transaminase-to-platelet ratio index (APRI), and the fibrosis index based on 4 factors (FIB-4) in them. Results Of these 160 CHB patients, the numbers of F0, F1, F2, F3, and F4 are 34 (21.3%), 62 (38.8%), 18 (11.3%), 24 (15%), and 22 (13.8%), respectively. The area under the receiver operating characteristic curves (AUROC) of GPR for fibrosis (0.77 versus 0.70, P = 0.03), significant fibrosis (0.70 versus 0.63, P = 0.02), and extensive fibrosis (0.71 versus 0.64, P = 0.02) were significantly higher than those of APRI. The AUROCs of GPR and Fib-4 for fibrosis (0.77 versus 0.75, P = 0.14), significant fibrosis (0.70 versus 0.70, P = 0.22), extensive fibrosis (0.71 versus 0.68, P = 0.13), and cirrhosis (0.64 versus 0.67, P = 0.24) were comparable. Conclusions The GPR can be a routine laboratory marker to stage liver fibrosis in patients with CHB in China. PMID:28831282

[Analysis of the cost-effectiveness of antiviral therapies in chronic hepatitis B patients in Korea].

PubMed

Kim, Byung Kook; Kwon, So Young; Lee, Chang Hong; Choe, Won Hyeok; Choi, Hong Mi; Koo, Hye Won

2009-03-01

The purpose of this study was to evaluate the cost-effectiveness of 1 year and up to 5 years of antiviral treatment for chronic hepatitis B (CHB). Two ten-health-state Markov models were developed for CHB patients. The proportion of patients remaining alive in each health state, and healthcare costs and quality-adjusted life years (QALYs) were determined during annual cycles of these Markov models. The total healthcare costs, life years, and QALYs over the 40-year time horizon of the model were calculated. The perspectives of the cost-effectiveness analysis were the Korean healthcare system and the healthcare needs of the CHB patient. Short-course therapy with alpha-interferon or 1-year treatment with pegylated interferon alpha-2a, lamivudine (LMV), or adefovir (ADV) had limited impact on disease progression. In contrast, either LMV-ADV or ADV-LMV as rescue medication administered for 5 years resulted in a more sustained decrease in the rate of disease progression. The cost-effectiveness threshold in Korea was estimated to be approximately 25,000,000 South Korean won. LMV administered for 1 year is cost-effective in comparison with no treatment for both HBeAg-positive and HBeAg-negative CHB patients, but longer duration antiviral therapies administered for up to 5 years in CHB patients were found to be highly cost-effective by international standards. Antiviral treatment of CHB with LMV or ADV for up to 5 years using the alternative antiviral agent as rescue medication appears to be a cost-effective strategy for both HBeAg-positive and HBeAg-negative CHB patients in Korea. Economic evaluation of antiviral therapies should be studied further and updated, particularly for newer agents.

Hepatitis B Core Antigen in Hepatocytes of Chronic Hepatitis B: Comparison between Indirect Immunofluorescence and Immunoperoxidase Method

PubMed Central

Tabassum, Shahina; Al-Mahtab, Mamun; Nessa, Afzalun; Jahan, Munira; Shamim Kabir, Chowdhury Mohammad; Kamal, Mohammad; Cesar Aguilar, Julio

2015-01-01

Background Hepatitis B virus (HBV) infection has many faces. Precore and core promoter mutants resemble inactive carrier status. The identification of hepatitis B core antigen (HBcAg) in hepatocytes may have variable clinical significance. The present study was undertaken to detect HBcAg in chronic hepatitis B (CHB) patients and to assess the efficacy of detection system by indirect immunofluorescence (IIF) and indirect immunoperoxidase (IIP). Materials and methods The study was done in 70 chronic HBV-infected patients. Out of 70 patients, eight (11.4%) were hepatitis B e antigen (HBeAg) positive and 62 (88.57%) were HBeAg negative. Hepatitis B core antigen was detected by indirect immunofluorescence (IIF) and indirect immunoperoxidase (IIP) methods in liver tissue. Results All HBeAg positive patients expressed HBcAg by both IIF and IIP methods. Out of 62 patients with HBeAg-negative CHB, HBcAg was detected by IIF in 55 (88.7%) patients and by IIP in 51 (82.26%) patients. A positive relation among viral load and HBcAg detection was also found. This was more evident in the case of HBeAg negative patients and showed a positive relation with HBV DNA levels. Conclusion Hepatitis B core antigen can be detected using the IIF from formalin fixed paraffin block preparation and also by IIP method. This seems to reflect the magnitudes of HBV replication in CHB. How to cite this article Raihan R, Tabassum S, Al-Mahtab M, Nessa A, Jahan M, Kabir CMS, Kamal M, Aguilar JC. Hepatitis B Core Antigen in Hepatocytes of Chronic Hepatitis B: Comparison between Indirect Immunofluorescence and Immunoperoxidase Method. Euroasian J Hepato-Gastroenterol 2015;5(1):7-10. PMID:29201677

Cost effectiveness of tenofovir disoproxil fumarate for the treatment of chronic hepatitis B from a Canadian public payer perspective.

PubMed

Dakin, Helen; Sherman, Morris; Fung, Scott; Fidler, Carrie; Bentley, Anthony

2011-12-01

Previous research has demonstrated that tenofovir disoproxil fumarate (DF) is the most cost-effective nucleos(t)ide treatment for chronic hepatitis B (CHB) in the UK, Spain, Italy and France. However, to our knowledge, no published studies have yet evaluated the cost effectiveness of any treatments for CHB in a Canadian setting, where relative prices and management of CHB differ from those in Europe. Our objective was to determine the cost effectiveness of tenofovir DF compared with other nucleos(t)ide therapies licensed for CHB in Canada from the perspective of publicly funded healthcare payers. A Markov model was used to calculate the costs and benefits of nucleos(t)ide therapy in three groups of patients with hepatitis B e antigen (HBeAg)-positive and -negative CHB: nucleos(t)ide-naive patients without cirrhosis; nucleos(t)ide-naive patients with compensated cirrhosis; and lamivudine-resistant patients. Disease progression was modelled as annual transitions between 18 disease states. Transition probabilities, quality of life and costs were based on published studies. Health benefits were measured in QALYs. The reference year for costs was 2007 and costs and outcomes were discounted at 5% per annum. First-line tenofovir DF was the most effective nucleos(t)ide strategy for managing CHB, generating 6.85-9.39 QALYs per patient. First-line tenofovir DF was also the most cost-effective strategy in all patient subgroups investigated, costing between $Can43,758 and $Can48,015 per QALY gained compared with lamivudine then tenofovir. First-line tenofovir DF strongly dominated first-line entecavir. Giving tenofovir DF monotherapy immediately after lamivudine resistance developed was less costly and more effective than any other active treatment strategy investigated for lamivudine-resistant CHB, including second-line use of adefovir or adefovir + lamivudine. Probabilistic sensitivity analysis demonstrated 50% confidence that first-line tenofovir DF is the most cost-effective nucleos(t)ide strategy for treatment-naive patients with CHB, at a $Can50,000 per QALY threshold, and confirmed that first-line tenofovir DF has the highest expected net benefits. First-line tenofovir DF appears to be the most cost-effective nucleos(t)ide treatment for both cirrhotic and non-cirrhotic CHB patients in Canada, providing that society is willing to pay at least $Can48,015 per QALY gained, although sensitivity analyses highlighted uncertainty around the results.

Challenges in managing patients in Australia with chronic hepatitis B: the General Practitioners' perspective.

PubMed

Wallace, Jack; Hajarizadeh, Behzad; Richmond, Jacqui; McNally, Stephen

2013-10-01

General Practitioners (GPs) are essential to reducing the impact of chronic hepatitis B (CHB) given their clinical management role where only 56% of people with the infection in Australia have been diagnosed. This qualitative study aimed to identify the challenges GPs face in effectively responding to CHB. Semi-structured interviews were conducted with 26 GPs self-identifying as having a 'high caseload' of patients and/or a particular interest in CHB. Participants were recruited from five jurisdictions and came from diverse ethnicities, clinical experience and practice profile. Interview data were analysed according to the principles of grounded theory. Patient and GP knowledge, a lack of community awareness, and language and cultural diversity impeded the GP response to CHB. Communication with specialists was reported as challenging with unclear referral pathways, limited feedback from specialists after referral, and poor liaison and support for managing people living with CHB. Regulations restricting GPs capacity to respond included the lack of prescribing opportunities, fear of Medicare auditing for screening the populations most at risk, and inadequate financial support given the complexity of CHB and the communities most affected by the infection. General Practitioners require additional skills and resources to support the effective management of people with CHB. These include improved awareness and knowledge about the infection, adequate financial resources to support patient management, and effective referral pathways and support. © 2013 The Authors. ANZJPH © 2013 Public Health Association of Australia.

Clinical management of chronic hepatitis B infection: results from a registry at a German tertiary referral center.

PubMed

Demir, M; Nigemeier, J; Kütting, F; Bowe, A; Schramm, C; Hoffmann, V; Waldschmidt, D; Goeser, T; Steffen, H-M

2015-04-01

We studied a cohort of adult patients with chronic hepatitis B (CHB) infection, followed at a tertiary referral liver center in Germany over 12.5 years to analyze the clinical features and impact of management on disease progression and survival of CHB patients in general and of those with CHB and HCC in particular. We retrospectively evaluated the medical records of 242 adult (age ≥ 18 years) patients. CHB was defined as positive hepatitis B surface antigen (HBsAg) and/or HBV-DNA levels >10 IU/mL for at least 6 months. Patient demographics, HBV markers, antiviral treatment, laboratory parameters, liver imaging and histology were recorded for each visit. HCC patients were divided into two groups and separately analyzed (group 1: n = 24, HCC at first visit and group 2: n = 11, HCC during surveillance). The mean age was 44 years in CHB patients without HCC (63% male) and about 59 years in patients with HCC (77% male). Antiviral therapy was given to 59% of patients without HCC compared to only 25% in group 1 and 18% in group 2 with comparable median HBV DNA levels of approximately 36,000 IU/mL. There was no statistically significant difference concerning the HCC stages (Milan, UCSF, BCLC) at first diagnosis. Five-year survival was 19% in group 1 vs. 64% in group 2 (p = 0.019), with LTx performed in 12 vs. 45%, respectively. Surveillance of CHB patients did not result in early stage detection of HCC but in a higher likelihood to receive potentially curative treatments.

Characteristics of liver fibrosis with different etiologies using a fully quantitative fibrosis assessment tool.

PubMed

Wu, Q; Zhao, X; You, H

2017-05-18

This study aimed to test the diagnostic performance of a fully quantitative fibrosis assessment tool for liver fibrosis in patients with chronic hepatitis B (CHB), primary biliary cirrhosis (PBC) and non-alcoholic steatohepatitis (NASH). A total of 117 patients with liver fibrosis were included in this study, including 50 patients with CHB, 49 patients with PBC and 18 patients with NASH. All patients underwent liver biopsy (LB). Fibrosis stages were assessed by two experienced pathologists. Histopathological images of LB slices were processed by second harmonic generation (SHG)/two-photon excited fluorescence (TPEF) microscopy without staining, a system called qFibrosis (quantitative fibrosis) system. Altogether 101 quantitative features of the SHG/TPEF images were acquired. The parameters of aggregated collagen in portal, septal and fibrillar areas increased significantly with stages of liver fibrosis in PBC and CHB (P<0.05), but the same was not found for parameters of distributed collagen (P>0.05). There was a significant correlation between parameters of aggregated collagen in portal, septal and fibrillar areas and stages of liver fibrosis from CHB and PBC (P<0.05), but no correlation was found between the distributed collagen parameters and the stages of liver fibrosis from those patients (P>0.05). There was no significant correlation between NASH parameters and stages of fibrosis (P>0.05). For CHB and PBC patients, the highest correlation was between septal parameters and fibrosis stages, the second highest was between portal parameters and fibrosis stages and the lowest correlation was between fibrillar parameters and fibrosis stages. The correlation between the septal parameters of the PBC and stages is significantly higher than the parameters of the other two areas (P<0.05). The qFibrosis candidate parameters based on CHB were also applicable for quantitative analysis of liver fibrosis in PBC patients. Different parameters should be selected for liver fibrosis assessment in different stages of PBC compared with CHB.

Characteristics of liver fibrosis with different etiologies using a fully quantitative fibrosis assessment tool

PubMed Central

Wu, Q.; Zhao, X.; You, H.

2017-01-01

This study aimed to test the diagnostic performance of a fully quantitative fibrosis assessment tool for liver fibrosis in patients with chronic hepatitis B (CHB), primary biliary cirrhosis (PBC) and non-alcoholic steatohepatitis (NASH). A total of 117 patients with liver fibrosis were included in this study, including 50 patients with CHB, 49 patients with PBC and 18 patients with NASH. All patients underwent liver biopsy (LB). Fibrosis stages were assessed by two experienced pathologists. Histopathological images of LB slices were processed by second harmonic generation (SHG)/two-photon excited fluorescence (TPEF) microscopy without staining, a system called qFibrosis (quantitative fibrosis) system. Altogether 101 quantitative features of the SHG/TPEF images were acquired. The parameters of aggregated collagen in portal, septal and fibrillar areas increased significantly with stages of liver fibrosis in PBC and CHB (P<0.05), but the same was not found for parameters of distributed collagen (P>0.05). There was a significant correlation between parameters of aggregated collagen in portal, septal and fibrillar areas and stages of liver fibrosis from CHB and PBC (P<0.05), but no correlation was found between the distributed collagen parameters and the stages of liver fibrosis from those patients (P>0.05). There was no significant correlation between NASH parameters and stages of fibrosis (P>0.05). For CHB and PBC patients, the highest correlation was between septal parameters and fibrosis stages, the second highest was between portal parameters and fibrosis stages and the lowest correlation was between fibrillar parameters and fibrosis stages. The correlation between the septal parameters of the PBC and stages is significantly higher than the parameters of the other two areas (P<0.05). The qFibrosis candidate parameters based on CHB were also applicable for quantitative analysis of liver fibrosis in PBC patients. Different parameters should be selected for liver fibrosis assessment in different stages of PBC compared with CHB. PMID:28538834

[Illness experience of people with chronic hepatitis B in Korea].

PubMed

Yi, Myungsun; Choi, Eun Ok; Paik, Seung Woon; Kim, Keum Soon; Kwak, Sangman; Lee, Hwa Jin

2007-08-01

The purpose of this study was to explore the experiences of people with chronic hepatitis B (CHB) in Korea. The specific aim was to identify major problems that people with CHB face and strategies that they are dealing with. A grounded theory method was utilized. The data were collected by individual in-depth interviews from 12 CHB patients from one of the major hospitals in Korea. After constant comparative analysis, a core category emerged as "illness management with self-reliance and will." Seven major strategies that were identified in dealing with the illness were maintaining receptive and positive attitudes; restraining excessive work and greed; searching for information; controlling illness information; adhering to practices for not spreading the viral disease; abstaining from alcohol and smoking and maintaining healthy eating habits; nd using alternative therapies. The outcomes that result from employing these strategies were identified as burden, depression and helplessness, stress for maintaining compliance, and dispirited interpersonal relationships. The results of this study suggest that most people with CHB in Korea have problems in psychosocial area. Thus health professionals need to provide not only informational support but also emotional one to improve quality of life of the people with CHB.

Relationship between liver injury and serum cytokeratin 18 levels in asymptomatic hepatitis B virus carriers and in patients with chronic hepatitis B infection.

PubMed

Balkan, Ayhan; Yılmaz, Nimet; Balkan, Yasemin; Koruk, Irfan; Örkmez, Mustafa; Aydınlı, Musa; Koruk, Mehmet

2017-06-01

Apoptosis represents a well-known mechanism of cell death involved in most chronic liver injuries. Our aim was to investigate the serum fragment level of cytokeratin 18 (CK18), M30, in asymptomatic hepatitis B virus (HBV) carriers and patients with chronic hepatitis B (CHB) and to evaluate the relationship between serum M30 levels and the severity of hepatic injury. Asymptomatic HBV carriers (n=169), patients with CHB (n=100), and healthy control subjects (n=43) were enrolled in the study. Serum CK18 (M30) levels were analysed in all subjects. Liver biopsy for histopathological assessment was performed in asymptomatic HBV carriers and in patients with CHB infection. Serum CK18 (M30) levels were significantly higher in asymptomatic HBV carriers (198.77±77.62U/L) than in healthy control subjects (146.92±40.18U/L). Patients with CHB (283.02±147.45U/L) had significantly higher CK18 (M30) levels than asymptomatic HBV carriers (p=0.001). The diagnostic efficacy of CK18 (M30) levels in distinguishing patients with HBeAg-negative CHB from asymptomatic HBV carriers was found to be moderate (c-statistics: 0.695), and the diagnostic cut-off value of CK18 (M30) was 262U/L (specificity: 85%, sensitivity: 48%, positive likelihood ratio: 3.35, and negative likelihood ratio: 0.60). There was a positive correlation between serum CK18 (M30) levels and histological activity index scores in asymptomatic HBV carriers and patients with CHB. Serum CK18 (M30) levels may be a valuable indicator in distinguishing asymptomatic HBV carriers from patients with HBeAg-negative CHB when considered together with ALT and HBV-DNA levels. Copyright © 2017 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.

Methotrexate is not associated with increased liver cirrhosis in a population-based cohort of rheumatoid arthritis patients with chronic hepatitis B

PubMed Central

Tang, Kuo-Tung; Hung, Wei-Ting; Chen, Yi-Hsing; Lin, Ching-Heng; Chen, Der-Yuan

2016-01-01

A few studies showed that long-term methotrexate (MTX) use exacerbates liver fibrosis and even leads to liver cirrhosis in rheumatoid arthritis (RA) patients. We therefore conducted a population-based cohort study to investigate the impact of long-term MTX use on the risk of chronic hepatitis B (CHB)-related cirrhosis among RA patients. We analyzed data from the National Health Insurance Research Database in Taiwan and identified 631 incident cases of RA among CHB patients (358 MTX users and 273 MTX non-users) from January 1, 1998 to December 31, 2007. After a median follow-up of more than 6 years since the diagnosis of CHB, a total of 41 (6.5%) patients developed liver cirrhosis. We did not find an increased risk of liver cirrhosis among CHB patients with long-term MTX use for RA. Furthermore, there was no occurrence of liver cirrhosis among 56 MTX users with a cumulative dose ≧3 grams after 97 months’ treatment. In conclusion, our data showed that long-term MTX use is not associated with an increased risk for liver cirrhosis among RA patients with CHB. However, interpretation of the results should be cautious due to potential bias in the cohort. PMID:26928373

Serum adipokine levels in chronic liver diseases: association of resistin levels with fibrosis severity.

PubMed

Tsochatzis, Emmanuel; Papatheodoridis, George V; Hadziyannis, Emilia; Georgiou, Anastasia; Kafiri, Georgia; Tiniakos, Dina G; Manesis, Emanuel K; Archimandritis, Athanasios J

2008-01-01

Leptin and adiponectin have been implicated in the pathogenesis and progression of non-alcoholic steatohepatitis (NASH) and chronic hepatitis C (CHC), but little is known about the role of resistin in chronic liver diseases. The objective of this study was to investigate serum levels of the above three adipokines in relation to the etiology of liver disease and to determine their associations with histological severity. We prospectively evaluated 146 patients (HBeAg-negative chronic hepatitis B (CHB): 52, CHC: 70, NASH: 24) who consecutively underwent liver biopsy. Detailed epidemiological, anthropometric and laboratory data were recorded. Histological lesions were evaluated blindly according to the Ishak and the Brunt classifications for CHB/CHC and NASH, respectively. Serum adipokine levels were similar between CHB and CHC patients, while CHB/CHC patients had significantly lower leptin levels compared with NASH patients (8.3+/-7.3 versus 17.6+/-16.6 ng/ml, p=0.012) and higher adiponectin (10.2+/-5.1 versus 7.5+/-4 microg/ml, p=0.018) and resistin levels (7.1+/-2.5 versus 5.7+/-2.8 ng/ml, p=0.016). In CHB/CHC, there was no significant association between steatosis or necroinflammation and levels of adipokines, while the presence of moderate/severe fibrosis (stages 4-6) was associated with higher leptin and adiponectin levels in male but not in female patients and with lower resistin levels irrespective of gender or other factors (adjusted odds ratio=0.788, p=0.035). Serum adipokine levels depend on the etiology of liver disease differing between chronic viral hepatitis and NASH, but not between CHB and CHC. In CHB/CHC, resistin levels are independently associated with fibrosis severity, whereas in the association of leptin and adiponectin levels with fibrosis, it seems to be a gender effect.

Longitudinal monitoring of liver stiffness by acoustic radiation force impulse imaging in patients with chronic hepatitis B receiving entecavir.

PubMed

Wu, Sheng-Di; Ding, Hong; Liu, Li-Li; Zhuang, Yuan; Liu, Yun; Cheng, Li-Sha; Wang, Si-Qi; Tseng, Yu-Jen; Wang, Ji-Yao; Jiang, Wei

2018-06-01

Acoustic radiation force impulse (ARFI) imaging measures liver stiffness (LS), which significantly correlates with the stage of liver fibrosis in treatment-naive patients with chronic hepatitis B (CHB). We aimed to prospectively assess the clinical usefulness of ARFI during long-term antiviral therapy in CHB. Seventy-one CHB patients were consecutively recruited and paired liver biopsies were performed in 27 patients. LS was assessed by ARFI semiannually during entecavir therapy. LS gradually decreased with treatment and continued to decrease after normalization of alanine aminotransaminase. Overall, 97.2% patients achieved improvement of LS, whereas 19.7% patients had more than 30% reduction in LS values between baseline and week 104. Multivariate linear regression analysis showed that the degree of LS reduction significantly correlated with the baseline levels of LS value, platelet and cholinesterase. In the 27 patients who underwent paired liver biopsies, LS significantly correlated with stage of fibrosis and inflammatory grade at baseline. LS values decreased more significantly in patients with fibrosis regression than those with static histological fibrosis. In CHB patients, LS assessed by ARFI was gradually reduced during antiviral therapy. Longitudinal monitoring of LS may be a promising noninvasive assessment of fibrosis regression during long-term antiviral therapy in CHB. Further large sample studies are needed. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Optimizing Surveillance Performance of Alpha-Fetoprotein by Selection of Proper Target Population in Chronic Hepatitis B

PubMed Central

Chung, Jung Wha; Kim, Beom Hee; Lee, Chung Seop; Kim, Gi Hyun; Sohn, Hyung Rae; Min, Bo Young; Song, Joon Chang; Park, Hyun Kyung; Jang, Eun Sun; Yoon, Hyuk; Kim, Jaihwan; Shin, Cheol Min; Park, Young Soo; Hwang, Jin-Hyeok; Jeong, Sook-Hyang; Kim, Nayoung; Lee, Dong Ho; Lee, Jaebong; Ahn, Soyeon

2016-01-01

Although alpha-fetoprotein (AFP) is the most widely used biomarker in hepatocellular carcinoma (HCC) surveillance, disease activity may also increase AFP levels in chronic hepatitis B (CHB). Since nucleos(t)ide analog (NA) therapy may reduce not only HBV viral loads and transaminase levels but also the falsely elevated AFP levels in CHB, we tried to determine whether exposure to NA therapy influences AFP performance and whether selective application can optimize the performance of AFP testing in CHB during HCC surveillance. A retrospective cohort of 6,453 CHB patients who received HCC surveillance was constructed from the electronic clinical data warehouse. Covariates of AFP elevation were determined from 53,137 AFP measurements, and covariate-specific receiver operating characteristics regression analysis revealed that albumin levels and exposure to NA therapy were independent determinants of AFP performance. C statistics were largest in patients with albumin levels ≥ 3.7 g/dL who were followed without NA therapy during study period, whereas AFP performance was poorest when tested in patients with NA therapy during study and albumin levels were < 3.7 g/dL (difference in C statics = 0.35, p < 0.0001). Contrary to expectation, CHB patients with current or recent exposure to NA therapy showed poorer performance of AFP during HCC surveillance. Combination of concomitant albumin levels and status of NA therapy can identify subgroup of CHB patients who will show optimized AFP performance. PMID:27997559

A five years study of antiviral effect of entecavir in Chinese chronic hepatitis B patients.

PubMed

Liu, Kehui; Xiang, Xiaogang; Bao, Rebecca; Chen, Rong; Liu, Yunye; Xie, Jingdong; Guo, Qing; Bao, Shisan; Xie, Qing; Wang, Hui

2016-07-01

Entecavir (ETV) is a potent viral replication inhibitor for chronic hepatitis B (CHB) patients. To investigate the efficacy of ETV in Chinese nucleos(t)ide(NA)-experienced CHB patients. Among 89 CHB patients with ETV monotherapy for ≥6 months, 33/89 (37%) or 56/89 (73%) were NA-naïve or NA-experienced. During a median follow-up of 5.75 years, all NA-naïve CHB patients achieved VR without genotypic ETV-resistance. However, VR was observed in 50/56 (~90%) of NA-experienced CHB patients during a median follow-up of 4.75 years. Antiviral efficacy was not reduced in patients with previous lamivudine (LAM) with/without LAM-resistance (HR 0.465; 95% CI 0.196-1.100; p > 0.05) (HR 0.472; 95% CI 0.205-1.091; p > 0.05). Patients with a primary treatment failure to adefovir (ADV) had a reduced probability of achieving VR compared to NA-naïve (HR 0.496; 95% CI 0.287-0.857; p < 0.01). Previous ADV-experienced patients with a partial VR (HR 1.253; 95% CI 0.429-3.665; p > 0.05) did not influence antiviral response to ETV. The antiviral efficacy of ETV is not influenced by previous treatment LAM with/without LAM-resistance. ETV may still be an option in ADV-experienced patients with a partial VR, but not advised in patients with a primary treatment failure to ADV.

Evaluation of APRI and FIB-4 scoring systems for non-invasive assessment of hepatic fibrosis in chronic hepatitis B patients.

PubMed

Kim, W Ray; Berg, Thomas; Asselah, Tarik; Flisiak, Robert; Fung, Scott; Gordon, Stuart C; Janssen, Harry L A; Lampertico, Pietro; Lau, Daryl; Bornstein, Jeffrey D; Schall, Raul E Aguilar; Dinh, Phillip; Yee, Leland J; Martins, Eduardo B; Lim, Seng Gee; Loomba, Rohit; Petersen, Jörg; Buti, Maria; Marcellin, Patrick

2016-04-01

While the gold standard in the assessment of liver fibrosis remains liver biopsy, non-invasive methods have been increasingly used for chronic hepatitis B (CHB). This study aimed to evaluate the performance of two commonly used non-invasive scoring systems (aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4)) to predict fibrosis stage in CHB patients. Demographic, histologic and clinical laboratory data from two trials investigating tenofovir disoproxil fumarate in CHB were analyzed. Predicted fibrosis stage, based on established scales and cut-off values for APRI and FIB-4 scores, was compared with Ishak scores obtained from liver biopsy at baseline and at 240 week follow-up. In the 575 patients with a baseline liver biopsy, APRI and FIB-4 scores correlated with Ishak stage (p<0.01); however extensive overlap in the distribution of both scores across Ishak stages prevented accurate determination of fibrosis. The majority (81-89%) of patients with advanced fibrosis or cirrhosis were missed by the scores. Similarly, 71% patients without fibrosis were misclassified as having clinically significant fibrosis. APRI and FIB-4 scores at week 240 tended to be low and underestimate fibrosis stage in the patients with liver biopsies after 240 weeks of therapy. APRI or FIB-4 reduction did not correlate with fibrosis regression after 240 weeks of antiviral therapy. APRI and FIB-4 scores are not suitable for use in clinical practice in CHB patients for assessment of hepatic fibrosis according to Ishak stage, especially in gauging improvements in liver fibrosis following therapy. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Simple and Reliable Method to Quantify the Hepatitis B Viral Load and Replicative Capacity in Liver Tissue and Blood Leukocytes

PubMed Central

Minosse, Claudia; Coen, Sabrina; Visco Comandini, Ubaldo; Lionetti, Raffaella; Montalbano, Marzia; Cerilli, Stefano; Vincenti, Donatella; Baiocchini, Andrea; Capobianchi, Maria R.; Menzo, Stefano

2016-01-01

Background A functional cure of chronic hepatitis B (CHB) is feasible, but a clear view of the intrahepatic viral dynamics in each patient is needed. Intrahepatic covalently closed circular DNA (cccDNA) is the stable form of the viral genome in infected cells, and represents the ideal marker of parenchymal colonization. Its relationships with easily accessible peripheral parameters need to be elucidated in order to avoid invasive procedures in patients. Objectives The goal of this study was to design, set up, and validate a reliable and straightforward method for the quantification of the cccDNA and total DNA of the hepatitis B virus (HBV) in a variety of clinical samples. Patients and Methods Clinical samples from a cohort of CHB patients, including liver biopsies in some, were collected for the analysis of intracellular HBV molecular markers using novel molecular assays. Results A plasmid construct, including sequences from the HBV genome and from the human gene hTERT, was generated as an isomolar multi-standard for HBV quantitation and normalization to the cellular contents. The specificity of the real-time assay for the cccDNA was assessed using Dane particles isolated on a density gradient. A comparison of liver tissue from 6 untreated and 6 treated patients showed that the treatment deeply reduced the replicative capacity (total DNA/cccDNA), but had limited impact on the parenchymal colonization. The peripheral blood mononuclear cells (PBMCs) and granulocytes from the treated and untreated patients were also analyzed. Conclusions A straightforward method for the quantification of intracellular HBV molecular parameters in clinical samples was developed and validated. The widespread use of such versatile assays could better define the prognosis of CHB, and allow a more rational approach to time-limited tailored treatment strategies. PMID:27882060

Blocking and reversing hepatic fibrosis in patients with chronic hepatitis B treated by traditional Chinese medicine (tablets of biejia ruangan or RGT): study protocol for a randomized controlled trial.

PubMed

Qu, Jianhui; Yu, Zujiang; Li, Qin; Chen, Yongping; Xiang, Dedong; Tan, Lin; Lei, Chunliang; Bai, Wenlin; Li, Hongyan; Shang, Qinghua; Chen, Liang; Hu, Xiaoyu; Lu, Wei; Li, Zhiqin; Chen, Da; Wang, Xiaodong; Zhang, Changjiang; Xiao, Guangming; Qi, Xun; Chen, Jing; Zhou, Li; Chen, Guofeng; Li, Yonggang; Zeng, Zhen; Rong, Guanghua; Dong, Zheng; Chen, Yan; Lou, Min; Wang, Chunping; Lu, Yinying; Zhang, Cuihong; Yang, Yongping

2014-11-10

Chronic hepatitis B (CHB) can progress to cirrhosis, hepatocellular carcinoma (HCC) and ultimately liver-related death. Although oral antiviral therapy for patients with CHB reduces the risk of such complications, once cirrhosis is established, the benefits of antiviral therapy are not robustly demonstrated. According to traditional Chinese medicine (TCM), some Chinese herbal medicines promote blood circulation and soften hard masses, and therefore they may block and reverse hepatic fibrosis. The aim of this study is to evaluate the effects of TCM tablets of the compound biejia ruangan (RGT) administered for fibrosis, and entecavir (ETV), on the development of HCC in patients with CHB or hepatitis B virus (HBV)-related compensated cirrhosis. This multicenter, centrally randomized, double-blind, placebo-controlled, parallel-group study is planned to complete within 5 years. For the study, 1,000 with CHB or HBV-related compensated cirrhosis are randomly assigned in a 1:1 ratio to a treatment group (0.5 mg ETV once daily; 2 g RGT three times daily) or a control group (0.5 mg ETV once daily; 2 g RGT dummy agent three times daily). The primary end points are the development of HCC and liver-related death. Secondary end points include disease progression and overall survival. Although antiviral therapy can achieve sustained suppression of HBV replication, thereby preventing cirrhosis, patients with CHB treated with nucleos(t)ide analogs (NUCs) retain a higher risk for HCC compared with patients with inactive disease. Although previous clinical trials with RGT have confirmed the efficacy of blocking and reversing hepatic fibrosis in patients with CHB or compensated cirrhosis, the long-term risk for HCC or disease progression in these patients treated with combination of RGT and NUCs compared with NUCs alone is unclear. Therefore, it is necessary to investigate the effects of the RGT blockade and reversal of hepatic fibrosis on the development of HCC in patients with CHB or HBV-related compensated cirrhosis in large, prospective, multicenter, double-blind, randomized, controlled trials in China. ClinicalTrials.gov Identifier: NCT01965418. Date registered: 17 October 2013.

Sociocultural factors that potentially affect the institution of prevention and treatment strategies for prevention of hepatitis B in Chinese Canadians.

PubMed

Wu, Harry; Yim, Colina; Chan, Alex; Ho, Michael; Heathcote, Jenny

2009-01-01

Despite the availability of screening for chronic hepatitis B (CHB) infection and effective treatments now available, many at-risk individuals fail to seek appropriate medical attention. To identify the barriers to care for CHB infection in a Chinese Canadian community. A survey conducted in English or Chinese collected information from individuals with CHB infection that evaluated the level of understanding and identified the barriers that may prevent Chinese patients from undergoing monitoring, screening and/or treatment for CHB infection. Among the 204 patients enrolled, common misconceptions were that sharing food transmits hepatitis B and that patients with severe disease are always symptomatic. Patients with a better understanding of hepatitis B were better educated, younger and were being followed at a tertiary care centre (P<0.01 for all). Prominent barriers to health care were time, inconvenience and language difficulties. Patients under the care of family physicians who had extended office hours were less likely to cite time (P=0.06) and distance (P=0.05) as barriers. Patient misconceptions that severe liver disease due to hepatitis B infection is symptomatic may factor into the unwillingness to spare the time and undergo the inconvenience associated with regular medical follow-up. Implementation of programs that increase awareness of the silent progression of CHB infection and provide culturally responsive clinics, better able to work within patients' time constraints may improve Chinese patients' access to health care.

The rs2296651 (S267F) variant on NTCP (SLC10A1) is inversely associated with chronic hepatitis B and progression to cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis B.

PubMed

Hu, Hui-Han; Liu, Jessica; Lin, Yu-Ling; Luo, Wun-Sheng; Chu, Yu-Ju; Chang, Chia-Lin; Jen, Chin-Lan; Lee, Mei-Hsuan; Lu, Sheng-Nan; Wang, Li-Yu; You, San-Lin; Yang, Hwai-I; Chen, Chien-Jen

2016-09-01

The sodium taurocholate co-transporting polypeptide (NTCP), encoded by SLC10A1, was recently identified as a receptor for HBV. We assessed the association of the p.Ser267Phe variant (rs2296651) with chronic hepatitis B (CHB) serostatus, cirrhosis and hepatocellular carcinoma (HCC) in patients with CHB. The variant was genotyped in 3801 patients with CHB and 3801 matched hepatitis B surface antigen (HBsAg) seronegative individuals. ORs with 95% CIs for the variant's association with CHB, cirrhosis and HCC were estimated using logistic regression. In patients with CHB, the S267F variant was observed in 515 (18.5%) controls, 40 (17.2%) cirrhosis only cases, 49 (13.2%) non-cirrhotic HCC cases, and 52 (12.7%) cirrhotic-HCC cases. After adjustment for known risk factors, S267F was significantly associated with decreased risk for cirrhosis (OR 0.65 (95% CI 0.49 to 0.86), p=0.002) and HCC (OR 0.55 (95% CI 0.42 to 0.72), p<0.001). This association persisted for non-cirrhotic and cirrhotic-HCC. Compared with patients with HBV DNA levels greater than 10(5) copies/mL who carried the GG genotype, patients who had undetectable HBV DNA and the GA or AA genotypes had a 25-fold decreased risk of developing HCC (OR 0.04 (95% CI 0.02 to 0.11), p<0.001). The AA genotype was also associated with HBsAg seronegativity (OR 0.13 (95% CI 0.05 to 0.34), p<0.001). The SLC10A1 (NTCP) S267F variant is independently associated with decreased risk of cirrhosis and HCC, and resistance to CHB infection. Together with serum HBV DNA levels, S267F may help to identify patients with CHB with very low risk of HCC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Virological Characteristics of Acute Hepatitis B in Eastern India: Critical Differences with Chronic Infection.

PubMed

Sarkar, Neelakshi; Pal, Ananya; Das, Dipanwita; Saha, Debraj; Biswas, Avik; Bandopadhayay, Bhaswati; Chakraborti, Mandira; Ghosh, Mrinmoy; Chakravarty, Runu

2015-01-01

Hepatitis B Virus (HBV) manifests high genetic variability and is classifiable into ten genotypes (A-J). HBV infection can lead to variable clinical outcomes, ranging from self-limiting acute hepatitis to active chronic hepatitis, cirrhosis and hepatocellular carcinoma. The present study characterizes HBV strains circulating among patients with acute (AHB) and chronic HBV infection (CHB). Among a total of 653 HBsAg positive cases, 40 manifested acute infection. After sequencing the surface(S), basal core promoter/pre-core(BCP/PC) and the X gene regions, phylogenetic tree was constructed using MEGA4 by neighbor-joining method. Statistical robustness was established with bootstrap analysis. Nucleotide diversity was determined by Shannon entropy per site using the Entropy program of the Los Alamos National Laboratories. Analyses of acute patients revealed that HBV/D2 is the major circulating sub-genotype and commonly associated with sexual promiscuity and the age group between15-30 years. Comparison of AHB and CHB patients revealed that HBeAg positivity, ALT levels and genotype D were significantly high in AHB, whereas CHB patients were predominantly male, had a high viral load, and were commonly associated with genotype C. The frequencies of mutations in the S, BCP/PC, and X gene were low in AHB as compared to CHB. Drug resistant mutations were not detectable in the polymerase gene of AHB. Average nucleotide diversity in AHB was considerably low as compared to CHB. Further, the highest average ΔH (average difference in entropy between chronic and acute infection) was observed in the BCP/PC region implying that this region was most vulnerable to mutations upon HBV persistence, especially in case of genotype C. Additionally, among all substitutions, the A1762T and G1764A BCP mutations were the strongest indicators of chronicity. In conclusion, the study exhibits a general portrait of HBV strains circulating among acute hepatitis B patients in Eastern India and their intricate differences with chronic patients which should be useful from the clinical point of view.

Serum adiponectin is increased in advancing liver fibrosis and declines with reduction in fibrosis in chronic hepatitis B.

PubMed

Hui, Chee-Kin; Zhang, Hai-Ying; Lee, Nikki P; Chan, Weng; Yueng, Yui-Hung; Leung, Kar-Wai; Lu, Lei; Leung, Nancy; Lo, Chung-Mau; Fan, Sheung-Tat; Luk, John M; Xu, Aimin; Lam, Karen S; Kwong, Yok-Lam; Lau, George K K

2007-08-01

Despite the possible role of adiponectin in the pathogenesis of liver cirrhosis, few data have been collected from patients in different stages of liver fibrosis. We studied the role of adiponectin in 2 chronic hepatitis B (CHB)-patient cohorts. Serum adiponectin was quantified by enzyme-linked immunosorbent assay. One-hundred liver biopsy specimens from CHB patients with different stages of fibrosis and 38 paired liver biopsies from hepatitis B e antigen-positive patients randomized to lamivudine (n=15), pegylated interferon alfa-2a (n=15) or pegylated interferon alfa-2a plus lamivudine (n=8) therapy for 48 weeks were assessed. Serum adiponectin was detected at levels ranging over fourfold magnitude with advancing fibrosis stage and correlated positively with fibrosis stage [r=0.45, p<0.001]. CHB patients with stage 0-1 fibrosis had higher composition of high molecular weight (HMW) form of adiponectin when compared with CHB patients with liver cirrhosis [mean+/-SEM 51.2+/-2.1% vs. 40.9+/-1.7%, respectively, p=0.001]. After antiviral therapy, patients with fibrosis reduction had marked decline in serum adiponectin level and increase in HMW form of adiponectin [mean+/-SEM 43.5+/-1.2% vs. 37.0+/-3.0%, respectively, p=0.04]. Serum adiponectin may have a role in fibrosis progression in CHB infection. A marked decline in serum adiponectin after antiviral therapy is associated with fibrosis reduction.

Risk Factors for Hepatocellular Carcinoma in Cirrhotic Patients with Chronic Hepatitis B.

PubMed

Zhang, Yuan-Qing; Peng, Li-Jun; Cao, Yi-Rong; Zeng, Zhi-Ping; Wu, Yu-Jing; Shi, Hong; Cheng, Shi-Yao; Wang, Ji-Yao; Friedman, Scott L; Sninsky, John J; Guo, Jin-Sheng

2016-09-01

To investigate the clinical and genetic risk factors associated with hepatocellular carcinoma (HCC) in cirrhotic patients with chronic hepatitis B (CHB). Nine hundred forty-nine Chinese Han patients with CHB were studied, including noncirrhotic patients without HCC (N = 234), cirrhotic patients without (N = 281) and with HCC (N = 434). Patients were genotyped for 10 candidate single nucleotide polymorphisms (SNPs) by the polymerase chain reaction (PCR)-ligase detection reaction (LDR) method. By multivariate logistic regression analysis adjusted for Child-Pugh scores, noneffective antiviral treatment, drinking history, family history of HCC, and age ≥50 years old were associated with HCC risk (odds ratio [OR] = 5.923, 2.456, 2.241, 1.955, respectively). Sixty-two of 170 cirrhotic patients who achieved sustained virological suppression by antiviral treatment developed HCC, with fatty liver disease, family history of HCC, and family history of hepatitis B virus (HBV) infection as the risk factors (OR = 11.646, 3.339, 2.537, respectively). The SNPs associated with HCC risk in patients with cirrhosis and CHB were rs11536889 in TLR4 and rs2853744 in SPP1. Polymorphisms of TLR4 rs2149356, AP3S2 rs2290351, STXBP5L rs2169302, MLEC rs7976497, and SOCS3 rs4969168 were associated with HCC risk in specific stratified analyses with gender, age, and drinking history in the cirrhotic patients. Inadequate antiviral treatment, family history of HCC, drinking history, and age ≥50 years old are risk factors for HCC. Sustained suppression of HBV does not eliminate the risk of HCC. Specific host genetic factors may impact HCC development in Han Chinese cirrhotic patients with CHB, including SNPs in TLR4, SPP1, AP3S2, STXBP5L, MLEC, and SOCS3, which warrant further validation in additional cohorts.

Restored Circulating Invariant NKT Cells Are Associated with Viral Control in Patients with Chronic Hepatitis B

PubMed Central

Jiang, Xiaotao; Zhang, Mingxia; Lai, Qintao; Huang, Xuan; Li, Yongyin; Sun, Jian; Abbott, William G.H.; Ma, Shiwu; Hou, Jinlin

2011-01-01

Invariant NKT (iNKT) cells are involved in the pathogenesis of various infectious diseases. However, their role in hepatitis B virus (HBV) infection is not fully understood, especially in human species. In this study, 35 chronic hepatitis B (CHB) patients, 25 inactive carriers (IC) and 36 healthy controls (HC) were enrolled and the proportions of circulating iNKT cells in fresh isolated peripheral blood mononuclear cells (PBMC) were detected by flow cytometry. A longitudinal analysis was also conducted in 19 CHB patients who received antiviral therapy with telbivudine. Thereafter, the immune functions of iNKT cells were evaluated by cytokine secretion and a two-chamber technique. The median frequency of circulating iNKT cells in CHB patients (0.13%) was lower than that in HC (0.24%, P = 0.01) and IC (0.19%, P = 0.02), and increased significantly during antiviral therapy with telbivudine (P = 0.0176). The expressions of CC chemokine receptor 5 (CCR5) and CCR6 were dramatically higher on iNKT cells (82.83%±9.87%, 67.67%±16.83% respectively) than on conventional T cells (30.5%±5.65%, 14.02%±5.92%, both P<0.001) in CHB patients. Furthermore, iNKT cells could migrate toward the CC chemokine ligand 5. Patients with a high ratio (≥1.0) of CD4−/CD4+ iNKT cells at baseline had a higher rate (58.33%) of HBeAg seroconversion than those with a low ratio (<1.0, 0%, P = 0.0174). In conclusion, there is a low frequency of peripheral iNKT cells in CHB patients, which increases to normal levels with viral control. The ratio of CD4−/CD4+ iNKT cells at baseline may be a useful predictor for HBeAg seroconversion in CHB patients on telbivudine therapy. PMID:22194934

Nucleoside Analog-treated Chronic Hepatitis B Patients showed Reduced Expression of PECAM-1 Gene in Peripheral Blood Mononuclear Cells in Bangladesh

PubMed Central

Tabassum, Shahina; Ullah Munshi, Saif; Hossain, Marufa; Imam, Akhter

2014-01-01

ABSTRACT Background and aim Assessment of therapeutic response is important for monitoring the prognosis and to take decision for cessation of nucleoside analogues therapy in chronic hepatitis B patients. In addition to serum alanine aminotransferase (ALT), hepatitis B virus (HBV) deoxyribonucleic acid (DNA) load and HBeAg status, identification of molecular markers associated with host immune response would be essential to assess therapeutic response. In this regard the current study was performed with the aim to detect expression of platelet endothelial cell adhesion molecule (PECAM)-I gene in peripheral blood monocytes (PBMCs) of treated chronic hepatitis B patients and also to correlate expression of this gene with serum HBV DNA load and serum ALT levels. Materials and methods The study analyzed 60 chronic hepatitis B (CHB) patients, including 30 untreated and 30 nucleoside analogs treated and 10 healthy controls. PECAM-1 gene expression/ transcripts were detected by conventional RT-PCR. Results The expression PECAM-1 mRNA in the PBMCs of CHB patients was significantly higher in untreated (3.17 ± 0.75) than the treated patients (1.64 ± 0.29) (p < 0.01). Expression of PECAM-1 was positively correlated with serum ALT levels of both untreated (r = 0.580) and treated (r = 0.566) CHB patients. Moreover, in both untreated and treated groups, these gene expressions were positively correlated to serum HBV DNA load with the correlation coefficient r = 0.545 and r = 0.591 respectively. Conclusion PECAM-1 may be used as a biomarker for assessment of inflammatory activity as well as therapeutic response in CHB patients. How to cite this article: Sultana N, Tabassum S, Munshi SU, Hossain M, Imam A. Nucleoside Analog-treated Chronic Hepatitis B Patients showed Reduced Expression of PECAM-1 Gene in Peripheral Blood Mononuclear Cells in Bangladesh. Euroasian J Hepato-Gastroenterol 2014;4(2):87-91. PMID:29699354

Psychometrics of the chronic liver disease questionnaire for Southern Chinese patients with chronic hepatitis B virus infection

PubMed Central

Lam, Elegance Ting Pui; Lam, Cindy Lo Kuen; Lai, Ching Lung; Yuen, Man Fung; Fong, Daniel Yee Tak

2009-01-01

AIM: To test the psychometric properties of a Chinese [(Hong Kong) HK] translation of the chronic liver disease questionnaire (CLDQ). METHODS: A Chinese (HK) translation of the CLDQ was developed by iterative translation and cognitive debriefing. It was then administered to 72 uncomplicated and 78 complicated chronic hepatitis B (CHB) patients in Hong Kong together with a structured questionnaire on service utilization, and the Chinese (HK) SF-36 Health Survey Version 2 (SF-36v2). RESULTS: Scaling success was ≥ 80% for all but three items. A new factor assessing sleep was found and items of two (Fatigue and Systemic Symptoms) subscales tended to load on the same factor. Internal consistency and test-retest reliabilities ranged from 0.58-0.90 for different subscales. Construct validity was confirmed by the expected correlations between the SF-36v2 Health Survey and CLDQ scores. Mean scores of CLDQ were significantly lower in complicated compared with uncomplicated CHB, supporting sensitivity in detecting differences between groups. CONCLUSION: The Chinese (HK) CLDQ is valid, reliable and sensitive for patients with CHB. Some modifications to the scaling structure might further improve its psychometric properties. PMID:19598306

Labile glycated haemoglobin and carbamylated haemoglobin are still critical points for HbA1c measurement.

PubMed

Desmons, Aurore; Jaisson, Stéphane; Leroy, Nathalie; Gillery, Philippe; Guillard, Emmanuelle

2017-06-15

Haemoglobin A 1c (HbA 1c ) is a key analyte for the monitoring of glycemic balance in diabetic patients and is used for diabetes diagnosis in many countries. The potential interference of carbamylated haemoglobin (cHb) and labile glycated haemoglobin (LA 1c ) on HbA 1c assays must remain a matter of vigilance. Such a situation has occurred in our laboratory with a kit replacement on the Bio-Rad Variant™ II testing system, a cation-exchange high performance liquid chromatography (HPLC) system. With this method, LA 1c and cHb coeluted in a same peak which may have different consequences on HbA 1c values. The influence of increasing LA 1c and cHb values on HbA 1c results was studied with in vitro glycation and carbamylation of samples. Samples from patients with high and normal blood urea concentrations were assayed by HPLC and immunological assay. We observed that the degree of interference greatly varied depending on the nature of the interfering Hb fractions found under the so-called "LA 1c peak". Thus, we have decided to apply a decision tree using "LA 1c " thresholds depending on: (i) the retention time, (ii) the shape of the peak, (iii) other analytes, like urea. If the peak recognized as "LA 1c " is mainly formed by LA 1c, we consider that there is no interference until 4%. If the peak is mainly formed by cHb, we consider an interference threshold equal to 2%. This situation reminds that cHb and LA 1c remain critical issues in chromatography-based HbA 1c assays and that adapted criteria must be set up for result interpretation.

Is the neutrophil to lymphocyte ratio associated with liver fibrosis in patients with chronic hepatitis B?

PubMed

Kekilli, Murat; Tanoglu, Alpaslan; Sakin, Yusuf Serdar; Kurt, Mevlut; Ocal, Serkan; Bagci, Sait

2015-05-14

To determine the association between the neutrophil to lymphocyte (N/L) ratio and the degree of liver fibrosis in patients with chronic hepatitis B (CHB) infection. Between December 2011 and February 2013, 129 consecutive CHB patients who were admitted to the study hospitals for histological evaluation of chronic hepatitis B-related liver fibrosis were included in this retrospective study. The patients were divided into two groups based on the fibrosis score: individuals with a fibrosis score of F0 or F1 were included in the "no/minimal liver fibrosis" group, whereas patients with a fibrosis score of F2, F3, or F4 were included in the "advanced liver fibrosis" group. The Statistical Package for Social Sciences 18.0 for Windows was used to analyze the data. A P value of < 0.05 was accepted as statistically significant. Three experienced and blinded pathologists evaluated the fibrotic status and inflammatory activity of 129 liver biopsy samples from the CHB patients. Following histopathological examination, the "no/minimal fibrosis" group included 79 individuals, while the "advanced fibrosis" group included 50 individuals. Mean (N/L) ratio levels were notably lower in patients with advanced fibrosis when compared with patients with no/minimal fibrosis. The mean value of the aspartate aminotransferase-platelet ratio index was markedly higher in cases with advanced fibrosis compared to those with no/minimal fibrosis. Reduced levels of the peripheral blood N/L ratio were found to give high sensitivity, specificity and predictive values in CHB patients with significant fibrosis. The prominent finding of our research suggests that the N/L ratio can be used as a novel noninvasive marker of fibrosis in patients with CHB.

Immune Cell Subsets Evaluation as a Predictive Tool for Hepatitis B Infection Outcome and Treatment Responsiveness.

PubMed

Kandilarova, Snezhina M; Georgieva, Atanaska I; Mihaylova, Anastasiya P; Baleva, Marta P; Atanasova, Valentina K; Petrova, Diana V; Popov, Georgi T; Naumova, Elissaveta J

2017-03-01

The patient's immune response is one of the major factors influencing HBV eradication or chronification, and it is thought to be responsible for the treatment success. Our study aimed to investigate whether cellular defense mechanisms are associated with the course of HBV infection (spontaneous recovery [SR] or chronification [CHB]) and with the therapeutic approach. A total of 139 patients (118 with CHB, 21 SR) and 29 healthy individuals (HI) were immunophenotyped by flowcytometry. Fifty-six patients were treatment-naïve, 20 were treated with interferons and 42 with nucleoside/ nucleotide analogues. Deficiency of T lymphocytes, helper-inducer (CD3+CD4+), suppressorcytotoxic (CD8+CD3+) and cytotoxic (CD8+CD11b-, CD8+CD28+) subsets, activated T cells (CD3+HLA-DR+, CD8+CD38+) and increased CD57+CD8- cells, elevated percentages of B lymphocytes and NKT cells were observed in CHB patients compared with HI. In SR patients, elevated CD8+CD11b+, NKT and activated T cells were found in comparison with controls. The higher values of T cells and their subsets in SR patients than in CHB patients reflect a recovery of cellular immunity in resolved HBV infection individuals. In both groups of treated patients, reduced T lymphocytes, CD3+CD4+ and CD8+CD38+ subsets were found in comparison with HI. Higher proportions of cytotoxic subsets were observed in treated patients compared with treatment-naïve CHB patients, more pronounced in the group with interferon therapy. Our data demonstrate that cellular immune profiles may be of prognostic value in predicting the clinical course of HBV infection, and the determination of the therapeutic response.

IL-18 promoter -137G/C polymorphism correlates with chronic hepatitis B and affects the expression of interleukins.

PubMed

Jiang, H; Cao, H; Liu, G; Huang, Q; Li, Y

2014-01-01

The relationship between the interleukin (IL)-18 promoter -137G/C polymorphism and plasma levels of IL-18, IL-12, IL-4, and IFN-γ in chronic hepatitis B (CHB) patients and healthy subjects was investigated. The polymorphism was genotyped by a ligase detection reaction-PCR (LDR-PCR), while the cytokines were assayed by ELISA. Compared with healthy subjects, CHB patients exhibited an increased frequency of the G allele, GG genotype and increased IL-4 levels, but decreased levels of IL-18, IL-12, and IFN-γ. A positive correlation for IL-18 ~ IL-12 ~ IFN-γ and a negative correlation for IL-18 ~ IL-4 were found. We conclude that the IL-18 promoter -137G polymorphisms correlated with CHB infection and influenced the expression of IL-18. The studied interleukins represent an immunomodulatory network that plays important roles in host immune responses to CHB infection.

Predictive model for inflammation grades of chronic hepatitis B: Large-scale analysis of clinical parameters and gene expressions.

PubMed

Zhou, Weichen; Ma, Yanyun; Zhang, Jun; Hu, Jingyi; Zhang, Menghan; Wang, Yi; Li, Yi; Wu, Lijun; Pan, Yida; Zhang, Yitong; Zhang, Xiaonan; Zhang, Xinxin; Zhang, Zhanqing; Zhang, Jiming; Li, Hai; Lu, Lungen; Jin, Li; Wang, Jiucun; Yuan, Zhenghong; Liu, Jie

2017-11-01

Liver biopsy is the gold standard to assess pathological features (eg inflammation grades) for hepatitis B virus-infected patients although it is invasive and traumatic; meanwhile, several gene profiles of chronic hepatitis B (CHB) have been separately described in relatively small hepatitis B virus (HBV)-infected samples. We aimed to analyse correlations among inflammation grades, gene expressions and clinical parameters (serum alanine amino transaminase, aspartate amino transaminase and HBV-DNA) in large-scale CHB samples and to predict inflammation grades by using clinical parameters and/or gene expressions. We analysed gene expressions with three clinical parameters in 122 CHB samples by an improved regression model. Principal component analysis and machine-learning methods including Random Forest, K-nearest neighbour and support vector machine were used for analysis and further diagnosis models. Six normal samples were conducted to validate the predictive model. Significant genes related to clinical parameters were found enriching in the immune system, interferon-stimulated, regulation of cytokine production, anti-apoptosis, and etc. A panel of these genes with clinical parameters can effectively predict binary classifications of inflammation grade (area under the ROC curve [AUC]: 0.88, 95% confidence interval [CI]: 0.77-0.93), validated by normal samples. A panel with only clinical parameters was also valuable (AUC: 0.78, 95% CI: 0.65-0.86), indicating that liquid biopsy method for detecting the pathology of CHB is possible. This is the first study to systematically elucidate the relationships among gene expressions, clinical parameters and pathological inflammation grades in CHB, and to build models predicting inflammation grades by gene expressions and/or clinical parameters as well. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Long-term lamivudine treatment achieves regression of advanced liver fibrosis/cirrhosis in patients with chronic hepatitis B.

PubMed

Xu, Bei; Lin, Lanyi; Xu, Guoguang; Zhuang, Yan; Guo, Qing; Liu, Yunye; Wang, Hui; Zhou, Xiaqiu; Wu, Shanming; Bao, Shisan; Cai, Wei; Xie, Qing

2015-02-01

Antiviral therapy is important in advanced liver fibrosis/cirrhosis with chronic hepatitis B (AdLF-CHB) patients, but complete regression of cirrhosis remains to be the challenge. We aimed to investigate whether up to 10 years lamivudine treatment achieves liver fibrosis/cirrhosis regression in AdLF-CHB patients. Improvement of hepatic fibrosis/cirrhosis, virological response and disease progression were evaluated in 28 AdLF-CHB patients with up to 10 years lamivudine treatment. Liver biopsy was performed in all of the 28 patients at baseline, but only 19 patients had second biopsy at year 10. There were 24 hepatitis B e antigen (HBeAg)-positive and 4 HBeAg-negative patients within the original 28 AdLF-CHB patients. At the end of 10 years lamivudine treatment, 20 of the 24 HBeAg-positive patients had HBeAg loss. HBeAg seroconversion was detected in 10 of these 20 HBeAg loss patients. HBsAg loss was observed in 4 of the original 28 patients. Among these four HBsAg loss patients, three had HBsAg seroconversion. All patients achieved hepatitis B virus DNA (HBV DNA) undetectable. Histopathology was evaluated between paired original and final liver biopsies among 19 patients as follows: 4/19 achieved complete liver fibrosis/cirrhosis regression; 9/19 improved in Ishak fibrosis score; whereas 6/19 showed no fibrosis improvement. About 75% patients achieved inflammatory/fibrotic improvement. No significant disease progression was observed in 24/28 patients. Furthermore, no significant difference in histopathology improvement, cirrhosis regression, disease progression between non-resistance and rescue for resistance was observed. Long-term lamivudine therapy achieves regression of fibrosis/cirrhosis and improvement of histological and disease progression in AdLF-CHB patients. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Frequency of interleukin 28B rs12979860 C>T variants in Filipino patients chronically infected with hepatitis B virus.

PubMed

Baclig, Michael O; Reyes, Karen G; Mapua, Cynthia A; Gopez-Cervantes, Juliet; Natividad, Filipinas F

2015-03-01

Hepatitis B virus (HBV) is one of the most prevalent viral infections worldwide. Nearly 400 million individuals are chronic carriers of HBV. The aim of the present study was to determine the frequency of human interleukin 28B (IL28B) variants among treatment naive Filipino patients clinically diagnosed with chronic hepatitis B (CHB), and to compare the IL28B frequency distribution with various ethnic populations. Fifty-seven CHB patients and 43 normal controls were enrolled in this study. Real-time PCR was performed using the TaqMan genotyping assay for IL28B rs12979860. The allelic frequencies among normal controls were 0.94 and 0.06 for the IL28B rs12979860 C and T alleles, respectively. Eighty-eight percent were identified as homozygous for the IL28B C/C genotype and 12% were identified as heterozygous for the IL28B C/T genotype. Among CHB patients, the allelic frequencies were 0.90 for the IL28B C allele and 0.10 for the IL28B T allele. No IL28B T/T genotype was observed between the two groups. No significant difference in the distribution of IL28B genotypes was observed between normal controls and CHB patients. Allelic frequencies of IL28B among Filipinos were similar with other Asian populations but significantly different from Caucasians. The frequency of rs12979860 C>T variants among Filipino CHB patients has not yet been reported. These data provided new insight into the geographical frequency distribution of IL28B variants. Further studies are needed to determine the possible association between IL28B variants and response to pegylated-interferon-α plus ribavirin combination therapy among Filipino patients chronically infected with HBV.

Antibody to hepatitis B core antigen levels in the natural history of chronic hepatitis B: a prospective observational study.

PubMed

Jia, Wei; Song, Liu-Wei; Fang, Yu-Qing; Wu, Xiao-Feng; Liu, Dan-Yang; Xu, Chun; Wang, Xiao-Mei; Wang, Wen; Lv, Dong-Xia; Li, Jun; Deng, Yong-Qiong; Wang, Yan; Huo, Na; Yu, Min; Xi, Hong-Li; Liu, Dan; Zhou, Yi-Xing; Wang, Gui-Qiang; Xia, Ning-Shao; Zhang, Ming-Xiang

2014-12-01

Previous studies have revealed antibody to hepatitis B core antigen (anti-HBc) levels as a predictor of treatment response in hepatitis B early antigen (HBeAg)-positive chronic hepatitis B (CHB) patients in both interferon and nucleos(t)ide analog therapy cohorts. However, there is no information about anti-HBc levels in the natural history of CHB. This study aimed to define anti-HBc levels of different phases in the natural history of CHB. Two hundred eleven treatment-naive CHB patients were included in the study. They were classified into 4 phases: immune tolerance (IT) phase (n = 39), immune clearance (IC) phase (n = 48), low or no-replicative (LR) phase (n = 55), and HBeAg-negative hepatitis (ENH, n = 69). Fifty patients who were HBsAg negative and anti-HBc positive were also recruited as past HBV infection (PBI) control group. Anti-HBc levels were measured by a newly developed double-sandwich immunoassay. Correlation of anti-HBc levels with alanine aminotransferase (ALT) and other HBV-related markers within each phase was performed. Serum anti-HBc levels were statistically significant between patients in different phases of CHB (P < 0.001). The median anti-HBc levels were: IT (3.17 log 10 IU/mL), IC (4.39 log 10 IU/mL), LR (3.29 log 10 IU/mL), ENH (4.12 log 10 IU/mL), and PBI (0.61 log 10 IU/mL). There existed a strong correlation in IC (r = 0.489, P < 0.001), a poor correlation in ENH (r = 0.275, P = 0.042), and no correlation in patients with ALT reached 5 times upper limit of normal (r = 0.120, P = 0.616). Anti-HBc levels show significant differences during the natural course of CHB. These results may provide some potentially useful insights into hepatitis B pathogenesis and immune activation against hepatitis B virus.

Tenofovir alafenamide (TAF) treatment of HBV, what are the unanswered questions?

PubMed

Viganò, Mauro; Loglio, Alessandro; Grossi, Glenda; Lampertico, Pietro

2018-02-01

Tenofovir disoproxil fumarate (TDF), an ester prodrug of tenofovir (TFV), is one of the recommended drugs for chronic hepatitis B (CHB) patients. However, reduced kidney function and loss of bone mineral density have been reported in some CHB patients treated with TDF. Consequent to these safety issues, tenofovir alafenamide (TAF) [Vemlidy®], a phosphonate prodrug of TFV, was developed for the treatment of CHB patients. Areas covered: The favourable pharmacological profile of TAF allows a marked reduction in dosage (25 mg/day) thus reducing systemic exposure to tenofovir and improving the bone and renal safety, keeping however the same virological efficacy, compared to TDF 300 mg/day. In two ongoing 96-week phase III trials in mainly treatment-naive HBeAg-positive or -negative patients, TAF showed similar viral suppression but was associated with significantly higher alanine aminotransferase normalization rates and more favourable renal and bone safety compared to TDF. In a 48-week TAF switch study enrolling patients treated with TDF for 96 weeks, glomerular, tubular and bone safety parameters rapidly improved while virological suppression was maintained. Expert commentary: Waiting long-term large scale clinical practice studies aimed to confirm these advantages, TAF represents an helpful treatment option for both naïve and TDF-exposed CHB patients.

Validation of Ten Noninvasive Diagnostic Models for Prediction of Liver Fibrosis in Patients with Chronic Hepatitis B

PubMed Central

Cheng, Jieyao; Hou, Jinlin; Ding, Huiguo; Chen, Guofeng; Xie, Qing; Wang, Yuming; Zeng, Minde; Ou, Xiaojuan; Ma, Hong; Jia, Jidong

2015-01-01

Background and Aims Noninvasive models have been developed for fibrosis assessment in patients with chronic hepatitis B. However, the sensitivity, specificity and diagnostic accuracy in evaluating liver fibrosis of these methods have not been validated and compared in the same group of patients. The aim of this study was to verify the diagnostic performance and reproducibility of ten reported noninvasive models in a large cohort of Asian CHB patients. Methods The diagnostic performance of ten noninvasive models (HALF index, FibroScan, S index, Zeng model, Youyi model, Hui model, APAG, APRI, FIB-4 and FibroTest) was assessed against the liver histology by ROC curve analysis in CHB patients. The reproducibility of the ten models were evaluated by recalculating the diagnostic values at the given cut-off values defined by the original studies. Results Six models (HALF index, FibroScan, Zeng model, Youyi model, S index and FibroTest) had AUROCs higher than 0.70 in predicting any fibrosis stage and 2 of them had best diagnostic performance with AUROCs to predict F≥2, F≥3 and F4 being 0.83, 0.89 and 0.89 for HALF index, 0.82, 0.87 and 0.87 for FibroScan, respectively. Four models (HALF index, FibroScan, Zeng model and Youyi model) showed good diagnostic values at given cut-offs. Conclusions HALF index, FibroScan, Zeng model, Youyi model, S index and FibroTest show a good diagnostic performance and all of them, except S index and FibroTest, have good reproducibility for evaluating liver fibrosis in CHB patients. Registration Number ChiCTR-DCS-07000039. PMID:26709706

PNPLA3 rs1010023 Predisposes Chronic Hepatitis B to Hepatic Steatosis but Improves Insulin Resistance and Glucose Metabolism.

PubMed

Pan, Qin; Chen, Mei-Mei; Zhang, Rui-Nan; Wang, Yu-Qin; Zheng, Rui-Dan; Mi, Yu-Qiang; Liu, Wen-Bin; Shen, Feng; Su, Qing; Fan, Jian-Gao

2017-01-01

PNPLA3 polymorphisms serve as the genetic basis of hepatic steatosis in normal population and lead to dysregulated glucose metabolism. Whether it underlies the hepatic steatosis and glucose homeostasis in chronic hepatitis B patients remains uncertain. Here, we investigated the PNPLA3 polymorphisms in biopsy-proven chronic hepatitis B patients with (CHB+HS group, n = 52) or without hepatic steatosis (CHB group, n = 47) and non-CHB subjects with (HS group, n = 37) or without hepatic steatosis (normal group, n = 45). When compared to the TT genotype, C-allele at PNPLA3 rs1010023 (CC and TC genotypes) conferred higher risk to hepatic steatosis in chronic hepatitis B patients (odds ratio (OR) = 1.768, 95% confidence interval (CI): 1.027-3.105; P = 0.045) independent of age, gender, and body mass index. In contrast to their role in hepatic steatosis, CC and TC genotypes of PNPLA3 rs1010023 were correlated to significant improvement of homeostasis model assessment index (HOMA-IR) as compared to TT genotype in the CHB+HS group. Downregulated fasting blood glucose also characterized the CHB+HS patients with C-allele at PNPLA3 rs1010023 (CC/TC versus TT: 4.81 ± 0.92 mmol/L versus 5.86 ± 2.11 mmol/L, P = 0.02). These findings suggest that PNPLA3 rs1010023 may predispose chronic hepatitis B patients to hepatic steatosis but protects them from glucose dysregulation by attenuating insulin resistance.

PNPLA3 rs1010023 Predisposes Chronic Hepatitis B to Hepatic Steatosis but Improves Insulin Resistance and Glucose Metabolism

PubMed Central

Chen, Mei-Mei; Wang, Yu-Qin; Zheng, Rui-Dan; Mi, Yu-Qiang; Liu, Wen-Bin; Su, Qing

2017-01-01

PNPLA3 polymorphisms serve as the genetic basis of hepatic steatosis in normal population and lead to dysregulated glucose metabolism. Whether it underlies the hepatic steatosis and glucose homeostasis in chronic hepatitis B patients remains uncertain. Here, we investigated the PNPLA3 polymorphisms in biopsy-proven chronic hepatitis B patients with (CHB+HS group, n = 52) or without hepatic steatosis (CHB group, n = 47) and non-CHB subjects with (HS group, n = 37) or without hepatic steatosis (normal group, n = 45). When compared to the TT genotype, C-allele at PNPLA3 rs1010023 (CC and TC genotypes) conferred higher risk to hepatic steatosis in chronic hepatitis B patients (odds ratio (OR) = 1.768, 95% confidence interval (CI): 1.027–3.105; P = 0.045) independent of age, gender, and body mass index. In contrast to their role in hepatic steatosis, CC and TC genotypes of PNPLA3 rs1010023 were correlated to significant improvement of homeostasis model assessment index (HOMA-IR) as compared to TT genotype in the CHB+HS group. Downregulated fasting blood glucose also characterized the CHB+HS patients with C-allele at PNPLA3 rs1010023 (CC/TC versus TT: 4.81 ± 0.92 mmol/L versus 5.86 ± 2.11 mmol/L, P = 0.02). These findings suggest that PNPLA3 rs1010023 may predispose chronic hepatitis B patients to hepatic steatosis but protects them from glucose dysregulation by attenuating insulin resistance. PMID:28695131

Clinical features of acute hepatitis E super-infections on chronic hepatitis B

PubMed Central

Chen, Chong; Zhang, Shu-Ye; Zhang, Dan-Dan; Li, Xin-Yan; Zhang, Yu-Ling; Li, Wei-Xia; Yan, Jing-Jing; Wang, Min; Xun, Jing-Na; Lu, Chuan; Ling, Yun; Huang, Yu-Xian; Chen, Liang

2016-01-01

AIM To examine the clinical features and risk factors for adverse outcomes in chronic hepatitis B (CHB) superimposed with hepatitis E virus (HEV). METHODS This retrospective cohort study included 228 patients with acute HEV infection (showing clinical acute hepatitis symptomology and positivity for anti-HEV immunoglobulin M) with underlying CHB (confirmed by positivity for hepatitis B surface antigen and/or hepatitis B virus (HBV) DNA over 6 mo) who had been admitted to the Shanghai Public Health Clinical Center, which represents the regional tertiary hospital for infectious diseases in Shanghai city, China. Data for adverse outcomes were collected, and included severe liver diseases (defined as liver failure and/or acute liver decompensation) and liver-related mortality. Logistic regression modeling was performed to determine the risk factors for adverse outcomes. RESULTS The symptoms caused by superimposed acute hepatitis E (AHE) were much more severe in cirrhotic patients (n = 94) than in non-cirrhotic patients (n = 134), as evidenced by significantly higher liver complications (77.7% vs 28.4%, P < 0.001) and mortality rate (21.3% vs 7.5%, P = 0.002). Most of the cirrhotic patients (n = 85, 90.4%) had no prior decompensation. Among the non-cirrhotic patients, superimposed AHE caused progressively more severe diseases that corresponded with the CHB disease stages, from immune tolerant to immune reactivation phases. Few risk factors were identified in the cirrhotic patients, but risk factors for non-cirrhotic patients were found to be intermediate HBV DNA levels (OR: 5.1, P = 0.012), alcohol consumption (OR: 6.4, P = 0.020), and underlying diabetes (OR: 7.5, P = 0.003) and kidney diseases (OR: 12.7, P = 0.005). Only 28.7% of the cirrhotic patients and 9.0% of the non-cirrhotic patients had received anti-HBV therapy previously and, in all cases, the efficacy had been suboptimal. CONCLUSION CHB-related cirrhosis and intermediate HBV DNA level were associated with severe disease in superinfected patients, and successful antiviral treatment might counter this outcome. PMID:28058019

Clinical features of hepatitis B and C virus infections, with high α-fetoprotein levels but not hepatocellular carcinoma

PubMed Central

Kim, Cha Young; Kim, Bo Ra; Lee, Sang Soo; Jeon, Dae-Hong; Lee, Chang Min; Kim, Wan Soo; Cho, Hyun Chin; Kim, Jin Joo; Lee, Jae Min; Kim, Hong Jun; Ha, Chang Yoon; Kim, Hyun Jin; Kim, Tae Hyo; Jung, Woon Tae; Lee, Ok-Jae

2017-01-01

Abstract The appropriate α-fetoprotein (AFP) level to confirm hepatocellular carcinoma (HCC) could be 100 ng/mL; however, the clinical significance of falsely elevated AFP in patients without HCC has not been fully studied. We investigated the clinical features and outcome of patients without HCC but with high AFP levels (100 ng/mL), especially with chronic hepatitis B (CHB) or C (CHC). The sample included 124 consecutive patients with CHB (n = 97) or CHC (n = 27), with AFP levels >100 ng/mL and without HCC at baseline. Multivariate Cox proportional regression analysis was performed to determine the factors associated with AFP normalization and HCC development. During the mean 52-month follow-up, the proportion of patients with CHB with AFP normalization (90.7%) was significantly higher than the proportion of patients with CHC (59.3%, P < 0.001). Initial aspartate aminotransferase levels (hazard ratio [HR] = 1.02 per 10 U/L increase, P = 0.021) and antiviral therapy (HR = 2.89, P < 0.001) were significantly associated with AFP normalization. Of the 16 (12.9%) patients who developed HCC, hepatitis B virus infection (HR = 10.82, P = 0.001), initiation of antiviral treatment postenrollment (HR = 0.23, P = 0.030), and AFP normalization within 12 months (HR = 0.13, P = 0.011) were associated with HCC development. CHB and CHC were the most common causes of falsely elevated AFP (>100 ng/mL). With either CHB or CHC, persistent AFP elevation (>12 months), regardless of antiviral treatment, might be an important marker of HCC development. PMID:28079817

Role of Shear Wave Elastography in Evaluating the Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B

PubMed Central

Jeong, Jae Yoon; Sohn, Joo Hyun; Sohn, Won; Park, Chan Hyuk; Kim, Tae Yeob; Jun, Dae Won; Kim, Yongsoo; Jeong, Woo Kyoung

2017-01-01

Background/Aims To investigate the use of measurements of liver stiffness (LS) by two-dimensional real-time shear wave elastography (SWE) for predicting the development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). Methods We retrospectively collected data on 291 enrolled patients with CHB whose LS had been measured using SWE. Results The mean age of the patients was 46.8 years; males predominated (67%), and 40 of the patients (14%) had clinical cirrhosis. Among the patients, 165 (56.7%) received antiviral treatment. The median LS value was 7.4 kPa, and the median follow-up period was 35.8 months (range, 3.0 to 52.8 months). During follow-up, HCC developed in 13 patients (4.5%), and the cumulative incidence rates of HCC at 1, 2, and 4 years were 1.1%, 3.6%, and 8.4%, respectively. Based on a multivariate analysis, older age (≥50 years) and higher LS value (≥10 kPa) were independently associated with the risk of developing HCC (hazard ratio [HR], 4.53, p=0.023; and HR, 4.08, p=0.022). The cumulative incidence rate of HCC was significantly higher in patients with higher LS values (≥10 kPa) than in those with lower LS values (<10 kPa) (p=0.001). Conclusions Increased LS measured by SWE at any time point regardless of antiviral treatment is associated with an increased risk of HCC in patients with CHB. PMID:28651307

Serum dihydroxyacetone kinase peptide m/z 520.3 as predictor of disease severity in patients with compensated chronic hepatitis B

PubMed Central

2013-01-01

Background & aim Due to known limitations of liver biopsy, reliable non-invasive serum biomarkers for chronic liver diseases are needed. We performed serum peptidomics for such investigation in compensated chronic hepatitis B (CHB) patients. Methods Liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) was used to identify differentially expressed peptides in sera from 40 CHB patients (20 with S0G0-S1G1 and 20 with S3G3-S4G4). Ion pair quantification from differentially expressed peptides in a validation set of sera from 86 CHB patients was done with multiple reaction monitoring (MRM). Results 21 differentially represented peptide peaks were found through LC-MS/MS. Ion pairs generated from eleven of these peptides (m/z < 800) were quantified by MRM. Summed peak area ratios of 6 ion pairs from peptide m/z 520.3 (176.1, 353.7, 459.8, 503.3, 351.3, 593.1), which was identified as dihydroxyacetone kinase (DAK) fragment, decreased from mild to advanced stages of fibrosis or inflammation. Area Under Receiver Operating Characteristic Curves (AUROCs) of five ion models discriminating fibrosis degrees were 0.871 ~ 0.915 (S2-4 versus S0-1) and 0.804 ~ 0.924 (S3-4 versus S0-2). AUROCs discriminating inflammation grades were 0.840 ~ 0.902 (G2-4 versus G0-1) and 0.787 ~ 0.888 (G3-4 versus G0-2). The diagnostic power of these models provides improved sensitivity and specificity for predicting disease progression as compared to aspartate aminotransferase to platelet ratio index (APRI), FIB-4, Forn’s index and serum DAK protein. Conclusions The peptide fragment (m/z 520.3) of DAK is a promising biomarker to guide timing of antiviral treatment and to avoid liver biopsy in compensated CHB patients. PMID:24289155

Gamma-glutamyl-transpeptidase to platelet ratio is not superior to APRI,FIB-4 and RPR for diagnosing liver fibrosis in CHB patients in China.

PubMed

Huang, Rui; Wang, Guiyang; Tian, Chen; Liu, Yong; Jia, Bei; Wang, Jian; Yang, Yue; Li, Yang; Sun, Zhenhua; Yan, Xiaomin; Xia, Juan; Xiong, Yali; Song, Peixin; Zhang, Zhaoping; Ding, Weimao; Wu, Chao

2017-08-17

The gamma-glutamyl transpeptidase to platelet ratio (GPR) is a novel index to estimate liver fibrosis in chronic hepatitis B (CHB). Few studies compared diagnostic accuracy of GPR with other non-invasive fibrosis tests based on blood parameters. We analyzed diagnostic values of GPR for detecting liver fibrosis and compared diagnostic performances of GPR with APRI (aspartate aminotransferase-to-platelet ratio index), FIB-4 (fibrosis index based on the four factors), NLR (neutrophil-to-lymphocyte ratio), AAR (aspartate aminotransferase/alanine aminotransferase ratio) and RPR (red cell distribution width-to-platelet ratio) in HBeAg positive CHB and HBeAg negative CHB. We found AUROCs of GPR in predicting significant liver fibrosis, advanced liver fibrosis and liver cirrhosis were 0.732 (95% CI 0.663 to 0.801), 0.788 (95% CI 0.729 to 0.847) and 0.753 (95% CI 0.692 to 0.814), respectively. Further comparisons showed the diagnostic performance of GPR was not significantly different with APRI, FIB-4 and RPR in identifying significant fibrosis, advanced fibrosis and cirrhosis, but it was significantly superior to AAR and NLR in both HBeAg positive CHB and HBeAg negative CHB. In conclusion, GPR does not show advantages than APRI, FIB-4 and RPR in identifying significant liver fibrosis, advanced liver fibrosis and liver cirrhosis in both HBeAg positive CHB and HBeAg negative CHB in China.

A cost-utility analysis of drug treatments in patients with HBeAg-positive chronic hepatitis B in Thailand

PubMed Central

2014-01-01

Background Only lamivudine has been included for patients with chronic hepatitis B (CHB) in the National List of Essential Drugs (NLED), a pharmaceutical reimbursement list in Thailand. There have also been no economic evaluation studies of CHB drug treatments conducted in Thailand yet. In order to fill this gap in policy research, the objective of this study was to compare the cost-utility of each drug therapy (Figure 1) with palliative care in patients with HBeAg-positive CHB. Methods A cost-utility analysis using an economic evaluation model was performed to compare each drug treatment for HBeAg-positive CHB patients. A Markov model was used to estimate the relevant costs and health outcomes during a lifetime horizon based on a societal perspective. Direct medical costs, direct non-medical costs, and indirect costs were included, and health outcomes were denoted in life years (LYs) and quality-adjusted life years (QALYs). The results were presented as an incremental cost effectiveness ratio (ICER) in Thai baht (THB) per LY or QALY gained. One-way sensitivity and probabilistic sensitivity analyses were applied to investigate the effects of model parameter uncertainties. Results The ICER values of providing generic lamivudine with the addition of tenofovir when drug resistance occurred, generic lamivudine with the addition of tenofovir based on the road map guideline, and tenofovir monotherapy were -14,000 (USD -467), -8,000 (USD -267) , and -5,000 (USD -167) THB per QALY gained, respectively. However, when taking into account all parameter uncertainties in the model, providing generic lamivudine with the addition of tenofovir when drug resistance occurred (78% and 75%) and tenofovir monotherapy (18% and 24%) would yield higher probabilities of being cost-effective at the societal willingness to pay thresholds of 100,000 (USD 3,333) and 300,000 (USD 10,000) THB per QALY gained in Thailand, respectively. Conclusions Based on the policy recommendations from this study, the Thai government decided to include tenofovir into the NLED in addition to generic lamivudine which is already on the list. Moreover, the results have shown that the preferred treatment regimen involves using generic lamivudine as the first-line drug with tenofovir added if drug resistance occurs in HBeAg-positive CHB patients. PMID:24731689

RGB camera-based imaging of cerebral tissue oxygen saturation, hemoglobin concentration, and hemodynamic spontaneous low-frequency oscillations in rat brain following induction of cortical spreading depression

PubMed Central

Mustari, Afrina; Nakamura, Naoki; Kawauchi, Satoko; Sato, Shunichi; Sato, Manabu; Nishidate, Izumi

2018-01-01

To evaluate cerebral hemodynamics and spontaneous low-frequency oscillations (SLFOs) of cerebral blood flow in rat brain, we investigated an imaging method using a digital RGB camera. In this method, the RGB values were converted into tristimulus values in the CIE (Commission Internationale de l’Eclairage) XYZ color space, which is compatible with the common RGB working spaces. Monte Carlo simulation for light transport in tissue was then used to specify the relationship among the tristimulus XYZ values and the concentrations of oxygenated hemoglobin (CHbO), deoxygenated hemoglobin (CHbR), and total hemoglobin (CHbT) and cerebral tissue oxygen saturation (StO2). Applying the fast Fourier transform to each pixel of the sequential images of CHbT along the timeline, SLFOs of cerebral blood volume were visualized as a spatial map of power spectral density (PSD) at specific frequencies related to vasomotion. To confirm the feasibility of this method, we performed in vivo experiments using exposed rat brain during a cortical spreading depression (CSD) evoked by topical application of KCl. Cerebral hemodynamic responses to CSD such as initial hypoperfusion, profound hyperemia, and post-CSD oligemia and hypoxemia were successfully visualized with this method. At the transition to the hyperemia phase from hypoperfusion, CHbO and StO2 were significantly increased, which implied vasodilatation in arterioles and increased cerebral blood volume in response to CSD. In the wake of the hyperemic phase, CHbO and CHbT were significantly reduced to 25 ± 12% and 3.5 ± 1% of baseline, respectively, suggesting long-lasting vasoconstriction after CSD. In this persistent oligemia, StO2 significantly dropped to at most 23 ± 12% of the level before CSD, indicating long-lasting hypoxemia. The PSD value of SLFOs in CHbT for arteriole regions during CSD was significantly reduced to 28 ± 20% of baseline with respect to the pre-CSD level, which was correlated with the reduction in StO2. The results showed the possibility of RGB camera-based diffuse reflectance spectroscopy imaging for evaluating cerebral hemodynamics and SLFOs under normal and pathologic conditions. PMID:29541495

HBV-Derived Synthetic Long Peptide Can Boost CD4+ and CD8+ T-Cell Responses in Chronic HBV Patients Ex Vivo

PubMed Central

Dou, Yingying; van Montfoort, Nadine; van den Bosch, Aniek; de Man, Robert A; Zom, Gijs G; Krebber, Willem-Jan; Melief, Cornelis J M; Buschow, Sonja I; Woltman, Andrea M

2018-01-01

Abstract Background Vaccination with synthetic long peptides (SLP) is a promising new treatment strategy for chronic hepatitis B virus (CHB). SLP can induce broad T-cell responses for all HLA types. Here we investigated the ability of a prototype HBV-core (HBc)-sequence-derived SLP to boost HBV-specific T cells in CHB patients ex vivo. Methods HBc-SLP was used to assess cross-presentation by monocyte-derived dendritic cells (moDC) and BDCA1+ blood myeloid DC (mDC) to engineered HBV-specific CD8+ T cells. Autologous SLP-loaded and toll-like receptor (TLR)-stimulated DC were used to activate patient HBc-specific CD8+ and CD4+ T cells. Results HBV-SLP was cross-presented by moDC, which was further enhanced by adjuvants. Patient-derived SLP-loaded moDC significantly increased autologous HBcAg18-27-specific CD8+ T cells and CD4+ T cells ex vivo. HBV-specific T cells were functional as they synthesized tumor necrosis factor-alpha and interferon-gamma. In 6/7 of patients blockade of PD-L1 further increased SLP effects. Also, importantly, patient-derived BDCA1+ mDC cross-presented and activated autologous T-cell responses ex vivo. Conclusions As a proof of concept, we showed a prototype HBc-SLP can boost T-cell responses in patients ex vivo. These results pave the way for the development of a therapeutic SLP-based vaccine to induce effective HBV-specific adaptive immune responses in CHB patients. PMID:29220492

Disease burden of chronic hepatitis B among immigrants in Canada

PubMed Central

Wong, William WL; Woo, Gloria; Heathcote, E Jenny; Krahn, Murray

2013-01-01

BACKGROUND: The prevalence of chronic hepatitis B (CHB) infection among immigrants to North America ranges from 2% to 15%, 40% of whom develop advanced liver disease. Screening for hepatitis B surface antigen is not recommended for immigrants. OBJECTIVE: To estimate the disease burden of CHB among immigrants in Canada using Markov cohort models comparing a cohort of immigrants with CHB versus a control cohort of immigrants without CHB. METHODS: Markov cohort models were used to estimate life years, quality-adjusted life years and lifetime direct medical costs (adjusted to 2008 Canadian dollars) for a cohort of immigrants with CHB living in Canada in 2006, and an age-matched control cohort of immigrants without CHB living in Canada in 2006. Parameter values were derived from the published literature. RESULTS: At the baseline estimate, the model suggested that the cohort of immigrants with CHB lost an average of 4.6 life years (corresponding to 1.5 quality-adjusted life years), had an increased average of $24,249 for lifetime direct medical costs, and had a higher lifetime risk for decompensated cirrhosis (12%), hepatocellular carcinoma (16%) and need for liver transplant (5%) when compared with the control cohort. DISCUSSION: Results of the present study showed that the socio-economic burden of CHB among immigrants living in Canada is sub-stantial. Governments and health systems need to develop policies that promote early recognition of CHB and raise public awareness regarding hepatitis B to extend the lives of infected immigrants. PMID:23516678

Conduction disturbances after TAVR: Electrophysiological studies and pacemaker dependency.

PubMed

Makki, Nader; Dollery, Jenn; Jones, Danielle; Crestanello, Juan; Lilly, Scott

Permanent pacemaker (PPM) placement occurs in 5-20% of patients after transcatheter aortic valve replacement (TAVR). Although predictors of pacemaker implantation have been established, features that predispose patients to pacemaker utilization on follow up have not been widely reported. We performed a retrospective review of patients undergoing commercial TAVR between 2011 and 2016. We collated patients that underwent in-hospital PPM implantation and had a follow up of at least 3months. Data abstraction was performed for electrophysiological studies (EPS), pacemaker indication, timing, and device interrogation for pacemaker dependency on follow up. A total of 24 patients received in-hospital PPM post-TAVR (14% of total cohort), and mean follow up was 22months. Indications for PPM included resting complete heart block (CHB; 15/24, 63%), left bundle branch block and abnormal electrophysiological study (EPS; 7/24, 29%), alternating bundle branch block (1/24, 4%) and tachy-brady syndrome (1/24, 4%). Pacemaker dependency (underlying ventricular asystole, complete heart block, or >50% pacing) occurred in 8/24 patients (33%) during follow-up, 7 of whom had resting CHB, and one with CHB invoked during EPS. Pacemaker dependency after TAVR is common among those that exhibited CHB, but not among those with a prolonged HV delay during EPS. Although preliminary, these observations are relevant to management of rhythm disturbances after TAVR, and may inform the practice of EPS-based PPM implantation. Copyright © 2017 Elsevier Inc. All rights reserved.

Timing of chronic hepatitis B diagnosis after migration and its determinants among Sub-Saharan African migrants living in France.

PubMed

Pannetier, Julie; Gigonzac, Virginie; Lydié, Nathalie; Desgrées du Loû, Annabel; Dray Spira, Rosemary

2017-01-01

In European countries, chronic hepatitis B (CHB) disproportionately affects migrants from medium- and high-endemic areas and is largely underdiagnosed. To inform policy and improve screening strategies, we measured the timing of CHB diagnosis after migration and its determinants among sub-Saharan migrants living in the Paris metropolitan area (France). The PARCOURS study is a retrospective life-event history survey conducted in health care services in 2012-2013 among 779 migrants from sub-Saharan Africa who were receiving care for CHB. We investigated the timing of CHB diagnosis from the time of arrival in France using the Kaplan-Meier method and characteristics associated with CHB diagnosis since the time of arrival in France using discrete-time multivariate logistic regression models. The median CHB diagnosis occurred during the fourth year spent in France for men and during the second year spent in France for women. Among men, the probability of CHB diagnosis increased during years with (versus without) a temporary resident permit (aOR: 1.6, 95%CI: 1.1-2.2), a precarious accommodation (aOR: 1.7, 95%CI: 1.1-2.6), and hospitalization (aOR: 7.7, 95%CI: 3.4-15.1). Among women, CHB diagnosis was more likely to occur during years with unemployment (aOR: 1.9, 95%CI: 1.1-3.94), pregnancy (aOR: 6.6, 95%CI: 3.5-12.5) and hospitalization (aOR: 9.0, 95%CI: 2.95-32.3). For both sexes, the probability of CHB diagnosis was higher among those who migrated to France because they were threatened in their country. This study shows that social hardships (residential, economic, administrative) and contact with the health care system after arrival in France hasten access to a CHB diagnosis.

Interleukin-7 in Patients With Chronic Hepatitis B May Have Effect on T Follicular Helper Cells and Specific Cellular Immunity.

PubMed

Zhong, Hua; Xibing, Gu; Yaping, Dai; Zheng, Wang; Decai, Fu; Xiaoye, Guo; Hangyuan, Wu; Dong, Wang; Zhonghua, Lu

2016-09-01

In patients with chronic hepatitis B (CHB), the relation of interkeukin-7 (IL-7) to either the T follicular helper cells (Tfh cells) or to a specific cellular immune response is not clear. The present study aims to explore the possible relationship of IL-7 to Tfh cells and to hepatitis B virus (HBV)-specific cellular immune response in patients with CHB. Ninety-one adult patients with CHB were divided into groups A, B, and C, according to the patients' IL-7 levels (low, medium, and high). Tfh cells and HBV-specific cytotoxic T lymphocytes (CTLs) were detected with flow cytometry; IL-7 and IL-21 were determined with a double antibody sandwich enzyme-linked immunosorbent assay; and HBV DNA was determined by using a real-time fluorescent quantitative polymerase chain reaction. The results showed that the levels of IL-7, Tfh cells, IL-21, and HBV-specific CTLs of patients in group C were significantly higher than those of patients in group B, (P < 0.01 for each comparison) and that the levels of these four parameters of patients in group B were significantly higher than those of the patients in group A (P < 0.01 for each comparison). Meanwhile, the level of HBV DNA of the patients in group C was significantly lower than that of the patients in group B (P < 0.01), and that of the patients in group B was significantly lower than that of the patients in group A (P < 0.05). Multiple linear regression analyses showed that IL-7, Tfh cells, IL-21, and HBV-specific CTL might have effects on HBV DNA and that only the HBV-specific CTL had an independent effect on HBV DNA (P < 0.01). IL-7, Tfh cells, and IL-21 showed independent effects on HBV-specific CTL (P < 0.05, P < 0.01, and P < 0.01). This study suggests that the IL-7 level of CHB patients may be related to Tfh cells. In CHB patients, IL-7 possibly increases the level of Tfh cells and HBV-specific cellular immune responses and thereby reduces the HBV DNA level.

[Analysis of the risk factors of hepatocellular carcinoma in cirrhotic patients with chronic hepatitis B].

PubMed

Zhang, Yuanqing; Peng, Lijun; Cao, Yirong; Zeng, Zhiping; Wu, Yujing; Shi, Hong; Chen, Shiyao; Guo, Jinsheng

2015-07-01

To identify risk factors of hepatocellular carcinoma (HCC) in cirrhotic patients with chronic hepatitis B (CHB). A total of 715 cirrhotic patients with CHB were recruited from the Zhongshan Hospital Affiliated to Fudan University and enrolled in this case-control study between January 2009 and September 2014. All participants were Chinese Han residing in Shanghai and the surrounding areas. The patients were divided into a cirrhosis group (n =281) and a HCC group (n=434). History of hepatitis B infection and HCC, as well as clinical data from serological, imaging and pathological examinations were collected for analysis.SPSS software, version 19.0, was used for all statistical comparisons. Single factor analysis indicated that development of HCC in cirrhotic patients with CHB was significantly associated with male sex, age of 50 years or more, family history of HCC, alcohol consumption,fatty liver, detectable levels of hepatitis B virus (HBV) DNA, and history of HBV infection without effective antiviral treatment. Multivariate logistic regression analysis indicated that age of 50 years or more (P =0.005, odds ratio [OR] =1.766), history of alcohol consumption (P =0.002, Or = 2.570), family history of HCC (P =0.014, Or = 2.268), fatty liver (P =0.023, Or = 3.390), and history of HBV infection without effective antiviral treatment (P < 0.001,Or = 5.389) were risk factors of HCC.The risk factors for development of HCC in cirrhotic patients with hepatitis B after achieving sustained virologic suppression (SVS) were family history of HBV infection (P =0.014, Or = 2.537), family history of HCC (P =0.037,Or = 3.339) and fatty liver (P =0.018, Or = 11.646). Risk factors of HCC in cirrhotic patients with CHB include age,drinking history,family history of HCC, fatty liver, and ineffective antiviral treatment of CHB.Family history of HBV infection or HCC, and fatty liver disease, were significantly associated with HCC development after SVS in patients with hepatitis B-related cirrhosis.

HBeAg negative variants and their role in the natural history of chronic hepatitis B virus infection.

PubMed

Alexopoulou, Alexandra; Karayiannis, Peter

2014-06-28

Molecular virology methods including polymerase chain reaction, cloning and sequencing have revolutionised our understanding of viral genome variation. In the case of hepatitis B virus (HBV), sequencing studies have identified a number of virus variants normally found during the natural course of chronic infection. The appearance of the precore stop codon (with G-for-A substitution at position 1896) and basal core promoter (BCP) (with A-for-T and G-for-A, at positions 1762 and 1764, respectively) variants which reduce or abrogate hepatitis B e antigen (HBeAg) production, heralds the initiation of the seroconversion phase from HBeAg to anti-HBe positivity. The gradual removal of the tolerogenic effect of HBeAg leads to the awakening of the immune response (immune clearance phase). Most patients after HBeAg seroconversion become "inactive HBsAg carriers". However during the course of infection precore and/or BCP variants may emerge and be selected leading to HBeAg negative chronic hepatitis B (CHB) with high viremia levels (reactivation phase). The prevalence of HBeAg negative CHB has been increasing over the last few decades and has become the commonest type of HBV infection in many countries of the world. This probably reflects the aging of existing HBV carriers and the effective prevention measures restricting new HBV infections. Frequent acute exacerbations accompanied by high viral replication, elevated alanine aminotransferase levels and histological activity are a common feature of HBeAg negative CHB leading to cirrhosis much faster than in HBeAg positive CHB patients.

Fault detection and diagnosis in asymmetric multilevel inverter using artificial neural network

NASA Astrophysics Data System (ADS)

Raj, Nithin; Jagadanand, G.; George, Saly

2018-04-01

The increased component requirement to realise multilevel inverter (MLI) fallout in a higher fault prospect due to power semiconductors. In this scenario, efficient fault detection and diagnosis (FDD) strategies to detect and locate the power semiconductor faults have to be incorporated in addition to the conventional protection systems. Even though a number of FDD methods have been introduced in the symmetrical cascaded H-bridge (CHB) MLIs, very few methods address the FDD in asymmetric CHB-MLIs. In this paper, the gate-open circuit FDD strategy in asymmetric CHB-MLI is presented. Here, a single artificial neural network (ANN) is used to detect and diagnose the fault in both binary and trinary configurations of the asymmetric CHB-MLIs. In this method, features of the output voltage of the MLIs are used as to train the ANN for FDD method. The results prove the validity of the proposed method in detecting and locating the fault in both asymmetric MLI configurations. Finally, the ANN response to the input parameter variation is also analysed to access the performance of the proposed ANN-based FDD strategy.

Serum levels of angiotensin converting enzyme as a biomarker of liver fibrosis

PubMed Central

Miranda, Aline Silva; Simões e Silva, Ana Cristina

2017-01-01

The renin angiotensin system (RAS) is classically conceived as a circulating hormonal system involved in blood pressure control and hydroelectrolyte balance. The discovery that RAS components are locally expressed in a wide range of organs and tissues, including the liver, pointed to a role for this system in the pathogenesis of several conditions including hepatic fibrosis and cirrhosis. It has been widely reported that the classical RAS axis composed by the angiotensin converting enzyme (ACE)-angiotensin (Ang) II-Ang type 1 (AT1) receptor mediates pro-inflammatory, pro-thrombotic, and pro-fibrotic processes. On the other hand, the alternative axis comprising ACE2-Ang-(1-7)-Mas receptor seems to play a protective role by frequently opposing Ang II action. Chronic hepatitis B (CHB) is one of the leading causes of liver fibrosis, accounting for the death of nearly one million people worldwide. Liver fibrosis is a key factor to determine therapeutic interventions for patients with CHB. However, the establishment of non-invasive and accurate methods to detect reversible stages of liver fibrosis is still a challenge. In an elegant study published in the 36th issue of the World Journal of Gastroenterology, Noguchi et al showed the predictive value of serum ACE levels in detecting not only advanced stages of liver fibrosis but also initial and intermediate fibrotic stages. The serum levels of ACE might represent an accurate, non-invasive, widely available, and easy method to evaluate fibrosis related to CHB. Moreover, therapies involving the inhibition of the classical RAS axis components might be promising in the control of CHB-related liver fibrosis. PMID:29358853

Serum levels of angiotensin converting enzyme as a biomarker of liver fibrosis.

PubMed

Miranda, Aline Silva; Simões E Silva, Ana Cristina

2017-12-28

The renin angiotensin system (RAS) is classically conceived as a circulating hormonal system involved in blood pressure control and hydroelectrolyte balance. The discovery that RAS components are locally expressed in a wide range of organs and tissues, including the liver, pointed to a role for this system in the pathogenesis of several conditions including hepatic fibrosis and cirrhosis. It has been widely reported that the classical RAS axis composed by the angiotensin converting enzyme (ACE)-angiotensin (Ang) II-Ang type 1 (AT1) receptor mediates pro-inflammatory, pro-thrombotic, and pro-fibrotic processes. On the other hand, the alternative axis comprising ACE2-Ang-(1-7)-Mas receptor seems to play a protective role by frequently opposing Ang II action. Chronic hepatitis B (CHB) is one of the leading causes of liver fibrosis, accounting for the death of nearly one million people worldwide. Liver fibrosis is a key factor to determine therapeutic interventions for patients with CHB. However, the establishment of non-invasive and accurate methods to detect reversible stages of liver fibrosis is still a challenge. In an elegant study published in the 36 th issue of the World Journal of Gastroenterology , Noguchi et al showed the predictive value of serum ACE levels in detecting not only advanced stages of liver fibrosis but also initial and intermediate fibrotic stages. The serum levels of ACE might represent an accurate, non-invasive, widely available, and easy method to evaluate fibrosis related to CHB. Moreover, therapies involving the inhibition of the classical RAS axis components might be promising in the control of CHB-related liver fibrosis.

Impact of etiology of chronic liver disease on hepatocellular carcinoma biomarkers.

PubMed

Ricco, Gabriele; Cavallone, Daniela; Cosma, Chiara; Caviglia, Gian Paolo; Oliveri, Filippo; Biasiolo, Alessandra; Abate, Maria Lorena; Plebani, Mario; Smedile, Antonina; Bonino, Ferruccio; Pontisso, Patrizia; Brunetto, Maurizia Rossana

2018-02-14

The role of serum biomarkers in the surveillance of hepatocellular carcinoma (HCC) is controversial. We assessed the diagnostic performances of alpha-fetoprotein (AFP) and protein-induced by vitamin-K-absence/antagonist-II (PIVKA-II) in 388 cirrhotic patients with chronic liver disease (CLD). Biomarkers were quantified by automated chemiluminescent-enzyme-immunoassays (Fujirebio, Tokyo, Japan) at HCC diagnosis in 258 patients (204 males; median age 66.9 years) and in 130 cirrhotics without HCC (104 males; median-age 60.6 years). CLD etiology in HCC/non-HCC was CHB in 48/35, CHC in 126/56 and Non-Viral in 84/39. Overall AUROC values for AFP and PIVKA-II were 0.698 (95%CI = 0.642-0.753, P< 0.001) and 0.780 (95%CI = 0.730-0.831, P< 0.001). AFP/PIVKA-II AUROC (95%CI) were: 0.822 (0.728-0.915)/0.833 (0.739-0.926) in CHB, 0.648 (0.560-0.736)/0.732 (0.650-0.814) in CHC; 0.640 (0.540-0.740)/0.806 (0.722-0.889) in Non-Viral-CLD. AFP/PIVKA-II diagnostic accuracy was 40.5-59.8%/62.7-73.5% and combining both markers 78.2% for CHB, 77% for Non-Viral-CLD and 75% for CHC. AFP correlated with ALT in HCC patients with CHC (ρ= 0.463/P< 0.001) and Non-Viral CLD (ρ= 0.359/P= 0.047), but not in CHB (treated with antivirals). PIVKA-II correlated with tumour size independently of CLD-etiology (P< 0.001) and AFP in CHB patients only (P= 0.007). The diagnostic performance of AFP and PIVKA-II is significantly influenced by the etiology and activity of CLD; their combination provides a better diagnostic accuracy.

Duration of storage influences the hemoglobin rising effect of red blood cells in patients undergoing major abdominal surgery.

PubMed

Hunsicker, Oliver; Hessler, Katarina; Krannich, Alexander; Boemke, Willehad; Braicu, Ioana; Sehouli, Jalid; Meyer, Oliver; Pruß, Axel; Spies, Claudia; Feldheiser, Aarne

2018-04-17

After transfusion of senescent red blood cells (RBCs) a considerable fraction is rapidly cleared from the recipients' circulation. Thus, transfusion of senescent RBCs may be less effective in terms of increasing hemoglobin concentration (cHb) after transfusion. Data were retrospectively obtained in patients who underwent major abdominal surgery between 2006 and 2012. Patients were eligible if they received RBCs during surgery and had at least two arterial blood gas analyses performed. The primary endpoint was the increase of recipients' cHb related to the transfusion of 1 unit of RBCs with respect to different storage periods. Four storage periods were defined according to the distribution of RBC storage of the study population. General estimating equation was used for calculation of the primary endpoint and to adjust for confounding variables. A total of 598 arterial blood gas samples from 120 patients, receiving 429 RBC units, were analyzed. Mean (±SD) RBC storage was 21 (±9) days. RBC storage duration and the increase in recipients' cHb were inversely and gradually related; that is, the older the RBCs, the lower the increase in the recipients' cHb after transfusion (storage < 12 days, ΔcHb per unit RBCs +0.82 [95% confidence interval, 0.42-1.21] g/dL, p < 0.01; storage 12-20 days, +0.66 [0.46-0.86] g/dL, p < 0.01; storage 21-29 days, +0.56 [0.33-0.79] g/dL, p < 0.01; storage ≥30 days, +0.39 [0.07 to 0.71] g/dL, p = 0.02). Transfusion of senescent RBCs increased cHb less effectively than transfusion of fresher RBCs. © 2018 AABB.

A systematic review of RCTs and quasi-RCTs on traditional Chinese patent medicines for treatment of chronic hepatitis B.

PubMed

Zhan, Tao; Wei, Xing; Chen, Ze-Qi; Wang, Dong-Sheng; Dai, Xing-Ping

2011-12-01

Traditional Chinese patent medicines (TCPMs) are widely used for treatment of chronic hepatitis B (CHB) in China. To estimate the overall effectiveness of TCPMs for CHB, we performed a systematic review of clinical reports designed as randomized controlled trials (RCTs). One hundred and thirty-eight available RCTs and quasi-RCTs on 62 TCPMs, involving 16,393 patients, were included. The methodological quality of these trials was generally "poor". Few trials (6.52%) reported the methods of randomization correctly. Another common problem was the lack of allocation concealment, proper blinding, and the reporting of lost cases and dropouts. Forty-two trials (30.43%) on 27 TCPMs reported some anti-viral effect of TCPMs. Others reported beneficial aspects, including improvements of liver function (79.71% of the studies), liver fibrosis (29.99%), and CHB symptoms (92.75%). Forty-one articles (29.71%) reported mild adverse events with TCPMs but these occurred infrequently. In summary, the outcome of the report on currently registered TCPMs may be biased due to poor methodology. The data from these trials, therefore, is too weak to use in forming a recommendation for treatment of CHB. Nevertheless, five drugs (Dan Shen agents, Da Huang Zhe Chong pill/capsule, Shuang Hu Qing Gan granule, Fu Zheng Hua Yu granule and Cao Xian Yi Gan capsule) appear to be more effective than the other TCPMs.

Associations between prescribed Chinese herbal medicine and risk of hepatocellular carcinoma in patients with chronic hepatitis B: a nationwide population-based cohort study.

PubMed

Tsai, Tzung-Yi; Livneh, Hanoch; Hung, Tsung-Hsing; Lin, I-Hsin; Lu, Ming-Chi; Yeh, Chia-Chou

2017-01-25

Patients with chronic hepatitis B (CHB) are reported to exhibit higher risk of subsequent hepatocellular carcinoma (HCC). However, it remains unclear if Chinese herbal medicine (CHM), an important category of traditional Chinese medicine (TCM), may lower HCC risk in this population. So this study aimed to investigate the effects of CHM on HCC risk among patients with CHB. This cohort study used the Taiwanese National Health Insurance Research Database to identify 21 020 newly diagnosed patients with CHB from 1998 to 2007. Among them, 8640 received CHM products after CHB onset (CHM users), and the remaining 12 380 patients were designated as a control group (non-CHM users). All enrolees were followed until the end of 2012 to measure the incidence rate and HR of HCC. During 15 years of follow-up, 371 CHM users and 958 non-CHM users developed HCC, representing an incidence rate of 5.28% and 10.18% per 1000 person-years, respectively. CHM users had significantly lower HCC risk compared with non-CHM users (adjusted HR=0.63, 95% CI 0.56 to 0.72). The predominant effect was observed in those receiving CHM products for more than 180 days (adjusted HR=0.52). Some CHM products, such as Hedyotis diffusa, Scutellaria barbata, Rehmannia glutinosa, Isatis tinctoria, Yi Guan Jian, Xiao Chai Hu Tang, Wu Ling San and Gan Lu Yin, were significantly associated with lower risk of HCC. The use of CHM was associated with a significantly reduced HCC risk in patients with CHB, which supports the integration of TCM with CHM into clinical practice to influence a favourable prognosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Hepatitis B surface antigen levels during natural history of chronic hepatitis B: a Chinese perspective study.

PubMed

Zeng, Lin-Yan; Lian, Jiang-Shan; Chen, Jian-Yang; Jia, Hong-Yu; Zhang, Yi-Min; Xiang, Dai-Rong; Yu, Liang; Hu, Jian-Hua; Lu, Ying-Feng; Zheng, Lin; Li, Lan-Juan; Yang, Yi-Da

2014-07-21

To determine the baseline hepatitis B surface antigen (HBsAg) levels during the different phases of chronic hepatitis B (CHB) patients in China. Six hundred and twenty-three hepatitis B virus or un-infected patients not receiving antiviral therapy were analyzed in a cross-sectional study. The CHB patients were classified into five phases: immune-tolerant (IT, n = 108), immune-clearance (IC, n = 161), hepatitis B e antigen negative hepatitis (ENH, n = 149), low-replicative (LR, n = 135), and liver cirrhosis (LC, n = 70). HBsAg was quantified (Abbott ARCHITECT assay) and correlated with hepatitis B virus (HBV) DNA, and serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) in each phase of CHB was also determined. Median HBsAg titers were different in each phase of CHB (P < 0.001): IT (4.85 log10 IU/mL), IC (4.36 log10 IU/mL), ENH (2.95 log10 IU/mL), LR (3.18 log10 IU/mL) and LC (2.69 log10 IU/mL). HBsAg titers were highest in the IT phase and lowest in the LC phase. Serum HBsAg titers showed a strong correlation with HBV viral load in the IC phase (r = 0.683, P < 0.001). No correlation between serum HBsAg level and ALT/AST was observed. The mean baseline HBsAg levels differ significantly during the five phases of CHB, providing evidence on the natural history of HBV infection. HBsAg quantification may predict the effects of immune-modulator or oral nucleos(t)ide analogue therapy.

Timing of chronic hepatitis B diagnosis after migration and its determinants among Sub-Saharan African migrants living in France

PubMed Central

Gigonzac, Virginie; Lydié, Nathalie; Desgrées du Loû, Annabel; Dray Spira, Rosemary

2017-01-01

Objective In European countries, chronic hepatitis B (CHB) disproportionately affects migrants from medium- and high-endemic areas and is largely underdiagnosed. To inform policy and improve screening strategies, we measured the timing of CHB diagnosis after migration and its determinants among sub-Saharan migrants living in the Paris metropolitan area (France). Design The PARCOURS study is a retrospective life-event history survey conducted in health care services in 2012–2013 among 779 migrants from sub-Saharan Africa who were receiving care for CHB. We investigated the timing of CHB diagnosis from the time of arrival in France using the Kaplan-Meier method and characteristics associated with CHB diagnosis since the time of arrival in France using discrete-time multivariate logistic regression models. Results The median CHB diagnosis occurred during the fourth year spent in France for men and during the second year spent in France for women. Among men, the probability of CHB diagnosis increased during years with (versus without) a temporary resident permit (aOR: 1.6, 95%CI: 1.1–2.2), a precarious accommodation (aOR: 1.7, 95%CI: 1.1–2.6), and hospitalization (aOR: 7.7, 95%CI: 3.4–15.1). Among women, CHB diagnosis was more likely to occur during years with unemployment (aOR: 1.9, 95%CI: 1.1–3.94), pregnancy (aOR: 6.6, 95%CI: 3.5–12.5) and hospitalization (aOR: 9.0, 95%CI: 2.95–32.3). For both sexes, the probability of CHB diagnosis was higher among those who migrated to France because they were threatened in their country. Conclusion This study shows that social hardships (residential, economic, administrative) and contact with the health care system after arrival in France hasten access to a CHB diagnosis. PMID:29283994

The factors associated with longitudinal changes in liver stiffness in patients with chronic hepatitis B

PubMed Central

Yo, In Ku; Park, Jin Woong; Lee, Jong Joon; Lee, Jung Hyun; Won, In Sik; Na, Sun Young; Jang, Pil Kyu; Park, Pyung Hwa; Choi, Duck Joo; Kim, Yun Soo; Kim, Ju Hyun

2015-01-01

Background/Aims Liver stiffness (LS) as assessed by transient elastography (TE) can change longitudinally in patients with chronic hepatitis B (CHB). The aim of this study was to identify the factors that improve LS. Methods Between April 2007 and December 2012, 151 patients with CHB who underwent two TE procedures with an interval of about 2 years were enrolled. Ninety-six of the 151 patients were treated with nucleos(t)ide analogues [the antiviral therapy (+) group], while the remaining 55 patients were not [the antiviral therapy (-) group]. The two groups of patients were stratified according to whether they exhibited an improvement or a deterioration in LS during the study period (defined as an LS change of ≤0 or >0 kPa, respectively, over a 1-year period), and their data were compared. Results No differences were observed between the antiviral therapy (+) and (-) groups with respect to either their clinical characteristics or their initial LS. The observed LS improvement was significantly greater in the antiviral therapy (+) group than in the antiviral therapy (-) group (-3.0 vs. 0.98 kPa, P=0.011). In the antiviral therapy (+) group, the initial LS was higher in the LS improvement group (n=63) than in the LS deterioration group (n=33; 7.9 vs. 4.8 kPa, P<0.001). However, there were no differences in any other clinical characteristic. In the antiviral therapy (-) group, the initial LS was also higher in the LS improvement group (n=29) than in the LS deterioration group (n=26; 8.3 vs. 6.5 kPa, P=0.021), with no differences in any other clinical characteristic. Conclusions A higher initial LS was the only factor associated with LS improvement in patients with CHB in this study. PMID:25834800

Validation of the cardiac health behavior scale for Korean adults with cardiovascular risks or diseases.

PubMed

Song, Rhayun; Oh, Hyunkyoung; Ahn, Sukhee; Moorhead, Sue

2018-02-01

The purpose of this study was to validate the Cardiac Health Behavior Scale for Korean adults (CHB-K) to determine its validity and reliability. Cardiovascular diseases (CVDs) are one of the most important chronic diseases due to their high prevalence and mortality rates. Patients with cardiovascular risks or diseases need to perform appropriate cardiac health behaviors that help to prevent the progression of the disease and improve their health status. This secondary analysis obtained data from two clinical trials of cardiac rehabilitation. Data from 298 patients with cardiovascular risks or diseases were analyzed for validation. Data analyses included correlation coefficients, t-tests, and exploratory and confirmatory factor analyses using SPSS (version WIN 22.0) and AMOS (version 20.0). The Self-Efficacy Scale was used to assess convergent validity, while reliability was assessed using Cronbach's alpha coefficients. Five main factors were verified: health responsibility, physical activity, diet habit (eating habit and food choice), stress management, and smoking cessation. A set of 21 items from the 25-item scale was verified after performing item analysis, factor analyses, and critical evaluation of the statistical results. The 21-item CHB-K (CHB-K21) exhibited acceptable validity, and the model of the CHB-K21 provided a good fit to the data. Most of the factors were found to be moderately correlated with SES scores (r=0.45-0.52, p<0.001). The CHB-K21 also demonstrated acceptable reliability (Cronbach's alpha=0.83). The CHB-K21 demonstrates strong validity and reliability. It can be used to assess cardiac health behaviors in Korean adults with cardiovascular risks or diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficacy and Safety of Peginterferon Alfa-2a (40KD) in Children with Chronic Hepatitis B: The PEG-B-ACTIVE Study.

PubMed

Wirth, Stefan; Zhang, Hongfei; Hardikar, Winita; Schwarz, Kathleen B; Sokal, Etienne; Yang, Weibo; Fan, Huimin; Morozov, Vyacheslav; Mao, Qing; Deng, Hong; Yang Huang; Yang, Lei; Frey, Nicolas; Nasmyth-Miller, Clare; Pavlovic, Vedran; Wat, Cynthia

2018-04-24

Children with chronic hepatitis B (CHB) represent an area of unmet medical need, due to increased lifetime risk of CHB sequelae and limited therapeutic options compared with adult CHB patients. The PEG-B-ACTIVE (NCT01519960) phase III study evaluated peginterferon (PegIFN) alfa-2a treatment in children aged 3 to <18 years with CHB. A total of 161 hepatitis B e antigen (HBeAg)-positive immune-active patients without advanced fibrosis/cirrhosis were randomized (2:1) to PegIFN alfa-2a (Group A, n = 101) or no treatment (Group B, n = 50); patients with advanced fibrosis were assigned to PegIFN alfa-2a (Group C, n = 10). PegIFN alfa-2a was administered for 48 weeks by body surface area category, based on 180 µg/1.73m 2 . HBeAg seroconversion rates at 24 weeks post-treatment were significantly higher in Group A (25.7% vs. 6%, P = 0.0043), as were the rates of Hepatitis B s antigen (HBsAg) clearance (8.9% vs. 0%, P = 0.03), hepatitis B virus (HBV) DNA <2,000 IU/mL (28.7% vs. 2.0%, P < 0.001) or undetectable (16.8% vs. 2.0%, P = 0.0069), and alanine aminotransferase (ALT) normalization (51.5% vs. 12%, P < 0.001). Safety, including incidence of ALT flares and neutropenia, was comparable to the established PegIFN alfa-2a profile in HBV-infected adults or hepatitis C virus-infected children. Changes in growth parameters were minimal during treatment and comparable to those in untreated patients. Safety and efficacy outcomes in Group C were in line with Group A. PegIFN alfa-2a treatment of children in the immune-active phase of CHB was efficacious and well tolerated, and associated with higher incidence of HBsAg clearance than in adults. This represents an important advance to the treatment options for children with CHB. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

Association of KIR genotypes and haplotypes with susceptibility to chronic hepatitis B virus infection in Chinese Han population.

PubMed

Lu, Zhiming; Zhang, Bingchang; Chen, Shijun; Gai, Zhongtao; Feng, Zhaolei; Liu, Xiangdong; Liu, Yiqing; Wen, Xin; Li, Li; Jiao, Yulian; Ma, Chunyan; Shao, Song; Cui, Xiangfa; Chen, Guojian; Li, Jianfeng; Zhao, Yueran

2008-12-01

Killer immunoglobulin-like receptor (KIR) genes can regulate the activation of NK and T cells upon interaction with HLA class I molecules. Hepatitis B virus (HBV) infection has been regarded as a multi-factorial disorder disease. Previous studies revealed that KIRs were involved in HCV and HIV infection or clearance. The aim of this study was to explore the possibility of the inheritance of KIR genotypes and haplotypes as a candidate for susceptibility to persistent HBV infection or HBV clearance. The sequence specific primer polymerase chain reaction (SSP-PCR) was employed to identify the KIR genes and pseudogenes in 150 chronic hepatitis B (CHB) patients, 251 spontaneously recovered (SR) controls, and 412 healthy controls. The frequencies of genotype G, M, FZ1 increased in CHB patients compared with healthy control subjects. The frequency of genotype AH was higher in SR controls than that in both CHB patients and healthy controls. The carriage frequencies of genotype G and AH were higher; while, the frequencies of AF and AJ were lower in SR controls than those in healthy control subjects. The frequency of A haplotype was lower, whereas, the frequency of B haplotype was higher in CHB patients and SR controls than those in healthy controls. In healthy controls, haplotype 4 was found lower compared with that in CHB patients and SR controls and the frequency of haplotype 5 was higher in SR controls than that in other two groups. Based on these findings, it seems that the genotypes M and FZ1 are HBV susceptive genotypes; AH, on the other hand, may be protective genotypes that facilitate the clearance of HBV. It appears that the haplotype 4 is HBV susceptive haplotype, whereas, haplotype 5 may be the protective haplotype that facilitates the clearance of HBV.

Application of Bayesian Approach to Cost-Effectiveness Analysis of Antiviral Treatments in Chronic Hepatitis B.

PubMed

Zhang, Hua; Huo, Mingdong; Chao, Jianqian; Liu, Pei

2016-01-01

Hepatitis B virus (HBV) infection is a major problem for public health; timely antiviral treatment can significantly prevent the progression of liver damage from HBV by slowing down or stopping the virus from reproducing. In the study we applied Bayesian approach to cost-effectiveness analysis, using Markov Chain Monte Carlo (MCMC) simulation methods for the relevant evidence input into the model to evaluate cost-effectiveness of entecavir (ETV) and lamivudine (LVD) therapy for chronic hepatitis B (CHB) in Jiangsu, China, thus providing information to the public health system in the CHB therapy. Eight-stage Markov model was developed, a hypothetical cohort of 35-year-old HBeAg-positive patients with CHB was entered into the model. Treatment regimens were LVD100mg daily and ETV 0.5 mg daily. The transition parameters were derived either from systematic reviews of the literature or from previous economic studies. The outcome measures were life-years, quality-adjusted lifeyears (QALYs), and expected costs associated with the treatments and disease progression. For the Bayesian models all the analysis was implemented by using WinBUGS version 1.4. Expected cost, life expectancy, QALYs decreased with age. Cost-effectiveness increased with age. Expected cost of ETV was less than LVD, while life expectancy and QALYs were higher than that of LVD, ETV strategy was more cost-effective. Costs and benefits of the Monte Carlo simulation were very close to the results of exact form among the group, but standard deviation of each group indicated there was a big difference between individual patients. Compared with lamivudine, entecavir is the more cost-effective option. CHB patients should accept antiviral treatment as soon as possible as the lower age the more cost-effective. Monte Carlo simulation obtained costs and effectiveness distribution, indicate our Markov model is of good robustness.

In vivo imaging of cerebral hemodynamics and tissue scattering in rat brain using a surgical microscope camera system

NASA Astrophysics Data System (ADS)

Nishidate, Izumi; Kanie, Takuya; Mustari, Afrina; Kawauchi, Satoko; Sato, Shunichi; Sato, Manabu; Kokubo, Yasuaki

2018-02-01

We investigated a rapid imaging method to monitor the spatial distribution of total hemoglobin concentration (CHbT), the tissue oxygen saturation (StO2), and the scattering power b in the expression of musp=a(lambda)^-b as the scattering parameters in cerebral cortex using a digital red-green-blue camera. In the method, Monte Carlo simulation (MCS) for light transport in brain tissue is used to specify a relation among the RGB-values and the concentration of oxygenated hemoglobin (CHbO), that of deoxygenated hemoglobin (CHbR), and the scattering power b. In the present study, we performed sequential recordings of RGB images of in vivo exposed brain of rats while changing the fraction of inspired oxygen (FiO2), using a surgical microscope camera system. The time courses of CHbO, CHbR, CHbT, and StO2 indicated the well-known physiological responses in cerebral cortex. On the other hand, a fast decrease in the scattering power b was observed immediately after the respiratory arrest, which is similar to the negative deflection of the extracellular DC potential so-called anoxic depolarization. It is said that the DC shift coincident with a rise in extracellular potassium and can evoke cell deformation generated by water movement between intracellular and extracellular compartments, and hence the light scattering by tissue. Therefore, the decrease in the scattering power b after the respiratory arrest is indicative of changes in light scattering by tissue. The results in this study indicate potential of the method to evaluate the pathophysiological conditions and loss of tissue viability in brain tissue.

Predictive value of serum ALT and T-cell receptor beta variable chain for HBeAg seroconversion in chronic hepatitis B patients during tenofovir treatment.

PubMed

Yang, Jiezuan; Yan, Dong; Guo, Renyong; Chen, Jiajia; Li, Yongtao; Fan, Jun; Fu, Xuyan; Yao, Xinsheng; Diao, Hongyan; Li, Lanjuan

2017-03-01

Effective antiviral therapy plays a key role in slowing the progression of chronic hepatitis B (CHB). Identification of serum indices, including hepatitis B e antigen (HBeAg) expression and seroconversion, will facilitate evaluation of the efficacy of antiviral therapy in HBeAg-positive CHB patients. The biochemical, serological, virological parameters, and the frequency of circulating CD4CD25 regulatory T cell (Treg) in 32 patients were measured at baseline and every 12 weeks during 96 weeks of tenofovir disoproxil fumarate (TDF) treatment. The relationship between the hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and Treg and alanine aminotransferase (ALT) levels was analyzed, respectively. The molecular profiles of T-cell receptor beta variable chain (TRBV) were determined using gene melting spectral pattern. For the seroconverted 12 patients, ALT declined to normal levels by week 24 and remained at this level in subsequent treatment; moreover, the predictive cutoff value of ALT for HBeAg seroconversion (SC) was 41.5 U/L at week 24. The positive correlation between HBV DNA and Treg and ALT was significant in SC patients, but not in non-SC patients. Six TRBV families (BV3, BV11, BV12, BV14, BV20, and BV24) were predominantly expressed in SC patients at baseline. The decline of ALT could be used to predict HBeAg seroconversion for CHB patients during TDF treatment. In addition, the profile of Tregs and TRBVs may be associated with HBeAg seroconversion and could also be a potential indicator for predicting HBeAg SC and treatment outcome for CHB patients.

Lamivudine switch therapy in chronic hepatitis B patients achieving undetectable hepatitis B virus DNA after 3 years of entecavir therapy: A prospective, open-label, multicenter study.

PubMed

Yeh, Ming-Lun; Huang, Ching-I; Hsieh, Ming-Yen; Huang, Chung-Feng; Hsieh, Meng-Hsuan; Huang, Jee-Fu; Dai, Chia-Yen; Lin, Zu-Yau; Chen, Shinn-Chern; Yu, Ming-Lung; Chuang, Wan-Long

2016-11-01

The subsequent maintenance therapy in chronic hepatitis B (CHB) patients after long-term viral replication suppression is still uncertain. We aim to evaluate the efficacy of lamivudine (LAM) maintenance therapy in CHB patients achieving undetectable hepatitis B virus (HBV) DNA after 3 years of entecavir (ETV) therapy. Consecutive CHB patients who received at least 3 years of ETV and achieved HBV DNA negativity were allocated either LAM switch therapy or stopped ETV therapy in a prospective, open-label study. Another group of sex- and age-matched patients with continuous ETV therapy for at least 4 years served as historical control group. The primary outcome measurement of the study was relapse of HBV DNA (defined as serum HBV DNA level ≥ 2000 IU/mL). A total of 74 patients, including 42 of LAM switch and 32 of the nonswitch group, were enrolled. There were no significant differences in demographics, except a higher proportion of patients with positive hepatitis B envelope antigen in the nonswitch group at the initiation of ETV therapy. The LAM switch group had significantly lower 1-year relapse rate of HBV within 1 year compared to the nonswitch group (14.3% vs. 75%, p<0.001). However, none of the 48 historical control patients developed relapse of HBV, which was significantly lower than the rate in LAM switch group (p < 0.001). LAM switch was the only factor associated with HBV DNA relapse. In conclusion, continuous long-term potent nucleot(s)ide analogue therapy is mandatory for prevention of viral relapse in CHB patients. Copyright © 2016 Kaohsiung Medical University. Published by Elsevier Taiwan.. All rights reserved.

Adherence to follow-up and treatment recommendations in Greek and immigrant patients with chronic hepatitis B in Greece.

PubMed

Voulgaris, Theodoros; Vlachogiannakos, John; Ioannidou, Panagiota; Papageorgiou, Maria-Vasiliki; Zampeli, Evi; Karagiannakis, Dimitrios; Georgiou, Anastasia; Papazoglou, Afroditi; Karamanolis, George; Papatheodoridis, George V

2017-03-01

Immigrants have multiple barriers to access to health care systems. We evaluated the adherence to follow-up and treatment recommendations of chronic hepatitis B virus (HBV) Greek and immigrant patients. In total, 1001 consecutive adult patients with chronic HBV infection who visited our clinics for the first time between 2002 and 2011 were included. All patients born outside Greece were considered immigrants. Diagnosis was considered to be complete if patients could be classified into HBeAg-positive chronic hepatitis B (CHB), inactive carriers, HBeAg-negative CHB, or decompensated cirrhosis. Of the patients, 56% were Greeks and 44% were immigrants. Greeks visited our clinics at a significantly older mean age (50 vs. 35 years, P<0.001) and more frequently with advanced liver disease (11.4 vs. 6.4%, P=0.007). During the first year, Greeks more frequently had several tests and eventually a complete diagnosis (68 vs. 55%, P<0.001). Greeks were more frequently in the phase of HBeAg-negative CHB and less frequently in the phase of inactive carrier or HBeAg-positive CHB, but age was the main determinant for these differences in multivariate analysis. Treatment was initiated more frequently by Greeks than immigrants with treatment indications (86 vs. 65%, P<0.001). Only 30-33% of treated and 4-10% of untreated patients remained under follow-up at year 5, without significant differences between Greeks and immigrants. Adherence to follow-up recommendations is rather poor for all chronic HBV patients. Immigrants are lost more frequently during the first year, but only small proportions of treated and particularly untreated Greek or immigrant patients remain under long-term follow-up.

Cost of chronic hepatitis B infection in South Korea.

PubMed

Yang, Bong-Min; Kim, Cheol-Hwan; Kim, Ji-Yun

2004-01-01

To estimate the direct medical costs of chronic hepatitis B (CHB) infection and its liver disease sequelae in South Korea. Korea is a hepatitis B-endemic area with 5.79% to 10.87% of males and 1.51% to 4.44% of females over 20 years of age carrying the virus. It is estimated that 25% of carriers will develop serious hepatitis B virus (HBV)-related complications. While vaccination programs have reduced the prevalence of hepatitis B in people younger than 20 years, significant CHB-related morbidity will continue to occur for the next 15 to 30 years until the benefits of the vaccination programs take effect. Direct medical costs for six CHB-related disease states, including hepatocellular carcinoma and liver transplant, were estimated for the year 2001. Four data sources were used to gather information: the National Health Insurance Corporation database, patients' medical charts, expert opinion, and patient survey data. In 2001, the total medical costs of six CHB-related diseases were 250 million Korean Won (KRW) (equivalent to U.S. 208.6 million dollars), based on an exchange rate of KRW 1200 = US 1 dollar. Annual treatment costs per patient ranged from KRW297,392 (US 248 dollars) for chronic hepatitis B to KRW 80.6 million (U.S. 67,156 dollars) for liver transplant. The cost of treatment rose continuously with liver disease progression. The main cost driver was inpatient hospitalizations (including surgical costs). CHB-related diseases are a significant cost burden to the South Korean healthcare system. In addition to the obvious clinical benefits, the prevention or delay of chronic hepatitis B liver disease progression in South Korea could result in substantial economic benefits to the whole society.

Vaccination rate and seroepidemiology of hepatitis a in chronic-hepatitis-B-infected individuals in the korean army.

PubMed

Shin, Dong Hyuk; Han, Sang Kuk; Choi, Pil Cho; Lim, Seong Woo; Kim, Kyung Mook; Sinn, Dong Hyun

2010-06-01

Vaccination against hepatitis A virus (HAV) is recommended for patients with chronic hepatitis B (CHB), since they are potentially at an increased risk of HAV-related morbidity and mortality. However, little is known about the adherence to these recommendations in the community. This study evaluated the current vaccination status and immunity against HAV among Korean military soldiers with CHB. We performed a prospective study of Korean military soldiers from August 2008 to January 2009. We enrolled 96 soldiers with CHB on a consecutive basis. We assessed their vaccination history and the presence of anti-HAV immunoglobulin G (IgG). The HAV vaccination rate of the soldiers enrolled in our study was 2% (2 of the 96 soldiers). The seroprevalence rates of anti-HAV IgG among military soldiers without a vaccination history were 0%, 50%, and 100% for those aged 19-29 years (n=71), 30-39 years (n=8), and 40 years or older (n=15), respectively (p<0.001). The HAV vaccination rate is very low among military soldiers. Public health efforts aimed at raising awareness about HAV vaccination in patients with CHB should be strongly encouraged.

Classification and Progression Based on CFS-GA and C5.0 Boost Decision Tree of TCM Zheng in Chronic Hepatitis B.

PubMed

Chen, Xiao Yu; Ma, Li Zhuang; Chu, Na; Zhou, Min; Hu, Yiyang

2013-01-01

Chronic hepatitis B (CHB) is a serious public health problem, and Traditional Chinese Medicine (TCM) plays an important role in the control and treatment for CHB. In the treatment of TCM, zheng discrimination is the most important step. In this paper, an approach based on CFS-GA (Correlation based Feature Selection and Genetic Algorithm) and C5.0 boost decision tree is used for zheng classification and progression in the TCM treatment of CHB. The CFS-GA performs better than the typical method of CFS. By CFS-GA, the acquired attribute subset is classified by C5.0 boost decision tree for TCM zheng classification of CHB, and C5.0 decision tree outperforms two typical decision trees of NBTree and REPTree on CFS-GA, CFS, and nonselection in comparison. Based on the critical indicators from C5.0 decision tree, important lab indicators in zheng progression are obtained by the method of stepwise discriminant analysis for expressing TCM zhengs in CHB, and alterations of the important indicators are also analyzed in zheng progression. In conclusion, all the three decision trees perform better on CFS-GA than on CFS and nonselection, and C5.0 decision tree outperforms the two typical decision trees both on attribute selection and nonselection.

FibroScan, aspartate aminotransferase and alanine aminotransferase ratio (AAR), aspartate aminotransferase to platelet ratio index (APRI), fibrosis index based on the 4 factor (FIB-4), and their combinations in the assessment of liver fibrosis in patients with hepatitis B.

PubMed

Ding, Deping; Li, Hongbing; Liu, Ping; Chen, Lingli; Kang, Jian; Zhang, Yinhua; Ma, Deqiang; Chen, Yue; Luo, Jie; Meng, Zhongji

2015-01-01

The aim of this study was to assess the effects of FibroScan, aspartate aminotransferase and alanine aminotransferase ratio (AAR), aspartate aminotransferase to platelet ratio index (APRI), fibrosis index based on the 4 factor (FIB-4) and their combinations on liver fibrosis in patients with hepatitis B. 406 hospitalized patients with chronic hepatitis B (CHB) and cirrhosis in our hospital were analyzed retrospectively and collected patients clinical indicators, including liver stiffness (LS), AAR, APRI and FIB-4, and then compared the differences of these indicators between CHB group and hepatitis B with cirrhosis group. Receiver operating curve (ROC) was used to evaluate the differentiating capacity of these indicators on CHB and liver cirrhosis. Four indicators related to liver cirrhosis had a statistical significance between two groups (P < 0.01); the under ROC curve areas of LS, AAR, APRI and FIB-4 for differential diagnosis of CHB and liver cirrhosis were 0.866, 0.772, 0.632 and 0.885, respectively. The under ROC curve areas of LS, AAR, APRI and FIB-4 for differential diagnosis of liver cirrhosis at compensatory stage and de-compensatory stage were 0.627, 0.666, 0.795 and 0.820, respectively. LS, AAR, APRI and FIB-4 were good indicators as clinical diagnosis and differential diagnosis on hepatitis B related cirrhosis.

Comparison of FIB-4 index and aspartate aminotransferase to platelet ratio index on carcinogenesis in chronic hepatitis B treated with entecavir

PubMed Central

Nishikawa, Hiroki; Nishijima, Norihiro; Enomoto, Hirayuki; Sakamoto, Azusa; Nasu, Akihiro; Komekado, Hideyuki; Nishimura, Takashi; Kita, Ryuichi; Kimura, Toru; Iijima, Hiroko; Nishiguchi, Shuhei; Osaki, Yukio

2017-01-01

Aims: We sought to compare the effects of FIB-4 index and aspartate aminotransferase to platelet ratio index (APRI) on hepatocellular carcinoma (HCC) incidence in chronic hepatitis B (CHB) patients undergoing entecavir (ETV) therapy. Patient and methods: A total of 338 nucleosides analogue therapy naïve CHB patients initially treated with ETV were analyzed. The optimal cutoff points in each continuous variable were determined by receiver operating curve (ROC) analysis. The effects of FIB-4 index and APRI on HCC incidence were compared using time-dependent ROC analysis and factors linked to HCC incidence were also examined using univariate and multivariate analyses. Results: There were 215 males and 123 females with the median age of 52 years and the median baseline HBV-DNA level of 6.6 log copies/ml. The median follow-up interval after the initiation of ETV therapy was 4.99 years. During the follow-up period, 33 patients (9.8%) developed HCC. The 3-, 5- 7-year cumulative HCC incidence rates in all cases were 4.4%, 9.2% and 13.5%, respectively. In the multivariate analysis, FIB-4 index revealed to be an independent predictor associated with HCC incidence, while APRI was not. In the time-dependent ROC analyses for all cases and for all subgroups analyses stratified by viral status or cirrhosis status, all area under the ROCs in each time point (2-, 3-, 4-, 5-, 6-, and 7-year) of FIB-4 index were higher than those of APRI. Conclusion: FIB-4 index rather than APRI can be a useful predictor associated with HCC development for CHB patients undergoing ETV therapy. PMID:28243319

An audit of chronic hepatitis B contact tracing in metropolitan Western Australia.

PubMed

Mascarenhas, Lester; Mak, Donna B

2014-03-01

People with chronic hepatitis B (CHB) are a source of transmission and those in contact with them are a national priority population for hepatitis B testing and vaccination. This audit examined contact tracing success rate and barriers. Success was defined as contacts tested and vaccinated if required. An online survey of 26 general practitioners (GPs), and computer-assisted telephone interviews of 40 patients with CHB notified between 1 September 2011 and 1 September 2012. Half of the patients with CHB (16/31) were asked to take responsibility for informing contacts; contacts of five patients were traced by doctors and those of three patients were traced by nurses. The overall success rate was 75%. Contact tracing by nurses was 100% successful; after excluding nurse contact tracing from the analysis, the success rate was 57%. GPs reported 'insufficient resources' as the most frequent doctor-related barrier to contact tracing and 58% of doctors reported that public health units should be responsible for contact tracing. Increasing contact tracing by nurses could improve success rates. Public health unit assistance for contact tracing of complex cases should continue.

The role of the NLRP3 inflammasome and the activation of IL-1β in the pathogenesis of chronic viral hepatic inflammation.

PubMed

Molyvdas, Adam; Georgopoulou, Urania; Lazaridis, Nikolaos; Hytiroglou, Prodromos; Dimitriadis, Alexios; Foka, Pelagia; Vassiliadis, Themistoklis; Loli, Georgia; Phillipidis, Athanasios; Zebekakis, Pantelis; Germenis, Anastasios E; Speletas, Matthaios; Germanidis, Georgios

2018-05-23

Chronic viral hepatitis is a prevalent disease with major health implications. Its underlying pathophysiological mechanisms are not fully understood. IL-1β and the NLRP3 inflammasome involvement has been suggested in recent years, from in vitro data and data from peripheral blood samples. Therefore, we investigated IL-1β and the NLRP3 inflammasome in liver tissues in an effort to clarify their role in the pathophysiology of chronic viral hepatitis. We studied liver biopsies from patients with a new diagnosis of either chronic hepatitis B (CHB) and chronic hepatitis C (CHC) or patients with chronic hepatitis B in remission (CHB-rem). The biopsies were separated in two parts. The first part was sent to histology to determine the grade of inflammation and fibrosis. From the second part, RNA was extracted and converted to cDNA used in semi-quantitative Real-Time PCR to measure the levels of IL1B, CASP1, NLRP3, ASC and IL1RA. The cell lines used in the in vitro experiments were Huh7.5, LX2 and THP-1 in variety of combinations of monocultures, co-cultures and triple cultures with one of the cell lines infected with the JFH-1 HCV clone. From the cell cultures RNA was extracted and converted to cDNA. For cell lines, we focused in the expression of IL1B and NLRP3. The expression of IL1B, CASP1 and NLRP3 were found significantly different between our groups (p = 0.001, p = 0.001 and p = 0.038, respectively). CHB patients displayed significantly higher IL1B and CASP1 mRNA levels compared to both CHB-rem and CHC patients. IL1B expression significantly correlates with liver biochemical data in CHB patients (AST: p = 0.006, r = 0.457; ALT p = 0.002, r = 0.497). Finally, mRNA levels of IL1B in CHB patients significantly correlate with the degree of inflammation (p = 0.016) but not the stage of fibrosis (p = 0.362). Interestingly, the relative expression of IL1B in triple culture experiments in vitro was below of 1.5-fold, suggesting no activation of IL1B. Moreover, no activation of NLRP3 was demonstrated in all investigated in vitro conditions. IL-1β might play an important role in the pathogenesis of chronic hepatic inflammation from HBV, but not from HCV. Copyright © 2018 Elsevier Ltd. All rights reserved.

The cascade of care for Australians living with chronic hepatitis B: measuring access to diagnosis, management and treatment.

PubMed

Allard, Nicole L; MacLachlan, Jennifer H; Cowie, Benjamin C

2015-06-01

To estimate the level of access to diagnosis, management and treatment for people living with chronic hepatitis B (CHB) in Australia, and to identify the gaps in clinical care for people living with CHB. Analysis of publicly available population level data including infectious disease notifications, Medicare and Pharmaceutical Benefits Scheme utilisation data, census-based estimates of CHB prevalence and burden, and mathematical modelling. In 2012, of the estimated 218,567 Australians living with CHB, 57% had been diagnosed, 17,367 people (8%) received recommended HBV DNA viral load testing (without treatment) and 10,987 (5%) received antiviral therapy. This analysis reveals substantial gaps in the cascade of care for CHB in Australia, most notably in diagnosis (with 43% undiagnosed) and in recommended yearly monitoring (87% not in care). The number receiving therapy represents only one-third of those estimated to require treatment to prevent progressive liver disease and liver cancer. These findings demonstrate that the majority of those affected are not receiving guideline-based care; highlight the need for improvements in opportunistic screening, engagement in care, and access to therapy; and provide a method to assess the impact of public health and clinical interventions in response to CHB over time. © 2015 Public Health Association of Australia.

Kushenin Combined with Nucleos(t)ide Analogues for Chronic Hepatitis B: A Systematic Review and Meta-Analysis

PubMed Central

Chen, Zhe; Ma, Xiao; Zhao, Yanling; Wang, Jiabo; Zhang, Yaming; Zhu, Yun; Wang, Lifu; Chen, Chang; Wei, Shizhang; Yang, Zhirui; Gong, Man; Shen, Honghui; Bai, Zhaofang; Guo, Yuming; Niu, Ming; Xiao, Xiaohe

2015-01-01

Objective. To evaluate the efficacy and safety of Kushenin (KS) combined with nucleoside analogues (NAs) for chronic hepatitis B (CHB). Methods. Randomized controlled trials (RCTs) of KS combined with NAs for CHB were identified through 7 databases. Frequencies of loss of serum HBeAg, HBeAg seroconversion, undetectable serum HBV-DNA, ALT normalization, and adverse events at 48 weeks were abstracted by two reviewers. The Cochrane software was performed to assess the risk of bias in the included trials. Data were analyzed with Review Manager 5.3 software. Results. 18 RCTs involving 1684 subjects with CHB were included in the analysis. KS combined with NAs including lamivudine (LAM), entecavir (ETV), adefovir dipivoxil (ADV), and telbivudine (TLV) showed different degree of improvement in CHB indices. KS combined with NAs increased the frequency of loss of serum HBeAg, HBeAg seroconversion, undetectable HBV-DNA levels, and ALT normalization compared with single agents. It also decreased serum ALT and AST level after one-year treatment. However, KS combined with TLV did not show a significant difference in CHB indices. The side-effects of KS combined with NAs were light and of low frequency. Conclusion. KS combined with NAs improves the efficacy of NAs in CHB. PMID:26347789

Impact of FIB-4 index on hepatocellular carcinoma incidence during nucleos(t)ide analogue therapy in patients with chronic hepatitis B: An analysis using time-dependent receiver operating characteristic.

PubMed

Tada, Toshifumi; Kumada, Takashi; Toyoda, Hidenori; Tsuji, Kunihiko; Hiraoka, Atsushi; Tanaka, Junko

2017-02-01

Nucleos(t)ide analogue (NA) therapy has been reported to reduce the risk of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis B (CHB). However, even during NA therapy, development of HCC has been observed in patients with CHB. Therefore, we clarified the predictive power of clinical factors for HCC incidence using receiver operating characteristic (ROC) analysis that takes time dependence into account. A total of 539 patients with CHB treated with NAs were enrolled. Univariate, multivariate, and time-dependent ROC curves for clinical factors associated with the development of HCC were analyzed. Eighty-one patients developed HCC during the follow-up period (median duration, 5.9 years). α-fetoprotein (AFP) and FIB-4 index at 24 weeks from the initiation of treatment and sex were significantly associated with HCC incidence according to the log-rank test. Cox proportional hazards models including the covariates of sex, hepatitis B genotype, basal core promoter mutations, AFP at 24 weeks, and FIB-4 index at 24 weeks showed that FIB-4 index >2.65 (HR, 5.03; 95% CI, 3.06-8.26; P < 0.001) and male sex were independently associated with HCC incidence. In addition, time-dependent ROC analysis showed that compared with AFP at 24 weeks, FIB-4 index at 24 weeks had higher predictive power for HCC incidence throughout the follow-up period. Elevated FIB-4 index at 24 weeks in patients with CHB receiving NA therapy is a risk factor for developing HCC. The FIB-4 index is an excellent predictor of HCC development. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Intracellular levels of hepatitis B virus DNA and pregenomic RNA in peripheral blood mononuclear cells of chronically infected patients.

PubMed

Lu, L; Zhang, H-Y; Yueng, Y-H; Cheung, K-F; Luk, J M; Wang, F-S; Lau, G K K

2009-02-01

It remains uncertain whether hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and pregenomic RNA (pgRNA) can be detected in the serum or peripheral blood mononuclear cells (PBMC) of patients with chronic hepatitis B (CHB) infection. We examined HBV cccDNA and pgRNA in the serum and PBMC, and investigated the effect of lamivudine therapy on the viral loads in the PBMC of CHB patients. Paired serum and PBMC samples from 50 treatment-naïve CHB patients [25 hepatitis B e antigen (HBeAg) positive and 25 HBeAg negative] were quantified for total HBV DNA, cccDNA and pgRNA by real time polymerase chain reaction. HBV cccDNA and pgRNA were below the lower detection limit in all serum samples, and in 84% of PBMC. HBV DNA (r = 0.889, P < 0.001) and pgRNA (r = 0.696, P < 0.001) in PBMC correlated with the HBV DNA in serum. In the longitudinal study, 30 patients treated with lamivudine therapy for a median duration of 34 weeks (range 12-48 weeks) were examined. The median HBV DNA reduction in PBMC before and after treatment was 1.318 (range -0.471 to 3.846) log units, which was significantly lower than serum HBV DNA reduction [3.371 (range -0.883 to 9.454) log units, P < 0.05]. HBV cccDNA and pgRNA were undetectable in the serum of CHB patients. HBV viral loads in PBMC correlated with serum HBV DNA. Lamivudine therapy had less effect on the HBV viral loads in PBMC compared with the serum viral loads.

Challenges to the effective delivery of health care to people with chronic hepatitis B in Australia.

PubMed

Wallace, Jack; McNally, Stephen; Richmond, Jacqui; Hajarizadeh, Behzad; Pitts, Marian

2012-05-01

The complexity of the hepatitis B natural history and its prevalence in specific populations in Australia challenges the capacity of the health system to deliver health care effectively to affected people. This study explores the challenges in delivering health care to people with chronic hepatitis B (CHB) in Australia. We conducted a grounded theory based qualitative study in which data were gathered from 70 in-depth interviews with government program officers, clinicians and health and community workers across Australia, and four focus group discussions with 40 health and community workers from the communities most at risk of CHB. A systematic approach to screening populations at risk, including people born in countries with intermediate or high prevalence of CHB; consensus on clinical guidelines; development of a shared care framework for CHB involving general practitioners; and effective communication between patients and health professionals were identified as essential. Workforce development, particularly for primary health care professionals, and developing the knowledge and capacity of health professionals to communicate effectively with people with HBV were described as other major factors in reducing the barriers to CHB treatment in Australia. To improve the clinical management of people with CHB in Australia, the health system needs to encourage the screening of people at risk, improve access to clinical services, and the knowledge and communication skills of primary health care and community health service providers. This study supported developing a shared care model and related infrastructures including training programs, referral pathways and clinical guidelines.

Selected Cytokines Serve as Potential Biomarkers for Predicting Liver Inflammation and Fibrosis in Chronic Hepatitis B Patients With Normal to Mildly Elevated Aminotransferases.

PubMed

Deng, Yong-Qiong; Zhao, Hong; Ma, An-Lin; Zhou, Ji-Yuan; Xie, Shi-Bin; Zhang, Xu-Qing; Zhang, Da-Zhi; Xie, Qing; Zhang, Guo; Shang, Jia; Cheng, Jun; Zhao, Wei-Feng; Zou, Zhi-Qiang; Zhang, Ming-Xiang; Wang, Gui-Qiang

2015-11-01

Previous studies of small cohorts have implicated several circulating cytokines with progression of chronic hepatitis B (CHB). However, to date there have been no reliable biomarkers for assessing histological liver damage in CHB patients with normal or mildly elevated alanine aminotransferase (ALT). The aim of the present study was to investigate the association between circulating cytokines and histological liver damage in a large cohort. Also, this study was designed to assess the utility of circulating cytokines in diagnosing liver inflammation and fibrosis in CHB patients with ALT less than 2 times the upper limit of normal range (ULN). A total of 227 CHB patients were prospectively enrolled. All patients underwent liver biopsy and staging by Ishak system. Patients with at least moderate inflammation showed significantly higher levels of CXCL-11, CXCL-10, and interleukin (IL)-2 receptor (R) than patients with less than moderate inflammation (P < 0.001). Patients with significant fibrosis had higher levels of IL-8 (P = 0.027), transforming growth factor alpha (TGF-α) (P = 0.011), IL-2R (P = 0.002), and CXCL-11 (P = 0.032) than the group without significant fibrosis. In addition, 31.8% and 29.1% of 151 patients with ALT < 2 × ULN had at least moderate inflammation and significant fibrosis, respectively. Multivariate analysis demonstrated that CXCL-11 was independently associated with at least moderate inflammation, and TGF-α and IL-2R independently correlated with significant fibrosis in patients with ALT < 2 × ULN. Based on certain cytokines and clinical parameters, an inflammation-index and fib-index were developed, which showed areas under the receiver operating characteristics curve (AUROC) of 0.75 (95% CI 0.66-0.84) for at least moderate inflammation and 0.82 (95% CI 0.75-0.90) for significant fibrosis, correspondingly. Compared to existing scores, fib-index was significantly superior to aspartate aminotransferase (AST) to platelet ratio index (APRI) and FIB-4 score for significant fibrosis. In conclusion, CXCL-11 was independently associated with at least moderate inflammation, whereas IL-2R and TGF-α were independent indicators of significant fibrosis in both, total CHB patients and patients with normal or mildly elevated ALT. An IL-2R and TGF-α based score (fib-index) was superior to APRI and FIB-4 for the diagnosis of significant fibrosis in patients with normal or mildly elevated ALT.

Natural regression of fibrosis in chronic hepatitis B

PubMed Central

Ohkoshi, Shogo; Hirono, Haruka; Watanabe, Kazuhiko; Hasegawa, Katsuhiko; Kamimura, Kenya; Yano, Masahiko

2016-01-01

The fibrosis of liver cirrhosis was considered to be irreversible before the anti-viral drugs showed that it is reversible when they lead to continuous suppression of viral replication and inflammation. However, several reports previously showed that fibrosis of type B liver cirrhosis was almost completely absorbed after the natural remission of chronic inflammation. This phenomenon might not be limited to exceptional patients, but rather occur commonly, considering the dynamic clinical features of chronic hepatitis B (CHB), where inactive carrier stage normally follows aggravation of hepatitis and progression of fibrosis at the time of HBeAg seroconversion. Thus, fibrosis levels of CHB as a hepatocellular carcinoma (HCC)-surveillance marker, particularly those of the inactive stage, could be underestimated, because some of them might have been (pre)cirrhotic in the past and recovered with the natural regression of fibrosis. We argue that cirrhosis-induced HCC mechanisms, rather than direct action of viral genome, may be more common than generally considered in CHB patients. This may have some impact on reconsidering the surveillance rationale for HCC in CHB, from where advanced HCCs tended to be missed. In addition, a molecular marker to assess the cancer-prone characteristics of the liver will definitely be needed to resolve the issue. PMID:27350724

Disease-specific miR-34a as diagnostic marker of non-alcoholic steatohepatitis in a Chinese population

PubMed Central

Liu, Xiao-Lin; Pan, Qin; Zhang, Rui-Nan; Shen, Feng; Yan, Shi-Yan; Sun, Chao; Xu, Zheng-Jie; Chen, Yuan-Wen; Fan, Jian-Gao

2016-01-01

AIM To assess disease-specific circulating microRNAs (miRNAs) in non-alcoholic steatohepatitis (NASH) patients. METHODS A total of 111 biopsy-proven non-alcoholic fatty liver disease (NAFLD) or chronic hepatitis B (CHB) patients and healthy controls from mainland China were enrolled to measure their serum levels of miR-122, -125b, -146b, -16, -21, -192, -27b and -34a. The correlations between serum miRNAs and histological features of NAFLD were determined. The diagnostic value of miRNA in NASH and significant fibrosis was analyzed and compared with that of cytokeratin-18 (CK-18), fibrosis-4 (FIB-4), and aspartate aminotransferase to platelet ratio index (APRI), respectively. RESULTS Circulating miR-122, -16, -192 and -34a showed differential expression levels between NAFLD and CHB patients, and miR-34a had an approximately 2-fold increase in NAFLD samples compared with that of CHB samples (P < 0.01). Serum miR-122, -192 and -34a levels were correlated with steatosis (R = 0.302, 0.323 and 0.470, respectively, P < 0.05) and inflammatory activity (R = 0.445, 0.447 and 0.517, respectively, P < 0.01); only serum miR-16 levels were associated with fibrosis (R = 0.350, P < 0.05) in patients with NAFLD. The diagnostic value of miR-34a for NASH (area under the receiver operating characteristic, 0.811, 95%CI: 0.670-0.953) was superior to that of alanine aminotransferase, CK-18, FIB-4 and APRI in NAFLD, but miR-16 showed a limited performance in the diagnosis of significant fibrosis in NASH. CONCLUSION Circulating miR-34a may serve as a disease-specific noninvasive biomarker for the diagnosis of NASH. PMID:27956809

Changes of FibroScan, APRI, and FIB-4 in chronic hepatitis B patients with significant liver histological changes receiving 3-year entecavir therapy.

PubMed

Li, Qiang; Chen, Liang; Zhou, Yu

2018-05-01

Noninvasive fibrosis tests have been used widely for evaluation of liver fibrosis in patients with chronic hepatitis B (CHB). We aimed to investigate the influence of antiviral treatment on FibroScan, APRI, and FIB-4 in CHB patients with significant liver histological changes (SLHC) defined as inflammatory grade ≥ A2 and/or fibrosis stage ≥ F2. A total of 104 CHB patients with SLHC at the baseline were included. FibroScan, APRI, and FIB-4 values were compared before and after 3-year entecavir (ETV) treatment. Liver stiffness measurement values decreased significantly after 3-year ETV treatment in cirrhosis group (from 13.6 to 9.6 kPa, p = 0.018), significant fibrosis group (from 8.4 to 5.8 kPa, p = 0.001), and mild fibrosis group (from 5.5 to 4 kPa, p < 0.001). APRI decreased significantly after 3-year ETV treatment in patients with cirrhosis (from 0.80 to 0.25, p < 0.001), patients with significant fibrosis (from 0.54 to 0.24, p < 0.001), and those with mild fibrosis (from 0.35 to 0.23, p < 0.001). FIB-4 decreased significantly after 3-year ETV treatment in patients with cirrhosis (from 1.27 to 0.81, p = 0.007) and significant fibrosis (from 1.12 to 0.78, p < 0.001), while did not decrease significantly in patients with mild fibrosis (from 0.90 to 0.80, p = 0.389). FibroScan, APRI, and FIB-4 values decreased significantly after 3-year ETV treatment in CHB patients, which indicates that these noninvasive fibrosis tests might be useful for monitoring regression of liver fibrosis and assessing treatment efficacy during long-term ETV treatment.

Antiviral efficacy of entecavir in nucleos(t)ide-naïve patients of Black/African descent with chronic hepatitis B.

PubMed

Jeffers, L; Van Rensburg, C J; Banks, A; Schechter, M; Schmidt, S J; Hu, W; Llamoso, C; Parana, R

2014-01-01

This single-arm, open-label, descriptive study assessed the efficacy and safety of entecavir (ETV) in nucleos(t)ide-naïve Black/African American patients with chronic hepatitis B (CHB), a patient population underrepresented in ETV registration trials. Forty patients with HBeAg(+) or HBeAg(-) compensated CHB of self-described Black/African American race received ETV 0.5 mg daily for 52 weeks; 37 patients completed 52 weeks of treatment. At Week 48, 29/40 (72.5%, noncompleter = failure) patients achieved the primary endpoint of HBV DNA <50 IU/mL. Rates for HBeAg loss (11/22; 50%) and HBeAg seroconversion (9/22; 41%) were high, possibly due to the high HBV genotype A prevalence (70%). No patient experienced virological breakthrough. Samples for resistance testing were available in 6/8 patients with HBV DNA >50 IU/mL at Week 48 or last on-treatment visit. No ETV resistance was detected. The safety profile of ETV was consistent with that observed in ETV registration trials. This study shows that in Black/African American patients with CHB, ETV was well tolerated and demonstrated comparable antiviral efficacy to that observed in White and Asian patients in ETV Phase III studies. © 2013 John Wiley & Sons Ltd.

Psoriatic patients with chronic viral hepatitis do not have an increased risk of liver cirrhosis despite long-term methotrexate use: real-world data from a nationwide cohort study in Taiwan.

PubMed

Tang, Kuo-Tung; Chen, Yi-Ming; Chang, Shih-Ni; Lin, Ching-Heng; Chen, Der-Yuan

2018-05-09

Methotrexate (MTX) is commonly used in the treatment of patients with moderate to severe psoriasis. We conducted a nationwide population-based cohort study to investigate the impact of long-term MTX use on the risk of chronic viral hepatitis-related cirrhosis among psoriatic patients in Taiwan. This study obtained data from the National Health Insurance Research Database in Taiwan. We identified 2417 psoriatic patients with chronic hepatitis B (CHB) (370 MTX users and 2047 MTX non-users) and 1127 psoriatic patients with chronic hepatitis C (CHC) (174 MTX users and 953 MTX non-users) from January 1, 2000 to December 31, 2010. After a mean follow-up of more than 9 years since the diagnosis of chronic viral hepatitis, a total of 125 (5%) CHB patients and 120 (11%) CHC patients developed liver cirrhosis. A comparable proportion of MTX users and MTX non-users developed liver cirrhosis (4% vs. 5% in CHB patients and 11% and vs. 11% in CHC patients, both p < 0.05). There is possibly selection bias and medication nonadherence. Our real-world data show that long-term MTX use may not be associated with an increased risk of liver cirrhosis among psoriatic patients with chronic viral hepatitis. Copyright © 2018. Published by Elsevier Inc.

Hypophosphatemic osteomalacia and renal Fanconi syndrome induced by low-dose adefovir dipivoxil: a case report and literature review suggesting ethnic predisposition.

PubMed

Wu, C; Zhang, H; Qian, Y; Wang, L; Gu, X; Dai, Z

2013-08-01

Adefovir dipivoxil (ADV) is one of the commonly used antiviral agents in the treatment of chronic hepatitis B (CHB) infection. Safety of a daily dose of 10 mg ADV is advocated by the registration trials. We report a case of severe hypophosphatemic osteomalacia and renal Fanconi syndrome induced by low-dose ADV in a CHB-related cirrhosis patient, and discuss the case through a thorough review of other cases reported in the literature. A 48-yr-old Chinese man with CHB-related cirrhosis developed severe progressive generalized bone pain and muscle weakness after receiving ADV 10 mg daily for 54 months. The laboratory results showed severe hypophosphatemia and features of proximal renal tubule dysfunction. Imaging studies were consistent with osteomalacia. After discontinuation of ADV, his symptoms resolved, laboratory abnormalities normalized and imaging studies showed improvement. In addition to our case, 12 other patients have been reported to have developed hypophosphatemic osteomalacia induced by low-dose ADV. Most of the reported cases were of subjects of East-Asian ethnicity. After discontinuation or reduction of ADV, serum phosphate level increased and clinical symptoms significantly improved in all cases. Hypophosphatemic osteomalacia and renal Fanconi syndrome can be associated with low-dose ADV. Clinicians treating CHB patients with ADV 10 mg daily over long periods of time should be aware of this infrequent but serious complication. © 2013 John Wiley & Sons Ltd.

Economic Burden of Hepatitis B Virus-Related Diseases: Evidence From Iran

PubMed Central

Keshavarz, Khosro; Kebriaeezadeh, Abbas; Alavian, Seyed Moayed; Akbari Sari, Ali; Abedin Dorkoosh, Farid; Keshvari, Maryam; Malekhosseini, Seyed Ali; Nikeghbalian, Saman; Nikfar, Shekoufeh

2015-01-01

Background: Hepatitis B infection is still the main cause of chronic liver disease in Iran, which is associated with significant economic and social costs. Objectives: This study aimed to estimate the financial burden caused by CHB infection and its complications in Iran. Patients and Methods: Prevalence-based and bottom-up approaches were used to collect the data. Data on direct medical costs were extracted from outpatient medical records in a referral gastroenterology and hepatology research center, inpatient medical records in several major hospitals in Tehran and Shiraz in 2013, and the self-reports of specialists. Data on direct non-medical and indirect costs were collected based on the patients’ self-reports through face-to-face interviews performed in the mentioned centers. To calculate the indirect costs, friction cost approach was used. To calculate the total cost-of-illness in Iran, the total cost per patient at each stage of the disease was estimated and multiplied by the total number of patients. Results: The total annual cost for the activate population of CHB patients and for those receiving treatment at various disease stages were respectively 450 million and 226 million dollars, with 64% and 70% of which allocated to direct costs respectively, and 36% and 30% to indirect costs respectively. The total direct costs alone for each group were respectively 1.17% and 0.6% of the total health expenditure. Furthermore, the cost spent on drugs encompasses the largest proportion of the direct medical cost for all stages of the disease. Conclusions: According to the perspectives of payers, patients, and community, CHB infection can be considered as one of the diseases with a substantial economic burden; the disease, specifically in extreme cases, can be too expensive and costly for patients. Therefore, patients should be protected against more severe stages of the disease through proper treatment and early diagnosis. PMID:25977694

The impact of chronic hepatitis B on quality of life: a multinational study of utilities from infected and uninfected persons.

PubMed

Levy, Adrian R; Kowdley, Kris V; Iloeje, Uchenna; Tafesse, Eskinder; Mukherjee, Jayanti; Gish, Robert; Bzowej, Natalie; Briggs, Andrew H

2008-01-01

Chronic hepatitis B (CHB) is a condition that results in substantial morbidity and mortality worldwide because of progressive liver damage. Investigators undertaking economic evaluations of new therapeutic agents require estimates of health-related quality of life (HRQOL). Recently, evidence has begun to accumulate that differences in cultural backgrounds have a quantifiable impact on perceptions of health. The objective was to elicit utilities for six health states that occur after infection with the hepatitis B virus from infected and uninfected respondents living in jurisdictions with low and with high CHB endemicity. Standard gamble utilities were elicited from hepatitis patients and uninfected respondents using an interviewer-administered survey in the United States, Canada, United Kingdom, Spain, Hong Kong, and mainland China. Generalized linear models were used to the effect on utilities of current health, age and sex, jurisdiction and, for infected respondents, current disease state. The sample included 534 CHB-infected patients and 600 uninfected respondents. CHB and compensated cirrhosis had a moderate impact on HRQOL with utilities ranging from 0.68 to 0.80. Decompensated cirrhosis and hepatocellular carcinoma had a stronger impact with utilities ranging from 0.35 to 0.41. Significant variation was observed between countries, with both types of respondents in mainland China and Hong Kong reporting systematically lower utilities. Health states related to CHB infection have substantial reductions in HRQOL and the utilities reported in this study provide valuable information for comparing new treatment options. The observed intercountry differences suggest that economic evaluations may benefit from country-specific utility estimates. The extent that systematic intercountry differences in utilities hold true for other infectious and chronic diseases remains an open question and has considerable implications for the proper conduct and interpretation of economic evaluations.

Serum S100 calcium binding protein A4 improves the diagnostic accuracy of transient elastography for assessing liver fibrosis in hepatitis B.

PubMed

Yan, Li-Bo; Zhang, Qing-Bo; Zhu, Xia; He, Min; Tang, Hong

2018-02-01

The diagnostic performance of Fibroscan might be improved when combined with other serum fibrosis related markers. Previous study has demonstrated that S100A4 expression is associated with liver fibrosis in humans with hepatitis. This study aimed to clarify diagnostic accuracy of serum S100A4 levels for significant liver fibrosis in patients with chronic hepatitis B (CHB), and develop a combined algorithm of liver stiffness measurement (LSM) and S100A4 to predict significant liver fibrosis in CHB. One hundred and seventy-five CHB patients who had performed liver biopsy were consecutively included. We evaluated serum S100A4 levels, LSM values and other clinically-approved fibrosis scores. Serum S100A4 level was higher in CHB patients with significant fibrosis, compared to those without [199.58 (33.31-1971.96) vs. 107.15 (2.10-1038.94), P<0.001]. Using receiver-operating characteristic (ROC) analyses, the area under the curves (AUC), sensitivity, specificity and accuracy of S100A4 were found to be 0.749, 62.7%, 75.9% and 0.70 for significant fibrosis (≥Stage 2), respectively. Although not superior to LSM, these results were better than the fibrosis index based on the 4 factor (FIB-4) and the aspartate aminotransferase-to-platelet ratio index (APRI) for significant fibrosis detection. An algorithm consisting of S100A4 and LSM was derived. The AUC, sensitivity, specificity and accuracy of model based on serum S100A4 level and LSM were 0.866, 86.6%, 77.8% and 0.79 for significant fibrosis detection, superior to those based on LSM alone (0.834, 76.1%, 80.7% and 0.76, P=0.041). Serum S100A4 level was identified as a fibrosis marker of liver fibrosis in patients with CHB. Combining serum S100A4 with LSM improved the accuracy of transient elastography for hepatitis B significant fibrosis detection. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Value of gamma-glutamyltranspeptidase-to-platelet ratio in diagnosis of hepatic fibrosis in patients with chronic hepatitis B

PubMed Central

Hu, Yan-Chao; Liu, Hao; Liu, Xiao-Yan; Ma, Li-Na; Guan, Yu-Hua; Luo, Xia; Ding, Xiang-Chun

2017-01-01

AIM To investigate the value of the gamma-glutamyltraspeptidase (GGT)-to-platelet (PLT) ratio (GPR) in the diagnosis of hepatic fibrosis in patients with chronic hepatitis B (CHB). METHODS We included 390 untreated CHB patients in this study. The GPR, aspartate aminotransferase (AST)-to-PLT ratio index (APRI), and fibrosis-4 (FIB-4) of all patients were analysed to determine if these parameter were correlated with age, gender, medical history, liver function [total bilirubin (TBil), alanine aminotransferase (ALT), and AST], GGT, PLT count, or hepatic fibrosis stage. The GPR, APRI, and FIB-4, as well as the combination of the GPR and APRI or the GPR and FIB-4 were assessed in different cirrhosis stages using receiver operating characteristic (ROC) curve analysis to evaluate their value in diagnosing hepatic fibrosis in CHB patients. RESULTS The GPR, APRI, and FIB-4 were not correlated with CHB patients’ age, gender, or disease duration (P > 0.05), but all of these parameters were positively correlated with serum ALT, AST, GGT, and PLT count (P < 0.01). Additionally, the GPR, APRI, and FIB-4 were positively correlated with hepatic fibrosis (P < 0.01); the areas under the ROC curve for the GPR in F1, F2, F3, and F4 stages were 0.723, 0.741, 0.826, and 0.833, respectively, which were significantly higher than the respective values for the FIB-4 and APRI (F1: 0.581, 0.612; F2: 0.706, 0.711; F3: 0.73, 0.751; and F4: 0.799, 0.778). The respective diagnostic cut-off points for each stage were 0.402, 0.448, 0.548, and 0.833, respectively. The diagnostic sensitivity and specificity were, respectively, 88.8% and 87.5% in F1, 72.7% and 89.7% in F2, 81.3% and 98.6% in F3, and 80% and 97.4% in F4 when the GPR and APRI were connected in parallel; 86.6% and 90.2%, 78.4% and 96%, 78.6% and 97.4%, and 73.2% and 97.9%, respectively, when the GPR and APRI were connected in series; 80.2% and 89%, 65% and 89%, 70.3% and 98.5%, and 78.8% and 96.8%, respectively, when the GPR and FIB-4 were connected in parallel; and 83.6% and 87.9%, 76.8% and 96.6%, 72.7% and 98%, and 74.4% and 97.7%, respectively, when the GPR and FIB-4 were connected in series. CONCLUSION The GPR, as a serum diagnostic index of liver fibrosis, is more accurate, sensitive, and easy to use than the FIB-4 and APRI, and the GPR can significantly improve the sensitivity and specificity of hepatic fibrosis diagnosis in CHB when combined with the FIB-4 or APRI. PMID:29151696

Factors Associated With Persistent Increase in Level of Alanine Aminotransferase in Patients With Chronic Hepatitis B Receiving Oral Antiviral Therapy.

PubMed

Jacobson, Ira M; Washington, Mary K; Buti, Maria; Thompson, Alexander; Afdhal, Nezam; Flisiak, Robert; Akarca, Ulus Salih; Tchernev, Konstantin G; Flaherty, John F; Aguilar Schall, Raul; Myers, Robert P; Subramanian, G Mani; McHutchison, John G; Younossi, Zobair; Marcellin, Patrick; Patel, Keyur

2017-07-01

Despite complete suppression of viral DNA with antiviral agents, in some patients with chronic hepatitis B (CHB), serum levels of alanine aminotransferase (ALT) do not normalize. We investigated factors associated with persistent increases in ALT level in patients with CHB given long-term tenofovir disoproxil fumarate. We analyzed data from 471 hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with CHB participating in 2 phase 3 trials. We identified patients with an increased level of ALT (above the upper limit of normal range) after 5 years (240 weeks) of tenofovir disoproxil fumarate therapy. We analyzed findings from liver biopsy specimens collected from 467 patients (99%) at baseline and 339 patients (72%) at year 5 of treatment; biopsy specimens were evaluated by an independent pathologist. We performed stepwise, forward, multivariate regression analyses of specified baseline characteristics and on-treatment response parameters to identify factors associated with persistent increases in ALT level. Of the 471 patients, 87 (18%) still had an increased ALT level at year 5 of treatment. Factors associated significantly with a persistent increase in ALT level were a steatosis score of 5% or greater (grade 1 or more) at baseline (odds ratio [OR], 2.236; 95% confidence interval [CI], 1.031-4.852; P = .042) and at year 5 (OR, 3.392; 95% CI, 1.560 ≥ 7.375; P = .002), HBeAg seropositivity at baseline (OR, 3.297; 95% CI, 1.653-6.576; P < .001), and age 40 years or older (OR, 2.099; 95% CI, 1.014-4.342; P = .046). Of the 42 HBeAg-positive patients with steatosis at baseline, 21 (50%) had an increased ALT level at year 5 of treatment. Patients with persistent increases in ALT level were more likely to have an increase in steatosis at year 5 than those with a normal ALT level. HBeAg seropositivity and hepatic steatosis contribute to persistent increases in ALT level in patients with CHB receiving suppressive antiviral treatment. ClinicalTrials.gov registration numbers: NCT00117676 and NCT00116805. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Baseline quantitative hepatitis B core antibody titre alone strongly predicts HBeAg seroconversion across chronic hepatitis B patients treated with peginterferon or nucleos(t)ide analogues

PubMed Central

Fan, Rong; Sun, Jian; Yuan, Quan; Xie, Qing; Bai, Xuefan; Ning, Qin; Cheng, Jun; Yu, Yanyan; Niu, Junqi; Shi, Guangfeng; Wang, Hao; Tan, Deming; Wan, Mobin; Chen, Shijun; Xu, Min; Chen, Xinyue; Tang, Hong; Sheng, Jifang; Lu, Fengmin; Jia, Jidong; Zhuang, Hui; Xia, Ningshao; Hou, Jinlin

2016-01-01

Objective The investigation regarding the clinical significance of quantitative hepatitis B core antibody (anti-HBc) during chronic hepatitis B (CHB) treatment is limited. The aim of this study was to determine the performance of anti-HBc as a predictor for hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive CHB patients treated with peginterferon (Peg-IFN) or nucleos(t)ide analogues (NUCs), respectively. Design This was a retrospective cohort study consisting of 231 and 560 patients enrolled in two phase IV, multicentre, randomised, controlled trials treated with Peg-IFN or NUC-based therapy for up to 2 years, respectively. Quantitative anti-HBc evaluation was conducted for all the available samples in the two trials by using a newly developed double-sandwich anti-HBc immunoassay. Results At the end of trials, 99 (42.9%) and 137 (24.5%) patients achieved HBeAg seroconversion in the Peg-IFN and NUC cohorts, respectively. We defined 4.4 log10 IU/mL, with a maximum sum of sensitivity and specificity, as the optimal cut-off value of baseline anti-HBc level to predict HBeAg seroconversion for both Peg-IFN and NUC. Patients with baseline anti-HBc ≥4.4 log10 IU/mL and baseline HBV DNA <9 log10 copies/mL had 65.8% (50/76) and 37.1% (52/140) rates of HBeAg seroconversion in the Peg-IFN and NUC cohorts, respectively. In pooled analysis, other than treatment strategy, the baseline anti-HBc level was the best independent predictor for HBeAg seroconversion (OR 2.178; 95% CI 1.577 to 3.009; p<0.001). Conclusions Baseline anti-HBc titre is a useful predictor of Peg-IFN and NUC therapy efficacy in HBeAg-positive CHB patients, which could be used for optimising the antiviral therapy of CHB. PMID:25586058

Decreased frequency and function of circulating plasmocytoid dendritic cells (pDC) in hepatitis B virus infected humans.

PubMed

Duan, Xue-Zhang; Wang, Min; Li, Han-Wei; Zhuang, Hui; Xu, Dongping; Wang, Fu-Sheng

2004-11-01

The Type 2 precursor plasmacytoid dendritic cells (pDC) represent the most important cell type in antiviral innate immunity. To understand the function of pDC during hepatitis B virus infection, the frequency and function of circulating pDC were analyzed by flow cytometric analysis, and IFN-alpha secretion of total PBMCs was determined by ELISA assay in 25 healthy subjects and 116 patients at various stages of chronic hepatitis B virus infection (CHB). The number of circulating pDC was found to be significantly lower in patients with CHB and associated liver cirrhosis (LC). The ability of PBMCs to secrete IFN-alpha also decreased significantly. There was a corresponding decrease of circulating NK cells and CD8+ T cells. We observed that lamuvidine antiviral therapy restored the number of circulating pDC and there was a reversal of pDC frequency with the control of HBV replication in chronic HBV patients, indicating these subjects are unlikely to be totally immunocompromised. The decrease of pDC was found to be related to nosocomial infections in LC patients. Our results suggest that CHB patients probably have a quantitative and qualitative impairment of circulating pDC or NK cells, which may be associated with HBV persistent infection as well as the nosocomial infections that arise in LC patients.

Care of the suicidal pediatric patient in the ED: a case study.

PubMed

Schmid, Alexis M; Truog, Amy W; Damian, Frances J

2011-09-01

The suicide rate among children and adolescents has increased worldwide over the past few decades, and many who attempt suicide are first seen at EDs. At Childrens Hospital Boston (CHB), an algorithm-the Risk of Suicidality Clinical Practice Algorithm-has been developed to ensure evidence-based care supported by best practice guidelines. The authors of this article provide an overview of pediatric suicide and suicide attempts; describe screening, assessment, and interventions used at CHB; and discuss the nursing implications. An illustrative case study is also provided. algorithm, Asperger's syndrome, attempted suicide, bullying, emergency, emergency department, patient safety, pediatrics, pediatric suicide, suicide, suicide screening, triage.

No histologic evidence of foetal cardiotoxicity following exposure to maternal hydroxychloroquine.

PubMed

Friedman, Deborah; Lovig, Leif; Halushka, Marc; Clancy, Robert M; Izmirly, Peter M; Buyon, Jill P

2017-01-01

It is currently recommended that hydroxychloroquine (HCQ) be maintained during pregnancy in patients with systemic lupus erythematosus. Recent data suggest that this Toll-like receptor inhibitor may also reduce the recurrence rate of anti-SSA/Ro associated congenital heart block (CHB). This case report describes a unique situation in which a CHB-afflicted, HCQ-exposed pregnancy was electively terminated. The heart did not reveal any characteristic features of cardiotoxicity, providing further evidence supporting the safety of foetal exposure to HCQ.

A meta-analysis of the association between gestational diabetes mellitus and chronic hepatitis B infection during pregnancy

PubMed Central

2014-01-01

Background Chronic hepatitis B (CHB) infection during pregnancy is associated with insulin resistance. A meta-analytic technique was used to quantify the evidence of an association between CHB infection and the risk of gestational diabetes (GDM) among pregnant women. Methods We searched PubMed for studies up to September 5th 2013. Additional studies were obtained from other sources. We selected studies using a cohort-study design and reported a quantitative association between CHB infection during pregnancy and risk of GDM. A total of 280 articles were identified, of which fourteen publications involving 439,514 subjects met the inclusion criteria. A sequential algorithm was used to reduce between-study heterogeneity, and further meta-analysis was conducted using a random-effects model. Results Ten out of the fourteen studies were highly homogeneous, indicating an association of 1.11 [the adjusted odds ratio, 95% confidence interval 0.96 - 1.28] between CHB infection during pregnancy and the risk of developing GDM. The heterogeneity of the additional four studies may be due to selection bias or possible aetiological differences for special subsets of pregnant women. Conclusions These results indicate that CHB infection during pregnancy is not associated with an increased risk of developing GDM among pregnant women except those from Iran. PMID:24618120

Normal on-treatment ALT during antiviral treatment is associated with a lower risk of hepatic events in patients with chronic hepatitis B.

PubMed

Wong, Grace Lai-Hung; Chan, Henry Lik-Yuen; Tse, Yee-Kit; Yip, Terry Cheuk-Fung; Lam, Kelvin Long-Yan; Lui, Grace Chung-Yan; Wong, Vincent Wai-Sun

2018-06-18

Recent studies reveal that the rate of normal on-treatment alanine aminotransferase (ALT) appears different for different nucleos(t)ide analogues (NAs); yet its clinical significance is unclear. We aimed to evaluate the impact of normal on-treatment ALT during antiviral treatment with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB). A territory-wide cohort of patients with CHB who received ETV and/or TDF in 2005-2016 was identified. Serial on-treatment ALT levels were collected and analyzed. Normal on-treatment ALT (ALT-N) was defined as ALT <30 U/L in males and <19 U/L in females. The primary and secondary outcomes were composite hepatic events (including hepatocellular carcinoma) based on diagnostic codes. Patients with hepatic events before or during the first year of antiviral treatment or follow-up <1 year were excluded. A total of 21,182 patients with CHB (10,437 with and 10,745 without ALT-N at 12 months after antiviral treatment) were identified and followed for 4.0 ± 1.7 years. Patients with and without ALT-N differed in baseline ALT (58 vs. 61 U/L), hepatitis B virus DNA (4.9 vs. 5.1 log10 IU/ml) and cirrhosis status (8.8% vs. 10.5%). A total of 627 (3.0%) patients developed composite hepatic events. Compared to no ALT-N, ALT-N at 3, 6, 9 and 12 months reduced the risk of hepatic events, after adjustment for baseline ALT and other important covariates, with adjusted hazard ratios (95% CI) of 0.61 (0.49-0.77), 0.55 (0.45-0.67), 0.54 (0.44-0.65) and 0.51 (0.42-0.61) respectively (all p <0.001). The cumulative incidence (95% CI) of composite hepatic events at six years was 3.51% (3.06%-4.02%) in ALT-N and 5.70% (5.15%-6.32%) in the no ALT-N group (p <0.001). Normal on-treatment ALT is associated with a lower risk of hepatic events in patients with CHB receiving NA treatment, translating into improved clinical outcomes in these patients. We investigated 21,182 patients with chronic hepatitis B receiving antiviral treatment. Alanine aminotransferase is a laboratory marker of liver function, with raised levels indicating liver dysfunction and in severe cases hepatitis. Normal on-treatment alanine aminotransferase during the first year of treatment in patients with CHB is associated with a lower risk of hepatic events. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

[Value of non-invasive models of liver fibrosis in judgment of treatment timing in chronic hepatitis B patients with ALT < 2×upper limit of normal].

PubMed

Zhou, Q Q; Hu, Y B; Zhou, K; Zhang, W W; Li, M H; Dong, P; Di, J G; Hong, L; Du, Q W; Xie, Y; Sun, Q F

2016-09-20

Objective: To investigate the value of non-invasive liver fibrosis models, FIB-4, S index, aspartate aminotransferase to platelet ratio index(APRI), globulin-platelet(GP)model, aspartate aminotransferase/platelet/gamma-glutamyl transpeptidase/alpha-fetoprotein(APGA), and platelet/age/phosphatase/alpha-fetoprotein/aspartate aminotransferase(PAPAS), in the diagnosis of marked liver fibrosis in chronic hepatitis B(CHB)patients with ALT < 2×upper limit of normal(ULN), as well as treatment timing for this population. Methods: A total of 389 CHB patients with ALT < 2×ULN who were admitted to Beijing Ditan Hospital and whose treatment timing was difficult to judge were enrolled. Transdermal liver biopsy was performed to obtain pathological results, and routine serological tests were performed, including routine blood test, serum biochemical parameters, hepatitis B virus(HBV)markers, and HBV DNA. According to liver pathology, the patients were divided into non-marked liver fibrosis group(S < 2)with 324 patients and marked liver fibrosis group(S≥2)with 65 patients. The non-invasive models for predicting liver fibrosis was established with reference to original articles. SPSS 19.0 software was used for statistical analysis, and the receiver operating characteristic(ROC)curve was used to compare the value of different non-invasive models in predicting marked liver fibrosis in this population. Results: All the non-invasive models had a certain diagnostic value for liver fibrosis degree in these patients, and the areas under the ROC curve for APRI, FIB-4, APGA, S index, PAPAS, and GP model were 0.718, 0.691, 0.758, 0.729, 0.673, and 0.691, respectively. APGA had the largest area under the ROC curve(0.758, 95% CI 0.673-0.844), and gamma-glutamyl transpeptidase was significantly positively correlated with liver fibrosis degree. Conclusion: The non-invasive models of liver fibrosis can identify marked liver fibrosis in CHB patients with ALT < 2×ULN in whom it is difficult to judge treatment timing and help to determine treatment timing for them. APGA model has the highest value and can reduce the need for liver biopsy to the certain degree.

Effect of S267F variant of NTCP on the patients with chronic hepatitis B.

PubMed

Lee, Hye Won; Park, Hye Jung; Jin, Bora; Dezhbord, Mehrangiz; Kim, Do Young; Han, Kwang-Hyub; Ryu, Wang-Shick; Kim, Seungtaek; Ahn, Sang Hoon

2017-12-15

Sodium taurocholate cotransporting polypeptide (NTCP) was identified as an entry receptor for hepatitis B virus (HBV) infection. The substitution of serine at position 267 of NTCP with phenylalanine (S267F) is an Asian-specific variation that hampers HBV entry in vitro. In this study, we aimed to evaluate the prevalence of S267F polymorphism in Korean patients with chronic hepatitis B (CHB) and its association with disease progression and potential viral evolution in the preS1 domain of HBV. We found that the frequency of the S267F variant of NTCP in CHB patients and controls was 2.7% and 5.7% (P = 0.031), respectively, and that those who had S267F variant were less susceptible to chronic HBV infection. The frequency of the S267F variant in CHB, cirrhosis and hepatocellular carcinoma (HCC) patients was 3.3%, 0.9%, and 3.5%, respectively. Thus, the S267F variant correlated significantly with a lower risk for cirrhosis (P = 0.036). Sequencing preS1 domain of HBV from the patients who had S267F variant revealed no significant sequence change compared to the wild type. In conclusion, the S267F variant of NTCP is clinically associated with a lower risk of chronic HBV infection and cirrhosis development, which implicates suppressing HBV entry could reduce the disease burden.

Serum dihydroxyacetone kinase peptide m/z 520.3 as predictor of disease severity in patients with compensated chronic hepatitis B.

PubMed

Xu, Ming-Yi; Jia, Xiao-Fang; Qu, Ying; Zheng, Rui-Dan; Yuan, Zheng-Hong; Weng, Hong-Lei; Dooley, Steven; Wang, Xing-Peng; Zhang, Li-Jun; Lu, Lun-Gen

2013-09-27

Due to known limitations of liver biopsy, reliable non-invasive serum biomarkers for chronic liver diseases are needed. We performed serum peptidomics for such investigation in compensated chronic hepatitis B (CHB) patients. Liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) was used to identify differentially expressed peptides in sera from 40 CHB patients (20 with S0G0-S1G1 and 20 with S3G3-S4G4). Ion pair quantification from differentially expressed peptides in a validation set of sera from 86 CHB patients was done with multiple reaction monitoring (MRM). 21 differentially represented peptide peaks were found through LC-MS/MS. Ion pairs generated from eleven of these peptides (m/z < 800) were quantified by MRM. Summed peak area ratios of 6 ion pairs from peptide m/z 520.3 (176.1, 353.7, 459.8, 503.3, 351.3, 593.1), which was identified as dihydroxyacetone kinase (DAK) fragment, decreased from mild to advanced stages of fibrosis or inflammation. Area Under Receiver Operating Characteristic Curves (AUROCs) of five ion models discriminating fibrosis degrees were 0.871 ~ 0.915 (S2-4 versus S0-1) and 0.804 ~ 0.924 (S3-4 versus S0-2). AUROCs discriminating inflammation grades were 0.840 ~ 0.902 (G2-4 versus G0-1) and 0.787 ~ 0.888 (G3-4 versus G0-2). The diagnostic power of these models provides improved sensitivity and specificity for predicting disease progression as compared to aspartate aminotransferase to platelet ratio index (APRI), FIB-4, Forn's index and serum DAK protein. The peptide fragment (m/z 520.3) of DAK is a promising biomarker to guide timing of antiviral treatment and to avoid liver biopsy in compensated CHB patients.

An OX40/OX40L interaction directs successful immunity to hepatitis B virus

PubMed Central

Publicover, Jean; Gaggar, Anuj; Jespersen, Jillian M.; Halac, Ugur; Johnson, Audra J.; Goodsell, Amanda; Avanesyan, Lia; Nishimura, Stephen L.; Holdorf, Meghan; Mansfield, Keith G.; Judge, Joyce Bousquet; Koshti, Arya; Croft, Michael; Wakil, Adil E.; Rosenthal, Philip; Pai, Eric; Cooper, Stewart; Baron, Jody L.

2018-01-01

Depending on age of acquisition, hepatitis B virus (HBV) can induce a cell-mediated immune response that results in either cure or progressive liver injury. In adult-acquired infection, HBV antigens are usually cleared, whereas in infancy-acquired infection, they persist. Individuals infected during infancy therefore represent the majority of patients chronically infected with HBV (CHB). A therapy that can promote viral antigen clearance in most CHB patients has not been developed and would represent a major health care advance and cost mitigator. Using an age-dependent mouse model of HBV clearance and persistence in conjunction with human blood and liver tissue, we studied mechanisms of viral clearance to identify new therapeutic targets. We demonstrate that age-dependent expression of the costimulatory molecule OX40 ligand (OX40L) by hepatic innate immune cells is pivotal in determining HBV immunity, and that treatment with OX40 agonists leads to improved HBV antigen clearance in young mice, as well as increased strength of T cell responses in young mice and adult mice that were exposed to HBV when they were young and developed a CHB serological profile. Similarly, in humans, we show that hepatic OX40L transcript expression is age-dependent and that increased OX40 expression on peripheral CD4+ T cells in adults is associated with HBV clearance. These findings provide new mechanistic understanding of the immune pathways and cells necessary for HBV immunity and identify potential therapeutic targets for resolving CHB. PMID:29563320

Complement C4a inhibits the secretion of hepatitis B virus screened by surface-enhanced laser desorption ionization time-flight mass spectrometry-based ProteinChip analysis.

PubMed

Song, Ya-Nan; Zhang, Gui-Biao; Hu, Xue-Qing; Lu, Yi-Yu; Zhao, Yu; Yang, Yang; Yang, Yi-Fu; Zhang, Yong-Yu; Hu, Yi-Yang; Su, Shi-Bing

2015-12-01

Chronic hepatitis B (CHB) is a kind of chronic liver disease caused by persistent hepatitis B virus (HBV) infection. The study aims to seek the factors of host resistance to HBV and investigate their roles. Protein profiles of 58 healthy controls and 121 CHB patients were obtained by SELDI-TOF/MS. Predicted protein was validated by ELISA. Protein expression was evaluated by Western blot in the persistently HBV expressing cell line HepG2.2.15 and non-HBV expressing cell line HepG2. The level of HBV DNA was subsequently detected by quantitative real-time PCR in HepG2.2.15 cells with complement C4a treatment. Significantly altered protein peaks were found through statistical analysis, and m/z 4300 was predicted by databases and successfully matched with the fragment of complement C4a. According to ELISA, serum complement C4a was found to be significantly lower in CHB patients compared with healthy controls (p < 0.001) and the area under receiver operating characteristics curve is 0.78. Furthermore, complement C4a showed lower expression in HepG2.2.5 cells and the secretion of HBV DNA was inhibited by complement C4a. The present study implied the important role of complement C4a in inhibiting the HBV DNA secretion in CHB. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Serum proteomic MRM identify peptide ions of transferrin as new fibrosis markers in chronic hepatitis B.

PubMed

Xu, Ming-Yi; Qu, Ying; Jia, Xiao-Fang; Wang, Mei-Ling; Liu, Heng; Wang, Xing-Peng; Zhang, Li-Jun; Lu, Lun-Gen

2013-09-01

Because of the limitations of liver biopsy, reliable non-invasive serum biomarkers of liver fibrosis are needed. The aim of this study was to identify such markers by the use of serum proteomics in chronic hepatitis B (CHB). Two-dimensional gel electrophoresis (2-DE) was used to identify differentially expressed protein spots in sera from 40 CHB patients [20 with mild fibrosis (S0-S1) and 20 with severe fibrosis (S3-S4)]. Mass spectrometry (MS) based multiple reaction monitoring (MRM) was used to quantify peptide ions of differential protein spots in another set of sera from 86 CHB patients with different liver fibrosis (S0-S4). Seven differentially expressed protein spots were found by 2-DE. Fourteen peptide ions of seven target protein spots were quantified by MS-based MRM. Summed peak areas ratio (SPAR) values of peptide ions from protein spot 1, 4 and 8, identified as apo serum transferrin, complement component C3c and transferrin, were significantly different from non-fibrosis (S0) to fibrosis stage 4. AUROCs of models established by peptide ions (protein spot 1, 4, 8) and model consisting of a combination of all ions were 0.848∼0.966 (S2-S4 versus S0-S1) and 0.785∼0.875 (S3-S4 versus S0-S2). Only the peptide ions model of transferrin had better sensitivity and specificity for predicting fibrosis stages than did aspartate aminotransferase-to-platelet ratio index (APRI), FIB-4 and Forn's index. Serum peptide ions of transferrin, detected by proteomic MRM, are new and promising biomarkers for staging liver fibrosis in CHB patients. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Hepatitis delta virus infection in a large cohort of chronic hepatitis B patients in Ethiopia.

PubMed

Aberra, Hanna; Gordien, Emmanuel; Desalegn, Hailemichael; Berhe, Nega; Medhin, Girmay; Mekasha, Bitsatab; Gundersen, Svein G; Gerber, Athenaïs; Stene-Johansen, Kathrine; Øverbø, Joakim; Johannessen, Asgeir

2018-06-01

Hepatitis D virus (HDV) infection is associated with a more severe outcome in patients with chronic hepatitis B (CHB); however, little is known about the presence of HDV in sub-Saharan Africa. We aimed to determine the prevalence of HDV infection, as well as its clinical, biological and virological characteristics, in a large CHB cohort in Ethiopia. In total, 1267 HIV-negative CHB patients at St. Paul's Hospital Millennium Medical College in Addis Ababa were screened for anti-HDV antibodies using ELISA assays. Confirmed positive samples were further tested for HDV RNA using a consensus commercial real-time RT-PCR assay. HDV genotypes were also determined for RNA-positive samples by nucleotide sequencing followed by phylogenetic analyses. Demographical, clinical and biological data from patients were recorded and compared based on HDV RNA results. Most patients (n = 748, 59.0%) were men, and the median age was 31 years (interquartile range 26-40). Anti-HDV antibodies were detected in 19 individuals (1.5%), 12 of whom were HDV RNA-positive with a viral load ranging from <2 to >8 log 10 IU/mL. All strains were genotype 1. HDV RNA-positive patients were more likely to have significant liver fibrosis (63.6% vs 24.7%, P = .007) and cirrhosis (45.5% vs 16.4%, P = .024). HDV infection is rare in Ethiopia but is associated with more advanced liver fibrosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Oedema of gallbladder wall: correlation with chronic hepatitis B on MR imaging.

PubMed

Shu, Jian; Zhao, Jian Nong; Han, Fu Gang; Tang, Guang Cai; Luo, Yin Deng; Chen, Xin; Luo, Li

2013-10-01

The aim of this study was to characterise gallbladder wall oedema and correlate it with chronic hepatitis B (CHB) on magnetic resonance (MR) imaging. Sixty-seven patients who were clinically and histologically diagnosed with CHB and 18 healthy individuals without any history of liver disease underwent abdominal MR imaging. Hepatic inflammation (grade 0-4) and fibrosis (stage 0-4) for patients were assessed histologically. Gallbladder wall oedema was noted. Twelve patients showed gallbladder wall oedema on MR imaging, including six with grade 3 and six with grade 4 disease. There was a statistically significant difference for the presence of gallbladder wall oedema among groups with grade 0-4 (p=0.000), but not between groups with grades 3 and 4 (p=0.729). Gallbladder wall oedema was related to moderate-severe inflammatory activity (p<0.05), alanine transaminase (ALT) (p=0.012) and aspartate aminotransferase (AST) (p=0.027) levels but not to fibrosis or other laboratory data, including serum quantitative DNA for hepatitis B virus (HBV), with the p=0.105-0.846. Sensitivity and specificity for the diagnosis of hepatic moderate-severe inflammation using gallbladder wall oedema were 33.33% and 100%, respectively. Gallbladder wall oedema for patients with CHB can be specifically demonstrated on MR imaging and is correlated with hepatic moderate-severe inflammatory activity, elevated ALT and AST levels but not with fibrosis or other laboratory data, including viremia.

Disease burden of chronic hepatitis B among immigrants in Canada.

PubMed

Wong, William W L; Woo, Gloria; Heathcote, E Jenny; Krahn, Murray

2013-03-01

The prevalence of chronic hepatitis B (CHB) infection among immigrants to North America ranges from 2% to 15%, 40% of whom develop advanced liver disease. Screening for hepatitis B surface antigen is not recommended for immigrants. To estimate the disease burden of CHB among immigrants in Canada using Markov cohort models comparing a cohort of immigrants with CHB versus a control cohort of immigrants without CHB. Markov cohort models were used to estimate life years, quality-adjusted life years and lifetime direct medical costs (adjusted to 2008 Canadian dollars) for a cohort of immigrants with CHB living in Canada in 2006, and an age-matched control cohort of immigrants without CHB living in Canada in 2006. Parameter values were derived from the published literature. At the baseline estimate, the model suggested that the cohort of immigrants with CHB lost an average of 4.6 life years (corresponding to 1.5 quality-adjusted life years), had an increased average of $24,249 for lifetime direct medical costs, and had a higher lifetime risk for decompensated cirrhosis (12%), hepatocellular carcinoma (16%) and need for liver transplant (5%) when compared with the control cohort. Results of the present study showed that the socio-economic burden of CHB among immigrants living in Canada is substantial. Governments and health systems need to develop policies that promote early recognition of CHB and raise public awareness regarding hepatitis B to extend the lives of infected immigrants.

The Gamma-Glutamyl-Transpeptidase to Platelet Ratio Does not Show Advantages than APRI and Fib-4 in Diagnosing Significant Fibrosis and Cirrhosis in Patients With Chronic Hepatitis B: A Retrospective Cohort Study in China.

PubMed

Li, Qiang; Song, Jie; Huang, Yuxian; Li, Xinyan; Zhuo, Qibin; Li, Weixia; Chen, Chong; Lu, Chuan; Qi, Xun; Chen, Liang

2016-04-01

The gamma-glutamyl-transpeptidase to platelet ratio (GPR) is a new liver fibrosis model, which is reported to be more accurate than aspartate transaminase (AST) to platelet ratio index (APRI) and fibrosis index based on the four factors (Fib-4) for diagnosing significant fibrosis and cirrhosis in patients with chronic hepatitis B (CHB) in West Africa. The aim of this study is to assess the diagnostic accuracy of GPR for significant fibrosis and cirrhosis in Chinese CHB patients, and explore whether GPR deserves to be popularized in China. A total of 372 CHB patients who underwent liver biopsies and routine laboratory tests were retrospectively studied. The Scheuer scoring system was adopted as the pathological standard of liver fibrosis. Using liver histology as a gold standard, the diagnostic accuracies of GPR, APRI, and Fib-4 for significant fibrosis and cirrhosis are evaluated and compared by the receiver operating characteristic (ROC) curves and the area under the ROC curves (AUROCs). Of these 372 patients, 176 (47.3%), 129 (34.7%), and 72 (19.4%) were classified as having significant fibrosis (≥ S2), severe fibrosis (≥ S3), and cirrhosis (S4), respectively. The AUROCs of GPR for significant fibrosis (0.72 vs. 0.78; P = 0.01), severe fibrosis (0.75 vs. 0.80; P = 0.04), and cirrhosis (0.78 vs. 0.83; P = 0.02) were lower than those of APRI. The AUROCs of GPR and Fib-4 for diagnosing significant fibrosis (0.72 vs. 0.70; P = 0.29), severe fibrosis (0.75 vs. 0.73; P = 0.33), and cirrhosis (0.78 vs. 0.75; P = 0.38) were comparable. GPR is a new serum diagnostic model for liver fibrosis and cirrhosis, but does not show advantages than APRI and Fib-4 in identifying significant fibrosis, severe fibrosis, and cirrhosis in CHB patients in China.

Longitudinal profiles of highly sensitive hepatitis B surface antigen levels: re-evaluation of HBsAg seroclearance.

PubMed

Seto, Wai-Kay; Tanaka, Yasuhito; Wong, Danny K-H; Shinkai, Noboru; Cheung, Ka-Shing; Liu, Kevin S-H; Fung, James; Lai, Ching-Lung; Yuen, Man-Fung

2016-05-01

Serologic profiles after hepatitis B surface antigen (HBsAg) seroclearance in chronic hepatitis B (CHB) have not been well-studied. We employed a highly sensitive HBsAg (hs-HBsAg) assay (lower detection limit 0.5 mIU/ml), 100 times more sensitive than conventional HBsAg measurements. CHB patients achieving HBsAg seroclearance defined by conventional assays were followed up for serum hs-HBsAg, HBV DNA and antibody to HBsAg (anti-HBs) levels at 0 months, 6-12 months and 3-5 years after HBsAg seroclearance. Factors associated with hs-HBsAg detectability were determined. One hundred and nine patients were recruited; 94 (86.2%) were followed up to years 3-5; and 25 patients (22.9%) were on nucleoside analogue therapy for a median duration of 6.0 (range 1.5-12.7) years before HBsAg seroclearance. Detectable hs-HBsAg was noted in 88 (80.7%), 60 (55.0%) and 20 (21.3%) patients at 0 months, 6-12 months and 3-5 years respectively. At years 3-5, genotype B patients, when compared to genotype C patients, had a higher anti-HBs positive rate (63.2% and 41.1% respectively, P = 0.036). Serum anti-HBs positivity, when compared to persistent anti-HBs negativity, was associated with a lower rate of hs-HBsAg detection (7.4% and 40% respectively, P < 0.001). Multivariate analysis showed anti-HBs negativity at years 3-5 to be independently associated with persistently positive hs-HBsAg (P = 0.007, odds ratio 7.1, 95% confidence interval 1.7-29.3). Serum hs-HBsAg could detect HBsAg presence in a substantial proportion of CHB after HBsAg seroclearance defined by conventional assays, especially among anti-HBs negative individuals. Serum hs-HBsAg could potentially assist differentiating HBsAg-negative CHB from individuals with only past HBV exposure without carrier state. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Subcirrhotic liver stiffness by FibroScan correlates with lower risk of hepatocellular carcinoma in patients with HBV-related cirrhosis.

PubMed

Jeon, Mi Young; Lee, Hye Won; Kim, Seung Up; Heo, Ja Yoon; Han, Sojung; Kim, Beom Kyung; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Han, Kwang-Hyub

2017-05-01

The risk of developing hepatocellular carcinoma (HCC) varies, even in the context of cirrhosis. We investigated the relationship between liver stiffness (LS) in subcirrhotic range, assessed via transient elastography (TE), and risk of HCC development in patients with chronic hepatitis B (CHB)-related cirrhosis. Data on 540 patients presenting with clinically evident CHB-related cirrhosis between April 2006 and December 2014 were reviewed retrospectively. Subcirrhotic range of LS was defined by TE values ≤13 kPa. Of the study population, 214 (39.6%) had LS values in the subcirrhotic range. During follow-up (median 54.1 months), 81 patients (15.0%) developed HCC. In conjunction with age, male gender, and diabetes mellitus, subcirrhotic LS value (hazard ratio = 0.462) was an independent predictor of HCC development on multivariate analysis (all p < 0.05). Cumulative HCC incidence was significantly lower for patients in subcirrhotic (versus cirrhotic) LS range (log-rank test, p < 0.05). In our cohort, the modified REACH-B score performed better than other prediction models, namely REACH-B, CU-HCC, and LSM-HCC scoring systems (area under receiver operating characteristic curve: 0.717 versus 0.669, 0.578, and 0.624, respectively, for 7-year HCC risk). A significant association between subcirrhotic range of LS value and lower risk of HCC development was identified in patients with clinically evident CHB-related cirrhosis. Thus, different TE-based HCC surveillance strategies may be required even in patients with identical liver cirrhosis disease category.

TCRγδ+CD4−CD8− T Cells Suppress the CD8+ T-Cell Response to Hepatitis B Virus Peptides, and Are Associated with Viral Control in Chronic Hepatitis B

PubMed Central

Lai, Qintao; Ma, Shiwu; Ge, Jun; Huang, Zuxiong; Huang, Xuan; Jiang, Xiaotao; Li, Yongyin; Zhang, Mingxia; Zhang, Xiaoyong; Sun, Jian; Abbott, William G. H.; Hou, Jinlin

2014-01-01

The immune mechanisms underlying failure to achieve hepatitis B e antigen (HBeAg) seroconversion associated with viral control in chronic hepatitis B (CHB) remain unclear. Here we investigated the role of CD4−CD8− T (double-negative T; DNT) cells including TCRαβ+ DNT (αβ DNT) and TCRγδ+ DNT (γδ DNT) cells. Frequencies of circulating DNT cell subsets were measured by flow cytometry in a retrospective cohort of 51 telbivudine-treated HBeAg-positive CHB patients, 25 immune tolerant carriers (IT), 33 inactive carriers (IC), and 37 healthy controls (HC). We found that γδ DNT cell frequencies did not significantly change during treatment, being lower at baseline (P = 0.019) in patients with HBeAg seroconversion after 52 weeks of antiviral therapy (n = 20) than in those without (n = 31), and higher in the total CHB and IT than IC and HC groups (P<0.001). αβ DNT cell frequencies were similar for all groups. In vitro, γδ DNT cells suppressed HBV core peptide-stimulated interferon-γ and tumor necrosis factor-α production in TCRαβ+CD8+ T cells, which may require cell–cell contact, and could be partially reversed by anti-NKG2A. These findings suggest that γδ DNT cells limit CD8+ T cell response to HBV, and may impede HBeAg seroconversion in CHB. PMID:24551107

Tenofovir-Based Alternate Therapies for Chronic Hepatitis B Patients with Partial Virological Response to Entecavir

PubMed Central

Lu, Louis; Yip, Benjamin; Trinh, Huy; Pan, Calvin Q.; Han, Steven-Huy B.; Wong, Christopher C.; Li, Jiayi; Chan, Stanley; Krishnan, Gomathi; Wong, Clifford C.; Nguyen, Mindie H.

2014-01-01

Entecavir (ETV) is a first-line antiviral therapy for treating chronic hepatitis B (CHB); however, some patients have suboptimal response to ETV. Currently, there are limited data on how to approach these patients. Therefore our aim was to compare the effectiveness of two alternate therapies – tenofovir (TDF) monotherapy and combination therapy of ETV+TDF – in CHB patients with ETV partial virological response. We conducted a retrospective study of 68 patients who had partial virological response to ETV, defined as having detectable HBV DNA following at least 12 months of ETV, and were switched to TDF monotherapy (n=25) or ETV+TDF (n=43). Patients were seen in 7 US liver/community-based clinics and started on ETV between 2005-2009. The majority of patients were male; the vast majority were Asian and had positive hepatitis B e antigen (HBeAg). Patients in both groups had similar pre-treatment characteristics. Complete viral suppression (CVS) rates with TDF monotherapy and ETV+TDF were similar after 6 months (71% vs. 83, p=0.23) and 12 months (86% vs. 84%, p=0.85), and there was no statistically significant difference in CVS rates even when only patients with higher HBV DNA levels at switch (>1,000 IU/mL) were evaluated. Multivariate analysis indicated that ETV+TDF was not an independent predictor of CVS compared to TDF monotherapy (OR=1.19, p=0.63). In conclusion, TDF monotherapy and ETV+TDF are comparable in achieving CVS in CHB patients with partial virological response to ETV. Long-term alternate therapy with one pill (TDF monotherapy) vs. two pills (ETV+TDF) could lead to lower non-adherence rates and better treatment outcomes. PMID:25417914

Characteristics and management of patients with chronic hepatitis B in an integrated care setting.

PubMed

Sarkar, Monika; Shvachko, Valentina A; Ready, Joanna B; Pauly, Mary Pat; Terrault, Norah A; Peters, Marion G; Manos, M Michele

2014-09-01

Few population-based studies have described characteristics and management of patients with chronic hepatitis B (CHB) in the USA. We retrospectively studied adults with CHB in the Northern California Kaiser Permanente Medical Care Program (KPNC) from July 2009 to December 2010 (n = 12,016). Laboratory tests, treatment patterns, and hepatocellular carcinoma (HCC) surveillance were ascertained during a "recent" 18-month study window (July 2009-December 2010), or as "ever" based on records dating to 1995. The mean age was 49 years; 51 % were men, 83 % Asian, and 87 % KPNC members >5 years. Overall, 51 % had ≥ 1 liver-related visit, 14 % with gastroenterology or infectious disease specialists, and 37 % with primary care providers (PCP) only. Less than 40 % of patients had both hepatitis B virus (HBV) DNA and ALT testing conducted recently, while 56 % of eligible patients had received HCC surveillance. Recent laboratory testing and HCC surveillance were more frequent in patients seen by a specialist versus PCP only (90 vs. 47 % and 92 vs. 73 %, respectively, p values <0.001). During the study period, 1,649 (14 %) received HBV treatment, while 5 % of untreated patients had evidence of treatment eligibility. Among 599 patients newly initiated on HBV therapy, 76 % had guideline-based indications for treatment. Most patients initiated on HBV treatment met eligibility, and very few patients with evidence of needing treatment were left untreated. However, monitoring of ALT and HBV DNA levels, as well as HCC surveillance, were not frequent, underestimating the proportion of patients that warranted HBV therapy. Viral monitoring and cancer surveillance are therefore important targets for improving the scope of CHB care in the community setting.

Management of chronic hepatitis B infection: Current treatment guidelines, challenges, and new developments

PubMed Central

Tang, Ceen-Ming; Yau, Tung On; Yu, Jun

2014-01-01

Chronic hepatitis B (CHB) virus infection is a global public health problem, affecting more than 400 million people worldwide. The clinical spectrum is wide, ranging from a subclinical inactive carrier state, to progressive chronic hepatitis, cirrhosis, decompensation, and hepatocellular carcinoma. However, complications of hepatitis B virus (HBV)-related chronic liver disease may be reduced by viral suppression. Current international guidelines recommend first-line treatment of CHB infection with pegylated interferon, entecavir, or tenofovir, but the optimal treatment for an individual patient is controversial. The indications for treatment are contentious, and increasing evidence suggests that HBV genotyping, as well as serial on-treatment measurements of hepatitis B surface antigen and HBV DNA kinetics should be used to predict antiviral treatment response. The likelihood of achieving a sustained virological response is also increased by extending treatment duration, and using combination therapy. Hence the paradigm for treatment of CHB is constantly evolving. This article summarizes the different indications for treatment, and systematically reviews the evidence for the efficacy of various antiviral agents. It further discusses the shortcomings of current guidelines, use of rescue therapy in drug-resistant strains of HBV, and highlights the promising clinical trials for emerging therapies in the pipeline. This concise overview presents an updated practical approach to guide the clinical management of CHB. PMID:24876747

Using a population-based approach to prevent hepatocellular cancer in New South Wales, Australia: effects on health services utilisation

PubMed Central

2010-01-01

Background Australians born in countries where hepatitis B infection is endemic are 6-12 times more likely to develop hepatocellular cancer (HCC) than Australian-born individuals. However, a program of screening, surveillance and treatment of chronic hepatitis B (CHB) in high risk populations could significantly reduce disease progression and death related to end-stage liver disease and HCC. Consequently we are implementing the B Positive pilot project, aiming to optimise the management of CHB in at-risk populations in south-west Sydney. Program participants receive routine care, enhanced disease surveillance or specialist referral, according to their stage of CHB infection, level of viral load and extent of liver injury. In this paper we examine the program's potential impact on health services utilisation in the study area. Methods Estimated numbers of CHB infections were derived from Australian Bureau of Statistics data and applying estimates of HBV prevalence rates from migrants' countries of birth. These figures were entered into a Markov model of disease progression, constructing a hypothetical cohort of Asian-born adults with CHB infection. We calculated the number of participants in different CHB disease states and estimated the numbers of GP and specialist consultations and liver ultrasound examinations the cohort would require annually over the life of the program. Results Assuming a 25% participation rate among the 5,800 local residents estimated to have chronic hepatitis B infection, approximately 750 people would require routine follow up, 260 enhanced disease surveillance and 210 specialist care during the first year after recruitment is completed. This translates into 5 additional appointments per year for each local GP, 25 for each specialist and 420 additional liver ultrasound examinations. Conclusions While the program will not greatly affect the volume of local GP consultations, it will lead to a significant increase in demand for specialist services. New models of CHB care may be required to aid program implementation and up scaling the program will need to factor in additional demands on health care utilisation in areas of high hepatitis B sero-prevalence. PMID:20663140

Increased ERp57 Expression in HBV-Related Hepatocellular Carcinoma: Possible Correlation and Prognosis.

PubMed

Liu, Miao; Du, Lingyao; He, Zhiliang; Yan, Libo; Shi, Ying; Shang, Jin; Tang, Hong

2017-01-01

Aim. ERp57 is involved in virus induced endoplasmic reticulum stress (ERS) and plays an important role in tumorigenesis. This study aimed to find whether HBV infection altered ERp57 expression and whether ERp57 regulation was involved in hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) genesis. Materials and Methods. HBV-HCC tissues, chronic hepatitis B (CHB) liver tissues, and normal liver tissues were acquired. ERp57 expressions in these tissues were detected through immunohistochemistry (IHC). And ERp57 expression in liver cell line L02, HBV replicative liver cell line L02-pHBV4.1, and HCC cell lines were detected through western blot for verification. Then medical data on patients providing HCC tissues were collected and analyzed along with ERp57 expression. Results. Higher ERp57 expression was found in HCC and CHB tissues ( p < 0.001). And HCC cell lines and L02-pHBV4.1 presented higher ERp57 expression as well. In patients, ERp57 expression showed significant differences between death and survival groups ( p = 0.037). And cumulative survival in patients with higher ERp57 (score ⩾ 8.75) is significantly lower ( p = 0.009). Conclusion. Our study found increased expression of ERp57 in HBV-HCC. Such altered expression could be related to HBV infection and high ERp57 expression may lead to poor prognosis of HBV-HCC patients.

A Cost-Utility and Cost-Effectiveness Analysis of Different Oral Antiviral Medications in Patients With HBeAg-Negative Chronic Hepatitis B in Iran: An Economic Microsimulation Decision Model.

PubMed

Keshavarz, Khosro; Kebriaeezadeh, Abbas; Alavian, Seyed Moayed; Akbari Sari, Ali; Rezaei Hemami, Mohsen; Lotfi, Farhad; Hashemi Meshkini, Amir; Javanbakht, Mehdi; Keshvari, Maryam; Nikfar, Shekoufeh

2016-09-01

Although hepatitis B infection is the major cause of chronic liver disease in Iran, no studies have employed economic evaluations of the medications used to treat Iranian patients with chronic hepatitis B (CHB). Therefore, the cost-effectiveness of the different treatment options for this disease in Iran is unknown. The aim of this study was to compare the cost utility and cost-effectiveness of medication strategies tailored to local conditions in patients with HB e antigen (HBeAg)-negative CHB infection in Iran. An economic evaluation of the cost utility of the following five oral medication strategies was conducted: adefovir (ADV), lamivudine (LAM), ADV + LAM, entecavir (ETV), and tenofovir (TDF). A Markov microsimulation model was used to estimate the clinical and economic outcomes over the course of the patient's lifetime and based on a societal perspective. Medical and nonmedical direct costs and indirect costs were included in the study and life-years gained (LYG) and quality-adjusted life-years (QALY) were determined as measures of effectiveness. The results are presented in terms of the incremental cost-effectiveness ratio (ICER) per QALY or LYG. The model consisted of nine stages of the disease. The transition probabilities for the movement between the different stages were based on clinical evidence and international expert opinion. A probabilistic sensitivity analysis (PSA) was used to measure the effects of uncertainty in the model parameters. The results revealed that the TDF treatment strategy was more effective and less costly than the other options. In addition, TDF had the highest QALY and LYG in the HBeAg-negative CHB patients, with 13.58 and 21.26 (discounted) in all comparisons. The PSA proved the robustness of the model results. The cost-effectiveness acceptability curves showed that TDF was the most cost-effective treatment in 59% - 78% of the simulations of HBeAg-negative patients, with WTP thresholds less than $14010 (maximum WTP per QALY). The use of TDF in patients with HBeAg-negative CHB seemed to be a highly cost-effective strategy. Compared with the other available medication options, TDF was the most cost-saving strategy. Thus, TDF may be the best option as a first-line medication. Patients can also be switched from other medications to TDF.

HBsAg level and hepatitis B viral load correlation with focus on pregnancy

PubMed Central

Belopolskaya, Maria; Avrutin, Viktor; Firsov, Sergey; Yakovlev, Alexey

2015-01-01

Background Viral load measurement is necessary to estimate mother-to-child transmission risk for women with chronic hepatitis B (CHB), however, it is expensive. The present study aimed to investigate the relationship between HBsAg and hepatitis B virus (HBV) DNA levels, and to determine potential applications of HBsAg level monitoring for estimating viral load. Methods 85 patients with CHB (31 pregnant women, 26 non-pregnant women, 28 men) were included in the study. HBV DNA level was measured by real-time PCR, and HBsAg level by chemiluminescent immunoassay method. Dependency between viral load and HBsAg level was determined by Spearman correlation coefficient ρ. Results The correlation between HBsAg and HBV DNA levels was significant for all patients [ρ=0.3762 (P<0.0005; n=85)]. In the group of pregnant women, a low (unmeasurable) HBV DNA level led to a decrease in the Spearman coefficient ρ. In almost all cases a low level of the HBsAg corresponded to a low HBV DNA level. Only 2 patients had a low level of HBsAg and a relatively high viral load. By contrast, a high HBsAg level was observed in patients both with high and low viral load. Conclusions Correlation between HBsAg and HBV DNA levels is significant. In most cases, a low level of HBsAg indicates a low HBV DNA level, whereas a high HBsAg level does not always correspond to a high viral load. The measurement of HBV DNA level is necessary for pregnant women with a high HBsAg level. PMID:26127004

The gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa.

PubMed

Lemoine, Maud; Shimakawa, Yusuke; Nayagam, Shevanthi; Khalil, Mustapha; Suso, Penda; Lloyd, Jo; Goldin, Robert; Njai, Harr-Freeya; Ndow, Gibril; Taal, Makie; Cooke, Graham; D'Alessandro, Umberto; Vray, Muriel; Mbaye, Papa Saliou; Njie, Ramou; Mallet, Vincent; Thursz, Mark

2016-08-01

Simple and inexpensive non-invasive fibrosis tests are highly needed but have been poorly studied in sub-Saharan Africa. Using liver histology as a gold standard, we developed a novel index using routine laboratory tests to predict significant fibrosis in patients with chronic HBV infection in The Gambia, West Africa. We prospectively assessed the diagnostic accuracy of the novel index, Fibroscan, aspartate transaminase-to-platelet ratio index (APRI), and Fib-4 in Gambian patients with CHB (training set) and also in French and Senegalese CHB cohorts (validation sets). Of 135 consecutive treatment-naïve patients with CHB who had liver biopsy, 39% had significant fibrosis (Metavir fibrosis stage ≥F2) and 15% had cirrhosis (F4). In multivariable analysis, gamma-glutamyl transpeptidase (GGT) and platelet count were independent predictors of significant fibrosis. Consequently, GGT-to-platelet ratio (GPR) was developed. In The Gambia, the area under the receiver operating characteristic curve (AUROC) of the GPR was significantly higher than that of APRI and Fib-4 to predict ≥F2, ≥F3 and F4. In Senegal, the AUROC of GPR was significantly better than Fib-4 and APRI for ≥F2 (0.73, 95% CI 0.59 to 0.86) and better than Fib-4 and Fibroscan for ≥F3 (0.93, 0.87 to 0.99). In France, the AUROC of GPR to diagnose ≥F2 (0.72, 95% CI 0.59 to 0.85) and F4 (0.87, 0.76 to 0.98) was equivalent to that of APRI and Fib-4. The GPR is a more accurate routine laboratory marker than APRI and Fib-4 to stage liver fibrosis in patients with CHB in West Africa. The GPR represents a simple and inexpensive alternative to liver biopsy and Fibroscan in sub-Saharan Africa. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Disease management of early childhood caries: results of a pilot quality improvement project.

PubMed

Ng, Man Wai; Torresyap, Gay; White, Alex; Melvin, Patrice; Graham, Dionne; Kane, Daniel; Scoville, Richard; Ohiomoba, Henry

2012-08-01

The purpose is to report findings of a quality improvement (QI) project implemented at two hospital-based dental clinics that care for children with early childhood caries (ECC). We tested a disease management (DM) approach in children younger than age 60 months with ECC. After 30 months, for the 403 and 234 DM patients at Children's Hospital Boston (CHB) and Saint Joseph Hospital (SJH) who returned for at least two visits, rates of new cavitation, pain, and referrals to the OR were 26.1, 13.4 and 10.9% for CHB and 41.0, 7.3 and 14.9% for SJH. Rates of new cavitation, pain, and referrals to the OR for historical controls were 75.2, 21.7, and 20.9% for CHB and 71.3, 31.3, and 25.0% for SJH. A risk-based DM approach utilizing QI strategies to address ECC can be implemented into practice and has the potential to improve care and health outcomes.

Diwu Yanggan capsule improving liver histological response for patients with HBeAg-negative chronic hepatitis B: a randomized controlled clinical trial.

PubMed

Li, Hanmin; Ye, Zhihua; Gao, Xiang; Zhang, Lisheng; Yao, Xin; Gu, Jianxun; Lu, Dingbo; Wan, Ming; Xiao, Lin; Cai, Wangxi; Yan, Xuesheng; Zhao, Binbin; Wu, Yu; Zhang, Jinrong

2018-01-01

The number of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) has shown a significant upward trend in recent years. However, antiviral drugs are not very effective. Regulation of liver regeneration by traditional Chinese medicine is an important way to improve clinical efficacy. This randomized controlled trial assessed the efficacy and safety of DWYG in patients with HBeAg-negative CHB. Overall, 130 subjects were randomized to (A) DWYG 1.2 g three times daily (n = 44), (B) entecavir 0.5 mg/day (n = 43) in combination with DWYG or (C) entecavir 0.5 mg/day (n = 43). The liver histological response rate was assessed as the primary efficacy endpoint. The results showed that the liver histological response rate in the combination treatment group was significantly higher than that in the group with entecavir (71.43% versus 22.22%; P = 0.036) after 48 weeks of treatment. And the pathological progression rate of liver in the group with DWYG was significantly lower than that of the entecavir group during 228 weeks of follow-up (0% versus 60.00%; P = 0.019). No significant adverse events occurred during the study. In conclusion, treating HBeAg-negative CHB with DWYG is safe and effective to improve liver histological response.

Protective Effect of Crocodile Hemoglobin and Whole Blood Against Hydrogen Peroxide-Induced Oxidative Damage in Human Lung Fibroblasts (MRC-5) and Inflammation in Mice.

PubMed

Phosri, Santi; Jangpromma, Nisachon; Patramanon, Rina; Kongyingyoes, Bunkerd; Mahakunakorn, Pramote; Klaynongsruang, Sompong

2017-02-01

A putative protective effect of cHb and cWb against H 2 O 2 -induced oxidative damage was evaluated in detail using MRC-5 cells. In addition, the carrageenan (Carr)-induced mouse paw edema model and the cotton pellet-induced granuloma model were employed to examine the in vivo anti-inflammatory activity of cHb and cWb in mice. It was demonstrated that both cHb and cWb treatments significantly increased cell viability and inhibited morphology alterations in MRC-5 cells exposed to H 2 O 2 . Orally administered cHb and cWb significantly reduced Carr-induced paw edema volume and cotton pellet-induced granuloma formation. Moreover, cHb and cWb decreased the expression levels of important pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α), while only cWb was found to increase the expression of the anti-inflammatory cytokine IL-10 significantly. Finally, the activity of antioxidant enzymes (SOD, CAT, and GPx) in the liver improved after cHb and cWb treatment under acute and chronic inflammation. Taken collectively, the results of this study suggest that both cHb and cWb protect against hydrogen peroxide-induced damage in fibroblast cells. Moreover, cHb and cWb were found to exhibit anti-inflammatory activity in both the acute and chronic stages of inflammation and appear to enhance antioxidant enzyme activity and decrease lipid peroxidation in the livers of mice. Therefore, this study indicates that cHb and cWb have great potential to be used in the development of dietary supplements for the prevention of oxidative stress related to inflammatory disorders.

The factors associated with longitudinal changes in liver stiffness in patients with chronic hepatitis B.

PubMed

Yo, In Ku; Kwon, Oh Sang; Park, Jin Woong; Lee, Jong Joon; Lee, Jung Hyun; Won, In Sik; Na, Sun Young; Jang, Pil Kyu; Park, Pyung Hwa; Choi, Duck Joo; Kim, Yun Soo; Kim, Ju Hyun

2015-03-01

Liver stiffness (LS) as assessed by transient elastography (TE) can change longitudinally in patients with chronic hepatitis B (CHB). The aim of this study was to identify the factors that improve LS. Between April 2007 and December 2012, 151 patients with CHB who underwent two TE procedures with an interval of about 2 years were enrolled. Ninety-six of the 151 patients were treated with nucleos(t)ide analogues [the antiviral therapy (+) group], while the remaining 55 patients were not [the antiviral therapy (-) group]. The two groups of patients were stratified according to whether they exhibited an improvement or a deterioration in LS during the study period (defined as an LS change of ≤0 or >0 kPa, respectively, over a 1-year period), and their data were compared. No differences were observed between the antiviral therapy (+) and (-) groups with respect to either their clinical characteristics or their initial LS. The observed LS improvement was significantly greater in the antiviral therapy (+) group than in the antiviral therapy (-) group (-3.0 vs. 0.98 kPa, P=0.011). In the antiviral therapy (+) group, the initial LS was higher in the LS improvement group (n=63) than in the LS deterioration group (n=33; 7.9 vs. 4.8 kPa, P<0.001). However, there were no differences in any other clinical characteristic. In the antiviral therapy (-) group, the initial LS was also higher in the LS improvement group (n=29) than in the LS deterioration group (n=26; 8.3 vs. 6.5 kPa, P=0.021), with no differences in any other clinical characteristic. A higher initial LS was the only factor associated with LS improvement in patients with CHB in this study.

Economic analysis between entecavir and lamivudine for the treatment of chronic hepatitis B in Hong Kong.

PubMed

Lee, Kenneth K C; Wu, David Bin Chia; Chow, Pui Yu; Lee, Vivian Wing Yan; Li, Hong

2012-07-01

Tremendous healthcare resources have been spent on the management of chronic hepatitis B (CHB) and its related complications. Therefore, a proper evaluation of the cost-effectiveness of pharmacotherapy is vital in aid of decision-making. The aim of the present study was to examine the long-term economic and clinical influence if lamivudine was replaced by entecavir in a group of CHB patients. A recently published decision analytic model was adapted to study the cost-effectiveness of 2 years of treatment of entecavir in a hypothetical cohort of 1000 hepatitis B e antigen (HBeAg)-negative CHB patients from a public hospital perspective. Compensated cirrhosis (CC) and de-compensated cirrhosis (DC) and hepatocellular carcinoma (HCC) events were projected to 10 years. Hong Kong-specific health care costs were used. Quality Adjusted Life Years (QALYs) were calculated using the utility values obtained from a local study. In the base case analysis, compared with lamivudine, the use of entecavir was expected to reduce the incidences of CC, DC and HCC by 41.8%, 57.1% and 49.3%, respectively, and lead to a saving of $US 1.17 million in medical cost. The overall disease management cost for entecavir, which was 67.7% higher than lamivudine for 2 years treatment was reduced to 17.2% after projecting 2-year treatment duration to 10 years. The incremental cost per QALY gained for entecavir compared with lamivudine was $US 13 759. Based on the recommended cost-effectiveness threshold of the World Health Organization, entecavir is considered cost-effective compared with lamivudine in treating CHB in Hong Kong when long term medical consequences were considered. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Pregnancy Outcomes in Patients with Autoimmune Diseases and Anti-Ro/SSA Antibodies

PubMed Central

Cimaz, Rolando; Caporali, Roberto; Ramoni, Véronique; Buyon, Jill

2013-01-01

Anti-Ro/SSA antibodies are associated with neonatal lupus (congenital heart block (CHB), neonatal transient skin rash, hematological and hepatic abnormalities), but do not negatively affects other gestational outcomes, and the general outcome of these pregnancies is now good, when followed by experienced multidisciplinary teams. The prevalence of CHB, defined as an atrioventricular block diagnosed in utero, at birth, or within the neonatal period (0–27 days after birth), in the offspring of an anti-Ro/SSA-positive women is 1–2%, of neonatal lupus rash around 10–20%, while laboratory abnormalities in asymptomatic babies can be detected in up to 27% of cases. The risk of recurrence of CHB is ten times higher. Most of the mothers are asymptomatic at delivery and are identified only by the birth of an affected child. Half of these asymptomatic women develop symptoms of a rheumatic disease, most commonly arthralgias and xerophtalmia, but few develop lupus nephritis. A standard therapy for CHB is still matter of investigation, although fluorinated corticosteroids have been reported to be effective for associated cardiomyopathy. Serial echocardiograms and obstetric sonograms, performed at least every 1–2 weeks starting from the 16th week of gestational age, are recommended in anti-Ro/SSA-positive pregnant women to detect early fetal abnormalities that might be a target of preventive therapy. PMID:20012231

Tenofovir vs lamivudine plus adefovir in chronic hepatitis B: TENOSIMP-B study

PubMed Central

Rodríguez, Manuel; Pascasio, Juan Manuel; Fraga, Enrique; Fuentes, Javier; Prieto, Martín; Sánchez-Antolín, Gloria; Calleja, José Luis; Molina, Esther; García-Buey, María Luisa; Blanco, María Ángeles; Salmerón, Javier; Bonet, María Lucía; Pons, José Antonio; González, José Manuel; Casado, Miguel Ángel; Jorquera, Francisco; Group, the TENOSIMP-B Research

2017-01-01

AIM To demonstrate the non-inferiority (15% non-inferiority limit) of monotherapy with tenofovir disoproxil fumarate (TDF) vs the combination of lamivudine (LAM) plus adefovir dipivoxil (ADV) in the maintenance of virologic response in patients with chronic hepatitis B (CHB) and prior failure with LAM. METHODS This study was a Phase IV prospective, randomized, open, controlled study with 2 parallel groups (TDF and LAM+ADV) of adult patients with hepatitis B e antigen (HBeAg)-negative CHB, prior failure with LAM, on treatment with LAM+ADV for at least 6 mo, without prior resistance to ADV and with an undetectable viral load at the start of the study, in 14 Spanish hospitals. The follow-up time for each patient was 48 wk after randomization, with quarterly visits in which the viral load, biochemical and serological parameters, adverse effects, adherence to treatment and consumption of hospital resources were analysed. RESULTS Forty-six patients were evaluated [median age: 55.4 years (30.2-75.2); 84.8% male], including 22 patients with TDF and 24 with LAM+ADV. During study development, hepatitis B virus DNA (HBV-DNA) remained undetectable, all patients remained HBeAg negative, and hepatitis B surface antigen (HBsAg) positive. Alanine aminotransferase (ALT) values at the end of the study were similar in the 2 groups (25.1 ± 7.65, TDF vs 24.22 ± 8.38, LAM+ADV, P = 0.646). No significant changes were observed in creatinine or serum phosphorus values in either group. No significant differences between the 2 groups were noted in the identification of adverse effects (AEs) (53.8%, TDF vs 37.5%, LAM+ADV, P = 0.170), and none of the AEs which occurred were serious. Treatment adherence was 95.5% and 83.3% in the TDF and the LAM+ADV groups, respectively (P = 0.488). The costs associated with hospital resource consumption were significantly lower with the TDF treatment than the LAM+ADV treatment (€4943 ± 1059 vs €5811 ± 1538, respectively, P < 0.001). CONCLUSION TDF monotherapy proved to be safe and not inferior to the LAM+ADV combination therapy in maintaining virologic response in patients with CHB and previous LAM failure. In addition, the use of TDF generated a significant savings in hospital costs. PMID:29151700

Pegylated Interferon α-2a Triggers NK-Cell Functionality and Specific T-Cell Responses in Patients with Chronic HBV Infection without HBsAg Seroconversion

PubMed Central

Bruder Costa, Juliana; Dufeu-Duchesne, Tania; Leroy, Vincent; Bertucci, Inga; Bouvier-Alias, Magali; Pouget, Noelle; Brevot-Lutton, Ophelie; Bourliere, Marc; Zoulim, Fabien

2016-01-01

Pegylated interferon α-2a (Peg-IFN-α) represents a therapeutic alternative to the prolonged use of nucleos(t)ide analog (NA) in chronic hepatitis B (CHB) infection. The mechanisms leading to a positive clinical outcome remain unclear. As immune responses are critical for virus control, we investigated the effects of Peg-IFN-α on both innate and adaptive immunity, and related it to the clinical evolution. The phenotypic and functional features of the dendritic cells (DCs), natural killer (NK) cells and HBV-specific CD4/CD8 T cells were analyzed in HBeAg-negative CHB patients treated for 48-weeks with NA alone or together with Peg-IFN-α, before, during and up to 2-years after therapy. Peg-IFN-α induced an early activation of DCs, a potent expansion of the CD56bright NK subset, and enhanced the activation and functionality of the CD56dim NK subset. Peg-IFN-α triggered an increase in the frequencies of Th1- and Th17-oriented HBV-specific CD4/CD8 T cells. Peg-IFN-α reversed the unresponsiveness of patients to a specific stimulation. Most of the parameters returned to baseline after the stop of Peg-IFN-α therapy. Peg-IFN-α impacts both innate and adaptive immunity, overcoming dysfunctional immune responses in CHB patients. These modulations were not associated with seroconversion, which questioned the benefit of the add-on Peg-IFN-α treatment. PMID:27348813

Serum DHCR24 Auto-antibody as a new Biomarker for Progression of Hepatitis C

PubMed Central

Ezzikouri, Sayeh; Kimura, Kiminori; Sunagozaka, Hajime; Kaneko, Shuichi; Inoue, Kazuaki; Nishimura, Tomohiro; Hishima, Tsunekazu; Kohara, Michinori; Tsukiyama-Kohara, Kyoko

2015-01-01

Background New biomarkers are needed to identify the stage of hepatitis C virus (HCV)-infected diseases in order to reduce the mortality rates. Herein, we investigated whether serum 3β-hydroxysterol Δ24-reductase antibody (DHCR24 Ab) may serve as a prognostic marker for hepatitis C infection progression to hepatocellular carcinoma (HCC). Methods Serum DHCR24 Abs from 395 HCV-positive patients, including 133 chronic hepatitis (CHC), 85 liver cirrhosis (LCC), and 177 HCC (HCC-C) patients; 232 hepatitis B virus (HBV)-positive patients, including 103 chronic hepatitis (CHB), 56 liver cirrhosis (LCB), and 73 HCC (HCC-B) patients; and 24 healthy controls, were measured using enzyme-linked immunosorbent assay. Results The serum DHCR24 Ab levels were significantly higher in patients with CHC than in healthy controls, in LCC than in CHC, and in LCC than in HCC-C (P < 0.0001 for all). The concentration of serum DHCR24 Ab in HCC-B patients showed no significant difference compared to CHB and LCB patients (P = 0.1247). The DHCR24 Ab levels were significantly higher in early HCC-C than CHC or LCC patients and in late HCC-C compared to early HCC-C patients. The sensitivity of the DHCR24 Ab for HCC-C detection (70.6%) was higher than that of alpha-fetoprotein (AFP; 54.8%) and protein induced by vitamin K absence or antagonist-II (PIVKA-II; 42 · 5%). Moreover, DHCR24 was up-regulated in HCV-positive, but not HBV-positive tissues or HBV-negative, HCV-negative HCC specimens. Conclusions DHCR24 auto-antibody represents a potential noninvasive biomarker for HCV-related liver disease and may facilitate the diagnosis of PIVKA-II and AFP-negative HCC. PMID:26288822

The risk of placental abruption and placenta previa in pregnant women with chronic hepatitis B viral infection: a systematic review and meta-analysis.

PubMed

Huang, Q T; Chen, J H; Zhong, M; Xu, Y Y; Cai, C X; Wei, S S; Hang, L L; Liu, Q; Yu, Y H

2014-08-01

Several epidemiological studies have found a positive association between chronic hepatitis B virus (CHB) infection and the risk of placental abruption and placenta previa, but various studies have reported conflicting findings. The objective was to systematically review the literature to determine a possible association between CHB infection and these two placental complications. We conducted a computerized search in electronic database through March 1, 2014, supplemented with a manual search of reference lists, to identify original published research on placental abruption and placenta previa rates in women with CHB infection. Data were independently extracted, and relative risks were calculated. The meta-analysis was performed using Stata version 10.0 software. Five studies involving 9088 placenta previa cases were identified. No significant association between CHB infection and placenta previa was identified (OR = 0.98, 95% CI = 0.60-1.62). Five studies involving 15571 placental abruption cases were identified. No significant association between CHB infection and placental abruption was identified (OR = 1.42, 95% CI, 0.93-2.15). The immune response against the virus represents a key factor in determining infection outcomes. No observation of significant increased risk of the placental complications could be partially explained by the complex immune response during CHB infection. Our meta-analysis found no evidence of significant associations between CHB infection and increased risk of placental abruption as well as placenta previa. Further well-designed studies were warranted to assess any potential association between CHB infection and increased risk of placental abruption as well as placenta previa. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cytokine levels and histopathology in chronic hepatitis B and chronic hepatitis C.

PubMed

Akcam, Fusun Zeynep; Tigli, Arzu; Kaya, Onur; Ciris, Metin; Vural, Huseyin

2012-12-01

The changes in balance of cytokine profile may result in either recovery or persistence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. This study aims to reveal a possible correlation between cytokine levels, ie, tumor necrosis factor (TNF)-α; interferon-gamma (IFN-γ); interleukin (IL)-10, IL-18, and transforming growth factor-beta (TGF-β); and Ishak score or fibrosis in patients with chronic hepatitis B (CHB) or chronic hepatitis C (CHC). Fifty patients with CHB (n=25), CHC (n=25), and the control group of subjects with negative hepatitis B and C serology (n=30) were included in the study. Patients who did not agree to participate in the study were excluded. Serum cytokine levels were measured by ELISA. Liver biopsies from the patients were also taken for pathological analyses by the same pathologist. The serum levels of TNF-α, IL-10, and IL-18 in the hepatitis C group were significantly high compared with those of the control group (P=0.017, P=0.001, and P=0.004 respectively), but, only IL-10 levels in the hepatitis B group were significantly high (P=0.001). These groups did not show any significant difference with respect to IFN-γ or TGF-β levels. In patients with CHB or CHC, there was a significant correlation (P=0.000) between TNF-α and Ishak score or fibrosis; but no such correlation was found with IFN-γ, IL-10, IL-18, or TGF-β. Result of the current study indicated that cytokine activities were important indicators of clinical severity and progression of HBV- and HCV infections. Further investigations on possible effects of cytokines on hepatocellular damage and fibrosis should be done to arrange new immunopathological approaches to viral hepatitis.

Abnormality of autophagic function and cathepsin expression in the liver from patients with non-alcoholic fatty liver disease.

PubMed

Fukuo, Yuka; Yamashina, Shunhei; Sonoue, Hiroshi; Arakawa, Atsushi; Nakadera, Eisuke; Aoyama, Tomonori; Uchiyama, Akira; Kon, Kazuyoshi; Ikejima, Kenichi; Watanabe, Sumio

2014-09-01

Recent evidences indicate that hepatic steatosis suppresses autophagic proteolysis. The present study evaluated the correlation between autophagic function and cathepsin expression in the liver from patients with non-alcoholic fatty liver disease (NAFLD). Liver biopsy specimens were obtained from patients with chronic liver diseases (chronic hepatitis C [CHC; n = 20], chronic hepatitis B [CHB; n = 16], primary biliary cirrhosis [PBC; n = 23], NAFLD [n = 22] and control [n = 14]). The number of autophagic vesicles in hepatocytes was counted by using transmission electron microscopy. Expression of cathepsin B, D, L and p62 in the liver section was analyzed by immunohistochemical staining. The histological severity of NAFLD is assessed by NAFLD activity score (NAS). The number of autophagic vesicles in hepatocytes was significantly increased in both CHC and NAFLD groups, but not CHB and PBC, more than control. Although hepatocytes with aggregation of p62 were observed in less than 15% of CHC, p62 aggregation was detected in approximately 65% of NAFLD. Cathepsin B, D and L expression was significantly suppressed in the liver from NAFLD patients. Suppression of cathepsin B, D and L expression was not observed in CHB, CHC and PBC. In NAFLD patients, p62 aggregation was correlated with serum alanine aminotransferase value and inflammatory activity by NAS. These results indicate that a decrease in hepatic cathepsin expression in NAFLD is associated with autophagic dysfunction. Hepatic inflammation correlates with autophagic dysfunction in NAFLD. These findings indicate that the suppression of autophagic proteolysis by hepatic steatosis is involved in the pathogenesis of NAFLD. © 2013 The Japan Society of Hepatology.

Evaluation of APRI and FIB-4 for noninvasive assessment of significant fibrosis and cirrhosis in HBeAg-negative CHB patients with ALT ≤ 2 ULN

PubMed Central

Li, Qiang; Ren, Xiaojing; Lu, Chuan; Li, Weixia; Huang, Yuxian; Chen, Liang

2017-01-01

Abstract To evaluate the performance of aspartate transaminase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) to predict significant fibrosis and cirrhosis in hepatitis B virus e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with alanine transaminase (ALT) ≤ twice the upper limit of normal (2 ULN). Histologic and laboratory data of 236 HBeAg-negative CHB patients with ALT ≤ 2 ULN were analyzed. Predicted fibrosis stage, based on established scales and cut-offs for APRI and FIB-4, was compared with METAVIR scores obtained from liver biopsy. In this study, the areas under the receiver operating characteristic curves (AUROCs) of APRI were lower than that of FIB-4 (0.62 vs 0.69; P = 0.019) for diagnosing significant fibrosis; however APRI and FIB-4 were comparable for diagnosing cirrhosis (0.77 vs 0.81; P = 0.374). When the cut-off proposed by WHO HBV guideline for APRI (>2.0) was used, no cirrhotic patients were correctly predicted. For FIB-4, the WHO proposed cut-off of 3.25 correctly identified significant fibrosis 83% of the time; but for APRI, the WHO proposed cut-off of 1.5 identified significant fibrosis 56%. In ruling out significant fibrosis, the WHO proposed APRI cut-off of 0.5 had a predictive value of 39%, and the FIB-4 cut-off of 1.45 correctly identified lack of significant fibrosis in 47% of the patients. In this study, based on ROC analysis, the optimal cut-offs were 0.46 and 0.65 for APRI, and 1.05 and 1.29 for FIB-4, for diagnosing significant fibrosis and cirrhosis, respectively. When the new cut-off of APRI (>0.65) was used, 82% of the cirrhotic patients were correctly predicted. In ruling out significant fibrosis, the new APRI cut-off (<0.46) had a predictive value of 80%, and new FIB-4 cut-off (<1.05) correctly identified lack of significant fibrosis in 84% of the patients. The WHO guidelines proposed cut-offs might be higher for HBeAg-negative CHB patients with ALT ≤2 ULN, and might underestimate the proportion of significant fibrosis and cirrhosis. A new set of cut-offs should be used to predict significant fibrosis and cirrhosis in this specific population. PMID:28328813

Evaluation of APRI and FIB-4 for noninvasive assessment of significant fibrosis and cirrhosis in HBeAg-negative CHB patients with ALT ≤ 2 ULN: A retrospective cohort study.

PubMed

Li, Qiang; Ren, Xiaojing; Lu, Chuan; Li, Weixia; Huang, Yuxian; Chen, Liang

2017-03-01

To evaluate the performance of aspartate transaminase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) to predict significant fibrosis and cirrhosis in hepatitis B virus e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with alanine transaminase (ALT) ≤ twice the upper limit of normal (2 ULN).Histologic and laboratory data of 236 HBeAg-negative CHB patients with ALT ≤ 2 ULN were analyzed. Predicted fibrosis stage, based on established scales and cut-offs for APRI and FIB-4, was compared with METAVIR scores obtained from liver biopsy.In this study, the areas under the receiver operating characteristic curves (AUROCs) of APRI were lower than that of FIB-4 (0.62 vs 0.69; P = 0.019) for diagnosing significant fibrosis; however APRI and FIB-4 were comparable for diagnosing cirrhosis (0.77 vs 0.81; P = 0.374). When the cut-off proposed by WHO HBV guideline for APRI (>2.0) was used, no cirrhotic patients were correctly predicted. For FIB-4, the WHO proposed cut-off of 3.25 correctly identified significant fibrosis 83% of the time; but for APRI, the WHO proposed cut-off of 1.5 identified significant fibrosis 56%. In ruling out significant fibrosis, the WHO proposed APRI cut-off of 0.5 had a predictive value of 39%, and the FIB-4 cut-off of 1.45 correctly identified lack of significant fibrosis in 47% of the patients. In this study, based on ROC analysis, the optimal cut-offs were 0.46 and 0.65 for APRI, and 1.05 and 1.29 for FIB-4, for diagnosing significant fibrosis and cirrhosis, respectively. When the new cut-off of APRI (>0.65) was used, 82% of the cirrhotic patients were correctly predicted. In ruling out significant fibrosis, the new APRI cut-off (<0.46) had a predictive value of 80%, and new FIB-4 cut-off (<1.05) correctly identified lack of significant fibrosis in 84% of the patients.The WHO guidelines proposed cut-offs might be higher for HBeAg-negative CHB patients with ALT ≤2 ULN, and might underestimate the proportion of significant fibrosis and cirrhosis. A new set of cut-offs should be used to predict significant fibrosis and cirrhosis in this specific population.

Linearized hepatitis B surface antigen and hepatitis B core-related antigen in the natural history of chronic hepatitis B.

PubMed

Seto, W-K; Wong, D K-H; Fung, J; Huang, F-Y; Liu, K S-H; Lai, C-L; Yuen, M-F

2014-11-01

Changes in two novel HBV serological markers, linearized hepatitis B surface antigen (HQ-HBsAg) and hepatitis B core-related antigen (HBcrAg), in the natural history of chronic hepatitis B (CHB) have not been well characterized. Serum HQ-HBsAg and HBcrAg levels of 404 Asian treatment-naïve CHB patients were analysed in a cross-sectional manner. Patients were categorized into five groups: immune tolerant (IT group, n=52), immune clearance (IC group, n=105), hepatitis B e antigen (HBeAg)-negative hepatitis (ENH group, n=97), HBeAg-negative quiescent group (ENQ group, n=95) and CHB with hepatitis B surface antigen (HBsAg) seroclearance (SC group, n=55). HQ-HBsAg and HBcrAg were measured and correlated with HBV DNA, HBsAg, HBV genotype and clinical parameters. HQ-HBsAg showed good correlation with HBsAg, especially in the ENQ group (r=0.874, p<0.001). Correlation of HQ-HBsAg with HBV DNA was less prominent and weakest in the ENH group (r=0.268, p 0.008). HBcrAg correlated best with HBV DNA in the ENQ group (r=0.537, p<0.001). In the ENQ group, 42.1% of patients had undetectable HBcrAg; this subgroup of patients, when compared with those with detectable HBcrAg, had significantly lower median HBV DNA (3.17/4.48 log IU/mL, p<0.001) and HBsAg (5.05/5.96 log mIU/mL, p<0.001) levels. Forty per cent of the SC group patients had detectable HQ-HBsAg and/or HBcrAg up to 42 months after HBsAg seroclearance. When comparing anti-HBs positivity and median time after HBsAg seroclearance in the SC group with and without detectable HQ-HBsAg/HBcrAg, there was no significant difference (22.7% and 36.4%, respectively, p 0.284, and 76.5 and 93.2 months, respectively, p 0.245). HQ-HBsAg and HBcrAg showed unique patterns of distribution throughout the five disease phases of CHB, including high detectability rates after HBsAg seroclearance, opening up different possibilities for their applicability. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

A novel zf-MYND protein, CHB-3, mediates guanylyl cyclase localization to sensory cilia and controls body size of Caenorhabditis elegans.

PubMed

Fujiwara, Manabi; Teramoto, Takayuki; Ishihara, Takeshi; Ohshima, Yasumi; McIntire, Steven L

2010-11-24

Cilia are important sensory organelles, which are thought to be essential regulators of numerous signaling pathways. In Caenorhabditis elegans, defects in sensory cilium formation result in a small-body phenotype, suggesting the role of sensory cilia in body size determination. Previous analyses suggest that lack of normal cilia causes the small-body phenotype through the activation of a signaling pathway which consists of the EGL-4 cGMP-dependent protein kinase and the GCY-12 receptor-type guanylyl cyclase. By genetic suppressor screening of the small-body phenotype of a cilium defective mutant, we identified a chb-3 gene. Genetic analyses placed chb-3 in the same pathway as egl-4 and gcy-12 and upstream of egl-4. chb-3 encodes a novel protein, with a zf-MYND motif and ankyrin repeats, that is highly conserved from worm to human. In chb-3 mutants, GCY-12 guanylyl cyclase visualized by tagged GFP (GCY-12::GFP) fails to localize to sensory cilia properly and accumulates in cell bodies. Our analyses suggest that decreased GCY-12 levels in the cilia of chb-3 mutants may cause the suppression of the small-body phenotype of a cilium defective mutant. By observing the transport of GCY-12::GFP particles along the dendrites to the cilia in sensory neurons, we found that the velocities and the frequencies of the particle movement are decreased in chb-3 mutant animals. How membrane proteins are trafficked to cilia has been the focus of extensive studies in vertebrates and invertebrates, although only a few of the relevant proteins have been identified. Our study defines a new regulator, CHB-3, in the trafficking process and also shows the importance of ciliary targeting of the signaling molecule, GCY-12, in sensory-dependent body size regulation in C. elegans. Given that CHB-3 is highly conserved in mammal, a similar system may be used in the trafficking of signaling proteins to the cilia of other species.

Two different carbon-hydrogen complexes in silicon with closely spaced energy levels

NASA Astrophysics Data System (ADS)

Stübner, R.; Kolkovsky, Vl.; Weber, J.

2015-08-01

An acceptor and a single donor state of carbon-hydrogen defects (CHA and CHB) are observed by Laplace deep level transient spectroscopy at 90 K. CHA appears directly after hydrogenation by wet chemical etching or hydrogen plasma treatment, whereas CHB can be observed only after a successive annealing under reverse bias at about 320 K. The activation enthalpies of these states are 0.16 eV for CHA and 0.14 eV for CHB. Our results reconcile previous controversial experimental results. We attribute CHA to the configuration where substitutional carbon binds a hydrogen atom on a bond centered position between carbon and the neighboring silicon and CHB to another carbon-hydrogen defect.

The HBV DNA cutoff value for discriminating patients with HBeAgnegative chronic hepatitis B from inactive carriers.

PubMed

Kim, Eun Sun; Seo, Yeon Seok; Keum, Bora; Kim, Ji Hoon; A, Hyonggin; Yim, Hyung Joon; Kim, Yong Sik; Jeen, Yoon Tae; Lee, Hong Sik; Chun, Hoon Jai; Um, Soon Ho; Duck Kim, Chang; Ryu, Ho Sang

2011-05-01

Patients with HBeAg-negative chronic hepatitis B (CHB) has a significantly different prognosis than inactive carriers; there is however, no reliable strategy for accurately differentiating these two disease conditions. To determine a strategy for discriminating patients with HBeAg-negative CHB from inactive carriers. Consecutive inactive carriers (i.e. HBeAg-negativity, anti-HBe-positivity, normal ALT levels, and HBV DNA < 2000 IU/mL) were enrolled. HBV reactivation was defined as the elevation of the HBV DNA level to ≥ 2000 IU/mL. Patients were classified into true inactive carriers when their HBV DNA levels remained at < 2000 IU/mL or false inactive carriers when their HBV DNA levels increased to ≥ 2000 IU/mL during the first year. The Mean ± SD age of 208 inactive carriers (140 males) was 47.7 ± 12.6 years. The Mean ± SD serum ALT and HBV DNA levels were 22.8 ± 8.6 IU/L and 360 ± 482 IU/mL, respectively. HBV reactivation developed in 41 (19.7%) patients during the first year. Baseline HBV DNA and ALT levels differed significantly between true inactive and false inactive carriers. The AUROCs of the baseline ALT and HBV DNA levels for predicting a false inactive carrier were 0.609 and 0.831, respectively. HBV reactivation developed more often in patients with a baseline HBV DNA level of ≥ 200 IU/mL than in those with a baseline HBV DNA level of < 200 IU/mL during a Mean ± SD follow-up of 622 ± 199 days. The HBV DNA level was useful for discriminating patients with HBeAg-negative CHB from true inactive carriers. The follow-up strategies applied to inactive carriers need to vary with their HBV DNA levels.

APRI, the FIB-4 score, and Forn's index have noninvasive diagnostic value for liver fibrosis in patients with chronic hepatitis B.

PubMed

Ucar, Fatma; Sezer, Sevilay; Ginis, Zeynep; Ozturk, Gulfer; Albayrak, Aynur; Basar, Omer; Ekiz, Fuat; Coban, Sahin; Yuksel, Osman; Armutcu, Ferah; Akbal, Erdem

2013-09-01

The aim of this study was to evaluate the potential use of serum transforming growth factor-β1 (TGF-β1), tissue inhibitor of metalloproteinase-1 (TIMP-1), fetuin-A, and fibroblast growth factor 21 (FGF21) in the detection of liver fibrosis in patients with chronic hepatitis B (CHB). The value of the noninvasive fibrosis models - that is, the aspartate aminotransferase to platelet ratio index (APRI), the fibrosis index based on the four factors (FIB-4) score, and Forn's index - was also examined. CHB patients who underwent liver biopsy for the evaluation of fibrosis were included in the study. A total of 73 patients were divided into two groups according to their METAVIR scores (F0-1, no/minimal fibrosis; F2-4, significant fibrosis). Serum levels of TGF-β1, TIMP-1, fetuin-A, and FGF21 were measured besides APRI, FIB-4, and Forn's scores. The area under the receiver operating characteristic curve was measured for each parameter, followed by calculation of sensitivity, specificity, and positive and negative predictive values. APRI, FIB-4, and Forn's index scores were significantly higher in patients with significant fibrosis (P<0.05). There was no difference between no/minimal fibrosis and significant fibrosis groups in terms of serum levels of TGFβ-1, TIMP-1, fetuin-A, and FGF21 (P>0.05). The areas under the receiver operating characteristic curve for TGF-β1, TIMP-1, fetuin-A, FGF21, APRI, FIB-4, and Forn's index were 0.445, 0.483, 0.436, 0.585, 0.662, 0.687, and 0.680, respectively. Our results suggest that serum TGF-β1, TIMP-1, fetuin-A, and FGF21 are not useful for the assessment of the extent of liver fibrosis in CHB in this patient group. However, APRI, FIB-4, and Forn's index have a better diagnostic value in patients with significant fibrosis than in those with no/minimal fibrosis.

Strong and multi-antigen specific immunity by hepatitis B core antigen (HBcAg)-based vaccines in a murine model of chronic hepatitis B: HBcAg is a candidate for a therapeutic vaccine against hepatitis B virus.

PubMed

Akbar, Sheikh Mohammad Fazle; Chen, Shiyi; Al-Mahtab, Mamun; Abe, Masanori; Hiasa, Yoichi; Onji, Morikazu

2012-10-01

Experimental evidence suggests that hepatitis B core antigen (HBcAg)-specific cytotoxic T lymphocytes (CTL) are essential for the control of hepatitis B virus (HBV) replication and prevention of liver damage in patients with chronic hepatitis B (CHB). However, most immune therapeutic approaches in CHB patients have been accomplished with hepatitis B surface antigen (HBsAg)-based prophylactic vaccines with unsatisfactory clinical outcomes. In this study, we prepared HBsAg-pulsed dendritic cells (DC) and HBcAg-pulsed DC by culturing spleen DC from HBV transgenic mice (HBV TM) and evaluated the immunomodulatory capabilities of these antigens, which may serve as a better therapy for CHB. The kinetics of HBsAg, antibody levels against HBsAg (anti-HBs), proliferation of HBsAg- and HBcAg-specific lymphocytes, production of antigen-specific CTL, and activation of endogenous DC were compared between HBV TM vaccinated with either HBsAg- or HBcAg-pulsed DC. Vaccination with HBsAg-pulsed DC induced HBsAg-specific immunity, but failed to induce HBcAg-specific immunity in HBV TM. However, immunization of HBV TM with HBcAg-pulsed DC resulted in: (1) HBsAg negativity, (2) production of anti-HBs, and (3) development of HBsAg- and HBcAg-specific T cells and CTL in the spleen and the liver. Additionally, significantly higher levels of activated endogenous DC were detected in HBV TM immunized with HBcAg-pulsed DC compared to HBsAg-pulsed DC (p<0.05). The capacity of HBcAg to modulate both HBsAg- and HBcAg-specific immunity in HBV TM, and activation of endogenous DC in HBV TM without inducing liver damage suggests that HBcAg should be an integral component of the therapeutic vaccine against CHB. Copyright © 2012 Elsevier B.V. All rights reserved.

Cost-Effectiveness Analysis of Alternative Antiviral Strategies for the Treatment of HBeAg-Positive and HBeAg-Negative Chronic Hepatitis B in the United Kingdom.

PubMed

Bermingham, Sarah L; Hughes, Ralph; Fenu, Elisabetta; Sawyer, Laura M; Boxall, Elizabeth; T Kennedy, Patrick; Dusheiko, Geoff; Hill-Cawthorne, Grant; Thomas, Howard

2015-09-01

Seven drugs are licensed for the treatment of chronic hepatitis B (CHB) in the United Kingdom. Which initial treatment, secondary therapy, and whether antivirals should be given alone or in combination are questions of considerable uncertainty. The aim of this model was to undertake a comprehensive economic evaluation of all antiviral treatments for CHB to recommend the most cost-effective therapeutic sequence. We developed a probabilistic Markov model to compare the cost-effectiveness of all clinically relevant antiviral treatment sequences for nucleos(t)ide-naive adults with hepatitis B e-antigen (HBeAg)-positive or HBeAg-negative CHB. Relative rates of HBeAg seroconversion and viral suppression were obtained from a network meta-analysis. Data on mortality, antiviral drug resistance, durability of response, adverse events, and costs were obtained from published literature. Results are reported in terms of lifetime costs, quality-adjusted life-years (QALYs), and expected net benefit. In the base-case analysis, pegylated interferon alpha-2a (peg-IFN α-2a) followed by tenofovir disoproxil fumarate was most effective and cost-effective in HBeAg-positive patients, with a cost of £7488 per QALY gained compared with no treatment. In HBeAg-negative patients, peg-IFN α-2a followed by entecavir was most effective and cost-effective, with a cost of £6981 per QALY gained. The model was robust to a wide range of sensitivity analyses. Peg-IFN α-2a followed by tenofovir disoproxil fumarate or entecavir is the most effective antiviral treatment strategy for people with both variants of CHB. At a cost of less than £10,000 per QALY gained, these sequences are considered cost-effective in England and Wales. The results of this analysis were used to inform 2013 National Institute for Health and Care Excellence guideline recommendations. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

HBV serum DNA and RNA levels in nucleos(t)ide analogue-treated or untreated patients during chronic and acute infection.

PubMed

Butler, Emily K; Gersch, Jeffrey; McNamara, Anne; Luk, Ka-Cheung; Holzmayer, Vera; de Medina, Maria; Schiff, Eugene; Kuhns, Mary; Cloherty, Gavin A

2018-05-07

Treatment of chronic hepatitis B (CHB) patients with nucleos(t)ide analogues (NA) suppresses HBV DNA synthesis but does not affect synthesis of HBV pregenomic RNA (pgRNA). HBV pgRNA is detectable in the serum during NA treatment and has been proposed as a marker of HBV covalently closed circular DNA (cccDNA) activity within the infected hepatocyte. We developed an automated assay for the quantification of serum HBV pgRNA using a dual-target qRT-PCR approach on the Abbott m2000sp/rt system. We demonstrate accurate detection and quantification of serum HBV RNA. HBV DNA was quantified using the Abbott RealTime HBV viral load assay. We further compared serum nucleic acid levels and kinetics in HBV-positive populations. Samples included: on-therapy CHB samples (N=16), samples (N=89) from 10 treatment naïve CHB subjects receiving 12-weeks of NA treatment with 8-week follow-up, HBsAg-positive blood donor samples (N=102), and 3 seroconversion series from plasmapheresis donors (N=79 samples). During NA treatment of CHB subjects, we observed low correlation of HBV DNA to pgRNA levels; pgRNA concentration was generally higher than HBV DNA concentrations. In contrast, when NA treatment was absent we observed serum pgRNA at concentrations that correlated to HBV DNA and were approximately 2 log lower than HBV DNA. Importantly, we observe this trend in untreated subject samples from both chronic infections and throughout seroconversion during acute infection. Results demonstrate that the presence of pgRNA in serum is part of the HBV lifecycle; constant relative detection of pgRNA and HBV DNA in the serum is suggestive of a linked mechanism for egress for HBV DNA or pgRNA containing virions. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

Comparison of FIB-4 index and aspartate aminotransferase to platelet ratio index on carcinogenesis in chronic hepatitis B treated with entecavir.

PubMed

Nishikawa, Hiroki; Nishijima, Norihiro; Enomoto, Hirayuki; Sakamoto, Azusa; Nasu, Akihiro; Komekado, Hideyuki; Nishimura, Takashi; Kita, Ryuichi; Kimura, Toru; Iijima, Hiroko; Nishiguchi, Shuhei; Osaki, Yukio

2017-01-01

We sought to compare the effects of FIB-4 index and aspartate aminotransferase to platelet ratio index (APRI) on hepatocellular carcinoma (HCC) incidence in chronic hepatitis B (CHB) patients undergoing entecavir (ETV) therapy. A total of 338 nucleosides analogue therapy naïve CHB patients initially treated with ETV were analyzed. The optimal cutoff points in each continuous variable were determined by receiver operating curve (ROC) analysis. The effects of FIB-4 index and APRI on HCC incidence were compared using time-dependent ROC analysis and factors linked to HCC incidence were also examined using univariate and multivariate analyses. There were 215 males and 123 females with the median age of 52 years and the median baseline HBV-DNA level of 6.6 log copies/ml. The median follow-up interval after the initiation of ETV therapy was 4.99 years. During the follow-up period, 33 patients (9.8%) developed HCC. The 3-, 5- 7-year cumulative HCC incidence rates in all cases were 4.4%, 9.2% and 13.5%, respectively. In the multivariate analysis, FIB-4 index revealed to be an independent predictor associated with HCC incidence, while APRI was not. In the time-dependent ROC analyses for all cases and for all subgroups analyses stratified by viral status or cirrhosis status, all area under the ROCs in each time point (2-, 3-, 4-, 5-, 6-, and 7-year) of FIB-4 index were higher than those of APRI. FIB-4 index rather than APRI can be a useful predictor associated with HCC development for CHB patients undergoing ETV therapy.

Management of Chronic Hepatitis B Infection in India.

PubMed

Amarapurkar, Deepak N; Mada, Kaushal; Kapoor, Dharmesh

2015-11-01

Chronic hepatitis B (CHB) infection is a substantial global health problem with highest prevalence observed in the sub-Saharan Africa and East Asia. India lies in the intermediate endemicity zone with prevalence ranging from 0.1% to 11.7%. The predominant route of transmission is horizontal and the most commonly occurring genotypes are A and D. The high mortality and morbidity associated with CHB constitutes significant health and economic burden in developing countries like India. Antiviral agents decrease HBV DNA load and prevent disease progression. Several regional and country expert associations have developed treatment guidelines for appropriate management of CHB; however, various factors like prevalence, disease awareness, immunization status, cost implications, availability of resources, type of transmission and emerging significance of HBV genotypes have influenced the management of CHB in a country. This article focuses on expert’s recommendations on CHB management including initiation, monitoring and termination of treatment with emphasis on borderline cases. The article also throws light on the challenges to optimum management and provides preferred therapeutic approaches in Indian perspective.

The Core Subunit of A Chromatin-Remodeling Complex, ZmCHB101, Plays Essential Roles in Maize Growth and Development.

PubMed

Yu, Xiaoming; Jiang, Lili; Wu, Rui; Meng, Xinchao; Zhang, Ai; Li, Ning; Xia, Qiong; Qi, Xin; Pang, Jinsong; Xu, Zheng-Yi; Liu, Bao

2016-12-05

ATP-dependent chromatin remodeling complexes play essential roles in the regulation of diverse biological processes by formulating a DNA template that is accessible to the general transcription apparatus. Although the function of chromatin remodelers in plant development has been studied in A. thaliana, how it affects growth and development of major crops (e.g., maize) remains uninvestigated. Combining genetic, genomic and bioinformatic analyses, we show here that the maize core subunit of chromatin remodeling complex, ZmCHB101, plays essential roles in growth and development of maize at both vegetative and reproductive stages. Independent ZmCHB101 RNA interference plant lines displayed abaxially curling leaf phenotype due to increase of bulliform cell numbers, and showed impaired development of tassel and cob. RNA-seq-based transcriptome profiling revealed that ZmCHB101 dictated transcriptional reprogramming of a significant set of genes involved in plant development, photosynthesis, metabolic regulation, stress response and gene expressional regulation. Intriguingly, we found that ZmCHB101 was required for maintaining normal nucleosome density and 45 S rDNA compaction. Our findings suggest that the SWI3 protein, ZmCHB101, plays pivotal roles in maize normal growth and development via regulation of chromatin structure.

Solution structure of the IIAChitobiose-IIBChitobiose complex of the N,N'-diacetylchitobiose branch of the Escherichia coli phosphotransferase system.

PubMed

Jung, Young-Sang; Cai, Mengli; Clore, G Marius

2010-02-05

The solution structure of the IIA-IIB complex of the N,N'-diacetylchitobiose (Chb) transporter of the Escherichia coli phosphotransferase system has been solved by NMR. The active site His-89 of IIA(Chb) was mutated to Glu to mimic the phosphorylated state and the active site Cys-10 of IIB(Chb) was substituted by serine to prevent intermolecular disulfide bond formation. Binding is weak with a K(D) of approximately 1.3 mm. The two complementary interaction surfaces are largely hydrophobic, with the protruding active site loop (residues 9-16) of IIB(Chb) buried deep within the active site cleft formed at the interface of two adjacent subunits of the IIA(Chb) trimer. The central hydrophobic portion of the interface is surrounded by a ring of polar and charged residues that provide a relatively small number of electrostatic intermolecular interactions that serve to correctly align the two proteins. The conformation of the active site loop in unphosphorylated IIB(Chb) is inconsistent with the formation of a phosphoryl transition state intermediate because of steric hindrance, especially from the methyl group of Ala-12 of IIB(Chb). Phosphorylation of IIB(Chb) is accompanied by a conformational change within the active site loop such that its path from residues 11-13 follows a mirror-like image relative to that in the unphosphorylated state. This involves a transition of the phi/psi angles of Gly-13 from the right to left alpha-helical region, as well as smaller changes in the backbone torsion angles of Ala-12 and Met-14. The resulting active site conformation is fully compatible with the formation of the His-89-P-Cys-10 phosphoryl transition state without necessitating any change in relative translation or orientation of the two proteins within the complex.

Maternal predictive factors for fetal congenital heart block in pregnant mothers positive for anti-SS-A antibodies.

PubMed

Tsuboi, Hiroto; Sumida, Takayuki; Noma, Hisashi; Yamagishi, Kazumasa; Anami, Ai; Fukushima, Kotaro; Horigome, Hitoshi; Maeno, Yasuki; Kishimoto, Mitsumasa; Takasaki, Yoshinari; Nakayama, Masahiro; Waguri, Masako; Sago, Haruhiko; Murashima, Atsuko

2016-07-01

To determine the maternal predictive factors for fetal congenital heart block (CHB) in pregnancy in mothers positive for anti-SS-A antibodies. The Research Team for Surveillance of Autoantibody-Exposed Fetuses and Treatment of Neonatal Lupus Erythematosus, the Research Program of the Japan Ministry of Health, Labor and Welfare, performed a national survey on pregnancy of mothers positive for anti-SS-A antibodies. We analyzed 635 pregnant mothers who tested positive for anti-SS-A antibodies before conception but had no previous history of fetal CHB. We performed univariate and multivariate analysis (models 1, 2, and 3 using different set of independent variables) investigated the relation between risk of fetal CHB and maternal clinical features. Of the 635 pregnant mothers, fetal CHB was detected in 16. Univariate analysis showed that fetal CHB associated with use of corticosteroids before conception (OR 3.72, p = 0.04), and negatively with use of corticosteroids (equivalent doses of prednisolone (PSL), at ≥10 mg/day) after conception before 16-week gestation (OR 0.17, p = 0.03). In multivariate analysis, model 1 identified the use of corticosteroids before conception (OR 4.28, p = 0.04) and high titer of anti-SS-A antibodies (OR 3.58, p = 0.02) as independent and significant risk factors, and model 3 identified use of corticosteroids (equivalent doses of PSL, at ≥10 mg/day) after conception before 16-week gestation as independent protective factor against the development of fetal CHB (OR 0.16, p = 0.03). Other maternal clinical features did not influence the development of fetal CHB. The results identified high titers of anti-SS-A antibodies and use of corticosteroids before conception as independent risk factors, and use of corticosteroids (equivalent doses of PSL, at ≥10 mg/day) after conception before 16-week gestation as an independent protective factor for fetal CHB.

Quantitative assessment of hepatic fibrosis in chronic hepatitis B and C: T1 mapping on Gd-EOB-DTPA-enhanced liver magnetic resonance imaging.

PubMed

Pan, Shen; Wang, Xiao-Qi; Guo, Qi-Yong

2018-05-14

To assess the accuracy of Look-Locker on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for staging liver fibrosis in chronic hepatitis B/C (CHB/C). We prospectively included 109 patients with CHB or CHC who underwent a 3.0-Tesla MRI examination, including T1-weighted and Look-Locker sequences for T1 mapping. Hepatocyte fractions (HeF) and relaxation time reduction rate (RE) were measured for staging liver fibrosis. A receiver operating characteristic analysis using the area under the receiver operating characteristic curve (AUC) was used to compare the diagnostic performance in predicting liver fibrosis between HeF and RE. A total of 73 patients had both pathological results and MRI information. The number of patients in each fibrosis stage was evaluated semiquantitatively according to the METAVIR scoring system: F0, n = 23 (31.5%); F1, n = 19 (26.0%); F2, n = 13 (17.8%); F3, n = 6 (8.2%), and F4, n = 12 (16.4%). HeF by EOB enhancement imaging was significantly correlated with fibrosis stage ( r = -0.808, P < 0.05). AUC values for diagnosis of any (≥ F1), significant (≥ F2) or advanced (≥ F3) fibrosis, and cirrhosis (F4) using HeF were 0.837 (0.733-0.913), 0.890 (0.795-0.951), 0.957 (0.881-0.990), and 0.957 (0.882-0.991), respectively. HeF measurement was more accurate than use of RE in establishing liver fibrosis staging, suggesting that calculation of HeF is a superior noninvasive liver fibrosis staging method. A T1 mapping-based HeF method is an efficient diagnostic tool for the staging of liver fibrosis.

Prevalence and genotype distribution of hepatitis delta virus among chronic hepatitis B carriers in Central Vietnam

PubMed Central

Trung, Nguyen Thanh; Hoan, Nghiem Xuan; Wedemeyer, Heiner; Velavan, Thirumalaisamy P.

2017-01-01

Hepatitis D virus (HDV) infection plays an important role in liver diseases. However, the molecular epidemiology and impact of HDV infection in chronic hepatitis B (CHB) remain uncertain in Vietnam. This cross-sectional study aimed to investigate the prevalence and genotype distribution of HDV among HBsAg-positive patients in Central Vietnam. 250 CHB patients were tested for HDV using newly established HDV-specific RT-PCR techniques. HDV genotypes were determined by direct sequencing. Of the 250 patients 25 (10%) had detectable copies of HDV viral RNA. HDV-2 was predominant (20/25; 80%) followed by HDV-1 (5/25; 20%). Proven HDV genotypes share the Asian nomenclature. Chronic hepatitis B patients with concomitant HDV-1 showed higher HBV loads as compared to HDV-2 infected patients [median log10 (HBV-DNA copies/ml): 8.5 vs. 4.4, P = 0.036]. Our findings indicate that HDV infection is highly prevalent and HDV-2 is predominant in Central Vietnam. The data will add new information to the management of HBsAg-positive patients in a highly HBV endemic region to in- or exclude HDV infection in terms of diagnostic and treatment options. PMID:28403190

qFibrosis: A fully-quantitative innovative method incorporating histological features to facilitate accurate fibrosis scoring in animal model and chronic hepatitis B patients

PubMed Central

Tai, Dean C.S.; Wang, Shi; Cheng, Chee Leong; Peng, Qiwen; Yan, Jie; Chen, Yongpeng; Sun, Jian; Liang, Xieer; Zhu, Youfu; Rajapakse, Jagath C.; Welsch, Roy E.; So, Peter T.C.; Wee, Aileen; Hou, Jinlin; Yu, Hanry

2014-01-01

Background & Aims There is increasing need for accurate assessment of liver fibrosis/cirrhosis. We aimed to develop qFibrosis, a fully-automated assessment method combining quantification of histopathological architectural features, to address unmet needs in core biopsy evaluation of fibrosis in chronic hepatitis B (CHB) patients. Methods qFibrosis was established as a combined index based on 87 parameters of architectural features. Images acquired from 25 Thioacetamide-treated rat samples and 162 CHB core biopsies were used to train and test qFibrosis and to demonstrate its reproducibility. qFibrosis scoring was analyzed employing Metavir and Ishak fibrosis staging as standard references, and collagen proportionate area (CPA) measurement for comparison. Results qFibrosis faithfully and reliably recapitulates Metavir fibrosis scores, as it can identify differences between all stages in both animal samples (p <0.001) and human biopsies (p <0.05). It is robust to sampling size, allowing for discrimination of different stages in samples of different sizes (area under the curve (AUC): 0.93–0.99 for animal samples: 1–16 mm2; AUC: 0.84–0.97 for biopsies: 10–44 mm in length). qFibrosis can significantly predict staging underestimation in suboptimal biopsies (<15 mm) and under- and over-scoring by different pathologists (p <0.001). qFibrosis can also differentiate between Ishak stages 5 and 6 (AUC: 0.73, p = 0.008), suggesting the possibility of monitoring intra-stage cirrhosis changes. Best of all, qFibrosis demonstrates superior performance to CPA on all counts. Conclusions qFibrosis can improve fibrosis scoring accuracy and throughput, thus allowing for reproducible and reliable analysis of efficacies of anti-fibrotic therapies in clinical research and practice. PMID:24583249

Analysis of East Asia Genetic Substructure Using Genome-Wide SNP Arrays

PubMed Central

Tian, Chao; Kosoy, Roman; Lee, Annette; Ransom, Michael; Belmont, John W.; Gregersen, Peter K.; Seldin, Michael F.

2008-01-01

Accounting for population genetic substructure is important in reducing type 1 errors in genetic studies of complex disease. As efforts to understand complex genetic disease are expanded to different continental populations the understanding of genetic substructure within these continents will be useful in design and execution of association tests. In this study, population differentiation (Fst) and Principal Components Analyses (PCA) are examined using >200 K genotypes from multiple populations of East Asian ancestry. The population groups included those from the Human Genome Diversity Panel [Cambodian, Yi, Daur, Mongolian, Lahu, Dai, Hezhen, Miaozu, Naxi, Oroqen, She, Tu, Tujia, Naxi, Xibo, and Yakut], HapMap [ Han Chinese (CHB) and Japanese (JPT)], and East Asian or East Asian American subjects of Vietnamese, Korean, Filipino and Chinese ancestry. Paired Fst (Wei and Cockerham) showed close relationships between CHB and several large East Asian population groups (CHB/Korean, 0.0019; CHB/JPT, 00651; CHB/Vietnamese, 0.0065) with larger separation with Filipino (CHB/Filipino, 0.014). Low levels of differentiation were also observed between Dai and Vietnamese (0.0045) and between Vietnamese and Cambodian (0.0062). Similarly, small Fst's were observed among different presumed Han Chinese populations originating in different regions of mainland of China and Taiwan (Fst's <0.0025 with CHB). For PCA, the first two PC's showed a pattern of relationships that closely followed the geographic distribution of the different East Asian populations. PCA showed substructure both between different East Asian groups and within the Han Chinese population. These studies have also identified a subset of East Asian substructure ancestry informative markers (EASTASAIMS) that may be useful for future complex genetic disease association studies in reducing type 1 errors and in identifying homogeneous groups that may increase the power of such studies. PMID:19057645

Chinese medicine for treatment of chronic hepatitis B.

PubMed

Wang, Guqi; Zhang, Lingyi; Bonkovsky, Herbert L

2012-04-01

Contemporary Western medicines approved by the U.S. Food and Drug Administration (FDA) for the treatment of chronic hepatitis B (CHB), although available in China, have high costs, or major side effects and limited effectiveness. Research efforts have focused on looking for natural products as alternative medicines with low cost and good safety for CHB treatment. Chinese medicine (CM) has ancient, time-honored theories about methods of diagnosis and treatment for liver diseases. In recent decades, a large number of clinical trials and pre-clinical studies, which were performed in China and other countries, indicated that CM has potential benefit in several aspects of the treatment of CHB, e.g., anti-inflammatory, anticancer, antioxidant, immunomodulating, antifibrosis, and antiviral. However, there are many concerns regarding the study design and the quality of clinical trials. Further larger, stringently designed, double-blind, placebo control, randomized clinical trials and long-term follow-up are needed to provide conclusive evidence of their efficacy and safety. Components of CM deserve further study in pre-clinical models of HBV infection and in clinical trials world-wide.

The clinical spectrum of autoimmune congenital heart block

PubMed Central

Brito-Zerón, Pilar; Izmirly, Peter M.; Ramos-Casals, Manuel; Buyon, Jill P.; Khamashta, Munther A.

2017-01-01

Autoimmune congenital heart block (CHB) is an immune-mediated acquired disease that is associated with the placental transference of maternal antibodies specific for Ro and La autoantigens. The disease develops in a fetal heart without anatomical abnormalities that could otherwise explain the block, and which is usually diagnosed in utero, but also at birth or within the neonatal period. Autoantibody-mediated damage of fetal conduction tissues causes inflammation and fibrosis and leads to blockage of signal conduction at the atrioventricular (AV) node. Irreversible complete AV block is the principal cardiac manifestation of CHB, although some babies might develop other severe cardiac complications, such as endocardial fibroelastosis or valvular insufficiency, even in the absence of cardiac block. In this Review, we discuss the epidemiology, classification and management of women whose pregnancies are affected by autoimmune CHB, with a particular focus on the autoantibodies associated with autoimmune CHB and how we should test for these antibodies and diagnose this disease. Without confirmed effective preventive or therapeutic strategies and further research on the aetiopathogenic mechanisms, autoimmune CHB will remain a severe life-threatening disorder. PMID:25800217

Fatal lactic acidosis in hepatitis B virus-associated decompensated cirrhosis treated with tenofovir: A case report.

PubMed

Jung, Tae Yang; Jun, Dae Won; Lee, Kang Nyeong; Lee, Hang Lak; Lee, Oh Young; Yoon, Byung Chul; Choi, Ho Soon

2017-06-01

Recently tenofovir disoproxil fumarate (TDF) has been widely used as a first-line therapy for chronic hepatitis B (CHB) infection. Although TDF demonstrates successful viral suppression, the possibility of renal failure and lactic acidosis has been proposed with TDF administration, especially in human immunodeficiency virus co-infected patients. However, TDF induced lactic acidosis has never been reported in CHB mono-infected patients. A 59-year-old man received TDF for hepatitis B associated with cirrhosis. After ten days of TDF administration, nausea, vomiting and abdominal pain developed. High anion gap acidosis with elevated lactate level (pH 7.341, pCO2 29.7 mmHg, HCO3- 15.6mmHg, lactate 3.2mmol/L, anion gap 15.4 mEq/L) was developed. With no infection, normal diagnostic paracentesis, and urinalysis together with high anion gap and increased blood lactate levels suggested lactic acidosis. TDF was stopped, and haemodialysis was performed to control lactic acidosis. Although stopping TDF instantly and treating lactic acidosis using hemodialysis, the patient died. Although, Fatal lactic acidosis is very rare in TDF patient, however, decompensated cirrhotic patients should be closely observed to keep the possibility of lactic acidosis in mind.

Relationship between virological response and FIB-4 index in chronic hepatitis B patients with entecavir therapy

PubMed Central

Li, Ni; Xu, Jing-Hang; Yu, Min; Wang, Sa; Si, Chong-Wen; Yu, Yan-Yan

2015-01-01

AIM: To investigate whether long-term low-level hepatitis B virus (HBV) DNA influences dynamic changes of the FIB-4 index in chronic hepatitis B (CHB) patients receiving entecavir (ETV) therapy with partial virological responses. METHODS: We retrospectively analyzed 231 nucleos(t)ide (NA) naïve CHB patients from our previous study (NCT01926288) who received continuous ETV or ETV maleate therapy for three years. The patients were divided into partial virological response (PVR) and complete virological response (CVR) groups according to serum HBV DNA levels at week 48. Seventy-six patients underwent biopsies at baseline and at 48 wk. The performance of the FIB-4 index and area under the receiver operating characteristic (AUROC) curve for predicting fibrosis were determined for the patients undergoing biopsy. The primary objective of the study was to compare the cumulative probabilities of virological responses between the two groups during the treatment period. The secondary outcome was to observe dynamic changes of the FIB-4 index between CVR patients and PVR patients. RESULTS: For hepatitis B e antigen (HBeAg)-positive patients (n = 178), the cumulative probability of achieving undetectable levels at week 144 was 95% and 69% for CVR and PVR patients, respectively (P < 0.001). In the Cox proportional hazards model, a lower pretreatment serum HBV DNA level was an independent factor predicting maintained viral suppression. The cumulative probability of achieving undetectable levels of HBV DNA for HBeAg-negative patients (n = 53) did not differ between the two groups. The FIB-4 index efficiently identified fibrosis, with an AUROC of 0.80 (95%CI: 0.69-0.89). For HBeAg-positive patients, the FIB-4 index was higher in CVR patients than in PVR patients at baseline (1.89 ± 1.43 vs 1.18 ± 0.69, P < 0.001). There was no significant difference in the reduction of the FIB-4 index between the CVR and PVR groups from weeks 48 to 144 (-0.11 ± 0.47 vs -0.13 ± 0.49, P = 0.71). At week 144, the FIB-4 index levels were similar between the two groups (1.24 ± 0.87 vs 1.02 ± 0.73, P = 0.06). After multivariate logistic regression analysis, a lower baseline serum HBV DNA level was associated with improvement of liver fibrosis. In HBeAg-negative patients, the FIB-4 index did not differ between the two groups. CONCLUSION: The cumulative probabilities of HBV DNA responses showed significant differences between CVR and PVR HBeAg-positive CHB patients undergoing entecavir treatment for 144 wk. However, long-term low-level HBV DNA did not deteriorate the FIB-4 index, which was used to evaluate liver fibrosis, at the end of three years. PMID:26604649

Novel HBV recombinants between genotypes B and C in 3'-terminal reverse transcriptase (RT) sequences are associated with enhanced viral DNA load, higher RT point mutation rates and place of birth among Chinese patients.

PubMed

Liu, Baoming; Yang, Jing-Xian; Yan, Ling; Zhuang, Hui; Li, Tong

2018-01-01

As one of the major global public health concerns, hepatitis B virus (HBV) can be divided into at least eight genotypes, which may be related to disease severity and treatment response. We previously demonstrated that genotypes B and C HBV, with distinct geographical distribution in China, had divergent genotype-dependent amino acid polymorphisms and variations in reverse transcriptase (RT) gene region, a target of antiviral therapy using nucleos(t)ide analogues. Recently recombination between HBV genotypes B and C was reported to occur in the RT region. However, their frequency and clinical significance is poorly understood. Here full-length HBV RT sequences from 201 Chinese chronic hepatitis B (CHB) patients were amplified and sequenced, among which 31.34% (63/201) were genotype B whereas 68.66% (138/201) genotype C. Although no intergenotypic recombination was detected among C-genotype HBV, 38.10% (24/63) of B-genotype HBV had recombination with genotype C in the 3'-terminal RT sequences. The patients with B/C intergenotypic recombinants had significantly (P<0.05) higher serum HBV DNA level than the "pure" B-genotype cohort did. Moreover, the B/C intergenotypic recombinants were prone to more substitutions at several specific residues in the RT region than genotype B or C. Besides, unlike their parental genotypes, the recombinant HBV appeared to display an altered geographic distribution feature in China. Our findings provide novel insight into the virological, clinical and epidemiological features of new HBV B/C intergenotypic recombinants at the 3' end of RT sequences among Chinese CHB patients. The highly complex genetic background of the novel recombinant HBV carrying new mutations affecting RT protein may contribute to an enhanced heterogeneity in treatment response or prognosis among CHB patients. Published by Elsevier B.V.

Naturally occurring deletions/insertions in HBV core promoter tend to decrease in hepatitis B e antigen-positive chronic hepatitis B patients during antiviral therapy.

PubMed

Peng, Yaqin; Liu, Baoming; Hou, Jinlin; Sun, Jian; Hao, Ran; Xiang, Kuanhui; Yan, Ling; Zhang, Jiangbo; Zhuang, Hui; Li, Tong

2015-01-01

Mutations in HBV core promoter (CP) are suggested to affect viral replication and disease progression. We investigated CP deletion/insertion mutations (Del/Ins) in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients before and during antiviral treatment. Direct and clone sequencings were used for detection of CP Del/Ins in 12 patients. The dynamic changes of CP Del/Ins were tracked in these cases until week 48 of treatment. The effects of Del/Ins on CP activities and hepatitis B X protein (HBx) were analysed using luciferase assay and sequence comparison, respectively. Furthermore, 292 untreated HBeAg-positive CHB cases were also analysed. Twelve cases with multi-peak PCR direct sequencing electropherograms at baseline were confirmed to have CP Del/Ins by clone sequencing, with detection rates varying from 14.8% to 93.3% of clones analysed. Follow-up studies showed the detection rates of CP Del/Ins in patients decreased from 100% (12/12) at baseline to 16.7% (2/12) at week 48 of treatment (P<0.001), in parallel with a decline in HBV DNA, hepatitis B surface antigen (HBsAg), alanine aminotransferase (ALT) and aspartate transaminase (AST) levels along with an increase in HBeAg loss. Luciferase assay results showed distinct promoter activities among Del/Ins-harbouring CP sequences. Importantly, 71.8% (148/206) of Del/Ins sequences potentially resulted in HBx carboxy-terminal truncations. CP Del/Ins mutations were also found in 27.4% (80/292) of untreated cases. Naturally occurring complex of CP Del/Ins mutants existed in untreated HBeAg-positive CHB patients. These mutations would affect HBV transcription activities and integrity of HBx, which might correlate with disease progression. Their prevalence decreases on antiviral therapy in parallel with the decline in HBV DNA, HBsAg and ALT and AST levels.

Detection of Hepatitis B Virus DNA among Chronic and potential Occult HBV patients in resource-limited settings by Loop-Mediated Isothermal Amplification assay.

PubMed

Akram, Arifa; Islam, S M Rashedul; Munshi, Saif Ullah; Tabassum, Shahina

2018-05-16

Transmission of Hepatitis B Virus (HBV) usually occurs due to the transfusion of blood or blood products from chronic HBV (CHB) or occult HBV infected (OBI) patients. Besides serological tests e.g. HBsAg and anti-HBc (total), detection of HBV-DNA is necessary for the diagnosis of OBI patients. Different nucleic acid tests (NATs) including real-time-Polymerase Chain Reaction (qPCR) are used for the detect HBV-DNA. The NATs are expensive and require technical expertise which are barriers to introducing them in resource-limited settings. This study was undertaken to evaluate the use of Loop-Mediated Isothermal Amplification (LAMP) assay as an alternative to qPCR for the detection of HBV-DNA in CHB and potential OBI patients in resource-limited settings. Following the published protocols with some modifications, a LAMP assay was developed for detection of HBV-DNA by either using a heat block followed by detection in an agarose gel or using a qPCR thermocycler. The LAMP assay was applied to supernatant prepared from heat treated serum collected from CHB and potential OBI patients. HBV viral load in serum was measured by qPCR using a single step HBV-DNA quantification kit. Among 200 samples tested, qPCR was capable to detect HBV-DNA in 25.5% of cases, whereas LAMP assay detected HBV-DNA in 43.5% cases. The qPCR was able to detect 11 (9.16%) potential OBI cases, whereas LAMP assay identified HBV-DNA in 43 (35.83%) cases. In addition to tests for HBsAg and/or anti-HBc (total), detection of HBV-DNA by LAMP assay may aid in preventing post-transfusion HBV infection in resource-limited settings. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Association of human leukocyte antigen polymorphism with outcomes of hepatitis B virus infection.

PubMed

Ramezani, Amitis; Hasanjani Roshan, Mohammad Reza; Kalantar, Ebrahim; Eslamifar, Ali; Banifazl, Mohammad; Taeb, Jaleh; Aghakhani, Arezoo; Gachkar, Latif; Velayati, Ali Akbar

2008-11-01

Host genetic and environmental factors are viewed as a common basis of the different outcomes of hepatitis B virus (HBV) infection. Human leukocyte antigen (HLA) plays an important role in immunological reaction to HBV infection. In this study, we aimed to determine the association between HBV infection and HLA-A, B, and DRB1 alleles in northern Iran. HLA-A, B, and DRB1 alleles in 33 patients with chronic hepatitis B (CHB) and 31 healthy carriers as the persistent group, and 30 subjects who had spontaneously recovered from HBV infection were analyzed by using the polymerase chain reaction (PCR)-sequence-specific primer (PCR-SSP) technique. The frequency of the HLA-A*33 allele was higher in the persistent group than in the recovered group (10.16% vs 0%, P < 0.008); the frequency of the DRB1*13 allele was lower in the persistent group than in the recovered group (3.13% vs 11.67%, P < 0.03). The frequency of the B*52 allele was higher in CHB patients than healthy carriers (7.58% vs 0%, P < 0.05). The logistic regression model showed that the presence of the HLA-DRB1*13 allele was the significant factor associated with protection against the persistency of HBV. There were significant differences between the HBV recovered group, CHB patients, and healthy carriers regarding age, hepatitis B e antigen, and anti-hepatitis B e positivity. HLA-A*33 was closely related with susceptibility to persisting hepatitis B infection, and HLA-DRB1*13 was closely related with protection against persisting hepatitis B in an Iranian population. These findings emphasized that the host HLA polymorphism is an important factor in determining the outcome of HBV infection.

Non-invasive tests in prediction of liver fibrosis in chronic hepatitis B and comparison with post-antiviral treatment results.

PubMed

Başar, Omer; Yimaz, Bariş; Ekiz, Fuat; Giniş, Zeynep; Altinbaş, Akif; Aktaş, Bora; Tuna, Yaşar; Çoban, Sahin; Delibaş, Namik; Yüksel, Osman

2013-04-01

The aim of this study was to assess and compare the performance of a series of non-invasive tests to detect fibrosis in patients with chronic hepatitis B (CHB). Seventy-six patients with CHB, whose blood samples were collected and biopsies were done on the same day, were included in this study. Pre-treatment calculations of aspartate aminotransferase to platelet ratio index (APRI), Forn's index, FIB-4, S-index, Shanghai Liver Fibrosis Group's index (SLFG) and Hepascore(®) were done and relations with mild and advanced fibrosis and cirrhosis were assessed. Post-treatment values of APRI, Forn's index, FIB-4, S-index with oral antiviral agents were also investigated. APRI, S-index, SLFG, FIB-4, Forn's index and Hepascore(®) had 0.669, 0.669, 0.739, 0.741, 0.753, 0.780; retrospectively Area Under the Receiver Operating Characteristic Curve (AUROC) for significant fibrosis. APRI, Forn's index, S-index, FIB-4, SLFG, and Hepascore(®) had 0.681, 0.714, 0.715, 0.738, 0.747, 0.777 retrospectively AUROC for advanced fibrosis. APRI, SLFG, FIB-4, Forn's index, S-index, and Hepascore(®) had 0.741, 0.742, 0.768, 0.779, 0.792, 0.824 retrospectively AUROC for cirrhosis. APRI, Forn's index, FIB-4 and S-index were significantly lower in post-treatment group compared with pre-treatment group (P-values: <0.05, 0.001, 0.003, 0.018; respectively). Hepascore(®) showed the best performance to predict significant fibrosis. Our study also suggests that the use of non-invasive test to predict fibrosis in patients with CHB may reduce the need for liver biopsy and may help to monitor the efficacy of treatment. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Then and now: The progress in hepatitis B treatment over the past 20 years

PubMed Central

Halegoua-De Marzio, Dina; Hann, Hie-Won

2014-01-01

The ultimate goals of treating chronic hepatitis B (CHB) is prevention of hepatocellular carcinoma (HCC) and hepatic decompensation. Since the advent of effective antiviral drugs that appeared during the past two decades, considerable advances have been made not only in controlling hepatitis B virus (HBV) infection, but also in preventing and reducing the incidence of liver cirrhosis and HCC. Furthermore, several recent studies have suggested the possibility of reducing the incidence of recurrent or new HCC in patients even after they have developed HCC. Currently, six medications are available for HBV treatment including, interferon and five nucleoside/nucleotide analogues. In this review, we will examine the antiviral drugs and the progresses that have been made with antiviral treatments in the field of CHB. PMID:24574709

Then and now: the progress in hepatitis B treatment over the past 20 years.

PubMed

Halegoua-De Marzio, Dina; Hann, Hie-Won

2014-01-14

The ultimate goals of treating chronic hepatitis B (CHB) is prevention of hepatocellular carcinoma (HCC) and hepatic decompensation. Since the advent of effective antiviral drugs that appeared during the past two decades, considerable advances have been made not only in controlling hepatitis B virus (HBV) infection, but also in preventing and reducing the incidence of liver cirrhosis and HCC. Furthermore, several recent studies have suggested the possibility of reducing the incidence of recurrent or new HCC in patients even after they have developed HCC. Currently, six medications are available for HBV treatment including, interferon and five nucleoside/nucleotide analogues. In this review, we will examine the antiviral drugs and the progresses that have been made with antiviral treatments in the field of CHB.

Analysis of hepatitis B virus preS1 variability and prevalence of the rs2296651 polymorphism in a Spanish population

PubMed Central

Casillas, Rosario; Tabernero, David; Gregori, Josep; Belmonte, Irene; Cortese, Maria Francesca; González, Carolina; Riveiro-Barciela, Mar; López, Rosa Maria; Quer, Josep; Esteban, Rafael; Buti, Maria; Rodríguez-Frías, Francisco

2018-01-01

AIM To determine the variability/conservation of the domain of hepatitis B virus (HBV) preS1 region that interacts with sodium-taurocholate cotransporting polypeptide (hereafter, NTCP-interacting domain) and the prevalence of the rs2296651 polymorphism (S267F, NTCP variant) in a Spanish population. METHODS Serum samples from 246 individuals were included and divided into 3 groups: patients with chronic HBV infection (CHB) (n = 41, 73% Caucasians), patients with resolved HBV infection (n = 100, 100% Caucasians) and an HBV-uninfected control group (n = 105, 100% Caucasians). Variability/conservation of the amino acid (aa) sequences of the NTCP-interacting domain, (aa 2-48 in viral genotype D) and a highly conserved preS1 domain associated with virion morphogenesis (aa 92-103 in viral genotype D) were analyzed by next-generation sequencing and compared in 18 CHB patients with viremia > 4 log IU/mL. The rs2296651 polymorphism was determined in all individuals in all 3 groups using an in-house real-time PCR melting curve analysis. RESULTS The HBV preS1 NTCP-interacting domain showed a high degree of conservation among the examined viral genomes especially between aa 9 and 21 (in the genotype D consensus sequence). As compared with the virion morphogenesis domain, the NTCP-interacting domain had a smaller proportion of HBV genotype-unrelated changes comprising > 1% of the quasispecies (25.5% vs 31.8%), but a larger proportion of genotype-associated viral polymorphisms (34% vs 27.3%), according to consensus sequences from GenBank patterns of HBV genotypes A to H. Variation/conservation in both domains depended on viral genotype, with genotype C being the most highly conserved and genotype E the most variable (limited finding, only 2 genotype E included). Of note, proline residues were highly conserved in both domains, and serine residues showed changes only to threonine or tyrosine in the virion morphogenesis domain. The rs2296651 polymorphism was not detected in any participant. CONCLUSION In our CHB population, the NTCP-interacting domain was highly conserved, particularly the proline residues and essential amino acids related with the NTCP interaction, and the prevalence of rs2296651 was low/null. PMID:29456407

Inferring the Joint Demographic History of Multiple Populations from Multidimensional SNP Frequency Data

PubMed Central

Gutenkunst, Ryan N.; Hernandez, Ryan D.; Williamson, Scott H.; Bustamante, Carlos D.

2009-01-01

Demographic models built from genetic data play important roles in illuminating prehistorical events and serving as null models in genome scans for selection. We introduce an inference method based on the joint frequency spectrum of genetic variants within and between populations. For candidate models we numerically compute the expected spectrum using a diffusion approximation to the one-locus, two-allele Wright-Fisher process, involving up to three simultaneous populations. Our approach is a composite likelihood scheme, since linkage between neutral loci alters the variance but not the expectation of the frequency spectrum. We thus use bootstraps incorporating linkage to estimate uncertainties for parameters and significance values for hypothesis tests. Our method can also incorporate selection on single sites, predicting the joint distribution of selected alleles among populations experiencing a bevy of evolutionary forces, including expansions, contractions, migrations, and admixture. We model human expansion out of Africa and the settlement of the New World, using 5 Mb of noncoding DNA resequenced in 68 individuals from 4 populations (YRI, CHB, CEU, and MXL) by the Environmental Genome Project. We infer divergence between West African and Eurasian populations 140 thousand years ago (95% confidence interval: 40–270 kya). This is earlier than other genetic studies, in part because we incorporate migration. We estimate the European (CEU) and East Asian (CHB) divergence time to be 23 kya (95% c.i.: 17–43 kya), long after archeological evidence places modern humans in Europe. Finally, we estimate divergence between East Asians (CHB) and Mexican-Americans (MXL) of 22 kya (95% c.i.: 16.3–26.9 kya), and our analysis yields no evidence for subsequent migration. Furthermore, combining our demographic model with a previously estimated distribution of selective effects among newly arising amino acid mutations accurately predicts the frequency spectrum of nonsynonymous variants across three continental populations (YRI, CHB, CEU). PMID:19851460

Binding of anti-SSA antibodies to apoptotic fetal cardiocytes stimulates urokinase plasminogen activator (uPA)/uPA receptor-dependent activation of TGF-β and potentiates fibrosis.

PubMed

Briassouli, Paraskevi; Rifkin, Daniel; Clancy, Robert M; Buyon, Jill P

2011-11-15

In congenital heart block (CHB), binding of maternal anti-SSA/Ro Abs to fetal apoptotic cardiocytes impairs their removal by healthy cardiocytes and increases urokinase plasminogen activator (uPA)/uPA receptor (uPAR)-dependent plasmin activation. Because the uPA/uPAR system plays a role in TGF-β activation, we evaluated whether anti-Ro binding to apoptotic cardiocytes enhances plasmin-mediated activation of TGF-β, thereby promoting a profibrosing phenotype. Supernatants from cocultures of healthy cardiocytes and apoptotic cardiocytes bound by IgG from a mother whose child had CHB (apoptotic-CHB-IgG [apo-CHB-IgG]) exhibited significantly increased levels of active TGF-β compared with supernatants from cocultures of healthy cardiocytes and apoptotic cardiocytes preincubated with IgG from a healthy donor. Treatment of the culture medium with anti-TGF-β Ab or TGF-β inhibitor (SB431542) abrogated the luciferase response, thereby confirming TGF-β dependency. Increased uPA levels and activity were present in supernatants generated from cocultures of healthy cardiocytes and apo-CHB-IgG cardiocytes compared with healthy cardiocytes and apoptotic cardiocytes preincubated with IgG from a healthy donor, respectively. Treatment of apo-CHB-IgG cardiocytes with anti-uPAR or anti-uPA Abs or plasmin inhibitor aprotinin prior to coculturing with healthy cardiocytes attenuated TGF-β activation. Supernatants derived from cocultures of healthy cardiocytes and apo-CHB-IgG cardiocytes promoted Smad2 phosphorylation and fibroblast transdifferentiation, as evidenced by increased smooth muscle actin and collagen expression, which decreased when fibroblasts were treated with supernatants from cocultures pretreated with uPAR Abs. These data suggested that binding of anti-Ro Abs to apoptotic cardiocytes triggers TGF-β activation, by virtue of increasing uPAR-dependent uPA activity, thus initiating and amplifying a cascade of events that promotes myofibroblast transdifferentiation and scar.

Experimental exposure of rats to methylene chloride at varying controlled barometric altitudes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lillquist, D.R.

1990-01-01

This study investigated combined effects of three methylene chloride (MC) volume/volume concentrations (0,50, and 500 ppm) at three controlled barometric altitudes (760, 640, and 560 torr). This provided a three by three study design. For each scenario, three altitude acclimated (6 days) adult male rats were studied for eight hours in a nose-only inhalation chamber. Blood (0.35 mL) was drawn from the cannulated left carotid artery of each rat at 0, 0.5, 1, 2, 4, and 8 hours and hematocrit, pO[sub 2], pCO[sub 2], pH , total hemoglobin (Hb) and carboxyhemoglobin (CHb) were measured. Time, MC concentration and altitude hadmore » significant effects on CHb production. CHb increased with increasing MC concentration over time. Increased barometric altitude (reduced partial pressure of MC vapor at altitude for equal ppm concentrations) resulted in lower blood CHb levels. A statistical model was derived to explain variation in CHb levels for these three independent variables (r = 0.983). The data were applied to an equation assessing the impact of altitude, MC concentration and time on the potential oxygen carrying capacity (POCC) of blood. The POCC of HB in the blood was calculated using blood Hb, CHb levels, Hb oxygen saturation (based on the blood pO[sub 2] and the oxygen dissociation curve for rats), and oxygen binding potential of Hb. It was determined for the altitudes and MC concentrations used, polycythemia associated with increased altitude had a greater impact on POCC than decreased pO[sub 2]. A regression equation was derived modeling variation in POCC of blood for the three independent variables (r = 0.995). This study demonstrated that altitude affects airborne ppm MC concentrations. This ultimately impacts CHb levels and oxygen carrying capacity of the blood. These finding indicate that occupationally acceptable ppm MC exposure levels at altitude do need barometric pressure correction.« less

A mutation in the interferon regulatory element of HBV may influence the response of interferon treatment in chronic hepatitis B patients.

PubMed

Lu, Jia-Jie; Chen, En-Qiang; Yang, Jia-Hong; Zhou, Tao-You; Liu, Li; Tang, Hong

2012-01-10

A functional interferon regulatory element (IRE) has been found in the EnhI/X promoter region of hepatitis B virus (HBV) genome. The purpose of this study is to compare the gene order of responder and non-responder to interferon therapy in patients with chronic hepatitis B (CHB), so as to evaluate the relationship between IRE mutation and the response to interferon treatment for CHB patients. Synthetic therapeutic effect is divided into complete response (CR), partial response (PR) and non-response (NR). Among the 62 cases included in this study, 40 cases (64.5%) were in the response group (CR and PR) and 22 (35.5%) cases were in the NR group. Wild type sequence of HBV IRE TTTCACTTTC were found in 35 cases (56.5%), and five different IRE gene sequences. included TTTtACTTTC, TTTCAtTTTC, TTTtAtTTTC, TTTtACTTTt and cTTtACcTTC, were found in 22 cases (35.5%), 1 case (1.6%), 1 case (1.6%), 2 cases (3.2%) and 1 case (1.6%) respectively. There were 41.9%cases (26/62) with forth base C→T mutation, consisted of 32.5% (13/40) cases in response group and 59.1% (13/22) cases in NR group. Among the 35 cases with IRE sequences, there were 67.5% (27/40) cases in response group and 36.4% (8/22) in NR group, and the difference in IRE sequences between two groups was statistic significantly (P = 0.027). The result suggested that there is likely relationship between the forth base mutation (C→T) of IRE region and the response of HBV to Interferon therapy, and this mutation may partially decrease the inhibition effect of interferon on HBV. The forth base C→T mutation in IRE element of HBV may partially influence the response of Interferon treatment in CHB patients.

Assessment of liver fibrosis in chronic hepatitis: comparison of shear wave elastography and transient elastography.

PubMed

Paul, Shashi B; Das, Prasenjit; Mahanta, Mousumi; Sreenivas, Vishnubhatla; Kedia, Saurabh; Kalra, Nancy; Kaur, Harpreet; Vijayvargiya, Maneesh; Ghosh, Shouriyo; Gamanagatti, Shivanand R; Shalimar; Gupta, Siddhartha Dutta; Acharya, Subrat K

2017-12-01

To evaluate the diagnostic accuracy of shear wave elastography (SWE) and transient elastography (TE) in the evaluation of liver fibrosis in chronic hepatitis B (CHB) and C (CHC) patients taking liver biopsy as gold standard. Ethics committee approved this prospective cross-sectional study. Between October 2012 and December 2014, consecutive CHB/CHC patients fulfilling the inclusion criteria were included-age more than 18 years, informed written consent, willing and suitable for liver biopsy. SWE, TE, and biopsy were performed the same day. Liver stiffness measurement (LSM) cut-offs for various stages of fibrosis were generated for SWE and TE. AUC, sensitivity, specificity, and positive/negative predictive values were estimated individually or in combination. CH patients (n = 240, CHB 172, CHC 68), 176 males, 64 females, mean age 32.6 ± 11.6 years were enrolled. Mean LSM of patients with no histological fibrosis (F0) was 5.0 ± 0.7 and 5.1+1.4 kPa on SWE and TE, respectively. For differentiating F2 and F3-4 fibrosis on SWE, at 7.0 kPa cut-off, the sensitivity was 81.3% and specificity 77.6%. For TE, at 8.3 kPa cut-off, sensitivity was 81.8% and specificity 83.1%. For F3 vs. F4, SWE sensitivity was 83.3% and specificity 90.7%. At 14.8 kPa cut-off, TE showed similar sensitivity (83.3%) but specificity increased to 96.5%. Significant correlation between SWE and TE was observed (r = 0.33, p < 0.001). On combining SWE and TE, a drop in sensitivity with increased specificity for all stages of liver fibrosis occured. SWE is an accurate technique for evaluating liver fibrosis. SWE compares favorably with TE especially for predicting advanced fibrosis/cirrhosis. Combining SWE and TE further improves specificity.

Modulation of Haemonchus contortus infection by depletion of γδ+ T cells in parasite resistant Canaria Hair Breed sheep.

PubMed

Hernández, Julia N; Meeusen, Els; Stear, Michael; Rodríguez, Francisco; Piedrafita, David; González, Jorge F

2017-04-15

Canaria Hair Breed (CHB) sheep display resistance against the adult stage of the nematode, Haemonchus contortus. Previous studies have suggested significant correlations between γδ + T lymphocytes and fecundity of female adult worms, suggesting a novel role in immune modulation by these cells. The largest proportion of γδ + T lymphocytes in sheep are the subpopulation of γδ + /WC1 + T cells. The aim of this study was to evaluate the effect of γδ + ⁄WC1 + T cell depletion via infusion of anti-γδ/WC1 monoclonal antibody (mAb) on the subsequent immune response of CHB sheep infected with H. contortus. Significantly lower γδ + T cell levels in both peripheral blood and in the basal layers of the abomasal tissue resulted following anti-γδ/WC1 mAb infusion of CHB sheep compared to control animals. Worms recovered from the anti-γδ/WC1 mAb treated CHB sheep had significantly longer female worms with correspondingly more eggs in utero than the saline control group. Significant correlations between eosinophils and worm length and fecundity were no longer apparent in the anti-γδ/WC1 mAb treated CHB sheep. These results support the notion that γδ + T cells in CHB sheep play a critical role in fecundity regulation (length and eggs in utero) of H. contortus adult female worms, and highlights a new mechanism of modulation by this lymphocyte population, possibly involving eosinophil activation. Copyright © 2017 Elsevier B.V. All rights reserved.

The impact of PNPLA3 (rs738409 C>G) polymorphisms on liver histology and long-term clinical outcome in chronic hepatitis B patients.

PubMed

Brouwer, Willem P; van der Meer, Adriaan J; Boonstra, Andre; Pas, Suzan D; de Knegt, Robert J; de Man, Rob A; Hansen, Bettina E; ten Kate, Fiebo J W; Janssen, Harry L A

2015-02-01

We aimed to assess the association between the patatin-like phospholipase domain-containing-3 (PNPLA3) I148M polymorphism, liver histology and long-term outcome in chronic hepatitis B (CHB) patients. We enrolled 531 consecutive treatment naïve CHB patients diagnosed from 1985 to 2012 with an available liver biopsy for reassessment, and sample for genetic testing. Data on all-cause mortality and hepatocellular carcinoma (HCC) at long-term follow-up were obtained from national database registries. The prevalence of steatohepatitis increased with PNPLA3 CC (14%), CG (20%) and GG (43%) (P < 0.001). The association was altered by both gender (P = 0.010) and overweight (P = 0.015): the effect of PNPLA3 on steatohepatitis was most pronounced among non-overweight females (adjusted OR 13.4, 95%CI: 3.7-51.6, P < 0.001), and non-overweight males (adjusted OR 2.4, 95%CI: 1.4-4.3, P = 0.002). Furthermore, PNPLA3 GG genotype was associated with iron depositions (OR 2.8, 95%CI: 1.2-6.4, P = 0.014) and lobular inflammation (OR 2.2, 95%CI: 1.1-4.5, P = 0.032), but not with advanced fibrosis (OR 1.1, 95%CI: 0.7-1.8, P = 0.566). The median follow-up was 10.1 years (interquartile range 5.6 - 15.8), during which 13 patients developed HCC and 28 died. Steatohepatitis was associated with all-cause mortality [Hazard ratio (HR) 3.1, 95%CI: 1.3-7.3, P = 0.006] and HCC (HR 2.8, 95%CI: 0.9-9.2, P = 0.078), but no significant association was observed for PNPLA3. In this cohort of biopsied CHB patients, PNPLA3 was independently associated with steatosis, steatohepatitis, lobular inflammation and iron depositions, but not with advanced fibrosis, HCC development or all-cause mortality. The effect of PNPLA3 on steatohepatitis was particularly pronounced among female patients without severe overweight. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prevalence of chronic hepatitis B virus infection in Thailand: a systematic review and meta-analysis.

PubMed

Leroi, Charline; Adam, Pierrick; Khamduang, Woottichai; Kawilapat, Suttipong; Ngo-Giang-Huong, Nicole; Ongwandee, Sumet; Jiamsiri, Suchada; Jourdain, Gonzague

2016-10-01

To estimate the number of people living in Thailand with chronic hepatitis B (CHB), a major cause of liver cirrhosis and cancer, in view of the implementation of programs to prevent CHB complications. Using PubMed/Medline and ScienceDirect, all studies reporting hepatitis B surface antigen (HBsAg) seroprevalence estimates conducted in Thailand and published between 1975 and 2015 were reviewed systematically. Pooled prevalence estimates and their 95% confidence intervals (CIs) were calculated, and potential sources of heterogeneity investigated. A high heterogeneity was observed between prevalence estimates. There was a significant decrease in the 150 estimates of HBsAg prevalence with more recent decades of birth (p<0.001), even before the implementation of the national universal immunization program in 1992. When restricted to the general population, the pooled prevalence estimate was 5.1% (95% CI 4.3-6.0%), which would translate to an estimated number of individuals with CHB living in Thailand in 2015 as high as three million. The high burden of CHB in Asian countries is a major challenge for the incorporation of national programs to prevent CHB complications within health care systems. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Anti-HBV response to toll-like receptor 7 agonist GS-9620 is associated with intrahepatic aggregates of T cells and B cells.

PubMed

Li, Li; Barry, Vivian; Daffis, Stephane; Niu, Congrong; Huntzicker, Erik; French, Dorothy M; Mikaelian, Igor; Lanford, Robert E; Delaney, William E; Fletcher, Simon P

2018-05-01

GS-9620, an oral agonist of toll-like receptor 7, is in clinical development for the treatment of chronic hepatitis B (CHB). GS-9620 was previously shown to induce prolonged suppression of serum viral DNA and antigens in the chimpanzee and woodchuck models of CHB. Herein, we investigated the immunomodulatory mechanisms underlying these antiviral effects. Archived liver biopsies and paired peripheral blood mononuclear cell samples from a previous chimpanzee study were analyzed by RNA sequencing, quantitative reverse transcription PCR, immunohistochemistry (IHC) and in situ hybridization (ISH). GS-9620 treatment of CHB chimpanzees induced an intrahepatic transcriptional profile significantly enriched with genes associated with hepatitis B virus (HBV) clearance in acutely infected chimpanzees. Type I and II interferon, CD8 + T cell and B cell transcriptional signatures were associated with treatment response, together with evidence of hepatocyte death and liver regeneration. IHC and ISH confirmed an increase in intrahepatic CD8 + T cell and B cell numbers during treatment, and revealed that GS-9620 transiently induced aggregates predominantly comprised of CD8 + T cells and B cells in portal regions. There were no follicular dendritic cells or IgG-positive cells in these lymphoid aggregates and very few CD11b + myeloid cells. There was no change in intrahepatic natural killer cell number during GS-9620 treatment. The antiviral response to GS-9620 treatment in CHB chimpanzees was associated with an intrahepatic interferon response and formation of lymphoid aggregates in the liver. Our data indicate these intrahepatic structures are not fully differentiated follicles containing germinal center reactions. However, the temporal correlation between development of these T and B cell aggregates and the antiviral response to treatment suggests they play a role in promoting an effective immune response against HBV. New therapies to treat chronic hepatitis B (CHB) are urgently needed. In this study we performed a retrospective analysis of liver and blood samples from a chimpanzee model of CHB to help understand how GS-9620, a drug in clinical trials, suppressed hepatitis B virus (HBV). We found that the antiviral response to GS-9620 was associated with accumulation of immune cells in the liver that can either kill cells infected with HBV or can produce antibodies that may prevent HBV from infecting new liver cells. These findings have important implications for how GS-9620 may be used in patients and may also help guide the development of new therapies to treat chronic HBV infection. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Performance analysis of cascaded h-bridge multilevel inverter using mixed switching frequency with various dc-link voltages

NASA Astrophysics Data System (ADS)

Citarsa, I. B. F.; Satiawan, I. N. W.; Wiryajati, I. K.; Supriono

2016-01-01

Multilevel inverters have been widely used in many applications since the technology is advantageous to increase the converter capability as well as to improve the output voltage quality. According to the applied switching frequency, multilevel modulations can be subdivided into three classes, i.e: fundamental switching frequency, high switching frequency and mixed switching frequency. This paper investigates the performance of cascaded H-bridge (CHB) multilevel inverter that is modulated using mixed switching frequency (MSF) PWM with various dc-link voltage ratios. The simulation results show the nearly sinusoidal load output voltages are successfully achieved. It is revealed that there is improvement in output voltages quality in terms of THD and low-order harmonics content. The CHB inverter that is modulated using MSF PWM with equal dc-link voltage ratio (½ Vdc: ½ Vdc) produces output voltage with the lowest low-order harmonics (less than 1% of fundamental) while the CHB inverter that is modulated using MSF PWM with un-equal dc-link voltage ratio (2/3 Vdc: 1/3 Vdc) produces a 7-level output voltage with the lowest THD (16.31%) compared to the other PWM methods. Improvement of the output voltage quality here is also in line with improvement of the number of available levels provided in the output voltage. Here only 2 cells H-bridge inverter (contain 8 switches) are needed to produce a 7- level output voltage, while in the conventional CHB inverter at least 3 cells of H-bridge inverter (contain 12 switches) are needed to produce a 7-level output voltage. Hence it is valuable in term of saving number of component.

Acoustic Structure Quantification Versus Point Shear Wave Speed Measurement for the Assessment of Liver Fibrosis in Viral Hepatitis B.

PubMed

Liu, Jianxue; Ren, Wei; Ai, Hong; Dun, Guoliang; Ji, Yonghao; Zhang, Yaoren; Wan, Qinyun; Lin, Shumei

2018-06-01

This study was conducted to evaluate the value of acoustic structure quantification (ASQ) technology versus that of point shear wave speed measurement (PSWSM) imaging technology for the assessment of liver fibrosis stage. A total of 104 patients with chronic hepatitis B (CHB) and 30 healthy control patients underwent ASQ and PSWSM examinations. Seven quantitative parameters were obtained from ASQ, and a principal component analysis was used to establish the integrative indicators. A quantitative parameter, known as the shear wave speed (SWS, m/s), was obtained from the PSWSM. The METAVIR scores for the assessment of pathologic liver fibrosis were used as a benchmark. Liver fibrosis stages exhibited a good correlation with the integrative indicators and SWS (r = 0.682, p <0.001; r = 0.651, p <0.001). The areas under the receiver operating characteristic curves for ASQ and PSWSM were 0.705 and 0.854 for mild liver fibrosis (F ≥ 1, p = 0.045), 0.813 and 0.743 for significant liver fibrosis (F ≥ 2, p = 0.115), 0.839 and 0.857 for severe liver fibrosis (F ≥ 3, p = 0.417) and 0.874 and 0.971 for liver cirrhosis (F = 4, p = 0.016), respectively. In conclusion, both ASQ and PSWSM were promising ultrasonic methods for assessing liver fibrosis in patients with CHB; however, PSWSM was more valuable for identifying mild liver fibrosis (F ≥ 1) and cirrhosis (F = 4) than ASQ, and the combination of PSWSM and ASQ improved the accuracy of diagnosing severe liver fibrosis (F ≥ 3). Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

Genotype and phenotype correlation in von Hippel-Lindau disease based on alteration of the HIF-α binding site in VHL protein.

PubMed

Liu, Sheng-Jie; Wang, Jiang-Yi; Peng, Shuang-He; Li, Teng; Ning, Xiang-Hui; Hong, Bao-An; Liu, Jia-Yuan; Wu, Peng-Jie; Zhou, Bo-Wen; Zhou, Jing-Cheng; Qi, Nie-Nie; Peng, Xiang; Zhang, Jiu-Feng; Ma, Kai-Fang; Cai, Lin; Gong, Kan

2018-03-29

PurposeVon Hippel-Lindau (VHL) disease is a rare hereditary cancer syndrome that reduces life expectancy. We aimed to construct a more valuable genotype-phenotype correlation based on alterations in VHL protein (pVHL).MethodsVHL patients (n = 339) were recruited and grouped based on mutation types: HIF-α binding site missense (HM) mutations, non-HIF-α binding site missense (nHM) mutations, and truncating (TR) mutations. Age-related risks of VHL-associated tumors and patient survival were compared.ResultsMissense mutations conferred an increased risk of pheochromocytoma (HR = 1.854, p = 0.047) compared with truncating mutations. The risk of pheochromocytoma was lower in the HM group than in the nHM group (HR = 0.298, p = 0.003) but was similar between HM and TR groups (HR = 0.901, p = 0.810). Patients in the nHM group had a higher risk of pheochromocytoma (HR = 3.447, p < 0.001) and lower risks of central nervous system hemangioblastoma (CHB) (HR = 0.700, p = 0.045), renal cell carcinoma (HR = 0.610, p = 0.024), and pancreatic tumor (HR = 0.382, p < 0.001) than those in the combined HM and TR (HMTR) group. Moreover, nHM mutations were independently associated with better overall survival (HR = 0.345, p = 0.005) and CHB-specific survival (HR = 0.129, p = 0.005) than HMTR mutations.ConclusionThe modified genotype-phenotype correlation links VHL gene mutation, substrate binding site, and phenotypic diversity (penetrance and survival), and provides more accurate information for genetic counseling and pathogenesis studies.Genetics in Medicine advance online publication, 29 March 2018; doi:10.1038/gim.2017.261.

HDV infection rates in northern Vietnam.

PubMed

Binh, Mai Thanh; Hoan, Nghiem Xuan; Van Tong, Hoang; Giang, Dao Phuong; Sy, Bui Tien; Toan, Nguyen Linh; Song, Le Huu; Bang, Mai Hong; Wedemeyer, Heiner; Meyer, Christian G; Kremsner, Peter G; Bock, C-Thomas; Velavan, Thirumalaisamy P

2018-05-23

Hepatitis D caused by the hepatitis delta virus (HDV) is a serious health problem in many regions of the world. A total of 546 HBV-infected patients were enrolled from 2013 to 2015 and classified clinically into the subgroups of chronic hepatitis B (CHB, n = 191), liver cirrhosis (LC, n = 147) and hepatocellular carcinoma (HCC, n = 208). The patients were screened for HDV-RNA by nested PCR assays. HDV genotypes were assessed by direct sequencing, followed by phylogenetic analysis. HDV-RNA was identified in 13% (71/546) of HBV-infected patients. The highest HDV prevalence was found in the LC group (19.7%), followed by the HCC (12%) and CHB (8.9%) groups (P = 0.017). HDV/HBV coinfections were significantly associated with a rather unfavourable clinical outcome, in particular with LC development compared to HBV monoinfection. Phylogenetic analyses indicated that the genotype HDV1 was, with a prevalence of 91%, by far the most common genotype in Vietnam, followed by HDV2 with 9%. Other HDV genotypes were not observed. In accordance with previous data obtained a decade ago, our results confirm a continuing high prevalence of HDV infection in hepatitis B patients in northern Vietnam with the HDV1 genotype still being the predominant genotype. HDV nucleic acid testing to minimize the associated risk should be considered.

[Knowledge about HBV, prevention behaviour and treatment adherence of patients with chronic hepatitis B in a large referral centre in Germany].

PubMed

Lutgehetmann, M; Meyer, F; Volz, T; Lohse, A W; Fischer, C; Dandri, M; Petersen, Jörg

2010-09-01

The incidence of chronic hepatitis B in Germany is approximately 0.5 %. Data regarding knowledge about HBV, prevention behaviour and treatment adherence in patients with chronic HBV are scarce. In this prospective study 201 consecutive patients with CHB infection were studied from a large urban academic outpatient clinic at the University Medical Centre in Hamburg. Patients were interviewed with a questionnaire that contained 47 questions covering social demographic dates, knowledge about HBV, treatment adherence and prevention. The success rate of interviews was 100 % with free translation service offered. 20.4 % of the CHB patients were born in Germany, but the majority of the patients were immigrants (80.6 %). 51 % of the patients had a good, 34 % a moderate and 15 % a poor knowledge about HBV. 89 % of the patients knew that HBV can be transmitted through blood contacts, but 34 % believed that inadequate hygienic conditions and 24 % that food products may transmit the virus. 96 % of the patients had knowledge about the existence of an HBV vaccine. Furthermore, 82 % considered a vaccination of all persons in the household important. Despite the knowledge of the existence and importance of a vaccine, only 61,7 % of the 300 affected children/siblings of HBV-positive family members were vaccinated. However, the child vaccination rate was significantly higher among patients with knowledge about the protective effect of the vaccine (p < 0.001), the free of charge vaccination program for children up to 18 years (p < 0.001) and higher school education (p < 0.001). Migrants with poor German language skills had lower knowledge scores (p < 0.001) and showed lower vaccination rates (p = 0.016) compared to immigrants with good German language skills. 43 % of all patients were treated with nucleot(s)ide analogues with a median treatment duration of 2 - 5 years. 65 % of these patients declared to never have missed a dose and 27 % missed less than one dose per month. 90 % of the patients tolerated the antiviral drugs very well and between patients with or without side effects there was no significant difference in quality of life. Chronic hepatitis B in Germany is characterised by awareness problems and language barriers. More attention is needed for HBV-infected immigrants in the form of multilingual information about CHB and awareness campaigns. © Georg Thieme Verlag KG Stuttgart · New York.

Neurodevelopment in children with and without congenital heart block born to anti-Ro/SSA-positive mothers.

PubMed

Skog, Amanda; Tingström, Joanna; Salomonsson, Stina; Sonesson, Sven-Erik; Wahren-Herlenius, Marie

2013-01-01

To define factors influencing neurodevelopment in children with and without complete congenital heart block (CHB) born to mothers with Ro/SSA autoantibodies. Medical records of a population-based cohort of siblings with (n = 60) and without (n = 54) CHB born 1974-2009 to anti-Ro/SSA-positive mothers were retrieved from children primary healthcare centres and school health services and used to extract data on neurodevelopment. Impaired neurodevelopment was reported in 16% of the children (18/114) during the follow-up time of 13.0 (8.2-17.5) years, median (quartiles). Reported problems included speech (9%), motor (8%) and learning (8%) impairment, attention deficit (5%) and behavioural impairment (4%). Impairment in motor skill development was more common in boys (p < 0.001) if the child was born preterm (p < 0.001). Learning impairment was significantly influenced by maternal SLE (p < 0.005), while attention deficits was influenced by both maternal SLE (p < 0.05) and CHB in the child (p < 0.05). Our data indicate that in addition to well-established factors such as male sex and being born preterm, both maternal SLE and CHB may influence neurodevelopment. Follow-up of neurodevelopment should therefore be considered for children with CHB, especially if the mother is diagnosed with SLE. ©2012 The Author(s)/Acta Paediatrica ©2012 Foundation Acta Paediatrica.

Association of PNPLA3 rs738409 polymorphism with liver steatosis but not with cirrhosis in patients with HBV infection: Systematic review with meta-analysis.

PubMed

Ghalamkari, Saman; Sharafi, Heidar; Alavian, Seyed Moayed

2018-01-01

Hepatitis B virus (HBV) infection is a worldwide health issue and is well known for being the main cause of developing secondary liver complications such as cirrhosis and hepatocellular carcinoma (HCC). The PNPLA3 rs738409 polymorphism has been investigated conclusively with occurrence risk of steatosis and cirrhosis. Therefore, performing a meta-analysis of the available studies with the aim of clarifying the association between rs738409 and occurrence risk of steatosis and cirrhosis among HBV-infected patients would be helpful. Chronic HBV infection was defined as the persistence of HBsAg for more than 6 months. To gather sufficient data for this meta-analysis, reliable databases were conclusively searched using appropriate keywords. Only studies that satisfied the inclusion criteria were enrolled in the present study. This meta-analysis pooled four studies with 1135 cases of chronic hepatitis B (CHB) to evaluate the impact of PNPLA3 SNP on liver steatosis and also pooled five studies with 3713 cases of CHB to evaluate the impact of PNPLA3 SNP on cirrhosis. The association of rs738409 with each complication was investigated. The rs738409 was found to be associated with steatosis in recessive [p = 4.57 × 10 -6 , odds ratio (OR) = 2.85], dominant (p = 4.35 × 10 -6 , OR = 1.84), co-dominant (p = 6.18 × 10 -8 ; OR = 3.74) and allelic (p = 9.79 × 10 -9 ; OR = 1.78) models. No association was found between rs738409 and cirrhosis development in recessive (p = 0.99, OR = 1.00), dominant (p = 0.30, OR = 0.92), co-dominant (p = 0.74; OR = 0.96) and allelic (p = 0.45; OR = 0.96) models. Although the PNPLA3 rs738409 G allele has been associated with the risk of steatosis in CHB patients, no association between this polymorphism and the risk of cirrhosis was seen. Copyright © 2017 John Wiley & Sons, Ltd.

Influence of IL10 gene polymorphisms on the severity of liver fibrosis and susceptibility to liver cirrhosis in HBV/HCV-infected patients.

PubMed

Guo, Peng-Fei; Jin, Juan; Sun, Xiangru

2015-03-01

Previous studies about the association of the interleukin-10 (IL-10) polymorphisms with the progression of liver fibrosis or cirrhosis susceptibility in chronic hepatitis B/C (CHB/C) disease were inconsistent. The aim of this meta-analysis was to derive a more precise estimation of the association. We searched Medline, PubMed, EMBASE and Web of Science electronic databases using the following key words: liver fibrosis/cirrhosis, IL10, and polymorphism. Statistical analyses were performed by STATA11.0 software, with odds ratios (ORs) and their 95% confidence intervals (CIs). 12 independent studies in relation to IL10-1082A/G, -819C/T and -592C/A polymorphisms were included in our study, which consisted of 197 moderate/severe liver fibrosis cases and 426 mild fibrosis controls as well as 536 liver cirrhosis cases and 881 non-cirrhosis controls. The results indicated that a significantly decreased risk of moderate/severe fibrosis was associated with the GCC haplotype (IL10-1082G, -819C and -592C) in the overall CHB/C patients (OR: 0.547, 95% CI: 0.317-0.946, P=0.031). We did not detect any significant association between these polymorphisms and liver cirrhosis susceptibility in the total population or a subgroup of Asians. However, subgroup analyses by different aetiologies showed that the -819T heterozygotes (TC) were associated with a significantly increased risk of HCV-related liver cirrhosis in the Japanese population (OR: 1.254, 95% CI: 1.033-1.522, P=0.022). The putative high IL-10 production haplotype GCC is more likely to be associated with less severe liver fibrosis in CHB/C patients. Additionally, the IL10-819T allele may be a susceptible factor for HCV-related liver cirrhosis in the Japanese population. Copyright © 2014. Published by Elsevier B.V.

Reimbursement policies in the Asia-Pacific for chronic hepatitis B.

PubMed

Lim, Seng Gee; Amarapurkar, Deepak N; Chan, Henry Lik-Yuen; Crawford, Darrell H; Gane, Edward J; Han, Kwang-Hyub; Ahn, Sang Hoon; Jafri, Wasim; Jia, Jidong; Kao, Jia-Horng; Lesmana, Laurentius A; Lesmana, C Rinaldi A; Mohamed, Rosmawati; Phiet, Pham Hoang; Piratvisuth, Teerha; Sarin, Shiv K; Sollarno, Jose D; Eguchi, Yuichiro; Mahtab, Mamun-Al; Lee, Keat Hong

2015-01-01

There is considerable variation in reimbursement policies in Asian countries and this is likely to have an impact on treatment practice for chronic hepatitis B (CHB). Consequently a survey of leading hepatologists was performed to evaluate such policies and their impact on management of CHB in the Asia Pacific region. A questionnaire was sent to key hepatologists in Asia Pacific for information on CHB reimbursement policy-its nature, coverage, funding source, duration, review strategy and impact on Asia Pacific Association for the Study of the Liver (APASL) CHB guidelines. The results were analysed and described. Leading hepatologists from 16 Asia Pacific countries responded. Almost all of the countries have reimbursement policies but eligibility varied from only a limited group (e.g. civil servants only) to universal access. In most instances reimbursement was from the central government (except China, Pakistan and Hong Kong). Reimbursement policies were usually created by Ministry of Health committees, who received input from medical professionals, although they may not be aware of the APASL guidelines. Policies were limited by available resources, funds and prioritization. Where there was a regular review this occurred between 1 and 5 years. The quantum of reimbursement varied from 50% in Singapore to 100% in the majority of other countries. The criteria for treatment reimbursement were based on doctor's opinion alone (Bangladesh, India, Pakistan, Philippines, Singapore and Vietnam) or specific clinical/laboratory criteria in the rest of the countries. In general, most countries offered unlimited duration for reimbursement except Taiwan, Indonesia and Pakistan. Monitoring tests for treatment response were reimbursed in all countries other than Vietnam. Viral resistance was diagnosed by viral or biochemical breakthrough, and viral resistance testing was uncommon. The main rescue therapy was adefovir. Reimbursement policies differed from country to country, the quantum and the proportion of patients who received reimbursement also varied significantly. Asia Pacific countries were able to follow APASL guidelines with variable success based on their reimbursement policies.

Assessment of Liver Fibrosis Using Real-time Shear-wave Elastography for Patients with Hepatitis B e Antigen-negative Chronic Hepatitis B and Alanine Transaminase <2 Times the Upper Limit of Normal.

PubMed

Liu, Jing-Hua; Zou, Yu; Chang, Wei; Wu, Jun; Zou, Yu; Xie, Yu-Chen; Lu, Yong-Ping; Wei, Jia

2017-01-01

We assessed liver fibrosis using real-time shear-wave elastography (SWE) combined with liver biopsy (LB) for patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) and alanine transaminase < 2 times the upper limit of normal and hepatitis B virus DNA < 2000 IU/ml. A total of 107 patients met the inclusion criteria. Real- ime SWE and ultrasoundassisted liver biopsies were consecutively performed. Fibrosis was staged according to the METAVIR scoring system. Analyses of receiver operating characteristic curve were performed to calculate the optimal area under the receiver operating characteristic curve for F0-F1 versus F2-F4, F0-F2 versus F3-F4, and F0-F3 versus F4 for real-time SWE. The most concurrent liver fibrosis degrees were between F1 and F2 for these HBeAg-negative CHB patients. Liver stiffness increased in parallel with the degree of liver fibrosis using SWE measurements. The area under the receiver operating characteristic curves was 0.881 (95% confidence interval [CI]: 0.704-1.000) for SWE (p = 0.004); 0.912 (95% CI: 0.836-0.987) for SWE (p = 0.000); 0.981 (95% CI: 0.956-1.000) for SWE (p = 0.000); 0.974 (95% CI: 0.936-1.000) for SWE (p = 0.000) when comparing F0 versus F1-F4, F0-F1 versus F2-F4, F0-F2 versus F3-F4, and F0-F3 versus F4, respectively. SWE has the advantage of providing an image of liver stiffness in real-time. As an alternative to LB, the development of all these noninvasive methods for dynamic evaluation of liver fibrosis will decrease the need for LB, making clinical care safer and more convenient for patients with liver diseases.

[A quantitative real time polymerase chain reaction for detection of HBV covalently closed circular DNA in livers of the HBV infected patients].

PubMed

Wang, Mei-Rong; Qiu, Ning; Lu, Shi-Chun; Xiu, Dian-Rong; Yu, Jian-Guo; Li, Tong; Liu, Xue-En; Zhuang, Hui

2011-05-01

To establish and optimize a sensitive and specific quantitative real-time polymerase chain reaction (PCR) method for detection of hepatitis B virus covalently closed circular DNA (HBV cccDNA) in liver tissue. Specific primers and probes were designed to detect HBV DNA (tDNA) and cccDNA. A series of plasmids (3.44 × 10(0) - 3.44 × 10(9) copies/µl) containing a full double-stranded copies of HBV genome (genotype C) were used to establish the standard curve of real-time PCR. Liver samples of 33 patients with HBV related hepatocellular carcinoma (HCC), 13 Chronic hepatitis B patients (CHB) and 10 non-HBV patients were collected to verify the sensitivity and specificity of the assay. A fraction of extracted DNA was digested with a Plasmid-Safe ATP-dependent Dnase (PSAD) for HBV cccDNA detection and the remaining was used for tDNA and β-globin detection. The amount (copies/cell) of HBV cccDNA and tDNA were measured by a real-time PCR, using β-globin housekeeping gene as a quantitation standard. The standard curves of real-time PCR with a linear range of 3.44 × 10(0) to 3.44 × 10(9) copies/µl were established for detecting HBV cccDNA and tDNA, and both of the lowest detection limits of HBV cccDNA and tDNA were 3.44 × 10(0) copies/µl. The lowest quantitation levels of HBV cccDNA in liver tissues tested in 33 HBV related HCC patients and 13 CHB patients were 0.003 copies/cell and 0.031 copies/cell, respectively. HBV cccDNA and tDNA in liver tissue of 10 non-HBV patient appeared to be negative. The true positive rate was increasing through the digestion of HBV DNA by PSAD, and the analytic specificity of cccDNA detection improved by 7.24 × 10(2) times. Liver tissues of 2 patients were retested 5 times in the PCR for detecting cccDNA and the coefficient of variations on cycle threshold (Ct) were between 0.224% - 0.609%. A highly sensitive and specific quantitative real time PCR method for the detection of HBV cccDNA in liver tissue was established and could be used for clinical and epidemiological studies.

Development of a model based on biochemical, real-time tissue elastography and ultrasound data for the staging of liver fibrosis and cirrhosis in patients with chronic hepatitis B

PubMed Central

Xu, Shi-Hao; Li, Qiao; Hu, Yuan-Ping; Ying, Li

2016-01-01

The liver fibrosis index (LFI), based on real-time tissue elastography (RTE), is a method currently used to assess liver fibrosis. However, this method may not consistently distinguish between the different stages of fibrosis, which limits its accuracy. The aim of the present study was to develop novel models based on biochemical, RTE and ultrasound data for predicting significant liver fibrosis and cirrhosis. A total of 85 consecutive patients with chronic hepatitis B (CHB) were prospectively enrolled and underwent a liver biopsy and RTE. The parameters for predicting significant fibrosis and cirrhosis were determined by conducting multivariate analyses. The splenoportal index (SPI; P=0.002) and LFI (P=0.023) were confirmed as independent predictors of significant fibrosis. Using multivariate analyses for identifying parameters that predict cirrhosis, significant differences in γ-glutamyl transferase (GGT; P=0.049), SPI (P=0.002) and LFI (P=0.001) were observed. Based on these observations, the novel model LFI-SPI score (LSPS) was developed to predict the occurrence of significant liver fibrosis, with an area under receiver operating characteristic curves (AUROC) of 0.87. The diagnostic accuracy of the LSPS model was superior to that of the LFI (AUROC=0.76; P=0.0109), aspartate aminotransferase-to-platelet ratio index (APRI; AUROC=0.64; P=0.0031), fibrosis-4 index (FIB-4; AUROC= 0.67; P= 0.0044) and FibroScan (AUROC=0.68; P=0.0021) models. In addition, the LFI-SPI-GGT score (LSPGS) was developed for the purposes of predicting liver cirrhosis, demonstrating an AUROC value of 0.93. The accuracy of LSPGS was similar to that of FibroScan (AUROC=0.85; P=0.134), but was superior to LFI (AUROC= 0.81; P= 0.0113), APRI (AUROC= 0.67; P<0.0001) and FIB-4 (AUROC=0.719; P=0.0005). In conclusion, the results of the present study suggest that the use of LSPS and LSPGS may complement current methods of diagnosing significant liver fibrosis and cirrhosis in patients with CHB. PMID:27573619

Development of a model based on biochemical, real‑time tissue elastography and ultrasound data for the staging of liver fibrosis and cirrhosis in patients with chronic hepatitis B.

PubMed

Xu, Shi-Hao; Li, Qiao; Hu, Yuan-Ping; Ying, Li

2016-10-01

The liver fibrosis index (LFI), based on real‑time tissue elastography (RTE), is a method currently used to assess liver fibrosis. However, this method may not consistently distinguish between the different stages of fibrosis, which limits its accuracy. The aim of the present study was to develop novel models based on biochemical, RTE and ultrasound data for predicting significant liver fibrosis and cirrhosis. A total of 85 consecutive patients with chronic hepatitis B (CHB) were prospectively enrolled and underwent a liver biopsy and RTE. The parameters for predicting significant fibrosis and cirrhosis were determined by conducting multivariate analyses. The splenoportal index (SPI; P=0.002) and LFI (P=0.023) were confirmed as independent predictors of significant fibrosis. Using multivariate analyses for identifying parameters that predict cirrhosis, significant differences in γ‑glutamyl transferase (GGT; P=0.049), SPI (P=0.002) and LFI (P=0.001) were observed. Based on these observations, the novel model LFI‑SPI score (LSPS) was developed to predict the occurrence of significant liver fibrosis, with an area under receiver operating characteristic curves (AUROC) of 0.87. The diagnostic accuracy of the LSPS model was superior to that of the LFI (AUROC=0.76; P=0.0109), aspartate aminotransferase‑to‑platelet ratio index (APRI; AUROC=0.64; P=0.0031), fibrosis‑4 index (FIB‑4; AUROC=0.67; P=0.0044) and FibroScan (AUROC=0.68; P=0.0021) models. In addition, the LFI‑SPI‑GGT score (LSPGS) was developed for the purposes of predicting liver cirrhosis, demonstrating an AUROC value of 0.93. The accuracy of LSPGS was similar to that of FibroScan (AUROC=0.85; P=0.134), but was superior to LFI (AUROC=0.81; P=0.0113), APRI (AUROC=0.67; P<0.0001) and FIB‑4 (AUROC=0.719; P=0.0005). In conclusion, the results of the present study suggest that the use of LSPS and LSPGS may complement current methods of diagnosing significant liver fibrosis and cirrhosis in patients with CHB.

Long-Term Telbivudine Treatment Results in Resolution of Liver Inflammation and Fibrosis in Patients with Chronic Hepatitis B.

PubMed

Hou, Jin-Lin; Xu, Daozheng; Shi, Guangfeng; Wan, Mobin; Goodman, Zachary; Tan, Deming; Xie, Qing; Chen, Chengwei; Wei, Lai; Niu, Junqi; Wang, Qinhuan; Ren, Hong; Wang, Yuming; Jia, Jidong; Bao, Weibin; Dong, Yuhong; Trylesinski, Aldo; Naoumov, Nikolai V

2015-08-01

The long-term goal of chronic hepatitis B (CHB) treatment is improvement of liver disease and prevention of cirrhosis. The aim of this study was to assess whether prolonged telbivudine treatment improves liver inflammation and fibrosis. The primary objective was to evaluate the proportion of patients with absence/minimal inflammation (Knodell necroinflammatory score ≤3) on liver biopsy at Year 5. Fifty-seven patients aged 16-70 years with a clinical history of CHB and active viral replication (38 hepatitis B e antigen [HBeAg] positive and 19 HBeAg negative) were followed for 6 years: 33 received telbivudine 600 mg/day continuously for 5 years; 24 received lamivudine 100 mg/day for 2 years and then telbivudine for 3 years. Liver biopsies were taken pre-treatment and after 5 years of treatment. At baseline, mean (standard deviation) serum hepatitis B virus (HBV) DNA load was 8.5 (1.7) log10 copies/mL, Knodell necroinflammatory score was 7.6 (2.9), and Ishak fibrosis score was 2.2 (1.1). After antiviral treatment (median duration: 261 weeks), liver histology improved with increased proportions of patients with absence/minimal liver inflammation (Knodell necroinflammatory score ≤3), from 16% (9/57) at baseline to 98% (56/57), and absence/minimal fibrosis (Ishak score ≤1), from 25% (14/57) at baseline to 84% (48/57). At Year 5, HBV DNA load was <300 copies/mL for all patients; cumulative HBeAg loss and seroconversion rates were 88% and 77%, respectively. At Year 6, 95% of patients with abnormal baseline glomerular filtration rate (60-90 mL/min/1.73 m(2)) improved to normal GFR (>90 mL/min/1.73 m(2)). Long-term telbivudine treatment with profound and durable viral suppression significantly improved liver histology, thus achieving the long-term goals of CHB treatment. FibroScan(®) results after 5 and 6 years of treatment (in almost 20% of patients) were consistent with this information. Novartis and National Science and Technology Major Project (2012ZX10002003). ClinicalTrials.gov # NCT00877149.

Natural history of chronic hepatitis B: phases in a complex relationship.

PubMed

Croagh, Catherine M N; Lubel, John S

2014-08-14

Chronic hepatitis B (CHB) is a condition of global prevalence and its sequelae include cirrhosis and hepatocellular carcinoma. The natural history of CHB is a complex interplay of virological, environmental and host factors. The dynamic relationship between the virus and host evolves over the duration of the infection and different phases of the disease have been observed and described. These have been conceptualized in terms of the state of balance between the host immune system and the hepatitis B virus and have been given the labels immune tolerant, immune clearance, immune control and immune escape although other nomenclature is also used. Host factors, such as age at infection, determine progression to chronicity. Virological factors including hepatitis B viral load, mutations and genotype also have an impact on the adverse outcomes of the infection, as do hepatotoxic cofactors such as alcohol. Our understanding of the natural history of CHB has evolved significantly over the past few decades and characterizing the phase of disease of CHB remains an integral part of managing this virus in the clinic.

Precore and core promoter mutations of hepatitis B virus and hepatitis B e antigen-negative chronic hepatitis B in Korea.

PubMed

Yoo, Byung Chul; Park, Joong-Won; Kim, Hyung Joon; Lee, Dong Ho; Cha, Young Ju; Park, Sill Moo

2003-01-01

The aims of this study were to determine the frequency of precore/core promoter mutations and hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (e-CHB) in Korea. Patients with chronic hepatitis B virus (HBV) infection were tested for HBeAg, anti-HBe, liver profile and HBV-DNA by a branched DNA (bDNA) assay. Serum HBV-DNA was amplified by a polymerase chain reaction and the precore/core promoter sequence was determined. Among the 413 consecutive HBeAg-negative patients, 19.6% were bDNA-positive. Evidence of liver disease was found in 90.1% of bDNA-positive and 41.7% of bDNA-negative patients. Overall, 17.7% of HBeAg-negative patients had e-CHB. Precore mutation (A1896) was detected in 93.7% of HBeAg-negative bDNA-positive and 93.9% of HBeAg-negative bDNA-negative patients. In 59 HBeAg-positive patients, 78% had wild-type and 22% had a mixture of wild-type and A1896 mutant. Core promoter TA mutation was detected in 89.9% of HBeAg-negative bDNA-positive patients, 89.8% of HBeAg-negative bDNA-negative patients, and 74.6% of HBeAg-positive patients. No correlation was found between the presence of precore/core promoter mutations and HBV-DNA levels or disease severity. In Korean patients infected with HBV genotype C, precore mutation occurred almost invariably along with HBeAg seroconversion and core promoter TA mutation was frequent irrespective of viral replication levels or disease severity.

A comparison of hepatic steatosis index, controlled attenuation parameter and ultrasound as noninvasive diagnostic tools for steatosis in chronic hepatitis B.

PubMed

Xu, Liang; Lu, Wei; Li, Ping; Shen, Feng; Mi, Yu-Qiang; Fan, Jian-Gao

2017-08-01

To evaluate the value of noninvasive tools for diagnosis of hepatic steatosis in patients with chronic hepatitis B (CHB). Consecutive treatment-naïve patients with CHB with body mass index less than 30kg/m 2 who underwent liver biopsy, ultrasound and FibroScan ® were enrolled. The diagnostic performance of controlled attenuation parameter (CAP), hepatic steatosis index (HSI) and ultrasound for hepatic steatosis compared with liver biopsy was assessed. The areas under receiver operating characteristics curves (AUROCs) were calculated to determine the diagnostic efficacy, with comparisons using the DeLong test. CAP and HSI accuracies were significantly higher than that of ultrasound to detect patients with biopsy-proven mild steatosis (S1, 65.3%, 56.5%, respectively, vs. 17.7%, χ 2 =46.305, 31.736, both P<0.05)and moderate-severe (S2-3) steatosis (92.3%, 100%, respectively, vs. 53.8%, χ 2 =4.887, 7.800, P=0.037, 0.007, respectively). Both CAP and HSI had lower underestimation rates of steatosis grade than ultrasound (12%, 14.8%, respectively, vs. 29.5%, χ 2 =9.765, 6.452; P<0.05 for both), but they exhibited higher overestimation rates (30.5%, 38.2%, respectively, vs. 12.4%, χ 2 =39.222, 70.986; both P<0.05). The AUROCs of CAP and HSI were 0.780 (95% confidence intervals [CIs] 0.735-0.822) and 0.655 (95%CI 0.604-0.704) for S ≥1, 0.932 (95%CI 0.902-0.956) and 0.755 (95%CI 0.707-0.799) for S ≥2, 0.990 (95%CI 0.974-0.998) and 0.786 (95% CI 0.740-0.827) for S3, respectively. CAP might be more accurate for detecting hepatic steatosis than HSI and ultrasound in patients with CHB, but further studies are needed to reduce the overestimation rates. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Efficacy of telbivudine in HBeAg-positive chronic hepatitis B patients with high baseline ALT levels

PubMed Central

Lv, Guo-Cai; Ma, Wen-Jiang; Ying, Lin-Jung; Jin, Xi; Zheng, Lin; Yang, Yi-Da

2010-01-01

AIM: To evaluate the efficacy and safety of telbivudine (LDT) in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients who have high baseline alanine aminotransferase (ALT) levels between 10 and 20 times the upper limit of normal. METHODS: Forty HBeAg-positive CHB patients with high baseline ALT levels between 10 and 20 times the upper limit of normal were enrolled and received LDT monotherapy for 52 wk. Another forty patients with baseline ALT levels between 2 and 10 times the upper limit of normal were included as controls. We compared the virological, biochemical, serological and side effect profiles between the two groups at 52 wk. RESULTS: By week 52, the mean decrease in hepatitis B virus (HBV) DNA level compared with baseline was 7.03 log10 copies/mL in the high baseline ALT group and 6.17 log10 copies/mL in the control group, respectively (P < 0.05). The proportion of patients in whom serum HBV DNA levels were undetectable by polymerase chain reaction assay was 72.5% in the high baseline ALT group and 60% in the control group, respectively (P < 0.05). In addition, 45.0% of patients in the high baseline ALT group and 27.5% of controls became HBeAg-negative, and 37.5% of those in the high baseline group and 22.5% of controls, respectively, had HBeAg seroconversion (P < 0.05) at week 52. Moreover, in the high baseline group, 4 out of 40 patients (10%) became hepatitis B surface antigen (HBsAg)-negative and 3 (7.5%) of them seroconverted (became HBsAg-positive). Only 1 patient in the control group became HBsAg-negative, but had no seroconversion. The ALT normalization rate, viral breakthrough, genotypic resistance to LDT, and elevations in creatine kinase levels were similar in the two groups over the 52 wk. CONCLUSION: High baseline ALT level is a strong predictor for optimal results during LDT treatment. PMID:20731026

Short- and long-term outcome of interferon therapy for chronic hepatitis B infection

PubMed Central

Seo, Yasushi; Yano, Yoshihiko

2014-01-01

Hepatitis B virus (HBV) infection is a serious clinical problem worldwide. Conventional interferon (IFN)-α has been approved for the treatment of chronic hepatitis B (CHB). Short-term studies have demonstrated that IFN-based therapy is moderately effective in inducing the loss of hepatitis e antigen (HBeAg) or seroconversion (30%-40%) in HBeAg-positive patients and also produces sustained HBV DNA suppression (20%-30%) in HBeAg-negative patients. Many studies have reported a correlation between the HBV genotype and response to IFN treatment. The highest response rate to IFN treatment was found in patients infected with HBV genotype A, followed by HBV genotypes B, C, and D. The long-term effect of IFN-α on CHB has not yet been elucidated. The ability of IFN-α treatment to prevent new cirrhosis, complications associated with cirrhosis, and development of hepatocellular carcinoma (HCC) is controversial. The beneficial effect of IFN-α treatment in reducing the development of HCC has mainly been observed in treatment responders who already have cirrhosis. These inconsistent findings may be attributed to the inevitable limitations of comparisons across studies, including differences in the baseline characteristics of the study and the moderate suppression of HBV replication by IFN-α relative to nucleoside/nucleos(t)ide analogs. PMID:25309065

Impact of skin capsular distance on the performance of controlled attenuation parameter in patients with chronic liver disease.

PubMed

Shen, Feng; Zheng, Rui-Dan; Shi, Jun-Ping; Mi, Yu-Qiang; Chen, Guo-Feng; Hu, Xiqi; Liu, Yong-Gang; Wang, Xiao-Ying; Pan, Qin; Chen, Guang-Yu; Chen, Jian-Neng; Xu, Liang; Zhang, Rui-Nan; Xu, Lei-Ming; Fan, Jian-Gao

2015-11-01

Controlled attenuation parameter (CAP) is a non-invasive method for evaluating hepatic steatosis. However, larger skin capsular distance (SCD) can affect the accuracy. The aim of this study was to investigate the impact of SCD on the diagnostic performance of CAP and liver stiffness measurement (LSM). Of 101 patients with non-alcoholic fatty liver disease (NAFLD) and 280 patients with chronic hepatitis B (CHB) who underwent liver biopsy were prospectively recruited. CAP, LSM and SCD were performed using FibroScan with M probe. The areas under receiver operating characteristics curves (AUROCs) were calculated to determine the diagnostic efficacy. The optimal thresholds were defined by the maximum Youden index. SCD (B 30.34, P < 0.001) and hepatic steatosis (B 23.04, P < 0.001) were independently associated with CAP by multivariate analysis. The AUROCs were slightly higher for SCD <25 mm compared to those for SCD ≥25 mm for steatosis ≥5% (0.88 vs. 0.81), >33% (0.90 vs. 0.85) and >66% (0.84 vs. 0.72). For SCD <25 mm, the optimal CAP cut-offs for differentiating steatosis ≥5%, >33% and >66% were 255.0 dB/m, 283.5 dB/m and 293.5 dB/m. However, cut-offs were elevated by approximately 60-70 dB/m for SCD ≥25 mm. When stratified by fibrosis grade, LSM was significantly affected by SCD ≥25 mm for advanced fibrosis (≥F3) in NAFLD, but not in CHB. CAP is a promising tool for detecting and quantifying hepatic steatosis. SCD ≥25 mm may cause overestimation of steatosis. Similarly, SCD ≥25 mm affects the detection of advanced fibrosis by LSM in NAFLD patients. © 2015 The Authors. Liver International Published by John Wiley & Sons Ltd.

Sera DNA Methylation of CDH1, DNMT3b and ESR1 Promoters as Biomarker for the Early Diagnosis of Hepatitis B Virus-Related Hepatocellular Carcinoma.

PubMed

Dou, Cheng-Yun; Fan, Yu-Chen; Cao, Chuang-Jie; Yang, Yang; Wang, Kai

2016-04-01

DNA methylation mainly affects tumor suppressor genes in the development of hepatocellular carcinoma (HCC). However, sera methylation of specific genes in hepatitis B virus (HBV)-related HCC remains unknown. The purpose of this study was to identify methylation frequencies of sera E-cadherin (CDH1), DNA methyltransferase 3b (DNMT3b) and estrogen receptor 1 (ESR1) promoter in HBV-related HCC and analyze the associated clinical significance. Methylation-specific PCR was used to determine the frequencies of DNA methylation for CDH1, DNMT3b and ESR1 genes in sera from 183 patients with HCC, 47 liver cirrhosis (LC), 126 chronic hepatitis B (CHB), and 50 normal controls (NCs). Significantly higher frequencies of methylation of CDH1, DNMT3b and ESR1 were found in HBV-related HCC compared with LC, CHB and NCs. Nodule numbers, tumor size and the presence of liver cirrhosis were significantly associated with gene methylation status in HBV-related HCC. Moreover, HBV may have a strong and enhanced effect on the concurrent methylation of CDH1, DNMT3b and ESR1 in HBV-related HCC. More importantly, combined methylation as a biomarker displayed significantly higher diagnostic value than AFP to discriminate HCC from CHB and LC. Aberrant sera DNA methylation of CDH1, DNMT3b and ESR1 gene promoters could be a biomarker in the early diagnosis of HBV-related HCC.

Relationship between virological response and FIB-4 index in chronic hepatitis B patients with entecavir therapy.

PubMed

Li, Ni; Xu, Jing-Hang; Yu, Min; Wang, Sa; Si, Chong-Wen; Yu, Yan-Yan

2015-11-21

To investigate whether long-term low-level hepatitis B virus (HBV) DNA influences dynamic changes of the FIB-4 index in chronic hepatitis B (CHB) patients receiving entecavir (ETV) therapy with partial virological responses. We retrospectively analyzed 231 nucleos(t)ide (NA) naïve CHB patients from our previous study (NCT01926288) who received continuous ETV or ETV maleate therapy for three years. The patients were divided into partial virological response (PVR) and complete virological response (CVR) groups according to serum HBV DNA levels at week 48. Seventy-six patients underwent biopsies at baseline and at 48 wk. The performance of the FIB-4 index and area under the receiver operating characteristic (AUROC) curve for predicting fibrosis were determined for the patients undergoing biopsy. The primary objective of the study was to compare the cumulative probabilities of virological responses between the two groups during the treatment period. The secondary outcome was to observe dynamic changes of the FIB-4 index between CVR patients and PVR patients. For hepatitis B e antigen (HBeAg)-positive patients (n = 178), the cumulative probability of achieving undetectable levels at week 144 was 95% and 69% for CVR and PVR patients, respectively (P < 0.001). In the Cox proportional hazards model, a lower pretreatment serum HBV DNA level was an independent factor predicting maintained viral suppression. The cumulative probability of achieving undetectable levels of HBV DNA for HBeAg-negative patients (n = 53) did not differ between the two groups. The FIB-4 index efficiently identified fibrosis, with an AUROC of 0.80 (95%CI: 0.69-0.89). For HBeAg-positive patients, the FIB-4 index was higher in CVR patients than in PVR patients at baseline (1.89 ± 1.43 vs 1.18 ± 0.69, P < 0.001). There was no significant difference in the reduction of the FIB-4 index between the CVR and PVR groups from weeks 48 to 144 (-0.11 ± 0.47 vs -0.13 ± 0.49, P = 0.71). At week 144, the FIB-4 index levels were similar between the two groups (1.24 ± 0.87 vs 1.02 ± 0.73, P = 0.06). After multivariate logistic regression analysis, a lower baseline serum HBV DNA level was associated with improvement of liver fibrosis. In HBeAg-negative patients, the FIB-4 index did not differ between the two groups. The cumulative probabilities of HBV DNA responses showed significant differences between CVR and PVR HBeAg-positive CHB patients undergoing entecavir treatment for 144 wk. However, long-term low-level HBV DNA did not deteriorate the FIB-4 index, which was used to evaluate liver fibrosis, at the end of three years.

Comparison of Hybrid Capture 2 Assay with Real-time-PCR for Detection and Quantitation of Hepatitis B Virus DNA

PubMed Central

Jahan, Munira; Lutful Moben, Ahmed; Tabassum, Shahina

2014-01-01

ABSTRACT Background Both real-time-polymerase chain reaction (PCR) and hybrid capture 2 (HC2) assay can detect and quantify hepatitis B virus (HBV) DNA. However, real-time-PCR can detect a wide range of HBV DNA, while HC2 assay could not detect lower levels of viremia. The present study was designed to detect and quantify HBV DNA by real-time-PCR and HC2 assay and compare the quantitative data of these two assays. Materials and methods A cross-sectional study was conducted in between July 2010 and June 2011. A total of 66 serologically diagnosed chronic hepatitis B (CHB) patients were selected for the study. Real-time-PCR and HC2 assay was done to detect HBV DNA. Data were analyzed by statistical Package for the social sciences (SPSS). Results Among 66 serologically diagnosed chronic hepatitis B patients 40 (60.61%) patients had detectable and 26 (39.39%) had undetectable HBV DNA by HC2 assay. Concordant results were obtained for 40 (60.61%) out of these 66 patients by real-time-PCR and HC2 assay with mean viral load of 7.06 ± 1.13 log10 copies/ml and 6.95 ± 1.08 log10 copies/ml, respectively. In the remaining 26 patients, HBV DNA was detectable by real-time-PCR in 20 patients (mean HBV DNA level was 3.67 ± 0.72 log10 copies/ml. However, HBV DNA could not be detectable in six cases by the both assays. The study showed strong correlation (r = 0.915) between real-time-PCR and HC2 assay for the detection and quantification of HBV DNA. Conclusion HC2 assay may be used as an alternative to real-time-PCR for CHB patients. How to cite this article: Majid F, Jahan M, Moben AL, Tabassum S. Comparison of Hybrid Capture 2 Assay with Real-time-PCR for Detection and Quantitation of Hepatitis B Virus DNA. Euroasian J Hepato-Gastroenterol 2014;4(1):31-35. PMID:29264316

Prediction of risk for hepatocellular carcinoma by response of serum α-fetoprotein to entecavir therapy.

PubMed

Yang, Sung Wook; Kim, Gi Hyun; Chung, Jung Wha; Sohn, Hyung Rae; Lee, Sang Soo; Hong, Sukho; Chung, Seong Min; Jang, Eun Sun; Jeong, Sook-Hyang; Kim, Jin-Wook

2015-07-01

Serum α-fetoprotein (AFP) is frequently elevated in patients with chronic hepatitis B (CHB) who do not have hepatocellular carcinoma (HCC). Entecavir (ETV) treatment reduces AFP levels in these patients, but the clinical significance of AFP response to ETV has not been fully studied. The aims of this study were to elucidate the temporal response of AFP to ETV therapy and to determine the relationship between AFP response and the subsequent development of HCC. All consecutive nucleos(t)ide-naïve CHB patients who started ETV therapy between March 2007 and February 2009 were selected from an electronic medical record database at a tertiary referral center (BESTCare). Clinical, biochemical, and virologic parameters were evaluated in relation to the serial AFP levels tested during ETV treatment. Among the 244 enrolled patients, 66 had elevated AFP levels before ETV therapy. Low serum albumin was a significant predictor for elevated AFP. During 12 months of ETV therapy, AFP levels normalized in approximately three fourths of these patients. The decrease in AFP was delayed in patients with high baseline hepatitis B virus titers and in patients who subsequently developed HCC during ETV therapy. Incidence of HCC was similar regardless of baseline AFP levels. Among patients with elevated AFP, however, HCC developed exclusively in the subgroup where elevated AFP persisted for more than 6 months of ETV therapy. Delayed AFP response to ETV may serve as an indicator of high HCC risk. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Construction of a chimeric thermostable pyrophosphatase to facilitate its purification and immobilization by using the choline-binding tag.

PubMed

Moldes, Cristina; García, José L; García, Pedro

2004-08-01

The thermophilic inorganic pyrophosphatase (Pyr) from Thermus thermophilus has been produced in Escherichia coli fused to the C terminus of the choline-binding tag (ChB tag) derived from the choline-binding domain (ChBD) of pneumococcal LytA autolysin. The chimeric ChBD-Pyr protein retains its thermostable activity and can be purified in a single step by DEAE-cellulose affinity chromatography. Pyr can be further released from the ChBD by thrombin, using the specific protease recognition site incorporated in the C terminus of this tag. Remarkably, the ChB tag provides a selective and very strong thermostable noncovalent immobilization of ChBD-Pyr in the DEAE-cellulose matrix. The binding of choline or choline analogues, such as DEAE, confers a high thermal stability to this tag; therefore, the immobilized chimeric enzyme can be assayed at high temperature without protein leakage, demonstrating the usefulness of the ChB tag for noncovalent immobilization of thermophilic proteins. Moreover, ChBD-Pyr can be purified and immobilized in a single step on commercial DEAE-cellulose paper. The affinity of the ChB tag for this versatile solid support can be very helpful in developing many biotechnological applications.

Hepatitis B in the Greater San Francisco Bay Area: an integrated programme to respond to a diverse local epidemic

PubMed Central

Gish, RG; Cooper, SL

2011-01-01

Although chronic hepatitis B (CHB) affects approximately 2 million United States residents, there is no systematic screening of at-risk individuals, and most remain unaware of their hepatitis B virus (HBV) infection. Unmonitored and untreated, CHB results in a 25–30% risk of death from liver cancer and/or cirrhosis, inflicting an increasing healthcare burden in high-prevalence regions. Despite high prevalence in immigrant Asians and Pacific Islanders, among whom CHB is a leading cause of death, community and healthcare provider awareness remains low. Because safe and effective vaccines and effective antiviral treatments exist, there is an urgent need for integrated programmes that identify, follow and treat people with existing CHB, while vaccinating the susceptible. We describe an extant San Francisco programme that integrates culturally targeted, population-based, HBV screening, vaccination or reassurance, management and research. After screening over 3000 at-risk individuals, we here review our operational and practical experience and describe a simple, rationally designed model that could be successfully used to greatly improve the current approach to hepatitis B while ultimately reducing the related healthcare costs, especially in the high-risk populations, which are currently underserved. PMID:21143342

Quantification of hepatitis B surface antigen with the novel DiaSorin LIAISON XL Murex HBsAg Quant: correlation with the ARCHITECT quantitative assays.

PubMed

Burdino, Elisa; Ruggiero, Tina; Proietti, Alex; Milia, Maria Grazia; Olivero, Antonella; Caviglia, Gian Paolo; Marietti, Milena; Rizzetto, Mario; Smedile, Antonina; Ghisetti, Valeria

2014-08-01

Recent technologic innovations allow for quantitative assessment of hepatitis B surface antigen (HBsAg) levels in serum; this has been used to monitor the course of chronic HBV hepatitis (CHB) and predict treatment response. LIAISON-XL Murex HBsAg Quant assay (DiaSorin, Saluggia, I) is the newest immunoassay CE approved to quantify HBsAg. To compare LIAISON-XL performances with ARCHITECT-QT HBsAg (Abbott Diagnostics, IL, USA), as reference test. Sequential serum samples (n=152) from 14 HBe-negative patients with CHB, the majority of them infected by HBV genotype D undergoing antiviral treatment, were retrospectively tested with both assays. The 2nd WHO Standard 00/588 for HBsAg was used as reference. LIAISON-XL and ARCHITECT-QT correlated by r=0.95, p<0.0001; by Bland-Altman analysis agreement of mean difference was 0.21 ± 0.15 log 10 IU/mL, 95% CI: -0.07 to 0.5). Performance of LIAISON-XL against the 2nd WHO Standard was r=0.998, p<0.0001 (95% CI: 0.993-0.999) with results nearer to the expected WHO values compared to ARCHITECT-QT. Median baseline HBsAg level was similar with the two methods before antiviral treatment, throughout fluctuations of HBsAg level in treatment non-responders and during the decrease of HBsAg titer in treatment responders. Correlation between HBsAg levels and HBV DNA was statistically significant for both the two immunoassays (LIAISON-XL: r=0.4988, 95% CI: 0.3452-0.6264, p<0.0001; ARCHITECT-QT: r=0.480, 95% CI: 0.3233-0.6111, p<0.0001). Correlation between HBsAg measurement with LIAISON-XL and ARCHITECT-QT was high. LIAISON-XL accurately quantified HBsAg in clinical samples at baseline or during antiviral therapy; it can be applied for HBsAg quantification in clinical practice and decision making in CHB. Copyright © 2014 Elsevier B.V. All rights reserved.

Identification of UQCRB as an oxymatrine recognizing protein using a T7 phage display screen.

PubMed

Sun, Yan-Hui; Zhang, Xiao-Yuan; Xie, Wei-Qun; Liu, Guang-Jian; He, Xi-Xin; Huang, Ya-Li; Zhang, Guang-Xian; Wang, Jian; Kuang, Zao-Yuan; Zhang, Ren

2016-12-04

Sophora flavescens Aiton (Radix Sophorae Flavescentis, Kushen) is used in traditional Chinese medicine to treat chronic hepatitis B (CHB), and has the ability to clear heat and dampness from the body. Oxymatrine is one of the major bioactive compounds extracted from Sophora flavescens Aiton and constitutes more than 90% of the oxymatrine injection commonly used for CHB treatment in clinics in China. We aim to analyze the protein binding target of oxymatrine in treating CHB by screening a T7 phage display cDNA library of human CHB and examine the biochemistry of protein-ligand binding between oxymatrine and its ligands. A T7 phage cDNA library of human CHB was biopanned by affinity selection using oxymatrine as bait. The interaction of oxymatrine with its candidate binding protein was investigated by affinity assay, molecular docking, Isothermal Titration Calorimetry (ITC) and Surface Plasmon Resonance (SPR). A library of potential oxymatrine binding peptides was generated. Ubiquinol-cytochrome c reductase binding protein (UQCRB) was one of the candidate binding proteins of oxymatrine. UQCRB-displaying T7 phage binding numbers in the oxymatrine group were significantly higher than that in the control group, biotin group, and matrine group (p<0.05 or p<0.01). Three-dimensional structure modeling of the UQCRB with oxymatrine showed that their binding interfaces matched and oxymatrine inserted into a deeper pocket of UQCRB, which mainly involved amino acid residues Tyr21, Arg33, Tyr83, Glu84, Asp86, Pro88, and Glu91. The binding affinity constant (Kb) from SPR was 4.2mM. The Kb from ITC experiment was 3.9mM and stoichiometry was fixed as 1, which fit very well with the result of SPR. The binding of oxymatrine to UQCRB was driven by strong enthalpy forces such as hydrogen bonds and polar interactions as the heat released was about 157kcal/mol and ΔG was less than zero. In this study, using the T7 phage display system, we have identified UQCRB as a direct binding protein of oxymatrine. Furthermore, the specificity and molecular interaction of oxymatrine with UQCRB were also determined. The binding of UQCRB to oxymatrine suggests that UQCRB is a potential target of oxymatrine in treating CHB. These results provide new understanding into the mechanism of oxymatrine and insights into the strategy on the treatment of CHB. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Analysis of related factors for primary hepatic carcinoma caused by chronic hepatitis B and hepatitis C].

PubMed

Nie, L; Wang, X C; Niu, J Q; Shang, J; Han, Y; Xin, G J; Jia, G; Li, J L; Ding, G W; Liu, Z F

2017-06-06

Objective: To explore the related factors for primary hepatic carcinoma (PHC) caused by chronic hepatitis B (CHB) and hepatitis C (CHC). Methods: According to the principle of cross-sectional study, a cluster random sample method was used, a total of 366 chronic hepatitis patients in hospitals were recruited from three provincial tertiary hospitals in Shanxi, Henan and Jilin between July 2016 and October 2016, respectively. Using a self-designed unified questionnaire, face-to-face interviews was conducted on subjects, including sex, age, alcohol consumption, coffee consumption, green tea consumption, fish consumption, smoking, HBV/HCV diagnosis and treatment, diabetes mellitus, family history of PHC (whether PHC in first-degree relatives), etc . Multivariate unconditional logistic regression were performed to identify the related factors for PHC with CHB and CHC. According to the clinical diagnosis the patients were divided into a chronic hepatitis group (not developing to PHC) and a PHC group. Results: Among 366 cases patients, 287 (78.4%) cases were male, 79 cases were female (21.6%), average age was (52.7±9.3) years. 202 cases were chronic hepatitis group, 164 cases were PHC group. Multivariate unconditional logistics regression analysis indicated that alcohol consumption (odds ratio ( OR )=2.11, 95 %CI: 1.18-3.75), family history of PHC ( OR= 5.12, 95 %CI: 2.60-10.08) were positively correlated with the development of PHC in chronic b, green tea consumption ( OR= 0.45, 95 %CI: 0.23-0.88), antiviral treatment ( OR= 0.19, 95 %CI: 0.11-0.32) were negatively correlated. Alcohol consumption ( OR= 3.98, 95 %CI: 1.14-13.85) was positively correlated with the development of PHC in chronic c, antiviral treatment ( OR= 0.14, 95 %CI: 0.04-0.50) was negatively correlated. Conclusion: Alcohol consumption, family history of PHC, green tea consumption and antiviral treatment were the related factors for the development of PHC in chronic hepatitis b. Alcohol consumption and antiviral treatment were the related factors for the development of PHC in chronic hepatitis c.

TEMs but not DKK1 could serve as complementary biomarkers for AFP in diagnosing AFP-negative hepatocellular carcinoma.

PubMed

Mao, Liping; Wang, Yueguo; Wang, Delin; Han, Gang; Fu, Shouzhong; Wang, Jianxin

2017-01-01

Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is prevalent worldwide. Despite its limitations, serum alpha-fetoprotein (AFP) remains the most widely-used biomarker for the diagnosis of HCC. This study aimed to assess whether measurement of peripheral plasma Dickkopf-1 (DKK1) and Tie2-expressing monocytes (TEMs) could overcome the limitations of AFP and improve the diagnostic accuracy of HCC. Plasma DKK1 level and the percentage of TEMs in peripheral CD14+CD16+ monocytes from HCC patients (n = 82), HBV-related liver cirrhosis (LC) patients (n = 29), chronic hepatitis B (CHB) infected patients (n = 28) and healthy volunteers (n = 31) were analyzed by ELISA and flow cytometry. Receiver operating characteristic (ROC) curves were used to analyze a single biomarker, or a combination of two or three biomarkers. Univariate and multivariate analyses were performed to assess the significance of each marker in prediction of HCC and AFP-negative HCC from LC patients. The percentage of TEMs in peripheral CD14+CD16+ monocytes and plasma level of DKK1 in HCC group were significantly higher than those in LC, CHB and healthy control groups (all P-values <0.05). The percentage of TEMs alone was also significantly higher in AFP-negative HCC group than that in LC, CHB and healthy control groups (all P-values <0.05). Plasma DKK1 level alone could not distinguish between AFP-negative HCC and LC patients. ROC curves showed that the optimal diagnostic cutoff value was 550.93 ng/L for DKK1 and 4.95% for TEMs. There was no significant difference in AUC of DKK1, TEMs and AFP in HCC diagnosis between the four groups (all P>0.05). A combination of DKK1, TEMs and AFP measurements increased the AUC for HCC diagnosis as compared with either marker alone (0.833; 95%CI 0.768-0.886). The AUC for TEMs was 0.692 (95% CI 0.564-0.819) in differentiating AFP-negative HCC from LC, with a sensitivity of 80.0% and a specificity of 65.52%. Only TEMs prevailed as a significant predictor for AFP-negative HCC differentiating from LC patients in univariate and multivariate analyses (P = 0.016, P = 0.023). TEMs and DKK1 may prove to be potential complementary biomarkers for AFP in the diagnosis of HCC. TEMs rather than DKK1 could serve as a complementary biomarker for AFP in the differential diagnosis of AFP-negative HCC versus LC patients.

Evaluation of a Rapid One-step Real-time PCR Method as a High-throughput Screening for Quantification of Hepatitis B Virus DNA in a Resource-limited Setting.

PubMed

Rashed-Ul Islam, S M; Jahan, Munira; Tabassum, Shahina

2015-01-01

Virological monitoring is the best predictor for the management of chronic hepatitis B virus (HBV) infections. Consequently, it is important to use the most efficient, rapid and cost-effective testing systems for HBV DNA quantification. The present study compared the performance characteristics of a one-step HBV polymerase chain reaction (PCR) vs the two-step HBV PCR method for quantification of HBV DNA from clinical samples. A total of 100 samples consisting of 85 randomly selected samples from patients with chronic hepatitis B (CHB) and 15 samples from apparently healthy individuals were enrolled in this study. Of the 85 CHB clinical samples tested, HBV DNA was detected from 81% samples by one-step PCR method with median HBV DNA viral load (VL) of 7.50 × 10 3 lU/ml. In contrast, 72% samples were detected by the two-step PCR system with median HBV DNA of 3.71 × 10 3 lU/ml. The one-step method showed strong linear correlation with two-step PCR method (r = 0.89; p < 0.0001). Both methods showed good agreement at Bland-Altman plot, with a mean difference of 0.61 log 10 IU/ml and limits of agreement of -1.82 to 3.03 log 10 IU/ml. The intra-assay and interassay coefficients of variation (CV%) of plasma samples (4-7 log 10 IU/ml) for the one-step PCR method ranged between 0.33 to 0.59 and 0.28 to 0.48 respectively, thus demonstrating a high level of concordance between the two methods. Moreover, elimination of the DNA extraction step in the one-step PCR kit allowed time-efficient and significant labor and cost savings for the quantification of HBV DNA in a resource limited setting. Rashed-Ul Islam SM, Jahan M, Tabassum S. Evaluation of a Rapid One-step Real-time PCR Method as a High-throughput Screening for Quantification of Hepatitis B Virus DNA in a Resource-limited Setting. Euroasian J Hepato-Gastroenterol 2015;5(1):11-15.

Evaluation of a Rapid One-step Real-time PCR Method as a High-throughput Screening for Quantification of Hepatitis B Virus DNA in a Resource-limited Setting

PubMed Central

Jahan, Munira; Tabassum, Shahina

2015-01-01

Virological monitoring is the best predictor for the management of chronic hepatitis B virus (HBV) infections. Consequently, it is important to use the most efficient, rapid and cost-effective testing systems for HBV DNA quantification. The present study compared the performance characteristics of a one-step HBV polymerase chain reaction (PCR) vs the two-step HBV PCR method for quantification of HBV DNA from clinical samples. A total of 100 samples consisting of 85 randomly selected samples from patients with chronic hepatitis B (CHB) and 15 samples from apparently healthy individuals were enrolled in this study. Of the 85 CHB clinical samples tested, HBV DNA was detected from 81% samples by one-step PCR method with median HBV DNA viral load (VL) of 7.50 × 103 lU/ml. In contrast, 72% samples were detected by the two-step PCR system with median HBV DNA of 3.71 × 103 lU/ml. The one-step method showed strong linear correlation with two-step PCR method (r = 0.89; p < 0.0001). Both methods showed good agreement at Bland-Altman plot, with a mean difference of 0.61 log10 IU/ml and limits of agreement of -1.82 to 3.03 log10 IU/ml. The intra-assay and interassay coefficients of variation (CV%) of plasma samples (4-7 log10 IU/ml) for the one-step PCR method ranged between 0.33 to 0.59 and 0.28 to 0.48 respectively, thus demonstrating a high level of concordance between the two methods. Moreover, elimination of the DNA extraction step in the one-step PCR kit allowed time-efficient and significant labor and cost savings for the quantification of HBV DNA in a resource limited setting. How to cite this article Rashed-Ul Islam SM, Jahan M, Tabassum S. Evaluation of a Rapid One-step Real-time PCR Method as a High-throughput Screening for Quantification of Hepatitis B Virus DNA in a Resource-limited Setting. Euroasian J Hepato-Gastroenterol 2015;5(1):11-15. PMID:29201678

High maternal expression of SIGLEC1 on monocytes as a surrogate marker of a type I interferon signature is a risk factor for the development of autoimmune congenital heart block.

PubMed

Lisney, Anna R; Szelinski, Franziska; Reiter, Karin; Burmester, Gerd R; Rose, Thomas; Dörner, Thomas

2017-08-01

Autoimmune congenital heart block (CHB) is associated with placental transcytosis of maternal autoantibodies directed against Ro/SS-A and La/SS-B. However, only about 2% of children born to mothers with the respective antibodies are affected, indicating that further risk factors exist, which are not yet fully understood. In this study, we investigated whether a maternal type I interferon (IFN) signature represents a risk factor for the development of CHB. Blood samples, clinical data and serological parameters from 9 women with CHB pregnancies, 14 pregnant women with antibodies against Ro/SS-A but without a CHB complication and another 30 healthy pregnant women as controls were studied. SIGLEC1 expression was measured by flow cytometry and was correlated to plasma IFN-α levels measured by ELISA, and IFN-γ-induced protein 10 (IP-10) levels measured by Bio-Plex technique. Mothers of affected children had a significantly higher expression of SIGLEC1 (p=0.0034) and IFN-α (p=0.014), but not of IP-10 (p=0.14, all MWU) compared to mothers of unaffected children. SIGLEC1 and IFN-α expression were reduced by hydroxychloroquine and oral glucocorticoids. High expression of SIGLEC1 in pregnant women with autoantibodies against Ro/SS-A indicates an enhanced risk for CHB development, and these women may benefit especially from IFN-α directed therapy, for example with hydroxychloroquine. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Levels of toxaphene congeners in white whales (Delphinapterus leucas) from Svalbard, Norway.

PubMed

Andersen, G; Føreid, S; Skaare, J U; Jenssen, B M; Lydersen, C; Kovacs, K M

2006-03-15

This study reports concentrations of three pesticide toxaphene congeners (CHBs; CHB-26, -50 and -62) from the blubber of ten adult, male white whales (Delphinapterus leucas) from Svalbard, Norway. The CHB congeners that occurred at the highest levels in the blubber of the white whales were, as expected, CHB-26 (4636+/-1992 (SD) ng/g l.w.) and CHB-50 (6579+/-2214 ng/g l.w.); CHB-62 (232+/-231 ng/g l.w.) was also present, but at much lower concentrations. The mean level of the sum of the three CHBs (SigmaCHBs = 11,447+/-4208 ng/g l.w.) in this study is more than twice the mean concentrations of the well-known organochlorine (OC) pollutants SigmaDDTs (sum of pp'-DDT, pp'-DDE, pp'-DDD) and SigmaPCBs (sum of 27 PCB congeners) previously reported from the same individual white whales. The concentrations of CHBs in white whales from Svalbard are at the high end of the range for concentrations of these compounds compared to other Arctic white whale populations. Additionally, the contribution of CHBs to the overall OC burden is larger in white whales from Svalbard compared with their counterparts from other areas in the Arctic. Male white whales from Svalbard have several orders of magnitude higher concentrations of SigmaCHBs compared to seals and polar bears (Ursus maritimus) from the same area. The high levels of CHBs in these whales, and their dominance in the OC pattern, suggests that white whales in Svalbard are exposed to high levels of this group of contaminants. Further studies are needed to investigate possible effects of CHBs and other OC contaminants on the white whale population in Svalbard.

Evaluation of the Potential Risk of Hepatitis B Virus Transmission in Skin Allografting.

PubMed

Wang, D; Xie, W; Chen, T; Dong, C; Zhao, C; Tan, H; Tian, H; Xie, Q

2015-01-01

Skin transplantation is associated with potential risk of infectious disease transmission; however, the exclusion of donors owing to hepatitis B virus (HBV) infection will worsen the shortage of allograft skin supply. We report a paired study to evaluate the potential risk of HBV transmission in skin allografting. The presence of HBV DNA in the serum and skin from 37 burn patients with chronic HBV infection (CHB) was monitored by a HBV polymerase chain reaction (PCR) and the positive rates were compared by Fisher's exact probability test. There was a high consistency in the HBV serology profile between HBV DNA PCR (83.78%) and the clinical HBV test. Only 2 patients who were positive for hepatitis B surface antigen, hepatitis B e antigen, and hepatitis B core antibody had detectable HBV DNA in the skin tissue; however, no hepatitis B surface antigen was detected as examined by immunohistochemistry staining. There was a significant difference between the positive rates of HBV DNA in the serum and skin (χc(2) = 27.03; P < .001). The potential risk for HBV transmission by skin allografting is very low. Given that China has a large population of patients with HBV, the acceptance of skin from donors with CHB to the skin bank would increase the number of tissue donations to meet the urgent medical need for skin transplantation. Copyright © 2015 Elsevier Inc. All rights reserved.

Association of Inducible T Cell Costimulator Polymorphisms with Susceptibility and Outcome of Hepatitis B Virus Infection in a Chinese Han Population.

PubMed

Hu, J; Li, Q-L; Hou, S-H; Peng, H; Guo, J-J

2015-09-01

Inducible T cell costimulator (ICOS) functions to regulate cell-cell signalling, immune responses and cell proliferation. ICOS single nucleotide polymorphism (SNP) may affect protein expression and functions. This study investigated the association of ICOS SNPs with hepatitis B virus (HBV) infection and outcome in a Chinese population. A total of 1290 Chinese Han individuals were enrolled, including 63 asymptomatic HBV carriers, 220 chronic hepatitis B patients (CHB), 249 HBV-related liver cirrhosis patients (LC), 108 patients with HBV-related hepatocellular carcinoma (HCC), 338 patients with natural HBV clearance and 312 healthy subjects (as controls). DNA samples from these subjects were genotyped for four ICOS SNPs (rs11883722, rs10932029, rs1559931 and rs4675379) using TaqMan SNP Genotyping Assay and analysed. The data showed that genotype and allele frequencies of ICOS SNPs in cases and controls followed the Hardy-Weinberg distribution. The CC genotype of rs4675379 was higher in patients with HBV infection (including AC, CHB, LC and HCC) than in patients with HBV clearance (P = 0.006). Furthermore, the genotype 'GA' and the minor allele 'A' of rs1559931 were associated with a decreased HCC susceptibility (P < 0.001). Haplotype analysis data showed that 'GC' haplotype in block 2 (rs1559931 and rs4675379) had a lower frequency in patients than in HBV-cleared subjects (P = 0.034), although its overall frequency was only 1.6%. Our study found that ICOS rs1559931 SNP was associated with decreased HBV-related HCC risk in the studied Chinese Han population, except for patients with natural clearance of HBV. © 2015 The Foundation for the Scandinavian Journal of Immunology.

The preS deletion of hepatitis B virus (HBV) is associated with liver fibrosis progression in patients with chronic HBV infection.

PubMed

Li, Fan; Li, Xiaodong; Yan, Tao; Liu, Yan; Cheng, Yongqian; Xu, Zhihui; Shao, Qing; Liao, Hao; Huang, Pengyu; Li, Jin; Chen, Guo-Feng; Xu, Dongping

2018-03-01

Limited data are available regarding the association of hepatitis B virus (HBV) mutations with liver fibrosis in HBV infection. The study aimed to clarify whether HBV preS deletion mutation is associated with liver fibrosis progression. A total of 469 patients were enrolled, including 324 with chronic hepatitis B (CHB), 28 with HBV-related compensated liver cirrhosis (LC), and 117 with HBV-related decompensated LC. All CHB and compensated LC patients received liver biopsy. Fibrosis grade was assessed using METAVIR score. HBV preS deletion was determined by direct sequencing and verified by clonal sequencing. Overall preS deletion was detected in 12.6% (59/469) patients, specifically, in 7.51% (13/173), 10.60% (16/151), and 20.69% (30/145) of patients with no-to-mild liver fibrosis (F0-1), moderate-to-severe liver fibrosis (F2-3), and cirrhosis (F4), respectively (p < 0.01). Patients with preS-deleted HBV had lower serum HBV DNA and albumin levels compared to patients with wild-type HBV. The median length of preS deletion was 39-base pairs (bp) (3-204 bp) and the deletion most frequently emerged in preS2 initial region. Multivariate analysis identified the preS2 deletion rather than preS1 deletion to be an independent risk factor of significant fibrosis, i.e., METAVIR F ≥ 2 (p = 0.007). In addition, preS-deleted viral sequences were detected in the pool of intrahepatic HBV covalently closed circular DNA. HBV preS deletion is positively associated with liver fibrosis progression in chronic HBV-infected patients. HBV preS2 deletion may serve as a warning indicator for liver fibrosis progression.

Tenofovir disoproxil fumarate in Asian or Pacific Islander chronic hepatitis B patients with high viral load (≥ 9 log10 copies/ml).

PubMed

Fung, Scott; Gordon, Stuart C; Krastev, Zahary; Horban, Andrzej; Petersen, Jörg; Sperl, Jan; Gane, Edward; Jacobson, Ira M; Yee, Leland J; Dinh, Phillip; Martins, Eduardo B; Flaherty, John F; Kitrinos, Kathryn M; Dusheiko, Geoffrey; Trinh, Huy; Flisiak, Robert; Rustgi, Vinod K; Buti, Maria; Marcellin, Patrick

2015-02-01

We evaluated the antiviral response of Asian or Pacific Islander (API) patients with chronic hepatitis B (CHB) who had baseline high viral load (HVL), defined as pre-treatment hepatitis B virus (HBV) DNA ≥9 log10 copies/ml, following up to 288 weeks of tenofovir disoproxil fumarate (TDF) treatment. A total of 205 HBeAg-negative and HBeAg-positive self-described API patients received 48 weeks of TDF 300 mg (HVL n = 18) or adefovir dipivoxil 10 mg (HVL n = 15) in a blinded fashion, followed by open-label TDF for an additional 240 weeks. The proportions of HVL vs. non-HVL patients with HBV DNA <400 copies/ml were compared. Mean declines in HBV DNA were evaluated in API vs. non-API patients. Throughout the first 72 weeks of treatment, a smaller proportion of HVL API patients reached HBV DNA <400 copies/ml than non-HVL API patients. However, after this timepoint similar proportions of HVL and non-HVL API patients achieved HBV DNA <400 copies/ml (100% vs. 97%, respectively), which was maintained through week 288, where 92% of HVL patients and 99% of non-HVL API patients on treatment had HBV DNA <400 copies/ml. During the 288 weeks of treatment, API patients had similar mean HBV DNA declines as non-API patients, regardless of whether patients were HVL or non-HVL. No API HVL patient had persistent viremia at week 288. No resistance was detected among HVL or non-HVL patients. API patients with HVL CHB achieve HBV DNA <400 copies/ml with long-term TDF treatment; however, achieving viral suppression may take longer for HVL patients relative to non-HVL API patients. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sequential therapy with entecavir and PEG-INF in patients affected by chronic hepatitis B and high levels of HBV-DNA with non-D genotypes.

PubMed

Boglione, L; D'Avolio, A; Cariti, G; Milia, M G; Simiele, M; De Nicolò, A; Ghisetti, V; Di Perri, G

2013-04-01

Complete eradication of hepatitis B virus (HBV) is rarely achieved. Treatment options include currently available nucleos(t)ide analogues and pegylated interferon. The aim of our exploratory study was to assess the effectiveness of sequential therapy for chronic hepatitis B (CHB) vs the current standard of care. We evaluated an association with entecavir and pegylated interferon alfa-2a (PEG-IFN) in 20 patients with hepatitis B, high HBV viremia and genotypes A, B, C and E. Patients received entecavir alone for 12 weeks, then entecavir and PEG-IFN for 12 weeks, lastly PEG-IFN alone for 36 weeks. The results were compared with 20 patients (control group) treated in the past with 48 weeks of PEG-IFN monotherapy. Our results show that complete sustained virological response (SVR) and partial SVR were, respectively, 60% and 80% in the study group and 10% and 30% in the control group; anti-HBe seroconversion rate were 76.9% vs 15%, and anti-HBs seroconversion were 20% vs 0%, respectively. We found a correlation among different genotypes and virological and serological outcomes - genotype C has a better virological response, while genotype A had a better serological response, and E genotype had a poor response. These results show that a sequential approach is a promising strategy of treatment in patients with CHB and high viremia in comparison with PEG-IFN monotherapy. The E genotype seems to have the worse rate of response and requires other treatment strategies. © 2013 Blackwell Publishing Ltd.

Prognostic value of the combined use of transient elastography and fibrotest in patients with chronic hepatitis B.

PubMed

Park, Mi Sung; Kim, Seung Up; Kim, Beom Kyung; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Shin, Seung Hwan; Kang, Wonseok; Moon, Chansoo; Han, Kwang-Hyub

2015-02-01

Liver stiffness (LS) measurement using transient elastography and the FibroTest (FT) are alternatives to liver biopsy (LB) in assessing liver fibrosis. We investigated the prognostic role of the combined use of LS and FT in predicting liver-related events (LREs) in patients with chronic hepatitis B (CHB). Consecutive patients with CHB who underwent LB, along with LS and FT on the same day were recruited. LRE was defined as hepatic decompensation, hepatocellular carcinoma (HCC) or liver-related death. A total of 151 patients (86 male) were analyzed. During follow-up (median 59.9 months), overall 18 (11.9%) patients experienced LREs. The areas under receiver-operating characteristic curves of LS, FT, LS + FT and LS × FT in predicting LRE were 0.701, 0.668, 0.702 and 0.741 respectively. After adjusting for age and histological fibrosis staging, significant variables in univariate analysis (both P < 0.05), LS + FT and LS × FT were independent predictors of LREs with hazard ratios (HRs) of 1.080 and 1.126 (all P < 0.05) respectively. When subjects were divided into three groups according to quartile stratification (low quartile, interquartile and high quartile) using LS + FT and LS × FT, cumulative LRE development rate significantly increased with a corresponding increase in value among three groups respectively (log-rank test, all P < 0.05). The combined use of LS and FT significantly predicted forthcoming LRE development, but with only a slight additional benefit compared to LS or FT alone. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Epidemiology, disease burden and outcomes of cirrhosis in a large secondary care hospital in South Auckland, New Zealand.

PubMed

Hsiang, J C; Bai, W W; Raos, Z; Stableforth, W; Upton, A; Selvaratnam, S; Gane, E J; Gerred, S J

2015-02-01

Liver cirrhosis is an important cause of morbidity and mortality; however, little is known about its impact in New Zealand. We aim to determine the disease burden, epidemiology and outcomes of cirrhotic patients. This is a retrospective study of cirrhosis patients under secondary public hospital care in a geographically defined region, between the years 2000 and 2011. Cirrhosis complications and mortality was recorded. Poisson log-linear regression analysis was performed for incidence rate ratio (IRR) and Cox regression analysis was used to analyse time-related events. Seven hundred and forty-six cirrhotic patients were analysed; most were European/Other (39.9%), Pacific islanders (21.6%), Southeast Asian/Chinese (17.8%) and Maori (12.3%). 68.4% were male. The common primary aetiologies for cirrhosis were chronic hepatitis B (CHB) cirrhosis (37.3%), alcoholic liver disease (ALD) cirrhosis (24.1%), chronic hepatitis C (CHC) cirrhosis (22.3%) and non-alcoholic fatty liver disease (NAFLD) cirrhosis (16.4%). The hepatocellular carcinoma (HCC) mortality rates were highest in NAFLD and CHB cirrhosis groups (3.0 and 3.1 per 100 patient-year respectively), compared with ALD and CHC groups (2.2 and 1.4 per 100 patient-year, all P < 0.05 respectively). Patients with ALD and NAFLD cirrhosis had the highest all-cause and non-HCC mortality rate compared with viral hepatitis cirrhosis groups. The IRR for HCC incidence, liver-related mortality and HCC mortality were 1.087, 1.098 and 1.114, respectively (all P < 0.001), suggesting increasing incidence and disease burden over the study period. The number of cirrhotic patients in secondary care is increasing steadily. Cirrhosis complications and mortality rates are also rising, particularly the incidence and mortality of HCC. © 2014 Royal Australasian College of Physicians.

A straightforward access to TMG-chitooligomycins and their evaluation as β-N-acetylhexosaminidase inhibitors.

PubMed

Halila, Sami; Samain, Eric; Vorgias, Constantin E; Armand, Sylvie

2013-03-07

A chemo-biotechnological approach is reported for the synthesis of TMG-chitooligomycins, CO-n (NMe(3)). Their abilities to inhibit β-N-acetylhexosaminidases (HexNAcases), from Aspergillus oryzae (AoHex, fungi), Canavalia ensiformis (CeHex, plant) HexNAcases and a chitobiase from Serratia marcescens (SmCHB, bacteria) were studied and compared with their precursors CO-n (N). CO-n (NMe(3)) were revealed as potent inhibitors for AoHex and SmCHB with a proved chain length effect while CO-n (N) was a highly selective inhibitor of SmCHB. This route can be considered as the privileged way to produce easily and in large scale a wide range of size-defined chitooligosaccharide-based inhibitors to fine-tune the structure-activity relationships for inhibition of HexNAcases from various origins. Copyright © 2012 Elsevier Ltd. All rights reserved.

Autoimmune liver diseases in the Asia-Pacific region: Proceedings of APASL symposium on AIH and PBC 2016.

PubMed

Tanaka, Atsushi; Ma, Xiong; Yokosuka, Osamu; Weltman, Martin; You, Hong; Amarapurkar, Deepak N; Kim, Yoon Jun; Abbas, Zaigham; Payawal, Diana A; Chang, Ming-Ling; Efe, Cumali; Ozaslan, Ersan; Abe, Masanori; Mitchell-Thain, Robert; Zeniya, Mikio; Han, Kwang Hyub; Vierling, John M; Takikawa, Hajime

2016-11-01

During the 25th annual meeting of the Asia-Pacific Association for the Study of the Liver (APASL 2016) in Tokyo, we organized and moderated an inaugural satellite symposium on the autoimmune liver diseases, autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC). Following the keynote lecture by John M. Vierling (USA), speakers from the Asia-Pacific region provided an up-to-date perspective on the epidemiology, clinical practice and research in AIH and PBC in the Asia-Pacific region. Although epidemiology and clinical features of AIH seem to be similar in East Asia compared to those in western countries, the majority of patients with AIH are detected at an advanced stage and have higher mortality rates in South Asia, indicating an unmet need for earlier diagnosis and the initiation of appropriate immunosuppressive treatment. PBC is more commonly seen in Australia and East Asia. As of 2016, clinical practice guidelines (CPG) for PBC have been published in Japan and China. Ursodeoxycholic acid (UDCA) is recommended as a first-line therapy by both CPG. Nevertheless, one of the unmet therapeutic needs in PBC is the treatment of patients refractory to or intolerant of UDCA. It is of interest that the prevalence of chronic hepatitis B (CHB) in PBC patients was low in Taiwan and mainland China where the prevalence of CHB is very high. In this review, we overview this exciting and epoch-making symposium.

Cost-effectiveness comparison of lamivudine plus adefovir combination treatment and nucleos(t)ide analog monotherapies in Chinese chronic hepatitis B patients.

PubMed

Zhang, Chi; Ke, Weixia; Liu, Li; Gao, Yanhui; Yao, Zhenjiang; Ye, Xiaohua; Zhou, Shudong; Yang, Yi

2016-01-01

Lamivudine (LAM) plus adefovir (ADV) combination therapy is clinically efficacious for treating chronic hepatitis B (CHB) patients in China, but no pharmacoeconomic evaluations of this strategy are available. The aim of this study was to examine the cost-effectiveness of LAM plus ADV combination treatment compared with five other nucleos(t)ide analog monotherapies (LAM, ADV, telbivudine [TBV], entecavir [ETV], and tenofovir [TDF]). To simulate the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs) for different therapy options, a Markov model that included five initial monotherapies and LAM plus ADV combination as an initial treatment was developed. Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV; alternative: direct use of ETV + ADV) were considered separately for treating patients refractory to initial therapy. One-way and probabilistic sensitivity analyses were used to explore model uncertainties. In base-case analysis, ETV had the lowest lifetime cost and served as the reference therapy. Compared to the reference, LAM, ADV, and TBV had higher costs and lower efficacy, and were completely dominated by ETV. LAM plus ADV combination therapy or TDF was more efficacious than ETV, but also more expensive. Although the incremental cost-effectiveness ratios of combination therapy or TDF were both higher than the willingness-to-pay threshold of $20,466/QALY gained for the reference treatment, in an alternative scenario analysis LAM plus ADV combination therapy would be the preferable treatment option. ETV and LAM plus ADV combination therapy are both cost-effective strategies for treating Chinese CHB patients.

Antibodies to P450IID6, SLA, PDH-E2 and BCKD-E2 in Japanese patients with chronic hepatitis.

PubMed

Nishioka, M; Morshed, S A; Parveen, S; Kono, K; Matsuoka, H; Manns, M P

1997-12-01

Auto-antibodies specific to various antigens in chronic hepatitis (CH) have been detected but their specificities and implications were uncertain. The aims of the present study were to investigate the frequency and the significance of seropositivity of antibodies to P450IID6 or liver/kidney microsome 1 (LKM1), soluble liver antigen (SLA), pyruvate dehydrogenase (PDH) and branched-chain keto acid dehydrogenase (BCKD) in 188 Japanese patients with different forms of CH by western blot or enzyme immunoassay (EIA). Anti-LKM1 was also measured by indirect immunofluorescent test. Anti-P450IID6 was found in 6/188 (3.2%) CH patients including 5/104 (4.8%) with hepatitis C virus (C) infection and 1/12 (8.3%) CH-C patients with antibodies to nuclear and smooth muscle antigens and hypergammaglobulinaemia (> 2.5 g/dL). This patient was the only one diagnosed with autoimmune hepatitis (AIH). All CH patients with hepatitis B (B), hepatitis non-B non-C (NBNC) and AIH were seronegative for anti-LKM1. Antibodies to soluble liver antigen were found in two of 188 (1%) patients, one with AIH and one with CH-B. Anti-BCKD-E2 but not anti-PDH-E2 was found in four patients (2.5%), one with AIH, two with CH-C, and one with NBNC. There was no obvious difference in age, sex ratio and laboratory findings in patients with or without anti-SLA and anti-BCKD-E2. Antibodies to P450IID6, SLA, PDH-E2 and BCKD-E2 are uncommon in adult CH-C, CH-B, CH-NBNC and AIH patients in Japan. Some of these patients positive for auto-antibodies appear to have autoimmune features and might require a careful follow up. The heterogeneity of these antibodies in CH preclude further justification for subtyping of AIH by the presence of the distinct auto-antibodies.

Complementary Effects of Interleukin-15 and Alpha Interferon Induce Immunity in Hepatitis B Virus Transgenic Mice.

PubMed

Di Scala, Marianna; Otano, Itziar; Gil-Fariña, Irene; Vanrell, Lucia; Hommel, Mirja; Olagüe, Cristina; Vales, Africa; Galarraga, Miguel; Guembe, Laura; Ortiz de Solorzano, Carlos; Ghosh, Indrajit; Maini, Mala K; Prieto, Jesús; González-Aseguinolaza, Gloria

2016-10-01

In chronic hepatitis B (CHB), failure to control hepatitis B virus (HBV) is associated with T cell dysfunction. HBV transgenic mice mirror many features of the human disease, including T cell unresponsiveness, and thus represent an appropriate model in which to test novel therapeutic strategies. To date, the tolerant state of CD8(+) T cells in these animals could be altered only by strong immunogens or by immunization with HBV antigen-pulsed dendritic cells; however, the effectors induced were unable to suppress viral gene expression or replication. Because of the known stimulatory properties of alpha interferon (IFN-α) and interleukin-15 (IL-15), this study explored the therapeutic potential of liver-directed gene transfer of these cytokines in a murine model of CHB using adeno-associated virus (AAV) delivery. This combination not only resulted in a reduction in the viral load in the liver and the induction of an antibody response but also gave rise to functional and specific CD8(+) immunity. Furthermore, when splenic and intrahepatic lymphocytes from IFN-α- and IL-15-treated animals were transferred to new HBV carriers, partial antiviral immunity was achieved. In contrast to previous observations made using either cytokine alone, markedly attenuated PD-L1 induction in hepatic tissue was observed upon coadministration. An initial study with CHB patient samples also gave promising results. Hence, we demonstrated synergy between two stimulating cytokines, IL-15 and IFN-α, which, given together, constitute a potent approach to significantly enhance the CD8(+) T cell response in a state of immune hyporesponsiveness. Such an approach may be useful for treating chronic viral infections and neoplastic conditions. With 350 million people affected worldwide and 600,000 annual deaths due to HBV-induced liver cirrhosis and/or hepatocellular carcinoma, chronic hepatitis B (CHB) is a major health problem. However, current treatment options are costly and not very effective and/or need to be administered for life. The unprecedented efficacy of the strategy described in our paper may offer an alternative and is relevant for a broad spectrum of readers because of its clear translational importance to other chronic viral infections in which a hyporesponsive antigen-specific T cell repertoire prevents clearance of the pathogen. Copyright © 2016 Di Scala et al.

[Health care access of Sub-Saharan African migrants living with chronic hepatitis B].

PubMed

Vignier, Nicolas; Spira, Rosemary Dray; Lert, France; Pannetier, Julie; Ravalihasy, Andrainolo; Gosselin, Anne; Lydié, Nathalie; Bouchaud, Olivier; Desgrées du Loû, Annabel

2017-07-10

Objective: The objective of this study was to analyse health care access of Sub-Saharan African migrants living with chronic hepatitis B (CHB) in France. Methods: The ANRS-Parcours survey was a life-event survey conducted in 2012-2013 among Sub-Saharan African migrants recruited by health care facilities managing CHB in the Paris region. Data were collected by face-to-face interview using a biographical grid and a standardized questionnaire. Results: 96.4% of the 619 participants basic health insurance coverage with CMU universal health insurance coverage in 18.6% of cases and AME state medical assistance in 23.4% of cases. One-third of basic health insurance beneficiaries did not have any complementary health insurance and 75.7% had long-term disease status. The median time to acquisition of health insurance cover after arrival in France was one year. 22.0% of participants reported delaying health care for financial reasons since their arrival in France and 9.7% reported being refused health care usually due to refusal of CMU or AME. Health care access was effective within one year of the diagnosis. Delayed health care access was more common among people without health insurance coverage in the year of diagnosis. Patients lost to follow-up for more than 12 months were rare. Conclusion: Sub-Saharan African migrants living with chronic hepatitis B rapidly access health insurance coverage and health care. However, barriers to health care access persist for some people, essentially due to absent or incomplete health insurance cover and refusal of care for AME or CMU beneficiaries.

Late-glacial and early Holocene changes in vegetation and lake-level at Hauterive/Rouges-Terres, Lake Neuchâtel (Switzerland)

NASA Astrophysics Data System (ADS)

Magny, Michel; Thew, Nigel; Hadorn, Philippe

2003-01-01

Palynological and sedimentological analyses of a sedimentary sequence sampled at Hauterive/Rouges-Terres, Lake Neuchâtel (Switzerland) provide documentation of changes in vegetation and lake-level during the Bølling, Younger Dryas and Preboreal pollen zones, and have allowed a comparison with sequences covering the same period from other sites located in the western part of the Swiss Plateau. The Juniperus-Hippophaë zone (regional pollen assemblage zone (RPAZ) CHb-2, first part of the Bølling, ca. 14 650-14 450 cal. yr BP) was characterised by a generally low lake-level. A weak rise occurred during this zone. The Juniperus-Hippophaë to Betula zone transition coincided with a lake-level lowering, interrupted by a short-lived but marked phase of higher lake-level recorded at the neighbouring site of Hauterive-Champréveyres, but not present at Hauterive/Rouges-Terres owing to an erosion surface. Shortly after the beginning of the Betula zone (RPAZ CHb-3, second part of the Bølling, ca 14 450-14 000 cal. yr BP), a marked rise in lake-level occurred. It was composed of two successive periods of higher level, coinciding with high values of Betula, separated by a short episode of relatively lower lake-level associated with raised values in Artemisia and other non-arboreal pollen. The last part of RPAZ CHb-3 saw a fall in lake-level. The lower lake-levels during RPAZ CHb-2 to early RPAZ CHb-3 can be correlated with the abrupt warming at the beginning of the Greenland Interstadial (GI) 1e thermal maximum. The successive episodes of higher lake-level punctuating the GI 1e might be linked to the so-called Intra-Bølling Cold Oscillations identified from several palaeoclimatic records in the North Atlantic area, and also documented in oxygen-isotope data sets from Swiss Plateau lakes. The Hauterive/Rouges-Terres lake-level record provides evidence for marked climatic drying through the second part of the Younger Dryas event (GS1), during the GS1-Preboreal (RPAZ CHb-4b-4c) transition (except for a rise at ca. 11 450-11 400 cal. yr BP), and at the RPAZ CHb-4c-5 (Preboreal-Boreal) transition, following the Preboreal Oscillation (after 11 150 cal. yr BP). The Preboreal Oscillation coincided with higher lake-levels, its end being followed by a rapid expansion of Corylus, Quercus, Ulmus and Tilia. The Hauterive/Rouges-Terres lake-level record suggests that radiocarbon plateau at 12 600, 10 000 and 9500 14C yr BP corresponded to periods of generally lower lake-level. This suggests that an increase in solar activity may have contributed to both climatic dryness and a decrease in atmospheric radiocarbon content.

Transient Elastography is Superior to FIB-4 in Assessing the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B

PubMed Central

Kim, Seung Up; Kim, Beom Kyung; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Song, Kijun; Han, Kwang-Hyub

2016-01-01

Abstract Liver stiffness (LS), assessed using transient elastography (TE), and (FIB-4) can both estimate the risk of developing hepatocellular carcinoma (HCC). We compared prognostic performances of LS and FIB-4 to predict HCC development in patients with chronic hepatitis B (CHB). Data from 1308 patients with CHB, who underwent TE, were retrospectively analyzed. FIB-4 was calculated for all patients. The cumulative rate of HCC development was assessed using Kaplan–Meier curves. The predictive performances of LS and FIB-4 were evaluated using time-dependent receiver-operating characteristic (ROC) curves. The mean age (883 men) was 50 years. During follow-up (median 6.1 years), 119 patients developed HCC. The areas under the ROC curves (AUROCs) predicting HCC risk at 3, 5, and 7 years were consistently greater for LS than for FIB-4 (0.791–0.807 vs 0.691–0.725; all P < 0.05). Similarly, when the respective AUROCs for LS and FIB-4 at every time point during the 7-year follow-up were plotted, LS also showed consistently better performance than FIB-4 after 1 year of enrollment. The combined use of LS and FIB-4 significantly enhanced the prognostic performance compared with the use of FIB-4 alone (P < 0.05), but the performance of the combined scores was statistically similar to that of LS alone (P > 0.05). LS showed significantly better performance than FIB-4 in assessing the risk of HCC development, and the combined use of LS and FIB-4 did not provide additional benefit compared with the use of LS alone. Hence, LS assessed using TE might be helpful for optimizing HCC surveillance strategies. PMID:27196449

Transient Elastography is Superior to FIB-4 in Assessing the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B.

PubMed

Kim, Seung Up; Kim, Beom Kyung; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Song, Kijun; Han, Kwang-Hyub

2016-05-01

Liver stiffness (LS), assessed using transient elastography (TE), and (FIB-4) can both estimate the risk of developing hepatocellular carcinoma (HCC). We compared prognostic performances of LS and FIB-4 to predict HCC development in patients with chronic hepatitis B (CHB).Data from 1308 patients with CHB, who underwent TE, were retrospectively analyzed. FIB-4 was calculated for all patients. The cumulative rate of HCC development was assessed using Kaplan-Meier curves. The predictive performances of LS and FIB-4 were evaluated using time-dependent receiver-operating characteristic (ROC) curves.The mean age (883 men) was 50 years. During follow-up (median 6.1 years), 119 patients developed HCC. The areas under the ROC curves (AUROCs) predicting HCC risk at 3, 5, and 7 years were consistently greater for LS than for FIB-4 (0.791-0.807 vs 0.691-0.725; all P < 0.05). Similarly, when the respective AUROCs for LS and FIB-4 at every time point during the 7-year follow-up were plotted, LS also showed consistently better performance than FIB-4 after 1 year of enrollment. The combined use of LS and FIB-4 significantly enhanced the prognostic performance compared with the use of FIB-4 alone (P < 0.05), but the performance of the combined scores was statistically similar to that of LS alone (P > 0.05).LS showed significantly better performance than FIB-4 in assessing the risk of HCC development, and the combined use of LS and FIB-4 did not provide additional benefit compared with the use of LS alone. Hence, LS assessed using TE might be helpful for optimizing HCC surveillance strategies.

Epidemiological, virological and clinical characteristics of HBV infection in 223 HIV co-infected patients: a French multi-centre collaborative study.

PubMed

Thibault, Vincent; Gaudy-Graffin, Catherine; Colson, Philippe; Gozlan, Joël; Schnepf, Nathalie; Trimoulet, Pascale; Pallier, Coralie; Saune, Karine; Branger, Michel; Coste, Marianne; Thoraval, Francoise Roudot

2013-03-15

Chronic hepatitis B (CHB) is a clinical concern in human immunodeficiency virus (HIV)-infected individuals due to substantial prevalence, difficulties to treat, and severe liver disease outcome. A large nationwide cross-sectional multicentre analysis of HIV-HBV co-infected patients was designed to describe and identify parameters associated with virological and clinical outcome of CHB in HIV-infected individuals with detectable HBV viremia. A multicenter collaborative cross-sectional study was launched in 19 French University hospitals distributed through the country. From January to December 2007, HBV load, genotype, clinical and epidemiological characteristics of 223 HBV-HIV co-infected patients with an HBV replication over 1000 IU/mL were investigated. Patients were mostly male (82%, mean age 42 years). Genotype distribution (A 52%; E 23.3%; D 16.1%) was linked to risk factors, geographic origin, and co-infection with other hepatitis viruses. This genotypic pattern highlights divergent contamination event timelines by HIV and HBV viruses. Most patients (74.7%) under antiretroviral treatment were receiving a drug with anti-HBV activity, including 47% receiving TDF. Genotypic lamivudine-resistance detected in 26% of the patients was linked to duration of lamivudine exposure, age, CD4 count and HIV load. Resistance to adefovir (rtA181T/V) was detected in 2.7% of patients. Advanced liver lesions were observed in 54% of cases and were associated with an older age and lower CD4 counts but not with viral load or genotype. Immune escape HBsAg variants were seldom detected. Despite the detection of advanced liver lesions in most patients, few were not receiving anti-HBV drugs and for those treated with the most potent anti-HBV drugs, persistent replication suggested non-optimal adherence. Heterogeneity in HBV strains reflects epidemiological differences that may impact liver disease progression. These findings are strong arguments to further optimize clinical management and to promote vaccination in HIV-infected patients.

DNMT1 modulation in chronic hepatitis B patients and hypothetic influence on mitochondrial DNA methylation status during long-term nucleo(t)side analogs therapy.

PubMed

Madeddu, Giordano; Ortu, Silvia; Garrucciu, Giovanni; Maida, Ivana; Melis, Michela; Muredda, Alberto Augusto; Mura, Maria Stella; Babudieri, Sergio

2017-07-01

Inhibition of viral replication is the most important goal in patients with Hepatitis B virus chronic infection (CHB). Currently, five oral nucleo(t)side analogs (NAs), including Lamivudine, Adefovir, Telbivudine, Entecavir, and Tenofovir, have been approved for treatment. The widespread use of NAs has also been linked with a progressive growth of unlikely anomaly attributable to mitochondrial dysfunctions, not previously recognized. Here, we explore the hypothesis that NAs may cause persistent epigenetic changes during prolonged NAs therapy in CHB patients. We obtained peripheral blood mononuclear cells (PBMC) from whole blood samples of consecutive patients with chronic HBV infection, 18 receiving NAs and 20 untreated patients. All patients were Caucasian and Italians. Epigenetic analysis was performed by Bisulphite sequencing PCR to search the existence of methylated cytosine residues in the Light (L)-strands of mitochondrial DNA control region (D-loop). Gene expression analysis of DNA methyltransferases 1 was performed by a quantitative relative Real-Time Polymerase Chain Reaction (PCR). DNMT1 expression was significantly (P < 000001) higher in NA treated patients (4.09, IQR 3.52-5.15) when compared with HBV naives (0.61, IQR 0.34-0.82). Besides, DNMT1 expression was significantly correlated with NA therapy duration (Spearman Rho = 0.67; P < 0.05). Furthermore, NA therapy duration was the only significant predictor of DNMT1 expression at multivariate analysis (Beta = 0.95, P < 0.0000001). Bisulphite PCR sequencing showed that methylation of cytosine residues occurred in a higher percentage in patients treated with NAs in comparison with untreated patients and healthy controls. Our data showed a DNMT1 overexpression significantly correlated to NA therapy duration and an higher regional mtDNA hypermethylation. This might suggest an epigenetic alteration that could be involved in one of the possible mechanisms of mitochondrial gene regulation during NAs therapy. © 2017 Wiley Periodicals, Inc.

Refinement of intraperitoneal injection of sodium pentobarbital for euthanasia in laboratory rats (Rattus norvegicus).

PubMed

Zatroch, Katie K; Knight, Cameron G; Reimer, Julie N; Pang, Daniel S J

2017-02-21

The Canadian Council on Animal Care and American Veterinary Medical Association classify intraperitoneal (IP) pentobarbital as an acceptable euthanasia method in rats. However, national guidelines do not exist for a recommended dose or volume and IP euthanasia has been described as unreliable, with misinjections leading to variable success in ensuring a timely death. The aims of this study were to assess and improve efficacy and consistency of IP euthanasia. In a randomized, blinded study, 51 adult female Sprague-Dawley rats (170-495 g) received one of four treatments: low-dose low-volume (LL) IP pentobarbital (n = 13, 200 mg/kg pentobarbital), low-dose high-volume (LH) IP pentobarbital (n = 14, 200 mg/kg diluted 1:3 with phosphate buffered saline), high-dose high-volume (HH, n = 14, 800 mg/kg pentobarbital), or saline. Times to loss of righting reflex (LORR) and cessation of heartbeat (CHB) were recorded. To identify misinjections, necropsy examinations were performed on all rats. Video recordings of LL and HH groups were analyzed for pain-associated behaviors. Between-group comparisons were performed with 1-way ANOVA and Games-Howell post hoc tests. Variability in CHB was assessed by calculating the coefficient of variation (CV). The fastest euthanasia method (CHB) was HH (283.7 ± 38.0 s), compared with LL (485.8 ± 140.7 s, p = 0.002) and LH (347.7 ± 72.0 s, p = 0.039). Values for CV were: HH, 13.4%; LH, 20.7%; LL, 29.0%. LORR time was longest in LL (139.5 ± 29.6 s), compared with HH (111.6 ± 19.7 s, p = 0.046) and LH (104.2 ± 19.3 s, p = 0.01). Misinjections occurred in 17.0% (7/41) of euthanasia attempts. Pain-associated behavior incidence ranged from 36% (4/11, LL) to 46% (5/11, HH). These data illustrate refinement of the IP pentobarbital euthanasia technique. Both dose and volume contribute to speed of death, with a dose of 800 mg/kg (HH) being the most effective method. An increase in volume alone does not significantly reduce variability. The proportion of misinjections was similar to that of previous studies.

Safety and efficacy of anti-PD-L1 therapy in the woodchuck model of HBV infection

PubMed Central

Balsitis, Scott; Gali, Volodymyr; Mason, Pamela J.; Chaniewski, Susan; Levine, Steven M.; Wichroski, Michael J.; Feulner, Michael; Song, Yunling; Granaldi, Karen; Loy, James K.; Thompson, Chris M.; Lesniak, Jacob A.; Brockus, Catherine; Kishnani, Narendra; Menne, Stephan; Cockett, Mark I.; Iyer, Renuka; Mason, Stephen W.

2018-01-01

Immune clearance of Hepatitis B virus (HBV) is characterized by broad and robust antiviral T cell responses, while virus-specific T cells in chronic hepatitis B (CHB) are rare and exhibit immune exhaustion that includes programmed-death-1 (PD-1) expression on virus-specific T cells. Thus, an immunotherapy able to expand and activate virus-specific T cells may have therapeutic benefit for CHB patients. Like HBV-infected patients, woodchucks infected with woodchuck hepatitis virus (WHV) can have increased hepatic expression of PD-1-ligand-1 (PD-L1), increased PD-1 on CD8+ T cells, and a limited number of virus-specific T cells with substantial individual variation in these parameters. We used woodchucks infected with WHV to assess the safety and efficacy of anti-PD-L1 monoclonal antibody therapy (αPD-L1) in a variety of WHV infection states. Experimentally-infected animals lacked PD-1 or PD-L1 upregulation compared to uninfected controls, and accordingly, αPD-L1 treatment in lab-infected animals had limited antiviral effects. In contrast, animals with naturally acquired WHV infections displayed elevated PD-1 and PD-L1. In these same animals, combination therapy with αPD-L1 and entecavir (ETV) improved control of viremia and antigenemia compared to ETV treatment alone, but with efficacy restricted to a minority of animals. Pre-treatment WHV surface antigen (sAg) level was identified as a statistically significant predictor of treatment response, while PD-1 expression on peripheral CD8+ T cells, T cell production of interferon gamma (IFN-γ) upon in vitro antigen stimulation (WHV ELISPOT), and circulating levels of liver enzymes were not. To further assess the safety of this strategy, αPD-L1 was tested in acute WHV infection to model the risk of liver damage when the extent of hepatic infection and antiviral immune responses were expected to be the greatest. No significant increase in serum markers of hepatic injury was observed over those in infected, untreated control animals. These data support a positive benefit/risk assessment for blockade of the PD-1:PD-L1 pathway in CHB patients and may help to identify patient groups most likely to benefit from treatment. Furthermore, the efficacy of αPD-L1 in only a minority of animals, as observed here, suggests that additional agents may be needed to achieve a more robust and consistent response leading to full sAg loss and durable responses through anti-sAg antibody seroconversion. PMID:29444087

A data-driven modeling approach to stochastic computation for low-energy biomedical devices.

PubMed

Lee, Kyong Ho; Jang, Kuk Jin; Shoeb, Ali; Verma, Naveen

2011-01-01

Low-power devices that can detect clinically relevant correlations in physiologically-complex patient signals can enable systems capable of closed-loop response (e.g., controlled actuation of therapeutic stimulators, continuous recording of disease states, etc.). In ultra-low-power platforms, however, hardware error sources are becoming increasingly limiting. In this paper, we present how data-driven methods, which allow us to accurately model physiological signals, also allow us to effectively model and overcome prominent hardware error sources with nearly no additional overhead. Two applications, EEG-based seizure detection and ECG-based arrhythmia-beat classification, are synthesized to a logic-gate implementation, and two prominent error sources are introduced: (1) SRAM bit-cell errors and (2) logic-gate switching errors ('stuck-at' faults). Using patient data from the CHB-MIT and MIT-BIH databases, performance similar to error-free hardware is achieved even for very high fault rates (up to 0.5 for SRAMs and 7 × 10(-2) for logic) that cause computational bit error rates as high as 50%.

An image processing study of a reentrant discotic cholesteric - biaxial cholesteric phase transition

NASA Astrophysics Data System (ADS)

Luders, D. D.; Zoner, G. A.; Santos, O. R.; Braga, W. S.; Sampaio, A. R.; Kimura, N. M.; Palangana, A. J.; Simões, M.

2018-04-01

In this work, we study and characterize the cholesteric sequence of phases (ChDr - ChB - ChD), where the first ChDr is the reentrant cholesteric discotic phase, ChB is the cholesteric biaxial phase and the second ChD is the cholesteric discotic phase. This sequence of phases is studied through polarized light microscopy and image processing technique, where, for the first time, the domains and borders of these transitions are established and characterized. They are also investigated and optically characterized throughout their textures.

[Successful outcome of a pregnancy with an extremely low fetal heart rate (34 bpm) due to isolated complete heart block--case report].

PubMed

Hamela-Olkowska, Anita; Dangel, Joanna; Miszczak-Knecht, Maria

2009-09-01

Isolated complete congenital heart block (CHB) in the majority of cases is associated with the presence of autoantibodies to SSA (Ro) and SSB (La) antigens in the maternal serum. The prognosis is less favorable in fetuses with a ventricular rate < 55bpm. We have reported a case of a fetus with an isolated non-autoimmune CHB with an extremely low ventricular rate (34bpm) in which the outcome was favorable. In the neonate the non-compaction of the myocardium was diagnosed.

Association of Ghrelin Gene Polymorphisms and Serum Ghrelin Levels with the Risk of Hepatitis B Virus-Related Liver Diseases in a Chinese Population

PubMed Central

Rong, Chengzhi; Qin, Xue; Li, Shan

2015-01-01

Background The functions of ghrelin (GHRL) include anti-inflammatory effects, reduction of the fibrogenic response, protection of liver tissue, and regulation of cell proliferation. Genetic variations in the GHRL gene may play an important role in the development of chronic hepatitis B (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Therefore, we investigated whether GHRL gene polymorphisms and its serum levels are associated with hepatitis B virus (HBV)-related diseases risk in a Chinese population. Methods 176 patients with CHB, 106 patients with HBV-related LC, 151 patients with HBV-related HCC, and 167 healthy controls were recruited in the study. Genotyping of GHRL rs26311, rs27647, rs696217, and rs34911341 polymorphisms were determined with the polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) and DNA sequencing. The serum GHRL concentrations were determined using enzyme-linked immunosorbent assay (ELISA). Results Binary logistic regression analyses adjusting for gender and age revealed that a significant increased risk of LC was found in the GHRL rs26311 GC genotype and combined GC+CC genotypes when compared with the GG genotype (GC vs. GG: OR = 1.671, 95% CI = 1.013–2.757, P = 0.044; GC+CC vs. GG: OR = 1.674, 95% CI = 1.040–2.696, P = 0.034). In subgroup analysis by gender, binary logistic regression analyses adjusting for age showed that the GHRL rs26311 C allele and combined GC+CC genotypes were associated with a significantly increased risk to LC in males (C vs. G OR = 1.416, 95% CI = 1.017–1.972, P = 0.040; GC+CC vs. GG: OR = 1.729, 95% CI = 1.019–2.933, P = 0.042). In addition, we found significant decreased serum GHRL levels in LC patients compared with the healthy controls. However, there was no significant association of the GHRL rs26311 polymorphism with serum GHRL levels in LC patients. Conclusions These observations suggest that the GHRL rs26311 polymorphism is associated with an increased risk to HBV-related LC, especially in men. We also found an inverse association of serum GHRL levels with LC. PMID:26599409

Serum Levels of M2BPGi as Short-Term Predictors of Hepatocellular Carcinoma in Untreated Chronic Hepatitis B Patients.

PubMed

Liu, Jessica; Hu, Hui-Han; Lee, Mei-Hsuan; Korenaga, Masaaki; Jen, Chin-Lan; Batrla-Utermann, Richard; Lu, Sheng-Nan; Wang, Li-Yu; Mizokami, Masashi; Chen, Chien-Jen; Yang, Hwai-I

2017-10-30

This study examines the role of M2BPGi, a novel seromarker for chronic hepatitis, in predicting hepatocellular carcinoma (HCC) among untreated chronic hepatitis B (CHB) patients. In this nested case-control study, 1070 samples were assayed for M2BPGi, including 357 samples from HCC cases, and 713 samples from non-HCC controls, collected at various times throughout follow-up. HCC case samples were stratified according to years prior to diagnosis. Associations between M2BPGi and HCC were examined with multivariate logistic regression. M2BPGi, α-fetoprotein (AFP), and hepatitis B surface antigen (HBsAg) levels were significant independent short-term predictors of HCC, while M2BPGi was insignificant in long-term analyses. Compared to M2BPGi levels <1.0 cut-off index (COI), those with levels ≥2.0 COI had multivariate odds ratios (95% CI) for HCC of 7.40 (2.40-22.78), 6.46 (2.58-16.18), and 2.24 (0.97-5.15), respectively, for prediction of HCC within 1-2, 2-5, and ≥5 years. Higher proportions of individuals had M2BPGi levels ≥2.0 COI in samples closer to HCC diagnosis. Areas under receiver operating characteristic curves for models with M2BPGi, AFP, and HBsAg levels predicting HCC within 1-2, 2-5, and >5 years were 0.84, 0.81, and 0.75. M2BPGi is a strong and independent short-term predictor of HCC in CHB patients.

Gamma-glutamyl transpeptidase to cholinesterase and platelet ratio in predicting significant liver fibrosis and cirrhosis of chronic hepatitis B.

PubMed

Liu, Danping; Li, Jian; Lu, Wei; Wang, Yanbing; Zhou, Xinlan; Huang, Dan; Li, Xiufen; Ding, Rongrong; Zhang, Zhanqing

2018-06-12

To evaluate the performance of a new mathematical model gamma- glutamyl transpeptidase to cholinesterase and platelet ratio (GCPR) versus gamma- glutamyl transpeptidase to platelet ratio (GPR) in predicting significant fibrosis and cirrhosis of chronic hepatitis B (CHB). A complete cohort of 2343 patients was divided into early and late cohort depending on the time of liver biopsy. With reference to the Scheuer standard, liver pathological stage ≥S2 and ≥S4 were defined as significant fibrosis and cirrhosis, respectively. ROC curve was used to evaluate the performance of investigated models. In early cohort，the areas under ROC curves (AUROCs) of GCPR in predicting significant fibrosis of HBeAg-positive and HBeAg-negative patients (0.782 and 0.775) were both significantly greater than those of GPR (0.748 and 0.747) (Z＝8.198 and Z＝6.023, both P<0.0001); the AUROCs of GCPR in predicting cirrhosis of HBeAg-positive and HBeAg-negative patients (0.842 and 0.861) were both significantly greater than those of GPR (0.802 and 0.823) (Z＝6.686 and Z＝6.116, both P<0.0001). In early, late and complete cohort, using a single cutoff of GPCR>0.080, the specificities of GCPR in predicting significant fibrosis of HBeAg-positive patients were 83.3%, 88.2% and 85.0%, and of HBeAg-negative patients were 87.6%, 87.4% and 87.6%, respectively; and the sensitivities of GCPR in predicting cirrhosis of HBeAg-positive patients were 81.9%, 88.7% and 84.2%, and of HBeAg-negative patients were 83.1%,82.1% and 82.7%, respectively. GCPR has higher performance than GPR in predicting significant fibrosis and cirrhosis of CHB. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Comparison of Hybrid Capture 2 Assay with Real-time-PCR for Detection and Quantitation of Hepatitis B Virus DNA.

PubMed

Majid, Farjana; Jahan, Munira; Lutful Moben, Ahmed; Tabassum, Shahina

2014-01-01

Both real-time-polymerase chain reaction (PCR) and hybrid capture 2 (HC2) assay can detect and quantify hepatitis B virus (HBV) DNA. However, real-time-PCR can detect a wide range of HBV DNA, while HC2 assay could not detect lower levels of viremia. The present study was designed to detect and quantify HBV DNA by real-time-PCR and HC2 assay and compare the quantitative data of these two assays. A cross-sectional study was conducted in between July 2010 and June 2011. A total of 66 serologically diagnosed chronic hepatitis B (CHB) patients were selected for the study. Real-time-PCR and HC2 assay was done to detect HBV DNA. Data were analyzed by statistical Package for the social sciences (SPSS). Among 66 serologically diagnosed chronic hepatitis B patients 40 (60.61%) patients had detectable and 26 (39.39%) had undetectable HBV DNA by HC2 assay. Concordant results were obtained for 40 (60.61%) out of these 66 patients by real-time-PCR and HC2 assay with mean viral load of 7.06 ± 1.13 log 10 copies/ml and 6.95 ± 1.08 log 10 copies/ml, respectively. In the remaining 26 patients, HBV DNA was detectable by real-time-PCR in 20 patients (mean HBV DNA level was 3.67 ± 0.72 log 10 copies/ml. However, HBV DNA could not be detectable in six cases by the both assays. The study showed strong correlation (r = 0.915) between real-time-PCR and HC2 assay for the detection and quantification of HBV DNA. HC2 assay may be used as an alternative to real-time-PCR for CHB patients. How to cite this article: Majid F, Jahan M, Moben AL, Tabassum S. Comparison of Hybrid Capture 2 Assay with Real-time-PCR for Detection and Quantitation of Hepatitis B Virus DNA. Euroasian J Hepato-Gastroenterol 2014;4(1):31-35.

First case-control study of zoonotic brucellosis in Gafsa district, Southwest Tunisia.

PubMed

Khamassi Khbou, Médiha; Htira, Samaher; Harabech, Kaouther; Benzarti, M'hammed

2018-06-01

A case-control study was conducted, aimed to describe the clinical human brucellosis (CHB) pattern during 2015 in the Gafsa region (Southwest Tunisia) and to investigate the main risk factors involved in the disease occurrence. One hundred and four CHB cases were notified in 2015 in Gafsa district. All CHB cases that own ruminants were contacted, but only 32 accepted to participate in a matched case-control study. Thirty-two and thirty-one CHB cases and controls, respectively, were included in the study. The subjects were interviewed using a structured questionnaire. A total of 662 domestic ruminants (cattle, sheep and goats) belonging to cases and controls, were screened using the Rose Bengal Test, as recommended by the World Organisation of Animal Health. During 2015, the incidence of CHB was estimated to 30.8 per 100,000 inhabitants affecting mainly males aged between 30 and 39 years. The overall animal seropositivity to Brucella , was 21 and 1.9% in case and control farms, respectively (p < 0.0001). Only five risk factors were found to be significant: overall animal seropositivity (OR = 65.2; 95%CI: 13.3-318.7); handling aborted females (OR = 43.1; 95%CI: 8.3-222.7); presence of male ruminants in the herds (OR = 18.5; 95%CI: 5.18-66); owning seropositive goats (OR = 18.3; 95%CI: 2.4-137.6), owning seropositive sheep (OR = 9.66; 95%CI: 2.9-31.5) and history of abortion during the previous year in the herd (OR = 4.6; 95%CI: 1.3-12.6). Vaccination of animals against brucellosis was associated with lower odds of human brucellosis (OR = 0.03; 95%CI: 0.004-0.2). Raw milk and derivatives consumption was not a risk factor of human brucellosis. Based on this study, ruminants' vaccination coverage should be increased by enhancing the number of vaccinated animals and systematically including male ruminants in Tunisia. Comprehensive education programmes targeting both farmers and general population should be implemented.

Inclusion of Whole Flour from Latin-American Crops into Bread Formulations as Substitute of Wheat Delays Glucose Release and Uptake.

PubMed

Laparra, José Moisés; Haros, Monika

2018-03-01

Bakery formulations limiting glucose availability for uptake without compromising product quality are required. Herein, bread formulations containing whole flour from Amaranthus hypochondriacus (AB), Chenopodium quinoa (QB), Salvia hispanica L (ChB) or wheat (WWB) were compared to white bread (WB) for glycaemic index (GI) in fasted animals. The hepatic expression (mRNA) of PPAR-γ receptor as key regulator in substrate fractionation towards energy expenditure was monitored. GIs were associated to fluxes of glucose release (F Gluc ) and metabolic response (MTT assay) of HepG2 cells. ChB (19.7%) and AB (13.5%) decreased GI to a higher extent than QB (2.7%), but all increased expression of PPARγ in relation to WB. F Gluc (AB> > ChB, WWB, WB > QB) showed a reciprocal relationship with the area under curve (AUC) in vivo, and decreased MTT conversion values (WB > WWB, ChB, AB, QB) by HepG2 cells. Thus, inclusion of latin-american crops (LAcs) reducing GI, without compromising bread quality, could help preventing metabolic diseases.

Chemical Properties of Dialkyl Halonium Ions (R2Hal+) and Their Neutral Analogues, Methyl Carboranes, CH3-(CHB11Hal11), Where Hal = F, Cl.

PubMed

Stoyanov, Evgenii S

2017-04-20

Chloronium cations in their salts (C n H 2n+1 ) 2 Cl + {CHB 11 Cl 11 - }, with n = 1 to 3 and exceptionally stable carborane anions, are stable at ambient and elevated temperatures. The temperature at which they decompose to carbocations with HCl elimination (below 150 °C) decreases with the increasing n from 1 to 3 because of increasing ionicity of C-Cl bonds in the C-Cl + -C bridge. At room temperature, the salts of cations with n ≥ 4 [starting from t-Bu 2 Cl + or (cyclo-C 5 H 11 ) 2 Cl + ] are unstable and decompose. With decreasing chloronium ion stability, their ability to interact with chloroalkanes to form oligomeric cations increases. It was shown indirectly that unstable salt of fluoronium ions (CH 3 ) 2 F + (CHB 11 F 11 - ) must exist at low temperatures. The proposed (CH 3 ) 2 F + cation is much more reactive than the corresponding chloronium, showing at room temperature chemical properties expected of (CH 3 ) 2 Cl + at elevated temperatures.

Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: a randomised open-label trial (OSST trial).

PubMed

Ning, Qin; Han, Meifang; Sun, Yongtao; Jiang, Jiaji; Tan, Deming; Hou, Jinlin; Tang, Hong; Sheng, Jifang; Zhao, Mianzhi

2014-10-01

Durable post-treatment response is uncommon in chronic hepatitis B (CHB) patients on nucleos(t)ide analogue therapy. Response, response predictors and safety were assessed in patients who switched from long-term entecavir (ETV) to peginterferon alfa-2a. Hepatitis B e antigen (HBeAg)-positive CHB patients who had received ETV for 9-36 months, with HBeAg <100 PEIU/ml and HBV DNA ⩽1000 copies/ml, were randomised 1:1 to receive peginterferon alfa-2a 180 μg/week or ETV 0.5mg/day for 48 weeks. The primary endpoint was HBeAg seroconversion at week 48 (ClinicalTrials.gov: NCT00940485). 200 patients were randomised; 197 received ⩾1 study drug dose. Five patients who were anti-HBe-positive at baseline were excluded from the modified intention-to-treat population (peginterferon alfa-2a, n = 94; ETV, n = 98). Patients who switched to peginterferon alfa-2a achieved higher week 48 HBeAg seroconversion rates vs. those who continued ETV (14.9% vs. 6.1%; p = 0.0467). Only patients receiving peginterferon alfa-2a achieved HBsAg loss (8.5%). Among peginterferon alfa-2a-treated patients with HBeAg loss and HBsAg <1500 IU/ml at randomisation, 33.3% and 22.2% achieved HBeAg seroconversion and HBsAg loss, respectively. Early on-treatment HBsAg decline predicted response at week 48; highest rates were observed in patients with week 12 HBsAg <200 IU/ml (HBeAg seroconversion, 66.7%; HBsAg loss, 77.8%). Alanine aminotransferase elevations were not associated with viral rebound (n = 38). Peginterferon alfa-2a was well-tolerated. For patients who achieve virological suppression with ETV, switching to a finite course of peginterferon alfa-2a significantly increases rates of HBeAg seroconversion and HBsAg loss. A response-guided approach may identify patients with the greatest chance of success. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

[A cross-racial analysis on the susceptible gene polymorphisms of salt-sensitive hypertension].

PubMed

Lu, Jia-peng; Zhang, Ling; Wang, Wei

2010-10-01

To compare the genetic distributions of salt-sensitivity of four ethnic populations in Hapmap database. The frequencies data (395 subjects) of salt-sensitivity polymorphisms (AGT/M235T, ACE/ID, CYP11B2/C-344T, ADDI/Gly460Trp, GNB3/C825 and CYP3A5/A6986G)of Utah residents with ancestry from northern and western Europe (CEU), Han Chinese in Beijing (CHB), Japanese in Tokyo (JPT) and Yoruba mother-father-child trios in Ibadan, Nigeria (YRI) were obtained from International HapMap Project. The good-fit χ(2) test was performed to test whether the frequencies of each genotype reached Hardy-Weinberg equilibrium. The differences of the genotype and allele distribution and trend analysis were detected via χ(2) test. Furthermore, multiple comparisons between two populations were analyzed by Lancaster's partition of chi-squares. There were significant differences of each genotype distribution among four ethnic populations (P < 0.05). The distribution of genotype frequencies and susceptible allele frequencies of salt sensitive candidate genes were similar between CHB and JPT. Excepted for GNB3/825T allele (38.8% vs.34.4%, P = 0.521), susceptible allele frequencies in AGT/235T (79.2% vs. 41.2%, P < 0.001), ACE/I (56.5% vs. 43.5%, P < 0.001), CYP11B2/-344T (74.1% vs. 56.7%, P = 0.001), ADDI/460Trp (51.8% vs. 20.4%, P < 0.001) and CYP3A5/A6986 (30.1% vs. 3.6%, P < 0.001) were significantly higher in CHB than in CEU. There distribution of ADDI/460Trp allele was significant lower in YRI (4%) than in CHB (51.8%, P < 0.001). However frequencies of AGT/235T, CYP11B2/-334T, GNB3/825T and CYP3A5/6986A in CHB were significantly lower than those in YRI (P < 0.05). Trend analyses showed significantly increased trend in AGT/235T (41.2% < 79.2% < 92.0%, P < 0.001), CYP11B2/-334T (56.7% < 74.1% < 84.8%, P < 0.001) and CYP3A5/6986A (3.6% < 30.1% < 84.5%, P < 0.001) in CEU, CHB and YRI. There are significant discrepancy of salt-sensitivity variant distributions among four ethnic populations in Hapmap database. The frequencies of the susceptible polymorphisms related to salt-sensitivity in Beijing Han population was similar with JPT, higher than in CEU but lower than in YRI, suggesting high salt-sensitive and risk for hypertension in Beijing Han population. Prevention and individual therapy for high-risk population will help to reduce the prevalence of salt-sensitive hypertension and cardiovascular diseases.

Measuring spleen stiffness to predict varices in chronic hepatitis B cirrhotic patients with or without receiving non-selective beta-blockers.

PubMed

Wong, Grace Lai-Hung; Kwok, Raymond; Chan, Henry Lik-Yuen; Tang, Stephen Pui-Kit; Lee, Eugenia; Lam, Thomas Chi-Ho; Lau, Tiffany Wing-Yan; Ma, Teresa Man-Kee; Wong, Betsy Chi-Kuen; Wong, Vincent Wai-Sun

2016-08-01

we aimed to investigate the accuracy of liver (LSM) spleen stiffness measurement (SSM) with transient elastography (TE) to predict varices in the presence of non-selective beta-blockers (NSBB). In this cross-sectional study of consecutive patients with chronic hepatitis B (CHB) and cirrhosis, all patients underwent TE and upper endoscopic examinations. LSM and SSM in predicting varices in patients receiving and not receiving NSBB were evaluated. Altogether 144 CHB patients (29 receiving NSBB; 35 with any varices, 31 and 11 with esophageal and gastric varices, respectively) were recruited. Their mean LSM and SSM were 13.3 ± 9.0 kPa and 32.8 ± 19.2 kPa, respectively. The correlation between LSM and SSM was better in the NSBB subgroup (r = 0.525, P = 0.003) than its counterpart (r = 0.329, P  < 0.001). The area under receiver operating characteristic curve (AUROC) of LSM and SSM for any varices was 0.675 and 0.685 (P = 0.002 and 0.001), respectively. SSM of 18.9 kPa had a negative predictive value of 92.1% and negative likelihood ratio of 0.27 for ruling out any varices; and SSM of 54.9 kPa had a positive predictive value of 56.5% and a positive likelihood ratio of 4.05 to rule in varices. The AUROC of LSM for varices was 0.742 and 0.549 in patients with or without NSBB, respectively; the corresponding AUROC of SSM was 0.572 and 0.603, respectively. SSM only has modest accuracy to predict varices independent of NSBB use. An SSM cutoff value of 18.9 kPa may be adopted to achieve a high negative predictive value to rule out varices. © 2016 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Comparative evaluation of GPR versus APRI and FIB-4 in predicting different levels of liver fibrosis of chronic hepatitis B.

PubMed

Liu, D-P; Lu, W; Zhang, Z-Q; Wang, Y-B; Ding, R-R; Zhou, X-L; Huang, D; Li, X-F

2018-05-01

It is of great significance to develop and evaluate noninvasive indexes predicting the level of liver fibrosis. The aim of this study was to comparatively evaluate gamma-glutamyl transpeptidase-to-platelet ratio (GPR) versus aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on 4 factors (FIB-4) in predicting different levels of liver fibrosis of chronic hepatitis B (CHB) within the framework of HBeAg-positive and HBeAg-negative patients. A total of 1157 HBeAg-positive and 859 HBeAg-negative CHB patients were enrolled, among whom the pathological stage ≥S2, ≥S3, ≥S4 were defined as significant fibrosis, extensive fibrosis and cirrhosis, respectively. Receiver operating characteristic (ROC) curves were used to evaluate the performance of GPR, APRI and FIB-4 in predicting different levels of liver fibrosis. In HBeAg-positive patients, the area under ROC curves (AUROCs) of GPR in predicting extensive fibrosis and cirrhosis were both significantly larger than those of APRI (P = .0001 and P < .0001). In HBeAg-negative patients, the AUROCs of GPR in predicting significant fibrosis and cirrhosis were significantly larger than those of FIB-4 (P = .0006 and P = .0041). The AUROC of GPR in predicting extensive fibrosis was significantly larger than that of APRI and FIB-4 (P = .0320 and P = .0018). Using a cut-off of GPR > 0.500 as standard, the sensitivities and specificities of GPR in predicting significant fibrosis in HBeAg-positive patients were 59.6% and 81.2%, and for cirrhosis 80.9% and 63.8%, respectively; and those of HBeAg-negative patients were 60.3% and 78.3%, 84.5% and 66.1%, respectively. Regardless of HBeAg-positive or HBeAg-negative status, GPR had the best performance in predicting different levels of liver fibrosis. © 2017 John Wiley & Sons Ltd.

Genetic variations of NTCP are associated with susceptibility to HBV infection and related hepatocellular carcinoma.

PubMed

Wang, Peng; Mo, Ruidong; Lai, Rongtao; Xu, Yumin; Lu, Jie; Zhao, Gangde; Liu, Yuhan; Cao, Zhujun; Wang, Xiaolin; Li, Ziqiang; Lin, Lanyi; Zhou, Huijuan; Cai, Wei; Wang, Hui; Bao, Shisan; Xiang, Xiaogang; Xie, Qing

2017-12-01

Sodium taurocholate cotransporting polypeptide (NTCP), encoded by gene SLC10A1, is a receptor for hepatitis B virus (HBV). The aim of the current study was to investigate the role of NTCP polymorphisms in HBV susceptibility, cirrhosis and hepatocarcinogenesis. A total 1221 cases [including 866 chronic hepatitis B (CHB), 238 liver cirrhosis (LC), 117 hepatocellular carcinoma (HCC) patients] and 1232 healthy controls (HCs) were recruited, and 6 single nucleotide polymorphisms (SNPs) were genotyped. Meta-analysis was executed among 14591 CHBs and 12396 HCs to determine the association between NTCP polymorphisms and HBV infection, cirrhosis or hepatocarcinogenesis. The frequency of rs2296651-GA was inversely correlated with CHB, LC or HCC patients [adjusted OR(95%CI)=0.16(0.11-0.23), p <0.001; 0.34(0.21-0.55), p =0.001; or 0.46(0.25-0.83), p =0.008], respectively, compared with HCs. Meta-analysis also showed that NTCP rs2296651-GA was inversely associated with HBV infection [OR(95%CI)=0.532(0.287-0.986), p =0.028, codominant] or HBV-related HCC [OR(95%CI)=0.701(0.564-0.872), p =0.001, recessive]. Furthermore, the frequency of rs943277-GA was positively correlated with HBV infection [adjusted OR(95%CI)=2.42(1.05-5.54), p =0.032, codominant]. Our data suggest that NTCP mutants contribute to the susceptibility of HBV infection or HBV-related HCC.

Genetic variations of NTCP are associated with susceptibility to HBV infection and related hepatocellular carcinoma

PubMed Central

Xu, Yumin; Lu, Jie; Zhao, Gangde; Liu, Yuhan; Cao, Zhujun; Wang, Xiaolin; Li, Ziqiang; Lin, Lanyi; Zhou, Huijuan; Cai, Wei; Wang, Hui; Bao, Shisan; Xiang, Xiaogang; Xie, Qing

2017-01-01

Sodium taurocholate cotransporting polypeptide (NTCP), encoded by gene SLC10A1, is a receptor for hepatitis B virus (HBV). The aim of the current study was to investigate the role of NTCP polymorphisms in HBV susceptibility, cirrhosis and hepatocarcinogenesis. A total 1221 cases [including 866 chronic hepatitis B (CHB), 238 liver cirrhosis (LC), 117 hepatocellular carcinoma (HCC) patients] and 1232 healthy controls (HCs) were recruited, and 6 single nucleotide polymorphisms (SNPs) were genotyped. Meta-analysis was executed among 14591 CHBs and 12396 HCs to determine the association between NTCP polymorphisms and HBV infection, cirrhosis or hepatocarcinogenesis. The frequency of rs2296651-GA was inversely correlated with CHB, LC or HCC patients [adjusted OR(95%CI)=0.16(0.11-0.23), p<0.001; 0.34(0.21-0.55), p=0.001; or 0.46(0.25-0.83), p=0.008], respectively, compared with HCs. Meta-analysis also showed that NTCP rs2296651-GA was inversely associated with HBV infection [OR(95%CI)=0.532(0.287-0.986), p=0.028, codominant] or HBV-related HCC [OR(95%CI)=0.701(0.564-0.872), p=0.001, recessive]. Furthermore, the frequency of rs943277-GA was positively correlated with HBV infection [adjusted OR(95%CI)=2.42(1.05-5.54), p=0.032, codominant]. Our data suggest that NTCP mutants contribute to the susceptibility of HBV infection or HBV-related HCC. PMID:29285260

Prospective multi-center study of an automatic online seizure detection system for epilepsy monitoring units.

PubMed

Fürbass, F; Ossenblok, P; Hartmann, M; Perko, H; Skupch, A M; Lindinger, G; Elezi, L; Pataraia, E; Colon, A J; Baumgartner, C; Kluge, T

2015-06-01

A method for automatic detection of epileptic seizures in long-term scalp-EEG recordings called EpiScan will be presented. EpiScan is used as alarm device to notify medical staff of epilepsy monitoring units (EMUs) in case of a seizure. A prospective multi-center study was performed in three EMUs including 205 patients. A comparison between EpiScan and the Persyst seizure detector on the prospective data will be presented. In addition, the detection results of EpiScan on retrospective EEG data of 310 patients and the public available CHB-MIT dataset will be shown. A detection sensitivity of 81% was reached for unequivocal electrographic seizures with false alarm rate of only 7 per day. No statistical significant differences in the detection sensitivities could be found between the centers. The comparison to the Persyst seizure detector showed a lower false alarm rate of EpiScan but the difference was not of statistical significance. The automatic seizure detection method EpiScan showed high sensitivity and low false alarm rate in a prospective multi-center study on a large number of patients. The application as seizure alarm device in EMUs becomes feasible and will raise the efficiency of video-EEG monitoring and the safety levels of patients. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Additional N-glycosylation mutation in the major hydrophilic region of hepatitis B virus S gene is a risk indicator for hepatocellular carcinoma occurrence in patients with coexistence of HBsAg/anti-HBs.

PubMed

Qiao, Yan; Lu, Shanshan; Xu, Zhihui; Li, Xiaodong; Zhang, Kai; Liu, Yan; Zhao, Li; Chen, Rongjuan; Si, Lanlan; Lin, Shumei; Xu, Dongping; Li, Jin

2017-09-22

The study aimed to determine the association of additional N-glycosylation mutations in the major hydrophilic region (MHR) of hepatitis B virus (HBV) S gene with hepatocellular carcinoma (HCC) occurrence in HBsAg/anti-HBs coexistent patients. A total of 288 HBsAg/anti-HBs coexistent patients and 490 single HBsAg-positive patients were enrolled, including 193 with HCC, 433 with chronic hepatitis B (CHB), and 152 with acute-on-chronic liver failure (ACLF). The HBV S genes were amplified from serum and sequenced. The frequency of additional N-glycosylation mutations was significantly higher in HCC patients (12.37%) than in CHB patients (4.39%) and ACLF patients (2.63%). The frequency escalated by an order of single HBsAg-positive non-HCC (1.61%), single HBsAg-positive HCC (5.98%), HBsAg/anti-HBs coexistent non-HCC (8.01%), and HBsAg/anti-HBs coexistent HCC (22.36%). Twelve kinds of mutations/mutation patterns were detected, five of which have not been reported. Multivariate analysis showed that age > 40 years [ OR , 3.005; 95% CI, 1.177-7.674; P = 0.021], alpha-fetoprotein > 10 ng/mL [ OR , 4.718; 95% CI, 2.406-9.251; P <0.001], cirrhosis [ OR , 6.844; 95% CI, 2.773-16.891, P < 0.001], Hepatitis B e antigen negativity [ OR , 2.218; 95% CI, 4.335, P = 0.020], and additional N-glycosylation mutation [ OR , 2.831; 95% CI, 1.157-6.929; P = 0.023] were independent risk factors for HCC in HBsAg/anti-HBs coexistent patients. Dynamical analysis showed that the additional N-glycosylation mutations existed 1-4 years prior to HCC occurrence in eight of 18 patients observed. In conclusion, the dditional N-glycosylation mutations together with HBsAg/anti-HBs coexistence might serve as a predictive indicator for HCC occurrence in chronic HBV-infected patients.

Additional N-glycosylation mutation in the major hydrophilic region of hepatitis B virus S gene is a risk indicator for hepatocellular carcinoma occurrence in patients with coexistence of HBsAg/anti-HBs

PubMed Central

Qiao, Yan; Lu, Shanshan; Xu, Zhihui; Li, Xiaodong; Zhang, Kai; Liu, Yan; Zhao, Li; Chen, Rongjuan; Si, Lanlan; Lin, Shumei; Xu, Dongping; Li, Jin

2017-01-01

The study aimed to determine the association of additional N-glycosylation mutations in the major hydrophilic region (MHR) of hepatitis B virus (HBV) S gene with hepatocellular carcinoma (HCC) occurrence in HBsAg/anti-HBs coexistent patients. A total of 288 HBsAg/anti-HBs coexistent patients and 490 single HBsAg-positive patients were enrolled, including 193 with HCC, 433 with chronic hepatitis B (CHB), and 152 with acute-on-chronic liver failure (ACLF). The HBV S genes were amplified from serum and sequenced. The frequency of additional N-glycosylation mutations was significantly higher in HCC patients (12.37%) than in CHB patients (4.39%) and ACLF patients (2.63%). The frequency escalated by an order of single HBsAg-positive non-HCC (1.61%), single HBsAg-positive HCC (5.98%), HBsAg/anti-HBs coexistent non-HCC (8.01%), and HBsAg/anti-HBs coexistent HCC (22.36%). Twelve kinds of mutations/mutation patterns were detected, five of which have not been reported. Multivariate analysis showed that age > 40 years [OR, 3.005; 95% CI, 1.177−7.674; P = 0.021], alpha-fetoprotein > 10 ng/mL [OR, 4.718; 95% CI, 2.406−9.251; P <0.001], cirrhosis [OR, 6.844; 95% CI, 2.773−16.891, P < 0.001], Hepatitis B e antigen negativity [OR, 2.218; 95% CI, 4.335, P = 0.020], and additional N-glycosylation mutation [OR, 2.831; 95% CI, 1.157−6.929; P = 0.023] were independent risk factors for HCC in HBsAg/anti-HBs coexistent patients. Dynamical analysis showed that the additional N-glycosylation mutations existed 1-4 years prior to HCC occurrence in eight of 18 patients observed. In conclusion, the dditional N-glycosylation mutations together with HBsAg/anti-HBs coexistence might serve as a predictive indicator for HCC occurrence in chronic HBV-infected patients. PMID:28977899

Feasibility of dynamic risk prediction for hepatocellular carcinoma development in patients with chronic hepatitis B.

PubMed

Jeon, Mi Young; Lee, Hye Won; Kim, Seung Up; Kim, Beom Kyung; Park, Jun Yong; Kim, Do Young; Han, Kwang-Hyub; Ahn, Sang Hoon

2018-04-01

Several risk prediction models for hepatocellular carcinoma (HCC) development are available. We explored whether the use of risk prediction models can dynamically predict HCC development at different time points in chronic hepatitis B (CHB) patients. Between 2006 and 2014, 1397 CHB patients were recruited. All patients underwent serial transient elastography at intervals of >6 months. The median age of this study population (931 males and 466 females) was 49.0 years. The median CU-HCC, REACH-B, LSM-HCC and mREACH-B score at enrolment were 4.0, 9.0, 10.0 and 8.0 respectively. During the follow-up period (median, 68.0 months), 87 (6.2%) patients developed HCC. All risk prediction models were successful in predicting HCC development at both the first liver stiffness (LS) measurement (hazard ratio [HR] = 1.067-1.467 in the subgroup without antiviral therapy [AVT] and 1.096-1.458 in the subgroup with AVT) and second LS measurement (HR = 1.125-1.448 in the subgroup without AVT and 1.087-1.249 in the subgroup with AVT). In contrast, neither the absolute nor percentage change in the scores from the risk prediction models predicted HCC development (all P > .05). The mREACH-B score performed similarly or significantly better than did the other scores (AUROCs at 5 years, 0.694-0.862 vs 0.537-0.875). Dynamic prediction of HCC development at different time points was achieved using four risk prediction models, but not using the changes in the absolute and percentage values between two time points. The mREACH-B score was the most appropriate prediction model of HCC development among four prediction models. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Detection of Epileptic Seizure Event and Onset Using EEG

PubMed Central

Ahammad, Nabeel; Fathima, Thasneem; Joseph, Paul

2014-01-01

This study proposes a method of automatic detection of epileptic seizure event and onset using wavelet based features and certain statistical features without wavelet decomposition. Normal and epileptic EEG signals were classified using linear classifier. For seizure event detection, Bonn University EEG database has been used. Three types of EEG signals (EEG signal recorded from healthy volunteer with eye open, epilepsy patients in the epileptogenic zone during a seizure-free interval, and epilepsy patients during epileptic seizures) were classified. Important features such as energy, entropy, standard deviation, maximum, minimum, and mean at different subbands were computed and classification was done using linear classifier. The performance of classifier was determined in terms of specificity, sensitivity, and accuracy. The overall accuracy was 84.2%. In the case of seizure onset detection, the database used is CHB-MIT scalp EEG database. Along with wavelet based features, interquartile range (IQR) and mean absolute deviation (MAD) without wavelet decomposition were extracted. Latency was used to study the performance of seizure onset detection. Classifier gave a sensitivity of 98.5% with an average latency of 1.76 seconds. PMID:24616892

Epileptic Seizures Prediction Using Machine Learning Methods

PubMed Central

Usman, Syed Muhammad

2017-01-01

Epileptic seizures occur due to disorder in brain functionality which can affect patient's health. Prediction of epileptic seizures before the beginning of the onset is quite useful for preventing the seizure by medication. Machine learning techniques and computational methods are used for predicting epileptic seizures from Electroencephalograms (EEG) signals. However, preprocessing of EEG signals for noise removal and features extraction are two major issues that have an adverse effect on both anticipation time and true positive prediction rate. Therefore, we propose a model that provides reliable methods of both preprocessing and feature extraction. Our model predicts epileptic seizures' sufficient time before the onset of seizure starts and provides a better true positive rate. We have applied empirical mode decomposition (EMD) for preprocessing and have extracted time and frequency domain features for training a prediction model. The proposed model detects the start of the preictal state, which is the state that starts few minutes before the onset of the seizure, with a higher true positive rate compared to traditional methods, 92.23%, and maximum anticipation time of 33 minutes and average prediction time of 23.6 minutes on scalp EEG CHB-MIT dataset of 22 subjects. PMID:29410700

Assessment of non-invasive models for liver fibrosis in chronic hepatitis B virus related liver disease patients in resource limited settings.

PubMed

Shrivastava, Rakesh; Sen, Sourav; Banerji, Debabrata; Praharaj, Ashok K; Chopra, Gurvinder Singh; Gill, Satyajit Singh

2013-01-01

A total of 350 million individuals are affected by chronic hepatitis B virus infection world-wide. Historically, liver biopsy has been instrumental in adequately assessing patients with chronic liver disease. A number of non-invasive models have been studied world-wide. The aim of this study is to assess the utility of non-invasive mathematical models of liver fibrosis in chronic hepatitis B (CHB). Indian patients in a resource limited setting using routinely performed non-invasive laboratory investigations. A cross-sectional study carried out at a tertiary care center. A total of 52 consecutive chronic liver disease patients who underwent percutaneous liver biopsy and 25 healthy controls were enrolled in the study. Routine laboratory investigations included serum aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Gama glutamyl transpeptidase (GGT), total bilirubin, total cholesterol, prothrombin time and platelet count. Three non-invasive models for namely aspartate aminotransferase to platelet ratio index (APRI), Fibrosis 4 (FIB-4) and Forn's index were calculated. Outcomes were compared for the assessment of best predictor of fibrosis by calculating the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of each index. Medcalc online software and by Microsoft Excel Worksheet. Chi-square test was used for significance. P value < 0.05 was taken as significant. While the serum levels of AST, ALT and GGT were significantly higher in patients group as compare with the healthy controls (P < 0.01), the platelet counts were significantly lower in patient group as compared to the control group (P < 0.01). Mean value of all 3 indices were significantly higher in patients group as compare with the controls (P < 0.01). Out of the three indices, APRI index with a NPV of 95% appeared to be a better model for excluding significant liver fibrosis while FIB-4 with a PPV of 61% showed fair correlation with significant fibrosis. Thus, these two non-invasive models for predicting of liver fibrosis, namely APRI and FIB-4, can be utilized in combination as screening tools in monitoring of CHB patients, especially in resource limiting settings.

Cost-effectiveness analysis of oral anti-viral drugs used for treatment of chronic hepatitis B in Turkey.

PubMed

Kockaya, Guvenc; Kose, Akin; Yenilmez, Fatma Betul; Ozdemir, Oktay; Kucuksayrac, Ece

2015-01-01

All international guidelines suggested that Tenofovir and Entecavir are the primary drugs at the first line therapy for the treatment of chronic hepatitis B (CHB). However, in Turkey these medications reimbursed at the second line therapy according to the Healthcare Implementation Notification. The aim of this study is to compare the cost effectiveness of oral antiviral treatment strategies in CHB for Turkey using lamuvidine, telbuvidine, entecavir, and tenofovir as medications. The analysis was conducted using Markov models. The analysis scenarios based on first line treatment options with Lamuvidine, Telbuvidine, Entecavir, and Tenofovir as the medications. In the analysis, inadequate response or resistance after receiving 12 months of the treatment with Entecavir and Telbivudine were compared to the results found from switching from Entecavir to Tenofovir or from switching from Telbuvidine to Tenofovir. In additional, inadequate response or resistance after receiving 6 months of the treatment for Lamivudine was compared to the results found from switching from Lamivudine to Tenofovir. The study population included men and women, who were 40 years of age. The patients` compliance was estimated 100 % for all of the therapy options. The model duration was constructed to evaluate, treatment strategy duration of 40 years. The cost of medications, examinations/follow-ups and complications were included in the model. Years of Potential Life Lost was used as the health outcome. An incremental cost-effectiveness ratio analysis has been conducted. While the minimum years of life lost was found as 0.22 with tenofovir treatment in 5 years, treatment cost was calculated as 12,169 TL. These values were detected as 0.56 years and 7727 TL, 0.37 years and 12,770 TL, respectively for lamuvidine and telbuvidine treatments. The maximum years of life lost and treatment cost was with lamuvidine treatment were detected as 1.60 years and 18,813 TL and, secondly 0.89 years and 24,007 TL for lamuvidine-tenofovir treatment during 10 years. The minimum years of life lost and cost are 0.54 year and 35,821 TL for tenofovir treatment during 10 years. The minimum years of life lost and cost were determined as 1.21 years and 52,839 TL for tenofovir treatment strategy during 20 years. During 30 years period, tenofovir treatment was found to have the minimum years of life lost (1.73 years) and minimum cost (84,149 TL). When the results of 40 years period were analyzed, years of life lost and costs are 2.06 years and 119,604 TL, 2.13 years and 162,115 TL, 2.13 years and 161,642 TL, 6.52 years and 147,245 TL, 3.20 years and 132,157 TL, 4.10 years and 151,059 TL and 3.05 years and 138,182 TL for tenofovir, entecavir, entecavir-tenofovir, lamuvidine, lamuvidine-tenofovir, telbivudine and telbivudine-tenofovir. In the model presented in this study, in cost effectiveness analysis about CHB treatments, Tenofovir was found to be one of the cost effective methods in comparison with other treatment strategies different time intervals. Beyond this achievement Tenofovir has shown to reduce cumulative treatment cost in first line CHB treatment when compared with regard to 40 year cumulative treatment cost.

Soluble FGL2, a novel effector molecule of activated hepatic stellate cells, regulates T-cell function in cirrhotic patients with hepatocellular carcinoma.

PubMed

Sun, Ying; Xi, Dong; Ding, Wen; Wang, Faxi; Zhou, Haili; Ning, Qin

2014-10-01

To investigate the effects of soluble FGL2 (sFGL2) secreted by hepatic stellate cells (HSCs) on immune suppression in cirrhotic patients with hepatocellular carcinoma (HCC). Serum sFGL2 levels were examined by ELISA in 40 patients with HCC, liver cirrhosis (LC) or chronic HBV (CHB) infection. A double staining of the immunofluorescence analysis of α-SMA and FGL2 was performed in two cirrhotic liver specimens. The expression of FGL2 in the LX2 cell line was analyzed by immunofluorescence, Western blot and flow cytometry. T-cells purified from HCC patients using magnetic beads were cultured with LX2 cells at different ratios with anti-CD3-stimulating or FGL2-blocking antibodies. The proliferation index (PI) of CD8 + T cells was assessed by flow cytometry, and the secretion of IFN-γ was measured by ELISA. sFGL2 levels are significantly higher in patients with HCC or LC compared with those with CHB (p = 0.0039/p = 0.0020). Among HCC patients, those with cirrhosis exhibited significantly higher levels of sFGL2 compared with non-cirrhotic individuals (p = 0.0108). The expressions of FGL2 and α-SMA overlapped in HSCs in liver specimens. FGL2 protein secreted by LX2 cells inhibited T-cell proliferation of HCC patients in a dose-dependent manner in vitro. The PI of CD8 + T cells was significantly enhanced following addition of FGL2 antibody to the culture system (LX2/T-cell ratio of 1:10, p = 0.002). The level of IFN-γ in mixed cultures was inversely correlated with the number of HSCs and was reversed by incubation with FGL2 blocking antibody. sFGL2 protein is a novel effector molecule of activated HSCs, which suppresses CD8 + T cell proliferation and interferon-γ production, and it subsequently might contribute to immune suppression during fibrosis and tumorigenesis in the liver.

[Detection and the production mechanism of antinuclear antibodies (ANA) and anti-liver/kidney microsomal tpe 1 antibodies (anti-LKM1) in patients with chronic hepatitis C].

PubMed

Bai, Li; Lu, Hai-Ying; Feng, Zhen-Ru; Yu, Min; Li, Wen-Gang; Gong, Wei-Bo; Zhao, Nu-en-ji-ya; Xu, Xiao-Yuan

2009-08-01

To investigate the prevalence of antinuclear antibodies (ANA) and anti-liver/ kidney microsomal type 1 antibodies (anti-LKM1) in patients with chronic hepatitis C (CHC)and to explore the mechanism of production of these autoantibodies. Serum samples were collected from 360 patients with CHC (case group), 69 patients with chronic hepatitis B (CHB) and 69 patients with autoimmune hepatitis (AIH) (control group). Serum ANA and anti-LKM1 were detected by indirect immunofluorescence (HF) technique and enzyme-linked immunosorbent assay (ELISA), respectively. Multi-factor analysis was performed to explore the correlations of the production of autoantibodies with some factors such as age, sex, viral loads, HCV genotype, biochemical parameters and clinical characteristics. Fifty-four (15%) of 360 patients infected with HCV were positive in autoantibodies. The prevalence of ANA and anti-LKM1 were 12.5% (45/360) and 2.5% (9/ 360), respectively. The positive rate of autoantibodies in patients with CHC was significantly higher than that in patients with CHB (15% vs 2.9%, P = 0.006), but significantly lower than that in patients with AIH (15% vs 47.9%, P < 0.001). Twenty-one (11.35%) of 185 male patients and 33 (18.86%) of 175 female patients were positive in autoantibodies, the difference in positive rate was significant (P < 0.05). HCV virus loads in the autoantibodies negative group were higher than that in the autoantibodies positive group (7.2 x 10(7) copies/L vs 1.23 x 10(7) copies/L, P < 0.05). There were not significant differences in age and genotype between the autoantibody positive group and the autoantibody negative group. The serum biochemical parameters of the autoantibody positive group were similar to those of the autoantibody negative group. The differences were not significant for the course of disease, clinical symptom, the incidence of cirrhosis between the autoantibody positive group and the autoantibody negative group. The prevalence of autoantibodies was not different for patients with or without interferon treatment (P > 0.05). Autoantibodies related to AIH can be detected in CHC patients; interferon may not induce the production of autoantibodies; it is very likely that HCV infection induces the autoimmune reaction and the production of autoantibodies.

Diffusion coefficients of oxygen and hemoglobin measured by facilitated oxygen diffusion through hemoglobin solutions.

PubMed

Bouwer, S T; Hoofd, L; Kreuzer, F

1997-03-07

Diffusion coefficients of oxygen (DO2) and hemoglobin (DHb) were obtained from measuring the oxygen flux through thin layers of hemoglobin solutions at 20 degrees C. The liquid layers were supported by a membrane and not soaked in any filter material. Oxygen fluxes were measured from the changes in oxygen partial pressure in the gas phases at both sides of the layer. A mathematical treatment is presented for correct evaluation of the measurements. Measurements were done for bovine and for human hemoglobin. Hemoglobin concentrations (CHb) were between 11 and 42 g/dl, which covers the concentrations in the erythrocyte. Both DO2 and DHb could be fitted to the empirical equation D = D0(1-CHb/C1)10-CHb/C2. The following parameters were obtained: DO = 1.80 x 10(-9) m2/s, C1 = 100 g/dl, C2 = 119 g/dl, for oxygen and D0 = 7.00 x 10(-11) m2/s, C1 = 46 g/dl, C2 = 128 g/dl, for hemoglobin. No difference between the diffusion coefficients of bovine or human hemoglobin was found. The diffusion coefficients of hemoglobin were higher than most values reported in the literature, probably because in this study the mobility of hemoglobin was not hindered by surrounding filter material.

Liver-Targeted Anti-HBV Single-Stranded Oligonucleotides with Locked Nucleic Acid Potently Reduce HBV Gene Expression In Vivo.

PubMed

Javanbakht, Hassan; Mueller, Henrik; Walther, Johanna; Zhou, Xue; Lopez, Anaïs; Pattupara, Thushara; Blaising, Julie; Pedersen, Lykke; Albæk, Nanna; Jackerott, Malene; Shi, Tianlai; Ploix, Corinne; Driessen, Wouter; Persson, Robert; Ravn, Jacob; Young, John A T; Ottosen, Søren

2018-06-01

Chronic hepatitis B infection (CHB) is an area of high unmet medical need. Current standard-of-care therapies only rarely lead to a functional cure, defined as durable hepatitis B surface antigen (HBsAg) loss following treatment. The goal for next generation CHB therapies is to achieve a higher rate of functional cure with finite treatment duration. To address this urgent need, we are developing liver-targeted single-stranded oligonucleotide (SSO) therapeutics for CHB based on the locked nucleic acid (LNA) platform. These LNA-SSOs target hepatitis B virus (HBV) transcripts for RNase-H-mediated degradation. Here, we describe a HBV-specific LNA-SSO that effectively reduces intracellular viral mRNAs and viral antigens (HBsAg and HBeAg) over an extended time period in cultured human hepatoma cell lines that were infected with HBV with mean 50% effective concentration (EC 50 ) values ranging from 1.19 to 1.66 μM. To achieve liver-specific targeting and minimize kidney exposure, this LNA-SSO was conjugated to a cluster of three N-acetylgalactosamine (GalNAc) moieties that direct specific binding to the asialoglycoprotein receptor (ASGPR) expressed specifically on the surface of hepatocytes. The GalNAc-conjugated LNA-SSO showed a strikingly higher level of potency when tested in the AAV-HBV mouse model as compared with its non-conjugated counterpart. Remarkably, higher doses of GalNAc-conjugated LNA-SSO resulted in a rapid and long-lasting reduction of HBsAg to below the detection limit for quantification, i.e., by 3 log10 (p < 0.0003). This antiviral effect depended on a close match between the sequences of the LNA-SSO and its HBV target, indicating that the antiviral effect is not due to non-specific oligonucleotide-driven immune activation. These data support the development of LNA-SSO therapeutics for the treatment of CHB infection. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Natural history of chronic hepatitis B in Euro-Mediterranean and African countries.

PubMed

Hadziyannis, Stephanos J

2011-07-01

Data derived from population, case-control, and cohort studies conducted in several Euro-Mediterranean and African countries disclose impressive similarities in the age and modes of hepatitis B virus (HBV) transmission and in the prevalence, duration, and outcome of the four phases of the natural history of chronic infection. Perinatal HBV infection is rare while the vast majority of chronic infections originate from horizontal HBV transmission to infants and children. HBeAg loss and seroconversion to anti-HBe occur in a few years time, usually during the second decade of life. HBeAg-negative/anti-HBe-positive chronic hepatitis B (CHB), predominates in these countries being 7-9 times more frequent than HBeAg-positive CHB. The predominance of HBeAg-negative CHB is largely linked to the molecular characteristics of HBV genotype D prevailing in European and African countries of the Mediterranean basin and of genotype E and subgenotype A1 that prevail in the other parts of Africa. The molecular characteristics of the African subgenotype A1 differ from those of European subgenotype A2 explaining the fact that patients infected subgenotype A1 demonstrate an earlier loss of HBeAg and seroconversion to anti-HBe during the natural course of HBV infection compared to those infected with subgenotype A2. It is proposed that the molecular characteristics of HBV genotypes and subgenotypes prevailing in Euro-Mediterranean and African countries acting in concert with host and environmental factors largely determine the natural history of chronic HBV infection and its significant differences from countries of HBV genotype C and B and of subgenotype Ae predominance. The knowledge of the natural history of chronic HBV infection in Euro-Mediterranean and African countries combined with wide screening programs for prompt recognition and treatment of chronic HBV infection both in its HBeAg-positive and -negative immune reactive phases can be expected to increase the efficacy of current and future therapeutic strategies. Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Fatty acid translocase promoted hepatitis B virus replication by upregulating the levels of hepatic cytosolic calcium.

PubMed

Huang, Jian; Zhao, Lei; Yang, Ping; Chen, Zhen; Ruan, Xiong Z; Huang, Ailong; Tang, Ni; Chen, Yaxi

2017-09-15

Hepatitis B virus (HBV) is designated a "metabolovirus" due to the intimate connection between the virus and host metabolism. The nutrition state of the host plays a relevant role in the severity of HBV infection. Metabolic syndrome (MS) is prone to increasing HBV DNA loads and accelerating the progression of liver disease in patients with chronic hepatitis B (CHB). Cluster of differentiation 36 (CD36), also named fatty acid translocase, is known to facilitate long-chain fatty acid uptake and contribute to the development of MS. We recently found that CD36 overexpression enhanced HBV replication. In this study, we further explored the mechanism by which CD36 overexpression promotes HBV replication. Our data showed that CD36 overexpression increased HBV replication, and CD36 knockdown inhibited HBV replication. RNA sequencing found some of the differentially expressed genes were involved in calcium ion homeostasis. CD36 overexpression elevated the cytosolic calcium level, and CD36 knockdown decreased the cytosolic calcium level. Calcium chelator BAPTA-AM could override the HBV replication increased by CD36 overexpression, and the calcium activator thapsigargin could improve the HBV replication reduced by CD36 knockdown. We further found that CD36 overexpression activated Src kinase, which plays an important role in the regulation of the store-operated Ca 2+ channel. An inhibitor of Src kinase (SU6656) significantly reduced the CD36-induced HBV replication. We identified a novel link between CD36 and HBV replication, which is associated with cytosolic calcium and the Src kinase pathway. CD36 may represent a potential therapeutic target for the treatment of CHB patients with MS. Copyright © 2017 Elsevier Inc. All rights reserved.

Natural history of chronic hepatitis B: what exactly has REVEAL revealed?

PubMed

Iloeje, Uchenna H; Yang, Hwai-I; Chen, Chien-Jen

2012-10-01

Chronic hepatitis B virus (HBV) infection is a serious public health problem because of its worldwide prevalence and potential to cause adverse consequences. The Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus (REVEAL-HBV) study carried out in Taiwan was used to investigate the natural history of chronic hepatitis B. The REVEAL-HBV study has established an HBV viral load paradigm in the natural history of chronic hepatitis B (CHB). Serum HBV DNA level has been shown to be significantly and independently associated with incidence of hepatocellular carcinoma (HCC) and cirrhosis and liver-related mortality across a biological gradient. It is also a major predictor of HBsAg seroclearance. Genetic features including HBV genotype and basal core promoter A1762T/G1764A mutant, and precore G1896A mutant were documented as predictors of HCC risk. Inactive HBV carriers still had an increased risk on HCC development and liver-related mortality compared with HBsAg -seronegatives. Nomograms focusing on facilitating risk communication between patients and clinicians were developed incorporating non-invasive clinical parameters to predict long-term HCC risk. These will hopefully contribute to evidence-based decisions in the clinical management of CHB patients. A somewhat provocative and novel finding from the REVEAL-HBV study is the association of chronic HBV infection in active replication with an increased pancreatic cancer risk especially in women less than 50 years old. This finding will hopefully spur further research in this area seeking confirmatory evidence. Finally, we hope that the REVEAL-HBV study will continue to be a source of data to answer other important questions in chronic hepatitis B research going forward. © 2012 John Wiley & Sons A/S.

Spontaneous hepatitis B surface antigen clearance in a long-term follow-up study of patients with chronic type B hepatitis. Lack of correlation with hepatitis C and D virus superinfection.

PubMed

Da Silva, L C; Madruga, C L; Carrilho, F J; Pinho, J R; Saéz-Alquezar, A; Santos, C; Bassit, L; Barreto, C; Fonseca, L E; Alves, V A; Leitão, R; Vianna, R; Cardoso, R A; França, A V; Gayotto, L C

1996-10-01

We investigated the frequency of HBsAg clearance and the possible role of viral superinfection in a long-term follow-up of 184 patients with chronic hepatitis B (CHB). Our subjects were 184 patients with chronic hepatitis B and the follow-up was 12-216 months (mean 66.2 +/- 53.7 months). The investigative methods used were: immunoenzymatic assays for HBV, HCV, HDV, and HIV markers; polymerase chain reaction (PCR) for HBV DNA; and liver biopsy and immunoperoxidase. During the follow-up, 20 of the 184 patients cleared serum HBsAg. A comparison of patients with persistent HBsAg(group I) and of those who cleared this marker (group II) showed a significant difference in mortality (P = 0.002) between the two groups and a tendency to a more severe exacerbation (flare) in group II (P = 0.07). Antibodies to hepatitis C and D virus as well as antibodies to HIV were equally distributed in both groups. Thirteen patients (7.9%) from group I, but none from group II, subsequently developed hepatocellular carcinoma. These results suggest that the frequency of spontaneous clearance of HBsAg during chronic HBV infection is low. No determinant factor for the clearance was found, including the presence of liver cirrhosis. Serum HBV DNA was undetectable by PCR after clearance in 16 out of 17 patients.

Association of Ghrelin Gene Polymorphisms and Serum Ghrelin Levels with the Risk of Hepatitis B Virus-Related Liver Diseases in a Chinese Population.

PubMed

Zhang, Xiaolian; Zhai, Limin; Rong, Chengzhi; Qin, Xue; Li, Shan

2015-01-01

The functions of ghrelin (GHRL) include anti-inflammatory effects, reduction of the fibrogenic response, protection of liver tissue, and regulation of cell proliferation. Genetic variations in the GHRL gene may play an important role in the development of chronic hepatitis B (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Therefore, we investigated whether GHRL gene polymorphisms and its serum levels are associated with hepatitis B virus (HBV)-related diseases risk in a Chinese population. 176 patients with CHB, 106 patients with HBV-related LC, 151 patients with HBV-related HCC, and 167 healthy controls were recruited in the study. Genotyping of GHRL rs26311, rs27647, rs696217, and rs34911341 polymorphisms were determined with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. The serum GHRL concentrations were determined using enzyme-linked immunosorbent assay (ELISA). Binary logistic regression analyses adjusting for gender and age revealed that a significant increased risk of LC was found in the GHRL rs26311 GC genotype and combined GC+CC genotypes when compared with the GG genotype (GC vs. GG: OR = 1.671, 95% CI = 1.013-2.757, P = 0.044; GC+CC vs. GG: OR = 1.674, 95% CI = 1.040-2.696, P = 0.034). In subgroup analysis by gender, binary logistic regression analyses adjusting for age showed that the GHRL rs26311 C allele and combined GC+CC genotypes were associated with a significantly increased risk to LC in males (C vs. G OR = 1.416, 95% CI = 1.017-1.972, P = 0.040; GC+CC vs. GG: OR = 1.729, 95% CI = 1.019-2.933, P = 0.042). In addition, we found significant decreased serum GHRL levels in LC patients compared with the healthy controls. However, there was no significant association of the GHRL rs26311 polymorphism with serum GHRL levels in LC patients. These observations suggest that the GHRL rs26311 polymorphism is associated with an increased risk to HBV-related LC, especially in men. We also found an inverse association of serum GHRL levels with LC.

Restoring homeostasis of CD4+ T cells in hepatitis-B-virus-related liver fibrosis

PubMed Central

Cheng, Li-Sha; Liu, Yun; Jiang, Wei

2015-01-01

Immune-mediated liver injury is widely seen during hepatitis B virus (HBV) infection. Unsuccessful immune clearance of HBV results in chronic hepatitis and increases the risk of liver cirrhosis and hepatocellular carcinoma. HBV-related liver fibrosis (HBVLF), occurring as a result of HBV-induced chronic hepatitis, is a reversible, intermediate stage of chronic hepatitis B (CHB) and liver cirrhosis. Therefore, defining the pathogenesis of HBVLF is of practical significance for achieving better clinical outcomes. Recently, the homeostasis of CD4+ T cells was considered to be pivotal in the process of HBVLF. To better uncover the underlying mechanisms, in this review, we systematically retrospect the impacts of different CD4+ T-cell subsets on CHB and HBVLF. We emphasize CD4+ T-cell homeostasis and the important balance between regulatory T (Treg) and T helper 17 (Th17) cells. We discuss some cytokines associated with Treg and Th17 cells such as interleukin (IL)-17, IL-22, IL-21, IL-23, IL-10, IL-35 and IL-33, as well as surface molecules such as programmed cell death protein 1, cytotoxic T lymphocyte-associated antigen 4, T cell immunoglobulin domain and mucin domain-containing molecule 3 and cannabinoid receptor 2 that have potential therapeutic implications for the homeostasis of CD4+ T cells in CHB and HBVLF. PMID:26478664

Investigating the Weak to Evaluate the Strong: An Experimental Determination of the Electron Binding Energy of Carborane Anions and the Gas phase Acidity of Carborane Acids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meyer, Matthew M; Wang, Xue B; Reed, Christopher A

2009-12-23

Five CHB 11X 6Y 5 - carborane anions from the series X = Br, Cl, I and Y = H, Cl, CH 3 were generated by electrospray ionization, and their reactivity with a series of Brønsted acids and electron transfer reagents were examined in the gas phase. The undecachlorocarborane acid, H(CHB 11Cl 11), was found to be far more acidic than the former record holder, (1-C 4F 9SO 2) 2NH (i.e., ΔH° acid = 241 ± 29 vs 291.1 ± 2.2 kcal mol -1) and bridges the gas-phase acidity and basicity scales for the first time. Its conjugate base, CHBmore » 11Cl 11 -, was found by photoelectron spectroscopy to have a remarkably large electron binding energy (6.35 ± 0.02 eV) but the value for the (1-C 4F 9SO 2) 2N - anion is even larger (6.5 ± 0.1 eV). Consequently, it is the weak H-(CHB 11Cl 11) BDE (70.0 kcal mol -1, G3(MP2)) compared to the strong BDE of (1-C 4F 9SO 2) 2N-H (127.4 ± 3.2 kcal mol -1) that accounts for the greater acidity of carborane acids.« less

A real-time and closed-loop control algorithm for cascaded multilevel inverter based on artificial neural network.

PubMed

Wang, Libing; Mao, Chengxiong; Wang, Dan; Lu, Jiming; Zhang, Junfeng; Chen, Xun

2014-01-01

In order to control the cascaded H-bridges (CHB) converter with staircase modulation strategy in a real-time manner, a real-time and closed-loop control algorithm based on artificial neural network (ANN) for three-phase CHB converter is proposed in this paper. It costs little computation time and memory. It has two steps. In the first step, hierarchical particle swarm optimizer with time-varying acceleration coefficient (HPSO-TVAC) algorithm is employed to minimize the total harmonic distortion (THD) and generate the optimal switching angles offline. In the second step, part of optimal switching angles are used to train an ANN and the well-designed ANN can generate optimal switching angles in a real-time manner. Compared with previous real-time algorithm, the proposed algorithm is suitable for a wider range of modulation index and results in a smaller THD and a lower calculation time. Furthermore, the well-designed ANN is embedded into a closed-loop control algorithm for CHB converter with variable direct voltage (DC) sources. Simulation results demonstrate that the proposed closed-loop control algorithm is able to quickly stabilize load voltage and minimize the line current's THD (<5%) when subjecting the DC sources disturbance or load disturbance. In real design stage, a switching angle pulse generation scheme is proposed and experiment results verify its correctness.

Single-Molecule Sequencing Reveals Complex Genome Variation of Hepatitis B Virus during 15 Years of Chronic Infection following Liver Transplantation

PubMed Central

Betz-Stablein, B. D.; Töpfer, A.; Littlejohn, M.; Yuen, L.; Colledge, D.; Sozzi, V.; Angus, P.; Thompson, A.; Revill, P.; Beerenwinkel, N.; Warner, N.

2016-01-01

ABSTRACT Chronic hepatitis B (CHB) is prevalent worldwide. The infectious agent, hepatitis B virus (HBV), replicates via an RNA intermediate and is error prone, leading to the rapid generation of closely related but not identical viral variants, including those that can escape host immune responses and antiviral treatments. The complexity of CHB can be further enhanced by the presence of HBV variants with large deletions in the genome generated via splicing (spHBV variants). Although spHBV variants are incapable of autonomous replication, their replication is rescued by wild-type HBV. spHBV variants have been shown to enhance wild-type virus replication, and their prevalence increases with liver disease progression. Single-molecule deep sequencing was performed on whole HBV genomes extracted from samples, including the liver explant, longitudinally collected from a subject with CHB over a 15-year period after liver transplantation. By employing novel bioinformatics methods, this analysis showed that the dynamics of the viral population across a period of changing treatment regimens was complex. The spHBV variants detected in the liver explant remained present posttransplantation, and a highly diverse novel spHBV population as well as variants with multiple deletions in the pre-S genes emerged. The identification of novel mutations outside the HBV reverse transcriptase gene that co-occurred with known drug resistance-associated mutations highlights the relevance of using full-genome deep sequencing and supports the hypothesis that drug resistance involves interactions across the full length of the HBV genome. IMPORTANCE Single-molecule sequencing allowed the characterization, in unprecedented detail, of the evolution of HBV populations and offered unique insights into the dynamics of defective and spHBV variants following liver transplantation and complex treatment regimens. This analysis also showed the rapid adaptation of HBV populations to treatment regimens with evolving drug resistance phenotypes and evidence of purifying selection across the whole genome. Finally, the new open-source bioinformatics tools with the capacity to easily identify potential spliced variants from deep sequencing data are freely available. PMID:27252524

Hepatitis B Virus Infection Predicts Better Survival In Patients With Colorectal Liver-only Metastases Undergoing Liver Resection

PubMed Central

Zhao, Yujie; Lin, Junzhong; Peng, Jianhong; Deng, Yuxiang; Zhao, Ruixia; Sui, Qiaoqi; Lu, Zhenhai; Wan, Desen; Pan, Zhizhong

2018-01-01

Objective: Hepatitis B virus (HBV) infection has been shown to decrease the risk of liver metastasis in patients with non-metastatic colorectal cancer (CRC). However, the prognostic value of HBV infection in long-term survival of patients with colorectal liver-only metastases (CRLM) after liver resection has not yet been evaluated. This study aims to explore the association between HBV infection and survival in CRLM patients. Methods: A total of 289 CRLM patients undergoing liver resection were recruited at our center from September 1999 to August 2015. Patients were divided into an HBV infection group and a non-HBV infection group. Progression-free survival (PFS) and overall survival (OS) related to HBV infection were analyzed using both Kaplan-Meier and multivariate Cox regression methods. Results: HBV infection was found in 12.1 %(35/289) of patients. Of these patients, 31.4 %(11/35) had chronic hepatitis B (CHB), 42.9 % (15/35) were inactive hepatitis B surface antigen (HBsAg) carriers (IC) and 25.7 % (9/35) did not undergo HBV DNA detection. HBV infection was associated with more liver metastases (P = 0.025) and larger-sized liver metastases (P = 0.049). The 3-year OS and PFS rates in the HBV infection group were higher than those in the HBV non-infected group (OS: 75.0 % vs 64.8 %, P = 0.031; PFS: 55.9 % vs 39.6 %, P = 0.034). In multivariate Cox analysis, HBV infection was identified as an independent factor for better 3-year OS (hazard ratio (HR), 0.446; 95 %confidence interval (CI), 0.206-0.966; P = 0.041) but not an independent factor for 3-year PFS. Conclusions: HBV-infected CRLM patients survived longer than non-infected patients. In clinical work, therapeutic regimens and follow-up for HBsAg-positive patients may be different from that for HBsAg-negative patients, even though objective prospective studies are still needed. PMID:29760793

The cost-effectiveness of alternative therapeutic strategies for the management of chronic hepatitis B in Poland.

PubMed

Orlewska, Ewa

2002-01-01

The aim of the study was to estimate the cost-effectiveness of alternative therapeutic strategies for the management of chronic hepatitis B (CHB) in Poland. The model for the Polish health-care context was based on clinical data from the literature and local data on health-care resource utilization and unit costs. Costs and effects of a population of CHB patients were modeled using four scenarios, which attempt to reflect real-life practice in which patients may receive any of the treatment options available and in which a proportion of patients may still receive no treatment because therapy is not suitable. Strategies A and B assumed the availability of both treatment options: the first choice of treatment is in A, lamivudine, and in B, interferon alpha (IFN-alpha). In strategy C, the only approved treatment is IFN-alpha, and in strategy D, the patients receive no antiviral treatment. The outcome measures were HBeAg seroconversion and nonprogression to cirrhosis-the surrogate marker with predictive value for improved survival. Only direct medical costs were analyzed. The payer's perspective and time horizon of 1 year were adopted. One-way sensitivity analysis and extreme scenario analysis were performed. The best results in terms of seroconversion and nonprogression to cirrhosis were achieved for strategy A, costs were lowest for strategy D, and strategies B and C were dominated by strategy A. The incremental cost/effectiveness ratio (ICER) comparing strategy A with strategy D was 57,855 Polish new zloty (PLN) per extra seroconversion and 79,550 PLN per cirrhosis case avoided. Cirrhosis reduces estimated life expectancy by 37.76 years and by 20 years among 30- and 50-year-olds, respectively. The ICER for strategies A and D was 2105 PLN and 3978 PLN per life-years gained for the population at ages 30 and 50, respectively, and was below the suggested threshold for cost-effectiveness, based on treatment costs for 1 year of hemodialysis in Poland (62,400 PLN). Changing the value of key drivers for sensitivity analysis did not have a significant effect on the ICER.

Effect of modified Xiaochaihu decoction-containing serum on HepG2.2.15 cells via the JAK2/STAT3 signaling pathway

PubMed Central

Chen, Shaofang; Wang, Zhanglin; Wan, Shichuan; Huang, Hai; Liang, Huiqing

2017-01-01

The present study aimed to investigate the possible mechanisms underlying the effect of modified Xiaochaihu decoction (mXCHD) in the treatment of chronic hepatitis B (CHB). Patients with CHB, in addition to liver stagnation and spleen deficiency syndrome were randomly assigned to receive either Chinese (mXCHD) or western (entecavir) treatment, with 30 cases in each group. Serum was collected following treatment with mXCHD or entecavir for 7 days. A healthy group of 30 individuals was also included. HepG2.2.15 cells were cultured in vitro and randomly divided into four groups: Healthy; entecavir-treated; 10% mXCHD-treated; and 20% mXCHD-treated. The HepG2.2.15 cells in the four groups were treated with either serum from the healthy volunteers, entecavir-containing serum, or mXCHD-containing serum at different concentrations (10 or 20%, respectively). Following treatment with the corresponding serum, cell proliferation was examined using an MTT assay, and the expression of hepatitis B surface antigen (HBsAg) in the cell supernatant was detected using an enzyme-linked immunosorbent assay. The mRNA and protein expression levels of Janus kinase (JAK)2 and signal transducer and activator of transcription (STAT)3 were measured using reverse transcription-quantitative polymerase chain reaction and western blot analyses, respectively. The results indicated that the most effective treatment for the promotion of HepG2.2.15 cell proliferation was a 20% concentration of mXCHD serum. The expression of HBsAg was significantly decreased in the groups treated with 10 and 20% mXCHD 48 h following intervention (P<0.01). The mRNA and protein expression levels of STAT3 in the 20% mXCHD serum group were significantly increased, compared with those in the healthy group (P<0.01 and P<0.05, respectively), whereas no significant difference was observed in the expression of JAK2 among the four groups. These results indicated that mXCHD suppressed the hepatitis B virus, and treatment of the cells with mXCHD-containing serum promoted HepG2.2.15 cell proliferation via modulating the expression of STAT3, which may contribute to the clinical efficacy of mXCHD against CHB. PMID:28944901

Bioaccumulation and enantiomeric profiling of organochlorine pesticides and persistent organic pollutants in the killer whale (Orcinus orca) from British and Irish waters.

PubMed

McHugh, Brendan; Law, Robin J; Allchin, Colin R; Rogan, Emer; Murphy, Sinead; Foley, M Barry; Glynn, Denise; McGovern, Evin

2007-11-01

Concentrations and enantiomeric profiles for a range of organochlorine compounds are reported in blubber samples from a number of individual killer whales (Orcinus orca) from British and Irish waters. Elevated contaminant levels and enriched isotopic ratios were determined in one individual whale sampled in the Scottish Western Isles compared to the others suggesting marine mammal based dietary influences. The potential application of isotopic ratios to model contaminant uptake, enantioselective enrichment and accumulation is demonstrated. Data are presented which provide information on enantioselective enrichment factors (EFs) for o,p'-DDT, alpha-HCH and toxaphene congeners CHB26 and CHB 50. This dataset further improves the current database on reported levels of a number of contaminants and provides additional background information on potential metabolic processes in killer whales from British and Irish waters.

Higher efficacy of pegylated interferon-α2b add-on therapy in hepatitis B envelope antigen-positive chronic hepatitis B patients on tenofovir monotherapy.

PubMed

Jindal, Ankur; Vyas, Ashish Kumar; Kumar, Devesh; Kumar, Guresh; Sharma, Manoj Kumar; Sarin, Shiv Kumar

2018-05-01

Monotherapy with pegylated interferon-α (Peg-IFNα) or the nucleos(t)ide analogs (NA) currently approved for treating chronic hepatitis B (CHB) has limited efficacy. Studies on the combination of Peg-IFNα/NA have shown conflicting results. We investigated whether sequentially adding on Peg-IFNα to tenofovir enhances serological response rates. Treatment-naïve, hepatitis B envelope antigen (HBeAg)-positive CHB patients with moderately elevated alanine aminotransferase (ALT; 48-200 IU/mL) were started on tenofovir (300 mg/day) and enrolled at week 12 in a 1:1 ratio to either receive Peg-IFNα2b add-on (1.5 μg/kg/week) from week 12 to 36 (n = 53) or continue tenofovir monotherapy (n = 53). Both treatment arms received tenofovir consolidation therapy until week 72. The primary end-point was HBeAg loss at week 72. At week 72, the rate of HBeAg loss was higher in the Peg-IFNα2b add-on group (35.8%) compared to the tenofovir monotherapy group (17%) (P = 0.028; odds ratio, 2.73, 95% confidence interval, 1.09-6.79), and considerably higher in patients with a baseline hepatitis B virus (HBV)-DNA level >6 log IU/mL (32.6% vs 11.4%; P = 0.021). Rates of HBV-DNA loss (77.4% vs 71.7%; P = 0.51), ALT normalization (62.3% vs 52.8%; P = 0.32), and sustained virologic response (20.8% vs 11.3%; P = 0.18) at week 72 were comparable between the two groups. Significantly more patients in the add-on group had >3 log HBV-DNA reduction at week 36 (92.5% vs 66%; P = 0.001). Four patients treated with Peg-IFNα2b add-on achieved hepatitis B surface antigen (HBsAg) loss compared with one patient receiving tenofovir monotherapy. Decline of HBV-DNA of >2 log at week 4 led to higher HBeAg loss at week 72, independent of treatment arm. No patient had treatment-related adverse effects requiring treatment discontinuation. Twenty-four weeks of Peg-IFNα2b as an add-on sequential regimen to tenofovir is safe and resulted in greater loss of HBeAg and HBsAg compared to tenofovir monotherapy in selected HBeAg-positive patients. Viral load reduction followed by immune modulation is a potentially useful approach. © 2018 The Japan Society of Hepatology.

Ivabradine vs metoprolol in patients with acute inferior wall myocardial infarction-"Expanding arena for ivabradine".

PubMed

Priti, Kumari; Ranwa, Bhanwar L; Gokhroo, Rajendra K; Kishore, Kamal; Bisht, Devendra Singh; Gupta, Sajal

2017-08-01

Atrioventricular (AV) blocks are of concern with the use of beta blockers in inferior wall myocardial infarction (MI). Ivabradine lowers heart rate with a lesser risk of AV blocks. To compare ivabradine with metoprolol in acute inferior wall MI in terms of feasibility, tolerability, and efficacy. It was a prospective double-blind single-center randomized controlled study. Of 1032 patients with acute inferior wall MI, 468 eligible patients were randomized in 1:1 manner to ivabradine (group A) and metoprolol (group B). Intention to treat analysis of 426 patients (group A-232 and group B-232) was performed. The primary endpoint was 30-day incidence of major adverse cardiovascular events including death, reinfarction, complete heart block (CHB), and heart failure. Secondary endpoints included 30 days incidence of recurrent angina, readmission, first- or second-degree AV block, and tachyarrhythmias. Both the drugs decreased the mean heart rate to 62.22±2.95 (group A) vs 62.53±3.59 (group B) beats per minute (P=0.33). Ejection fraction improved in both the groups (5.15±1.93% in group A vs 5.52±2.18% in group B, P=0.065). The two groups did not differ significantly in their primary endpoints in terms of death (group A=1.72% vs group B=1.72%, OR=1.00, 95% CI=0.25-4.05, P=1.00), reinfarction (group A=0.86% vs group B=0.86%, OR=1.00, 95% CI=0.14-7.16, P=1.00), heart failure (group A=4.31% vs group B=2.59%, OR=1.70, 95% CI=0.61-4.75, P=0.31), or CHB (0% vs 2.59%, OR=0.07, 95% CI=0.00-1.34, P=0.08). There were no significant differences in the secondary endpoints of recurrent angina, readmission, and tachyarrhythmias except for more first- and second-degree AV blocks with metoprolol (12.93% vs 2.59%, OR=5.59, 95% CI=2.28-13.72, P=0.0002). Ivabradine is well tolerated and equally effective as metoprolol in acute inferior wall ST elevation myocardial infarction patients for lowering the heart rate with lesser risk of AV blocks. © 2017 John Wiley & Sons Ltd.

Antiviral therapy in hepatitis B virus-infected children with immune-tolerant characteristics: A pilot open-label randomized study.

PubMed

Zhu, Shishu; Zhang, Hongfei; Dong, Yi; Wang, Limin; Xu, Zhiqiang; Liu, Weiwei; Gan, Yu; Tang, Hongmei; Chen, Dawei; Wang, Fuchuan; Zhao, Pan

2018-06-01

Chronic infection with hepatitis B virus (HBV) in children is a serious health problem worldwide. How to treat children with immune-tolerant chronic hepatitis B infection, commonly characterized by hepatitis B e antigen (HBeAg) positivity, high viral load, normal or mildly elevated alanine aminotransferase and no or minimal inflammation in liver histology, remains unresolved. This trial aims to study the benefits of antiviral therapy in children with these characteristics. This is a pilot open-label randomized controlled study. From May 2014 to April 2015, 69 treatment-naive chronically HBV-infected children, aged 1 to 16 years, who had immune-tolerant characteristics were recruited to this trial and randomly assigned, in a 2:1 ratio, to treatment group and control group. Patients in the treatment group received either interferon-α (IFN) monotherapy or consecutively received IFN monotherapy, combination therapy of IFN and lamivudine (LAM), and LAM therapy alone. All patients were observed until week 96. At baseline, epidemiological, biochemical, serological, virological and histological indices were consistent across the treatment and control groups. Of the 46 patients in the treatment group, 73.91% had undetectable serum HBV DNA, 32.61% achieved HBeAg seroconversion and 21.74% lost hepatitis B surface antigen (HBsAg) at the endpoint. No LAM resistance emerged at week 96. In the control group, only one (4.35%) patient underwent spontaneous HBeAg seroconversion and had undetectable serum HBV DNA during observation, and moreover, none developed HBsAg clearance. For all patients, no serious adverse events were observed. Antiviral treatment with a sequential combination of IFN and LAM resulted in a significant improvement in the rates of undetectable serum HBV DNA, HBeAg seroconversion and HBsAg loss in children with chronic HBV infection and immune-tolerant characteristics. There is a lack of data regarding treatment of immune-tolerant chronic hepatitis B (CHB). It remains unresolved how children with immune-tolerant CHB should be treated. This paper reports the outcomes from a pilot open-label randomized controlled trial on antiviral therapy in children with immune-tolerant characteristics. It shows that a sequential combination of interferon-α and lamivudine was beneficial. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Calibration procedures for imaging spectrometers: improving data quality from satellite missions to UAV campaigns

NASA Astrophysics Data System (ADS)

Brachmann, Johannes F. S.; Baumgartner, Andreas; Lenhard, Karim

2016-10-01

The Calibration Home Base (CHB) at the Remote Sensing Technology Institute of the German Aerospace Center (DLR-IMF) is an optical laboratory designed for the calibration of imaging spectrometers for the VNIR/SWIR wavelength range. Radiometric, spectral and geometric characterization is realized in the CHB in a precise and highly automated fashion. This allows performing a wide range of time consuming measurements in an efficient way. The implementation of ISO 9001 standards ensures a traceable quality of results. DLR-IMF will support the calibration and characterization campaign of the future German spaceborne hyperspectral imager EnMAP. In the context of this activity, a procedure for the correction of imaging artifacts, such as due to stray light, is currently being developed by DLR-IMF. Goal is the correction of in-band stray light as well as ghost images down to a level of a few digital numbers in the whole wavelength range 420-2450 nm. DLR-IMF owns a Norsk Elektro Optikks HySpex airborne imaging spectrometer system that has been thoroughly characterized. This system will be used to test stray light calibration procedures for EnMAP. Hyperspectral snapshot sensors offer the possibility to simultaneously acquire hyperspectral data in two dimensions. Recently, these rather new spectrometers have arisen much interest in the remote sensing community. Different designs are currently used for local area observation such as by use of small unmanned aerial vehicles (sUAV). In this context the CHB's measurement capabilities are currently extended such that a standard measurement procedure for these new sensors will be implemented.

Luteolin-7-O-Glucoside Present in Lettuce Extracts Inhibits Hepatitis B Surface Antigen Production and Viral Replication by Human Hepatoma Cells in Vitro

PubMed Central

Cui, Xiao-Xian; Yang, Xiao; Wang, Hui-Jing; Rong, Xing-Yu; Jing, Sha; Xie, You-Hua; Huang, Dan-Feng; Zhao, Chao

2017-01-01

Hepatitis B virus (HBV) infection is endemic in Asia and chronic hepatitis B (CHB) is a major public health issue worldwide. Current treatment strategies for CHB are not satisfactory as they induce a low rate of hepatitis B surface antigen (HBsAg) loss. Extracts were prepared from lettuce hydroponically cultivated in solutions containing glycine or nitrate as nitrogen sources. The lettuce extracts exerted potent anti-HBV effects in HepG2 cell lines in vitro, including significant HBsAg inhibition, HBV replication and transcription inhibition, without exerting cytotoxic effects. When used in combination interferon-alpha 2b (IFNα-2b) or lamivudine (3TC), the lettuce extracts synergistically inhibited HBsAg expression and HBV replication. By using differential metabolomics analysis, Luteolin-7-O-glucoside was identified and confirmed as a functional component of the lettuce extracts and exhibited similar anti-HBV activity as the lettuce extracts in vitro. The inhibition rate on HBsAg was up to 77.4%. Moreover, both the lettuce extracts and luteolin-7-O-glucoside functioned as organic antioxidants and, significantly attenuated HBV-induced intracellular reactive oxygen species (ROS) accumulation. Luteolin-7-O-glucoside also normalized ROS-induced mitochondrial membrane potential damage, which suggests luteolin-7-O-glucoside inhibits HBsAg and HBV replication via a mechanism involving the mitochondria. Our findings suggest luteolin-7-O-glucoside may have potential value for clinical application in CHB and may enhance HBsAg and HBV clearance when used as a combination therapy. PMID:29270164

Anti-hepatitis B virus (HBV) response of imiquimod based toll like receptor 7 ligand in hbv-positive human hepatocelluar carcinoma cell line.

PubMed

Das, Dipanwita; Sengupta, Isha; Sarkar, Neelakshi; Pal, Ananya; Saha, Debraj; Bandopadhyay, Manikankana; Das, Chandrima; Narayan, Jimmy; Singh, Shivaram Prasad; Chakrabarti, Sekhar; Chakravarty, Runu

2017-01-14

Toll like receptors (TLRs) play an important role in innate immunity and various studies suggest that TLRs play a crucial role in pathogenesis of hepatitis B virus (HBV) infection. The present study aims in looking into the status of crucial host and viral gene expression on inciting TLR7. The transcription of TLR7 pathway signaling molecules and HBV DNA viral load were quantified by Real Time-PCR after stimulation of TLR7 with its imiquimod based ligand, R837. Cell cycle analysis was performed using flow-cytometry. Expression of TLR7 and chief cell cycle regulator governing G1/S transition, p53 was also seen in liver biopsysss samples of CHB patients. HBV induced alteration in histone modifications in HepG2 cells and its restoration on TLR7 activation was determined using western blot. The TLR7 expression remains downregulated in HepG2.2.15 cells and in liver biopsy samples from CHB patients. Interestingly HBV DNA viral load showed an inverse relationship with the TLR7 expression in the biopsy samples. We also evaluated the anti-viral activity of R837, an agonist of TLR7. It was observed that there was a suppression of HBV replication and viral protein production upon TLR7 stimulation. R837 triggers the anti-viral action probably through the Jun N-terminal Kinase (JNK) pathway. We also observed a downregulation of histone H3K9Me3 repression mark upon R837 treatment in HBV replicating HepG2.2.15 cells, mimicking that of un-infected HepG2 cells. Additionally, the G1/S cell cycle arrest introduced by HBV in HepG2.2.15 cells was released upon ligand treatment. The study thus holds a close insight into the changes in hepatocyte micro-environment on TLR7 stimulation in HBV infection.

Aberrant GSTP1 promoter methylation predicts short-term prognosis in acute-on-chronic hepatitis B liver failure.

PubMed

Gao, S; Sun, F-K; Fan, Y-C; Shi, C-H; Zhang, Z-H; Wang, L-Y; Wang, K

2015-08-01

Glutathione-S-transferase P1 (GSTP1) methylation has been demonstrated to be associated with oxidative stress induced liver damage in acute-on-chronic hepatitis B liver failure (ACHBLF). To evaluate the methylation level of GSTP1 promoter in acute-on-chronic hepatitis B liver failure and determine its predictive value for prognosis. One hundred and five patients with acute-on-chronic hepatitis B liver failure, 86 with chronic hepatitis B (CHB) and 30 healthy controls (HC) were retrospectively enrolled. GSTP1 methylation level in peripheral mononuclear cells (PBMC) was detected by MethyLight. Clinical and laboratory parameters were obtained. GSTP1 methylation levels were significantly higher in patients with acute-on-chronic hepatitis B liver failure (median 16.84%, interquartile range 1.83-59.05%) than those with CHB (median 1.25%, interquartile range 0.48-2.47%; P < 0.01) and HC (median 0.80%, interquartile range 0.67-1.27%; P < 0.01). In acute-on-chronic hepatitis B liver failure group, nonsurvivors showed significantly higher GSTP1 methylation levels (P < 0.05) than survivors. GSTP1 methylation level was significantly correlated with total bilirubin (r = 0.29, P < 0.01), prothrombin time activity (r = -0.24, P = 0.01) and model for end-stage liver disease (MELD) score (r = 0.26, P = 0.01). When used to predict 1- or 2-month mortality of acute-on-chronic hepatitis B liver failure, GSTP1 methylation showed significantly better predictive value than MELD score [area under the receiver operating characteristic curve (AUC) 0.89 vs. 0.72, P < 0.01; AUC 0.83 vs. 0.70, P < 0.05 respectively]. Meanwhile, patients with GSTP1 methylation levels above the cut-off points showed significantly poorer survival than those below (P < 0.05). Aberrant GSTP1 promoter methylation exists in acute-on-chronic hepatitis B liver failure and shows high predictive value for short-term mortality. It might serve as a potential prognostic marker for acute-on-chronic hepatitis B liver failure. © 2015 John Wiley & Sons Ltd.

Oxygen consumption estimation with combined color doppler ultrasound and photoacoustic microscopy: a phantom study

NASA Astrophysics Data System (ADS)

Jiang, Yan; Harrison, Tyler; Forbrich, Alex; Zemp, Roger J.

2011-03-01

The metabolic rate of oxygen consumption (MRO2) quantifies tissue metabolism, which is important for diagnosis of many diseases. For a single vessel model, the MRO2 can be estimated in terms of the mean flow velocity, vessel crosssectional area, total concentration of hemoglobin (CHB), and the difference between the oxygen saturation (sO2) of blood flowing into and out of the tissue region. In this work, we would like to show the feasibility to estimate MRO2 with our combined photoacoustic and high-frequency ultrasound imaging system. This system uses a swept-scan 25-MHz ultrasound transducer with confocal dark-field laser illumination optics. A pulse-sequencer enables ultrasonic and laser pulses to be interlaced so that photoacoustic and Doppler ultrasound images are co-registered. Since the mean flow velocity can be measured by color Doppler ultrasound, the vessel cross-sectional area can be measured by power Doppler or photoacoustic imaging, and multi-wavelength photoacoustic methods can be used to estimate sO2 and CHB, all of these parameters necessary for MRO2 estimation can be provided by our system. Experiments have been performed on flow phantoms to generate co-registered color Doppler and photoacoustic images. To verify the sO2 estimation, two ink samples (red and blue) were mixed in various concentration ratios to mimic different levels of sO2, and the result shows a good match between the calculated concentration ratios and actual values.

Phase IV randomized clinical study: Peginterferon alfa-2a with adefovir or entecavir pre-therapy for HBeAg-positive chronic hepatitis B.

PubMed

Hsu, Chao-Wei; Su, Wei-Wen; Lee, Chuan-Mo; Peng, Cheng-Yuan; Chuang, Wan-Long; Kao, Jia-Horng; Chu, Heng-Cheng; Huang, Yi-Hsiang; Chien, Rong-Nan; Liaw, Yun-Fan

2018-07-01

Efficacy of sequential therapy with nucleos(t)ide analogues and interferons versus monotherapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) remains unexplored. We aimed to assess efficacy and safety of sequential therapy with adefovir (ADV) or entecavir (ETV) followed by peginterferon (PEG-IFN) alfa-2a in Taiwanese patients with HBeAg-positive. This randomized, placebo-controlled, double-blind trial was conducted at nine sites in Taiwan from April 2010 to October 2013. Patients (N = 280) were randomized 1:1:1 to receive placebo, ETV or ADV alone for four weeks, combined with PEG-IFN alfa-2a for two weeks, then PEG-IFN alfa-2a alone for 46 weeks. The primary efficacy end point was HBeAg seroconversion at 48 weeks post-treatment. No significant differences were observed among groups for HBeAg seroconversion (PEG-IFN alfa-2a+placebo, 36.3%; PEG-IFN alfa-2a+ETV, 29.5%; and PEG-IFN alfa-2a+ADV, 27.4%), HBeAg loss (37.4%, 32.2%, and 28.6%, respectively) or change in hepatitis B surface antigen (HBsAg) levels from baseline (-0.56 IU/mL, -0.60 IU/mL, and -0.41 IU/mL, respectively). However, hepatitis B virus DNA levels were higher with PEG-IFN alfa-2a+placebo than PEG-IFN alfa+ETV at week 64 (p = 0.0412), 76 (p = 0.0311), and 88 (p = 0.0113), and alanine aminotransferase (ALT) normalization rate was higher with PEG-IFN alfa-2a+placebo than PEG-IFN alfa-2a+ADV (p = 0.0283) or PEG-IFN alfa-2a+ETV (p = 0.0369) at week 88. Sub-analysis of results revealed an association between on-treatment HBsAg and ALT levels and efficacy 48 weeks post-treatment. Safety was comparable among treatment groups. Pre-therapy with ADV or ETV followed by PEG-IFN alfa-2a is not superior to PEG-IFN alfa-2a monotherapy in Taiwanese patients with HBeAg-positive CHB. NCT: 00922207. Copyright © 2018. Published by Elsevier B.V.

Dynamic Control of Facts Devices to Enable Large Scale Penetration of Renewable Energy Resources

NASA Astrophysics Data System (ADS)

Chavan, Govind Sahadeo

This thesis focuses on some of the problems caused by large scale penetration of Renewable Energy Resources within EHV transmission networks, and investigates some approaches in resolving these problems. In chapter 4, a reduced-order model of the 500 kV WECC transmission system is developed by estimating its key parameters from phasor measurement unit (PMU) data. The model was then implemented in RTDS and was investigated for its accuracy with respect to the PMU data. Finally it was tested for observing the effects of various contingencies like transmission line loss, generation loss and large scale penetration of wind farms on EHV transmission systems. Chapter 5 introduces Static Series Synchronous Compensators (SSSC) which are seriesconnected converters that can control real power flow along a transmission line. A new application of SSSCs in mitigating Ferranti effect on unloaded transmission lines was demonstrated on PSCAD. A new control scheme for SSSCs based on the Cascaded H-bridge (CHB) converter configuration was proposed and was demonstrated using PSCAD and RTDS. A new centralized controller was developed for the distributed SSSCs based on some of the concepts used in the CHB-based SSSC. The controller's efficacy was demonstrated using RTDS. Finally chapter 6 introduces the problem of power oscillations induced by renewable sources in a transmission network. A power oscillation damping (POD) controller is designed using distributed SSSCs in NYPA's 345 kV three-bus AC system and its efficacy is demonstrated in PSCAD. A similar POD controller is then designed for the CHB-based SSSC in the IEEE 14 bus system in PSCAD. Both controllers were noted to have significantly damped power oscillations in the transmission networks.

Cost effectiveness of screening immigrants for hepatitis B.

PubMed

Wong, William W L; Woo, Gloria; Jenny Heathcote, E; Krahn, Murray

2011-09-01

The prevalence of chronic hepatitis B (CHB) infection among the immigrants of North America ranges from 2 to 15%, among whom 40% develop advanced liver disease. Screening for hepatitis B surface antigen is not recommended for immigrants. The objective of this study is to estimate the health and economic effects of screening strategies for CHB among immigrants. We used the Markov model to examine the cost-effectiveness of three screening strategies: (i) 'No screening'; (ii) 'Screen and Treat' and (iii) 'Screen, Treat and Vaccinate' for 20-65 years old individuals who were born abroad but are currently living in Canada. Model data were obtained from the published literature. We measured predicted hepatitis B virus (HBV)-related deaths, costs (2008 Canadian Dollars), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). Our results show that screening all immigrants will prevent 59 HBV-related deaths per 10, 000 persons screened over the lifetime of the cohort. Screening was associated with an increase in quality-adjusted life expectancy (0.024 QALYs) and cost ($1665) per person with an ICER of $69, 209/QALY gained compared with 'No screening'. The 'Screen, Treat and Vaccinate' costs an additional $81, generates an additional 0.000022 QALYs per person, with an ICER of $3, 648,123/QALY compared with the 'Screen and Treat'. Sensitivity analyses suggested that the 'Screen and Treat' is likely to be moderately cost-effective. We show that a selective hepatitis B screening programme targeted at all immigrants in Canada is likely to be moderately cost-effective. Identification of silent CHB infection with the offer of treatment when appropriate can extend the lives of immigrants at reasonable cost. © 2011 John Wiley & Sons A/S.

Staging liver fibrosis in chronic hepatitis B with T1 relaxation time index on gadoxetic acid-enhanced MRI: Comparison with aspartate aminotransferase-to-platelet ratio index and FIB-4.

PubMed

Yang, Li; Ding, Ying; Rao, Shengxiang; Chen, Caizhong; Wu, Lifang; Sheng, Ruofan; Fu, Caixia; Zeng, Mengsu

2017-04-01

To assess the accuracy of the T 1 relaxation time index on gadoxetic acid-enhanced magnetic resonance imaging (MRI) for staging liver fibrosis in chronic hepatitis B (CHB), in comparison and combination with the aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4). A retrospective study of gadoxetic acid-enhanced T 1 mapping and serum biochemical tests was performed on 126 CHB patients who underwent gadoxetic acid-enhanced 1.5T MRI, and the histological score used as the gold standard. The reduction rate of T 1 relaxation time before and 20 minutes after gadoxetic acid injection (ΔT 1 , ΔR1%), the contrast uptake rate (K Hep ), APRI, and FIB-4 were calculated. The diagnostic efficacy of ΔT 1 , ΔR1%, K Hep , APRI, and FIB-4 for predicting stage 2 or greater (≥S2), stage 3 or greater (≥S3), and stage 4 (S4) was compared. ΔT 1 (r = -0.513, P < 0.001), ΔR1% (r = -0.626, P < 0.001), K Hep (r = -0.527, P < 0.001), APRI (r = 0.519, P < 0.001), and FIB-4 (r = 0.476, P < 0.001) correlated significantly with fibrosis stages. Areas under the curves (AUCs) of ΔR1% for detecting ≥S2, ≥S3, and S4 were 0.849, 0.827, and 0.809, which were greater than that of APRI (0.763, 0.745, 0.787) and FIB-4 (0.727, 0.738, 0.772), but significant difference was found only in discriminating ≥S2 between ΔR1% and FIB-4 (P = 0.027). The combination of all five indices performed best, with AUC, sensitivity, and specificity of 0.860, 87.21%, and 72.50% for diagnosing ≥S2, 0.878, 82.81%, and 85.48% for ≥S3, and 0.867, 80.00%, and 83.95% for S4. The gadoxetic acid-enhanced T 1 relaxation time index appears to be superior to APRI and FIB-4 for predicting hepatic fibrosis. The combined use of gadoxetic acid-enhanced T 1 mapping, APRI, and FIB-4 may be more reliable for staging liver fibrosis in CHB. 4 J. Magn. Reson. Imaging 2017;45:1186-1194. © 2016 International Society for Magnetic Resonance in Medicine.

Impact of age on the diagnostic performances and cut-offs of APRI and FIB-4 for significant fibrosis and cirrhosis in chronic hepatitis B

PubMed Central

Li, Qiang; Lu, Chuan; Li, Weixia; Huang, Yuxian; Chen, Liang

2017-01-01

Aims Assessing the diagnostic performances of APRI and FIB-4 using age as a categorical marker. Methods 822 chronic hepatitis B (CHB) patients were included. Using METAVIR scoring system as a reference, the performances of APRI and FIB-4 were compared between patients aged≥30 and patients aged<30 years. Results The APRI AUROC in patients aged<30 years was lower than that in patients aged≥30 years for significant fibrosis (0.61 vs 0.70, p<0.001) and cirrhosis (0.64 vs 0.78, p<0.001). The FIB-4 AUROC in patients aged<30 years was lower than that in patients aged≥30 years for significant fibrosis (0.57 vs 0.65, p<0.001) and cirrhosis (0.63 vs 0.72, p<0.001). Using specificity≥90%, the APRI cut-off in patients aged<30 years was lower than patients aged≥30 years for significant fibrosis (1.0 vs 1.2) and cirrhosis (1.2 vs 1.5). Using sensitivity≥90%, the APRI cut-off in patients aged<30 years was also lower than patients aged≥30 years for significant fibrosis (0.2 vs 0.4) and cirrhosis (0.3 vs 0.5). Using specificity≥90%, the FIB-4 cut-off in patients aged<30 years was lower than that in patients aged≥30 years for significant fibrosis (1.2 vs 2.1) and cirrhosis (1.4 vs 2.6). Using sensitivity≥90%, the FIB-4 cut-off in patients aged<30 years was also lower than that in patients aged≥30 years for significant fibrosis (0.5 vs 0.8) and cirrhosis (0.8 vs 1.2). Conclusions Evaluation of the diagnostic performances of APRI and FIB-4 should take age into consideration. PMID:28514753

Cancer Control: A Look to the Future

Cancer.gov

Judith Mackay, MB ChB, FRCP (Edin), FRCP (Lon), an international expert from Hong Kong in tobacco control, with posts as a senior advisor for the World Lung Foundation and the Bloomberg Initiative to Reduce Tobacco Use, presented "Cancer Control: A Look to the Future".

Cardiac fibroblast transcriptome analyses support a role for interferogenic, profibrotic, and inflammatory genes in anti-SSA/Ro-associated congenital heart block.

PubMed

Clancy, Robert M; Markham, Androo J; Jackson, Tanisha; Rasmussen, Sara E; Blumenberg, Miroslav; Buyon, Jill P

2017-09-01

The signature lesion of SSA/Ro autoantibody-associated congenital heart block (CHB) is fibrosis and a macrophage infiltrate, supporting an experimental focus on cues influencing the fibroblast component. The transcriptomes of human fetal cardiac fibroblasts were analyzed using two complementary approaches. Cardiac injury conditions were simulated in vitro by incubating human fetal cardiac fibroblasts with supernatants from macrophages transfected with the SSA/Ro-associated noncoding Y ssRNA. The top 10 upregulated transcripts in the stimulated fibroblasts reflected a type I interferon (IFN) response [e.g., IFN-induced protein 44-like (IFI44L), of MX dynamin-like GTPase (MX)1, MX2, and radical S -adenosyl methionine domain containing 2 (Rsad2)]. Within the fibrotic pathway, transcript levels of endothelin-1 (EDN1), phosphodiesterase (PDE)4D, chemokine (C-X-C motif) ligand (CXCL)2, and CXCL3 were upregulated, while others, including adenomedullin, RAP guanine nucleotide exchange factor 3 (RAPGEF3), tissue inhibitor of metalloproteinase (TIMP)1, TIMP3, and dual specificity phosphatase 1, were downregulated. Agnostic Database for Annotation, Visualization and Integrated Discovery analysis revealed a significant increase in inflammatory genes, including complement C3A receptor 1 (C3AR1), F2R-like thrombin/trypsin receptor 3, and neutrophil cytosolic factor 2. In addition, stimulated fibroblasts expressed high levels of phospho-MADS box transcription enhancer factor 2 [a substrate of MAPK5 (ERK5)], which was inhibited by BIX-02189, a specific inhibitor of ERK5. Translation to human disease leveraged an unprecedented opportunity to interrogate the transcriptome of fibroblasts freshly isolated and cell sorted without stimulation from a fetal heart with CHB and a matched healthy heart. Consistent with the in vitro data, five IFN response genes were among the top 10 most highly expressed transcripts in CHB fibroblasts. In addition, the expression of matrix-related genes reflected fibrosis. These data support the novel finding that cardiac injury in CHB may occur secondary to abnormal remodeling due in part to upregulation of type 1 IFN response genes. NEW & NOTEWORTHY Congenital heart block is a rare disease of the fetal heart associated with maternal anti-Ro autoantibodies which can result in death and for survivors, lifelong pacing. This study provides in vivo and in vitro transcriptome-support that injury may be mediated by an effect of Type I Interferon on fetal fibroblasts. Copyright © 2017 the American Physiological Society.

Effective population size of korean populations.

PubMed

Park, Leeyoung

2014-12-01

Recently, new methods have been developed for estimating the current and recent changes in effective population sizes. Based on the methods, the effective population sizes of Korean populations were estimated using data from the Korean Association Resource (KARE) project. The overall changes in the population sizes of the total populations were similar to CHB (Han Chinese in Beijing, China) and JPT (Japanese in Tokyo, Japan) of the HapMap project. There were no differences in past changes in population sizes with a comparison between an urban area and a rural area. Age-dependent current and recent effective population sizes represent the modern history of Korean populations, including the effects of World War II, the Korean War, and urbanization. The oldest age group showed that the population growth of Koreans had already been substantial at least since the end of the 19th century.

Interleukin-23 mediates the pathogenesis of LPS/GalN-induced liver injury in mice.

PubMed

Bao, Suxia; Zhao, Qiang; Zheng, Jianming; Li, Ning; Huang, Chong; Chen, Mingquan; Cheng, Qi; Zhu, Mengqi; Yu, Kangkang; Liu, Chenghai; Shi, Guangfeng

2017-05-01

Interleukin-23 (IL-23) is required for T helper 17 (Th17) cell responses and IL-17 production in hepatitis B virus infection. A previous study showed that the IL-23/IL-17 axis aggravates immune injury in patients with chronic hepatitis B virus infection. However, the role of IL-23 in acute liver injury remains unclear. The purpose of this study was to determine the role of the inflammatory cytokine IL-23 in lipopolysaccharide/d-galactosamine (LPS/GalN)-induced acute liver injury in mice. Serum IL-23 from patients with chronic hepatitis B virus (CHB), acute-on-chronic liver failure (ACLF) and healthy individuals who served as healthy controls (HCs) was measured by ELISA. An IL-23p19 neutralizing antibody or an IL-23p40 neutralizing antibody was administered intravenously at the time of challenge with LPS (10μg/kg) and GalN (400mg/kg) in C57BL/6 mice. Hepatic pathology and the expression of Th17-related cytokines, including IL-17 and TNF-α; neutrophil chemoattractants, including Cxcl1, Cxcl2, Cxcl9, and Cxcl10; and the stabilization factor Csf3 were assessed in liver tissue. Serum IL-23 was significantly upregulated in ACLF patients compared with CHB patients and HCs (P<0.05 for both). Serum IL-23 was significantly upregulated in the non-survival group compared with the survival group of ACLF patients, which was consistent with LPS/GalN-induced acute hepatic injury in mice (P<0.05 for both). Moreover, after treatment, serum IL-23 was downregulated in the survival group of ACLF patients (P<0.001). Compared with LPS/GalN mice, mice treated with either an IL-23p19 neutralizing antibody or an IL-23p40 neutralizing antibody showed less severe liver tissue histopathology and significant reductions in the expression of Th17-related inflammatory cytokine, including IL-17 and TNF-α; neutrophil chemoattractants, including Cxcl1, Cxcl2, Cxcl9, and Cxcl10; and stabilization factors Csf3 within the liver tissue compared with LPS/GalN mice (P<0.05 for all). High serum IL-23 was associated with mortality in ACLF patients and LPS/GalN-induced acute liver injury in mice. IL-23 neutralizing antibodies attenuated liver injury by reducing the expression of Th17-related inflammatory cytokines, neutrophil chemoattractants and stabilization factors within the liver tissue, which indicated that IL-23 likely functions upstream of Th17-related cytokine and chemokine expression to recruit inflammatory cells into the liver. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterisation methods for the hyperspectral sensor HySpex at DLR's calibration home base

NASA Astrophysics Data System (ADS)

Baumgartner, Andreas; Gege, Peter; Köhler, Claas; Lenhard, Karim; Schwarzmaier, Thomas

2012-09-01

The German Aerospace Center's (DLR) Remote Sensing Technology Institute (IMF) operates a laboratory for the characterisation of imaging spectrometers. Originally designed as Calibration Home Base (CHB) for the imaging spectrometer APEX, the laboratory can be used to characterise nearly every airborne hyperspectral system. Characterisation methods will be demonstrated exemplarily with HySpex, an airborne imaging spectrometer system from Norsk Elektro Optikks A/S (NEO). Consisting of two separate devices (VNIR-1600 and SWIR-320me) the setup covers the spectral range from 400 nm to 2500 nm. Both airborne sensors have been characterised at NEO. This includes measurement of spectral and spatial resolution and misregistration, polarisation sensitivity, signal to noise ratios and the radiometric response. The same parameters have been examined at the CHB and were used to validate the NEO measurements. Additionally, the line spread functions (LSF) in across and along track direction and the spectral response functions (SRF) for certain detector pixels were measured. The high degree of lab automation allows the determination of the SRFs and LSFs for a large amount of sampling points. Despite this, the measurement of these functions for every detector element would be too time-consuming as typical detectors have 105 elements. But with enough sampling points it is possible to interpolate the attributes of the remaining pixels. The knowledge of these properties for every detector element allows the quantification of spectral and spatial misregistration (smile and keystone) and a better calibration of airborne data. Further laboratory measurements are used to validate the models for the spectral and spatial properties of the imaging spectrometers. Compared to the future German spaceborne hyperspectral Imager EnMAP, the HySpex sensors have the same or higher spectral and spatial resolution. Therefore, airborne data will be used to prepare for and validate the spaceborne system's data.

77 FR 31067 - Cleveland Commercial Railroad Company, LLC-Continuance in Control Exemption-Cleveland Harbor Belt...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-24

... becoming a Class III rail carrier. CCR has established CHB as a limited liability company and has the... Commercial Railroad Company, LLC--Continuance in Control Exemption--Cleveland Harbor Belt Railroad Cleveland Commercial Railroad Company, LLC (CCR), a Class III rail carrier, has filed a verified notice of exemption...

Design and Comparison of Cascaded H-Bridge, Modular Multilevel Converter, and 5-L Active Neutral Point Clamped Topologies for Motor Drive Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marzoughi, Alinaghi; Burgos, Rolando; Boroyevich, Dushan

This paper presents the design procedure and comparison of converters currently used in medium-voltage high-power motor drive applications. For this purpose, the cascaded H-bridge (CHB), modular multilevel converter (MMC), and five-level active neutral point clamped (5-L ANPC) topologies are targeted. The design is performed using 1.7-kV insulated gate bipolar transistors (IGBTs) for CHB and MMC converters, and utilizing 3.3- and 4.5-kV IGBTs for 5-L ANPC topology as normally done in industry. The comparison is done between the designed converter topologies at three different voltage levels (4.16, 6.9, and 13.8 kV, with only the first two voltage levels in case ofmore » the 5-L ANPC) and two different power levels (3 and 5 MVA), in order to elucidate the dependence of different parameters on voltage and power rating. Finally, the comparison is done from several points of view such as efficiency, capacitive energy storage, semiconductor utilization, parts count (for measure of reliability), and power density.« less

Tenofovir disoproxil fumarate is superior to lamivudine plus adefovir in lamivudine-resistant chronic hepatitis B patients.

PubMed

Yang, Dan-Hong; Xie, Yuan-Jun; Zhao, Nian-Feng; Pan, Hong-Ying; Li, Ming-Wei; Huang, Hai-Jun

2015-03-07

To assess the efficacy of tenofovir disoproxil fumarate (TDF) in lamivudine (LAM)-resistant patients with a suboptimal response to LAM plus adefovir (ADV). We retrospectively analyzed the efficacy of switching to tenofovir disoproxil fumarate in suboptimal responders to lamivudine plus adefovir. Charts were reviewed for LAM-resistant chronic hepatitis B (CHB) patients who visited the Zhejiang Province People's Hospital and The First Affiliated Hospital, College of Medicine, Zhejiang University, from June 2009 to May 2013. Patients whose serum hepatitis B virus (HBV) DNA remained detectable despite at least 6 mo of LAM plus ADV combination therapy were included. Patients with a suboptimal response to LAM plus ADV were randomized to switch to TDF monotherapy (300 mg/d orally; TDF group) or to continuation with LAM (100 mg/d orally) plus ADV (10 mg/d orally; LAM plus ADV group) and were followed for 48 wk. Serum HBV DNA was determined at baseline and weeks 4, 12, 24, 36, and 48. HBV serological markers and biochemistry were assessed at baseline and weeks 12, 24, and 48. Resistance surveillance and side effects were monitored during therapy. Fifty-nine patient were randomized to switch to TDF (n = 28) or continuation with LAM plus ADV (n = 31). No significant differences were found between the groups at baseline. Prior to TDF therapy, all patients had been exposed to LAM plus ADV for a median of 11 mo (range: 6-24 mo). No difference was seen in baseline serum HBV DNA between the two groups [5.13 ± 1.08 log10 copies/mL (TDF) vs 5.04 ± 31.16 log10 copies/mL (LAM + ADV), P = 0.639]. There was no significant difference in the rates of achieving complete virological response (CVR) at week 4 between the TDF and LAM + ADV groups (17.86% vs 6.45%, P = 0.24). The rate of achieving CVR in the TDF and LAM plus ADV groups was 75% vs 16.13% at week 12, 82.14% vs 22.58% at week 24, 89.29% vs 25.81% at week 36, and 96.43% vs 29.03% at week 48, respectively (P < 0.001). The rate of alanine aminotransferase normalization was significantly higher in the TDF than in the LAM plus ADV group at week 12 (75% vs 17.86%, P < 0.001), but not at week 24 (78.57% vs 54.84%, P = 0.097) or 48 (89.26% vs 67.74%, P = 0.062). Patients were hepatitis B e antigen (HBeAg) positive at baseline. There was no significant difference in HBeAg negativity between the TDF and LAM plus ADV groups at week 48 (4% vs 0%, P = 0.481). There were no drug-related adverse effects at week 48 in either group. Switching to TDF monotherapy was superior to continuous add-on therapy in patients with LAM-resistant CHB with a suboptimal response to LAM plus ADV.

Serum hepatitis B core-related antigen is a satisfactory surrogate marker of intrahepatic covalently closed circular DNA in chronic hepatitis B.

PubMed

Chen, En-Qiang; Feng, Shu; Wang, Meng-Lan; Liang, Ling-Bo; Zhou, Ling-Yun; Du, Ling-Yao; Yan, Li-Bo; Tao, Chuan-Min; Tang, Hong

2017-03-14

Recently, hepatitis B core-related antigen (HBcrAg) has been suggested as an additional marker of hepatitis B virus (HBV) infection. This study aimed to investigate whether serum quantitative HBcrAg (qHBcrAg) was a satisfactory surrogate marker of intrahepatic covalently closed circular DNA (cccDNA). A total of 139 patients with liver biopsy were enrolled, consisting of 59 patients in immune tolerance (IT) phase, 52 patients in immune clearance (IC) phase, 18 patients in low-replication (LR) phase, and 10 patients in reactivation phase. All patients in IC phase have received entecavir (ETV) therapy, and 32 of them undergone a second liver biopsy at 24 months. Among those patients, qHBcrAg was strongly correlated with intrahepatic cccDNA, which is superior to that of qHBsAg and HBV DNA. And similar findings were also observed in patients in IT, IC, LR and reactivation phases. Among the 32 ETV-treated patients with a second liver biopsy in IC phase, the decline of intrahepatic cccDNA was accompanied by changes in both qHBcrAg and qHBsAg. However, as compared to qHBsAg, the change of qHBcrAg was more strongly associated with intrahepatic cccDNA-decline. In summary, serum qHBcrAg should be a satisfactory surrogate of intrahepatic HBV cccDNA in CHB patients.

Incidence, risk factors, and mortality of neonatal and late-onset dilated cardiomyopathy associated with cardiac neonatal lupus.

PubMed

Morel, Nathalie; Lévesque, Kateri; Maltret, Alice; Baron, Gabriel; Hamidou, Mohamed; Orquevaux, Pauline; Piette, Jean-Charles; Barriere, François; Le Bidois, Jérôme; Fermont, Laurent; Fain, Olivier; Theulin, Arnaud; Sassolas, François; Hauet, Quentin; Guettrot-Imbert, Gaëlle; Georgin-Lavialle, Sophie; Deligny, Christophe; Hachulla, Eric; Mouthon, Luc; Le Jeunne, Claire; Ravaud, Philippe; Le Mercier, Delphine; Romefort, Bénédicte; Villain, Elisabeth; Bonnet, Damien; Costedoat-Chalumeau, Nathalie

2017-12-01

Dilated cardiomyopathy (DCM), a well-known complication of cardiac neonatal lupus, is associated with high mortality rate. Its risk factors remain unclear. We analyzed occurrence of postnatal DCM among children with high-degree congenital heart block (CHB) and mothers with anti-SSA and/or anti-SSB antibodies. Among 187 neonates with CHB, 35 (18.8%, one missing data) had DCM and 22 (11.8%) died during a median follow-up of 7years [range: birth-36years]. On multivariate analysis, factors associated with postnatal DCM were in utero DCM (P=0.0199; HR=3.13 [95% CI: 1.20-8.16]), non-European origin (P=0.0052; HR=4.10 [95% CI: 1.81-9.28]) and pacemaker implantation (P=0.0013; HR=5.48 [95% CI: 1.94-15.47]). Postnatal DCM could be categorized in two subgroups: neonatal DCM (n=13, diagnosed at a median age of 0day [birth-4days]) and late-onset DCM (n=22, diagnosed at a median age of 15.2months [3.6months-22.8years]). Factors associated with neonatal DCM were in utero DCM, hydrops, endocardial fibroelastosis and pericardial effusion, whereas those associated with late-onset DCM were non-European origin, in utero mitral valve insufficiency, and pacemaker implantation. Fluorinated steroids showed no protective effect against late-onset DCM (P=0.27; HR=1.65 [95% CI: 0.63-4.25]). Probability of survival at 10years was 23.1% for newborns diagnosed neonatally with DCM, 53.9% for those who developed late-onset DCM, and 98.6% for those without DCM. Neonatal and late-onset DCM appear to be two different entities. None of the known risk factors associated with neonatal DCM predicted late-onset DCM. Long-term follow-up of cardiac function is warranted in all children with CHB. Copyright © 2017 Elsevier B.V. All rights reserved.

Association of IRF5 polymorphisms with activation of the interferon α pathway

PubMed Central

Rullo, Ornella J; Woo, Jennifer M P; Wu, Hui; Hoftman, Alice D C; Maranian, Paul; Brahn, Brittany A; McCurdy, Deborah; Cantor, Rita M; Tsao, Betty P

2011-01-01

Objective The genetic association of interferon regulatory factor 5 (IRF5) with systemic lupus erythematosus (SLE) susceptibility has been convincingly established. To gain understanding of the effect of IRF5 variation in individuals without SLE, a study was undertaken to examine whether such genetic variation predisposes to activation of the interferon α (IFNα) pathway. Methods Using a computer simulated approach, 14 single nucleotide polymorphisms (SNPs) and haplotypes of IRF5 were tested for association with mRNA expression levels of IRF5, IFNα and IFN-inducible genes and chemokines in lymphoblastoid cell lines (LCLs) from individuals of European (CEU), Han Chinese (CHB), Japanese (JPT) and Yoruba Nigerian (YRI) backgrounds. IFN-inducible gene expression was assessed in LCLs from children with SLE in the presence and absence of IFNα stimulation. Results The major alleles of IRF5 rs13242262 and rs2280714 were associated with increased IRF5 mRNA expression levels in the CEU, CHB+JPT and YRI samples. The minor allele of IRF5 rs10488631 was associated with increased IRF5, IFNα and IFN-inducible chemokine expression in CEU (pc=0.0005, 0.01 and 0.04, respectively). A haplotype containing these risk alleles of rs13242262, rs10488631 and rs2280714 was associated with increased IRF5, IFNα and IFN-inducible chemokine expression in CEU LCLs. In vitro studies showed specific activation of IFN-inducible genes in LCLs by IFNα. Conclusions SNPs of IRF5 in healthy individuals of a number of ethnic groups were associated with increased mRNA expression of IRF5. In European-derived individuals, an IRF5 haplotype was associated with increased IRF5, IFNα and IFN-inducible chemokine expression. Identifying individuals genetically predisposed to increased IFN-inducible gene and chemokine expression may allow early detection of risk for SLE. PMID:19854706

Harmonic analysis and FPGA implementation of SHE controlled three phase CHB 11-level inverter in MV drives using deterministic and stochastic optimization techniques.

PubMed

Vesapogu, Joshi Manohar; Peddakotla, Sujatha; Kuppa, Seetha Rama Anjaneyulu

2013-01-01

With the advancements in semiconductor technology, high power medium voltage (MV) Drives are extensively used in numerous industrial applications. Challenging technical requirements of MV Drives is to control multilevel inverter (MLI) with less Total harmonic distortion (%THD) which satisfies IEEE standard 519-1992 harmonic guidelines and less switching losses. Among all modulation control strategies for MLI, Selective harmonic elimination (SHE) technique is one of the traditionally preferred modulation control technique at fundamental switching frequency with better harmonic profile. On the other hand, the equations which are formed by SHE technique are highly non-linear in nature, may exist multiple, single or even no solution at particular modulation index (MI). However, in some MV Drive applications, it is required to operate over a range of MI. Providing analytical solutions for SHE equations during the whole range of MI from 0 to 1, has been a challenging task for researchers. In this paper, an attempt is made to solve SHE equations by using deterministic and stochastic optimization methods and comparative harmonic analysis has been carried out. An effective algorithm which minimizes %THD with less computational effort among all optimization algorithms has been presented. To validate the effectiveness of proposed MPSO technique, an experiment is carried out on a low power proto type of three phase CHB 11- level Inverter using FPGA based Xilinx's Spartan -3A DSP Controller. The experimental results proved that MPSO technique has successfully solved SHE equations over all range of MI from 0 to 1, the %THD obtained over major range of MI also satisfies IEEE 519-1992 harmonic guidelines too.

Comparison of three luminescent immunoassays for hepatitis B virus surface antigen quantification during the natural history of chronic hepatitis B virus infection.

PubMed

Cheng, Xiao-Dong; Song, Liu-Wei; Fang, Lin-Lin; Yang, Lin; Wu, Yong; Ge, Sheng-Xiang; Yuan, Quan; Zhang, Jun; Xia, Ning-Shao; Hao, Xiao-Ke

2014-11-01

Hepatitis B surface antigen (HBsAg) quantification has garnered attention because of its high predictive value in determining treatment responses. The HBsAg quantification assays, such as Architect and Elecsys, are commercially available, and more assays are in development. We aimed to compare the results of the Architect and Elecsys assays with those of a new assay, WTultra. The WTultra HBsAg assay is a sandwich chemiluminescent microplate enzyme immunoassay and provides an alternative choice which is more cost-effective and potentially applicable in developing or resource-constrained countries and areas. A total of 411 serum samples were collected from patients during various phases of chronic hepatitis B (CHB) infection. The samples were assessed using the three assays, and the results were compared and analyzed. The results for the Architect, Elecsys, and WTultra assays were well correlated according to the overall results for the samples (correlation coefficients, rArchitect versus WTultra = 0.936, rArchitect versus Elecsys = 0.952, and rWTultra versus Elecsys = 0.981) and the various infection phases (rArchitect versus WTultra ranging from 0.67 to 0.975, rArchitect versus Elecsys ranging from 0.695 to 0.982, and rWTultra versus Elecsys ranging from 0.877 to 0.99). Additionally, consistent results were observed according to genotype (genotype B: rArchitect versus WTultra = 0.976, rArchitect versus Elecsys = 0.978, and rWTultra versus Elecsys = 0.979; genotype C: rArchitect versus WTultra = 0.950, rArchitect versus Elecsys = 0.963, and rWTultra versus Elecsys = 0.981) and hepatitis B virus (HBV) DNA levels (rArchitect = 0.540, rWTultra = 0.553, and rElecsys = 0.580). In conclusion, the Elecsys and WTultra assays were well correlated with the Architect assay, irrespective of the CHB infection phase or genotype. All of these assays are reliable for HBsAg quantification. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

A burnout prediction model based around char morphology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tao Wu; Edward Lester; Michael Cloke

Several combustion models have been developed that can make predictions about coal burnout and burnout potential. Most of these kinetic models require standard parameters such as volatile content and particle size to make a burnout prediction. This article presents a new model called the char burnout (ChB) model, which also uses detailed information about char morphology in its prediction. The input data to the model is based on information derived from two different image analysis techniques. One technique generates characterization data from real char samples, and the other predicts char types based on characterization data from image analysis of coalmore » particles. The pyrolyzed chars in this study were created in a drop tube furnace operating at 1300{sup o}C, 200 ms, and 1% oxygen. Modeling results were compared with a different carbon burnout kinetic model as well as the actual burnout data from refiring the same chars in a drop tube furnace operating at 1300{sup o}C, 5% oxygen, and residence times of 200, 400, and 600 ms. A good agreement between ChB model and experimental data indicates that the inclusion of char morphology in combustion models could well improve model predictions. 38 refs., 5 figs., 6 tabs.« less

Epidemiology of Hepatocellular Carcinoma in the Asia-Pacific Region.

PubMed

Zhu, Ran Xu; Seto, Wai-Kay; Lai, Ching-Lung; Yuen, Man-Fung

2016-05-23

Hepatocellular carcinoma (HCC) is the predominant primary liver cancer in many countries and is the third most common cause of cancer-related death in the Asia-Pacific region. The incidence of HCC is higher in men and in those over 40 years old. In the Asia-Pacific region, chronic hepatitis B virus and hepatitis C virus infections are the main etiological agents; in particular, chronic hepatitis B infection (CHB) is still the major cause in all Asia-Pacific countries except for Japan. Over the past two decades, the incidence of HCC has remained stable in countries in the region except for Singapore and Hong Kong, where the incidence for both sexes is currently decreasing. Chronic hepatitis C infection (CHC) is an important cause of HCC in Japan, representing 70% of HCCs. Over the past several decades, the prevalence of CHC has been increasing in many Asia-Pacific countries, including Australia, New Zealand, and India. Despite advancements in treatment, HCC is still an important health problem because of the associated substantial mortality. An effective surveillance program could offer early diagnosis and hence better treatment options. Antiviral treatment for both CHB and CHC is effective in reducing the incidence of HCC.

Human-Pathogenic Enterocytozoon bieneusi in Captive Giant Pandas (Ailuropoda melanoleuca) in China.

PubMed

Li, Wei; Zhong, Zhijun; Song, Yuan; Gong, Chao; Deng, Lei; Cao, Yuying; Zhou, Ziyao; Cao, Xuefeng; Tian, Yinan; Li, Haozhou; Feng, Fan; Zhang, Yue; Wang, Chengdong; Li, Caiwu; Yang, Haidi; Huang, Xiangming; Fu, Hualin; Geng, Yi; Ren, Zhihua; Wu, Kongju; Peng, Guangneng

2018-04-26

Human and animal infections of Enterocytozoon bieneusi (E. bieneusi) have consistently been reported worldwide, garnering public attention; however, the molecular epidemiology of E. bieneusi in the giant panda remains limited. We surveyed captive giant pandas in China for the presence of E. bieneusi by using PCR and sequence analysis of the ribosomal internal transcribed spacer (ITS) revealing a 34.5% positive rate, with seven known genotypes (SC02, EpbC, CHB1, SC01, D, F, and Peru 6) and five novel genotypes (SC04, SC05, SC06, SC07, and SC08) identified. We similarly analyzed water samples, and E. bieneusi was detected in two samples, with genotype SC02 identified. Phylogenetic analysis revealed that CHB1 did not cluster with any recognized group, while the remaining genotypes belonged to group 1. The predominance of zoonotic group 1 genotypes indicates a public health threat that giant pandas could spread E. bieneusi to humans. The identification of E. bieneusi in water samples suggests giant pandas could contribute to water contamination. Effective control measures are therefore needed to minimize the contamination of the water and prevent a human microsporidiosis outbreak.

Diagnostic value of serum Golgi protein 73 for HBV-related primary hepatic carcinoma

PubMed Central

Gao, Guosheng; Dong, Feibo; Xu, Xiaozhen; Hu, Airong; Hu, Yaoren

2015-01-01

Background: Alpha-fetoprotein (AFP) levels are routinely used for diagnosis and monitoring of hepatic diseases, but it has a limited value. Golgi protein 73 (GP73) has been suggested as a new marker for hepatic diseases. Objective: To explore the clinical value of serum GP73 in different diseases associated with hepatitis B virus (HBV) infection. Method: Between January 2010 and August 2014, serum samples from 88 patients with chronic hepatitis B (CHB), 78 patients with HBV-related liver cirrhosis (LC), and 194 patients with HBV-related primary hepatic cancer (PHC) were collected. Serum samples from 30 healthy volunteers were used as controls. ELISA and microparticle enzyme immunoassay were used to measure serum GP73 and AFP levels. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic value of serum GP73 and AFP for PHC. Results: For the diagnosis of PHC, GP73 showed a sensitivity of 65.5% and specificity of 66.3%, while AFP levels showed sensitivity of 64.4% and specificity of 76.5%. Serial testing (both tests are positive) could increase the specificity (sensitivity of 45.9% and specificity of 85.5%) while parallel testing (any single positive test result) could increase the sensitivity (sensitivity of 84.0% and specificity of 57.2%). Serum GP73 and AFP levels were significantly different between Child-Pugh grades (P<0.001 for GP73 and P=0.044 for AFP). Significant differences in serum GP73 and AFP were found between TNM stages (all P<0.001). Conclusion: Serum GP73 had limited diagnostic value for HBV-related PHC. The combined use of serum GP73 and AFP levels improved the diagnostic efficacy. PMID:26617863

Decreased Diversity of the Oral Microbiota of Patients with Hepatitis B Virus-Induced Chronic Liver Disease: A Pilot Project

PubMed Central

Ling, Zongxin; Liu, Xia; Cheng, Yiwen; Jiang, Xiawei; Jiang, Haiyin; Wang, Yuezhu; Li, Lanjuan

2015-01-01

Increasing evidence suggests that altered gut microbiota is implicated in the pathogenesis of hepatitis B virus-induced chronic liver disease (HBV-CLD). However, the structure and composition of the oral microbiota of patients with HBV-CLD remains unclear. High-throughput pyrosequencing showed that decreased oral bacterial diversity was found in patients with HBV-CLD. The Firmicutes/Bacteroidetes ratio was increased significantly, which indicated that dysbiosis of the oral microbiota participated in the process of HBV-CLD development. However, the changing patterns of the oral microbiota in patients with HBV-induced liver cirrhosis (LC) were almost similar to patients with chronic hepatitis B (CHB). HBV infection resulted in an increase in potential H2S- and CH3SH-producing phylotypes such as Fusobacterium, Filifactor, Eubacterium, Parvimonas and Treponema, which might contribute to the increased oral malodor. These key oral-derived phylotypes might invade into the gut as opportunistic pathogens and contribute to altering the composition of the gut microbiota. This study provided important clues that dysbiosis of the oral microbiota might be involved in the development of HBV-CLD. Greater understanding of the relationships between the dysbiosis of oral microbiota and the development of HBV-CLD might facilitate the development of non-invasive differential diagnostic procedures and targeted treatments of HBV-CLD patients harbouring specific oral phylotypes. PMID:26606973

Clinical Usefulness of Measuring Red Blood Cell Distribution Width in Patients with Hepatitis B Virus-Related Acute-On-Chronic Liver Failure.

PubMed

Jin, Lei; Gao, Yufeng; Ye, Jun; Zou, Guizhou; Li, Xu

2017-09-01

The red blood cell distribution width (RDW) is increased in chronic liver disease, but its clinical significance in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is still unclear. The aim of the present study was to investigate the clinical significance of RDW in HBV-ACLF patients. The medical records of HBV-ACLF patients who were admitted to The Second Affiliated Hospital of Anhui Medical University between April 2012 and December 2015 were retrospectively reviewed. Correlations between RDW, neutrophil lymphocyte ratio (NLR), and the model for end-stage liver disease (MELD) scores were analyzed using the Spearman's approach. Multivariable stepwise logistic regression test was used to evaluate independent clinical parameters predicting 3-month mortality of HBV-ACLF patients. The association between RDW and hospitalization outcome was estimated by receiver operating curve (ROC) analysis. Patient survival was estimated by Kaplan-Meier analysis and subsequently compared by log-rank test. Sixty-two HBV-ACLF patients and sixty CHB patients were enrolled. RDW were increased in HBVACLF patients and positively correlated with the NLR as well as MELD scores. Multivariate analysis demonstrated that RDW value was an independent predictor for mortality. RDW had an area under the ROC of 0.799 in predicting 3-month mortality of HBV-ACLF patients. Patients with HBV-ACLF who had RDW > 17% showed significantly poorer survival than those who had RDW ≤ 17%. RDW values are significantly increased in patients with HBV-ACLF. Moreover, RDW values are an independent predicting factor for an in-hospital mortality in patients with HBV-ACLF.

Sediment microbial activity and its relation to environmental variables along the eastern Gulf of Finland coastline

NASA Astrophysics Data System (ADS)

Polyak, Yulia; Shigaeva, Tatyana; Gubelit, Yulia; Bakina, Ludmila; Kudryavtseva, Valentina; Polyak, Mark

2017-07-01

Sediment microbial activity and its relationship with the main environmental factors and pollutants were examined in the coastal area of the eastern Gulf of Finland, Baltic Sea. The activity of two common oxidoreductase enzymes: dehydrogenase (DA) and catalase (CA) varied significantly between 13 study sites. In the Neva Bay the highest microbial activities (DA: 2.64 mg TFF (10 g- 1) day- 1, CA: 6.29 mg H2O2 g- 1) were recorded, while in the outer estuary the minimum values of dehydrogenase and catalase were measured. DA, CA, and abundances of culturable heterotrophic bacteria (CHB) were positively correlated with each other, while biomass of green opportunistic algae was independent of both microbial activities and CHB. Enzymatic activity was found to be strongly positively correlated with sediment particle size and organic matter content, but unrelated to the other studied environmental parameters (temperature, pH, and salinity). Principal components analysis (PCA), controlling for environmental variables, supported direct effects of metal and oil contamination on sediment microbial activity. Also it had shown the similar patterns for algal biomass and metals. Our results suggest that copper and hydrocarbons are the main anthropogenic variables influencing enzyme distribution along the eastern Gulf of Finland coastline.

Genetic polymorphisms of pharmacogenomic VIP variants in the Kyrgyz population from northwest China.

PubMed

Yunus, Zulfiya; Liu, Lijun; Wang, Hong; Zhang, Le; Li, Xiaolan; Geng, Tingting; Kang, Longli; Jin, Tianbo; Chen, Chao

2013-10-15

Pharmacogenomic variant information is well known for major human populations; however, this information is less commonly studied in minorities. In the present study, we genotyped 85 very important pharmacogenetic (VIP) variants (selected from the PharmGKB database) in the Kyrgyz population and compared our data with other four major human populations including Han Chinese in Beijing, China (CHB), the Japanese in Tokyo, Japan (JPT), a northern and western Europe population (CEU), and the Yoruba in Ibadan, Nigeria (YRI). There were 13, 12 and 16 of the selected VIP variant genotype frequencies in the Kyrgyz which differed from those of the CHB, JPT and CEU, respectively (p<0.005). In the YRI, there were 32 different variants, compared to the Kyrgyz (p<0.005). Genotype frequencies of ADH1B, AHR, CYP3A5, PTGS2, VDR, and VKORC1 in the Kyrgyz differed widely from those in the four populations. Haplotype analyses also showed differences among the Kyrgyz and the other four populations. Our results complement the information provided by the database of pharmacogenomics on Kyrgyz. We provide a theoretical basis for safer drug administration and individualized treatment plans for the Kyrgyz. We also provide a template for the study of pharmacogenomics in various ethnic minority groups in China. © 2013 Elsevier B.V. All rights reserved.

Elevated liver fibrosis index FIB-4 is not reliable for HCC risk stratification in predominantly non-Asian CHB patients

PubMed Central

Demir, Münevver; Grünewald, Friederike; Lang, Sonja; Schramm, Christoph; Bowe, Andrea; Mück, Vera; Kütting, Fabian; Goeser, Tobias; Steffen, Hans-Michael

2016-01-01

Abstract We aimed to validate the liver fibrosis index FIB-4 as a model for risk stratification of hepatocellular carcinoma development in predominantly non-Asian patients with chronic hepatitis B infection seen at a tertiary referral center in Germany. We retrospectively analyzed 373 adult patients with chronic hepatitis B infection. Patient demographics, hepatitis B markers, antiviral treatment, laboratory parameters, results from liver imaging and histology were recorded. Patients were divided into 2 groups according to their FIB-4 levels and their hazard ratios for developing hepatocellular carcinoma were analyzed adjusted for age, sex, body mass index, alcohol consumption, and antiviral medication. Median follow-up was 8.7 years (range 1–21.3 years), 93% of patients were of non-Asian origin, and 64% were male. Compared with patients with a low FIB-4 (<1.25) patients with FIB-4 ≥1.25 showed a hazard ratio for incidence of hepatocellular carcinoma of 3.03 (95% confidence interval (CI): 1.24–7.41) and an adjusted hazard ratio of 1.75 (95% CI: 0.64–4.74). Notably, 68% of patients with liver cirrhosis and 68% of those who developed HCC during observation had a low FIB-4 (<1.25). We could not confirm that a FIB-4 value ≥1.25 is a reliable clinical indicator for incidence of hepatocellular carcinoma in predominantly non-Asian patients with chronic hepatitis B. Further studies in geographically and ethnically diverse populations are needed to prove its utility as a predictive tool. PMID:27661015

Elevated liver fibrosis index FIB-4 is not reliable for HCC risk stratification in predominantly non-Asian CHB patients.

PubMed

Demir, Münevver; Grünewald, Friederike; Lang, Sonja; Schramm, Christoph; Bowe, Andrea; Mück, Vera; Kütting, Fabian; Goeser, Tobias; Steffen, Hans-Michael

2016-09-01

We aimed to validate the liver fibrosis index FIB-4 as a model for risk stratification of hepatocellular carcinoma development in predominantly non-Asian patients with chronic hepatitis B infection seen at a tertiary referral center in Germany.We retrospectively analyzed 373 adult patients with chronic hepatitis B infection. Patient demographics, hepatitis B markers, antiviral treatment, laboratory parameters, results from liver imaging and histology were recorded. Patients were divided into 2 groups according to their FIB-4 levels and their hazard ratios for developing hepatocellular carcinoma were analyzed adjusted for age, sex, body mass index, alcohol consumption, and antiviral medication.Median follow-up was 8.7 years (range 1-21.3 years), 93% of patients were of non-Asian origin, and 64% were male. Compared with patients with a low FIB-4 (<1.25) patients with FIB-4 ≥1.25 showed a hazard ratio for incidence of hepatocellular carcinoma of 3.03 (95% confidence interval (CI): 1.24-7.41) and an adjusted hazard ratio of 1.75 (95% CI: 0.64-4.74). Notably, 68% of patients with liver cirrhosis and 68% of those who developed HCC during observation had a low FIB-4 (<1.25).We could not confirm that a FIB-4 value ≥1.25 is a reliable clinical indicator for incidence of hepatocellular carcinoma in predominantly non-Asian patients with chronic hepatitis B. Further studies in geographically and ethnically diverse populations are needed to prove its utility as a predictive tool.

Single-virion sequencing of lamivudine-treated HBV populations reveal population evolution dynamics and demographic history.

PubMed

Zhu, Yuan O; Aw, Pauline P K; de Sessions, Paola Florez; Hong, Shuzhen; See, Lee Xian; Hong, Lewis Z; Wilm, Andreas; Li, Chen Hao; Hue, Stephane; Lim, Seng Gee; Nagarajan, Niranjan; Burkholder, William F; Hibberd, Martin

2017-10-27

Viral populations are complex, dynamic, and fast evolving. The evolution of groups of closely related viruses in a competitive environment is termed quasispecies. To fully understand the role that quasispecies play in viral evolution, characterizing the trajectories of viral genotypes in an evolving population is the key. In particular, long-range haplotype information for thousands of individual viruses is critical; yet generating this information is non-trivial. Popular deep sequencing methods generate relatively short reads that do not preserve linkage information, while third generation sequencing methods have higher error rates that make detection of low frequency mutations a bioinformatics challenge. Here we applied BAsE-Seq, an Illumina-based single-virion sequencing technology, to eight samples from four chronic hepatitis B (CHB) patients - once before antiviral treatment and once after viral rebound due to resistance. With single-virion sequencing, we obtained 248-8796 single-virion sequences per sample, which allowed us to find evidence for both hard and soft selective sweeps. We were able to reconstruct population demographic history that was independently verified by clinically collected data. We further verified four of the samples independently through PacBio SMRT and Illumina Pooled deep sequencing. Overall, we showed that single-virion sequencing yields insight into viral evolution and population dynamics in an efficient and high throughput manner. We believe that single-virion sequencing is widely applicable to the study of viral evolution in the context of drug resistance and host adaptation, allows differentiation between soft or hard selective sweeps, and may be useful in the reconstruction of intra-host viral population demographic history.

Impact of age on the diagnostic performances and cut-offs of APRI and FIB-4 for significant fibrosis and cirrhosis in chronic hepatitis B.

PubMed

Li, Qiang; Lu, Chuan; Li, Weixia; Huang, Yuxian; Chen, Liang

2017-07-11

Assessing the diagnostic performances of APRI and FIB-4 using age as a categorical marker. 822 chronic hepatitis B (CHB) patients were included. Using METAVIR scoring system as a reference, the performances of APRI and FIB-4 were compared between patients aged≥30 and patients aged<30 years. The APRI AUROC in patients aged<30 years was lower than that in patients aged≥30 years for significant fibrosis (0.61 vs 0.70, p<0.001) and cirrhosis (0.64 vs 0.78, p<0.001). The FIB-4 AUROC in patients aged<30 years was lower than that in patients aged≥30 years for significant fibrosis (0.57 vs 0.65, p<0.001) and cirrhosis (0.63 vs 0.72, p<0.001). Using specificity≥90%, the APRI cut-off in patients aged<30 years was lower than patients aged≥30 years for significant fibrosis (1.0 vs 1.2) and cirrhosis (1.2 vs 1.5). Using sensitivity≥90%, the APRI cut-off in patients aged<30 years was also lower than patients aged≥30 years for significant fibrosis (0.2 vs 0.4) and cirrhosis (0.3 vs 0.5). Using specificity≥90%, the FIB-4 cut-off in patients aged<30 years was lower than that in patients aged≥30 years for significant fibrosis (1.2 vs 2.1) and cirrhosis (1.4 vs 2.6). Using sensitivity≥90%, the FIB-4 cut-off in patients aged<30 years was also lower than that in patients aged≥30 years for significant fibrosis (0.5 vs 0.8) and cirrhosis (0.8 vs 1.2). Evaluation of the diagnostic performances of APRI and FIB-4 should take age into consideration.

Establishing a Suitable Tactical Design Model for Clear-Hold-Build Counterinsurgency Operations

DTIC Science & Technology

2009-06-12

Vietnam capitol of Saigon. Cedar Falls was tactically designed to achieve this result through two measures . First, U.S. Army forces would separate...provide a higher force ratio for the operation. This tethering would mitigate risk for the Soldiers themselves. Because risk management is so integrated...Vietnam) BCT Brigade Combat Team BCTP Battle Command Training Program BN Battalion BSP Baghdad Security Plan CF Coalition Forces C-H-B Clear-Hold

Graph Learning for Anomaly Detection using Psychological Context GLAD-PC

DTIC Science & Technology

2015-08-03

comparison study of user behavior on Facebook and Gmail, ArXiv: 1305.6082, (11 2013): 0. doi: 10.1016/j.chb.2013.06.043 TOTAL: 1 Received Paper...Fournelle, Steve Gaffigan, Oliver Brdiczka, Jianqiang Shen, Juan Liu, Kendra E. Moore. Characterizing user behavior and information propagation on a...media data; and c) detecting unusual and anomalous behavior from on-line activities. (5) Summary of the most important results With regard to

Increasing hepatitis B viral load is associated with risk of significant liver fibrosis in HBeAg-negative but not HBeAg-positive chronic hepatitis B.

PubMed

Croagh, Catherine M N; Bell, Sally J; Slavin, John; Kong, Yu X G; Chen, Robert Y; Locarnini, Stephen; Desmond, Paul V

2010-09-01

To evaluate the association between demographical features, serum ALT and HBV DNA and the prevalence of significant fibrosis and inflammation on liver biopsy in patients with chronic hepatitis B. In this cross-sectional study of patients on St Vincent's Hospital HBV database, patients were classified into three groups on the basis of HBeAg status and HBV DNA level and the prevalence of significant (F2/3/4) fibrosis and (A2/3) inflammation in each group was established. Patients were also divided into HBeAg-positive and -negative groups and examined for the prevalence of significant fibrosis/inflammation in the strata of HBV DNA and ALT. Predictors of significant fibrosis and inflammation in HBeAg-positive and -negative patients were examined by logistic regression. Three hundred and ninety four patients (HBeAg positive=198; HBeAg negative=196) with liver biopsy were identified. Fifty-eight percent of HBeAg-negative patients with HBV DNA >25,000 IU/ml had F2/3/4 fibrosis. HBV DNA and F2/3/4 were positively correlated in HBeAg-negative patients [odds ratio (OR) 1.42, P=0.001] but inversely correlated in HBeAg-positive patients (OR 0.71, P=0.03). HBV DNA was an independent predictor of significant fibrosis in HBeAg negative (P=0.03) but not HBeAg-positive patients. In HBeAg-positive patients, age was the only predictor of significant fibrosis (P=0.001) and ALT the only predictor of significant inflammation (P=0.003). In the whole cohort there was a close positive association between inflammation and fibrosis. Increasing levels of HBV DNA are associated with increasing prevalence of significant fibrosis only in patients with HBeAg-negative CHB.

Abnormal liver function in different patients with Schistosoma japonicum.

PubMed

Ning, An; Wu, Xiaoying; Li, Hongyu; Liang, Jinyi; Gao, Zulu; Shen, Jia; Liu, Zhen; Xu, Jun; Hu, Fei; Wu, Feng; Ji, Pengyu; Wu, Zhongdao; Sun, Xi

2015-01-01

Schistosomiasis japonica, caused by Schistosoma japonicum, is still a serious public health problem in China. It is important for schistosomiasis control to prevent from infection and advanced patients. Recent years, however, the form of the prevalence of schistosomiasis japonica in China was changed these days. Paying attention to the quality of life of these patients already infected with S. japonicum becomes a new objective to schistosomiasis control program. Although most of the chronic infections with S. japonicum will finally appear as liver fibrosis symptoms, it is still unknown liver function abnormalities in patients with severe forms of schistosomiasis, and there is also no evidence whether S. japonicum infection will directly cause damage to liver cells. Thus, this study investigated 494 patients diagnosed with S. japonicum (87.7%) and 69 healthy subjects from a endemic areas belonging to Jiangxi Province of China and aimed to evaluate the liver function abnormalities in patients with severe forms of schistosomiasis and possible associations with coinfection with HBV. The results showed that the hepatic metabolism situation significantly changed in patients infected with S. japonicum; meanwhile, the abnormal rates of ALT and AST in patients with schistosomiasis were significantly higher than that in the control group, which confirmed that patients infected with S. japonicum not only had damaged liver function but also the hepatic cells were directly influenced. And the coinfection of CHB and schistosomiasis japonica can be a risk factor for more serious outcomes in patients from endemic areas. These results give us the advice that in the further treatment of patients infected with S. japonicum, especially these coinfections, we should better give the routine liver-protection treatment in advance.

Soluble ST2 Plasma Concentrations Predict Mortality in HBV-Related Acute-on-Chronic Liver Failure

PubMed Central

Mo, Zhishuo; Zhu, Jianyun; Pang, Xiuqing; Wu, Zhebin; Wang, Ke; Li, Xinhua; Xie, Dongying; Gao, Zhiliang

2015-01-01

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a rapidly progressing and frequently fatal condition. The aim of this study was to determine whether interleukin- (IL-) 33 and soluble ST2 (sST2) were associated with disease severity and mortality in HBV-ACLF. We found that plasma levels of sST2 but not IL-33 were higher in HBV-ACLF patients compared with chronic hepatitis B (CHB) patients and healthy controls. However, plasma levels of IL-33, TNF-α, IFN-γ, and IL-10 did not correlate with sST2 levels. Similarly, immunohistochemistry revealed low IL-33 expression and high ST2 expression in liver sections of patients with HBV-ACLF. Evaluation of dynamic changes of sST2 in HBV-ACLF showed that plasma sST2 levels increased over time in patients who died during the 180-day follow-up but decreased in those who survived. In addition, plasma sST2 level after week 1 correlated with disease severity, as assessed by total bilirubin, prothrombin time, and model for end-stage liver disease score. Results of Kaplan-Meier survival analysis showed that higher sST2 concentration (≥87 ng/mL) at week 3 was associated with poor survival. These findings indicate the potential usefulness of sST2 as a predictor of disease severity and in making treatment decisions for patients with HBV-ACLF. PMID:25892854

Five-year efficacy and safety of tenofovir-based salvage therapy for patients with chronic hepatitis B who previously failed LAM/ADV therapy.

PubMed

Lim, Lucy; Thompson, Alexander; Patterson, Scott; George, Jacob; Strasser, Simone; Lee, Alice; Sievert, William; Nicoll, Amanda; Desmond, Paul; Roberts, Stuart; Marion, Kaye; Bowden, Scott; Locarnini, Stephen; Angus, Peter

2017-06-01

Multidrug-resistant HBV continues to be an important clinical problem. The TDF-109 study demonstrated that TDF±LAM is an effective salvage therapy through 96 weeks for LAM-resistant patients who previously failed ADV add-on or switch therapy. We evaluated the 5-year efficacy and safety outcomes in patients receiving long-term TDF±LAM in the TDF-109 study. A total of 59 patients completed the first phase of the TDF-109 study and 54/59 were rolled over into a long-term prospective open-label study of TDF±LAM 300 mg daily. Results are reported at the end of year 5 of treatment. At year 5, 75% (45/59) had achieved viral suppression by intent-to-treat analysis. Per-protocol assessment revealed 83% (45/54) were HBV DNA undetectable. Nine patients remained HBV DNA detectable, however 8/9 had very low HBV DNA levels (<264IU/mL) and did not meet virological criteria for virological breakthrough (VBT). One patient experienced VBT, but this was in the setting of documented non-compliance. The response was independent of baseline LAM therapy or mutations conferring ADV resistance. Four patients discontinued TDF, one patient was lost to follow-up and one died from hepatocellular carcinoma. Long-term TDF treatment appears to be safe and effective in patients with prior failure of LAM and a suboptimal response to ADV therapy. These findings confirm that TDF has a high genetic barrier to resistance is active against multidrug-resistant HBV, and should be the preferred oral anti-HBV agent in CHB patients who fail treatment with LAM and ADV. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Disruptive effects of persistent organohalogen contaminants on thyroid function in white whales (Delphinapterus leucas) from Svalbard.

PubMed

Villanger, G D; Lydersen, C; Kovacs, K M; Lie, E; Skaare, J U; Jenssen, B M

2011-06-01

We analysed levels of 56 organohalogen contaminants (OHCs) including brominated flame retardants, polychlorinated biphenyls (PCBs), and organochlorine pesticides in the blubber of white (beluga) whales (Delphinapterus leucas) from Svalbard, Norway (N=12; 6 adults [5 males and 1 female] and 6 subadults [4 males and 2 females]) collected in 1996-2001. We also measured circulating levels of thyroid hormones (THs) and thyroid stimulating hormone (TSH) in the whales. The results confirm that OHC levels in these white whales are among the highest levels recorded in wildlife from Svalbard, and at the high end of the range when compared to white whales from the North American Arctic. A projection to latent structure (PLS) model (subadults and adult males grouped together) revealed that known or suspected thyroid disruptive contaminants (polybrominated diphenylether [PBDE]-28, -47, -99, -100, and -154, hexachlorobenzene [HCB], and PCB-105) were negatively correlated with circulating levels of total thyroxin (TT4), free T4 (FT4) and free triiodothyronine (FT3). Most of these negative relationships were also confirmed using partial correlations controlling for length (and thus age) of the whales. The positive correlations of TT4, FT4 and FT3 with hexabromocyclododecane (HBCD), α-hexachlorocyclohexane (α-HCH), chlorinated bornanes CHB-40 and CHB-62 revealed by the PLS model were not confirmed by partial correlations. TH levels in the present study appeared to be somewhat lower than levels measured in beluga whales from the Canadian Arctic. However, we were not able to determine if this was caused by different levels of OHCs, or differences in biological factors (e.g. age, sex, moulting status, and season) and analytical methods between the studies. Although the sample sizes were low and statistical models cannot depict the biological cause-effect relationships, this study suggests negative influences of specific OHCs, particularly PBDEs, on thyroid hormone levels in white whales. The impact this might have on individual and population health is unknown. Copyright © 2011 Elsevier B.V. All rights reserved.

Coffee-Ring-Free Quantum Dot Thin Film Using Inkjet Printing from a Mixed-Solvent System on Modified ZnO Transport Layer for Light-Emitting Devices.

PubMed

Jiang, Congbiao; Zhong, Zhiming; Liu, Baiquan; He, Zhiwei; Zou, Jianhua; Wang, Lei; Wang, Jian; Peng, JunBiao; Cao, Yong

2016-10-05

Inkjet printing has been considered an available way to achieve large size full-color RGB quantum dots LED display, and the key point is to obtain printed film with uniform and flat surface profile. In this work, mixed solvent of 20 vol % 1,2-dichlorobenzene (oDCB) with cyclohexylbenzene (CHB) was used to dissolve green quantum dots (QDs) with CdSe@ZnS/ZnS core/shell structure. Then, by inkjet printing, a flat dotlike QDs film without the coffee ring was successfully obtained on polyetherimide (PEI)-modified ZnO layer, and the printed dots array exhibited great stability and repeatability. Here, adding oDCB into CHB solutions was used to reduce surface tension, and employing ZnO nanoparticle layer with PEI-modified was used to increase the surface free energy. As a result, a small contact angle is formed, which leads to the enhancement of evaporation rate, and then the coffee ring effect was suppressed. The printed dots with flat surface profile were eventually realized. Moreover, inverted green QD-LEDs with PEI-modified ZnO film as electron transport layer (ETL) and printed green QDs film as emission layer were successfully fabricated. The QD-LEDs exhibited the maximum luminance of 12 000 cd/m 2 and the peak current efficiency of 4.5 cd/A at luminance of 1500 cd/m 2 .

Seasonal abundance and diversity of culturable heterotrophic bacteria in relation to environmental factors in the Gulf of Antalya, Eastern Mediterranean, Turkey.

PubMed

Çardak, Mine; Özgür Özbek, Elif; Kebapçioğlu, Turhan

2015-04-01

The abundance of culturable heterotropic bacteria studied on and according to depth levels and seasons in the Gulf of Antalya. Environmental factors were compared regarding culturable heterotrophic bacteria abundance and diversities of bacteria. During the study period (between August 2009 and April 2010, seasonally in the Gulf of Antalya, at six stations and six depth levels (0-20 cm, 10, 25, 50, 100, 200 m). The bacterial isolates were identified in the automated micro identification system VITEK 2 Compact 30 (Biomereux, France). The mean abundance was higher in Sts. D, E and F than Sts. A, B and C, located in the eastern part of the gulf. The mean abundance decreased as the depth level increased. The mean abundance of CHB ranged between 8.15 × 10(6) and 2.54 × 10(8) CFU ml(-1) throughout the year. Abundance of CHB differed according to the variations of biotic and abiotic factors. A total of 27 taxa of bacteria including six bacterial classes were reported in this study as the first records for the Gulf of Antalya. Six bacterial classes: Gamma Proteobacteria (46.81 %), Bacilli (27.66 %), Beta Proteobacteria (12.77 %), Alfa Proteobacteria (6.38 %), Actinobacteria (4.26 %) and Flavobacteria (2.13 %) were determined. The study resulted in increased knowledge on the composition and biochemical response of bacteria isolated from eutrophic and oligotrophic areas. 23 bacteria species belonging to 16 families were reported.

Genetic variability comparison of cultured Israeli carp (Cyprinus carpio) from Korea using microsatellites.

PubMed

Kim, Jung Eun; Goo, In Bon; Hwang, Ju-Ae; Kim, Hyeong Su; Choi, Hye-Sung; Lee, Jeong-Ho

2018-06-01

In aquaculture, cultured fish often undergo continuous cross-fertilization without any inflow of new broodstock. This lowers genetic diversity, leading to increased disease rates and decreased survival rates. To improve the mass production and easy culture of Israeli carp, it is essential to investigate the population structure and genetic diversity of these fish. However, such a survey has not yet been performed on Korean Israeli carp. In this study, we used seven microsatellite markers to analyze the genetic diversity and association of cultured Israeli carp from Korea and China. The average numbers of alleles per locus (N A ) for two Korean (KorA and KorB) and two Chinese (ChA and ChB) populations were as follows: KorA (10.42), KorB (14.43), ChA (20.57) and ChB (20.71). The expected heterozygosity (H e ) ranged from 0.672 to 0.897 and from 0.827 to 0.938 in the Korean sample and Chinese sample respectively. The genetic diversity of the Korean Israeli carp was about half that of the Chinese carp. The diversity of the Korean Israeli carp was very low, suggesting that the immunity of this population could be weak, and that diversity-recovery studies are urgently needed. Therefore, our results may therefore form the foundation for future research efforts towards genetic monitoring and selective breeding, continuous research needs to be conducted in order to recover the genetic diversity of the Korean Israeli carp.

Cloning, Expression, and Characterization of a Novel Thermophilic Monofunctional Catalase from Geobacillus sp. CHB1.

PubMed

Jia, Xianbo; Chen, Jichen; Lin, Chenqiang; Lin, Xinjian

2016-01-01

Catalases are widely used in many scientific areas. A catalase gene (Kat) from Geobacillus sp. CHB1 encoding a monofunctional catalase was cloned and recombinant expressed in Escherichia coli (E. coli), which was the first time to clone and express this type of catalase of genus Geobacillus strains as far as we know. This Kat gene was 1,467 bp in length and encoded a catalase with 488 amino acid residuals, which is only 81% similar to the previously studied Bacillus sp. catalase in terms of amino acid sequence. Recombinant catalase was highly soluble in E. coli and made up 30% of the total E. coli protein. Fermentation broth of the recombinant E. coli showed a high catalase activity level up to 35,831 U/mL which was only lower than recombinant Bacillus sp. WSHDZ-01 among the reported catalase production strains. The purified recombinant catalase had a specific activity of 40,526 U/mg and K m of 51.1 mM. The optimal reaction temperature of this recombinant enzyme was 60°C to 70°C, and it exhibited high activity over a wide range of reaction temperatures, ranging from 10°C to 90°C. The enzyme retained 94.7% of its residual activity after incubation at 60°C for 1 hour. High yield and excellent thermophilic properties are valuable features for this catalase in industrial applications.

Cloning, Expression, and Characterization of a Novel Thermophilic Monofunctional Catalase from Geobacillus sp. CHB1

PubMed Central

2016-01-01

Catalases are widely used in many scientific areas. A catalase gene (Kat) from Geobacillus sp. CHB1 encoding a monofunctional catalase was cloned and recombinant expressed in Escherichia coli (E. coli), which was the first time to clone and express this type of catalase of genus Geobacillus strains as far as we know. This Kat gene was 1,467 bp in length and encoded a catalase with 488 amino acid residuals, which is only 81% similar to the previously studied Bacillus sp. catalase in terms of amino acid sequence. Recombinant catalase was highly soluble in E. coli and made up 30% of the total E. coli protein. Fermentation broth of the recombinant E. coli showed a high catalase activity level up to 35,831 U/mL which was only lower than recombinant Bacillus sp. WSHDZ-01 among the reported catalase production strains. The purified recombinant catalase had a specific activity of 40,526 U/mg and K m of 51.1 mM. The optimal reaction temperature of this recombinant enzyme was 60°C to 70°C, and it exhibited high activity over a wide range of reaction temperatures, ranging from 10°C to 90°C. The enzyme retained 94.7% of its residual activity after incubation at 60°C for 1 hour. High yield and excellent thermophilic properties are valuable features for this catalase in industrial applications. PMID:27579320

Patient-Specific Seizure Detection in Long-Term EEG Using Signal-Derived Empirical Mode Decomposition (EMD)-based Dictionary Approach.

PubMed

Kaleem, Muhammad; Gurve, Dharmendra; Guergachi, Aziz; Krishnan, Sridhar

2018-06-25

The objective of the work described in this paper is development of a computationally efficient methodology for patient-specific automatic seizure detection in long-term multi-channel EEG recordings. Approach: A novel patient-specific seizure detection approach based on signal-derived Empirical Mode Decomposition (EMD)-based dictionary approach is proposed. For this purpose, we use an empirical framework for EMD-based dictionary creation and learning, inspired by traditional dictionary learning methods, in which the EMD-based dictionary is learned from the multi-channel EEG data being analyzed for automatic seizure detection. We present the algorithm for dictionary creation and learning, whose purpose is to learn dictionaries with a small number of atoms. Using training signals belonging to seizure and non-seizure classes, an initial dictionary, termed as the raw dictionary, is formed. The atoms of the raw dictionary are composed of intrinsic mode functions obtained after decomposition of the training signals using the empirical mode decomposition algorithm. The raw dictionary is then trained using a learning algorithm, resulting in a substantial decrease in the number of atoms in the trained dictionary. The trained dictionary is then used for automatic seizure detection, such that coefficients of orthogonal projections of test signals against the trained dictionary form the features used for classification of test signals into seizure and non-seizure classes. Thus no hand-engineered features have to be extracted from the data as in traditional seizure detection approaches. Main results: The performance of the proposed approach is validated using the CHB-MIT benchmark database, and averaged accuracy, sensitivity and specificity values of 92.9%, 94.3% and 91.5%, respectively, are obtained using support vector machine classifier and five-fold cross-validation method. These results are compared with other approaches using the same database, and the suitability of the approach for seizure detection in long-term multi-channel EEG recordings is discussed. Significance: The proposed approach describes a computationally efficient method for automatic seizure detection in long-term multi-channel EEG recordings. The method does not rely on hand-engineered features, as are required in traditional approaches. Furthermore, the approach is suitable for scenarios where the dictionary once formed and trained can be used for automatic seizure detection of newly recorded data, making the approach suitable for long-term multi-channel EEG recordings. © 2018 IOP Publishing Ltd.

Is it possible to stop nucleos(t)ide analogue treatment in chronic hepatitis B patients?

PubMed Central

Moreno-Cubero, Elia; del Arco, Robert T Sánchez; Peña-Asensio, Julia; de Villalobos, Eduardo Sanz; Míquel, Joaquín; Larrubia, Juan Ramón

2018-01-01

Chronic hepatitis B (CHB) remains a challenging global health problem, with nearly one million related deaths per year. Nucleos(t)ide analogue (NA) treatment suppresses viral replication but does not provide complete cure of the hepatitis B virus (HBV) infection. The accepted endpoint for therapy is the loss of hepatitis B surface antigen (HBsAg), but this is hardly ever achieved. Therefore, indefinite treatment is usually required. Many different studies have evaluated NA therapy discontinuation after several years of NA treatment and before HBsAg loss. The results have indicated that the majority of patients can remain off therapy, with some even reaching HBsAg seroconversion. Fortunately, this strategy has proved to be safe, but it is essential to consider the risk of liver damage and other comorbidities and to ensure a close follow-up of the candidates before considering this strategy. Unanswered questions remain, namely in which patients could this strategy be effective and what is the optimal time point at which to perform it. To solve this enigma, we should keep in mind that the outcome will ultimately depend on the equilibrium between HBV and the host’s immune system. Viral parameters that have been described as good predictors of response in HBeAg(+) cases, have proven useless in HBeAg(-) ones. Since antiviral immunity plays an essential role in the control of HBV infection, we sought to review and explain potential immunological biomarkers to predict safe NA discontinuation in both groups. PMID:29740199

The roles of BDNF, S100B, and oxidative stress in interferon-induced depression and the effect of antidepressant treatment in patients with chronic viral hepatitis: a prospective study.

PubMed

Cicek, Ismet Esra; Cicek, Erdinc; Kayhan, Fatih; Uguz, Faruk; Erayman, Ibrahim; Kurban, Sevil; Yerlikaya, F Hümeyra; Kaya, Nazmiye

2014-03-01

The aim of the study was to research the relationship between interferon (IFN) induced depression and sociodemographic characteristics, neurotrophic factors and oxidative stress. Sixty four cases, 34 with Chronic Hepatitis B (CHB) and 30 with Chronic Hepatitis C (CHC), were included in the study. The patients were assessed with Structured Clinical Interview for DSM-IV (SCID-I), Hamilton Anxiety Rating Scale (HARS) and Hamilton Depression Rating Scale (HDRS) at baseline on the 2nd and 6th weeks of treatment. S100 calcium binding protein B (S100B), brain-derived neurotrophic factor (BDNF), total antioxidant status (TAS) and total oxidative stress (TOS) levels were measured at the same visits. In total, 20 patients were diagnosed with major depression (MD) on the sixth week. A significant relationship was found between depression developed after IFN therapy and baseline HARS scores and the type of IFN-α. When the pretreatment levels of HDRS, HARS, S100B, BDNF, TAS, and TOS were compared to those after treatment on the 2nd week, there was a significant increase in HDRS and HARS levels and a significant decrease in the levels of S100B and BDNF. No significant change was determined for TAS and TOS levels. Our study suggests that the pathogenesis of IFN induced depression may involve neurotrophic factors. Copyright © 2014 Elsevier Inc. All rights reserved.

Evidence of two genetic clusters of manatees with low genetic diversity in Mexico and implications for their conservation.

PubMed

Nourisson, Coralie; Morales-Vela, Benjamín; Padilla-Saldívar, Janneth; Tucker, Kimberly Pause; Clark, Annmarie; Olivera-Gómez, Leon David; Bonde, Robert; McGuire, Peter

2011-07-01

The Antillean manatee (Trichechus manatus manatus) occupies the tropical coastal waters of the Greater Antilles and Caribbean, extending from Mexico along Central and South America to Brazil. Historically, manatees were abundant in Mexico, but hunting during the pre-Columbian period, the Spanish colonization and throughout the history of Mexico, has resulted in the significantly reduced population occupying Mexico today. The genetic structure, using microsatellites, shows the presence of two populations in Mexico: the Gulf of Mexico (GMx) and Chetumal Bay (ChB) on the Caribbean coast, with a zone of admixture in between. Both populations show low genetic diversity (GMx: N(A) = 2.69; H(E) = 0.41 and ChB: N(A) = 3.0; H(E) = 0.46). The lower genetic diversity found in the GMx, the largest manatee population in Mexico, is probably due to a combination of a founder effect, as this is the northern range of the sub-species of T. m. manatus, and a bottleneck event. The greater genetic diversity observed along the Caribbean coast, which also has the smallest estimated number of individuals, is possibly due to manatees that come from the GMx and Belize. There is evidence to support limited or unidirectional gene flow between these two important areas. The analyses presented here also suggest minimal evidence of a handful of individual migrants possibly between Florida and Mexico. To address management issues we suggest considering two distinct genetic populations in Mexico, one along the Caribbean coast and one in the riverine systems connected to the GMx.

Seasonal variations and relationships between environmental parameters and heavy metal concentrations in tissues of Crassostrea species and in its ambience from the tropical estuaries.

PubMed

Shenai-Tirodkar, Prachi; Gauns, Mangesh; Kumar, Girish; Ansari, Zakir

2018-05-15

This study aimed to evaluate the relationship between physicochemical parameters and heavy metal (Cu, Ni, Pb, and Cd) concentrations from sediment, seawater, and its accumulation in tissues of oyster species (Crassostrea madrasensis and C. gryphoides) from the three sites (Chicalim Bay (CB), Nerul Creek (NC), Chapora Bay (ChB)) along the Goa coast (India). Results showed enrichment of Cu and Ni in sediment exceeding the effect range low (ERL) level. The higher concentrations of Cu and Ni in sediments and in suspended particulate matter (SPM) from all the study sites are indicative of severe contamination of estuarine and associated habitats. Moreover, particulate Ni (at all the sites), Cu (at NC and ChB), Pb (at NC), and Cd (at CB and NC) concentrations were recorded more than its total loadings in surface sediment. Concentration of Cu and Cd in oyster tissue was several folds higher than its concentration in ambience. Further, this study showed that the levels of metal in oysters and their ambient environment were higher during the monsoon season. Hence, the consumption of oysters needs to be considered carefully with respect to the health hazards posed by the elevated levels of metal contaminants in certain seasons. The present study concludes that metals associated with the particulate matter in water column are the main source of metal accumulation in oyster. It is also suggested that concentration of metal pollutants in coastal and estuarine water bodies should be monitored regularly to ensure the acceptable limits of metal concentrations.

Evidence of two genetic clusters of manatees with low genetic diversity in Mexico and implications for their conservation

USGS Publications Warehouse

Nourisson, C.; Morales-Vela, B.; Padilla-Saldivar, J.; Tucker, K.P.; Clark, A.; Olivera-Gomez, L. D.; Bonde, R.; McGuire, P.

2011-01-01

The Antillean manatee (Trichechus manatus manatus) occupies the tropical coastal waters of the Greater Antilles and Caribbean, extending from Mexico along Central and South America to Brazil. Historically, manatees were abundant in Mexico, but hunting during the pre-Columbian period, the Spanish colonization and throughout the history of Mexico, has resulted in the significantly reduced population occupying Mexico today. The genetic structure, using microsatellites, shows the presence of two populations in Mexico: the Gulf of Mexico (GMx) and Chetumal Bay (ChB) on the Caribbean coast, with a zone of admixture in between. Both populations show low genetic diversity (GMx: NA=2.69; HE=0.41 and ChB: NA=3.0; HE=0.46). The lower genetic diversity found in the GMx, the largest manatee population in Mexico, is probably due to a combination of a founder effect, as this is the northern range of the sub-species of T. m. manatus, and a bottleneck event. The greater genetic diversity observed along the Caribbean coast, which also has the smallest estimated number of individuals, is possibly due to manatees that come from the GMx and Belize. There is evidence to support limited or unidirectional gene flow between these two important areas. The analyses presented here also suggest minimal evidence of a handful of individual migrants possibly between Florida and Mexico. To address management issues we suggest considering two distinct genetic populations in Mexico, one along the Caribbean coast and one in the riverine systems connected to the GMx. ?? 2011 Springer Science+Business Media B.V.

Evidence of two genetic clusters of manatees with low genetic diversity in Mexico and implications for their conservation

USGS Publications Warehouse

Nourisson, Coralie; Morales-Vela, Benjamin; Padilla-Saldivar, Janneth; Tucker, Kimberly Pause; Clark, Ann Marie; Olivera-Gomez, Leon David; Bonde, Robert; McGuire, Peter

2011-01-01

The Antillean manatee (Trichechus manatus manatus) occupies the tropical coastal waters of the Greater Antilles and Caribbean, extending from Mexico along Central and South America to Brazil. Historically, manatees were abundant in Mexico, but hunting during the pre-Columbian period, the Spanish colonization and throughout the history of Mexico, has resulted in the significantly reduced population occupying Mexico today. The genetic structure, using microsatellites, shows the presence of two populations in Mexico: the Gulf of Mexico (GMx) and Chetumal Bay (ChB) on the Caribbean coast, with a zone of admixture in between. Both populations show low genetic diversity (GMx: NA = 2.69; HE = 0.41 and ChB: NA = 3.0; HE = 0.46). The lower genetic diversity found in the GMx, the largest manatee population in Mexico, is probably due to a combination of a founder effect, as this is the northern range of the sub-species of T. m. manatus, and a bottleneck event. The greater genetic diversity observed along the Caribbean coast, which also has the smallest estimated number of individuals, is possibly due to manatees that come from the GMx and Belize. There is evidence to support limited or unidirectional gene flow between these two important areas. The analyses presented here also suggest minimal evidence of a handful of individual migrants possibly between Florida and Mexico. To address management issues we suggest considering two distinct genetic populations in Mexico, one along the Caribbean coast and one in the riverine systems connected to the GMx.

Formation of Fused-Ring 2′-Deoxycytidine Adducts from 1-Chloro-3-buten-2-one, an in Vitro 1,3-Butadiene Metabolite, under in Vitro Physiological Conditions

PubMed Central

Sun, Liang; Pelah, Avishay; Zhang, Dong-Ping; Zhong, Yu-Fang; An, Jing; Yu, Ying-Xin; Zhang, Xin-Yu; Elfarra, Adnan A.

2013-01-01

1-Chloro-3-buten-2-one (CBO) is a potential metabolite of 1,3-butadiene (BD), a carcinogenic air pollutant. CBO is a bifunctional alkylating agent that readily reacts with glutathione (GSH) to form mono-GSH and di-GSH adducts. Recently, CBO and its precursor 1-chloro-2-hydroxy-3-butene (CHB) were found to be cytotoxic and genotoxic in human liver cells in culture with CBO being approximately 100-fold more potent than CHB. In the present study, CBO was shown to react readily with 2′-deoxycytidine (dC) under in vitro physiological conditions (pH 7.4, 37 °C) to form four dC adducts with the CBO moieties forming fused rings with the N3 and N4 atoms of dC. The four products were structurally characterized as 2-hydroxy-2-hydroxymethyl-7-(2-deoxy-β-D-erythro-pentofuranosyl)-1,2,3,4-tetrahy dro-6-oxo-6H,7H-pyrimido[1,6-a]pyrimidin-5-ium (dC-1 and dC-2, a pair of diastereomers), 4-chloromethyl-4-hydroxy-7-(2-deoxy-β-D-erythro-pentofuranosyl)-1,2,3,4-tetrahydr o-6-oxo-6H,7H-pyrimido[1,6-a]pyrimidin-5-ium (dC-3), and 2-chloromethyl-2-hydroxy-7-(2-deoxy-β-D-erythro-pentofuranosyl)-1,2,3,4-tetrahydr o-6-oxo-6H,7H-pyrimido[1,6-a]pyrimidin-5-ium (dC-4). Interestingly, dC-1 and dC-2 were stable under our experimental conditions (pH 7.4, 37 °C, 6 h) and existed in equilibrium as indicated by HPLC analysis, whereas dC-3 and dC-4 were labile with the half-lives being 3.0 ± 0.36 and 1.7 ± 0.06 h, respectively. Decomposition of dC-4 produced both dC-1 and dC-2, whereas acid hydrolysis of dC-1/dC-2 and dC-4 in 1 M HCl at 100 °C for 30 min yielded the deribosylated adducts dC-1H/dC-2H and dC-4H, respectively. Because fused-ring dC adducts of other chemicals are mutagenic, the characterized CBO-dC adducts could be mutagenic and play a role in the cytotoxicity and genotoxicity of CBO and its precursors, CHB and BD. The CBO-dC adducts may also be used as standards to characterize CBO-DNA adducts and to develop potential biomarkers for CBO formation in vivo. PMID:24020501

Serum HBV DNA level at week 12 is superior to viral response at week 24 in predicting long-term treatment outcome of telbivudine for chronic hepatitis B patients.

PubMed

Lü, Wei; Yang, Hai-Hong; Fan, Yun-Ming; Li, Takming; Zhang, Li-Fan; Mui, Chongseong; Fan, Hong-Wei; Zhou, Bao-Tong; Liu, Zheng-Yin; Ng, Hou; Liu, Xiao-Qing

2013-06-01

Telbivudine, one of the five nucleos(t)ide antiviral drugs, was reported to be superior to lamivudine in a better biochemical, virological, and histological response for treatment-naive patients in the GLOBE trial. The aim of this study was to determine the antiviral potency, viral resistance, and the signifcance of early response for long-term telbivudine treatment. We recruited 161 patients of chronic hepatitis B (CHB) on telbivudine between January 2009 and September 2011 in Macau, China. The serum hepatitis B virus DNA levels, hepatitis B e antigen (HBeAg) seroconversion, alanine aminotransferase (ALT) normalization, and viral resistance were analyzed. The median age and follow-up duration were 48 years and 16.9 months. All patients were followed up for at least 6 months, while data were collected for 132, 120, 95, and 53 patients at 12, 24, 48, and 96 weeks respectively. The cumulative HBeAg seroconversion rate was 20.8% and only three patients (1.9%) presented with telbivudine low level resistance. The ALT normalization rates were 76.9% at 48 weeks and 77.6% at 96 weeks. Undetectable HBV DNA was achieved by 1.8%, 31.6%, 60%, and 74.1% in HBeAg positive patients and 29.3%, 60.3%, 84%, and 84.6% in HBeAg negative patients at each time point. Week 12 HBV DNA level < 1000 copies/ml (< 200 IU/ml) was a better predictor of viral suppression at 2-year follow-up (P = 0.001, OR = 27.00) than undetectable HBV DNA level at week 24 (P = 0.120, OR = 4.81). Two-year telbivudine treatment yielded high rates of viral suppression and ALT normalization. Serum HBV DNA level at week 12 is a superior predictor for long-term viral suppression.

In vivo imaging of tissue scattering parameter and cerebral hemodynamics in rat brain with a digital red-green-blue camera

NASA Astrophysics Data System (ADS)

Nishidate, Izumi; Mustari, Afrina; Kawauchi, Satoko; Sato, Shunichi; Sato, Manabu; Kokubo, Yasuaki

2017-02-01

We propose a rapid imaging method to monitor the spatial distribution of total hemoglobin concentration (CHbT), the tissue oxygen saturation, and the scattering power b in the expression of μs'=aλ-b as the scattering parameters in cerebral cortex using a digital red-green-blue camera. In the method, the RGB-values are converted into the tristimulus values in CIEXYZ color space which is compatible with the common RGB working spaces. Monte Carlo simulation (MCS) for light transport in tissue is used to specify a relation among the tristimulus XYZ-values and the concentration of oxygenated hemoglobin, that of deoxygenated hemoglobin, and the scattering power b. In the present study, we performed sequential recordings of RGB images of in vivo exposed rat brain during the cortical spreading depolarization evoked by the topical application of KCl. Changes in the total hemoglobin concentration and the tissue oxygen saturation imply the temporary change in cerebral blood flow during CSD. Decrease in the scattering power b was observed before the profound increase in the total hemoglobin concentration, which is indicative of the reversible morphological changes in brain tissue during CSD. The results in this study indicate potential of the method to evaluate the pathophysiological conditions in brain tissue with a digital red-green-blue camera.

Roles of Chondroitin Sulfate and Dermatan Sulfate in the Formation of a Lesion Scar and Axonal Regeneration after Traumatic Injury of the Mouse Brain

PubMed Central

Li, Hong-Peng; Komuta, Yukari; Kimura-Kuroda, Junko; van Kuppevelt, Toin H.

2013-01-01

Abstract Dermatan sulfate (DS) is synthesized from chondroitin sulfate (CS) by epimerization of glucuronic acid of CS to yield iduronic acid. In the present study, the role of CS and DS was examined in mice that received transection of nigrostriatal dopaminergic pathway followed by injection of glycosaminoglycan degrading enzymes into the lesion site. Two weeks after injury, fibrotic and glial scars were formed around the lesion, and transected axons did not regenerate beyond the fibrotic scar. Injection of chondroitinase ABC (ChABC), which degrades both CS and DS, completely suppressed the fibrotic scar formation, reduced the glial scar, and promoted the regeneration of dopaminergic axons. Injection of the DS-degrading enzyme chondroitinase B (ChB) also yielded similar results. By contrast, injection of chondroitinase AC (ChAC), a CS-degrading enzyme, did not suppress the fibrotic and glial scar formation, but reduced CS immunoreactivity and promoted the axonal regeneration. Addition of transforming growth factor-β1 (TGF-β1) to a co-culture of meningeal fibroblasts and cerebral astrocytes induces a fibrotic scar-like cell cluster. The effect of TGF-β1 on cluster formation was suppressed by treatment with ChABC or ChB, but not by ChAC. TGF-β1-induced cell cluster repelled neurites of neonatal cerebellar neurons, but addition of ChABC or ChAC suppressed the inhibitory property of clusters on neurite outgrowth. The present study is the first to demonstrate that DS and CS play different functions after brain injury: DS is involved in the lesion scar formation, and CS inhibits axonal regeneration. PMID:23438307

Epidemiological, clinical and laboratory features of chronic hepatitis B infection in a cohort of immigrant and Italian patients from Ferrara, Italy.

PubMed

Contini, Carlo; Badia, Lorenzo; Cultrera, Rosario; Grilli, Anastasio; De Togni, Aldo

2012-01-01

Italy has recently become a land of immigration. Two hundred and fifty thousand carriers are immigrants and chronic HBV infection is the prevalent form. Considering the elevated number of foreigners resident in our province and the potential risk of transmission to local people, we retrospectively investigated the patterns of chronic hepatitis B (CHB) in 154 patients (76 foreigners, 78 Italians) observed in our Institution, with regard to demographic and clinical/laboratory characteristics. The immigrants were younger (mean age 31 years) compared to Italians (51.5) and mainly came from East Europe. Regarding exposure to HBV, the intra-familial risk factor was most frequently observed in foreigners, compared to Italians (p = 0.03). Foreigners also showed a higher prevalence of HBeAg positive forms, HDV co-infection (7.9%) and abnormal ALT and/or HBV-DNA values, compared to Italians. HBeAg positivity was more associated with increased ALT (OR = 36.6, p = 0.001) than with elevated HBV viremia (OR = 6.5, p = 0.049); age was a protective factor (OR = 0.1; p = 0.014). No significant association was found between increased ALT and foreign nationality. The simultaneous presence of increased ALT and viremia was more frequent among foreigners, (OR = 7.6, p = 0,014) and increased with age (OR = 1.06, p = 0.013). Antiviral therapy was given in 7.8% of foreign citizens. Immigrants constitute a vulnerable population subgroup that would benefit from a more active approach regarding doctor patient relationship for early recognition of HBV and treatment programmes.

Long-term follow up of peginterferon-α-2a treatment of hepatitis B e-antigen (HBeAg) positive and HBeAg negative chronic hepatitis B patients in phase II and III studies.

PubMed

Okanoue, Takeshi; Shima, Toshihide; Hasebe, Chitomi; Karino, Yoshiyasu; Imazeki, Fumio; Kumada, Takashi; Minami, Masahito; Imai, Yasuharu; Yoshihara, Harumasa; Mita, Eiji; Morikawa, Teruhisa; Nishiguchi, Shuhei; Kawakami, Yoshiiku; Nomura, Hideyuki; Sakisaka, Shotaro; Kurosaki, Masayuki; Yatsuhashi, Hiroshi; Oketani, Makoto; Kohno, Hiroshi; Masumoto, Akihide; Ikeda, Kenji; Kumada, Hiromitsu

2016-09-01

We analyzed the 5-year post-treatment response to peginterferon α-2a (PEG IFN-α-2a) in hepatitis B e-antigen (HBeAg) positive and negative chronic hepatitis B patients. One hundred and thirty-seven chronic hepatitis B (CHB) patients receiving 90 μg or 180 μg of PEG IFN-α-2a for 24 or 48 weeks in phase II or III studies were enrolled in the study, including 100 HBeAg positive patients and 37 HBeAg negative patients; 121 patients (88.4%) had genotype C. Of the 137 patients, 94 received additional antiviral therapy because of viral reactivation and 43 did not receive any additional antiviral treatment during follow up. Five years upon PEG IFN-α-2a treatment, 32 patients (23.4%) who did not receive any additional antiviral agent after PEG IFN-α-2a therapy achieved a good response (normal serum alanine aminotransferase, low-level hepatitis B virus [HBV] DNA, and HBeAg negativity). Female sex and low HBV DNA levels by the end of treatment were independently associated with favorable 5-year post-treatment responses. Forty-eight-week administration of PEG IFN-α-2a showed a better response (26.4%) than 24-week administration (18.0%). Six patients (4.3%), four males and two females, cleared hepatitis B surface antigen (HBsAg) during the 5-year follow-up period. The 48-week administration of PEG IFN-α-2a achieved better biochemical and virological responses than the 24-week administration, particularly in younger females. The 5-year post-treatment response rate was 23.4%; however, more than two-thirds of the patients received additional antiviral therapy because of viral reactivation after PEG IFN-α-2a treatment. HBsAg clearance was noted in six patients (4.3%). PEG IFN-α-2a is effective in young female patients. © 2016 The Japan Society of Hepatology.

A short history of medical degrees in the University of Aberdeen.

PubMed

Rix, K J

1990-08-01

Aberdeen University was the first university in Great Britain to recognise the teaching of medicine by the creation of a teaching post, that of "mediciner." It was first occupied by James Cumyne, the burgh medical officer. The first medical degree granted by the university was doctus in medicina--learned in medicine. The degree was first awarded in 1630. The first examination paper for the M.D. was set in 1787 at the time of proposal to unit King's and Marischal Colleges and following criticism of the sale of degrees in medicine and midwifery "for ready money." The present degrees of M.B., ChB. were introduced in 1895.

Prognostic factors in patients with hepatitis B virus-related hepatocellular carcinoma undergoing nucleoside analog antiviral therapy

PubMed Central

NISHIKAWA, HIROKI; NISHIJIMA, NORIHIRO; ARIMOTO, AKIRA; INUZUKA, TADASHI; KITA, RYUICHI; KIMURA, TORU; OSAKI, YUKIO

2013-01-01

In the present era of entecavir (ETV) use for chronic hepatitis B (CHB), the prognostic factors in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain unclear. The aims of the present study were to investigate the prognostic factors in patients with HBV-related HCC treated with ETV who underwent curative therapy. A total of 74 HBV-related HCC patients treated with ETV who underwent curative therapy were analyzed. Predictive factors associated with overall survival (OS) and recurrence-free survival (RFS) were examined using univariate and multivariate analysis. Our study population included 49 males and 25 females with a median age of 62 years. The median observation period was 3.4 years (range, 0.2–11.5 years). The 1-, 3- and 5-year cumulative OS rates were 100, 89.8 and 89.8%, respectively. The corresponding RFS rates were 82.8, 52.1 and 25.6%, respectively. In this study, 73 patients (98.6%) achieved an HBV DNA level of <400 copies/ml during the follow-up period. No viral breakthrough hepatitis, as defined by 1 log increase from nadir, was observed during ETV therapy. According to multivariate analysis, only hepatitis B e antigen (HBeAg) positivity was significantly associated with OS [hazard ratio (HR), 0.058; 95% confidence interval (CI), 0.005–0.645; P=0.020)], whereas HCC stage (HR, 0.359; 95% CI, 0.150–0.859; P=0.021), HBeAg positivity (HR, 0.202; 95% CI, 0.088–0.463; P<0.001) and γ-glutamyl transpeptidase ≥50 IU/l (HR, 0.340; 95% CI, 0.152–0.760; P=0.009) were significant predictive factors linked to RFS. In conclusion, HBeAg positivity was significantly associated with OS and RFS in HBV-related HCC patients treated with ETV who underwent curative therapy. In such patients, close observation is required, even after curative therapy for HCC. PMID:24179497

Incidence and predictors of permanent pacemaker implantation following treatment with the repositionable Lotus™ transcatheter aortic valve.

PubMed

Zaman, Sarah; McCormick, Liam; Gooley, Robert; Rashid, Hashrul; Ramkumar, Satish; Jackson, Damon; Hui, Samuel; Meredith, Ian T

2017-07-01

To determine the incidence and predictors of permanent pacemaker (PPM) requirement following transcatheter aortic valve replacement (TAVR) with the mechanically expanded Lotus TM Valve System (Boston Scientific). Pacemaker implantation is the most common complication following TAVR. Predictors of pacing following TAVR with the Lotus valve have not been systematically assessed. Consecutive patients with severe aortic stenosis who underwent Lotus valve implantation were prospectively recruited at a single-centre. Patients with a pre-existing PPM were excluded. Baseline ECG, echocardiographic and multiple detector computed tomography as well as procedural telemetry and depth of implantation were independently analyzed in a blinded manner. The primary endpoint was 30-day incidence of pacemaker requirement (PPM implantation or death while pacing-dependent). Multivariate analysis was performed to identify independent predictors of the primary endpoint. A total of 104 consecutive patients underwent TAVR with the Lotus valve with 9/104 (9%) with a pre-existing PPM excluded. New or worsened procedural LBBB occurred in 78%. Thirty-day incidence of the primary pacing endpoint was 28%. The most common indication for PPM implantation was complete heart block (CHB) (69%). Independent predictors of the primary endpoint included pre-existing RBBB (hazard ratio [HR] 2.8, 95% CI 1.1-7.0; P = 0.032) and depth of implantation below the noncoronary cusp (NCC) (HR 2.4, 95% CI 1.0-5.7; P = 0.045). Almost a third of Lotus valve recipients require pacemaker implantation within 30 days. The presence of pre-existing RBBB and the depth of prosthesis implantation below the NCC were significant pacing predictors. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Higher baseline viral diversity correlates with lower HBsAg decline following PEGylated interferon-alpha therapy in patients with HBeAg-positive chronic hepatitis B.

PubMed

Li, Hu; Zhang, Li; Ren, Hong; Hu, Peng

2018-01-01

Viral diversity seems to predict treatment outcomes in certain viral infections. The aim of this study was to evaluate the association between baseline intra-patient viral diversity and hepatitis B surface antigen (HBsAg) decline following PEGylated interferon-alpha (Peg-IFN-α) therapy. Twenty-six HBeAg-positive patients who were treated with Peg-IFN-α were enrolled. Nested polymerase chain reaction (PCR), cloning, and sequencing of the hepatitis B virus S gene were performed on baseline samples, and normalized Shannon entropy (Sn) was calculated as a measure of small hepatitis B surface protein (SHBs) diversity. Multiple regression analysis was used to estimate the association between baseline Sn and HBsAg decline. Of the 26 patients enrolled in the study, 65.4% were male and 61.5% were infected with hepatitis B virus genotype B. The median HBsAg level at baseline was 4.5 log 10 IU/mL (interquartile range: 4.1-4.9) and declined to 3.0 log 10 IU/mL (interquartile range: 1.7-3.9) after 48 weeks of Peg-IFN-α treatment. In models adjusted for baseline alanine aminotransferase (ALT) and HBsAg, the adjusted coefficients (95% CI) for ΔHBsAg and relative percentage HBsAg decrease were -1.3 (-2.5, -0.2) log 10 IU/mL for higher SHBs diversity (Sn≥0.58) patients and -26.4% (-50.2%, -2.5%) for lower diversity (Sn<0.58) patients. Further analysis showed that the "a" determinant upstream flanking region and the first loop of the "a" determinant (nucleotides 341-359, 371-389, and 381-399) were the main sources of higher SHBs diversity. Baseline intra-patient SHBs diversity was inverse to HBsAg decline in HBeAg-positive chronic hepatitis B (CHB) patients receiving Peg-IFN-α monotherapy. Also, more sequence variations within the "a" determinant upstream flanking region and the first loop of the "a" determinant were the main sources of the higher SHBs diversity.

More doctors and dentists are needed in South Africa.

PubMed

Strachan, B; Zabow, T; van der Spuy, Z

2011-07-25

BACKGROUND. An aim of the Colleges of Medicine of South Africa (CMSA) project 'Strengthening Academic Medicine and Specialist Training' was to research the number and needs of specialists and subspecialists within South Africa. METHODS. Data were collected from several sources: Deans of the 8 Faculties of Health Sciences and the Presidents of the 27 constituent Colleges of the CMSA completed a survey; and the HPCSA's Register of Approved Registrar Posts for Faculties of Health Sciences was examined and the results tabulated. RESULTS. South Africa compares unfavourably with middle-income countries on the ratios of medical and dental professionals; many districts have limited access to specialists and subspecialists. The unacceptable ratio of doctors, dentists and other health professionals per capita needs to be remedied, given South Africa's impressive reputation for its output of health professionals, including the areas of medical training, clinical practice and clinical research. The existing output from South Africa's 8 medical schools of MB ChB and specialist graduates is not being absorbed into the public health system, and neither are other health professionals. CONCLUSION. Dynamic leadership and policy interventions are required to advocate and finance the planned increase of medical, dental and other health professionals in South Africa.

Novel haemoglobin-derived antimicrobial peptides from chicken (Gallus gallus) blood: purification, structural aspects and biological activity.

PubMed

Vasilchenko, A S; Rogozhin, E A; Vasilchenko, A V; Kartashova, O L; Sycheva, M V

2016-12-01

To purify and characterize antimicrobial peptides derived from the acid extract of Gallus gallus blood cells. Two polypeptides (i.e. CHb-1 and CHb-2) with antibacterial activity were detected in the acidic extract of blood cells from chicken (G. gallus). The isolated peptides that possessed a potent antibacterial activity were purified using a two-step chromatography procedure that involved solid-phase extraction of a total protein/peptide extract followed by thin fractionation by reversed-phase high performance liquid chromatography (RP-HPLC). The molecular masses of the purified peptides were similar and were 4824·4 and 4825·2 Da, which have been measured by matrix-assisted laser desorption/ionization mass spectrometry (MALDI TOF MS). Their amino acid sequences were determined by Edman degradation and showed that the peptides were fully identical to the two fragments of G. gallus α-haemoglobin localized into different subunits (A and D respectively). The peptides were active in micromolar concentrations against Gram-negative Escherichia coli K12 TG1. Using the 1-N-phenylnaphthylamine, the FITC-dextran labelled probes and the live/dead staining allowed to show the hemocidin mode of action and estimate the pore size. In this study, for the first time, α-haemoglobin from chicken (G. gallus) has been investigated as a donor of the two high homologous native peptide fragments that possess potent antibacterial activity in vitro. These are membrane-active peptides and their mechanism of action against E. coli involves a toroidal pore formation. The obtained results expand the perception of the role of haemoglobin in a living system, describing it as a source of multifunction substances. Additionally, the data presented in this paper may contribute to the development of new, cost-effective, antimicrobial agents. © 2016 The Society for Applied Microbiology.

Assessment of Coriolopsis gallica-treated olive mill wastewater phytotoxicity on tomato plants.

PubMed

Daâssi, Dalel; Sellami, Sahar; Frikha, Fakher; Rodriguez-Couto, Susana; Nasri, Moncef; Mechichi, Tahar

2016-08-01

The aim of the present study was to evaluate the phytotoxicity of olive mill wastewater (OMW) after being treated by the white-rot fungus Coriolopsis gallica. For this, the effect of irrigation with treated OMW (TOMW) and untreated OMW (UOMW) on tomato plants (Lycopersicon esculentum) for 3 weeks was studied. The control plants were irrigated with distilled water. Agronomic tests were performed in pot experiments in a greenhouse using the randomized complete block (RCB) experimental design. The relative leaf height (RLH), as a morphological parameter, and the content of total phenols in the roots and total chlorophyll [Cha + Chb] and reducing sugars in the leaves, as physiological parameters, were selected as responses of the experimental design. The results obtained showed that [Cha + Chb] in the leaves of tomato growth under TOMW was enhanced by 36.3 and 19.4 % compared to the plant growth under UOMW and to the controls, respectively. Also, reducing sugar concentrations were closed to those of the control plants, ranging from 0.424 to 0.678 g/L for the different dilutions tested. However, the plants irrigated with UOMW showed lower reducing sugar concentrations ranging from 0.042 to 0.297g/L. The optimum RLH (0.537) was observed in the plants irrigated with TOMW diluted at (1:4), this value being higher than that observed in the controls (0.438). Our study proved that the irrigation with TOMW significantly improved tomato growth and photosynthesis activity over those irrigated with UOMW. Optimization of TOMW as a fertilizer was obtained for a dilution of 1:4. From the obtained results, it can be concluded that OMW treated by C. gallica holds potential to be used as a fertilizer for tomato plants. Graphical Abstract ᅟ Please provide a caption for the graphical abstract.The graphical abstract is improved and sent as attachment Please replace it.

[A comparative study on characterizations of genetic recombination hotspots in PPARG gene between Kirgiz and Uyghur ethnic groups in Xinjiang].

PubMed

Zohra, Rozi; Song, M S; Iliham, Nizam; Dolikun, Mamatyusupu

2016-08-16

To investigate the characterizations of genetic recombination hotspots and linkage disequilibrium (LD) patterns in peroxisome proliferative activated receptor gamma (PPARG) gene in Kirgiz and Uyghur ethnic groups. Blood samples were collected from 100 Kirgiz (50 healthy controls and 50 patients with type 2 diabetes mellitus) residents in Halajun County, Artux City, Kizilsu Kirgiz Autonomous Prefecture, Xinjiang in August 2013, and 50 healthy Uyghur residents in Hotan Prefecture of Xinjiang Uygur Autonomous Region in May 2012.Thirty-one tagSNPs in PPARG gene were genotyped using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS) method.The recombination hotspots and LD patterns within the PPARG gene were estimated by analyzing the SNP genotying data using the Hotspot Fisher program and Haploview software, respectively. Eighteen tagSNPs (rs1151999, rs1175540, rs1875796, rs1899951, rs2292101, rs2921190, rs2938397, rs2959272, rs2959273, rs2972162, rs3856806, rs4135247, rs4135275, rs709151, rs4135354, rs6805419, rs17036700 and rs4135304) were same with relatively higher recombination rates between the patients with type 2 diabetes mellitus (T2DM) and healthy controls of Kirgiz ethnic group, and healthy controls of Uyghur ethnic group.Five haplotype blocks with LD coefficient D' value of 1, indicating no genetic recombination occurred within the region, were observed in the healthy controls of Kirgiz ethnic groups, whereas five haplotype blocks with LD coefficient D' value less than 1 were observed in the Kirgiz patients with T2DM, indicating historical recombination events occurred within the region.Four haplotype blocks with LD coefficient D' value of 1 were observed in the Uyghur healthy controls, indicating no genetic recombination occurred within the region.There were significantly different recombination hotspot profiles between the Kirgiz, Uyghur, Utah residents with Northern and Western European ancestry (CEU), Yoruban in Ibadan, Nigeria (YRI) and Han Chinese in Beijing (CHB) and Japanese in Tokyo (JPT) samples.There are six recombination hotspots in the HapMap profile of genetic recombination.The last 5 SNPs within the PPARG gene were shown with lower recombination rates in the Kirgiz, whereas no recombination hotspot was found in the Uyghur. Variable recombination rates may be present in certain chromosome region between patients and healthy controls within the same or between the different ethnic groups.There may be presence of recombination hotspots of ethnic specificity and with variable recombination rates.

The role of Compensatory Health Beliefs in eating behavior change: A mixed method study.

PubMed

Amrein, Melanie A; Rackow, Pamela; Inauen, Jennifer; Radtke, Theda; Scholz, Urte

2017-09-01

Compensatory Health Beliefs (CHBs), defined as beliefs that an unhealthy behavior can be compensated for by engaging in another healthy behavior, are assumed to hinder health behavior change. The aim of the present study was to investigate the role of CHBs for two distinct eating behaviors (increased fruit and vegetable consumption and eating fewer unhealthy snacks) with a mixed method approach. Participants (N = 232, mean age = 27.3 years, 76.3% women) were randomly assigned to a fruit and vegetable or an unhealthy snack condition. For the quantitative approach, path models were fitted to analyze the role of CHBs within a social-cognitive theory of health behavior change, the Health Action Process Approach (HAPA). With a content analysis, the qualitative approach investigated the occurrence of CHBs in smartphone chat groups when pursuing an eating goal. Both analyses were conducted for each eating behavior separately. Path models showed that CHBs added predictive value for intention, but not behavior over and above HAPA variables only in the unhealthy snack condition. CHBs were significantly negatively associated with intention and action planning. Content analysis revealed that people generated only a few CHB messages. However, CHBs were more likely to be present and were also more diverse in the unhealthy snack condition compared to the fruit and vegetable condition. Based on a mixed method approach, this study suggests that CHBs play a more important role for eating unhealthy snacks than for fruit and vegetable consumption. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inhibitory Phenotype of HBV-Specific CD4+ T-Cells Is Characterized by High PD-1 Expression but Absent Coregulation of Multiple Inhibitory Molecules

PubMed Central

Kurktschiev, Peter; Schraut, Winfried; Zachoval, Reinhart; Wendtner, Clemens; Wächtler, Martin; Spannagl, Michael; Denk, Gerald; Ulsenheimer, Axel; Bengsch, Bertram; Pircher, Hanspeter; Diepolder, Helmut M.; Grüner, Norbert H.; Jung, Maria-Christina

2014-01-01

Background T-cell exhaustion seems to play a critical role in CD8+ T-cell dysfunction during chronic viral infections. However, up to now little is known about the mechanisms underlying CD4+ T-cell dysfunction during chronic hepatitis B virus (CHB) infection and the role of inhibitory molecules such as programmed death 1 (PD-1) for CD4+ T-cell failure. Methods The expression of multiple inhibitory molecules such as PD-1, CTLA-4, TIM-3, CD244, KLRG1 and markers defining the grade of T-cell differentiation as CCR7, CD45RA, CD57 and CD127 were analyzed on virus-specific CD4+ T-cells from peripheral blood using a newly established DRB1*01-restricted MHC class II Tetramer. Effects of in vitro PD-L1/2 blockade were defined by investigating changes in CD4+ T-cell proliferation and cytokine production. Results CD4+ T-cell responses during chronic HBV infection was characterized by reduced Tetramer+CD4+ T-cell frequencies, effector memory phenotype, sustained PD-1 but low levels of CTLA-4, TIM-3, KLRG1 and CD244 expression. PD-1 blockade revealed individualized patterns of in vitro responsiveness with partly increased IFN-γ, IL-2 and TNF-α secretion as well as enhanced CD4+ T-cell expansion almost in treated patients with viral control. Conclusion HBV-specific CD4+ T-cells are reliably detectable during different courses of HBV infection by MHC class II Tetramer technology. CD4+ T-cell dysfunction during chronic HBV is basically linked to strong PD-1 upregulation but absent coregulation of multiple inhibitory receptors. PD-L1/2 neutralization partly leads to enhanced CD4+ T-cell functionality with heterogeneous patterns of CD4+ T-cell rejunivation. PMID:25144233

Feasibility and Pilot Study of the Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) Project

PubMed Central

Sun, Lena S.; Li, Guohua; DiMaggio, Charles J.; Byrne, Mary W.; Ing, Caleb; Miller, Tonya LK; Bellinger, David C.; Han, Sena; McGowan, Francis X.

2012-01-01

Background Animal studies have documented that exposure of the developing brain to commonly used anesthetic agents induce neurotoxicity and late abnormal neurobehavioral functions as adults. Results from clinical studies have all been performed using existing datasets, and produced inconsistent results. To provide more definitive evidence to address the clinical relevance of anesthetic neurotoxicity in children, an interdisciplinary team of investigators designed and developed the Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) project. We present pilot study results in 28 sibling pairs recruited and tested at Columbia University Medical Center (CUMC) and Children’s Hospital of Boston (CHB) for the PANDA project. Methods The PANDA project uses an ambi-directional cohort design. We performed prospective neuropsychological assessment in 28 exposed-unexposed sibling pairs ages 6–11 years old. The exposed siblings were ASA 1 or 2 and had received a single episode of anesthesia for inguinal hernia repair prior to age 36 months and the unexposed siblings had no anesthesia before age 36 months. All sibling pairs were English speaking and were 36 weeks gestational age or greater. Each sibling pair underwent direct testing using WASI and NEPSY II, and the parents completed questionnaires related to behavior using CBCL and Conners’ rating. Data are presented as means ± SD. We conducted descriptive analyses of demographic data. We compared exposed and unexposed sibling groups on WASI and NEPSY II, and total and T-scores from CBCL and Conners’ as continuous data by paired t test between. A P< 0.05 was considered significant. Results Following IRB approval for the study at both CUMC and CHB, the full PANDA study protocol was implemented to perform a pilot feasibility study. Our success rate was 96.7% in obtaining detailed medical and anesthesia records in our historical cohort. Scores for verbal IQ (Exposed=106.1±16.3,Unexposed=109.2±17.9), performance IQ (Exposed=109.1±16.0, Unexposed=113.9±15.9) and full IQ (Exposed=108.2±14.0, Unexposed=112.8±16.8) were comparable between siblings. There were no differences between the two groups in T scores for any of the NEPSY II sub-domains, CBCL or Conners’. An abstraction protocol with web-based electronic data capture forms also was developed in conjunction with the International Center for Health Outcomes and Innovation Research (InCHOIR). Conclusions The pilot study provided useful information for feasibility to recruit the sample size and to obtain relevant clinical data. For the final study protocol, both the neuropsychological battery and the age range for testing were revised. Our results confirmed the feasibility of our study approach, and yielded pilot data from neuropsychological testing. PMID:23076226

Telbivudine plus tenofovir in combination therapy in patients with chronic hepatitis B infection--an Indian experience.

PubMed

Panda, Chittaranjan

2013-11-01

To investigate the efficacy and safety ofTelbivudine +Tenofovir combination therapy in chronic hepatitis B patients, over a period of 52 weeks, in real life clinical settings. HBeAg-positive and HBeAg-negative adult CHB patients, with hepatitis B virus (HBV) DNA > 4 log10 copies/ml and ALT 1.2 times above upper limit of normal (> 30 IU/L) were started on a combination of Telbivudine 600 mg + Tenofovir 300 mg in a real life clinical setting. The reduction in serum HBV DNA levels from baseline was evaluated at Week 24 and 52. The HBV DNA was measured using the PCR test with a lower limit of detection of 100 IU/ml 21 (2 female/19 male) patients, with mean (SD) age of 46.2 (13.2), were prescribed this regimen. 70% of them were HBeAg negative at baseline. Data of 11 out of 21 patients was available at week 52. The mean HBA-DNA reduction from baseline to week 24 (n = 15) was 2.6 log10 copies/mL (p = .000) and 4.0 log10 copies/mL (p = .001) at week 52 (n = 11). By the end of study visit at week 52, 10 out of 11 patients had achieved the HBV-DNA levels of < 100 lu/ml. The mean ALT levels came down by 101.4 IU/L (p = .005) at week 24 (n = 15) and by 104.6 IU/L at week 52 (n = 11). 7 patients achieved ALT normalisation (ALT < 40 IU/L) at week 24, with additional 4 achieving the goals at week 52. Combination therapy was well tolerated, with no safety related concerns. No cases of virological breakthrough or primary treatment failure were observed. Being a real life setting, there were certain limitations: Out of 10 patients whose data was not available at 52 weeks, 5 patients were lost to follow-up; another 2 coming from far off remote areas were unable to report for follow-up every 3 months. 1 patient who was on chemotherapy expired due to progression of the malignancy, another patient with decompensated liver disease expired due to disease progression. Yet another patient was a pregnant lady on therapy who stopped treatment post partum to breast feed the baby. Chronic hepatitis B patients treated with Telbivudine + Tenofovir combination exhibited significant virologic and biochemical responses, over the period of 1 year. However, the mean decline in HBV DNA over 1 year with combination therapy was not higher than that seen with monotherapy.

High-throughput matrix-assisted laser desorption ionization-time of flight mass spectrometry as an alternative approach to monitoring drug resistance of hepatitis B virus.

PubMed

Rybicka, Magda; Stalke, Piotr; Dreczewski, Marcin; Smiatacz, Tomasz; Bielawski, Krzysztof Piotr

2014-01-01

Long-term antiviral therapy of chronic hepatitis B virus (HBV) infection can lead to the selection of drug-resistant HBV variants and treatment failure. Moreover, these HBV strains are possibly present in treatment-naive patients. Currently available assays for the detection of HBV drug resistance can identify mutants that constitute ≥5% of the viral population. Furthermore, drug-resistant HBV variants can be detected when a viral load is >10(4) copies/ml (1,718 IU/ml). The aim of this study was to compare matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and multitemperature single-strand conformation polymorphism (MSSCP) with commercially available assays for the detection of drug-resistant HBV strains. HBV DNA was extracted from 87 serum samples acquired from 45 chronic hepatitis B (CHB) patients. The 37 selected HBV variants were analyzed in 4 separate primer extension reactions on the MALDI-TOF MS. Moreover, MSSCP for identifying drug-resistant HBV YMDD variants was developed and turned out to be more sensitive than INNOLiPA HBV DR and direct sequencing. MALDI-TOF MS had the capability to detect mutant strains within a mixed viral population occurring with an allelic frequency of approximately 1% (with a specific value of ≥10(2) copies/ml, also expressed as ≥17.18 IU/ml). In our study, MSSCP detected 98% of the HBV YMDD variants among strains detected by the MALDI-TOF MS assay. The routine tests revealed results of 40% and 11%, respectively, for INNOLiPA and direct sequencing. The commonly available HBV tests are less sensitive than MALDI-TOF MS in the detection of HBV-resistant variants, including quasispecies.

Identification of Susceptible Loci and Enriched Pathways for Bipolar II Disorder Using Genome-Wide Association Studies.

PubMed

Kao, Chung-Feng; Chen, Hui-Wen; Chen, Hsi-Chung; Yang, Jenn-Hwai; Huang, Ming-Chyi; Chiu, Yi-Hang; Lin, Shih-Ku; Lee, Ya-Chin; Liu, Chih-Min; Chuang, Li-Chung; Chen, Chien-Hsiun; Wu, Jer-Yuarn; Lu, Ru-Band; Kuo, Po-Hsiu

2016-12-01

This study aimed to identify susceptible loci and enriched pathways for bipolar disorder subtype II. We conducted a genome-wide association scan in discovery samples with 189 bipolar disorder subtype II patients and 1773 controls, and replication samples with 283 bipolar disorder subtype II patients and 500 controls in a Taiwanese Han population using Affymetrix Axiom Genome-Wide CHB1 Array. We performed single-marker and gene-based association analyses, as well as calculated polygeneic risk scores for bipolar disorder subtype II. Pathway enrichment analyses were employed to reveal significant biological pathways. Seven markers were found to be associated with bipolar disorder subtype II in meta-analysis combining both discovery and replication samples (P<5.0×10 -6 ), including markers in or close to MYO16, HSP90AB3P, noncoding gene LOC100507632, and markers in chromosomes 4 and 10. A novel locus, ETF1, was associated with bipolar disorder subtype II (P<6.0×10 -3 ) in gene-based association tests. Results of risk evaluation demonstrated that higher genetic risk scores were able to distinguish bipolar disorder subtype II patients from healthy controls in both discovery (P=3.9×10 -4 ~1.0×10 -3 ) and replication samples (2.8×10 -4 ~1.7×10 -3 ). Genetic variance explained by chip markers for bipolar disorder subtype II was substantial in the discovery (55.1%) and replication (60.5%) samples. Moreover, pathways related to neurodevelopmental function, signal transduction, neuronal system, and cell adhesion molecules were significantly associated with bipolar disorder subtype II. We reported novel susceptible loci for pure bipolar subtype II disorder that is less addressed in the literature. Future studies are needed to confirm the roles of these loci for bipolar disorder subtype II. © The Author 2016. Published by Oxford University Press on behalf of CINP.

HBsAg plasma level kinetics: a new role for an old marker as a therapy response predictor in vertically infected children on combination therapy.

PubMed

Carey, I; Bruce, M; Horner, M; Zen, Y; D'Antiga, L; Bansal, S; Vergani, D; Mieli-Vergani, G

2015-04-01

We aimed to investigate the ability of HBsAg plasma level kinetics to predict therapy response by studying 23 children with infancy-acquired chronic hepatitis B (CHB) during combination sequential therapy with lead-in lamivudine (LAM) and add-on interferon-α (IFN-α) [5 responders (R = anti-HBs seroconversion) and 18 nonresponders (NR)] and to assess their relationship with pretreatment intrahepatic HBV-DNA and cccDNA and HBsAg and HBcAg liver expression. Plasma HBsAg levels were measured in samples before (treatment week 0 = TW0), during (TW9, TW28, TW52) and after (follow-up week = FUW24) therapy by Abbott ARCHITECT(®) assay [log10 IU/mL]. Baseline liver HBV-DNA and cccDNA were quantified by real-time TaqMan PCR [log10 copies/ng genomic DNA]. HBsAg and HBcAg liver expression was evaluated by immunostaining of formalin-fixed, paraffin-embedded specimens [number of positive cells/1000 hepatocytes]. All results are presented as medians. Plasma: at baseline, on-treatment and during follow-up, HBsAg levels were lower in R than NR (TW0: 4.36 vs 4.75;TW28: 2.44 vs 4.35;TW52: 0 vs 4.08 and FUW24: 0.17 vs 4.35, all P < 0.05). Liver: baseline HBV-DNA (3.82 vs 4.71, P = 0.16) and cccDNA (1.98 vs 2.26, P = 0.18) tended to be lower in R than NR, HBsAg expression was lower in R than NR (0.5 vs 4.7, P = 0.03), and HBcAg expression was similar between R and NR. There were positive correlations between plasma HBsAg levels and liver HBV-DNA (r = 0.44, P = 0.04), cccDNA (r = 0.41, P = 0.04) and HBsAg liver expression (r = 0.38, P = 0.05). Lower baseline HBsAg plasma levels, lower HBsAg expression in liver and on-treatment decline of plasma HBsAg levels heralds HBsAg clearance and response to treatment in tolerant children with CHB. © 2014 John Wiley & Sons Ltd.

Effect of in vivo jet fuel exposure on subsequent in vitro dermal absorption of individual aromatic and aliphatic hydrocarbon fuel constituents.

PubMed

Muhammad, F; Monteiro-Riviere, N A; Baynes, R E; Riviere, J E

2005-05-14

The percutaneous absorption of topically applied jet fuel hydrocarbons (HC) through skin previously exposed to jet fuel has not been investigated, although this exposure scenario is the occupational norm. Pigs were exposed to JP-8 jet fuel-soaked cotton fabrics for 1 and 4 d with repeated daily exposures. Preexposed and unexposed skin was then dermatomed and placed in flow-through in vitro diffusion cells. Five cells with exposed skin and four cells with unexposed skin were dosed with a mixture of 14 different HC consisting of nonane, decane, undecane, dodecane, tridecane, tetradecane, pentadecane, hexadecane, ethyl benzene, o-xylene, trimethyl benzene (TMB), cyclohexyl benzene (CHB), naphthalene, and dimethyl naphthalene (DMN) in water + ethanol (50:50) as diluent. Another five cells containing only JP-8-exposed skin were dosed solely with diluent in order to determine the skin retention of jet fuel HC. The absorption parameters of flux, diffusivity, and permeability were calculated for the studied HC. The data indicated that there was a two-fold and four-fold increase in absorption of specific aromatic HC like ethyl benzene, o-xylene, and TMB through 1- and 4-dJP-8 preexposed skin, respectively. Similarly, dodecane and tridecane were absorbed more in 4-d than 1-dJP-8 preexposed skin experiments. The absorption of naphthalene and DMN was 1.5 times greater than the controls in both 1- and 4-d preexposures. CHB, naphthalene, and DMN had significant persistent skin retention in 4-d preexposures as compared to 1-d exposures that might leave skin capable of further absorption several days postexposure. The possible mechanism of an increase in HC absorption in fuel preexposed skin may be via lipid extraction from the stratum corneum as indicated by Fourier transform infrared (FTIR) spectroscopy. This study suggests that the preexposure of skin to jet fuel enhances the subsequent in vitro percutaneous absorption of HC, so single-dose absorption data for jet fuel HC from naive skin may not be optimal to predict the toxic potential for repeated exposures. For certain compounds, persistent absorption may occur days after the initial exposure.

Gene Flow between the Korean Peninsula and Its Neighboring Countries

PubMed Central

Cho, Yoon Shin; Oh, Ji Hee; Ryu, Min Hyung; Chung, Hye Won; Seo, Jeong-Sun; Lee, Jong-Eun; Oh, Bermseok; Bhak, Jong; Kim, Hyung-Lae

2010-01-01

SNP markers provide the primary data for population structure analysis. In this study, we employed whole-genome autosomal SNPs as a marker set (54,836 SNP markers) and tested their possible effects on genetic ancestry using 320 subjects covering 24 regional groups including Northern ( = 16) and Southern ( = 3) Asians, Amerindians ( = 1), and four HapMap populations (YRI, CEU, JPT, and CHB). Additionally, we evaluated the effectiveness and robustness of 50K autosomal SNPs with various clustering methods, along with their dependencies on recombination hotspots (RH), linkage disequilibrium (LD), missing calls and regional specific markers. The RH- and LD-free multi-dimensional scaling (MDS) method showed a broad picture of human migration from Africa to North-East Asia on our genome map, supporting results from previous haploid DNA studies. Of the Asian groups, the East Asian group showed greater differentiation than the Northern and Southern Asian groups with respect to Fst statistics. By extension, the analysis of monomorphic markers implied that nine out of ten historical regions in South Korea, and Tokyo in Japan, showed signs of genetic drift caused by the later settlement of East Asia (South Korea, Japan and China), while Gyeongju in South East Korea showed signs of the earliest settlement in East Asia. In the genome map, the gene flow to the Korean Peninsula from its neighboring countries indicated that some genetic signals from Northern populations such as the Siberians and Mongolians still remain in the South East and West regions, while few signals remain from the early Southern lineages. PMID:20686617

Dr Catherine Louisa Corbett MB ChB DPH (1877-1960), Diary in Serbia. Her work with the Scottish Women's Hospitals in Serbia and Russia, 1915-1917.

PubMed

Mohr, Peter D

2018-01-01

Catherine Corbett was the second woman to gain a medical degree from the University of Manchester Medical School in 1905; however, little was known about her life or work, apart from the fact that she was a School Medical Inspector (SMI) and never married. The rediscovery of her Diary in Serbia (1916) has revealed her work for the Scottish Women's Hospitals (SWH) during the First World War in Serbia (1915-1916). Her time alongside her female colleagues was a good experience, however the harsh conditions, especially those she experienced during a further period working in Russia (1916-1917), left her exhausted and psychologically stressed. After the war, her job as a SMI in Burnley and her pursuit of rock climbing helped her adjust to a normal life and allowed her to promote her views on female education.

Antimicrobial Effect of Nisin against Bacillus cereus in Beef Jerky during Storage

PubMed Central

Lee, Na-Kyoung; Kim, Hyoun Wook; Lee, Joo Yeon; Ahn, Dong Uk; Kim, Cheon-Jei; Paik, Hyun-Dong

2015-01-01

The microbial distribution of raw materials and beef jerky, and the effect of nisin on the growth of Bacillus cereus inoculated in beef jerky during storage, were studied. Five strains of pathogenic B. cereus were detected in beef jerky, and identified with 99.8% agreement using API CHB 50 kit. To evaluate the effect of nisin, beef jerky was inoculated with approximately 3 Log CFU/g of B. cereus mixed culture and nisin (100 IU/g and 500 IU/g). During the storage of beef jerky without nisin, the number of mesophilic bacteria and B. cereus increased unlikely for beef jerky with nisin. B. cereus started to grow after 3 d in 100 IU nisin/g treatment, and after 21 d in 500 IU nisin/g treatment. The results suggest that nisin could be an effective approach to extend the shelf-life, and improve the microbial safety of beef jerky, during storage. PMID:26761838

Adding pegylated interferon to entecavir for hepatitis B e antigen-positive chronic hepatitis B: A multicenter randomized trial (ARES study).

PubMed

Brouwer, Willem Pieter; Xie, Qing; Sonneveld, Milan J; Zhang, Ningping; Zhang, Qin; Tabak, Fehmi; Streinu-Cercel, Adrian; Wang, Ji-Yao; Idilman, Ramazan; Reesink, Hendrik W; Diculescu, Mircea; Simon, Krzysztof; Voiculescu, Mihai; Akdogan, Meral; Mazur, Wlodzimierz; Reijnders, Jurrien G P; Verhey, Elke; Hansen, Bettina E; Janssen, Harry L A

2015-05-01

Entecavir (ETV) is a potent inhibitor of hepatitis B viral replication, but long-term therapy may be required. We investigated whether adding on pegylated interferon (Peg-IFN) to ETV therapy enhances serological response rates. In this global investigator-initiated, open-label, multicenter, randomized trial, hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients with compensated liver disease started on ETV monotherapy (0.5 mg/day) and were randomized in a 1:1 ratio to either Peg-IFN add-on therapy (180 µg/week) from week 24 to 48 (n = 85) or to continue ETV monotherapy (n = 90). Response was defined as HBeAg loss with HBV DNA <200 IU/mL at week 48. Responders discontinued ETV at week 72. All patients were followed until week 96. Response was achieved in 16 of 85 (19%) patients allocated to the add-on arm versus 9 of 90 (10%) in the monotherapy arm (P = 0.095). Adjusted for HBV DNA levels before randomized therapy, Peg-IFN add-on was significantly associated with response (odds ratio: 4.8; 95% confidence interval: 1.6-14.0; P = 0.004). Eleven (13%) of the add-on-treated patients achieved disease remission after ETV cessation versus 2 of 90 (2%) of those treated with monotherapy (P = 0.007), which was 79% (11 of 14) versus 25% (2 of 8) of those who discontinued ETV (P = 0.014). At week 96, 22 (26%) patients assigned add-on versus 12 (13%) assigned monotherapy achieved HBeAg seroconversion (P = 0.036). Peg-IFN add-on led to significantly more decline in hepatitis B surface antigen, HBeAg, and HBV DNA (all P < 0.001). Combination therapy was well tolerated. Although the primary endpoint was not reached, 24 weeks of Peg-IFN add-on therapy led to a higher proportion of HBeAg response, compared to ETV monotherapy. Add-on therapy resulted in more viral decline and appeared to prevent relapse after stopping ETV. Hence, Peg-IFN add-on therapy may facilitate the discontinuation of nucleos(t)ide analogs. © 2014 by the American Association for the Study of Liver Diseases.

Amino acid similarities and divergences in the small surface proteins of genotype C hepatitis B viruses between nucleos(t)ide analogue-naïve and lamivudine-treated patients with chronic hepatitis B.

PubMed

Ding, Hai; Liu, Baoming; Zhao, Chengyu; Yang, Jingxian; Yan, Chunhui; Yan, Ling; Zhuang, Hui; Li, Tong

2014-02-01

Entire C-genotype small hepatitis B surface (SHBs) sequences were isolated from 139 nucleos(t)ide analogues (NA)-naïve and 74 lamivudine (LMV)-treated chronic hepatitis B (CHB) patients. The conservation and variability of total 226 amino acids (AAs) within the sequences were determined individually, revealing significant higher mutant isolate rate and mutation frequency in LMV-treated cohort than those in the NA-naïve one (P=0.009 and 0.0001, respectively). Three absolutely conserved fragments (s16-s19, s176-s181 and s185-s188) and seven moderately conserved regions (a few AA sites acquiring increased variability after LMV-treatment) were identified. The significant mutation rate increase after LMV-treatment occurred primarily in major hydrophilic region (except 'a' determinant) and transmembrane domain 3/4, but not in other upstream functional regions of SHBs. With little influence on immune escape-associated mutation frequencies within 'a' determinant, LMV-monotherapy significantly induced classical LMVr-associated mirror changes sE164D/rtV173L, sI195M/rtM204V and sW196L/S/rtM204I, as well as non-classical ones sG44E/rtS53N, sT47K/A/rtH55R/Q and sW182stop/rtV191I outside 'a' determinant. Interestingly, another newly-identified truncation mutation sC69stop/rtS78T decreased from 7.91% (11/139) in NA-naïve cohort to 2.70% (2/74) in LMV-treated one. Altogether, the altered AA conservation and diversity in SHBs sequences after LMV-treatment in genotype-C HBV infection might shed new insights into how LMV-therapy affects the SHBs variant evolution and its antigenicity. Copyright © 2013 Elsevier B.V. All rights reserved.

A functional brain-derived neurotrophic factor (BDNF) gene variant increases the risk of moderate-to-severe allergic rhinitis.

PubMed

Jin, Peng; Andiappan, Anand Kumar; Quek, Jia Min; Lee, Bernett; Au, Bijin; Sio, Yang Yie; Irwanto, Astrid; Schurmann, Claudia; Grabe, Hans Jörgen; Suri, Bani Kaur; Matta, Sri Anusha; Westra, Harm-Jan; Franke, Lude; Esko, Tonu; Sun, Liangdan; Zhang, Xuejun; Liu, Hong; Zhang, Furen; Larbi, Anis; Xu, Xin; Poidinger, Michael; Liu, Jianjun; Chew, Fook Tim; Rotzschke, Olaf; Shi, Li; Wang, De Yun

2015-06-01

Brain-derived neurotrophic factor (BDNF) is a secretory protein that has been implicated in the pathogenesis of allergic rhinitis (AR), atopic asthma, and eczema, but it is currently unknown whether BDNF polymorphisms influence susceptibility to moderate-to-severe AR. We sought to identify disease associations and the functional effect of BDNF genetic variants in patients with moderate-to-severe AR. Tagging single nucleotide polymorphisms (SNPs) spanning the BDNF gene were selected from the human HapMap Han Chinese from Beijing (CHB) data set, and associations with moderate-to-severe AR were assessed in 2 independent cohorts of Chinese patients (2216 from Shandong province and 1239 living in Singapore). The functional effects of the BDNF genetic variants were determined by using both in vitro and ex vivo assays. The tagging SNP rs10767664 was significantly associated with the risk of moderate-to-severe AR in both Singapore Chinese (P = .0017; odds ratio, 1.324) and Shandong Chinese populations (P = .039; odds ratio, 1.180). The coding nonsynonymous SNP rs6265 was in perfect linkage with rs10767664 and conferred increased BDNF protein secretion by a human cell line in vitro. Subjects bearing the AA genotype of rs10767664 exhibited increased risk of moderate-to-severe AR and displayed increased BDNF protein and total IgE levels in plasma. Using a large-scale expression quantitative trait locus study, we demonstrated that BDNF SNPs are significantly associated with altered BDNF concentrations in peripheral blood. A common genetic variant of the BDNF gene is associated with increased risk of moderate-to-severe AR, and the AA genotype is associated with increased BDNF mRNA levels in peripheral blood. Together, these data indicate that functional BDNF gene variants increase the risk of moderate-to-severe AR. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Chronic hepatitis B: Virology, natural history, current management and a glimpse at future opportunities.

PubMed

Gish, Robert G; Given, Bruce D; Lai, Ching-Lung; Locarnini, Stephen A; Lau, Johnson Y N; Lewis, David L; Schluep, Thomas

2015-09-01

The host immune system plays an important role in chronic hepatitis B (CHB), both in viral clearance and hepatocellular damage. Advances in our understanding of the natural history of the disease have led to redefining the major phases of infection, with the "high replicative, low inflammatory" phase now replacing what was formerly termed the "immune tolerant" phase, and the "nonreplicative phase" replacing what was formerly termed the "inactive carrier" phase. As opposed to the earlier view that HBV establishes chronic infection by exploiting the immaturity of the neonate's immune system, new findings on trained immunity show that the host is already somewhat "matured" following birth, and is actually very capable of responding immunologically, potentially altering future hepatitis B treatment strategies. While existing therapies are effective in reducing viral load and necroinflammation, often restoring the patient to near-normal health, they do not lead to a cure except in very rare cases and, in many patients, viremia rebounds after cessation of treatment. Researchers are now challenged to devise therapies that will eliminate infection, with a particular focus on eliminating the persistence of viral cccDNA in the nuclei of hepatocytes. In the context of chronic hepatitis B, new definitions of 'cure' are emerging, such as 'functional' and 'virological' cure, defined by stable off-therapy suppression of viremia and antigenemia, and the normalization of serum ALT and other liver-related laboratory tests. Continued advances in the understanding of the complex biology of chronic hepatitis B have resulted in the development of new, experimental therapies targeting viral and host factors and pathways previously not accessible to therapy, approaches which may lead to virological cures in the near term and functional cures upon long term follow-up. This article forms part of a symposium in Antiviral Research on "An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for hepatitis B." Copyright © 2015 Elsevier B.V. All rights reserved.

Inhibition of alpha interferon (IFN-α)-induced microRNA-122 negatively affects the anti-hepatitis B virus efficiency of IFN-α.

PubMed

Hao, Junli; Jin, Wensong; Li, Xinghui; Wang, Saifeng; Zhang, Xiaojun; Fan, Hongxia; Li, Changfei; Chen, Lizhao; Gao, Bin; Liu, Guangze; Meng, Songdong

2013-01-01

Alpha interferon (IFN-α)-based therapy can effectively treat chronic hepatitis B virus (HBV) infection, which causes life-threatening complications. Responses to IFN-α therapy vary greatly in chronic hepatitis B (CHB) patients, but underlying mechanisms are almost unknown. In this study, we found that IFN-α treatment induced a marked decrease of microRNA-122 (miR-122) expression in hepatocytes. We next showed that IFN-α-induced miR-122 downregulation was only partly due to transcriptional suppression. One IFN-stimulated gene (ISG), NT5C3, which was identified as a miR-122 target, efficiently inhibited miR-122 by binding and sequestering miR-122 with its mRNA 3'-untranslated region (3'-UTR), indicating that this ISG is involved in IFN-α-mediated miR-122 suppression. Notably, the inhibitory effect of IFN-α on miR-122 was completely abolished by blocking IFN-α-induced upregulation of NT5C3 mRNA expression by RNA interference (RNAi). Meanwhile, we observed that miR-122 dramatically inhibited HBV expression and replication. Finally, we showed that IFN-α-mediated HBV-inhibitory effects could be enhanced significantly by blocking IFN-α-induced downregulation of miR-122. We therefore concluded that IFN-α-induced inhibition of miR-122 may negatively affect the anti-HBV function of IFN-α. These data provide valuable insights for a better understanding of the antiviral mechanism of IFN-α and raise further potential interest in enhancing its anti-HBV efficacy.

Inhibition of Alpha Interferon (IFN-α)-Induced MicroRNA-122 Negatively Affects the Anti-Hepatitis B Virus Efficiency of IFN-α

PubMed Central

Hao, Junli; Jin, Wensong; Li, Xinghui; Wang, Saifeng; Zhang, Xiaojun; Fan, Hongxia; Li, Changfei; Chen, Lizhao; Gao, Bin

2013-01-01

Alpha interferon (IFN-α)-based therapy can effectively treat chronic hepatitis B virus (HBV) infection, which causes life-threatening complications. Responses to IFN-α therapy vary greatly in chronic hepatitis B (CHB) patients, but underlying mechanisms are almost unknown. In this study, we found that IFN-α treatment induced a marked decrease of microRNA-122 (miR-122) expression in hepatocytes. We next showed that IFN-α-induced miR-122 downregulation was only partly due to transcriptional suppression. One IFN-stimulated gene (ISG), NT5C3, which was identified as a miR-122 target, efficiently inhibited miR-122 by binding and sequestering miR-122 with its mRNA 3′-untranslated region (3′-UTR), indicating that this ISG is involved in IFN-α-mediated miR-122 suppression. Notably, the inhibitory effect of IFN-α on miR-122 was completely abolished by blocking IFN-α-induced upregulation of NT5C3 mRNA expression by RNA interference (RNAi). Meanwhile, we observed that miR-122 dramatically inhibited HBV expression and replication. Finally, we showed that IFN-α-mediated HBV-inhibitory effects could be enhanced significantly by blocking IFN-α-induced downregulation of miR-122. We therefore concluded that IFN-α-induced inhibition of miR-122 may negatively affect the anti-HBV function of IFN-α. These data provide valuable insights for a better understanding of the antiviral mechanism of IFN-α and raise further potential interest in enhancing its anti-HBV efficacy. PMID:23055569

APEX - the Hyperspectral ESA Airborne Prism Experiment

PubMed Central

Itten, Klaus I.; Dell'Endice, Francesco; Hueni, Andreas; Kneubühler, Mathias; Schläpfer, Daniel; Odermatt, Daniel; Seidel, Felix; Huber, Silvia; Schopfer, Jürg; Kellenberger, Tobias; Bühler, Yves; D'Odorico, Petra; Nieke, Jens; Alberti, Edoardo; Meuleman, Koen

2008-01-01

The airborne ESA-APEX (Airborne Prism Experiment) hyperspectral mission simulator is described with its distinct specifications to provide high quality remote sensing data. The concept of an automatic calibration, performed in the Calibration Home Base (CHB) by using the Control Test Master (CTM), the In-Flight Calibration facility (IFC), quality flagging (QF) and specific processing in a dedicated Processing and Archiving Facility (PAF), and vicarious calibration experiments are presented. A preview on major applications and the corresponding development efforts to provide scientific data products up to level 2/3 to the user is presented for limnology, vegetation, aerosols, general classification routines and rapid mapping tasks. BRDF (Bidirectional Reflectance Distribution Function) issues are discussed and the spectral database SPECCHIO (Spectral Input/Output) introduced. The optical performance as well as the dedicated software utilities make APEX a state-of-the-art hyperspectral sensor, capable of (a) satisfying the needs of several research communities and (b) helping the understanding of the Earth's complex mechanisms. PMID:27873868

Photoacoustic microscopy of cerebral hemodynamic and oxygen-metabolic responses to anesthetics

NASA Astrophysics Data System (ADS)

Cao, Rui; Li, Jun; Ning, Bo; Sun, Naidi; Wang, Tianxiong; Zuo, Zhiyi; Hu, Song

2017-02-01

General anesthetics are known to have profound effects on cerebral hemodynamics and neuronal activities. However, it remains a challenge to directly assess anesthetics-induced hemodynamic and oxygen-metabolic changes from the true baseline under wakefulness at the microscopic level, due to the lack of an enabling technology for high-resolution functional imaging of the awake mouse brain. To address this challenge, we have developed head-restrained photoacoustic microscopy (PAM), which enables simultaneous imaging of the cerebrovascular anatomy, total concentration and oxygen saturation of hemoglobin (CHb and sO2), and blood flow in awake mice. From these hemodynamic measurements, two important metabolic parameters, oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO2), can be derived. Side-by-side comparison of the mouse brain under wakefulness and anesthesia revealed multifaceted cerebral responses to isoflurane, a volatile anesthetic widely used in preclinical research and clinical practice. Key observations include elevated cerebral blood flow (CBF) and reduced oxygen extraction and metabolism.

The diploid genome sequence of an Asian individual

PubMed Central

Wang, Jun; Wang, Wei; Li, Ruiqiang; Li, Yingrui; Tian, Geng; Goodman, Laurie; Fan, Wei; Zhang, Junqing; Li, Jun; Zhang, Juanbin; Guo, Yiran; Feng, Binxiao; Li, Heng; Lu, Yao; Fang, Xiaodong; Liang, Huiqing; Du, Zhenglin; Li, Dong; Zhao, Yiqing; Hu, Yujie; Yang, Zhenzhen; Zheng, Hancheng; Hellmann, Ines; Inouye, Michael; Pool, John; Yi, Xin; Zhao, Jing; Duan, Jinjie; Zhou, Yan; Qin, Junjie; Ma, Lijia; Li, Guoqing; Yang, Zhentao; Zhang, Guojie; Yang, Bin; Yu, Chang; Liang, Fang; Li, Wenjie; Li, Shaochuan; Li, Dawei; Ni, Peixiang; Ruan, Jue; Li, Qibin; Zhu, Hongmei; Liu, Dongyuan; Lu, Zhike; Li, Ning; Guo, Guangwu; Zhang, Jianguo; Ye, Jia; Fang, Lin; Hao, Qin; Chen, Quan; Liang, Yu; Su, Yeyang; san, A.; Ping, Cuo; Yang, Shuang; Chen, Fang; Li, Li; Zhou, Ke; Zheng, Hongkun; Ren, Yuanyuan; Yang, Ling; Gao, Yang; Yang, Guohua; Li, Zhuo; Feng, Xiaoli; Kristiansen, Karsten; Wong, Gane Ka-Shu; Nielsen, Rasmus; Durbin, Richard; Bolund, Lars; Zhang, Xiuqing; Li, Songgang; Yang, Huanming; Wang, Jian

2009-01-01

Here we present the first diploid genome sequence of an Asian individual. The genome was sequenced to 36-fold average coverage using massively parallel sequencing technology. We aligned the short reads onto the NCBI human reference genome to 99.97% coverage, and guided by the reference genome, we used uniquely mapped reads to assemble a high-quality consensus sequence for 92% of the Asian individual's genome. We identified approximately 3 million single-nucleotide polymorphisms (SNPs) inside this region, of which 13.6% were not in the dbSNP database. Genotyping analysis showed that SNP identification had high accuracy and consistency, indicating the high sequence quality of this assembly. We also carried out heterozygote phasing and haplotype prediction against HapMap CHB and JPT haplotypes (Chinese and Japanese, respectively), sequence comparison with the two available individual genomes (J. D. Watson and J. C. Venter), and structural variation identification. These variations were considered for their potential biological impact. Our sequence data and analyses demonstrate the potential usefulness of next-generation sequencing technologies for personal genomics. PMID:18987735

Psychological benefits 2 and 4 weeks after a single treatment with near infrared light to the forehead: a pilot study of 10 patients with major depression and anxiety.

PubMed

Schiffer, Fredric; Johnston, Andrea L; Ravichandran, Caitlin; Polcari, Ann; Teicher, Martin H; Webb, Robert H; Hamblin, Michael R

2009-12-08

Many studies have reported beneficial effects from the application of near-infrared (NIR) light photobiomodulation (PBM) to the body, and one group has reported beneficial effects applying it to the brain in stroke patients. We have reported that the measurement of a patient's left and right hemispheric emotional valence (HEV) may clarify data and guide lateralized treatments. We sought to test whether a NIR treatment could 1. improve the psychological status of patients, 2. show a relationship between immediate psychological improvements when HEV was taken into account, and 3. show an increase in frontal pole regional cerebral blood flow (rCBF), and 4. be applied without side effects. We gave 10 patients, (5 M/5 F) with major depression, including 9 with anxiety, 7 with a past history of substance abuse (6 with an opiate abuse and 1 with an alcohol abuse history), and 3 with post traumatic stress disorder, a baseline standard diagnostic interview, a Hamilton Depression Rating Scale (HAM-D), a Hamilton Anxiety Rating Scale (HAM-A), and a Positive and Negative Affect Scale (PANAS). We then gave four 4-minute treatments in a random order: NIR to left forehead at F3, to right forehead at F4, and placebo treatments (light off) at the same sites. Immediately following each treatment we repeated the PANAS, and at 2-weeks and at 4-weeks post treatment we repeated all 3 rating scales. During all treatments we recorded total hemoglobin (cHb), as a measure of rCBF with a commercial NIR spectroscopy device over the left and the right frontal poles of the brain. At 2-weeks post treatment 6 of 10 patients had a remission (a score

A method to associate all possible combinations of genetic and environmental factors using GxE landscape plot.

PubMed

Nagaie, Satoshi; Ogishima, Soichi; Nakaya, Jun; Tanaka, Hiroshi

2015-01-01

Genome-wide association studies (GWAS) and linkage analysis has identified many single nucleotide polymorphisms (SNPs) related to disease. There are many unknown SNPs whose minor allele frequencies (MAFs) as low as 0.005 having intermediate effects with odds ratio between 1.5~3.0. Low frequency variants having intermediate effects on disease pathogenesis are believed to have complex interactions with environmental factors called gene-environment interactions (GxE). Hence, we describe a model using 3D Manhattan plot called GxE landscape plot to visualize the association of p-values for gene-environment interactions (GxE). We used the Gene-Environment iNteraction Simulator 2 (GENS2) program to simulate interactions between two genetic loci and one environmental factor in this exercise. The dataset used for training contains disease status, gender, 20 environmental exposures and 100 genotypes for 170 subjects, and p-values were calculated by Cochran-Mantel-Haenszel chi-squared test on known data. Subsequently, we created a 3D GxE landscape plot of negative logarithm of the association of p-values for all the possible combinations of genetic and environmental factors with their hierarchical clustering. Thus, the GxE landscape plot is a valuable model to predict association of p-values for GxE and similarity among genotypes and environments in the context of disease pathogenesis. GxE - Gene-environment interactions, GWAS - Genome-wide association study, MAFs - Minor allele frequencies, SNPs - Single nucleotide polymorphisms, EWAS - Environment-wide association study, FDR - False discovery rate, JPT+CHB - HapMap population of Japanese in Tokyo, Japan - Han Chinese in Beijing.

New Software for the Fast Estimation of Population Recombination Rates (FastEPRR) in the Genomic Era.

PubMed

Gao, Feng; Ming, Chen; Hu, Wangjie; Li, Haipeng

2016-06-01

Genetic recombination is a very important evolutionary mechanism that mixes parental haplotypes and produces new raw material for organismal evolution. As a result, information on recombination rates is critical for biological research. In this paper, we introduce a new extremely fast open-source software package (FastEPRR) that uses machine learning to estimate recombination rate [Formula: see text] (=[Formula: see text]) from intraspecific DNA polymorphism data. When [Formula: see text] and the number of sampled diploid individuals is large enough ([Formula: see text]), the variance of [Formula: see text] remains slightly smaller than that of [Formula: see text] The new estimate [Formula: see text] (calculated by averaging [Formula: see text] and [Formula: see text]) has the smallest variance of all cases. When estimating [Formula: see text], the finite-site model was employed to analyze cases with a high rate of recurrent mutations, and an additional method is proposed to consider the effect of variable recombination rates within windows. Simulations encompassing a wide range of parameters demonstrate that different evolutionary factors, such as demography and selection, may not increase the false positive rate of recombination hotspots. Overall, accuracy of FastEPRR is similar to the well-known method, LDhat, but requires far less computation time. Genetic maps for each human population (YRI, CEU, and CHB) extracted from the 1000 Genomes OMNI data set were obtained in less than 3 d using just a single CPU core. The Pearson Pairwise correlation coefficient between the [Formula: see text] and [Formula: see text] maps is very high, ranging between 0.929 and 0.987 at a 5-Mb scale. Considering that sample sizes for these kinds of data are increasing dramatically with advances in next-generation sequencing technologies, FastEPRR (freely available at http://www.picb.ac.cn/evolgen/) is expected to become a widely used tool for establishing genetic maps and studying recombination hotspots in the population genomic era. Copyright © 2016 Gao et al.

Comparison of Genetic Variants in Cancer-Related Genes between Chinese Hui and Han Populations

PubMed Central

Tian, Chaoyong; Chen, Zhiqiang; Ma, Xixian; Yang, Ming; Wang, Zhizhong; Dong, Ying; Yang, Ting; Yang, Wenjun

2015-01-01

Background The Chinese Hui population, as the second largest minority ethnic group in China, may have a different genetic background from Han people because of its unique demographic history. In this study, we aimed to identify genetic differences between Han and Hui Chinese from the Ningxia region of China by comparing eighteen single nucleotide polymorphisms in cancer-related genes. Methods DNA samples were collected from 99 Hui and 145 Han people from the Ningxia Hui Autonomous Region in China, and SNPs were detected using an improved multiplex ligase detection reaction method. Genotyping data from six 1000 Genomes Project population samples (99 Utah residents with northern and western European ancestry (CEU), 107 Toscani in Italy (TSI), 108 Yoruba in Ibadan (YRI), 61 of African ancestry in the southwestern US (ASW), 103 Han Chinese in Beijing (CHB), and 104 Japanese in Tokyo (JPT)) were also included in this study. Differences in the distribution of alleles among the populations were assessed using χ2 tests, and FST was used to measure the degree of population differentiation. Results We found that the genetic diversity of many SNPs in cancer-related genes in the Hui Chinese in Ningxia was different from that in the Han Chinese in Ningxia. For example, the allele frequencies of four SNPs (rs13361707, rs2274223, rs465498, and rs753955) showed different genetic distributions (p<0.05) between Chinese Ningxia Han and Chinese Ningxia Hui. Five SNPs (rs730506, rs13361707, rs2274223, rs465498 and rs753955) had different FST values (FST >0.000) between the Hui and Han populations. Conclusions These results suggest that some SNPs associated with cancer-related genes vary among different Chinese ethnic groups. We suggest that population differences should be carefully considered in evaluating cancer risk and prognosis as well as the efficacy of cancer therapy. PMID:26683024

PXK locus in systemic lupus erythematosus: fine mapping and functional analysis reveals novel susceptibility gene ABHD6.

PubMed

Oparina, Nina Y; Delgado-Vega, Angelica M; Martinez-Bueno, Manuel; Magro-Checa, César; Fernández, Concepción; Castro, Rafaela Ortega; Pons-Estel, Bernardo A; D'Alfonso, Sandra; Sebastiani, Gian Domenico; Witte, Torsten; Lauwerys, Bernard R; Endreffy, Emoke; Kovács, László; Escudero, Alejandro; López-Pedrera, Chary; Vasconcelos, Carlos; da Silva, Berta Martins; Frostegård, Johan; Truedsson, Lennart; Martin, Javier; Raya, Enrique; Ortego-Centeno, Norberto; de Los Angeles Aguirre, Maria; de Ramón Garrido, Enrique; Palma, María-Jesús Castillo; Alarcon-Riquelme, Marta E; Kozyrev, Sergey V

2015-03-01

To perform fine mapping of the PXK locus associated with systemic lupus erythematosus (SLE) and study functional effects that lead to susceptibility to the disease. Linkage disequilibrium (LD) mapping was conducted by using 1251 SNPs (single nucleotide polymorphism) covering a 862 kb genomic region on 3p14.3 comprising the PXK locus in 1467 SLE patients and 2377 controls of European origin. Tag SNPs and genotypes imputed with IMPUTE2 were tested for association by using SNPTEST and PLINK. The expression QTLs data included three independent datasets for lymphoblastoid cells of European donors: HapMap3, MuTHER and the cross-platform eQTL catalogue. Correlation analysis of eQTLs was performed using Vassarstats. Alternative splicing for the PXK gene was analysed on mRNA from PBMCs. Fine mapping revealed long-range LD (>200 kb) extended over the ABHD6, RPP14, PXK, and PDHB genes on 3p14.3. The highly correlated variants tagged an SLE-associated haplotype that was less frequent in the patients compared with the controls (OR=0.89, p=0.00684). A robust correlation between the association with SLE and enhanced expression of ABHD6 gene was revealed, while neither expression, nor splicing alterations associated with SLE susceptibility were detected for PXK. The SNP allele frequencies as well as eQTL pattern analysed in the CEU and CHB HapMap3 populations indicate that the SLE association and the effect on ABHD6 expression are specific to Europeans. These results confirm the genetic association of the locus 3p14.3 with SLE in Europeans and point to the ABHD6 and not PXK, as the major susceptibility gene in the region. We suggest a pathogenic mechanism mediated by the upregulation of ABHD6 in individuals carrying the SLE-risk variants. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Fabrication of thermoplastic ductile films of chitin butyrate/poly(ɛ-caprolactone) blends and their cytocompatibility.

PubMed

Hashiwaki, Hiroki; Teramoto, Yoshikuni; Nishio, Yoshiyuki

2014-12-19

We fabricate thermoplastic films of chitin burtyrate (ChB)/poly(ɛ-caprolactone) (PCL) blends with different degree of miscibility (miscible (M), partially miscible (PM), and immiscible (IM)), and examined the feasibility as a cell scaffold system through evaluating mechanical properties and cytocompatibility. We found a remediation of the brittleness and an increase in ductility of ChB by blending PCL for the M and PM blends. The blend films were subjected to alkaline hydrolysis (2-M NaOH/37°C/48 h) with expectation of the improvement of the surface hydrophilicity and cell accessibility. ATR-FTIR spectroscopy of the alkaline-treated PM and IM films revealed that PCL component and ester side-chains of acyl chitin were selectively removed from the surface domain. L929 fibroblast cells well adhered and proliferated on these films. Therefore, the materials possess a great potential for the utilization as a thermoplastic cell scaffold in tissue engineering by adequate selection of the degree of miscibility and post treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Optimization of Hyaluronidase Inhibition Activity from Prunus davidiana (Carriere) Franch Fruit Extract Fermented by its Isolated Bacillus subtilis Strain SPF4211.

PubMed

Kim, Won-Baek; Park, So Hae; Koo, Kyoung Yoon; Kim, Bo Ram; Kim, Minji; Lee, Heeseob

2016-09-28

Strain SPF4211, having hyaluronidase (HAase) inhibition activity, was isolated from P. davidiana (Carriere) Franch fruit (PrDF) sugar extract. The phenotypic and biochemical properties based on 16S rDNA sequencing and an API 50 CHB kit suggested that the organism was B. subtilis. To optimize the HAase inhibition activity of PrDF extract by fermentation of strain SPF4211, a central composite design (CCD) was introduced based on three variables: concentration of PrDF extract (X₁: 1-5%), amount of starter culture (X₂: 1-5%), and fermentation time (X₃: 0-7 days). The experimental data were fitted with quadratic regression equations, and the accuracy of the equations was analyzed by ANOVA. The statistical model predicted the highest HAase inhibition activity of 37.936% under the optimal conditions of X₁ = 1%, X₂ = 2.53%, and X₃ = 7 days. The optimized conditions were validated by observation of an actual HAase inhibition activity of 38.367% from extract of PrDF fermented by SPF4211. These results agree well with the predicted model value.

APRI and FIB-4 are good predictors of the stage of liver fibrosis in chronic hepatitis B: the Chronic Hepatitis Cohort Study (CHeCS).

PubMed

Teshale, E; Lu, M; Rupp, L B; Holmberg, S D; Moorman, A C; Spradling, P; Vijayadeva, V; Boscarino, J A; Schmidt, M A; Gordon, S C

2014-12-01

We aim to determine the predictive ability of APRI, FIB-4 and AST/ALT ratio for staging of liver fibrosis and to differentiate significant fibrosis (F2-F4) from none to minimal fibrosis (F0-F1) in chronic hepatitis B (CHB). Liver biopsy results were mapped to an F0-4 equivalent fibrosis stage. Mean APRI and FIB-4 scores were significantly higher for each successive fibrosis level from F1 to F4 (P < 0.05). Based on optimized cut-offs, the AUROCs in distinguishing F2-F4 from F0 to F1 were 0.81 (0.76-0.87) for APRI, 0.81 (0.75-0.86) for FIB-4 and 0.56 (0.49-0.64) for AST/ALT ratio. APRI and FIB-4 distinguished F2-F4 from F0 to F1 with good sensitivity and specificity and can be useful for treatment decisions and monitoring progression of fibrosis. © 2014 John Wiley & Sons Ltd.

Training of surgeons for primary health care.

PubMed

Mulimba, J A

1997-08-01

It has been the view of the Association of Surgeons of East Africa (ASEA) that, like primary health care, there is primary surgery. The unit of provision of primary surgery is the district hospital. The training of surgeons for district hospitals starts at the undergraduate level, leading to the attainment of Bachelor of Medicine and Bachelor of Surgery (M.B. Ch.B.) degree. After internship the doctor works in a district or provincial hospital for 2-3 years, then trains for the degree of Master of Medicine (M. Med. (Surg.)) for a period of 3 years. The training involves rotation through all branches of surgery, so that the surgeon should be able to handle all aspects of routine surgery in a district hospital. To equip the surgeon further, a period in an outside setting is considered advisable. There are arrangements for regional surgical colleges to standardise the form of surgical training in the ASEA region. To keep surgeons in touch with the outside world, specialist training is done outside the region, but arrangements are being made for localised specialised units to offer this training.

Effects of amino acid substitutions in hepatitis B virus surface protein on virion secretion, antigenicity, HBsAg and viral DNA.

PubMed

Xiang, Kuan-Hui; Michailidis, Eleftherios; Ding, Hai; Peng, Ya-Qin; Su, Ming-Ze; Li, Yao; Liu, Xue-En; Dao Thi, Viet Loan; Wu, Xian-Fang; Schneider, William M; Rice, Charles M; Zhuang, Hui; Li, Tong

2017-02-01

As important virological markers, serum hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA levels show large fluctuations among chronic hepatitis B patients. The aim of this study was to reveal the potential impact and mechanisms of amino acid substitutions in small hepatitis B surface proteins (SHBs) on serum HBsAg and HBV DNA levels. Serum samples from 230 untreated chronic hepatitis B patients with genotype C HBV were analyzed in terms of HBV DNA levels, serological markers of HBV infection and SHBs sequences. In vitro functional analysis of the identified SHBs mutants was performed. Among 230 SHBs sequences, there were 39 (16.96%) sequences with no mutation detected (wild-type) and 191 (83.04%) with single or multiple mutations. SHBs consist of 226 amino acids, of which 104 (46.02%) had mutations in our study. Some mutations (e.g., sE2G, sL21S, sR24K, sT47A/K, sC69stop (sC69∗), sL95W, sL98V, and sG145R) negatively correlated with serum HBsAg levels. HBsAg and HBV DNA levels from this group of patients had a positive correlation (r=0.61, p<0.001). In vitro analysis showed that these mutations reduced extracellular HBsAg and HBV DNA levels by restricting virion secretion and antibody binding capacity. Virion secretion could be rescued for sE2G, sC69∗, and sG145R by co-expression of wild-type HBsAg. The serum HBsAg levels were lower in untreated CHB patients with novel SHBs mutations outside the major antigenic region than those without mutations. Underlying mechanisms include impairment of virion secretion and lower binding affinity to antibodies used for HBsAg measurements. The hepatitis B surface antigen (HBsAg) is a major viral protein of the hepatitis B virus (HBV) secreted into patient blood serum and its quantification value serves as an important marker for the evaluation of chronic HBV infection and antiviral response. We found a few new amino acid substitutions in HBsAg associated with lower serum HBsAg and HBV DNA levels. These different substitutions might impair virion secretion, change the ability of HBsAg to bind to antibodies, or impact HBV replication. These could all result in decreased detectable levels of serum HBsAg. The factors affecting circulating HBsAg level and HBsAg detection are varied and caution is needed when interpreting clinical significance of serum HBsAg levels. Clinical trial number: NCT01088009. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Identification of bacteria in pasteurized zucchini purées stored at different temperatures and comparison with those found in other pasteurized vegetable purées.

PubMed

Guinebretiere, M H; Berge, O; Normand, P; Morris, C; Carlin, F; Nguyen-The, C

2001-10-01

One hundred nineteen isolates from a commercial zucchini purée stored at 4, 10, and 20 to 25 degrees C were fingerprinted using repetitive sequence-based PCR (REP-PCR) and classified into 35 REP types. One representative isolate of each REP type was subsequently identified by API50CHB/20E profile and partial rrs gene sequence analysis. Nine REP types were misidentified by the API system. Strains were misidentified as being in the Bacillus circulans (group 2) API taxon or in taxa with a low number of positive API characters such as Brevibacillus brevis. A phylogenetic analysis pointed to one new species of Bacillus and three new species of Paenibacillus among the misidentified REP types. Bacterial components in zucchini purée were compared phenotypically with those obtained in previous work on broccoli, carrot, leek, potato, and split pea purées, based on simple matching coefficient and unweighted pair group method with averages cluster analysis. Out of 254 strains, 69 strains previously identified as B. circulans (group 2) or B. circulans/B. macerans/B. polymyxa were assigned to a new Paenibacillus taxon phylogenetically related to P. azotofixans. Storage conditions at 4 degrees C favored the development of "B. macroides/B. maroccanus" and Paenibacillus spp. in zucchini purées and Paenibacillus spp. in other purées. Storage conditions at 20 to 25 degrees C favored the development of B. subtilis group (B. licheniformis and B. subtilis) and B. cereus group strains. At 10 degrees C, Paenibacillus spp. were always present at high frequencies, whereas the occurrence of B. macroides/B. maroccanus (in zucchini purées), B. cereus, and B. pumilus varied with the experiment.

Identification of Bacteria in Pasteurized Zucchini Purées Stored at Different Temperatures and Comparison with Those Found in Other Pasteurized Vegetable Purées

PubMed Central

Guinebretiere, Marie-Hélène; Berge, Odile; Normand, Philippe; Morris, Cindy; Carlin, Frédéric; Nguyen-The, Christophe

2001-01-01

One hundred nineteen isolates from a commercial zucchini purée stored at 4, 10, and 20 to 25°C were fingerprinted using repetitive sequence-based PCR (REP-PCR) and classified into 35 REP types. One representative isolate of each REP type was subsequently identified by API50CHB/20E profile and partial rrs gene sequence analysis. Nine REP types were misidentified by the API system. Strains were misidentified as being in the Bacillus circulans (group 2) API taxon or in taxa with a low number of positive API characters such as Brevibacillus brevis. A phylogenetic analysis pointed to one new species of Bacillus and three new species of Paenibacillus among the misidentified REP types. Bacterial components in zucchini purée were compared phenotypically with those obtained in previous work on broccoli, carrot, leek, potato, and split pea purées, based on simple matching coefficient and unweighted pair group method with averages cluster analysis. Out of 254 strains, 69 strains previously identified as B. circulans (group 2) or B. circulans/B. macerans/B. polymyxa were assigned to a new Paenibacillus taxon phylogenetically related to P. azotofixans. Storage conditions at 4°C favored the development of “B. macroides/B. maroccanus” and Paenibacillus spp. in zucchini purées and Paenibacillus spp. in other purées. Storage conditions at 20 to 25°C favored the development of B. subtilis group (B. licheniformis and B. subtilis) and B. cereus group strains. At 10°C, Paenibacillus spp. were always present at high frequencies, whereas the occurrence of B. macroides/B. maroccanus (in zucchini purées), B. cereus, and B. pumilus varied with the experiment. PMID:11571151

ARG-walker: inference of individual specific strengths of meiotic recombination hotspots by population genomics analysis.

PubMed

Chen, Hao; Yang, Peng; Guo, Jing; Kwoh, Chee Keong; Przytycka, Teresa M; Zheng, Jie

2015-01-01

Meiotic recombination hotspots play important roles in various aspects of genomics, but the underlying mechanisms for regulating the locations and strengths of recombination hotspots are not yet fully revealed. Most existing algorithms for estimating recombination rates from sequence polymorphism data can only output average recombination rates of a population, although there is evidence for the heterogeneity in recombination rates among individuals. For genome-wide association studies (GWAS) of recombination hotspots, an efficient algorithm that estimates the individualized strengths of recombination hotspots is highly desirable. In this work, we propose a novel graph mining algorithm named ARG-walker, based on random walks on ancestral recombination graphs (ARG), to estimate individual-specific recombination hotspot strengths. Extensive simulations demonstrate that ARG-walker is able to distinguish the hot allele of a recombination hotspot from the cold allele. Integrated with output of ARG-walker, we performed GWAS on the phased haplotype data of the 22 autosome chromosomes of the HapMap Asian population samples of Chinese and Japanese (JPT+CHB). Significant cis-regulatory signals have been detected, which is corroborated by the enrichment of the well-known 13-mer motif CCNCCNTNNCCNC of PRDM9 protein. Moreover, two new DNA motifs have been identified in the flanking regions of the significantly associated SNPs (single nucleotide polymorphisms), which are likely to be new cis-regulatory elements of meiotic recombination hotspots of the human genome. Our results on both simulated and real data suggest that ARG-walker is a promising new method for estimating the individual recombination variations. In the future, it could be used to uncover the mechanisms of recombination regulation and human diseases related with recombination hotspots.

An unusual haplotype structure on human chromosome 8p23 derived from the inversion polymorphism.

PubMed

Deng, Libin; Zhang, Yuezheng; Kang, Jian; Liu, Tao; Zhao, Hongbin; Gao, Yang; Li, Chaohua; Pan, Hao; Tang, Xiaoli; Wang, Dunmei; Niu, Tianhua; Yang, Huanming; Zeng, Changqing

2008-10-01

Chromosomal inversion is an important type of genomic variations involved in both evolution and disease pathogenesis. Here, we describe the refined genetic structure of a 3.8-Mb inversion polymorphism at chromosome 8p23. Using HapMap data of 1,073 SNPs generated from 209 unrelated samples from CEPH-Utah residents with ancestry from northern and western Europe (CEU); Yoruba in Ibadan, Nigeria (YRI); and Asian (ASN) samples, which were comprised of Han Chinese from Beijing, China (CHB) and Japanese from Tokyo, Japan (JPT)-we successfully deduced the inversion orientations of all their 418 haplotypes. In particular, distinct haplotype subgroups were identified based on principal component analysis (PCA). Such genetic substructures were consistent with clustering patterns based on neighbor-joining tree reconstruction, which revealed a total of four haplotype clades across all samples. Metaphase fluorescence in situ hybridization (FISH) in a subset of 10 HapMap samples verified their inversion orientations predicted by PCA or phylogenetic tree reconstruction. Positioning of the outgroup haplotype within one of YRI clades suggested that Human NCBI Build 36-inverted order is most likely the ancestral orientation. Furthermore, the population differentiation test and the relative extended haplotype homozygosity (REHH) analysis in this region discovered multiple selection signals, also in a population-specific manner. A positive selection signal was detected at XKR6 in the ASN population. These results revealed the correlation of inversion polymorphisms to population-specific genetic structures, and various selection patterns as possible mechanisms for the maintenance of a large chromosomal rearrangement at 8p23 region during evolution. In addition, our study also showed that haplotype-based clustering methods, such as PCA, can be applied in scanning for cryptic inversion polymorphisms at a genome-wide scale.

Glucose-Specific Enzyme IIA of the Phosphoenolpyruvate:Carbohydrate Phosphotransferase System Modulates Chitin Signaling Pathways in Vibrio cholerae.

PubMed

Yamamoto, Shouji; Ohnishi, Makoto

2017-09-15

In Vibrio cholerae , the genes required for chitin utilization and natural competence are governed by the chitin-responsive two-component system (TCS) sensor kinase ChiS. In the classical TCS paradigm, a sensor kinase specifically phosphorylates a cognate response regulator to activate gene expression. However, our previous genetic study suggested that ChiS stimulates the non-TCS transcriptional regulator TfoS by using mechanisms distinct from classical phosphorylation reactions (S. Yamamoto, J. Mitobe, T. Ishikawa, S. N. Wai, M. Ohnishi, H. Watanabe, and H. Izumiya, Mol Microbiol 91:326-347, 2014, https://doi.org/10.1111/mmi.12462). TfoS specifically activates the transcription of tfoR , encoding a small regulatory RNA essential for competence gene expression. Whether ChiS and TfoS interact directly remains unknown. To determine if other factors mediate the communication between ChiS and TfoS, we isolated transposon mutants that turned off tfoR :: lacZ expression but possessed intact chiS and tfoS genes. We demonstrated an unexpected association of chitin-induced signaling pathways with the glucose-specific enzyme IIA (EIIA glc ) of the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) for carbohydrate uptake and catabolite control of gene expression. Genetic and physiological analyses revealed that dephosphorylated EIIA glc inactivated natural competence and tfoR transcription. Chitin-induced expression of the chb operon, which is required for chitin transport and catabolism, was also repressed by dephosphorylated EIIA glc Furthermore, the regulation of tfoR and chb expression by EIIA glc was dependent on ChiS and intracellular levels of ChiS were not affected by disruption of the gene encoding EIIA glc These results define a previously unknown connection between the PTS and chitin signaling pathways in V. cholerae and suggest a strategy whereby this bacterium can physiologically adapt to the existing nutrient status. IMPORTANCE The EIIA glc protein of the PTS coordinates a wide variety of physiological functions with carbon availability. In this report, we describe an unexpected association of chitin-activated signaling pathways in V. cholerae with EIIA glc The signaling pathways are governed by the chitin-responsive TCS sensor kinase ChiS and lead to the induction of chitin utilization and natural competence. We show that dephosphorylated EIIA glc inhibits both signaling pathways in a ChiS-dependent manner. This inhibition is different from classical catabolite repression that is caused by lowered levels of cyclic AMP. This work represents a newly identified connection between the PTS and chitin signaling pathways in V. cholerae and suggests a strategy whereby this bacterium can physiologically adapt to the existing nutrient status. Copyright © 2017 American Society for Microbiology.

Possible Origin of High-Amplitude Reflection Packages (HARPs) in the Canada Basin, Arctic Ocean

NASA Astrophysics Data System (ADS)

Lebedeva-Ivanova, Nina; Hutchinson, Deborah; Shimeld, John; Chian, Deping; Hart, Patrick; Jackson, Ruth; Saltus, Richard; Mosher, David

2013-04-01

The Canada Basin (CB) of the Arctic Ocean is a semi-enclosed ocean basin surrounded by the Alaskan and Canadian margins to the south and east, the Alpha-Mendeleev Large Igneous Province (AMLIP) to the north and the subsided continental Chukchi Borderland (ChB) to the west. During 2007-2011, US-Canada expeditions collected ~15,000 km multichannel seismic data and sonobuoy reflection and refraction seismic data with average spacing of ~80 km mostly over the CB and AMLIP. High-amplitude reflective packages (HARPs) underlie the mostly flat-lying sediments of CB. Although HARPs are discontinuous in the central CB, they become more continuous toward ChB and AMLIP. HARPs are often the most reflective events in the seismic section, exceeding even the seafloor reflection. Only rarely are reflections seen beneath HARPs. Where best developed, HARPs are ~100-300 ms TWTT, consisting of several high-amplitude wavelets with a pronounced narrow frequency band within the limits of ~10-30 Hz. This character of HARPs is consistent with patterns produced by constructive interference of thin beds (Widess, 1973). Forward modeling of sonobuoy data, synthetic tests, and frequency analysis of the tuning effect suggest that HARPs are composed of a series of alternating high- and low-velocity layers. The high-velocity layers are ~100-200 m thick with P-velocities of ~3.5-4.5 km/s. The low-velocity layers are about half as thick with velocities of ~2-3 km/s. A broad range of possible interpretations of rock composition exists from these velocities, e.g. sandstone and interbedded shale (Prince Patrick Island, Harrison and Brent, 2005); or tholeiitic basalts flows and sediments (Voring volcanic margin, Olanke and Eldholm, 1994); or sills and sediments (Newfoundland margin, Peron-Pinvidic et all, 2010). HARP can be associated with several origins. In the central and southern CB, where oceanic spreading is interpreted, HARPs are discontinuous among high-relief, but otherwise low-amplitude reflections interpreted to be large basement blocks. These discontinuous HARPs, associated with basement, are presumed synchronous with the seafloor spreading event that opened CB. Further north, near AMLIP, HARPs are more continuous over 10s of km, suggesting an origin associated with magmatism of AMLIP. In several areas in northern CB, HARPs have a shingled, en-echelon character, suggestive of sills intruding younger (i.e., post-rift) sediments. These relations suggest that HARPs are associated with basalts (flows and sills) interbedded with or separated by thinner sediment layers. Although the deep sediments and basement of CB are unsampled, seismic stratigraphic relationships suggest HARPs are of at least two ages: one associated with rifting/seafloor spreading (~125 Ma?) and a younger one associated with a post-rift magmatic pulse on AMLIP (~90-80 Ma?).

A Public Health Analysis on Gaps in Disease Monitoring and Opportunities for Improved Care for the Management of Hepatitis B and C.

PubMed

Akhtar, Faisal; Rehman, Sabah

2018-01-16

Hepatitis B and Hepatitis C have been major disease-causing agents among humans since they were discovered in the 1960s. Both cause jaundice-like symptoms initially but their prognosis and treatment are somehow different and depend upon many demographic details, such as the age and susceptibility of the patients and any other comorbid conditions. They clinically present primarily with hepatitis and can have many adverse effects or even be life-threatening at times, if not treated properly. However, their epidemiological background and findings in terms of morbidity, mortality, and case fatality rates are different. The disease burden, impact on the healthcare system, and prevention of the two diseases are quite different. The treatment and management options along with the prevention and control measures share unique strategies for handling the two diseases. The purpose of this review is to highlight the gaps in disease monitoring and to find ways and opportunities that can lead to improved care and better management of Hepatitis B and C locally and globally. Online databases were searched and peer-reviewed articles were selected. Key issues identified were lack of education globally in resource-limited settings, leading to a decreased understanding of the potential hazards associated with needle sharing and lack of access to healthcare because of a lack of insurance. The failure of compliance with vaccination leads to an increase in mother-to-child transmission (MTCT)-related infections. Increased global travel demands a systematic program in most immigrant-receiving countries to screen for hepatitis B virus (HBV)/hepatitis c virus (HCV) infections. Delayed U.S. Food and Drug Administration (FDA) licensing for new drugs hampers the treatment of chronic Hepatitis-B (CHB) among children. With the advancement in science, an effective vaccine against HCV will definitely help in eradicating the infection.

Cost Assessment of Hepatitis B Virus-related Hepatitis in Bangladesh.

PubMed

Mahtab, Mamun Al; Chaudhury, Muntasir; Uddin, Mohammad H; Noor-E Alam, Sheikh M; Rahim, Mohammad A; Alam, Mohammad A; Moben, Ahmed L; Khondaker, Faiz A; Choudhury, Mohammad Fi; Sarkar, Mohammad Ja; Poddar, Provat K; Foez, Syed A; Akbar, Sheikh Mf

2016-01-01

Hepatitis B virus (HBV) infection is endemic in Bangladesh. Studies have indicated that HBV is the major cause of chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC) in this country. Recently, HBV-related acute on chronic liver failure (HBV-ACLF) has emerged as a serious and emergent medical problem in Bangladesh. To develop a strategy to address HBV-related problems and their influence on health care delivery system, proper understandings about extent of problems and nature of economic burden should be explored. Conservative estimates indicate that about 50 million or more of Bangladeshi have been infected by HBV at some point of their life. Out of the total Bangladeshi population, about 2 to 5% is chronically infected with HBV (about 3-8 million) (1-6%) and considerable number of these patients will eventually develop LC, HCC, or ACLF (about 1 million). Although proper statistics is lacking, it is estimated that HBV-related liver diseases account for a majority of hospital admissions and around 20,000 deaths every year in Bangladesh. In addition, complex clinical features of HBV-related liver diseases have been documented in Bangladesh that show similarity and differences from HBV infection in other Asian countries. Although vaccination against HBV and containment of horizontal transmission are in progress in Bangladesh for reduction of new HBV infection, there is a lack of national strategy for treatment of millions of chronic HBV-infected subjects. This paper will provide an insight regarding the economic impact of HBV in Bangladesh that may act as a primary impetus for developing national HBV eradication program, a goal set by World Health Organization (WHO). Al Mahtab M, Chaudhury M, Uddin MH, Noor-E-Alam SM, Rahim MA, Alam MA, Moben AL, Khondaker FA, Choudhury MFI, Sarkar MJA, Poddar PK, Foez SA, Akbar SMF. Cost Assessment of Hepatitis B Virus-related Hepatitis in Bangladesh. Euroasian J Hepato-Gastroenterol 2016;6(2):163-166.

Population differences in the rate of proliferation of international HapMap cell lines.

PubMed

Stark, Amy L; Zhang, Wei; Zhou, Tong; O'Donnell, Peter H; Beiswanger, Christine M; Huang, R Stephanie; Cox, Nancy J; Dolan, M Eileen

2010-12-10

The International HapMap Project is a resource for researchers containing genotype, sequencing, and expression information for EBV-transformed lymphoblastoid cell lines derived from populations across the world. The expansion of the HapMap beyond the four initial populations of Phase 2, referred to as Phase 3, has increased the sample number and ethnic diversity available for investigation. However, differences in the rate of cellular proliferation between the populations can serve as confounders in phenotype-genotype studies using these cell lines. Within the Phase 2 populations, the JPT and CHB cell lines grow faster (p < 0.0001) than the CEU or YRI cell lines. Phase 3 YRI cell lines grow significantly slower than Phase 2 YRI lines (p < 0.0001), with no widespread genetic differences based on common SNPs. In addition, we found significant growth differences between the cell lines in the Phase 2 ASN populations and the Han Chinese from the Denver metropolitan area panel in Phase 3 (p < 0.0001). Therefore, studies that separate HapMap panels into discovery and replication sets must take this into consideration. Copyright © 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Identification of Bacillus spp. from Bikalga, fermented seeds of Hibiscus sabdariffa: phenotypic and genotypic characterization.

PubMed

Ouoba, L I I; Parkouda, C; Diawara, B; Scotti, C; Varnam, A H

2008-01-01

To identify Bacillus spp. responsible of the fermentation of Hibiscus sabdariffa for production of Bikalga, an alkaline fermented food used as a condiment in Burkina Faso. Seventy bacteria were isolated from Bikalga produced in different regions of Burkina Faso and identified by phenotyping and genotyping using PCR amplification of the 16S-23S rDNA intergenic transcribed spacer (ITS-PCR), repetitive sequence-based PCR (rep-PCR) and DNA sequencing. The isolates were characterized as motile, rod-shaped, endospore forming, catalase positive, Gram-positive bacteria. ITS-PCR allowed typing mainly at species level. Rep-PCR was more discriminative and allowed a typing at ssp. level. The DNA sequencing combined with the Blast search program and fermentation profiles using API 50CHB system allowed an identification of the bacteria as Bacillus subtilis, B. licheniformis, B. cereus, B. pumilus, B. badius, Brevibacillus bortelensis, B. sphaericus and B. fusiformis. B. subtilis were the predominant bacterium (42) followed by B. licheniformis (16). Various species and ssp. of Bacillus are involved in fermentation of H. sabdariffa for production of Bikalga. Selection of starter cultures of Bacillus for controlled production of Bikalga, selection of probiotic bacteria.

Ultrasound-aided Multi-parametric Photoacoustic Microscopy of the Mouse Brain.

PubMed

Ning, Bo; Sun, Naidi; Cao, Rui; Chen, Ruimin; Kirk Shung, K; Hossack, John A; Lee, Jin-Moo; Zhou, Qifa; Hu, Song

2015-12-21

High-resolution quantitative imaging of cerebral oxygen metabolism in mice is crucial for understanding brain functions and formulating new strategies to treat neurological disorders, but remains a challenge. Here, we report on our newly developed ultrasound-aided multi-parametric photoacoustic microscopy (PAM), which enables simultaneous quantification of the total concentration of hemoglobin (CHb), the oxygen saturation of hemoglobin (sO2), and cerebral blood flow (CBF) at the microscopic level and through the intact mouse skull. The three-dimensional skull and vascular anatomies delineated by the dual-contrast (i.e., ultrasonic and photoacoustic) system provide important guidance for dynamically focused contour scan and vessel orientation-dependent correction of CBF, respectively. Moreover, bi-directional raster scan allows determining the direction of blood flow in individual vessels. Capable of imaging all three hemodynamic parameters at the same spatiotemporal scale, our ultrasound-aided PAM fills a critical gap in preclinical neuroimaging and lays the foundation for high-resolution mapping of the cerebral metabolic rate of oxygen (CMRO2)-a quantitative index of cerebral oxygen metabolism. This technical innovation is expected to shed new light on the mechanism and treatment of a broad spectrum of neurological disorders, including Alzheimer's disease and ischemic stroke.

Feasibility and pilot study of the Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) project.

PubMed

Sun, Lena S; Li, Guohua; DiMaggio, Charles J; Byrne, Mary W; Ing, Caleb; Miller, Tonya L K; Bellinger, David C; Han, Sena; McGowan, Francis X

2012-10-01

Animal studies have documented that exposure of the developing brain to commonly used anesthetic agents induces neurotoxicity and late abnormal neurobehavioral functions as adults. Results from clinical studies have all been analyzed using existing data sets, and these studies produced inconsistent results. To provide more definitive evidence to address the clinical relevance of anesthetic neurotoxicity in children, an interdisciplinary team of investigators designed and developed the Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) project. We present pilot study results in 28 sibling pairs recruited and tested at the Columbia University Medical Center (CUMC) and Children's Hospital of Boston (CHB) for the PANDA project. The PANDA project uses an ambidirectional cohort design. We performed prospective neuropsychological assessment in 28 exposed-unexposed sibling pairs from 6 to 11 years of age. The exposed siblings were ASA 1 or 2 and had received a single episode of anesthesia for inguinal hernia repair before the age of 36 months and the unexposed siblings had no anesthesia before the age of 36 months. All the sibling pairs were English speaking and were 36 weeks of gestational age or older. Each sibling pair underwent a direct testing using the Wechsler Abbreviated Scale of Intelligence (WASI) and the NEuroPSYchological Assessment, second edition (NEPSY II), and the parents completed questionnaires related to behavior using CBCL and Conners rating. Data are presented as means±SD. We conducted descriptive analyses of the demographic data. We compared both the exposed and the unexposed sibling groups on WASI and NEPSY II, and total and T scores from CBCL and Conners rating were analyzed as continuous data using the paired t test between the two groups. A P<0.05 was considered significant. After the Institutional Review Board approval for the study at both CUMC and CHB, the full PANDA study protocol was implemented to perform a pilot feasibility study. Our success rate was 96.7% in obtaining detailed medical and anesthesia records in our historical cohort. The scores for verbal IQ (exposed=106.1±16.3, unexposed=109.2±17.9), performance IQ (exposed=109.1±16.0, unexposed=113.9±15.9), and full IQ (exposed=108.2±14.0, unexposed=112.8±16.8) were comparable between the siblings. There were no differences between the two groups in T scores for any of the NEPSY II subdomains, CBCL, or Conners rating. An abstraction protocol with web-based electronic data capture forms also was developed in conjunction with the International Center for Health Outcomes and Innovation Research (InCHOIR). The pilot study provided useful information for feasibility to recruit the sample size and to obtain relevant clinical data. For the final study protocol, both the neuropsychological battery and the age range for testing were revised. Our results confirmed the feasibility of our study approach and yielded pilot data from neuropsychological testing.

[Development of Markov models for economics evaluation of strategies on hepatitis B vaccination and population-based antiviral treatment in China].

PubMed

Yang, P C; Zhang, S X; Sun, P P; Cai, Y L; Lin, Y; Zou, Y H

2017-07-10

Objective: To construct the Markov models to reflect the reality of prevention and treatment interventions against hepatitis B virus (HBV) infection, simulate the natural history of HBV infection in different age groups and provide evidence for the economics evaluations of hepatitis B vaccination and population-based antiviral treatment in China. Methods: According to the theory and techniques of Markov chain, the Markov models of Chinese HBV epidemic were developed based on the national data and related literature both at home and abroad, including the settings of Markov model states, allowable transitions and initial and transition probabilities. The model construction, operation and verification were conducted by using software TreeAge Pro 2015. Results: Several types of Markov models were constructed to describe the disease progression of HBV infection in neonatal period, perinatal period or adulthood, the progression of chronic hepatitis B after antiviral therapy, hepatitis B prevention and control in adults, chronic hepatitis B antiviral treatment and the natural progression of chronic hepatitis B in general population. The model for the newborn was fundamental which included ten states, i.e . susceptiblity to HBV, HBsAg clearance, immune tolerance, immune clearance, low replication, HBeAg negative CHB, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma (HCC) and death. The susceptible state to HBV was excluded in the perinatal period model, and the immune tolerance state was excluded in the adulthood model. The model for general population only included two states, survive and death. Among the 5 types of models, there were 9 initial states assigned with initial probabilities, and 27 states for transition probabilities. The results of model verifications showed that the probability curves were basically consistent with the situation of HBV epidemic in China. Conclusion: The Markov models developed can be used in economics evaluation of hepatitis B vaccination and treatment for the elimination of HBV infection in China though the structures and parameters in the model have uncertainty with dynamic natures.

Comparison of Genetic Variants in Cancer-Related Genes between Chinese Hui and Han Populations.

PubMed

Tian, Chaoyong; Chen, Zhiqiang; Ma, Xixian; Yang, Ming; Wang, Zhizhong; Dong, Ying; Yang, Ting; Yang, Wenjun

2015-01-01

The Chinese Hui population, as the second largest minority ethnic group in China, may have a different genetic background from Han people because of its unique demographic history. In this study, we aimed to identify genetic differences between Han and Hui Chinese from the Ningxia region of China by comparing eighteen single nucleotide polymorphisms in cancer-related genes. DNA samples were collected from 99 Hui and 145 Han people from the Ningxia Hui Autonomous Region in China, and SNPs were detected using an improved multiplex ligase detection reaction method. Genotyping data from six 1000 Genomes Project population samples (99 Utah residents with northern and western European ancestry (CEU), 107 Toscani in Italy (TSI), 108 Yoruba in Ibadan (YRI), 61 of African ancestry in the southwestern US (ASW), 103 Han Chinese in Beijing (CHB), and 104 Japanese in Tokyo (JPT)) were also included in this study. Differences in the distribution of alleles among the populations were assessed using χ2 tests, and FST was used to measure the degree of population differentiation. We found that the genetic diversity of many SNPs in cancer-related genes in the Hui Chinese in Ningxia was different from that in the Han Chinese in Ningxia. For example, the allele frequencies of four SNPs (rs13361707, rs2274223, rs465498, and rs753955) showed different genetic distributions (p<0.05) between Chinese Ningxia Han and Chinese Ningxia Hui. Five SNPs (rs730506, rs13361707, rs2274223, rs465498 and rs753955) had different FST values (FST>0.000) between the Hui and Han populations. These results suggest that some SNPs associated with cancer-related genes vary among different Chinese ethnic groups. We suggest that population differences should be carefully considered in evaluating cancer risk and prognosis as well as the efficacy of cancer therapy.

Automatic Seizure Detection Based on Morphological Features Using One-Dimensional Local Binary Pattern on Long-Term EEG.

PubMed

Shanir, P P Muhammed; Khan, Kashif Ahmad; Khan, Yusuf Uzzaman; Farooq, Omar; Adeli, Hojjat

2017-12-01

Epileptic neurological disorder of the brain is widely diagnosed using the electroencephalography (EEG) technique. EEG signals are nonstationary in nature and show abnormal neural activity during the ictal period. Seizures can be identified by analyzing and obtaining features of EEG signal that can detect these abnormal activities. The present work proposes a novel morphological feature extraction technique based on the local binary pattern (LBP) operator. LBP provides a unique decimal value to a sample point by weighing the binary outcomes after thresholding the neighboring samples with the present sample point. These LBP values assist in capturing the rising and falling edges of the EEG signal, thus providing a morphologically featured discriminating pattern for epilepsy detection. In the present work, the variability in the LBP values is measured by calculating the sum of absolute difference of the consecutive LBP values. Interquartile range is calculated over the preprocessed EEG signal to provide dispersion measure in the signal. For classification purpose, K-nearest neighbor classifier is used, and the performance is evaluated on 896.9 hours of data from CHB-MIT continuous EEG database. Mean accuracy of 99.7% and mean specificity of 99.8% is obtained with average false detection rate of 0.47/h and sensitivity of 99.2% for 136 seizures.

Epileptic seizure detection from EEG signals with phase-amplitude cross-frequency coupling and support vector machine

NASA Astrophysics Data System (ADS)

Liu, Yang; Wang, Jiang; Cai, Lihui; Chen, Yingyuan; Qin, Yingmei

2018-03-01

As a pattern of cross-frequency coupling (CFC), phase-amplitude coupling (PAC) depicts the interaction between the phase and amplitude of distinct frequency bands from the same signal, and has been proved to be closely related to the brain’s cognitive and memory activities. This work utilized PAC and support vector machine (SVM) classifier to identify the epileptic seizures from electroencephalogram (EEG) data. The entropy-based modulation index (MI) matrixes are used to express the strength of PAC, from which we extracted features as the input for classifier. Based on the Bonn database, which contains five datasets of EEG segments obtained from healthy volunteers and epileptic subjects, a 100% classification accuracy is achieved for identifying seizure ictal from healthy data, and an accuracy of 97.67% is reached in the classification of ictal EEG signals from inter-ictal EEGs. Based on the CHB-MIT database which is a group of continuously recorded epileptic EEGs by scalp electrodes, a 97.50% classification accuracy is obtained and a raising sign of MI value is found at 6s before seizure onset. The classification performance in this work is effective, and PAC can be considered as a useful tool for detecting and predicting the epileptic seizures and providing reference for clinical diagnosis.

Observation of CH A 2X 2Πr and 2Σ--->X 2Πr emissions in gas-phase collisions of fast O(3P) atoms with acetylene

NASA Astrophysics Data System (ADS)

Orient, O. J.; Chutjian, A.; Murad, E.

1995-03-01

Optical emissions in single-collision, beam-beam reactions of fast (3-22-eV translational energy) O(3P) atoms with C2H2 have been measured in the wavelength range 300-850 nm. Two features were observed, one with a peak wavelength at 431 nm, corresponding to the CH A 2X 2Πr transition, and a second weaker emission in the range 380-400 nm corresponding to the B 2Σ--->X 2Πr transition. Both the A-->X and B-->X emissions were fit to a synthetic spectrum of CH(A) at a vibrational temperature Tv of 10 000 K (0.86 eV) and a rotational temperature Tr of approximately 5000 K (0.43 eV); and CH(B) to Tv=2500 K (0.22 eV) and Tr=1000 K (0.09 eV). The energy threshold for the A-->X emission was measured to be 7.3+/-0.4 eV (lab) or 4.5+/-0.2 eV (c.m.). This agrees with the energy threshold of 7.36 eV (lab) for the reaction O(3P)+C2H2-->CH(A)+HCO.

Activating the innate immune response to counter chronic hepatitis B virus infection.

PubMed

Lamb, Camilla; Arbuthnot, Patrick

2016-12-01

Chronic infection with hepatitis B virus (HBV) is endemic to several populous parts of the world, where resulting complicating cirrhosis and hepatocellular carcinoma occur commonly. Licensed drugs to treat the infection have limited curative efficacy, and development of therapies that eliminate all replication intermediates of HBV is a priority. Areas covered: The recent demonstration that the activation of the innate immune response may eradicate HBV from infected hepatocytes has a promising therapeutic application. Small molecule stimulators of Toll-like receptors (TLRs) inhibit replication of woodchuck hepatitis virus in woodchucks and HBV in chimpanzees and mice. Early stage clinical trials using GS-9620, a TLR7 agonist, indicate that this candidate antiviral is well tolerated in humans. Using an alternative approach, triggering the innate immune response with agonists of lymphotoxin-β receptor caused efficient APOBEC-mediated deamination and degradation of viral covalently closed circular DNA. Expert opinion: Eliminating HBV cccDNA from infected individuals would constitute a cure, and has become the focus of intensive research that employs various therapeutic approaches, including gene therapy. Immunomodulation through innate immune activation shows promise for the treatment of chronic infection of HBV (CHB) and, used in combination with other therapeutics, may contribute to the global control of infections and ultimately to the eradication of HBV.

Role of serum hepatitis B virus marker quantitation to differentiate natural history phases of HBV infection.

PubMed

Wang, Li; Zou, Zhi-Qiang; Wang, Kai; Yu, Ji-Guang; Liu, Xiang-Zhong

2016-01-01

The purpose of this study was to characterize roles of serum hepatitis B virus marker quantitation in differentiation of natural phases of HBV infection. A total of 184 chronic hepatitis B (CHB) patients were analyzed retrospectively. Patients were classified into four categories: immune tolerant phase (IT, n = 36), immune clearance phase (IC, n = 81), low-replicative phase (LR, n = 31), and HBeAg-negative hepatitis phase (ENH, n = 36), based on clinical, biochemical, serological, HBV DNA level and histological data. Hepatitis B surface antigen (HBsAg) quantitation in four phases were 4.7 ± 0.2, 3.8 ± 0.5, 2.5 ± 1.2 and 3.4 ± 0.4 log10 IU/mL, respectively. There were significant differences between IT and IC (p < 0.001) and between LR and ENH phases (p < 0.001). Quantitation of hepatitis B e antigen (HBeAg) in IT and IC phases are 1317.9 ± 332.9 and 673.4 ± 562.1 S/CO, respectively (p < 0.001). Hepatitis B core antibody (HBcAb) quantitation in the four groups were 9.48 ± 3.3, 11.7 ± 2.8, 11.2 ± 2.6 and 13.2 ± 2.9 S/CO, respectively. Area under receiver operating characteristic curve (AUCs) of HBsAg and HBeAg at cutoff values of 4.41 log10 IU/mL and 1118.96 S/CO for differentiation of IT and IC phases are 0.984 and 0.828, with sensitivity 94.4 and 85.2 %, specificity 98.7 and 75 %, respectively. AUCs of HBsAg and HBcAb at cutoff values of 3.4 log10 IU/mL and 10.5 S/CO for differentiation of LR and ENT phases are 0.796 and 0.705, with sensitivity 58.1 and 85.7 %, and specificity 94.4 and 46.2 %, respectively. HBsAg quantitation has high predictive value and HBeAg quantitation has moderate predictive value for discriminating IT and IC phase. HBsAg and HBcAb quantitations have moderate predictive values for differentiation of LR and ENH phase.

Transferability and Fine-Mapping of Genome-Wide Associated Loci for Adult Height across Human Populations

PubMed Central

Shriner, Daniel; Adeyemo, Adebowale; Gerry, Norman P.; Herbert, Alan; Chen, Guanjie; Doumatey, Ayo; Huang, Hanxia; Zhou, Jie; Christman, Michael F.; Rotimi, Charles N.

2009-01-01

Human height is the prototypical polygenic quantitative trait. Recently, several genetic variants influencing adult height were identified, primarily in individuals of East Asian (Chinese Han or Korean) or European ancestry. Here, we examined 152 genetic variants representing 107 independent loci previously associated with adult height for transferability in a well-powered sample of 1,016 unrelated African Americans. When we tested just the reported variants originally identified as associated with adult height in individuals of East Asian or European ancestry, only 8.3% of these loci transferred (p-values≤0.05 under an additive genetic model with directionally consistent effects) to our African American sample. However, when we comprehensively evaluated all HapMap variants in linkage disequilibrium (r 2≥0.3) with the reported variants, the transferability rate increased to 54.1%. The transferability rate was 70.8% for associations originally reported as genome-wide significant and 38.0% for associations originally reported as suggestive. An additional 23 loci were significantly associated but failed to transfer because of directionally inconsistent effects. Six loci were associated with adult height in all three groups. Using differences in linkage disequilibrium patterns between HapMap CEU or CHB reference data and our African American sample, we fine-mapped these six loci, improving both the localization and the annotation of these transferable associations. PMID:20027299

[Efficiency of 27-plex single nucleotide polymorphism multiplex system for ancestry inference in different populations].

PubMed

Feng, Xing-Ling; Sun, Qi-Fan; Liu, Hong; Wei, Yi-Liang; DU, Wei-An; Li, Cai-Xia; Chen, Ling; Liu, Chao

2016-04-20

To validate the efficiency of 27-plex single nucleotide polymorphism (SNP) multiplex system for ancestry inference. The 27-plex SNP system was validated for its sensitivity and species specificity. A total of 533 samples were collected from African, Southern Chinese Han, China's ethic minorities (Yi, Hui, Miao, Tibet, and Uygur), European, Central Asian, Western Asian, Southern Asian, Southeast Asian and South American populations for clustering analysis of the genotypes by citing 3 representative continental ancestral groups [East Asia (CHB), Europe (CEU), and Africa (YRI)] from HapMap database. The system sensitivity is 0.125 ng. Twenty and six genotypes were detected in chimpanzee and monkeys, respectively. Except in rs10496971, no more products were found in other animals. The system was capable of differentiating intercontinental populations but not of distinguishing between East Asian and Southeast Asian population or between Southern Chinese Han population and Chinese Ethnic populations (Hui, Miao, Yi and Tibet). This system achieved a 100% accuracy for intercontinental population source inference for 46 blind test samples. 27-plex SNPs multiplex system has a high sensitivity and species specificity and can correctly differentiate the ancestry origins of individuals from African, European and East Asian for criminal case investigation. But this system is not capable of distinguishing subpopulation groups and more specific ancestry-informative markers are needed to improve its recognition of Southeast Asian and Chinese ethnic populations.

Bacillus isolates from the spermosphere of peas and dwarf French beans with antifungal activity against Botrytis cinerea and Pythium species.

PubMed

Walker, R; Powell, A A; Seddon, B

1998-05-01

A range of isolation procedures including washing, sonication and incubation in nutrient broth were used separately and in combination to obtain potential bacterial antagonists to Botrytis cinerea and Pythium mamillatum from the testae and cotyledons of peas and dwarf French beans. Heat treatment was also used to bias this selection towards spore-forming bacteria. Ninety-two bacterial isolates were obtained, 72 of which were provisionally characterized as species of Bacillus. Four of these Bacillus isolates (B3, C1, D4 and J7) displayed distinct antagonism in vitro against Botrytis cinerea and P. mamillatum when screened using dual culture analysis. Further characterization of these antagonists using API 50CHB biochemical profiling identified isolate D4 as Bacillus polymyxa and isolates B3, C1 and J7 as strains of B. subtilis. In vitro screening techniques, using cell-free and heat-killed extracts of liquid cultures against Botrytis cinerea, demonstrated the production of antifungal compounds by these four Bacillus antagonists. With each isolate the antifungal activity was found not to be either exclusively spore-bound nor released entirely into the medium but present in both fractions. The antifungal compounds produced by these isolates were shown to be heat-stable. Their identification, production and release require further study for exploitation as biocontrol systems.

Genetic and Biochemical Diversity among Isolates of Paenibacillus alvei Cultured from Australian Honeybee (Apis mellifera) Colonies

PubMed Central

Djordjevic, Steven P.; Forbes, Wendy A.; Smith, Lisa A.; Hornitzky, Michael A.

2000-01-01

Twenty-five unique CfoI-generated whole-cell DNA profiles were identified in a study of 30 Paenibacillus alvei isolates cultured from honey and diseased larvae collected from honeybee (Apis mellifera) colonies in geographically diverse areas in Australia. The fingerprint patterns were highly variable and readily discernible from one another, which highlighted the potential of this method for tracing the movement of isolates in epidemiological studies. 16S rRNA gene fragments (length, 1,416 bp) for all 30 isolates were enzymatically amplified by PCR and subjected to restriction analysis with DraI, HinfI, CfoI, AluI, FokI, and RsaI. With each enzyme the restriction profiles of the 16S rRNA genes from all 30 isolates were identical (one restriction fragment length polymorphism [RFLP] was observed in the HinfI profile of the 16S rRNA gene from isolate 17), which confirmed that the isolates belonged to the same species. The restriction profiles generated by using DraI, FokI, and HinfI differentiated P. alvei from the phylogenetically closely related species Paenibacillus macerans and Paenibacillus macquariensis. Alveolysin gene fragments (length, 1,555 bp) were enzymatically amplified from some of the P. alvei isolates (19 of 30 isolates), and RFLP were detected by using the enzymes CfoI, Sau3AI, and RsaI. Extrachromosomal DNA ranging in size from 1 to 10 kb was detected in 17 of 30 (57%) P. alvei whole-cell DNA profiles. Extensive biochemical heterogeneity was observed among the 28 P. alvei isolates examined with the API 50CHB system. All of these isolates were catalase, oxidase, and Voges-Proskauer positive and nitrate negative, and all produced acid when glycerol, esculin, and maltose were added. The isolates produced variable results for 16 of the 49 biochemical tests; negative reactions were recorded in the remaining 30 assays. The genetic and biochemical heterogeneity in P. alvei isolates may be a reflection of adaptation to the special habitats in which they originated. PMID:10698777

Genetic and biochemical diversity among isolates of Paenibacillus alvei cultured from Australian honeybee (Apis mellifera) colonies.

PubMed

Djordjevic, S P; Forbes, W A; Smith, L A; Hornitzky, M A

2000-03-01

Twenty-five unique CfoI-generated whole-cell DNA profiles were identified in a study of 30 Paenibacillus alvei isolates cultured from honey and diseased larvae collected from honeybee (Apis mellifera) colonies in geographically diverse areas in Australia. The fingerprint patterns were highly variable and readily discernible from one another, which highlighted the potential of this method for tracing the movement of isolates in epidemiological studies. 16S rRNA gene fragments (length, 1,416 bp) for all 30 isolates were enzymatically amplified by PCR and subjected to restriction analysis with DraI, HinfI, CfoI, AluI, FokI, and RsaI. With each enzyme the restriction profiles of the 16S rRNA genes from all 30 isolates were identical (one restriction fragment length polymorphism [RFLP] was observed in the HinfI profile of the 16S rRNA gene from isolate 17), which confirmed that the isolates belonged to the same species. The restriction profiles generated by using DraI, FokI, and HinfI differentiated P. alvei from the phylogenetically closely related species Paenibacillus macerans and Paenibacillus macquariensis. Alveolysin gene fragments (length, 1, 555 bp) were enzymatically amplified from some of the P. alvei isolates (19 of 30 isolates), and RFLP were detected by using the enzymes CfoI, Sau3AI, and RsaI. Extrachromosomal DNA ranging in size from 1 to 10 kb was detected in 17 of 30 (57%) P. alvei whole-cell DNA profiles. Extensive biochemical heterogeneity was observed among the 28 P. alvei isolates examined with the API 50CHB system. All of these isolates were catalase, oxidase, and Voges-Proskauer positive and nitrate negative, and all produced acid when glycerol, esculin, and maltose were added. The isolates produced variable results for 16 of the 49 biochemical tests; negative reactions were recorded in the remaining 30 assays. The genetic and biochemical heterogeneity in P. alvei isolates may be a reflection of adaptation to the special habitats in which they originated.

Evaluation of miR-216a and miR-217 as Potential Biomarkers of Acute Exocrine Pancreatic Toxicity in Rats.

PubMed

Wang, Jianying; Huang, Wenhu; Thibault, Stephane; Brown, Thomas P; Bobrowski, Walter; Gukasyan, Hovhannes J; Evering, Winston; Hu, Wenyue; John-Baptiste, Annette; Vitsky, Allison

2017-02-01

Detecting and monitoring exocrine pancreatic damage during nonclinical and clinical testing is challenging because classical biomarkers amylase and lipase have limited sensitivity and specificity. Novel biomarkers for drug-induced pancreatic injury are needed to improve safety assessment and reduce late-stage attrition rates. In a series of studies, miR-216a and miR-217 were evaluated as potential biomarkers of acute exocrine pancreatic toxicity in rats. Our results revealed that miR-216a and miR-217 were almost exclusively expressed in rat pancreas and that circulating miR-216a and miR-217 were significantly increased in rats following administration of established exocrine pancreatic toxicants caerulein (CL) and 1-cyano-2-hydroxy-3-butene (CHB) as well as in rats administered a proprietary molecule known to primarily affect the exocrine pancreas. Conversely, neither microRNA was increased in rats administered a proprietary molecule known to cause a lesion at the pancreatic endocrine-exocrine interface (EEI) or in rats administered an established renal toxicant. Compared with amylase and lipase, increases in miR-216a and miR-217 were of greater magnitude, persisted longer, and/or correlated better with microscopic findings within the exocrine pancreas. Our findings demonstrate that in rats, miR-216a and miR-217 are sensitive and specific biomarkers of acute exocrine pancreatic toxicity that may add value to the measurement of classical pancreatic biomarkers.

Genotypic and phenotypic diversity of Alicyclobacillus acidocaldarius isolates.

PubMed

Félix-Valenzuela, L; Guardiola-Avila, I; Burgara-Estrella, A; Ibarra-Zavala, M; Mata-Haro, V

2015-10-01

The fruit juice industry recognizes Alicyclobacillus as a major quality control target micro-organism. In this study, we analysed 19 bacterial isolates to identify Alicyclobacillus species by polymerase chain reaction (PCR) and sequencing analyses. Phenotypic and genomic diversity among isolates were investigated by API 50CHB system and ERIC-PCR (enterobacterial repetitive intergenic consensus-PCR) respectively. All bacterial isolates were identified as Alicyclobacillus acidocaldarius, and almost all showed identical DNA sequences according to their 16S rRNA (rDNA) gene partial sequences. Only few carbohydrates were fermented by A. acidocaldarius isolates, and there was little variability in the biochemical profile. Genotypic fingerprinting of the A. acidocaldarius isolates showed high diversity, and clusters by ERIC-PCR were distinct to those obtained from the 16S rRNA gene phylogenetic tree. There was no correlation between phenotypic and genotypic variability in the A. acidocaldarius isolates analysed in this study. Detection of Alicyclobacillus strains is imperative in fruit concentrates and juices due to the production of guaiacol. Identification of the genera originates rejection of the product by processing industry. However, not all the Alicyclobacillus species are deteriorative and hence the importance to differentiate among them. In this study, partial 16S ribosomal RNA sequence alignment allowed the differentiation of species. In addition, ERIC-PCR was introduced for the genotypic characterization of Alicyclobacillus, as an alternative for differentiation among isolates from the same species. © 2015 The Society for Applied Microbiology.

Patterns of population differentiation of candidate genes for cardiovascular disease.

PubMed

Kullo, Iftikhar J; Ding, Keyue

2007-07-12

The basis for ethnic differences in cardiovascular disease (CVD) susceptibility is not fully understood. We investigated patterns of population differentiation (FST) of a set of genes in etiologic pathways of CVD among 3 ethnic groups: Yoruba in Nigeria (YRI), Utah residents with European ancestry (CEU), and Han Chinese (CHB) + Japanese (JPT). We identified 37 pathways implicated in CVD based on the PANTHER classification and 416 genes in these pathways were further studied; these genes belonged to 6 biological processes (apoptosis, blood circulation and gas exchange, blood clotting, homeostasis, immune response, and lipoprotein metabolism). Genotype data were obtained from the HapMap database. We calculated FST for 15,559 common SNPs (minor allele frequency > or = 0.10 in at least one population) in genes that co-segregated among the populations, as well as an average-weighted FST for each gene. SNPs were classified as putatively functional (non-synonymous and untranslated regions) or non-functional (intronic and synonymous sites). Mean FST values for common putatively functional variants were significantly higher than FST values for nonfunctional variants. A significant variation in FST was also seen based on biological processes; the processes of 'apoptosis' and 'lipoprotein metabolism' showed an excess of genes with high FST. Thus, putative functional SNPs in genes in etiologic pathways for CVD show greater population differentiation than non-functional SNPs and a significant variance of FST values was noted among pairwise population comparisons for different biological processes. These results suggest a possible basis for varying susceptibility to CVD among ethnic groups.

Observation of CH A (sup 2)Delta approaches X (sup 2)Pi(sub r) and B (sup 2)Sigma(sup -) approaches X (sup 2)Pi(sub r) emissions in gas-phase collisions of fast O((sup 3)P) atoms with acetylene

NASA Technical Reports Server (NTRS)

Orient, O. J.; Chutjian, A.; Murad, E.

1995-01-01

Optical emissions in single-collision, beam-beam reactions of fast (3-22 eV translational energy) O(P-3) atoms with C2H2 have been measured in the wavelength range 300-850 nm. Two features were observed, one with a peak wavelength at 431 nm, corresponding to the CH A (sup 2)Delta yields X (sup 2)Pi(sub r) transition, and a second weaker emission in the range 380-400 nm corresponding to the B (sup 2)Sigma(sup -) yields X (sup 2)Pi(sub r) transition. Both the A yields X and B yields X emissions were fit to a synthetic spectrum of CH(A) at a vibrational temperature T(sub v) of 10,000 K (0.86 eV) and a rotational temperature T(r) of approximately 5000 K (0.43 eV); and CH(B) to T(sub v) = 2500 K (0.22 eV) and T(sub r) = 1000 K (0.09 eV). The energy threshold for the A yields X emission was measured to be 7.3 +/- 0.4 eV (lab) or 4.5 +/- 0.2 eV (c.m.). This agrees with the energy threshold of 7.36 eV (lab) for the reaction O(P-3) + C2H2 yields CH(A) + HCO.

Forensic genetic informativeness of an SNP panel consisting of 19 multi-allelic SNPs.

PubMed

Gao, Zehua; Chen, Xiaogang; Zhao, Yuancun; Zhao, Xiaohong; Zhang, Shu; Yang, Yiwen; Wang, Yufang; Zhang, Ji

2018-05-01

Current research focusing on forensic personal identification, phenotype inference and ancestry information on single-nucleotide polymorphisms (SNPs) has been widely reported. In the present study, we focused on tetra-allelic SNPs in the Chinese Han population. A total of 48 tetra-allelic SNPs were screened out from the Chinese Han population of the 1000 Genomes Database, including Chinese Han in Beijing (CHB) and Chinese Han South (CHS). Considering the forensic genetic requirement for the polymorphisms, only 11 tetra-allelic SNPs with a heterozygosity >0.06 were selected for further multiplex panel construction. In order to meet the demands of personal identification and parentage identification, an additional 8 tri-allelic SNPs were combined into the final multiplex panel. To ensure application in the degraded DNA analysis, all the PCR products were designed to be 87-188 bp. Employing multiple PCR reactions and SNaPshot minisequencing, 511 unrelated Chinese Han individuals from Sichuan were genotyped. The combined match probability (CMP), combined discrimination power (CDP), and cumulative probability of exclusion (CPE) of the panel were 6.07 × 10 -11 , 0.9999999999393 and 0.996764, respectively. Based on the population data retrieved from the 1000 Genomes Project, Fst values between Chinese Han in Sichuan (SCH) and all the populations included in the 1000 Genomes Project were calculated. The results indicated that two SNPs in this panel may contain ancestry information and may be used as markers of forensic biogeographical ancestry inference. Copyright © 2018 Elsevier B.V. All rights reserved.

RUNX1 positively regulates the ErbB2/HER2 signaling pathway through modulating SOS1 expression in gastric cancer cells.

PubMed

Mitsuda, Yoshihide; Morita, Ken; Kashiwazaki, Gengo; Taniguchi, Junichi; Bando, Toshikazu; Obara, Moeka; Hirata, Masahiro; Kataoka, Tatsuki R; Muto, Manabu; Kaneda, Yasufumi; Nakahata, Tatsutoshi; Liu, Pu Paul; Adachi, Souichi; Sugiyama, Hiroshi; Kamikubo, Yasuhiko

2018-04-23

The dual function of runt-related transcriptional factor 1 (RUNX1) as an oncogene or oncosuppressor has been extensively studied in various malignancies, yet its role in gastric cancer remains elusive. Up-regulation of the ErbB2/HER2 signaling pathway is frequently-encountered in gastric cancer and contributes to the maintenance of these cancer cells. This signaling cascade is partly mediated by son of sevenless homolog (SOS) family, which function as adaptor proteins in the RTK cascades. Herein we report that RUNX1 regulates the ErbB2/HER2 signaling pathway in gastric cancer cells through transactivating SOS1 expression, rendering itself an ideal target in anti-tumor strategy toward this cancer. Mechanistically, RUNX1 interacts with the RUNX1 binding DNA sequence located in SOS1 promoter and positively regulates it. Knockdown of RUNX1 led to the decreased expression of SOS1 as well as dephosphorylation of ErbB2/HER2, subsequently suppressed the proliferation of gastric cancer cells. We also found that our novel RUNX inhibitor (Chb-M') consistently led to the deactivation of the ErbB2/HER2 signaling pathway and was effective against several gastric cancer cell lines. Taken together, our work identified a novel interaction of RUNX1 and the ErbB2/HER2 signaling pathway in gastric cancer, which can potentially be exploited in the management of this malignancy.

CHRONICLE OF THE "ANGLO-YUGOSLAV CHILDREN'S HOSPITAL" IN SREMSKA KAMENICA.

PubMed

Dobanovački, Dušanka; Mikić, Želimir; Vučković, Nada

2015-01-01

As a peacetime work of Katherine S. Macphail (Glasgow, 1887- St.Andrews, 1974) MB ChB (Bachelor of Medicine and Surgery), the Anglo-Serbian Children's Hospital in Belgrade was established after World War I, and the English-Yugoslav Children's Hospital for Treatment of Osteoarticular Tuberculosis was founded in Sremska Kamenica in 1934. Situated on the Fruška Gora slope, the hospital-sanatorium was a well-equipped medical institution with an operating theatre and x-ray machine providing very advanced therapy, comparable to those in Switzerland and England: aero and heliotherapy, good quality nourishment, etc. In addition, school lessons were organized as well as several types of handwork as the work-therapy. It was a privately owned hospital but almost all the children were treated free of cost. The age for admission was up to 14. During the period from 1934 to 1937, around 458 children underwent hospital treatment, most of them with successful results. During the war years the Sanatorium was closed but after the war it was reactivated. In 1948 by the act of final nationalization of all medical institutions in the communist Yugoslavia, the hospital was transformed into a ward of orthopedic surgery under the supervision of the referent departments in Belgrade and Novi Sad. Today, hospital is out of work and deprived of its humanitarian mission. The building is neglected and in ruins although it has been proclaimed the national treasure by the Regional Institute for Protection of Monuments of Culture.

Levels and temporal trends of toxaphene congeners in beluga whales (Delphinapterus leucas) from the St. Lawrence Estuary, Canada.

PubMed

Gouteux, Bruno; Lebeuf, Michel; Muir, Derek C G; Gagné, Jean-Pierre

2003-10-15

Environmentally relevant toxaphene congeners were determined in blubber samples of stranded beluga whales (Delphinapterus leucas) from the St. Lawrence Estuary (SLE), Canada. The purpose of this study was to evaluate the levels and the temporal trends (1988-1999) of a suite of six chlorobornanes (P26, P40/41, P44, P50, and P62) in the SLE belugas. P26 and P50 mean concentrations were in the same range as those reported for animals living in the Arctic environment suggesting that the atmospheric transport represents the main input of toxaphene to the SLE. A general exponential decline of chlorobornane concentrations in belugas was observed, except for P26 and P50 in males. On average, concentrations decreased by a factor of two in 8.5 years during the 1988-1999 time period. This rate of decline is similar to the reduction of toxaphene emission from agricultural soils in the southern United States reported over the same time period. Some differences in decline rates were observed among the studied CHB congeners. For instance, P62 decreased more rapidly than P26 and P50 in both male and female belugas. Several hypotheses were advanced to explain these differences such as selective metabolism of specific chlorobornanes by SLE belugas or their prey. However, a most likely explanation is the selective degradation of the technical product in soils and atmosphere in the source region.

A Long Short-Term Memory deep learning network for the prediction of epileptic seizures using EEG signals.

PubMed

Tsiouris, Κostas Μ; Pezoulas, Vasileios C; Zervakis, Michalis; Konitsiotis, Spiros; Koutsouris, Dimitrios D; Fotiadis, Dimitrios I

2018-05-17

The electroencephalogram (EEG) is the most prominent means to study epilepsy and capture changes in electrical brain activity that could declare an imminent seizure. In this work, Long Short-Term Memory (LSTM) networks are introduced in epileptic seizure prediction using EEG signals, expanding the use of deep learning algorithms with convolutional neural networks (CNN). A pre-analysis is initially performed to find the optimal architecture of the LSTM network by testing several modules and layers of memory units. Based on these results, a two-layer LSTM network is selected to evaluate seizure prediction performance using four different lengths of preictal windows, ranging from 15 min to 2 h. The LSTM model exploits a wide range of features extracted prior to classification, including time and frequency domain features, between EEG channels cross-correlation and graph theoretic features. The evaluation is performed using long-term EEG recordings from the open CHB-MIT Scalp EEG database, suggest that the proposed methodology is able to predict all 185 seizures, providing high rates of seizure prediction sensitivity and low false prediction rates (FPR) of 0.11-0.02 false alarms per hour, depending on the duration of the preictal window. The proposed LSTM-based methodology delivers a significant increase in seizure prediction performance compared to both traditional machine learning techniques and convolutional neural networks that have been previously evaluated in the literature. Copyright © 2018 Elsevier Ltd. All rights reserved.

CO Self-Shielding as a Mechanism to Make O-16 Enriched Solids in the Solar Nebula

NASA Technical Reports Server (NTRS)

Nuth, Joseph A. III; Johnson, Natasha M.; Hill, Hugh G. M.

2014-01-01

Photochemical self-shielding of CO has been proposed as a mechanism to produce solids observed in the modern, O-16 depleted solar system. This is distinct from the relatively O-16 enriched composition of the solar nebula, as demonstrated by the oxygen isotopic composition of the contemporary sun. While supporting the idea that self-shielding can produce local enhancements in O-16 depleted solids, we argue that complementary enhancements of O-16 enriched solids can also be produced via CO-16 based, Fischer-Tropsch type (FTT) catalytic processes that could produce much of the carbonaceous feedstock incorporated into accreting planetesimals. Local enhancements could explain observed O-16 enrichment in calcium-aluminum-rich inclusions (CAIs), such as those from the meteorite, Isheyevo (CH/CHb), as well as in chondrules from the meteorite, Acfer 214 (CH3). CO selfshielding results in an overall increase in the O-17 and O-18 content of nebular solids only to the extent that there is a net loss of CO-16 from the solar nebula. In contrast, if CO-16 reacts in the nebula to produce organics and water then the net effect of the self-shielding process will be negligible for the average oxygen isotopic content of nebular solids and other mechanisms must be sought to produce the observed dichotomy between oxygen in the Sun and that in meteorites and the terrestrial planets. This illustrates that the formation and metamorphism of rocks and organics need to be considered in tandem rather than as isolated reaction networks.

Student giving health advice to family and friends.

PubMed

Tso, Simon; Yousuf, Asim

2016-06-01

This study explored graduate-entry medical students' experiences of health-advice requests from their family and friends. This was a descriptive thematic analysis study involving a convenience sample of medical students from the University of Warwick 4-year MB ChB graduate-entry medicine programme. Each participating student attended a one-to-one semi-structured interview. Audio recordings of the interviews were transcribed verbatim and analysed thematically. Data saturation of the main themes was achieved following 14 interviews. Of the 14 students, eight (57%) were males and six (43%) were females. Students were asked to advise on a range of human and veterinary health issues. They were prepared to offer advice on health issues that they felt competent to manage: for example, first-aid scenarios that a 'reasonable layperson' or a first-aider would be able to help with. The nature of health advice given by students became increasingly complex as they progressed through their degree programme; however, they generally refrained from giving advice on complex health issues and chose to refer the individual to seek help from competent professionals instead. Previous research highlighted inappropriate advice could delay individuals seeking help from competent professionals, resulting in adverse clinical outcomes; however, we recommend that students should not be discouraged to act as good Samaritans. Instead, educators could help them to explore the professionalism and ethical issues raised by these requests, and the practical ways of handling these requests sensitively through discussion of case scenarios with acceptable and inappropriate behaviours. This study explored graduate-entry medical students' experiences of health-advice requests from their family and friends. © 2015 John Wiley & Sons Ltd.

Major Population Expansion of East Asians Began before Neolithic Time: Evidence of mtDNA Genomes

PubMed Central

Qin, Zhen-Dong; Wang, Yi; Tan, Jing-Ze; Li, Hui; Jin, Li

2011-01-01

It is a major question in archaeology and anthropology whether human populations started to grow primarily after the advent of agriculture, i.e., the Neolithic time, especially in East Asia, which was one of the centers of ancient agricultural civilization. To answer this question requires an accurate estimation of the time of lineage expansion as well as that of population expansion in a population sample without ascertainment bias. In this study, we analyzed all available mtDNA genomes of East Asians ascertained by random sampling, a total of 367 complete mtDNA sequences generated by the 1000 Genome Project, including 249 Chinese (CHB, CHD, and CHS) and 118 Japanese (JPT). We found that major mtDNA lineages underwent expansions, all of which, except for two JPT-specific lineages, including D4, D4b2b, D4a, D4j, D5a2a, A, N9a, F1a1'4, F2, B4, B4a, G2a1 and M7b1'2'4, occurred before 10 kya, i.e., before the Neolithic time (symbolized by Dadiwan Culture at 7.9 kya) in East Asia. Consistent to this observation, the further analysis showed that the population expansion in East Asia started at 13 kya and lasted until 4 kya. The results suggest that the population growth in East Asia constituted a need for the introduction of agriculture and might be one of the driving forces that led to the further development of agriculture. PMID:21998705

Patterns of population differentiation of candidate genes for cardiovascular disease

PubMed Central

Kullo, Iftikhar J; Ding, Keyue

2007-01-01

Background The basis for ethnic differences in cardiovascular disease (CVD) susceptibility is not fully understood. We investigated patterns of population differentiation (FST) of a set of genes in etiologic pathways of CVD among 3 ethnic groups: Yoruba in Nigeria (YRI), Utah residents with European ancestry (CEU), and Han Chinese (CHB) + Japanese (JPT). We identified 37 pathways implicated in CVD based on the PANTHER classification and 416 genes in these pathways were further studied; these genes belonged to 6 biological processes (apoptosis, blood circulation and gas exchange, blood clotting, homeostasis, immune response, and lipoprotein metabolism). Genotype data were obtained from the HapMap database. Results We calculated FST for 15,559 common SNPs (minor allele frequency ≥ 0.10 in at least one population) in genes that co-segregated among the populations, as well as an average-weighted FST for each gene. SNPs were classified as putatively functional (non-synonymous and untranslated regions) or non-functional (intronic and synonymous sites). Mean FST values for common putatively functional variants were significantly higher than FST values for nonfunctional variants. A significant variation in FST was also seen based on biological processes; the processes of 'apoptosis' and 'lipoprotein metabolism' showed an excess of genes with high FST. Thus, putative functional SNPs in genes in etiologic pathways for CVD show greater population differentiation than non-functional SNPs and a significant variance of FST values was noted among pairwise population comparisons for different biological processes. Conclusion These results suggest a possible basis for varying susceptibility to CVD among ethnic groups. PMID:17626638

Implicit associations and compensatory health beliefs in smokers: exploring their role for behaviour and their change through warning labels.

PubMed

Glock, Sabine; Müller, Barbara C N; Krolak-Schwerdt, Sabine

2013-11-01

Smokers might think that the negative effects of smoking can be compensated for by other behaviours, such as doing exercise or eating healthily. This phenomenon is known as compensatory health beliefs (CHBs). Graphic warning labels on cigarette packets emphasize the negative effects of smoking, which may impact CHBs. Research so far has assessed CHBs explicitly only via questionnaires, although implicit cognition might be an important factor in continuing to smoke. This study investigated the impact of graphic warning labels on CHBs, by testing CHBs both implicitly and explicitly. The study had a three-group experimental design. ANOVAs and multiple regression analyses were run on the results. We assessed explicit CHBs among non-smokers, smokers, and smokers confronted with graphic warning labels (N = 107; 47 females, 23.89 years old, 78 daily smokers). Implicit associations between smoking and CHB-specific behaviours (e.g., eating healthy food) were measured using a Single-Target Implicit Association Test. After the experiment, participants were able to choose between a healthy and unhealthy food reward. Non-smokers and smokers differed in explicit CHBs but not in implicit cognitions. Warning labels influenced implicit associations among smokers but did not affect explicit CHBs. Most interestingly, implicit associations and explicit CHBs predicted food choice and smoking among smokers not confronted with warning labels. Graphic warning labels could be used in interventions to inhibit automatic associations between smoking and healthy behaviours. Unlearning implicit cognitions might in turn affect explicit CHBs, thus decreasing their role in reducing the negative feelings caused by smoking. © 2013 The British Psychological Society.

Isolation and Characterization of Gram-Positive Biosurfactant-Producing Halothermophilic Bacilli From Iranian Petroleum Reservoirs

PubMed Central

Zargari, Saeed; Ramezani, Amin; Ostvar, Sassan; Rezaei, Rasool; Niazi, Ali; Ayatollahi, Shahab

2014-01-01

Background: Petroleum reservoirs have long been known as the hosts of extremophilic microorganisms. Some of these microorganisms are known for their potential biotechnological applications, particularly production of extra and intracellular polymers and enzymes. Objectives: Here, 14 petroleum liquid samples from southern Iranian oil reservoirs were screened for presence of biosurfactant‐producing halothermophiles. Materials and Methods: Mixture of the reservoir fluid samples with a minimal growth medium was incubated under an N2 atmosphere in 40°C; 0.5 mL samples were transferred from the aqueous phase to agar plates after 72 hours of incubation; 100 mL cell cultures were prepared using the MSS-1 (mineral salt solution 1) liquid medium with 5% (w/v) NaCl. The time-course samples were analyzed by recording the absorbance at 600 nm using a spectrophotometer. Incubation was carried out in 40°C with mild shaking in aerobic conditions. Thermotolerance was evaluated by growing the isolates at 40, 50, 60 and 70°C with varying NaCl concentrations of 5% and 10% (w/v). Halotolerance was evaluated using NaCl concentrations of 5%, 10%, 12.5% and 15% (w/v) and incubating them at 40°C under aerobic and anaerobic conditions. Different phenotypic characteristics were evaluated, as outlined in Bergey's manual of determinative bacteriology. Comparing 16S rDNA sequences is one of the most powerful tools for classification of microorganisms. Results: Among 34 isolates, 10 demonstrated biosurfactant production and growth at temperatures between 40°C and 70°C in saline media containing 5%‐15% w/v NaCl. Using partial 16S rDNA sequencing (and amplified ribosomal DNA restriction analysis [ARDRA]) and biochemical tests (API tests 20E and 50 CHB), all the 10 isolates proved to be facultative anaerobic, Gram-positive moderate thermohalophiles of the genus Bacillus (B. thermoglucosidasius, B. thermodenitrificans, B. thermoleovorans, B. stearothermophilus and B. licheniformis), exhibiting surface-active behaviors. Conclusions: General patterns include decreasing the thermotolerance with increasing the salt concentrations and also more halotolerance in the aerobic environment compared with anaerobic conditions. The results demonstrated that Iranian petroleum reservoirs enjoy a source of indigenous extremophilic microorganisms with potential applications in microbial enhanced oil recovery and commercial enzyme production. PMID:25485045

Evaluation of dysphagia in early stroke patients by bedside, endoscopic, and electrophysiological methods.

PubMed

Umay, Ebru Karaca; Unlu, Ece; Saylam, Guleser Kılıc; Cakci, Aytul; Korkmaz, Hakan

2013-09-01

We aimed in this study to evaluate dysphagia in early stroke patients using a bedside screening test and flexible fiberoptic endoscopic evaluation of swallowing (FFEES) and electrophysiological evaluation (EE) methods and to compare the effectiveness of these methods. Twenty-four patients who were hospitalized in our clinic within the first 3 months after stroke were included in this study. Patients were evaluated using a bedside screening test [including bedside dysphagia score (BDS), neurological examination dysphagia score (NEDS), and total dysphagia score (TDS)] and FFEES and EE methods. Patients were divided into normal-swallowing and dysphagia groups according to the results of the evaluation methods. Patients with dysphagia as determined by any of these methods were compared to the patients with normal swallowing based on the results of the other two methods. Based on the results of our study, a high BDS was positively correlated with dysphagia identified by FFEES and EE methods. Moreover, the FFEES and EE methods were positively correlated. There was no significant correlation between NEDS and TDS levels and either EE or FFEES method. Bedside screening tests should be used mainly as an initial screening test; then FFEES and EE methods should be combined in patients who show risks. This diagnostic algorithm may provide a practical and fast solution for selected stroke patients.

Mapping of HLA- DQ haplotypes in a group of Danish patients with celiac disease.

PubMed

Lund, Flemming; Hermansen, Mette N; Pedersen, Merete F; Hillig, Thore; Toft-Hansen, Henrik; Sölétormos, György

2015-10-01

A cost-effective identification of HLA- DQ risk haplotypes using the single nucleotide polymorphism (SNP) technique has recently been applied in the diagnosis of celiac disease (CD) in four European populations. The objective of the study was to map risk HLA- DQ haplotypes in a group of Danish CD patients using the SNP technique. Cohort A: Among 65 patients with gastrointestinal symptoms we compared the HLA- DQ2 and HLA- DQ8 risk haplotypes obtained by the SNP technique (method 1) with results based on a sequence specific primer amplification technique (method 2) and a technique used in an assay from BioDiagene (method 3). Cohort B: 128 patients with histologically verified CD were tested for CD risk haplotypes (method 1). Patients with negative results were further tested for sub-haplotypes of HLA- DQ2 (methods 2 and 3). Cohort A: The three applied methods provided the same HLA- DQ2 and HLA- DQ8 results among 61 patients. Four patients were negative for the HLA- DQ2 and HLA- DQ8 haplotypes (method 1) but were positive for the HLA- DQ2.5-trans and HLA- DQ2.2 haplotypes (methods 2 and 3). Cohort B: A total of 120 patients were positive for the HLA- DQ2.5-cis and HLA- DQ8 haplotypes (method 1). The remaining seven patients were positive for HLA- DQ2.5-trans or HLA- DQ2.2 haplotypes (methods 2 and 3). One patient was negative with all three HLA methods. The HLA- DQ risk haplotypes were detected in 93.8% of the CD patients using the SNP technique (method 1). The sensitivity increased to 99.2% by combining methods 1 - 3.

The Olson method for detection of acute myocardial ischemia in patients with coronary occlusion.

PubMed

Lindow, Thomas; Olson, Charles W; Swenne, Cees A; Man, Sumche; Pahlm, Olle

An automated ECG-based method may provide diagnostic support in the management of patients with acute coronary syndrome. The Olson method has previously proved to accurately identify the culprit artery in patients with acute coronary occlusion. The Olson method was applied to 360 patients without acute myocardial ischemia and 52 patients with acute coronary occlusion. This study establishes the normal variation of the Olson wall scores in patients without acute myocardial ischemia, which provides the basis for implementation of the Olson method for triage of patients with acute coronary syndrome. All patients with acute occlusion had Olson wall scores above the upper limit of normal. The Olson method can be used for ischemia detection with very high sensitivity. Future studies are needed to explore specificity in patients with non-ischemic ST elevation. Copyright © 2016 Elsevier Inc. All rights reserved.

Examination of an Electronic Patient Record Display Method to Protect Patient Information Privacy.

PubMed

Niimi, Yukari; Ota, Katsumasa

2017-02-01

Electronic patient records facilitate the provision of safe, high-quality medical care. However, because personnel can view almost all stored information, this study designed a display method using a mosaic blur (pixelation) to temporarily conceal information patients do not want shared. This study developed an electronic patient records display method for patient information that balanced the patient's desire for personal information protection against the need for information sharing among medical personnel. First, medical personnel were interviewed about the degree of information required for both individual duties and team-based care. Subsequently, they tested a mock display method that partially concealed information using a mosaic blur, and they were interviewed about the effectiveness of the display method that ensures patient privacy. Participants better understood patients' demand for confidentiality, suggesting increased awareness of patients' privacy protection. However, participants also indicated that temporary concealment of certain information was problematic. Other issues included the inconvenience of removing the mosaic blur to obtain required information and risk of insufficient information for medical care. Despite several issues with using a display method that temporarily conceals information according to patient privacy needs, medical personnel could accept this display method if information essential to medical safety remains accessible.

Measuring the effectiveness of patient-chosen reminder methods in a private orthodontic practice.

PubMed

Wegrzyniak, Lauren M; Hedderly, Deborah; Chaudry, Kishore; Bollu, Prashanti

2018-05-01

To evaluate the effectiveness of patient-chosen appointment reminder methods (phone call, e-mail, or SMS text) in reducing no-show rates. This was a retrospective case study that determined the correlation between patient-chosen appointment reminder methods and no-show rates in a private orthodontic practice. This study was conducted in a single office location of a multioffice private orthodontic practice using data gathered in 2015. The subjects were patients who self-selected the appointment reminder method (phone call, e-mail, or SMS text). Patient appointment data were collected over a 6-month period. Patient attendance was analyzed with descriptive statistics to determine any significant differences among patient-chosen reminder methods. There was a total of 1193 appointments with an average no-show rate of 2.43% across the three reminder methods. No statistically significant differences ( P = .569) were observed in the no-show rates between the three methods: phone call (3.49%), e-mail (2.68%), and SMS text (1.90%). The electronic appointment reminder methods (SMS text and e-mail) had lower no-show rates compared with the phone call method, with SMS text having the lowest no-show rate of 1.90%. However, since no significant differences were observed between the three patient-chosen reminder methods, providers may want to allow patients to choose their reminder method to decrease no-shows.

Using qualitative methods to understand factors contributing to patient satisfaction among dermatology patients: a systematic review.

PubMed

Gibbons, Caitlin; Singh, Sanminder; Gibbons, Brittany; Clark, Caitlin; Torres, Josefina; Cheng, Michelle Y; Wang, Elizabeth A; Armstrong, April W

2018-05-01

In this systematic review, we aimed to synthesize data that identify factors contributing to patient satisfaction in dermatology care using qualitative methods. We performed a comprehensive search of the literature using the PubMed database for articles published between January 1, 2000 and February 9, 2015. The initial search yielded 186 articles, of which 13 were included after applying inclusion and exclusion criteria. The systematic review of 13 articles included a total of 330 patients. Using in-field observations and semistructured interviews, studies found that qualitative methods and analysis increased the provider's sensitivity to patient needs and enhanced patient care. Analyses using qualitative methods found increased patient satisfaction in their healthcare provider is associated with (1) confidence in the provider's diagnosis, (2) perception of patient-centered, individualized recommendations and (3) quality of patient education and provider explanation during a visit. Patient satisfaction is measured using either quantitative or qualitative methods. Quantitative methods result in standardized data that often does not capture the nuances of patient experience. In contrast, qualitative methodology is integral to gathering patient perspectives on patient care and satisfaction and should be included in future research models.

Spatial learning of female mice: a role of the mineralocorticoid receptor during stress and the estrous cycle

PubMed Central

ter Horst, Judith P.; Kentrop, Jiska; Arp, Marit; Hubens, Chantal J.; de Kloet, E. Ron; Oitzl, Melly S.

2013-01-01

Corticosterone facilitates behavioral adaptation to a novel experience in a coordinate manner via mineralocorticoid (MR) and glucocorticoid receptors (GR). Initially, MR mediates corticosterone action on appraisal processes, risk assessment and behavioral flexibility and then, GR activation promotes consolidation of the new information into memory. Here, we studied on the circular holeboard (CHB) the spatial performance of female mice with genetic deletion of MR from the forebrain (MRCaMKCre) and their wild type littermates (MRflox/flox mice) over the estrous cycle and in response to an acute stressor. The estrous cycle had no effect on the spatial performance of MRflox/flox mice and neither did the acute stressor. However, the MRCaMKCre mutants needed significantly more time to find the exit and made more hole visit errors than the MRflox/flox mice, especially when in proestrus and estrus. In addition, stressed MRCaMKCre mice in estrus had a shorter exit latency than the control estrus MRCaMKCre mice. About 70% of the female MRCaMKCre and MRflox/flox mice used a hippocampal (spatial, extra maze cues) rather than the caudate nucleus (stimulate-response, S-R, intra-maze cue) strategy and this preference did neither change over the estrous cycle nor after stress. However, stressed MRCaMKCre mice using the S-R strategy needed significantly more time to find the exit hole as compared to the spatial strategy using mice suggesting that the MR could be needed for the stress-induced strategy switch toward a spatial strategy. In conclusion, the results suggest that loss of MR interferes with performance of a spatial task especially when estrogen levels are high suggesting a strong interaction between stress and sex hormones. PMID:23754993

Spatial learning of female mice: a role of the mineralocorticoid receptor during stress and the estrous cycle.

PubMed

Ter Horst, Judith P; Kentrop, Jiska; Arp, Marit; Hubens, Chantal J; de Kloet, E Ron; Oitzl, Melly S

2013-01-01

Corticosterone facilitates behavioral adaptation to a novel experience in a coordinate manner via mineralocorticoid (MR) and glucocorticoid receptors (GR). Initially, MR mediates corticosterone action on appraisal processes, risk assessment and behavioral flexibility and then, GR activation promotes consolidation of the new information into memory. Here, we studied on the circular holeboard (CHB) the spatial performance of female mice with genetic deletion of MR from the forebrain (MR(CaMKCre)) and their wild type littermates (MR(flox/flox) mice) over the estrous cycle and in response to an acute stressor. The estrous cycle had no effect on the spatial performance of MR(flox/flox) mice and neither did the acute stressor. However, the MR(CaMKCre) mutants needed significantly more time to find the exit and made more hole visit errors than the MR(flox/flox) mice, especially when in proestrus and estrus. In addition, stressed MR(CaMKCre) mice in estrus had a shorter exit latency than the control estrus MR(CaMKCre) mice. About 70% of the female MR(CaMKCre) and MR(flox/flox) mice used a hippocampal (spatial, extra maze cues) rather than the caudate nucleus (stimulate-response, S-R, intra-maze cue) strategy and this preference did neither change over the estrous cycle nor after stress. However, stressed MR(CaMKCre) mice using the S-R strategy needed significantly more time to find the exit hole as compared to the spatial strategy using mice suggesting that the MR could be needed for the stress-induced strategy switch toward a spatial strategy. In conclusion, the results suggest that loss of MR interferes with performance of a spatial task especially when estrogen levels are high suggesting a strong interaction between stress and sex hormones.

HapMap tagSNP transferability in multiple populations: general guidelines

PubMed Central

Xing, Jinchuan; Witherspoon, David J.; Watkins, W. Scott; Zhang, Yuhua; Tolpinrud, Whitney; Jorde, Lynn B.

2008-01-01

This PDF receipt will only be used as the basis for generating PubMed Central (PMC) documents. PMC documents will be made available for review after conversion (approx. 2–3 weeks time). Any corrections that need to be made will be done at that time. No materials will be released to PMC without the approval of an author. Only the PMC documents will appear on PubMed Central -- this PDF Receipt will not appear on PubMed Central. Linkage disequilibrium (LD) has received much recent attention because of its value in localizing disease-causing genes. Due to the extensive LD between neighboring loci in the human genome, it is believed that a subset of the single nucleotide polymorphisms in a region (tagSNPs) can be selected to capture most of the remaining SNP variants. In this study, we examined LD patterns and HapMap tagSNP transferability in more than 300 individuals. A South Indian and an African Mbuti Pygmy population sample were included to evaluate the performance of HapMap tagSNPs in geographically distinct and genetically isolated populations. Our results show that HapMap tagSNPs selected with r2 >= 0.8 can capture more than 85% of the SNPs in populations that are from the same continental group. Combined tagSNPs from HapMap CEU and CHB+JPT serve as the best reference for the Indian sample. The HapMap YRI are a sufficient reference for tagSNP selection in the Pygmy sample. In addition to our findings, we reviewed over 25 recent studies of tagSNP transferability and propose a general guideline for selecting tagSNPs from HapMap populations. PMID:18482828

A Noninvasive Body Setup Method for Radiotherapy by Using a Multimodal Image Fusion Technique

PubMed Central

Zhang, Jie; Chen, Yunxia; Wang, Chenchen; Chu, Kaiyue; Jin, Jianhua; Huang, Xiaolin; Guan, Yue; Li, Weifeng

2017-01-01

Purpose: To minimize the mismatch error between patient surface and immobilization system for tumor location by a noninvasive patient setup method. Materials and Methods: The method, based on a point set registration, proposes a shift for patient positioning by integrating information of the computed tomography scans and that of optical surface landmarks. An evaluation of the method included 3 areas: (1) a validation on a phantom by estimating 100 known mismatch errors between patient surface and immobilization system. (2) Five patients with pelvic tumors were considered. The tumor location errors of the method were measured using the difference between the proposal shift of cone-beam computed tomography and that of our method. (3) The collected setup data from the evaluation of patients were compared with the published performance data of other 2 similar systems. Results: The phantom verification results showed that the method was capable of estimating mismatch error between patient surface and immobilization system in a precision of <0.22 mm. For the pelvic tumor, the method had an average tumor location error of 1.303, 2.602, and 1.684 mm in left–right, anterior–posterior, and superior–inferior directions, respectively. The performance comparison with other 2 similar systems suggested that the method had a better positioning accuracy for pelvic tumor location. Conclusion: By effectively decreasing an interfraction uncertainty source (mismatch error between patient surface and immobilization system) in radiotherapy, the method can improve patient positioning precision for pelvic tumor. PMID:29333959

Sampling for Patient Exit Interviews: Assessment of Methods Using Mathematical Derivation and Computer Simulations.

PubMed

Geldsetzer, Pascal; Fink, Günther; Vaikath, Maria; Bärnighausen, Till

2018-02-01

(1) To evaluate the operational efficiency of various sampling methods for patient exit interviews; (2) to discuss under what circumstances each method yields an unbiased sample; and (3) to propose a new, operationally efficient, and unbiased sampling method. Literature review, mathematical derivation, and Monte Carlo simulations. Our simulations show that in patient exit interviews it is most operationally efficient if the interviewer, after completing an interview, selects the next patient exiting the clinical consultation. We demonstrate mathematically that this method yields a biased sample: patients who spend a longer time with the clinician are overrepresented. This bias can be removed by selecting the next patient who enters, rather than exits, the consultation room. We show that this sampling method is operationally more efficient than alternative methods (systematic and simple random sampling) in most primary health care settings. Under the assumption that the order in which patients enter the consultation room is unrelated to the length of time spent with the clinician and the interviewer, selecting the next patient entering the consultation room tends to be the operationally most efficient unbiased sampling method for patient exit interviews. © 2016 The Authors. Health Services Research published by Wiley Periodicals, Inc. on behalf of Health Research and Educational Trust.

Image and Imaging an Emergency Department: Expense and Benefit of Different Quality Assessment Methods

PubMed Central

Pfortmueller, Carmen Andrea; Keller, Michael; Mueller, Urs; Zimmermann, Heinz; Exadaktylos, Aristomenis Konstantinos

2013-01-01

Introduction. In this era of high-tech medicine, it is becoming increasingly important to assess patient satisfaction. There are several methods to do so, but these differ greatly in terms of cost, time, and labour and external validity. The aim of this study is to describe and compare the structure and implementation of different methods to assess the satisfaction of patients in an emergency department. Methods. The structure and implementation of the different methods to assess patient satisfaction were evaluated on the basis of a 90-minute standardised interview. Results. We identified a total of six different methods in six different hospitals. The average number of patients assessed was 5012, with a range from 230 (M5) to 20 000 patients (M2). In four methods (M1, M3, M5, and M6), the questionnaire was composed by a specialised external institute. In two methods, the questionnaire was created by the hospital itself (M2, M4).The median response rate was 58.4% (range 9–97.8%). With a reminder, the response rate increased by 60% (M3). Conclusion. The ideal method to assess patient satisfaction in the emergency department setting is to use a patient-based, in-emergency department-based assessment of patient satisfaction, planned and guided by expert personnel. PMID:23984073

Multidisciplinary ALS Telemedicine Care: The Store and Forward Method.

PubMed

Pulley, Michael T; Brittain, Rebecca; Hodges, Wayne; Frazier, Christine; Miller, Leslie; Matyjasik-Liggett, Maria; Maurer, Susan; Peters, Melissa; Solomon, Kimberly; Berger, Alan R

2018-05-26

ALS patients benefit from multidisciplinary care in an ALS clinic. We studied whether multidisciplinary care of ALS patients using the store and forward method of telemedicine was feasible and acceptable to patients and providers. ALS patients seen in the UF Jacksonville ALS clinic were eligible. A trained telemedicine nurse performed and recorded a multidisciplinary assessment of the patient in their home. Clinic team members reviewed the assessments, provided recommendations and the clinic director discussed the plan with the patient via videoconference. Patient and provider satisfaction was evaluated using surveys. 18 patients completed a total of 27 telemedicine visits. Patient satisfaction was excellent and provider satisfaction was very good. The store and forward method of telemedicine is an acceptable alternative to live telemedicine for the multidisciplinary care of ALS patients. This method of care may improve access to multidisciplinary care for this patient population. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Peritonitis related to percutaneous endoscopic gastrostomy using the direct method for cancer patients.

PubMed

Osera, Shozo; Yano, Tomonori; Odagaki, Tomoyuki; Oono, Yasuhiro; Ikematsu, Hiroaki; Ohtsu, Atsushi; Kaneko, Kazuhiro

2015-10-01

Percutaneous endoscopic gastrostomy (PEG) using the direct method is generally indicated for cancer patients. However, there are little available data about peritonitis related to this method. The aim of this retrospective analysis was to assess peritonitis related to PEG using the direct method in patients with cancer. We assessed the prevalence of peritonitis and the relationship between peritonitis and patients' backgrounds, as well as the clinical course after peritonitis. Between December 2008 and December 2011, peritonitis was found in 9 (2.1 %) of 421 patients. Of the 9 patients with peritonitis, 4 had received PEG prior to chemoradiotherapy. Emergency surgical drainage was required in 1 patient, and the remaining 8 recovered with conservative treatment. Peritonitis occurred within 8 days of PEG for 8 of the 9 patients and occurred within 2 days of suture removal for 4 of the 9 patients. Peritonitis related to PEG using the direct method was less frequent for cancer patients. Peritonitis tended to occur within a few days after removal of securing suture and in patients with palliative stage.

[Significance of bacteria detection with filter paper method on diagnosis of diabetic foot wound infection].

PubMed

Zou, X H; Zhu, Y P; Ren, G Q; Li, G C; Zhang, J; Zou, L J; Feng, Z B; Li, B H

2017-02-20

Objective: To evaluate the significance of bacteria detection with filter paper method on diagnosis of diabetic foot wound infection. Methods: Eighteen patients with diabetic foot ulcer conforming to the study criteria were hospitalized in Liyuan Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from July 2014 to July 2015. Diabetic foot ulcer wounds were classified according to the University of Texas diabetic foot classification (hereinafter referred to as Texas grade) system, and general condition of patients with wounds in different Texas grade was compared. Exudate and tissue of wounds were obtained, and filter paper method and biopsy method were adopted to detect the bacteria of wounds of patients respectively. Filter paper method was regarded as the evaluation method, and biopsy method was regarded as the control method. The relevance, difference, and consistency of the detection results of two methods were tested. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of filter paper method in bacteria detection were calculated. Receiver operating characteristic (ROC) curve was drawn based on the specificity and sensitivity of filter paper method in bacteria detection of 18 patients to predict the detection effect of the method. Data were processed with one-way analysis of variance and Fisher's exact test. In patients tested positive for bacteria by biopsy method, the correlation between bacteria number detected by biopsy method and that by filter paper method was analyzed with Pearson correlation analysis. Results: (1) There were no statistically significant differences among patients with wounds in Texas grade 1, 2, and 3 in age, duration of diabetes, duration of wound, wound area, ankle brachial index, glycosylated hemoglobin, fasting blood sugar, blood platelet count, erythrocyte sedimentation rate, C-reactive protein, aspartate aminotransferase, serum creatinine, and urea nitrogen (with F values from 0.029 to 2.916, P values above 0.05), while there were statistically significant differences among patients with wounds in Texas grade 1, 2, and 3 in white blood cell count and alanine aminotransferase (with F values 4.688 and 6.833 respectively, P <0.05 or P <0.01). (2) According to the results of biopsy method, 6 patients were tested negative for bacteria, and 12 patients were tested positive for bacteria, among which 10 patients were with bacterial number above 1×10(5)/g, and 2 patients with bacterial number below 1×10(5)/g. According to the results of filter paper method, 8 patients were tested negative for bacteria, and 10 patients were tested positive for bacteria, among which 7 patients were with bacterial number above 1×10(5)/g, and 3 patients with bacterial number below 1×10(5)/g. There were 7 patients tested positive for bacteria both by biopsy method and filter paper method, 8 patients tested negative for bacteria both by biopsy method and filter paper method, and 3 patients tested positive for bacteria by biopsy method but negative by filter paper method. Patients tested negative for bacteria by biopsy method did not tested positive for bacteria by filter paper method. There was directional association between the detection results of two methods ( P =0.004), i. e. if result of biopsy method was positive, result of filter paper method could also be positive. There was no obvious difference in the detection results of two methods ( P =0.250). The consistency between the detection results of two methods was ordinary (Kappa=0.68, P =0.002). (3) The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of filter paper method in bacteria detection were 70%, 100%, 1.00, 0.73, and 83.3%, respectively. Total area under ROC curve of bacteria detection by filter paper method in 18 patients was 0.919 (with 95% confidence interval 0-1.000, P =0.030). (4) There were 13 strains of bacteria detected by biopsy method, with 5 strains of Acinetobacter baumannii, 5 strains of Staphylococcus aureus, 1 strain of Pseudomonas aeruginosa, 1 strain of Streptococcus bovis, and 1 strain of bird Enterococcus . There were 11 strains of bacteria detected by filter paper method, with 5 strains of Acinetobacter baumannii, 3 strains of Staphylococcus aureus, 1 strain of Pseudomonas aeruginosa, 1 strain of Streptococcus bovis, and 1 strain of bird Enterococcus . Except for Staphylococcus aureus, the sensitivity and specificity of filter paper method in the detection of the other 4 bacteria were all 100%. The consistency between filter paper method and biopsy method in detecting Acinetobacter baumannii was good (Kappa=1.00, P <0.01), while that in detecting Staphylococcus aureus was ordinary (Kappa=0.68, P <0.05). (5) There was no obvious correlation between the bacteria number of wounds detected by filter paper method and that by biopsy method ( r =0.257, P =0.419). There was obvious correlation between the bacteria numbers detected by two methods in wounds with Texas grade 1 and 2 (with r values as 0.999, P values as 0.001). There was no obvious correlation between the bacteria numbers detected by two methods in wounds with Texas grade 3 ( r =-0.053, P =0.947). Conclusions: The detection result of filter paper method is in accordance with that of biopsy method in the determination of bacterial infection, and it is of great importance in the diagnosis of local infection of diabetic foot wound.

Quantifying the proportion of general practice and low-acuity patients in the emergency department.

PubMed

Nagree, Yusuf; Camarda, Vanessa J; Fatovich, Daniel M; Cameron, Peter A; Dey, Ian; Gosbell, Andrew D; McCarthy, Sally M; Mountain, David

2013-06-17

To accurately estimate the proportion of patients presenting to the emergency department (ED) who may have been suitable to be seen in general practice. Using data sourced from the Emergency Department Information Systems for the calendar 2013s 2009 to 2011 at three major tertiary hospitals in Perth, Western Australia, we compared four methods for calculating general practice-type patients. These were the validated Sprivulis method, the widely used Australasian College for Emergency Medicine method, a discharge diagnosis method developed by the Tasmanian Department of Human and Health Services, and the Australian Institute of Health and Welfare (AIHW) method. General practice-type patient attendances to EDs, estimated using the four methods. All methods except the AIHW method showed that 10%-12% of patients attending tertiary EDs in Perth may have been suitable for general practice. These attendances comprised 3%-5% of total ED length of stay. The AIHW method produced different results (general practice-type patients accounted for about 25% of attendances, comprising 10%-11% of total ED length of stay). General practice-type patient attendances were not evenly distributed across the week, with proportionally more patients presenting during weekday daytime (08:00-17:00) and proportionally fewer overnight (00:00-08:00). This suggests that it is not a lack of general practitioners that drives patients to the ED, as weekday working hours are the time of greatest GP availability. The estimated proportion of general practice-type patients attending the EDs of Perth's major hospitals is 10%-12%, and this accounts for < 5% of the total ED length of stay. The AIHW methodology overestimates the actual proportion of general practice-type patient attendances.

Respiratory mechanics by least squares fitting in mechanically ventilated patients: application on flow-limited COPD patients.

PubMed

Volta, Carlo A; Marangoni, Elisabetta; Alvisi, Valentina; Capuzzo, Maurizia; Ragazzi, Riccardo; Pavanelli, Lina; Alvisi, Raffaele

2002-01-01

Although computerized methods of analyzing respiratory system mechanics such as the least squares fitting method have been used in various patient populations, no conclusive data are available in patients with chronic obstructive pulmonary disease (COPD), probably because they may develop expiratory flow limitation (EFL). This suggests that respiratory mechanics be determined only during inspiration. Eight-bed multidisciplinary ICU of a teaching hospital. Eight non-flow-limited postvascular surgery patients and eight flow-limited COPD patients. Patients were sedated, paralyzed for diagnostic purposes, and ventilated in volume control ventilation with constant inspiratory flow rate. Data on resistance, compliance, and dynamic intrinsic positive end-expiratory pressure (PEEPi,dyn) obtained by applying the least squares fitting method during inspiration, expiration, and the overall breathing cycle were compared with those obtained by the traditional method (constant flow, end-inspiratory occlusion method). Our results indicate that (a) the presence of EFL markedly decreases the precision of resistance and compliance values measured by the LSF method, (b) the determination of respiratory variables during inspiration allows the calculation of respiratory mechanics in flow limited COPD patients, and (c) the LSF method is able to detect the presence of PEEPi,dyn if only inspiratory data are used.

Innovative research methods for studying treatments for rare diseases: methodological review.

PubMed

Gagne, Joshua J; Thompson, Lauren; O'Keefe, Kelly; Kesselheim, Aaron S

2014-11-24

To examine methods for generating evidence on health outcomes in patients with rare diseases. Methodological review of existing literature. PubMed, Embase, and Academic Search Premier searched for articles describing innovative approaches to randomized trial design and analysis methods and methods for conducting observational research in patients with rare diseases. We assessed information related to the proposed methods, the specific rare disease being studied, and outcomes from the application of the methods. We summarize methods with respect to their advantages in studying health outcomes in rare diseases and provide examples of their application. We identified 46 articles that proposed or described methods for studying patient health outcomes in rare diseases. Articles covered a wide range of rare diseases and most (72%) were published in 2008 or later. We identified 16 research strategies for studying rare disease. Innovative clinical trial methods minimize sample size requirements (n=4) and maximize the proportion of patients who receive active treatment (n=2), strategies crucial to studying small populations of patients with limited treatment choices. No studies describing unique methods for conducting observational studies in patients with rare diseases were identified. Though numerous studies apply unique clinical trial designs and considerations to assess patient health outcomes in rare diseases, less attention has been paid to innovative methods for studying rare diseases using observational data. © Gagne et al 2014.

Screw-Wire Osteo-Traction: An Adjunctive or Alternative Method of Anatomical Reduction of Multisegment Midfacial Fractures? A Description of Technique and Prospective Study of 40 Patients

PubMed Central

O'Regan, Barry; Devine, Maria; Bhopal, Sats

2013-01-01

Stable anatomical fracture reduction and segment control before miniplate fixation can be difficult to achieve in comminuted midfacial fractures. Fracture mobilization and reduction methods include Gillies elevation, malar hook, and Dingman elevators. No single method is used universally. Disadvantages include imprecise segment alignment and poor segment stability/control. We have employed screw-wire osteo-traction (SWOT) to address this problem. A literature review revealed two published reports. The aims were to evaluate the SWOT technique effectiveness as a fracture reduction method and to examine rates of revision fixation and plate removal. We recruited 40 consecutive patients requiring open reduction and internal fixation of multisegment midfacial fractures (2009–2012) and employed miniplate osteosynthesis in all patients. SWOT was used as a default reduction method in all patients. The rates of successful fracture reduction achieved by SWOT alone or in combination and of revision fixation and plate removal, were used as outcome indices of the reduction method effectiveness. The SWOT technique achieved satisfactory anatomical reduction in 27/40 patients when used alone. Other reduction methods were also used in 13/40 patients. No patient required revision fixation and three patients required late plate removal. SWOT can be used across the midface fracture pattern in conjunction with other methods or as a sole reduction method before miniplate fixation. PMID:24436763

Patients admitted to hospital after suicide attempt with violent methods compared to patients with deliberate self-poisoning -a study of background variables, somatic and psychiatric health and suicidal behavior.

PubMed

Persett, Per Sverre; Grimholt, Tine K; Ekeberg, Oivind; Jacobsen, Dag; Myhren, Hilde

2018-01-24

In Norway, there are about 550 suicides recorded each year. The number of suicide attempts is 10-15 times higher. Suicide attempt is a major risk factor for suicide, in particular when violent methods are used. Suicide attempts with violent methods have hardly been studied in Norway. This study describes demographic, psychiatric and somatic health in patients admitted to somatic hospitals in Norway after suicide attempt by violent methods compared with suicide attempters using deliberate self-poisoning (DSP). Patients admitted to somatic hospital after suicide attempt aged > 18 years were included in a prospective cohort study, enrolled from December 2010 to April 2015. Demographics (gender, age, marital and living condition, educational and employment status), previous somatic and psychological health were registered. Patients who had used violent methods were compared with patients admitted after suicide attempt by DSP. The study included 80 patients with violent methods and 81 patients with DSP (mean age both groups 42 yrs.). Violent methods used were cutting (34%), jumping from heights (32%), hanging (14%), others (10%), shooting (7%) and drowning (4%). Patients with violent methods had more often psychosis than patients admitted with DSP (14% vs 4%, p <  0.05), less anxiety disorders (4% vs 19%, p <  0.01) and less affective disorders (21% vs. 36%, p <  0.05). There were no significant differences between the numbers of patients who received psychiatric treatment at the time of the suicide attempt (violent 55% versus DSP 48%) or reported previous suicide attempt, 58% in patients with violent methods and 47% in DSP. Patients with violent methods stayed longer in hospital (14.3 (mean 8.3-20.3) vs. 2.3 (mean 1.6-3.1) days, p <  0.001), stayed longer in intensive care unit (5 days vs. 0.5 days, p <  0.001) and were in need of longer mechanical ventilation (1.4 vs 0.1 days, p <  0.001). Patients with violent methods had more often psychosis, less anxiety disorders and affective disorders than patients with DSP. Psychiatric treatment before the attempt and previous suicide attempt was not significantly different between the groups and about half of the patients in both groups were in psychiatric treatment at the time of the suicide attempt.

[Clinical effect of three dimensional human body scanning system BurnCalc in the evaluation of burn wound area].

PubMed

Lu, J; Wang, L; Zhang, Y C; Tang, H T; Xia, Z F

2017-10-20

Objective: To validate the clinical effect of three dimensional human body scanning system BurnCalc developed by our research team in the evaluation of burn wound area. Methods: A total of 48 burn patients treated in the outpatient department of our unit from January to June 2015, conforming to the study criteria, were enrolled in. For the first 12 patients, one wound on the limbs or torso was selected from each patient. The stability of the system was tested by 3 attending physicians using three dimensional human body scanning system BurnCalc to measure the area of wounds individually. For the following 36 patients, one wound was selected from each patient, including 12 wounds on limbs, front torso, and side torso, respectively. The area of wounds was measured by the same attending physician using transparency tracing method, National Institutes of Health (NIH) Image J method, and three dimensional human body scanning system BurnCalc, respectively. The time for getting information of 36 wounds by three methods was recorded by stopwatch. The stability among the testers was evaluated by the intra-class correlation coefficient (ICC). Data were processed with randomized blocks analysis of variance and Bonferroni test. Results: (1) Wound area of patients measured by three physicians using three dimensional human body scanning system BurnCalc was (122±95), (121±95), and (123±96) cm(2,) respectively, and there was no statistically significant difference among them ( F =1.55, P >0.05). The ICC among 3 physicians was 0.999. (2) The wound area of limbs of patients measured by transparency tracing method, NIH Image J method, and three dimensional human body scanning system BurnCalc was (84±50), (76±46), and (84±49) cm(2,) respectively. There was no statistically significant difference in the wound area of limbs of patients measured by transparency tracing method and three dimensional human body scanning system BurnCalc ( P >0.05). The wound area of limbs of patients measured by NIH Image J method was smaller than that measured by transparency tracing method and three dimensional human body scanning system BurnCalc (with P values below 0.05). There was no statistically significant difference in the wound area of front torso of patients measured by transparency tracing method, NIH Image J method, and three dimensional human body scanning system BurnCalc ( F =0.33, P >0.05). The wound area of side torso of patients measured by transparency tracing method, NIH Image J method, and three dimensional human body scanning system BurnCalc was (169±88), (150±80), and (169±86) cm(2,) respectively. There was no statistically significant difference in the wound area of side torso of patients measured by transparency tracing method and three dimensional human body scanning system BurnCalc ( P >0.05). The wound area of side torso of patients measured by NIH Image J method was smaller than that measured by transparency tracing method and three dimensional human body scanning system BurnCalc (with P values below 0.05). (3) The time for getting information of wounds of patients by transparency tracing method, NIH Image J method, and three dimensional human body scanning system BurnCalc was (77±14), (10±3), and (9±3) s, respectively. The time for getting information of wounds of patients by transparency tracing method was longer than that by NIH Image J method and three dimensional human body scanning system BurnCalc (with P values below 0.05). The time for getting information of wounds of patients by three dimensional human body scanning system BurnCalc was close to that by NIH Image J method ( P >0.05). Conclusions: The three dimensional human body scanning system BurnCalc is stable and can accurately evaluate the wound area on limbs and torso of burn patients.

[The clinical value of sentinel lymph node detection in laryngeal and hypopharyngeal carcinoma patients with clinically negative neck by methylene blue method and radiolabeled tracer method].

PubMed

Zhao, Xin; Xiao, Dajiang; Ni, Jianming; Zhu, Guochen; Yuan, Yuan; Xu, Ting; Zhang, Yongsheng

2014-11-01

To investigate the clinical value of sentinel lymph node (SLN) detection in laryngeal and hypopharyngeal carcinoma patients with clinically negative neck (cN0) by methylene blue method, radiolabeled tracer method and combination of these two methods. Thirty-three patients with cN0 laryngeal carcinoma and six patients with cN0 hypopharyngeal carcinoma underwent SLN detection using both of methylene blue and radiolabeled tracer method. All these patients were accepted received the injection of radioactive isotope 99 Tc(m)-sulfur colloid (SC) and methylene blue into the carcinoma before surgery, then all these patients underwent intraopertive lymphatic mapping with a handheld gamma-detecting probe and blue-dyed SLN. After the mapping of SLN, selected neck dissections and tumor resections were peformed. The results of SLN detection by radiolabeled tracer, dye and combination of both methods were compared. The detection rate of SLN by radiolabeled tracer, methylene blue and combined method were 89.7%, 79.5%, 92.3% respectively. The number of detected SLN was significantly different between radiolabeled tracer method and combined method, and also between methylene blue method and combined method. The detection rate of methylene blue and radiolabeled tracer method were significantly different from combined method (P < 0.05). Nine patients were found to have lymph node metastasis by final pathological examination. The accuracy and negative rate of SLN detection of the combined method were 97.2% and 11.1%. The combined method using radiolabeled tracer and methylene blue can improve the detection rate and accuracy of sentinel lymph node detection. Furthermore, sentinel lymph node detection can accurately represent the cervical lymph node status in cN0 laryngeal and hypopharyngeal carcinoma.

Low complication rate of sellar reconstruction by artificial dura mater during endoscopic endonasal transsphenoidal surgery.

PubMed

Ye, Yuanliang; Wang, Fuyu; Zhou, Tao; Luo, Yi

2017-12-01

To evaluate effect of sellar reconstruction during pituitary adenoma resection surgery by the endoscopic endonasal transsphenoidal approach using artificial cerebral dura mater patch.This was a retrospective study of 1281 patients who underwent endoscopic transsphenoidal resection for the treatment of pituitary adenomas between December 2006 and May 2014 at the Neurosurgery Department of the People's Liberation Army General Hospital. The patients were classified into 4 grades according to intraoperative cerebrospinal fluid (CSF) leakage site. All patients were followed up for 3 months by telephone and outpatient visits.One thousand seventy three (83.7%) patients underwent sellar reconstruction using artificial dura matter patched outside the sellar region (method A), 106 (8.3%) using artificial dura matter patched inside the sellar region (method B), and 102 (8.0%) using artificial dura matter and a mucosal flap (method C). Method A was used for grade 0-1 leakage, method B for grade 1 to 2 leakage, and method C for grade 2 to 3 leakage. During the 3-month follow-up, postoperative CSF leakage was observed in 7 patients (0.6%): 2 among patients who underwent method B (1.9%) and 5 among those who underwent method C (4.9%). Meningitis was diagnosed in 13 patients (1.0%): 2 among patients who underwent method A (0.2%), 4 among those who underwent method B (3.8%), and 7 among those who underwent method C (6.7%).Compared with other reconstruction methods, sellar reconstruction surgery that only use artificial dura mater as repair material had a low rate of complications. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Awareness of dysgeusia and gustatory tests in patients undergoing chemotherapy for breast cancer.

PubMed

Kuba, Sayaka; Fujiyama, Rie; Yamanouchi, Kosho; Morita, Michi; Sakimura, Chika; Hatachi, Toshiko; Matsumoto, Megumi; Yano, Hiroshi; Takatsuki, Mitsuhisa; Hayashida, Naomi; Nagayasu, Takeshi; Eguchi, Susumu

2018-05-12

We analyzed the prevalence of gustatory test abnormalities in breast cancer (BC) patients undergoing chemotherapy. We enrolled 43 BC patients undergoing chemotherapy and 38 BC patients who had never undergone chemotherapy (control group). Two gustatory tests were conducted: an instillation method examining the threshold for four basic taste stimuli and an electrogustometry method measuring the threshold for perception with electric stimulation at the front two-thirds of the tongue (cranial nerve VII) and at the back third of the tongue (cranial nerve IX). The results of the two gustatory tests and clinicopathological factors were compared between the chemotherapy and control groups and between patients with and without awareness of dysgeusia in the chemotherapy group. In the chemotherapy group, 19 (44%) patients were aware of dysgeusia and 8 (19%) had hypogeusia using the instillation method. Although more patients had parageusia in the chemotherapy than control group, no significant differences in the results of the two gustatory tests were observed. Patients with dysgeusia awareness had a higher threshold at cranial nerve IX using the electrogustometry method than those without dysgeusia awareness; no significant differences in hypogeusia were observed using the instillation method. In fact, 74% (14/19) of patients with dysgeusia awareness could identify the four tastes accurately using the instillation method. Similar results were observed for the instillation and electrogustometry methods at cranial nerve VII. While approximately half of the chemotherapy patients were aware of dysgeusia, 81% (35/43) of them could accurately identify the four basic tastes using the instillation method.

Effect of patient selection method on provider group performance estimates.

PubMed

Thorpe, Carolyn T; Flood, Grace E; Kraft, Sally A; Everett, Christine M; Smith, Maureen A

2011-08-01

Performance measurement at the provider group level is increasingly advocated, but different methods for selecting patients when calculating provider group performance have received little evaluation. We compared 2 currently used methods according to characteristics of the patients selected and impact on performance estimates. We analyzed Medicare claims data for fee-for-service beneficiaries with diabetes ever seen at an academic multispeciality physician group in 2003 to 2004. We examined sample size, sociodemographics, clinical characteristics, and receipt of recommended diabetes monitoring in 2004 for the groups of patients selected using 2 methods implemented in large-scale performance initiatives: the Plurality Provider Algorithm and the Diabetes Care Home method. We examined differences among discordantly assigned patients to determine evidence for differential selection regarding these measures. Fewer patients were selected under the Diabetes Care Home method (n=3558) than the Plurality Provider Algorithm (n=4859). Compared with the Plurality Provider Algorithm, the Diabetes Care Home method preferentially selected patients who were female, not entitled because of disability, older, more likely to have hypertension, and less likely to have kidney disease and peripheral vascular disease, and had lower levels of predicted utilization. Diabetes performance was higher under Diabetes Care Home method, with 67% versus 58% receiving >1 A1c tests, 70% versus 65% receiving ≥1 low-density lipoprotein (LDL) test, and 38% versus 37% receiving an eye examination. The method used to select patients when calculating provider group performance may affect patient case mix and estimated performance levels, and warrants careful consideration when comparing performance estimates.

Long-Term Follow-Up on the Donor Foot After Thumb Reconstruction Using Big Toe Wrap-Around Flap in Two Different Operation Methods.

PubMed

Ma, Zhi-Guo; Guo, Yong-Jun; Yan, Hou-Jun; Li, Qi-Ming; Ma, Bin

2017-02-01

The function of the donor foot has been affected after using big toe wrap-around flap for thumb reconstruction. A modified operation method has been developed to reduce the adverse effect on the donor foot. The current study compared the long-term effect of the classic and the modified operation methods on the donor foot. Gait analysis was carried out, including how the patient walked, the walking speed and walking distance, and how the patient jumped and ran. Plantar pressure was measured while the patient was standing and moving. A total of 45 patients who received the 2 different operation methods were included. The follow-up time was 4-10 years with a mean of 6.5 years. Various degrees of complications occurred for the 21 patients who received the classic operation method. For these patients, plantar pressure of the donor foot was obviously different comparing with the healthy unaffected foot while the patient was standing or walking. For the 24 patients who received the modified operation method, no obvious complications were observed and the plantar pressure of the donor foot and the healthy unaffected foot was similar while the patient was standing or walking. In conclusion, both the classic and the modified operation methods have affected the function of the donor foot after using the big toe wrap-around flap for thumb reconstruction. However, the donor foot was less affected when the modified operation method was used.

Continuous Subcutaneous Insulin Infusion as an Effective Method of Desensitization Therapy for Diabetic Patients with Insulin Allergy: A 4-year Single-center Experience.

PubMed

Yuan, Tao; Zhao, Weigang; Wang, Lianglu; Dong, Yingyue; Li, Naishi

2016-11-01

This article summarizes our experiences in the application of continuous subcutaneous insulin infusion (CSII) as a method of rapid desensitization therapy for diabetic patients with insulin allergy that was subsequently switched to a regimen of multiple-dose injections for long-term insulin therapy. The clinical data of 11 diabetic patients with insulin allergy in Peking Union Medical College Hospital from April 1, 2008, through December 31, 2011, were retrospectively analyzed. All 11 conditions were diagnosed by case history, skin testing, determination of serum specific anti-insulin IgE, and reaction to withdrawal of insulin. Seven patients accepted the traditional injection method of desensitization, and 5 patients accepted CSII with the protocol designed for this study (1 patient accepted CSII after failure by the formal method). Six of the 7 patients who accepted the traditional method and all 5 patients who accepted CSII had successful results. All 5 patients in the CSII group switched to a regimen of multiple dosage injections. In a survey of 28 nurses, both experienced nurses and practical nurses preferred to use CSII as the method of desensitization. It is feasible and effective for diabetic patients with insulin allergy to use CSII as a method of rapid desensitization with subsequent switching to a regimen of multiple-dose injections for long-term insulin therapy. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

SU-F-J-06: Optimized Patient Inclusion for NaF PET Response-Based Biopsies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roth, A; Harmon, S; Perk, T

Purpose: A method to guide mid-treatment biopsies using quantitative [F-18]NaF PET/CT response is being investigated in a clinical trial. This study aims to develop methodology to identify patients amenable to mid-treatment biopsy based on pre-treatment imaging characteristics. Methods: 35 metastatic prostate cancer patients had NaF PET/CT scans taken prior to the start of treatment and 9–12 weeks into treatment. For mid-treatment biopsy targeting, lesions must be at least 1.5 cm{sup 3} and located in a clinically feasible region (lumbar/sacral spine, pelvis, humerus, or femur). Three methods were developed based on number of lesions present prior to treatment: a feasibility-restricted method,more » a location-restricted method, and an unrestricted method. The feasibility restricted method only utilizes information from lesions meeting biopsy requirements in the pre-treatment scan. The unrestricted method accounts for all lesions present in the pre-treatment scan. For each method, optimized classification cutoffs for candidate patients were determined. Results: 13 of the 35 patients had enough lesions at the mid-treatment for biopsy candidacy. Of 1749 lesions identified in all 35 patients at mid-treatment, only 9.8% were amenable to biopsy. Optimizing the feasibility-restricted method required 4 lesions at pre-treatment meeting volume and region requirements for biopsy, resulting patient identification sensitivity of 0.8 and specificity of 0.7. Of 6 false positive patients, only one patient lacked lesions for biopsy. Restricting for location alone showed poor results (sensitivity 0.2 and specificity 0.3). The optimized unrestricted method required patients have at least 37 lesions in pretreatment scan, resulting in a sensitivity of 0.8 and specificity of 0.8. There were 5 false positives, only one lacked lesions for biopsy. Conclusion: Incorporating the overall pre-treatment number of NaF PET/CT identified lesions provided best prediction for identifying candidate patients for mid-treatment biopsy. This study provides validity for prediction-based inclusion criteria that can be extended to various clinical trial scenarios. Funded by Prostate Cancer Foundation.« less

A comparison of indocyanine green fluorescence imaging plus blue dye and blue dye alone for sentinel node navigation surgery in breast cancer patients.

PubMed

Hirano, Akira; Kamimura, Mari; Ogura, Kaoru; Kim, Naomi; Hattori, Akinori; Setoguchi, Yumika; Okubo, Fumie; Inoue, Hiroaki; Miyamoto, Reiko; Kinoshita, Jun; Fujibayashi, Mariko; Shimizu, Tadao

2012-12-01

To evaluate two methods of sentinel node navigation surgery (SNNS) using blue dye with and without indocyanine green (ICG) fluorescence imaging (FI) to determine the usefulness of combined ICG and blue dye. Between 2005 and 2010, a total of 501 patients underwent SNNS in our hospital. Detection of sentinel lymph node (SLN) was performed with sulfan blue (SB) alone until 2008 and with a combination of SB and ICG-FI since 2009. ICG 5 mg and SB 15 mg were injected in the subareolar region, and FI was obtained by a fluorescence imaging device. We attempted to identify SLNs in 393 patients by SB alone and in 108 patients by a combination of SB and FI. The mean number of SLNs detected was 1.6 (0-5) for SB alone and 2.2 (1-6) for the combination method. The SLN identification rate was 95.7 % for SB alone and 100 % for the combination method so that the combination was significantly superior to SB in terms of the identification rate (p = 0.0037). In patients who received the combination method, detection of SLN was made through only SB in 1 patient, only ICG in 8 patients, and both in 99 patients. Lymph node metastasis was found in 56 patients with SB alone and in 16 patients with the combination method. Recurrence of an axillary node was observed in 3 patients (0.8 %) with SB alone and in no patients with the combination method. ICG-FI is a useful method and is especially recommended in cases where no radiotracers are available.

The development of a patient-specific method for physiotherapy goal setting: a user-centered design.

PubMed

Stevens, Anita; Köke, Albère; van der Weijden, Trudy; Beurskens, Anna

2018-08-01

To deliver client-centered care, physiotherapists need to identify the patients' individual treatment goals. However, practical tools for involving patients in goal setting are lacking. The purpose of this study was to improve the frequently used Patient-Specific Complaints instrument in Dutch physiotherapy, and to develop it into a feasible method to improve physiotherapy goal setting. An iterative user-centered design was conducted in co-creation with the physiotherapists and patients, in three phases. Their needs and preferences were identified by means of group meetings and questionnaires. The new method was tested in several field tests in physiotherapy practices. Four main objectives for improvement were formulated: clear instructions for the administration procedure, targeted use across the physiotherapy process, client-activating communication skills, and a client-centered attitude of the physiotherapist. A theoretical goal-setting framework and elements of shared decision making were integrated into the new-called, Patient-Specific Goal-setting method, together with a practical training course. The user-centered approach resulted in a goal-setting method that is fully integrated in the physiotherapy process. The new goal-setting method contributes to a more structured approach to goal setting and enables patient participation and goal-oriented physiotherapy. Before large-scale implementation, its feasibility in physiotherapy practice needs to be investigated. Implications for rehabilitation Involving patients and physiotherapists in the development and testing of a goal-setting method, increases the likelihood of its feasibility in practice. The integration of a goal-setting method into the physiotherapy process offers the opportunity to focus more fully on the patient's goals. Patients should be informed about the aim of every step of the goal-setting process in order to increase their awareness and involvement. Training physiotherapists to use a patient-specific method for goal setting is crucial for a correct application.

Winograd Method Versus Winograd Method With Electrocoagulation in the Treatment of Ingrown Toenails.

PubMed

Acar, Erdinc

An important component of the Winograd surgical method for an ingrown toenail is total excision of the associated germinal matrix. However, this might not always be accomplished with the procedure. We hypothesized that the surgical results might be improved by adding electrocoagulation of the germinal matrix to the Winograd method. The objective of the present study was to compare the recurrence, satisfaction, and complication rates of the Winograd method with those of the Winograd method with electrocoagulation. We retrospectively evaluated the records of 102 patients with single Heifetz stage 2 or 3 ingrown toenails who had undergone surgery from January 2013 to October 2014 using 1 of these 2 methods. Of the 102 patients, 50 (49%) underwent the Winograd method and 52 (51%) underwent the Winograd method with electrocoagulation. The mean follow-up period of our patients was 12 (range 6 to 22) months. An ingrown toenail recurred in 3 patients (6%) in the Winograd group and in no patient in the Winograd with electrocoagulation group (p = .04). Among the patients in the Winograd group, 46 (92.0%) were satisfied or very satisfied. Among the patients in the Winograd plus electrocoagulation group, 49 (94.2%) were satisfied or very satisfied (p = .04). No complications developed in either group. In conclusion, the Winograd method for ingrown toenails results in high satisfaction rates, low recurrence rates, and low complication rates. The addition of electrocoagulation of the germinal matrix to the Winograd method could result in even lower recurrence rates, while maintaining high patient satisfaction and without increasing the risk of complications. Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Real-Time Tracking of Knee Adduction Moment in Patients with Knee Osteoarthritis

PubMed Central

Kang, Sang Hoon; Lee, Song Joo; Zhang, Li-Qun

2014-01-01

Background The external knee adduction moment (EKAM) is closely associated with the presence, progression, and severity of knee osteoarthritis (OA). However, there is a lack of convenient and practical method to estimate and track in real-time the EKAM of patients with knee OA for clinical evaluation and gait training, especially outside of gait laboratories. New Method A real-time EKAM estimation method was developed and applied to track and investigate the EKAM and other knee moments during stepping on an elliptical trainer in both healthy subjects and a patient with knee OA. Results Substantial changes were observed in the EKAM and other knee moments during stepping in the patient with knee OA. Comparison with Existing Method(s) This is the first study to develop and test feasibility of real-time tracking method of the EKAM on patients with knee OA using 3-D inverse dynamics. Conclusions The study provides us an accurate and practical method to evaluate in real-time the critical EKAM associated with knee OA, which is expected to help us to diagnose and evaluate patients with knee OA and provide the patients with real-time EKAM feedback rehabilitation training. PMID:24361759

Significance of ultrasound in the diagnosis and treatment of achilles tendon rupture.

PubMed

Poposka, A; Georgieva, D; Dzoleva-Tolevska, R

2012-01-01

The aim of this study is to show the importance of ultrasound method in the diagnosis of Achilles tendon rupture, the choice of method of treatment and monitoring of treatment using the same method. Between 1999 and 2009, 134 patients with Achilles tendon rupture were referred to our Clinic. 66 patients (with a mean age of 38 years) were treated with surgical suture followed by plaster immobilization for a period of 8 weeks. 68 patients (with a mean age of 42 years) were treated conservatively with plaster immobilization for a period of 8 weeks. The follow-up in both groups of patients was 2 years. During the clinical and ultrasound monitoring of the patients it was proved that repeated rupture of the same tendon occurs on average within 12 months. Return to sports activities showed in 57% of the conservatively treated patients and in 55% of surgically treated patients. The patients with Achilles tendon rupture were treated at our Clinic with previously standardized protocol which, besides the clinical examination, used the ultrasound method. Ultrasound examination is a very important method in the diagnosis and the choice of the method of treatment, as well as in the evaluation of results in patients with Achilles tendon rupture, either in operative or conservative treatment.

Comparing two methods of thoracoscopic sympathectomy for palmar hyperhidrosis.

PubMed

Ibrahim, Magdi; Allam, Abdulla

2014-09-01

Hyperhidrosis can cause significant professional and social handicaps. Thoracic endoscopic sympathectomy has become the surgical technique of choice for treating intractable palmar hyperhidrosis and can be performed through multiple ports or a single port. This prospective study compares outcomes between the two methods. The study followed 71 consecutive patients who underwent video-assisted sympathectomy for palmar hyperhidrosis between January 2008 and June 2012. In all patients, the procedure was bilateral and performed in one stage. The multiple-port method was used in 35 patients (group A) and the single-port method in 36 patients (group B). Preoperative, intraoperative, and postoperative variables; morbidity, recurrence; and survival were compared in both groups. The procedure was successful in 100% of the patients; none experienced a recurrence of palmar hyperhidrosis, Horner syndrome (oculosympathetic palsy), or serious postoperative complications, and none died. No patients required conversion to an open procedure. Residual minimal pneumothorax occurred in two patients (5.7%) in group A and in one patient (2.8%) in group B. Minimal hemothorax occurred in one patient (2.9%) in group A and in three patients (8.3%) in group B. Compensatory hyperhidrosis occurred in seven patients (20%) in group A and in eight patients (22.2%) in group B. No difference was found between the multiple- and single-port methods. Both are effective, safe minimally invasive procedures that permanently improve quality of life in patients with palmar hyperhidrosis.

Estimating patient-specific and anatomically correct reference model for craniomaxillofacial deformity via sparse representation

PubMed Central

Wang, Li; Ren, Yi; Gao, Yaozong; Tang, Zhen; Chen, Ken-Chung; Li, Jianfu; Shen, Steve G. F.; Yan, Jin; Lee, Philip K. M.; Chow, Ben; Xia, James J.; Shen, Dinggang

2015-01-01

Purpose: A significant number of patients suffer from craniomaxillofacial (CMF) deformity and require CMF surgery in the United States. The success of CMF surgery depends on not only the surgical techniques but also an accurate surgical planning. However, surgical planning for CMF surgery is challenging due to the absence of a patient-specific reference model. Currently, the outcome of the surgery is often subjective and highly dependent on surgeon’s experience. In this paper, the authors present an automatic method to estimate an anatomically correct reference shape of jaws for orthognathic surgery, a common type of CMF surgery. Methods: To estimate a patient-specific jaw reference model, the authors use a data-driven method based on sparse shape composition. Given a dictionary of normal subjects, the authors first use the sparse representation to represent the midface of a patient by the midfaces of the normal subjects in the dictionary. Then, the derived sparse coefficients are used to reconstruct a patient-specific reference jaw shape. Results: The authors have validated the proposed method on both synthetic and real patient data. Experimental results show that the authors’ method can effectively reconstruct the normal shape of jaw for patients. Conclusions: The authors have presented a novel method to automatically estimate a patient-specific reference model for the patient suffering from CMF deformity. PMID:26429255

Anti-dsDNA antibodies in systemic lupus erythematosus: A combination of two quantitative methods and the ANA pattern is the most efficient strategy of detection.

PubMed

Almeida González, Delia; Roces Varela, Alfredo; Marcelino Rodríguez, Itahisa; González Vera, Alexander; Delgado Sánchez, Mónica; Aznar Esquivel, Antonio; Casañas Rodríguez, Carlos; Cabrera de León, Antonio

2015-12-01

Several methods have been used to measure anti-double-stranded DNA auto-antibody (anti-dsDNA). Our aim was to determine the most efficient strategy to test anti-dsDNA in systemic lupus erythematosus (SLE). In this study, anti-dsDNA and anti-nuclear antibody (ANA) tests were requested for 644 patients. Anti-dsDNA was tested by RIA, ELISA and CLIA in all patients. The results indicated that 78 patients had a positive anti-dsDNA test according to at least one of the methods. After a 3-year follow-up period only 26 patients were diagnosed with SLE. We evaluated each method and combination of methods. Specificity and positive predictive value (PPV) increased with the number of assay methods used (p=0.002 for trend), and PPV was 100% in patients whose results were positive by all three anti-dsDNA assay methods. The proportion of anti-dsDNA-positive patients who had SLE was highest (82%; p b 0.001) among those with a homogeneous pattern of ANA staining, followed by those with a speckled pattern. In ANA positive patients, when only RIA was considered, 59% of anti-dsDNA-positive patients had SLE, but when RIA and CLIA were both considered, all patients with positive results on both tests had SLE. The combination of RIA+CLIA in patients with homogeneous and speckled ANA staining showed a similar cost and higher sensitivity than RIA alone in ANA positive patients (p b 0.001). We conclude that the most efficient strategy was to combine simultaneously two quantitative and sensitive methods but only in patients with a homogeneous or speckled pattern of ANA staining. This approach maximized specificity and PPV, and reduced costs. Copyright © 2015 Elsevier B.V. All rights reserved.

Multi-criteria clinical decision support: A primer on the use of multiple criteria decision making methods to promote evidence-based, patient-centered healthcare.

PubMed

Dolan, James G

2010-01-01

Current models of healthcare quality recommend that patient management decisions be evidence-based and patient-centered. Evidence-based decisions require a thorough understanding of current information regarding the natural history of disease and the anticipated outcomes of different management options. Patient-centered decisions incorporate patient preferences, values, and unique personal circumstances into the decision making process and actively involve both patients along with health care providers as much as possible. Fundamentally, therefore, evidence-based, patient-centered decisions are multi-dimensional and typically involve multiple decision makers.Advances in the decision sciences have led to the development of a number of multiple criteria decision making methods. These multi-criteria methods are designed to help people make better choices when faced with complex decisions involving several dimensions. They are especially helpful when there is a need to combine "hard data" with subjective preferences, to make trade-offs between desired outcomes, and to involve multiple decision makers. Evidence-based, patient-centered clinical decision making has all of these characteristics. This close match suggests that clinical decision support systems based on multi-criteria decision making techniques have the potential to enable patients and providers to carry out the tasks required to implement evidence-based, patient-centered care effectively and efficiently in clinical settings.The goal of this paper is to give readers a general introduction to the range of multi-criteria methods available and show how they could be used to support clinical decision-making. Methods discussed include the balance sheet, the even swap method, ordinal ranking methods, direct weighting methods, multi-attribute decision analysis, and the analytic hierarchy process (AHP).

Multi-criteria clinical decision support: A primer on the use of multiple criteria decision making methods to promote evidence-based, patient-centered healthcare

PubMed Central

Dolan, James G.

2010-01-01

Current models of healthcare quality recommend that patient management decisions be evidence-based and patient-centered. Evidence-based decisions require a thorough understanding of current information regarding the natural history of disease and the anticipated outcomes of different management options. Patient-centered decisions incorporate patient preferences, values, and unique personal circumstances into the decision making process and actively involve both patients along with health care providers as much as possible. Fundamentally, therefore, evidence-based, patient-centered decisions are multi-dimensional and typically involve multiple decision makers. Advances in the decision sciences have led to the development of a number of multiple criteria decision making methods. These multi-criteria methods are designed to help people make better choices when faced with complex decisions involving several dimensions. They are especially helpful when there is a need to combine “hard data” with subjective preferences, to make trade-offs between desired outcomes, and to involve multiple decision makers. Evidence-based, patient-centered clinical decision making has all of these characteristics. This close match suggests that clinical decision support systems based on multi-criteria decision making techniques have the potential to enable patients and providers to carry out the tasks required to implement evidence-based, patient-centered care effectively and efficiently in clinical settings. The goal of this paper is to give readers a general introduction to the range of multi-criteria methods available and show how they could be used to support clinical decision-making. Methods discussed include the balance sheet, the even swap method, ordinal ranking methods, direct weighting methods, multi-attribute decision analysis, and the analytic hierarchy process (AHP) PMID:21394218

Determination of glycated hemoglobin in patients with advanced liver disease

PubMed Central

Lahousen, Theresa; Hegenbarth, Karin; Ille, Rottraut; Lipp, Rainer W.; Krause, Robert; Little, Randie R.; Schnedl, Wolfgang J.

2004-01-01

AIM: To evaluate the glycated hemoglobin (HbA 1c) determination methods and to determine fructosamine in patients with chronic hepatitis, compensated cirrhosis and in patients with chronic hepatitis treated with ribavirin. METHODS: HbA1c values were determined in 15 patients with compensated liver cirrhosis and in 20 patients with chronic hepatitis using the ion-exchange high performance liquid chromatography and the immunoassay methods. Fructosamine was determined using nitroblue tetrazolium. RESULTS: Forty percent of patients with liver cirrhosis had HbA1c results below the non-diabetic reference range by at least one HbA1c method, while fructosamine results were either within the reference range or elevated. Twenty percent of patients with chronic hepatitis (hepatic fibrosis) had HbA1c results below the non -diabetic reference range by at least one HbA1c method. In patients with chronic hepatitis treated with ribavirin, 50% of HbA1c results were below the non-diabetic reference using at least one of the HbA1c methods. CONCLUSION: Only evaluated in context with all liver function parameters as well as a red blood count including reticulocytes, HbA 1c results should be used in patients with advanced liver disease. HbA 1c and fructosamine measurements should be used with caution when evaluating long-term glucose control in patients with hepatic cirrhosis or in patients with chronic hepatitis and ribavirin treatment. PMID:15259084

Nutritional status in patients with active inflammatory bowel disease: prevalence of malnutrition and methods for routine nutritional assessment.

PubMed

Mijac, Dragana D; Janković, Goran L J; Jorga, Jagoda; Krstić, Miodrag N

2010-08-01

Malnutrition is a common feature of inflammatory bowel disease (IBD). There are numerous methods for the assessment of nutritional status, but the gold standard has not yet been established. The aims of the study were to estimate the prevalence of undernutrition and to evaluate methods for routine nutritional assessment of active IBD patients. Twenty-three patients with active Crohn disease, 53 patients with active ulcerative colitis and 30 controls were included in the study. The nutritional status was assessed by extensive anthropometric measurements, percentage of weight loss in the past 1-6 months and biochemical markers of nutrition. All investigated nutritional parameters were significantly different in IBD patients compared to control subjects, except MCV, tryglicerides and serum total protein level. Serum albumin level and body mass index (BMI) were the most predictive parameters of malnutrition. According to different assessment methods the prevalence of undernutrition and severe undernutrition in patients with active IBD were 25.0%-69.7% and 1.3%-31.6%, respectively, while in the control subjects no abnormalities have been detected. There was no statistically significant difference of nutritional parameters between UC and CD patients except lower mid-arm muscle circumference in UC group. Malnutrition is common in IBD patients. BMI and serum albumin are simple and convenient methods for the assessment of the nutritional status in IBD patients. Further studies with larger group of patients are necessary to elucidate the prevalence of malnutrition and the most accurate assessment methods in IBD patients.

Quality of life among dermatology patients: a systematic review of investigations using qualitative methods.

PubMed

Singh, Sanminder; Ehsani-Chimeh, Nazanin; Kornmehl, Heather; Armstrong, April W

2017-07-13

Quality of life may be assessed using quantitative or qualitative methods. Quantitative methods are commonly used in research settings; however, they may fail to capture the full range of patient experiences and impact on quality of life. Qualitative methods may be used to address this limitation. In this systematic review, we aim to synthesize data from articles utilizing qualitative methods to assess quality of life in dermatology patients. We performed a systematic review search using the MEDLINE, EMBASE, and SCOPUS databases. The search was conducted using the following search criteria: ("Dermatology" [MeSH]) AND ("Quality of Life" [MeSH]), AND ("Qualitative Research" [MeSH]), searching literature spanning from January 1, 1946- October 5, 2016. The systematic review of 15 articles included 533 dermatology patients. Patients expressed frustration over the unpredictability of disease symptoms and having to compensate for the subsequent limitations by altering their daily routines. Patients also reported profound helplessness due to chronic skin disease and social isolation in an effort to hide their disease. Patients noted the patient-provider relationship as a source of support and information exchange, with the goal to form easy to use treatment plans that met both physician and patient expectations. Qualitative assessment of patient quality of life can provide new insights into the patient experience and the impact of their skin disease. Qualitative methodology may capture meaningful information that may be overlooked by quantitative methods, and it should be included in quality of life research.

Current Trends in Robot-Assisted Upper-Limb Stroke Rehabilitation: Promoting Patient Engagement in Therapy.

PubMed

Blank, Amy A; French, James A; Pehlivan, Ali Utku; O'Malley, Marcia K

2014-09-01

Stroke is one of the leading causes of long-term disability today; therefore, many research efforts are focused on designing maximally effective and efficient treatment methods. In particular, robotic stroke rehabilitation has received significant attention for upper-limb therapy due to its ability to provide high-intensity repetitive movement therapy with less effort than would be required for traditional methods. Recent research has focused on increasing patient engagement in therapy, which has been shown to be important for inducing neural plasticity to facilitate recovery. Robotic therapy devices enable unique methods for promoting patient engagement by providing assistance only as needed and by detecting patient movement intent to drive to the device. Use of these methods has demonstrated improvements in functional outcomes, but careful comparisons between methods remain to be done. Future work should include controlled clinical trials and comparisons of effectiveness of different methods for patients with different abilities and needs in order to inform future development of patient-specific therapeutic protocols.

[Development of Patient Transfer Techniques based on Postural-stability Principles for the Care Helpers in Nursing Homes and Evaluation of Effectiveness].

PubMed

Ma, Ryewon; Jung, Dukyoo

2016-02-01

This study was done to develop a postural-stability patient transfer technique for care helpers in nursing homes and to evaluate its effectiveness. Four types of patient transfer techniques (Lifting towards the head board of the bed, turning to the lateral position, sitting upright on the bed, transferring from wheel chair to bed) were practiced in accordance with the following three methods; Care helpers habitually used transfer methods (Method 1), patient transfer methods according to care helper standard textbooks (Method 2), and a method developed by the author ensuring postural-stability (Method 3). The care helpers' muscle activity and four joint angles were measured. The collected data were analyzed using the program SPSS Statistic 21.0. To differentiate the muscle activity and joint angle, the Friedman test was executed and the post-hoc analysis was conducted using the Wilcoxon Signed Rank test. Muscle activity was significantly lower during Method 3 compared to Methods 1 and 2. In addition, the joint angle was significantly lower for the knee and shoulder joint angle while performing Method 3 compared to Methods 1 and 2. Findings indicate that using postural-stability patient transfer techniques can contribute to the prevention of musculoskeletal disease which care helpers suffer from due to physically demanding patient care in nursing homes.

A comparison study of size-specific dose estimate calculation methods.

PubMed

Parikh, Roshni A; Wien, Michael A; Novak, Ronald D; Jordan, David W; Klahr, Paul; Soriano, Stephanie; Ciancibello, Leslie; Berlin, Sheila C

2018-01-01

The size-specific dose estimate (SSDE) has emerged as an improved metric for use by medical physicists and radiologists for estimating individual patient dose. Several methods of calculating SSDE have been described, ranging from patient thickness or attenuation-based (automated and manual) measurements to weight-based techniques. To compare the accuracy of thickness vs. weight measurement of body size to allow for the calculation of the size-specific dose estimate (SSDE) in pediatric body CT. We retrospectively identified 109 pediatric body CT examinations for SSDE calculation. We examined two automated methods measuring a series of level-specific diameters of the patient's body: method A used the effective diameter and method B used the water-equivalent diameter. Two manual methods measured patient diameter at two predetermined levels: the superior endplate of L2, where body width is typically most thin, and the superior femoral head or iliac crest (for scans that did not include the pelvis), where body width is typically most thick; method C averaged lateral measurements at these two levels from the CT projection scan, and method D averaged lateral and anteroposterior measurements at the same two levels from the axial CT images. Finally, we used body weight to characterize patient size, method E, and compared this with the various other measurement methods. Methods were compared across the entire population as well as by subgroup based on body width. Concordance correlation (ρ c ) between each of the SSDE calculation methods (methods A-E) was greater than 0.92 across the entire population, although the range was wider when analyzed by subgroup (0.42-0.99). When we compared each SSDE measurement method with CTDI vol, there was poor correlation, ρ c <0.77, with percentage differences between 20.8% and 51.0%. Automated computer algorithms are accurate and efficient in the calculation of SSDE. Manual methods based on patient thickness provide acceptable dose estimates for pediatric patients <30 cm in body width. Body weight provides a quick and practical method to identify conversion factors that can be used to estimate SSDE with reasonable accuracy in pediatric patients with body width ≥20 cm.

The Ponseti method in Latin America: initial impact and barriers to its diffusion and implementation.

PubMed

Boardman, Allison; Jayawardena, Asitha; Oprescu, Florin; Cook, Thomas; Morcuende, Jose A

2011-01-01

The Ponseti method for correcting clubfoot is a safe, effective, and minimally invasive treatment that has recently been implemented in Latin America. This study evaluates the initial impact and unique barriers to the diffusion of the Ponseti method throughout this region. Structured interviews were conducted with 30 physicians practicing the Ponseti method in three socioeconomically diverse countries: Chile, Peru and Guatemala. Since learning the Ponseti method, these physicians have treated approximately 1,740 clubfoot patients, with an estimated 1,705 (98%) patients treated using the Ponseti method, and 35 (2%) patients treated using surgical techniques. The barriers were classified into the following themes: physician education, health care system of the country, culture and beliefs of patients, physical distance and transport, financial barriers for patients, and parental compliance with the method. The results yielded several common barriers throughout Latin America including lack of physician education, physical distance to the treatment centers, and financial barriers for patients. Information from this study can be used to inform, and to implement and evaluate specific strategies to improve the diffusion of the Ponseti method for treating clubfoot throughout Latin America.

Automatic patient-adaptive bleeding detection in a capsule endoscopy

NASA Astrophysics Data System (ADS)

Jung, Yun Sub; Kim, Yong Ho; Lee, Dong Ha; Lee, Sang Ho; Song, Jeong Joo; Kim, Jong Hyo

2009-02-01

We present a method for patient-adaptive detection of bleeding region for a Capsule Endoscopy (CE) images. The CE system has 320x320 resolution and transmits 3 images per second to receiver during around 10-hour. We have developed a technique to detect the bleeding automatically utilizing color spectrum transformation (CST) method. However, because of irregular conditions like organ difference, patient difference and illumination condition, detection performance is not uniform. To solve this problem, the detection method in this paper include parameter compensation step which compensate irregular image condition using color balance index (CBI). We have investigated color balance through sequential 2 millions images. Based on this pre-experimental result, we defined ΔCBI to represent deviate of color balance compared with standard small bowel color balance. The ΔCBI feature value is extracted from each image and used in CST method as parameter compensation constant. After candidate pixels were detected using CST method, they were labeled and examined with a bleeding character. We tested our method with 4,800 images in 12 patient data set (9 abnormal, 3 normal). Our experimental results show the proposed method achieves (before patient adaptive method : 80.87% and 74.25%, after patient adaptive method : 94.87% and 96.12%) of sensitivity and specificity.

A survey on psychiatric patients' use of non-medical alternative practitioners: incidence, methods, estimation, and satisfaction.

PubMed

Demling, J H; Neubauer, S; Luderer, H-J; Wörthmüller, M

2002-12-01

We investigated to what extent psychiatric inpatients consult Heilpraktiker, i.e. non-academically trained providers of complementary and alternative medicine (CAM), which diagnostic and therapeutic methods Heilpraktiker employ, how patients assess Heilpraictikers' professional competence, CAM in general and issues of satisfaction for those who have had experience with Heilpraktiker. Four hundred and seventy three patients admitted to a psychiatric university department during a 9-month period filled out a questionnaire developed for this investigation. About one third of the patients had consulted a Heilpraktiker, a quarter of these for their current psychiatric illness. Women were in the majority. Patients with the highest secondary school education consulted Heilpraktiker less often. There was considerable 'customer loyalty' towards Heilpraktiker. Largely the same diagnostic and treatment methods were employed for mental illness as for somatic complaints. Except for iridology, exotic or dangerous methods played a secondary role. Patients generally revealed a very positive attitude toward Heilpraktiker and CAM, although methods were rated differently. CAM enjoyed greater appreciation among women and patients who had consulted Heilpraktiker. Patients with personal experience were, on the whole, very satisfied with the professional competence, with the atmosphere in the practice and staff concern for the patient's well-being. Degree of satisfaction correlated closely with frequency of consultation. More patients with neurotic disorders considered the cost unreasonable than others, despite comparatively frequent visits. Psychiatric patients seek out Heilpraktiker to a considerable degree. Especially those who have relevant experience rank Heilpraktiker highly, in particular due to their 'psychotherapeutic' attitude, but professional competence is also valued. Methods of CAM received mixed reviews from patients but are generally seen in a positive light. It is recommended that doctors collecting case history data on their patients also ask about experience with alternative practitioners and treatments.

What are the most effective methods for assessment of nutritional status in outpatients with gastric and colorectal cancer?

PubMed

Abe Vicente, Mariana; Barão, Katia; Silva, Tiago Donizetti; Forones, Nora Manoukian

2013-01-01

To evaluate methods for the identification of nutrition risk and nutritional status in outpatients with colorectal (CRC) and gastric cancer (GC), and to compare the results to those obtained for patients already treated for these cancers. A cross-sectional study was conducted on 137 patients: group 1 (n = 75) consisting of patients with GC or CRC, and group 2 (n = 62) consisting of patients after treatment of GC or CRC under follow up, who were tumor free for a period longer than 3 months. Nutritional status was assessed in these patients using objective methods [body mass index (BMI), phase angle, serum albumin]; nutritional screening tools [Malnutrition Universal Screening Tool (MUST), Malnutrition Screening Tool (MST), Nutritional Risk Index (NRI)], and subjective assessment [Patient-Generated Subjective Global Assessment (PGSGA)]. The sensitivity and specificity of each method was calculated in relation to the PG-SGA used as gold standard. One hundred thirty seven patients participated in the study. Stage IV cancer patients were more common in group 1. There was no difference in BMI between groups (p = 0.67). Analysis of the association between methods of assessing nutritional status and PG-SGA showed that the nutritional screening tools provided more significant results (p < 0.05) than the objective methods in the two groups. PG-SGA detected the highest proportion of undernourished patients in group 1. The nutritional screening tools MUST, NRI and MST were more sensitive than the objective methods. Phase angle measurement was the most sensitive objective method in group 1. The nutritional screening tools showed the best association with PG-SGA and were also more sensitive than the objective methods. The results suggest the combination of MUST and PG-SGA for patients with cancer before and after treatment. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

[The effectiveness of physical therapy methods (Bobath and motor relearning program) in rehabilitation of stroke patients].

PubMed

Krutulyte, Grazina; Kimtys, Algimantas; Krisciūnas, Aleksandras

2003-01-01

The purpose of this study was to examine whether two different physiotherapy regimes caused any differences in outcome in the rehabilitation after stroke. We examined 240 patients with stroke. Examination was carried out at the Rehabilitation Center of Kaunas Second Clinical Hospital. Patients were divided into 2 groups: Bobath method was applied to the first (I) group (n=147), motor relearning program (MRP) method was applied to the second (II) group (n=93). In every group of patients we established samples according to sex, age, hospitalization to rehab unit as occurrence of CVA degree of disorder (hemiplegia, hemiparesis). The mobility of patients was evaluated according to European Federation for Research in Rehabilitation (EFRR) scale. Activities of daily living were evaluated by Barthel index. Analyzed groups were evaluated before physical therapy. When preliminary analysis was carried out it proved no statically reliable differences between analyzed groups (reliability 95%). The same statistical analysis was carried out after physical therapy. The results of differences between patient groups were compared using chi(2) method. Bobath method was applied working with the first group of patients. The aim of the method is to improve quality of the affected body side's movements in order to keep both sides working as harmoniously as possible. While applying this method at work, physical therapist guides patient's body on key-points, stimulating normal postural reactions, and training normal movement pattern. MRP method was used while working with the second group patients. This method is based on movement science, biomechanics and training of functional movement. Program is based on idea that movement pattern shouldn't be trained; it must be relearned. CONCLUSION. This study indicates that physiotherapy with task-oriented strategies represented by MRP, is preferable to physiotherapy with facilitation/inhibition strategies, such the Bobath programme, in the rehabilitation of stroke patients (p< 0.05).

[Measuring the blood pressure in both arms is of little use; longitudinal study into blood pressure differences between both arms and its reproducibility in patients with diabetes mellitus type 2].

PubMed

Kleefstra, N; Houweling, S T; Meyboom-de Jong, B; Bilo, H J G

2007-07-07

To determine the prevalence of inter-arm blood pressure differences > 10 mmHg in patients with diabetes mellitus type 2 (DM2) and to determine whether these differences are consistent over time. Descriptive. In an evaluation study of 169 DM2 patients from 5 general practices in 2003 and 2004, different methods of oscillatory measurement were used to investigate inter-arm blood pressure differences > 10 mmHg systolic or diastolic. These methods were: one measurement in each arm non-simultaneously (method A), one measurement simultaneously (B) and the mean of two simultaneous measurements (C). With method A an inter-arm blood pressure difference was found in 33% of patients. This percentage diminished to 9 with method C. In 44% (n = 7) of the patients in whom method C detected a relevant blood pressure difference, this difference was not found with method A. In 79% of patients the inter-arm blood pressure difference was not reproduced after one year. In daily practice, one non-simultaneous blood pressure measurement in each arm (method A) was of little value for identification of patients with inter-arm blood pressure differences. The reproducibility was poor one year later. Bilateral blood pressure measurement is therefore of little value.

Frequency and clinical features of patients who attempted suicide by charcoal burning in Japan.

PubMed

Kato, Koji; Akama, Fumiaki; Yamada, Keigo; Maehara, Mizuki; Kimoto, Keitaro; Kimoto, Kousuke; Takahashi, Yuki; Sato, Reiko; Onishi, Yuichi; Matsumoto, Hideo

2013-02-15

To date, the clinical features between patients in Japan who have attempted suicide by charcoal burning and those who have attempted suicide by other methods in the context of a mental disorder diagnosis as assessed by structured interviews have not been reported. We enrolled 647 consecutive patients who attempted suicide and were hospitalized for inpatient treatment. Psychiatric diagnoses, frequency of suicide attempts, and clinical features were compared between charcoal burning and other suicide methods. Twenty of the 647 patients (3.1%) had attempted suicide by charcoal burning. The ratio of men to women was significantly higher by this method compared with that of other methods. The proportion of patients with mood disorders was significantly higher in the charcoal burning group than that in the other methods group. The occurrence of a psychiatric history in patients in the charcoal burning group was significantly lower than that in the other methods group. The study sample was limited to a single hospital. The results demonstrate the clinical characteristics of patients who attempted suicide by charcoal burning. Therefore, it is necessary to identify the clinical features of patients who have attempted suicide by charcoal burning in Japan. Copyright © 2012 Elsevier B.V. All rights reserved.

BAYESIAN BICLUSTERING FOR PATIENT STRATIFICATION.

PubMed

Khakabimamaghani, Sahand; Ester, Martin

2016-01-01

The move from Empirical Medicine towards Personalized Medicine has attracted attention to Stratified Medicine (SM). Some methods are provided in the literature for patient stratification, which is the central task of SM, however, there are still significant open issues. First, it is still unclear if integrating different datatypes will help in detecting disease subtypes more accurately, and, if not, which datatype(s) are most useful for this task. Second, it is not clear how we can compare different methods of patient stratification. Third, as most of the proposed stratification methods are deterministic, there is a need for investigating the potential benefits of applying probabilistic methods. To address these issues, we introduce a novel integrative Bayesian biclustering method, called B2PS, for patient stratification and propose methods for evaluating the results. Our experimental results demonstrate the superiority of B2PS over a popular state-of-the-art method and the benefits of Bayesian approaches. Our results agree with the intuition that transcriptomic data forms a better basis for patient stratification than genomic data.

Use of multiple methods to determine factors affecting quality of care of patients with diabetes.

PubMed

Khunti, K

1999-10-01

The process of care of patients with diabetes is complex; however, GPs are playing a greater role in its management. Despite the research evidence, the quality of care of patients with diabetes is variable. In order to improve care, information is required on the obstacles faced by practices in improving care. Qualitative and quantitative methods can be used for formation of hypotheses and the development of survey procedures. However, to date few examples exist in general practice research on the use of multiple methods using both quantitative and qualitative techniques for hypothesis generation. We aimed to determine information on all factors that may be associated with delivery of care to patients with diabetes. Factors for consideration on delivery of diabetes care were generated by multiple qualitative methods including brainstorming with health professionals and patients, a focus group and interviews with key informants which included GPs and practice nurses. Audit data showing variations in care of patients with diabetes were used to stimulate the brainstorming session. A systematic literature search focusing on quality of care of patients with diabetes in primary care was also conducted. Fifty-four potential factors were identified by multiple methods. Twenty (37.0%) were practice-related factors, 14 (25.9%) were patient-related factors and 20 (37.0%) were organizational factors. A combination of brainstorming and the literature review identified 51 (94.4%) factors. Patients did not identify factors in addition to those identified by other methods. The complexity of delivery of care to patients with diabetes is reflected in the large number of potential factors identified in this study. This study shows the feasibility of using multiple methods for hypothesis generation. Each evaluation method provided unique data which could not otherwise be easily obtained. This study highlights a way of combining various traditional methods in an attempt to overcome the deficiencies and bias that may occur when using a single method. Similar methods can also be used to generate hypotheses for other exploratory research. An important responsibility of health authorities and primary care groups will be to assess the health needs of their local populations. Multiple methods could also be used to identify and commission services to meet these needs.

A combined learning algorithm for prostate segmentation on 3D CT images.

PubMed

Ma, Ling; Guo, Rongrong; Zhang, Guoyi; Schuster, David M; Fei, Baowei

2017-11-01

Segmentation of the prostate on CT images has many applications in the diagnosis and treatment of prostate cancer. Because of the low soft-tissue contrast on CT images, prostate segmentation is a challenging task. A learning-based segmentation method is proposed for the prostate on three-dimensional (3D) CT images. We combine population-based and patient-based learning methods for segmenting the prostate on CT images. Population data can provide useful information to guide the segmentation processing. Because of inter-patient variations, patient-specific information is particularly useful to improve the segmentation accuracy for an individual patient. In this study, we combine a population learning method and a patient-specific learning method to improve the robustness of prostate segmentation on CT images. We train a population model based on the data from a group of prostate patients. We also train a patient-specific model based on the data of the individual patient and incorporate the information as marked by the user interaction into the segmentation processing. We calculate the similarity between the two models to obtain applicable population and patient-specific knowledge to compute the likelihood of a pixel belonging to the prostate tissue. A new adaptive threshold method is developed to convert the likelihood image into a binary image of the prostate, and thus complete the segmentation of the gland on CT images. The proposed learning-based segmentation algorithm was validated using 3D CT volumes of 92 patients. All of the CT image volumes were manually segmented independently three times by two, clinically experienced radiologists and the manual segmentation results served as the gold standard for evaluation. The experimental results show that the segmentation method achieved a Dice similarity coefficient of 87.18 ± 2.99%, compared to the manual segmentation. By combining the population learning and patient-specific learning methods, the proposed method is effective for segmenting the prostate on 3D CT images. The prostate CT segmentation method can be used in various applications including volume measurement and treatment planning of the prostate. © 2017 American Association of Physicists in Medicine.

Evaluation of prognostic models developed using standardised image features from different PET automated segmentation methods.

PubMed

Parkinson, Craig; Foley, Kieran; Whybra, Philip; Hills, Robert; Roberts, Ashley; Marshall, Chris; Staffurth, John; Spezi, Emiliano

2018-04-11

Prognosis in oesophageal cancer (OC) is poor. The 5-year overall survival (OS) rate is approximately 15%. Personalised medicine is hoped to increase the 5- and 10-year OS rates. Quantitative analysis of PET is gaining substantial interest in prognostic research but requires the accurate definition of the metabolic tumour volume. This study compares prognostic models developed in the same patient cohort using individual PET segmentation algorithms and assesses the impact on patient risk stratification. Consecutive patients (n = 427) with biopsy-proven OC were included in final analysis. All patients were staged with PET/CT between September 2010 and July 2016. Nine automatic PET segmentation methods were studied. All tumour contours were subjectively analysed for accuracy, and segmentation methods with < 90% accuracy were excluded. Standardised image features were calculated, and a series of prognostic models were developed using identical clinical data. The proportion of patients changing risk classification group were calculated. Out of nine PET segmentation methods studied, clustering means (KM2), general clustering means (GCM3), adaptive thresholding (AT) and watershed thresholding (WT) methods were included for analysis. Known clinical prognostic factors (age, treatment and staging) were significant in all of the developed prognostic models. AT and KM2 segmentation methods developed identical prognostic models. Patient risk stratification was dependent on the segmentation method used to develop the prognostic model with up to 73 patients (17.1%) changing risk stratification group. Prognostic models incorporating quantitative image features are dependent on the method used to delineate the primary tumour. This has a subsequent effect on risk stratification, with patients changing groups depending on the image segmentation method used.

The influence of NDT-Bobath and PNF methods on the field support and total path length measure foot pressure (COP) in patients after stroke.

PubMed

Krukowska, Jolanta; Bugajski, Marcin; Sienkiewicz, Monika; Czernicki, Jan

In stroke patients, the NDT - (Bobath - Neurodevelopmental Treatment) and PNF (Proprioceptive Neuromuscular Facilitation) methods are used to achieve the main objective of rehabilitation, which aims at the restoration of maximum patient independence in the shortest possible period of time (especially the balance of the body). The aim of the study is to evaluate the effect of the NDT-Bobath and PNF methods on the field support and total path length measure foot pressure (COP) in patients after stroke. The study included 72 patients aged from 20 to 69 years after ischemic stroke with Hemiparesis. The patients were divided into 4 groups by a simple randomization. The criteria for this division were: the body side (right or left) affected by paresis and the applied rehabilitation methods. All the patients were applied the recommended kinesitherapeutic method (randomized), 35 therapy sessions, every day for a period of six weeks. Before initiation of therapy and after 6 weeks was measured the total area of the support and path length (COP (Center Of Pressure) measure foot pressure) using stabilometer platform - alpha. The results were statistically analyzed. After treatment studied traits decreased in all groups. The greatest improvement was obtained in groups with NDT-Bobath therapy. NDT-Bobath method for improving the balance of the body is a more effective method of treatment in comparison with of the PNF method. In stroke patients, the effectiveness of NDT-Bobath method does not depend on hand paresis. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Postoperative ambulation in thoracic surgery patients: standard versus modern ambulation methods.

PubMed

Nesbitt, Jonathan C; Deppen, Stephen; Corcoran, Richard; Cogdill, Shari; Huckabay, Sarah; McKnight, Drew; Osborne, Breanne F; Werking, Kristin; Gardner, Megan; Perrigo, Laurel

2012-01-01

A single-subject study of two methods of postoperative ambulation of patients recovering from thoracic surgery. During the postoperative setting, patients are often burdened by their condition that reduces their ability to ambulate. This problem is compounded by the addition of devices that make walking more cumbersome. To simplify the process of ambulation during the postoperative period, an intravenous pole/walker (IVPW) was specifically designed to allow all patient devices and attachments to accompany the patient during ambulation, without the need for supplemental caregiver assistance. The IVPW method of ambulation was compared with standard method of ambulation (SMA) in a single-subject clinical trial. Thirty-nine consecutive thoracic surgery patients with at least an IV and chest tube were ambulated using alternatively either the IVPW or the SMA. Immediately following the ambulation periods, the patient and patient's health care worker assessed both methods using satisfaction surveys consisting of several questions about the episodes of ambulation and the number of health care workers needed to assist during ambulation. Patient satisfaction was significantly higher in the ability of the IVPW to provide support and assist in ambulation in comparison with the SMA (p < 0·001). Nurses felt the IVPW both facilitated and provided a safer method for ambulation compared with the SMA (p < 0·001). On average, one less employee was required during ambulation with the IVPW (p < 0·001). The IVPW provided better support and was perceived as a safer method for ambulation compared with the SMA. The IVPW also required one less person to assist with ambulation. Facilitation of ambulation in the postoperative setting can impact nursing care and patient satisfaction. © 2012 The Authors. Nursing in Critical Care © 2012 British Association of Critical Care Nurses.

Diagnosis and Monitoring of Chronic Myeloid Leukemia: Chiang Mai University Experience.

PubMed

Tantiworawit, Adisak; Kongjarern, Supanat; Rattarittamrong, Ekarat; Lekawanvijit, Suree; Bumroongkit, Kanokkan; Boonma, Nonglak; Rattanathammethee, Thanawat; Hantrakool, Sasinee; Chai-Adisaksopha, Chatree; Norasetthada, Lalita

2016-01-01

A diagnosis of chronic myeloid leukemia (CML) is made on discovery of the presence of a Philadelphia (Ph) chromosome. The success of the treatment of this form of leukemia with tyrosine kinase inhibitor (TKI) is monitored by reduction of the Ph chromosome. To compare the role of conventional cytogenetic (CC) methods with a real time quantitative polymerase chain reaction (RQ-PCR) and fluorescence in situ hybridization (FISH) for diagnosis and treatment monitoring of CML patients. The secondary outcome was to analyze the treatment responses to TKI in CML patients. This was a retrospective study of CML patients who attended the Hematology clinic at Chiang Mai University Hospital from 2005-2010. Medical records were reviewed for demographic data, risk score, treatment response and the results of CC methods, FISH and RQ-PCR. One hundred and twenty three cases were included in the study, 57.7% of whom were male with a mean age of 46.9 years. Most of the patients registered as intermediate to high risk on the Sokal score. At diagnosis, 121 patients were tested using the CC method and 118 (95.9%) were identified as positive. Five patients failed to be diagnosed by CC methods but were positive for BCR-ABL1 using the FISH method. Imatinib was the first-line treatment used in 120 patients (97.6%). In most patients (108 out of 122, 88.5%), a complete cytogenetic response (CCyR) was achieved after TKI therapy and in 86 patients (70.5%) CCyR was achieved long term by the CC method. Five out of the 35 analyzed patients in which CCyR was achieved by the CC method had a positive FISH result. Out of the 76 patients in which CCyR was achieved, RQ-PCR classified patients to only CCyR in 17 patients (22.4%) with a deeper major molecular response (MMR) in 4 patients (5.3%) and complete molecular response (CMR) in 55 patients (72.4%). In the case of initial therapy, CCyR was achieved in 95 patients (79.1%) who received imatinib and in both patients who received dasatinib (100%). For the second line treatment, nilotinib were used in 30 patients and in 19 of them (63.3%) CCyR was achieved. In half of the 6 patients (50%) who received dasatinib as second line or third line treatment CCyR was also achieved. CML patients had a good response to TKI treatment. FISH could be useful for diagnosis in cases where CC analysis failed to detect the Ph chromosome. RQ-PCR was helpful in detecting any residual disease and determining the depth of the treatment response at levels greater than the CC methods.

Barriers to patient involvement in health service planning and evaluation: an exploratory study.

PubMed

Gagliardi, Anna R; Lemieux-Charles, Louise; Brown, Adalsteinn D; Sullivan, Terrence; Goel, Vivek

2008-02-01

Patient involvement in health service planning and evaluation is considered important yet not widely practiced. This study explored stakeholder beliefs about patient participation in performance indicator selection to better understand hypothesized barriers. Interviews with 30 cancer patients and health professionals from two teaching hospitals were analyzed qualitatively. All groups believed patients, not members of the public, should be involved in the selection of indicators. Ongoing, interactive methods such as committee involvement, rather than single, passive efforts such as surveys were preferred. Health professionals recommended patients assume a consultative, rather than decision-making role. Older patients agreed with this. Variable patient interest, health professional attitudes, and a lack of insight on appropriate methods may be limiting patient involvement in this, and other service planning and evaluation activities. More research is required to validate expressed views among the populations these stakeholders represent, and to establish effective methods for engaging patients. Efforts to encourage a change in health professional attitude may be required, along with dedicated organizational resources, coordinators and training. Methods to engage patients should involve deliberation, which can be achieved through modified Delphi panel or participatory research approaches.

[Metabolic surgery in treatment of diabetes mellitus of type II].

PubMed

Sedov, V M; Fishman, M B

2013-01-01

Nowadays, according to data of WHO, the diabetes mellitus was diagnosed in more than 280 million people. The diabetes mellitus type II had 90% patients. The applied methods of conservative therapy seldom lead to euglycemia condition of patients. Last years the treatment of diabetes mellitus was carried out by the method of different bariatic interventions. Good results was obtained, they should be analyzed and investigate. The results of treatment of 142 patients from 628 patients (with type II) were estimated. The patients were undergone by different bariatic interventions. Modern laparoscopic operations were performed on all the patients. Controlled bandage of stomach had 81 of patients. Gastric resection was performed in 28. Gastric bypass surgery was carried out in 22 of patients and biliopancreatic diversion - in 11. The improvement of control of leukemia level was obtained. Diabetes type II could be treated by surgical methods. The best results were obtained after combined operations, which potentially could present an alternative method of treatment of type II diabetes.

Comparison of four different reduction methods for anterior dislocation of the shoulder.

PubMed

Guler, Olcay; Ekinci, Safak; Akyildiz, Faruk; Tirmik, Uzeyir; Cakmak, Selami; Ugras, Akin; Piskin, Ahmet; Mahirogullari, Mahir

2015-05-28

Shoulder dislocations account for almost 50% of all major joint dislocations and are mainly anterior. The aim is a comparative retrospective study of different reduction maneuvers without anesthesia to reduce the dislocated shoulder. Patients were treated with different reduction maneuvers, including various forms of traction and external rotation, in the emergency departments of four training hospitals between 2009 and 2012. Each of the four hospitals had different treatment protocols for reduction and applying one of four maneuvers: Spaso, Chair, Kocher, and Matsen methods. Thirty-nine patients were treated by the Spaso method, 47 by the Chair reduction method, 40 by the Kocher method, and 27 patients by Matsen's traction-countertraction method. All patients' demographic data were recorded. Dislocation number, reduction time, time interval between dislocation and reduction, and associated complications, pre- and post-reduction period, were recorded prospectively. No anesthetic method was used for the reduction. All of the methods used included traction and some external rotation. The Chair method had the shortest reduction time. All surgeons involved in the study agreed that the Kocher and Matsen methods needed more force for the reduction. Patients could contract their muscles because of the pain in these two methods. The Spaso method includes flexion of the shoulder and blocks muscle contraction somewhat. The Chair method was found to be the easiest because the patients could not contract their muscles while sitting on a chair with the affected arm at their side. We suggest that the Chair method is an effective and fast reduction maneuver that may be an alternative for the treatment of anterior shoulder dislocations. Further prospective studies with larger sample size are needed to compare safety of different reduction techniques.

Exploring how nurses assess, monitor and manage acute pain for adult critically ill patients in the emergency department: protocol for a mixed methods study.

PubMed

Varndell, Wayne; Fry, Margaret; Elliott, Doug

2017-08-01

Many critically ill patients experience moderate to severe acute pain that is frequently undetected and/or undertreated. Acute pain in this patient cohort not only derives from their injury and/or illness, but also as a consequence of delivering care whilst stabilising the patient. Emergency nurses are increasingly responsible for the safety and wellbeing of critically ill patients, which includes assessing, monitoring and managing acute pain. How emergency nurses manage acute pain in critically ill adult patients is unknown. The objective of this study is to explore how emergency nurses manage acute pain in critically ill patients in the Emergency Department. In this paper, we provide a detailed description of the methods and protocol for a multiphase sequential mixed methods study, exploring how emergency nurses assess, monitor and manage acute pain in critically ill adult patients. The objective, method, data collection and analysis of each phase are explained. Justification of each method and data integration is described. Synthesis of findings will generate a comprehensive picture of how emergency nurses' perceive and manage acute pain in critically ill adult patients. The results of this study will form a knowledge base to expand theory and inform research and practice.