Hepatitis A, B, and A/B vaccination series completion among US adults: a claims-based analysis.

PubMed

Ghaswalla, Parinaz K; Patterson, Brandon J; Cheng, Wendy Y; Duchesneau, Emilie; Macheca, Monica; Duh, Mei Sheng

2018-06-20

Hepatitis A and B disease burden persists in the US. We assessed hepatitis A and hepatitis B vaccination series completion rates among 350,240 commercial/Medicare and 12,599 Medicaid enrollees aged ≥19 years. A vaccination series was considered as completed provided that the minimum interval between doses, as defined by the CDC, and the minimum number of doses were reached. We stratified completion rates by vaccine type (i.e. monovalent or bivalent) at initial vaccination for each cohort. In the commercial/Medicare cohort, the series completion rate was 32.0% for hepatitis A and 39.6% for hepatitis B among those who initiated with a monovalent vaccine, and it was 36.2% for hepatitis A and 48.9% for hepatitis B among those who initiated with a bivalent vaccine. In the Medicaid cohort, the series completion rate was 21.0% for hepatitis A and 24.0% for hepatitis B among those who initiated with a monovalent vaccine, and it was 19.0% for hepatitis A and 24.6% for hepatitis B among those who initiated with a bivalent vaccine. In conclusion, hepatitis A and B vaccination series completion rates were low, and appeared to be lower among Medicaid than among commercial/Medicare enrollees. Commercial/Medicare enrollees who initiated with a bivalent vaccine had higher series completion rates than those who initiated with monovalent vaccines - an observation that was not made among Medicaid enrollees.

Elevated hepatic expression of H19 long noncoding RNA contributes to diabetic hyperglycemia.

PubMed

Zhang, Na; Geng, Tingting; Wang, Zhangsheng; Zhang, Ruling; Cao, Tiefeng; Camporez, Joao Paulo; Cai, Shi-Ying; Liu, Ya; Dandolo, Luisa; Shulman, Gerald I; Carmichael, Gordon G; Taylor, Hugh S; Huang, Yingqun

2018-05-17

Excessive hepatic glucose production (HGP) contributes significantly to the hyperglycemia of type 2 diabetes; however, the molecular mechanism underlying this dysregulation remains poorly understood. Here, we show that fasting temporally increases the expression of H19 long noncoding RNA (lncRNA) in nondiabetic mouse liver, whereas its level is chronically elevated in diet-induced diabetic mice, consistent with the previously reported chronic hepatic H19 increase in diabetic patients. Importantly, liver-specific H19 overexpression promotes HGP, hyperglycemia, and insulin resistance, while H19 depletion enhances insulin-dependent suppression of HGP. Using genome-wide methylation and transcriptome analyses, we demonstrate that H19 knockdown in hepatic cells alters promoter methylation and expression of Hnf4a, a master gluconeogenic transcription factor, and that this regulation is recapitulated in vivo. Our findings offer a mechanistic explanation of lncRNA H19's role in the pathogenesis of diabetic hyperglycemia and suggest that targeting hepatic H19 may hold the potential of new treatment for this disease.

Hepatitis B Foundation

MedlinePlus

... worldwide 2 Billion People have been infected with Hepatitis B Worldwide The Hepatitis B Foundation is working ... of people living with hepatitis B. Learn About Hepatitis B in 11 Other Languages . Resource Video See ...

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.

Predictors of Infant Hepatitis B Immunization in Cameroon: Data to Inform Implementation of a Hepatitis B Birth Dose.

PubMed

Dionne-Odom, Jodie; Westfall, Andrew O; Nzuobontane, Divine; Vinikoor, Michael J; Halle-Ekane, Gregory; Welty, Thomas; Tita, Alan T N

2018-01-01

Although most African countries offer hepatitis B immunization through a 3-dose vaccine series recommended at 6, 10 and 14 weeks of age, very few provide birth dose vaccination. In support of Cameroon's national plan to implement the birth dose vaccine in 2017, we investigated predictors of infant hepatitis B virus (HBV) vaccination under the current program. Using the 2011 Demographic Health Survey in Cameroon, we identified women with at least one living child (age 12-60 months) and information about the hepatitis B vaccine series. Vaccination rates were calculated, and logistic regression modeling was used to identify factors associated with 3-dose series completion. Changes over time were assessed with linear logistic model. Among 4594 mothers analyzed, 66.7% (95% confidence interval [CI]: 64.1-69.3) of infants completed the hepatitis B vaccine series; however, an average 4-week delay in series initiation was noted with median dose timing at 10, 14 and 19 weeks of age. Predictors of series completion included facility delivery (adjusted odds ratio [aOR]: 2.1; 95% CI: 1.7-2.6), household wealth (aOR: 1.9; 95% CI: 1.2-3.1 comparing the highest and lowest quintiles), Christian religion (aOR: 1.8; 95% CI: 1.3-2.5 compared with Muslim religion) and older maternal age (aOR: 1.4; 95% CI: 1.2-1.7 for 10 year units). Birth dose vaccination to reduce vertical and early childhood transmission of hepatitis B may overcome some of the obstacles to timely and complete HBV immunization in Cameroon. Increased awareness of HBV is needed among pregnant women and high-risk groups about vertical transmission, the importance of facility delivery and the effectiveness of prevention beginning with monovalent HBV vaccination at birth.

Epidemiology of hepatitis B and hepatitis C in Lebanon.

PubMed

Abou Rached, Antoine; Abou Kheir, Selim; Saba, Jowana; Ammar, Walid

2016-03-01

Hepatitis B and C are two potentially life threatening liver infections. Lebanon is ranked as a zone of moderate endemicity. This study aimed to determine the prevalence of hepatitis B and C in Lebanon and their distribution according to age, region and sex. This national prospective cross-sectional study was conducted from January 2011 till December 2012 in the six Lebanese Governorates in collaboration with municipalities, the Ministry of Public Health, Health Centres and dispensaries. An upcoming screening for hepatitis B and C was announced? in different districts of each Governorate. All individuals presenting to local laboratory, not known to have chronic hepatitis, were asked for a blood sample and answered a questionnaire addressing sex, age, place of birth and residence. Screening tests were "Abbots" for hepatitis B and "Human Hexagon" for hepatitis C. PCR testing was used to confirm the positivity of the previous tests. Of 31147 individuals screened, 542 had a rapid test positive for HBV (prevalence 1.74%, 95% CI 1.6-1.89) with a male to female ratio of 1.08. This prevalence was higher in the South and Nabatieh (1.9%) compared to Beirut (0.73%). Of 31,147 individuals screened, 64 had a rapid test positive for HCV (prevalence 0.21%, 95% CI 0.16-0.27) with a male to female ratio of 0.85. This prevalence was higher in Nabatieh (0.61%) compared to Mount Lebanon (0.08%). The prevalence of HBV and HCV in Lebanon is 1.74% and 0.21%, respectively with a higher prevalence in South and Nabatieh districts. These data rank Lebanon amongst countries with low endemicity for both viruses. Decrease in the prevalence of HBV is due to awareness campaign as well as success of the MOPH National Hepatitis Program in vaccinating all new born since 1998 and in screening and vaccinating high risk groups. Copyright © 2016 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.

Involvement of the TNF and FasL produced by CD11b Kupffer cells/macrophages in CCl4-induced acute hepatic injury.

PubMed

Sato, Atsushi; Nakashima, Hiroyuki; Nakashima, Masahiro; Ikarashi, Masami; Nishiyama, Kiyoshi; Kinoshita, Manabu; Seki, Shuhji

2014-01-01

We previously reported that F4/80(+) Kupffer cells are subclassified into CD68(+) Kupffer cells with phagocytic and ROS producing capacity, and CD11b(+) Kupffer cells with cytokine-producing capacity. Carbon tetrachloride (CCl4)-induced hepatic injury is a well-known chemical-induced hepatocyte injury. In the present study, we investigated the immunological role of Kupffer cells/macrophages in CCl4-induced hepatitis in mice. The immunohistochemical analysis of the liver and the flow cytometry of the liver mononuclear cells showed that clodronate liposome (c-lipo) treatment greatly decreased the spindle-shaped F4/80(+) or CD68(+) cells, while the oval-shaped F4/80+ CD11b(+) cells increased. Notably, severe hepatic injury induced by CCl4 was further aggravated by c-lipo-pretreatment. The population of CD11b(+) Kupffer cells/macrophages dramatically increased 24 hour (h) after CCl4 administration, especially in c-lipo-pretreated mice. The CD11b(+) Kupffer cells expressed intracellular TNF and surface Fas-ligand (FasL). Furthermore, anti-TNF Ab pretreatment (which decreased the FasL expression of CD11b(+) Kupffer cells), anti-FasL Ab pretreatment or gld/gld mice attenuated the liver injury induced by CCl4. CD1d-/- mouse and cell depletion experiments showed that NKT cells and NK cells were not involved in the hepatic injury. The adoptive transfer and cytotoxic assay against primary cultured hepatocytes confirmed the role of CD11b(+) Kupffer cells in CCl4-induced hepatitis. Interestingly, the serum MCP-1 level rapidly increased and peaked at six h after c-lipo pretreatment, suggesting that the MCP-1 produced by c-lipo-phagocytized CD68(+) Kupffer cells may recruit CD11b(+) macrophages from the periphery and bone marrow. The CD11b(+) Kupffer cells producing TNF and FasL thus play a pivotal role in CCl4-induced acute hepatic injury.

Involvement of the TNF and FasL Produced by CD11b Kupffer Cells/Macrophages in CCl4-Induced Acute Hepatic Injury

PubMed Central

Sato, Atsushi; Nakashima, Hiroyuki; Nakashima, Masahiro; Ikarashi, Masami; Nishiyama, Kiyoshi; Kinoshita, Manabu; Seki, Shuhji

2014-01-01

We previously reported that F4/80+ Kupffer cells are subclassified into CD68+ Kupffer cells with phagocytic and ROS producing capacity, and CD11b+ Kupffer cells with cytokine-producing capacity. Carbon tetrachloride (CCl4)-induced hepatic injury is a well-known chemical-induced hepatocyte injury. In the present study, we investigated the immunological role of Kupffer cells/macrophages in CCl4-induced hepatitis in mice. The immunohistochemical analysis of the liver and the flow cytometry of the liver mononuclear cells showed that clodronate liposome (c-lipo) treatment greatly decreased the spindle-shaped F4/80+ or CD68+ cells, while the oval-shaped F4/80+ CD11b+ cells increased. Notably, severe hepatic injury induced by CCl4 was further aggravated by c-lipo-pretreatment. The population of CD11b+ Kupffer cells/macrophages dramatically increased 24 hour (h) after CCl4 administration, especially in c-lipo-pretreated mice. The CD11b+ Kupffer cells expressed intracellular TNF and surface Fas-ligand (FasL). Furthermore, anti-TNF Ab pretreatment (which decreased the FasL expression of CD11b+ Kupffer cells), anti-FasL Ab pretreatment or gld/gld mice attenuated the liver injury induced by CCl4. CD1d−/− mouse and cell depletion experiments showed that NKT cells and NK cells were not involved in the hepatic injury. The adoptive transfer and cytotoxic assay against primary cultured hepatocytes confirmed the role of CD11b+ Kupffer cells in CCl4-induced hepatitis. Interestingly, the serum MCP-1 level rapidly increased and peaked at six h after c-lipo pretreatment, suggesting that the MCP-1 produced by c-lipo-phagocytized CD68+ Kupffer cells may recruit CD11b+ macrophages from the periphery and bone marrow. The CD11b+ Kupffer cells producing TNF and FasL thus play a pivotal role in CCl4-induced acute hepatic injury. PMID:24667392

Post-infectious acute glomerulonephritis with podocytopathy induced by parvovirus B19 infection.

PubMed

Hara, Satoshi; Hirata, Masayoshi; Ito, Kiyoaki; Mizushima, Ichiro; Fujii, Hiroshi; Yamada, Kazunori; Nagata, Michio; Kawano, Mitsuhiro

2018-03-01

Human parvovirus B19 infection causes a variety of glomerular diseases such as post-infectious acute glomerulonephritis and collapsing glomerulopathy. Although each of these appears independently, it has not been fully determined why parvovirus B19 provokes such a variety of different glomerular phenotypes. Here, we report a 68-year-old Japanese man who showed endocapillary proliferative glomerulonephritis admixed with podocytopathy in association with parvovirus B19 infection. The patient showed acute onset of heavy proteinuria, microscopic hematuria and kidney dysfunction with arthralgia and oliguria after close contact with a person suffering from erythema infectiosum. In the kidney biopsy specimen, glomeruli revealed diffuse and global endocapillary infiltration of inflammatory cells, with some also showing tuft collapse with aberrant vacuolation, swelling, and hyperplasia of glomerular epithelial cells. Immunofluorescence revealed dense granular C3 deposition that resembled the "starry sky pattern". Intravenous glucocorticoid pulse therapy followed by oral prednisolone and cyclosporine combination therapy resulted in considerable amelioration of the kidney dysfunction and urinary abnormalities. The present case reveals that parvovirus B19 infection can induce different glomerular phenotypes even in the same kidney structure. This finding may provide hints useful for the further elucidation of the pathogenesis of parvovirus B19-induced glomerular lesions. © 2018 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Hepatitis B

MedlinePlus

... this page: //medlineplus.gov/ency/article/000279.htm Hepatitis B To use the sharing features on this page, please enable JavaScript. Hepatitis B is irritation and swelling (inflammation) of the ...

Hepatitis B vaccination among primary health care workers in Northwest Pakistan

PubMed Central

Yousafzai, Mohammad Tahir; Qasim, Rubina; Khalil, Rehana; Kakakhel, Mohammad Fazil; Rehman, Shafiq Ur

2014-01-01

Background We assessed hepatitis B vaccination and its determinants among health care workers (HCW) in rural Northwest Pakistan. Methods This cross sectional study was conducted among 485 HCWs from both public and private clinics. Data about hepatitis B vaccination, socio-demographic, knowledge regarding modes of transmission of hepatitis B virus, perceived disease severity and benefits of vaccination was collected through questionnaire. Multivariable logistic regression analysis was performed. Results Prevalence of complete hepatitis B vaccination was 40% (among Physicians with MBBS/MD qualification; 86% and lowest among non-qualified Dispensers;16%). Also, prevalence was higher among HCWs from public Dispensaries (77%) than those working in private clinics (35%). Being MBBS/MD Physician (Adj. OR 26.60; 95%CI 9.27–73.23), Non-MBBS/MD Physician (Adj.OR 1.89; 95%CI 0.78–4.59), qualified Dispensers (Adj. OR 3.58; 95%CI 1.34–9.54) compared to non-qualified Dispensers, working in public clinics (Adj. OR 2.54; 95%CI 1.13–5.69) as compared to private, perceived disease threat after exposure to blood and body fluids (Adj. OR 1.11; 95%CI 1.03–1.19) and perceived benefits of hepatitis B vaccination (Adj. OR 1.13; 95%CI 1.09–1.19) were significant predictors of complete hepatitis B vaccination. Conclusion Improved perception of disease threat and benefits of vaccination and qualification of HCWs are associated with hepatitis B vaccination among Primary HCWs. PMID:24899881

Tumor-induced CD11b(+) Gr-1(+) myeloid-derived suppressor cells exacerbate immune-mediated hepatitis in mice in a CD40-dependent manner.

PubMed

Kapanadze, Tamar; Medina-Echeverz, José; Gamrekelashvili, Jaba; Weiss, Jonathan M; Wiltrout, Robert H; Kapoor, Veena; Hawk, Nga; Terabe, Masaki; Berzofsky, Jay A; Manns, Michael P; Wang, Ena; Marincola, Francesco M; Korangy, Firouzeh; Greten, Tim F

2015-04-01

Immunosuppressive CD11b(+) Gr-1(+) myeloid-derived suppressor cells (MDSCs) accumulate in the livers of tumor-bearing (TB) mice. We studied hepatic MDSCs in two murine models of immune-mediated hepatitis. Unexpectedly, treatment of TB mice with Concanavalin A (Con A) or α-galactosylceramide resulted in increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serum levels in comparison to tumor-free mice. Adoptive transfer of hepatic MDSCs into naïve mice exacerbated Con A induced liver damage. Hepatic CD11b(+) Gr-1(+) cells revealed a polarized proinflammatory gene signature after Con A treatment. An IFN-γ-dependent upregulation of CD40 on hepatic CD11b(+) Gr-1(+) cells along with an upregulation of CD80, CD86, and CD1d after Con A treatment was observed. Con A treatment resulted in a loss of suppressor function by tumor-induced CD11b(+) Gr-1(+) MDSCs as well as enhanced reactive oxygen species (ROS)-mediated hepatotoxicity. CD40 knockdown in hepatic MDSCs led to increased arginase activity upon Con A treatment and lower ALT/AST serum levels. Finally, blockade of arginase activity in Cd40(-/-) tumor-induced myeloid cells resulted in exacerbation of hepatitis and increased ROS production in vivo. Our findings indicate that in a setting of acute hepatitis, tumor-induced hepatic MDSCs act as proinflammatory immune effector cells capable of killing hepatocytes in a CD40-dependent manner. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

A novel therapeutic hepatitis B vaccine induces cellular and humoral immune responses and breaks tolerance in hepatitis B virus (HBV) transgenic mice.

PubMed

Buchmann, Pascale; Dembek, Claudia; Kuklick, Larissa; Jäger, Clemens; Tedjokusumo, Raindy; von Freyend, Miriam John; Drebber, Uta; Janowicz, Zbigniew; Melber, Karl; Protzer, Ulrike

2013-02-06

Therapeutic vaccines are currently being developed for chronic hepatitis B and C. As an alternative to long-term antiviral treatment or to support only partially effective therapy, they should activate the patient's immune system effectively to fight and finally control the virus. A paradigm of therapeutic vaccination is the potent induction of T-cell responses against key viral antigens - besides activation of a humoral immune response. We have evaluated the potential of a novel vaccine formulation comprising particulate hepatitis B surface (HBsAg) and core antigen (HBcAg), and the saponin-based ISCOMATRIX™ adjuvant for its ability to stimulate T and B cell responses in C57BL/6 mice and its ability to break tolerance in syngeneic HBV transgenic (HBVtg) mice. In C57BL/6 mice, the vaccine induced multifunctional HBsAg- and HBcAg-specific CD8+ T cells detected by staining for IFNγ, TNFα and IL-2, as well as high antibody titers against both antigens. Vaccination of HBVtg animals induced potent HBsAg- and HBcAg-specific CD8+ T-cell responses in spleens and HBcAg-specific CD8+ T-cell responses in livers as well as anti-HBs seroconversion two weeks post injection. Vaccination further reduced HBcAg expression in livers of HBVtg mice without causing liver damage. In summary, this study demonstrates therapeutic efficacy of a novel vaccine formulation in a mouse model of immunotolerant, chronic HBV infection. Copyright © 2013 Elsevier Ltd. All rights reserved.

Hepatitis B Vaccine

MedlinePlus

... a combination product containing Haemophilus influenzae type b, Hepatitis B Vaccine) ... combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis, Hepatitis B, Polio Vaccine)

Phenylbutyric acid protects against carbon tetrachloride-induced hepatic fibrogenesis in mice

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

Wang, Jian-Qing; Second Affiliated Hospital, Anhui Medical University, Hefei 230601; Chen, Xi

2013-01-15

A recent report showed that the unfolded protein response (UPR) signaling was activated in the pathogenesis of carbon tetrachloride (CCl{sub 4})-induced hepatic fibrosis. Phenylbutyric acid (PBA) is a well-known chemical chaperone that inhibits endoplasmic reticulum (ER) stress and unfolded protein response (UPR) signaling. In the present study, we investigated the effects of PBA on CCl{sub 4}-induced hepatic fibrosis in mice. All mice were intraperitoneally (i.p.) injected with CCl{sub 4} (0.15 ml/kg BW, twice per week) for 8 weeks. In CCl{sub 4} + PBA group, mice were i.p. injected with PBA (150 mg/kg, twice per day) from the beginning of CCl{submore » 4} injection to the end. As expected, PBA significantly attenuated CCl{sub 4}-induced hepatic ER stress and UPR activation. Although PBA alleviated, only to a less extent, hepatic necrosis, it obviously inhibited CCl{sub 4}-induced tumor necrosis factor alpha (TNF-α) and transforming growth factor beta (TGF-β). Moreover, PBA inhibited CCl{sub 4}-induced hepatic nuclear factor kappa B (NF-κB) p65 translocation and extracellular signal-regulated kinase (ERK) and c-Jun N-terminal Kinase (JNK) phosphorylation. Interestingly, CCl{sub 4}-induced α-smooth muscle actin (α-SMA), a marker for the initiation phase of HSC activation, was significantly attenuated in mice pretreated with PBA. Correspondingly, CCl{sub 4}-induced hepatic collagen (Col)1α1 and Col1α2, markers for the perpetuation phase of HSC activation, were inhibited in PBA-treated mice. Importantly, CCl{sub 4}-induced hepatic fibrosis, as determined using Sirius red staining, was obviously attenuated by PBA. In conclusion, PBA prevents CCl{sub 4}-induced hepatic fibrosis through inhibiting hepatic inflammatory response and HSC activation. Highlights: ► CCl{sub 4} induces hepatic ER stress, inflammation, HSC activation and hepatic fibrosis. ► PBA alleviates CCl{sub 4}-induced hepatic ER stress and UPR signaling activation. ► PBA inhibits CCl{sub 4

Readability of Healthcare Literature for Hepatitis B and C.

PubMed

Meillier, Andrew; Patel, Shyam; Al-Osaimi, Abdullah M S

2015-12-01

Patients increasingly use the Internet for educational material concerning health and diseases. This information can be utilized to teach the population of hepatitis B and C if properly written at the necessary grade level of the intended patient population. We explored the readability of online resources concerning hepatitis B and C. Google searches were performed for "Hepatitis B" and "Hepatitis C." The Internet resources that were intended for patient education were used with specific exclusions. Articles were taken from 19 and 23 different websites focusing on the symptoms, diagnosis, and treatment of hepatitis B and C, respectively. The articles were analyzed using Readability Studio Professional Edition (Oleander Solutions, Vandalia, OH) using 10 different readability scales. The results were compared and averaged to identify the anticipated academic grade level required to understand the information. The average readability scores of the 10 scales had ranges of 9.7-16.4 for hepatitis B and 9.2-16.4 for hepatitis C. The average academic reading grade level for hepatitis B was 12.6 ± 2.1 and for hepatitis C was 12.7 ± 2.1. There was no significant discrepancy between the hepatitis B and C Internet resource averaged grade levels. The resources accessed by patients are higher than the previously determined necessary grade level for patients to properly understand the intended information. The American Medical Association recommends material should be simplified to grade levels below the sixth grade level to benefit the ideal proportion of the patient population.

Liver Cancer and Hepatitis B

MedlinePlus

... Clinical Trials Physician Directory HBV Meeting What Is Hepatitis B? What Is Hepatitis B? The ABCs of Viral Hepatitis Liver Cancer and Hepatitis B Hepatitis Delta Coinfection Hepatitis C Coinfection HIV/AIDS ...

Hepatitis B & C and HIV

MedlinePlus

... HIV SERVICES LOCATOR Locator Search Search Hepatitis B & C Topics Hepatitis B Hepatitis C Hepatitis Testing Day ... Women's Health Issues Hepatitis B Virus and Hepatitis C Virus Infection People with HIV infection in the ...

Hepatitis B Virus X Protein Induces Hepatic Steatosis by Enhancing the Expression of Liver Fatty Acid Binding Protein.

PubMed

Wu, Yun-Li; Peng, Xian-E; Zhu, Yi-Bing; Yan, Xiao-Li; Chen, Wan-Nan; Lin, Xu

2016-02-15

Hepatitis B virus (HBV) has been implicated as a potential trigger of hepatic steatosis although molecular mechanisms involved in the pathogenesis of HBV-associated hepatic steatosis still remain elusive. Our prior work has revealed that the expression level of liver fatty acid binding protein 1 (FABP1), a key regulator of hepatic lipid metabolism, was elevated in HBV-producing hepatoma cells. In this study, the effects of HBV X protein (HBx) mediated FABP1 regulation on hepatic steatosis and the underlying mechanism were determined. mRNA and protein levels of FABP1 were measured by quantitative RT-PCR (qPCR) and Western blotting. HBx-mediated FABP1 regulation was evaluated by luciferase assay, coimmunoprecipitation, and chromatin immunoprecipitation. Hepatic lipid accumulation was measured by using Oil-Red-O staining and the triglyceride level. It was found that expression of FABP1 was increased in HBV-producing hepatoma cells, the sera of HBV-infected patients, and the sera and liver tissues of HBV-transgenic mice. Ectopic overexpression of HBx resulted in upregulation of FABP1 in HBx-expressing hepatoma cells, whereas HBx abolishment reduced FABP1 expression. Mechanistically, HBx activated the FABP1 promoter in an HNF3β-, C/EBPα-, and PPARα-dependent manner, in which HBx increased the gene expression of HNF3β and physically interacted with C/EBPα and PPARα. On the other hand, knockdown of FABP1 remarkably blocked lipid accumulation both in long-chain free fatty acids treated HBx-expressing HepG2 cells and in a high-fat diet-fed HBx-transgenic mice. Therefore, FABP1 is a key driver gene in HBx-induced hepatic lipid accumulation via regulation of HNF3β, C/EBPα, and PPARα. FABP1 may represent a novel target for treatment of HBV-associated hepatic steatosis. Accumulating evidence from epidemiological and experimental studies has indicated that chronic HBV infection is associated with hepatic steatosis. However, the molecular mechanism underlying HBV-induced

Potential mechanisms of hepatitis B virus induced liver injury

PubMed Central

Suhail, Mohd; Abdel-Hafiz, Hany; Ali, Ashraf; Fatima, Kaneez; Damanhouri, Ghazi A; Azhar, Esam; Chaudhary, Adeel GA; Qadri, Ishtiaq

2014-01-01

Chronic active hepatitis (CAH) is acknowledged as an imperative risk factor for the development of liver injury and hepatocellular carcinoma. The histological end points of CAH are chronic inflammation, fibrosis and cirrhosis which are coupled with increased DNA synthesis in cirrhotic vs healthy normal livers. The potential mechanism involved in CAH includes a combination of processes leading to liver cell necrosis, inflammation and cytokine production and liver scaring (fibrosis). The severity of liver damage is regulated by Hepatitis B virus genotypes and viral components. The viral and cellular factors that contribute to liver injury are discussed in this article. Liver injury caused by the viral infection affects many cellular processes such as cell signaling, apoptosis, transcription, DNA repair which in turn induce radical effects on cell survival, growth, transformation and maintenance. The consequence of such perturbations is resulted in the alteration of bile secretion, gluconeogenesis, glycolysis, detoxification and metabolism of carbohydrates, proteins, fat and balance of nutrients. The identification and elucidation of the molecular pathways perturbed by the viral proteins are important in order to design effective strategy to minimize and/or restore the hepatocytes injury. PMID:25253946

Suppressive role of hepatic dendritic cells in concanavalin A-induced hepatitis

PubMed Central

Tomiyama, C; Watanabe, H; Izutsu, Y; Watanabe, M; Abo, T

2011-01-01

Concanavalin A (Con A)-induced hepatitis is a mouse model of acute autoimmune hepatitis. The aim of this study was to investigate the role of hepatic dendritic cells (DC) in the immune modulation of tissue damage. Almost all hepatic DC were plasmacytoid DC (CD11c+ I-Alow B220+); however, conventional DC were CD11c+ I-Ahigh B220–. At an early stage (3–6 h) after Con A administration, the number of DC in both the liver and spleen decreased, increasing thereafter (12–24 h) in parallel with hepatic failure. The hepatic CD11c+ DC population contained many CD11b- cells, while the majority of splenic CD11c+ DC were CD11b+. After Con A administration, the proportion of I-A+ and CD11b+ cells within the CD11c+ DC population tended to increase in the liver, but not in the spleen. Similarly, expression of the activation markers CD80, CD86 and CD40 by CD11c+ DC increased in the liver, but not in the spleen. Next, adoptive transfer of DC isolated from the liver and spleen was performed 3 h after Con A administration to examine the immunomodulatory function of DC. Only hepatic DC had the ability to suppress hepatic failure. Analysis of cytokine production and subsequent identification of the effector cells showed that hepatic DC achieved this by suppressing the production of interleukin (IL)-12 and IL-2, rather than modulating effector cell function. PMID:21985372

Booster dose vaccination for preventing hepatitis B.

PubMed

Poorolajal, Jalal; Hooshmand, Elham

2016-06-07

Antibodies against hepatitis B surface antigen (HBsAg) wane over time following hepatitis B immunisation; hence, it is unclear whether people vaccinated in three-dose or four-dose schedules of the hepatitis B vaccine are still immune when the hepatitis B surface antibody (anti-HBs) level in their body is undetectable, or lower than the level usually considered protective. This question may potentially be answered indirectly by measuring the anamnestic immune response to a booster dose of vaccine. The term 'booster' (or revaccination) refers to an additional dose of hepatitis B vaccine (HBV) given some time post-primary vaccination to induce immune memory and improve protection against hepatitis B virus (HBV) infection. To assess the benefits and harms of booster dose hepatitis B vaccination, more than five years after the primary vaccination, for preventing HBV infection in healthy individuals previously vaccinated with the hepatitis B vaccine, and with hepatitis B surface antibody (anti-HBs) levels below 10 mIU/mL. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded, conference databases, and reference lists of articles to January 2016. We also contacted authors of articles. In addition, we searched ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials (May 2016). Randomised clinical trials addressing anamnestic immune response to a booster dose of hepatitis B vaccine, more than five years after the primary vaccination, in apparently healthy participants, vaccinated in a three-dose or four-dose schedule of the hepatitis B vaccine during the primary vaccination, without receiving an additional dose or immunoglobulin. Both review authors decided if the identified studies met the inclusion criteria or not. Primary outcomes included the proportion of participants

Oxidative stress, a trigger of hepatitis C and B virus-induced liver carcinogenesis

PubMed Central

Ivanov, Alexander V.; Valuev-Elliston, Vladimir T.; Tyurina, Daria A.; Ivanova, Olga N.; Kochetkov, Sergey N.; Bartosch, Birke; Isaguliants, Maria G.

2017-01-01

Virally induced liver cancer usually evolves over long periods of time in the context of a strongly oxidative microenvironment, characterized by chronic liver inflammation and regeneration processes. They ultimately lead to oncogenic mutations in many cellular signaling cascades that drive cell growth and proliferation. Oxidative stress, induced by hepatitis viruses, therefore is one of the factors that drives the neoplastic transformation process in the liver. This review summarizes current knowledge on oxidative stress and oxidative stress responses induced by human hepatitis B and C viruses. It focuses on the molecular mechanisms by which these viruses activate cellular enzymes/systems that generate or scavenge reactive oxygen species (ROS) and control cellular redox homeostasis. The impact of an altered cellular redox homeostasis on the initiation and establishment of chronic viral infection, as well as on the course and outcome of liver fibrosis and hepatocarcinogenesis will be discussed The review neither discusses reactive nitrogen species, although their metabolism is interferes with that of ROS, nor antioxidants as potential therapeutic remedies against viral infections, both subjects meriting an independent review. PMID:27965466

Parvovirus B19 Infection in a Fatal Case of Acute Liver Failure.

PubMed

Leon, Luciane Almeida Amado; Alves, Arthur Daniel Rocha; Garcia, Rita de Cássia Nasser Cubel; Melgaço, Juliana Gil; de Paula, Vanessa Salete; Pinto, Marcelo Alves

2017-12-01

B19V has been proposed as an etiologic agent for hepatitis, mainly in children, but this is a rare clinical occurrence. In this article, we report a case of non-A-E acute liver failure in an immunocompetent child with B19 infection. The clinical findings of severe anemia and pancytopenia combined with the detection of anti-B19 Immunoglobulin G (IgG), B19 DNA and B19 mRNA in liver indicate a persistent infection and suggest a diagnosis of parvovirus B19-associated acute liver failure.

[Evaluation of the virus-elimination efficacy of nanofiltration (Viresolve NFP) for the parvovirus B19 and hepatitis A virus].

PubMed

Oh, Deok Ja; Lee, Yoo La; Kang, Jae Won; Kwon, So Yong; Cho, Nam Sun; Kim, In Seop

2010-02-01

The safety of plasma derivatives has been reinforced since 1980s by variable pathogen inactivation or elimination techniques. Nucleic acid amplification test (NAT) for the source plasma has also been implemented worldwide. Recently nanofiltration has been used in some country for ensuring safety of plasma derivatives to eliminate non-enveloped viruses such as parvovirus B19 (B19V) and hepatitis A virus (HAV). We evaluated the efficacy of nanofiltration for the elimination of B19V and HAV. To verify the efficacy of nanofiltration, we adopted a 20 nm Viresolve NFP (Millipore, USA) in the scaling down (1:1,370) model of the antithrombin III production. As virus stock solutions, we used B19V reactive plasma and porcine parvovirus (PPV) and HAV obtained from cell culture. And 50% tissue culture infectious dose was consumed as infectious dose. The methods used to evaluate the virus-elimination efficacy were reverse-transcriptase polymerase chain reaction for B19V and the cytopathic effect calculation after filtration for PPV and HAV. B19V was not detected by RT-PCR in the filtered antithrombin III solutions with initial viral load of 6.42 x 10(5) IU/mL and 1.42 x 10(5) IU/mL before filtration. The virus-elimination efficacy of nanofiltration for PPV and HAV were > or = (3.32) and > or = (3.31), respectively. Nanofiltration would be an effective method for the elimination of B19V and HAV. It may be used as a substitute for NAT screening of these viruses in source plasma to ensure safety of plasma derivatives in Korea.

Cost-Effectiveness of Nationwide Hepatitis B Catch-up Vaccination Among Children and Adolescents in China

PubMed Central

Hutton, David W.; So, Samuel K.; Brandeau, Margaret L.

2011-01-01

Liver disease and liver cancer associated with childhood-acquired chronic hepatitis B are leading causes of death among adults in China. Despite expanded newborn hepatitis B vaccination programs, approximately 20% of children under age 5 years and 40% of children aged 5-19 years remain unprotected from hepatitis B. Although immunizing them will be beneficial, no studies have examined the cost-effectiveness of hepatitis B catch-up vaccination in an endemic country like China. We examined the cost-effectiveness of a hypothetical nationwide free hepatitis B catch-up vaccination program in China for unvaccinated children and adolescents aged 1 to 19 years. We used a Markov model for disease progression and infections. Cost variables were based on data published by the Chinese Ministry of Health, peer-reviewed Chinese and English publications, and the GAVI Alliance. We measured costs (2008 U.S. dollars and Chinese renminbi), quality-adjusted life years (QALYs), and incremental cost-effectiveness from a societal perspective. Our results show that hepatitis B catch-up vaccination for children and adolescents in China is cost-saving across a range of parameters, even for adolescents aged 15-19 years old. We estimate that if all 150 million susceptible children under 19 were vaccinated, more than 8 million infections and 65,000 deaths due to hepatitis B would be prevented. Conclusion The adoption of a nationwide free catch-up hepatitis B vaccination program for unvaccinated children and adolescents in China, in addition to ongoing efforts to improve birth dose and newborn vaccination coverage, will be cost-saving and can generate significant population-wide health benefits. The success of such a program in China could serve as a model for other endemic countries. PMID:19839061

Diabetes and Hepatitis B Vaccination

MedlinePlus

Diabetes and Hepatitis B Vaccination Information for Diabetes Educators What is hepatitis B? Hepatitis B is a contagious liver disease that results from infection with the hepatitis B virus. When first infected, a person can develop ...

Ascorbic acid deficiency decreases hepatic cytochrome P-450, especially CYP2B1/2B2, and simultaneously induces heme oxygenase-1 gene expression in scurvy-prone ODS rats.

PubMed

Kobayashi, Misato; Hoshinaga, Yukiko; Miura, Natsuko; Tokuda, Yuki; Shigeoka, Shigeru; Murai, Atsushi; Horio, Fumihiko

2014-01-01

The mechanisms underlying the decrease in hepatic cytochrome P-450 (CYP) content in ascorbic acid deficiency was investigated in scurvy-prone ODS rats. First, male ODS rats were fed a diet containing sufficient ascorbic acid (control) or a diet without ascorbic acid (deficient) for 18 days, with or without the intraperitoneal injection of phenobarbital. Ascorbic acid deficiency decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial cytochrome oxidase (COX) complex IV subunit I protein, and simultaneously increased heme oxygenase-1 protein in microsomes and mitochondria. Next, heme oxygenase-1 inducers, that is lipopolysaccharide and hemin, were administered to phenobaribital-treated ODS rats fed sufficient ascorbic acid. The administration of these inducers decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial COX complex IV subunit I protein. These results suggested that the stimulation of hepatic heme oxygenase-1 expression by ascorbic acid deficiency caused the decrease in CYP content in liver.

Clinical evaluation of the branched DNA assay for hepatitis B virus DNA detection in patients with chronic hepatitis B lacking hepatitis B e antigen and treated with interferon-alpha.

PubMed

Habersetzer, F; Zoulim, F; Jusot, J F; Zhang, X; Trabaud, M A; Chevallier, P; Chevallier, M; Ahmed, S N; Sepetjan, M; Comanor, L; Minor, J; Trépo, C

1998-11-01

The aim of this study was to evaluate the Chiron branched DNA (bDNA) assay for detection of serum hepatitis B virus (HBV) DNA in patients with chronic hepatitis B lacking hepatitis B e antigen (HBeAg) and undergoing interferon (IFN) therapy. Results obtained with the bDNA assay were compared with those obtained using the Abbott liquid hybridization (LH) assay and the polymerase chain reaction (PCR). Serial samples (274) from 34 patients were analysed. Analysis of variance results indicated that bDNA values were more significantly correlated than LH values with both PCR positive/negative results (probability of artifact (Prob > F) = 0.7 and 0.09 for LH and bDNA assays, respectively) and presence/absence of precore mutations (Prob > F = 0.21 and 0.001 for LH and bDNA assays, respectively). Both bDNA and LH results correlated highly with alanine aminotransferase (ALT) values (both had Prob > F values of 0.0) while PCR was not correlated with ALT (Prob > F = 0.05). In 26 evaluable patients, a model based on a generalized Knodell score was used to predict response to IFN therapy, as defined by normalization of ALT values during therapy. This model discriminated well between non-responders and responders. The bDNA results correlated well with the generalized Knodell score, while the LH results did not (Prob > F = 0.04 and 0.19 for the bDNA and LH assays, respectively). In conclusion, the bDNA assay appears to be useful for quantification of HBV DNA levels in HBeAg-negative chronic hepatitis as it correlates with biochemical and histological indications of disease severity as well as with response to IFN therapy.

Hepatitis B Immunoprophylactic Failure and Characteristics of the Hepatitis B Virus Gene in Mother-Infant Pairs in Parts of China.

PubMed

Yin, Wen Jiao; Shen, Li Ping; Wang, Fu Zhen; Zhang, Guo Min; Zheng, Hui; Wang, Feng; Liu, Tie Zhu; Meng, Qing Ling; Yi, Yao; Cui, Fu Qiang; Bi, Sheng Li

2016-11-01

To determine the hepatitis B immunoprophylactic failure rate in infants born to hepatitis B virus (HBV) infected mothers and to characterize HBV genes. HBV-serological testing was conducted for pregnant women and infants. The complete genomes of 30 HBV isolates were sequenced, and genetic characteristics were analyzed using MEGA 5 software. The immunoprophylactic failure rate for infants who had completed the scheduled hepatitis B vaccination program was 5.76% (32/556). High sequence homology (99.8%-100%) was observed in 8 of the 10 mother-infant pairs. We identified 19 subgenotype C2 strains, 9 subgenotype B2 strains, and 2 subgenotype C1 strains. Three serotypes were detected: adr (19/30), adw (9/30), and ayw (2/30). The frequency of amino acid mutation of the 'a' determinant region was 16.67% (5/30), including that of Q129H, F134Y, S136Y, and G145E. We detected 67 amino acid mutations in the basal core promoter, precore, and core regions of the genome. The immunoprophylactic failure rate in infants born to HBV-infected mothers is low in the regions of China examined during this study. Moreover, HBV mutation in the 'a' determinant region could not account for immunoprophylactic failure for all infants. Copyright © 2016 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Adult Living with Hepatitis B

MedlinePlus

... Is Hepatitis B? The ABCs of Viral Hepatitis Liver Cancer and Hepatitis B Hepatitis Delta Coinfection Hepatitis C ... Project Princeton Workshop Public Health and International Programs Liver Cancer Connect Coalition Against Hepatitis for People of African ...

Insulin-Inducible SMILE Inhibits Hepatic Gluconeogenesis.

PubMed

Lee, Ji-Min; Seo, Woo-Young; Han, Hye-Sook; Oh, Kyoung-Jin; Lee, Yong-Soo; Kim, Don-Kyu; Choi, Seri; Choi, Byeong Hun; Harris, Robert A; Lee, Chul-Ho; Koo, Seung-Hoi; Choi, Hueng-Sik

2016-01-01

The role of a glucagon/cAMP-dependent protein kinase-inducible coactivator PGC-1α signaling pathway is well characterized in hepatic gluconeogenesis. However, an opposing protein kinase B (PKB)/Akt-inducible corepressor signaling pathway is unknown. A previous report has demonstrated that small heterodimer partner-interacting leucine zipper protein (SMILE) regulates the nuclear receptors and transcriptional factors that control hepatic gluconeogenesis. Here, we show that hepatic SMILE expression was induced by feeding in normal mice but not in db/db and high-fat diet (HFD)-fed mice. Interestingly, SMILE expression was induced by insulin in mouse primary hepatocyte and liver. Hepatic SMILE expression was not altered by refeeding in liver-specific insulin receptor knockout (LIRKO) or PKB β-deficient (PKBβ(-/-)) mice. At the molecular level, SMILE inhibited hepatocyte nuclear factor 4-mediated transcriptional activity via direct competition with PGC-1α. Moreover, ablation of SMILE augmented gluconeogenesis and increased blood glucose levels in mice. Conversely, overexpression of SMILE reduced hepatic gluconeogenic gene expression and ameliorated hyperglycemia and glucose intolerance in db/db and HFD-fed mice. Therefore, SMILE is an insulin-inducible corepressor that suppresses hepatic gluconeogenesis. Small molecules that enhance SMILE expression would have potential for treating hyperglycemia in diabetes. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

De novo activation of HBV with escape mutations from hepatitis B surface antibody after living donor liver transplantation.

PubMed

Ueda, Yoshihide; Marusawa, Hiroyuki; Egawa, Hiroto; Okamoto, Shinya; Ogura, Yasuhiro; Oike, Fumitaka; Nishijima, Norihiro; Takada, Yasutsugu; Uemoto, Shinji; Chiba, Tsutomu

2011-01-01

De novo activation of HBV occurs after liver transplantation from hepatitis B surface antigen (HBsAg)-negative and hepatitis B core antibody (anti-HBc)-positive donors, even under hepatitis B immunoglobulin (HBIG) prophylaxis. One reason for the activation of HBV is the emergence of HBV with escape mutations from hepatitis B surface antibody (anti-HBs). The aim of this study is to clarify the clinical features for de novo activation of HBV with anti-HBs escape mutations after liver transplantation. Clinical features of 75 patients who received HBIG prophylaxis >6 months after liver transplantation with liver grafts from anti-HBc-positive donors were retrospectively analysed. Among the 75 recipients, 19 (25%) developed de novo activation of HBV. Of the 19 recipients, the emergence of HBV with anti-HBs escape mutations was confirmed in 7 patients. The rate of de novo activation of HBV with anti-HBs escape mutations was 12% at 5 years. Sequence analysis revealed mutations in the common 'a' determinant region of the surface gene, including G145R, G145A and Q129P, in HBsAg. Administration of entecavir immediately after the occurrence of de novo HBV activation resolved hepatitis and induced clearance of serum HBsAg and HBV DNA in all four patients receiving entecavir. Escape mutations from anti-HBs caused de novo activation of HBV under HBIG prophylaxis after liver transplantation. Early administration of entecavir was effective on de novo activation of HBV with anti-HBs escape mutations.

Hepatitis B virus (image)

MedlinePlus

Hepatitis B is also known as serum hepatitis and is spread through blood and sexual contact. It is ... population. This photograph is an electronmicroscopic image of hepatitis B virus particles. (Image courtesy of the Centers for ...

Nephrolithiasis and Osteomalacia associated with adefovir-induced Fanconi syndrome in a patient with hepatitis B.

PubMed

Lin, Jueying; Zhuo, Yufeng; Zhang, Dongdong

2017-08-29

An increasing number of case reports suggest that acquired renal Fanconi syndrome may be associated with prolonged use of adefovir against hepatitis B virus. Renal Fanconi syndrome is an uncommon disease, and its complication with nephrolithiasis is quite rare. Herein, we report a rare coexistence of nephrolithiasis and acquired renal Fanconi syndrome in a chronic hepatitis B-positive patient with prolonged adefovir therapy. The patient presented with osteomalacia and nephrolithiasis. Consequently, extracorporeal shock-wave lithotripsy and left double-J ureteral stent insertion were considered for obstructive nephropathy, which was caused by nephrolithiasis. However, osteomalacia had been misdiagnosed as osteoporosis before admission to our hospital. On admission, a complexity of multiple fractures, hypophosphataemia, glycosuria without hyperglycaemia and non-anion-gap metabolic acidosis indicated a diagnosis of acquired renal Fanconi syndrome induced by adefovir. After switching from adefovir to entecavir, the patient's symptoms and laboratory findings improved significantly. The mechanism responsible for nephrolithiasis in renal Fanconi syndrome is still unclear. We recommend regularly monitoring renal function and serum calcium and serum phosphate to prevent renal Fanconi syndrome during the prolonged use of adefovir for hepatitis B virus.

Old and new adjuvants for hepatitis B vaccines.

PubMed

Leroux-Roels, Geert

2015-02-01

The safety and immunogenicity profiles of currently available recombinant hepatitis B vaccines are excellent. However, it remains a real challenge to induce protective immunity in the target groups that respond poorly or not at all to conventional vaccines. Ideally, a hepatitis B vaccine can be developed that conveys lifelong protection against infection rapidly after the injection of a single dose. Although this goal is far from being reached, important improvements have been made. Novel vaccine adjuvants have been developed that enhance the immunogenicity of recombinant hepatitis B vaccines while maintaining a good safety profile. The different adjuvants and adjuvant systems that are discussed herein have all been thoroughly evaluated in clinical trials and some have reached or are close to reach the market.

Postprandial lysophospholipid suppresses hepatic fatty acid oxidation: the molecular link between group 1B phospholipase A2 and diet-induced obesity

PubMed Central

Labonté, Eric D.; Pfluger, Paul T.; Cash, James G.; Kuhel, David G.; Roja, Juan C.; Magness, Daniel P.; Jandacek, Ronald J.; Tschöp, Matthias H.; Hui, David Y.

2010-01-01

Decrease in fat catabolic rate on consuming a high-fat diet contributes to diet-induced obesity. This study used group 1B phospholipase A2 (Pla2g1b)-deficient mice, which are resistant to hyperglycemia, to test the hypothesis that Pla2g1b and its lipolytic product lysophospholipid suppress hepatic fat utilization and energy metabolism in promoting diet-induced obesity. The metabolic consequences of hypercaloric diet, including body weight gain, energy expenditure, and fatty acid oxidation, were compared between Pla2g1b+/+ and Pla2g1b−/− mice. The Pla2g1b−/− mice displayed normal energy balance when fed chow, but were resistant to obesity when challenged with a hypercaloric diet. Obesity resistance in Pla2g1b−/− mice is due to their ability to maintain elevated energy expenditure and core body temperature when subjected to hypercaloric diet, which was not observed in Pla2g1b+/+ mice. The Pla2g1b−/− mice also displayed increased postprandial hepatic fat utilization due to increased expression of peroxisome proliferator-activated receptor (PPAR)-α, PPAR-δ, PPAR-γ, cd36/Fat, and Ucp2, which coincided with reduced postprandial plasma lysophospholipid levels. Lysophospholipids produced by Pla2g1b hydrolysis suppress hepatic fat utilization and down-regulate energy expenditure, thereby preventing metabolically beneficial adaptation to a high-fat diet exposure in promoting diet-induced obesity and type 2 diabetes.—Labonté, E. D., Pfluger, P. T., Cash, J. G., Kuhel, D. G., Rojas, J. C., Magness, D. P., Jandacek, R. J., Tschöp, M. H., Hui, D. Y. Postprandial lysophospholipid suppresses hepatic fatty acid oxidation: the molecular link between group 1B phospholipase A2 and diet-induced obesity. PMID:20215528

Prevalence of hepatitis B virus infection among black children in Soweto.

PubMed Central

Dibisceglie, A M; Kew, M C; Dusheiko, G M; Berger, E L; Song, E; Paterson, A C; Hodkinson, H J

1986-01-01

Roughly 15% of black children in rural areas of southern Africa are carriers of the hepatitis B virus. The purpose of the present study was to determine the prevalence of chronic hepatitis B virus infection among urban black children born and growing up in Soweto. A total of 2364 children were studied, ranging in age from 3 to 19 years, and of these, 1319 (56%) were girls. The children were drawn from the highest and the lowest socioeconomic classes. Serum samples were tested for all hepatitis B virus markers as well as IgG antibody against hepatitis A virus. HBsAg was detected in 23 (0.97%) of the children, anti-HBc and anti-HBs together in 155 (6.6%), anti-HBc alone in 17 (0.7%), and anti-HBs alone in 72 (3%). Of the 2364 children, 2097 (88.5%) were negative for all hepatitis B virus markers. IgG antibody to hepatitis A virus was present in 175 (97%) of a sample of 179 children. There was no difference in prevalence of hepatitis B virus markers between children from the upper and lower socioeconomic classes. HBsAg was more common in boys (16 out of 1043 (1.5%) than girls (seven out of 1321 (0.57%), and the prevalence of all hepatitis B virus markers increased with age. The youngest carrier of hepatitis B virus was 7 years old. The remarkable difference in the hepatitis B virus carrier rate between urban and rural black children offers a unique opportunity to investigate the favourable influences operating in an urban environment to limit the prevalence of hepatitis B virus infection. PMID:3087462

[Parvovirus B19 infection after kidney transplantation].

PubMed

Brodin-Sartorius, Albane; Mekki, Yahia; Bloquel, Bénédicte; Rabant, Marion; Legendre, Christophe

2012-02-01

Prevalence for human parvovirus B19 infection is estimated to be between 2% and 30% in renal transplant recipients. In post-transplant settings, parvovirus B19 infection may occur either as a primary infection or a reactivation. Parvovirus transmission most commonly occurs through respiratory tract but may also result from graft or blood packs contamination. Co-infections with HHV-6 and CMV viruses are frequent. The hallmark symptom is anemia, more rarely pancytopenia and hemophagocytic syndrome. In respect to renal involvement, parvovirus B19 infection has been associated with graft dysfunction in 10% of cases. Both thrombotic microangiopathies and collapsing glomerulopathies have been reported concomitantly with parvovirus B19 infection but the causal link remains unclear. Other complications are seldomly reported, including hepatitis, encephalitis, and myocarditis. Diagnosis is based on pre and post-transplant serological status. In addition, the management of parvovirus B19 infection in immunocompromised patients requires quantitative assessment of blood viral load by PCR. The treatment relies primarily on reduction of immunosuppression combined with intravenous immunoglobulin infusions. Relapses occur in 30% of cases. Copyright © 2011 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Hepatitis B Foundation Newsletter: B Informed

MedlinePlus

... CDC Awards Hepatitis B Foundation 5-Year Cooperative Agreement It Takes a Coalition to Fight Hepatitis B ... Dr. Baruch S. Blumberg HBF Awarded 3-Year Cooperative Agreement from CDC About "A Nobel Challenge" Cure Agenda ...

CD40 dependent exacerbation of immune mediated hepatitis by hepatic CD11b+ Gr-1+ myeloid derived suppressor cells in tumor bearing mice

PubMed Central

Kapanadze, Tamar; Medina-Echeverz, José; Gamrekelashvili, Jaba; Weiss, Jonathan M.; Wiltrout, Robert H.; Kapoor, Veena; Hawk, Nga; Terabe, Masaki; Berzofsky, Jay A.; Manns, Michael P.; Wang, Ena; Marincola, Francesco M.; Korangy, Firouzeh; Greten, Tim F.

2015-01-01

Immunosuppressive CD11b+Gr-1+ myeloid-derived suppressor cells (MDSC) accumulate in the livers of tumor-bearing mice. We studied hepatic MDSC in two murine models of immune mediated hepatitis. Unexpectedly, treatment of tumor bearing mice with Concanavalin A or α-Galactosylceramide resulted in increased ALT and AST serum levels in comparison to tumor free mice. Adoptive transfer of hepatic MDSC into naïve mice exacerbated Concanavalin A induced liver damage. Hepatic CD11b+Gr-1+ cells revealed a polarized pro-inflammatory gene signature after Concanavalin A treatment. An interferon gamma- dependent up-regulation of CD40 on hepatic CD11b+Gr-1+ cells along with an up-regulation of CD80, CD86, and CD1d after Concanavalin A treatment was observed. Concanavalin A treatment resulted in a loss of suppressor function by tumor-induced CD11b+Gr-1+ MDSC as well as enhanced reactive oxygen species-mediated hepatotoxicity. CD40 knockdown in hepatic MDSC led to increased arginase activity upon Concanavalin A treatment and lower ALT/AST serum levels. Finally, blockade of arginase activity in Cd40−/− tumor-induced myeloid cells resulted in exacerbation of hepatitis and increased reactive oxygen species production in vivo. Our findings indicate that in a setting of acute hepatitis, tumor-induced hepatic MDSC act as pro-inflammatory immune effector cells capable of killing hepatocytes in a CD40-dependent manner. PMID:25616156

Hepatoprotective Effects of Grape Seed Procyanidin B2 in Rats With Carbon Tetrachloride-induced Hepatic Fibrosis.

PubMed

Wang, Zhenli; Zhang, Zemin; Du, Ning; Wang, Kai; Li, Lei

2015-01-01

Infectious hepatitis is a serious problem affecting millions of people worldwide, particularly in China and other developing countries, and it is the major risk factor for hepatic cirrhosis. To date, the pathogenesis of hepatic cirrhosis is complex and unclear. Traditional Chinese medicine (TCM) has long been used in its treatment; however, little is known to date about the effects of grape seed procyanidin B2 (GSPB2) on liver fibrosis. Using a rat model of carbon tetrachloride (CCl4)-induced hepatic fibrosis, the study intended to investigate the hepatoprotective effects of GSPB2 and to determine the possible pathway by which GSPB2 exerts its activities. Design • Thirty-six male, Sprague-Dawley rats were used in the study. Rats in a model (CCl4 only) group and the GSPB2 group were given CCl4 to induce hepatic fibrosis. Simultaneously, animals in the GSPB2 group were treated with GSPB2 by intragastric administration for 12 wk. In addition, the rat's Kupffer cells were cultured with CCl4 and GSPB2. The study took place at the central laboratory of Qilu Hospital at Shandong University in Jinan, China. The following parameters were investigated: (1) hepatic function; (2) the liver fibrosis index-serum hyaluronic acid (HA), laminin (LN), type 3 procollagen (PC-3), collagen 4, and hepatic hydroxyproline; (3) the expression in the liver of transforming growth factor β-1 (TGF-β1); (4) inflammatory cytokines in the liver and cell culture medium-tumor necrosis factor α (TNF-α), interleukin (IL) 1-β (IL-1β), IL-6, and IL-17; (5) oxidative stress markers in the liver and cell culture medium-malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), total superoxide dismutase (T-SOD), and total antioxidant capacity (T-AOC); and (6) levels of angiotensin 2 (Ang 2) in the liver. The CCl4 induced (1) significant hepatic-function damage; (2) elevated levels of the measures of the liver fibrosis index, TGF-β1, inflammatory cytokines, MDA, and 8-OHdG; (3) a reduction in

Inhibition of interferon-inducible MxA protein expression by hepatitis B virus capsid protein.

PubMed

Rosmorduc, O; Sirma, H; Soussan, P; Gordien, E; Lebon, P; Horisberger, M; Bréchot, C; Kremsdorf, D

1999-05-01

Chronic hepatitis B treatment has been significantly improved by interferon (IFN) treatment. However, some studies have suggested that hepatitis B virus (HBV) might have a direct effect on the resistance to IFN. Defective particles, generated by spliced HBV RNA and associated with chronic hepatitis B, have been previously characterized; expression of these particles leads to cytoplasmic accumulation of the capsid protein. The aim of this study was to investigate the role of these defective genomes in IFN resistance. The global antiviral activity of IFN was studied by virus yield reduction assays, the expression of three IFN-induced antiviral proteins was analysed by Western blotting and confocal microscopy, and the regulation of MxA gene expression was studied by Northern blotting and the luciferase assay, in Huh7 cells transfected with a complete or the defective HBV genome. Results showed that the expression of the defective genome reduces the antiviral activity of IFN and that this modulation involves a selective inhibition of MxA protein induction by the HBV capsid protein. Our results also show the trans-suppressive effect of the HBV capsid on the MxA promoter, which might participate in this phenomenon. In conclusion, this study shows a direct interplay between the IFN-sensitive pathway and the capsid protein and might implicate this defective HBV genome in virus persistence.

[Efficacy and safety of heptral, vitamin B6 and folic acid during toxic hepatitis induced by CCL4].

PubMed

Antelava, N A; Gogoluari, M I; Gogoluari, L I; Pirtskhalaĭshvili, N N; Okudzhava, M V

2007-09-01

The aim of this work was to evaluate of efficacy and safety of complex Heptral, Vitamin B6 and Folic Acid in experimental hepatitis therapy compared with monotherapy. Experiments were carried out on pubertal rats. Eperimental hepatitis models were induced by Tetrachlormethane. The tetrachlormethane intoxication was reproduced by subcutaneous injection of CCL(4) 1ml/kg dissolved in 1ml of olive oil. Cytochrome P450, cytochrome b5, reduced glutation,activity of glutationetranspherase and content of ATP in hepatocytes were measured by the spectrophotometric techniques,but content of homocysteine by chromophtography techniques. Under CCL(4) intoxication disturbance of liver detoxication function, energy deficit and surplus of homocysteine were observed. Treatment of the toxic hepatitis with heptral increased the level of cytochrome P450, cytochrome b5, glutation activity of glutationetranspherase glutathione and reduced content of homocysteine. Complex therapy with Heptral and B6 and folic acid reveal more expressive hepatoprotective effect and safety than monotherapy with Heptral. Complex therapy improves not only the parameters of biotransformation (metabolic and conjugation phase), but also normalizes the level of ATP and homocystein. Vitamins B6 and folic acid increases the efficacy and safety of Heptral. This complex was recomended for treatment of hepatitis.

Structural basis for host membrane remodeling induced by protein 2B of hepatitis A virus.

PubMed

Vives-Adrián, Laia; Garriga, Damià; Buxaderas, Mònica; Fraga, Joana; Pereira, Pedro José Barbosa; Macedo-Ribeiro, Sandra; Verdaguer, Núria

2015-04-01

The complexity of viral RNA synthesis and the numerous participating factors require a mechanism to topologically coordinate and concentrate these multiple viral and cellular components, ensuring a concerted function. Similarly to all other positive-strand RNA viruses, picornaviruses induce rearrangements of host intracellular membranes to create structures that act as functional scaffolds for genome replication. The membrane-targeting proteins 2B and 2C, their precursor 2BC, and protein 3A appear to be primarily involved in membrane remodeling. Little is known about the structure of these proteins and the mechanisms by which they induce massive membrane remodeling. Here we report the crystal structure of the soluble region of hepatitis A virus (HAV) protein 2B, consisting of two domains: a C-terminal helical bundle preceded by an N-terminally curved five-stranded antiparallel β-sheet that displays striking structural similarity to the β-barrel domain of enteroviral 2A proteins. Moreover, the helicoidal arrangement of the protein molecules in the crystal provides a model for 2B-induced host membrane remodeling during HAV infection. No structural information is currently available for the 2B protein of any picornavirus despite it being involved in a critical process in viral factory formation: the rearrangement of host intracellular membranes. Here we present the structure of the soluble domain of the 2B protein of hepatitis A virus (HAV). Its arrangement, both in crystals and in solution under physiological conditions, can help to understand its function and sheds some light on the membrane rearrangement process, a putative target of future antiviral drugs. Moreover, this first structure of a picornaviral 2B protein also unveils a closer evolutionary relationship between the hepatovirus and enterovirus genera within the Picornaviridae family. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Structural Basis for Host Membrane Remodeling Induced by Protein 2B of Hepatitis A Virus

PubMed Central

Vives-Adrián, Laia; Garriga, Damià; Buxaderas, Mònica; Fraga, Joana; Pereira, Pedro José Barbosa

2015-01-01

ABSTRACT The complexity of viral RNA synthesis and the numerous participating factors require a mechanism to topologically coordinate and concentrate these multiple viral and cellular components, ensuring a concerted function. Similarly to all other positive-strand RNA viruses, picornaviruses induce rearrangements of host intracellular membranes to create structures that act as functional scaffolds for genome replication. The membrane-targeting proteins 2B and 2C, their precursor 2BC, and protein 3A appear to be primarily involved in membrane remodeling. Little is known about the structure of these proteins and the mechanisms by which they induce massive membrane remodeling. Here we report the crystal structure of the soluble region of hepatitis A virus (HAV) protein 2B, consisting of two domains: a C-terminal helical bundle preceded by an N-terminally curved five-stranded antiparallel β-sheet that displays striking structural similarity to the β-barrel domain of enteroviral 2A proteins. Moreover, the helicoidal arrangement of the protein molecules in the crystal provides a model for 2B-induced host membrane remodeling during HAV infection. IMPORTANCE No structural information is currently available for the 2B protein of any picornavirus despite it being involved in a critical process in viral factory formation: the rearrangement of host intracellular membranes. Here we present the structure of the soluble domain of the 2B protein of hepatitis A virus (HAV). Its arrangement, both in crystals and in solution under physiological conditions, can help to understand its function and sheds some light on the membrane rearrangement process, a putative target of future antiviral drugs. Moreover, this first structure of a picornaviral 2B protein also unveils a closer evolutionary relationship between the hepatovirus and enterovirus genera within the Picornaviridae family. PMID:25589659

Hepatitis B, HIV, and Syphilis Seroprevalence in Pregnant Women and Blood Donors in Cameroon

PubMed Central

Mbah, Rahel; Rembert, Nicole J.; Tancho, Samuel; Halle-Ekane, Gregory E.; Enah, Comfort; Welty, Thomas K.; Tih, Pius M.; Tita, Alan T. N.

2016-01-01

Objectives. We estimated seroprevalence and correlates of selected infections in pregnant women and blood donors in a resource-limited setting. Methods. We performed a cross-sectional analysis of laboratory seroprevalence data from pregnant women and voluntary blood donors from facilities in Cameroon in 2014. Rapid tests were performed to detect hepatitis B surface antigen, syphilis treponemal antibodies, and HIV-1/2 antibodies. Blood donations were also tested for hepatitis C and malaria. Results. The seroprevalence rates and ranges among 7069 pregnant women were hepatitis B 4.4% (1.1–9.6%), HIV 6% (3.0–10.2%), and syphilis 1.7% (1.3–3.8%) with significant variability among the sites. Correlates of infection in pregnancy in adjusted regression models included urban residence for hepatitis B (aOR 2.9, CI 1.6–5.4) and HIV (aOR 3.5, CI 1.9–6.7). Blood donor seroprevalence rates and ranges were hepatitis B 6.8% (5.0–8.8%), HIV 2.2% (1.4–2.8%), syphilis 4% (3.3–4.5%), malaria 1.9%, and hepatitis C 1.7% (0.5–2.5%). Conclusions. Hepatitis B, HIV, and syphilis infections are common among pregnant women and blood donors in Cameroon with higher rates in urban areas. Future interventions to reduce vertical transmission should include universal screening for these infections early in pregnancy and provision of effective prevention tools including the birth dose of univalent hepatitis B vaccine. PMID:27578957

Tumor induced hepatic myeloid derived suppressor cells can cause moderate liver damage.

PubMed

Eggert, Tobias; Medina-Echeverz, José; Kapanadze, Tamar; Kruhlak, Michael J; Korangy, Firouzeh; Greten, Tim F

2014-01-01

Subcutaneous tumors induce the accumulation of myeloid derived suppressor cells (MDSC) not only in blood and spleens, but also in livers of these animals. Unexpectedly, we observed a moderate increase in serum transaminases in mice with EL4 subcutaneous tumors, which prompted us to study the relationship of hepatic MDSC accumulation and liver injury. MDSC were the predominant immune cell population expanding in livers of all subcutaneous tumor models investigated (RIL175, B16, EL4, CT26 and BNL), while liver injury was only observed in EL4 and B16 tumor-bearing mice. Elimination of hepatic MDSC in EL4 tumor-bearing mice using low dose 5-fluorouracil (5-FU) treatment reversed transaminase elevation and adoptive transfer of hepatic MDSC from B16 tumor-bearing mice caused transaminase elevation indicating a direct MDSC mediated effect. Surprisingly, hepatic MDSC from B16 tumor-bearing mice partially lost their damage-inducing potency when transferred into mice bearing non damage-inducing RIL175 tumors. Furthermore, MDSC expansion and MDSC-mediated liver injury further increased with growing tumor burden and was associated with different cytokines including GM-CSF, VEGF, interleukin-6, CCL2 and KC, depending on the tumor model used. In contrast to previous findings, which have implicated MDSC only in protection from T cell-mediated hepatitis, we show that tumor-induced hepatic MDSC themselves can cause moderate liver damage.

Tumor Induced Hepatic Myeloid Derived Suppressor Cells Can Cause Moderate Liver Damage

PubMed Central

Eggert, Tobias; Medina-Echeverz, José; Kapanadze, Tamar; Kruhlak, Michael J.; Korangy, Firouzeh; Greten, Tim F.

2014-01-01

Subcutaneous tumors induce the accumulation of myeloid derived suppressor cells (MDSC) not only in blood and spleens, but also in livers of these animals. Unexpectedly, we observed a moderate increase in serum transaminases in mice with EL4 subcutaneous tumors, which prompted us to study the relationship of hepatic MDSC accumulation and liver injury. MDSC were the predominant immune cell population expanding in livers of all subcutaneous tumor models investigated (RIL175, B16, EL4, CT26 and BNL), while liver injury was only observed in EL4 and B16 tumor-bearing mice. Elimination of hepatic MDSC in EL4 tumor-bearing mice using low dose 5-fluorouracil (5-FU) treatment reversed transaminase elevation and adoptive transfer of hepatic MDSC from B16 tumor-bearing mice caused transaminase elevation indicating a direct MDSC mediated effect. Surprisingly, hepatic MDSC from B16 tumor-bearing mice partially lost their damage-inducing potency when transferred into mice bearing non damage-inducing RIL175 tumors. Furthermore, MDSC expansion and MDSC-mediated liver injury further increased with growing tumor burden and was associated with different cytokines including GM-CSF, VEGF, interleukin-6, CCL2 and KC, depending on the tumor model used. In contrast to previous findings, which have implicated MDSC only in protection from T cell-mediated hepatitis, we show that tumor-induced hepatic MDSC themselves can cause moderate liver damage. PMID:25401795

[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

Immunity to hepatitis A and B persists for at least 15 years after immunisation of adolescents with a combined hepatitis A and B vaccine.

PubMed

Beran, Jiri; Van Der Meeren, Olivier; Leyssen, Maarten; D'silva, Priya

2016-05-23

The exact duration of antibody persistence to hepatitis A and B and the need for booster dosing following primary immunisation remains undefined. A long-term study was designed to follow antibody persistence and immune memory on an annual basis for up to 15 years following vaccination during adolescence. Subjects received a combined hepatitis A and B vaccine (Twinrix™, GSK Vaccines, Belgium) at 12-15 years of age, either as 2-dose of the adult formulation or 3-dose of the paediatric formulation. Blood samples were taken every year thereafter to assess antibody persistence and immune memory to hepatitis A and B. Antibodies to hepatitis A virus (anti-HAV) and hepatitis B surface antigen (anti-HBs) were measured at Years 11-15. At Year 15 immune memory was further assessed by measuring the anamnestic response to a challenge dose of the monovalent vaccine, which was administered to subjects whose antibody concentrations fell below the pre-defined cut-offs (anti-HAV: <15mIU/mL; anti-HBs: <10mIU/mL). 209 subjects returned for follow-up at Year 15 of whom 162 were included in the long-term according-to-protocol immunogenicity cohort. All subjects remained seropositive for anti-HAV antibodies, while 81.1% and 81.8% still had anti-HBs antibodies ≥10mIU/mL in the 2- and 3-dose groups, respectively. Following hepatitis B vaccine challenge dose administration to 19 subjects, all except one in the 3-dose group, mounted a robust anamnestic response. The safety and reactogenicity profile of the hepatitis B challenge was consistent with previous experience. Immunity to hepatitis A and B persists 15 years after adolescent vaccination with a combined hepatitis A and B vaccine. Highly effective anamnestic response indicates that a booster dose should not be required for 15 years after primary vaccination. http://www.clinicaltrials.govNCT00875485. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Preventing hepatitis B or C

MedlinePlus

... ency/patientinstructions/000401.htm Preventing hepatitis B or C To use the sharing features on this page, please enable JavaScript. Hepatitis B and hepatitis C infections cause irritation and swelling of the liver. ...

Omega-3 polyunsaturated fatty acids alleviate hepatic steatosis-induced inflammation through Sirt1-mediated nuclear translocation of NF-κB p65 subunit in hepatocytes of large yellow croaker (Larmichthys crocea).

PubMed

Wang, Tianjiao; Yang, Bo; Ji, Renlei; Xu, Wei; Mai, Kangsen; Ai, Qinghui

2017-12-01

Hepatic steatosis induced inflammation is becoming increasingly prevalent in farmed fish. This study was conducted to investigate the protective effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) against hepatic steatosis-induced inflammation and its potential molecular mechanisms in hepatocyte of large yellow croaker (Larmichthys crocea). We found that the hepatic steatosis-induced inflammation was relieved by ω-3 PUFAs, meanwhile, the Sirt1 activity and transcript expression was increased by ω-3 PUFAs. The increased Sirt1 activity can decrease the hepatic steatosis-induced inflammation. The protective effects of ω-3 PUFAs against hepatic steatosis-induced inflammation was reversed by the treatment with Sirt1 inhibitor EX-527. The nuclear translocation of nuclear transcription factor kappa-B (NF-κB) p65 was significantly decreased after ω-3 PUFAs treatments compared to the palmitic acid stimulation group. The ω-3 PUFAs induced cytoplasm translocation of NF-κB p65 was reversed by EX-527. Together, ω-3 PUFAs alleviate hepatic steatosis-induced inflammation through Sirt1-mediated nuclear translocation of NF-κB p65 subunit in hepatocytes of large yellow croaker. The present study provides important insight into the mechanisms of the protective effects of ω-3 PUFAs, providing theory bases for alleviating the hepatic steatosis induced inflammation of farmed fish, thereby offering great benefits to the aquaculture industry and fish consumers. Copyright © 2017. Published by Elsevier Ltd.

In vitro differentiated hepatic oval-like cells enhance hepatic regeneration in CCl4 -induced hepatic injury.

PubMed

Awan, Sana Javaid; Baig, Maria Tayyab; Yaqub, Faiza; Tayyeb, Asima; Ali, Gibran

2017-01-01

Hepatic oval cells are likely to be activated during advanced stage of liver fibrosis to reconstruct damaged hepatic tissue. However, their scarcity, difficulties in isolation, and in vitro expansion hampered their transplantation in fibrotic liver. This study was aimed to investigate the repair potential of in vitro differentiated hepatic oval-like cells in CCl 4 -induced liver fibrosis. BMSCs and oval cells were isolated and characterized from C57BL/6 GFP + mice. BMSCs were differentiated into oval cells by preconditioning with HGF, EGF, SCF, and LIF and analyzed for the oval cells-specific genes. Efficiency of oval cells to reduce hepatocyte injury was studied by determining cell viability, release of LDH, and biochemical tests in a co-culture system. Further, in vivo repair potential of differentiated oval cells was determined in CCl 4 -induced fibrotic model by gene expression analysis, biochemical tests, mason trichrome, and Sirius red staining. Differentiated oval cells expressed hepatic oval cells-specific markers AFP, ALB, CK8, CK18, CK19. These differentiated cells when co-cultured with injured hepatocytes showed significant hepato-protection as measured by reduction in apoptosis, LDH release, and improvement in liver functions. Transplantation of differentiated oval cells like cells in fibrotic livers exhibited enhanced homing, reduced liver fibrosis, and improved liver functions by augmenting hepatic microenvironment by improved liver functions. This preconditioning strategy to differentiate BMSCs into oval cell leads to improved survival and homing of transplanted cells. In addition, reduction in fibrosis and functional improvement in mice with CCl 4 -induced liver fibrosis was achieved. © 2016 International Federation for Cell Biology.

Requirements for Hepatitis B Vaccinations among Optometry Students.

ERIC Educational Resources Information Center

Bowyer, Norma K.; And Others

1995-01-01

Data on the incidence of hepatitis B viral infection are examined, and a telephone survey of 19 schools of optometry concerning administrative policy about student immunization is reported. Results show less than one-third of schools require student vaccination. It is recommended that schools mandate immunization for all students. (MSE)

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.

Hepatic protein phosphatase 1 regulatory subunit 3B (Ppp1r3b) promotes hepatic glycogen synthesis and thereby regulates fasting energy homeostasis.

PubMed

Mehta, Minal B; Shewale, Swapnil V; Sequeira, Raymond N; Millar, John S; Hand, Nicholas J; Rader, Daniel J

2017-06-23

Maintenance of whole-body glucose homeostasis is critical to glycemic function. Genetic variants mapping to chromosome 8p23.1 in genome-wide association studies have been linked to glycemic traits in humans. The gene of known function closest to the mapped region, PPP1R3B (protein phosphatase 1 regulatory subunit 3B), encodes a protein (G L ) that regulates glycogen metabolism in the liver. We therefore sought to test the hypothesis that hepatic PPP1R3B is associated with glycemic traits. We generated mice with either liver-specific deletion ( Ppp1r3b Δ hep ) or liver-specific overexpression of Ppp1r3b The Ppp1r3b deletion significantly reduced glycogen synthase protein abundance, and the remaining protein was predominantly phosphorylated and inactive. As a consequence, glucose incorporation into hepatic glycogen was significantly impaired, total hepatic glycogen content was substantially decreased, and mice lacking hepatic Ppp1r3b had lower fasting plasma glucose than controls. The concomitant loss of liver glycogen impaired whole-body glucose homeostasis and increased hepatic expression of glycolytic enzymes in Ppp1r3b Δ hep mice relative to controls in the postprandial state. Eight hours of fasting significantly increased the expression of two critical gluconeogenic enzymes, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, above the levels in control livers. Conversely, the liver-specific overexpression of Ppp1r3b enhanced hepatic glycogen storage above that of controls and, as a result, delayed the onset of fasting-induced hypoglycemia. Moreover, mice overexpressing hepatic Ppp1r3b upon long-term fasting (12-36 h) were protected from blood ketone-body accumulation, unlike control and Ppp1r3b Δ hep mice. These findings indicate a major role for Ppp1r3b in regulating hepatic glycogen stores and whole-body glucose/energy homeostasis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

B cell gene signature with massive intrahepatic production of antibodies to hepatitis B core antigen in hepatitis B virus-associated acute liver failure.

PubMed

Farci, Patrizia; Diaz, Giacomo; Chen, Zhaochun; Govindarajan, Sugantha; Tice, Ashley; Agulto, Liane; Pittaluga, Stefania; Boon, Denali; Yu, Claro; Engle, Ronald E; Haas, Mark; Simon, Richard; Purcell, Robert H; Zamboni, Fausto

2010-05-11

Hepatitis B virus (HBV)-associated acute liver failure (ALF) is a dramatic clinical syndrome due to a sudden loss of hepatic cells leading to multiorgan failure. The mechanisms whereby HBV induces ALF are unknown. Here, we show that liver tissue collected at the time of liver transplantation in two patients with HBV-associated ALF is characterized by an overwhelming B cell response apparently centered in the liver with massive accumulation of plasma cells secreting IgG and IgM, accompanied by complement deposition. We demonstrate that the molecular target of these antibodies is the hepatitis B core antigen (HBcAg); that these anti-bodies display a restricted variable heavy chain (V(H)) repertoire and lack somatic mutations; and that these two unrelated individuals with ALF use an identical predominant V(H) gene with unmutated variable domain (IGHV1-3) for both IgG and IgM anti-HBc antibodies, indicating that HBcAg is the target of a germline human V(H) gene. These data suggest that humoral immunity may exert a primary role in the pathogenesis of HBV-associated ALF.

Immunizations with chimeric hepatitis B virus-like particles to induce potential anti-hepatitis C virus neutralizing antibodies.

PubMed

Vietheer, Patricia T K; Boo, Irene; Drummer, Heidi E; Netter, Hans-Jürgen

2007-01-01

Virus-like particles (VLPs) are highly immunogenic and proven to induce protective immunity. The small surface antigen (HBsAg-S) of hepatitis B virus (HBV) self-assembles into VLPs and its use as a vaccine results in protective antiviral immunity against HBV infections. Chimeric HBsAg-S proteins carrying foreign epitopes allow particle formation and have the ability to induce anti-foreign humoral and cellular immune responses. The insertion of the hypervariable region 1 (HVR1) sequence derived from the envelope protein 2 (E2) of hepatitis C virus (HCV) into the major antigenic site of HBsAg-S ('a'-determinant) resulted in the formation of highly immunogenic VLPs that retained the antigenicity of the inserted HVR1 sequence. BALB/c mice were immunized with chimeric VLPs, which resulted in antisera with anti-HCV activity. The antisera were able to immunoprecipitate native HCV envelope complexes (E1E2) containing homologous or heterologous HVR1 sequences. HCV E1E2 pseudotyped HIV-1 particles (HCVpp) were used to measure entry into HuH-7 target cells in the presence or absence of antisera that were raised against chimeric VLPs. Anti-HVR1 VLP sera interfered with entry of entry-competent HCVpps containing either homologous or heterologous HVR1 sequences. Also, immunizations with chimeric VLPs induced antisurface antigen (HBsAg) antibodies, indicating that HBV-specific antigenicity and immunogenicity of the 'a'-determinant region is retained. A multivalent vaccine against different pathogens based on the HBsAg delivery platform should be possible. We hypothesize that custom design of VLPs with an appropriate set of HCV-neutralizing epitopes will induce antibodies that would serve to decrease the viral load at the initial infecting inoculum.

[Consistency analysis on acute hepatitis B inpatients reported by hepatitis B surveillance pilot spots in six provinces of China].

PubMed

Miao, N; Zhang, G M; Wang, F Z; Zheng, H; Sun, X J; Ma, X J; Cui, F Q

2017-02-10

Objective: To understand the characteristics of acute hepatitis B inpatients reported by the hepatitis B surveillance pilot points and to estimate the consistency between the diagnosed and reported types of hepatitis B by the clinicians involved. Methods: Data related to acute hepatitis B was from the NNDRS and the characteristics of acute hepatitis B were classified by querying Hospital Information System. We recorded the results based on clinical diagnosis and analyzed the consistency between the reported and diagnosed types that the clinicians made, on hepatitis B. Results: A total of 179 patients were included in this study with all of them as acute hepatitis B reported through NNDRS in 2015-2016. In terms of the durations of disease, among the 179 cases who were HBsAg positive, 32.40% (58/179) of them exceeding 6 months, 2.79% (5/179) within 6 months and 64.80% (116/179) tested the first time or never. Among the 179 cases who claimed having the history of hepatitis, 33.52% (60/179) of them identified as having hepatitis B, 1.12% (2/179) were hepatitis A, C or E, 41.34% (74/179) did not have the signs on hepatitis, while the rest 24.02% (43/179) did not know the situation. Only 79.89% (143/179) of the patients showed the symptoms or signs of hepatitis, but the rest 20.11% (36/179) did not. Among the 179 reported acute hepatitis patients, 67 of them were diagnosed as acute hepatitis B while 112 cases were as non-acute hepatitis B. The consistent rate of acute hepatitis B was 37.43% (67/179). Among the 112 cases that were diagnosed as non-acute hepatitis B, proportions of chronic hepatitis B and cirrhosis were 49.11%(55/112) and 16.07%(18/112) respectively. Conclusion: Consistency between the reported type of acute hepatitis B inpatients and the types diagnosed by clinicians was poor. Our results suggested that clinicians should make the accurate diagnosis at first place and then report to the Network in accordance with the clinical diagnosis classification

Hepatitis A and B immunity and vaccination in chronic hepatitis B and C patients in a large United States cohort.

PubMed

Henkle, Emily; Lu, Mei; Rupp, Lora B; Boscarino, Joseph A; Vijayadeva, Vinutha; Schmidt, Mark A; Gordon, Stuart C

2015-02-15

Hepatitis A and B vaccines are effective in preventing superinfection and sequelae in patients with chronic hepatitis B or C. We describe immunity and vaccination against hepatitis A and B in chronic hepatitis patients from the US Chronic Hepatitis Cohort Study. We identified chronic hepatitis B and C patients with healthcare utilization during 2006-2008 and 12 months of enrollment. We used electronic laboratory records to determine immunity and medical and billing records for vaccination history. Immunity against hepatitis A was defined by positive hepatitis A antibody or documented vaccination. Immunity against hepatitis B was defined as hepatitis B surface antibody level ≥10 mIU/mL or core antibody positive, or by documented vaccination. Among 1635 chronic hepatitis B patients, 978 (59.8%) were immune or vaccinated against hepatitis A, 122 (7.5%) had negative hepatitis A antibody tests, and 535 (32.7%) had no testing or vaccination record. Among 5328 chronic hepatitis C patients, 2998 (56.3%) were immune or vaccinated against hepatitis A, 659 (12.4%) had negative hepatitis A antibody tests, and 1671 (31.4%) had no testing or vaccination record. Additionally, 3150 (59.1%) chronic hepatitis C patients were immune or vaccinated against hepatitis B, 1003 (18.8%) had a negative test result, and 1175 (22.1%) were neither tested for nor vaccinated against hepatitis B. Approximately 40% of chronic hepatitis B and C patients are susceptible to or have no documented immunity or vaccination against hepatitis A or hepatitis B. Clinicians should consider antibody testing and vaccination for this vulnerable population. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

[Ketoconazole-induced hepatitis. Case report].

PubMed

Henning, H; Kasper, B; Lüders, C J

1983-12-01

Since Oct. 1981 a new systemic antifungal drug Ketoconazole is available in the Federal Republic of Germany that has proven effective even in severe cases with fungal infections. This case-study will call attention on a rare but important side effect, namely Ketoconazole induced hepatitis. As an acute icteric viral hepatitis, type Non-A-Non-B-hepatitis possibly misdiagnosed only a carefully compiled history of the recent intake of drugs points at the real cause of hepatitis. In our case-report we observed a considerable increase in serum enzymes, especially GOT, GPT and GLDH after a drug-challenge with two tablets. We recommend so-called liver functions tests 2 to 3 weeks after beginning of therapy and further-on in monthly intervals. Histologically at that time toxic hydropic changes of the liver cells and a mesenchymal reaction with portal and intralobular mainly eosinophilic infiltration could be established. The serum enzymes came to normal only after 12 weeks.

Hepatitis B virus infection and vaccine-induced immunity in Madrid (Spain).

PubMed

Pedraza-Flechas, Ana María; García-Comas, Luis; Ordobás-Gavín, María; Sanz-Moreno, Juan Carlos; Ramos-Blázquez, Belén; Astray-Mochales, Jenaro; Moreno-Guillén, Santiago

2014-01-01

To estimate the prevalence of hepatitis B virus (HBV) infection and vaccine-induced immunity in the region of Madrid, and to analyze their evolution over time. An observational, analytical, cross-sectional study was carried out in the population aged 16-80 years between 2008 and 2009. This was the last of four seroprevalence surveys in the region of Madrid. The prevalence of HBV infection and vaccine-induced immunity was estimated using multivariate logistic models and were compared with the prevalences in the 1989, 1993 and 1999 surveys. In the population aged 16-80 years, the prevalence of HBV infection was 11.0% (95% CI: 9.8-12.3) and that of chronic infection was 0.7% (95% CI: 0.5-1.1). The prevalence of vaccine-induced immunity in the population aged 16-20 years was 73.0% (95% CI: 70.0-76.0). Compared with previous surveys, there was a decrease in the prevalence of HBV infection. Based on the prevalence of chronic infection (<1%), Madrid is a region with low HBV endemicity. Preventive strategies against HBV should especially target the immigrant population. Copyright © 2013. Published by Elsevier Espana.

Hepatitis B -- children

MedlinePlus

... kissing, coughing, or sneezing. Breast-feeding by a mother with hepatitis B is safe if the child is treated properly at the time of birth. Teenagers who are not vaccinated can get HBV during unprotected sex or drug use. Symptoms Most children with hepatitis ...

Progress toward Elimination of Hepatitis B Virus Transmission in Oman: Impact of Hepatitis B Vaccination

PubMed Central

Thabit Al Awaidy, Salah; Pandurang Bawikar, Shyam; Salim Al Busaidy, Suleiman; Al Mahrouqi, Salim; Al Baqlani, Said; Al Obaidani, Idris; Alexander, James; Patel, Minal K.

2013-01-01

Approximately 2–7% of the Omani population has chronic hepatitis B virus (HBV) infection. To decrease this burden, universal childhood hepatitis B vaccination was introduced in Oman in 1990. The hepatitis B vaccination strategy and reported coverage were reviewed. To assess the impact of the program on chronic HBV seroprevalence, a nationally representative seroprevalence study was conducted in Oman in 2005. Since 1991, hepatitis B vaccination in Oman has reached almost every eligible child, with reported coverage of ≥ 97% for the birth dose and ≥ 94% for three doses. Of 175 children born pre-vaccine introduction, 16 (9.1%) had evidence of HBV exposure, and 4 (2.3%) had evidence of chronic infection. Of 1,890 children born after vaccine introduction, 43 (2.3%) had evidence of HBV exposure, and 10 (0.5%) had evidence of chronic infection. Oman has a strong infant hepatitis B vaccination program, resulting in a dramatic decrease in chronic HBV seroprevalence. PMID:23958910

Progress toward elimination of hepatitis B virus transmission in Oman: impact of hepatitis B vaccination.

PubMed

Al Awaidy, Salah Thabit; Bawikar, Shyam Pandurang; Al Busaidy, Suleiman Salim; Al Mahrouqi, Salim; Al Baqlani, Said; Al Obaidani, Idris; Alexander, James; Patel, Minal K

2013-10-01

Approximately 2-7% of the Omani population has chronic hepatitis B virus (HBV) infection. To decrease this burden, universal childhood hepatitis B vaccination was introduced in Oman in 1990. The hepatitis B vaccination strategy and reported coverage were reviewed. To assess the impact of the program on chronic HBV seroprevalence, a nationally representative seroprevalence study was conducted in Oman in 2005. Since 1991, hepatitis B vaccination in Oman has reached almost every eligible child, with reported coverage of ≥ 97% for the birth dose and ≥ 94% for three doses. Of 175 children born pre-vaccine introduction, 16 (9.1%) had evidence of HBV exposure, and 4 (2.3%) had evidence of chronic infection. Of 1,890 children born after vaccine introduction, 43 (2.3%) had evidence of HBV exposure, and 10 (0.5%) had evidence of chronic infection. Oman has a strong infant hepatitis B vaccination program, resulting in a dramatic decrease in chronic HBV seroprevalence.

Hepatitis B virus pathogenesis: Fresh insights into hepatitis B virus RNA.

PubMed

Sekiba, Kazuma; Otsuka, Motoyuki; Ohno, Motoko; Yamagami, Mari; Kishikawa, Takahiro; Suzuki, Tatsunori; Ishibashi, Rei; Seimiya, Takahiro; Tanaka, Eri; Koike, Kazuhiko

2018-06-07

Hepatitis B virus (HBV) is still a worldwide health concern. While divergent factors are involved in its pathogenesis, it is now clear that HBV RNAs, principally templates for viral proteins and viral DNAs, have diverse biological functions involved in HBV pathogenesis. These functions include viral replication, hepatic fibrosis and hepatocarcinogenesis. Depending on the sequence similarities, HBV RNAs may act as sponges for host miRNAs and may deregulate miRNA functions, possibly leading to pathological consequences. Some parts of the HBV RNA molecule may function as viral-derived miRNA, which regulates viral replication. HBV DNA can integrate into the host genomic DNA and produce novel viral-host fusion RNA, which may have pathological functions. To date, elimination of HBV-derived covalently closed circular DNA has not been achieved. However, RNA transcription silencing may be an alternative practical approach to treat HBV-induced pathogenesis. A full understanding of HBV RNA transcription and the biological functions of HBV RNA may open a new avenue for the development of novel HBV therapeutics.

Human Parvovirus B19 Induced Apoptotic Bodies Contain Altered Self-Antigens that are Phagocytosed by Antigen Presenting Cells

PubMed Central

Thammasri, Kanoktip; Rauhamäki, Sanna; Wang, Liping; Filippou, Artemis; Kivovich, Violetta; Marjomäki, Varpu; Naides, Stanley J.; Gilbert, Leona

2013-01-01

Human parvovirus B19 (B19V) from the erythrovirus genus is known to be a pathogenic virus in humans. Prevalence of B19V infection has been reported worldwide in all seasons, with a high incidence in the spring. B19V is responsible for erythema infectiosum (fifth disease) commonly seen in children. Its other clinical presentations include arthralgia, arthritis, transient aplastic crisis, chronic anemia, congenital anemia, and hydrops fetalis. In addition, B19V infection has been reported to trigger autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. However, the mechanisms of B19V participation in autoimmunity are not fully understood. B19V induced chronic disease and persistent infection suggests B19V can serve as a model for viral host interactions and the role of viruses in the pathogenesis of autoimmune diseases. Here we investigate the involvement of B19V in the breakdown of immune tolerance. Previously, we demonstrated that the non-structural protein 1 (NS 1) of B19V induces apoptosis in non-permissive cells lines and that this protein can cleave host DNA as well as form NS1-DNA adducts. Here we provide evidence that through programmed cell death, apoptotic bodies (ApoBods) are generated by B19V NS1 expression in a non-permissive cell line. Characterization of purified ApoBods identified potential self-antigens within them. In particular, signature self-antigens such as Smith, ApoH, DNA, histone H4 and phosphatidylserine associated with autoimmunity were present in these ApoBods. In addition, when purified ApoBods were introduced to differentiated macrophages, recognition, engulfment and uptake occurred. This suggests that B19V can produce a source of self-antigens for immune cell processing. The results support our hypothesis that B19V NS1-DNA adducts, and nucleosomal and lysosomal antigens present in ApoBods created in non-permissive cell lines, are a source of self-antigens. PMID:23776709

Hepatitis B FAQs for the Public

MedlinePlus

... the virus from: Birth (spread from an infected mother to her baby during birth) Sex with an infected partner Sharing needles, syringes, or ... hepatitis B virus. This includes: Infants born to mothers with hepatitis B Health Care ... patients Sex partners of someone with hepatitis B Any other ...

Hepatitis A and Hepatitis B vaccination coverage among adults with chronic liver disease

PubMed Central

Yue, Xin; Black, Carla L.; O’Halloran, Alissa; Lu, Peng-Jun; Williams, Walter W.; Nelson, Noele P.

2018-01-01

Background Infection with hepatitis A and hepatitis B virus can increase the risk of morbidity and mortality in persons with chronic liver disease (CLD). The Advisory Committee on Immunization Practices recommends hepatitis A (HepA) and hepatitis B (HepB) vaccination for persons with CLD. Methods Data from the 2014 and 2015 National Health Interview Surveys (NHIS), nationally representative, in-person interview surveys of the non-institutionalized US civilian population, were used to assess self-reported HepA (≥1 and ≥2 doses) and HepB vaccination (≥1 and ≥3 doses) coverage among adults who reported a chronic or long-term liver condition. Multivariable logistic regression was used to identify factors independently associated with HepA and HepB vaccination among adults with CLD. Results Overall, 19.4% and 11.5% of adults aged ≥18 years with CLD reported receiving ≥1 dose and ≥2 doses of HepA vaccine, respectively, compared with 14.7% and 9.1% of adults without CLD (p<0.05 comparing those with and without CLD, ≥1dose). Age, education, geographic region, and international travel were associated with receipt of ≥2 doses HepA vaccine among adults with CLD. Overall, 35.7% and 29.1% of adults with CLD reported receiving ≥1 dose and ≥3 doses of HepB vaccine, respectively, compared with 30.2% and 24.7% of adults without CLD (p<0.05 comparing those with and without CLD, ≥1 dose). Age, education, and receipt of influenza vaccination in the past 12 months were associated with receipt of ≥3 doses HepB vaccine among adults with CLD. Among adults with CLD and ≥10 provider visits, only 13.8% and 35.3% had received ≥2 doses HepA and ≥3 doses HepB vaccine, respectively. Conclusions HepA and HepB vaccination among adults with CLD is suboptimal and missed opportunities to vaccinate occurred. Providers should adhere to recommendations to vaccinate persons with CLD to increase vaccination among this population. PMID:29395521

Cynomolgus monkeys (Macaca fascicularis) experimentally infected with B19V and hepatitis A virus: no evidence of the co-infection as a cause of acute liver failure.

PubMed

Leon, Luciane Almeida Amado; Marchevsky, Renato Sergio; Gaspar, Ana Maria Coimbra; Garcia, Rita de Cassia Nasser Cubel; Almeida, Adilson José de; Pelajo-Machado, Marcelo; Castro, Tatiana Xavier de; Nascimento, Jussara Pereira do; Brown, Kevin E; Pinto, Marcelo Alves

2016-04-01

This study was conducted to analyse the course and the outcome of the liver disease in the co-infected animals in order to evaluate a possible synergic effect of human parvovirus B19 (B19V) and hepatitis A virus (HAV) co-infection. Nine adult cynomolgus monkeys were inoculated with serum obtained from a fatal case of B19V infection and/or a faecal suspension of acute HAV. The presence of specific antibodies to HAV and B19V, liver enzyme levels, viraemia, haematological changes, and necroinflammatory liver lesions were used for monitoring the infections. Seroconversion was confirmed in all infected groups. A similar pattern of B19V infection to human disease was observed, which was characterised by high and persistent viraemia in association with reticulocytopenia and mild to moderate anaemia during the period of investigation (59 days). Additionally, the intranuclear inclusion bodies were observed in pro-erythroblast cell from an infected cynomolgus and B19V Ag in hepatocytes. The erythroid hypoplasia and decrease in lymphocyte counts were more evident in the co-infected group. The present results demonstrated, for the first time, the susceptibility of cynomolgus to B19V infection, but it did not show a worsening of liver histopathology in the co-infected group.

Cynomolgus monkeys (Macaca fascicularis) experimentally infected with B19V and hepatitis A virus: no evidence of the co-infection as a cause of acute liver failure

PubMed Central

Leon, Luciane Almeida Amado; Marchevsky, Renato Sergio; Gaspar, Ana Maria Coimbra; Garcia, Rita de Cassia Nasser Cubel; de Almeida, Adilson José; Pelajo-Machado, Marcelo; de Castro, Tatiana Xavier; do Nascimento, Jussara Pereira; Brown, Kevin E; Pinto, Marcelo Alves

2016-01-01

This study was conducted to analyse the course and the outcome of the liver disease in the co-infected animals in order to evaluate a possible synergic effect of human parvovirus B19 (B19V) and hepatitis A virus (HAV) co-infection. Nine adult cynomolgus monkeys were inoculated with serum obtained from a fatal case of B19V infection and/or a faecal suspension of acute HAV. The presence of specific antibodies to HAV and B19V, liver enzyme levels, viraemia, haematological changes, and necroinflammatory liver lesions were used for monitoring the infections. Seroconversion was confirmed in all infected groups. A similar pattern of B19V infection to human disease was observed, which was characterised by high and persistent viraemia in association with reticulocytopenia and mild to moderate anaemia during the period of investigation (59 days). Additionally, the intranuclear inclusion bodies were observed in pro-erythroblast cell from an infected cynomolgus and B19V Ag in hepatocytes. The erythroid hypoplasia and decrease in lymphocyte counts were more evident in the co-infected group. The present results demonstrated, for the first time, the susceptibility of cynomolgus to B19V infection, but it did not show a worsening of liver histopathology in the co-infected group. PMID:27074255

Rituximab-based treatment, HCV replication, and hepatic flares.

PubMed

Sagnelli, Evangelista; Pisaturo, Mariantonietta; Sagnelli, Caterina; Coppola, Nicola

2012-01-01

Rituximab, a chimeric mouse-human monoclonal antibody directed to the CD20 antigen expressed on pre-B lymphocytes and mature lymphocytes, causes a profound B-cell depletion. Due to its peculiar characteristics, this drug has been used to treat oncohaematological diseases, B cell-related autoimmune diseases, rheumatoid arthritis, and, more recently, HCV-associated mixed cryoglobulinaemic vasculitis. Rituximab-based treatment, however, may induce an increased replication of several viruses such as hepatitis B virus, cytomegalovirus, varicella-zoster virus, echovirus, and parvovirus B19. Recent data suggest that rituximab-based chemotherapy induces an increase in HCV expression in hepatic cells, which may become a target for a cell-mediated immune reaction after the withdrawal of treatment and the restoration of the immune control. Only a few small studies have investigated the occurrence of HCV reactivation and an associated hepatic flare in patients with oncohaematological diseases receiving R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). These studies suggest that the hepatic flares are frequently asymptomatic, but life-threatening liver failure occurs in nearly 10% of cases.

Dynamic of Immune Response induced in Hepatitis B Surface Antigen-transgenic Mice Immunized with a Novel Therapeutic Formulation

PubMed Central

Almeida, Freya M Freyre; Blanco, Aracelys; Trujillo, Heidy; Hernández, Dunia; García, Daymir; Alba, José S; Abad, Matilde López; Merino, Nelson; Lobaina, Yadira

2016-01-01

ABSTRACT The development of therapeutic vaccines against chronic hepatitis B requires the capacity of the formulation to subvert a tolerated immune response as well as the evaluation of histopathological damage resulting from the treatment. In the present study, the dynamicity of induced immune response to hepatitis B surface antigen (HBsAg) was evaluated in transgenic mice that constitutively express the HBsAg gene (HBsAg-tg mice). After immunization with a vaccine candidate containing both surface (HBsAg) and core (HBcAg) antigens of hepatitis B virus (HBV), the effect of vaccination on clearance of circulating HBsAg and the potential histological alterations were examined. Transgenic (tg) and non-transgenic (Ntg) mice were immunized by intranasal (IN) and subcutaneous (SC) routes simultaneously. A control group received phosphate-buffered saline (PBS) by IN route and aluminum by SC route. Positive responses, at both humoral and cellular levels, were obtained after five immunizations in HBsAg-tg mice. Such responses were delayed and of lower intensity in tg mice, compared to vaccinated Ntg mice. Serum IgG response was characterized by a similar IgG subclass pattern. Even when HBsAg-specific CD8+ T cell responses were clearly detectable by gamma-interferon ELISPOT assay, histopathological alterations were not detected in any organ, including the liver and kidneys. Our study demonstrated, that it is possible to subvert the immune tolerance against HBsAg in tg mice, opening a window for new studies to optimize the schedule, dose, and formulation to improve the immune response to the therapeutic vaccine candidate. These results can be considered a safety proof to support clinical developments for the formulation under study. How to cite this article Freyre FM, Blanco A, Trujillo H, Hernández D, García D, Alba JS, Lopez M, Merino N, Lobaina Y, Aguilar JC. Dynamic of Immune Response induced in Hepatitis B Surface Antigen-transgenic Mice Immunized with a Novel

Multicenter evaluation of a commercial multiplex polymerase chain reaction test for screening plasma donations for parvovirus B19 DNA and hepatitis A virus RNA.

PubMed

Koppelman, Marco H G M; Cuijpers, H Theo M; Wessberg, Susanna; Valkeajärvi, Anne; Pichl, Lutz; Schottstedt, Volkmar; Saldanha, John

2012-07-01

Three European laboratories evaluated the TaqScreen DPX test (DPX test), a multiplex nucleic acid test assay for the simultaneous detection and quantitation of parvovirus B19 (B19V) DNA and the detection of hepatitis A virus (HAV) RNA. The 95% limit of detection of the test for B19V and HAV was determined using the respective WHO International Standards. The reproducibility of the test was evaluated by testing replicate samples of B19V at log 4.0 and 40 IU/mL and HAV at 5 IU/mL. The accuracy of the DPX test for B19V was evaluated by replicate testing of B19V samples containing log 3.0, log 4.0, and log 5.0 IU/mL. Panels of B19V Genotypes 1, 2, and 3 and HAV genotypes were evaluated. Cross-contamination was evaluated. For comparison of the DPX test and the established tests, the sites tested plasma samples in pools of either 96 or 480 donations. The mean 95% lower limits of detection of the three laboratories for B19V and HAV were 20.30 and 1.85 IU/mL. The test showed good reproducibility with the major part of the variance of the test being attributed to intermediate assay variation. The test showed great accuracy for B19V, especially at log 4.0 IU/mL. Spiking of test pools of 480 donations and manufacturing pools with log 4.0 IU/mL B19 DNA and 4 IU/mL HAV RNA showed that the DPX assay was robust. The test was able to detect the three genotypes of B19V and HAV genotypes. No cross-contamination was seen. Test results of routine samples correlated well with those of the established tests. The DPX test is a robust and sensitive test for the detection of B19V and HAV in plasma samples. The quantitative B19V results obtained with the test are accurate, and the test is able to detect all the known genotypes of B19V and HAV and fulfills all the European Pharmacopoeia and Food and Drug Administration requirements for a B19V and HAV test for screening of plasma donations and samples from plasma pools for manufacture. © 2012 American Association of Blood Banks.

Human parvovirus B19 antibodies induce altered membrane protein expression and apoptosis of BeWo trophoblasts.

PubMed

Tzang, Bor-Show; Chiang, Szu-Yi; Chan, Hsu-Chin; Liu, Chung-Hsien; Hsu, Tsai-Ching

2016-11-01

Human parvovirus B19 (B19) is harmful during pregnancy since it can be vertically transmitted to the developing fetus. In addition, the anti‑B19 antibodies induced by B19 infection are believed to have a cytopathic role in B19 transmission; however, knowledge regarding the effects of anti‑B19 antibodies during pregnancy is limited. To investigate the possible roles of anti‑B19 antibodies during pregnancy, the present study examined the effects of anti‑B19‑VP1 unique region (VP1u), anti‑B19‑VP2 and anti‑B19‑nonstructural protein 1 (NS1) immunoglobulin G (IgG) antibodies on BeWo trophoblasts. Briefly, BeWo trophoblasts were incubated with purified IgG against B19‑VP1u, B19‑VP2 and B19‑NS1. Subsequently, the expression of surface proteins and apoptotic molecules were assessed in BeWo trophoblasts using flow cytometry, ELISA and western blotting. The expression levels of human leukocyte antigen (HLA)‑G were significantly increased on BeWo trophoblasts treated with rabbit anti‑B19‑VP1u IgG, and were unchanged in those treated with rabbit anti‑B19‑NS1 and anti‑B19‑VP2 IgG, as compared with the control group. Furthermore, the expression levels of globoside (P blood group antigen) and cluster of differentiation (CD)29 (β1 integrin) were significantly increased in BeWo trophoblasts treated with rabbit anti‑B19‑NS1 and anti‑B19‑VP2 IgG, whereas only CD29 was also significantly increased in cells treated with anti‑B19‑VP1u IgG. In addition, the number of cells at sub‑G1 phase; caspase‑3 activity; and the expression of intrinsic and extrinsic apoptotic molecules, including Fas‑associated death domain protein, activated caspase‑8, activated caspase‑3, B‑cell lymphoma 2‑associated X protein, cytochrome c, apoptotic peptidase activating factor 1 and activated caspase‑9, were significantly increased in BeWo trophoblasts treated with anti‑B19‑VP1u and anti‑B19‑NS1 IgG. In conclusion, the present

Clinical and virological improvement of hepatitis B virus-related or hepatitis C virus-related chronic hepatitis with concomitant hepatitis A virus infection.

PubMed

Sagnelli, Evangelista; Coppola, Nicola; Pisaturo, Mariantonietta; Pisapia, Raffaella; Onofrio, Mirella; Sagnelli, Caterina; Catuogno, Antonio; Scolastico, Carlo; Piccinino, Felice; Filippini, Pietro

2006-06-01

We evaluated the clinical and virological characteristics of hepatitis A virus infection in persons concomitantly infected with hepatitis B virus (HBV) or hepatitis C virus (HCV). We enrolled 21 patients with acute hepatitis A and chronic hepatitis with no sign of liver cirrhosis, 13 patients who were positive for hepatitis B surface antigen (case B group), 8 patients who were anti-HCV positive (case C group), and 21 patients with acute hepatitis A without a preexisting liver disease (control A group). Two control groups of patients with chronic hepatitis B (control B group) or C (control C group) were also chosen. All control groups were pair-matched by age and sex with the corresponding case group. Fulminant hepatitis A was never observed, and hepatitis A had a severe course in 1 patient in the case B group and in 1 patient in the control A group. Both patients recovered. On admission, HBV DNA was detected in 1 patient in the case B group (7.7%) and in 13 patients (50%) in the control B group; HCV RNA was found in no patient in the case C group and in 16 patients (81.2%) in the control C group. Of 9 patients in the case B group who were followed up for 6 months, 3 became negative for hepatitis B surface antigen and positive for hepatitis B surface antibody, 2 remained positive for hepatitis B surface antigen and negative for HBV DNA, and 4 became positive for HBV DNA with a low viral load [corrected] Of 6 patients in the case C group who were followed up for 6 months, 3 remained negative for HCV RNA, and 3 had persistently low viral loads. Concomitant hepatitis A was always self-limited, associated with a marked inhibition of HBV and HCV genomes, and possibly had a good prognosis for the underlying chronic hepatitis.

Primary Epstein-Barr virus infection and probable parvovirus B19 reactivation resulting in fulminant hepatitis and fulfilling five of eight criteria for hemophagocytic lymphohistiocytosis.

PubMed

Karrasch, Matthias; Felber, Jörg; Keller, Peter M; Kletta, Christine; Egerer, Renate; Bohnert, Jürgen; Hermann, Beate; Pfister, Wolfgang; Theis, Bernhard; Petersen, Iver; Stallmach, Andreas; Baier, Michael

2014-11-01

A case of primary Epstein-Barr virus (EBV) infection/parvovirus B19 reactivation fulfilling five of eight criteria for hemophagocytic lymphohistiocytosis (HLH) is presented. Despite two coinciding viral infections, massive splenomegaly, and fulminant hepatitis, the patient had a good clinical outcome, probably due to an early onset form of HLH with normal leukocyte count, normal natural killer (NK) cell function, and a lack of hemophagocytosis.

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

Oral immunization with hepatitis B surface antigen expressed in transgenic plants

PubMed Central

Kong, Qingxian; Richter, Liz; Yang, Yu Fang; Arntzen, Charles J.; Mason, Hugh S.; Thanavala, Yasmin

2001-01-01

Oral immunogenicity of recombinant hepatitis B surface antigen (HBsAg) derived from yeast (purified product) or in transgenic potatoes (uncooked unprocessed sample) was compared. An oral adjuvant, cholera toxin, was used to increase immune responses. Transgenic plant material containing HBsAg was the superior means of both inducing a primary immune response and priming the mice to respond to a subsequent parenteral injection of HBsAg. Electron microscopy of transgenic plant samples revealed evidence that the HBsAg accumulated intracellularly; we conclude that natural bioencapsulation of the antigen may provide protection from degradation in the digestive tract until plant cell degradation occurs near an immune effector site in the gut. The correlate of protection from hepatitis B virus infection is serum antibody titers induced by vaccination; the protective level in humans is 10 milliunits/ml or greater. Mice fed HBsAg-transgenic potatoes produced HBsAg-specific serum antibodies that exceeded the protective level and, on parenteral boosting, generated a strong long-lasting secondary antibody response. We have also shown the effectiveness of oral delivery by using a parenteral prime-oral boost immunization schedule. The demonstrated success of oral immunization for hepatitis B virus with an “edible vaccine” provides a strategy for contributing a means to achieve global immunization for hepatitis B prevention and eradication. PMID:11553782

Does chronic hepatitis B infection affect the clinical course of acute hepatitis A?

PubMed

Shin, Su Rin; Moh, In Ho; Jung, Sung Won; Kim, Jin Bae; Park, Sang Hoon; Kim, Hyoung Su; Jang, Myung Kuk; Lee, Myung Seok

2013-01-01

The impact of chronic hepatitis B on the clinical outcome of acute hepatitis A remains controversial. The aim of present study was to evaluate the clinical characteristics of acute hepatitis A in cases with underlying chronic hepatitis B compared to cases of acute hepatitis A alone. Data on 758 patients with acute hepatitis A admitted at two university-affiliated hospitals were reviewed. Patients were classified into three groups: group A, patients with both acute hepatitis A and underlying chronic hepatitis B (n = 27); group B, patients infected by acute hepatitis A alone whose sexes and ages were matched with patients in group A (n  = 54); and group C, patients with acute hepatitis A alone (n = 731). None of the demographic features of group A were significantly different from those of group B or C, except for the proportion of males and body weight, which differed from group C. When comparing to group B, clinical symptoms were more frequent, and higher total bilirubin and lower albumin levels were observed in group A. When comparing to group C, the albumin levels were lower in group A. There were no differences in the duration of hospital stay, occurrence of acute kidney injury, acute liver failure, prolonged cholestasis, or relapsing hepatitis. This study revealed that clinical symptoms and laboratory findings were less favorable for patients with acute hepatitis A and chronic hepatitis B compared to those with acute hepatitis A alone. However, there were no differences in fatal outcomes or serious complications. Copyright © 2012 Wiley Periodicals, Inc.

Hepatitis B markers and vaccination-induced protection rate among Albanian pregnant women in Greece

PubMed Central

Elefsiniotis, Ioannis S; Vezali, Elena; Brokalaki, Hero; Tsoumakas, Konstantinos

2009-01-01

Hepatitis B has long been a serious public health problem both in Greece and in Albania. In the February 2009 issue of World Journal of Gastroenterology, Resuli et al presented the interesting epidemiological data concerning hepatitis B virus infection in Albania. The results of this study were discussed and several data from our similar research were provided. PMID:19916183

Parvovirus B19 induced lupus-like syndrome with nephritis.

PubMed

Georges, Elodie; Rihova, Zuzana; Cmejla, Radek; Decleire, Pierre-Yves; Langen, Corinne

2016-12-01

We report a case of a 65-year-old man who developed an acute illness with fever, arthralgia and nephritic syndrome. Antinuclear antibodies were slightly positive and complement levels were low. Renal biopsy showed exudative diffuse proliferative endocapillary glomerulonephritis with diffuse immunoglobulin (IgG, IgA, IgM) and complement deposition (C3d, C4d, C1q) on immunofluorescence. The patient was first treated with corticosteroids and mycophenolate mofetil for suspected lupus with WHO class IV glomerulonephritis. The diagnosis was questioned and a diagnosis of parvovirus B19-associated nephritis was made based on elevation of serum IgM antibodies for parvovirus B19 and detection of parvovirus B19 DNA on renal biopsy. The immunosuppressive treatment was stopped and progressive spontaneous regression of clinical and laboratory abnormalities was observed. We conclude that human parvovirus B19 infection should be considered as a cause of lupus-like symptomatology and acute glomerulonephritis.

Experience with hepatitis A and B vaccines.

PubMed

Davis, Jeffrey P

2005-10-01

The lengthy history of efforts to understand the pathogenesis and means of preventing and controlling both hepatitis A and B is noteworthy for many exceptional scientific achievements. Among these are the development of vaccines to prevent the spread of infection through induction of active immunity to hepatitis A virus (HAV) and hepatitis B virus (HBV). The first plasma-derived hepatitis B vaccine was licensed in the United States in 1981 and was replaced by recombinant hepatitis B vaccines in 1986 and 1989. Vaccines to prevent HAV infection were licensed in the United States in 1995 and 1996. Subsequently, combination vaccines that included both hepatitis A and B vaccine components, or the hepatitis B component in combination with other commonly administered vaccines, were licensed in the United States. Despite significant reductions in hepatitis-related morbidity and mortality that have resulted from widespread use of these vaccines, vaccine-preventable morbidity and mortality still occur. The purposes of this article are to review clinical trial and other experience with hepatitis A and B vaccines in healthy individuals as well as in those with chronic liver disease, infected with the human immunodeficiency virus, or requiring hemodialysis; describe the impact that these vaccines and national recommendations for vaccination have had on reducing the incidence of HAV and HBV infection; and recommend expansion of these recommendations to include universal vaccination of adults as a means of further reducing the burden of viral hepatitis.

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

Genomic Diversity of Hepatitis B Virus Infection Associated With Fulminant Hepatitis B Development.

PubMed

Mina, Thomas; Amini Bavil Olyaee, Samad; Tacke, Frank; Maes, Piet; Van Ranst, Marc; Pourkarim, Mahmoud Reza

2015-06-01

After five decades of Hepatitis B Virus (HBV) vaccine discovery, HBV is still a major public health problem. Due to the high genetic diversity of HBV and selective pressure of the host immune system, intra-host evolution of this virus in different clinical manifestations is a hot topic of research. HBV infection causes a range of clinical manifestations from acute to chronic infection, cirrhosis and hepatocellular carcinoma. Among all forms of HBV infection manifestations, fulminant hepatitis B infection possesses the highest fatality rate. Almost 1% of the acutely infected patients develop fulminant hepatitis B, in which the mortality rate is around 70%. All published papers deposited in Genbank, on the topic of fulminant hepatitis were reviewed and their virological aspects were investigated. In this review, we highlight the genomic diversity of HBV reported from patients with fulminant HBV infection. The most commonly detected diversities affect regulatory motifs of HBV in the core and S region, indicating that these alterations may convert the virus to an aggressive strain. Moreover, mutations at T-cell and B-cell epitopes located in pre-S1 and pre-S2 proteins may lead to an immune evasion of the virus, likely favoring a more severe clinical course of infection. Furthermore, point and frame shift mutations in the core region increase the viral replication of HBV and help virus to evade from immune system and guarantee its persistence. Fulminant hepatitis B is associated with distinct mutational patterns of HBV, underlining that genomic diversity of the virus is an important factor determining its pathogenicity.

[Progress in research of occult hepatitis B virus infection].

PubMed

Huang, X Y; Shi, Q F; Huang, T

2017-05-10

Occult hepatitis B virus infection is a worldwide public health problem, which seriously affects the clinical diagnosis of hepatitis B and threatens the safety of blood transfusion. The concept of occult hepatitis B virus infection, the pathogenesis of occult hepatitis B virus infection, the prevalence of occult hepatitis B virus infection in different groups, including healthy population and different patients, and the possibility of transmission were summarized. The prevalence of occult hepatitis B virus infection was found in healthy population and different patients, and there is possibility of occult hepatitis B virus infection to be transmitted through blood transfusion. The paper provides a comprehensive introduction of the pathogenesis and prevalence of occult hepatitis B virus infection. More attention should be paid to occult hepatitis B virus infection.

Gut microbiota and hepatitis-B-virus-induced chronic liver disease: implications for faecal microbiota transplantation therapy.

PubMed

Kang, Y; Cai, Y

2017-08-01

Hepatitis B is one of the most common infectious diseases globally. It has been estimated that there are 350 million chronic hepatitis B virus (HBV) carriers worldwide. The liver is connected to the small intestine by the bile duct, which carries bile formed in the liver to the intestine. Nearly all of the blood that leaves the stomach and intestines must pass through the liver. Human intestines contain a wide diversity of microbes, collectively termed the 'gut microbiota'. Gut microbiota play a significant role in host metabolic processes and host immune modulation, and influence host development and physiology (organ development). Altered gut microbiota is a common complication in liver disease. Changes in intestinal microbiota seem to play an important role in induction and promotion of HBV-induced chronic liver disease progression, and specific species among the intestinal commensal bacteria may play either a pathogenic or a protective role in the development of HBV-induced chronic liver disease. Thus, the gut microbiome may represent fertile targets for prevention or management of HBV-induced chronic liver disease. Faecal microbiota transplantation (FMT) may be a useful therapy for HBV-related disease in the future. However, the data available in this field remain limited, and relevant scientific work has only just commenced. New technologies have enabled systematic studies of gut microbiota, and provided more realistic information about its composition and pathological variance. This review summarizes the cutting edge of research into the relationship between gut microbiota and HBV-induced chronic liver disease, and the future prospects of FMT therapy. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Reduced hepatic injury in Toll-like receptor 4-deficient mice following D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure.

PubMed

Ben Ari, Ziv; Avlas, Orna; Pappo, Orit; Zilbermints, Veacheslav; Cheporko, Yelena; Bachmetov, Larissa; Zemel, Romy; Shainberg, Asher; Sharon, Eran; Grief, Franklin; Hochhauser, Edith

2012-01-01

Liver transplantation is the only therapy of proven benefit in fulminant hepatic failure (FHF). Lipopolysaccharide (LPS), D-galactosamine (GalN)-induced FHF is a well established model of liver injury in mice. Toll-Like Receptor 4 (TLR4) has been identified as a receptor for LPS. The aim of this study was to investigate the role of TLR4 in FHF induced by D-GalN/LPS administration in mice. Wild type (WT) and TLR4 deficient (TLR4ko) mice were studied in vivo in a fulminant model induced by GalN/LPS. Hepatic TLR4 expression, serum liver enzymes, hepatic and serum TNF-α and interleukin-1β levels were determined. Apoptotic cells were identified by immunohistochemistry for caspase-3. Nuclear factor-kappaβ (NF-κ β) and phosphorylated c-Jun hepatic expression were studied using Western blot analysis. All WT mice died within 24 hours after administration of GalN/LPS while all TLR4ko mice survived. Serum liver enzymes, interleukin-1β, TNF-α level, TLR4 mRNA expression, hepatic injury and hepatocyte apoptosis all significantly decreased in TLR4ko mice compared with WT mice. A significant decrease in hepatic c-Jun and IκB signaling pathway was noted in TLR4ko mice compared with WT mice. In conclusion, following induction of FHF, the inflammatory response and the liver injury in TLR4ko mice was significantly attenuated through decreased hepatic c-Jun and NF-κB expression and thus decreased TNF-α level. Down-regulation of TLR4 expression plays a pivotal role in GalN/LPS induced FHF. These findings might have important implications for the use of the anti TLR4 protein signaling as a potential target for therapeutic intervention in FHF. Copyright © 2012 S. Karger AG, Basel.

SEIR model simulation for Hepatitis B

NASA Astrophysics Data System (ADS)

Side, Syafruddin; Irwan, Mulbar, Usman; Sanusi, Wahidah

2017-09-01

Mathematical modelling and simulation for Hepatitis B discuss in this paper. Population devided by four variables, namely: Susceptible, Exposed, Infected and Recovered (SEIR). Several factors affect the population in this model is vaccination, immigration and emigration that occurred in the population. SEIR Model obtained Ordinary Differential Equation (ODE) non-linear System 4-D which then reduces to 3-D. SEIR model simulation undertaken to predict the number of Hepatitis B cases. The results of the simulation indicates the number of Hepatitis B cases will increase and then decrease for several months. The result of simulation using the number of case in Makassar also found the basic reproduction number less than one, that means, Makassar city is not an endemic area of Hepatitis B. With approval from the proceedings editor article 020185 titled, "SEIR model simulation for Hepatitis B," is retracted from the public record, as it is a duplication of article 020198 published in the same volume.

Influence of occult hepatitis B virus infection in chronic hepatitis C outcomes

PubMed Central

Fernandez-Rodriguez, Conrado M; Gutierrez, Maria Luisa; Lledó, José Luis; Casas, Maria Luisa

2011-01-01

Persistence of hepatitis B virus-DNA in the sera, peripheral blood mononuclear cells or in the liver of hepatitis B surface antigen (HBsAg)-negative patients with or without serological markers of previous exposure (antibodies to HBsAg and/or to HB-core antigen) defines the entity called occult hepatitis B infection (OBI). Co-infection with hepatitis B and hepatitis C viruses is frequent in highly endemic areas. While this co-infection increases the risk of liver disease progression, development of cirrhosis and hepatocellular carcinoma and also increases the rate of therapeutic failure to interferon-based treatments than either virus alone, a potentially negative effect of OBI on clinical outcomes and of therapeutic response to current antiviral regimes of patients with chronic hepatitis C remains inconclusive. PMID:21472121

The status of hepatitis B control in the African region

PubMed Central

Breakwell, Lucy; Tevi-Benissan, Carol; Childs, Lana; Mihigo, Richard; Tohme, Rania

2017-01-01

The World Health Organization (WHO) African Region has approximately 100 million people with chronic hepatitis B virus (HBV) infection. This review describes the status of hepatitis B control in the Region. We present hepatitis B vaccine (HepB) coverage data and from available data in the published literature, the impact of HepB vaccination on hepatitis B surface antigen (HBsAg) prevalence, a marker of chronic infection, among children, HBsAg prevalence in pregnant women, and risk of perinatal transmission. Lastly, we describe challenges with HepB birth dose (HepB-BD) introduction reported in the Region, and propose strategies to increase coverage. In 2015, regional three dose HepB coverage was 76%, and 16(34%) of 47 countries reported ≥ 90% coverage. Overall, 11 countries introduced HepB-BD; only nine provide universal HepB-BD, and of these, five reported ≥ 80% coverage. From non-nationally representative serosurveys among children, HBsAg prevalence was lower among children born after HepB introduction compared to those born before HepB introduction. However, some studies still found HBsAg prevalence to be above 2%. From limited surveys among pregnant women, the median HBsAg prevalence varied by country, ranging from 1.9% (Madagascar) to 16.1% (Niger); hepatitis B e antigen (HBeAg) prevalence among HBsAg-positive women ranged from 3.3% (Zimbabwe) to 28.5% (Nigeria). Studies in three countries indicated that the risk of perinatal HBV transmission was associated with HBeAg expression or high HBV DNA viral load. Major challenges for timely HepB-BD administration were poor knowledge of or lack of national HepB-BD vaccination guidelines, high prevalence of home births, and unreliable vaccine supply. Overall, substantial progress has been made in the region. However, countries need to improve HepB3 coverage and some countries might need to consider introducing the HepB-BD to help achieve the regional hepatitis B control goal of < 2% HBsAg prevalence among children

Hepatitis B, HIV, and Syphilis Seroprevalence in Pregnant Women and Blood Donors in Cameroon.

PubMed

Dionne-Odom, Jodie; Mbah, Rahel; Rembert, Nicole J; Tancho, Samuel; Halle-Ekane, Gregory E; Enah, Comfort; Welty, Thomas K; Tih, Pius M; Tita, Alan T N

2016-01-01

Objectives. We estimated seroprevalence and correlates of selected infections in pregnant women and blood donors in a resource-limited setting. Methods. We performed a cross-sectional analysis of laboratory seroprevalence data from pregnant women and voluntary blood donors from facilities in Cameroon in 2014. Rapid tests were performed to detect hepatitis B surface antigen, syphilis treponemal antibodies, and HIV-1/2 antibodies. Blood donations were also tested for hepatitis C and malaria. Results. The seroprevalence rates and ranges among 7069 pregnant women were hepatitis B 4.4% (1.1-9.6%), HIV 6% (3.0-10.2%), and syphilis 1.7% (1.3-3.8%) with significant variability among the sites. Correlates of infection in pregnancy in adjusted regression models included urban residence for hepatitis B (aOR 2.9, CI 1.6-5.4) and HIV (aOR 3.5, CI 1.9-6.7). Blood donor seroprevalence rates and ranges were hepatitis B 6.8% (5.0-8.8%), HIV 2.2% (1.4-2.8%), syphilis 4% (3.3-4.5%), malaria 1.9%, and hepatitis C 1.7% (0.5-2.5%). Conclusions. Hepatitis B, HIV, and syphilis infections are common among pregnant women and blood donors in Cameroon with higher rates in urban areas. Future interventions to reduce vertical transmission should include universal screening for these infections early in pregnancy and provision of effective prevention tools including the birth dose of univalent hepatitis B vaccine.

Hepatitis A and hepatitis B vaccination coverage among adults with chronic liver disease.

PubMed

Yue, Xin; Black, Carla L; O'Halloran, Alissa; Lu, Peng-Jun; Williams, Walter W; Nelson, Noele P

2018-02-21

Infection with hepatitis A and hepatitis B virus can increase the risk of morbidity and mortality in persons with chronic liver disease (CLD). The Advisory Committee on Immunization Practices recommends hepatitis A (HepA) and hepatitis B (HepB) vaccination for persons with CLD. Data from the 2014 and 2015 National Health Interview Surveys (NHIS), nationally representative, in-person interview surveys of the non-institutionalized US civilian population, were used to assess self-reported HepA (≥1 and ≥2 doses) and HepB vaccination (≥1 and ≥3 doses) coverage among adults who reported a chronic or long-term liver condition. Multivariable logistic regression was used to identify factors independently associated with HepA and HepB vaccination among adults with CLD. Overall, 19.4% and 11.5% of adults aged ≥ 18 years with CLD reported receiving ≥1 dose and ≥2 doses of HepA vaccine, respectively, compared with 14.7% and 9.1% of adults without CLD (p < .05 comparing those with and without CLD, ≥1dose). Age, education, geographic region, and international travel were associated with receipt of ≥2 doses HepA vaccine among adults with CLD. Overall, 35.7% and 29.1% of adults with CLD reported receiving ≥1 dose and ≥3 doses of HepB vaccine, respectively, compared with 30.2% and 24.7% of adults without CLD (p < .05 comparing those with and without CLD, ≥1 dose). Age, education, and receipt of influenza vaccination in the past 12 months were associated with receipt of ≥3 doses HepB vaccine among adults with CLD. Among adults with CLD and ≥10 provider visits, only 13.8% and 35.3% had received ≥2 doses HepA and ≥3 doses HepB vaccine, respectively. HepA and HepB vaccination among adults with CLD is suboptimal and missed opportunities to vaccinate occurred. Providers should adhere to recommendations to vaccinate persons with CLD to increase vaccination among this population. Copyright © 2018 Elsevier Ltd. All rights reserved.

Core promoter mutations 3 years after anti-hepatitis B e seroconversion in patients with chronic hepatitis B or hepatitis B and C infection and cancer remission.

PubMed

Zampino, Rosa; Marrone, Aldo; Karayiannis, Peter; Cirillo, Grazia; del Giudice, Emanuele Miraglia; Rania, Giovanni; Utili, Riccardo; Ruggiero, Giuseppe

2002-09-01

In this study, we aimed to evaluate the persistence of hepatitis B virus (HBV) DNA and the role of HBV core promoter and precore region mutations in 28 young cancer survivor patients with HBV or HBV and hepatitis C virus (HCV) infections, and persistently normal ALT levels, after spontaneous or interferon (IFN)-induced anti-hepatitis B e (HBe) seroconversion. Sera from 15 patients with HBV and 13 with dual HBV-HCV infection were analyzed for the presence of HBV-DNA and HCV-RNA by polymerase chain reaction 3 yr after anti-HBe seroconversion. A total of 21 patients had seroconverted spontaneously and seven did so after IFN treatment. The core promoter and the precore regions were amplified sequenced directly. Among patients with HBV infection, HBV-DNA was detected in five of nine (55%) with spontaneous anti-HBe and in all six treated patients (p = 0.092). In the coinfected patients, four had cleared both HBV-DNA and HCV-RNA, five were HBV-DNA negative/HCV-RNA positive and four had the reverse viral pattern. Among the 15 patients with persistence of HBV-DNA, a 7-base pair nucleotide deletion in the core promoter (1757-1763) was present in seven of 10 patients with spontaneous and in one of five patients with IFN-induced seroconversion (p = 0.033). The G1896A precore stop codon mutation was never observed. HBV-DNA levels were significantly lower in patients with the core promoter deletion (p = 0.011). The 7-base pair deletion generated a truncated X protein at amino-acid position 132. A core promoter deletion after anti-HBe seroconversion was associated with low HBV-DNA levels, probably because of downregulation of pregenomic RNA production and truncation of the X protein. HBV-DNA persistence was a frequent event, even in the absence of active liver disease.

Hepatitis B

MedlinePlus

... 12 hours after birth, followed by a second shot 1 month later, and the third shot 5 months ... the hepatitis B virus should get the first shot within 1 to 2 months after birth, the second shot ...

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

Pancreatitis induced by pegylated interferon alfa-2b in a patient affected by chronic hepatitis C.

PubMed

Cecchi, Enrica; Forte, Paolo; Cini, Elisabetta; Banchelli, Grazia; Ferlito, Chiara; Mugelli, Alessandro

2004-01-01

A middle-aged man was admitted to the ED because of nausea and vomiting, abdominal distention and fainting. A blood analysis revealed high levels of serum amylase and lipase, confirming a diagnosis of acute pancreatitis. The history showed that the patient had self-administered a single dose of pegylated interferon alfa-2b and ribavirin daily for 7 days for chronic hepatitis C. The medications were stopped and his condition gradually improved. In agreement with the literature and the Naranjo algorythm result, pegylated interferon alfa-2b is associated with acute pancreatitis. Identification of a few signs and symptoms is the first 'signal' in preventing a serious drug-induced adverse event.

Hepatitis B Among the Khmer

PubMed Central

Jackson, J Carey; Rhodes, Lorna A; Inui, Thomas S; Buchwald, Dedra

1997-01-01

OBJECTIVE To assess the comprehensibility of hepatitis B translations for Cambodian refugees, to identify Cambodian illnesses that include the symptoms of hepatitis, and to combine these observations with critical theoretical perspectives of language to reflect on the challenges of medical translation generally. DESIGN Open-ended, semistructured interviews, and participant-observation of a refugee community in Seattle, Washington. SETTING Homes of Cambodian residents of inner-city neighborhoods. PARTICIPANTS Thirty-four adult Cambodian refugees who had each been educated about hepatitis B through public health outreach. RESULTS Medical interpreters translated hepatitis B as rauk tlaam, literally “liver disease.” Unfortunately, while everyone knew of the liver (tlaam), rauk tlaam was a meaningless term to 28 (82%) of 34 respondents and conveyed none of the chronicity and communicability intended by refugee health workers for 34 (100%) of the respondents. In contrast, all respondents knew illnesses named after symptom complexes that include the symptoms of acute and chronic hepatitis, but do not refer to diseased organs. The Cambodian words chosen to translate hepatitis B reflect the medical thinking and medical authority that can unintentionally overwhelm attempts at meaningful communication with non–English-speaking patients. CONCLUSIONS To improve comprehension of hepatitis B translations for the Khmer, translators must choose between medical terminology focused on the liver and Khmer terminology which identifies recognizable experiences, but represents important Khmer health concepts. A critical linguistic view of this situation suggests that for these translations to be meaningful clinicians and health educators must first analyze and then monitor the contextual significance of medical language. In cross-cultural settings, this means a partnership with medical interpreters to pay close attention to the expe-rience of illness and social context of the

Fighting Hepatitis B in North Korea: Feasibility of a Bi-modal Prevention Strategy.

PubMed

Unnewehr, Markus; Stich, August

2015-11-01

In North Korea, the prevalence of hepatitis B is high due to natural factors, gaps in vaccination, and the lack of antiviral treatment. Aid projects are urgently needed, however impeded by North Korea's political and economical situation and isolation. The feasibility of a joint North Korean and German humanitarian hepatitis B prevention program was assessed. Part 1: Hepatitis B vaccination catch-up campaign. Part 2: Implementation of endoscopic ligation of esophageal varices (EVL) by trainings in Germany and North Korea. By vaccinating 7 million children between 2010 and 2012, the hepatitis B vaccination gap was closed. Coverage of 99.23% was reached. A total of 11 hepatitis B-induced liver cirrhosis patients (mean age 41.1 yr) with severe esophageal varices and previous bleedings were successfully treated by EVL without major complications. A clinical standard operating procedure, a feedback system and a follow-up plan were developed. The bi-modal preventive strategy was implemented successfully. Parts of the project can serve as an example for other low-income countries, however its general transferability is limited due to the special circumstances in North Korea.

SEIR model simulation for Hepatitis B

NASA Astrophysics Data System (ADS)

Side, Syafruddin; Irwan, Mulbar, Usman; Sanusi, Wahidah

2017-09-01

Mathematical modelling and simulation for Hepatitis B discuss in this paper. Population devided by four variables, namely: Susceptible, Exposed, Infected and Recovered (SEIR). Several factors affect the population in this model is vaccination, immigration and emigration that occurred in the population. SEIR Model obtained Ordinary Differential Equation (ODE) non-linear System 4-D which then reduces to 3-D. SEIR model simulation undertaken to predict the number of Hepatitis B cases. The results of the simulation indicates the number of Hepatitis B cases will increase and then decrease for several months. The result of simulation using the number of case in Makassar also found the basic reproduction number less than one, that means, Makassar city is not an endemic area of Hepatitis B.

Hepatitis B X-interacting protein promotes cisplatin resistance and regulates CD147 via Sp1 in ovarian cancer.

PubMed

Zou, Wei; Ma, Xiangdong; Yang, Hong; Hua, Wei; Chen, Biliang; Cai, Guoqing

2017-03-01

Ovarian cancer is the highest mortality rate of all female reproductive malignancies. Drug resistance is a major cause of treatment failure in malignant tumors. Hepatitis B X-interacting protein acts as an oncoprotein, regulates cell proliferation, and migration in breast cancer. We aimed to investigate the effects and mechanisms of hepatitis B X-interacting protein on resistance to cisplatin in human ovarian cancer cell lines. The mRNA and protein levels of hepatitis B X-interacting protein were detected using RT-PCR and Western blotting in cisplatin-resistant and cisplatin-sensitive tissues, cisplatin-resistant cell lines A2780/CP and SKOV3/CP, and cisplatin-sensitive cell lines A2780 and SKOV3. Cell viability and apoptosis were measured to evaluate cellular sensitivity to cisplatin in A2780/CP cells. Luciferase reporter gene assay was used to determine the relationship between hepatitis B X-interacting protein and CD147. The in vivo function of hepatitis B X-interacting protein on tumor burden was assessed in cisplatin-resistant xenograft models. The results showed that hepatitis B X-interacting protein was highly expressed in ovarian cancer of cisplatin-resistant tissues and cells. Notably, knockdown of hepatitis B X-interacting protein significantly reduced cell viability in A2780/CP compared with cisplatin treatment alone. Hepatitis B X-interacting protein and cisplatin cooperated to induce apoptosis and increase the expression of c-caspase 3 as well as the Bax/Bcl-2 ratio. We confirmed that hepatitis B X-interacting protein up-regulated CD147 at the protein expression and transcriptional levels. Moreover, we found that hepatitis B X-interacting protein was able to activate the CD147 promoter through Sp1. In vivo, depletion of hepatitis B X-interacting protein decreased the tumor volume and weight induced by cisplatin. Taken together, these results indicate that hepatitis B X-interacting protein promotes cisplatin resistance and regulated CD147 via Sp1 in

[Observations on human parvovirus B19 infection diagnosed in 2011].

PubMed

Mihály, Ilona; Trethon, András; Arányi, Zsuzsanna; Lukács, Adrienne; Kolozsi, Tímea; Prinz, Gyula; Marosi, Anikó; Lovas, Nóra; Dobner, Ilona Sarolta; Prinz, Géza; Szalai, Zsuzsanna; Pék, Tamás

2012-12-09

The incidence of human parvovirus B19 infection is unknown. A retrospective analysis of clinical and laboratory findings was carried out in patients diagnosed with human parvovirus B19 infection in 2011 in a virologic laboratory of a single centre in Hungary. Clinical and laboratory data of patients with proven human parvovirus B19 infection were analysed using in- and out-patient files. In 2011, 72 patients proved to have human parvovirus B19 infection with the use of enzyme immunoassay. The clinical diagnoses of these patients were as follows: human parvovirus B19 infection (30.6%), transient aplastic crisis (16.7%), arthritis (8.3%) and acute hepatitis (4.1%). Symptoms of each of the four phases of the infection occurred in various combinations with the exception of the monophase of cheek exanthema. This occurred without the presence of other symptoms in some cases. Leading symptoms and signs were exanthema (in 74.6% of cases), haematological disorders (in 69% of cases), fever (in 54.9% of cases) and arthritis (in 33.8% of cases). Several atypical dermatological symptoms were also observed. Acute arthritis without exanthema was noted in 8 patients. Of the 72 patients with proven human parvovirus B19 infection there were 7 pregnant women, and one of them had hydrops foetalis resulting spontaneous abortion. In 16 patients (22.5%) human parvovirus B19 IgG was undetectable despite an optimal time for testing. The observations of this study may contribute to a better recognition of clinical symptoms of human parvovirus B19 infection.

[Present situation of hepatitis B in Chile].

PubMed

Pereira S, Ana; Valenzuela B, María Teresa; Mora, Judith; Vera, Lilian

2008-06-01

Hepatitis B virus infection generates carriers and 8% will evolve to a chronic phase. To perform a compilation of studies on hepatitis B in Chile and other sources of information to estimate the impact of this disease in our country. Published and unpublished evidence about the infection, in the general population and risk groups in our country, was compiled and reviewed critically. Informal interviews with experts, revision of the mandatory notification book of the Ministry of Health and collection of data from laboratories that study hepatitis B virus, were also carried out. The seroprevalence of chronic carriers in blood donors is nearly O.3%. Among risk groups such as health care personnel, the figure is O.7%, among homosexuals 29%, among HIV positive patients 30%, among sexual workers 2% and among children with chronic hemodialysis, 9%. Prevalence rate according to notified cases in 2004 was 1.8 x 100,000 inhabitants. Detection of viral hepatitis B surface antigen in laboratories occurs in 0.2% of donors and 1.396 of non donors. The seroprevalence of hepatitis B virus, the lack of notification, and the introduction of hepatitis B vaccine to our Regular Program of Immunizations, are arguments to develop in Chile a hepatitis B and C surveillance system.

Immunological Properties of Hepatitis B Core Antigen Fusion Proteins

NASA Astrophysics Data System (ADS)

Francis, Michael J.; Hastings, Gillian Z.; Brown, Alan L.; Grace, Ken G.; Rowlands, David J.; Brown, Fred; Clarke, Berwyn E.

1990-04-01

The immunogenicity of a 19 amino acid peptide from foot-and-mouth disease virus has previously been shown to approach that of the inactivated virus from which it was derived after multimeric particulate presentation as an N-terminal fusion with hepatitis B core antigen. In this report we demonstrate that rhinovirus peptide-hepatitis B core antigen fusion proteins are 10-fold more immunogenic than peptide coupled to keyhole limpet hemocyanin and 100-fold more immunogenic than uncoupled peptide with an added helper T-cell epitope. The fusion proteins can be readily administered without adjuvant or with adjuvants acceptable for human and veterinary application and can elicit a response after nasal or oral dosing. The fusion proteins can also act as T-cell-independent antigens. These properties provide further support for their suitability as presentation systems for "foreign" epitopes in the development of vaccines.

Recurrent paratyphoid fever A co-infected with hepatitis A reactivated chronic hepatitis B.

PubMed

Liu, Yanling; Xiong, Yujiao; Huang, Wenxiang; Jia, Bei

2014-05-12

We report here a case of recurrent paratyphoid fever A with hepatitis A co-infection in a patient with chronic hepatitis B. A 26-year-old male patient, who was a hepatitis B virus carrier, was co-infected with Salmonella enterica serovar Paratyphi A and hepatitis A virus. The recurrence of the paratyphoid fever may be ascribed to the coexistence of hepatitis B, a course of ceftriaxone plus levofloxacin that was too short and the insensitivity of paratyphoid fever A to levofloxacin. We find that an adequate course and dose of ceftriaxone is a better strategy for treating paratyphoid fever. Furthermore, the co-infection of paratyphoid fever with hepatitis A may stimulate cellular immunity and break immunotolerance. Thus, the administration of the anti-viral agent entecavir may greatly improve the prognosis of this patient with chronic hepatitis B, and the episodes of paratyphoid fever and hepatitis A infection prompt the use of timely antiviral therapy.

Recurrent paratyphoid fever A co-infected with hepatitis A reactivated chronic hepatitis B

PubMed Central

2014-01-01

We report here a case of recurrent paratyphoid fever A with hepatitis A co-infection in a patient with chronic hepatitis B. A 26-year-old male patient, who was a hepatitis B virus carrier, was co-infected with Salmonella enterica serovar Paratyphi A and hepatitis A virus. The recurrence of the paratyphoid fever may be ascribed to the coexistence of hepatitis B, a course of ceftriaxone plus levofloxacin that was too short and the insensitivity of paratyphoid fever A to levofloxacin. We find that an adequate course and dose of ceftriaxone is a better strategy for treating paratyphoid fever. Furthermore, the co-infection of paratyphoid fever with hepatitis A may stimulate cellular immunity and break immunotolerance. Thus, the administration of the anti-viral agent entecavir may greatly improve the prognosis of this patient with chronic hepatitis B, and the episodes of paratyphoid fever and hepatitis A infection prompt the use of timely antiviral therapy. PMID:24884719

Hepatitis B immunization for indigenous adults, Australia

PubMed Central

Yin, J Kevin; Beard, Frank; Wesselingh, Steve; Cowie, Benjamin; Ward, James; Macartney, Kristine

2016-01-01

Abstract Objective To quantify the disparity in incidence of hepatitis B between indigenous and non-indigenous people in Australia, and to estimate the potential impact of a hepatitis B immunization programme targeting non-immune indigenous adults. Methods Using national data on persons with newly acquired hepatitis B disease notified between 2005 and 2012, we estimated incident infection rates and rate ratios comparing indigenous and non-indigenous people, with adjustments for underreporting. The potential impact of a hepatitis B immunization programme targeting non-immune indigenous adults was projected using a Markov chain Monte Carlo simulation model. Findings Of the 54 522 persons with hepatitis B disease notified between 1 January 2005 and 31 December 2012, 1953  infections were newly acquired. Acute hepatitis B infection notification rates were significantly higher for indigenous than non-indigenous Australians. The rates per 100 000 population for all ages were 3.6 (156/4 368 511) and 1.1 (1797/168 449 302) for indigenous and non-indigenous people respectively. The rate ratio of age-standardized notifications was 4.0 (95% confidence interval: 3.7–4.3). If 50% of non-immune indigenous adults (20% of all indigenous adults) were vaccinated over a 10-year programme a projected 527–549 new cases of acute hepatitis B would be prevented. Conclusion There continues to be significant health inequity between indigenous and non-indigenous Australians in relation to vaccine-preventable hepatitis B disease. An immunization programme targeting indigenous Australian adults could have considerable impact in terms of cases of acute hepatitis B prevented, with a relatively low number needed to vaccinate to prevent each case. PMID:27821885

Human parvovirus B19: a review.

PubMed

Rogo, L D; Mokhtari-Azad, T; Kabir, M H; Rezaei, F

2014-01-01

Parvovirus B19 (B19V) is a small non-enveloped single-stranded DNA (ssDNA) virus of the family Parvoviridae, the subfamily Parvovirinae, the genus Erythrovirus and Human parvovirus B19 type species. It is a common community-acquired respiratory pathogen without ethnic, socioeconomic, gender, age or geographic boundaries. Moreover, the epidemiological and ecological relationships between human parvovirus B19, man and environment have aroused increasing interest in this virus. B19V infection is associated with a wide spectrum of clinical manifestations, some of which were well established and some are still controversial, however, it is also underestimated from a clinical perspective. B19V targets the erythroid progenitors in the bone marrow by binding to the glycosphingolipid globoside (Gb4), leading to large receptor-induced structural changes triggering cell death either by lysis or by apoptosis mediated by the nonstructural (NS)1 protein. The pattern of genetic evolution, its peculiar properties and functional profile, the characteristics of its narrow tropism and restricted replication, its complex relationship with the host and its ample pathogenetic potential are all topics that are far from a comprehensive understanding. The lack of efficient adaptation to in vitro cellular cultures and the absence of animal models have limited classical virological studies and made studies on B19V dependent on molecular biology. The present review looks at the nature of this virus with the view to provide more information about its biology, which may be useful to the present and future researchers. human parvovirus B19; respiratory pathogen; biology; genome; fifth disease; transient aplastic crisis; anemia.

Human induced pluripotent stem cell-derived hepatic cell lines as a new model for host interaction with hepatitis B virus

PubMed Central

Kaneko, Shun; Kakinuma, Sei; Asahina, Yasuhiro; Kamiya, Akihide; Miyoshi, Masato; Tsunoda, Tomoyuki; Nitta, Sayuri; Asano, Yu; Nagata, Hiroko; Otani, Satoshi; Kawai-Kitahata, Fukiko; Murakawa, Miyako; Itsui, Yasuhiro; Nakagawa, Mina; Azuma, Seishin; Nakauchi, Hiromitsu; Nishitsuji, Hironori; Ujino, Saneyuki; Shimotohno, Kunitada; Iwamoto, Masashi; Watashi, Koichi; Wakita, Takaji; Watanabe, Mamoru

2016-01-01

Hepatitis B virus (HBV) is not eradicated by current antiviral therapies due to persistence of HBV covalently closed circular DNA (cccDNA) in host cells, and thus development of novel culture models for productive HBV infection is urgently needed, which will allow the study of HBV cccDNA eradication. To meet this need, we developed culture models of HBV infection using human induced pluripotent stem cell-derived hepatocyte lineages, including immature proliferating hepatic progenitor-like cell lines (iPS-HPCs) and differentiated hepatocyte-like cells (iPS-Heps). These cells were susceptible to HBV infection, produced HBV particles, and maintained innate immune responses. The infection efficiency of HBV in iPS-HPCs predominantly depended on the expression levels of sodium taurocholate cotransporting polypeptide (NTCP), and was low relative to iPS-Heps: however, long-term culture of iPS-Heps was difficult. To provide a model for HBV persistence, iPS-HPCs overexpressing NTCP were established. The long-term persistence of HBV cccDNA was detected in iPS-HPCs overexpressing NTCP, and depended on the inhibition of the Janus-kinase signaling pathway. In conclusion, this study provides evidence that iPS-derived hepatic cell lines can be utilized for novel HBV culture models with genetic variation to investigate the interactions between HBV and host cells and the development of anti-HBV strategies. PMID:27386799

Hepatic steatosis background in chronic hepatitis B and C - significance of similarities and differences.

PubMed

Moroşan, Eugenia; Mihailovici, Maria Sultana; Giuşcă, Simona Eliza; Cojocaru, Elena; Avădănei, Elena Roxana; Căruntu, Irina Draga; Teleman, Sergiu

2014-01-01

The aim of our study was to investigate comparatively the steatotic background in viral chronic hepatitis B, C and mixed types, in correlation with the severity degree of specific liver lesions. The study group consisted of 1206 liver biopsy specimens, etiologically diagnosed as hepatitis C - 1021 (84.66%) cases, hepatitis B - 100 (8.29%) cases, hepatitis B and C - 39 (3.23%) cases, hepatitis B and D - 39 (3.23%) cases, hepatitis C and toxicity - six (0.49%) cases, hepatitis B, C and D - one case (0.08%). The histopathological assessment focused on the steatotic lesions associated with inflammation and fibrosis. The cases were classified according to necrosis and inflammatory activity (score between 0-12) and fibrosis (score between 0-4). Our data indicates significant association of steatotic lesions in hepatitis C (76.59%) as opposed to other types of viral hepatitis. In mixed hepatitis B and C, steatotic lesions are more frequent (66.66%) than in chronic hepatitis B (47%) and in mixed chronic B and D hepatitis (48.72%). Steatosis was present in all cases with chronic hepatitis C and associated toxicity. These observations confirm the important aggressiveness of hepatitis C virus as opposed to hepatitis B and D virus. The analysis of the pattern of steatosis in correlation with necrosis and inflammatory activity and fibrosis, respectively, lead to the identification of certain specific elements. Thus, for all types of hepatitis, steatosis is associated predominantly with moderate severity (score 6-8) and progressive expansion of fibrosis (score 2-3). The presence of steatosis does not define hepatic lesions with severe inflammation (score 9-12) nor those with extended fibrosis (score 4). The type of steatosis present is mostly macrovesicular, the transformation into lipid cysts being uncommon. Based on the scoring systems applied in the evaluation of the entire investigated study group, we believe that a possible inclusion of a quantifiable criterion for

Hepatitis B virus enhances cisplatin-induced hepatotoxicity via a mechanism involving suppression of glucose-regulated protein of 78 Kda.

PubMed

Zhang, Xiaoxue; Zhang, Rui; Yang, HuiOu; Xiang, Qian; Jiang, Qing; He, Qi; Zhang, Ting; Chen, Chen; Zhu, Huifen; Wang, Qiang; Ning, Qin; Li, Yiwu; Lei, Ping; Shen, Guanxin

2016-07-25

Cisplatin is a classical platinum-based chemotherapeutic drug used in the treatment of many cancer types, including hepatocellular carcinoma (HCC). The application of cisplatin is significantly limited by its toxicity, which may be affected by various biological factors. Persistence of Hepatitis B virus (HBV) infection leads to HCC development and may be associated with higher incidence of severe hepatitis during chemotherapy. However, whether HBV alters the susceptibility of hepatocytes to cisplatin remains poorly understood. Here, we demonstrate that HBV transfection enhanced cisplatin-induced hepatotoxicity via a mechanism involving suppression of glucose-regulated protein of 78 KDa (Grp78), a major stress-induced chaperone that localizes to the endoplasmic reticulum. Silencing Grp78 gene increased the susceptibility of HepG2 to cisplatin by activating caspase-3. Grp78 expression was down-regulated by HBV infection both in vitro and in liver tissues of patients. We compared the cisplatin sensitivity of hepatoma cells either expressing (HepG2.2.15 cells) or not expressing the entire Hepatitis B Virus genome (HepG2). HepG2.2.15 cells showed increased sensitivity to cisplatin and a higher apoptosis rate. Overexpression of Grp78 counteracted the increase of sensitivity of HepG2.215 cells to cisplatin. Furthermore, we found that HBV disrupted Grp78 synthesis in response to cisplatin stimulation, which may trigger severe and prolonged endoplasmic reticulum (ER) stress that can induce cellular apoptosis. Our findings provide new information into the effect of HBV in the modulation of Grp78 expression, and, consequently on cisplatin-induced hepatotoxicity during viral infection. Copyright © 2016. Published by Elsevier Ireland Ltd.

Quantitative hepatitis B core antibody levels in the natural history of hepatitis B virus infection.

PubMed

Song, L-W; Liu, P-G; Liu, C-J; Zhang, T-Y; Cheng, X-D; Wu, H-L; Yang, H-C; Hao, X-K; Yuan, Q; Zhang, J; Kao, J-H; Chen, D-S; Chen, P-J; Xia, N-S

2015-02-01

We previously demonstrated that pretreatment quantitative anti-hepatitis B core protein (qAnti-HBc) levels can predict the treatment response for both interferon and nucleoside analogue therapy, but the characteristics of qAnti-HBc during chronic hepatitis B virus (HBV) infection remain poorly understood. To understand this issue, the qAnti-HBc levels were evaluated in individuals with past HBV infection, occult HBV infection and chronic HBV infection in the immune tolerance phase, immune clearance phase, low-replicative phase and hepatitis B e antigen (HBeAg)-negative hepatitis phase. Individuals with hepatitis B surface antigen (n = 598, 3.74 ± 0.90 log10 IU/mL) had significantly higher (p < 0.001, approximately 1000-fold) serum qAnti-HBc levels than those who had occult HBV, and serum qAnti-HBc levels were significantly higher in the occult HBV group than in the past HBV infection group (p < 0.001). qAnti-HBc levels were positively correlated with alanine aminotransferase levels (R = 0.663, p < 0.001), and subjects with an abnormal alanine aminotransferase level had a higher qAnti-HBc level (p < 0.001). Serum qAnti-HBc level varied in different phases of HBV infection, as determined by host immune status. Serum qAnti-HBc level is strongly associated with hepatitis activity in subjects with chronic HBV infection. Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Effects of Complementary Combination Therapy of Korean Red Ginseng and Antiviral Agents in Chronic Hepatitis B.

PubMed

Choi, Seung-Hwa; Yang, Keum-Jin; Lee, Dong-Soo

2016-12-01

Chronic hepatitis B management is commonly targeted at reducing viral replication. However, the currently available antiviral therapies are associated with some problems, including resistance and numerous adverse effects. Ginseng has been reported to be effective for treating viral infections such as influenza and human immunodeficiency virus. However, there are currently few studies on the effects of ginseng in chronic hepatitis B. Thus, this study investigated the effects of ginseng together with antiviral agents in chronic hepatitis B. This was a prospective, single-blinded, randomized controlled trial, and single-center study. Thirty-eight patients were enrolled. The control group (n = 19) was administered antiviral agents alone. The experimental group (n = 19) was administered antiviral agents along with Korean Red Ginseng powder capsules (each dose is 1 gram (two capsules), a one-day dose is 3 grams). The baseline characteristics did not differ between the two groups. Differences in several non-invasive fibrosis serologic markers (type IV collagen, hyaluronic acid, transforming growth factor-β) and in the hepatitis B virus DNA levels were compared between the groups. The non-invasive fibrosis serologic markers were further decreased in the experimental group, with significant differences after treatment observed for hyaluronic acid (p = 0.032) and transforming growth factor-β (p = 0.008), but not for type IV collagen (p = 0.174). This study suggests the possibility of Korean Red Ginseng as a complementary therapy for chronic hepatitis B.

Comparison of circulating, hepatocyte specific messenger RNA and microRNA as biomarkers for chronic hepatitis B and C.

PubMed

Zhang, Xiaonan; Zhang, Zhanqing; Dai, Fahui; Shi, Bisheng; Chen, Liang; Zhang, Xinxin; Zang, Guoqing; Zhang, Jiming; Chen, Xiaorong; Qian, Fangxing; Hu, Yunwen; Yuan, Zhenghong

2014-01-01

Circulating microRNAs have been widely recognized as a novel category of biomarker in a variety of physiological and pathological conditions. Other reports revealed that fragments of organ specific messenger RNAs are also detectable in serum/plasma and can be utilized as sensitive indicators of liver pathology and cancer. In order to assess the sensitivity and reliability of these two class of RNAs as marker of hepatitis B or C induced chronic liver disease, we collected plasma samples from 156 chronic hepatitis B or C patients (HBV active n = 112, HBV carrier n = 19, hepatitis C n = 25) and 22 healthy donors and quantified their circulating mRNA for albumin, HP (haptoglobin), CYP2E1 (cytochrome P450, family 2, subfamily E) and ApoA2 (Apolipoprotein A2) in conjunction with microRNA-122, a well established marker for acute and chronic liver injury. We found that plasma microRNA-122 level is significantly elevated in patients with active HBV but not in HBV carriers. Furthermore, microRNA-122 is not elevated in HCV patients even though their median serum alanine aminotransferase (sALT) was three fold of the healthy donors. Nevertheless, circulating mRNAs, especially albumin mRNA, showed much more sensitivity in distinguishing active hepatitis B, hepatitis B carrier or HCV patients from healthy control. Correlation and multiple linear regression analysis suggested that circulating mRNAs and miRNAs are much more related to HBsAg titre than to sALT. Immunoprecipitation of HBsAg in HBV patients' plasma resulted in enrichment of albumin and HP mRNA suggesting that fragments of liver specific transcripts can be encapsidated into HBsAg particles. Taken together, our results suggest that hepatocyte specific transcripts in plasma like albumin mRNA showed greater sensitivity and specificity in differentiating HBV or HCV induced chronic liver disease than microRNA-122. Circulating mRNA fragments merit more attention in the quest of next generation biomarkers for

Comparison of Circulating, Hepatocyte Specific Messenger RNA and microRNA as Biomarkers for Chronic Hepatitis B and C

PubMed Central

Zhang, Xiaonan; Zhang, Zhanqing; Dai, Fahui; Shi, Bisheng; Chen, Liang; Zhang, Xinxin; Zang, Guoqing; Zhang, Jiming; Chen, Xiaorong; Qian, Fangxing; Hu, Yunwen; Yuan, Zhenghong

2014-01-01

Circulating microRNAs have been widely recognized as a novel category of biomarker in a variety of physiological and pathological conditions. Other reports revealed that fragments of organ specific messenger RNAs are also detectable in serum/plasma and can be utilized as sensitive indicators of liver pathology and cancer. In order to assess the sensitivity and reliability of these two class of RNAs as marker of hepatitis B or C induced chronic liver disease, we collected plasma samples from 156 chronic hepatitis B or C patients (HBV active n = 112, HBV carrier n = 19, hepatitis C n = 25) and 22 healthy donors and quantified their circulating mRNA for albumin, HP (haptoglobin), CYP2E1 (cytochrome P450, family 2, subfamily E) and ApoA2 (Apolipoprotein A2) in conjunction with microRNA-122, a well established marker for acute and chronic liver injury. We found that plasma microRNA-122 level is significantly elevated in patients with active HBV but not in HBV carriers. Furthermore, microRNA-122 is not elevated in HCV patients even though their median serum alanine aminotransferase (sALT) was three fold of the healthy donors. Nevertheless, circulating mRNAs, especially albumin mRNA, showed much more sensitivity in distinguishing active hepatitis B, hepatitis B carrier or HCV patientsfrom healthy control. Correlation and multiple linear regression analysis suggested that circulating mRNAs and miRNAs are much more related to HBsAg titre than to sALT. Immunoprecipitation of HBsAg in HBV patients’ plasma resulted in enrichment of albumin and HP mRNA suggesting that fragments of liver specific transcripts can be encapsidated into HBsAg particles. Taken together, our results suggest that hepatocyte specific transcripts in plasma like albumin mRNA showed greater sensitivity and specificity in differentiating HBV or HCV induced chronic liver disease than microRNA-122. Circulating mRNA fragments merit more attention in the quest of next generation biomarkers for

BIP induces mice CD19(hi) regulatory B cells producing IL-10 and highly expressing PD-L1, FasL.

PubMed

Tang, Youfa; Jiang, Qing; Ou, Yanghui; Zhang, Fan; Qing, Kai; Sun, Yuanli; Lu, Wenjie; Zhu, Huifen; Gong, Feili; Lei, Ping; Shen, Guanxin

2016-01-01

Many studies have shown that B cells possess a regulatory function in mouse models of autoimmune diseases. Regulatory B cells can modulate immune response through many types of molecular mechanisms, including the production of IL-10 and the expression of PD-1 Ligand and Fas Ligand, but the microenvironmental factors and mechanisms that induce regulatory B cells have not been fully identified. BIP (binding immunoglobulin protein), a member of the heat shock protein 70 family, is a type of evolutionarily highly conserved protein. In this article, we have found that IL-10(+), PD-L1(hi) and FasL(hi) B cells are discrete cell populations, but enriched in CD19(hi) cells. BIP can induce IL-10-producing splenic B cells, IL-10 secretion and B cells highly expressing PD-L1 and FasL. CD40 signaling acts in synergy with BIP to induce regulatory B cells. BIP increased surface CD19 molecule expression intensity and IL-10(+), PD-L1(hi) and FasL(hi) B cells induced by BIP share the CD19(hi) phenotype. Furthermore, B cells treated with BIP and anti-CD40 can lead to suppression of T cell proliferation and the effect is partially IL-10-dependent and mainly BIP-induced. Taken together, our findings identify a novel function of BIP in the induction of regulatory B cells and add a new reason for the therapy of autoimmune disorders or other inflammatory conditions. Copyright © 2015. Published by Elsevier Ltd.

Reactivation of hepatitis B in patients of chronic hepatitis C with hepatitis B virus infection treated with direct acting antivirals.

PubMed

Yeh, Ming-Lun; Huang, Chung-Feng; Hsieh, Meng-Hsuan; Ko, Yu-Min; Chen, Kuan-Yu; Liu, Ta-Wei; Lin, Yi-Hung; Liang, Po-Cheng; Hsieh, Ming-Yen; Lin, Zu-Yau; Chen, Shinn-Cherng; Huang, Ching-I; Huang, Jee-Fu; Kuo, Po-Lin; Dai, Chia-Yen; Yu, Ming-Lung; Chuang, Wan-Long

2017-10-01

Hepatitis B virus (HBV) may reactivate when treating chronic hepatitis C (CHC) with direct acting antivirals (DAA). We aim to investigate the risk of HBV reactivation during DAA therapy. Chronic hepatitis C patients receiving pan-oral DAA therapy from December 2013 to August 2016 were evaluated. Fifty-seven patients that had a past HBV infection (negative hepatitis B surface antigen [HBsAg] and positive hepatitis B core antibody) and seven patients that had a current HBV infection (positive HBsAg) were enrolled. Serum HBV and hepatitis C virus (HCV) markers were regularly measured. The endpoints were the HCV sustained virological response (SVR) and the HBV virological/clinical reactivation. The overall SVR 12 rate was 96.9%, and two patients, one with positive HBsAg, had a relapse of HCV. No episodes of HBV virological reactivation were observed among the patients with a past HBV infection. For the seven patients with a current HBV infection, HBV virological reactivation was found in four (57.1%) of the seven patients. Clinical reactivation of HBV was observed in one patient with pretreatment detectable HBV DNA and recovered after entecavir administration. For the other three patients with HBV virological reactivation, the reappearance of low level HBV DNA without clinical reactivation was observed. HBsAg levels demonstrated only small fluctuations in all the patients. There was a minimal impact of hepatitis B core antibody seropositivity on HCV efficacy and safety. For CHC patients with current HBV infection, the risk of HBV reactivation was present, and monitoring the HBV DNA level during therapy is warranted. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Hepatitis B reactivation and timing for prophylaxis

PubMed Central

Tuna, Nazan; Karabay, Oguz

2015-01-01

It is known that immunotherapy and cancer chemotherapy may cause hepatitis B virus (HBV) reactivation in hepatitis B surface antigen carriers and inactive chronic hepatitis B patients. Guidelines recommend antiviral prophylaxis regardless of HBV DNA levels to prevent reactivation. We read from the article written by Liu et al that Lamivudine was given inadequate time for antiviral prophylaxis. PMID:25717269

Vitamin E for the treatment of children with hepatitis B e antigen-positive chronic hepatitis: A systematic review and meta-analysis.

PubMed

Fiorino, Sirio; Bacchi-Reggiani, Maria Letizia; Leandri, Paolo; Loggi, Elisabetta; Andreone, Pietro

2017-02-28

To assess vitamin E efficacy, defined as its ability to induce hepatitis B e antigen (HBeAg) seroconversion, in children with HBeAg-positive persistent hepatitis. In July 2016, we extracted articles published in MEDLINE and the Cochrane Library using the following search terms: "chronic hepatitis B", "children", "childhood", "therapy", "treatment", "vitamin E", "tocopherols", "tocotrienols". Only randomized controlled trials (RCTs) published in English language were collected. Three RCTs met inclusion criteria and were considered in the present meta-analysis. Overall, 23/122 children in the treatment group underwent HBeAg seroconversion vs 3/74 in the control group (OR = 3.96, 95%CI: 1.18-13.25, P = 0.025). Although our meta-analysis has several limits, including the very small number of available studies and enrolled children with HBeAg positivity-related hepatitis, it suggests that vitamin E use may enhance the probability to induce HBeAg seroconversion in these patients. Further well designed and adequately sized trials are required to confirm or deny these very preliminary results.

Seroprevalence of Hepatitis A Virus Antibodies among the Patients with Chronic Hepatitis B in Turkey.

PubMed

Tulek, Necla; Ozsoy, Metin; Moroglu, Cigdem; Cagla Sonmezer, Meliha; Temocin, Fatih; Tuncer Ertem, Gunay; Sebnem Erdinc, Fatma

2015-01-01

Hepatitis A virus (HAV) can cause significant pathology in patients with chronic hepatitis B virus (HBV), however, HAV can be prevented by vaccination. The aim of this study was to determine the implication of vaccination against HAV vaccine in patients with chronic hepatitis B. The seroprevalence of anti-HAV IgG antibodies was investigated in the patients with chronic hepatitis B. Anti-HAV IgG antibodies were detected by commercially available ELISA kit. A total of 673 patients (354 males, 319 females with age range of 17-78 years) with chronic hepatitis B were included the study. Hepatitis A virus seropositivity rate was 34% in the patients younger than 20 years, 79% in the age group of 20 to 29 years, and 100% after 35 years of age. Hepatitis A virus vaccination may be recommended for young adult patients with chronic hepatitis B in Turkey. Tulek N, Ozsoy M, Moroglu C, Sonmezer MC, Temocin F, Ertem GT, Erdinc FS. Seroprevalence of Hepatitis A Virus Antibodies among the Patients with Chronic Hepatitis B in Turkey. Euroasian J Hepato-Gastroenterol 2015;5(2):95-97.

Prevalence of hepatitis B virus subgenotypes and basal core promoter, precore variants in patients with acute hepatitis B in central Vietnam.

PubMed

Hayashi, Kazuhiko; Katano, Yoshiaki; Chuong, Tran Xuan; Takeda, Yasushi; Ishigami, Masatoshi; Itoh, Akihiro; Hirooka, Yoshiki; Nakano, Isao; Huy, Tran Van; Minh, Nguyen Ngoc; Diem, Tran thi Minh; An, Dong thi Hoai; Phiet, Pham Hoang; Goto, Hidemi

2009-01-01

Hepatitis B virus (HBV) has been classified into 8 genotypes that have different geographic distributions. The clinical outcomes of acute hepatitis are dependent on genotype. The aim of this study was to investigate the distribution of HBV subgenotypes and basal core promoter (BCP)/precore (PC) regions in acute hepatitis patients in Central Vietnam to clarify the distributions and the clinical and virological differences. 27 patients with acute hepatitis B were studied. HBV subgenotypes and BCP/PC variants were determined by direct sequencing of the preS, BCP/PC regions, respectively. HBV subgenotypes B4/Ba (n = 22) and C1/Cs (n = 5) were detected. Of the 27 patients, 3 developed fulminant hepatic failure, and all were infected with B4/Ba. Three patients had a BCP mutation, and 10 patients had a PC mutation in subgenotype B4/Ba. Three patients with C1/Cs had a BCP mutation. Two of 3 patients who progressed to fulminant hepatic failure had T1762, A1764, and A1896 simultaneously. None of the patients with acute, self-limited hepatitis carried these triple mutations. The prevalent HBV subgenotypes in patients with acute hepatitis B in Central Vietnam were B4/Ba and C1/Cs. BCP/PC variants have an association with the development of fulminant hepatic failure in subgenotype B4/Ba. Copyright 2009 S. Karger AG, Basel.

Prospective evaluation of FibroTest®, FibroMeter®, and HepaScore® for staging liver fibrosis in chronic hepatitis B: comparison with hepatitis C.

PubMed

Leroy, Vincent; Sturm, Nathalie; Faure, Patrice; Trocme, Candice; Marlu, Alice; Hilleret, Marie-Noëlle; Morel, Françoise; Zarski, Jean-Pierre

2014-07-01

Fibrosis blood tests have been validated in chronic hepatitis C. Their diagnostic accuracy is less documented in hepatitis B. The aim of this study was to describe the diagnostic performance of FibroTest®, FibroMeter®, and HepaScore® for liver fibrosis in hepatitis B compared to hepatitis C. 510 patients mono-infected with hepatitis B or C and matched on fibrosis stage were included. Blood tests were performed the day of the liver biopsy. Histological lesions were staged according to METAVIR. Fibrosis stages were distributed as followed: F0 n=76, F1 n=192, F2 n=132, F3 n=54, F4 n=56. Overall diagnostic performance of blood tests were similar between hepatitis B and C with AUROC ranging from 0.75 to 0.84 for significant fibrosis, 0.82 to 0.85 for extensive fibrosis and 0.84 to 0.87 for cirrhosis. Optimal cut-offs were consistently lower in hepatitis B compared to hepatitis C, especially for the diagnosis of extensive fibrosis and cirrhosis, with decreased sensitivity and negative predictive values. More hepatitis B than C patients with F ⩾3 were underestimated: FibroTest®: 47% vs. 26%, FibroMeter®: 24% vs. 6%, HepaScore®: 41% vs. 24%, p<0.01. Multivariate analysis showed that hepatitis B (0R 3.4, 95% CI 1.2-19.2, p<0.02) and low γGT (OR 7.3, 95% CI 2.0-27.0, p<0.003) were associated with fibrosis underestimation. Overall the diagnostic performance of blood tests is similar in hepatitis B and C. The risk of underestimating significant fibrosis and cirrhosis is however greater in hepatitis B and cannot be entirely corrected by the use of more stringent cut-offs. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Prediction of occult hepatitis B virus infection in liver transplant donors through hepatitis B virus blood markers.

PubMed

Tandoi, Francesco; Caviglia, Gian Paolo; Pittaluga, Fabrizia; Abate, Maria Lorena; Smedile, Antonina; Romagnoli, Renato; Salizzoni, Mauro

2014-11-01

Occult hepatitis B virus infection is defined as detectable HBV-DNA in liver of HBsAg-negative individuals, with or without detectable serum HBV-DNA. In deceased liver donors, results of tissue analysis cannot be obtained prior to allocation for liver transplantation. we investigated prevalence and predictability of occult hepatitis B using blood markers of viral exposure/infection in deceased liver donors. In 50 consecutive HBsAg-negative/anti-HBc-positive and 20 age-matched HBsAg-negative/anti-HBc-negative donors, a nested-PCR assay was employed in liver biopsies for diagnosis of occult hepatitis B according to Taormina criteria. All donors were characterized for plasma HBV-DNA and serum anti-HBs/anti-HBe. In liver tissue, occult hepatitis B was present in 30/50 anti-HBc-positive (60%) and in 0/20 anti-HBc-negative donors (p<0.0001). All anti-HBc-positive donors with detectable HBV-DNA in plasma (n=5) or anti-HBs>1,000 mIU/mL (n=5) eventually showed occult infection, i.e, 10/30 occult hepatitis B-positive donors which could have been identified prior to transplantation. In the remaining 40 anti-HBc-positive donors, probability of occult infection was 62% for anti-HBe-positive and/or anti-HBs ≥ 58 mIU/mL; 29% for anti-HBe-negative and anti-HBs<58 mIU/mL. In deceased donors, combining anti-HBc with other blood markers of hepatitis B exposure/infection allows to predict occult hepatitis B with certainty and speed in one third of cases. These findings might help refine the allocation of livers from anti-HBc-positive donors. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Fighting Hepatitis B in North Korea: Feasibility of a Bi-modal Prevention Strategy

PubMed Central

Stich, August

2015-01-01

In North Korea, the prevalence of hepatitis B is high due to natural factors, gaps in vaccination, and the lack of antiviral treatment. Aid projects are urgently needed, however impeded by North Korea's political and economical situation and isolation. The feasibility of a joint North Korean and German humanitarian hepatitis B prevention program was assessed. Part 1: Hepatitis B vaccination catch-up campaign. Part 2: Implementation of endoscopic ligation of esophageal varices (EVL) by trainings in Germany and North Korea. By vaccinating 7 million children between 2010 and 2012, the hepatitis B vaccination gap was closed. Coverage of 99.23% was reached. A total of 11 hepatitis B-induced liver cirrhosis patients (mean age 41.1 yr) with severe esophageal varices and previous bleedings were successfully treated by EVL without major complications. A clinical standard operating procedure, a feedback system and a follow-up plan were developed. The bi-modal preventive strategy was implemented successfully. Parts of the project can serve as an example for other low-income countries, however its general transferability is limited due to the special circumstances in North Korea. PMID:26539001

Hepatitis A, B, and C: Learn the Differences

MedlinePlus

... People with clotting factor disorders (e.g., hemophilia) Hepatitis B caused by the hepatitis B virus (HBV) HBV is found in blood and ... users • Travelers to regions of the world where hepatitis B is common (Asia, Africa, the Amazon Basin in ...

Secondary Symptomatic Parvovirus B19 Infection in a Healthy Adult

PubMed Central

Kaufmann, Julie; Buccola, Janet M.; Stead, Wendy; Rowley, Christopher; Wong, Michael

2007-01-01

Parvovirus B19 is a common infection in adults and children. There are reports of secondary parvovirus infection in immunocompromised persons, but no reports of symptomatic secondary infection in healthy persons. We describe a healthy 39-year-old woman who presented with fever, rash, and arthralgia. Her symptoms were thought most compatible with parvovirus B19 infection, but she reported prior positive parvovirus antibody 2 years earlier during prenatal care. Tests were therefore also sent for HIV, streptococcal infection, hepatitis C, and Lyme disease. Testing revealed both elevated IgG and IgM antibodies for parvovirus B19; previously, the patient was positive only for IgG. On a subsequent visit she related that a community outbreak of parvovirus developed in her town and church group. We believe this case demonstrates that a symptomatic secondary infection with parvovirus can occur in healthy persons, and that prior positive antibody test does not preclude the development of acute infection. PMID:17384979

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.

Sero-prevalence and factors associated with Hepatitis B and C co-infection in pregnant Nigerian women living with HIV Infection

PubMed Central

Ezechi, Oliver Chukwujekwu; Kalejaiye, Olufunto Olufela; Gab-Okafor, Chidinma Vivian; Oladele, David Ayola; Oke, Bamidele Oludare; Musa, Zaidat Adesola; Ekama, Sabdat Ozichu; Ohwodo, Harry; Agahowa, Endurance; Gbajabiamilla, Titilola; Ezeobi, Paschal Mbanefo; Okwuraiwe, Azuka; Audu R, Rosemary Ajuma; Okoye, Rosemary Nwakaego; David, Agatha Nkiru; Odunukwe, Nkiruka Nonyelum; Onwujekwe, Dan Ifeanyi; Ujah, Innocent Achanya

2014-01-01

Introduction Perinatal and horizontal transmission of Hepatitis B occur in areas of high endemicity as most infections are acquired in the first 5 years of life. Unless Hepatitis B and C infected pregnant women identified, and appropriate treatment provided, children born to these women are at high risk of chronic Hepatitis B (and C) virus infection. The objecive of this study was to determined the prevalence and the factors associated with Hepatitis B and C Virus infection in pregnant HIV positive Nigerians. Methods A cross sectional study among HIV Positive pregnant women seen at a large PMTCT clinic in Lagos Nigeria. The women were screened for Hepatitis B and C Virus infection at enrollment. HIV viral load, CD4 count, liver transaminases and hemoglobin levels were also determined. Data were managed with SPSS for windows version. Ethical approval was obtained from the Institutions Ethical Review Board. Results Of the 2391 studied subjects, 101(4.2%) and 37(1.5%) respectively were seropositive for Hepatitis B and C Virus infection. Twowomen (0. 08%) had triple infections. blood transfusion, (cOR: 2.3; 95% CI:1.1 - 4.6), history of induced abortion (cOR:2. 2;95% CI:1.3 - 3.6), and elevated baseline ALT (cOR:2. 2; 95%CI:2. 2;4.2) were significantly associated with HBV. History of induced abortion was the only factor found to be associated with HIV/ HCV (cOR: 1.9;95%CI:1. 3-3.9). Conclusion Hepatitis B Virus infection (4.2%) is relatively common in our environment and associated with induced abortion, blood transfusion and elevated baseline transaminase. Hepatitis C Virus infection (1.5%) is less common and associated with only history of induced abortion. PMID:25396023

Pre-travel advice, attitudes and hepatitis A and B vaccination rates among travellers from seven countries†

PubMed Central

Heywood, Anita E.; Nothdurft, Hans; Tessier, Dominique; Moodley, Melissa; Rombo, Lars; Marano, Cinzia; De Moerlooze, Laurence

2017-01-01

Background: Knowledge about the travel-associated risks of hepatitis A and B, and the extent of pre-travel health-advice being sought may vary between countries. Methods: An online survey was undertaken to assess the awareness, advice-seeking behaviour, rates of vaccination against hepatitis A and B and adherence rates in Australia, Finland, Germany, Norway, Sweden, the UK and Canada between August and October 2014. Individuals aged 18–65 years were screened for eligibility based on: travel to hepatitis A and B endemic countries within the past 3 years, awareness of hepatitis A, and/or combined hepatitis A&B vaccines; awareness of their self-reported vaccination status and if vaccinated, vaccination within the last 3 years. Awareness and receipt of the vaccines, sources of advice, reasons for non-vaccination, adherence to recommended doses and the value of immunization reminders were analysed. Results: Of 27 386 screened travellers, 19 817 (72%) were aware of monovalent hepatitis A or combined A&B vaccines. Of these 13 857 (70%) had sought advice from a healthcare provider (HCP) regarding combined hepatitis A&B or monovalent hepatitis A vaccination, and 9328 (67%) were vaccinated. Of 5225 individuals eligible for the main survey (recently vaccinated = 3576; unvaccinated = 1649), 27% (841/3111) and 37% (174/465) of vaccinated travellers had adhered to the 3-dose combined hepatitis A&B or 2-dose monovalent hepatitis A vaccination schedules, respectively. Of travellers partially vaccinated against combined hepatitis A&B or hepatitis A, 84% and 61%, respectively, believed that they had received the recommended number of doses. Conclusions: HCPs remain the main source of pre-travel health advice. The majority of travellers who received monovalent hepatitis A or combined hepatitis A&B vaccines did not complete the recommended course. These findings highlight the need for further training of HCPs and the provision of reminder services to improve traveller

Pre-travel advice, attitudes and hepatitis A and B vaccination rates among travellers from seven countries†.

PubMed

Heywood, Anita E; Nothdurft, Hans; Tessier, Dominique; Moodley, Melissa; Rombo, Lars; Marano, Cinzia; De Moerlooze, Laurence

2016-07-01

Knowledge about the travel-associated risks of hepatitis A and B, and the extent of pre-travel health-advice being sought may vary between countries. An online survey was undertaken to assess the awareness, advice-seeking behaviour, rates of vaccination against hepatitis A and B and adherence rates in Australia, Finland, Germany, Norway, Sweden, the UK and Canada between August and October 2014. Individuals aged 18-65 years were screened for eligibility based on: travel to hepatitis A and B endemic countries within the past 3 years, awareness of hepatitis A, and/or combined hepatitis A&B vaccines; awareness of their self-reported vaccination status and if vaccinated, vaccination within the last 3 years. Awareness and receipt of the vaccines, sources of advice, reasons for non-vaccination, adherence to recommended doses and the value of immunization reminders were analysed. Of 27 386 screened travellers, 19 817 (72%) were aware of monovalent hepatitis A or combined A&B vaccines. Of these 13 857 (70%) had sought advice from a healthcare provider (HCP) regarding combined hepatitis A&B or monovalent hepatitis A vaccination, and 9328 (67%) were vaccinated. Of 5225 individuals eligible for the main survey (recently vaccinated = 3576; unvaccinated = 1649), 27% (841/3111) and 37% (174/465) of vaccinated travellers had adhered to the 3-dose combined hepatitis A&B or 2-dose monovalent hepatitis A vaccination schedules, respectively. Of travellers partially vaccinated against combined hepatitis A&B or hepatitis A, 84% and 61%, respectively, believed that they had received the recommended number of doses. HCPs remain the main source of pre-travel health advice. The majority of travellers who received monovalent hepatitis A or combined hepatitis A&B vaccines did not complete the recommended course. These findings highlight the need for further training of HCPs and the provision of reminder services to improve traveller awareness and adherence to vaccination

Hepatitis A, B and nAnB: The Viruses and their Prevention

PubMed Central

Minuk, G. Y.

1985-01-01

Three viruses commonly infect the liver: hepatitis A virus (HAV), hepatitis B virus (HBV) and the virus(es) responsible for non A non B hepatitis (nAnB). HAV infection occurs predominantly by the fecal-oral route and thus is more common in areas where living conditions are poor and personal hygiene suboptimal. Immune serum globulin (ISG) prevents this form of hepatitis. HBV infection can be spread by either parenteral (e.g. drug abuse) or non-parenteral (e.g. intimate contact) routes. High risk, susceptible individuals should be vaccinated with the HBV vaccine for longterm protection. Hepatitis B immune globulin (HBIG) remains the treatment of choice after exposure, but its protective effect does not exceed three to four months. The nAnB agent is spread by the same routes as HBV infection. At present there is no convincing evidence that any form of active or passive prophylaxis is beneficial for this form of hepatitis. PMID:21279152

Aloe-induced Toxic Hepatitis

PubMed Central

Yang, Ha Na; Kim, Young Mook; Kim, Byoung Ho; Sohn, Kyoung Min; Choi, Myung Jin; Choi, Young Hee

2010-01-01

Aloe has been widely used in phytomedicine. Phytomedicine describes aloe as a herb which has anti-inflammatory, anti-proliferative, anti-aging effects. In recent years several cases of aloe-induced hepatotoxicity were reported. But its pharmacokinetics and toxicity are poorly described in the literature. Here we report three cases with aloe-induced toxic hepatitis. A 57-yr-old woman, a 62-yr-old woman and a 55-yr-old woman were admitted to the hospital for acute hepatitis. They had taken aloe preparation for months. Their clinical manifestation, laboratory findings and histologic findings met diagnostic criteria (RUCAM scale) of toxic hepatitis. Upon discontinuation of the oral aloe preparations, liver enzymes returned to normal level. Aloe should be considered as a causative agent in hepatotoxicity. PMID:20191055

Addressing cultural diversity: the hepatitis B clinical specialist perspective.

PubMed

Wallace, Jack; Smith, Elizabeth; Hajarizadeh, Behzad; Richmond, Jacqueline; Lucke, Jayne

2017-08-31

Hepatitis B is a viral infection primarily affecting people from culturally diverse communities in Australia. While vaccination prevents infection, there is increasing mortality resulting from liver damage associated with chronic infection. Deficits in the national policy and clinical response to hepatitis B result in a low diagnosis rate, inadequate testing and diagnosis processes, and poor access to hepatitis B treatment services. While research identifies inadequate hepatitis B knowledge among people with the virus and primary health care workers, this project sought to identify how specialist clinicians in Australia negotiate cultural diversity, and provide often complex clinical information to people with hepatitis B. A vignette was developed and presented to thirteen viral hepatitis specialist clinicians prior to an electronically recorded interview. Recruitment continued until saturation of themes was reached. Data were thematically coded into themes outlined in the interview schedule. Ethical approval for the research was provided by the La Trobe University Human Research Ethics Committee. Key messages provided to patients with hepatitis B by clinical specialists were identified. These messages were not consistently provided to all patients with hepatitis B, but were determined on perceptions of patient knowledge, age and highest educational level. While the vignette stated that English was not an issue for the patient, most specialists identified the need for an interpreter. Combating stigma related to hepatitis B was seen as important by the specialists and this was done through normalising the virus. Having an awareness of different cultural understandings about hepatitis B specifically, and health and well-being generally, was noted as a communication strategy. Key core competencies need to be developed to deliver educational messages to people with hepatitis B within clinical encounters. The provision of adequate resources to specialist clinics will

Suppression of NF-κB activation by PDLIM2 restrains hepatic lipogenesis and inflammation in high fat diet induced mice.

PubMed

Hao, Ya-Rong; Tang, Feng-Juan; Zhang, Xue; Wang, Hui

2018-05-28

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, insulin resistance, dyslipidemia and a systemic pro-inflammatory response, a leading cause of cirrhosis and hepatocellular carcinoma. Here, we showed that PDZ-LIM domain-containing protein 2 (PDLIM2) was an effective suppressor of steatohepatitis. After 16 weeks on a high fat diet (HFD), obesity, insulin resistance, hepatic dyslipidemia and inflammation were markedly aggravated in PDLIM2-knockout (KO) mice. PDLIM2 deletion resulted in lipid accumulation in liver tissue samples of HFD-induced mice, as evidenced by the significant increase of hepatic TG and TC through reducing the expression of lipogenesis- and transcriptional regulators of lipid metabolism-related genes and enhancing fatty acid oxidation-associated molecules. In addition, PDLIM2-ablation promoted the expression of pro-inflammatory cytokines by activating nuclear factor kappa-B (NF-κB) signaling pathway, as supported by the remarkable increase of phosphorylated IKKβ, IκBα and NF-κB expressions in liver of HFD-fed mice. Of note, the in vitro study demonstrated that PDLIM2 ablation-enhanced inflammatory response and disorder of lipid metabolism were abrogated by suppressing NF-κB activity. Collectively, the findings could lead to the development of potential therapeutic strategy to prevent NAFLD and associated metabolic disorders by targeting PDLIM2. Copyright © 2018. Published by Elsevier Inc.

SREBP-1c overactivates ROS-mediated hepatic NF-κB inflammatory pathway in dairy cows with fatty liver.

PubMed

Li, Xinwei; Huang, Weikun; Gu, Jingmin; Du, Xiliang; Lei, Lin; Yuan, Xue; Sun, Guoquan; Wang, Zhe; Li, Xiaobing; Liu, Guowen

2015-10-01

Dairy cows with fatty liver are characterized by hepatic lipid accumulation and a severe inflammatory response. Sterol receptor element binding protein-1c (SREBP-1c) and nuclear factor κB (NF-κB) are components of the main pathways for controlling triglyceride (TG) accumulation and inflammatory levels, respectively. A previous study demonstrated that hepatic inflammatory levels are positively correlated with hepatic TG content. We therefore speculated that SREBP-1c might play an important role in the overactivation of the hepatic NF-κB inflammatory pathway in cows with fatty liver. Compared with healthy cows, cows with fatty liver exhibited severe hepatic injury and high blood concentrations of the inflammatory cytokines TNF-α, IL-6 and IL-1β. Hepatic SREBP-1c-mediated lipid synthesis and the NF-κB inflammatory pathway were both overinduced in cows with fatty liver. In vitro, treatment with non-esterified fatty acids (NEFA) further increased SREBP-1c expression and NF-κB pathway activation, which then promoted TG and inflammatory cytokine synthesis. SREBP-1c overexpression overactivated the NF-κB inflammatory pathway in hepatocytes by increasing ROS content and not through TLR4. Furthermore, SREBP-1c silencing decreased ROS content and further attenuated the activation of the NEFA-induced NF-κB pathway, thereby decreasing TNF-α, IL-6 and IL-1β synthesis. SREBP-1c-overexpressing mice exhibited hepatic steatosis and an overinduced hepatic NF-κB pathway. Taken together, these results indicate that SREBP-1c enhances the NEFA-induced overactivation of the NF-κB inflammatory pathway by increasing ROS in cow hepatocytes, thereby further increasing hepatic inflammatory injury in cows with fatty liver. Copyright © 2015. Published by Elsevier Inc.

Valproate induced hepatic steatosis by enhanced fatty acid uptake and triglyceride synthesis

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

Bai, Xupeng; Hong, Weipeng; Cai, Peiheng

Steatosis is the characteristic type of VPA-induced hepatotoxicity and may result in life-threatening hepatic lesion. Approximately 61% of patients treated with VPA have been diagnosed with hepatic steatosis through ultrasound examination. However, the mechanisms underlying VPA-induced intracellular fat accumulation are not yet fully understood. Here we demonstrated the involvement of fatty acid uptake and lipogenesis in VPA-induced hepatic steatosis in vitro and in vivo by using quantitative real-time PCR (qRT-PCR) analysis, western blotting analysis, fatty acid uptake assays, Nile Red staining assays, and Oil Red O staining assays. Specifically, we found that the expression of cluster of differentiation 36 (CD36),more » an important fatty acid transport, and diacylglycerol acyltransferase 2 (DGAT2) were significantly up-regulated in HepG2 cells and livers of C57B/6J mice after treatment with VPA. Furthermore, VPA treatment remarkably enhanced the efficiency of fatty acid uptake mediated by CD36, while this effect was abolished by the interference with CD36-specific siRNA. Also, VPA treatment significantly increased DGAT2 expression as a result of the inhibition of mitogen-activated protein kinase kinase (MEK) – extracellular regulated kinase (ERK) pathway; however, DGAT2 knockdown significantly alleviated VPA-induced intracellular lipid accumulation. Additionally, we also found that sterol regulatory element binding protein-1c (SREBP-1c)-mediated fatty acid synthesis may be not involved in VPA-induced hepatic steatosis. Overall, VPA-triggered over-regulation of CD36 and DGAT2 could be helpful for a better understanding of the mechanisms underlying VPA-induced hepatic steatosis and may offer novel therapeutic strategies to combat VPA-induced hepatotoxicity. - Highlights: • VPA induced hepatic steatosis and modulated genes associated with lipid metabolism. • CD36-mediated fatty acid uptake contributed to VPA-induced lipid accumulation. • PA increased the

21 CFR 660.40 - Hepatitis B Surface Antigen.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Hepatitis B Surface Antigen. 660.40 Section 660.40...) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.40 Hepatitis B Surface Antigen. (a) Proper name and definition. The proper name of this product...

21 CFR 660.40 - Hepatitis B Surface Antigen.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Hepatitis B Surface Antigen. 660.40 Section 660.40...) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.40 Hepatitis B Surface Antigen. (a) Proper name and definition. The proper name of this product...

21 CFR 660.40 - Hepatitis B Surface Antigen.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Hepatitis B Surface Antigen. 660.40 Section 660.40...) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.40 Hepatitis B Surface Antigen. (a) Proper name and definition. The proper name of this product...

21 CFR 660.40 - Hepatitis B Surface Antigen.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Hepatitis B Surface Antigen. 660.40 Section 660.40...) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.40 Hepatitis B Surface Antigen. (a) Proper name and definition. The proper name of this product...

21 CFR 660.40 - Hepatitis B Surface Antigen.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Hepatitis B Surface Antigen. 660.40 Section 660.40...) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.40 Hepatitis B Surface Antigen. (a) Proper name and definition. The proper name of this product...

β-Cell Hyperplasia Induced by Hepatic Insulin Resistance

PubMed Central

Escribano, Oscar; Guillén, Carlos; Nevado, Carmen; Gómez-Hernández, Almudena; Kahn, C. Ronald; Benito, Manuel

2009-01-01

OBJECTIVE Type 2 diabetes results from a combination of insulin resistance and impaired insulin secretion. To directly address the effects of hepatic insulin resistance in adult animals, we developed an inducible liver-specific insulin receptor knockout mouse (iLIRKO). RESEARCH DESIGN AND METHODS Using this approach, we were able to induce variable insulin receptor (IR) deficiency in a tissue-specific manner (liver mosaicism). RESULTS iLIRKO mice presented progressive hepatic and extrahepatic insulin resistance without liver dysfunction. Initially, iLIRKO mice displayed hyperinsulinemia and increased β-cell mass, the extent of which was proportional to the deletion of hepatic IR. Our studies of iLIRKO suggest a cause-and-effect relationship between progressive insulin resistance and the fold increase of plasma insulin levels and β-cell mass. Ultimately, the β-cells failed to secrete sufficient insulin, leading to uncontrolled diabetes. We observed that hepatic IGF-1 expression was enhanced in iLIRKO mice, resulting in an increase of circulating IGF-1. Concurrently, the IR-A isoform was upregulated in hyperplastic β-cells of iLIRKO mice and IGF-1–induced proliferation was higher than in the controls. In mouse β-cell lines, IR-A, but not IR-B, conferred a proliferative capacity in response to insulin or IGF-1, providing a potential explanation for the β-cell hyperplasia induced by liver insulin resistance in iLIRKO mice. CONCLUSIONS Our studies of iLIRKO mice suggest a liver-pancreas endocrine axis in which IGF-1 functions as a liver-derived growth factor to promote compensatory pancreatic islet hyperplasia through IR-A. PMID:19136656

Hepatitis B vaccine booster dose: low-dose recombinant hepatitis B vaccines as a booster dose.

PubMed

Bryan, J P; MacArthy, P; Rudock, A; Fogarty, J P; Dowd, H; Legters, L J; Perine, P L

1997-06-01

The timing and best regimen for a booster dose of hepatitis B vaccine have not been determined. Two studies were conducted to determine the response to a booster dose of 5 micrograms recombinant hepatitis B vaccine. In the first study, a 5 micrograms (0.5 ml) dose of Recombivax HB was administered intramuscularly 38 months after the initial dose to 71 volunteers. In a second study, we offered a 5 micrograms dose recombinant hepatitis B vaccine, either Recombivax HB (0.5 ml) or Engerix B (0.25 ml), to students who had previously been immunized with three doses of vaccine. In the first study, among the 44 persons for whom postbooster sera were available, the geometric mean concentration of anti-hepatitis B surface antigens increased from 42 to 2090 mIU/ml after the 5 micrograms (0.5 ml) dose of Recombivax. In the second study, after a 5 micrograms (0.5 ml) dose of Recombivax, the geometric mean concentration increased from 43 to 990 mIU/ml (n = 48), and in the group that received a 5 micrograms (0.25 ml) dose of Engerix B, the concentration increased from 83 to 2337 mIU/ml (n = 45) (p = 0.18 for postdose concentrations). A 5 micrograms dose of recombinant vaccine results in an excellent booster response at a cost one fourth to one half that of a full 1 ml dose of vaccine.

Comparing the Clinical Features and Outcomes of Acute Hepatitis E Viral Infections with Those of Acute Hepatitis A, B, and C Infections in Korea.

PubMed

Oh, Hye Won; Cha, Ra Ri; Lee, Sang Soo; Lee, Chang Min; Kim, Wan Soo; Jo, Yun Won; 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

This study investigated the etiology of acute viral hepatitis and compared the clinical features of hepatitis E virus (HEV) infections with those of other acute viral hepatitis infections in Korea. This study included 2,357 consecutive patients who were diagnosed with acute hepatitis, based on acute illness with jaundice or elevated alanine aminotransferase levels (>100 IU/L), between January 2007 and January 2016. Acute viral infections were observed in 23 (19.8%) patients with HEV, 49 (42.2%) patients with hepatitis A virus, 28 (24.1%) patients with hepatitis B virus, and 16 (13.8%) patients with hepatitis C virus. The incidence of acute HEV infection was higher among older patients (median age: 49 years) and male patients (69.6%), and was associated with the consumption of undercooked or uncooked meat (43.5%). Half of the acute HEV infections involved underlying liver disease, such as alcoholic liver disease, chronic hepatitis B, common bile duct stones, and autoimmune hepatitis. Two HEV-infected patients were diagnosed with Guillain-Barré syndrome, although no patients developed fulminant hepatitis. Our findings indicate that HEV infection in Korea is frequently transmitted through the consumption of raw meat and may cause acute or chronic liver disease. © 2017 S. Karger AG, Basel.

Ferret hepatitis E virus infection induces acute hepatitis and persistent infection in ferrets.

PubMed

Li, Tian-Cheng; Yang, Tingting; Yoshizaki, Sayaka; Ami, Yasushi; Suzaki, Yuriko; Ishii, Koji; Kishida, Noriko; Shirakura, Masayuki; Asanuma, Hideki; Takeda, Naokazu; Wakita, Takaji

2016-02-01

Ferret hepatitis E virus (HEV), a novel hepatitis E virus, has been identified in ferrets. However, the pathogenicity of ferret HEV remains unclear. In the present study, we compared the HEV RNA-positivity rates and alanine aminotransferase (ALT) levels of 63 ferrets between before and after import from the US to Japan. We found that the ferret HEV-RNA positivity rates were increased from 12.7% (8/63) to 60.3% (38/63), and ALT elevation was observed in 65.8% (25/38) of the ferret HEV RNA-positive ferrets, indicating that ferret HEV infection is responsible for liver damage. From long term-monitoring of ferret HEV infection we determined that this infection in ferrets exhibits three patterns: sub-clinical infection, acute hepatitis, and persistent infection. The ALT elevation was also observed in ferret HEV-infected ferrets in a primary infection experiment. These results indicate that the ferret HEV infection induced acute hepatitis and persistent infection in ferrets, suggesting that the ferrets are a candidate animal model for immunological as well as pathological studies of hepatitis E. Copyright © 2015 Elsevier B.V. All rights reserved.

Natural history of acute and chronic hepatitis B: The role of HBV genotypes and mutants.

PubMed

Lin, Chih-Lin; Kao, Jia-Horng

2017-06-01

Molecular epidemiologic studies reveal remarkable differences in the geographical distribution of hepatitis B virus (HBV) genotypes. The frequency of mutants among HBV genotypes also varies. The role of HBV genotypes/mutants in the pathogenesis of HBV infection and natural history of HBV infection has been extensively investigated. The distribution of HBV genotypes in acute hepatitis B patients reflects the predominant genotypes in a given geographic area. In chronic hepatitis B patients, genotype C and D have a higher frequency of basal core promoter A1762T/G1764A mutations than genotype A and B. HBV genotypes C, D and F carry a higher lifetime risk of cirrhosis and HCC development than genotype A and B. HBV pre-S/S gene mutations were associated with immune escape of hepatitis B immunoglobulin or vaccine-induced immunity. Mutations in the pre-S, core promoter and X regions correlate with an increased risk of cirrhosis and HCC. In summary, HBV genotypes and mutants are associated with the disease progression and long-term outcome of HBV infection. They may serve as viral genetic markers for risk stratification of chronic hepatitis B patients in clinical practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hepatitis B virus x gene and cyanobacterial toxins promote aflatoxin B1-induced hepatotumorigenesis in mice

PubMed Central

Lian, Min; Liu, Ying; Yu, Shun-Zhang; Qian, Geng-Sun; Wan, Shu-Guang; Dixon, Kenneth R

2006-01-01

AIM: To assess the combinative role of aflatoxin B1 (AFB1), cyanobacterial toxins (cyanotoxins), and hepatitis B virus (HBV) x gene in hepatotumorigenicity. METHODS: One-week-old animals carrying HBV x gene and their wild-type littermates were intraperitoneally (ip) injected with either single-dose AFB1 [6 mg/kg body weight (bw)], repeated-dose cyanotoxins (microcystin-LR or nodularin, 10 μg/kg bw once a week for 15 wk), DMSO (vehicle control) alone, or AFB1 followed by cyanotoxins a week later, and were sacrificed at 24 and 52 wk post-treatment. RESULTS: AFB1 induced liver tumors in 13 of 29 (44.8%) transgenic mice at 52 wk post-treatment, significantly more frequent than in wild-type mice (13.3%). This significant difference was not shown in the 24-wk study. Compared with AFB1 exposure alone, MC-LR and nodularin yielded approximately 3-fold and 6-fold increases in the incidence of AFB1-induced liver tumors in wild-type animals at 24 wk, respectively. HBV x gene did not further elevate the risk associated with co-exposure to AFB1 and cyanotoxins. With the exception of an MC-LR-dosed wild-type mouse, no liver tumor was observed in mice treated with cyanotoxins alone at 24 wk. Neither DMSO-treated transgenic mice nor their wild-type littermates had pathologic alterations relevant to hepatotumorigenesis in even up to 52 wk. CONCLUSION: HBV x gene and nodularin promote the development of AFB1-induced liver tumors. Co-exposure to AFB1 and MC-LR tends to elevate the risk of liver tumors at 24 wk relative to exposure to one of them. The combinative effect of AFB1, cyanotoxins and HBVx on hepatotumorigenesis is weak at 24 wk. PMID:16718789

Enhanced expression of rat hepatic CYP2B1/2B2 and 2E1 by pyridine: differential induction kinetics and molecular basis of expression.

PubMed

Kim, H; Putt, D; Reddy, S; Hollenberg, P F; Novak, R F

1993-11-01

Expression of the cytochrome P450 (CYP) 2B subfamily in rat and rabbit hepatic tissues after pyridine (PY) treatment has been examined, and the molecular basis for enhanced 2B1/2B2 expression has been determined. P450 expression was monitored using metabolic activity, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analyses, and the identity of the proteins was confirmed through N-terminus microsequence analysis. PY caused a dose-dependent elevation of hepatic CYP2B1/B2B levels in rats, which ranged from 4- to 22-fold over the dosing regimen of 100 to 400 mg PY/kg/day, for 3 days, respectively. PY at low dose failed to induce CYP2B in rabbit hepatic tissue, suggesting a species-dependent response in 2B expression. Anti-2B1 IgG addition to PY-induced microsomes inhibited benzphetamine N-demethylase activity by only approximately 15%, in sharp contrast to the approximately 73% inhibition observed for phenobarbital-induced microsomes, suggesting the induction of other form(s) of P450 having benzphetamine N-demethylase activity. Northern blot analysis revealed that PY treatment increased 2B1 and 2B2 poly(A)+ RNA levels approximately 69- and approximately 34-fold, respectively, whereas the 2E1 poly(A)+ RNA levels failed to increase. The results of this study show that PY induces CYP2B1/2B2 and that induction is species-dependent and kinetically distinguishable from 2E1 induction. Moreover, 2B1/2B2 induction occurs as a result of elevated mRNA levels associated with either transcriptional activation or mRNA stabilization, and it differs from the mechanism of hepatic 2E1 induction by PY.

Breaking Hepatitis B Virus Tolerance and Inducing Protective Immunity Based on Mimicking T Cell-Independent Antigen.

PubMed

Li, Xiaoyan; Ni, Runzhou

2016-11-01

There are over 350 million chronic carriers of hepatitis B virus (HBV) in the world, of whom about a third eventually develop severe HBV-related complications. HBV contributes to liver cirrhosis and hepatocellular carcinoma development. Remarkable progress has been made in selective inhibition of HBV replication by nucleoside analogs. However, how to generate protective antibody of HBsAb in HBV-infected patients after HBV-DNA becomes negative still remains a challenge for scientists. In this study, we show that OmpC-HBsAg 'a' epitope chimeric protein vaccine can break HBV tolerance and induce protective immunity in HBV transgenic mice based on mimicking T cell-independent antigen to bypass T cells from the adaptive immune system. The antibodies induced by the vaccine have the ability to prevent HBV virion infection of human hepatocytes.

Parvovirus B19.

PubMed

Landry, Marie Louise

2016-06-01

Primary parvovirus B19 infection is an infrequent, but serious and treatable, cause of chronic anemia in immunocompromised hosts. Many compromised hosts have preexisting antibody to B19 and are not at risk. However, upon primary infection, some patients may be able to mount a sufficient immune response to terminate active parvovirus B19 infection of erythroid precursors. The most common consequence of B19 infection in the compromised host is pure red-cell aplasia, resulting in chronic or recurrent anemia with reticulocytopenia. Anemia persists until neutralizing antibody is either produced by the host or passively administered. Parvovirus B19 should be suspected in compromised hosts with unexplained or severe anemia and reticulocytopenia, or when bone-marrow examination shows either giant pronormoblasts or absence of red-cell precursors. Diagnosis is established by detection of B19 DNA in serum in the absence of IgG antibody to B19. In some cases, IgG antibody is detected but is not neutralizing. Anti-B19 IgM may or may not be present. Therapy includes any or all of the following: red-cell transfusion, adjustment in medications to restore or improve the patient's immune system, and administration of intravenous immunoglobulin (IVIG). Following treatment, patients should be closely monitored, especially if immunosuppression is unchanged or increased. Should hematocrit trend downward and parvovirus DNA trend upward, the therapeutic options above should be revisited. In a few instances, monthly maintenance IVIG may be indicated. Caregivers should be aware that B19 variants, though rarely encountered, can be missed or under-quantitated by some real-time polymerase-chain reaction methods.

[Detection of human parvovirus B19, human bocavirus and human parvovirus 4 infections in blood samples among 95 patients with liver disease in Nanjing by nested PCR].

PubMed

Tong, Rui; Zhou, Wei-Min; Liu, Xi-Jun; Wang, Yue; Lou, Yong-Liang; Tan, Wen-Jie

2013-04-01

To analyze the infection of human parvovirus B19, human bocavirus (HBoV) and human parvovirus 4 (PARV4) in blood samples among patients with liver disease in Nanjing by molecular detection. Nested PCR assays were designed and validated to detect B19, HBoV and PARV4, respectively. The assays were used to screen three parvoviruses in blood samples from 95 patients with different liver disease in Nanjing. The parvovirus infection was analyzed statistically. The detection limits were 10 copies of genomic DNA equivalents per reaction for each assays and the good specificity were observed. The frequency of B19 and HBoV were 2/95 (2.1%) and 9/95 (9.5%) in blood samples respectively. No PARV4 was detected. HBoV was detected in 3/5 patients with drug-induced hepatitis. Both B19 and HBoV infection were detected in blood from patients with liver disease.

[Prevalences of HIV, hepatitis B and hepatitis C in blood donors in the Republic of Djibouti].

PubMed

Dray, X; Dray-Spira, R; Bronstein, J A; Mattera, D

2005-01-01

Screening for hepatitis B (HBV) surface antigen (Ag HBs) and for antibodies to hepatitis C (HCV) and human: immunodeficiency virus (HIV) was carried out in 9006 volunteer blood donors at the National Blood Bank in the Republic of Djibouti from 1998 to 2000. Results demonstrated the presence of Ag HBs in 934 patients (10.4%), antibodies to HCV in 21 patients (0.3%), and antibodies to HIV in 175 patients (1.9%). In comparison with neighboring countries the prevalence of HBV, HCV, and HIV infection in Djibouti was low. These findings should be used to guide preventive action against these viral infections in the Republic of Djibouti. Estimations of HIV infection (11.7%) based on modeling by the World Health Organization should be reviewed.

Long noncoding RNA H19 interacts with polypyrimidine tract-binding protein 1 to reprogram hepatic lipid homeostasis.

PubMed

Liu, Chune; Yang, Zhihong; Wu, Jianguo; Zhang, Li; Lee, Sangmin; Shin, Dong-Ju; Tran, Melanie; Wang, Li

2018-05-01

H19 is an imprinted long noncoding RNA abundantly expressed in embryonic liver and repressed after birth. We show that H19 serves as a lipid sensor by synergizing with the RNA-binding polypyrimidine tract-binding protein 1 (PTBP1) to modulate hepatic metabolic homeostasis. H19 RNA interacts with PTBP1 to facilitate its association with sterol regulatory element-binding protein 1c mRNA and protein, leading to increased stability and nuclear transcriptional activity. H19 and PTBP1 are up-regulated by fatty acids in hepatocytes and in diet-induced fatty liver, which further augments lipid accumulation. Ectopic expression of H19 induces steatosis and pushes the liver into a "pseudo-fed" state in response to fasting by promoting sterol regulatory element-binding protein 1c protein cleavage and nuclear translocation. Deletion of H19 or knockdown of PTBP1 abolishes high-fat and high-sucrose diet-induced steatosis. Our study unveils an H19/PTBP1/sterol regulatory element-binding protein 1 feedforward amplifying signaling pathway to exacerbate the development of fatty liver. (Hepatology 2018;67:1768-1783). © 2017 by the American Association for the Study of Liver Diseases.

Risk factors for hepatitis B in an outbreak of hepatitis B and D among injection drug users.

PubMed

Bialek, Stephanie R; Bower, William A; Mottram, Karen; Purchase, Dave; Nakano, T; Nainan, Omana; Williams, Ian T; Bell, Beth P

2005-09-01

During January-April, 2000, 12 cases of acute hepatitis B were reported in Pierce County, Washington, compared with seven in all of 1999. Seven (58.3%) case patients were injection drug users (IDUs), three of whom were coinfected with hepatitis D virus (HDV) and died of fulminant hepatitis. Vaccination clinics were implemented at the local health department and needle exchange program to control the outbreak. We investigated this outbreak to determine risk factors for hepatitis B virus (HBV) transmission among IDUs. Hepatitis B cases were ascertained through routine surveillance and prevaccination testing at vaccination clinics. We conducted a case-control study comparing IDU case patients with HBV-susceptible IDUs identified at the vaccination clinics. Fifty-eight case patients were identified during January-December, 2000, 20 (34.5%) of whom were coinfected with HDV. Thirty-eight case patients (65.5%) reported current IDU. In the case-control study, the 17 case patients were more likely than the 141 controls to report having more than one sex partner [odds ratio (OR) =4.8, 95% confidence interval (CI) =1.5-15.0], injecting more than four times a day (OR = 4.5, 95% CI =1.2-15.6) and sharing drug cookers with more than two people (58.8% vs. 14.0%, OR =14.0, 95% CI =2.4-81.5). Results were similar after controlling for syringe sharing in multivariable analysis. IDUs should be vaccinated against hepatitis B and should be advised against sharing drug injection equipment.

Prevalence of antibodies to hepatitis B, hepatitis C, and HIV and risk factors in entrants to Irish prisons: a national cross sectional survey

PubMed Central

Long, Jean; Allwright, Shane; Barry, Joseph; Reynolds, Sheilagh Reaper; Thornton, Lelia; Bradley, Fiona; Parry, John V

2001-01-01

Objectives To determine the prevalence of antibodies to hepatitis B core antigen, hepatitis C virus, and HIV in entrants to Irish prisons and to examine risk factors for infection. Design Cross sectional, anonymous survey, with self completed risk factor questionnaire and oral fluid specimen for antibody testing. Setting Five of seven committal prisons in the Republic of Ireland. Participants 607 of the 718 consecutive prison entrants from 6 April to 1 May 1999. Main outcome measures Prevalence of antibodies to hepatitis B core antigen, hepatitis C virus, and HIV in prison entrants, and self reported risk factor status. Results Prevalence of antibodies to hepatitis B core antigen was 37/596 (6%; 95% confidence interval 4% to 9%), to hepatitis C virus was 130/596 (22%; 19% to 25%), and to HIV was 12/596 (2%; 1% to 4%). A third of the respondents had never previously been in prison; these had the lowest prevalence of antibodies to hepatitis B core antigen (4/197, 2%), to hepatitis C (6/197, 3%), and to HIV (0/197). In total 29% of respondents (173/593) reported ever injecting drugs, but only 7% (14/197) of those entering prison for the first time reported doing so compared with 40% (157/394) of those previously in prison. Use of injected drugs was the most important predictor of antibodies to hepatitis B core antigen and hepatitis C virus. Conclusions Use of injected drugs and infection with hepatitis C virus are endemic in Irish prisons. A third of prison entrants were committed to prison for the first time. Only a small number of first time entrants were infected with one or more of the viruses. These findings confirm the need for increased infection control and harm reduction measures in Irish prisons. What is already known on this topicHigh rates of using injected drugs, initiation of use of injected drugs, and sharing injecting equipment occur in Irish prisonsInjecting drug users have high rates of infection with hepatitis B and C viruses, and hepatitis C is

A Randomized Controlled Trial to Evaluate a Potential Hepatitis B Booster Vaccination Strategy Using Combined Hepatitis A and B Vaccine.

PubMed

Li, Fangjun; Hu, Yuansheng; Zhou, Youming; Chen, Lixin; Xia, Wei; Song, Yufei; Tan, Zhengliang; Gao, Lidong; Yang, Zhong; Zeng, Gang; Han, Xing; Li, Junhua; Li, Jing

2017-05-01

Booster doses could play a major role in no responders or low responders to primary hepatitis B (HB) vaccine. Planed time point for hepatitis A vaccination in China provides a good opportunity to carry out HB booster dose by using combined hepatitis A and B vaccine. A randomized, double-blinded clinical trial was conducted to compare the immunogenicity and safety of toddlers 18-24 months of age receiving 3 different vaccination regimens: 2 doses of inactivated hepatitis A vaccine (group 1), 1 dose of inactivated hepatitis A vaccine plus 1 dose of combined hepatitis A and B vaccine (group 2) or 2 doses of combined hepatitis A and B vaccine (group 3). All 3 groups showed 100% seroprotection for antihepatitis A virus antibody after vaccination. Seroprotection rate for anti-HB antibody before vaccination ranged from 79.5% to 92.9% in the 3 groups. After second inoculation, anti-HBs seroprotection increased from 92.9% to 100% in group 2 with postvaccination geometric mean concentration (GMC) of 2258.3 mIU/mL and from 79.5% to 98.9% in group 3 with postvaccination GMC of 2055.3 mIU/mL. The adverse events were not statistically different among groups (P = 0.345). Combined hepatitis A and B vaccine could stimulate high level of both antihepatitis A virus and anti-HBs antibodies and not increase adverse events, providing a new choice for HB booster.

Excellent response rate to a double dose of the combined hepatitis A and B vaccine in previous nonresponders to hepatitis B vaccine.

PubMed

Cardell, Kristina; Akerlind, Britt; Sällberg, Matti; Frydén, Aril

2008-08-01

Hepatitis B vaccine has been shown to be highly efficient in preventing hepatitis B. However, 5%-10% of individuals fail to develop protective levels (>or=10 mIU/mL) of antibodies to hepatitis B surface antigen (anti-HBs) and are considered to be nonresponders. A total of 48 nonresponders and 20 subjects naive to the HBV vaccine received a double dose of combined hepatitis A and B vaccine (Twinrix) at 0, 1, and 6 months. The levels of anti-HBs and antibodies to hepatitis A virus (anti-HAV) were determined before vaccination and 1 month after each dose. Among 44 nonresponders, protective anti-HBs levels were found in 26 (59%) after the first dose and in 42 (95%) after the third dose. Among the control subjects, the corresponding figures were 10% and 100%, respectively. All subjects seroconverted to anti-HAV. The titers of both anti-HBs and anti-HAV were lower in the previously nonresponsive subjects (P< .01). Revaccination of nonresponders to the standard hepatitis B vaccine regimen with a double dose of the combined hepatitis A and B vaccine was highly effective. This is most likely explained by the increased dose, a positive bystander effect conferred by the hepatitis A vaccine, or both.

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.

Sero-prevalence and vaccination status of hepatitis A and hepatitis B among adults with cirrhosis in Sri Lanka: a hospital based cohort study.

PubMed

Niriella, Madunil Anuk; Kobbegala, Vipuli Jayendra; Karalliyadda, Hasnatha Nuwan; Ranawaka, Chamila Kumara; de Silva, Arjuna Priyadarshin; Dassanayake, Anuradha Supun; de Silva, Hithanadura Janaka

2017-07-21

As acute viral hepatitis can be fatal in patients with cirrhosis, vaccination against hepatitis A (HAV) and hepatitis B (HBV) is recommended for non-immune patients. With increasing affluence the incidence of hepatitis A in childhood has decreased leading to a significant proportion of non-immune adults. As part of their routine investigation, hepatitis A IgG antibodies (anti-HAV IgG), hepatitis B surface antigen (HBsAg) and anti-HCV antibodies was checked and immunization status was assessed among consenting newly diagnosed cirrhotic patients presenting to a tertiary referral center. Out of 135 patients, 107 [79.3%; males 91; mean age (SD) at presentation: 55.5 (11.6) years] with complete data were included for analysis. Most patients had either cryptogenic cirrhosis (62.6%) or alcoholic cirrhosis (29.9%); 2 (1.9%) had HBV cirrhosis, none had hepatitis C (HCV) cirrhosis. None of the patients had received vaccination against hepatitis A, while 71 (67.6%) had been vaccinated against HBV. The majority [62 (58%)] were negative for anti-HAV IgG. Most cirrhotic patients in this cohort were not immune to hepatitis A. None had been vaccinated against HAV, while a third of patients had not been vaccinated against HBV. Cirrhotic patients should be routinely investigated for immunity against HAV and HBV, and vaccination offered to those found to be non-immune.

Rifampicin-Induced Concomitant Renal Injury and Hepatitis

PubMed Central

Chogtu, Bharti; Surendra, Vyshak Uddur; Acharya, Preetam Rajgopal; Yerrapragada, Devesh Bhaskar

2016-01-01

Adverse drug reactions are not unusual during Anti-Tubercular Therapy (ATT). One of the common complications of anti-tubercular treatment is drug induced hepatitis and renal insufficiency has also been reported. Renal failure and/or hepatitis encountered during treatment of tuberculosis can have varied aetiologies: drug induced, concomitant viral infection, pre-existing co-morbidities or a combination of these. Since, hepatitis and/or renal insufficiency can be life threatening a prompt diagnosis is warranted, where drugs should be kept as one of the important cause. Identifying the drug helps in treating hepatitis and/or renal insufficiency along with helping the physician to change the combination of ATT regimen. Rifampicin is one of the most important first line drugs in the treatment of tuberculosis. Hepatitis, epigastric distress, anaemia, thrombocytopenia, and interstitial nephritis are reported adverse drug reactions to rifampicin. As per literature rifampicin induced renal toxicity is usually seen on rifampicin re-exposure, or rifampicin administration on alternate days, both being present in this case. Here we are reporting a case of ATT induced renal failure with concomitant hepatitis where rifampicin was suspected to be the cause. PMID:27790502

Role of superoxide radical anion in the mechanism of apoB100 degradation induced by DHA in hepatic cells

PubMed Central

Andreo, Ursula; Elkind, Josh; Blachford, Courtney; Cederbaum, Arthur I.; Fisher, Edward A.

2011-01-01

VLDL is produced by the liver. Its major protein is apoB100. Docosahexaenoic acid (DHA), a dietary polyunsaturated fatty acid (PUFA), reduces VLDL levels and is used therapeutically for hypertriglyceridemia. In model systems, DHA lowers VLDL secretion by inducing presecretory apoB100 degradation, a process dependent on PUFA-derived lipid peroxides. We hypothesized that superoxide (SO) was a major participant in DHA-induced apoB100 degradation, given its promotion of lipid peroxidation. SO levels in a model of VLDL metabolism, rat hepatoma McArdle cells, were either decreased by a mimetic of superoxide dismutase 1 (SOD1) or by overexpressing SOD1 or increased by SOD1 siRNA. ApoB100 recovery was assessed by immunoprecipitation, SO by 2-hydroxyethidine, and lipid peroxides by thiobarbituric acid reactive substances. The SOD1 mimetic or SOD1 overexpression reduced SO and inhibited apoB100 degradation in DHA-treated cells by up to 100%. Surprisingly, silencing SOD1 did not increase DHA-induced degradation, although levels of SO were higher (+44%); those of lipid peroxides were similar, and their reduction by α-tocopherol decreased degradation by 50%. SO is required for lipid peroxidation in DHA-induced apoB100 degradation, but it is the peroxide level that has a tighter relationship to the level of degradation and the regulation of VLDL production.—Andreo, U., Elkind, J., Blachford, C., Cederbaum, A. I., Fisher, E. A. Role of superoxide radical anion in the mechanism of apoB100 degradation induced by DHA in hepatic cells. PMID:21757500

Prevalence of markers for HIV, hepatitis B and hepatitis C infection in UK military recruits.

PubMed

Brown, A E; Ross, D A; Simpson, A J H; Erskine, R S; Murphy, G; Parry, J V; Gill, O N

2011-08-01

An unlinked anonymous survey was conducted to measure the prevalence of selected markers for HIV, hepatitis B and C infection in recruits to the UK Armed Forces to inform future screening and hepatitis B vaccination policies. During 2007, nearly 14 000 left-over samples taken from new recruits for blood typing were collected, unlinked from identifiers and anonymously tested for HIV, hepatitis C and current and past cleared hepatitis B infection. Overall, serological evidence of HIV and hepatitis C was found in 0·06% and 0·06% of recruits, respectively. Evidence of past cleared and current hepatitis B infection was found in 3·63% and 0·37% of recruits, respectively. Overall, prevalence rates were broadly consistent with UK population estimates of infection. However, HIV and hepatitis B prevalence was higher in recruits of African origin than in those from the UK (P<0·0001). Screening for these infections is an option that could be considered for those entering Services from high-prevalence countries.

Hepatitis B vaccine - what you need to know

MedlinePlus

... is taken in its entirety from the CDC Hepatitis B Vaccine Information Statement (VIS): www.cdc.gov/vaccines/ ... statements/hep-b.html CDC review information for Hepatitis B VIS: Page last reviewed: July 20, 2016 Page ...

21 CFR 660.1 - Antibody to Hepatitis B Surface Antigen.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Antibody to Hepatitis B Surface Antigen. 660.1... Hepatitis B Surface Antigen § 660.1 Antibody to Hepatitis B Surface Antigen. (a) Proper name and definition. The proper name of this product shall be Antibody to Hepatitis B Surface Antigen. The product is...

21 CFR 660.1 - Antibody to Hepatitis B Surface Antigen.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Antibody to Hepatitis B Surface Antigen. 660.1... Hepatitis B Surface Antigen § 660.1 Antibody to Hepatitis B Surface Antigen. (a) Proper name and definition. The proper name of this product shall be Antibody to Hepatitis B Surface Antigen. The product is...

21 CFR 660.1 - Antibody to Hepatitis B Surface Antigen.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Antibody to Hepatitis B Surface Antigen. 660.1... Hepatitis B Surface Antigen § 660.1 Antibody to Hepatitis B Surface Antigen. (a) Proper name and definition. The proper name of this product shall be Antibody to Hepatitis B Surface Antigen. The product is...

21 CFR 660.1 - Antibody to Hepatitis B Surface Antigen.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Antibody to Hepatitis B Surface Antigen. 660.1... Hepatitis B Surface Antigen § 660.1 Antibody to Hepatitis B Surface Antigen. (a) Proper name and definition. The proper name of this product shall be Antibody to Hepatitis B Surface Antigen. The product is...

21 CFR 660.1 - Antibody to Hepatitis B Surface Antigen.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Antibody to Hepatitis B Surface Antigen. 660.1... Hepatitis B Surface Antigen § 660.1 Antibody to Hepatitis B Surface Antigen. (a) Proper name and definition. The proper name of this product shall be Antibody to Hepatitis B Surface Antigen. The product is...

Standard-b-Value Versus Low-b-Value Diffusion-Weighted Imaging in Hepatic Lesion Discrimination: A Meta-analysis.

PubMed

Xiong, Hui; Zeng, Yuan-Lin

2016-01-01

We sought to determine the comparative diagnostic performance of standard-b-value (500-1000s/mm) versus low-b-value (≤500 s/mm) diffusion-weighted imaging (DWI) in the discrimination of hepatic lesions. A total of 1775 hepatic malignant lesions and 1120 benign hepatic lesions from 21 studies were included. (1) The global sensitivity was 0.86 (95% confidence interval [CI], 0.847-0.879), the specificity was 0.82 (95% CI, 0.797-0.842), the positive likelihood ratio (PLR) was 6.234 (95% CI, 4.260-9.123), the negative likelihood ratio (NLR) was 0.175 (95% CI, 0.135-0.227), and diagnostic odds ratio (DOR) was 42.836 (95% CI, 24.134-76.031). The area under the curve (AUC) and Q* index were 0.93 and 0.87. Publication bias was not present (P > 0.05). (2)The sensitivity of a subgroup meta-analysis of standard-b-value DWI was 0.858 (95% CI, 0.835-0.880), the specificity was 0.836 (95% CI, 0.807-0.863), the PLR was 6.527 (95% CI, 3.857-11.046), the NLR was 0.168 (95% CI, 0.123-0.239), and the DOR was 49.716 (95% CI, 22.897-107.98). The AUC and Q* index were 0.941 and 0.88. (3)The sensitivity of a subgroup meta-analysis of low-b-value DWI was 0.87 (95% CI, 0.84-0.89), the specificity was 0.80 (95% CI, 0.76-0.83), the PLR was 6.22 (95% CI, 3.29-11.76), the NLR was 0.19 (95% CI, 0.12-0.29), and the DOR was 37.14 (95% CI, 14.80-93.18). The AUC and Q* index were 0.922 and 0.86. Hepatic DWI is useful in differentiating between malignant and benign hepatic lesions. Standard-b-value DWI displayed an overall superior diagnostic accuracy over low-b-value DWI. Further trials needed to determine whether increasing b values beyond 1000 s/mm affects the diagnostic accuracy of hepatic lesion discrimination.

Epidemiology of hepatitis B infection in Liberian infants.

PubMed

Prince, A M; White, T; Pollock, N; Riddle, J; Brotman, B; Richardson, L

1981-05-01

To provide background for a hepatitis B vaccine efficacy trial, sera were collected from 0- to 4-year-old Liberian infants and their mothers, on two occasions an average of 14.75 months apart, and tested for serological markers of hepatitis B virus infection. The prevalence of the hepatitis B surface antigen (HBsAg) was 2.9% in the 0- to 6-month age group and 23% in infants 3 to 4 years of age. HBsAg persisted for the 14.75-month average follow-up period in 80.8% of the infants tested. The annual incidence of development of HBsAg was 18.9% for infants less than 1 year of age and 13.6% in infants 3 to 4 years of age. Infants born to HBsAg carrier mothers had significantly higher age-specific prevalence and incidence of hepatitis B virus infection. However, it was estimated that only a minor proportion of hepatitis B infections in Liberia are derived by vertical transmission from carrier mothers.

Forced expression of Hnf1b/Foxa3 promotes hepatic fate of embryonic stem cells.

PubMed

Yahoo, Neda; Pournasr, Behshad; Rostamzadeh, Jalal; Hakhamaneshi, Mohammad Saeed; Ebadifar, Asghar; Fathi, Fardin; Baharvand, Hossein

2016-05-20

Embryonic stem (ES) cell-derived hepatocytes have the potential to be used for basic research, regenerative medicine, and drug discovery. Recent reports demonstrated that in addition to conventional differentiation inducers such as chemical compounds and cytokines, overexpression of lineage-specific transcription factors could induce ES cells to differentiate to a hepatic fate. Here, we hypothesized that lentivirus-mediated inducible expression of hepatic lineage transcription factors could enhance mouse ES cells to hepatocyte-like cells. We screened the effects of candidate transcription factors Hnf1b, Hnf1a, Hnf4a, Foxa1, Foxa3 and Hex, and determined that the combination of Hnf1b/Foxa3 promoted expression of several hepatic lineage-specific markers and proteins, in addition to glycogen storage, ICG uptake, and secretion of albumin and urea. The differentiated cells were engraftable and expressed albumin when transplanted into a carbon tetrachloride-injured mouse model. These results demonstrated the crucial role of Hnf1b and Foxa3 in hepatogenesis in vitro and provided a valuable tool for the efficient differentiation of HLCs from ES cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Serum from CCl4-induced acute rat injury model induces differentiation of ADSCs towards hepatic cells and reduces liver fibrosis.

PubMed

Baig, Maria Tayyab; Ali, Gibran; Awan, Sana Javaid; Shehzad, Umara; Mehmood, Azra; Mohsin, Sadia; Khan, Shaheen N; Riazuddin, Sheikh

2017-10-01

Cellular therapies hold promise to alleviate liver diseases. This study explored the potential of allogenic serum isolated from rat with acute CCl 4 injury to differentiate adipose derived stem cells (ADSCs) towards hepatic lineage. Acute liver injury was induced by CCl 4 which caused significant increase in serum levels of VEGF, SDF1α and EGF. ADSCs were preconditioned with 3% serum isolated from normal and acute liver injury models. ADSCs showed enhanced expression of hepatic markers (AFP, albumin, CK8 and CK19). These differentiated ADSCs were transplanted intra-hepatically in CCl 4 -induced liver fibrosis model. After one month of transplantation, fibrosis and liver functions (alkaline phosphatase, ALAT and bilirubin) showed marked improvement in acute injury group. Elevated expression of hepatic (AFP, albumin, CK 18 and HNF4a) and pro survival markers (PCNA and VEGF) and improvement in liver architecture as deduced from results of alpha smooth muscle actin, Sirius red and Masson's trichome staining was observed.

Drug-induced hepatitis

MedlinePlus

... induced hepatitis. Painkillers and fever reducers that contain acetaminophen are a common cause of liver injury, particularly ... problem. However, if you took high doses of acetaminophen , treatment should be started as soon as possible ...

Persistence of antibodies 20 y after vaccination with a combined hepatitis A and B vaccine

PubMed Central

Van Damme, Pierre; Leroux-Roels, Geert; Suryakiran, P.; Folschweiller, Nicolas; Van Der Meeren, Olivier

2017-01-01

ABSTRACT Vaccination is the most effective and well-tolerated method of conferring long-term protection against hepatitis A and B viruses (HAV; HBV). Long-term studies are required to characterize the duration of protection and need for boosters. Following primary immunization of 150 and 157 healthy adults with 3-doses of combined hepatitis A/hepatitis B vaccine (HAB; Twinrix™, GSK Vaccines, Belgium) at 0-1-6 months in 2 separate studies, we measured vaccine-induced antibody persistence against HAV and HBV annually for 20 y (Study A: NCT01000324; Study B: NCT01037114). Subjects with circulating anti-HAV antibodies < 15 mIU/mL or with anti-hepatitis B surface antigen < 10 mIU/mL were offered an additional monovalent hepatitis A and/or B vaccine dose (Havrix™/Engerix™-B, GSK Vaccines, Belgium). Applying the immunogenicity results from these studies, mathematical modeling predicted long-term persistence. After 20 y, 18 and 25 subjects in studies A and B, respectively, comprised the long-term according-to-protocol cohort for immunogenicity; 100% and 96.0% retained anti-HAV antibodies ≥ 15 mIU/mL, respectively; 94.4% and 92.0% had anti-HBs antibodies ≥ 10 mIU/mL, respectively. Between Years 16–20, 4 subjects who received a challenge dose of monovalent hepatitis A vaccine (N = 2) or hepatitis B vaccine (N = 2), all mounted a strong anamnestic response suggestive of immune memory despite low antibody levels. Mathematical modeling predicts that 40 y after vaccination ≥ 97% vaccinees will maintain anti-HAV ≥ 15 mIU/mL and ≥ 50% vaccinees will retain anti-HBs ≥ 10 mIU/mL. Immunogenicity data confirm that primary immunization with 3-doses of HAB induces persisting anti-HAV and anti-HBs specific antibodies in most adults for up to 20 y; mathematical modeling predicts even longer-term protection. PMID:28281907

Persistence of antibodies 20 y after vaccination with a combined hepatitis A and B vaccine.

PubMed

Van Damme, Pierre; Leroux-Roels, Geert; Suryakiran, P; Folschweiller, Nicolas; Van Der Meeren, Olivier

2017-05-04

Vaccination is the most effective and well-tolerated method of conferring long-term protection against hepatitis A and B viruses (HAV; HBV). Long-term studies are required to characterize the duration of protection and need for boosters. Following primary immunization of 150 and 157 healthy adults with 3-doses of combined hepatitis A/hepatitis B vaccine (HAB; Twinrix™, GSK Vaccines, Belgium) at 0-1-6 months in 2 separate studies, we measured vaccine-induced antibody persistence against HAV and HBV annually for 20 y (Study A: NCT01000324; Study B: NCT01037114). Subjects with circulating anti-HAV antibodies < 15 mIU/mL or with anti-hepatitis B surface antigen < 10 mIU/mL were offered an additional monovalent hepatitis A and/or B vaccine dose (Havrix™/Engerix™-B, GSK Vaccines, Belgium). Applying the immunogenicity results from these studies, mathematical modeling predicted long-term persistence. After 20 y, 18 and 25 subjects in studies A and B, respectively, comprised the long-term according-to-protocol cohort for immunogenicity; 100% and 96.0% retained anti-HAV antibodies ≥ 15 mIU/mL, respectively; 94.4% and 92.0% had anti-HBs antibodies ≥ 10 mIU/mL, respectively. Between Years 16-20, 4 subjects who received a challenge dose of monovalent hepatitis A vaccine (N = 2) or hepatitis B vaccine (N = 2), all mounted a strong anamnestic response suggestive of immune memory despite low antibody levels. Mathematical modeling predicts that 40 y after vaccination ≥ 97% vaccinees will maintain anti-HAV ≥ 15 mIU/mL and ≥ 50% vaccinees will retain anti-HBs ≥ 10 mIU/mL. Immunogenicity data confirm that primary immunization with 3-doses of HAB induces persisting anti-HAV and anti-HBs specific antibodies in most adults for up to 20 y; mathematical modeling predicts even longer-term protection.

Maternal hepatitis B infection and gestational diabetes mellitus.

PubMed

Lao, Terence T; Chan, Ben C P; Leung, Wing-Cheong; Ho, Lai-Fong; Tse, Ka-Yu

2007-07-01

This retrospective cohort study was performed to examine the relationship between maternal hepatitis B virus infection, as indicated by the surface antigen status, with the development of gestational diabetes mellitus in a normal-risk Chinese obstetric population. Maternal demographics, risk factors, and pregnancy outcome of 13,683 singleton pregnancies delivering in 1998-2001 were analysed according to maternal hepatitis B surface antigen status, which was routinely screened. Multiple logistic regression analysis was performed to examine the role of hepatitis B infection in the development of gestational diabetes mellitus. The 1138 women (8.3%) with hepatitis B infection had lower mean weight and body mass index, similar prevalence of chronic medical diseases and smokers, but increased prevalence of gestational diabetes mellitus, which remained significant (odds ratio 1.24, 95% confidence interval 1.01-1.51) after adjustment for confounding variables. However, there was no difference in pregnancy outcome. Our results confirmed the independent association between hepatitis B infection with gestational diabetes mellitus. The magnitude of chronic hepatitis B infection in the developing world and certain ethnic groups could have contributed to the high prevalence of gestational and possibly type 2 diabetes in these populations. Further studies on the long-term implications of our finding are warranted.

A key role for Pre-B cell colony-enhancing factor in experimental hepatitis.

PubMed

Moschen, Alexander R; Gerner, Romana; Schroll, Andrea; Fritz, Teresa; Kaser, Arthur; Tilg, Herbert

2011-08-01

Pre-B cell colony-enhancing factor (PBEF), also known as nicotinamide phosphoribosyltransferase or visfatin, plays an important role in metabolic, inflammatory, and malignant diseases. Recent evidence suggests that blocking its enzymatic activity using a specific small-molecule inhibitor (FK866) might be beneficial in acute experimental inflammation. We investigated the role of PBEF in human liver disease and experimental hepatitis. PBEF serum levels and hepatic expression were determined in patients with chronic liver diseases. These studies were followed by in vivo experiments using concanavalin A (ConA) and D-galactosamine/lipopolysaccharide (LPS) models of experimental hepatitis. PBEF was either overexpressed by hydrodynamic perfusion or inhibited by FK866. In vivo findings were corroborated studying inflammatory responses of lentivirally PBEF-silenced or control FL83B mouse hepatocytes. Here, we demonstrate that PBEF serum levels were increased in patients with chronic liver diseases irrespective of disease stage and etiology. In particular, we observed enhanced PBEF expression in hepatocytes. Liver-targeted overexpression of PBEF rendered mice more susceptible to ConA- and D-galactosamine/LPS-induced hepatitis compared with control animals. In contrast, inhibition of PBEF using FK866 protected mice from ConA-induced liver damage and apoptosis. Administration of FK866 resulted in depletion of liver nicotinamide adenine dinucleotide+ levels and reduced proinflammatory cytokine expression. Additionally, FK866 protected mice in the D-galactosamine/LPS model of acute hepatitis. In vitro, PBEF-silenced mouse hepatocytes showed decreased responses after stimulation with LPS, lipoteichoic acid, and tumor necrosis factor α. In primary murine Kupffer cells, FK866 suppressed LPS-induced interleukin (IL)-6 production, whereas incubation with recombinant PBEF resulted in increased IL-6 release. Our data suggest that PBEF is of key importance in experimental hepatitis

Hepatitis B Vaccination Status among Japanese Travelers.

PubMed

Yaita, Kenichiro; Yahara, Koji; Sakai, Yoshiro; Iwahashi, Jun; Masunaga, Kenji; Hamada, Nobuyuki; Watanabe, Hiroshi

2017-05-08

This study clarified the characteristics of travelers who received hepatitis B vaccinations. Subjects were 233 Japanese travelers who visited our clinic prior to travel. We summarized the characteristics of the clients and performed two comparative studies: first, we compared a hepatitis B-vaccinated group with an unvaccinated group; second, we compared a group that had completed the hepatitis B vaccine series with a group that did not complete the series. The hepatitis B vaccine was administered to 152 clients. Factors positively associated with the hepatitis B vaccination (after adjusting for age and sex) included the following: travel for business or travel as an accompanying family member; travel to Asia; travel for a duration of a month or more; and, inclusion of the vaccine in a company or organization's payment plan. Meanwhile, factors negatively associated with the vaccination were travel for leisure or education, and travel to North America or Africa. Among 89 record-confirmed cases, only 53 completed 3 doses. The completion rate was negatively associated with the scheduled duration of travel if it was from a month to less than a year (after adjusting for age and sex). The present study provides a basis for promoting vaccination compliance more vigorously among Japanese adults.

[Appearance of hepatitis B in a family environment].

PubMed

Marinković, V; Letica, Z; Zivanović-Marinković, V; Mijusković, P; Kapulica, I; Dokić, M

1981-01-01

The study comprised 20 families with total of 83 members of whom 45 with hepatitis B. The selection was made of families with at least two members diseased which was the most common case, the marital couples being in question. Of other families, three families had three members and one family four members with hepatitis B virus infection. The largest number had severe clinical picture (44%) and 13 (28%) chronic active hepatitis. Four patients with the most severe clinical picture of chronic active hepatitis, together with HBeantigens, had positive HBeantigen for more than two years since the onset of the disease. Importance of damaged skin and mucosa in spreading of hepatitis B infection in family environment has been pointed out.

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

Hepatitis B (HBV)

MedlinePlus

... syringes for injecting drugs transmission from HBV-infected mothers to their newborn babies Who Is at Risk for Hepatitis B? In the United States, the most common way people get infected with HBV is through unprotected sex with someone who has the disease. People who ...

Altered Hepatic Transport by Fetal Arsenite Exposure in Diet-Induced Fatty Liver Disease.

PubMed

Ditzel, Eric J; Li, Hui; Foy, Caroline E; Perrera, Alec B; Parker, Patricia; Renquist, Benjamin J; Cherrington, Nathan J; Camenisch, Todd D

2016-07-01

Non-alcoholic fatty liver disease can result in changes to drug metabolism and disposition potentiating adverse drug reactions. Furthermore, arsenite exposure during development compounds the severity of diet-induced fatty liver disease. This study examines the effects of arsenite potentiated diet-induced fatty liver disease on hepatic transport in male mice. Changes were detected for Mrp2/3/4 hepatic transporter gene expression as well as for Oatp1a4/2b1/1b2. Plasma concentrations of Mrp and Oatp substrates were increased in arsenic exposure groups compared with diet-only controls. In addition, murine embryonic hepatocytes and adult primary hepatocytes show significantly altered transporter expression after exposure to arsenite alone: a previously unreported phenomenon. These data indicate that developmental exposure to arsenite leads to changes in hepatic transport which could increase the risk for ADRs during fatty liver disease. © 2016 Wiley Periodicals, Inc.

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.

MicroRNA-19a/b-3p protect the heart from hypertension-induced pathological cardiac hypertrophy through PDE5A.

PubMed

Liu, Kun; Hao, Qiongyu; Wei, Jie; Li, Gong-Hao; Wu, Yong; Zhao, Yun-Feng

2018-04-16

PDE5A is a leading factor contributing to cGMP signaling and cardiac hypertrophy. However, microRNA-mediated posttranscriptional regulation of PDE5A has not been reported. The aim of this study is to screen the microRNAs that are able to regulate PDE5A and explore the function of the microRNAs in cardiac hypertrophy and remodeling. Although miR-19a/b-3p (microRNA-19a-3p and microRNA-19b-3p) have been reported to be differentially expressed during cardiac hypertrophy, the direct targets and the functions of this microRNA family for regulation of cardiac hypertrophy have not yet been investigated. The present study identified some direct targets and the underlying functions of miR-19a/b-3p by using bioinformatics tools and gene manipulations within mouse neonatal cardiomyocytes. Transfection of miR-19a/b-3p down-regulated endogenous expressions of PDE5A at both mRNA and protein levels with real-time PCR and western blot. Luciferase reporter assays showed that PDE5A was a direct target of miR-19a/b-3p. In mouse models of cardiac hypertrophy, we found that miR-19a/b-3p was expressed in cardiomyocytes and that its expression was reduced in pressure overload-induced hypertrophic hearts. miR-19a/b-3p transgenic mice prevented the progress of cardiac hypertrophy and cardiac remodeling in response to angiotensin II infusion with echocardiographic assessment and pressure-volume relation analysis. Our study elucidates that PDE5A is a novel direct target of miR-19a/b-3p, and demonstrates that antihypertrophic roles of the miR-19a/b-3p family in Ang II-induced hypertrophy and cardiac remodeling, suggests that endogenous miR-19a/b-3p might have clinical potential to suppress cardiac hypertrophy and heart failure.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any

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

Expression of Fibroblast Growth Factor 21 and β-Klotho Regulates Hepatic Fibrosis through the Nuclear Factor-κB and c-Jun N-Terminal Kinase Pathways.

PubMed

Lee, Kyong Joo; Jang, Yoon Ok; Cha, Seung-Kuy; Kim, Moon Young; Park, Kyu-Sang; Eom, Young Woo; Baik, Soon Koo

2018-04-27

Fibroblast growth factor (FGF) 21 is associated with hepatic inflammation and fibrosis. However, little is known regarding the effects of inflammation and fibrosis on the β-Klotho and FGF21 pathway in the liver. Enrolled patients had biopsy-confirmed viral or alcoholic hepatitis. FGF19, FGF21 and β-Klotho levels were evaluated using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and Western blotting. Furthermore, we explored the underlying mechanisms for this process by evaluating nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) pathway involvement in Huh-7 cells. We observed that the FGF19 and FGF21 serum and mRNA levels in the biopsied liver tissue gradually increased and were correlated with fibrosis stage. Inflammatory markers (interleukin 1β [IL-1β], IL-6, and tumor necrosis factor-α) were positively correlated, while β-Klotho expression was negatively correlated with the degree of fibrosis. In Huh-7 cells, IL-1β increased FGF21 levels and decreased β-Klotho levels. NF-κB and JNK inhibitors abolished the effect of IL-1β on both FGF21 and β-Klotho expression. FGF21 protected IL-1β-induced growth retardation in Huh-7 cells. These results indicate that the inflammatory response during fibrogenesis increases FGF21 levels and suppresses β-Klotho via the NF-κB and JNK pathway. In addition, FGF21 likely protects hepatocytes from hepatic inflammation and fibrosis.

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

Right upper-quadrant pain in a patient with drug abuse, secondary syphilis and occult hepatitis B virus.

PubMed

Fielding, Cory M; Angulo, Paul

2014-01-01

To describe the etiology of hepatitis and identify occult hepatitis B virus (HBV) infection. A 40-year-old man presented with severe abdominal pain and jaundice, a history of acute HBV infection that had cleared as well as the use of acetaminophen, methamphetamine, buprenorphine and marijuana. He admitted to having had unprotected sex with multiple partners of both genders. A thorough skin examination revealed papulosquamous lesions on his penis, scrotum, upper and lower extremities and feet. Transaminases and bilirubin were elevated. His rapid plasma reagin was reactive, and hepatitis serologies showed occult HBV. Liver biopsy showed severe hepatitis, but the stains for hepatitis B surface antigen and hepatitis B core antigen were negative. The pathological findings were highly indicative of drug-induced hepatitis without evidence of chronic hepatitis, reactivation of HBV or syphilitic hepatitis. With supportive management and abstinence from drugs, his condition improved. This case describes a patient with multiple potential causes for hepatitis and highlights the importance of obtaining a detailed social history. Further, one should consider the presence of occult HBV and recognize the serologic pattern. © 2014 S. Karger AG, Basel.

Hepatitis B antigen and viral hepatitis type B in India*

PubMed Central

John, T. Jacob; Carman, Robert H.; Hill, Peter G.

1974-01-01

Surveys were conducted to determine the occurrence of overt hepatitis manifested by jaundice in groups of hospital patients who had survived their initial illness. Of those who had been given blood that had not been screened for the presence of hepatitis B antigen (HB Ag) 9.4% reported that they had had jaundice during the 6 months following transfusion. During a similar period jaundice was reported by only 1.1% of those who had received blood found to be negative for HB Ag by the cross-over electrophoresis test. This difference is highly significant. Jaundice was reported by 25.5% of recipients of HB Ag-positive blood. Of a control population of hospitalized but non-transfused patients 2.2% reported jaundice within 6 months of hospitalization. The risk of overt hepatitis from HB Ag in transfused blood is high in southern India and is similar to that in temperate countries where the occurrence of antigen carriers, and presumably of immune status, are lower than in the tropics. PMID:4549611

Epidemiology of hepatitis B infection in Liberian infants.

PubMed Central

Prince, A M; White, T; Pollock, N; Riddle, J; Brotman, B; Richardson, L

1981-01-01

To provide background for a hepatitis B vaccine efficacy trial, sera were collected from 0- to 4-year-old Liberian infants and their mothers, on two occasions an average of 14.75 months apart, and tested for serological markers of hepatitis B virus infection. The prevalence of the hepatitis B surface antigen (HBsAg) was 2.9% in the 0- to 6-month age group and 23% in infants 3 to 4 years of age. HBsAg persisted for the 14.75-month average follow-up period in 80.8% of the infants tested. The annual incidence of development of HBsAg was 18.9% for infants less than 1 year of age and 13.6% in infants 3 to 4 years of age. Infants born to HBsAg carrier mothers had significantly higher age-specific prevalence and incidence of hepatitis B virus infection. However, it was estimated that only a minor proportion of hepatitis B infections in Liberia are derived by vertical transmission from carrier mothers. PMID:7251143

Responses to hepatitis B vaccine in isolated anti-HBc positive adults

PubMed Central

Yao, Jun; Ren, Wen; Chen, Yongdi; Jiang, Zhenggang; Shen, Lingzhi; Shan, Huan; Dai, Xuewei; Li, Jing; Liu, Ying; Qiu, Yan; Ren, Jingjing

2016-01-01

ABSTRACT Immune responses of isolated anti-HBc subjects are not well characterized in populations in China. This study aimed to evaluate immune responses to hepatitis B vaccination in isolated anti-HBc positive subjects. A cohort of 608 subjects were selected and separated into isolated anti-HBc (negative for HBsAg and anti-HBs, positive for anti-HBc) and control (negative for HBsAg, anti-HBs, and anti-HBc) groups, who were matched by age and sex. All subjects received 3 doses of hepatitis B vaccine (20μg) at months 0, 1, and 3, followed by testing for serological responses 1 month after the third vaccination. The positive seroprotection rate and geometric mean titer (GMT) for hepatitis B surface antibody (anti-HBs) of isolated anti-HBc subjects were significantly lower than those in the control group(86.2% vs.92.1%, P = 0.02; 47.26 vs.97.81 mIU/mL, P < 0.001). When stratified by age, positive seroprotection rate in the isolated anti-HBc group were 92%, 88.5% and 79.4% in the 20–34, 35–49, and 50–60 y old subgroups, respectively (χ2 = 5.919, P = 0.04). Additionally, the GMT level for anti-HBs in the isolated anti-HBc group for different age subgroups were 104.43, 47.87 and 31.79 mIU/mL respectively (χ2 = 19.44, P < 0.001). The GMT level for anti-HBc before vaccination were negatively correlated with GMT for anti-HBs after 3 doses of hepatitis B vaccine (r = −0.165, P < 0.001). In conclusion, isolated anti-HBc positive subjects can achieve good immune responses after hepatitis B vaccination, and the positive seroprotection rate and GMT level for anti-HBs were lower than the control group. Better responses could be observed in young adults, and significant negative correlations were found between GMT of anti-HBc before vaccination and GMT of anti-HBs after vaccination. PMID:27065099

Responses to hepatitis B vaccine in isolated anti-HBc positive adults.

PubMed

Yao, Jun; Ren, Wen; Chen, Yongdi; Jiang, Zhenggang; Shen, Lingzhi; Shan, Huan; Dai, Xuewei; Li, Jing; Liu, Ying; Qiu, Yan; Ren, Jingjing

2016-07-02

Immune responses of isolated anti-HBc subjects are not well characterized in populations in China. This study aimed to evaluate immune responses to hepatitis B vaccination in isolated anti-HBc positive subjects. A cohort of 608 subjects were selected and separated into isolated anti-HBc (negative for HBsAg and anti-HBs, positive for anti-HBc) and control (negative for HBsAg, anti-HBs, and anti-HBc) groups, who were matched by age and sex. All subjects received 3 doses of hepatitis B vaccine (20μg) at months 0, 1, and 3, followed by testing for serological responses 1 month after the third vaccination. The positive seroprotection rate and geometric mean titer (GMT) for hepatitis B surface antibody (anti-HBs) of isolated anti-HBc subjects were significantly lower than those in the control group(86.2% vs.92.1%, P = 0.02; 47.26 vs.97.81 mIU/mL, P < 0.001). When stratified by age, positive seroprotection rate in the isolated anti-HBc group were 92%, 88.5% and 79.4% in the 20-34, 35-49, and 50-60 y old subgroups, respectively (χ2 = 5.919, P = 0.04). Additionally, the GMT level for anti-HBs in the isolated anti-HBc group for different age subgroups were 104.43, 47.87 and 31.79 mIU/mL respectively (χ2 = 19.44, P < 0.001). The GMT level for anti-HBc before vaccination were negatively correlated with GMT for anti-HBs after 3 doses of hepatitis B vaccine (r = -0.165, P < 0.001). In conclusion, isolated anti-HBc positive subjects can achieve good immune responses after hepatitis B vaccination, and the positive seroprotection rate and GMT level for anti-HBs were lower than the control group. Better responses could be observed in young adults, and significant negative correlations were found between GMT of anti-HBc before vaccination and GMT of anti-HBs after vaccination.

Infection with hepatitis A, B, C, and delta viruses among patients with acute hepatitis in Mongolia.

PubMed

Tsatsralt-Od, Bira; Takahashi, Masaharu; Endo, Kazunori; Buyankhuu, Osorjin; Baatarkhuu, Oidov; Nishizawa, Tsutomu; Okamoto, Hiroaki

2006-05-01

One hundred ten consecutive patients (60 males and 50 females; age, mean +/- standard deviation [SD], 22.6 +/- 6.4 years; range 16-48 years) who were clinically diagnosed with sporadic acute hepatitis between December 2004 and January 2005 in Ulaanbaatar, Mongolia, were studied. IgM antibodies to hepatitis A virus were detected in 18 patients (16.4%), IgM antibodies to hepatitis B core (anti-HBc IgM) in 38 patients (34.5%) including two patients with concurrent hepatitis delta virus (HDV) infection, and hepatitis C virus RNA in nine patients (8.2%). There were 30 hepatitis B virus (HBV) carriers who had detectable hepatitis B surface antigen and antibodies to HDV but were negative for anti-HBc IgM, suggesting that they acquired type D acute hepatitis due to superinfection of HDV on a background of chronic HBV infection. None had IgM antibodies to hepatitis E virus (HEV). Consequently, 16.4, 32.7, 6.4, 1.8, and 27.3% of the patients were diagnosed as having acute hepatitis of type A, B, C, type B + D (HBV/HDV coinfection), and type D (superinfection of HDV), respectively. The cause of hepatitis was not known in the remaining 17 patients (15.5%). All 18 HAV isolates were genotyped as IA, all 9 HCV isolates were genotyped as 1b, and all 32 HDV isolates were classified into genotype I. The distribution of HBV genotypes among the 67 HBV isolates was A (1.5%, n = 1) and D (98.5%, n = 66). The present study indicates that de novo infections of HAV, HBV, HCV, and HDV are prevalent among young adults in Mongolia. Copyright 2006 Wiley-Liss, Inc.

MicroRNA-19a/b mediates grape seed procyanidin extract-induced anti-neoplastic effects against lung cancer.

PubMed

Mao, Jenny T; Xue, Bingye; Smoake, Jane; Lu, Qing-Yi; Park, Heesung; Henning, Susanne M; Burns, Windie; Bernabei, Alvise; Elashoff, David; Serio, Kenneth J; Massie, Larry

2016-08-01

Oncomirs are microRNAs (miRNA) associated with carcinogenesis and malignant transformation. They have emerged as potential molecular targets for anti-cancer therapy. We hypothesize that grape seed procyanidin extract (GSE) exerts antineoplastic effects through modulations of oncomirs and their downstream targets. We found that GSE significantly down-regulated oncomirs miR-19a and -19b in a variety of lung neoplastic cells. GSE also increased mRNA and protein levels of insulin-like growth factor II receptor (IGF-2R) and phosphatase and tensin homolog (PTEN), both predicted targets of miR-19a and -19b. Furthermore, GSE significantly increased PTEN activity and decreased AKT phosphorylation in A549 cells. Transfection of miR-19a and -19b mimics reversed the up-regulations of IGF2R and PTEN gene expression and abrogated the GSE induced anti-proliferative response. Additionally, oral administration of leucoselect phytosome, comprised of standardized grape seed oligomeric procyanidins complexed with soy phospholipids, to athymic nude mice via gavage, significantly down-regulated miR-19a, -19b and the miR-17-92 cluster host gene (MIR17HG) expressions, increased IGF-2R, PTEN, decreased phosphorylated-AKT in A549 xenograft tumors, and markedly inhibited tumor growth. To confirm the absorption of orally administered GSE, plasma procyanidin B1 levels, between 60 and 90 min after gavage of leucoselect phytosome (400 mg/kg), were measured by LC/MS at week 2 and 8 of treatment; the estimated concentration that was associated with 50% growth inhibition (IC50) (1.3 μg/mL) in vitro was much higher than the IC50 (0.032-0.13 μg/ml) observed in vivo. Our findings reveal novel antineoplastic mechanisms by GSE and support the clinical translation of leucoselect phytosome as an anti-neoplastic and chemopreventive agent for lung cancer. Published by Elsevier Inc.

Ameliorative Effect of Gallic Acid on Cyclophosphamide-Induced Oxidative Injury and Hepatic Dysfunction in Rats

PubMed Central

Olayinka, Ebenezer Tunde; Ore, Ayokanmi; Ola, Olaniyi Solomon; Adeyemo, Oluwatobi Adewumi

2015-01-01

Cyclophosphamide (CP), a bifunctional alkylating agent used in chemotherapy has been reported to induce organ toxicity mediated by generation of reactive oxygen species and oxidative stress. Gallic acid (GA), a phenolic substance, is a natural antioxidant with proven free radical scavenging activity and offers protection against oxidative damage. This research study was designed to investigate the ameliorative effect of GA against CP-induced toxicity in rats. Twenty-five male Wistar rats (180–200 g) were randomized into five treatment groups: (A) control, (B) CP, 2 mg/kg body weight (b.w.), (C) pre-treatment with GA (20 mg/kg b.w.) for seven days followed by CP (2 mg/kg b.w.) for seven days, (D) co-treatment with GA (20 mg/kg b.w) and CP (2 mg/kg b.w.) for seven days, and (E) GA (20 mg/kg b.w.) for seven days. CP induced marked renal and hepatic damages as plasma levels of urea, creatinine, bilirubin and activities of AST, ALT, ALP and GGT were significantly elevated (p < 0.05) in the CP-treated group relative to control. In addition, hepatic levels of GSH, vitamin C and activities of SOD, catalase and GST significantly reduced in the CP-treated group when compared with control. This was accompanied with a significant increase in hepatic lipid peroxidation. The restoration of the markers of renal and hepatic damages as well as antioxidant indices and lipid peroxidation by pre- and co-treatment with GA clearly shows that GA offers ameliorative effect by scavenging the reactive oxygen species generated by CP. This protective effect may be attributed to the antioxidant property of gllic acid. PMID:29083393

Human Parvovirus B19 Utilizes Cellular DNA Replication Machinery for Viral DNA Replication.

PubMed

Zou, Wei; Wang, Zekun; Xiong, Min; Chen, Aaron Yun; Xu, Peng; Ganaie, Safder S; Badawi, Yomna; Kleiboeker, Steve; Nishimune, Hiroshi; Ye, Shui Qing; Qiu, Jianming

2018-03-01

Human parvovirus B19 (B19V) infection of human erythroid progenitor cells (EPCs) induces a DNA damage response and cell cycle arrest at late S phase, which facilitates viral DNA replication. However, it is not clear exactly which cellular factors are employed by this single-stranded DNA virus. Here, we used microarrays to systematically analyze the dynamic transcriptome of EPCs infected with B19V. We found that DNA metabolism, DNA replication, DNA repair, DNA damage response, cell cycle, and cell cycle arrest pathways were significantly regulated after B19V infection. Confocal microscopy analyses revealed that most cellular DNA replication proteins were recruited to the centers of viral DNA replication, but not the DNA repair DNA polymerases. Our results suggest that DNA replication polymerase δ and polymerase α are responsible for B19V DNA replication by knocking down its expression in EPCs. We further showed that although RPA32 is essential for B19V DNA replication and the phosphorylated forms of RPA32 colocalized with the replicating viral genomes, RPA32 phosphorylation was not necessary for B19V DNA replication. Thus, this report provides evidence that B19V uses the cellular DNA replication machinery for viral DNA replication. IMPORTANCE Human parvovirus B19 (B19V) infection can cause transient aplastic crisis, persistent viremia, and pure red cell aplasia. In fetuses, B19V infection can result in nonimmune hydrops fetalis and fetal death. These clinical manifestations of B19V infection are a direct outcome of the death of human erythroid progenitors that host B19V replication. B19V infection induces a DNA damage response that is important for cell cycle arrest at late S phase. Here, we analyzed dynamic changes in cellular gene expression and found that DNA metabolic processes are tightly regulated during B19V infection. Although genes involved in cellular DNA replication were downregulated overall, the cellular DNA replication machinery was tightly

HIV and Hepatitis B

MedlinePlus

... AIDS Drugs Clinical Trials Apps skip to content HIV and Opportunistic Infections, Coinfections, and Conditions Home Understanding ... 4 p.m. ET) Send us an email HIV and Hepatitis B Last Reviewed: July 24, 2017 ...

Acute hepatitis A, B and C but not D is still prevalent in Mongolia: a time trend analysis.

PubMed

Baatarkhuu, Oidov; Lee, Hye Won; George, Jacob; Munkh-Orshikh, Dashchirev; Enkhtuvshin, Baasankhuu; Ariunaa, Sosorbaram; Eslam, Mohammed; Ahn, Sang Hoon; Han, Kwang-Hyub; Kim, Do Young

2017-06-01

Mongolia has one of the highest hepatitis A, C, B and D infection incidences worldwide. We sought to investigate changes in the proportion of acute viral hepatitis types in Mongolia over the last decade. The cohort comprised 546 consecutive patients clinically diagnosed with acute viral hepatitis from January 2012 to December 2014 in Ulaanbaatar Hospital, Mongolia. A time trend analysis investigating the change in proportion of acute hepatitis A virus, hepatitis C virus (HCV), hepatitis B virus (HBV) and hepatitis delta virus (HDV) infection among the cohort with respect to a previous published study was undertaken. Acute hepatitis A, B and C was diagnosed in 50.9%, 26.2% and 6.0% of the cohort. Notably, 16.8% of the cohort had a dual infection. The etiologies of acute viral hepatitis were varied by age groups. The most common cause of acute viral hepatitis among 2-19 year olds was hepatitis A, HBV and superinfection with HDV among 20-40 year olds, and HCV among 40-49 year olds. Patients with more than one hepatitis virus infection were significantly older, more likely to be male and had a higher prevalence of all risk factors for disease acquisition. These patients also had more severe liver disease at presentation compared to those with mono-infection. Acute viral hepatitis is still prevalent in Mongolia. Thus, the need for proper infection control is increasing in this country.

Acute hepatitis A, B and C but not D is still prevalent in Mongolia: a time trend analysis

PubMed Central

Baatarkhuu, Oidov; Lee, Hye Won; George, Jacob; Munkh-Orshikh, Dashchirev; Enkhtuvshin, Baasankhuu; Ariunaa, Sosorbaram; Eslam, Mohammed; Ahn, Sang Hoon; Han, Kwang-Hyub

2017-01-01

Background/Aims Mongolia has one of the highest hepatitis A, C, B and D infection incidences worldwide. We sought to investigate changes in the proportion of acute viral hepatitis types in Mongolia over the last decade. Methods The cohort comprised 546 consecutive patients clinically diagnosed with acute viral hepatitis from January 2012 to December 2014 in Ulaanbaatar Hospital, Mongolia. A time trend analysis investigating the change in proportion of acute hepatitis A virus, hepatitis C virus (HCV), hepatitis B virus (HBV) and hepatitis delta virus (HDV) infection among the cohort with respect to a previous published study was undertaken. Results Acute hepatitis A, B and C was diagnosed in 50.9%, 26.2% and 6.0% of the cohort. Notably, 16.8% of the cohort had a dual infection. The etiologies of acute viral hepatitis were varied by age groups. The most common cause of acute viral hepatitis among 2-19 year olds was hepatitis A, HBV and superinfection with HDV among 20-40 year olds, and HCV among 40-49 year olds. Patients with more than one hepatitis virus infection were significantly older, more likely to be male and had a higher prevalence of all risk factors for disease acquisition. These patients also had more severe liver disease at presentation compared to those with mono-infection. Conclusions Acute viral hepatitis is still prevalent in Mongolia. Thus, the need for proper infection control is increasing in this country. PMID:28535669

Hepatitis B virus-triggered autophagy targets TNFRSF10B/death receptor 5 for degradation to limit TNFSF10/TRAIL response.

PubMed

Shin, Gu-Choul; Kang, Hong Seok; Lee, Ah Ram; Kim, Kyun-Hwan

2016-12-01

Death receptors of TNFSF10/TRAIL (tumor necrosis factor superfamily member 10) contribute to immune surveillance against virus-infected or transformed cells by promoting apoptosis. Many viruses evade antiviral immunity by modulating TNFSF10 receptor signaling, leading to persistent infection. Here, we report that hepatitis B virus (HBV) X protein (HBx) restricts TNFSF10 receptor signaling via macroautophagy/autophagy-mediated degradation of TNFRSF10B/DR5, a TNFSF10 death receptor, and thus permits survival of virus-infected cells. We demonstrate that the expression of the TNFRSF10B protein is dramatically reduced both in liver tissues of chronic hepatitis B patients and in cell lines transfected with HBV or HBx. HBx-mediated downregulation of TNFRSF10B is caused by the lysosomal, but not proteasomal, degradation pathway. Immunoblotting analysis of LC3B and SQSTM1, and microscopy analysis of tandem-fluorescence-tagged LC3B revealed that HBx promotes complete autophagy. Inhibition of autophagy with a pharmacological inhibitor and LC3B knockdown revealed that HBx-induced autophagy is crucial for TNFRSF10B degradation. Immunoprecipitation and GST affinity isolation assays showed that HBx directly interacts with TNFRSF10B and recruits it to phagophores, the precursors to autophagosomes. We confirmed that autophagy activation is related to the downregulation of the TNFRSF10B protein in liver tissues of chronic hepatitis B patients. Inhibition of autophagy enhanced the susceptibility of HBx-infected hepatocytes to TNFSF10. These results identify the dual function of HBx in TNFRSF10B degradation: HBx plays a role as an autophagy receptor-like molecule, which promotes the association of TNFRSF10B with LC3B; HBx is also an autophagy inducer. Our data suggest a molecular mechanism for HBV evasion from TNFSF10-mediated antiviral immunity, which may contribute to chronic HBV infection.

Lysine Acetylation of CREBH Regulates Fasting-Induced Hepatic Lipid Metabolism

PubMed Central

Kim, Hyunbae; Mendez, Roberto; Chen, Xuequn; Fang, Deyu

2015-01-01

Cyclic AMP-responsive element-binding protein 3-like 3, hepatocyte specific (CREBH), is a hepatic transcription factor that functions as a key regulator of energy homeostasis. Here, we defined a regulatory CREBH posttranslational modification process, namely, lysine-specific acetylation, and its functional involvement in fasting-induced hepatic lipid metabolism. Fasting induces CREBH acetylation in mouse livers in a time-dependent manner, and this event is critical for CREBH transcriptional activity in regulating hepatic lipid homeostasis. The histone acetyltransferase PCAF-mediated acetylation and the deacetylase sirtuin-1-mediated deacetylation coexist to maintain CREBH acetylation states under fasting conditions. Site-directed mutagenesis and functional analyses revealed that the lysine (K) residue at position 294 (K294) within the bZIP domain of the CREBH protein is the site where fasting-induced acetylation/deacetylation occurs. Introduction of the acetylation-deficient (K294R) or acetylation-mimicking (K294Q) mutation inhibited or enhanced CREBH transcriptional activity, respectively. Importantly, CREBH acetylation at lysine 294 was required for the interaction and synergy between CREBH and peroxisome proliferator-activated receptor α (PPARα) in activating their target genes upon fasting or glucagon stimulation. Introduction of the CREBH lysine 294 mutation in the liver leads to hepatic steatosis and hyperlipidemia in animals under prolonged fasting. In summary, our study reveals a molecular mechanism by which fasting or glucagon stimulation modulates lipid homeostasis through acetylation of CREBH. PMID:26438600

The Management of Hepatitis B in Liver Transplant Recipients.

PubMed

Saab, Sammy; Chen, Ping-Yu; Saab, Clara E; Tong, Myron J

2016-11-01

Liver transplant (LT) is now an established indication for patients with chronic hepatitis B, mainly because of the development and use of hepatitis B immunoglobulin (HBIG) and oral antivirals for prophylaxis. The combination of low-dose HBIG and antivirals has been considered the standard prophylaxis regimen to prevent post-LT recurrence of hepatitis B. The important remaining issues are related to the long-term cost of HBIG and the risk of escape hepatitis B virus (HBV) mutants. Strategies for prevention of HBV after LT are constantly improving. With the availability of new nucleoside/nucleotide analogues, new post-LT strategies also should emerge. Copyright © 2016 Elsevier Inc. All rights reserved.

Protect Your Baby for Life: When a Pregnant Woman Has Hepatitis B

MedlinePlus

... Hepatitis B. Can doctors prevent a baby from getting Hepatitis B? Yes. Babies born to women with Hepatitis B get two shots soon after birth. One is the first dose of the Hepatitis ... prevent the baby from getting Hepatitis B. The shots work best when they ...

[Latest Treatment of Viral Hepatitis--Overcoming Hepatitis C and Reactivation of Hepatitis B].

PubMed

Tanaka, Yasuhito

2016-02-01

Hepatitis B virus (HBV) and hepatitis C virus (HCV), discovered as causative viruses of post-transfusion hepatitis, become persistent infections, leading to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). For HCV, recent IFN-free direct-acting antiviral (DAA) therapies have increased sustained virological response (SVR) rates and reduced adverse events. IFN-based therapies, still the standard of care in Asian countries, are influenced by IL28B genetic variants and the liver fibrosis stage, but the DAA combinations obscure the influence of these factors. These new therapies can eradicate HCV and prevent HCC development. On the other hand, it is difficult to eradicate HBV completely. Although HBV infection can be prevented by vaccination, reactivation of HBV following anti-cancer chemotherapy and immunosuppressive therapy is a well-known complication. HBV reactivation has been reported to be associated with anti-CD20 monoclonal antibody rituximab-containing chemotherapy and TNF-α inhibitor-containing immunosuppressive therapy in HBV-resolved patients. Our prospective observational study revealed that monthly monitoring of HBV DNA was useful for preventing HBV reactivation-related hepatitis among B-cell non-Hodgkin lymphoma patients with resolved HBV infection following rituximab-steroid-chemo, suggesting that preemptive therapy guided by serial HBV DNA monitoring should be recommended. Recently, highly sensitive HBsAg detection by Lumipulse HBsAg-HQ may be useful for several clinical applications. The sensitivity of this assay (5 mIU/mL) was approximately 10-fold higher than Abbott ARCHITECT, but still lower than HBV-DNA assays. The convenient HBsAg-HQ may be useful for detecting occult HBV infection and HBV reactivation in relatively low-risk groups except for those receiving rituximab-steroid-chemo. [

Role of occult hepatitis B virus infection in chronic hepatitis C

PubMed Central

Coppola, Nicola; Onorato, Lorenzo; Pisaturo, Mariantonietta; Macera, Margherita; Sagnelli, Caterina; Martini, Salvatore; Sagnelli, Evangelista

2015-01-01

The development of sensitive assays to detect small amounts of hepatitis B virus (HBV) DNA has favored the identification of occult hepatitis B infection (OBI), a virological condition characterized by a low level of HBV replication with detectable levels of HBV DNA in liver tissue but an absence of detectable surface antigen of HBV (HBsAg) in serum. The gold standard to diagnose OBI is the detection of HBV DNA in the hepatocytes by highly sensitive and specific techniques, a diagnostic procedure requiring liver tissue to be tested and the use of non-standardized non-commercially available techniques. Consequently, in everyday clinical practice, the detection of anti-hepatitis B core antibody (anti-HBc) in serum of HBsAg-negative subjects is used as a surrogate marker to identify patients with OBI. In patients with chronic hepatitis C (CHC), OBI has been identified in nearly one-third of these cases. Considerable data suggest that OBI favors the increase of liver damage and the development of hepatocellular carcinoma (HCC) in patients with CHC. The data from other studies, however, indicate no influence of OBI on the natural history of CHC, particularly regarding the risk of developing HCC. PMID:26576082

Vitamin E for the treatment of children with hepatitis B e antigen-positive chronic hepatitis: A systematic review and meta-analysis

PubMed Central

Fiorino, Sirio; Bacchi-Reggiani, Maria Letizia; Leandri, Paolo; Loggi, Elisabetta; Andreone, Pietro

2017-01-01

AIM To assess vitamin E efficacy, defined as its ability to induce hepatitis B e antigen (HBeAg) seroconversion, in children with HBeAg-positive persistent hepatitis. METHODS In July 2016, we extracted articles published in MEDLINE and the Cochrane Library using the following search terms: “chronic hepatitis B”, “children”, “childhood”, “therapy”, “treatment”, “vitamin E”, “tocopherols”, “tocotrienols”. Only randomized controlled trials (RCTs) published in English language were collected. RESULTS Three RCTs met inclusion criteria and were considered in the present meta-analysis. Overall, 23/122 children in the treatment group underwent HBeAg seroconversion vs 3/74 in the control group (OR = 3.96, 95%CI: 1.18-13.25, P = 0.025). CONCLUSION Although our meta-analysis has several limits, including the very small number of available studies and enrolled children with HBeAg positivity-related hepatitis, it suggests that vitamin E use may enhance the probability to induce HBeAg seroconversion in these patients. Further well designed and adequately sized trials are required to confirm or deny these very preliminary results. PMID:28293383

Adenovirus E1B 19-Kilodalton Protein Modulates Innate Immunity through Apoptotic Mimicry

PubMed Central

Grigera, Fernando; Ucker, David S.; Cook, James L.

2014-01-01

ABSTRACT Cells that undergo apoptosis in response to chemical or physical stimuli repress inflammatory reactions, but cells that undergo nonapoptotic death in response to such stimuli lack this activity. Whether cells dying from viral infection exhibit a cell death-type modulatory effect on inflammatory reactions is unknown. We compared the effects on macrophage inflammatory responses of cells dying an apoptotic or a nonapoptotic death as a result of adenoviral infection. The results were exactly opposite to the predictions from the conventional paradigm. Cells dying by apoptosis induced by infection with an adenovirus type 5 (Ad5) E1B 19-kilodalton (E1B 19K) gene deletion mutant did not repress macrophage NF-κB activation or cytokine responses to proinflammatory stimuli, whereas cells dying a nonapoptotic death from infection with E1B 19K-competent, wild-type Ad5 repressed these macrophage inflammatory responses as well as cells undergoing classical apoptosis in response to chemical injury. The immunorepressive, E1B 19K-related cell death activity depended upon direct contact of the virally infected corpses with responder macrophages. Replacement of the viral E1B 19K gene with the mammalian Bcl-2 gene in cis restored the nonapoptotic, immunorepressive cell death activity of virally infected cells. These results define a novel function of the antiapoptotic, adenoviral E1B 19K protein that may limit local host innate immune inflammation during accumulation of virally infected cells at sites of infection and suggest that E1B 19K-deleted, replicating adenoviral vectors might induce greater inflammatory responses to virally infected cells than E1B 19K-positive vectors, because of the net effect of their loss-of-function mutation. IMPORTANCE We observed that cells dying a nonapoptotic cell death induced by adenovirus infection repressed macrophage proinflammatory responses while cells dying by apoptosis induced by infection with an E1B 19K deletion mutant virus did not

Combined branched-DNA and conventional HBV PCR assays for detection of serum HBV-DNA in hepatitis B e antigen-positive chronic hepatitis B patients.

PubMed

Ozdarendeli, Aykut; Toroman, Zulal Asci; Bulut, Yasemin; Demirbag, Kutbeddin; Kalkan, Ahmet; Ozden, Mehmet; Kilic, Suleyman Sirri

2006-01-01

Monitoring of HBV replication level is very useful for the management of patients with chronic HBV. However, the use of the correct tools to quantify HBV-DNA levels in serum and monitor the replication of HBV is of paramount importance in terms of diagnosis, and antiviral treatment of patients with chronic HBV infection. The aim of this study was to combine the bDNA assay and HBV PCR to improve detection of viremia the patients with HBeAg-positive chronic hepatitis B infection. In this study, 67 HBeAg-positive chronic hepatitis B patients were analyzed to determine viremia level using bDNA and HBV PCR assays. Sixty-four patients with HBeAg-positive chronic hepatitis B showed positivity by conventional HBV PCR, whereas 56 subjects with HBeAg-positive chronic hepatitis B showed HBV-DNA levels by bDNA. The results indicated that it is reasonable to use the bDNA assay to determine HBV replicative activity first, and use conventional HBV-PCR for HBeAg-positive chronic hepatitis B patient samples that are negative in bDNA assay.

Prophylaxis Among Hepatitis B Core Antibody-positive Deceased-donor Liver Transplant Recipients: Hepatitis B Immunoglobulin Plus Oral Antiviral Agents Versus Antiviral Agents Alone: A Single-center Experience.

PubMed

Malik, Mohammad U; Ucbilek, Enver; Trilianos, Panagiotis; Cameron, Andrew M; Gurakar, Ahmet

2017-04-01

Hepatitis B core antibody immunoglobulin G seropositivity is evidence of past exposure to hepatitis B virus. Donor or recipient hepatitis B core antibody positivity may pose a risk of reactivation, especially early after liver transplant. Although most centers advocate using antiviral agents plus hepatitis B immunoglobulin, some have recently relied on antivirals only as prophylaxis after liver transplant. Here, we retrospectively investigated patient survival in hepatitis B core antibody-positive recipients, comparing those treated with antivirals plus hepatitis B immunoglobulin versus antivirals alone. After Internal Review Board approval, we reviewed medical records of deceased-donor liver transplant recipients between 1995 and 2013. Demographic characteristics, transplant indication, hepatitis B core antibody status, time to death, and type of posttransplant prophylaxis were recorded. We also recorded whether donors showed hepatitis B core antibody positivity. Patients who died within 30 days of liver transplant were excluded. There were 148 hepatitis B core antibody-positive recipients. Prophylaxis was given to 75 recipients after transplant: 8 (5%) received hepatitis B immunoglobulin, 22 (15%) received antivirals, and 45 (30%) received the combination. There were 34 deaths: 3 (38%) in hepatitis B immunoglobulin only, 3 (14%) in antiviral only, 8 (18%) in the combination, and 20 (27%) in no prophylaxis groups. One- and 5-year survival rates were similar for binary comparisons among prophylaxis groups (P > .05). Preliminary results support the current practice of using hepatitis B immunoglobulin plus antivirals for prophylaxis after liver transplant. The similar survival benefit with the combination versus antiviral agents alone suggests equal effectivity for prophylaxis posttransplant. However, a clear benefit of antivirals was not evident in our analysis. Future larger prospective studies are warranted to identify potential benefits of using antivirals alone

The extrahepatic manifestations of hepatitis B virus.

PubMed

Baig, Saeeda; Alamgir, Mohiuddin

2008-07-01

Hepatitis B Virus (HBV) leads to a number of hepatic complications, from acute to chronic hepatitis, cirrhosis and hepatocellular carcinoma, is a well-established fact. Upcoming clinical research, over the years, associates numerous extrahepatic manifestations during the acute and chronic episodes of hepatitis B with significant morbidity and mortality. A causal relationship between HBV and serious autoimmune disorders has also been observed among certain susceptible vaccine recipients in a defined temporal period following immunization. The cause of these extrahepatic manifestations is generally believed to be immune mediated. The most commonly described include skin rash, arthritis, arthralgia, glomerulonephritis, polyarteritis nodosa, and papular acrodermatitis etc. The serum-sickness like "arthritis-dermatitis" prodrome has also been observed in approximately one-third of patients acquiring HBV infections. Skin manifestations of HBV infection typically present as palpable purpura reported to be caused by chronic HBV, although this association remains controversial. To consider the relationship between HBV and other clinically significant disorders as well as serious autoimmune disorders among certain vaccine recipients is the topic of this review. Variable factors that influence extrahepatic manifestation are discussed, including possible synergy between hepatitis B virus and the immune system.

A population-based prevalence study of hepatitis A, B and C virus using oral fluid in Flanders, Belgium.

PubMed

Quoilin, Sophie; Hutse, Veronik; Vandenberghe, Hans; Claeys, Françoise; Verhaegen, Els; De Cock, Liesbet; Van Loock, Frank; Top, Geert; Van Damme, Pierre; Vranckx, Robert; Van Oyen, Herman

2007-01-01

Ten years after the first seroprevalence study performed in Flanders, the aim of this cross sectional study was to follow the evolution of hepatitis A, B and C prevalence. The prevalence of hepatitis A antibodies, hepatitis B surface antigen and hepatitis C antibodies was measured in oral fluid samples collected by postal survey. Using the National Population Register, an incremental sampling plan was developed to obtain a representative sampling of the general population. A total of 24,000 persons were selected and 6,000 persons among them contacted in a first wave. With 1834 participants a response rate of 30.6% was achieved. The prevalence was weighted for age and was 20.2% (95% CI 19.43-21.08) for hepatitis A, 0.66% (95% CI 0.51-0.84) for hepatitis B surface antigen and 0.12% (95% CI 0.09-0.39) for hepatitis C. The prevalence of hepatitis A and C in the Flemish population is lower in 2003 compared with the results of the study performed in 1993. The difference may be due to a real decrease of the diseases but also to differences in the methodology. The prevalence of hepatitis B surface antigen remains stable. Considering the 30% response rate and the high quality of the self-collected samples as reflect of a good participation of the general population, saliva test for prevalence study is a good epidemiological monitoring tool.

Impact of liver steatosis on response to pegylated interferon therapy in patients with chronic hepatitis B

PubMed Central

Ateş, Fehmi; Yalnız, Mehmet; Alan, Saadet

2011-01-01

AIM: To evaluate the impact of liver steatosis upon response to given therapy in chronic hepatitis B (CHB) patients. METHODS: 84 consecutive CHB patients treated with 48-wk PEGylated interferon (PEG-IFN) therapy were enrolled. Baseline characteristics and sustained viral response (SVR) to PEG-IFN therapy were evaluated. RESULTS: Mean body mass index (BMI) was 27.36 ± 4.4 kg/m2. Six (7.1%) had hypertension and three (3.5%) had diabetes mellitus. Steatosis was present in 22.6% (19/84) of liver biopsy samples. Age, BMI, and triglyceride levels of the patients with hepatic steatosis were significantly higher than those without hepatic steatosis (P < 0.05). SVR to PEG-IFN therapy was 21.4% (18/84). Sixteen of these 18 CHB patients with SVR (88.9%) did not have any histopathologically determined steatosis. On the other hand, only two of the 19 CHB patients with hepatic steatosis had SVR (10.5%). Although the SVR rate observed in patients without steatosis (16/65, 24.6%) was higher compared to those with steatosis (2/19, 10.5%), the difference was not statistically significant (P > 0.05). CONCLUSION: Occurrence of hepatic steatosis is significantly high in CHB patients and this association leads to a trend of decreased, but statistically insignificant, SVR rates to PEG-IFN treatment. PMID:22110283

Hepatitis B vaccination for injection drug users--Pierce County, Washington, 2000.

PubMed

2001-05-18

Hepatitis B vaccination has been recommended for injection drug users (IDUs) since 1982, but vaccination coverage of IDUs remains low (1), and outbreaks of hepatitis B among IDUs continue to occur. An outbreak of hepatitis B primarily among IDUs in Pierce County, Washington, detected in April 2000, included 60 cases and resulted in three deaths among IDUs co-infected with hepatitis delta virus. A program to administer hepatitis B vaccine to IDUs was implemented to control the outbreak, and the number of cases identified decreased from 13 per month in May to two cases since November. This report describes a vaccination program during which IDUs accepted hepatitis B vaccination provided free of charge in community-based settings and illustrates how effective hepatitis B vaccination programs targeted at IDUs can be implemented through collaborations between departments of health and corrections and community organizations.

Genotyping of occult hepatitis B virus infection in Egyptian hemodialysis patients without hepatitis C virus infection.

PubMed

Esmail, Mona A; Mahdi, Wafaa K M; Khairy, Rasha M; Abdalla, Nilly H

2016-01-01

Occult hepatitis B viral infection is the presence of hepatitis B viral nucleic acids in the serum and/or liver in the absence of hepatitis B surface antigen. The study aimed to determine the prevalence of occult hepatitis B virus infection among hepatitis C virus-negative hemodialysis patients and to identify their genotypes. of 144 patients on maintenance hemodialysis, 50 hepatitis B surface antigen and hepatitis C virus nucleic acid-negative patients were selected according to strict inclusion criteria to avoid the effect of confounding variables. The following investigations were done: serum AST and ALT; HBsAg; HBcAb; HCV-Ab; HCV-RNA; and HBV-DNA. Positive hepatitis B viral nucleic acid was confirmed in 12/144 (8.3%) hemodialysis patients and 12/50 (24%) in our study group (occult infection). Mean hemodialysis periods for negative patients and occult hepatitis B virus patients were 27.3±18.8 and 38.4±8.14 months, respectively, and this difference was significant (p-value=0.02). Mean alanine transaminase levels were 20.27±5.5IU/L and 25.3±9.6 in negative patients and occult infection patients, respectively. This difference was non-significant. Aspartate transaminase levels were 21.4±10.2IU/L and 27.3±4.6IU/L, respectively, in negative patients and infected patients; this difference was significant (p-value=0.03). Half (6/12) of the positive samples belonged to genotype 'B', 33.3% (4/12) to 'C', and 16.6% (2/12) to genotype 'D'. OBI is likely among hemodialysis patients even without HCV coinfection (24%). Genotype D cannot be the only genotype distributed in Upper Egypt, as the current study reported relatively new results that 50% of the patients with occult B carry genotype B, 33.3% carry genotype C and only 16.6% carry genotype D. Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Hepatitis B Virus Induces IL-23 Production in Antigen Presenting Cells and Causes Liver Damage via the IL-23/IL-17 Axis

PubMed Central

Tian, Zhiqiang; Tang, Jun; Zheng, Yanhua; Huang, Zemin; Tian, Yi; Jia, Zhengcai; Tang, Yan; van Velkinburgh, Jennifer C.; Mao, Qing; Bian, Xiuwu; Ping, Yifang; Ni, Bing; Wu, Yuzhang

2013-01-01

IL-23 regulates myriad processes in the innate and adaptive immune systems, and is a critical mediator of the proinflammatory effects exerted by Th17 cells in many diseases. In this study, we investigated whether and how hepatitis B virus (HBV) causes liver damage directly through the IL-23 signaling pathway. In biopsied liver tissues from HBV-infected patients, expression of both IL-23 and IL-23R was remarkably elevated. In vivo observations also indicated that the main sources of IL-23 were myeloid dendritic cells (mDCs) and macrophages. Analysis of in vitro differentiated immature DCs and macrophages isolated from healthy donors revealed that the HBV surface antigen (HBsAg) efficiently induces IL-23 secretion in a mannose receptor (MR)-dependent manner. Culture with an endosomal acidification inhibitor and the dynamin inhibitor showed that, upon binding to the MR, the HBsAg is taken up by mDCs and macrophages through an endocytosis mechanism. In contrast, although the HBV core antigen (HBcAg) can also stimulate IL-23 secretion from mDCs, the process was MR- and endocytosis-independent. In addition, IL-23 was shown to be indispensible for HBsAg-stimulated differentiation of naïve CD4+ T cells into Th17 cells, which were determined to be the primary source of IL-17 in HBV-infected livers. The cognate receptor, IL-17R, was found to exist on the hepatic stellate cells and mDCs, both of which might represent the potential target cells of IL-17 in hepatitis B disease. These data provide novel insights into a yet unrecognized mechanism of HBV-induced hepatitis, by which increases in IL-23 expression, through an MR/endocytosis-dependent or -independent manner, produce liver damage through the IL-23/IL-17 axis. PMID:23825942

Sulfamoylbenzamide Derivatives Inhibit the Assembly of Hepatitis B Virus Nucleocapsids

PubMed Central

Campagna, Matthew R.; Liu, Fei; Mao, Richeng; Mills, Courtney; Cai, Dawei; Guo, Fang; Zhao, Xuesen; Ye, Hong; Cuconati, Andrea; Guo, Haitao; Chang, Jinhong; Xu, Xiaodong; Block, Timothy M.

2013-01-01

Chronic hepatitis B virus (HBV) infection, a serious public health problem leading to cirrhosis and hepatocellular carcinoma, is currently treated with either pegylated alpha interferon (pegIFN-α) or one of the five nucleos(t)ide analogue viral DNA polymerase inhibitors. However, neither pegIFN-α nor nucleos(t)ide analogues are capable of reliably curing the viral infection. In order to develop novel antiviral drugs against HBV, we established a cell-based screening assay by using an immortalized mouse hepatocyte-derived stable cell line supporting a high level of HBV replication in a tetracycline-inducible manner. Screening of a library consisting of 26,900 small molecules led to the discovery of a series of sulfamoylbenzamide (SBA) derivatives that significantly reduced the amount of cytoplasmic HBV DNA. Structure-activity relationship studies have thus far identified a group of fluorine-substituted SBAs with submicromolar antiviral activity against HBV in human hepatoma cells. Mechanistic analyses reveal that the compounds dose dependently inhibit the formation of pregenomic RNA (pgRNA)-containing nucleocapsids of HBV but not other animal hepadnaviruses, such as woodchuck hepatitis virus (WHV) and duck hepatitis B virus (DHBV). Moreover, heterologous genetic complementation studies of capsid protein, DNA polymerase, and pgRNA between HBV and WHV suggest that HBV capsid protein confers sensitivity to the SBAs. In summary, SBAs represent a novel chemical entity with superior activity and a unique antiviral mechanism and are thus warranted for further development as novel antiviral therapeutics for the treatment of chronic hepatitis B. PMID:23576513

Epidemiology of hepatitis D in patients infected with hepatitis B virus in bucharest: a cross-sectional study.

PubMed

Popescu, G A; Otelea, D; Gavriliu, L C; Neaga, E; Popescu, C; Paraschiv, S; Fratila, M

2013-05-01

Epidemiological analyses indicate a decreasing level of hepatitis D (HDV) infections in most developed countries during the last 15 years. Romania, however, is one of the European countries that still has high morbidity from HDV; this study was performed in order to estimate the HDV prevalence in the Bucharest area. Three thousand four hundred sixty-one hepatitis B (HBV) infected patients were invited to participate and 1,094 were recruited. Serum anti-HDV IgG was detected in 223 patients indicating a hepatitis D seroprevalence of 20.4% (95% CI = 18.1-22.9) in patients chronically infected with HBV, less than that seen in previous studies. Seroprevalence was not gender related, but patients over 40 years were more likely to have anti-HDV antibodies, RR = 1.9 (1.2; 3.0). Detectable hepatitis D viraemia was found in 67.7% of the patients who were positive for anti-HDV. The HDV genotype was characterized for 40 isolates; all were very similar and belonged to genotype 1. Serum HBV-DNA was detectable less frequently in patients positive for anti-HDV than in patients infected with HBV alone: 68.5% versus 89.3%, OR 3.9 (1.7; 10.0), but the extent of this HDV replicative dominance varies with the sensitivity of the HBV-DNA detection. 19.3% of the subjects who tested positive for anti-HDV IgG had a HBV-DNA level higher than four logs. This high prevalence prompts the need for better HBV vaccination coverage and measures to prevent super infection with HDV in patients infected with HBV. Copyright © 2013 Wiley Periodicals, Inc.

Characteristics of an outpatient chronic hepatitis B virus infection cohort

PubMed Central

de Assis, Danyenne Rejane; Tenore, Simone de Barros; Pinho, João Renato Rebello; Lewi, David Salomão; Ferreira, Paulo Roberto Abrão

2015-01-01

ABSTRACT Objective: To characterize a chronic hepatitis B cohort based on initial and follow-up clinical evaluations. Methods: A retrospective and descriptive analysis of clinical and laboratory data from chronic HBsAg adult carriers, without HIV, unexposed to treatment, with at least two outpatient visits, between February 2006 and November 2012. Fisher´s exact test, χ², Wilcoxon, Spearman, multiple comparisons and Kappa tests were applied, the level of significance adopted was 5%, with a 95% confidence interval. Results: 175 patients with mean age of 42.95±12.53 years were included: 93 (53.1%) were men, 152 (86.9%) were negative for hepatitis B e-antigen (HBeAg), 3 (1.7%) had hepatitis C coinfection, 15 (8.6%) had cirrhosis, and 2 (1.1%) had hepatocellular carcinoma. Genotype A predominated. Sixty-six patients (37.7%) had active hepatitis, 6 (3.4%) presented immune tolerance, and 38 (21.7%) were inactive carriers. Exacerbations and/or viral breakthrough were detected in 16 patients (9.1%). In 32 patients (18.3%), hepatitis B virus DNA remained persistently elevated and alanine aminotransferase levels were normal, whereas in 17 (9.7%), there was low hepatitis B virus DNA and alterated alanine aminotransferase. If only initial alanine aminotransferase and hepatitis B virus DNA values were considered, 15 cases of active hepatitis would not have been detected. Advanced fibrosis was more common in HBeAg-positive patients, and it was significantly associated with transaminases, hepatitis B virus DNA, and age. Conclusion: Many patients had active hepatitis, but almost 25%, who were HBeAg non-reactive, were only identified because of combined analyses of the hepatitis B virus DNA and transaminases levels, sometimes associated with histological data, after clinical follow-up. PMID:26154539

Prevalence and influencing factors of hepatitis B among a rural residential population in Zhejiang Province, China: a cross-sectional study.

PubMed

Yang, Shigui; Ding, Cheng; Cui, Yuanxia; Wu, Jie; Yu, Chengbo; Chen, Ping; Xu, Kaijin; Deng, Min; Li, Yiping; Liu, Juanjuan; Yin, Pei; Ren, Wen; Qiu, Yan; Cao, Qing; Zhou, Yuqing; Yao, Jun; Ruan, Bing; Ren, Jingjing; Li, Lanjuan

2017-04-03

To reveal the prevalence and associated influencing factors of hepatitis B among a rural residential population in Zhejiang, China, in order to help develop specific control strategies. We conducted a cross-sectional study among a rural residential population in Zhejiang, China. Stratified multistage cluster sampling was utilised in five districts; a structured questionnaire was used to collect the information such as age, gender, education, occupation, living status, and other health related information of the participants by trained local staff; and the hepatitis B virus (HBV) infection status of the participants was determined by the chemiluminescence immunoassay test. Univariate and multivariate analyses were applied to evaluate the influencing factors of HBV infection. The odds ratio of each related factor was assessed with or without adjustment separately. The mean age of the 16 601 participants (7881 males and 8720 females) who completed the survey was 40.28±19.47 years. The positive rate of hepatitis B surface antigen (HBsAg) was 4.04% (95% CI 3.74% to 4.35%), and 3.85% when standardised by age and gender. Univariate analysis showed that age, educational level, occupation, living status, history of hepatitis B examinations, history of blood transfusion, vaccination, family history, coastal living, and district were the potential influencing factors. Multivariate logistic regression indicated that occupation, living status, history of hepatitis B examinations, vaccination and district were the influencing factors. Undertaking a service-based tertiary industry job (OR a 1.19, 95% CI 0.94 to 1.51) and non-single living (OR a 2.84, 95% CI 2.17 to 3.70) might be risk factors, while vaccination (OR a 0.43, 95% CI 0.34 to 0.53) and history of hepatitis B examinations (OR a 0.71, 95% CI 0.48 to 1.03) were potential protective factors. The prevalence of hepatitis B is at an intermediate epidemic level in a rural residential population in Zhejiang, China

Valproate induced hepatic steatosis by enhanced fatty acid uptake and triglyceride synthesis.

PubMed

Bai, Xupeng; Hong, Weipeng; Cai, Peiheng; Chen, Yibei; Xu, Chuncao; Cao, Di; Yu, Weibang; Zhao, Zhongxiang; Huang, Min; Jin, Jing

2017-06-01

Steatosis is the characteristic type of VPA-induced hepatotoxicity and may result in life-threatening hepatic lesion. Approximately 61% of patients treated with VPA have been diagnosed with hepatic steatosis through ultrasound examination. However, the mechanisms underlying VPA-induced intracellular fat accumulation are not yet fully understood. Here we demonstrated the involvement of fatty acid uptake and lipogenesis in VPA-induced hepatic steatosis in vitro and in vivo by using quantitative real-time PCR (qRT-PCR) analysis, western blotting analysis, fatty acid uptake assays, Nile Red staining assays, and Oil Red O staining assays. Specifically, we found that the expression of cluster of differentiation 36 (CD36), an important fatty acid transport, and diacylglycerol acyltransferase 2 (DGAT2) were significantly up-regulated in HepG2 cells and livers of C57B/6J mice after treatment with VPA. Furthermore, VPA treatment remarkably enhanced the efficiency of fatty acid uptake mediated by CD36, while this effect was abolished by the interference with CD36-specific siRNA. Also, VPA treatment significantly increased DGAT2 expression as a result of the inhibition of mitogen-activated protein kinase kinase (MEK) - extracellular regulated kinase (ERK) pathway; however, DGAT2 knockdown significantly alleviated VPA-induced intracellular lipid accumulation. Additionally, we also found that sterol regulatory element binding protein-1c (SREBP-1c)-mediated fatty acid synthesis may be not involved in VPA-induced hepatic steatosis. Overall, VPA-triggered over-regulation of CD36 and DGAT2 could be helpful for a better understanding of the mechanisms underlying VPA-induced hepatic steatosis and may offer novel therapeutic strategies to combat VPA-induced hepatotoxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

Dentistry and the Issue of Hepatitis B.

DTIC Science & Technology

1980-06-07

Handpieces Relative to Transmission of Hepatitis B Virus. Journal of the American Dental Association. Vol. 96, April 1978, p. 621. 21. Survey of 23 Dental ...7 AD-A" 609 ARMY INST OF DENTAL RESEARCH WASHINGTON DC F/B /5 DENTISTRY AND THE ISSUE OF HEPATITIS B.(U) UNLS .. RM 6U 0 W 0 SHIELDS NmNCASSFIE i...ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT. PROJECT, TASK USLAzmy Institute of Dental Research S Washington. DC 20012 _____________ LI S Army

Hepatitis B virus surface antigen (HBsAg)-positive and HBsAg-negative hepatitis B virus infection among mother-teenager pairs 13 years after neonatal hepatitis B virus vaccination.

PubMed

Yao, Qing-Qing; Dong, Xiao-Lian; Wang, Xue-Cai; Ge, Sheng-Xiang; Hu, An-Qun; Liu, Hai-Yan; Wang, Yueping Alex; Yuan, Quan; Zheng, Ying-Jie

2013-02-01

It is unclear whether a mother who is negative for hepatitis B virus surface antigen (HBsAg) but positive for hepatitis B virus (HBV) is at potential risk for mother-to-child transmission of HBV. This study, using a paired mother-teenager population, aimed to assess whether maternal HBsAg-negative HBV infection ((hn)HBI) is a significant source of child HBV infection (HBI). A follow-up study with blood collection has been conducted on the 93 mother-teenager pairs from the initial 135 pregnant woman-newborn pairs 13 years after neonatal HBV vaccination. Serological and viral markers of HBV have been tested, and phylogenetic analysis of HBV isolates has been done. The HBI prevalence was 1.9% (1 (hn)HBI/53) for teenage children of non-HBI mothers, compared with 16.7% (1 (hn)HBI/6) for those of (hn)HBI mothers and 2.9% (1 HBsAg-positive HBV infection [(hp)HBI]/34) for those of (hp)HBI mothers. Similar viral sequences have been found in one pair of whom both the mother and teenager have had (hn)HBI. In comparison with the (hp)HBI cases, those with (hn)HBI had a lower level of HBV load and a higher proportion of genotype-C strains, which were accompanied by differentiated mutations (Q129R, K141E, and Y161N) of the "a" determinant of the HBV surface gene. Our findings suggest that mother-to-teenager transmission of (hn)HBI can occur among those in the neonatal HBV vaccination program.

Hepatitis B Virus Surface Antigen (HBsAg)-Positive and HBsAg-Negative Hepatitis B Virus Infection among Mother-Teenager Pairs 13 Years after Neonatal Hepatitis B Virus Vaccination

PubMed Central

Yao, Qing-Qing; Dong, Xiao-Lian; Wang, Xue-Cai; Ge, Sheng-Xiang; Hu, An-Qun; Liu, Hai-Yan; Wang, Yueping Alex

2013-01-01

It is unclear whether a mother who is negative for hepatitis B virus surface antigen (HBsAg) but positive for hepatitis B virus (HBV) is at potential risk for mother-to-child transmission of HBV. This study, using a paired mother-teenager population, aimed to assess whether maternal HBsAg-negative HBV infection (hnHBI) is a significant source of child HBV infection (HBI). A follow-up study with blood collection has been conducted on the 93 mother-teenager pairs from the initial 135 pregnant woman-newborn pairs 13 years after neonatal HBV vaccination. Serological and viral markers of HBV have been tested, and phylogenetic analysis of HBV isolates has been done. The HBI prevalence was 1.9% (1 hnHBI/53) for teenage children of non-HBI mothers, compared with 16.7% (1 hnHBI/6) for those of hnHBI mothers and 2.9% (1 HBsAg-positive HBV infection [hpHBI]/34) for those of hpHBI mothers. Similar viral sequences have been found in one pair of whom both the mother and teenager have had hnHBI. In comparison with the hpHBI cases, those with hnHBI had a lower level of HBV load and a higher proportion of genotype-C strains, which were accompanied by differentiated mutations (Q129R, K141E, and Y161N) of the “a” determinant of the HBV surface gene. Our findings suggest that mother-to-teenager transmission of hnHBI can occur among those in the neonatal HBV vaccination program. PMID:23254298

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.

Prevalence and risk factors of hepatitis B in Spanish prostitutes.

PubMed Central

Requena Caballero, L.; Requena Caballero, C.; Requena Caballero, I.; Sánchez López, M.; Vázquez López, F.; Romero Guerrero, J.; Casado Jiménez, M.

1987-01-01

Eighty prostitutes were tested by solid-phase radioimmunoassay for serum markers of hepatitis B virus (HBV). Of 8 (10%) with hepatitis B surface antigen (HBsAg), 6 (75%) also had hepatitis Be antigen (HBeAg). Antibodies to HBsAg (anti-HBs) and to hepatitis B core antigen (anti-HBc) were found in 52 (65%). Antibodies to HBeAg (anti-HBe) were positive in 32 (40%). Anti-HBc alone was found in 5 (6%) and anti-HBs alone in 2 (2%). Sixty-seven (84%) were positive for at least one HBV marker and 13 (16%) were still susceptible to infection. Hepatitis B markers were more prevalent in prostitutes than in the normal Spanish population. Age, a history of sexually transmitted diseases (STD), drug abuse and promiscuity are factors which were highly related to hepatitis B markers. We concluded that screening prostitutes for the presence of markers and vaccinating those who are negative would be worth while. PMID:3428379

Impact of the Hepatitis Testing and Linkage to Care (HepTLC) Initiative on Linkage to Care for Minnesota Refugees with Hepatitis B, 2012-2014.

PubMed

Linde, Ann C; Sweet, Kristin A; Nelson, Kailey; Mamo, Blain; Chute, Sara M

2016-01-01

The Hepatitis Testing and Linkage to Care (HepTLC) initiative promoted viral hepatitis B and hepatitis C screening, posttest counseling, and linkage to care at 34 U.S. sites from 2012 to 2014. Through the HepTLC initiative, the Minnesota Department of Health (MDH) and clinic partners began conducting linkage-to-care activities with hepatitis B-positive refugees in October 2012. This intervention provided culturally appropriate support to link refugees to follow-up care for hepatitis B. MDH refugee health and viral hepatitis surveillance programs, along with clinics that screened newly arrived refugees in Hennepin and Ramsey counties in Minnesota, collaborated on the project, which took place from October 1, 2012, through September 30, 2014. Bilingual care navigators contacted refugees to provide education, make appointments, and arrange transportation. We compared the linkage-to-care rate for participants with the rates for refugees screened the year before project launch using a two-sample test of proportions. In the year preceding the project (October 2011 through September 2012), 87 newly arrived refugees had a positive hepatitis B surface antigen (HBsAg) test. Fifty-six (64%) refugees received follow-up care, 12 (14%) refugees did not receive follow-up care, and 19 (22%) refugees could not be located and had no record of follow-up care. During the project, 174 HBsAg-positive, newly arrived refugees were screened. Of those 174 refugees, 162 (93%) received follow-up care, seven (4%) did not receive follow-up care, and five (3%) could not be located and had no record of follow-up care. The one-year linkage-to-care rate for project participants (93%) was significantly higher than the rate for refugees screened the previous year (64%) (p<0.001). In the context of a strong screening and surveillance infrastructure, a simple intervention improved the linkage-to-care rate for HBsAg-positive refugees.

ALLYLISOPROPYLACETAMIDE INDUCES RAT HEPATIC ORNITHINE DECARBOXYLASE

EPA Science Inventory

In rat liver, allylisopropylacetamide (AIA) treatment strongly induced (25-fold) the activity of rat hepatic ornithine decarboxylase (ODC). y either the oral or the subcutaneous routes, AIA produced a long-lasting induction (30 to 4O hours) of hepatic ODC activity. hree analogs o...

Hepatic Differentiation of Human Induced Pluripotent Stem Cells in a Perfused Three-Dimensional Multicompartment Bioreactor.

PubMed

Freyer, Nora; Knöspel, Fanny; Strahl, Nadja; Amini, Leila; Schrade, Petra; Bachmann, Sebastian; Damm, Georg; Seehofer, Daniel; Jacobs, Frank; Monshouwer, Mario; Zeilinger, Katrin

2016-01-01

The hepatic differentiation of human induced pluripotent stem cells (hiPSC) holds great potential for application in regenerative medicine, pharmacological drug screening, and toxicity testing. However, full maturation of hiPSC into functional hepatocytes has not yet been achieved. In this study, we investigated the potential of a dynamic three-dimensional (3D) hollow fiber membrane bioreactor technology to improve the hepatic differentiation of hiPSC in comparison to static two-dimensional (2D) cultures. A total of 100 × 10(6) hiPSC were seeded into each 3D bioreactor (n = 3). Differentiation into definitive endoderm (DE) was induced by adding activin A, Wnt3a, and sodium butyrate to the culture medium. For further maturation, hepatocyte growth factor and oncostatin M were added. The same differentiation protocol was applied to hiPSC maintained in 2D cultures. Secretion of alpha-fetoprotein (AFP), a marker for DE, was significantly (p < 0.05) higher in 2D cultures, while secretion of albumin, a typical characteristic for mature hepatocytes, was higher after hepatic differentiation of hiPSC in 3D bioreactors. Functional analysis of multiple cytochrome P450 (CYP) isoenzymes showed activity of CYP1A2, CYP2B6, and CYP3A4 in both groups, although at a lower level compared to primary human hepatocytes (PHH). CYP2B6 activities were significantly (p < 0.05) higher in 3D bioreactors compared with 2D cultures, which is in line with results from gene expression. Immunofluorescence staining showed that the majority of cells was positive for albumin, cytokeratin 18 (CK18), and hepatocyte nuclear factor 4-alpha (HNF4A) at the end of the differentiation process. In addition, cytokeratin 19 (CK19) staining revealed the formation of bile duct-like structures in 3D bioreactors similar to native liver tissue. The results indicate a better maturation of hiPSC in the 3D bioreactor system compared to 2D cultures and emphasize the potential of dynamic 3D culture systems

Hepatic Differentiation of Human Induced Pluripotent Stem Cells in a Perfused Three-Dimensional Multicompartment Bioreactor

PubMed Central

Freyer, Nora; Knöspel, Fanny; Strahl, Nadja; Amini, Leila; Schrade, Petra; Bachmann, Sebastian; Damm, Georg; Seehofer, Daniel; Jacobs, Frank; Monshouwer, Mario; Zeilinger, Katrin

2016-01-01

Abstract The hepatic differentiation of human induced pluripotent stem cells (hiPSC) holds great potential for application in regenerative medicine, pharmacological drug screening, and toxicity testing. However, full maturation of hiPSC into functional hepatocytes has not yet been achieved. In this study, we investigated the potential of a dynamic three-dimensional (3D) hollow fiber membrane bioreactor technology to improve the hepatic differentiation of hiPSC in comparison to static two-dimensional (2D) cultures. A total of 100 × 106 hiPSC were seeded into each 3D bioreactor (n = 3). Differentiation into definitive endoderm (DE) was induced by adding activin A, Wnt3a, and sodium butyrate to the culture medium. For further maturation, hepatocyte growth factor and oncostatin M were added. The same differentiation protocol was applied to hiPSC maintained in 2D cultures. Secretion of alpha-fetoprotein (AFP), a marker for DE, was significantly (p < 0.05) higher in 2D cultures, while secretion of albumin, a typical characteristic for mature hepatocytes, was higher after hepatic differentiation of hiPSC in 3D bioreactors. Functional analysis of multiple cytochrome P450 (CYP) isoenzymes showed activity of CYP1A2, CYP2B6, and CYP3A4 in both groups, although at a lower level compared to primary human hepatocytes (PHH). CYP2B6 activities were significantly (p < 0.05) higher in 3D bioreactors compared with 2D cultures, which is in line with results from gene expression. Immunofluorescence staining showed that the majority of cells was positive for albumin, cytokeratin 18 (CK18), and hepatocyte nuclear factor 4-alpha (HNF4A) at the end of the differentiation process. In addition, cytokeratin 19 (CK19) staining revealed the formation of bile duct-like structures in 3D bioreactors similar to native liver tissue. The results indicate a better maturation of hiPSC in the 3D bioreactor system compared to 2D cultures and emphasize the potential of dynamic 3D culture

No Definite Association between Human Parvovirus B19 Infection and Behçet Disease

PubMed Central

Habibagahi, Mojtaba; Habibagahi, Zahra; Saidmardani, Said-Mostafa; Sadeghian, Faezeh

2015-01-01

Background: The etiology of the Behçet disease (BD) has remained obscured. There have been studies to show the association of BD to infections like herpes simplex, hepatitis, and parvovirus B19 however, the findings are rather controversial. Materials and Methods: We selected 55 patients with the best matched symptoms of BD and measured the loads of B19 DNA in their plasma by quantitative real time PCR and verified their seropositivity by ELISA. All findings were compared to the results from 42 healthy persons. Results: Patients showed a wide spectrum of BD symptoms. Serologic studies showed high prevalence of B19 IgG among the tested patients which was not statistically different with the healthy population (72.7% vs. 85.7%, respectively). Similarly, the prevalence of B19 IgM between patients and controls was not different (18% vs. 11.9%, respectively). No correlation was found between the presence of anti-B19 antibodies and the clinical observations. Only one person from the patient and control groups had detectable levels of B19 DNA without any difference or correlation with the disease symptoms. Conclusion: Our data could not establish an association between B19 parvovirus infection and Behçet disease, although there have been reports of such correlation. Nevertheless, there might be indirect relation in genetically susceptible individuals after viral infections. More studies on designed animal models and surveys on patients should be done to resolve this controversy. PMID:26538777

No Definite Association between Human Parvovirus B19 Infection and Behçet Disease.

PubMed

Habibagahi, Mojtaba; Habibagahi, Zahra; Saidmardani, Said-Mostafa; Sadeghian, Faezeh

2015-11-01

The etiology of the Behçet disease (BD) has remained obscured. There have been studies to show the association of BD to infections like herpes simplex, hepatitis, and parvovirus B19 however, the findings are rather controversial. We selected 55 patients with the best matched symptoms of BD and measured the loads of B19 DNA in their plasma by quantitative real time PCR and verified their seropositivity by ELISA. All findings were compared to the results from 42 healthy persons. Patients showed a wide spectrum of BD symptoms. Serologic studies showed high prevalence of B19 IgG among the tested patients which was not statistically different with the healthy population (72.7% vs. 85.7%, respectively). Similarly, the prevalence of B19 IgM between patients and controls was not different (18% vs. 11.9%, respectively). No correlation was found between the presence of anti-B19 antibodies and the clinical observations. Only one person from the patient and control groups had detectable levels of B19 DNA without any difference or correlation with the disease symptoms. Our data could not establish an association between B19 parvovirus infection and Behçet disease, although there have been reports of such correlation. Nevertheless, there might be indirect relation in genetically susceptible individuals after viral infections. More studies on designed animal models and surveys on patients should be done to resolve this controversy.

Hepatitis E virus as an etiology of acute exacerbation of previously unrecognized asymptomatic patients with hepatitis B virus-related chronic liver disease.

PubMed

Kumar, Manoj; Sharma, Barjesh C; Sarin, Shiv K

2008-06-01

Hepatitis E virus (HEV) has recently been implicated in episodes of acute decompensation in patients having underlying chronic liver disease (CLD) of varying etiology. However, HEV as a cause of acute exacerbation of previously asymptomatic and unrecognized hepatitis B virus (HBV)-infected patients is less well described. The aim of the present study was to investigate the etiology of acute exacerbation of previously asymptomatic and unrecognized HBV-infected patients and to evaluate the relative role of HEV. We also investigated the effect of superinfection on the clinical spectrum of underlying HBV infection. Forty-three patients presented with the following were retrospectively analyzed: (i) clinical features suggestive of acute hepatitis; (ii) with hepatitis B surface antigen (HBsAg) (+); (iii) IgM hepatitis B core antibody (IgM anti-HBc) (-); (iv) no previous history of liver disease; (v) no features suggestive of CLD at presentation; (vi) HBsAg remaining (+) for at least 12 months on follow up; and (vii) having a follow-up biopsy during the convalescent phase showing evidence of chronic hepatitis B. Of the 43 patients, 21 were hepatitis e antigen (HBeAg) (+) (Gr.1) and 22 HBeAg (-) (Gr.2) at presentation. In Gr.1, only two (9.5%) had superinfection (both with hepatitis A virus), whereas in Gr.2, 11 (50%) had superinfection (27.3% hepatitis E, 13.6% hepatitis A and 9.1% both) (P = 0.007). In Gr.1, the remaining 19 (90.5%) patients had spontaneous exacerbation (immune clearance with spontaneous seroconversion) whereas in Gr.2, the remaining 11 (50%) had spontaneous exacerbation (due to reactivation). Overall, HEV superinfection contributed to 20% of acute exacerbation episodes and, in particular, 36% of episodes in initially HBeAg (-) patients. Time to alanine aminotransferase normalization was longer in patients with superinfection (n = 13) as compared to spontaneous exacerbation (n = 30) (median [range] 36 [8-48]vs 16 [6-36] weeks, P = 0.001). During

High prevalence of occult hepatitis B virus genotype H infection among children with clinical hepatitis in west Mexico

PubMed Central

Escobedo-Melendez, Griselda; Panduro, Arturo; Fierro, Nora A; Roman, Sonia

2014-01-01

Studies on the prevalence of infection with hepatitis B virus (HBV) among children are scarce in Latin American countries, especially in Mexico. This study was aimed to investigate the prevalence of HBV infection, occult hepatitis B infection (OBI) and HBV genotypes among children with clinical hepatitis. In total, 215 children with clinical hepatitis were evaluated for HBV infection. HBV serological markers and HBV DNA were analysed. OBI diagnosis and HBV genotyping was performed. HBV infection was found in 11.2% of children with clinical hepatitis. Among these HBV DNA positive-infected children, OBI was identified in 87.5% (n = 21/24) of the cases and 12.5% (n = 3/24) were positive for both HBV DNA and hepatitis B surface antigen. OBI was more frequent among children who had not been vaccinated against hepatitis B (p < 0.05) than in those who had been vaccinated. HBV genotype H was prevalent in 71% of the children followed by genotype G (8%) and genotype A (4%). In conclusion, OBI is common among Mexican children with clinical hepatitis and is associated with HBV genotype H. The results show the importance of the molecular diagnosis of HBV infection in Mexican paediatric patients with clinical hepatitis and emphasise the necessity of reinforcing hepatitis B vaccination in children. PMID:25099333

Primary Seronegative but Molecularly Evident Hepadnaviral Infection Engages Liver and Induces Hepatocarcinoma in the Woodchuck Model of Hepatitis B

PubMed Central

Mulrooney-Cousins, Patricia M.; Chauhan, Ranjit; Churchill, Norma D.; Michalak, Tomasz I.

2014-01-01

Hepadnavirus at very low doses establishes in woodchucks asymptomatic, serologically undetectable but molecularly evident persistent infection. This primary occult infection (POI) preferentially engages the immune system and initiates virus-specific T cell response in the absence of antiviral antibody induction. The current study aimed to determine whether POI with time may culminate in serologically identifiable infection and hepatitis, and what are, if any, its pathological consequences. Juvenile woodchucks were intravenously injected with inocula containing 10 or 100 virions of woodchuck hepatitis virus (WHV) to induce POI and followed for life or up to 5.5 years thereafter. All 10 animals established molecularly detectable infection with virus DNA in serum (<100–200 copies/mL) and in circulating lymphoid cells, but serum WHV surface antigen and antibodies to WHV core antigen remained undetectable for life. By approximately 2.5–3.5 years post-infection, circulating virus transiently increased to 103 copies/mL and virus replication became detectable in the livers, but serological markers of infection and biochemical or histological evidence of hepatitis remained undetectable. Nonetheless, typical hepatocellular carcinoma (HCC) developed in 2/10 animals. WHV DNA integration into hepatic and lymphatic system genomes was identified in 9/10 animals. Virus recovered from the liver virus-negative or virus-positive phases of POI displayed the wild-type sequence and transmitted infection to healthy woodchucks causing hepatitis and HCC. In summary, for the first time, our data demonstrate that an asymptomatic hepadnaviral persistence initiated by very small amounts of otherwise pathogenic virus, advancing in the absence of traditional serological markers of infection and hepatitis, coincides with virus DNA integration into the host's hepatic and immune system genomes, retains liver pro-oncogenic potency and is capable of transmitting liver pathogenic infection. This

Hepatitis A and B superimposed on chronic liver disease: vaccine-preventable diseases.

PubMed

Keeffe, Emmet B

2006-01-01

A number of studies have demonstrated that the acquisition of hepatitis A or hepatitis B in patients with chronic liver disease is associated with high rates of morbidity and mortality. Superimposition of acute hepatitis A in patients with chronic hepatitis C has been associated with a particularly high mortality rate, and chronic hepatitis B virus coinfection with hepatitis C virus is associated with an accelerated progression of chronic liver disease to cirrhosis, decompensated liver disease and hepatocellular carcinoma. With the availability of vaccines against hepatitis B and hepatitis A since 1981 and 1995, respectively, these are vaccine-preventable diseases. Studies have confirmed that hepatitis A and hepatitis B vaccines are safe and immunogenic in patients with mild to moderate chronic liver disease. However, hepatitis A and B vaccination is less effective in patients with advanced liver disease and after liver transplantation. These observations have led to the recommendation that patients undergo hepatitis A and B vaccination early in the natural history of their chronic liver disease. Vaccination rates are low in clinical practice, and public health and educational programs are needed to overcome barriers to facilitate timely implementation of these recommendations.

Hepatitis A and B Superimposed on Chronic Liver Disease: Vaccine-Preventable Diseases

PubMed Central

Keeffe, Emmet B

2006-01-01

A number of studies have demonstrated that the acquisition of hepatitis A or hepatitis B in patients with chronic liver disease is associated with high rates of morbidity and mortality. Superimposition of acute hepatitis A in patients with chronic hepatitis C has been associated with a particularly high mortality rate, and chronic hepatitis B virus coinfection with hepatitis C virus is associated with an accelerated progression of chronic liver disease to cirrhosis, decompensated liver disease and hepatocellular carcinoma. With the availability of vaccines against hepatitis B and hepatitis A since 1981 and 1995, respectively, these are vaccine-preventable diseases. Studies have confirmed that hepatitis A and hepatitis B vaccines are safe and immunogenic in patients with mild to moderate chronic liver disease. However, hepatitis A and B vaccination is less effective in patients with advanced liver disease and after liver transplantation. These observations have led to the recommendation that patients undergo hepatitis A and B vaccination early in the natural history of their chronic liver disease. Vaccination rates are low in clinical practice, and public health and educational programs are needed to overcome barriers to facilitate timely implementation of these recommendations. PMID:18528476

An oral vaccine based on U-Omp19 induces protection against B. abortus mucosal challenge by inducing an adaptive IL-17 immune response in mice.

PubMed

Pasquevich, Karina A; Ibañez, Andrés E; Coria, Lorena M; García Samartino, Clara; Estein, Silvia M; Zwerdling, Astrid; Barrionuevo, Paula; Oliveira, Fernanda S; Seither, Christine; Warzecha, Heribert; Oliveira, Sergio C; Giambartolomei, Guillermo H; Cassataro, Juliana

2011-01-14

As Brucella infections occur mainly through mucosal surfaces, the development of mucosal administered vaccines could be radical for the control of brucellosis. In this work we evaluated the potential of Brucella abortus 19 kDa outer membrane protein (U-Omp19) as an edible subunit vaccine against brucellosis. We investigated the protective immune response elicited against oral B. abortus infection after vaccination of mice with leaves from transgenic plants expressing U-Omp19; or with plant-made or E. coli-made purified U-Omp19. All tested U-Omp19 formulations induced protection against Brucella when orally administered without the need of adjuvants. U-Omp19 also induced protection against a systemic challenge when parenterally administered. This built-in adjuvant ability of U-Omp19 was independent of TLR4 and could be explained at least in part by its capability to activate dendritic cells in vivo. While unadjuvanted U-Omp19 intraperitoneally administered induced a specific Th1 response, following U-Omp19 oral delivery a mixed specific Th1-Th17 response was induced. Depletion of CD4(+) T cells in mice orally vaccinated with U-Omp19 resulted in a loss of the elicited protection, indicating that this cell type mediates immune protection. The role of IL-17 against Brucella infection has never been explored. In this study, we determined that if IL-17A was neutralized in vivo during the challenge period, the mucosal U-Omp19 vaccine did not confer mucosal protection. On the contrary, IL-17A neutralization during the infection did not influence at all the subsistence and growth of this bacterium in PBS-immunized mice. All together, our results indicate that an oral unadjuvanted vaccine based on U-Omp19 induces protection against a mucosal challenge with Brucella abortus by inducing an adaptive IL-17 immune response. They also indicate different and important new aspects i) IL-17 does not contribute to reduce the bacterial burden in non vaccinated mice and ii) IL-17 plays

Activation of the Farnesoid X Receptor Induces Hepatic Expression and Secretion of Fibroblast Growth Factor 21*

PubMed Central

Cyphert, Holly A.; Ge, Xuemei; Kohan, Alison B.; Salati, Lisa M.; Zhang, Yanqiao; Hillgartner, F. Bradley

2012-01-01

Previous studies have shown that starvation or consumption of a high fat, low carbohydrate (HF-LC) ketogenic diet induces hepatic fibroblast growth factor 21 (FGF21) gene expression in part by activating the peroxisome proliferator-activated receptor-α (PPARα). Using primary hepatocyte cultures to screen for endogenous signals that mediate the nutritional regulation of FGF21 expression, we identified two sources of PPARα activators (i.e. nonesterified unsaturated fatty acids and chylomicron remnants) that induced FGF21 gene expression. In addition, we discovered that natural (i.e. bile acids) and synthetic (i.e. GW4064) activators of the farnesoid X receptor (FXR) increased FGF21 gene expression and secretion. The effects of bile acids were additive with the effects of nonesterified unsaturated fatty acids in regulating FGF21 expression. FXR activation of FGF21 gene transcription was mediated by an FXR/retinoid X receptor binding site in the 5′-flanking region of the FGF21 gene. FGF19, a gut hormone whose expression and secretion is induced by intestinal bile acids, also increased hepatic FGF21 secretion. Deletion of FXR in mice suppressed the ability of an HF-LC ketogenic diet to induce hepatic FGF21 gene expression. The results of this study identify FXR as a new signaling pathway activating FGF21 expression and provide evidence that FXR activators work in combination with PPARα activators to mediate the stimulatory effect of an HF-LC ketogenic diet on FGF21 expression. We propose that the enhanced enterohepatic flux of bile acids during HF-LC consumption leads to activation of hepatic FXR and FGF19 signaling activity and an increase in FGF21 gene expression and secretion. PMID:22661717

[Financial burden of hepatitis B-related diseases and factors influencing the costs in Shenzhen, China].

PubMed

Liang, Sen; Zhang, Shun-xiang; Ma, Qi-shan; Xiao, He-wei; Lü, Qiu-ying; Xie, Xu; Mei, Shu-jiang; Hu, Dong-sheng; Zhou, Bo-ping; Li, Bing; Chen, Jing-fang; Cui, Fu-qiang; Wang, Fu-zhen; Liang, Xiao-feng

2010-12-01

sum total was 16:1. The proportions of total annual cost per patient with hepatitis B-related diseases accounted for annual patient income were 285.3%, and 75.4% for annual household income. Furthermore, proportions of direct costs accounted for annual patient income and annual household income were 108.1% and 28.6%. The total annual indirect cost per person was 8123.38 Yuan for patients of all hepatitis B-related diseases, while 7134.63 Yuan for caregivers. Corresponding work-loss days were 55.74 days for patients and 19.83 days for caregivers. Based on multiple linear stepwise regression analysis, age of patients was a common influencing factor to all kinds of costs. Other factors were as follows: complicated with other diseases, antiviral medication, monthly household income and self-medications. The economic burden of hepatitis B-related diseases was substantial for patients and their families. All costs tended to increase with the severity of disease. The direct costs were larger than the indirect costs. And the direct medical costs were more than the direct ones. Indirect costs based on patients were larger than the ones of caregivers.

Placental abruption possibly due to parvovirus B19 infection.

PubMed

Kawabe, Ayaka; Takai, Yasushi; Tamaru, Jun-Ichi; Samejima, Kouki; Seki, Hiroyuki

2016-01-01

There is concern about the development of anemia-associated fetal hydrops associated with maternal parvovirus B19 infection. Parvovirus B19 infection occurs via the globoside (P antigen) receptor, the main glycolipid of erythroid cells, which induces apoptosis. Similar findings have been reported for the P antigen of globoside-containing placental trophoblast cells. A 32-year-old woman was infected with human parvovirus B19 at week 32 of pregnancy, and had severe anemia at week 34. At week 37, an emergency cesarean section was performed because of sudden abdominal pain and fetal bradycardia; placental abruption was found. A live male infant was delivered with no sign of fetal hydrops or fetal infection. Placental tissue was positive for parvovirus B19 according to polymerase chain reaction. Immunohistochemical analysis using caspase-related M30 CytoDEATH monoclonal antibody revealed M30 staining of the placental villous trophoblasts. Placental trophoblasts and erythroid precursor cells have been reported to express globoside (P antigen), which is necessary for parvovirus B19 infectivity, and to show apoptotic activity as a result of infection. Placentas from three other pregnancies with documented abruption showed no M30 staining. The present case strongly suggests an association between placental abruption and apoptosis resulting from parvovirus B19 infection.

Trends in mortality burden of hepatocellular carcinoma, cirrhosis, and fulminant hepatitis before and after roll-out of the first pilot vaccination program against hepatitis B in Peru: An analysis of death certificate data.

PubMed

Ramírez-Soto, Max Carlos; Ortega-Cáceres, Gutia; Cabezas, César

2017-07-05

The first pilot vaccination program against hepatitis B in Peru was implemented in the hyperendemic Abancay province in 1991. To assess the impact of vaccination on mortality rates of hepatitis B-related hepatocellular carcinoma (HCC), cirrhosis, and fulminant hepatitis, we compared mortality trends before (1960-1990) and after (1991-2012) roll-out of the vaccination program, using death certificate data from the Municipalidad Provincial de Abancay. Our results showed that, following program roll-out, the overall mortality rates (per 100,000 population) decreased from 9.20 to 3.30 for HCC (95% CI, 1.28-10.48%; P<0.014), from 16.0 to 6.3 for cirrhosis (95% CI, 3.20-16.10%; P<0.004), and from 34.80 to 1.28 for fulminant hepatitis (95% CI, 16.70-50.30%; P<0.001). The absolute number of deaths attributable to cirrhosis (10 [8.80%] vs. 0.0%; P<0.001) and fulminant hepatitis (83 [40.0%] vs. 5 [19.20%]; P<0.026) decreased in 5-14-year-old children following vaccination. These findings showed reduced mortality rates of hepatitis B-related liver diseases, particularly cirrhosis and fulminant hepatitis in children under 15years, following implementation of the vaccination program against hepatitis B. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hepatitis B vaccination status and needlestick injuries among healthcare workers in syria.

PubMed

Yacoub, Rabi; Al Ali, Radwan; Moukeh, Ghamez; Lahdo, Ayham; Mouhammad, Yaser; Nasser, Mahmood

2010-01-01

Although a majority of countries in the Middle East show intermediate or high endemicity of hepatitis B virus (HBV) infection, which clearly poses a serious public health problem in the region, the situation in the Republic of Syria remains unclear. The aim of this study is to determine the hepatitis B vaccination status, to assess the number of vaccinations administered, and to estimate the annual incidence of needlestick injuries (NSIs) among healthcare workers (HCWs) in Aleppo University hospitals. A cross-sectional design with a survey questionnaire was used for exploring details of NSIs during 2008, hepatitis B vaccination status, and HBV infection among a random stratified sample of HCWs in three tertiary hospitals in Aleppo (n = 321). Two hundred and forty-six (76.6%) HCWs had sustained at least one NSI during 2008. Nine (2.8%) had HBV chronic infection and 75 HCWs (23.4%) were never vaccinated. Anesthesiology technicians had the greatest exposure risk when compared to office workers [OR = 16,95% CI (2.55-100), P < 0.01], doctors [OR = 10,95% CI (2.1 47.57), P < 0.01], and nurses [OR = 6.75,95% CI (1.56-29.03), P = 0.01]. HCWs under 25 and between the age of 25 and 35 years were at increased risk for NSI when compared to HCWs older than 45 years [OR = 3.12,95% CI (1.19-8.19), P = 0.02] and [OR = 3.05,95% CI (1.42-6.57), P < 0.01], respectively. HCWs at Aleppo University hospitals are frequently exposed to blood-borne infections. Precautions and protection from NSIs are important in preventing infection of HCWs. Education about the transmission of blood-borne infections, vaccination, and post-exposure prophylaxis must be implemented and strictly monitored.

Hepatitis B Vaccination Status and Needlestick Injuries Among Healthcare Workers in Syria

PubMed Central

Yacoub, Rabi; Al Ali, Radwan; Moukeh, Ghamez; Lahdo, Ayham; Mouhammad, Yaser; Nasser, Mahmood

2010-01-01

Background: Although a majority of countries in the Middle East show intermediate or high endemicity of hepatitis B virus (HBV) infection, which clearly poses a serious public health problem in the region, the situation in the Republic of Syria remains unclear. The aim of this study is to determine the hepatitis B vaccination status, to assess the number of vaccinations administered, and to estimate the annual incidence of needlestick injuries (NSIs) among healthcare workers (HCWs) in Aleppo University hospitals. Materials and Methods: A cross-sectional design with a survey questionnaire was used for exploring details of NSIs during 2008, hepatitis B vaccination status, and HBV infection among a random stratified sample of HCWs in three tertiary hospitals in Aleppo (n = 321). Results: Two hundred and forty-six (76.6%) HCWs had sustained at least one NSI during 2008. Nine (2.8%) had HBV chronic infection and 75 HCWs (23.4%) were never vaccinated. Anesthesiology technicians had the greatest exposure risk when compared to office workers [OR = 16,95% CI (2.55-100), P < 0.01], doctors [OR = 10,95% CI (2.1 47.57), P < 0.01], and nurses [OR = 6.75,95% CI (1.56-29.03), P = 0.01]. HCWs under 25 and between the age of 25 and 35 years were at increased risk for NSI when compared to HCWs older than 45 years [OR = 3.12,95% CI (1.19-8.19), P = 0.02] and [OR = 3.05,95% CI (1.42-6.57), P < 0.01], respectively. Conclusion: HCWs at Aleppo University hospitals are frequently exposed to blood-borne infections. Precautions and protection from NSIs are important in preventing infection of HCWs. Education about the transmission of blood-borne infections, vaccination, and post-exposure prophylaxis must be implemented and strictly monitored. PMID:20300414

Anti-pre-S responses and viral clearance in chronic hepatitis B virus infection.

PubMed

Budkowska, A; Dubreuil, P; Poynard, T; Marcellin, P; Loriot, M A; Maillard, P; Pillot, J

1992-01-01

Serial sera were collected prospectively during the clinical course of 13 HBsAg carriers with chronic liver disease and analyzed for ALT levels, pre-S1 and pre-S2 antigens and corresponding antibodies and other serological hepatitis B virus markers. In five patients, anti-pre-S1 and anti-pre-S2 antibodies became detectable in multiple serum samples, whereas in eight patients anti-pre-S was never detected or only appeared transiently during the follow-up. The first pattern was associated with normalization of ALT levels and undetectable pre-S antigens and viral DNA by the polymerase chain reaction assay at final follow-up. HBsAg clearance occurred in two of the five patients. The second pattern was one of persistence of HBsAg and pre-S antigens, associated with the presence of serum HBV DNA detectable by spot hybridization or polymerase chain reaction regardless of clinical outcome. These findings demonstrate the occurrence of anti-pre-S antibodies in chronic hepatitis B virus-induced liver disease and associate anti-pre-S appearance with the clearance of hepatitis B virus from serum.

Expression of hepatitis B virus 1.3-fold genome plasmid in an SV40 T-antigen-immortalized mouse hepatic cell line

PubMed Central

Song, Xiu-Guang; Bian, Peng-Fei; Yu, Shu-Li; Zhao, Xiu-Hua; Xu, Wei; Bu, Xue-Hui; Li, Xia; Ma, Li-Xian

2013-01-01

AIM: To investigate the expression of the hepatitis B virus (HBV) 1.3-fold genome plasmid (pHBV1.3) in an immortalized mouse hepatic cell line induced by SV40 T-antigen (SV40T) expression. METHODS: Mouse hepatic cells were isolated from mouse liver tissue fragments from 3-5 d old Kunming mice by the direct collagenase digestion method and cultured in vitro. The pRSV-T plasmid was transfected into mouse hepatic cells to establish an SV40LT-immortalized mouse hepatic cell line. The SV40LT-immortalized mouse hepatic cells were identified and transfected with the pHBV1.3 plasmid. The levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in the supernatant were determined by an electrochemiluminescence immunoassay at 24, 48, 72 and 96 h after transfection. The expressions of HBsAg and hepatitis B c antigen (HBcAg) in the cells were investigated by indirect immunofluorescence analysis. The presence of HBV DNA replication intermediates in the transfected cells and viral particles in the supernatant of the transfected cell cultures was monitored using the Southern hybridization assay and transmission electronic microscopy, respectively. RESULTS: The pRSV-T plasmid was used to immortalize mouse hepatocytes and an SV40LT-immortalized mouse hepatic cell line was successfully established. SV40LT-immortalized mouse hepatic cells have the same morphology and growth characteristics as primary mouse hepatic cells can be subcultured and produce albumin and cytokeratin-18 in vitro. Immortalized mouse hepatic cells did not show the characteristics of tumor cells, as alpha-fetoprotein levels were comparable (0.58 ± 0.37 vs 0.61 ± 0.31, P = 0.37). SV40LT-immortalized mouse hepatic cells were then transfected with the pHBV1.3 plasmid, and it was found that the HBV genome replicated in SV40LT-immortalized mouse hepatic cells. The levels of HBsAg and HBeAg continuously increased in the supernatant after the transfection of pHBV1.3, and began to decrease 72 h

Expression of hepatitis B virus 1.3-fold genome plasmid in an SV40 T-antigen-immortalized mouse hepatic cell line.

PubMed

Song, Xiu-Guang; Bian, Peng-Fei; Yu, Shu-Li; Zhao, Xiu-Hua; Xu, Wei; Bu, Xue-Hui; Li, Xia; Ma, Li-Xian

2013-11-28

To investigate the expression of the hepatitis B virus (HBV) 1.3-fold genome plasmid (pHBV1.3) in an immortalized mouse hepatic cell line induced by SV40 T-antigen (SV40T) expression. Mouse hepatic cells were isolated from mouse liver tissue fragments from 3-5 d old Kunming mice by the direct collagenase digestion method and cultured in vitro. The pRSV-T plasmid was transfected into mouse hepatic cells to establish an SV40LT-immortalized mouse hepatic cell line. The SV40LT-immortalized mouse hepatic cells were identified and transfected with the pHBV1.3 plasmid. The levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in the supernatant were determined by an electrochemiluminescence immunoassay at 24, 48, 72 and 96 h after transfection. The expressions of HBsAg and hepatitis B c antigen (HBcAg) in the cells were investigated by indirect immunofluorescence analysis. The presence of HBV DNA replication intermediates in the transfected cells and viral particles in the supernatant of the transfected cell cultures was monitored using the Southern hybridization assay and transmission electronic microscopy, respectively. The pRSV-T plasmid was used to immortalize mouse hepatocytes and an SV40LT-immortalized mouse hepatic cell line was successfully established. SV40LT-immortalized mouse hepatic cells have the same morphology and growth characteristics as primary mouse hepatic cells can be subcultured and produce albumin and cytokeratin-18 in vitro. Immortalized mouse hepatic cells did not show the characteristics of tumor cells, as alpha-fetoprotein levels were comparable (0.58 ± 0.37 vs 0.61 ± 0.31, P = 0.37). SV40LT-immortalized mouse hepatic cells were then transfected with the pHBV1.3 plasmid, and it was found that the HBV genome replicated in SV40LT-immortalized mouse hepatic cells. The levels of HBsAg and HBeAg continuously increased in the supernatant after the transfection of pHBV1.3, and began to decrease 72 h after transfection. The

Hepatitis A and hepatitis B infection prevalence and associated risk factors in men who have sex with men, Bangkok, 2006-2008.

PubMed

Linkins, Robert W; Chonwattana, Wannee; Holtz, Timothy H; Wasinrapee, Punneeporn; Chaikummao, Supaporn; Varangrat, Anchalee; Tongtoyai, Jaray; Mock, Philip A; Curlin, Marcel E; Sirivongrangson, Pachara; van Griensven, Frits; McNicholl, Janet M

2013-09-01

Despite the availability of safe and effective vaccines, little is known about prevalence and risk factors for hepatitis A (HAV) and hepatitis B virus (HBV) infection among Thai men who have sex with men. The prevalence of HAV and HBV infection among men who have sex with men cohort in Bangkok was assessed. Baseline blood specimens were drawn and demographic and behavioral data were collected. Bivariate and multivariate logistic regression analysis was used to analyze risk factors for prevalent HAV and HBV infection. One thousand two hundred ninety-nine Thai men who have sex with men 18 years and older were enrolled. Among those with results, 349/1,291 (27.0%) had evidence of past or current hepatitis A infection. Of the 1,117 (86.5%) men with unambiguous HBV test results, 442 (39.6%) had serologic evidence of past/current infection, 103 (9.2%) were immune due to hepatitis B vaccination, 572 (51.2%) had no evidence of immunological exposure to HBV or vaccine. Of those with past/current HBV infection, 130 (29.4%) were HIV positive. Age >35 years was independently associated with both HAV and HBV infection. University education was protective against both HAV and HBV infection. Increased alcohol consumption, number of lifetime male sexual partners ≥10, and prevalent HIV infection were also independently associated with HBV infection. The prevalence of past/current HAV and HBV infection was high in Bangkok men who have sex with men. Age-cohorts with a higher prevalence of hepatitis B vaccine induced immunity may be expected in the future. Hepatitis A and B vaccination is recommended. © 2013 WILEY PERIODICALS, INC. This is a US Government work, and, as such, is in the public domain in The United States.

Poly-ϵ-caprolactone/chitosan nanoparticles provide strong adjuvant effect for hepatitis B antigen.

PubMed

Jesus, Sandra; Soares, Edna; Borchard, Gerrit; Borges, Olga

2017-10-01

This work aims to investigate the adjuvant effect of poly-ϵ-caprolactone/chitosan nanoparticles (NPs) for hepatitis B surface antigen (HBsAg) and the plasmid DNA encoding HBsAg (pRC/CMV-HBs). Both antigens were adsorbed onto preformed NPs. Vaccination studies were performed in C57BL/6 mice. Transfection efficiency was investigated in A549 cell line. HBsAg-adsorbed NPs generated strong anti-HBsAg IgG titers, mainly of IgG1 isotype, and induced antigen-specific IFN-γ and IL-17 secretion by spleen cells. The addition of pRC/CMV-HBs to the HBsAg-adsorbed NPs inhibited IL-17 secretion but had minor effect on IFN-γ levels. Lastly, pRC/CMV-HBs-loaded NPs generated a weak serum antibody response. Poly-ϵ-caprolactone/chitosan NPs provide a strong humoral adjuvant effect for HBsAg and induce a Th1/Th17-mediated cellular immune responses worth explore for hepatitis B virus vaccination.

Forced Hepatic Overexpression of CEACAM1 Curtails Diet-Induced Insulin Resistance

PubMed Central

Al-Share, Qusai Y.; DeAngelis, Anthony M.; Lester, Sumona Ghosh; Bowman, Thomas A.; Ramakrishnan, Sadeesh K.; Abdallah, Simon L.; Russo, Lucia; Patel, Payal R.; Kaw, Meenakshi K.; Raphael, Christian K.; Kim, Andrea Jung; Heinrich, Garrett; Lee, Abraham D.; Kim, Jason K.; Kulkarni, Rohit N.; Philbrick, William M.

2015-01-01

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) regulates insulin sensitivity by promoting hepatic insulin clearance. Liver-specific inactivation or global null-mutation of Ceacam1 impairs hepatic insulin extraction to cause chronic hyperinsulinemia, resulting in insulin resistance and visceral obesity. In this study we investigated whether diet-induced insulin resistance implicates changes in hepatic CEACAM1. We report that feeding C57/BL6J mice a high-fat diet reduced hepatic CEACAM1 levels by >50% beginning at 21 days, causing hyperinsulinemia, insulin resistance, and elevation in hepatic triacylglycerol content. Conversely, liver-specific inducible CEACAM1 expression prevented hyperinsulinemia and markedly limited insulin resistance and hepatic lipid accumulation that were induced by prolonged high-fat intake. This was partly mediated by increased hepatic β-fatty acid oxidation and energy expenditure. The data demonstrate that the high-fat diet reduced hepatic CEACAM1 expression and that overexpressing CEACAM1 in liver curtailed diet-induced metabolic abnormalities by protecting hepatic insulin clearance. PMID:25972571

Protective Effect of Quercetin on Melphalan-Induced Oxidative Stress and Impaired Renal and Hepatic Functions in Rat

PubMed Central

Ola, Olaniyi Solomon; Adeyemo, Oluwatobi Adewumi

2014-01-01

One major challenge with the use of anticancer agents is the phenomenon of drug-induced toxicity. Melphalan (MPLN) is an alkylating anticancer agent, while quercetin (QCT) is an antioxidant. We investigated the protective role of quercetin against MPLN-induced toxicity. Twenty-five male Wistar rats (160–170 g) were randomized into five treatment groups; (I) control, (II) MPLN (0.2 mg/kg b.w.), (III) pre-treated with QCT (20 mg/kg b.w.) for 7 days followed by MPLN (0.2 mg/kg b.w.) for 7 days, (IV) cotreated with QCT (20 mg/kg b.w.) and MPLN (0.2 mg/kg b.w.) for 7 days, and (V) QCT (20 mg/kg b.w.) alone. MPLN caused a significant increase in plasma bilirubin, urea, and creatinine by 122.2%, 102.3%, and 188%, respectively (P < 0.05). Similarly, plasma ALP, ALT, AST, and γ-GT activities increased significantly by 57.9%, 144.3%, 71.3%, and 307.2%, respectively, relative to control. However, pre or cotreatment with QCT ameliorated the levels of renal and hepatic function indices. Hepatic ascorbic acid and GSH and activities of glutathione-S-transferase, SOD, and catalase decreased significantly by 36.2%, 188%, 46.5%, 34.4%, and 55.2%, respectively, followed by increase in MDA content by 46.5% relative to control. Pre- and cotreatment with QCT reestablished the hepatic antioxidant status and lipid peroxidation. Overall, quercetin protected against MPLN-induced renal and hepatic toxicity in rats. PMID:25574394

Liver transplantation outcomes among Caucasians, Asian Americans, and African Americans with hepatitis B.

PubMed

Bzowej, Natalie; Han, Steven; Degertekin, Bulent; Keeffe, Emmet B; Emre, Sukru; Brown, Robert; Reddy, Rajender; Lok, Anna S

2009-09-01

Several previous studies found that Asians transplanted for hepatitis B virus (HBV) infection had worse post-transplant outcomes than Caucasians. Data on post-transplant outcomes of African Americans and waitlist outcomes of Asian Americans and African Americans with hepatitis B are scant. The aim of this study was to compare waitlist and post-transplant outcomes among Asian Americans, African Americans, and Caucasians who had HBV-related liver disease. Data from a retrospective-prospective study on liver transplantation for HBV infection were analyzed. A total of 274 patients (116 Caucasians, 135 Asians, and 23 African Americans) from 15 centers in the United States were enrolled. African Americans were younger and more Asian Americans had hepatocellular carcinoma (HCC) at the time of liver transplant listing. The probability of undergoing transplantation and the probability of survival on the waitlist were comparable in the 3 racial groups. Of the 170 patients transplanted, 19 died during a median follow-up of 31 months. The probability of post-transplant survival at 5 years was 94% for African Americans, 85% for Asian Americans, and 89% for Caucasians (P = 0.93). HCC recurrence was the only predictor of post-transplant survival, and recurrence rates were similar in the 3 racial groups. Caucasians had a higher rate of HBV recurrence: 4-year recurrence was 19% versus 7% and 6% for Asian Americans and African Americans, respectively (P = 0.043). In conclusion, we found similar waitlist and post-transplant outcomes among Caucasians, Asian Americans, and African Americans with hepatitis B. Our finding of a higher rate of HBV recurrence among Caucasians needs to be validated in other studies. (c) 2009 AASLD.

S-phase arrest after vincristine treatment may promote hepatitis B virus replication

PubMed Central

Xu, Lei; Tu, Zeng; Xu, Ge; Hu, Jie-Li; Cai, Xue-Fei; Zhan, Xing-Xing; Wang, Yu-Wei; Huang, Yuan; Chen, Juan; Huang, Ai-Long

2015-01-01

AIM: To observe the effect of vincristine on hepatitis B virus (HBV) replication in vitro and to study its possible mechanisms. METHODS: Vincristine was added to the cultures of two cell lines stably expressing HBV. Then, the levels of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and hepatitis B core antigen (HBcAg) in the supernatants or cytoplasm were examined using by enzyme-linked immunosorbent assay and Western blot. The HBV pregenome RNA (pgRNA) was detected using reverse transcription-PCR and real-time fluorescent quantitative PCR (RT-qPCR), and viral DNA was detected using Southern blot and RT-qPCR. Cell proliferation after drug treatment was detected using the BrdU incorporation test and the trypan blue exclusion assay. Cell cycle and cell apoptosis were examined using flow cytometry and Western blot. RESULTS: Vincristine up-regulated HBV replication directly in vitro in a dose-dependent manner, and 24-h exposure to 0.1 μmol/L vincristine induced more than 4-fold and 3-fold increases in intracellular HBV DNA and the secretion of viral DNA, respectively. The expression of HBV pgRNA, intracellular HBsAg and HBcAg, and the secretion of HBeAg were also increased significantly after drug treatment. Most importantly, vincristine promoted the cell excretion of HBV nucleocapsids instead of HBV Dane particles, and the nucleocapsids are closely related to the HBV pathogenesis. Furthermore, vincristine inhibited the proliferation of cells stably expressing HBV. The higher the concentration of the drug, the more significant the inhibition of the cell proliferation and the stronger the HBV replication ability in cells. Flow cytometry indicated that cell cycle arrest at S-phase was responsible for the cell proliferation inhibition. CONCLUSION: Vincristine has a strong stimulatory effect on HBV replication and induces cell cycle arrest, and cell proliferation inhibition may be conducive to viral replication. PMID:25663769

[Acute hepatitis A despite regular vaccination against hepatitis A and B].

PubMed

Junge, U; Melching, J; Dziuba, S

2002-07-26

A 59-year-old woman, her 55-year-old husband, their daughter, son and the son's girlfriend were admitted with acute icterus 32-34 days after a dinner when they had eaten shellfish. The father had been immunised against hepatitis A and B with a combined vaccine (Twinrix(R)) and had completed the full vaccination schedule 47 days prior to this meal. His wife had been incompletely vaccinated with one injection 16 days prior and a second injection 13 days after the dinner. The other three participants of the dinner had not been immunised. The incubation time and clinical picture did not differ between the vaccinated and non-vaccinated patients. All 5 patients were anti-HAV IgM-positive, had high serum aminotransferases and serum bilirubin. All patients had an uneventful recovery. There was no difference in the clinical course between the vaccinated and non-vaccinated patients. Combined hepatitis A/B vaccination according to the recommended schedule does not guarantee protection in elderly persons. Before travelling in endemic areas, their antibody response after basic hepatitis A/B vaccination should be determined.

Combating Hepatitis B and C through immunological approach

NASA Astrophysics Data System (ADS)

Nugraha Susilawati, Tri; Setyawan, Sigit; Pramana, T. Y.; Mudigdo, Ambar; Agung Prasetyo, Afiono

2018-05-01

Infections with hepatitis B and C viruses are the main factors contributing to the development of chronic liver disease and have been known as the major global health problems. This paper examines evidence that demonstrates the involvement of host immune responses in hepatitis B and C, particularly in the protection against immune-mediated liver injury. The proposed mechanisms of protection range from T cell responses that facilitate spontaneous resolution during acute infection and prevent persistent infection to immunoregulatory cytokines that inhibit destructive immune responses. Regulatory T cells (Tregs), TGF-β1, IL-4, and IL-10 are the main components of the immune system that play an important role in the protection mechanisms against the detrimental effects of hepatitis B and C viruses in liver tissues. Thus, factors contributing to increased Tregs activity and immunoregulatory cytokines should be elaborated. Recent studies reported factors that facilitate the development of Tregs during hepatitis C viral infection include HCV epitope, expression of miR 146a in monocytes and the Tim-3/Gal-9 pathway. On the other hand, the generation of Tregs is inhibited by IL-6 produced during inflammation. These findings suggest that immunomodulation strategy should be further developed and applied in the management of hepatitis B and C.

Prevalence of hepatitis B and hepatitis C infection in Libya: results from a national population based survey

PubMed Central

2014-01-01

Background Libya is one of the largest countries in Africa and has the longest coast in the Mediterranean basin facing southern Europe. High rates of prevalence of viral hepatitis have been observed in various regions in Africa, but the prevalence in Libya is not well documented. We report on a large-scale nationwide study that evaluated the epidemiology of hepatitis B and hepatitis C in Libya and assessed the risk factors involved. Methods A cross-sectional study was carried out in 2008 on 65,761 individuals all over Libya. The country was divided into 12 regions according to the population density and sampling within each region was carried out under the supervision of the National Centre for Prevention of Infectious Diseases. Serum samples were collected from both males and females of all ages in both urban and rural areas and tested for HBsAg for hepatitis B and anti-HCV antibody for hepatitis C. Prevalence rates were determined in regions and in different groups and correlated with different demographic and risk factors involved in the spread of these viruses. Results The prevalence of hepatitis B and hepatitis C viruses varied regionally across the country. The overall prevalence of hepatitis B was 2.2% (95% CI 2.1%-2.3%) and was higher among males than females (1.4:1.0). Hepatitis C virus (HCV) prevalence was 1.2% (95% CI 1.1-1.3) and it increased gradually after the age of 30 years (0.7-0.9% for < 30 years; 3.6% for ≥ 60 years). Prevalence of HBsAg was 0.8-0.9% below the age of 10 years, and higher but similar in older age groups (2.3-2.7%). There was an association between literacy and prevalence of hepatitis, particularly for HCV. Hospital admission, surgical operation, blood transfusion, and intravenous drug use were the main risk factors, and they were associated independently with a higher prevalence rate of viral hepatitis. Conclusions Libya may be considered an area of low-intermediate endemicity for hepatitis B virus infection, with lower

Prevalence of hepatitis B and hepatitis C infection in Libya: results from a national population based survey.

PubMed

Daw, Mohamed A; El-Bouzedi, Abdallah

2014-01-09

Libya is one of the largest countries in Africa and has the longest coast in the Mediterranean basin facing southern Europe. High rates of prevalence of viral hepatitis have been observed in various regions in Africa, but the prevalence in Libya is not well documented. We report on a large-scale nationwide study that evaluated the epidemiology of hepatitis B and hepatitis C in Libya and assessed the risk factors involved. A cross-sectional study was carried out in 2008 on 65,761 individuals all over Libya. The country was divided into 12 regions according to the population density and sampling within each region was carried out under the supervision of the National Centre for Prevention of Infectious Diseases. Serum samples were collected from both males and females of all ages in both urban and rural areas and tested for HBsAg for hepatitis B and anti-HCV antibody for hepatitis C. Prevalence rates were determined in regions and in different groups and correlated with different demographic and risk factors involved in the spread of these viruses. The prevalence of hepatitis B and hepatitis C viruses varied regionally across the country. The overall prevalence of hepatitis B was 2.2% (95% CI 2.1%-2.3%) and was higher among males than females (1.4:1.0). Hepatitis C virus (HCV) prevalence was 1.2% (95% CI 1.1-1.3) and it increased gradually after the age of 30 years (0.7-0.9% for < 30 years; 3.6% for ≥ 60 years). Prevalence of HBsAg was 0.8-0.9% below the age of 10 years, and higher but similar in older age groups (2.3-2.7%). There was an association between literacy and prevalence of hepatitis, particularly for HCV. Hospital admission, surgical operation, blood transfusion, and intravenous drug use were the main risk factors, and they were associated independently with a higher prevalence rate of viral hepatitis. Libya may be considered an area of low-intermediate endemicity for hepatitis B virus infection, with lower rates in young age groups, and an area of low

Human parvovirus B19-induced anaemia in pre-school children in Ilorin, Nigeria

PubMed Central

Agbede, Olajide O.; Omoare, Adesuyi A.; Ernest, Samuel K.

2018-01-01

Sera collected from 57 anaemic and 115 non-anaemic age-matched pre-school children in Ilorin, Nigeria, between November 2014 and December 2015 were assayed for human parvovirus B19-specific IgM antibodies by using the enzyme linked immunosorbent assay technique. A total of 17 (29.8%) anaemic children and 18 (15.7%) non-anaemic children were positive for parvovirus B19 infection. Infection with parvovirus B19 is common in this population, and screening for the virus during differential diagnosis is recommended. PMID:29850435

Noninvasive scoring system for significant inflammation related to chronic hepatitis B

NASA Astrophysics Data System (ADS)

Hong, Mei-Zhu; Ye, Linglong; Jin, Li-Xin; Ren, Yan-Dan; Yu, Xiao-Fang; Liu, Xiao-Bin; Zhang, Ru-Mian; Fang, Kuangnan; Pan, Jin-Shui

2017-03-01

Although a liver stiffness measurement-based model can precisely predict significant intrahepatic inflammation, transient elastography is not commonly available in a primary care center. Additionally, high body mass index and bilirubinemia have notable effects on the accuracy of transient elastography. The present study aimed to create a noninvasive scoring system for the prediction of intrahepatic inflammatory activity related to chronic hepatitis B, without the aid of transient elastography. A total of 396 patients with chronic hepatitis B were enrolled in the present study. Liver biopsies were performed, liver histology was scored using the Scheuer scoring system, and serum markers and liver function were investigated. Inflammatory activity scoring models were constructed for both hepatitis B envelope antigen (+) and hepatitis B envelope antigen (-) patients. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve were 86.00%, 84.80%, 62.32%, 95.39%, and 0.9219, respectively, in the hepatitis B envelope antigen (+) group and 91.89%, 89.86%, 70.83%, 97.64%, and 0.9691, respectively, in the hepatitis B envelope antigen (-) group. Significant inflammation related to chronic hepatitis B can be predicted with satisfactory accuracy by using our logistic regression-based scoring system.

Hepatitis B and Hepatitis C Infection Biomarkers and TP53 Mutations in Hepatocellular Carcinomas from Colombia

PubMed Central

Navas, Maria-Cristina; Suarez, Iris; Carreño, Andrea; Uribe, Diego; Rios, Wilson Alfredo; Cortes-Mancera, Fabian; Martel, Ghyslaine; Vieco, Beatriz; Lozano, Diana; Jimenez, Carlos; Gouas, Doriane; Osorio, German; Hoyos, Sergio; Restrepo, Juan Carlos; Correa, Gonzalo; Jaramillo, Sergio; Lopez, Rocio; Bravo, Luis Eduardo; Arbelaez, Maria Patricia; Scoazec, Jean-Yves; Abedi-Ardekani, Behnoush; Santella, Regina M.; Chemin, Isabelle; Hainaut, Pierre

2011-01-01

Hepatocellular Carcinoma (HCC) is a leading cause of cancer-related death worldwide. Globally, the most important HCC risk factors are Hepatitis B Virus (HBV) and/or Hepatitis C Virus (HCV), chronic alcoholism, and dietary exposure to aflatoxins. We have described the epidemiological pattern of 202 HCC samples obtained from Colombian patients. Additionally we investigated HBV/HCV infections and TP53 mutations in 49 of these HCC cases. HBV biomarkers were detected in 58.1% of the cases; HBV genotypes F and D were characterized in three of the samples. The HCV biomarker was detected in 37% of the samples while HBV/HCV coinfection was found in 19.2%. Among TP53 mutations, 10.5% occur at the common aflatoxin mutation hotspot, codon 249. No data regarding chronic alcoholism was available from the cases. In conclusion, in this first study of HCC and biomarkers in a Colombian population, the main HCC risk factor was HBV infection. PMID:22114738

The Hepatitis B Virus Ribonuclease H as a Drug Target

PubMed Central

Tavis, John E.; Lomonosova, Elena

2015-01-01

Chronic hepatitis B virus (HBV) infection is a leading cause of hepatitis, liver failure, and hepatocellular carcinoma. An outstanding vaccine is available; however the number of infections remains high. Current anti-HBV treatments with interferon α and nucleos(t)ide analogs clear the infection in only a small minority of patients, and either induce serious side-effects or are of very long duration. HBV is a small, enveloped DNA virus that replicates by reverse transcription via an RNA intermediate. The HBV ribonuclease H (RNaseH) is essential for viral replication, but it has not been exploited as a drug target. Recent low-throughput screening of compound classes with anti-Human Immunodeficiency Virus RNaseH activity led to identification of HBV RNaseH inhibitors in three different chemical families that block HBV replication. These inhibitors are promising candidates for development into new anti-HBV drugs. The RNaseH inhibitors may help improve treatment efficacy enough to clear the virus from the liver when used in combination with existing anti-HBV drugs and/or with other novel inhibitors under development. 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.” PMID:25862291

Possible prevention of chronic hepatitis B by early interferon therapy.

PubMed

Trépo, C; Chemin, I; Petit, M A; Chossegros, P; Zoulim, F; Chevallier, P; Sepetjan, M

1990-01-01

A study is currently underway to investigate the efficacy of interferon therapy in patients with prolonged (greater than or equal to 10 weeks but less than 6 months) hepatitis B infection. To date, a total of 15 patients have been enrolled in the study and randomly assigned to receive either placebo for 24 weeks (n = 8) or interferon 5 million units subcutaneously 3 times a week for 24 weeks (n = 7), with follow up for 1 year. Thirteen patients have completed the follow-up period: seven patients in the placebo group and six in the treated group. Five of the six treated patients completely eradicated the infection during interferon therapy, with clearance of hepatitis B e and surface antigens, and seroconversion to antibody positivity in each case. Two of the eight placebo patients seroconverted during the placebo period. Clearance of hepatitis B e antigen was associated with a sudden rise in serum transaminase levels and an exacerbation of hepatitis, a phenomenon that has also been reported in chronic hepatitis B patients who have responded well to interferon therapy. Therapy was well tolerated in all cases. Our results suggest that interferon treatment of patients with prolonged hepatitis B infection may prevent progression to chronicity. If confirmed by further study, they should trigger more vigilant screening for patients with raised serum transaminase levels and viral markers of hepatitis B infection.

Mangiferin, a Natural Xanthone, Protects Murine Liver in Pb(II) Induced Hepatic Damage and Cell Death via MAP Kinase, NF-κB and Mitochondria Dependent Pathways

PubMed Central

Pal, Pabitra Bikash; Sinha, Krishnendu; Sil, Parames C.

2013-01-01

One of the most well-known naturally occurring environmental heavy metals, lead (Pb) has been reported to cause liver injury and cellular apoptosis by disturbing the prooxidant-antioxidant balance via oxidative stress. Several studies, on the other hand, reported that mangiferin, a naturally occurring xanthone, has been used for a broad range of therapeutic purposes. In the present study, we, therefore, investigated the molecular mechanisms of the protective action of mangiferin against lead-induced hepatic pathophysiology. Lead [Pb(II)] in the form of Pb(NO3)2 (at a dose of 5 mg/kg body weight, 6 days, orally) induced oxidative stress, hepatic dysfunction and cell death in murine liver. Post treatment of mangiferin at a dose of 100 mg/kg body weight (6 days, orally), on the other hand, diminished the formation of reactive oxygen species (ROS) and reduced the levels of serum marker enzymes [alanine aminotranferase (ALT) and alkaline phosphatase (ALP)]. Mangiferin also reduced Pb(II) induced alterations in antioxidant machineries, restored the mitochondrial membrane potential as well as mutual regulation of Bcl-2/Bax. Furthermore, mangiferin inhibited Pb(II)-induced activation of mitogen-activated protein kinases (MAPKs) (phospho-ERK 1/2, phosphor-JNK phospho- p38), nuclear translocation of NF-κB and apoptotic cell death as was evidenced by DNA fragmentation, FACS analysis and histological assessment. In vitro studies using hepatocytes as the working model also showed the protective effect of mangiferin in Pb(II) induced cytotoxicity. All these beneficial effects of mangiferin contributes to the considerable reduction of apoptotic hepatic cell death induced by Pb(II). Overall results demonstrate that mangiferin exhibit both antioxidative and antiapoptotic properties and protects the organ in Pb(II) induced hepatic dysfunction. PMID:23451106

Natural history of chronic hepatitis B virus infection.

PubMed

Busch, Katrin; Thimme, Robert

2015-02-01

Hepatitis B virus infection represents a major global health problem. Currently, there are more than 240 million chronically infected people worldwide. The development of chronic hepatitis B virus-mediated liver disease may lead to liver fibrosis, cirrhosis and eventually hepatocellular carcinoma. Recently, the discovery of the viral entry receptor sodium taurocholate cotransporting polypeptide has facilitated new approaches for a better understanding of viral physiopathology. Hopefully, these novel insights may give rise to the development of more effective antiviral therapy concepts during the next years. In this review, we will discuss the natural history of hepatitis B virus infection including the viral biology, the clinical course of infection and the role of the immune response.

Inhibition of inhibitor of kappaB kinases stimulates hepatic stellate cell apoptosis and accelerated recovery from rat liver fibrosis.

PubMed

Oakley, Fiona; Meso, Muriel; Iredale, John P; Green, Karen; Marek, Carylyn J; Zhou, Xiaoying; May, Michael J; Millward-Sadler, Harry; Wright, Matthew C; Mann, Derek A

2005-01-01

Resolution of liver fibrosis is associated with clearance of hepatic myofibroblasts by apoptosis; development of strategies that promote this process in a selective way is therefore important. The aim of this study was to determine whether the inhibitor of kappaB kinase suppressor sulfasalazine stimulates hepatic myofibroblast apoptosis and recovery from fibrosis. Hepatic myofibroblasts were generated by culture activation of rat and human hepatic stellate cells. Fibrosis was established in rat livers by chronic injury with carbon tetrachloride followed by recovery with or without sulfasalazine (150 mg/kg) treatment. Treatment of hepatic stellate cells with sulfasalazine (0.5-2.0 mmol/L) induced apoptosis of activated rat and human hepatic stellate cells. A single in vivo administration of sulfasalazine promoted accelerated recovery from fibrosis as assessed by improved fibrosis score, selective clearance of smooth muscle alpha-actin-positive myofibroblasts, reduced hepatic procollagen I and tissue inhibitor of metalloproteinase 1 messenger RNA expression, and increased matrix metalloproteinase 2 activity. Mechanistic studies showed that sulfasalazine selectively blocks nuclear factor-kappaB-dependent gene transcription, inhibits hepatic stellate cell expression of Gadd45beta, stimulates phosphorylation of Jun N-terminal kinase 2, and promotes apoptosis by a mechanism that is prevented by the Jun N-terminal kinase inhibitor SP600125. As further evidence for a survival role for the inhibitor of kappaB kinase/nuclear factor-kappaB pathway in activated hepatic stellate cells, a highly selective cell-permeable peptide inhibitor of kappaB kinase activation also stimulated hepatic stellate cell apoptosis via a Jun N-terminal kinase-dependent mechanism. Inhibition of the inhibitor of kappaB kinase/nuclear factor-kappaB pathway is sufficient to increase the rate at which activated hepatic stellate cells undergo apoptosis both in vitro and in vivo, and drugs that

The clinical features of chronic hepatitis C are not affected by the coexistence of hepatitis B virus DNA in patients negative for hepatitis B surface antigen.

PubMed

Nirei, K; Kaneko, M; Moriyama, M; Arakawa, Y

2000-01-01

Hepatitis B virus (HBV) DNA has been detected in the sera of hepatitis patients who are negative for hepatitis B surface antigen (HBsAg) by polymerase chain reaction (PCR). The purpose of the present study was to clarify the clinical characteristics of patients with chronic hepatitis C who are negative for serum HBsAg and positive for HBV DNA. The subjects included 49 patients with chronic hepatitis C who were negative for serum HBsAg and 119 blood donors who served as healthy controls. Serum samples were tested for the presence of HBV DNA by the nested PCR method. Serum HBV DNA was detected in 18 (37.7%) of the 49 chronic hepatitis C patients and in none (0%) of the 119 blood donors. Among the hepatitis C patients, HBV DNA was detected in 20.7% of those who were negative for all HBV-associated markers and in 57.1% of those who were positive for one or more HBV-associated marker. The HBV DNA-positive rate among those in each F stage did not significantly differ. The liver function parameters of the HBV DNA-positive and the HBV DNA-negative chronic hepatitis C patients did not significantly differ. These results suggest that hepatitis C virus is frequently coinfected with serum HBsAg-negative HBV, and that the incidence of HBV infection in blood donors is low. However, it is considered that HBsAg-negative HBV infection does not modify the blood biochemical features of chronic hepatitis C. Copyright 2000 S. Karger AG, Basel

The impact of immigration and vaccination in reducing the incidence of hepatitis B in Catalonia (Spain)

PubMed Central

2012-01-01

Background The Hepatitis B virus (HBV) infection is a major cause of liver disease and liver cancer worldwide according to the World Health Organization. Following acute HBV infection, 1-5% of infected healthy adults and up to 90% of infected infants become chronic carriers and have an increased risk of cirrhosis and primary hepatocellular carcinoma. The aim of this study was to investigate the relationship between the reduction in acute hepatitis B incidence and the universal vaccination programme in preadolescents in Catalonia (Spain), taking population changes into account, and to construct a model to forecast the future incidence of cases that permits the best preventive strategy to be adopted. Methods Reported acute hepatitis B incidence in Catalonia according to age, gender, vaccination coverage, percentage of immigrants and the year of report of cases was analysed. A statistical analysis was made using three models: generalized linear models (GLM) with Poisson or negative binomial distribution and a generalized additive model (GAM). Results The higher the vaccination coverage, the lower the reported incidence of hepatitis B (p <0.01). In groups with vaccination coverage > 70%, the reduction in incidence was 2-fold higher than in groups with a coverage <70% (p <0.01). The increase in incidence was significantly-higher in groups with a high percentage of immigrants and more than 15% (p <0.01) in immigrant males of working age (19-49 years). Conclusions The results of the adjusted models in this study confirm that the global incidence of hepatitis B has declined in Catalonia after the introduction of the universal preadolescent vaccination programme, but the incidence increased in male immigrants of working age. Given the potential severity of hepatitis B for the health of individuals and for the community, universal vaccination programmes should continue and programmes in risk groups, especially immigrants, should be strengthened. PMID:22867276

Impact of the timing of hepatitis B virus identification and anti-hepatitis B virus therapy initiation on the risk of adverse liver outcomes for patients receiving cancer therapy.

PubMed

Hwang, Jessica P; Suarez-Almazor, Maria E; Cantor, Scott B; Barbo, Andrea; Lin, Heather Y; Ahmed, Sairah; Chavez-MacGregor, Mariana; Donato-Santana, Christian; Eng, Cathy; Ferrajoli, Alessandra; Fisch, Michael J; McLaughlin, Peter; Simon, George R; Rondon, Gabriela; Shpall, Elizabeth J; Lok, Anna S

2017-09-01

Data on the incidence of adverse liver outcomes are limited for cancer patients with chronic (hepatitis B surface antigen [HBsAg]-positive/hepatitis B core antibody [anti-HBc]-positive) or past (HBsAg-negative/anti-HBc-positive) hepatitis B virus (HBV) after chemotherapy. This study was aimed at determining the impact of test timing and anti-HBV therapy on adverse liver outcomes in these patients. Patients with solid or hematologic malignancies who received chemotherapy between 2004 and 2011 were retrospectively studied. HBV testing and anti-HBV therapy were defined as early at the initiation of cancer therapy and as late after initiation. Outcomes included hepatitis flares, hepatic impairment, liver failure, and death. Time-to-event analysis was used to determine incidence, and multivariate hazard models were used to determine predictors of outcomes. There were 18,688 study patients (80.4% with solid tumors). The prevalence of chronic HBV was 1.1% (52 of 4905), and the prevalence of past HBV was 7.1% (350 of 4905). Among patients with solid tumors, late identification of chronic HBV was associated with a higher risk of hepatitis flare (hazard ratio [HR], 4.02; 95% confidence interval [CI], 1.26-12.86), hepatic impairment (HR, 8.48; 95% CI, 1.86-38.66), liver failure (HR, 9.38; 95% CI, 1.50-58.86), and death (HR, 3.90; 95% CI, 1.19-12.83) in comparison with early identification. Among patients with hematologic malignancies and chronic HBV, the risk of death was 7.8 (95% CI, 1.73-35.27) times higher for persons with late initiation of anti-HBV therapy versus early initiation. Patients with late identification of chronic HBV had late or no anti-HBV therapy. Chronic HBV predicted liver failure in patients with solid or hematologic malignancies, whereas male sex and late identification were predictors for patients with solid tumors. Early identification correlates with early anti-HBV therapy and reduces the risk of liver failure and death in chronic HBV patients

Seroprevalence of occult hepatitis B among Egyptian paediatric hepatitis C cancer patients.

PubMed

Raouf, H E; Yassin, A S; Megahed, S A; Ashour, M S; Mansour, T M

2015-02-01

Occult hepatitis B infection is characterized by the presence of hepatitis B virus (HBV) DNA in the serum in the absence of hepatitis B surface antigen (HBsAg). Prevalence of hepatitis C virus (HCV) infections in Egypt is among the highest in the world. In this study, we aim at analysing the rates of occult HBV infections among HCV paediatric cancer patients in Egypt. The prevalence of occult HBV was assessed in two groups of paediatric cancer patients (HCV positive and HCV negative), in addition to a third group of paediatric noncancer patients, which was used as a general control. All groups were negative for HBsAg and positive for HCV antibody. HBV DNA was detected by nested PCR and real-time PCR. HCV was detected by real-time PCR. Sequencing was carried out in order to determine HBV genotypes to all HBV patients as well as to detect any mutation that might be responsible for the occult phenotype. Occult hepatitis B infection was observed in neither the non-HCV paediatric cancer patients nor the paediatric noncancer patients but was found in 31% of the HCV-positive paediatric cancer patients. All the detected HBV patients belonged to HBV genotype D, and mutations were found in the surface genome of HBV leading to occult HBV. Occult HBV infection seems to be relatively frequent in HCV-positive paediatric cancer patients, indicating that HBsAg negativity is not sufficient to completely exclude HBV infection. These findings emphasize the importance of considering occult HBV infection in HCV-positive paediatric cancer patients especially in endemic areas as Egypt. © 2014 John Wiley & Sons Ltd.

Community-based prevention of hepatitis-B-related liver cancer: Australian insights

PubMed Central

Kansil, Melanie Q; Porwal, Mamta; Penman, Andrew G; George, Jacob

2014-01-01

Abstract Problem Although most primary hepatocellular cancers (HCCs) are attributable to chronic viral hepatitis and largely preventable, such cancers remain a leading cause of cancer-related mortality wherever chronic hepatitis B is endemic. Approach Many HCCs could be prevented by increasing awareness and knowledge of hepatitis B, optimizing the monitoring of chronic hepatitis B and using antiviral treatments – but there are gaps in the implementation of such strategies. Local setting The “B Positive” programme, based in Sydney, Australia, is designed to improve hepatitis-B-related health outcomes among immigrants from countries with endemic hepatitis B. The programme offers information about disease screening, vaccination and treatment options, as well as optimized access to care. Relevant changes The B Positive programme has been informed by economic modelling. The programme offers culturally tailored education on chronic hepatitis B to target communities and their health practitioners and regular follow-up through a population-based registry of cases. Lessons learnt As the costs of screening for chronic hepatitis B and follow-up are relatively low and less than one in every four cases may require antiviral drugs, optimizing access to treatment seems an appropriate and cost-effective management option. The identification and accurate staging of cases and the judicious use of antiviral medications are predicated upon an informed and educated health workforce. As establishing community trust is a lengthy process, delaying the implementation of programmes against chronic hepatitis B until antiviral drugs become cheaper is unwarranted. PMID:24839327

Mineral metabolism in dimethylnitrosamine-induced hepatic fibrosis.

PubMed

George, Joseph

2006-10-01

Complications such as ascites during the pathogenesis of hepatic fibrosis and cirrhosis may lead to several abnormalities in mineral metabolism. In the present investigation, we have monitored serum and liver concentrations of calcium, magnesium, sodium and potassium during experimentally induced hepatic fibrosis in rats. The liver injury was induced by intraperitoneal injections of dimethylnitrosamine (DMN; N-nitrosodimethylamine, NDMA) in doses 1 mg/100 g body weight on 3 consecutive days of each week over a period of 21 days. Calcium, magnesium, sodium and potassium were measured by atomic absorption spectrophotometry in the serum and liver on days 7, 14 and 21 after the start of DMN administration. Negative correlations were observed between liver function tests and serum mineral levels, except with albumin. Calcium, magnesium, potassium and sodium concentrations in the serum were decreased after the induction of liver injury. The liver calcium content was increased after DMN treatment. No change occurred in liver sodium content. However, magnesium and potassium content was significantly reduced in the hepatic tissue. The results suggest that DMN-induced hepatic fibrosis plays certain role in the alteration of essential elements. The low levels of albumin and the related ascites may be one of the major causes of the imbalance of mineral metabolism in hepatic fibrosis and further aggravation of the disease.

Hepatitis B maternal screening, infant vaccination, and infant prophylaxis practices in North Carolina.

PubMed

Pierce, R L; Smith, S; Rowe-West, B; Sterritt, B

1999-06-01

To determine if the Advisory Committee on Immunization Practices hepatitis B screening, vaccination, and prophylaxis recommendations were being followed in North Carolina, and to establish a baseline hepatitis B seroprevalence rate. A survey of mother and infant birthing facility medical records. Four birthing facilities selected from each of the 7 districts in North Carolina (a total of 28 facilities). A probability proportional to size survey design was used to select 4763 mother-infant record pairs. All records came from the 1996 birth cohort. Maternal hepatitis B screening status, infant vaccination status, infants prophylaxis status, hepatitis B seroprevalence rate, demographic and clinical predictors for maternal infection, failure to receive prenatal care or for whom status was unknown, failure to screen, and failure to vaccinate. Ninety-two percent of pregnant women were screened for hepatitis B surface antigen. Eighty-six percent of infants received dose 1 of the hepatitis B vaccine. Four of the 9 infants with mothers who were hepatitis B surface antigen-positive did not receive both vaccine and hepatitis B immune globulin. The hepatitis B seroprevalence rate was 0.2%. Mothers who were not screened for infection were 3.4 times more likely to have infants who were not vaccinated. White mothers were twice as likely not to have their child vaccinated as mothers of other races. Not all infants with hepatitis B-infected mothers were receiving vaccine and hepatitis B immune globulin as recommended. Seroprevalence of hepatitis B infection may be lower in North Carolina than in other states. Hepatitis B laboratory test results should be included in every mother's medical record.

Methodology of a nationwide cross-sectional survey of prevalence and epidemiological patterns of hepatitis A, B and C infection in Brazil.

PubMed

Ximenes, Ricardo Arraes de Alencar; Pereira, Leila Maria Beltrão; Martelli, Celina Maria Turchi; Merchán-Hamann, Edgar; Stein, Airton Tetelbom; Figueiredo, Gerusa Maria; Braga, Maria Cynthia; Montarroyos, Ulisses Ramos; Brasil, Leila Melo; Turchi, Marília Dalva; Fonseca, José Carlos Ferraz da; Lima, Maria Luiza Carvalho de; Alencar, Luis Cláudio Arraes de; Costa, Marcelo; Coral, Gabriela; Moreira, Regina Celia; Cardoso, Maria Regina Alves

2010-09-01

A population-based survey to provide information on the prevalence of hepatitis viral infection and the pattern of risk factors was carried out in the urban population of all Brazilian state capitals and the Federal District, between 2005 and 2009. This paper describes the design and methodology of the study which involved a population aged 5 to 19 for hepatitis A and 10 to 69 for hepatitis B and C. Interviews and blood samples were obtained through household visits. The sample was selected using stratified multi-stage cluster sampling and was drawn with equal probability from each domain of study (region and age-group). Nationwide, 19,280 households and ~31,000 residents were selected. The study is large enough to detect prevalence of viral infection around 0.1% and risk factor assessments within each region. The methodology seems to be a viable way of differentiating between distinct epidemiological patterns of hepatitis A, B and C. These data will be of value for the evaluation of vaccination policies and for the design of control program strategies.

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

Antibody titers and response to vaccination against hepatitis A and B in pediatric patients with portal hypertension.

PubMed

Rosa, Mariana Nogueira de Paula; Hessel, Gabriel; Alves De Tommaso, Adriana María

2008-09-01

In Brazil, approximately 130 new cases of hepatitis A per 100,000 inhabitants occur annually and 15% of the population has been in contact with hepatitis B virus. Portal hypertension causes hypersplenism and reduces T cell production, which may lead to less effective response to hepatitis vaccination. The objective of the study was to evaluate the response to hepatitis A and B vaccination in patients with portal hypertension secondary to chronic liver disease or portal vein thrombosis. Twenty-three patients (2 to 18 years) with portal hypertension seen at the Pediatric Hepatology Service of Hospital das Clínicas, Universidade Estadual de Campinas, between 1994 and 2006 were studied. Hepatitis A and B serology was tested in all patients. Patients who had not been vaccinated before their visits received the vaccines during the study period. Patients who had been vaccinated before but had negative anti-HB antibodies received a booster dose, and their serology was repeated Blood counts were performed in each patient to assess for immunosuppression. Eighteen patients received hepatitis A vaccine and all became positive for anti-HAV antibodies. All patients had received hepatitis B vaccine and 17 (73.9%) were anti-HBs positive at the time of the study The other 6 received a booster dose and became anti-HBs positive afterward. The anti-HBs-positive and -negative patients did not differ significantly in age, leukocytes, lymphocytes, or duration between the vaccination and positive serology. In this study, hepatitis A vaccines elicited a 100% response and hepatitis B vaccine conferred protection and induced an anamnestic response in pediatric patients with portal hypertension.

[Vaccines against hepatitis A and B in Chile].

PubMed

Valenzuela, M Teresa

2009-06-01

The mode of transmission and epidemiological approach for hepatitis A and B are different. However, both are preventable with vaccines whose efficacy and long lasting protection has been demonstrated. This review describes the secular tendency of both infections in Chile, their risk factors that have contributed to their persistence in the country and the interventions that have been carried out to reduce the disease burden. Although the vaccine for hepatitis B was incorporated to the immunization program in 2005, the vaccine for hepatitis A persists in the list of interventions that must be assumed with priority by the Ministry of Health. If Chilean health authorities pretend to reach the enteric disease indicators of developed countries, they must accelerate the epidemiological transition towards the elimination of hepatitis A.

[Seroprevalence of antibodies against hepatitis A virus and hepatitis B virus in nonvaccinated adult population over 40 years of age].

PubMed

Chlíbek, R; Cecetková, B; Smetana, J; Prymula, R; Kohl, I

2006-08-01

To determine prevalence rates of antibodies against hepatitis A virus (HAV) and hepatitis B virus (HBV) in the general adult male and female population over 40 years of age with no history of viral hepatitis A (VHA) and viral hepatitis B (VHB) who have never been vaccinated against hepatitis and to assess the cost-effectiveness of the pre-vaccination serological screening. In 2003-2004, a total of 972 persons of three age categories: 41-50 years, 51-60 years, 61 and more years, were screened. Persons with a history of VHA and/or VHB and those who had been vaccinated against hepatitis were not included in the study. The following four indicators were determined from a 5 ml specimen of whole venous blood by electrochemiluminiscence assay: total anti-HAV antibodies, total anti-HBc antibodies, anti-HBs antibodies and HBsAg, as the most suitable markers of experienced hepatitis or previous vaccination. The prevalence rates of anti-HAV antibodies were lower in females compared to males for all of the three age categories. These antibodies were detected in 16.8%, 52.9% and 77.5% of 41-50-year-olds, 51-60-year-olds and > or = 61-year-olds, respectively. The total prevalence rate for the three age groups was 61.6%. The anti-HBc antibody seroprevalence rates were 1.9%, 5.3% and 6.1%, respectively. The results show high prevalence of VHA in higher age groups. Such a high seroprevalence of antibodies in nonvaccinated persons with no history of viral hepatitis is suggestive of a very frequent incidence of asymptomatic infection. For this reason, the prevaccination screening of anti-HAV antibodies is cost-effective in the population over 50 years of age but is not justified in persons under 40 years of age. Prevaccination screening for anti-HBc antibodies appears not to be cost-effective regardless of age in view of their low prevalence in the Czech population.

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

Role of hypoxia-inducible factor-{alpha} in hepatitis-B-virus X protein-mediated MDR1 activation

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

Han, Hyo-Kyung; Han, Chang Yeob; Cheon, Eun-Pa

2007-06-01

The transition from chemotherapy-responsive cancer cells to chemotherapy-resistant cancer cells is mainly accompanied by the increased expression of multi-drug resistance 1 (MDR1). We found that hepatitis-B-virus X protein (HBx) increases the transcriptional activity and protein level of MDR1 in a hepatoma cell line, H4IIE. In addition, HBx overexpression made H4IIE cells more resistant to verapamil-uptake. HBx stabilized hypoxia-inducible factor-1{alpha} (HIF-1{alpha}) and induced the nuclear translocation of C/EBP{beta}. Reporter gene analyses showed that HBx increased the reporter activity in the cells transfected with the reporter containing MDR1 gene promoter. Moreover, the luciferase reporter gene activity was significantly inhibited by HIF-1{alpha} siRNAmore » but not by overexpression of C/EBP dominant negative mutant. These results imply that HBx increases the MDR1 transporter activity through the transcriptional activation of the MDR1 gene with HIF-1{alpha} activation, and suggest HIF-1{alpha} for the therapeutic target of HBV-mediated chemoresistance.« less

[Role of mutations on the "hepatitis B virus 'a' determinant hotpoint" to the efficacy of hepatitis B vaccine].

PubMed

Zhang, Rui; Li, Rong-cheng; Zhu, Feng-cai; Li, Yan-ping; Liu, She-lan; Zhang, Xian-chen; Wang, Sheng-qi; Liang, Zheng-lun; Li, He-min; Zhuang, Hui

2007-04-01

To study how hepatitis B virus(HBV) 'a' determinant hotpoint mutations were influecing the hepatitis B vaccine efficacy. Primers were designed in HBV conservative region, and the degenerate probes for detecting 16 'a' determinant hotpoint mutations were developed for gene chips. Sensitivity and specificity of the gene chips were evaluated by clone sequencing. Sera of 47 pairs of mothers and infants with immune failure and 323 mothers of children with immune protection of HB vaccine were detected by the gene chips. Result from clone sequencing demonstrated that the gene chips were specific for the detection of 'a' determinant hotpoint mutations. The wild type of HBV was still dominant, with the prevalence of 78.66%, and the mutation frequencies of 126A, 145R, 126S-1, 126S-2, 129H, 144A, and 129R were 11.27%, 5.76%, 5.28%, 4.56%, 1.20%, 0.72% and 0.24%, respectively. The prevalence of 126A mutation was significantly higher than that of other mutations(P < 0.01). No significant differences were found in mother-infant transmission rates of 126A, 126S-1, 126S-2 and 145R variants. The currently available hepatitis B vaccine could block mother-infant transmission of 126A, 126S and 145R variants. It appears that there is no need to develop a new hepatitis B vaccine against 126 and 145 variants at present, but the consistent epidemiological surveillance on HBV mutants should be carried out.

Hepatitis B virus X protein shifts human hepatic transforming growth factor (TGF)-beta signaling from tumor suppression to oncogenesis in early chronic hepatitis B.

PubMed

Murata, Miki; Matsuzaki, Koichi; Yoshida, Katsunori; Sekimoto, Go; Tahashi, Yoshiya; Mori, Shigeo; Uemura, Yoshiko; Sakaida, Noriko; Fujisawa, Junichi; Seki, Toshihito; Kobayashi, Kazuki; Yokote, Koutaro; Koike, Kazuhiko; Okazaki, Kazuichi

2009-04-01

Hepatitis B virus X (HBx) protein is suspected to participate in oncogenesis during chronic hepatitis B progression. Transforming growth factor beta (TGF-beta) signaling involves both tumor suppression and oncogenesis. TGF-beta activates TGF-beta type I receptor (TbetaRI) and c-Jun N-terminal kinase (JNK), which differentially phosphorylate the mediator Smad3 to become C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). Reversible shifting of Smad3-mediated signaling between tumor suppression and oncogenesis in HBx-expressing hepatocytes indicated that TbetaRI-dependent pSmad3C transmitted a tumor-suppressive TGF-beta signal, while JNK-dependent pSmad3L promoted cell growth. We used immunostaining, immunoblotting, and in vitro kinase assay to compare pSmad3L- and pSmad3C-mediated signaling in biopsy specimens representing chronic hepatitis, cirrhosis, or hepatocellular carcinoma (HCC) from 90 patients chronically infected with hepatitis B virus (HBV) with signaling in liver specimens from HBx transgenic mice. In proportion to plasma HBV DNA levels, early chronic hepatitis B specimens showed prominence of pSmad3L in hepatocytic nuclei. HBx-activated JNK/pSmad3L/c-Myc oncogenic pathway was enhanced, while the TbetaRI/pSmad3C/p21(WAF1) tumor-suppressive pathway was impaired as human and mouse HBx-associated hepatocarcinogenesis progressed. Of 28 patients with chronic hepatitis B who showed strong oncogenic pSmad3L signaling, six developed HCC within 12 years; only one of 32 patients showing little pSmad3L developed HCC. In contrast, seven of 30 patients with little Smad3C phosphorylation developed HCC, while no patient who retained hepatocytic tumor-suppressive pSmad3C developed HCC within 12 years. HBx shifts hepatocytic TGF-beta signaling from the tumor-suppressive pSmad3C pathway to the oncogenic pSmad3L pathway in early carcinogenic process. Hepatocytic pSmad3L and pSmad3C assessment in HBV-infected liver specimens should prove

Glucose-regulated protein 78 is an intracellular antiviral factor against hepatitis B virus.

PubMed

Ma, Yan; Yu, Jun; Chan, Henry L Y; Chen, Yang-chao; Wang, Hua; Chen, Ying; Chan, Chu-yan; Go, Minnie Y Y; Tsai, Sau-na; Ngai, Sai-ming; To, Ka-fai; Tong, Joanna H M; He, Qing-Yu; Sung, Joseph J Y; Kung, Hsiang-fu; Cheng, Christopher H K; He, Ming-liang

2009-11-01

Hepatitis B virus (HBV) infection is a global public health problem that plays a crucial role in the pathogenesis of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. However, the pathogenesis of HBV infection and the mechanisms of host-virus interactions are still elusive. In this study, two-dimensional gel electrophoresis and mass spectrometry-based comparative proteomics were applied to analyze the host response to HBV using an inducible HBV-producing cell line, HepAD38. Twenty-three proteins were identified as differentially expressed with glucose-regulated protein 78 (GRP78) as one of the most significantly up-regulated proteins induced by HBV replication. This induction was further confirmed in both HepAD38 and HepG2 cells transfected with HBV-producing plasmids by real time RT-PCR and Western blotting as well as in HBV-infected human liver biopsies by immunohistochemistry. Knockdown of GRP78 expression by RNA interference resulted in a significant increase of both intracellular and extracellular HBV virions in the transient HBV-producing HepG2 cells concomitant with enhanced levels of hepatitis B surface antigen and e antigen in the culture medium. Conversely overexpression of GRP78 in HepG2 cells led to HBV suppression concomitant with induction of the positive regulatory circuit of GRP78 and interferon-beta1 (IFN-beta1). In this connection, the IFN-beta1-mediated 2',5'-oligoadenylate synthetase and RNase L signaling pathway was noted to be activated in GRP78-overexpressing HepG2 cells. Moreover GRP78 was significantly down-regulated in the livers of chronic hepatitis B patients after effective anti-HBV treatment (p = 0.019) as compared with their counterpart pretreatment liver biopsies. In conclusion, the present study demonstrates for the first time that GRP78 functions as an endogenous anti-HBV factor via the IFN-beta1-2',5'-oligoadenylate synthetase-RNase L pathway in hepatocytes. Induction of hepatic GRP78 may provide a novel therapeutic

Glucose-regulated Protein 78 Is an Intracellular Antiviral Factor against Hepatitis B Virus*

PubMed Central

Ma, Yan; Yu, Jun; Chan, Henry L. Y.; Chen, Yang-chao; Wang, Hua; Chen, Ying; Chan, Chu-yan; Go, Minnie Y. Y.; Tsai, Sau-na; Ngai, Sai-ming; To, Ka-fai; Tong, Joanna H. M.; He, Qing-Yu; Sung, Joseph J. Y.; Kung, Hsiang-fu; Cheng, Christopher H. K.; He, Ming-liang

2009-01-01

Hepatitis B virus (HBV) infection is a global public health problem that plays a crucial role in the pathogenesis of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. However, the pathogenesis of HBV infection and the mechanisms of host-virus interactions are still elusive. In this study, two-dimensional gel electrophoresis and mass spectrometry-based comparative proteomics were applied to analyze the host response to HBV using an inducible HBV-producing cell line, HepAD38. Twenty-three proteins were identified as differentially expressed with glucose-regulated protein 78 (GRP78) as one of the most significantly up-regulated proteins induced by HBV replication. This induction was further confirmed in both HepAD38 and HepG2 cells transfected with HBV-producing plasmids by real time RT-PCR and Western blotting as well as in HBV-infected human liver biopsies by immunohistochemistry. Knockdown of GRP78 expression by RNA interference resulted in a significant increase of both intracellular and extracellular HBV virions in the transient HBV-producing HepG2 cells concomitant with enhanced levels of hepatitis B surface antigen and e antigen in the culture medium. Conversely overexpression of GRP78 in HepG2 cells led to HBV suppression concomitant with induction of the positive regulatory circuit of GRP78 and interferon-β1 (IFN-β1). In this connection, the IFN-β1-mediated 2′,5′-oligoadenylate synthetase and RNase L signaling pathway was noted to be activated in GRP78-overexpressing HepG2 cells. Moreover GRP78 was significantly down-regulated in the livers of chronic hepatitis B patients after effective anti-HBV treatment (p = 0.019) as compared with their counterpart pretreatment liver biopsies. In conclusion, the present study demonstrates for the first time that GRP78 functions as an endogenous anti-HBV factor via the IFN-β1-2′,5′-oligoadenylate synthetase-RNase L pathway in hepatocytes. Induction of hepatic GRP78 may provide a novel therapeutic

Hepatitis B Virus Lacks Immune Activating Capacity, but Actively Inhibits Plasmacytoid Dendritic Cell Function

PubMed Central

Woltman, Andrea M.; Shi, Cui C.; Janssen, Harry L. A.

2011-01-01

Chronic hepatitis B virus (HBV) infection is caused by inadequate anti-viral immunity. Activation of plasmacytoid dendritic cells (pDC) leading to IFNα production is important for effective anti-viral immunity. Hepatitis B virus (HBV) infection lacks IFNα induction in animal models and patients and chronic HBV patients display impaired IFNα production by pDC. Therefore, HBV and HBV-derived proteins were examined for their effect on human pDC in vitro. In addition, the in vitro findings were compared to the function of pDC derived from chronic HBV patients ex vivo. In contrast to other viruses, HBV did not activate pDC. Moreover, HBV and HBsAg abrogated CpG-A/TLR9-induced, but not Loxoribine/TLR7-induced, mTOR-mediated S6 phosphorylation, subsequent IRF7 phosphorylation and IFNα gene transcription. HBV/HBsAg also diminished upregulation of co-stimulatory molecules, production of TNFα, IP-10 and IL-6 and pDC-induced NK cell function, whereas TLR7-induced pDC function was hardly affected. In line, HBsAg preferentially bound to TLR9-triggered pDC demonstrating that once pDC are able to bind HBV/HBsAg, the virus exerts its immune regulatory effect. HBV not only directly interfered with pDC function, but also indirectly by interfering with monocyte-pDC interaction. Also HBeAg diminished pDC function to a certain extent, but via another unknown mechanism. Interestingly, patients with HBeAg-positive chronic hepatitis B displayed impaired CpG-induced IFNα production by pDC without significant alterations in Loxoribine-induced pDC function compared to HBeAg-negative patients and healthy controls. The lack of activation and the active inhibition of pDC by HBV may both contribute to HBV persistence. The finding that the interaction between pDC and HBV may change upon activation may aid in the identification of a scavenging receptor supporting immunosuppressive effects of HBV and also in the design of novel treatment strategies for chronic HBV. PMID:21246041

Comparative efficacy of two dosages of recombinant hepatitis B vaccine in healthy adolescents in India.

PubMed

Velu, Vijayakumar; Nandakumar, Subhadra; Shanmugam, Saravanan; Shankar, Esaki Muthu; Thangavel, Sundararajan; Kulkarni, Prasad Suryakant; Thyagarajan, Sadras Panchatcharam

2007-11-01

Inclusion of hepatitis B vaccine in the Universal Programme of Immunization of all Asian and African countries is hampered by the economic burden on the health budget because of the cost of hepatitis B vaccines. Here we evaluated the immunogenicity, safety, efficacy, and the persistence of antibody to hepatitis B surface antigen (anti-HBs) titers of a new and a low cost recombinant hepatitis B vaccine GeneVac B, with 2 different dosages in healthy adolescents in India. GeneVac-B, a recombinant hepatitis B vaccine (Serum Institute of India, Pune, India), was administered in 10 or 20 microg dose intramuscularly to 2 groups of 100 healthy school-going adolescents at 0-, 1-, and 6-month intervals, who were followed up for 1 year. Group I received 20 mug doses whereas Group II received 10 mug doses. Blood samples were collected 1 month after each dose and 1 year after the third dose. The anti-HBs titers were assayed using commercially available kits to assess the immunogenicity of the 2 dosage schedules. Safety studies were also carried out. The geometric mean titer value of the anti-HBs titer 1 month after the third dose was 2629 (mlU/mL) in Group I and 1373 mlU/mL for Group II subjects. One year after the third dose, the persistence of anti-HBs in those who had received 20 mug was 2262 mlU/mL whereas it was 1039 mlU/mL in the group receiving 10 microg doses. All the subjects in both the groups were seroprotected at 1 year after vaccination. None of the vaccinees exhibited serious adverse reactions throughout the study period. The study demonstrated the immunogenicity of the recombinant hepatitis B vaccine, and confirms that the 0.5 mL (10 microg) dose of GeneVac B can be administered with satisfactory safety and immunogenicity to adolescents up to 19 years of age, reducing the cost to less than U.S. $1.00 per dose making it acceptable for the Universal Programme of Immunization of developing and under developed countries.