Occult hepatitis B virus infection is not associated with disease progression of chronic hepatitis C virus infection.

PubMed

Cho, Junhyeon; Lee, Sang Soo; Choi, Yun Suk; Jeon, Yejoo; Chung, Jung Wha; Baeg, Joo Yeong; Si, Won Keun; Jang, Eun Sun; Kim, Jin-Wook; Jeong, Sook-Hyang

2016-11-14

To clarify the prevalence of occult hepatitis B virus (HBV) infection (OBI) and the association between OBI and liver disease progression, defined as development of liver cirrhosis or hepatocellular carcinoma (HCC), worsening of Child-Pugh class, or mortality in cases of chronic hepatitis C virus (HCV) infection. This prospective cohort study enrolled 174 patients with chronic HCV infection (chronic hepatitis, n = 83; cirrhosis, n = 47; HCC, n = 44), and evaluated disease progression during a mean follow-up of 38.7 mo. OBI was defined as HBV DNA positivity in 2 or more different viral genomic regions by nested polymerase chain reaction using 4 sets of primers in the S, C, P and X open reading frame of the HBV genome. The overall OBI prevalence in chronic HCV patients at enrollment was 18.4%, with 16.9%, 25.5% and 13.6% in the chronic hepatitis C, liver cirrhosis and HCC groups, respectively ( P = 0.845). During follow-up, 52 patients showed disease progression, which was independently associated with aspartate aminotransferase > 40 IU/L, Child-Pugh score and sustained virologic response (SVR), but not with OBI positivity. In 136 patients who were not in the SVR state during the study period, OBI positivity was associated with neither disease progression, nor HCC development. The prevalence of OBI in chronic HCV patients was 18.4%, and OBI was not associated with disease progression in South Koreans.

[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.

Increased CD56(bright) NK cells in HIV-HCV co-infection and HCV mono-infection are associated with distinctive alterations of their phenotype.

PubMed

Bhardwaj, Suvercha; Ahmad, Fareed; Wedemeyer, Heiner; Cornberg, Marcus; Schulze Zur Wiesch, Julian; van Lunzen, Jan; Sarin, Shiv K; Schmidt, Reinhold E; Meyer-Olson, Dirk

2016-04-18

HIV-HCV co-infection is associated with accelerated progression to hepatic fibrosis, cirrhosis and hepatocellular carcinoma than HCV mono-infection. The contribution of innate immunity during HIV-HCV co-infection has been a relatively under-investigated area. Natural killer (NK) cells are pivotal sentinels of innate immunity against viruses and tumour cells. In this study we evaluated the effect of HIV-HCV co-infection on peripheral blood NK cell subsets with emphasis on the phenotype of CD56(bright) NK cells. Sixty patients were included in the study; HIV mono-infected (n = 12), HCV mono-infected (n = 15), HCV-HIV co-infected (n = 21) and healthy controls (n = 16). PBMCs were isolated and immunophenotyping of NK cells was performed by flowcytometry. We observed an expansion of CD56(bright) NK cell subset in HIV-HCV co-infection as compared to healthy controls and HIV mono-infected group. All the infected groups had an upregulated expression of the activating receptor NKG2D on CD56(bright) NK cells in comparison to healthy controls while not differing amongst themselves. The expression of NKp46 in HIV-HCV co-infected group was significantly upregulated as compared to both HIV as well as HCV mono-infections while NKp30 expression in the HIV-HCV co-infected group significantly differed as compared to HIV mono-infection. The CD56(bright) NK cell subset was activated in HIV-HCV co-infection as assessed by the expression of CD69 as compared to healthy controls but was significantly downregulated in comparison to HIV mono-infection. CD95 expression on CD56(bright) NK cells followed the same pattern where there was an increased expression of CD95 in HIV mono-infection and HIV-HCV co-infection as compared to healthy controls. In contrast to CD69 expression, CD95 expression in HCV mono-infection was decreased when compared to HIV mono-infection and HIV-HCV co-infection. Finally, expression of CXCR3 on CD56(bright) NK cells was increased in HIV-HCV co-infection in comparison

HCV avidity as a tool for detection of recent HCV infection: Sensitivity depends on HCV genotype.

PubMed

Shepherd, Samantha J; McDonald, Scott A; Palmateer, Norah E; Gunson, Rory N; Aitken, Celia; Dore, Gregory J; Goldberg, David J; Applegate, Tanya L; Lloyd, Andrew R; Hajarizadeh, Behzad; Grebely, Jason; Hutchinson, Sharon J

2018-01-01

Accurate detection of incident hepatitis C virus (HCV) infection is required to target and evaluate public health interventions, but acute infection is largely asymptomatic and difficult to detect using traditional methods. Our aim was to evaluate a previously developed HCV avidity assay to distinguish acute from chronic HCV infection. Plasma samples collected from recent seroconversion subjects in two large Australian cohorts were tested using the avidity assay, and the avidity index (AI) was calculated. Demographic and clinical characteristics of patients with low/high AI were compared via logistic regression. Sensitivity and specificity of the assay for recent infection and the mean duration of recent infection (MDRI) were estimated stratified by HCV genotype. Avidity was assessed in 567 samples (from 215 participants), including 304 with viraemia (defined as ≥250 IU/mL). An inverse relationship between AI and infection duration was found in viraemic samples only. The adjusted odds of a low AI (<30%) decreased with infection duration (odds ratio [OR] per week of 0.93; 95% CI:0.89-0.97), and were lower for G1 compared with G3 samples (OR = 0.14; 95% CI:0.05-0.39). Defining recent infection as <26 weeks, sensitivity (at AI cut-off of 20%) was estimated at 48% (95% CI:39-56%), 36% (95% CI:20-52%), and 65% (95% CI:54-75%) and MDRI was 116, 83, and 152 days for all genotypes, G1, and G3, respectively. Specificity (≥52 weeks infection duration, all genotypes) was 96% (95% CI:90-98%). HCV avidity testing has utility for detecting recent HCV infection in patients, and for assessing progress in reaching incidence targets for eliminating transmission, but variation in assay performance across genotype should be recognized. © 2017 Wiley Periodicals, Inc.

Molecular Mechanisms Underlying Occult Hepatitis B Virus Infection

PubMed Central

Samal, Jasmine; Kandpal, Manish

2012-01-01

Summary: Chronic hepatitis B virus (HBV) infection is a complex clinical entity frequently associated with cirrhosis and hepatocellular carcinoma (HCC). The persistence of HBV genomes in the absence of detectable surface antigenemia is termed occult HBV infection. Mutations in the surface gene rendering HBsAg undetectable by commercial assays and inhibition of HBV by suppression of viral replication and viral proteins represent two fundamentally different mechanisms that lead to occult HBV infections. The molecular mechanisms underlying occult HBV infections, including recently identified mechanisms associated with the suppression of HBV replication and inhibition of HBV proteins, are reviewed in detail. The availability of highly sensitive molecular methods has led to increased detection of occult HBV infections in various clinical settings. The clinical relevance of occult HBV infection and the utility of appropriate diagnostic methods to detect occult HBV infection are discussed. The need for specific guidelines on the diagnosis and management of occult HBV infection is being increasingly recognized; the aspects of mechanistic studies that warrant further investigation are discussed in the final section. PMID:22232374

Occult HBV infection status among chronic hepatitis C and hemodialysis patients in Northeastern Egypt: regional and national overview.

PubMed

Mandour, Mohamed; Nemr, Nader; Shehata, Atef; Kishk, Rania; Badran, Dahlia; Hawass, Nashaat

2015-01-01

Occult hepatitis B infection (OBI) is considered to be one of the major risks for patients suffering from end-stage renal disease (ESRD) on regular hemodialysis (HD) and patients with chronic hepatitis C virus (HCV) infection. This study compared the prevalence of OBI among these two high-risk groups in the Suez Canal region, Northeastern Egypt, to obtain a better national overview of the magnitude of OBI in this region. Serum samples were collected from 165 HD patients and 210 chronic HCV-infected patients. Anti-HCV antibody, hepatitis B surface antigen (HBsAg), total hepatitis B core (anti-HBc) antibody, and hepatitis B surface antibody (anti-HBs) were detected by enzyme-linked immunosorbent assay (ELISA). HCV RNA was detected using a quantitative real-time RT-PCR assay, and HBV was detected using a nested PCR. All patients were negative for HBsAg. A total of 49.1% and 25.2% of the patients in the HD and HCV groups, respectively, were anti-HBc-positive. In addition, more anti-HBs-positive patients were detected in the HD group compared to the HCV group (52.1% and 11.4%, respectively). Three cases were positive for HBV DNA in the HD group, while eighteen positive cases were detected in the HCV group. Both study groups showed significant differences in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level as well as anti-HBc, anti-HBs and HBV-DNA positivity. OBI was more prevalent among chronic HCV patients than HD patients in the Suez Canal region, Egypt, with rates of 8.5% and 1.8%, respectively. However, more precise assessment of this infection requires regular patient follow-up using HBV DNA detection methods.

HCV mono-infected and HIV/HCV co-infected individuals treated with direct-acting antivirals: to what extent do they differ?

PubMed

Bruno, Giuseppe; Saracino, Annalisa; Scudeller, Luigia; Fabrizio, Claudia; Dell'Acqua, Raffaele; Milano, Eugenio; Milella, Michele; Ladisa, Nicoletta; Monno, Laura; Angarano, Gioacchino

2017-09-01

Direct-acting antiviral (DAA)-based treatment of hepatitis C virus (HCV) has been associated with high sustained virological response (SVR) rates and good tolerability in randomized clinical trials. This study was performed to assess the safety and effectiveness of DAAs in both HCV mono-infected and HIV/HCV co-infected patients. All consecutive HCV-infected patients, including HIV/HCV co-infected patients, receiving DAA-based treatment from February 2015 to September 2016 at the study clinic were included. Clinical, virological, and biochemical data were retrieved. The primary end-point was the SVR12 (HCV RNA undetectable 12 weeks after the end of treatment) is commonly used worldwide. The secondary end-point was the safety profile of DAAs during the treatment period. A total of 382 patients were included; 62 were HIV/HCV co-infected. Cirrhosis was found in 256 patients (67.4%). SVR12 was achieved in 365/382 (95.5%) individuals (58/62 HIV/HCV co-infected, 93.5%) in the intention-to-treat (ITT) analysis. A platelet count <90×10 9 /l (odds ratio (OR) 4.12, 95% confidence interval (CI) 1.5-11.3, p=0.006), HCV genotype 3 infection (OR 5.49, 95% CI 1.9-15.7, p=0.002), liver stiffness >20kPa (OR 3.05, 95% CI 1.03-8.96, p=0.04), and Model for End-Stage Liver Disease (MELD) score >10 (OR 5.27, 95% CI 1.16-23.8, p=0.03) were associated with lower SVR rates. On multivariate analysis, only genotype 3 infection remained a negative predictor of SVR (OR 21.6, 95% CI 3.81-123, p=0.001). Treatment discontinuation was observed in 10 subjects. Severe adverse events (SAEs) occurred in 17 patients (4.5%). High SVR12 rates were observed in both HCV mono-infected and HIV/HCV co-infected individuals. Overall, DAA-based treatment was safe and there were no differences in terms of SAEs and treatment discontinuation between the two groups. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Testing for Occult Heartworm Infection

PubMed Central

Stogdale, L.

1984-01-01

Heartworm infection in dogs is endemic in southern Ontario but occurs only sporadically throughout the remainder of Canada. The disease may either be associated with microfilariae in the patient's blood, a patent infection, or it may be occult. This paper describes a case of occult dirofilariasis in a dog, with emphasis on the diagnosis. A patent infection could be missed if the clinician tests an insufficient amount of blood. He should perform multiple concentration tests using either the modified Knott's technique or a filtration method. Occult infections occur in prepatent or unisexual infections, when the worms become sterile following therapy, or when the host produces antibodies that result in the destruction of the microfilariae. The recent release of a kit which detects the presence of antibodies to the adult heartworms now enables veterinarians to make an accurate diagnosis in the vast majority of dogs. PMID:17422386

Comprehensive longitudinal analysis of hepatitis C virus (HCV)-specific T cell responses during acute HCV infection in the presence of existing HIV-1 infection.

PubMed

van den Berg, C H S B; Ruys, T A; Nanlohy, N M; Geerlings, S E; van der Meer, J T; Mulder, J-W; Lange, J A; van Baarle, D

2009-04-01

The aim of this study was to study the development of HCV-specific T cell immunity during acute HCV infection in the presence of an existing HIV-1 infection in four HIV-1 infected men having sex with men. A comprehensive analysis of HCV-specific T cell responses was performed at two time points during acute HCV infection using a T cell expansion assay with overlapping peptide pools spanning the entire HCV genome Three patients with (near) normal CD4+ T cell counts (range 400-970 x 10(6)/L) either resolved (n=1) or temporary suppressed HCV RNA. In contrast, one patient with low CD4+ T cell counts (330 x 10(6)/L), had sustained high HCV RNA levels. All four patients had low HCV-specific CD8+ T cell responses, and similar magnitudes of CD4+ T cell responses. Interestingly, individuals with resolved infection or temporary suppression of HCV-RNA had HCV-specific CD4+ T cell responses predominantly against nonstructural (NS) proteins. While the individual with high HCV RNA plasma concentrations had CD4+ T cell responses predominantly directed against Core. Our data show that an acute HCV infection in an HIV-1 infected person can be suppressed in the presence of HCV-specific CD4+ T cell response targeting non-structural proteins. However further research is needed in a larger group of patients to evaluate the role of HIV-1 on HCV-specific T cell responses in relation to outcome of acute HCV infection.

Preclinical Evaluation of An Anti-HCV miRNA Cluster for Treatment of HCV Infection

PubMed Central

Yang, Xiao; Marcucci, Katherine; Anguela, Xavier; Couto, Linda B.

2013-01-01

We developed a strategy to treat hepatitis C virus (HCV) infection by replacing five endogenous microRNA (miRNA) sequences of a natural miRNA cluster (miR-17–92) with sequences that are complementary to the HCV genome. This miRNA cluster (HCV-miR-Cluster 5) is delivered to cells using adeno-associated virus (AAV) vectors and the miRNAs are expressed in the liver, the site of HCV replication and assembly. AAV-HCV-miR-Cluster 5 inhibited bona fide HCV replication in vitro by up to 95% within 2 days, and the spread of HCV to uninfected cells was prevented by continuous expression of the anti-HCV miRNAs. Furthermore, the number of cells harboring HCV RNA replicons decreased dramatically by sustained expression of the anti-HCV miRNAs, suggesting that the vector is capable of curing cells of HCV. Delivery of AAV-HCV-miR-Cluster 5 to mice resulted in efficient transfer of the miRNA gene cluster and expression of all five miRNAs in liver tissue, at levels up to 1,300 copies/cell. These levels achieved up to 98% gene silencing of cognate HCV sequences, and no liver toxicity was observed, supporting the safety of this approach. Therefore, AAV-HCV-miR-Cluster 5 represents a different paradigm for the treatment of HCV infection. PMID:23295950

Regulatory polymorphism of CXCL10 rs1439490 in seronegative occult hepatitis C virus infection.

PubMed

Wang, Xu; Wang, Song; Liu, Zhen-Hua; Qi, Wen-Qian; Zhang, Qian; Zhang, Yong-Gui; Sun, De-Rong; Xu, Yan; Wang, Hong-Guang; Li, Zhong-Xie; Cong, Xian-Ling; Zhao, Ping; Zhou, Chang-Yu; Wang, Jiang-Bin

2018-05-28

To examine the relationship between the single nucleotide polymorphism CXCL10 rs1439490 and seronegative occult hepatitis C virus (HCV) infection (OCI). One hundred and three cases of seronegative OCI and 155 cases of seropositive chronic HCV infection (CHC) were diagnosed at five Liver Centers in Northeastern China, from 2012 to 2016. CXCL10 rs1439490, rs1440802, and IL-28B rs12979860 were analyzed by sequencing. Serum CXCL10 was measured by ELISA. Intrahepatic CXCL10 was determined by quantitative PCR and immunohistochemical semi-quantitative scoring. Liver necroinflammation and fibrosis were scored according to the METAVIR system. CXCL10 rs1439490 G/G was more prevalent in OCI patients ( n = 93/103; 90.3%) than in CHC patients ( n = 116/155; 74.8%; P = 0.008). OCI patients had lower serum CXCL10 levels than CHC patients (192.91 ± 46.50 pg/mL vs 354.78 ± 102.91 pg/mL, P < 0.0001). Of IL-28B rs12979860 C/C patients, OCI patients with rs1439490 G/G had lower serum and liver levels of CXCL10 and lower levels of liver necroinflammation and fibrosis than non-G/G patients. OCI patients had higher alanine aminotransferase normalization rates after Peg-interferon treatment than CHC patients (P < 0.05) and serum CXCL10 decreased significantly (P < 0.0001). Liver necroinflammation and fibrosis were alleviated in 8 OCI patients after treatment. Multivariate analysis indicated that rs1439490 G/G significantly influenced the occurrence of OCI in HCV infection (OR = 0.31, 95%CI: 0.15-0.66, P = 0.002). CXCL10 rs1439490 G/G is positively associated with OCI in HCV infection and antiviral outcome.

Consensus statement on the management of patients with HCV infection in Romania

PubMed Central

Ancuța, Ioan

2017-01-01

Background HCV direct-acting antivirals (DAAs) have made treatment easier for both patients and healthcare practitioners, but have also brought new challenges in terms of patient management and monitoring prior to, during, and after treatment. Methods To sum up and unify the clinical experience of Romanian DAA prescribing physicians, we have organized a Consensus Meeting in November 2016 in Bucharest, Romania. Consensus Statement The Consensus Meeting has provided expert answers to ten significant questions regarding HCV infection, namely: How do we diagnose patients with HCV infection? How do we stage liver disease in patients with HCV infection? How do we monitor patients with HCV infection prior to treatment? Which patients with HCV infection do we treat? When do we start treatment for HCV infection? What regimens do we use for treating HCV infection? How do we monitor patients with HCV infection during treatment? What adverse events should we expect during treatment of HCV infection and how do we prevent/manage them? How do we monitor patients with HCV infection after treatment? How do we expect the landscape of HCV to change in the following years? PMID:28331840

High prevalence of human parvovirus 4 infection in HBV and HCV infected individuals in shanghai.

PubMed

Yu, Xuelian; Zhang, Jing; Hong, Liang; Wang, Jiayu; Yuan, Zhengan; Zhang, Xi; Ghildyal, Reena

2012-01-01

Human parvovirus 4 (PARV4) has been detected in blood and diverse tissues samples from HIV/AIDS patients who are injecting drug users. Although B19 virus, the best characterized human parvovirus, has been shown to co-infect patients with hepatitis B or hepatitis C virus (HBV, HCV) infection, the association of PARV4 with HBV or HCV infections is still unknown.The aim of this study was to characterise the association of viruses belonging to PARV4 genotype 1 and 2 with chronic HBV and HCV infection in Shanghai.Serum samples of healthy controls, HCV infected subjects and HBV infected subjects were retrieved from Shanghai Center for Disease Control and Prevention (SCDC) Sample Bank. Parvovirus-specific nested-PCR was performed and results confirmed by sequencing. Sequences were compared with reference sequences obtained from Genbank to derive phylogeny trees.The frequency of parvovirus molecular detection was 16-22%, 33% and 41% in healthy controls, HCV infected and HBV infected subjects respectively, with PARV4 being the only parvovirus detected. HCV infected and HBV infected subjects had a significantly higher PARV4 prevalence than the healthy population. No statistical difference was found in PARV4 prevalence between HBV or HCV infected subjects. PARV4 sequence divergence within study groups was similar in healthy subjects, HBV or HCV infected subjects.Our data clearly demonstrate that PARV4 infection is strongly associated with HCV and HBV infection in Shanghai but may not cause increased disease severity.

Occult HBV infection in HIV-infected adults and evaluation of pooled NAT for HBV.

PubMed

Dinesha, T R; Boobalan, J; Sivamalar, S; Subashini, D; Solomon, S S; Murugavel, K G; Balakrishnan, P; Smith, D M; Saravanan, S

2018-06-01

The study aimed to determine the prevalence of occult hepatitis B virus infection among HIV-infected persons and to evaluate the use of a pooling strategy to detect occult HBV infection in the setting of HIV infection. Five hundred and two HIV-positive individuals were tested for HBV, occult HBV and hepatitis C and D with serologic and nucleic acid testing (NAT). We also evaluated a pooled NAT strategy for screening occult HBV infection among the HIV-positive individuals. The prevalence of HBV infection among HIV-positive individuals was 32 (6.4%), and occult HBV prevalence was 10%. The pooling HBV NAT had a sensitivity of 66.7% and specificity of 100%, compared to HBV DNA NAT of individual samples. In conclusion, this study found a high prevalence of occult HBV infection among our HIV-infected population. We also demonstrated that pooled HBV NAT is highly specific, moderately sensitive and cost-effective. As conventional HBV viral load assays are expensive in resource-limited settings such as India, pooled HBV DNA NAT might be a good way for detecting occult HBV infection and will reduce HBV-associated complications. © 2018 John Wiley & Sons Ltd.

HCV RNA Genomic sequences and HCV-E2 glycoprotein in sural nerve biopsies from HCV-infected patients with peripheral neuropathy.

PubMed

Russi, S; Sansonno, D; Monaco, S; Mariotto, S; Ferrari, S; Pavone, F; Lauletta, G; Dammacco, F

2018-06-01

Peripheral neuropathy (PN), the major neurological complication of chronic HCV infection, is frequently associated with mixed cryoglobulinaemia (MC) and small-vessel systemic vasculitis. While humoral and cell-mediated immune mechanisms are suspected to act together in an aberrant immune response that results in peripheral nerve damage, the role of HCV remains largely speculative. The possible demonstration of HCV in peripheral nerve tissue would obviously assume important pathogenic implications. We studied sural nerve biopsies from 11 HCV-positive patients with neuropathic symptoms: five with and six without MC. In situ hybridization (ISH) and immunofluorescence studies were carried out to detect genomic and antigenomic HCV RNA sequences and HCV-encoded E2-glycoprotein, respectively. Epineurial vascular deposits of E2-glycoprotein were found in four (80%) MC and in two (33.3%) non-MC patients, respectively. These findings were enhanced by the perivascular deposition of positive-, though not negative-strand replicative RNA, as also found in the nerve extracts of all patients. Mild inflammatory cell infiltrates with no deposits of immunoglobulins and/or complement proteins were revealed around small vessels, without distinct vasculitis changes between MC and non-MC patients. These results indicate that nerve vascular HCV RNA/E2 deposits associated to perivascular inflammatory infiltrates were similar in chronically HCV-infected patients, regardless of cryoglobulin occurrence. Given the failure to demonstrate HCV productive infection in the examined sural nerve biopsies, nerve damage is likely to result from virus-triggered immune-mediated mechanisms. © 2017 British Neuropathological Society.

Maternal hepatitis C (HCV) infection and Anti-D immunoglobulin therapy: study testing antibodies, RNA and Genotype of HCV in Baghdad.

PubMed

Al-Kubaisy, Waqar; Daud, Suzanna; Al-Kubaisi, Mustafa Waseem; Al-Kubaisi, Omar Waseem; Abdullah, Nik Nairan

2018-04-30

Hepatitis C virus (HCV) infection is a serious health problem. It is a major contributor to end-stage liver disease. Worldwide, 1-8% of all pregnant women were infected. Women with viral hepatitis may be at an increased risk of pregnancy complications. There are several obstetrics intervention acts as risk factors, which are specific to women pertaining the HCV infection; anti-D immunoglobulin (Ig) therapy may be one of them. Our objectives were to estimate the prevalence of HCV antibodies (anti-HCV), RNA, and genotype distribution among women with anti-D Ig therapy. A cross sectional study was conducted. A sample of 154 Rhesus negative (Rh - ve) pregnant women regardless of the anti-D Ig therapy was collected. Anti-HCV were tested using third generation enzyme immunoassay (EIA-3) and immunoblot assay (Lia Tek-111), subsequently. In addition, 89 serum samples were subjected to molecular analysis using RT-PCR and DNA enzyme immunoassay (DEIA) method for the detection of HCV-RNA and genotypes. Anti-HCV, and HCV-RNA seroprevalence were significantly higher (17.1, 35.5%) among women with anti-D Ig than their counter group (6.4, 13.16%), p = .038, .018, respectively. Significant direct positive dose response correlation (r = 0.78, p = .005) had been seen between number of anti-D Ig therapy and anti-HCV seropositive rate. Anti-D Ig therapy act as a risk factor (odds ratio (OR) = 3.01, 95%CI: 1.01-8.9) especially from the third dose onward. Women with anti-D Ig therapy were at higher risk (3.6 times more) of positive HCV-RNA (OR =3.6, 95%CI =1.19-10.837). Genotype HCV-1b showed higher prevalent (52.9%) among the recipients of anti-D Ig therapy while genotype HCV-3a (6.6%) was the lowest. Our study showed that Anti-D immunoglobulin therapy acts as a risk factor for acquiring HCV infection. Screening for HCV should be recommended for all recipients of anti-D Ig. Not only HCV antibodies but HCV-RNA detection being recommended for the diagnosis of HCV

HCV replication in gastrointestinal mucosa: Potential extra-hepatic viral reservoir and possible role in HCV infection recurrence after liver transplantation

PubMed Central

Pizzillo, Paola; Iannolo, Gioacchin; Barbera, Floriana; Liotta, Rosa; Traina, Mario; Vizzini, Giovanni; Gridelli, Bruno

2017-01-01

Purpose Hepatitis C virus (HCV) predominantly infects hepatocytes, although it is known that receptors for viral entry are distributed on a wide array of target cells. Chronic HCV infection is indeed characterized by multiple non-liver manifestations, suggesting a more complex HCV tropism extended to extrahepatic tissues and remains to be fully elucidated. In this study, we investigated the gastrointestinal mucosa (GIM) as a potential extrahepatic viral replication site and its contribution to HCV recurrence. Methods We analyzed GIM biopsies from a cohort of 76 patients, 11 of which were HCV-negative and 65 HCV-positive. Of these, 54 biopsies were from liver-transplanted patients. In 29 cases, we were able to investigate gastrointestinal biopsies from the same patient before and after transplant. To evaluate the presence of HCV, we looked for viral antigens and genome RNA, whilst to assess viral replicative activity, we searched for the replicative intermediate minus-strand RNA. We studied the genetic diversity and the phylogenetic relationship of HCV quasispecies from plasma, liver and gastrointestinal mucosa of HCV-liver-transplanted patients in order to assess HCV compartmentalization and possible contribution of gastrointestinal variants to liver re-infection after transplantation. Results Here we show that HCV infects and replicates in the cells of the GIM and that the favorite hosts were mostly enteroendocrine cells. Interestingly, we observed compartmentalization of the HCV quasispecies present in the gastrointestinal mucosa compared to other tissues of the same patient. Moreover, the phylogenetic analysis revealed a high similarity between HCV variants detected in gastrointestinal mucosa and those present in the re-infected graft. Conclusions Our results demonstrated that the gastrointestinal mucosa might be considered as an extrahepatic reservoir of HCV and that could contribute to viral recurrence. Moreover, the finding that HCV infects and replicates in

Diagnostic strategy for occult hepatitis B virus infection

PubMed Central

Ocana, Sara; Casas, Maria Luisa; Buhigas, Ingrid; Lledo, Jose Luis

2011-01-01

In 2008, the European Association for the study of the liver (EASL) defined occult hepatitis B virus infection (OBI) as the “presence of hepatitis B virus (HBV) DNA in the liver (with detectable or undetectable HBV DNA in the serum) of individuals testing hepatitis B surface antigen (HBsAg) negative by currently available assays”. Several aspects of occult HBV infection are still poorly understood, including the definition itself and a standardized approach for laboratory-based detection, which is the purpose of this review. The clinical significance of OBI has not yet been established; however, in terms of public health, the clinical importance arises from the risk of HBV transmission. Consequently, it is important to detect high-risk groups for occult HBV infection to prevent transmission. The main issue is, perhaps, to identify the target population for screening OBI. Viremia is very low or undetectable in occult HBV infection, even when the most sensitive methods are used, and the detection of the viral DNA reservoir in hepatocytes would provide the best evaluation of occult HBV prevalence in a defined set of patients. However, this diagnostic approach is obviously unsuitable: blood detection of occult hepatitis B requires assays of the highest sensitivity and specificity with a lower limit of detection < 10 IU/mL for HBV DNA and < 0.1 ng/mL for HBsAg. PMID:21472120

Inferring Viral Dynamics in Chronically HCV Infected Patients from the Spatial Distribution of Infected Hepatocytes

DOE PAGES

Graw, Frederik; Balagopal, Ashwin; Kandathil, Abraham J.; ...

2014-11-13

Chronic liver infection by hepatitis C virus (HCV) is a major public health concern. Despite partly successful treatment options, several aspects of intrahepatic HCV infection dynamics are still poorly understood, including the preferred mode of viral propagation, as well as the proportion of infected hepatocytes. Answers to these questions have important implications for the development of therapeutic interventions. In this study, we present methods to analyze the spatial distribution of infected hepatocytes obtained by single cell laser capture microdissection from liver biopsy samples of patients chronically infected with HCV. By characterizing the internal structure of clusters of infected cells, wemore » are able to evaluate hypotheses about intrahepatic infection dynamics. We found that individual clusters on biopsy samples range in size from 4-50 infected cells. In addition, the HCV RNA content in a cluster declines from the cell that presumably founded the cluster to cells at the maximal cluster extension. These observations support the idea that HCV infection in the liver is seeded randomly (e.g. from the blood) and then spreads locally. Assuming that the amount of intracellular HCV RNA is a proxy for how long a cell has been infected, we estimate based on models of intracellular HCV RNA replication and accumulation that cells in clusters have been infected on average for less than a week. Further, we do not find a relationship between the cluster size and the estimated cluster expansion time. Lastly, our method represents a novel approach to make inferences about infection dynamics in solid tissues from static spatial data.« less

Inferring Viral Dynamics in Chronically HCV Infected Patients from the Spatial Distribution of Infected Hepatocytes

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

Graw, Frederik; Balagopal, Ashwin; Kandathil, Abraham J.

Chronic liver infection by hepatitis C virus (HCV) is a major public health concern. Despite partly successful treatment options, several aspects of intrahepatic HCV infection dynamics are still poorly understood, including the preferred mode of viral propagation, as well as the proportion of infected hepatocytes. Answers to these questions have important implications for the development of therapeutic interventions. In this study, we present methods to analyze the spatial distribution of infected hepatocytes obtained by single cell laser capture microdissection from liver biopsy samples of patients chronically infected with HCV. By characterizing the internal structure of clusters of infected cells, wemore » are able to evaluate hypotheses about intrahepatic infection dynamics. We found that individual clusters on biopsy samples range in size from 4-50 infected cells. In addition, the HCV RNA content in a cluster declines from the cell that presumably founded the cluster to cells at the maximal cluster extension. These observations support the idea that HCV infection in the liver is seeded randomly (e.g. from the blood) and then spreads locally. Assuming that the amount of intracellular HCV RNA is a proxy for how long a cell has been infected, we estimate based on models of intracellular HCV RNA replication and accumulation that cells in clusters have been infected on average for less than a week. Further, we do not find a relationship between the cluster size and the estimated cluster expansion time. Lastly, our method represents a novel approach to make inferences about infection dynamics in solid tissues from static spatial data.« less

Association of preS/S Mutations with Occult Hepatitis B Virus (HBV) Infection in South Korea: Transmission Potential of Distinct Occult HBV Variants

PubMed Central

Kim, Hong; Kim, Bum-Joon

2015-01-01

Occult hepatitis B virus infection (HBV) is characterized by HBV DNA positivity but HBV surface antigen (HBsAg) negativity. Occult HBV infection is associated with a risk of HBV transmission through blood transfusion, hemodialysis, and liver transplantation. Furthermore, occult HBV infection contributes to the development of cirrhosis and hepatocellular carcinoma. We recently reported the characteristic molecular features of mutations in the preS/S regions among Korean individuals with occult infections caused by HBV genotype C2; the variants of preS and S related to severe liver diseases among chronically infected patients were also responsible for the majority of HBV occult infections. We also reported that HBsAg variants from occult-infected Korean individuals exhibit lower HBsAg secretion capacity but not reduced HBV DNA levels. In addition, these variants exhibit increased ROS-inducing capacity compared with the wild-type strain, linking HBV occult infections to liver cell damage. Taken together, our previous reports suggest the transmission potential of distinct HBV occult infection-related variants in South Korea. PMID:26084041

Association of preS/S Mutations with Occult Hepatitis B Virus (HBV) Infection in South Korea: Transmission Potential of Distinct Occult HBV Variants.

PubMed

Kim, Hong; Kim, Bum-Joon

2015-06-15

Occult hepatitis B virus infection (HBV) is characterized by HBV DNA positivity but HBV surface antigen (HBsAg) negativity. Occult HBV infection is associated with a risk of HBV transmission through blood transfusion, hemodialysis, and liver transplantation. Furthermore, occult HBV infection contributes to the development of cirrhosis and hepatocellular carcinoma. We recently reported the characteristic molecular features of mutations in the preS/S regions among Korean individuals with occult infections caused by HBV genotype C2; the variants of preS and S related to severe liver diseases among chronically infected patients were also responsible for the majority of HBV occult infections. We also reported that HBsAg variants from occult-infected Korean individuals exhibit lower HBsAg secretion capacity but not reduced HBV DNA levels. In addition, these variants exhibit increased ROS-inducing capacity compared with the wild-type strain, linking HBV occult infections to liver cell damage. Taken together, our previous reports suggest the transmission potential of distinct HBV occult infection-related variants in South Korea.

Geographic differences in the epidemiological features of HCV infection in Korea

PubMed Central

Kim, Kyung-Ah; Jang, Eun Sun; Kim, Young Seok; Lee, Youn Jae; Jung, Eun Uk; Kim, In Hee; Cho, Sung Bum; Kee, Mee-Kyung; Kang, Chun

2014-01-01

Background/Aims The prevalence of hepatitis C virus (HCV) infection in Korea exhibits significant geographic variation, with it being higher in Busan and Jeonam than in other areas. The reason for this intranational geographic difference was investigated in this study by conducting a comparative analysis of the risk factors related to HCV infection among three geographic areas: the capital (Seoul), Busan, and the province of Jeolla. Methods In total, 990 patients with chronic HCV infection were prospectively enrolled at 5 university hospitals located in Seoul (n=374), Busan (n=264), and Jeolla (n=352). A standardized questionnaire survey on the risk factors for HCV infection was administered to these three groups of patients, and a comparative analysis of the findings was performed. Results The analysis revealed significant regional differences in exposure to the risk factors of HCV infection. By comparison with patients in Seoul as a control group in the multivariate analysis, patients in Busan had significantly more experience of invasive medical procedures, acupuncture, cosmetic procedures, and multiple sex partners. In contrast, patients in Jeolla were significantly older, and they had a higher prevalence of hepatocellular carcinoma, a lower prevalence of multiple sex partners, and had experienced fewer invasive procedures. Conclusions There was a significant geographic difference in the exposure to potential risk factors of HCV infection between patients from the three studied regions. This may explain the regional variation of the prevalence of HCV infection in Korea, and should be taken into account when planning strategies for the prevention and management of HCV infection. PMID:25548742

Anti-soluble liver antigen (SLA) antibodies in chronic HCV infection.

PubMed

Vitozzi, Susana; Lapierre, Pascal; Djilali-Saiah, Idriss; Marceau, Gabriel; Beland, Kathie; Alvarez, Fernando

2004-05-01

Hepatitis C infection is associated with autoimmune disorders, such as the production of autoantibodies. Anti-LKM1 and anti-LC1, immunomarkers of type 2 autoimmune hepatitis, have been previously associated with a HCV infection. Anti-Soluble-Liver-Antigen autoantibodies (SLA) are specifically associated with type 1 and type 2 autoimmune hepatitis and more closely related to patients who relapse after steroid therapy. The recent molecular cloning of the soluble liver antigen provides the opportunity to develop more specific tests for the detection of antibodies against it. The aim of this work is to characterize anti-soluble-liver autoantibodies in sera from patients chronically infected by HCV. A recombinant cDNA from activated Jurkat cells coding for the full length tRNP(Ser)Sec/SLA antigen was obtained. ELISA, Western Blot and immunoprecipitation tests were developed and used to search for linear and conformational epitopes recognized by anti-SLA antibodies in sera from patients chronically infected by HCV. Anti-soluble liver antigen antibodies were found in sera from 10.4% of HCV-infected patients. The prevalence was significantly increased to 27% when anti-LKM1 was also present. Most anti-SLA reactivity was directed against conformational epitopes on the antigen. The means titers by ELISA were lower than those obtained in type 2 AIH. The result of autoantibody isotyping showed a subclass restriction to IgG1 and also IgG4. This study shows the presence of anti-SLA antibodies in approximately 10% of HCV infected patients. The prevalence of SLA autoantibodies in HCV infected patients increases when LKM1 autoantibodies are also present. The relationship between the prevalence of this characteristic autoimmune hepatitis autoantibody and the implication of an autoimmune phenomenon in the liver injury of patients chronically infected by HCV needs further investigation.

Independent, parallel pathways to CXCL10 induction in HCV-infected hepatocytes.

PubMed

Brownell, Jessica; Wagoner, Jessica; Lovelace, Erica S; Thirstrup, Derek; Mohar, Isaac; Smith, Wesley; Giugliano, Silvia; Li, Kui; Crispe, I Nicholas; Rosen, Hugo R; Polyak, Stephen J

2013-10-01

The pro-inflammatory chemokine CXCL10 is induced by HCV infection in vitro and in vivo, and is associated with outcome of IFN (interferon)-based therapy. We studied how hepatocyte sensing of early HCV infection via TLR3 (Toll-like receptor 3) and RIG-I (retinoic acid inducible gene I) led to expression of CXCL10. CXCL10, type I IFN, and type III IFN mRNAs and proteins were measured in PHH (primary human hepatocytes) and hepatocyte lines harboring functional or non-functional TLR3 and RIG-I pathways following HCV infection or exposure to receptor-specific stimuli. HuH7 human hepatoma cells expressing both TLR3 and RIG-I produced maximal CXCL10 during early HCV infection. Neutralization of type I and type III IFNs had no impact on virus-induced CXCL10 expression in TLR3+/RIG-I+ HuH7 cells, but reduced CXCL10 expression in PHH. PHH cultures were positive for monocyte, macrophage, and dendritic cell mRNAs. Immunodepletion of non-parenchymal cells (NPCs) eliminated marker expression in PHH cultures, which then showed no IFN requirement for CXCL10 induction during HCV infection. Immunofluorescence studies also revealed a positive correlation between intracellular HCV Core and CXCL10 protein expression (r(2) = 0.88, p ≤ 0.001). While CXCL10 induction in hepatocytes during the initial phase of HCV infection is independent of hepatocyte-derived type I and type III IFNs, NPC-derived IFNs contribute to CXCL10 induction during HCV infection in PHH cultures. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Genetic variations of the NPC1L1 gene associated with hepatitis C virus (HCV) infection and biochemical characteristics of HCV patients in China.

PubMed

Zhang, A-Mei; Zhang, Cheng-Lin; Song, Yuzhu; Zhao, Ping; Feng, Yue; Wang, Binghui; Li, Zheng; Liu, Li; Xia, Xueshan

2016-12-01

About 2% of the world population is infected with hepatitis C virus (HCV), a leading cause of hepatic cirrhosis and hepatocellular carcinoma. The Niemann-Pick C1-like 1 cholesterol absorption receptor (NPC1L1) was recently identified to be an important factor for HCV entry into host cells. Whether genetic variations of the NPC1L1 gene are associated with HCV infection is unknown. In this study, five single nucleotide polymorphisms (SNPs) of the NPC1L1 gene were analyzed in 261 HCV-infected individuals and 265 general controls from Yunnan Province, China. No significant differences were identified in genotypes or alleles of the SNPs between the two groups. After constructing haplotypes based on the five SNPs, a significant difference between HCV-infected individuals and general controls was shown for two haplotypes. Haplotype GCCTT appeared to be a protective factor and haplotype GCCCT was a risk factor for HCV-infected individuals. Genotypes of four SNPs correlated with biochemical characteristics of HCV-infected persons. Genotypes of SNPs rs799444 and rs2070607 were correlated with total bilirubin. Genotype TT of rs917098 was a risk factor for the gamma-glutamyltransferase level. Furthermore, HCV-infected individuals carrying genotype GG of rs41279633 showed statistically higher gamma-glutamyltransferase levels than HCV-infected persons with GT and TT. The results of this study identified the association between genetic susceptibility of the NPC1L1 gene and HCV infection, as well as biochemical characteristics of HCV-infected persons in Yunnan, China. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Incidence of recent HCV infection among persons seeking voluntary counselling and testing for HIV and sexually transmitted infections in Taiwan.

PubMed

Su, Yi-Ching; Liu, Wen-Chun; Chang, Lan-Hsin; Wu, Pei-Ying; Luo, Yu-Zhen; Wu, Cheng-Hsin; Sun, Hsin-Yun; Chang, Sui-Yuan; Hung, Chien-Ching

2014-01-01

The incidence of recent hepatitis C virus infection (HCV) infection has been noted to be increasing among men who have sex with men (MSM), especially those with HIV infection, in several resource-rich settings. In Taiwan, the incidence of recent HCV infection increased from 0 in 1994-2000, 2.29 in 2001-2005 to 10.13 per 1000 person-years of follow-up (PYFU) in 2006-2010. In this study, we aimed to estimate the incidence rate of recent HCV infection among those individuals who sought voluntary counselling and testing (VCT) service at a University Hospital. Between May 2006 and December 2013, 18,246 tests for HIV antibody were performed among 12,143 individuals at the VCT services. A total of 2157 clients without HIV or HCV infection at baseline were included for estimation of incidence rate of recent HCV infection. Antibodies to HCV were determined with a third-generation enzyme immunoassay. A nested case-control study with four matched controls without HCV seroconversion for one HCV seroconverter was conducted to investigate the factors associated with recent HCV infection. Phylogenetic analysis was performed among the HCV strains obtained from VCT clients and patients coinfected with HIV and HCV between 2006 and 2013. During the study period, 2157 clients received a total of 8260 tests. The HCV seroprevalence at baseline was 0.3%. Of the 2150 HCV-negative clients who contributed 5074.99 PYFU, 17 developed HCV seroconversion (incidence rate, 3.35 per 1000 PYFU; 95% CI, 1.76-4.94); the rate increased from 2.28 per 1000 PYFU (95% CI, 0.05-4.51) in 2006-2009, to 3.33 per 1000 PYFU (95% CI, 0.86-5.80) in 2010-2011, to 4.94 per 1000 PYFU (95% CI, 0.99-8.99) in 2012-2013. In case-control study, HCV seroconverters were more likely to have HIV-infected partners, recent syphilis and a Rapid Plasma Reagin (RPR) titre of 4 or greater. In multivariate analysis, having HIV-infected partners remained as the only independent associated factors with HCV seroconversion (AOR, 6

[Occult hepatitis B virus infection in normal population, Xiamen].

PubMed

He, Shuizhen; Su, Chenghao; Shen, Litong; Niu, Jianjun

2015-02-01

To investigate the prevalence of occult HBV infection in the normal population in Xiamen. 4 437 registered permanent residents, aged 1-59 years old, were selected in Xiamen using stratified random sampling method from September to October in 2006. Serum samples were obtained, the basic characteristics, inoculation of HBV vaccine, and liver disease were surveyed. The serum samples were tested five HBV seroimmunological markers. The HBsAg-negative specimens were subjected to HBV-DNA detection by nested PCR targeting for multiple gene segments. The amplified products were sequenced and the sequence was used for determination of HBV genotype and mutation analysis of amino acids located in HBsAg "a" epitope. Subjects with serum detectable HBV-DNA and negative result of HBsAg were considered as occult HBV infection. Among the 4 437 subjects, 482 individuals were observed HBsAg positive and 3 944 were observed negative. Of the 3 955 HBsAg- negative specimens, 27 occult HBV infections were determined with the positive rate of 0.68% (27/3 955). There were 16 samples with genotype B and 11 with genotype C. 3 types of amino acid (AA) mutation (M133T, T140I, G145R) that influence "a" epitope conformation were observed in 9 subjects with occult HBV infection. S region was successfully sequenced in 312 of the 482 HBsAg positive samples. In subjects with occult HBV infection, the infection rate of genotype C HBV (40.74%, 11/27), inoculation rate of HBV vaccine (62.96%, 17/27), positive rate of HBsAb (51.85%, 14/27), and mutation rate of critical amino acid of "a" epitope (33.33%, 9/27) were higher than HBsAg positive individuals (22.76% (71/312), 13.78% (43/312),0.32% (1/312),0.99% (31/312), respectively), and all the difference were significant (χ(2) = 4.29, 41.26, 156.00, 13.07, respectively, and P value = 0.038, <0.001, <0.001, <0.001, respectively). While the average age in subjects with occult HBV infection (18.3 ± 16.2) were lower than that in HBsAg positive infection (34

Statin Utilization and Recommendations Among HIV- and HCV-infected Veterans: A Cohort Study

PubMed Central

Clement, Meredith E.; Park, Lawrence P.; Navar, Ann Marie; Okeke, Nwora Lance; Pencina, Michael J.; Douglas, Pamela S.; Naggie, Susanna

2016-01-01

Background. Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections are associated with increased risk of cardiovascular disease (CVD). The potential impact of recently updated cholesterol guidelines on treatment of HIV- and HCV-infected veterans is unknown. Methods. We performed a retrospective cohort study to assess statin use and recommendations among 13 579 HIV-infected, 169 767 HCV-infected, and 6628 HIV/HCV-coinfected male veterans aged 40–75 years. Prior 2004 Adult Treatment Panel (ATP-III) guidelines were compared with current 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines and 2014 US Department of Veterans Affairs (VA)/US Department of Defense (DoD) joint clinical practice guidelines using laboratory, medication, and comorbidity data from the VA Clinical Case Registry from 2008 through 2010. Results. Using risk criteria delineated by the ATP-III guidelines, 50.6% of HIV-infected, 45.9% of HCV-infected, and 33.8% of HIV/HCV-coinfected veterans had an indication for statin therapy. However, among those eligible, 22.7%, 30.5%, and 31.5%, respectively, were not receiving ATP-III recommended statin therapy. When current cholesterol guidelines were applied by VA/DoD and ACC/AHA criteria, increases in recommendations for statins were found in all groups (57.3% and 66.1% of HIV-infected, 64.4% and 73.7% of HCV-infected, 49.1% and 58.5% of HIV/HCV-coinfected veterans recommended). Conclusions. Statins were underutilized among veterans infected with HIV, HCV, and HIV/HCV according to previous ATP-III guidelines. Current VA/DoD and ACC/AHA guidelines substantially expand statin recommendations and widen the gap of statin underutilization in all groups. These gaps in care present an opportunity to improve CVD prevention efforts in these at-risk populations. PMID:27143663

Persistence of Circulating Hepatitis C Virus Antigens-Specific Immune Complexes in Patients with Resolved HCV Infection.

PubMed

Hu, Ke-Qin; Cui, Wei

2018-05-01

Our recent study indicated the possible presence of detectable hepatitis C virus antigens (HCV-Ags) after denaturation of sera with resolved HCV (R-HCV) infection. The present study determined and characterized persistent HCV-Ags-specific immune complexes (ICs) in these patients. Sixty-eight sera with R-HCV and 34 with viremic HCV (V-HCV) infection were tested for free and IC-bound HCV-Ags using HCV-Ags enzyme immunoassay (EIA), the presence of HCV-Ags-specific ICs by immunoprecipitation and Western blot (IP-WB), HCV ICs containing HCV virions using IP and HCV RNA RT-PCR, and correlation of HCV ICs with clinical presentation in these patients. Using HCV-Ags EIA, we found 57.4% of sera with R-HCV infection were tested positive for bound, but not free HCV-Ags. Using pooled or individual anti-HCV E1/E2, cAg, NS3, NS4b, and/or NS5a to precipitate HCV-specific-Ags, we confirmed persistent HCV-Ags ICs specific to various HCV structural and non-structural proteins not only in V-HCV infection, but also in R-HCV infection. Using IP and HCV RNA PCR, we then confirmed the presence of HCV virions within circulating ICs in V-HCV, but not in R-HCV sera. Multivariable analysis indicated significant and independent associations of persistent circulating HCV-Ags-specific ICs with both age and the presence of cirrhosis in patients with R-HCV infection. Various HCV-Ag-specific ICs, but not virions, persist in 57.4% of patients who had spontaneous or treatment-induced HCV clearance for 6 months to 20 years. These findings enriched our knowledge on HCV pathogenesis and support further study on its long-term clinical relevance, such as extrahepatic manifestation, transfusion medicine, and hepatocarcinogenesis.

The management of HCV-infected pregnant women.

PubMed

Valladares, Guillermo; Chacaltana, Alfonso; Sjogren, Maria H

2010-01-01

Hepatitis C is, at present, a worldwide health problem and is the most common cause of liver transplantation. Its prevalence in pregnant women is similar to that of the general population. In the absence of cirrhosis and portal hypertension, most HCV-infected pregnant women do not have obstetric complications. Screening of pregnant women that are asymptomatic and do not have risk factors is not cost effective. A high hepatitis C viral load reportedly increases vertical transmission and is higher in women who are coinfected with HIV or who are intravenous drug users. Prolonged rupture of the membrane for more than 6 h, amniocentesis, and perineal lacerations increase the potential risk of perinatal transmission. Although the hepatitis C virus can be transmitted intrapartum, prevention by caesarean delivery is not generally indicated. The HCV virus can be found in maternal milk; however, breast feeding is not contraindicated. In conclusion, there are no antiviral treatment recommendations for HCV-infected women during pregnancy, or guidelines for the prevention of vertical transmission.

Statin Utilization and Recommendations Among HIV- and HCV-infected Veterans: A Cohort Study.

PubMed

Clement, Meredith E; Park, Lawrence P; Navar, Ann Marie; Okeke, Nwora Lance; Pencina, Michael J; Douglas, Pamela S; Naggie, Susanna

2016-08-01

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections are associated with increased risk of cardiovascular disease (CVD). The potential impact of recently updated cholesterol guidelines on treatment of HIV- and HCV-infected veterans is unknown. We performed a retrospective cohort study to assess statin use and recommendations among 13 579 HIV-infected, 169 767 HCV-infected, and 6628 HIV/HCV-coinfected male veterans aged 40-75 years. Prior 2004 Adult Treatment Panel (ATP-III) guidelines were compared with current 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines and 2014 US Department of Veterans Affairs (VA)/US Department of Defense (DoD) joint clinical practice guidelines using laboratory, medication, and comorbidity data from the VA Clinical Case Registry from 2008 through 2010. Using risk criteria delineated by the ATP-III guidelines, 50.6% of HIV-infected, 45.9% of HCV-infected, and 33.8% of HIV/HCV-coinfected veterans had an indication for statin therapy. However, among those eligible, 22.7%, 30.5%, and 31.5%, respectively, were not receiving ATP-III recommended statin therapy. When current cholesterol guidelines were applied by VA/DoD and ACC/AHA criteria, increases in recommendations for statins were found in all groups (57.3% and 66.1% of HIV-infected, 64.4% and 73.7% of HCV-infected, 49.1% and 58.5% of HIV/HCV-coinfected veterans recommended). Statins were underutilized among veterans infected with HIV, HCV, and HIV/HCV according to previous ATP-III guidelines. Current VA/DoD and ACC/AHA guidelines substantially expand statin recommendations and widen the gap of statin underutilization in all groups. These gaps in care present an opportunity to improve CVD prevention efforts in these at-risk populations. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Diagnosis and monitoring of HCV infection using the cobas® HCV test for use on the cobas® 6800/8800 systems.

PubMed

Yao, Joseph D; Young, Stephen; Heilek, Gabrielle M; Marino, Enrique; Paxinos, Ellen E; Marins, Ed G; Valsamakis, Alexandra

2018-05-01

Accurate, sensitive, and specific tests for detection and monitoring of hepatitis C virus (HCV) RNA concentrations are essential for diagnosis and management of HCV infections. We evaluated the next-generation reverse-transcription real-time PCR test, cobas ® HCV test for use with the cobas ® 6800/8800 systems ("cobas HCV") by determining its analytical performance characteristics and clinical utility for the diagnosis and therapeutic monitoring of chronic HCV infections. The limit of detection (LOD), linearity, precision, specificity, matrix equivalence of plasma and serum, and quantitative agreement with the COBAS ® AmpliPrep/COBAS ® TaqMan ® HCV Test version 2.0 ("CAP/CTM HCV v2") were evaluated. Clinical utility for the diagnosis of chronic HCV infection was demonstrated by testing plasma from HCV seropositive individuals and comparing results to a nucleic acid amplification test (NAAT) approved for use in the diagnosis of chronic hepatitis C. Clinical specificity was investigated by testing plasma from HCV antibody negative subjects with non-HCV related liver diseases. Utility for monitoring treatment response was defined by testing plasma collected during treatment of HCV genotypes (GT) 1, 2, and 3 and determining positive predictive value (PPV), negative predictive value (NPV) and the odds ratio (OR) for predicting cure (sustained virologic response 12 weeks after treatment cessation, "SVR12"). The cobas HCV test demonstrated an LOD of at least 15 IU/mL and measurable range from 15 to at least 1.0E + 08 IU/mL (1.2-8.0 log 10 IU/mL) for GT 1-6, with high accuracy (≤0.16 log 10 difference) and precision (standard deviation 0.04-0.14 log 10 ) throughout the linear range. Paired plasma and serum samples showed highly correlated performance (R 2  = 0.97). Quantification was 100% specific for HCV in analytical studies. Correlation with CAP/CTM HCV v2 was high in patient samples (mean titer difference: 0.05 log 10 with a 95% CI: 0.03-0.06 log 10

gC1qR expression in chimpanzees with resolved and chronic infection: Potential role of HCV core/gC1qR-mediated T cell suppression in the outcome of HCV infection

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

Yao Zhiqang; Shata, Mohamed Tarek; Tricoche, Nancy

2006-03-15

Chimpanzee is a unique animal model for HCV infection, in which about 50% of infections resolve spontaneously. It has been reported that the magnitude of T cell responses to HCV core in recovered chimpanzees is greater than that in chronically infected ones. However, the mechanism(s) by which the chimpanzees with resolved infection overcome core-mediated immunosuppression remains unknown. In this study, we examined the effect of HCV core on T cell responsiveness in chimpanzees with resolved and chronic HCV infection. We found that core protein strongly inhibited T cell activation and proliferation in chimpanzees with chronic infection, while this inhibition wasmore » limited in chimpanzees with resolved infection. Notably, the level of gC1qR, as well as the binding of core protein, on the surface of T cells was lower in recovered chimpanzees when compared to chimpanzees with chronic HCV infection. Intriguingly, the observed differences in gC1qR expression levels and susceptibility to core-induced suppression amongst HCV-chronically infected and recovered chimpanzees were observed prior to HCV challenge, suggesting a possible genetic determination of the outcome of infection. These findings suggest that gC1qR expression on the surface of T cells is crucial for HCV core-mediated T cell suppression and viral clearance, and that represents a novel mechanism by which a virus usurps host machinery for persistence.« less

HCV Genotyping from NGS Short Reads and Its Application in Genotype Detection from HCV Mixed Infected Plasma

PubMed Central

Qiu, Ping; Stevens, Richard; Wei, Bo; Lahser, Fred; Howe, Anita Y. M.; Klappenbach, Joel A.; Marton, Matthew J.

2015-01-01

Genotyping of hepatitis C virus (HCV) plays an important role in the treatment of HCV. As new genotype-specific treatment options become available, it has become increasingly important to have accurate HCV genotype and subtype information to ensure that the most appropriate treatment regimen is selected. Most current genotyping methods are unable to detect mixed genotypes from two or more HCV infections. Next generation sequencing (NGS) allows for rapid and low cost mass sequencing of viral genomes and provides an opportunity to probe the viral population from a single host. In this paper, the possibility of using short NGS reads for direct HCV genotyping without genome assembly was evaluated. We surveyed the publicly-available genetic content of three HCV drug target regions (NS3, NS5A, NS5B) in terms of whether these genes contained genotype-specific regions that could predict genotype. Six genotypes and 38 subtypes were included in this study. An automated phylogenetic analysis based HCV genotyping method was implemented and used to assess different HCV target gene regions. Candidate regions of 250-bp each were found for all three genes that have enough genetic information to predict HCV genotypes/subtypes. Validation using public datasets shows 100% genotyping accuracy. To test whether these 250-bp regions were sufficient to identify mixed genotypes, we developed a random primer-based method to sequence HCV plasma samples containing mixtures of two HCV genotypes in different ratios. We were able to determine the genotypes without ambiguity and to quantify the ratio of the abundances of the mixed genotypes in the samples. These data provide a proof-of-concept that this random primed, NGS-based short-read genotyping approach does not need prior information about the viral population and is capable of detecting mixed viral infection. PMID:25830316

Is diabetes mellitus a risk factor for HCV infection?

PubMed

Picerno, I; Di Pietro, A; Spataro, P; Di Benedetto, A; Romano, G; Scoglio, M E

2002-01-01

The aim of this study was to investigate whether or not the diabetes mellitus may be considered a risk factor for the HCV infection. The HCV seroprevalence was evaluated in 254 diabetic subjects, whose anamnestic data and risk factors are known, in comparison to 223 first-time blood donors, carefully age- and gender-matched. The statistical analysis showed that the studied groups belonged to the same population (Mann-Whitney U test) and that there were no significant differences between cases and controls as regards HCV prevalence (Yates corrected chi 2 test). The obtained data underline the importance of the control group selection, especially in the studies considering age-related pathologies. The authors disprove type 2 diabetes as a risk factor for the HCV infection and consider that this is a valid hypothesis only when the hepatitis C was unknown and not adequate prevention was used.

Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection.

PubMed

Bourlière, Marc; Gordon, Stuart C; Flamm, Steven L; Cooper, Curtis L; Ramji, Alnoor; Tong, Myron; Ravendhran, Natarajan; Vierling, John M; Tran, Tram T; Pianko, Stephen; Bansal, Meena B; de Lédinghen, Victor; Hyland, Robert H; Stamm, Luisa M; Dvory-Sobol, Hadas; Svarovskaia, Evguenia; Zhang, Jie; Huang, K C; Subramanian, G Mani; Brainard, Diana M; McHutchison, John G; Verna, Elizabeth C; Buggisch, Peter; Landis, Charles S; Younes, Ziad H; Curry, Michael P; Strasser, Simone I; Schiff, Eugene R; Reddy, K Rajender; Manns, Michael P; Kowdley, Kris V; Zeuzem, Stefan

2017-06-01

Patients who are chronically infected with hepatitis C virus (HCV) and who do not have a sustained virologic response after treatment with regimens containing direct-acting antiviral agents (DAAs) have limited retreatment options. We conducted two phase 3 trials involving patients who had been previously treated with a DAA-containing regimen. In POLARIS-1, patients with HCV genotype 1 infection who had previously received a regimen containing an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive either the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the protease inhibitor voxilaprevir (150 patients) or matching placebo (150 patients) once daily for 12 weeks. Patients who were infected with HCV of other genotypes (114 patients) were enrolled in the sofosbuvir-velpatasvir-voxilaprevir group. In POLARIS-4, patients with HCV genotype 1, 2, or 3 infection who had previously received a DAA regimen but not an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir-voxilaprevir (163 patients) or sofosbuvir-velpatasvir (151 patients) for 12 weeks. An additional 19 patients with HCV genotype 4 infection were enrolled in the sofosbuvir-velpatasvir-voxilaprevir group. In the three active-treatment groups, 46% of the patients had compensated cirrhosis. In POLARIS-1, the rate of sustained virologic response was 96% with sofosbuvir-velpatasvir-voxilaprevir, as compared with 0% with placebo. In POLARIS-4, the rate of response was 98% with sofosbuvir-velpatasvir-voxilaprevir and 90% with sofosbuvir-velpatasvir. The most common adverse events were headache, fatigue, diarrhea, and nausea. In the active-treatment groups in both trials, the percentage of patients who discontinued treatment owing to adverse events was 1% or lower. Sofosbuvir-velpatasvir-voxilaprevir taken for 12 weeks provided high rates of sustained virologic response among patients across HCV genotypes in whom treatment with a DAA regimen

CD8+ T cells of chronic HCV-infected patients express multiple negative immune checkpoints following stimulation with HCV peptides.

PubMed

Barathan, Muttiah; Mohamed, Rosmawati; Vadivelu, Jamuna; Chang, Li Yen; Vignesh, Ramachandran; Krishnan, Jayalakshmi; Sigamani, Panneer; Saeidi, Alireza; Ram, M Ravishankar; Velu, Vijayakumar; Larsson, Marie; Shankar, Esaki M

2017-03-01

Hepatitis C virus (HCV)-specific CD4+ and CD8+ T cells are key to successful viral clearance in HCV disease. Accumulation of exhausted HCV-specific T cells during chronic infection results in considerable loss of protective functional immune responses. The role of T-cell exhaustion in chronic HCV disease remains poorly understood. Here, we studied the frequency of HCV peptide-stimulated T cells expressing negative immune checkpoints (PD-1, CTLA-4, TRAIL, TIM-3 and BTLA) by flow cytometry, and measured the levels of Th1/Th2/Th17 cytokines secreted by T cells by a commercial Multi-Analyte ELISArray™ following in vitro stimulation of T cells using HCV peptides and phytohemagglutinin (PHA). HCV peptide-stimulated CD4+ and CD8+ T cells of chronic HCV (CHC) patients showed significant increase of CTLA-4. Furthermore, HCV peptide-stimulated CD4+ T cells of CHC patients also displayed relatively higher levels of PD-1 and TRAIL, whereas TIM-3 was up-regulated on HCV peptide-stimulated CD8+ T cells. Whereas the levels of IL-10 and TGF-β1 were significantly increased, the levels of pro-inflammatory cytokines IL-2, TNF-α, IL-17A and IL-6 were markedly decreased in the T cell cultures of CHC patients. Chronic HCV infection results in functional exhaustion of CD4+ and CD8+ T cells likely contributing to viral persistence. Copyright © 2016 Elsevier Inc. All rights reserved.

Discovery of Cellular Proteins Required for the Early Steps of HCV Infection Using Integrative Genomics

PubMed Central

Yang, Jae-Seong; Kwon, Oh Sung; Kim, Sanguk; Jang, Sung Key

2013-01-01

Successful viral infection requires intimate communication between virus and host cell, a process that absolutely requires various host proteins. However, current efforts to discover novel host proteins as therapeutic targets for viral infection are difficult. Here, we developed an integrative-genomics approach to predict human genes involved in the early steps of hepatitis C virus (HCV) infection. By integrating HCV and human protein associations, co-expression data, and tight junction-tetraspanin web specific networks, we identified host proteins required for the early steps in HCV infection. Moreover, we validated the roles of newly identified proteins in HCV infection by knocking down their expression using small interfering RNAs. Specifically, a novel host factor CD63 was shown to directly interact with HCV E2 protein. We further demonstrated that an antibody against CD63 blocked HCV infection, indicating that CD63 may serve as a new therapeutic target for HCV-related diseases. The candidate gene list provides a source for identification of new therapeutic targets. PMID:23593195

Preserved MHC-II antigen processing and presentation function in chronic HCV infection

PubMed Central

DH, Canaday; CJ, Burant; L, Jones; H, Aung; L, Woc-Colburn; DD, Anthony

2010-01-01

Individuals with chronic HCV infection have impaired response to vaccine, though the etiology remains to be elucidated. Dendritic cells (DC) and monocytes (MN) provide antigen uptake, processing, presentation, and costimulatory functions necessary to achieve optimal immune responses. The integrity of antigen processing and presentation function within these antigen presenting cells (APC) in the setting of HCV infection has been unclear. We used a novel T cell hybridoma system that specifically measures MHC-II antigen processing and presentation function of human APC. Results demonstrate MHC-II antigen processing and presentation function is preserved in both myeloid DC (mDC) and MN in the peripheral blood of chronically HCV-infected individuals, and indicates that an alteration in this function does not likely underlie the defective HCV-infected host response to vaccination. PMID:21055734

Identification and Linkage to Care of HCV-Infected Persons in Five Health Centers - Philadelphia, Pennsylvania, 2012-2014.

PubMed

Coyle, Catelyn; Viner, Kendra; Hughes, Elizabeth; Kwakwa, Helena; Zibbell, Jon E; Vellozzi, Claudia; Holtzman, Deborah

2015-05-08

Approximately three million persons in the United States are infected with hepatitis C virus (HCV), a blood-borne pathogen that is an increasing cause of liver disease and mortality in the United States. Treatments for HCV are curative, of short duration, and have few associated side effects, increasing the importance of identifying HCV-infected persons. Many persons with HCV infection were infected decades ago, before implementation of prevention measures and most are unaware of their infection, regardless of when it occurred. Most newly diagnosed cases are associated with injection drug use. Persons born during 1945-1965 have a fivefold higher risk of HCV infection than other adults and the highest risk for HCV-related morbidity and mortality. CDC recommends testing for this group, for persons who inject drugs, and others at risk for HCV infection. From October 2012 through July 2014, the National Nursing Centers Consortium (NNCC) carried out a project to integrate routine HCV testing and linkage-to-care in five federally qualified health centers in Philadelphia, PA, that primarily serve homeless persons and public housing residents. During the project period, 4,514 patients across the five centers were tested for HCV. Of these, 595 (13.2%) were HCV-antibody positive and 550 (92.4%) had a confirmatory HCV-RNA test performed. Of those who had a confirmatory HCV-RNA test performed, 390 (70.9%) were identified as having current (i.e., chronic) HCV infection (overall prevalence = 8.6%). Of those currently infected with HCV, 90% were informed of their status, 78% were referred to an HCV care specialist, and 62% went to the referred specialist for care. Replicable system modifications that improved HCV testing and care included enhancements to electronic medical records (EMRs), simplification of HCV testing protocols, and addition of a linkage-to-care coordinator. Findings from this project highlight the need for innovative strategies for HCV testing, care, and

HCV Core Antigen Testing for Diagnosis of HCV Infection: A systematic review and meta-analysis

PubMed Central

Freiman, J. Morgan; Tran, Trang M.; Schumacher, Samuel G; White, Laura F.; Ongarello, Stefano; Cohn, Jennifer; Easterbrook, Philippa J.; Linas, Benjamin P.; Denkinger, Claudia M.

2017-01-01

Background Diagnosis of chronic Hepatitis C Virus (HCV) infection requires both a positive HCV antibody screen and confirmatory nucleic acid test (NAT). HCV core antigen (HCVcAg) is a potential alternative to NAT. Purpose This systematic review evaluated the accuracy of diagnosis of active HCV infection among adults and children for five HCVcAg tests compared to NAT. Data Sources EMBASE, PubMed, Web of Science, Scopus, and Cochrane from 1990 through March 31, 2016. Study Selection Cohort, cross-sectional, and randomized controlled trials were included without language restriction Data Extraction Two independent reviewers extracted data and assessed quality using an adapted Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Data Synthesis 44 studies evaluated 5 index tests. Studies for the ARCHITECT had the highest quality, while those for Ortho ELISA were the lowest. From bivariate analyses, the sensitivity and specificity with 95% CI were: ARCHITECT 93.4% (90.1, 96.4) and 98.8% (97.4, 99.5), Ortho ELISA 93.2% (81.6, 97.7) and 99.2% (87.9, 100), and Hunan Jynda 59.5% (46.0, 71.7) and 82.9% (58.6, 94.3). Insufficient data were available for a meta-analysis for Lumipulse and Lumispot. In three quantitative studies using ARCHITECT, HCVcAg correlated closely with HCV RNA above 3000 IU/mL. Limitations There was insufficient data on covariates such as HIV or HBV status for sub-group analyses. Few studies reported genotypes of isolates and there were scant data for genotypes 4, 5, and 6. Most studies were conducted in high resource settings within reference laboratories. Conclusions HCVcAg assays with signal amplification have high sensitivity, high specificity, and good correlation with HCV RNA above 3000 IU/mL. HCVcAg assays have the potential to replace NAT in high HCV prevalence settings. PMID:27322622

Proteome Analysis of Liver Cells Expressing a Full- Length Hepatitis C Virus (HCV) Replicon and Biopsy Specimens of Posttransplantation Liver from HCV-Infected Patients

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

Jacobs, Jon M.; Diamond, Deborah L.; Chan, Eric Y.

2005-06-01

The development of a reproducible model system for the study of Hepatitis C virus (HCV) infection has the potential to significantly enhance the study of virus-host interactions and provide future direction for modeling the pathogenesis of HCV. While there are studies describing global gene expression changes associated with HCV infection, changes in the proteome have not been characterized. We report the first large scale proteome analysis of the highly permissive Huh-7.5 cell line containing a full length HCV replicon. We detected > 4,400 proteins in this cell line, including HCV replicon proteins, using multidimensional liquid chromatographic (LC) separations coupled tomore » mass spectrometry (MS). The set of Huh-7.5 proteins confidently identified is, to our knowledge, the most comprehensive yet reported for a human cell line. Consistent with the literature, a comparison of Huh-7.5 cells (+) and (-) the HCV replicon identified expression changes of proteins involved in lipid metabolism. We extended these analyses to liver biopsy material from HCV-infected patients where > 1,500 proteins were detected from 2 {micro}g protein lysate using the Huh-7.5 protein database and the accurate mass and time (AMT) tag strategy. These findings demonstrate the utility of multidimensional proteome analysis of the HCV replicon model system for assisting the determination of proteins/pathways affected by HCV infection. Our ability to extend these analyses to the highly complex proteome of small liver biopsies with limiting protein yields offers the unique opportunity to begin evaluating the clinical significance of protein expression changes associated with HCV infection.« less

Multispecific T cell response and negative HCV RNA tests during acute HCV infection are early prognostic factors of spontaneous clearance

PubMed Central

Spada, E; Mele, A; Berton, A; Ruggeri, L; Ferrigno, L; Garbuglia, A R; Perrone, M P; Girelli, G; Del Porto, P; Piccolella, E; Mondelli, M U; Amoroso, P; Cortese, R; Nicosia, A; Vitelli, A; Folgori, A

2004-01-01

Background/Aims: Hepatitis C virus (HCV) infection results in a high frequency of chronic disease. The aim of this study was to identify early prognostic markers of disease resolution by performing a comprehensive analysis of viral and host factors during the natural course of acute HCV infection. Methods: The clinical course of acute hepatitis C was determined in 34 consecutive patients. Epidemiological and virological parameters, as well as cell mediated immunity (CMI) and distribution of human leukocyte antigens (HLA) alleles were analysed. Results: Ten out of 34 patients experienced self-limiting infection, with most resolving patients showing fast kinetics of viral clearance: at least one negative HCV RNA test during this phase predicted a favourable outcome. Among other clinical epidemiological parameters measured, the self-limiting course was significantly associated with higher median peak bilirubin levels at the onset of disease, and with the female sex, but only the latter parameter was independently associated after multivariate analysis. No significant differences between self-limiting or chronic course were observed for the distribution of DRB1 and DQB1 alleles. HCV specific T cell response was more frequently detected during acute HCV infection, than in patients with chronic HCV disease. A significantly broader T cell response was found in patients with self-limiting infection than in those with chronic evolving acute hepatitis C. Conclusion: The results suggest that host related factors, in particular sex and CMI, play a crucial role in the spontaneous clearance of this virus. Most importantly, a negative HCV RNA test and broad CMI within the first month after onset of the symptoms represent very efficacious predictors of viral clearance and could thus be used as criteria in selecting candidates for early antiviral treatment. PMID:15479691

HCV viraemia in anti-HCV-negative haemodialysis patients: Do we need HCV RNA detection test?

PubMed

Papadopoulos, Nikolaos; Griveas, Ioannis; Sveroni, Eirini; Argiana, Vasiliki; Kalliaropoulos, Antonios; Martinez-Gonzalez, Beatriz; Deutsch, Melanie

2018-03-01

Hepatitis C virus (HCV) infection is still common among dialysis patients, but the natural history of HCV in this group is not completely understood. The KDIGO HCV guidelines of 2009 recommend that chronic haemodialysis patients be screened for HCV antibody upon admission to the dialysis clinic and every 6 months thereafter if susceptible to HCV infection. However, previous studies have shown the presence of HCV viraemia in anti-HCV-negative haemodialysis patients as up to 22%. To evaluate the presence of HCV viraemia, using HCV RNA detection, among anti-HCV-negative haemodialysis patients from a tertiary dialysis unit in Athens. We enrolled 41 anti-HCV-negative haemodialysis patients diagnosed with third-generation enzyme immunoassay. HCV viraemia was evaluated using a sensitive (cut-off: 12 IU/mL) reverse transcriptase polymerase chain reaction (COBAS AmpliPrep/TaqMan system) for HCV RNA. None of the 41 anti-HCV-negative haemodialysis patients were shown to be viraemic. Routine HCV RNA testing appears not to be necessary in anti-HCV-negative haemodialysis patients.

Exosomes from Hepatitis C Infected Patients Transmit HCV Infection and Contain Replication Competent Viral RNA in Complex with Ago2-miR122-HSP90

PubMed Central

Kodys, Karen; Bala, Shashi; Szabo, Gyongyi

2014-01-01

Antibodies targeting receptor-mediated entry of HCV into hepatocytes confer limited therapeutic benefits. Evidence suggests that exosomes can transfer genetic materials between cells; however, their role in HCV infection remains obscure. Here, we show that exosomes isolated from sera of chronic HCV infected patients or supernatants of J6/JFH1-HCV-infected Huh7.5 cells contained HCV RNA. These exosomes could mediate viral receptor-independent transmission of HCV to hepatocytes. Negative sense HCV RNA, indicative of replication competent viral RNA, was present in exosomes of all HCV infected treatment non-responders and some treatment-naïve individuals. Remarkably, HCV RNA was associated with Ago2, HSP90 and miR-122 in exosomes isolated from HCV-infected individuals or HCV-infected Huh7.5 cell supernatants. Exosome-loading with a miR-122 inhibitor, or inhibition of HSP90, vacuolar H+-ATPases, and proton pumps, significantly suppressed exosome-mediated HCV transmission to naïve cells. Our findings provide mechanistic evidence for HCV transmission by blood-derived exosomes and highlight potential therapeutic strategies. PMID:25275643

In vitro antigen-specific induction of IL-22 in human subjects that resolved HCV infection

PubMed Central

Cusick, Matthew F; Libbey, Jane E; Fujinami, Robert S; Eckels, David D

2012-01-01

Aims To determine if in vitro production of IL-22 and IL-17 correlated with resolution of HCV infection. Materials & methods Human peripheral blood cells isolated from a well-defined cohort of resolved and chronic HCV-infected subjects were used to measure HCV-, influenza- and mitogen-activated T-cell proliferation. In addition, IL-22 and IL-17 production was measured via ELISAs and flow cytometry. Results Resolved HCV subjects had a significantly higher T-cell proliferative response to recombinant NS3 protein compared with chronic HCV subjects. Resolved subjects had a dose-dependent IL-22 response to recombinant NS3 compared with chronic HCV subjects. Conclusion IL-22 production is associated with antigen-specific induction of CD4 + T cells in individuals that resolved HCV infection, suggesting a potential role for IL-22 in HCV clearance. PMID:23185211

Identification of a Novel Drug Lead That Inhibits HCV Infection and Cell-to-Cell Transmission by Targeting the HCV E2 Glycoprotein

DOE PAGES

Al Olaby, Reem R.; Cocquerel, Laurence; Zemla, Adam; ...

2014-10-30

We report that Hepatitis C Virus (HCV) infects 200 million individuals worldwide. Although several FDA approved drugs targeting the HCV serine protease and polymerase have shown promising results, there is a need for better drugs that are effective in treating a broader range of HCV genotypes and subtypes without being used in combination with interferon and/or ribavirin. Recently, two crystal structures of the core of the HCV E2 protein (E2c) have been determined, providing structural information that can now be used to target the E2 protein and develop drugs that disrupt the early stages of HCV infection by blocking E2’smore » interaction with different host factors. Using the E2c structure as a template, we have created a structural model of the E2 protein core (residues 421–645) that contains the three amino acid segments that are not present in either structure. Computational docking of a diverse library of 1,715 small molecules to this model led to the identification of a set of 34 ligands predicted to bind near conserved amino acid residues involved in the HCV E2: CD81 interaction. We used surface plasmon resonance detection to screen the ligand set for binding to recombinant E2 protein, and the best binders were subsequently tested to identify compounds that inhibit the infection of Huh-7 cells by HCV. One compound, 281816, blocked E2 binding to CD81 and inhibited HCV infection in a genotype-independent manner with IC50’s ranging from 2.2 µM to 4.6 µM. 281816 blocked the early and late steps of cell-free HCV entry and also abrogated the cell-to-cell transmission of HCV. Collectively the results obtained with this new structural model of E2c suggest the development of small molecule inhibitors such as 281816 that target E2 and disrupt its interaction with CD81 may provide a new paradigm for HCV treatment.« less

Identification of a Novel Drug Lead That Inhibits HCV Infection and Cell-to-Cell Transmission by Targeting the HCV E2 Glycoprotein

PubMed Central

Al Olaby, Reem R.; Cocquerel, Laurence; Zemla, Adam; Saas, Laure; Dubuisson, Jean; Vielmetter, Jost; Marcotrigiano, Joseph; Khan, Abdul Ghafoor; Catalan, Felipe Vences; Perryman, Alexander L.; Freundlich, Joel S.; Forli, Stefano; Levy, Shoshana; Balhorn, Rod; Azzazy, Hassan M.

2014-01-01

Hepatitis C Virus (HCV) infects 200 million individuals worldwide. Although several FDA approved drugs targeting the HCV serine protease and polymerase have shown promising results, there is a need for better drugs that are effective in treating a broader range of HCV genotypes and subtypes without being used in combination with interferon and/or ribavirin. Recently, two crystal structures of the core of the HCV E2 protein (E2c) have been determined, providing structural information that can now be used to target the E2 protein and develop drugs that disrupt the early stages of HCV infection by blocking E2’s interaction with different host factors. Using the E2c structure as a template, we have created a structural model of the E2 protein core (residues 421–645) that contains the three amino acid segments that are not present in either structure. Computational docking of a diverse library of 1,715 small molecules to this model led to the identification of a set of 34 ligands predicted to bind near conserved amino acid residues involved in the HCV E2: CD81 interaction. Surface plasmon resonance detection was used to screen the ligand set for binding to recombinant E2 protein, and the best binders were subsequently tested to identify compounds that inhibit the infection of Huh-7 cells by HCV. One compound, 281816, blocked E2 binding to CD81 and inhibited HCV infection in a genotype-independent manner with IC50’s ranging from 2.2 µM to 4.6 µM. 281816 blocked the early and late steps of cell-free HCV entry and also abrogated the cell-to-cell transmission of HCV. Collectively the results obtained with this new structural model of E2c suggest the development of small molecule inhibitors such as 281816 that target E2 and disrupt its interaction with CD81 may provide a new paradigm for HCV treatment. PMID:25357246

Identification of a novel drug lead that inhibits HCV infection and cell-to-cell transmission by targeting the HCV E2 glycoprotein.

PubMed

Al Olaby, Reem R; Cocquerel, Laurence; Zemla, Adam; Saas, Laure; Dubuisson, Jean; Vielmetter, Jost; Marcotrigiano, Joseph; Khan, Abdul Ghafoor; Vences Catalan, Felipe; Perryman, Alexander L; Freundlich, Joel S; Forli, Stefano; Levy, Shoshana; Balhorn, Rod; Azzazy, Hassan M

2014-01-01

Hepatitis C Virus (HCV) infects 200 million individuals worldwide. Although several FDA approved drugs targeting the HCV serine protease and polymerase have shown promising results, there is a need for better drugs that are effective in treating a broader range of HCV genotypes and subtypes without being used in combination with interferon and/or ribavirin. Recently, two crystal structures of the core of the HCV E2 protein (E2c) have been determined, providing structural information that can now be used to target the E2 protein and develop drugs that disrupt the early stages of HCV infection by blocking E2's interaction with different host factors. Using the E2c structure as a template, we have created a structural model of the E2 protein core (residues 421-645) that contains the three amino acid segments that are not present in either structure. Computational docking of a diverse library of 1,715 small molecules to this model led to the identification of a set of 34 ligands predicted to bind near conserved amino acid residues involved in the HCV E2: CD81 interaction. Surface plasmon resonance detection was used to screen the ligand set for binding to recombinant E2 protein, and the best binders were subsequently tested to identify compounds that inhibit the infection of Huh-7 cells by HCV. One compound, 281816, blocked E2 binding to CD81 and inhibited HCV infection in a genotype-independent manner with IC50's ranging from 2.2 µM to 4.6 µM. 281816 blocked the early and late steps of cell-free HCV entry and also abrogated the cell-to-cell transmission of HCV. Collectively the results obtained with this new structural model of E2c suggest the development of small molecule inhibitors such as 281816 that target E2 and disrupt its interaction with CD81 may provide a new paradigm for HCV treatment.

Identification of a Novel Drug Lead That Inhibits HCV Infection and Cell-to-Cell Transmission by Targeting the HCV E2 Glycoprotein

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

Al Olaby, Reem R.; Cocquerel, Laurence; Zemla, Adam

We report that Hepatitis C Virus (HCV) infects 200 million individuals worldwide. Although several FDA approved drugs targeting the HCV serine protease and polymerase have shown promising results, there is a need for better drugs that are effective in treating a broader range of HCV genotypes and subtypes without being used in combination with interferon and/or ribavirin. Recently, two crystal structures of the core of the HCV E2 protein (E2c) have been determined, providing structural information that can now be used to target the E2 protein and develop drugs that disrupt the early stages of HCV infection by blocking E2’smore » interaction with different host factors. Using the E2c structure as a template, we have created a structural model of the E2 protein core (residues 421–645) that contains the three amino acid segments that are not present in either structure. Computational docking of a diverse library of 1,715 small molecules to this model led to the identification of a set of 34 ligands predicted to bind near conserved amino acid residues involved in the HCV E2: CD81 interaction. We used surface plasmon resonance detection to screen the ligand set for binding to recombinant E2 protein, and the best binders were subsequently tested to identify compounds that inhibit the infection of Huh-7 cells by HCV. One compound, 281816, blocked E2 binding to CD81 and inhibited HCV infection in a genotype-independent manner with IC50’s ranging from 2.2 µM to 4.6 µM. 281816 blocked the early and late steps of cell-free HCV entry and also abrogated the cell-to-cell transmission of HCV. Collectively the results obtained with this new structural model of E2c suggest the development of small molecule inhibitors such as 281816 that target E2 and disrupt its interaction with CD81 may provide a new paradigm for HCV treatment.« less

Occult hepatitis B virus infection in hematopoietic stem cell donors in a hepatitis B virus endemic area.

PubMed

Hui, Chee-kin; Sun, Jian; Au, Wing-yan; Lie, Albert K W; Yueng, Yui-hung; Zhang, Hai-ying; Lee, Nikki P; Hou, Jin-ling; Liang, Raymond; Lau, George K K

2005-06-01

The acquisition of hepatitis B virus (HBV) infection following organ transplantation from donors with occult HBV infection is an important cause of morbidity and mortality. The aim of this study is to determine the prevalence of occult HBV in allogeneic hematopoietic stem cell (HSC) transplantation donors. We performed a retrospective study on 124 consecutive hepatitis B surface antigen negative HSC donors. Their serum samples were analyzed by PCR for the pre-S/S, pre-core/core and X regions of the virus. Samples reactive by at least two PCR assays were considered HBV-DNA positive. Nineteen of the 124 HSC donors (15.3%) had occult HBV infection. Sixteen of these 19 donors with occult HBV infection (84.2%) tested positive for hepatitis B core antibody while 78 of 105 subjects (74.3%) without occult HBV infection were also positive (P=0.56). Fourteen of the 19 donors (73.7%) with occult HBV infection tested positive for hepatitis B surface antibody while 67 of the 105 subjects without occult HBV infection were also positive (P=0.45). The prevalence of occult HBV infection among HSC donors in Hong Kong is high. Anti-HBc and anti-HBs status had no significant correlation with the presence of occult HBV infection.

HIV/HCV Co-infection, Liver Disease Progression, and Age-Related IGF-1 Decline.

PubMed

Quinn, Jeffrey; Astemborski, Jacquie; Mehta, Shruti H; Kirk, Gregory D; Thomas, David L; Balagopal, Ashwin

2017-01-01

We have previously reported that persons co-infected with HIV and hepatitis C virus (HCV) had liver disease stages similar to HIV-uninfected individuals who were approximately 10 years older. Insulin-like growth factor 1(IGF-1) levels have long been known to decline with advancing age in humans and non-humans alike. We examined whether HIV infection affects the expected decline in IGF-1 in persons with chronic hepatitis C virus (HCV) infection and if that alteration in IGF-1 decline contributes to the link between HIV, aging, and liver disease progression. A total of 553 individuals with HCV infection were studied from the AIDS Linked to the Intravenous Experience (ALIVE) cohort for whom more than 10 years of follow-up was available. Serum IGF-1 levels were determined by ELISA and evaluated according to baseline characteristics and over time by HIV status and liver disease progression. Linear regression with generalized estimating equations was used to determine whether IGF-1 decline over time was independently associated with liver disease progression. Baseline IGF-1 levels were strongly associated with age ( P < 0.0001) but not with gender or HIV infection. Levels of IGF-1 declined at a rate of -1.75 ng/mL each year in HCV mono-infected individuals and at a rate of -1.23 ng/mL each year in HIV/HCV co-infected individuals ( P < 0.05). In a multivariable linear regression model, progression of liver fibrosis was associated with HIV infection and age, as well as with a slower rate of IGF-1 decline ( P = 0.001); however, the rate of IGF-1 decline did not alter the strength of the associations between HIV, liver disease, and age. The normal decline in IGF-1 levels with age was attenuated in HIV/HCV co-infected individuals compared to those with HCV mono-infection, and slower IGF-1 decline was independently associated with liver disease progression.

Seroprevalence of HBV, HCV & HIV co-infection and risk factors analysis in Tripoli-Libya.

PubMed

Daw, Mohamed A; Shabash, Amira; El-Bouzedi, Abdallah; Dau, Aghnya A

2014-01-01

In 1998 Libya experienced a major outbreak of multiple blood borne viral hepatitis and HIV infections. Since then, no studies have been done on the epidemic features and risk factors of HBV, HCV, HIV and co-infection among the general population. A prospective study was carried out using a multi-centre clustering method to collect samples from the general population. The participants were interviewed, and relevant information was collected, including socio-demographic, ethnic, and geographic variables. This information was correlated with the risk factors involved in the transmission of HBV, HCV and HIV. Blood samples were collected and the sera were tested for HBsAg, anti-HCV and anti-HIV using enzyme immunoassay. A total of 9,170 participants from the nine districts of Tripoli were enrolled. The average prevalence of HBsAg was 3.7%, anti-HCV 0.9%, anti-HIV 0.15% and co-infection 0.02%. The prevalence varied from one district to another. HBV was more prevalent among those aged over 50 years and was associated with family history. Anti-HCV and anti-HIV were more prevalent among those aged 20-40 years. Intravenous drug use and blood transfusion were the main risk factors for HCV and HIV infection. HBV, HCV, HIV and co-infection are relatively common in Libya. High prevalence was associated with geographic, ethnic and socioeconomic variability within the community. HCV and HIV infections among the younger age groups are becoming an alarming issue. Regulations and health care education need to be implemented and longer term follow-up should be planned.

VLPs of HCV local isolates for HCV immunoassay diagnostic approach in Indonesia

NASA Astrophysics Data System (ADS)

Prasetyo, Afiono Agung

2017-01-01

Hepatitis C Virus (HCV) infection is a major global disease which often leads to morbidity and mortality. Low survival is related to the lack of adequate diagnostic because HCV infection is frequently asymptomatic and there are no specific diagnostic tests due to the fast transformation of the virus. Here, we investigated the VLPs (virus-like particles) of HCV local isolate as an immunoassay diagnostic approach to detect HCV infection, especially in Indonesia. The core, E1, and E2 of HCV local isolate genes were cloned and molecular analyzed, either as single or in recombinant-VLP form, to determine the molecular and chemical characteristics of each VLPs related to their potential use as an immunoassay detection method for HCV infection. The results indicated the molecular and chemical character of each VLPs are comparable. Conclusion: VLPs of HCV has the potential as an immunoassay diagnostic approach to detect HCV infection.

Classical and emerging roles of vitamin D in hepatitis C virus (HCV) infection

PubMed Central

Gutierrez, Julio A.; Parikh, Neil; Branch, Andrea D.

2014-01-01

The risk of clinically-significant vitamin D deficiency increases at 25-hydroxyvitamin D levels below 20 ng/mL, according to the Institute of Medicine. By this standard, most cirrhotic hepatitis C virus (HCV)-positive patients and many non-cirrhotic patients are vitamin D deficient. The high prevalence of vitamin D deficiency among HCV patients is a cause for concern for several specific reasons. Classic studies established the importance of vitamin D and calcium in maintaining bone. Vitamin D's beneficial effects on bone are likely to be vital for HCV-infected patients because these individuals have a high prevalence of low bone mineral density. Many pharmaceutical agents reduce bone density and exposure to these drugs may increase bone disease in HCV-positive patients. Bone loss occurs following liver transplantation and bone density is often low in patients with HIV/HCV co-infection who are on combination antiretroviral therapy. Some evidence suggests that ribavirin reduces bone density, underscoring the special need to monitor vitamin D in patients receiving HCV treatment and to prescribe supplements, as appropriate. In addition to its role in calcium metabolism, vitamin D is also an immune modulator that reduces inflammation while enhancing protective immune responses. Higher vitamin D levels are associated with less liver fibrosis and less inflammation in HCV patients. Recent studies show that low vitamin D levels are associated with treatment failure among HCV-infected patients receiving pegylated-interferon and ribavirin. If confirmed, these findings will provide an additional reason to ensure adequate levels of vitamin D. The article concludes with information about how to monitor vitamin D status and how to use vitamin D supplements most effectively in HCV-infected patients. PMID:22189978

Ledipasvir-Sofosbuvir for 8 Weeks in Non-Cirrhotic Patients with Previously Untreated Genotype 1 HCV Infection ± HIV-1 Co-Infection.

PubMed

Isakov, Vasily; Gankina, Natalia; Morozov, Viacheslav; Kersey, Kathryn; Lu, Sophia; Osinusi, Anu; Svarovskaia, Evguenia; Brainard, Diana M; Salupere, Riina; Orlova-Morozova, Elena; Zhdanov, Konstantin

2018-03-01

BACKGROUND AND OBJECTIVES: The efficacy of < 12 weeks of hepatitis C virus (HCV) treatment in patients co-infected with HCV and human immunodeficiency virus type 1 (HIV-1) has not been established. We assessed the efficacy and safety of ledipasvir-sofosbuvir for 8 weeks in HCV mono-infected and HCV/HIV-1 co-infected patients. We enrolled patients mono-infected with genotype 1 HCV or co-infected with HCV and HIV-1 who were HCV treatment-naive and did not have cirrhosis. HCV/HIV-1 co-infected patients were either not receiving antiretroviral treatment and had a CD4 T-cell count > 500 cells/mm 3 or were receiving a protocol-approved antiretroviral regimen for ≥ 8 weeks (or ≥ 6 months for abacavir-containing regimens) and had HIV-1 RNA < 50 copies/mL and a CD4 T-cell count > 200 cells/mm 3 . Patients received ledipasvir-sofosbuvir (90/400 mg) once daily for 8 weeks. The primary efficacy endpoint was sustained virologic response 12 weeks after treatment discontinuation (SVR12). The SVR12 rate was 100% (67/67) for HCV mono-infected patients and 97% (57/59) for HCV/HIV-1 co-infected patients. Two patients relapsed by the week 4 post-treatment visit. Overall, the most common adverse events were headache (52%) and upper abdominal pain (26%). There were no serious adverse events or treatment discontinuations due to adverse events. No HCV/HIV-1 co-infected patients receiving antiretroviral treatment experienced HIV virologic rebound, and no clinically meaningful changes in CD4 T-cell counts were observed in any co-infected patient. Non-cirrhotic, treatment-naive patients with genotype 1 HCV mono-infection and HCV/HIV-1 co-infection achieved high rates of SVR12 with 8 weeks of treatment with ledipasvir/sofosbuvir. ClinicalTrials.gov identifier: NCT02472886.

Seroprevalence of HCV and HIV Infections by Year of Birth in Spain: Impact of US CDC and USPSTF Recommendations for HCV and HIV Testing

PubMed Central

Meijide, Héctor; Cañizares, Angelina; Castro-Iglesias, Ángeles; Delgado, Manuel; Pértega, Sonia; Pedreira, José; Bou, Germán; Poveda, Eva

2014-01-01

Background The US Centers for Disease Control and Prevention (CDC) recently add the advice of one-time testing of HCV infection in persons born during 1945–1965. Moreover, the US Preventive Services Task Force (USPSTF) newly recommended one-time HIV testing for persons aged 15–65. Herein, we evaluate the potential impact of these recommendations in a reference medical area of Spain. Methods All assays results entries for HCV and HIV serological markers ordered at a reference lab from primary care and specialized physicians between 2008 and 2012 were recorded in a medical area which covers 501,526 citizens in Northern Spain. The year of birth were also documented. Results A total of 108,159 anti-HCV-Ab results were generated during the study period. The global rate of anti-HCV-Ab+ was 7.7% (95% CI: 7.6%–7.9%), being more prevalent in men than women (8.6% vs. 4.5%). By year of birth, the highest prevalence was found in persons born between 1955 and 1970. HCV genotype 1 was the most prevalent (59.7%) followed by genotype 3 (22.7%). Regard HIV infection, among 65,279 anti-HIV results generated the prevalence of anti-HIV+ was 1.1% (95% CI: 1.0%–1.2%), being more frequent in men (2% vs 0.5%). The years of birth with highest rates of HIV infection exactly match with those for HCV infection. Conclusions The highest rates of HCV and HIV infections are found between 1960 and 1965. Different historical and social circumstances such as the huge intravenous drug use epidemic in the eighties in Spain, might explain it. Therefore, each country needs to determine its own HCV and HIV seroprevalences by year of birth to establish the proper recommendations for the screening of both infections. PMID:25436642

Seroprevalence of HBV, HCV & HIV Co-Infection and Risk Factors Analysis in Tripoli-Libya

PubMed Central

Daw, Mohamed A.; Shabash, Amira; El-Bouzedi, Abdallah; Dau, Aghnya A.

2014-01-01

Background In 1998 Libya experienced a major outbreak of multiple blood borne viral hepatitis and HIV infections. Since then, no studies have been done on the epidemic features and risk factors of HBV, HCV, HIV and co-infection among the general population. Methods A prospective study was carried out using a multi-centre clustering method to collect samples from the general population. The participants were interviewed, and relevant information was collected, including socio-demographic, ethnic, and geographic variables. This information was correlated with the risk factors involved in the transmission of HBV, HCV and HIV. Blood samples were collected and the sera were tested for HBsAg, anti-HCV and anti-HIV using enzyme immunoassay. Results A total of 9,170 participants from the nine districts of Tripoli were enrolled. The average prevalence of HBsAg was 3.7%, anti-HCV 0.9%, anti-HIV 0.15% and co-infection 0.02%. The prevalence varied from one district to another. HBV was more prevalent among those aged over 50 years and was associated with family history. Anti-HCV and anti-HIV were more prevalent among those aged 20–40 years. Intravenous drug use and blood transfusion were the main risk factors for HCV and HIV infection. Conclusion HBV, HCV, HIV and co-infection are relatively common in Libya. High prevalence was associated with geographic, ethnic and socioeconomic variability within the community. HCV and HIV infections among the younger age groups are becoming an alarming issue. Regulations and health care education need to be implemented and longer term follow-up should be planned. PMID:24936655

Review of HIV and HCV infection among drug users in China.

PubMed

Bao, Yan-ping; Liu, Zhi-min; Lu, Lin

2010-05-01

Drug abuse has resulted in a huge public health and economic burden in China, especially the rapid spread of HIV/AIDS and hepatitis C virus (HCV) infection. Multiple HIV and HCV subtypes were detected among drug users in China, this study reviews the molecular distribution of HIV and HCV among injection drug users (IDUs) and explores new epidemiologic trends of HIV and HCV among drug users in China. The 2009 National Narcotic Control Commission report showed that the percentage of users of 'new-type drugs', including amphetamine-type stimulants (ATS: methamphetamine and MDMA/ecstasy) and ketamine, was about 27% of total drug users. The pooled data from published papers showed that CRF07BC was the predominant HIV-1 subtype, which accounted for 38.8%, and it was followed by AE, which accounted for 22.7% among HIV-positive IDUs. Following these, the CRF08BC, B' and C subtypes accounted for about 10.8%, 9.9% and 9.2%, respectively. Subtype 6a was the predominant HCV subtype, accounting for 36.7%, and subtypes 3b, 1a, 3a and 1b were the next most predominant subtypes. With the increase of 'new-type drugs' use and AE HIV-1 subtype infection among IDUs, the situation regarding HIV/AIDS and HCV infection has become complicated. More comprehensive prevention and intervention strategies should be instigated for the extensive high-risk populations in China.

Environmental Stability and Infectivity of Hepatitis C Virus (HCV) in Different Human Body Fluids.

PubMed

Pfaender, Stephanie; Helfritz, Fabian A; Siddharta, Anindya; Todt, Daniel; Behrendt, Patrick; Heyden, Julia; Riebesehl, Nina; Willmann, Wiebke; Steinmann, Joerg; Münch, Jan; Ciesek, Sandra; Steinmann, Eike

2018-01-01

Background: Hepatitis C virus (HCV) is a hepatotropic, blood-borne virus, but in up to one-third of infections of the transmission route remained unidentified. Viral genome copies of HCV have been identified in several body fluids, however, non-parental transmission upon exposure to contaminated body fluids seems to be rare. Several body fluids, e.g., tears and saliva, are renowned for their antimicrobial and antiviral properties, nevertheless, HCV stability has never been systematically analyzed in those fluids. Methods: We used state of the art infectious HCV cell culture techniques to investigate the stability of HCV in different body fluids to estimate the potential risk of transmission via patient body fluid material. In addition, we mimicked a potential contamination of HCV in tear fluid and analyzed which impact commercially available contact lens solutions might have in such a scenario. Results: We could demonstrate that HCV remains infectious over several days in body fluids like tears, saliva, semen, and cerebrospinal fluid. Only hydrogen-peroxide contact lens solutions were able to efficiently inactivate HCV in a suspension test. Conclusion: These results indicate that HCV, once it is present in various body fluids of infected patients, remains infective and could potentially contribute to transmission upon direct contact.

CD81 expression on CD19+ peripheral blood lymphocytes is associated with chronic HCV disease and increased risk for HCV infection: a putative role for inflammatory cytokines.

PubMed

D'Agosto, G; Trento, E; Nosotti, L; Bordignon, V; Battista, M; Prignano, G; Pimpinelli, F; Biolcati, G; Macrì, A; Palamara, G; Miglioresi, L; Morrone, A; Di Carlo, A; Cordiali-Fei, P; Ensoli, F

2009-01-01

The level of CD81 cell surface expression, a cellular co-receptor for hepatitis C virus (HCV), is critical for productive HCV infection of host cells. In addition, the cross-linking of HCV-E2 protein to CD81 can alter the function of T and B lymphocytes as well as that of NK cells by interfering with the activation signalling pathway. The down-regulation of CD81 expression on peripheral blood lymphocytes (PBL) has been associated to effective therapy of HCV infection. The aim of the present study is to quantitatively assess the levels of CD81 expression in PBL from HCV-infected patients compared to subjects at high risk for HCV infection such as HIV-infected individuals or patients with Porphyria Cutanea Tarda (PCT). The expression of CD81 was quantified by flow-cytometry using Phycoerythrin-labelled standard beads. Determination of CD81 was performed on CD3+ and CD19+ lymphocytes from 34 healthy controls, 51 patients with HCV infection and different clinical outcomes [these included HCV-RNA-negative subjects (8), patients with chronic active hepatitis (16), recipients of liver transplantation under immunosuppressive therapy (12), a subgroup with concomitant HIV infection (9) or concomitant PCT (6)]. In addition, 60 HIV-infected subjects and 4 patients with PCT were studied. The putative role of inflammatory cytokines in modulating CD81 was explored in vitro by assessing the effect of IL-6 or IFN-gamma on cultured human hepatocytes. A significant increase of the CD81 expression was found on CD19+ lymphocytes in association with either HIV or HCV infection, as compared to the control group. Immunosuppressive therapy with FK506, subsequent to liver transplantation, restored CD81 expression at normal levels. Data gathered in vitro using the WRL 68 hepatocytic cell line confirmed that inflammatory cytokines can up-regulate CD81 expression in liver cell inclusion. Our data suggest that CD81 up-regulation can increase the risk of HCV infection, particularly in HIV-infected

Detection of viral antigens in renal tissue of glomerulonephritis patients without serological evidence of hepatitis B virus and hepatitis C virus infection.

PubMed

Kong, Dan; Wu, Di; Wang, Tianzhen; Li, Tianzhu; Xu, Shengjie; Chen, Fulai; Jin, Xiaoming; Lou, Ge

2013-07-01

Glomerulonephritis is an important extrahepatic manifestation of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. HBV and HCV infection may be occult, and they are often overlooked by both patients and doctors. The aim of this study was to assess the importance of HBV and HCV infection in glomerulonephritis patients with undetectable HBV surface antigen (HBsAg) and HCV antibody in serum. The HBsAg, the HBV core antigen (HBcAg), and the HCV antigen were detected using immunohistochemistry in frozen renal tissues of 500 glomerulonephritis patients without serological evidence of HBV and HCV infection. Electron microscopy was used to trace the virus particles, and clinicopathological features were also reviewed. HBsAg or HBcAg was positive in nine out of 500 cases (9/500, 1.8%). Three cases were HBsAg-positive and another six cases were HBcAg-positive. The HCV antigen was found in eight cases (8/500, 1.6%). There was one case of HBV and HCV co-infection (1/500, 0.2%). Under electron microscopy, virus particles were found in the base membrane and cytoplasm of endotheliocytes in the glomerulus. The most common clinical manifestation was nephrotic syndrome (9/18), followed by nephritic syndrome (7/18). Membranous nephropathy was the most common pathological diagnosis (5/18), followed by mesangioproliferative glomerulonephritis (4/18) and IgA nephropathy (4/18). Occult HBV and HCV infection might be implicated in HBV- or HCV-associated glomerulonephritis. More attention should be focused on the underlying cause. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Diagnostic Value of Anti-Hepatitis C Virus (HCV) Core Immunoglobulin M in Recurrence of HCV Infection after Orthotopic Liver Transplantation†

PubMed Central

Casino, Carmela; Lilli, Daniela; Rivanera, Daniela; Comanducci, Antonella; Rossi, Massimo; Casciaro, Giovanni; Pecorella, Irene; Alfani, Dario; Mancini, Carlo

1999-01-01

The significance of anti-hepatitis C virus (HCV) core immunoglobulin M (IgM) and its relationship with genotypes, alanine aminotransferase abnormality, and histological data were studied for 18 patients who had undergone orthotopic liver transplantation due to HCV-related end-stage disease. During follow-up, IgM response seemed to be associated with the recurrence of HCV infection but did not correlate with abnormal alanine aminotransferase levels and histological data. In addition, the results of this study indicated that the detection of HCV RNA is critical for diagnosis of reinfection in liver transplantation. PMID:10405433

An overview of occult hepatitis B virus infection

PubMed Central

Said, Zeinab Nabil Ahmed

2011-01-01

Occult hepatitis B virus (HBV) infection (OBI), alternatively defined as occult hepatitis B (OHB), is a challenging clinical entity. It is recognized by two main characteristics: absence of HBsAg, and low viral replication. The previous two decades have witnessed a remarkable progress in our understanding of OBI and its clinical implications. Appropriate diagnostic techniques must be adopted. Sensitive HBV DNA amplification assay is the gold standard assay for detection of OBI. Viral as well as host factors are implicated in the pathogenesis of OBI. However, published data reporting the infectivity of OBI by transfusion are limited. Several aspects including OBI transmission, infectivity and its relation to the development of chronic liver diseases and hepatocellular carcinoma have to be resolved. The aim of the present review is to highlight recent data on OBI with a focus on its virological diagnosis and clinical outcome. PMID:21528070

Occult infection related hepatitis B surface antigen variants showing lowered secretion capacity

PubMed Central

Kim, Hong; Lee, Seoung-Ae; Won, You-Sub; Lee, HyunJoo; Kim, Bum-Joon

2015-01-01

AIM: To elucidate the molecular mechanisms underlying hepatitis B virus (HBV) occult infection of genotype C. METHODS: A total of 10 types of hepatitis B surface antigen (HBsAg) variants from a Korean occult cohort were used. After a complete HBV genome plasmid mutated such that it does not express HBsAg and plasmid encoding, each HBsAg variant was transiently co-transfected into HuH-7 cells. The secretion capacity and intracellular expression of the HBV virions and HBsAgs in their respective variants were analyzed using real-time quantitative polymerase chain reaction assays and commercial HBsAg enzyme-linked immunosorbent assays, respectively. RESULTS: All variants exhibited lower levels of HBsAg secretion into the medium compared with the wild type. In particular, in eight of the ten variants, very low levels of HBsAg secretion that were similar to the negative control were detected. In contrast, most variants (9/10) exhibited normal virion secretion capacities comparable with, or even higher than, the wild type. This provided new insight into the intrinsic nature of occult HBV infection, which leads to HBsAg sero-negativeness but has horizontal infectivity. Furthermore, most variants generated higher reactive oxidative species production than the wild type. This finding provides potential links between occult HBV infection and liver disease progression. CONCLUSION: The presently obtained data indicate that deficiency in the secretion capacity of HBsAg variants may have a pivotal function in the occult infections of HBV genotype C. PMID:25684944

Sofosbuvir/Velpatasvir for 12 Weeks in Genotype 1-4 HCV-Infected Liver Transplant Recipients.

PubMed

Agarwal, Kosh; Castells, Lluís; Müllhaupt, Beat; Rosenberg, William M C; McNabb, Brian; Arterburn, Sarah; Camus, Gregory; McNally, John; Stamm, Luisa M; Brainard, Diana M; Subramanian, G Mani; Mariño, Zoe; Dufour, Jean-François; Forns, Xavier

2018-06-07

Sofosbuvir, an NS5B inhibitor, combined with velpatasvir, an NS5A inhibitor (SOF/VEL), produces high sustained virologic response rates 12 weeks after treatment (SVR12) in patients with genotype 1-6 HCV infection, and has no anticipated clinically relevant drug-drug interactions with immunosuppressants. This study evaluated the safety and efficacy of SOF/VEL in adults with recurrent chronic genotype 1-4 HCV infection after liver transplant. Patients received SOF/VEL 400/100 mg daily for 12 weeks. Patients could be treatment experienced or treatment naïve with no cirrhosis or with compensated cirrhosis. The primary endpoints were SVR12 and discontinuations due to adverse events. The study enrolled and treated 79 patients (37 [47%] had genotype 1, 3 [4%] genotype 2, 35 [44%] genotype 3, and 4 [5%] genotype 4 HCV). Of these, 81% were male, 82% were white, 18% had compensated cirrhosis, and 59% were treatment experienced. The most commonly used immunosuppressants were tacrolimus (71%), mycophenolic acid (24%), cyclosporine (14%), and azathioprine (11%). Median (range) time from liver transplantation was 7.5 (0.3, 24) years. The SVR12 rate was 96%. By genotype, SVR12 rates were 95% (genotype 1), 100% (genotype 2), 97% (genotype 3), and 100% (genotype 4). Two patients experienced virologic relapse: one with genotype 1a infection was non-cirrhotic and treatment naïve, and one with genotype 3 infection was non-cirrhotic and treatment experienced. One patient discontinued SOF/VEL due to hyperglycemia. No serious or severe adverse events were deemed SOF/VEL-related by the investigator, and no liver transplant rejection episodes or deaths occurred during the study period. Treatment with SOF/VEL for 12 weeks was highly effective and well tolerated in genotype 1-4 HCV-infected liver transplant recipients with and without cirrhosis. Sofosbuvir/velpatasvir is a combination of two drugs in one tablet that is approved for the treatment of patients with chronic hepatitis C virus

Occult hepatitis B virus infection and S gene escape mutants in HIV-infected patients after hepatitis B virus vaccination.

PubMed

Aghakhani, Arezoo; Mohraz, Minoo; Aghasadeghi, Mohammad Reza; Banifazl, Mohammad; Vahabpour, Rouhollah; Karami, Afsaneh; Foroughi, Maryam; Ramezani, Amitis

2016-10-01

Hepatitis B virus (HBV) vaccination is recommended for HIV patients. Despite the relative success of HBV vaccination, breakthrough infections can occur infrequently in patients, and it can be due to occult HBV infection, vaccine unresponsiveness and/or emergence of escape mutants. This study assessed the presence of occult HBV infection and S gene escape mutants in HIV-positive patients after HBV vaccination. Ninety-two HIV-positive patients were enrolled in this study, including 52 responders to HBV vaccine and 40 non-responders. All of the cases received HBV vaccine according to routine HBV vaccination protocols. The presence of HBV-DNA was determined by real-time polymerase chain reaction (PCR). In HBV-DNA positive samples, the most conserved regions of S gene sequences were amplified by nested PCR and PCR products were sequenced. Occult HBV infection was detected in two cases. Glycine to arginine mutation at residue 145 (G145R) within the 'a' region of the S gene was detected in one of the occult HBV infection cases who was in the non-responder group. This study showed that the prevalence of occult HBV infection and vaccine escape mutants was low in our HBV-vaccinated HIV-positive patients in both responder and non-responder groups, so there was no alarming evidence indicating breakthrough HBV infection in our vaccinated HIV-positive cases. © The Author(s) 2016.

Hepatic steatosis progresses faster in HIV mono-infected than HIV/HCV co-infected patients and is associated with liver fibrosis.

PubMed

Pembroke, Thomas; Deschenes, Marc; Lebouché, Bertrand; Benmassaoud, Amine; Sewitch, Maida; Ghali, Peter; Wong, Philip; Halme, Alex; Vuille-Lessard, Elise; Pexos, Costa; Klein, Marina B; Sebastiani, Giada

2017-10-01

Hepatic steatosis (HS) seems common in patients infected with human immunodeficiency virus (HIV). However, the relative effect of HIV, as well as hepatitis C virus (HCV) in those co-infected, and the influence of HS on liver fibrosis progression are unclear. The LIVEr disease in HIV (LIVEHIV) is a Canadian prospective cohort study using transient elastography and associated controlled attenuation parameter (CAP) to screen for HS and liver fibrosis, in unselected HIV-infected adults. HS progression was defined as development of any grade HS (CAP ⩾248dB/m), or transition to severe HS (CAP >292dB/m), for those with any grade HS at baseline. Fibrosis progression was defined as development of significant liver fibrosis (liver stiffness measurement [LSM] >7.1kPa), or transition to cirrhosis (LSM >12.5kPa) for those with significant liver fibrosis at baseline. Cox regression analysis was used to assess predictors of HS and fibrosis progression. A prospective cohort study was conducted, which included 726 HIV-infected patients (22.7% HCV co-infected). Prevalence of any grade HS did not differ between HIV mono-infected and HIV/HCV co-infected patients (36.1% vs. 38.6%, respectively). 313 patients were followed for a median of 15.4 (interquartile range 8.5-23.0) months. The rate of HS progression was 37.8 (95% confidence interval [CI] 29.2-49.0) and 21.9 (95% CI 15.6-30.7) per 100 person-years in HIV mono-infection and HIV/HCV co-infection, respectively. HCV co-infection was an independent negative predictor of HS progression (adjusted hazard ratio [aHR] 0.50, 95% CI 0.28-0.89). HS predicted liver fibrosis progression in HIV mono-infection (aHR 4.18, 95% CI 1.21-14.5), but not in HIV/HCV co-infection. HS progresses faster and is associated with liver fibrosis progression in HIV mono-infection but not in HIV/HCV co-infection. Lay summary: Fatty liver is the most frequent liver disease in Western countries. People living with HIV seem at high risk of fatty liver due to

Hepatitis A virus infection suppresses hepatitis C virus replication and may lead to clearance of HCV.

PubMed

Deterding, Katja; Tegtmeyer, Björn; Cornberg, Markus; Hadem, Johannes; Potthoff, Andrej; Böker, Klaus H W; Tillmann, Hans L; Manns, Michael P; Wedemeyer, Heiner

2006-12-01

The significance of hepatitis A virus (HAV) super-infection in patients with chronic hepatitis C had been a matter of debate. While some studies suggested an incidence of fulminant hepatitis A of up to 35%, this could not be confirmed by others. We identified 17 anti-HCV-positive patients with acute hepatitis A from a cohort of 3170 anti-HCV-positive patients recruited at a single center over a period of 12 years. Importantly, none of the anti-HCV-positive patients had a fulminant course of hepatitis A. HCV-RNA was detected by PCR in 84% of the anti-HCV-positive/anti-HAV-IgM-negative patients but only in 65% of anti-HCV-positive patients with acute hepatitis A (p=0.03), indicating suppression of HCV replication during hepatitis A. Previous HAV infection had no effect on HCV replication. After recovery from hepatitis A, an increased HCV replication could be demonstrated for 6 out of 9 patients with serial quantitative HCV-RNA values available while 2 patients remained HCV-RNA negative after clearance of HAV throughout follow-up of at least 2 years. HAV super-infection is associated with decreased HCV-RNA replication which may lead to recovery from HCV in some individuals. Fulminant hepatitis A is not frequent in patients with chronic hepatitis C recruited at a tertiary referral center.

Pathogenesis of occult chronic hepatitis B virus infection

PubMed Central

de la Fuente, Rocio Aller; Gutiérrez, María L; Garcia-Samaniego, Javier; Fernández-Rodriguez, Conrado; Lledó, Jose Luis; Castellano, Gregorio

2011-01-01

Occult hepatitis B infection (OBI) is characterized by hepatitis B virus (HBV) DNA in serum in the absence of hepatitis B surface antigen (HBsAg) presenting HBsAg-negative and anti-HBc positive serological patterns. Occult HBV status is associated in some cases with mutant viruses undetectable by HBsAg assays; but more frequently it is due to a strong suppression of viral replication and gene expression. OBI is an entity with world-wide diffusion. The failure to detect HBsAg, despite the persistence of the viral DNA, is due in most cases to the strong suppression of viral replication and gene expression that characterizes this “occult” HBV infection; although the mechanisms responsible for suppression of HBV are not well understood. The majority of OBI cases are secondary to overt HBV infection and represent a residual low viremia level suppressed by a strong immune response together with histological derangements which occurred during acute or chronic HBV infection. Much evidence suggests that it can favour the progression of liver fibrosis and the development of hepatocellular carcinoma. PMID:21472118

Naturally Occurring Mutations in Large Surface Genes Related to Occult Infection of Hepatitis B Virus Genotype C

PubMed Central

Kim, Hong; Lee, Seoung-Ae; Kim, Dong-Won; Lee, Sueng-Hyun; Kim, Bum-Joon

2013-01-01

Molecular mechanisms related to occult hepatitis B virus (HBV) infection, particularly those based on genotype C infection, have rarely been determined thus far in the ongoing efforts to determine infection mechanisms. Therefore, we aim to elucidate the mutation patterns in the surface open reading frame (S ORF) underlying occult infections of HBV genotype C in the present study. Nested PCRs were applied to 624 HBV surface antigen (HBsAg) negative Korean subjects. Cloning and sequencing of the S ORF gene was applied to 41 occult cases and 40 control chronic carriers. Forty-one (6.6%) of the 624 Korean adults with HBsAg-negative serostatus were found to be positive for DNA according to nested PCR tests. Mutation frequencies in the three regions labeled here as preS1, preS2, and S were significantly higher in the occult subjects compared to the carriers in all cases. A total of two types of deletions, preS1 deletions in the start codon and preS2 deletions as well as nine types of point mutations were significantly implicated in the occult infection cases. Mutations within the “a” determinant region in HBsAg were found more frequently in the occult subjects than in the carriers. Mutations leading to premature termination of S ORF were found in 16 occult subjects (39.0%) but only in one subject from among the carriers (2.5%). In conclusion, our data suggest that preS deletions, the premature termination of S ORF, and “a” determinant mutations are associated with occult infections of HBV genotype C among a HBsAg-negative population. The novel mutation patterns related to occult infection introduced in the present study can help to broaden our understanding of HBV occult infections. PMID:23349904

Linkage and retention in HCV care for HIV-infected populations: early data from the DAA era.

PubMed

Sacks-Davis, Rachel; Doyle, Joseph S; Rauch, Andri; Beguelin, Charles; Pedrana, Alisa E; Matthews, Gail V; Prins, Maria; van der Valk, Marc; Klein, Marina B; Saeed, Sahar; Lacombe, Karine; Chkhartishvili, Nikoloz; Altice, Frederick L; Hellard, Margaret E

2018-04-01

There is currently no published data on the effectiveness of DAA treatment for elimination of HCV infection in HIV-infected populations at a population level. However, a number of relevant studies and initiatives are emerging. This research aims to report cascade of care data for emerging HCV elimination initiatives and studies that are currently being evaluated in HIV/HCV co-infected populations in the context of implementation science theory. HCV elimination initiatives and studies in HIV co-infected populations that are currently underway were identified. Context, intervention characteristics and cascade of care data were synthesized in the context of implementation science frameworks. Seven HCV elimination initiatives and studies were identified in HIV co-infected populations, mainly operating in high-income countries. Four were focused mainly on HCV elimination in HIV-infected gay and bisexual men (GBM), and three included a combination of people who inject drugs (PWID), GBM and other HIV-infected populations. None were evaluating treatment delivery in incarcerated populations. Overall, HCV RNA was detected in 4894 HIV-infected participants (range within studies: 297 to 994): 48% of these initiated HCV treatment (range: 21% to 85%; within studies from a period where DAAs were broadly available the total is 57%, range: 36% to 74%). Among studies with treatment completion data, 96% of 1109 initiating treatment completed treatment (range: 94% to 99%). Among those who could be assessed for sustained virological response at 12 weeks (SVR12), 1631 of 1757 attained SVR12 (93%, range: 86% to 98%). Early results from emerging research on HCV elimination in HIV-infected populations suggest that HCV treatment uptake is higher than reported levels prior to DAA treatment availability, but approximately half of patients remain untreated. These results are among diagnosed populations and additional effort is required to increase diagnosis rates. Among those who have

Epidemic dispersion of HIV and HCV in a population of co-infected Romanian injecting drug users.

PubMed

Paraschiv, Simona; Banica, Leontina; Nicolae, Ionelia; Niculescu, Iulia; Abagiu, Adrian; Jipa, Raluca; Pineda-Peña, Andrea-Clemencia; Pingarilho, Marta; Neaga, Emil; Theys, Kristof; Libin, Pieter; Otelea, Dan; Abecasis, Ana

2017-01-01

Co-infections with HIV and HCV are very frequent among people who inject drugs (PWID). However, very few studies comparatively reconstructed the transmission patterns of both viruses in the same population. We have recruited 117 co-infected PWID during a recent HIV outbreak in Romania. Phylogenetic analyses were performed on HIV and HCV sequences in order to characterize and compare transmission dynamics of the two viruses. Three large HIV clusters (2 subtype F1 and one CRF14_BG) and thirteen smaller HCV transmission networks (genotypes 1a, 1b, 3a, 4a and 4d) were identified. Eighty (65%) patients were both in HIV and HCV transmission chains and 70 of those shared the same HIV and HCV cluster with at least one other patient. Molecular clock analysis indicated that all identified HIV clusters originated around 2006, while the origin of the different HCV clusters ranged between 1980 (genotype 1b) and 2011 (genotypes 3a and 4d). HCV infection preceded HIV infection in 80.3% of cases. Coincidental transmission of HIV and HCV was estimated to be rather low (19.65%) and associated with an outbreak among PWID during detention in the same penitentiary. This study has reconstructed and compared the dispersion of these two viruses in a PWID population.

Insulin-resistance HCV infection-related affects vascular stiffness in normotensives.

PubMed

Perticone, Maria; Maio, Raffaele; Tassone, Eliezer Joseph; Tripepi, Giovanni; Di Cello, Serena; Miceli, Sofia; Caroleo, Benedetto; Sciacqua, Angela; Licata, Anna; Sesti, Giorgio; Perticone, Francesco

2015-01-01

BACKGROUND AND AIMS. Arterial stiffness evaluated as pulse wave velocity, is an early marker of vascular damage and an independent predictor for cardiovascular events. We investigated if the insulin resistance/hyperinsulinemia chronic hepatitis C virus infection-related could influence arterial stiffness. METHODS. We enrolled 260 outpatients matched for age, body mass index, gender, ethnicity: 52 with never-treated uncomplicated chronic hepatitis C virus infection (HCV(+)), 104 never-treated hypertensives (HT) and 104 healthy subjects (NT). Pulse wave velocity was evaluated by a validated system employing high-fidelity applanation tonometry. We also measured: fasting plasma glucose and insulin, total, LDL- and HDL-cholesterol, triglyceride, creatinine, e-GFR-EPI, HOMA, quantitative HCV-RNA. RESULTS. HCV(+) patients with respect to NT had an increased pulse wave velocity (7.9 ± 2.1 vs 6.4 ± 2.1 m/s; P < 0.0001), similar to that observed in HT group (8.8 ± 3.2 m/s). HCV(+) patients, in comparison with NT, had higher triglyceride, creatinine, fasting insulin and HOMA (3.2 ± 1.3 vs 2.5 ± 1.0; P < 0.0001). At linear regression analysis, the correlation between pulse wave velocity and HOMA was similar in HT (r = 0.380, P < 0.0001) and HCV(+) (r = 0.369, P = 0.004) groups. At multiple regression analysis, HOMA resulted the major determinant of pulse wave velocity in all groups, explaining respectively 11.8%, 14.4% and 13.6% of its variation in NT, HT and HCV(+). At correlational analysis hepatitis C virus-RNA and HOMA demonstrated a strong and linear relationship between them, explaining the 72.4% of their variation (P = 0.022). CONCLUSIONS. We demonstrated a significant and direct correlation between HOMA and pulse wave velocity in HCV(+) patients, similar to that observed in hypertensives. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Logical Analysis of Regulation of Interleukin-12 Expression Pathway Regulation During HCV Infection.

PubMed

Farooqi, Zia-Ur-Rehman; Tareen, Samar H K; Ahmed, Jamil; Zaidi, Najam-Us-Sahar S

2016-01-01

Hepatitis C virus (HCV) triggers coordinated innate and adaptive response in host cell. HCV genome and proteins of the replicating virus are recognized as non-self-antigens by host cell to activate Toll Like Receptors (TLRs). Activated TLRs ultimately express cytokines, which can clear virus either by activating interferon (IFN), protein kinase C (PKC) and RNA Lase system or through activation of cytotoxic T-lymphocytes. Interleukin-12 (IL-12) is a potent antiviral cytokine, capable of clearing HCV by bridging both innate and adaptive antiviral immune response. Activation of TLR-4 on macrophages surface induces expression of IL-12 via NF-κB and AP-1 transcriptional pathway. After expression, IL- 12 releases IFN-γ, which activates anti-HCV cytotoxic lymphocytes. Conversely, in chronic HCV infection downregulation of IL-12 has been reported instead of by number of studies. Keeping in view of the above mentioned facts, this study was designed to evaluate HCV-core mediated down-regulation of IL-12 transcriptional pathway by employing a logical modeling approach based on the Ren´e Thomas formalism. The logical parameters of entities were estimated by using SMBioNet. The Logical model represents all possible dynamics of protein expression involved during course of HCV pathology. Results demonstrated that at chronic stage of infection, though TLR-4 was constantly active but yet it failed to express the NF-κB, AP-1, IL-12 and IFN-γ. This mechanism was indicative of incorporation of core mediated changes in IL-12 regulatory pathway. Moreover, results also indicate that HCV adopts different trajectories to accomplish the persistence of chronic phase of infection. It also implicated that human immune system tries to clear HCV but core is capable of inducing system oscillations to evade the immunity.

Evidence for neuroinflammation and neuroprotection in HCV infection-associated encephalopathy.

PubMed

Bokemeyer, M; Ding, X-Q; Goldbecker, A; Raab, P; Heeren, M; Arvanitis, D; Tillmann, H L; Lanfermann, H; Weissenborn, K

2011-03-01

Fatigue, mood disturbances and cognitive dysfunction are frequent in patients infected with hepatitis C virus (HCV) who have mild liver disease. The reason is still unclear. The present study aims to gain more insight into the pathomechanism by combining an extensive neuropsychological examination with magnetic resonance spectroscopy in four different brain regions in a patient group covering the whole spectrum of neuropsychiatric findings in patients afflicted with HCV who have only mild liver disease. 53 HCV-positive patients with only mild liver disease and differing degrees of neuropsychiatric symptoms were studied with single-voxel MRS of the parietal white matter, occipital grey matter, basal ganglia and pons. Brain metabolite concentrations were quantitatively analysed by using LCmodel. MRS data were compared to those of 23 healthy controls adjusted for age, and analysed for relationships with the extent of neuropsychiatric symptoms. Choline (p=0.02), creatine (p=0.047) and N-acetyl-aspartate plus N-acetyl-aspartyl-glutamate (NN, p=0.02) concentrations in the basal ganglia and choline concentrations in the white matter (p=0.045) were significantly higher in the patients than in controls. Interestingly, the difference was most evident for the patients with low fatigue scores (eg, white matter: choline: p=0.001, creatine: p=0.003, NN: p=0.031). Myo-inositol differed significantly between groups in the white (p=0.001) and grey matter (p=0.003). Fatigue correlated negatively with white matter NN, choline and creatine and myo-inositol levels in white and grey matter and basal ganglia (p<0.01). As the increase of choline, creatine and myo-inositol are usually interpreted to indicate glial activation and macrophage infiltration in chronic inflammation and slow virus infections of the brain the present data endorse the hypothesis, that HCV infection may induce neuroinflammation and brain dysfunction. The concomitant increase of NN and the negative correlation to the

Alterations in microRNA expression profile in HCV-infected hepatoma cells: Involvement of miR-491 in regulation of HCV replication via the PI3 kinase/Akt pathway

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

Ishida, Hisashi; Tatsumi, Tomohide; Hosui, Atsushi

2011-08-19

Highlights: {yields} HCV infection upregulated miR-192, -194, -215, downregulated miR-320, -491. {yields} Transfection of miR-192, -215, and -491 enhanced HCV replication. {yields} Transfection of miR-491 inhibited Akt phosphorylation. {yields} Akt inhibition could be responsible for augmentation of HCV replication by miR-491. -- Abstract: The aim of this study was to investigate the role of microRNA (miRNA) on hepatitis C virus (HCV) replication in hepatoma cells. Using miRNA array analysis, miR-192/miR-215, miR-194, miR-320, and miR-491 were identified as miRNAs whose expression levels were altered by HCV infection. Among them, miR-192/miR-215 and miR-491 were capable of enhancing replication of the HCV repliconmore » as well as HCV itself. HCV IRES activity or cell proliferation was not increased by forced expression of miR-192/miR-215 or miR-491. Investigation of signaling pathways revealed that miR-491 specifically suppressed the phosphoinositol-3 (PI3) kinase/Akt pathway. Under inhibition of PI3 kinase by LY294002, the suppressive effect of miR-491 on HCV replication was abolished, indicating that suppression of HCV replication by miR-491 was dependent on the PI3 kinase/Akt pathway. miRNAs altered by HCV infection would then affect HCV replication, which implies a complicated mechanism for regulating HCV replication. HCV-induced miRNA may be involved in changes in cellular properties including hepatocarcinogenesis.« less

Low prevalence of HCV infection with predominance of genotype 4 among HIV patients living in Libreville, Gabon.

PubMed

Ndjoyi-Mbiguino, Angélique; Kombe Kombe, Arnaud John; Bivigou-Mboumba, Berthold; Zoa-Assoumou, Samira; Akombi, Falone Larissa; Nzengui Nzengui, Francis; M'boyis Kamdem, Hervé; François-Souquière, Sandrine

2018-01-01

Gabon is an endemic area for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) and the risk of co-infection is high. Between November 2015 and April 2016, we conducted retrospective study on HCV infection among people living with HIV/AIDS (PLHA). A total of 491 PLHA were included in this study and tested for the presence of HCV infection. HIV viral loads were obtained using the Generic HIV viral Load® assay and the CD4+ T cells count was performed using BD FACSCount™ CD4 reagents. HCV screening was performed using the MP Diagnostics HCV ELISA 4.0 kit. HCV genotypes were determined by sequence analysis of NS5B and Core regions. The Mann-Whitney test was used to compare the groups. Chi-2 test and Fisher's Exact Test were used to compare prevalence. HCV seroprevalence was 2.9% (14/491), (95% confidence interval (CI):1.4-4.3%). The percentage of HCV viremic patients, defined by the detection of HCV RNA in plasma, was 57% (8/14), representing 1.6% of the total population. HCV seroprevalence and replicative infection were not statistically differ with gender. The percentage of co-infection increased with age. No correlation with CD4+ T cells count and HIV viral load level was registered in this study. Identified HCV strains were predominantly of genotype 4 (87.5%) including 4k, 4e, 4g, 4p, 4f and 4c subtypes. Only one strain belonged to genotype 2 (subtype 2q). Analysis of the NS5B region did not reveal the presence of resistance-associated substitutions for sofosbuvir. A systematic screening of hepatitis C is therefore strongly recommended as well as genotyping of HCV strains in order to adapt treatments for the specific case of people living with HIV/AIDS in Central Africa.

The undiagnosed chronically-infected HCV population in France. Implications for expanded testing recommendations in 2014.

PubMed

Brouard, Cécile; Le Strat, Yann; Larsen, Christine; Jauffret-Roustide, Marie; Lot, Florence; Pillonel, Josiane

2015-01-01

Recent HCV therapeutic advances make effective screening crucial for potential HCV eradication. To identify the target population for a possible population-based screening strategy to complement current risk-based testing in France, we aimed to estimate the number of adults with undiagnosed chronic HCV infection and age and gender distribution at two time points: 2004 and 2014. A model taking into account mortality, HCV incidence and diagnosis rates was applied to the 2004 national seroprevalence survey. In 2014, an estimated 74,102 individuals aged 18 to 80 were undiagnosed for chronic HCV infection (plausible interval: 64,920-83,283) compared with 100,868 [95%CI: 58,534-143,202] in 2004. Men aged 18-59 represented approximately half of the undiagnosed population in 2014. The proportion of undiagnosed individuals in 2004 (43%) varied from 21.9% to 74.1% in the 1945-1965 and 1924-1944 birth cohorts. Consequently, age and gender distributions between the chronically-infected (diagnosed and undiagnosed) and undiagnosed HCV populations were different, the 1945-1965 birth cohort representing 48.9% and 24.7%, respectively. Many individuals were still undiagnosed in 2014 despite a marked reduction with respect to 2004. The present work contributed to the 2014 recommendation of a new French complementary screening strategy, consisting in one-time simultaneous HCV, HBV and HIV testing in men aged 18-60. Further studies are needed to assess the cost-effectiveness and feasibility of such a strategy. We also demonstrated that data on the undiagnosed HCV population are crucial to help adapt testing strategies, as the features of the chronically-infected HCV population are very distinct.

Epidemiological profile and risk factors of HIV and HBV/HCV co-infection in Fujian Province, southeastern China.

PubMed

Wu, Shouli; Yan, Pingping; Yang, Tianfei; Wang, Zhenghua; Yan, Yansheng

2017-03-01

This study aimed to investigate the epidemiological features of HIV-infected subjects co-infected with HBV/HCV in Fujian Province, southeastern China, and identify the risk factors. Blood samples were collected from 2,028 HIV antibody-positive subjects in Fujian Province. Serum HBsAg and anti-HCV antibody were detected, and CD4 + T cell count was measured. Of the 2,028 subjects, the prevalence of HIV-HBV, HIV-HCV, and HIV-HBV-HCV co-infections was 16.22%, 3.7%, and 0.79%, respectively. Man (OR = 1.912, 95% CI: 1.371-2.667), key population (OR = 0.756, 95% CI: 0.57-0.976) and detainee (OR = 0.486, 95% CI: 0.259-0.909) were risk factors of HIV-HBV co-infection, and man (OR = 2.227, 95% CI: 1.096-4.525), minority (OR = 5.04, 95% CI: 1.696-14.98), junior high school or lower education (OR = 2.32, 95% CI: 1.071-5.025), intravenous drug use (OR = 38.46, 95% CI: 11.46-129.11) and detainee (OR = 5.687, 95% CI: 2.44-13.25) were risk factors of HIV-HCV co-infection. In addition, a lower mean CD4 + T cell count was measured in HIV/HBV and HIV/HCV co-infected subjects than in HIV-infected subjects among the untreated individuals, while in the treated populations, a higher mean CD4 + T cell count was detected in HIV/HBV and HIV/HCV co-infected subjects than in HIV-infected subjects. HIV co-infection with HBV or HCV, notably HIV-HBV co-infection, is widespread in southeastern China. Hepatitis virus screening should be included in monitoring of HIV infection, and HIV and hepatitis virus co-infection should be considered during the development of HIV antiretroviral therapy scheme. J. Med. Virol. 89:443-449, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

HBV or HCV Coinfection in HIV-1-Infected Pregnant Women in France: Prevalence and Pregnancy Outcomes.

PubMed

Benhammou, Valérie; Tubiana, Roland; Matheron, Sophie; Sellier, Pierre; Mandelbrot, Laurent; Chenadec, Jérôme Le; Marel, Emmanuelle; Khoshnood, Babak; Warszawski, Josiane

2018-04-15

Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is frequent in HIV-infected persons but their impact on pregnant HIV-infected women is understudied. We explored whether these coinfections are associated with adverse pregnancy outcomes and lower response to antiretroviral therapy (ART). Pregnancies in HIV-1-infected women included in the ANRS French Perinatal Cohort between 2005 and 2013 were analyzed if HBV and HCV infection statuses were available. Among 4236 women, the prevalence of HBV (HBs Ag+) and HCV (RNA+) were 6.2% (95% confidence interval: 5.4 to 6.8) and 1.7% (1.3 to 2.1), respectively. HCV coinfection was strongly associated with a history of drug use; HBV coinfection was 6 times more frequent in women born in Sub-Saharan Africa than in European France. Baseline HIV viral load, CD4 count, and HIV care during pregnancy were similar in coinfected and monoinfected HIV mothers, except that 90% of HBV/HIV women were receiving tenofovir and/or lamivudine or emtricitabine. HCV coinfection was significantly associated with cholestasis [adjusted odds ratio: 4.1 (1.5-10.8), P = 0.005], preterm delivery [3.0 (1.6-5.7), P < 0.001], lower CD4 [2.6 (1.0-6.4), P < 0.001], and detectable viral load [2.3 (1.0-5.5), P = 0.06] at the end of pregnancy. HBV coinfection was not associated with any of these outcomes. In HIV-infected women, chronic HBV infection, mostly treated using targeted ART, had no major impact on the course of pregnancy. By contrast, chronic HCV infection was associated with a higher risk of obstetrical complications and a poorer immune-virological response to ART. It is yet unknown whether cure of HCV infection before conception can limit these adverse outcomes.

Evaluation of the VIDAS Anti-HCV Assay for Detection of Hepatitis C Virus Infection.

PubMed

Hyun, Jungwon; Ko, Dae Hyun; Kang, Hee Jung; Whang, Dong Hee; Cha, Young Joo; Kim, Hyun Soo

2016-11-01

Anti-hepatitis C virus antibody (anti-HCV) assays are recommended for screening HCV-infected persons. The VIDAS Anti-HCV Assay (bioMérieux, France), based on the enzyme-linked fluorescence test principle, was recently introduced in Korea. We evaluated the clinical performance of the VIDAS assay. One hundred HCV-positive and 1,002 HCV-negative blood samples confirmed by Architect anti-HCV (Abbott Laboratories, USA) and COBAS TaqMan HCV real-time PCR (Roche Diagnostics, USA) or the Procleix Ultrio Plus Assay (Gen-Probe Incorporated, USA) were obtained from the Human Serum Bank (HSB) and tested by VIDAS. In case of discrepant results, we conducted a recombinant immunoblot assay (RIBA). The agreement rates for known HCV-positive and HCV-negative samples between the VIDAS assay and the HSB testing were 100% (95% confidence interval [CI]: 96.4-100%) and 99.5% (95% CI: 98.8-99.8%), respectively. One of the five discrepant samples was positive for Core 2+ and NS3-2 2+ reactivity, two samples were negative, and the other two were indeterminate regarding NS4 2+ reactivity in RIBA. We observed a significant but weak positive correlation between the titers of VIDAS and Architect assays (r=0.315, P<0.001). The VIDAS anti-HCV assay, developed on the VIDAS automated immunoassay platform based on the ready-to-use, single-sample test concept may be useful in small-to-medium-sized laboratories. It showed good agreement with Architect anti-HCV and COBAS PCR assays and is therefore useful for detection of HCV infection. Weakly test-positive (ambiguous) samples require additional testing by another anti-HCV, RIBA, or HCV RNA assay.

Evaluation of the VIDAS Anti-HCV Assay for Detection of Hepatitis C Virus Infection

PubMed Central

Hyun, Jungwon; Ko, Dae-Hyun; Kang, Hee Jung; Whang, Dong Hee

2016-01-01

Background Anti-hepatitis C virus antibody (anti-HCV) assays are recommended for screening HCV-infected persons. The VIDAS Anti-HCV Assay (bioMérieux, France), based on the enzyme-linked fluorescence test principle, was recently introduced in Korea. We evaluated the clinical performance of the VIDAS assay. Methods One hundred HCV-positive and 1,002 HCV-negative blood samples confirmed by Architect anti-HCV (Abbott Laboratories, USA) and COBAS TaqMan HCV real-time PCR (Roche Diagnostics, USA) or the Procleix Ultrio Plus Assay (Gen-Probe Incorporated, USA) were obtained from the Human Serum Bank (HSB) and tested by VIDAS. In case of discrepant results, we conducted a recombinant immunoblot assay (RIBA). Results The agreement rates for known HCV-positive and HCV-negative samples between the VIDAS assay and the HSB testing were 100% (95% confidence interval [CI]: 96.4-100%) and 99.5% (95% CI: 98.8-99.8%), respectively. One of the five discrepant samples was positive for Core 2+ and NS3-2 2+ reactivity, two samples were negative, and the other two were indeterminate regarding NS4 2+ reactivity in RIBA. We observed a significant but weak positive correlation between the titers of VIDAS and Architect assays (r=0.315, P<0.001). Conclusions The VIDAS anti-HCV assay, developed on the VIDAS automated immunoassay platform based on the ready-to-use, single-sample test concept may be useful in small-to-medium-sized laboratories. It showed good agreement with Architect anti-HCV and COBAS PCR assays and is therefore useful for detection of HCV infection. Weakly test-positive (ambiguous) samples require additional testing by another anti-HCV, RIBA, or HCV RNA assay. PMID:27578508

Modeling combination HCV prevention among HIV-infected men who have sex with men and people who inject drugs

PubMed Central

Martin, Natasha K.; Skaathun, Britt; Vickerman, Peter; Stuart, David

2017-01-01

Background People who inject drugs (PWID) and HIV-infected men who have sex with men (MSM) are key risk groups for hepatitis C virus (HCV) transmission. Mathematical modeling studies can help elucidate what level and combination of prevention intervention scale-up is required to control or eliminate epidemics among these key populations. Methods We discuss the evidence surrounding HCV prevention interventions and provide an overview of the mathematical modeling literature projecting the impact of scaled-up HCV prevention among PWID and HIV-infected MSM. Results Harm reduction interventions such as opiate substitution therapy and needle and syringe programs are effective in reducing HCV incidence among PWID. Modeling and limited empirical data indicate HCV treatment could additionally be used for prevention. No studies have evaluated the effectiveness of behavior change interventions to reduce HCV incidence among MSM, but existing interventions to reduce HIV risk could be effective. Mathematical modeling and empirical data indicates that scale-up of harm reduction could reduce HCV transmission, but in isolation is unlikely to eliminate HCV among PWID. By contrast, elimination is possibly achievable through combination scale-up of harm reduction and HCV treatment. Similarly, among HIV-infected MSM, eliminating the emerging epidemics will likely require HCV treatment scale-up in combination with additional interventions to reduce HCV-related risk behaviors. Conclusions Elimination of HCV will likely require combination prevention efforts among both PWID and HIV-infected MSM populations. Further empirical research is required to validate HCV treatment as prevention among these populations, and to identify effective behavioral interventions to reduce HCV incidence among MSM. PMID:28534885

Chemiluminescent microparticle immunoassay based detection and prevalence of HCV infection in district Peshawar Pakistan

PubMed Central

2014-01-01

Background Due to the high rate of asymptomatic infections an advanced screening assay is of prompt importance to be used for the clinical diagnosis of HCV. Early detection of anti HCV is the first step in the management of chronic hepatitis and in the selection of patients needing treatments. In the current study we have first time used the advanced serological diagnostic technique i.e. Chemiluminescent Microparticle Immuno Assay (CMIA) for the detection of HCV infection in Peshawar Pakistan. Methods A total number of 982 samples were collected among the general public belongs to the different areas of district Peshawar. The samples were centrifuged at high speed to obtain a clear supernatant serum. All the samples were run on Architect system a fully automated immuno analyzer CMIA base technology. Results Out of 982 blood samples analyzed in this study, 160 (15.9%) were confirmed to be positive for active HCV infection. The overall prevalence was found to be 13.4%. Gender wise prevalence was recorded to be higher in male (19.1%) than female (12.7%). The age group 21-30 years was identified as the highest risk group among the studied population. Conclusion Among the tested samples, overall prevalence of active HCV infection was found to be 13.4% in the general population of Peshawar Pakistan. The young middle aged population of this region was at higher risk of HCV ailments compared to the other age groups. PMID:25016473

Efficacy of Ledipasvir and Sofosbuvir Treatment of HCV Infection in Patients Coinfected With HBV.

PubMed

Liu, Chun-Jen; Chuang, Wan-Long; Sheen, I-Shyan; Wang, Horng-Yuan; Chen, Chi-Yi; Tseng, Kuo-Chih; Chang, Ting-Tsung; Massetto, Benedetta; Yang, Jenny C; Yun, Chohee; Knox, Steven J; Osinusi, Anu; Camus, Gregory; Jiang, Deyuan; Brainard, Diana M; McHutchison, John G; Hu, Tsung-Hui; Hsu, You-Chun; Lo, Gin-Ho; Chu, Chi-Jen; Chen, Jyh-Jou; Peng, Cheng-Yuan; Chien, Ron-Nan; Chen, Pei-Jer

2018-03-01

There have been reports of reactivation of hepatitis B virus (HBV) infection during treatment of hepatitis C virus (HCV) infection with direct-acting antiviral agents. We performed a prospective study of risks and outcomes of HCV infection treatment with ledipasvir and sofosbuvir in patients with HBV infection. We performed a phase 3b, multicenter, open-label study in Taiwan of 111 patients with HCV infection (61% HCV genotype 1, 39% HCV genotype 2 infection; 62% women, 16% with compensated cirrhosis) along with HBV infection. All but 1 were positive for the hepatitis B surface antigen (HBsAg); 1 patient who was HBsAg-positive at screening was found to be HBsAg-negative at baseline. Overall, 33% of participants had received prior treatment for HCV and 5% had previously been treated for HBV; no patient was on HBV therapy at the start of the study. All patients received a fixed-dose combination of 90 mg of the HCV NS5A inhibitor ledipasvir with 400 mg of the NS5B nucleotide analogue inhibitor sofosbuvir, once daily for 12 weeks. The primary endpoint was sustained virologic response 12 weeks after the end of therapy. All 111 patients (100%) achieved a sustained virologic response. Of the 37 patients with baseline HBV DNA below 20 IU/mL, 31 (84%) had at least 1 episode of quantifiable HBV DNA through posttreatment week 12. Of the 74 patients with baseline HBV DNA levels of 20 IU/mL or more, 39 (53%) had increases of HBV DNA greater than 1 log 10 IU/mL through posttreatment week 12. Overall, 5 patients had increased levels of HBV DNA concomitant with a level of alanine aminotransferase >2 times the upper limit of normal through posttreatment week 12. Of these, 3 patients started HBV treatment. In addition, 1 patient with HBV reactivation since week 8 and concomitant alanine aminotransferase elevation >2 times upper limit of normal at posttreatment week 48 started treatment at posttreatment week 53. This patient had clinical signs and symptoms associated with HBV

Prevalence of occult hepatitis B virus infection in hemodialysis patients in Isfahan, Iran.

PubMed

Kalantari, Hamid; Ferdowsi, Faezeh; Yaran, Majid

2016-01-01

The absence of a detectable hepatitis B surface antigen (HBsAg) with or without hepatitis B core antibody (anti-HBc) or hepatitis B surface antibody (anti-HBs) in the presence of hepatitis B virus-DNA (HBV-DNA) is defined as occult HBV infection. This study was aimed to evaluate the prevalence of occult HBV infection in patients receiving hemodialysis (HD) in Isfahan, Iran. This cross sectional study was done on 400 patients without acute or chronic HBV infection with end-stage renal disease undergoing regular HD. Blood samples were collected prior to the HD session, and serological markers of viral hepatitis B included HBsAg, anti-HBs and anti-HBc were measured using standard third generation commercially available enzyme immunoassays kit, then samples of positive anti-HBc and negative anti-HBs were tested for HBV DNA using quantitative real-time polymerase chain reaction techniques. Data were analyzed by SPSS using t -test and Chi-square test. The mean age of patients was 51.6 ± 11.2 years. Anti-HBc positive was observed in 32 (8%) of 400 studied patients with negative HBsAg. Of 32 patients with anti-HBc positive, 15 were males and 17 were females with mean age of 49.7 ± 12.6 years. Among 32 patients with anti-HBc positive, 10 patients were negative for anti-HBs. All of 10 patients were negative for HBV DNA. The prevalence of occult HBV infection was 0%. The prevalence of occult HBV infection in HBsAg negative patients undergoing HD was 0% and look to be among the lowest worldwide. So, occult HBV infection is not a significant health problem in HD patients in this region.

Performance comparison of new generation HCV core antigen test versus HCV RNA test in management of hepatitis C virus infection.

PubMed

Çetiner, Salih; Çetin Duran, Alev; Kibar, Filiz; Yaman, Akgün

2017-06-01

The study has evaluated the performance of HCV core antigen (Cag) test by comparing HCV RNA PCR assay which is considered the gold standard for management of HCV infection. Totally, 132 samples sent for HCV RNA (real-time PCR) test were included in the study. Anti-HCV antibody test and HCV Cag test were performed by chemiluminescent enzyme immunoassay (CMEI). Anti-HCV test was positive in all samples. HCV RNA was detected in 112/132 (84.8%) samples, and HCV Cag in 105/132 (79.5%). The most common HCV genotype was genotype 1 (86%). Considering the HCV RNA test as gold standard; the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of Cag test were found to be 93.75%, 100%, 100%, 74.07% and 94.69%, respectively, and paired test results were detected as highly concordant. A high level of correlation was seen between HCV RNA and Cag tests, however, the concordance between the two tests appeared to be disrupted at viral loads lower than 10 3 IU/mL. On the contrary, the correlation reached significance for the values higher than 10 3 IU/mL. Viral loads were in the 17-2500IU/mL range for the negative results for Cag test. Pearson's correlation coefficient revealed a considerably high correlation. The concordance between HCV RNA and Cag tests was disrupted under a viral load lower than 10 3 IU/mL. Therefore, it would be appropriate to consider cost effectiveness, advantages and limitations of the HCV RNA and Cag tests during the decision on which method to use for patient management. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Higher Correlation of HCV Core Antigen with CD4+ T Cell Counts Compared with HCV RNA in HCV/HIV-1 Coinfected Patients

PubMed Central

Zhang, Weidong; Xi, Yuanlin; Cao, Guanghua; Zhi, Yuhong; Wang, Shuiwang; Xu, Chunhui; Wei, Lai; Lu, Fengmin; Zhuang, Hui

2011-01-01

Development of HCV infection is typically followed by chronic hepatitis C (CHC) in most patients, while spontaneous HCV viral clearance (SVC) occurs in only a minority of subjects. Compared with the widespread application of HCV RNA testing by quantitative RT-PCR technique, HCV core antigen detection may be an alternative indicator in the diagnosis of hepatitis C virus infections and in monitoring the status of infectious individuals. However, the correlation and differences between these two indicators in HCV infection need more investigation, especially in patients coinfected by HIV-1. In this study, a total of 354 anti-HCV and/or anti-HIV serum positive residents from a village of central China were enrolled. Besides HCV-related hepatopathic variables including clinical status, ALT, AST, anti-HCV Abs, as well as the altered CD4+/CD8+ T cell counts, HCV core antigen and HCV viral load were also measured. The concentration of serum HCV core antigen was highly correlated with level of HCV RNA in CHC patients with or without HIV-1 coinfection. Of note, HCV core antigen concentration was negatively correlated with CD4+ T cell count, while no correlation was found between HCV RNA level and CD4+ T cell count. Our findings suggested that quantitative detection of plasma HCV core antigen may be an alternative indicator of HCV RNA qPCR assay when evaluating the association between HCV replication and host immune status in HCV/HIV-1 coinfected patients. PMID:21858166

HBV and HCV infection among non-European Union immigrants in North-East Italy.

PubMed Central

Chiaramonte, M.; Pupo, A.; Menegon, T.; Baldo, V.; Malatesta, R.; Trivello, R.

1998-01-01

The status of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection among non-European Union (non-EU) immigrants in North-East Italy was evaluated. Among the 1683 individuals tested the prevalence of HBsAg was 8.9% (150 subjects) and of HBV antibodies (anti-HBc with/without anti-HBs) was 38.9% (654 subjects). The distribution of HBV serological markers showed significant differences according to region of origin; the highest prevalence of infection (76.9%) and carriage (16.1%) was found in immigrants from sub-Saharan Africa. Among the 933 individuals screened for HCV infection, prevalence of antibody was much lower (0.9%) than that observed in the Italian general population (3.2-12.6%). The large number of HBV carriers among immigrants could increase the number of new adult infections due to life-style habits or professional risks in the host population. In contrast, the risk of HCV spread from non-EU immigrants is very low. PMID:9747770

A meta-analysis evaluating the relationship between IL-18 gene promoter polymorphisms and an individual's susceptibility to HCV infection.

PubMed

Chen, W; Jing, M; Zhang, Q; Yuan, R; Jing, S

2018-01-01

Several observational studies have investigated interleukin-18 (IL-18) gene polymorphisms with regard to susceptibility to hepatitis C virus (HCV) infection, but the results have been inconsistent. To evaluate the relationships between functional polymorphisms in the IL-18 gene and an individual's susceptibility to HCV infection, a meta-analysis was performed. Methods: A literature search was conducted using the PubMed, EMBASE, Web of Science and China BioMedicine databases to investigate the correlation between IL-18 gene polymorphisms and susceptibility to HCV infection. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The polymorphisms IL-18-607 C>A and -137 G>C were correlated with susceptibility to HCV infection in Asian populations. However, there was no evidence indicating a correlation between either of these polymorphisms and susceptibility to HCV infection in Caucasian populations. Our current meta-analysis suggests that the -607 C>A and -137 G>C polymorphisms in the IL-18 gene promoter play important roles in determining the response to HCV in Asian populations. More studies with larger sample sizes are needed to evaluate the associations between IL-18 genetic polymorphisms and HCV infection risk. © Acta Gastro-Enterologica Belgica.

Sofosbuvir and Simeprevir Combination Therapy for HCV Genotype 1 Infection: Results of a Single-Center VA Experience

PubMed Central

Hernandez, Maria Del Pilar; Vance, Evan; Gilinski, Dani; Youtseff, Helen; Toro, Maribel; Antoine, Marie; Jeffers, Lennox J.; Peyton, Adam

2016-01-01

Treatment of chronic hepatitis C virus (HCV) infection remains a priority in the veterans affairs (VA) health care system nationwide, as there is a high burden of liver disease due to HCV infection among US veterans. The combination of sofosbuvir and simeprevir was the first all-oral antiviral regimen used in clinical practice to treat veterans with HCV infection. In this study, we report a single-center experience showing both the feasibility and effectiveness of this all-oral combination to treat HCV genotype 1 infection. One hundred patients with HCV genotype 1 infection were treated between December 2013 and June 2014. Eighty-six patients were treated with sofosbuvir and simeprevir, with or without ribavirin, for 12 weeks; 12 patients were treated with sofosbuvir, pegylated interferon, and ribavirin for 12 weeks; and 2 patients were treated with sofosbuvir and ribavirin for 24 weeks. Overall, treatment was well tolerated and feasible, with compliance rates over 95% in patients treated with all-oral therapy. The sustained virologic response (SVR) rate for sofosbuvir and simeprevir (88.4%) was superior to the rate for sofosbuvir, pegylated interferon, and ribavirin (50.0%). Subgroup analysis showed diminished SVR rates in cirrhotic patients vs noncirrhotic patients. There were no significant differences in SVR when comparing treatment with or without ribavirin or among genotype subtypes. In conclusion, this study demonstrated excellent completion rates for all-oral treatment of veterans with chronic HCV infection. Additionally, treatment was highly effective, nearing a 90% cure rate. Thus, we recommend that the VA health care system continue to incorporate new HCV medications into its formulary so as to expand HCV treatment for US veterans. PMID:27917084

[Predictive factors of virological response in chronically HCV infected].

PubMed

Lapiński, Tadeusz Wojciech; Flisiak, Robert

2012-09-01

Research on new antivirals drugs applied in the treatment of chronically HCV infected indicate that even the most perfect therapeutic molecules do not guarantee 100% efficacy. Since the beginning of the history of HCV infection treatment clinicians looked for predictors of treatment efficacy. Numerous studies confirm the high probability of cure in patients who cleared HCVinfectional 4 and 12 weeks of therapy. However despite of viral factors, recent research demonstrated predictive role of some host dependent factors. The most important role seems to play genetic factors including polymorphism rs12979860, as well as chemokins including first of all CXCL10 (IP-10). Very interesting seems to be also results of studies on association between vitamine D concentration and treatment efficacy. However in the future the most important predictive factor remain probably early on-treatment viral response.

Sex-specific effects of TLR9 promoter variants on spontaneous clearance of HCV infection.

PubMed

Fischer, Janett; Weber, Alexander N R; Böhm, Stephan; Dickhöfer, Sabine; El Maadidi, Souhayla; Deichsel, Danilo; Knop, Viola; Klinker, Hartwig; Möller, Bernd; Rasenack, Jens; Wang, Lisa; Sharma, Manu; Hinrichsen, Holger; Spengler, Ulrich; Buggisch, Peter; Sarrazin, Christoph; Pawlita, Michael; Waterboer, Tim; Wiese, Manfred; Probst-Müller, Elsbeth; Malinverni, Raffaele; Bochud, Pierre-Yves; Gardiner, Clair; O'Farrelly, Cliona; Berg, Thomas

2017-10-01

As pathogen sensors, Toll-like receptors (TLR) play a role in the first defence line during HCV infection. However, the impact of the DNA sensor TLR9 on the natural course of HCV infection is unknown. To address this, TLR9 promoter polymorphisms (single nucleotide polymorphisms (SNPs)) rs187084 and rs5743836 were investigated for their effect on disease progression. Therefore, the TLR9 SNPs and the interferon lambda 4 ( IFNL4 ) rs12979860 were genotyped in chronically HCV type 1 infected (n=333), in patients who spontaneously cleared the infection (n=161), in the Swiss HCV cohort (n=1057) and the well-characterised German (n=305) and Irish (n=198) 'anti-D' cohorts. Functional analyses were done with promoter reporter constructs of human TLR9 in B cells and assessing TLR9 mRNA levels in whole blood of healthy volunteers. The TLR9 rs187084 C allele was associated with spontaneous virus clearance in women of the study cohort (OR=2.15 (95% CI 1.18 to 3.90) p=0.012), of the Swiss HCV cohort (OR=2.06 (95% CI 1.02 to 4.18) p=0.044) and in both 'anti-D' cohorts (German: OR=2.01 (95% CI 1.14 to 3.55) p=0.016; Irish: OR=1.93 (95% CI 1.10 to 3.68) p=0.047). Multivariate analysis in the combined study and Swiss HCV cohorts supported the results (OR=1.99 (95% CI 1.30 to 3.05) p=0.002). Functional analyses revealed higher transcriptional activities for both TLR9 variants and an association of the C allele of rs5743836 with allele-specific TLR9 mRNA regulation by oestrogens in women. TLR9 promoter SNPs are associated with the natural course of HCV infection and show higher transcriptional activities. Our results imply the DNA sensor TLR9 in natural immunity against the RNA virus, HCV. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Prevalence of HCV infection and associated factors among illicit drug users in Breves, State of Pará, northern Brazil.

PubMed

Pacheco, Suzy Danielly Barbosa; Silva-Oliveira, Gláucia Caroline; Maradei-Pereira, Luciana Maria Cunha; Crescente, José Ângelo Barletta; Lemos, José Alexandre Rodrigues de; Oliveira-Filho, Aldemir Branco de

2014-01-01

Illicit drug users (DUs) are vulnerable to hepatitis C virus (HCV) infection. The shared use of illicit drugs is the main method of HCV transmission. A cross-sectional study was conducted in Breves, in northern Brazil. We surveyed 187 DUs to determine the prevalence of and factors associated with HCV infection. The prevalence of anti-HCV antibodies was 36.9%, and the prevalence of hepatitis C virus-ribonucleic acid (HCV-RNA) was 31%. Hepatitis C virus infection was associated with tattoos, intravenous drug use, shared use of equipment for drug use, drug use for longer than 3 years, and daily drug use. Strategies for preventing and controlling HCV transmission should be implemented among DUs.

Relationship between occult hepatitis B virus infection and chronic kidney disease in a Chinese population-based cohort.

PubMed

Kong, Xiang-Lei; Ma, Xiao-Jing; Su, Hong; Xu, Dong-Mei

2016-03-01

Previous studies have revealed inconsistent results regarding the association between occult hepatitis B virus (HBV) infection and chronic kidney disease (CKD). Therefore, we conducted a prospective cohort study to evaluate the association between occult HBV infection and CKD. A total of 4329 adults, aged 46.2 ± 13.7 years, without CKD at baseline were enrolled while undergoing physical examinations. Occult HBV infection was defined as seropositivity for antibody to HBV core antigen. CKD was defined as decreased estimated glomerular filtration rate (eGFR < 60 ml·min -1 ·1.73 m -2 ) or presence of proteinuria ≥1+, assessed using a repeated dipstick method. eGFR was computed using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. The prevalence of occult HBV infection was 8.1% (352/4329). During 5 years of follow-up, 165 patients (3.8%) developed CKD. Univariate Logistic regression analysis showed that occult HBV infection was positively associated with decreased eGFR, with an odds ratio ( OR ) of 2.15 (95% confidence interval ( CI ): 1.05-4.11). In contrast, occult HBV infection was not associated with either proteinuria or CKD ( P  > 0.05). After adjustment for potential confounders in the multivariate Logistic regression analysis, age, hypertension, diabetes, and the highest quartile of uric acid were associated with CKD, with OR s of 1.04 (95% CI : 1.02-1.05), 2.1 (95% CI : 1.46-3.01), 2.02 (95% CI : 1.36-2.99), and 1.86 (95% CI : 1.17-2.95), respectively. However, occult HBV infection was not associated with CKD, with an OR of 1.12 (95% CI : 0.65-1.95). This study did not find an association between occult HBV infection and CKD. However, high-risk patients infected with HBV should still be targeted for monitoring for the development of CKD.

Prevalence and presentation of hepatitis B and C virus (HBV and HCV) infection in Vietnamese Americans via serial community serologic testing.

PubMed

Nguyen, Kelvin; Van Nguyen, Thai; Shen, Duke; Xia, Victor; Tran, Diep; Banh, Khanh; Ruan, Victor; Hu, Ke-Qin

2015-02-01

The prevalence of hepatitis B virus (HBV) infection is reportedly high in Vietnamese Americans (VAs), but most previous studies did not assess full HBV serology, and not the prevalence of HBV and hepatitis C virus (HCV) infection simultaneously. The aim of the study is to assess the prevalence of different HBV serologies and HCV infection in VAs. This study was based on the data collected by testing for Hepatitis B surface antigen (HBsAg), anti-hepatitis B core antibody (HBcAb IgG), anti-HBs antibody (HBsAb), and anti-HCV antibody (anti-HCV) in a series of community screening in VAs in Orange County, California. In 1,405 VA participants, the mean age was 51 (17-87) years, 45.1% were males; 68.2%, married; 97.2%, born in Vietnam. Most of the participants were non-US born with their primary language being non-English and with limited access to health care. Of the 1,405 cases, 124 (8.8%) were confirmed HBV infection by HBsAg+; 81 (5.8%), HCV infection by anti-HCV+; including four (0.3%) with HBV/HCV coinfection. Twelve percent of the participants with confirmed HBV infection thought they were previously tested negative, while 29.7% of the participants with confirmed HCV infection thought they were previously tested negative. In this cohort, 15.4% were HBsAg-/HBsAb-/HBcAb IgG-, i.e. being susceptible to HBV infection. In HCV infected participants, 65.4% were born between 1945 and 1965. This large serial survey and screening in the Vietnamese American community confirmed the rates of HBV and HCV infection to be as high as 8.8% and 5.8%, respectively. We have also identified factors related to HBV and HCV infection in this high-risk population.

Dynamics of an HBV/HCV infection model with intracellular delay and cell proliferation

NASA Astrophysics Data System (ADS)

Zhang, Fengqin; Li, Jianquan; Zheng, Chongwu; Wang, Lin

2017-01-01

A new mathematical model of hepatitis B/C virus (HBV/HCV) infection which incorporates the proliferation of healthy hepatocyte cells and the latent period of infected hepatocyte cells is proposed and studied. The dynamics is analyzed via Pontryagin's method and a newly proposed alternative geometric stability switch criterion. Sharp conditions ensuring stability of the infection persistent equilibrium are derived by applying Pontryagin's method. Using the intracellular delay as the bifurcation parameter and applying an alternative geometric stability switch criterion, we show that the HBV/HCV infection model undergoes stability switches. Furthermore, numerical simulations illustrate that the intracellular delay can induce complex dynamics such as persistence bubbles and chaos.

Safety and effectiveness of a 12-week course of sofosbuvir and simeprevir ± ribavirin in HCV-infected patients with or without HIV infection: a multicentre observational study.

PubMed

Bruno, Giuseppe; Saracino, Annalisa; Fabrizio, Claudia; Scudeller, Luigia; Milano, Eugenio; Dell'Acqua, Raffaele; Ladisa, Nicoletta; Fasano, Massimo; Minniti, Salvatore; Buccoliero, Giovanni; Tartaglia, Alessandra; Giammario, Adele; Milella, Michele; Angarano, Gioacchino

2017-03-01

The combination of sofosbuvir and simeprevir ± ribavirin (SOF + SMV ± RBV) for hepatitis C virus (HCV) treatment has been associated with high rates of sustained virological response (SVR). Few data are available regarding this regimen in HIV/HCV co-infected patients. This study evaluated the effectiveness and safety of a 12-week course of SOF + SMV ± RBV in a cohort of HCV monoinfected and HIV/HCV co-infected individuals. HCV-infected patients, with or without HIV infection, receiving a 12-week course of SOF + SMV ± RBV in four Italian centres from February to October 2015, were included in this retrospective observational study. Clinical and biochemical data were retrieved for all patients. A total of 88 individuals were evaluated: 29 (33.0%) HIV/HCV co-infected and 59 (67.0%) monoinfected. Most patients were males with HCV genotype 1b (62.5%) and 1a (25%) infection. RBV was used in 41 HCV monoinfected and 6 HIV/HCV co-infected patients. Cirrhosis was found in 67 patients (76.1%). The most common adverse events (AEs) were rash and/or pruritus (23.9%), fatigue (13.6%) and anaemia (9.1%). Serious AEs occurred in three patients (3.4%). No treatment discontinuations were observed. RBV use was associated with multiple AEs (P = 0.02). An overall SVR12 of 93.2% was achieved; 96.6% in HCV monoinfected and 86.2% in HIV/HCV co-infected individuals, without significance both in univariate (P = 0.09) and multivariate analyses (P = 0.12). A baseline platelet count ≥90 000/mm 3 was associated with higher rates of SVR (P = 0.005). A 12-week course of SOF + SMV ± RBV was associated with good safety and high SVR12 rate both in HCV monoinfected and HIV-HCV co-infected individuals. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Epidemiological Profile and Risk Factors for Acquiring HBV and/or HCV in HIV-Infected Population Groups in Nepal.

PubMed

Bhattarai, Manjula; Baniya, Jagat Bahadur; Aryal, Nirmal; Shrestha, Bimal; Rauniyar, Ramanuj; Adhikari, Anurag; Koirala, Pratik; Oli, Pardip Kumar; Pandit, Ram Deo; Stein, David A; Gupta, Birendra Prasad

2018-01-01

HBV and HCV infections are widespread among the HIV-infected individuals in Nepal. The goals of this study were to investigate the epidemiological profile and risk factors for acquiring HBV and/or HCV coinfection in disadvantaged HIV-positive population groups in Nepal. We conducted a retrospective study on blood samples from HIV-positive patients from the National Public Health Laboratory at Kathmandu to assay for HBsAg, HBeAg, and anti-HCV antibodies, HIV viral load, and CD4+ T cell count. Among 579 subjects, the prevalence of HIV-HBV, HIV-HCV, and HIV-HBV-HCV coinfections was 3.62%, 2.93%, and 0.34%, respectively. Multivariate regression analysis indicated that spouses of HIV-positive migrant labourers were at significant risk for coinfection with HBV infection, and an age of >40 years in HIV-infected individuals was identified as a significant risk factor for HCV coinfection. Overall our study indicates that disadvantaged population groups such as intravenous drug users, migrant workers and their spouses, female sex workers, and men who have sex with HIV-infected men are at a high and persistent risk of acquiring viral hepatitis. We conclude that Nepalese HIV patients should receive HBV and HCV diagnostic screening on a regular basis.

Prevalence of IL-28B and ITPA genotypes in Chinese Han population infected persistently with hepatitis C virus genotype 6 or HCV-1.

PubMed

Zhang, Xiao-Hong; Cai, Qing-Xian; Hong, Chun-Xia; Lin, Chao-Shuang; Zhao, Zhi-Xin

2013-07-01

The geographic distribution, demographics, epidemiology, host factors, and clinical characteristics of persistent HCV-6 infection in China need further characterization. This multicenter study enrolled 63 patients with persistent HCV-6 infection and 63 patients with persistent HCV-1 infection as controls. Blood biochemistry, quantitation of HCV RNA levels, and identification of host IL-28B genotypes (rs12979860, rs8099917, and rs12980275) and ITPA genotype (rs1127354) were performed to estimate potential variability in host factors that may affect response to treatment. The mean HCV-6 RNA level (3.8E6 IU/ml) was significantly higher than that in patients infected with HCV-1 (1.7E6 IU/ml; P < 0.001). Patients persistently infected with HCV-6 had a high prevalence of IL-28B rs12979860 CC genotype (92.1%), rs8099917 TT genotype (93.7%), and rs12980275 AA genotype (90.5%). Their prevalence in patients infected with HCV-1 was only modestly lower (82.5%, 84.1%, and 82.5%, respectively; P > 0.05). The inosine triphosphate pyrophosphatase (ITPA) SNP rs1127354 CC genotype was present in 66.7% of patients infected with HCV-6, comparable to that of patients infected with HCV-1 (65.1%; P > 0.05). There were no differences in the liver function, proportion of hepatic cirrhosis patients or patients with increased serum glucose between these two groups. Persistent HCV-6 infection in Chinese Han is found mainly in the southern China. Chinese Han with chronic HCV-1 or HCV-6 infection have IL-28B genotypes, suggesting responsiveness to interferon-based pharmacotherapy. Most patients (67%) possess the ITPA genotype associated with susceptibility to ribavirin-induced hemolysis. The routes of transmission for HCV-6 genotype were more diversified than HCV-1 genotype. The outbreak of HCV-6 infection through blood transfusion progressed faster than HCV-1. Copyright © 2013 Wiley Periodicals, Inc.

Prevalence, risk factors, and impact of isolated antibody to hepatitis B core antigen and occult hepatitis B virus infection in HIV-1-infected pregnant women.

PubMed

Khamduang, Woottichai; Ngo-Giang-Huong, Nicole; Gaudy-Graffin, Catherine; Jourdain, Gonzague; Suwankornsakul, Weerapong; Jarupanich, Tapnarong; Chalermpolprapa, Veeradate; Nanta, Sirisak; Puarattana-Aroonkorn, Noossara; Tonmat, Sakchai; Lallemant, Marc; Goudeau, Alain; Sirirungsi, Wasna

2013-06-01

Prevalence and risk factors for isolated antibody to hepatitis B core antigen (anti-HBc) and occult hepatitis B virus (HBV) infection are not well known in human immunodeficiency virus type 1 (HIV-1)-infected pregnant women. It is unclear if women with occult infections are at risk of transmitting HBV to their infants. HIV-1-infected and HBV surface antigen (HBsAg)-negative pregnant women were tested for antibody to HBsAg (anti-HBs) and anti-HBc using enzyme immunoassay. Women with isolated anti-HBc were assessed for occult HBV infection, defined as HBV DNA levels >15 IU/mL, using the Abbott RealTime HBV DNA assay. Infants born to women with isolated anti-HBc and detectable HBV DNA were tested at 4 months of age for HBV DNA. Logistic regression analysis was used to identify factors associated with isolated anti-HBc and occult HBV infection. Among 1812 HIV-infected pregnant women, 1682 were HBsAg negative. Fourteen percent (95% confidence interval [CI], 12%-15%) of HBsAg-negative women had an isolated anti-HBc that was independently associated with low CD4 count, age >35 years, birth in northern Thailand, and positive anti-hepatitis C virus serology. Occult HBV infection was identified in 24% (95% CI, 18%-30%) of women with isolated anti-HBc, representing 2.6% (95% CI, 1.9%-3.5%) of HIV-1-infected pregnant women, and was inversely associated with HIV RNA levels. None of the women with isolated anti-HBc and occult HBV infection transmitted HBV to their infants. HIV-1-infected pregnant women with isolated anti-HBc and occult HBV infection have very low HBV DNA levels and are thus at very low risk to transmit HBV to their infants.

Syndemics of syphilis, HCV infection, and methamphetamine use along the east coast of China

PubMed Central

2014-01-01

Background An upsurge in club drug use has been observed in recent years in some cities of China, especially methamphetamine, which is quickly replacing heroin to become the most widespread drug across the nation. This study investigated the type of drugs used, syphilis and hepatitis C virus (HCV) infection and the correlates for syphilis, HCV and unprotected commercial sex behavior among drug users in two cities along the east coast of China. Methods A cross-sectional survey conducted in 2010 provided demographics, sexual and drug use behaviors, HIV knowledge and the utilization of intervention services among drug users. Blood samples were tested for HIV, syphilis, and HCV infection. Results Of 805 eligible participants, 0.2% were infected with HIV, 3.7% with HCV, and 9.6% with syphilis. Of the participants, 96.6% were methamphetamine users, 11.9% reported ever having used ≥2 types of these drugs, and 11.4% reported ever injecting drugs. In the multivariable logistic regression analysis, participants infected with syphilis were more likely to be female (adjusted odds ratio (AOR)=2.8, 95% confidence interval (CI): 1.2-6.5), have ever had commercial sex in the past 12 months (AOR=2.0, 95% CI: 1.0-3.9), be infected with HCV (AOR=12.1, 95% CI: 4.1-20.3) and less likely to have ever had sex with regular partners in the past 12 months (AOR=0.2, 95% CI: 0.1-0.6). Participants infected with HCV were more likely to have ever injected drugs (AOR=2.7, 95% CI: 1.1-6.5) and be infected with syphilis (AOR=8.0, 95% CI: 3.5-18.0). Participants who had unprotected sex with commercial sex partners in the last sexual encounter were more likely to be female (AOR=2.9, 95% CI:1.7-4.9), have middle school or lower level education (AOR=3.4, 95% CI:2.0-5.5), never have received intervention in the last year (AOR=2.1, 95%CI:1.2-3.6) and be infected with syphilis (AOR=4.2, 95% CI:2.4-7.4). Conclusions Methamphetamine is the predominant drug used among the drug users, the prevalence of

Occult hepatitis B virus infection in HIV positive patients at a tertiary healthcare unit in eastern India

PubMed Central

Saha, Debraj; Pal, Ananya; Sarkar, Neelakshi; Das, Dipanwita; Blackard, Jason T.; Guha, Subhasish Kamal; Saha, Bibhuti

2017-01-01

Occult HBV infection (OBI), defined by the presence of HBV DNA in absence of hepatitis B surface antigen (HBsAg), is a significant concern in the HIV-infected population. Of 441 HIV+/HBsAg- patients analyzed, the overall prevalence of OBI was 6.3% (28/441). OBI was identified in 21 anti-HBc positives (17.8%), as well as among those who lacked any HBV-specific serological markers (2.2%). Comparison with HIV/HBV co-infection revealed that the levels of CD4, ALT, and HBV DNA were significantly lower during occult infection. Discrete differences were also observed with respect to quasispecies divergence. Additionally, subgenotype D1 was most frequent in occult infection, while D2 was widespread during chronic infection. The majority (~90%) of occult D1 sequences had the sQ129R mutation in the surface gene. This study highlights several distinct features of OBI in India and underscores the need for additional HBV DNA screening in HIV-positive individuals. PMID:28591184

Occult hepatitis B virus infection in HIV positive patients at a tertiary healthcare unit in eastern India.

PubMed

Saha, Debraj; Pal, Ananya; Sarkar, Neelakshi; Das, Dipanwita; Blackard, Jason T; Guha, Subhasish Kamal; Saha, Bibhuti; Chakravarty, Runu

2017-01-01

Occult HBV infection (OBI), defined by the presence of HBV DNA in absence of hepatitis B surface antigen (HBsAg), is a significant concern in the HIV-infected population. Of 441 HIV+/HBsAg- patients analyzed, the overall prevalence of OBI was 6.3% (28/441). OBI was identified in 21 anti-HBc positives (17.8%), as well as among those who lacked any HBV-specific serological markers (2.2%). Comparison with HIV/HBV co-infection revealed that the levels of CD4, ALT, and HBV DNA were significantly lower during occult infection. Discrete differences were also observed with respect to quasispecies divergence. Additionally, subgenotype D1 was most frequent in occult infection, while D2 was widespread during chronic infection. The majority (~90%) of occult D1 sequences had the sQ129R mutation in the surface gene. This study highlights several distinct features of OBI in India and underscores the need for additional HBV DNA screening in HIV-positive individuals.

Baclofen promotes alcohol abstinence in alcohol dependent cirrhotic patients with hepatitis C virus (HCV) infection

PubMed Central

Leggio, L.; Ferrulli, A.; Zambon, A.; Caputo, F.; Kenna, G.A.; Swift, R.M.; Addolorato, G.

2016-01-01

Hepatitis C virus (HCV) and alcoholic liver disease (ALD), either alone or in combination, count for more than two thirds of all liver diseases in the Western world. There is no safe level of drinking in HCV-infected patients and the most effective goal for these patients is total abstinence. Baclofen, a GABAB receptor agonist, represents a promising pharmacotherapy for alcohol dependence (AD). Previously, we performed a randomized clinical trial (RCT), which demonstrated the safety and efficacy of baclofen in patients affected by AD and cirrhosis. The goal of this post-hoc analysis was to explore baclofen's effect in a subgroup of alcohol-dependent HCV-infected cirrhotic patients. Any patient with HCV infection was selected for this analysis. Among the 84 subjects randomized in the main trial, 24 alcohol-dependent cirrhotic patients had a HCV infection; 12 received baclofen 10mg t.i.d. and 12 received placebo for 12-weeks. With respect to the placebo group (3/12, 25.0%), a significantly higher number of patients who achieved and maintained total alcohol abstinence was found in the baclofen group (10/12, 83.3%; p=0.0123). Furthermore, in the baclofen group, compared to placebo, there was a significantly higher increase in albumin values from baseline (p=0.0132) and a trend toward a significant reduction in INR levels from baseline (p=0.0716). In conclusion, baclofen was safe and significantly more effective than placebo in promoting alcohol abstinence, and improving some LFTs (i.e. albumin, INR) in alcohol-dependent HCV-infected cirrhotic patients. Baclofen may represent a clinically relevant alcohol pharmacotherapy for these patients. PMID:22244707

HCV core-antigen assay as an alternative to HCV RNA quantification: A correlation study for the assessment of HCV viremia.

PubMed

Alonso, Roberto; Pérez-García, Felipe; López-Roa, Paula; Alcalá, Luis; Rodeño, Pilar; Bouza, Emilio

2018-03-01

Detection of hepatitis C virus (HCV) RNA and the HCV core antigen assay (HCV-Ag) are reliable techniques for the diagnosis of active and chronic HCV infection. Our aim was to evaluate the HCV-Ag assay as an alternative to quantification of HVC RNA. A comparison was made of the sensitivity and specificity of an HCV-Ag assay (204 serum samples) with those of a PCR assay, and the correlation between the two techniques was determined. The sensitivity and specificity of HCV-Ag was 76.6% and 100%, respectively. Both assays were extremely well correlated (Pearson coefficient=0.951). The formula (LogCV=1.15*LogAg+2.26) was obtained to calculate the viral load by PCR from HCV-Ag values. HCV-Ag was unable to detect viral loads below 5000IU/mL. Although the HCV-Ag assay was less sensitive than the PCR assay, the correlation between both assays was excellent. HCV-Ag can be useful as a first step in the diagnosis of acute or chronic HCV infection and in emergency situations. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Risk factors for vertical transmission of hepatitis C virus: a single center experience with 710 HCV-infected mothers.

PubMed

Garcia-Tejedor, Amparo; Maiques-Montesinos, Vicente; Diago-Almela, Vicente José; Pereda-Perez, Antonio; Alberola-Cuñat, Vicente; López-Hontangas, José Luís; Perales-Puchalt, Alfredo; Perales, Alfredo

2015-11-01

The aim of this study was to analyze the risk factors on the perinatal transmission of hepatitis C virus (HCV). A retrospective cohort study with 711 infants born to 710 HCV-infected mothers was conducted at the Hospital La Fe, in Valencia, Spain, from 1986 to 2011. As potential risk factors for transmission we analyzed: maternal age, mode of acquisition of HCV infection, HIV co-infection, antiretroviral treatment against HIV, CD4 cell count, HIV and HCV viral load, liver enzyme levels during pregnancy, smoking habit, gestational age, intrapartum invasive procedures, length of rupture of membranes, length of labor, mode of delivery, episiotomy, birth weight, newborn gender and type of feeding. Overall perinatal HCV transmission rate was 2.4%. The significant risk factors related with HCV transmission were maternal virus load >615copies/mL (OR 9.3 [95% CI 1.11-78.72]), intrapartum invasive procedures (OR 10.1 [95% CI 2.6-39.02]) and episiotomy (OR 4.2 [95% CI 1.2-14.16]). HIV co-infection and newborn female were near significance (p=0.081 and 0.075, respectively). Invasive procedures as fetal scalp blood sampling or internal electrode and episiotomy increase vertical transmission of HCV, especially in patients with positive HCV RNA virus load at delivery. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Epidemiological aspects of HCV infection in non-injecting drug users in the Brazilian state of Pará, eastern Amazon

PubMed Central

2014-01-01

Background Currently, sharing of drug paraphernalia is the main form of HCV transmission worldwide. In South America, consistent findings indicate that shared sniffing equipment is an important factor in the spread of HCV among non-injecting drug users. Epidemiological data on the status of HCV infection in illicit drug users in the Amazon region are scarce, although reports of clinical cases of hepatitis or pathologies associated with HCV infection in other population groups are numerous. Thereby, this study investigated the prevalence, genotype frequency, and epidemiological factors associated with HCV infection in non-injecting drug users in the state of Pará, eastern Amazon. Results During 2008–2011, 300 non-injecting drug users attending drug-treatment centers participated in this study. Most non-injecting drug users were male (63.7%). The mean age was 32.5 years. The non-injecting drugs most consumed were: cannabis (15.6%), cocaine paste (21.3%), and oxi cocaine (25.7%). Tobacco (60.9%) and alcohol (79.4%) were also commonly consumed. One hundred six (35.1%; CI 95%: 29.8 - 41.1) non-injecting drug users presented anti-HCV antibodies by EIA. The HCV-RNA prevalence was 28.0% (95% CI: 20.6 - 35.8). Genotypes 1 (76.9%) and 3 (23.1%) of HCV have been identified. A multivariate analysis demonstrated that HCV infection was independently associated with the following factors: “age (≥ 35 years)”, “tattoos”, “use of a needle or syringe sterilized at home”, “shared use of drug paraphernalia”, “uses drugs for more than 5 years”, and “use of drugs everyday”. Conclusions This study revealed a high prevalence of HCV infection in non-injecting drug users, and most infections are occasioned by genotype 1. Likely, HCV transmission is associated with the tattoos, the use of needle or syringe sterilized at home by people over the age of 35 years, and sharing, time and frequency of use of non-injecting drugs. These findings should serve as an

Epidemiological aspects of HCV infection in non-injecting drug users in the Brazilian state of Pará, eastern Amazon.

PubMed

Oliveira-Filho, Aldemir B; Sawada, Leila; Pinto, Laine C; Locks, Daiane; Bahia, Santana L; Castro, Jairo A A; Hermes, Renata B; Brasil-Costa, Igor; Amaral, Carlos E M; Lemos, José Alexandre R

2014-02-25

Currently, sharing of drug paraphernalia is the main form of HCV transmission worldwide. In South America, consistent findings indicate that shared sniffing equipment is an important factor in the spread of HCV among non-injecting drug users. Epidemiological data on the status of HCV infection in illicit drug users in the Amazon region are scarce, although reports of clinical cases of hepatitis or pathologies associated with HCV infection in other population groups are numerous. Thereby, this study investigated the prevalence, genotype frequency, and epidemiological factors associated with HCV infection in non-injecting drug users in the state of Pará, eastern Amazon. During 2008-2011, 300 non-injecting drug users attending drug-treatment centers participated in this study. Most non-injecting drug users were male (63.7%). The mean age was 32.5 years. The non-injecting drugs most consumed were: cannabis (15.6%), cocaine paste (21.3%), and oxi cocaine (25.7%). Tobacco (60.9%) and alcohol (79.4%) were also commonly consumed. One hundred six (35.1%; CI 95%: 29.8 - 41.1) non-injecting drug users presented anti-HCV antibodies by EIA. The HCV-RNA prevalence was 28.0% (95% CI: 20.6 - 35.8). Genotypes 1 (76.9%) and 3 (23.1%) of HCV have been identified. A multivariate analysis demonstrated that HCV infection was independently associated with the following factors: "age (≥ 35 years)", "tattoos", "use of a needle or syringe sterilized at home", "shared use of drug paraphernalia", "uses drugs for more than 5 years", and "use of drugs everyday". This study revealed a high prevalence of HCV infection in non-injecting drug users, and most infections are occasioned by genotype 1. Likely, HCV transmission is associated with the tattoos, the use of needle or syringe sterilized at home by people over the age of 35 years, and sharing, time and frequency of use of non-injecting drugs. These findings should serve as an incentive for the establishment of a program of Hepatitis C

HCV co-infection and markers of liver injury and fibrosis among HIV-positive childbearing women in Ukraine: results from a cohort study.

PubMed

Bailey, Heather; Nizova, Nataliya; Martsynovska, Violeta; Volokha, Alla; Malyuta, Ruslan; Cortina-Borja, Mario; Thorne, Claire

2016-12-12

Ukraine's injecting drug use-driven HIV epidemic is among the most severe in Europe with high burden of HCV co-infection. HIV/HCV co-infected individuals are at elevated risk of HCV-related morbidity, but little is known about burden of liver disease and associated factors in the HIV-positive population in Ukraine, particularly among women. Characteristics of 2050 HIV-positive women enrolled into the Ukrainian Study of HIV-infected Childbearing Women were described by HCV serostatus. Aspartate transaminase (AST) to platelet ratio (APRI) and FIB-4 scores were calculated and exact logistic regression models fitted to investigate factors associated with significant fibrosis (APRI >1.5) among 762 women with an APRI score available. Of 2050 HIV-positive women (median age 27.7 years, IQR 24.6-31.3), 33% were HCV co-infected (79% of those with a history of injecting drug use vs 23% without) and 17% HBsAg positive. A quarter were on antiretroviral therapy at postnatal cohort enrolment. 1% of the HIV/HCV co-infected group had ever received treatment for HCV. Overall, 24% had an alanine aminotransferase level >41 U/L and 34% an elevated AST (53% and 61% among HIV/HCV co-infected). Prevalence of significant fibrosis was 4.5%; 2.5% among 445 HIV mono-infected and 12.3% among 171 HIV/HCV co-infected women. 1.2% had a FIB-4 score >3.25 indicating advanced fibrosis. HCV RNA testing in a sub-group of 56 HIV/HCV co-infected women indicated a likely spontaneous clearance rate of 18% and predominance of HCV genotype 1, with one-third having genotype 3 infection. Factors associated with significant fibrosis were HCV co-infection (AOR 2.53 95%CI 1.03-6.23), history of injecting drug use (AOR 3.51 95%CI 1.39-8.89), WHO stage 3-4 HIV disease (AOR 3.47 95%CI 1.51-7.99 vs stage 1-2 HIV disease) and not being on combination antiretroviral therapy (AOR 3.08 95%CI 1.23-7.74), adjusted additionally for HBV co-infection, smoking and age. Most HIV/HCV co-infected women had elevated liver

Impact of Food Insecurity on Depressive Symptoms Among HIV-HCV Co-infected People.

PubMed

Aibibula, Wusiman; Cox, Joseph; Hamelin, Anne-Marie; Moodie, Erica E M; Naimi, Ashley I; McLinden, Taylor; Klein, Marina B; Brassard, Paul

2017-12-01

Food insecurity (FI) is associated with depressive symptoms among HIV mono-infected people. Our objective was to examine to what extent this association holds among HIV-hepatitis C virus (HCV) co-infected people. We used data from a prospective cohort study of HIV-HCV co-infected people in Canada. FI was measured using the ten-item adult scale of Health Canada's Household Food Security Survey Module and was classified into three categories: food secure, moderate FI, and severe FI. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale (CES-D-10) and was classified into absence or presence of depressive symptoms. FI, depressive symptoms, and other covariates were updated every 6 months. The association between FI and depressive symptoms was assessed using a stabilized inverse probability weighted marginal structural model. The study sample included 725 HIV-HCV co-infected people with 1973 person-visits over 3 years of follow up. At baseline, 23% of participants experienced moderate food insecurity, 34% experienced severe food insecurity and 52% had depressive symptoms. People experiencing moderate FI had 1.63 times (95% CI 1.44-1.86) the risk of having depressive symptoms and people experiencing severe FI had 2.01 times (95% CI 1.79-2.25) the risk of having depressive symptoms compared to people who were food secure. FI is a risk factor for developing depressive symptoms among HIV-HCV co-infected people. Food supplementation, psychosocial support and counseling may improve patient health outcomes.

Host-Specific Response to HCV Infection in the Chimeric SCID-beige/Alb-uPA Mouse Model: Role of the Innate Antiviral Immune Response

PubMed Central

Thompson, Jill C; Smith, Maria W; Yeh, Matthew M; Proll, Sean; Zhu, Lin-Fu; Gao, T. J; Kneteman, Norman M; Tyrrell, D. Lorne; Katze, Michael G

2006-01-01

The severe combined immunodeficiency disorder (SCID)-beige/albumin (Alb)-urokinase plasminogen activator (uPA) mouse containing a human-mouse chimeric liver is currently the only small animal model capable of supporting hepatitis C virus (HCV) infection. This model was utilized to characterize the host transcriptional response to HCV infection. The purpose of these studies was to investigate the genetic component of the host response to HCV infection and also to distinguish virus-induced gene expression changes from adaptive HCV-specific immune-mediated effects. Gene expression profiles from HCV-infected mice were also compared to those from HCV-infected patients. Analyses of the gene expression data demonstrate that host factors regulate the response to HCV infection, including the nature of the innate antiviral immune response. They also indicate that HCV mediates gene expression changes, including regulation of lipid metabolism genes, which have the potential to be directly cytopathic, indicating that liver pathology may not be exclusively mediated by HCV-specific adaptive immune responses. This effect appears to be inversely related to the activation of the innate antiviral immune response. In summary, the nature of the initial interferon response to HCV infection may determine the extent of viral-mediated effects on host gene expression. PMID:16789836

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.

Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection.

PubMed

Feld, Jordan J; Jacobson, Ira M; Hézode, Christophe; Asselah, Tarik; Ruane, Peter J; Gruener, Norbert; Abergel, Armand; Mangia, Alessandra; Lai, Ching-Lung; Chan, Henry L Y; Mazzotta, Francesco; Moreno, Christophe; Yoshida, Eric; Shafran, Stephen D; Towner, William J; Tran, Tram T; McNally, John; Osinusi, Anu; Svarovskaia, Evguenia; Zhu, Yanni; Brainard, Diana M; McHutchison, John G; Agarwal, Kosh; Zeuzem, Stefan

2015-12-31

A simple treatment regimen that is effective in a broad range of patients who are chronically infected with the hepatitis C virus (HCV) remains an unmet medical need. We conducted a phase 3, double-blind, placebo-controlled study involving untreated and previously treated patients with chronic HCV genotype 1, 2, 4, 5, or 6 infection, including those with compensated cirrhosis. Patients with HCV genotype 1, 2, 4, or 6 were randomly assigned in a 5:1 ratio to receive the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir in a once-daily, fixed-dose combination tablet or matching placebo for 12 weeks. Because of the low prevalence of genotype 5 in the study regions, patients with genotype 5 did not undergo randomization but were assigned to the sofosbuvir-velpatasvir group. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. Of the 624 patients who received treatment with sofosbuvir-velpatasvir, 34% had HCV genotype 1a, 19% genotype 1b, 17% genotype 2, 19% genotype 4, 6% genotype 5, and 7% genotype 6. A total of 8% of patients were black, 19% had cirrhosis, and 32% had been previously treated for HCV. The rate of sustained virologic response among patients receiving sofosbuvir-velpatasvir was 99% (95% confidence interval, 98 to >99). Two patients receiving sofosbuvir-velpatasvir, both with HCV genotype 1, had a virologic relapse. None of the 116 patients receiving placebo had a sustained virologic response. Serious adverse events were reported in 15 patients (2%) in the sofosbuvir-velpatasvir group and none in the placebo group. Once-daily sofosbuvir-velpatasvir for 12 weeks provided high rates of sustained virologic response among both previously treated and untreated patients infected with HCV genotype 1, 2, 4, 5, or 6, including those with compensated cirrhosis. (Funded by Gilead Sciences; ClinicalTrials.gov number, NCT02201940.).

HCV Ag quantification as a one-step procedure in diagnosing chronic hepatitis C infection in Cameroon: the ANRS 12336 study.

PubMed

Duchesne, Léa; Njouom, Richard; Lissock, Frédéric; Tamko-Mella, Gishlaine Flore; Rallier, Sandrine; Poiteau, Lila; Soulier, Alexandre; Chevaliez, Stéphane; Vernet, Guy; Rouveau, Nicolas; Pawlotsky, Jean-Michel; Girard, Pierre-Marie; Lacombe, Karine

2017-05-15

The diagnostic procedure for chronic hepatitis C infection (CHC) usually combines anti-HCV antibody (HCV- Ab ) and HCV-RNA measurement. Quantifying HCV core antigen (cAg) as a one-step procedure could shorten the diagnostic process. We aimed to assess the performance of cAg quantification in diagnosing CHC and how it is influenced by concomitant HIV or HBV infections. The cAg was quantified by an automated assay (Abbott Diagnostics) in 465 HCV- Ab negative serum samples and 544 HCV-RNA positive serum samples ( n  = 1009) collected in patients from the Pasteur Center in Cameroon, some of whom were infected by HBV or HIV. Its performance was evaluated in comparison to the gold standard (ELISA or PCR) by estimating its sensitivity (Se) and specificity (Sp), and by comparing the area under ROC (AUROC) curves in each patient population: HCV mono-infected, HCV-HBV and HIV-HCV co-infected. Among the 465 HCV- Ab negative patients, 51 and 79 were HIV- and HBV-infected, respectively, whereas among the 544 patients with CHC, 27 and 28 were HIV- and HBV-infected, respectively. The Spearman ρ correlation coefficient between cAg and HCV-RNA was 0.75 ( p  < 0.00001). The assay had a sensitivity of 95.7% (95% CI: 93.2-97.5) and a specificity of 99.7% (95% CI: 98.1-10) in diagnosing CHC, corresponding to an AUROC of 0.99 (95% CI: 0.98-1.0). Being HIV- or HBV-infected did not impact the performance of cAg (Se = 96.4%, Sp = 96.2% and AUROC = 0.98 (95% CI: 0.95-1.0) in the HBV group, Se = 100%, Sp = 88.2% and AUROC = 0.99 (95% CI: 0.97-1.0) in the HIV group, p between AUROC = 0.69). The cAg quantification displayed a high specificity and sensitivity for the diagnosis of CHC in Cameroon, and its performance was not significantly modified by a concomitant HIV or HBV infection. In the context of CHC elimination on a global scale, using cAg quantification as a screening tool to directly identify CHC could be a reliable tool in a "test and treat" strategy.

Spontaneous and post-treatment HCV clearance: relationships with health-related quality of life in HIV infection (ANRS-VESPA2 study).

PubMed

Marcellin, Fabienne; Demoulin, Baptiste; Spire, Bruno; Suzan-Monti, Marie; Roux, Perrine; Protopopescu, Camelia; Sagaon-Teyssier, Luis; Duracinsky, Martin; Dray-Spira, Rosemary; Carrieri, Maria Patrizia

2015-05-01

Post-treatment clearance of HCV is associated with improved health-related quality of life (HRQL) in HIV-HCV co-infection. However, the potential differences in HRQL between post-treatment and spontaneous clearers remain poorly documented. Linear regression models were used to assess the relationships between HCV status and HRQL (PROQOL-HIV scale) in 411 co-infected adults followed-up in French hospitals in 2011 (ANRS-VESPA2 survey). After adjustment for socio-economic and clinical factors, patients previously exposed to HCV treatment showed better physical HRQL and better experience of HIV treatment than treatment-naive HCV-chronic patients. Post-treatment clearers showed better mental HRQL. Spontaneous clearers showed better experience of HIV treatment. Spontaneous and post-treatment HCV clearance may influence different dimensions of HRQL of HIV-HCV co-infected patients. Further studies in real-life settings are needed to document patient-reported outcomes in the era of direct-acting antiviral agents for HCV treatment.

Prevalence of HCV infection among clients in community-based health settings in Hawaii, 2002-2010: assessing risk factors.

PubMed

Porter, Jeremy C; Lusk, Heather M; Katz, Alan R

2014-08-01

We sought to determine the prevalence of HCV infection and identify risk factors associated with HCV infection among at-risk clients presenting to community-based health settings in Hawaii. Clients from 23 community-based sites were administered risk factor questionnaires and screened for HCV antibodies from December 2002 through May 2010. We performed univariate and multivariate logistic regression analyses. Of 3306 participants included in the analysis, 390 (11.8%) tested antibody positive for HCV. Highest HCV antibody prevalence (17.0%) was in persons 45 to 64 years old compared with all other age groups. Significant independent risk factors were current or prior injection drug use (P < .001), blood transfusion prior to July 1992 (P = .002), and having an HCV-infected sex partner (P = .03). Stratification by gender revealed sexual exposure to be significant for males (P = .001). Despite Hawaii's ethnic diversity, high hepatocellular carcinoma incidence, and a statewide syringe exchange program in place since the early 1990s, our HCV prevalence and risk factor findings are remarkably consistent with those reported from the mainland United States. Hence, effective interventions identified from US mainland population studies should be generalizable to Hawaii.

Recombinant expression of the alternate reading frame protein (ARFP) of hepatitis C virus genotype 4a (HCV-4a) and detection of ARFP and anti-ARFP antibodies in HCV-infected patients.

PubMed

Shehat, Michael G; Bahey-El-Din, Mohammed; Kassem, Mervat A; Farghaly, Faten A; Abdul-Rahman, Medhat H; Fanaki, Nourhan H

2015-08-01

HCV is a single-stranded RNA virus with a single open reading frame (ORF) that is translated into a polyprotein that is then processed to form 10 viral proteins. An additional eleventh viral protein, the alternative reading frame protein (ARFP), was discovered relatively recently. This protein results from a translational frameshift in the core region during the expression of the viral proteins. Recombinant expression of different forms of ARFP was previously done for HCV genotypes 1 and 2, and more recently, genotype 3. However, none of the previous studies addressed the expression of ARFP of HCV genotype 4a, which is responsible for 80 % of HCV infections in the Middle East and Africa. Moreover, the direct detection of the ARFP antigen in HCV-infected patients was never studied before for any HCV genotype. In the present study, recombinant ARFP derived from HCV genotype 4a was successfully expressed in E. coli and purified using metal affinity chromatography. The recombinant ARFP protein and anti-ARFP antibodies were used for detection of ARFP antigen in patients' sera, employing competitive enzyme-linked immunosorbent assay (ELISA) procedures. Furthermore, the recombinant antigen was also used to detect and quantify anti-ARFP antibodies in HCV-infected Egyptian patients at different stages of pegylated interferon/ribavirin therapy, using an ELISA assay. The ARFP antigen was detectable in 69.4 % of RNA-positive sera, indicating that ARFP antigen is produced during the natural course of HCV infection. In addition, significant levels of anti-ARFP antibodies were present in 41 % of the serum samples tested. The important diagnostic value of the recombinant ARFP antigen was also demonstrated.

Confronting the Emerging Epidemic of HCV Infection Among Young Injection Drug Users

PubMed Central

Khalsa, Jag; Dan, Corinna; Holmberg, Scott; Zibbell, Jon; Holtzman, Deborah; Lubran, Robert; Compton, Wilson

2014-01-01

Hepatitis C virus infection is a significant public health problem in the United States and an important cause of morbidity and mortality. Recent reports document HCV infection increases among young injection drug users in several US regions, associated with America’s prescription opioid abuse epidemic. Incident HCV infection increases among young injectors who have recently transitioned from oral opioid abuse present an important public health challenge requiring a comprehensive, community-based response. We summarize recommendations from a 2013 Office of HIV/AIDS and Infectious Disease Policy convening of experts in epidemiology, behavioral science, drug prevention and treatment, and other research; community service providers; and federal, state, and local government representatives. Their observations highlight gaps in our surveillance, program, and research portfolios and advocate a syndemic approach to this emerging public health problem. PMID:24625174

Liver disease in adult transfusion-dependent beta-thalassaemic patients: investigating the role of iron overload and chronic HCV infection.

PubMed

Kountouras, Dimitrios; Tsagarakis, Nikolaos J; Fatourou, Evangelia; Dalagiorgos, Efthimios; Chrysanthos, Nikolaos; Berdoussi, Helen; Vgontza, Niki; Karagiorga, Markissia; Lagiandreou, Athanasios; Kaligeros, Konstantinos; Voskaridou, Ersi; Roussou, Paraskevi; Diamanti-Kandarakis, Evanthia; Koskinas, John

2013-03-01

Iron overload and hepatitis-C virus (HCV) infection, have been implicated in the evolution of liver disease, in patients with transfusion-dependent beta-thalassaemia major (BTM). However, the impact of these factors in late stages of liver disease in adults with BTM, has not been extensively studied. To investigate serum indices of iron overload, HCV infection and liver disease, in a cohort of 211 adult Greek patients with BTM, in relation with the findings from liver biopsies. In this cross-sectional study, 211 patients with BTM were enrolled and studied, in relation with HCV infection, ferritin, transaminases, chelation treatment and antiviral treatment. Based on 109 patients biopsied, we correlated liver fibrosis, haemosiderosis and inflammation, with serum indices and HCV status Among all patients, 74.4% were anti-HCV positive (HCV+). Ferritin was positively correlated with transaminases and negatively correlated with age, while it was not significantly different among HCV+ and HCV- patients. Among the HCV+ patients, 55.4% reported antiviral treatment, while genotype 1 predominated. In a subfraction of 109 patients, in which liver biopsy was performed, 89% were HCV+ and 11% HCV-. Fibrosis was significantly correlated with age (P = 0.046), AST (P = 0.004), ALT (P = 0.044) and inflammation (P < 0.001). Advanced fibrosis was present with even minimal haemosiderosis, independently of ferritin values or HCV history. These data suggest that in the late stages of liver disease in BTM patients, iron overload may be the critical determinant, since fibrosis is related to the minimal haemosiderosis, independently of HCV history. © 2012 John Wiley & Sons A/S.

HCV Prevalence in Asian Americans in California.

PubMed

Lin, Oliver N; Chang, Christine; Lee, Joyce; Do, Ailinh; Martin, Marina; Martin, Andy; Nguyen, Mindie H

2017-02-01

The World Health Organization estimates that 170 million persons are infected with HCV worldwide, but only 22 million are from the Americas and Europe, compared to 94 million from Asia. HCV prevalence in the general US population is 1.6 %, but data for Asian Americans are limited. Our goal was to examine HCV prevalence in Asian Americans in a large ethnically diverse patient cohort seeking primary care at a free clinic in Northern California. A total of 1347 consecutive patients were seen from September 2009 to October 2012 and were studied via individual chart review using case report forms. HCV infection was defined as positive HCV antibody (anti-HCV) or HCV RNA by PCR. 699 out of 1347 patients were screened for HCV. Asian Americans comprised 57.2 % of these patients and 29 (4.1 %) patients tested positive for HCV. Of these 29 HCV-positive patients, 22 (75.9 %) were Asian, yielding a prevalence of 5.5 % for Asians and 2.3 % for non-Asians (P = 0.038). The highest HCV prevalence was seen in Vietnamese patients at 7.9 %, and 6.0 % in Chinese patients. Of the HCV-positive Asians, none had a history of intravenous drug use (IVDU), tattoos, or sexual exposure. On multivariate analysis, significant independent predictors for positive HCV infection were male gender (OR 2.53, P = 0.02) and presence of known risk factors (OR 21.1, P < 0.001). However, older age and Asian ethnicity were found to be significant predictors of HCV infection (OR 1.03, P = 0.05 and 2.31, P = 0.066, respectively). In our study, HCV prevalence in patients seeking routine primary care was 5.5 % in Asian Americans, which was over double the prevalence for non-Asians at 2.3 %. Known risk factors were also notably absent in Asian patients with HCV infection. The high prevalence of HCV in Asian-Americans is likely reflective of the higher prevalence of HCV in their countries of origin in Asia. Asian-Americans immigrants from endemic countries are at higher risk of HCV infection

Pulmonary uptake in Indium-111 leukocyte imaging: clinical significance in patients with suspected occult infections

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

Cook, P.S.; Datz, F.L.; Disbro, M.A.

1984-02-01

A retrospective review was undertaken to evaluate the frequency and significance of pulmonary activity noted on 306 indium-111 leukocyte studies involving 232 patients with suspected occult infections. Forty-eight studies showed pulmonary activity in one of two patterns of uptake, focal or diffuse. Fourteen of 27 studies (52%) with focal uptake and two of 21 studies (10%) with diffuse uptake were associated with infectious processes. Lung uptake of indium-111-labeled leukocytes was a poor predictor of pulmonary infection in patients studied for occult infection, although the focal pattern was more likely than the diffuse pattern to be associated with infection.

Evaluation of clinical sensitivity and specificity of hepatitis B virus (HBV), hepatitis C virus, and human immunodeficiency Virus-1 by cobas MPX: Detection of occult HBV infection in an HBV-endemic area.

PubMed

Ha, Jihye; Park, Younhee; Kim, Hyon-Suk

2017-11-01

Transfusion-transmitted infectious diseases remain a major concern for blood safety, particularly with hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). Nucleic acid testing (NAT) in donor screening shortens the serologically negative window period and reduces virus transmission. The cobas MPX (Roche Molecular Systems, Inc., Branchburg, New Jersey) is a recently developed multiplex qualitative PCR system that enables the simultaneous detection of HBV, HCV, and HIV with improved sensitivity and throughput using cobas 6800 and 8800 instruments. The aim of this study was to conduct an evaluation of the clinical sensitivity and specificity of cobas MPX detection of HBV, HCV, and HIV in clinical specimens. Among samples referred for HBV, HCV, and HIV-1 quantification at Severance Hospital, Yonsei University College of Medicine, positive samples were selected to evaluate sensitivity. A total of 843 samples was tested using both cobas MPX and COBAS AmpliPrep/COBAS TaqMan Tests for HBV, HCV, and HIV-1 using the cobas 8800 system and a COBAS TaqMan 96 analyzer, respectively. Samples that showed discrepancies were confirmed by nested PCR. The cobas MPX achieved excellent sensitivity and specificity for the detection of HBV, HCV, and HIV-1 in clinical samples. We found that the lower limit of detection (LOD) of blood screening by NAT actually improves clinical sensitivity, and occult HBV infection prevalence among healthy employees of the hospital was rather high. Copyright © 2017 Elsevier B.V. All rights reserved.

Association between depressive symptoms, CD4 count and HIV viral suppression among HIV-HCV co-infected people.

PubMed

Aibibula, Wusiman; Cox, Joseph; Hamelin, Anne-Marie; Moodie, Erica E M; Anema, Aranka; Klein, Marina B; Brassard, Paul

2018-05-01

Depressive symptoms are associated with poor HIV viral control and immune recovery among people living with HIV. However, no prior studies assessed this association exclusively among people co-infected with HIV-hepatitis C virus (HCV). While people with HIV only and those with HIV-HCV co-infection share many characteristics, co-infected people may become more susceptible to the effects of depressive symptoms on health outcomes. We assessed this association exclusively among people co-infected with HIV-HCV in Canada using data from the Food Security & HIV-HCV Sub-Study (FS Sub-Study) of the Canadian Co-Infection Cohort (CCC). Stabilized inverse probability weighted marginal structural model was used to account for potential time-varying confounders. A total of 725 participants were enrolled between 2012 and 2015. At baseline, 52% of participants reported depressive symptoms, 75% had undetectable HIV viral load, and median CD4 count was 466 (IQR 300-665). People experiencing depressive symptoms had 1.32 times (95% CI: 1.07, 1.63) the risk of having detectable HIV viral load, but had comparable CD4 count to people who did not experience depressive symptoms (fold change of CD4 = 0.96, 95% CI: 0.91, 1.03). Presence of depressive symptoms is a risk factor for incomplete short-term HIV viral suppression among people co-infected with HIV-HCV. Therefore, depressive symptoms screening and related counseling may improve HIV related health outcomes and reduce HIV transmission.

Torque Teno Midi Virus/Small Anellovirus in Sera of Healthy, HIV/HCV and HIV Infected Individuals in Lorestan Province, Iran

PubMed Central

Fatholahi, Maryam; Bouzari, Majid

2015-01-01

Background: Torque Teno Midi Virus/Small Anellovirus (TTMDV/SAV) is a member of the Gammatorquevirus genus within the family Anelloviridae. It is detected in healthy, Hepatitis B Virus, Hepatitis C Virus and HIV infected individuals and also patients with acute respiratory disease in different countries, but its role in clinical diseases and its full geographical distribution is still unclear. Objectives: The current study aimed to detect the frequency of infection with TTMDV/SAV in the sera of healthy blood donors, hepatitis C infected and HIV positive individuals in Lorestan province, Iran; and also investigate the possible role of TTMDV/SAV virus in liver diseases. Materials and Methods: Fifty two, 36, 4, and 110 serum samples from HIV positive, patients with HIV/HCV and HIV/HCV/HBV co-infections, and healthy individuals were collected in Khorramabad city, respectively. Nested-polymerase chain reaction was performed using SMAs/SMAr primers to detect TTMDV/SAV DNA. Serum aminotransferases were measured. Results: In the HIV/HCV, HIV/HCV/HBV, HIV, and control cases, 29 (80.5%), 3 (75%), 43 (82.7%), and 16 (14.5%) were positive for DNA of TTMDV/SAV, respectively. In the HIV/HCV infected cases and HIV positive cases the level of Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) were not significantly different in TTMDV/SAV infected and non-infected individuals (P > 0.05). Conclusions: Although significant differences (P < 0.01) were observed in the frequency of TTMDV/SAV between healthy controls and each of the HIV positive and HIV/HCV co-infected individuals, no significant difference was observed between HIV positive and HIV/HCV co-infected cases, which may be due to HIV associated immunodeficiency. This is the first time that TTMDV/SAV is reported in HIV infected individuals worldwide. Interpretation of the high frequency of the virus (82.7%) in HIV cases needs more detailed studies. PMID:26862377

Torque Teno Midi Virus/Small Anellovirus in Sera of Healthy, HIV/HCV and HIV Infected Individuals in Lorestan Province, Iran.

PubMed

Fatholahi, Maryam; Bouzari, Majid

2015-11-01

Torque Teno Midi Virus/Small Anellovirus (TTMDV/SAV) is a member of the Gammatorquevirus genus within the family Anelloviridae. It is detected in healthy, Hepatitis B Virus, Hepatitis C Virus and HIV infected individuals and also patients with acute respiratory disease in different countries, but its role in clinical diseases and its full geographical distribution is still unclear. The current study aimed to detect the frequency of infection with TTMDV/SAV in the sera of healthy blood donors, hepatitis C infected and HIV positive individuals in Lorestan province, Iran; and also investigate the possible role of TTMDV/SAV virus in liver diseases. Fifty two, 36, 4, and 110 serum samples from HIV positive, patients with HIV/HCV and HIV/HCV/HBV co-infections, and healthy individuals were collected in Khorramabad city, respectively. Nested-polymerase chain reaction was performed using SMAs/SMAr primers to detect TTMDV/SAV DNA. Serum aminotransferases were measured. In the HIV/HCV, HIV/HCV/HBV, HIV, and control cases, 29 (80.5%), 3 (75%), 43 (82.7%), and 16 (14.5%) were positive for DNA of TTMDV/SAV, respectively. In the HIV/HCV infected cases and HIV positive cases the level of Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) were not significantly different in TTMDV/SAV infected and non-infected individuals (P > 0.05). Although significant differences (P < 0.01) were observed in the frequency of TTMDV/SAV between healthy controls and each of the HIV positive and HIV/HCV co-infected individuals, no significant difference was observed between HIV positive and HIV/HCV co-infected cases, which may be due to HIV associated immunodeficiency. This is the first time that TTMDV/SAV is reported in HIV infected individuals worldwide. Interpretation of the high frequency of the virus (82.7%) in HIV cases needs more detailed studies.

HCV infection prevalence lower than expected among 18-40-year-old injection drug users in San Diego, CA.

PubMed

Garfein, Richard S; Rondinelli, Amanda; Barnes, Richard F W; Cuevas, Jazmine; Metzner, Mitcheal; Velasquez, Michele; Rodriguez, David; Reilly, Meredith; Xing, Jian; Teshale, Eyasu H

2013-06-01

San Diego, California shares the world's busiest land border crossing with Tijuana, Mexico-a city where 95 % of injection drug users (IDUs) test hepatitis C virus (HCV) antibody-positive. Yet, little is known about the prevalence and risk behaviors for HCV among IDUs in San Diego. In 2009-2010, 18-40-year-old IDUs in San Diego County completed a risk assessment interview and serologic testing for HCV and HIV infection. Recruitment involved respondent-driven sampling, venue-based sampling at a syringe exchange program, and convenience sampling. Correlates of HCV infection were identified by multivariable logistic regression. Among 510 current IDUs, 26.9 % (95 % CI 23.0-30.7 %) and 4.2 % (95 % CI 2.4-5.9 %) had been infected with HCV and HIV, respectively. Overall, median age was 28 years; 74 % were male; 60 % white and 29 % Hispanic; and 96 % were born in the U.S. Median years of injecting was 6; 41 % injected daily; 60 % injected heroin most often; 49 % receptively shared syringes and 68 % shared other injection paraphernalia; and only 22 % reported always using new syringes in the past 3 months. Two thirds had ever traveled to Mexico and 19 % injected in Mexico. HCV infection was independently associated with sharing injection paraphernalia (adjusted odds ratio [AOR] = 1.69) and SEP use (AOR = 2.17) in the previous 3 months, lifetime history of drug overdose (AOR = 2.66), and increased years of injecting (AOR = 2.82, all P values <0.05). Controlling for recruitment method did not alter results. HCV infection prevalence among IDUs in San Diego was modest compared to other US cities and much lower than Tijuana. Given that known individual-level HCV risk factors were common in San Diego, the city's lower HCV prevalence might be due to differences in social and structural factors between the cities.

Prevalence of HCV Infection in Adults with Congenital Heart Disease and Treatment with Direct Antiviral Agents.

PubMed

Gade, Ajay Reddy; Patel, Manisha; West, Donna R; Abrams, Gary A

2018-03-01

Hepatitis C virus (HCV) infection affects >3% of the US population, which over time can lead to cirrhosis and hepatocellular carcinoma. The lack of a reliable screening method for HCV before 1992 resulted in a higher prevalence of the virus in adults with congenital heart disease who underwent corrective surgery that required blood transfusions. Direct-acting antiviral agents such as sofosbuvir/ledipasvir have significantly increased the efficacy of HCV therapy, although use of these medications in adults with congenital heart disease has not been described. Ours was a retrospective study of 188 adults with congenital heart conditions who had cardiac surgery before 1992. These patients were screened for HCV using HCV antibody followed by HCV RNA if the screening test was positive. Of the 188 adults, 116 (43% male patients, 24-70 years) were screened for the HCV antibody, demonstrating that 104 individuals were negative and 12 subjects were positive for the virus. Subsequently, further testing for the presence of HCV demonstrated 11 of 12 were infected, with an overall prevalence of 9.5%. Five individuals chose to be treated with sofosbuvir/ledipasvir and 5 of 5 have successfully cleared the virus and are considered cured. Adults with congenital heart disease who underwent cardiac surgery before 1992 warrant being screened for HCV, and, if testing positive, may be considered for therapy using direct-acting antiviral agents with close monitoring for cardiac complications.

Occult Hepatitis B Virus Infection in Anti-HBs-Positive Infants Born to HBsAg-Positive Mothers in China

PubMed Central

Xu, Dezhong; Wang, Bo; Zhang, Lei; Li, Duan; Xiao, Dan; Li, Fan; Zhang, Jingxia; Yan, Yongping

2013-01-01

Objective To investigate the prevalence of occult HBV infection (OBI) among children and to characterize virology of occult HBV, we conducted an epidemiological survey. Methods 186 HB-vaccinated infants born to HBsAg-positive mothers were included in the study. Serological tests for HBV markers were performed using commercial ELISA kits. Real-time quantitative PCR and nested PCR were used to detect HBV DNA. PCR products of the C and pre-S/S regions were sequenced and analyzed. Results 1.61% (3/186) infants were HBsAg positive, and 4.92% (9/183) infants were considered as occult infection. The viral load of mothers was associated with occult infection (P = 0.020). Incomplete three-dose injections of HB vaccine was associated with HBV infection (P = 0.022). Six OBI infants were positive for anti-HBs, but their titers were not greater than 100 mIU/mL. Seven isolated HBV pre-S/S sequences were obtained from nine OBI infants. Three of the sequences were genotype C, and four of the sequences were genotype C/D. Escape mutation S143L was found in the four sequences of genotype C/D. All seven sequences lacked G145R and other escape mutation in S region. Conclusions Occult HBV infection was detected in anti-HBs positive infants born to HBsAg-positive mothers in China. Occult infection was associated with absent anti-HBs or with low anti-HBs level, high maternal viral loads and escape mutations in the S gene. PMID:23951004

Knowledge of Case Workers and Correctional Officers towards HIV and HCV Infections: Opportunity for Public Health Education in the Correctional System.

PubMed

Pérez, Cynthia M; del Carmen Santos, María; Torres, Aurinés; Grana, Carlos; Albizu-García, Carmen

2015-09-01

Given the heavy burden of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections in correctional facilities, we examined knowledge about these infections among case workers and correctional officers in penal institutions in Puerto Rico. We used data from a cross-sectional study of state prisons, commissioned by the Puerto Rico Department of Correction and Rehabilitation, to assess knowledge about HCV and HIV (10 items each) among 256 case workers and correctional officers from 18 penal institutions selected in the prison system. Total scores for each scale ranged from 0 to 10 points, with higher scores reflecting more knowledge. Of 256 participants, 64.8% were males, 39.6% were aged 30-39 years, and 70.3% were case workers. The percentage of correct responses for knowledge items ranged from 8.5% to 97.0% for HCV infection and from 38.7% to 99.6% for HIV infection. The vast majority (>96%) of participants knew that injection drug users should be tested for HCV infection and that sharing of needle injection equipment and multiple sex partners increase the risk of HIV infection. However, misconceptions about routes of transmission for these viral infections were found, with larger gaps in knowledge for HCV infection. Mean knowledge scores for HCV and HIV infections were 4.20±0.17 and 6.95±0.22, respectively, being significantly (p<0.05) higher for case workers. The findings about HCV and HIV knowledge in an important segment of the correctional system staff support the urgent need for increasing educational opportunities for correctional staff.

Detection of occult hepatitis B and window period infection among blood donors by individual donation nucleic acid testing in a tertiary care center in South India.

PubMed

Keechilot, Cinzia S; Shenoy, Veena; Kumar, Anil; Biswas, Lalitha; Vijayrajratnam, Sukhithasri; Dinesh, Kavitha; Nair, Prem

With the introduction of highly sensitive hepatitis B surface antigen immunoassay, transfusion associated HBV infection have reduced drastically but they still tend to occur due to blood donors with occult hepatitis B infection (OBI) and window period (WP) infection. Sera from, 24338 healthy voluntary blood donors were screened for HBsAg, HIV and HCV antibody using Vitros Enhanced Chemiluminescent Immunoassay. The median age of the donor population was 30 (range 18-54) with male preponderance (98%). All serologically negative samples were screened by nucleic acid testing (NAT) for viral DNA and RNA. NAT-positive samples were subjected to discriminatory NAT for HBV, HCV, and HIV and all samples positive for HBV DNA were tested for anti-HBc, anti-HBs, HBeAg. Viral load was determined using artus HBV RG PCR Kit. Of the 24,338 donors screened, 99.81% (24292/24338) were HBsAg negative of which NAT was positive for HBV DNA in 0.0205% (5/24292) donors. Four NAT positive donors had viral load of <200 IU/ml making them true cases of OBI. One NAT positive donor was negative for all antibodies making it a case of WP infection. Among OBI donors, 75% (3/4) were immune and all were negative for HBeAg. Precise HBV viral load could not be determined in all (5/5) NAT positive donors due to viral loads below the detection limit of the artus HBV RG PCR Kit. The overall incidence of OBI and WP infections was found to be low at 1 in 6503 and 1 in 24214 donations, respectively. More studies are needed to determine the actual burden of WP infections in Indian blood donors.

Prevalence of HCV Infection Among Clients in Community-Based Health Settings in Hawaii, 2002–2010: Assessing Risk Factors

PubMed Central

Porter, Jeremy C.; Lusk, Heather M.

2014-01-01

Objectives. We sought to determine the prevalence of HCV infection and identify risk factors associated with HCV infection among at-risk clients presenting to community-based health settings in Hawaii. Methods. Clients from 23 community-based sites were administered risk factor questionnaires and screened for HCV antibodies from December 2002 through May 2010. We performed univariate and multivariate logistic regression analyses. Results. Of 3306 participants included in the analysis, 390 (11.8%) tested antibody positive for HCV. Highest HCV antibody prevalence (17.0%) was in persons 45 to 64 years old compared with all other age groups. Significant independent risk factors were current or prior injection drug use (P < .001), blood transfusion prior to July 1992 (P = .002), and having an HCV-infected sex partner (P = .03). Stratification by gender revealed sexual exposure to be significant for males (P = .001). Conclusions. Despite Hawaii’s ethnic diversity, high hepatocellular carcinoma incidence, and a statewide syringe exchange program in place since the early 1990s, our HCV prevalence and risk factor findings are remarkably consistent with those reported from the mainland United States. Hence, effective interventions identified from US mainland population studies should be generalizable to Hawaii. PMID:24028267

Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection.

PubMed

Foster, Graham R; Afdhal, Nezam; Roberts, Stuart K; Bräu, Norbert; Gane, Edward J; Pianko, Stephen; Lawitz, Eric; Thompson, Alex; Shiffman, Mitchell L; Cooper, Curtis; Towner, William J; Conway, Brian; Ruane, Peter; Bourlière, Marc; Asselah, Tarik; Berg, Thomas; Zeuzem, Stefan; Rosenberg, William; Agarwal, Kosh; Stedman, Catherine A M; Mo, Hongmei; Dvory-Sobol, Hadas; Han, Lingling; Wang, Jing; McNally, John; Osinusi, Anu; Brainard, Diana M; McHutchison, John G; Mazzotta, Francesco; Tran, Tram T; Gordon, Stuart C; Patel, Keyur; Reau, Nancy; Mangia, Alessandra; Sulkowski, Mark

2015-12-31

In phase 2 trials, treatment with the combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir resulted in high rates of sustained virologic response in patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3. We conducted two randomized, phase 3, open-label studies involving patients who had received previous treatment for HCV genotype 2 or 3 and those who had not received such treatment, including patients with compensated cirrhosis. In one trial, patients with HCV genotype 2 were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir, in a once-daily, fixed-dose combination tablet (134 patients), or sofosbuvir plus weight-based ribavirin (132 patients) for 12 weeks. In a second trial, patients with HCV genotype 3 were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir for 12 weeks (277 patients) or sofosbuvir-ribavirin for 24 weeks (275 patients). The primary end point for the two trials was a sustained virologic response at 12 weeks after the end of therapy. Among patients with HCV genotype 2, the rate of sustained virologic response in the sofosbuvir-velpatasvir group was 99% (95% confidence interval [CI], 96 to 100), which was superior to the rate of 94% (95% CI, 88 to 97) in the sofosbuvir-ribavirin group (P=0.02). Among patients with HCV genotype 3, the rate of sustained virologic response in the sofosbuvir-velpatasvir group was 95% (95% CI, 92 to 98), which was superior to the rate of 80% (95% CI, 75 to 85) in the sofosbuvir-ribavirin group (P<0.001). The most common adverse events in the two studies were fatigue, headache, nausea, and insomnia. Among patients with HCV genotype 2 or 3 with or without previous treatment, including those with compensated cirrhosis, 12 weeks of treatment with sofosbuvir-velpatasvir resulted in rates of sustained virologic response that were superior to those with standard treatment with sofosbuvir-ribavirin. (Funded by Gilead Sciences

Block effect on HCV infection by HMGB1 released from virus-infected cells: An insight from mathematical modeling

NASA Astrophysics Data System (ADS)

Wang, Wei; Ma, Wanbiao

2018-06-01

The nuclear protein high-mobility group box 1 (HMGB1) can have an active role in deoxyribonucleic acid (DNA) organization and the regulation of transcription. Based on the new findings from a recent experimental study, the blocking effect on HCV infection by HMGB1 released from virus-infected cells is investigated using a diffusive model for viral infection dynamics. In the model, the diffusion of the virus depends not only on its concentration gradient, but also on the concentration of HMGB1. The basic reproduction number, threshold dynamics, stability properties of the steady states, travelling wave solutions, and spreading speed for the proposed model are studied. We show that the HMGB1-induced blocking of HCV infection slows the spread of virus compared with random diffusion only. Numerically, it is shown that a high concentration of HMGB1 can block the spread of virus and this confirms, not only qualitatively but also quantitatively, the experimental result.

Therapeutic Advances in HCV Genotype 1 Infection: Insights from the Society of Infectious Diseases Pharmacists.

PubMed

Deming, Paulina; Martin, Michelle T; Chan, Juliana; Dilworth, Thomas J; El-Lababidi, Rania; Love, Bryan L; Mohammad, Rima A; Nguyen, Amy; Spooner, Linda M; Wortman, Suzanne B

2016-02-01

Hepatitis C virus (HCV) is the most common blood-borne infection in the United States. The high morbidity and mortality due to untreated infection have prompted updated screening recommendations that now include one-time HCV screening for all patients born between 1945 and 1965, in addition to risk factor-based screening. Current guidelines recommend treatment for all patients with chronic HCV. Treatment for HCV genotype 1 has evolved dramatically since the approval of the direct-acting antivirals. The approval of ledipasvir-sofosbuvir, ombitasvir-paritaprevir-ritonavir and dasabuvir, and simeprevir with sofosbuvir has dramatically altered the treatment landscape. High sustained virologic response (SVR) rates favor treatment, yet access to care poses a challenge for patients and providers. Current and emerging data with new therapies indicate high SVR rates in treatment-naïve and treatment-experienced patients, including patients with cirrhosis and in other special populations. Additional data suggest the addition of ribavirin can decrease treatment duration without compromising SVR rates. Resistance is an increasing area of interest in HCV, with baseline mutations identified and the potential for the development of resistance-associate variants in patients undergoing treatment. Due to the rapid evolution of HCV treatment, pharmacists should address challenges and play an integral role in agent selection, dosing, drug interaction screening, adverse effect monitoring, and the coordination of treatment. Clinical application of the latest information will reduce patient risk and improve outcomes. © 2016 Pharmacotherapy Publications, Inc.

The geographic distribution patterns of HIV-, HCV- and co-infections among drug users in a national methadone maintenance treatment program in Southwest China.

PubMed

Zhou, Yi-Biao; Liang, Song; Wang, Qi-Xing; Gong, Yu-Han; Nie, Shi-Jiao; Nan, Lei; Yang, Ai-Hui; Liao, Qiang; Song, Xiu-Xia; Jiang, Qing-Wu

2014-03-10

HIV-, HCV- and HIV/HCV co-infections among drug users have become a rapidly emerging global public health problem. In order to constrain the dual epidemics of HIV/AIDS and drug use, China has adopted a methadone maintenance treatment program (MMTP) since 2004. Studies of the geographic heterogeneity of HIV and HCV infections at a local scale are sparse, which has critical implications for future MMTP implementation and health policies covering both HIV and HCV prevention among drug users in China. This study aimed to characterize geographic patterns of HIV and HCV prevalence at the township level among drug users in a Yi Autonomous Prefecture, Southwest of China. Data on demographic and clinical characteristics of all clients in the 11 MMTP clinics of the Yi Autonomous Prefecture from March 2004 to December 2012 were collected. A GIS-based geographic analysis involving geographic autocorrelation analysis and geographic scan statistics were employed to identify the geographic distribution pattern of HIV-, HCV- and co-infections among drug users. A total of 6690 MMTP clients was analyzed. The prevalence of HIV-, HCV- and co-infections were 25.2%, 30.8%, and 10.9% respectively. There were significant global and local geographic autocorrelations for HIV-, HCV-, and co-infection. The Moran's I was 0.3015, 0.3449, and 0.3155, respectively (P < 0.0001). Both the geographic autocorrelation analysis and the geographic scan statistical analysis showed that HIV-, HCV-, and co-infections in the prefecture exhibited significant geographic clustering at the township level. The geographic distribution pattern of each infection group was different. HIV-, HCV-, and co-infections among drug users in the Yi Autonomous Prefecture all exhibited substantial geographic heterogeneity at the township level. The geographic distribution patterns of the three groups were different. These findings imply that it may be necessary to inform or invent site-specific intervention strategies to

The geographic distribution patterns of HIV-, HCV- and co-infections among drug users in a national methadone maintenance treatment program in Southwest China

PubMed Central

2014-01-01

Background HIV-, HCV- and HIV/HCV co-infections among drug users have become a rapidly emerging global public health problem. In order to constrain the dual epidemics of HIV/AIDS and drug use, China has adopted a methadone maintenance treatment program (MMTP) since 2004. Studies of the geographic heterogeneity of HIV and HCV infections at a local scale are sparse, which has critical implications for future MMTP implementation and health policies covering both HIV and HCV prevention among drug users in China. This study aimed to characterize geographic patterns of HIV and HCV prevalence at the township level among drug users in a Yi Autonomous Prefecture, Southwest of China. Methods Data on demographic and clinical characteristics of all clients in the 11 MMTP clinics of the Yi Autonomous Prefecture from March 2004 to December 2012 were collected. A GIS-based geographic analysis involving geographic autocorrelation analysis and geographic scan statistics were employed to identify the geographic distribution pattern of HIV-, HCV- and co-infections among drug users. Results A total of 6690 MMTP clients was analyzed. The prevalence of HIV-, HCV- and co-infections were 25.2%, 30.8%, and 10.9% respectively. There were significant global and local geographic autocorrelations for HIV-, HCV-, and co-infection. The Moran’s I was 0.3015, 0.3449, and 0.3155, respectively (P < 0.0001). Both the geographic autocorrelation analysis and the geographic scan statistical analysis showed that HIV-, HCV-, and co-infections in the prefecture exhibited significant geographic clustering at the township level. The geographic distribution pattern of each infection group was different. Conclusion HIV-, HCV-, and co-infections among drug users in the Yi Autonomous Prefecture all exhibited substantial geographic heterogeneity at the township level. The geographic distribution patterns of the three groups were different. These findings imply that it may be necessary to inform or invent

Preclinical evaluation of multi antigenic HCV DNA vaccine for the prevention of Hepatitis C virus infection.

PubMed

Lee, Hyojin; Jeong, Moonsup; Oh, Jooyeon; Cho, Youngran; Shen, Xuefei; Stone, John; Yan, Jian; Rothkopf, Zachary; Khan, Amir S; Cho, Byung Mun; Park, Young K; Weiner, David B; Son, Woo-Chan; Maslow, Joel N

2017-03-07

Direct-acting antiviral treatment for hepatitis C virus (HCV) infection is costly and does not protect from re-infection. For human and chimpanzees, recovery from acute HCV infection correlates with host CD4+ and CD8+ T cell responses. DNA plasmids targeting the HCV non-structural antigens NS3, NS4, and NS5, were previously reported to induce robust and sustained T cell responses in mice and primates. These plasmids were combined with a plasmid encoding cytokine IL-28B, together named as VGX-6150. The dose-dependent T cell response and safety of VGX-6150 administered intramuscularly and followed by electroporation was assessed in mice. Immune responses plateaued at 20 μg/dose with IL-28B demonstrating significant immunoadjuvant activity. Mice administered VGX-6150 at 40, 400, and 800 μg given either as a single injection or as 14 injections given bi-weekly over 26 weeks showed no vaccine related changes in any clinical parameter compared to placebo recipients. There was no evidence of VGX-6150 accumulation at the injection site or in any organ 1 month following the 14 th vaccination. Based on these studies, the approximate lethal dose (ALD) exceeds 800 μg/dose and the NOAEL was 800 μg/dose in mouse. In conclusion, VGX-6150 appears safe and a promising preventive vaccine candidate for HCV infection.

Preclinical evaluation of multi antigenic HCV DNA vaccine for the prevention of Hepatitis C virus infection

PubMed Central

Lee, Hyojin; Jeong, Moonsup; Oh, Jooyeon; Cho, Youngran; Shen, Xuefei; Stone, John; Yan, Jian; Rothkopf, Zachary; Khan, Amir S.; Cho, Byung Mun; Park, Young K.; Weiner, David B.; Son, Woo-Chan; Maslow, Joel N.

2017-01-01

Direct-acting antiviral treatment for hepatitis C virus (HCV) infection is costly and does not protect from re-infection. For human and chimpanzees, recovery from acute HCV infection correlates with host CD4+ and CD8+ T cell responses. DNA plasmids targeting the HCV non-structural antigens NS3, NS4, and NS5, were previously reported to induce robust and sustained T cell responses in mice and primates. These plasmids were combined with a plasmid encoding cytokine IL-28B, together named as VGX-6150. The dose-dependent T cell response and safety of VGX-6150 administered intramuscularly and followed by electroporation was assessed in mice. Immune responses plateaued at 20 μg/dose with IL-28B demonstrating significant immunoadjuvant activity. Mice administered VGX-6150 at 40, 400, and 800 μg given either as a single injection or as 14 injections given bi-weekly over 26 weeks showed no vaccine related changes in any clinical parameter compared to placebo recipients. There was no evidence of VGX-6150 accumulation at the injection site or in any organ 1 month following the 14th vaccination. Based on these studies, the approximate lethal dose (ALD) exceeds 800 μg/dose and the NOAEL was 800 μg/dose in mouse. In conclusion, VGX-6150 appears safe and a promising preventive vaccine candidate for HCV infection. PMID:28266565

Incidence and Residual Risk of HIV, HBV and HCV Infections Among Blood Donors in Tehran.

PubMed

Saber, Hamid Reza; Tabatabaee, Seyed Morteza; Abasian, Ali; Jamali, Mostafa; SalekMoghadam, Ebadollah; Hajibeigi, Bashir; Alavian, Seyed Moayed; Mirrezaie, Seyed Mohammad

2017-09-01

Estimation of residual risk is essential to monitor and improve blood safety. Our epidemiologic knowledge in the Iranian donor population regarding transfusion transmitted viral infections (TTIs), is confined to a few studies based on prevalence rate. There are no reports on residual risk of TTIs in Iran. In present survey, a software database of donor records of Tehran Blood Transfusion Center (TBTC) was used to estimate the incidence and residual risk of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections, by applying the incidence rate/window period (IR-WP) model. A total of 1,207,155 repeat donations was included in the analysis and represented a mean of 8.4 donations per donor over 6 years. The incidence amongst repeat donors was estimated by dividing the number of confirmed seroconverting donors by the total number of person-years at risk. The residual risk was calculated using the incidence/window period model. Incidence rate and residual risk for HBV, HCV and HIV infections were calculated for total (2005-2010) and two consecutive periods (2005-2007 and 2008-2010) of the study. According to the IR-WP model, overall residual risk for HIV and HCV in the total study period was 0.4 and 12.5 per million units, respectively and for HBV 4.57/100,000 donations. The incidence and residual risk of TTIs, calculated on TBTC's blood supply was low and comparable with developed countries for HIV infection but high for HCV and HBV infections. Blood safety may therefore be better managed by applying other techniques like nucleic acid amplification tests.

Comparison of a newly developed automated and quantitative hepatitis C virus (HCV) core antigen test with the HCV RNA assay for clinical usefulness in confirming anti-HCV results.

PubMed

Kesli, Recep; Polat, Hakki; Terzi, Yuksel; Kurtoglu, Muhammet Guzel; Uyar, Yavuz

2011-12-01

Hepatitis C virus (HCV) is a global health care problem. Diagnosis of HCV infection is mainly based on the detection of anti-HCV antibodies as a screening test with serum samples. Recombinant immunoblot assays are used as supplemental tests and for the final detection and quantification of HCV RNA in confirmatory tests. In this study, we aimed to compare the HCV core antigen test with the HCV RNA assay for confirming anti-HCV results to determine whether the HCV core antigen test may be used as an alternative confirmatory test to the HCV RNA test and to assess the diagnostic values of the total HCV core antigen test by determining the diagnostic specificity and sensitivity rates compared with the HCV RNA test. Sera from a total of 212 treatment-naive patients were analyzed for anti-HCV and HCV core antigen both with the Abbott Architect test and with the molecular HCV RNA assay consisting of a reverse transcription-PCR method as a confirmatory test. The diagnostic sensitivity, specificity, and positive and negative predictive values of the HCV core antigen assay compared to the HCV RNA test were 96.3%, 100%, 100%, and 89.7%, respectively. The levels of HCV core antigen showed a good correlation with those from the HCV RNA quantification (r = 0.907). In conclusion, the Architect HCV antigen assay is highly specific, sensitive, reliable, easy to perform, reproducible, cost-effective, and applicable as a screening, supplemental, and preconfirmatory test for anti-HCV assays used in laboratory procedures for the diagnosis of hepatitis C virus infection.

Protective effect of coffee consumption on all-cause mortality of French HIV-HCV co-infected patients.

PubMed

Carrieri, Maria Patrizia; Protopopescu, Camelia; Marcellin, Fabienne; Rosellini, Silvia; Wittkop, Linda; Esterle, Laure; Zucman, David; Raffi, François; Rosenthal, Eric; Poizot-Martin, Isabelle; Salmon-Ceron, Dominique; Dabis, François; Spire, Bruno

2017-12-01

Coffee has anti-inflammatory and hepato-protective properties. In the general population, drinking ≥3cups of coffee/day has been associated with a 14% reduction in the risk of all-cause mortality. The aim of this study was to investigate the relationship between coffee consumption and the risk of all-cause mortality in patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). ANRS CO13 HEPAVIH is an ongoing French nationwide prospective cohort of patients co-infected with HIV-HCV collecting both medical and psychosocial/behavioural data (annual self-administered questionnaires). We used a Cox proportional hazards model to estimate the effect of elevated coffee consumption (≥3cups/day) at baseline on all-cause mortality during the cohort's five-year follow-up. Over a median [interquartile range] follow-up of 5.0 [3.9-5.9] years, 77 deaths occurred among 1,028 eligible patients (mortality rate 1.64/100 person-years; 95% confidence interval [CI] 1.31-2.05). Leading causes of death were HCV-related diseases (n=33, 43%), cancers unrelated to AIDS/HCV (n=9, 12%), and AIDS (n=8, 10%). At the first available visit, 26.6% of patients reported elevated coffee consumption. Elevated coffee consumption at baseline was associated with a 50% reduced risk of all-cause mortality (hazard ratio 0.5; CI 0.3-0.9; p=0.032), after adjustment for gender and psychosocial, behavioral and clinical time-varying factors. Drinking three or more cups of coffee per day halves all-cause mortality risk in patients co-infected with HIV-HCV. The benefits of coffee extracts and supplementing dietary intake with other anti-inflammatory compounds need to be evaluated in this population. Coffee has anti-inflammatory and hepato-protective properties but its effect on mortality risk has never been investigated in patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). This study shows that elevated coffee consumption (≥3cups

Kushenin induces the apoptosis of HCV-infected cells by blocking the PI3K-Akt-mTOR pathway via inhibiting NS5A

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

Zhou, Yi; Chen, Na; Liu, Xiaojing

With the increased burden induced by HCV, there is an urgent need to develop better-tolerated agents with good safety. In this study, we evaluated the anti-HCV capability of kushenin, as well as the possible mechanism to Huh7.5-HCV cells. The results demonstrated that kushenin significantly inhibited the HCV-RNA level. Similarly, the expression of HCV-specific protein NS5A was also decreased. Molecular docking results displayed that kushenin bonded well to the active pockets of HCV NS5A, further confirming the effects of kushenin on HCV replication. Coimmunoprecipitation assay determined that kushenin suppressed the interaction between PI3K and NS5A in HCV-replicon cells. Furthermore, kushenin exertedmore » an obviously induced function on HCV-replicon cells apoptosis by inhibiting PI3K-Akt-mTOR pathway, which could be ameliorated by the specific activator IGF-1 addition. Taken together, kushenin possesses the ability to inhibit HCV replication, and contributes to the increased apoptosis of HCV-infected cells by blocking the PI3K-Akt-mTOR pathway via inhibiting NS5A. Our results provide important evidence for a better understanding of the pathogenesis of HCV infection, and suggest that kushenin has the potential to treat HCV disease. - Highlights: • Kushenin inhibits HCV replication. • Kushenin bonds directly to NS5A protein. • Kushenin induces the apoptosis of HCV-infected cells. • kushenin suppresses the interaction between PI3K and NS5A. • Kushenin inhibits PI3K-Akt-mTOR pathway.« less

Clinical utility of the ARCHITECT HCV Ag assay for early treatment monitoring in patients with chronic hepatitis C genotype 1 infection.

PubMed

Vermehren, Johannes; Susser, Simone; Berger, Annemarie; Perner, Dany; Peiffer, Kai-Henrik; Allwinn, Regina; Zeuzem, Stefan; Sarrazin, Christoph

2012-09-01

Virologic response-monitoring is essential for determining therapy duration in patients with chronic hepatitis C virus (HCV) infection. This is usually performed using highly sensitive HCV-RNA assays. However, HCV-RNA assays are time-consuming, expensive and require highly trained personnel. Quantitative determination of HCV core-antigen (HCVAg) levels may be used to supplement treatment monitoring. The clinical utility of the ARCHITECT HCV Ag assay (Abbott Diagnostics) for response-guided therapy was investigated. We analyzed serum from 160 patients with HCV genotype 1 infection who had been treated with peg-interferon alfa-2b/ribavirin. HCVAg levels were determined at baseline, weeks 1, 2, 4 and 12. HCVAg levels were compared to those obtained with HCV-RNA assays: VERSANT HCV Quantitative 3.0 (bDNA) and Qualitative (TMA, both Siemens Healthcare) assay and the Abbott RealTime HCV assay (ART; Abbott Diagnostics). Baseline HCVAg levels correlated well with HCV-RNA as assessed by bDNA (r=0.91; p<0.0001) and ART (r=0.92; p<0.0001), respectively. Patients with undetectable HCVAg levels at week 1 had a 90.9% probability (positive predictive value) to achieve a rapid virologic response (HCV-RNA undetectable at week 4) based on TMA and 86.4% based on ART, respectively. Patients with less than 1 log(10) reduction in HCVAg between baseline and week 12 had a 90% probability (negative predictive value) to achieve a nonresponse (<2 log(10) decline in HCV-RNA between baseline and week 12) based on bDNA and 100% based on ART, respectively. Determination of HCVAg may be useful for antiviral response-monitoring in patients with HCV genotype 1 infection. Copyright © 2012 Elsevier B.V. All rights reserved.

Sero-Prevalence of Bloodborne Tumor Viruses (HCV, HBV, HTLV-I and KSHV Infections) and Related Risk Factors among Prisoners in Razavi Khorasan Province, Iran, in 2008

PubMed Central

Khajedaluee, Mohammad; Babaei, Ali; Vakili, Rosita; Valizade, Narges; Homaei Shandiz, Fateme; Alavian, Seyed Moayed; Seyed Nozadi, Mohsen; Jazayeri, Seyed Mohammad; Hassannia, Tahereh

2016-01-01

Background Prisoners are at high risk of blood borne and sexually transmitted infections due to their high involvement in risky behaviors. In this descriptive/cross-sectional study, the prevalence, sero-prevalence, and risk factors for bloodborne tumor viruses including HTLV-I, HBV, HCV, and KSHV were evaluated among inmates of two central prisons in the northeast of Iran. Methods Blood samples of 1114 inmates were analyzed for the presence of anti HTLV-I, KSHV, and HCV antibodies and HBsAg by ELISA. PCR tests were performed to confirm the presence of these viruses in plasma and identify the current infections. Results The sero-prevalence of HCV, HBV, HTLV-I, and KSHV was 24.5%, 4.2%, 3.4%, and 3.2% and the prevalence of HCV, HBV, HTLV-I, and KSHV was 19.1%, 2.1%, 2%, and 3%, respectively. HCV infection was significantly associated with history of imprisonment, tobacco consumption, alcohol consumption, intravenous drug use, length of imprisonment, and type of crime committed. Thirty one (2.8%) prisoners had HCV-KSHV co-infection, 16 (1.5%) had HCV-HTLV-I co-infection, and 14 (1.3%) had HBV-HCV co-infection. Triple co-infection was observed in seven cases and one case had four infections concomitantly. Conclusions This epidemiological study indicated different rates and transmission risks for these viruses. HCV was the most contagious viral infection and HTLV-I was the weakest in the prisoners. Apart from KSHV infection which its prevalence was as twice as in the general population, the prevalence of HBV and HTLV-I in prisoners was nearly in ranges of the general population. PMID:28123439

IFNL4 ss469415590 Variant Is Associated with Treatment Response in Japanese HCV Genotype 1 Infected Individuals Treated with IFN-Including Regimens

PubMed Central

Miyamura, Tatsuo; Kanda, Tatsuo; Nakamoto, Shingo; Arai, Makoto; Nakamura, Masato; Wu, Shuang; Jiang, Xia; Sasaki, Reina; Yasui, Shin; Ooka, Yoshihiko; Imazeki, Fumio; Mikami, Shigeru; Yokosuka, Osamu

2014-01-01

Aim. Eradication of hepatitis C virus (HCV) is still challenging even if interferon- (IFN-) free regimens with direct-acting antiviral agents (DAAs) for HCV-infected individuals are available in clinical practice. IFNL4 is a newly described protein, associated with human antiviral defenses. We investigated whether IFNL4 ss469415590 variant has an effect on the prediction of treatment response in HCV-infected patients treated with IFN-including regimens. Patients and Methods. In all, 185 patients infected with HCV genotype 1 treated with peg-IFN plus ribavirin, with or without telaprevir, were genotyped for IFNL4 ss469415590. We retrospectively investigated whether the role of IFNL4 ss469415590 variant and other factors could predict sustained virological response (SVR) in Japanese patients infected with HCV genotype 1. Results. There were 65.7%, 31.5%, and 2.8% patients in the IFNL4 ss469415590 TT/TT, TT/-G, and -G/-G groups, respectively. SVR rates were 82.1% or 49.3% in patients treated with peg-IFN plus ribavirin with or without telaprevir, respectively. IFNL4 ss469415590 variant and HCV viral loads or IFNL4 ss469415590 variant and early virological response were better predictors of SVR in patients treated with peg-IFN plus ribavirin with or without telaprevir, respectively. Conclusion. In the era of DAAs, measurement of IFNL4 ss469415590 variant could help the prediction of SVR in Japanese HCV genotype 1 infected individuals treated with IFN-including regimens. PMID:25548683

Comparison of the Bayer VERSANT HCV RNA 3.0 and the Roche COBAS Amplicor HCV Monitor, Version 2.0, assays in HCV genotype 4 infection.

PubMed

Jessner, W; Watkins-Riedel, T; Müller, C; Formann, E; Gschwantler, M; Ferenci, P

2007-11-01

Prediction of treatment response is clinically important in chronic hepatitis C virus (HCV) genotype 4 infection. Early viral kinetics is useful in this respect for genotype 1 but interpretation is dependent on assay linearity and reproducibility. The VERSANT HCV RNA 3.0 (bDNA-3.0) and the COBAS Amplicor HCV Monitor 2.0 (HCM-2.0) have been widely used quantitative assays. We wanted to comparatively evaluate the two tests in a large genotype 4 sample. Genotyping was performed by NS5b sequencing. Viral load was tested in parallel in 32 patients at least six times on antiviral therapy with interferon alpha (IFNalpha). Totally, 198 samples within a quantitative range from undetectable to about 7 x 10(6) IU/mL (bDNA-3.0) were obtained and compared. Twenty-two samples with viral load above 500 000 IU/mL tested by HCM-2.0 were 1:100 diluted and retested. Quantitative values were fitted to a third order polynomial (M = 0.118303 + 1.07503 x V+ 0.0112128 x V(2) - 0.0055504 x V(3); M...HCM-2.0, V...bDNA-3.0, both log IU/mL) showing progressive nonlinearity of HCM-2.0 above 100 000 IU/mL but better clinical sensitivity with respect to bDNA-3.0. Dilution lead to a gain of at least a factor of 2.7 and thus, overestimation compared with bDNA-3.0. Deviation from linearity and overestimation upon dilution by HCM-2.0 are similar with HCV genotype 4, compared with other HCV genotypes. Differences in test performance were not detected for subtypes but for individual patients possibly related to specific quasi-species patterns. The interpretation of viral kinetic data becomes difficult due to overestimation upon dilution of baseline values by HCM-2.0.

HIV/HCV Coinfection in Taiwan.

PubMed

Hsu, Ching-Sheng; Kao, Jia-Horng

2016-01-01

Both human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection are important global public health problems with shared transmission routes. Although HIV/HCV coinfection is not uncommon, the prevalence rates vary significantly across different studies and regions. In Taiwan, injection drug users have become the major contributors to the HIV/AIDS epidemic since 2005. Because the prevalence of HCV infection is high in injection drug users, this HIV epidemic is also associated with a significant increase of HIV/HCV coinfection in Taiwan. To control Taiwan's HIV epidemic, Taiwan Centers for Disease Control (CDC) launched a harm-reduction program in 2006. The HIV epidemic, the percentage attributed to injection drug users, and the prevalence of HIV/HCV coinfection gradually declined thereafter. In this article, we aimed to thoroughly examine the current literatures of HIV/HCV coinfection in Taiwan and hope to provide a better understanding of the needs for the management of this coinfection. We conducted a narrative review and searched for literature from PubMed, Ovid MEDLINE, and the Cochrane Library database untill August 2015. Studies relevant to the epidemiology and associated risk factors of HIV/HCV coinfection in Taiwan were examined and discussed.

Engaging HIV-HCV co-infected patients in HCV treatment: the roles played by the prescribing physician and patients' beliefs (ANRS CO13 HEPAVIH cohort, France)

PubMed Central

2012-01-01

Background Treatment for the hepatitis C virus (HCV) may be delayed significantly in HIV/HCV co-infected patients. Our study aims at identifying the correlates of access to HCV treatment in this population. Methods We used 3-year follow-up data from the HEPAVIH ANRS-CO13 nationwide French cohort which enrolled patients living with HIV and HCV. We included pegylated interferon and ribavirin-naive patients (N = 600) at enrolment. Clinical/biological data were retrieved from medical records. Self-administered questionnaires were used for both physicians and their patients to collect data about experience and behaviors, respectively. Results Median [IQR] follow-up was 12[12-24] months and 124 patients (20.7%) had started HCV treatment. After multiple adjustment including patients' negative beliefs about HCV treatment, those followed up by a general practitioner working in a hospital setting were more likely to receive HCV treatment (OR[95%CI]: 1.71 [1.06-2.75]). Patients followed by general practitioners also reported significantly higher levels of alcohol use, severe depressive symptoms and poor social conditions than those followed up by other physicians. Conclusions Hospital-general practitioner networks can play a crucial role in engaging patients who are the most vulnerable and in reducing existing inequities in access to HCV care. Further operational research is needed to assess to what extent these models can be implemented in other settings and for patients who bear the burden of multiple co-morbidities. PMID:22409788

Engaging HIV-HCV co-infected patients in HCV treatment: the roles played by the prescribing physician and patients' beliefs (ANRS CO13 HEPAVIH cohort, France).

PubMed

Salmon-Ceron, Dominique; Cohen, Julien; Winnock, Maria; Roux, Perrine; Sadr, Firouze Bani; Rosenthal, Eric; Martin, Isabelle Poizot; Loko, Marc-Arthur; Mora, Marion; Sogni, Philippe; Spire, Bruno; Dabis, François; Carrieri, Maria Patrizia

2012-03-12

Treatment for the hepatitis C virus (HCV) may be delayed significantly in HIV/HCV co-infected patients. Our study aims at identifying the correlates of access to HCV treatment in this population. We used 3-year follow-up data from the HEPAVIH ANRS-CO13 nationwide French cohort which enrolled patients living with HIV and HCV. We included pegylated interferon and ribavirin-naive patients (N = 600) at enrolment. Clinical/biological data were retrieved from medical records. Self-administered questionnaires were used for both physicians and their patients to collect data about experience and behaviors, respectively. Median [IQR] follow-up was 12[12-24] months and 124 patients (20.7%) had started HCV treatment. After multiple adjustment including patients' negative beliefs about HCV treatment, those followed up by a general practitioner working in a hospital setting were more likely to receive HCV treatment (OR[95%CI]: 1.71 [1.06-2.75]). Patients followed by general practitioners also reported significantly higher levels of alcohol use, severe depressive symptoms and poor social conditions than those followed up by other physicians. Hospital-general practitioner networks can play a crucial role in engaging patients who are the most vulnerable and in reducing existing inequities in access to HCV care. Further operational research is needed to assess to what extent these models can be implemented in other settings and for patients who bear the burden of multiple co-morbidities.

Comparison of liver fibrosis blood tests developed for HCV with new specific tests in HIV/HCV co-infection.

PubMed

Calès, Paul; Halfon, Philippe; Batisse, Dominique; Carrat, Fabrice; Perré, Philippe; Penaranda, Guillaume; Guyader, Dominique; d'Alteroche, Louis; Fouchard-Hubert, Isabelle; Michelet, Christian; Veillon, Pascal; Lambert, Jérôme; Weiss, Laurence; Salmon, Dominique; Cacoub, Patrice

2010-08-01

We compared 5 non-specific and 2 specific blood tests for liver fibrosis in HCV/HIV co-infection. Four hundred and sixty-seven patients were included into derivation (n=183) or validation (n=284) populations. Within these populations, the diagnostic target, significant fibrosis (Metavir F > or = 2), was found in 66% and 72% of the patients, respectively. Two new fibrosis tests, FibroMeter HICV and HICV test, were constructed in the derivation population. Unadjusted AUROCs in the derivation population were: APRI: 0.716, Fib-4: 0.722, Fibrotest: 0.778, Hepascore: 0.779, FibroMeter: 0.783, HICV test: 0.822, FibroMeter HICV: 0.828. AUROCs adjusted on classification and distribution of fibrosis stages in a reference population showed similar values in both populations. FibroMeter, FibroMeter HICV and HICV test had the highest correct classification rates in F0/1 and F3/4 (which account for high predictive values): 77-79% vs. 70-72% in the other tests (p=0.002). Reliable individual diagnosis based on predictive values > or = 90% distinguished three test categories: poorly reliable: Fib-4 (2.4% of patients), APRI (8.9%); moderately reliable: Fibrotest (25.4%), FibroMeter (26.6%), Hepascore (30.2%); acceptably reliable: HICV test (40.2%), FibroMeter HICV (45.6%) (p<10(-3) between tests). FibroMeter HICV classified all patients into four reliable diagnosis intervals (< or =F1, F1+/-1, > or =F1, > or =F2) with an overall accuracy of 93% vs. 79% (p<10(-3)) for a binary diagnosis of significant fibrosis. Tests designed for HCV infections are less effective in HIV/HCV infections. A specific test, like FibroMeter HICV, was the most interesting test for diagnostic accuracy, correct classification profile, and a reliable diagnosis. With reliable diagnosis intervals, liver biopsy can therefore be avoided in all patients. Copyright 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Randomized, Placebo-Controlled, Single-Ascending-Dose Study of BMS-791325, a Hepatitis C Virus (HCV) NS5B Polymerase Inhibitor, in HCV Genotype 1 Infection

PubMed Central

Lemm, Julie; Eley, Timothy; Liu, Menping; Berglind, Anna; Sherman, Diane; Lawitz, Eric; Vutikullird, Apinya B.; Tebas, Pablo; Gao, Min; Pasquinelli, Claudio; Grasela, Dennis M.

2014-01-01

BMS-791325 is a nonnucleoside inhibitor of hepatitis C virus (HCV) NS5B polymerase with low-nanomolar potency against genotypes 1a (50% effective concentration [EC50], 3 nM) and 1b (EC50, 7 nM) in vitro. BMS-791325 safety, pharmacokinetics, and antiviral activity were evaluated in a double-blind, placebo-controlled, single-ascending-dose study in 24 patients (interferon naive and experienced) with chronic HCV genotype 1 infection, randomized (5:1) to receive a single dose of BMS-791325 (100, 300, 600, or 900 mg) or placebo. The prevalence and phenotype of HCV variants at baseline and specific posttreatment time points were assessed. Antiviral activity was observed in all cohorts, with a mean HCV RNA decline of ≈2.5 log10 copies/ml observed 24 h after a single 300-mg dose. Mean plasma half-life among cohorts was 7 to 9 h; individual 24-hour levels exceeded the protein-adjusted EC90 for genotype 1 at all doses. BMS-791325 was generally well tolerated, with no serious adverse events or discontinuations. Enrichment for resistance variants was not observed at 100 to 600 mg. At 900 mg, variants (P495L/S) associated with BMS-791325 resistance in vitro were transiently observed in one patient, concurrent with an observed HCV RNA decline of 3.4 log10 IU/ml, but were replaced with wild type by 48 h. Single doses of BMS-791325 were well tolerated; demonstrated rapid, substantial, and exposure-related antiviral activity; displayed dose-related increases in exposure; and showed viral kinetic and pharmacokinetic profiles supportive of once- or twice-daily dosing. These results support its further development in combination with other direct-acting antivirals for HCV genotype 1 infection. (This trial has been registered at ClinicalTrials.gov under registration no. NCT00664625.) PMID:24733462

Genetic variation of occult hepatitis B virus infection

PubMed Central

Zhu, Hui-Lan; Li, Xu; Li, Jun; Zhang, Zhen-Hua

2016-01-01

Occult hepatitis B virus infection (OBI), characterized as the persistence of hepatitis B virus (HBV) surface antigen (HBsAg) seronegativity and low viral load in blood or liver, is a special form of HBV infection. OBI may be related mainly to mutations in the HBV genome, although the underlying mechanism of it remains to be clarified. Mutations especially within the immunodominant “α” determinant of S protein are “hot spots” that could contribute to the occurrence of OBI via affecting antigenicity and immunogenicity of HBsAg or replication and secretion of virion. Clinical reports account for a large proportion of previous studies on OBI, while functional analyses, especially those based on full-length HBV genome, are rare. PMID:27053845

Decreased sensitivity of early imaging with In-111 oxine-labeled leukocytes in detection of occult infection: concise communication

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

Datz, F.L.; Jacobs, J.; Baker, W.

1984-03-01

Imaging with leukocytes labeled with indium-111 oxine is a sensitive technique for detecting sites of occult infection. Traditionally, imaging is performed 24 hr after injection. The authors undertook a prospective study of 35 patients (40 studies) with possible occult infection to see whether a 24-hr delay in imaging is really necessary. Patients were imaged at 1-4 hr and again at 24 hr after injection. The early images had a sensitivity of only 33%, compared with 95% for the 24-hr images. Of the seven studies that were positive on both early and delayed images, 71% had more intense uptake at 24more » hr. There were no false-positive early images. It was concluded that imaging 1-4 hr after injection with In-111 oxine-labeled leukocytes has a low sensitivity for detecting occult infection. However, a positive early image is specific for a site of infection.« less

IL28B gene polymorphism rs12979860, but not rs8099917, contributes to the occurrence of chronic HCV infection in Uruguayan patients.

PubMed

Echeverría, Natalia; Chiodi, Daniela; López, Pablo; Sanchez Ciceron, Adriana; Angulo, Jenniffer; López-Lastra, Marcelo; Silvera, Paola; Canavesi, Adrian; Bianchi, Carla; Colistro, Valentina; Cristina, Juan; Hernandez, Nelia; Moreno, Pilar

2018-03-02

Host single-nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) locus are associated with sustained virological response to antiviral therapy and with spontaneous Hepatitis C Virus (HCV) clearance. Prevalence of these SNPs varies depending on ethnicity. The impact of IL28B SNPs in HCV-infected patients is currently unknown in Uruguay. Therefore, the aim of this study was to evaluate and compare the distribution of polymorphisms in the IL28B gene (rs12979860 and rs8099917) among HCV-infected patients and healthy individuals in Uruguay and thus assess their possible association with the establishment of HCV infection. DNA was recovered from 92 non-infected individuals and 78 HCV-infected patients and SNPs were determined by RFLP and allelic discrimination by real-time PCR. The distribution of rs12979860 genotypes for the infected population was 29.5%-CC, 47.4%-CT and 23.1%-TT and for the control group 45.7%, 42.4% and 11.9%, respectively. Prevalence in both infected and uninfected individuals is similar to that reported in other countries with admixed populations. The distribution of rs8099917 genotypes for the infected population was 57.7%-TT, 27.2%-TG and 14.1%-GG and for the control group 60.9%, 33.7% and 5.4%, respectively. The comparison of rs12979860 genotype distribution between the two populations evidenced a higher prevalence of the favourable genotype (CC) in the uninfected control group (p < 0.05). Additionally, results generated using logistic regression analysis show that individuals carrying rs12979860-TT or CT genotypes have a higher likelihood of developing chronic hepatitis upon infection with HCV, when compared to CC carriers, considering rs8099917 genotype as constant. Patients with HCV infection have a statistically significant lower prevalence of the favourable rs12979860 genotype when compared to uninfected individuals; therefore we can establish that only IL28B rs12979860-CT and TT genotypes seem to contribute to the occurrence

Stroke in HIV-infected individuals with and without HCV coinfection in Spain in the combination antiretroviral therapy era

PubMed Central

Alvaro-Meca, Alejandro; Díaz, Asunción; Micheloud, Dariela; Aldámiz-Echevarría, Teresa; Fanciulli, Chiara

2017-01-01

The incidence of stroke in human immunodeficiency virus (HIV)–infected individuals has been well analyzed in recent epidemiological studies. However, little is known about the specific contribution of hepatitis C virus (HCV) infection to stroke among HIV-infected individuals. The aims of this study were to analyze trends in the incidence rates of stroke in HIV-infected individuals during the combination antiretroviral (cART) era in Spain and to categorize them by the presence or absence of HCV coinfection. We analyzed hospital discharges with a diagnosis of stroke in Spain according to ICD-9-CM during 1997–2013. The study period was divided into four calendar periods (1997–1999, 2000–2003, 2004–2007, and 2008–2013). Patients were classified according to HCV serology. The number of HIV-infected patients was estimated based on data from the National Centre of Epidemiology. We calculated incidence rates (events per 10,000 patient-years) and in-hospital case fatality rates (CFR). The incidence of hemorrhagic stroke (HS) decreased in HIV-monoinfected patients (15.8 [1997–1999] to 6.5 [2008–2013]; P<0.001) and increased in HIV/HCV-coinfected patients (1.3 [1997–1999] to 5.5 [2008–2013]; P<0.001). The incidence of ischemic stroke (IS) decreased in HIV-monoinfected patients (27.4 [1997–1999] to 21.7 [2008–2013]; P = 0.005) and increased in HIV/HCV-coinfected patients (1.8 [1997–1999] to 11.9 [2008–2013]; P<0.001). The CFR was 3.3 times higher for HS than for IS for the whole study period. The CFR of HS in HIV-monoinfected patients decreased significantly (47.4% [1997–1999] to 30.6% [2008–2013]; P = 0.010) but did not change significantly among HIV/HCV-coinfected patients (41.4% [1997–1999] to 44.7% [2008–2013]; P = 0.784). The CFR of IS in the whole HIV-infected population decreased significantly (14.6% [1997–1999] to 10.9% [2008–2013]; P = 0.034), although no significant differences were found when each group was analyzed separately

Seroprevalence and diagnosis of HIV, HBV, HCV and syphilis infections among blood donors.

PubMed

Tafesse, Tadesse Bekele; Gebru, Addis Adera; Gobalee, Semgne; Belay, Gosaye Degu; Belew, Molla Teferi; Ataro, Demelash; Ebrahim, Belay Ali; Shebeshi, Getachew Mekonnon; Yimam, Yonas

2017-01-01

Blood transfusion is one of the most important therapeutic options of life-saving intervention for recipients who are in diseased or non-diseased conditions with severe blood loss. However, it is associated with certain risks which can lead to adverse consequences that may cause acute or delayed complications and bring the risk of transfusion-transmissible infections including HIV, Hepatitis B & C and Syphilis. So, there might be a fatal risk instead of life saving. This paper aims to provide a comprehensive and reliable tabulation of available data on seroprevalence and diagnosis of HIV, HBV, HCV and Syphilis infections among blood donors. We searched studies reporting the prevalence rate of HIV, HBV, HCV and Syphilis infections among blood donors that were published between October 2009 and June 2016, using databases of PubMed, Scopus, MEDLINE, Elsevier, ScienceDirect, EBSCO, Google Scholar, EMBASE, and Web of Science with keywords: ``Hepatitis C Virus'', ``Hepatitis B Virus'', ``HIV'', ``Syphilis'', ``Seroprevalence'', and ``blood donor''. The seroprevalence of HBV and HCV was highest in African countries as compared to others continents, predominantly the West African region with a range of 10.0% to 14.96% and 1.5% to 8.69%, respectively, while the overall seropositivity of HIV and syphilis infection show a significant declining pattern through successive years globally, even though relatively higher prevalence rate was observed among older age and those with low level of education. There is a problem during selection, diagnoses and screening process in developing nations primarily due to shortage of sensitive screening test kits, highly qualified human resource and lack of proper standard operating procedures and hence, the safety of blood and blood products are the primary threats in the region. Proper clinical diagnosis and screening method should be applied during blood donation and therefore, all the donated blood should be screened properly for

Distribution of HCV genotypes in Poland.

PubMed

Panasiuk, Anatol; Flisiak, Robert; Mozer-Lisewska, Iwona; Adamek, Agnieszka; Tyczyno, Małgorzata; Halota, Waldemar; Pawłowska, Małgorzata; Stańczak, Janusz; Berak, Hanna; Wawrzynowicz-Syczewska, Marta; Boroń-Kaczmarska, Anna; Łapiński, Tadeusz Wojciech; Grzeszczuk, Anna; Piekarska, Anna; Tomasiewicz, Krzysztof; Jabłkowski, Maciej; Kryczka, Wiesław; Zarebska-Michaluk, Dorota; Stepień, Piotr; Garlicki, Aleksander Michał; Kozłowska, Joanna; Wiercińska-Drapało, Alicja; Zasik, Ewelina; Mazur, Waldemar; Dobracka, Bozena; Dobracki, Witold; Simon, Krzysztof; Ryzko, Józef; Pawłowska, Joanna; Dzierzanowska-Fangrat, Katarzyna; Januszkiewicz-Lewandowska, Danuta; Szenborn, Leszek; Zaleska, Izabela; Rokitka, Maria; Strawińska, Elzbieta; Balinowska, Katarzyna; Smiatacz, Tomasz; Stalke, Piotr; Sikorska, Katarzyna; Lakomy, Anna; Zdrojewski, Maciej; Lachowicz, Anna

2013-01-01

Available data on prevalence of HCV genotypes in Poland are insufficient. The aim of the study was the analysis of distribution of HCV genotypes in Poland over the period of recent 10 years regarding the age of patients and the regions of the country. Analysis of HCV genotypes in Poland was carried out between 2003 and 2012, and included 14 651 patients from 22 centers where patients with chronic viral hepatitis C are diagnosed and treated. Genotypes were analyzed in age groups (< 20 years of age, 20-40 years of age, > 40 years of age) as well as in populations of HBV and HIV co-infections. Genotype (G) 1 infection was demonstrated in 79.4%, G2 -0.1%, G3- 13.8%, G4- 4.9%, G6-0.09% and mixed infections in 1.6%. There was no infection with genotype 5. The highest prevalence of G1 was observed in the Łódzkie voivodship (89.2%) and the Slaskie voivodship (86.7%) while the lowest one in the Warmińsko-mazurskie (62.0%) and the Podlaskie voivodships (68.2%). Genotype 3 most commonly occurs in the Warmińsko-mazurskie (28.1%), and the Podlaskie voivodships (23.0%) and is least common in the Małopolskie (7.9%) and the Łódzkie voivodships (9.0%). Genotype 4 is more common in the Kujawsko-pomorskie (11.7%) and the Podlaskie voivodships (8.6%) and relatively less common in the Lubelskie (1.1%) and the Łódzkie voivodships (1.8%). Prevalence of G1 infection in 2003-2004 was 72% and increased up to 85.6% in 2011-2012, that was accompanied by decrease of G3 prevalence from 17% to 8% in this period. In HBV co-infected (n = 83), G1 infection was demonstrated in 85.5%, G3 - in 7.2%, G4 -4.8%, and mixed genotypes in 6%. Among HIV co-infected (n = 391), a much lower prevalence of G1 (33.0%) and a high of G3 (40.4%) as well as G4 (24.0%) were observed. There is a geographic variability of HCV genotypes prevalence in Poland. Increase of HCV G1 infections and decrease of G3 and G4 were observed in the last 10 years. Genotypes G3 and G4 occur more often in HCV/HIV co-infected than

PML tumor suppressor protein is required for HCV production

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

Kuroki, Misao; Research Fellow of the Japan Society for the Promotion of Science; Center for AIDS Research, Kumamoto University, Kumamoto 860-0811

2013-01-11

Highlights: Black-Right-Pointing-Pointer PML tumor suppressor protein is required for HCV production. Black-Right-Pointing-Pointer PML is dispensable for HCV RNA replication. Black-Right-Pointing-Pointer HCV could not alter formation of PML-NBs. Black-Right-Pointing-Pointer INI1 and DDX5, PML-related proteins, are involved in HCV life cycle. -- Abstract: PML tumor suppressor protein, which forms discrete nuclear structures termed PML-nuclear bodies, has been associated with several cellular functions, including cell proliferation, apoptosis and antiviral defense. Recently, it was reported that the HCV core protein colocalizes with PML in PML-NBs and abrogates the PML function through interaction with PML. However, role(s) of PML in HCV life cycle is unknown.more » To test whether or not PML affects HCV life cycle, we examined the level of secreted HCV core and the infectivity of HCV in the culture supernatants as well as the level of HCV RNA in HuH-7-derived RSc cells, in which HCV-JFH1 can infect and efficiently replicate, stably expressing short hairpin RNA targeted to PML. In this context, the level of secreted HCV core and the infectivity in the supernatants from PML knockdown cells was remarkably reduced, whereas the level of HCV RNA in the PML knockdown cells was not significantly affected in spite of very effective knockdown of PML. In fact, we showed that PML is unrelated to HCV RNA replication using the subgenomic HCV-JFH1 replicon RNA, JRN/3-5B. Furthermore, the infectivity of HCV-like particle in the culture supernatants was significantly reduced in PML knockdown JRN/3-5B cells expressing core to NS2 coding region of HCV-JFH1 genome using the trans-packaging system. Finally, we also demonstrated that INI1 and DDX5, the PML-related proteins, are involved in HCV production. Taken together, these findings suggest that PML is required for HCV production.« less

Declining Hepatitis C Virus (HCV) Incidence in Dutch Human Immunodeficiency Virus-Positive Men Who Have Sex With Men After Unrestricted Access to HCV Therapy.

PubMed

Boerekamps, Anne; van den Berk, Guido E; Lauw, Fanny N; Leyten, Eliane M; van Kasteren, Marjo E; van Eeden, Arne; Posthouwer, Dirk; Claassen, Mark A; Dofferhoff, Anton S; Verhagen, Dominique W M; Bierman, Wouter F; Lettinga, Kamilla D; Kroon, Frank P; Delsing, Corine E; Groeneveld, Paul H; Soetekouw, Robert; Peters, Edgar J; Hullegie, Sebastiaan J; Popping, Stephanie; van de Vijver, David A M C; Boucher, Charles A; Arends, Joop E; Rijnders, Bart J

2018-04-17

Direct-acting antivirals (DAAa) cure hepatitis C virus (HCV) infections in 95% of infected patients. Modeling studies predict that universal HCV treatment will lead to a decrease in the incidence of new infections but real-life data are lacking. The incidence of HCV among Dutch human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) has been high for >10 years. In 2015 DAAs became available to all Dutch HCV patients and resulted in a rapid treatment uptake in HIV-positive MSM. We assessed whether this uptake was followed by a decrease in the incidence of HCV infections. Two prospective studies of treatment for acute HCV infection enrolled patients in 17 Dutch HIV centers, having 76% of the total HIV-positive MSM population in care in the Netherlands. Patients were recruited in 2014 and 2016, the years before and after unrestricted DAA availability. We compared the HCV incidence in both years. The incidence of acute HCV infection decreased from 93 infections during 8290 person-years of follow-up (PYFU) in 2014 (11.2/1000 PYFU; 95% confidence interval [CI], 9.1-13.7) to 49 during 8961 PYFU in 2016 (5.5/1000 PYFU; 4.1-7.2). The incidence rate ratio of 2016 compared with 2014 was 0.49 (95% CI, .35-.69). Simultaneously, a significant increase in the percentage positive syphilis (+2.2%) and gonorrhea (+2.8%) tests in HIV-positive MSM was observed at sexual health clinics across the Netherlands and contradicts a decrease in risk behavior as an alternative explanation. Unrestricted DAA availability in the Netherlands was followed by a 51% decrease in acute HCV infections among HIV-positive MSM.

Humanisation of a claudin-1-specific monoclonal antibody for clinical prevention and cure of HCV infection without escape.

PubMed

Colpitts, Che C; Tawar, Rajiv G; Mailly, Laurent; Thumann, Christine; Heydmann, Laura; Durand, Sarah C; Xiao, Fei; Robinet, Eric; Pessaux, Patrick; Zeisel, Mirjam B; Baumert, Thomas F

2018-04-01

HCV infection is a leading cause of chronic liver disease and a major indication for liver transplantation. Although direct-acting antivirals (DAAs) have much improved the treatment of chronic HCV infection, alternative strategies are needed for patients with treatment failure. As an essential HCV entry factor, the tight junction protein claudin-1 (CLDN1) is a promising antiviral target. However, genotype-dependent escape via CLDN6 and CLDN9 has been described in some cell lines as a possible limitation facing CLDN1-targeted therapies. Here, we evaluated the clinical potential of therapeutic strategies targeting CLDN1. We generated a humanised anti-CLDN1 monoclonal antibody (mAb) (H3L3) suitable for clinical development and characterised its anti-HCV activity using cell culture models, a large panel of primary human hepatocytes (PHH) from 12 different donors, and human liver chimeric mice. H3L3 pan-genotypically inhibited HCV pseudoparticle entry into PHH, irrespective of donor. Escape was likely precluded by low surface expression of CLDN6 and CLDN9 on PHH. Co-treatment of a panel of PHH with a CLDN6-specific mAb did not enhance the antiviral effect of H3L3, confirming that CLDN6 does not function as an entry factor in PHH from multiple donors. H3L3 also inhibited DAA-resistant strains of HCV and synergised with current DAAs. Finally, H3L3 cured persistent HCV infection in human-liver chimeric uPA-SCID mice in monotherapy. Overall, these findings underscore the clinical potential of CLDN1-targeted therapies and describe the functional characterisation of a humanised anti-CLDN1 antibody suitable for further clinical development to complement existing therapeutic strategies for HCV. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Prediction of minimal residual viremia in HCV type 1 infected patients receiving interferon-based therapy.

PubMed

Knop, Viola; Teuber, Gerlinde; Klinker, Hartwig; Möller, Bernd; Rasenack, Jens; Hinrichsen, Holger; Gerlach, Tilman; Spengler, Ulrich; Buggisch, Peter; Neumann, Konrad; Sarrazin, Christoph; Zeuzem, Stefan; Berg, Thomas

2013-01-01

Complete suppression of viral replication is crucial in chronic HCV treatment in order to prevent relapse and resistance development. We wanted to find out which factors influence the period from being already HCV RNA negative by bDNA assay (< 615 IU/mL) to become undetectable by the more sensitive TMA test (< 5.3 IU/mL). Evaluated were 433 HCV type 1-infected patients. All of them received 1.5 ug/kg Peg-IFNα-2b plus ribavirin for 18-48 weeks. bDNA was performed weekly during the first 8 weeks and thereafter at weeks 12, 24, and 48. Patients who became bDNA undetectable were additionally analysed by TMA. Of the 309 patients with on-treatment response (< 615 IU/mL), 289 also reached undetectable HCV RNA levels by TMA. Multivariate analysis revealed that viremia ≤ 400,000 IU/mL (p = 0.001), fast initial virologic decline (p = 0.004) and absence of fibrosis (p = 0.035) were independent predictors of an accelerated on-treatment response by TMA assay in already bDNA negative patients. bDNA negative patients becoming HCV RNA undetectable by TMA within the following 3 weeks had a frequency of relapse of 21%, whereas those showing TMA negativity after 3 weeks relapsed in 38% (p = 0.001). In RVR patients (bDNA < 615 IU/mL at week 4) the corresponding relapse rates were 15.3% vs. 37.5%, respectively (p = 0.003). Early viral kinetics, baseline viremia and fibrosis stage are important tools to predict persistent minimal viremia during interferon-based therapy. The data have implications for designing a more refined treatment strategy in HCV infection, even in the setting of protease inhibitor-based triple treatment.

Characteristics of escape mutations from occult hepatitis B virus infected patients with hematological malignancies in South Egypt.

PubMed

Elkady, Abeer; Iijima, Sayuki; Aboulfotuh, Sahar; Mostafa Ali, Elsayed; Sayed, Douaa; Abdel-Aziz, Nashwa M; Ali, Amany M; Murakami, Shuko; Isogawa, Masanori; Tanaka, Yasuhito

2017-03-28

To investigate the prevalence and virological characteristics of occult hepatitis B virus (HBV) infections in patients with hematological malignancies in South Egypt. Serum samples were collected from 165 patients with hematological malignancies to monitor titers of HBV DNA, hepatitis B surface antigen (HBsAg), and antibodies to HBV core (anti-HBc) and surface antigens. Serum samples negative for HBsAg and positive for anti-HBc were subjected to nucleic acid extraction and HBV DNA detection by real-time polymerase chain reaction. DNA sequences spanning the S region were analyzed in cases with occult HBV infection. In vitro comparative study of constructed 1.24-fold wild type and S protein mutant HBV genotype D clones was further performed. HBV DNA was detected in 23 (42.6%) of 54 patients with hematological malignancies who were HBsAg negative, but anti-HBc positive, suggesting the presence of occult HBV infection. The complete HBV genome was retrieved from 6 occult HBV patients, and P120T and S143L were detected in 3 and 2 cases, respectively. Site directed mutagenesis was done to produce 1.24-fold genotype D clones with amino acid mutations T120 and L143. The in vitro analyses revealed that a lower level of extracellular HBsAg was detected by chemiluminescence enzyme immunoassay (CLEIA) with the clone containing T120 mutation, compared with the wild type or the clone with S143L mutation despite the similar levels of extracellular and intracellular HBsAg detected by Western blot. Southern blot experiments showed that the levels of intracellular HBV DNA were not different between these clones. Occult HBV infection is common in patients with hematological malignancies and associated with P120T and S143L mutations. 120T mutation impairs the detection of HBsAg by CLEIA.

Characteristics of escape mutations from occult hepatitis B virus infected patients with hematological malignancies in South Egypt

PubMed Central

Elkady, Abeer; Iijima, Sayuki; Aboulfotuh, Sahar; Mostafa Ali, Elsayed; Sayed, Douaa; Abdel-Aziz, Nashwa M; Ali, Amany M; Murakami, Shuko; Isogawa, Masanori; Tanaka, Yasuhito

2017-01-01

AIM To investigate the prevalence and virological characteristics of occult hepatitis B virus (HBV) infections in patients with hematological malignancies in South Egypt. METHODS Serum samples were collected from 165 patients with hematological malignancies to monitor titers of HBV DNA, hepatitis B surface antigen (HBsAg), and antibodies to HBV core (anti-HBc) and surface antigens. Serum samples negative for HBsAg and positive for anti-HBc were subjected to nucleic acid extraction and HBV DNA detection by real-time polymerase chain reaction. DNA sequences spanning the S region were analyzed in cases with occult HBV infection. In vitro comparative study of constructed 1.24-fold wild type and S protein mutant HBV genotype D clones was further performed. RESULTS HBV DNA was detected in 23 (42.6%) of 54 patients with hematological malignancies who were HBsAg negative, but anti-HBc positive, suggesting the presence of occult HBV infection. The complete HBV genome was retrieved from 6 occult HBV patients, and P120T and S143L were detected in 3 and 2 cases, respectively. Site directed mutagenesis was done to produce 1.24-fold genotype D clones with amino acid mutations T120 and L143. The in vitro analyses revealed that a lower level of extracellular HBsAg was detected by chemiluminescence enzyme immunoassay (CLEIA) with the clone containing T120 mutation, compared with the wild type or the clone with S143L mutation despite the similar levels of extracellular and intracellular HBsAg detected by Western blot. Southern blot experiments showed that the levels of intracellular HBV DNA were not different between these clones. CONCLUSION Occult HBV infection is common in patients with hematological malignancies and associated with P120T and S143L mutations. 120T mutation impairs the detection of HBsAg by CLEIA. PMID:28396718

Asymptomatic Hepadnaviral Persistence and Its Consequences in the Woodchuck Model of Occult Hepatitis B Virus Infection

PubMed Central

Mulrooney-Cousins, Patricia M.; Michalak, Tomasz I.

2015-01-01

Woodchuck hepatitis virus (WHV) is molecularly and pathogenically closely related to hepatitis B virus (HBV). Both viruses display tropism towards hepatocytes and cells of the immune system and cause similar liver pathology, where acute hepatitis can progress to chronic hepatitis and to hepatocellular carcinoma (HCC). Two forms of occult hepadnaviral persistence were identified in the woodchuck-WHV model: secondary occult infection (SOI) and primary occult infection (POI). SOI occurs after resolution of a serologically apparent infection with hepatitis or after subclinical serologically evident virus exposure. POI is caused by small amounts of virus and progresses without serological infection markers, but the virus genome and its replication are detectable in the immune system and with time in the liver. SOI can be accompanied by minimal hepatitis, while the hallmark of POI is normal liver morphology. Nonetheless, HCC develops in about 20% of animals with SOI or POI within 3 to 5 years. The virus persists throughout the lifespan in both SOI and POI at serum levels rarely greater than 100 copies/mL, causes hepatitis and HCC when concentrated and administered to virus-naïve woodchucks. SOI is accompanied by virus-specific T and B cell immune responses, while only virus-specific T cells are detected in POI. SOI coincides with protection against reinfection, while POI does not and hepatitis develops after challenge with liver pathogenic doses >1000 virions. Both SOI and POI are associated with virus DNA integration into the liver and the immune system genomes. Overall, SOI and POI are two distinct forms of silent hepadnaviral persistence that share common characteristics. Here, we review findings from the woodchuck model and discuss the relevant observations made in human occult HBV infection (OBI). PMID:26623268

Asymptomatic Hepadnaviral Persistence and Its Consequences in the Woodchuck Model of Occult Hepatitis B Virus Infection.

PubMed

Mulrooney-Cousins, Patricia M; Michalak, Tomasz I

2015-09-28

Woodchuck hepatitis virus (WHV) is molecularly and pathogenically closely related to hepatitis B virus (HBV). Both viruses display tropism towards hepatocytes and cells of the immune system and cause similar liver pathology, where acute hepatitis can progress to chronic hepatitis and to hepatocellular carcinoma (HCC). Two forms of occult hepadnaviral persistence were identified in the woodchuck-WHV model: secondary occult infection (SOI) and primary occult infection (POI). SOI occurs after resolution of a serologically apparent infection with hepatitis or after subclinical serologically evident virus exposure. POI is caused by small amounts of virus and progresses without serological infection markers, but the virus genome and its replication are detectable in the immune system and with time in the liver. SOI can be accompanied by minimal hepatitis, while the hallmark of POI is normal liver morphology. Nonetheless, HCC develops in about 20% of animals with SOI or POI within 3 to 5 years. The virus persists throughout the lifespan in both SOI and POI at serum levels rarely greater than 100 copies/mL, causes hepatitis and HCC when concentrated and administered to virus-naïve woodchucks. SOI is accompanied by virus-specific T and B cell immune responses, while only virus-specific T cells are detected in POI. SOI coincides with protection against reinfection, while POI does not and hepatitis develops after challenge with liver pathogenic doses >1000 virions. Both SOI and POI are associated with virus DNA integration into the liver and the immune system genomes. Overall, SOI and POI are two distinct forms of silent hepadnaviral persistence that share common characteristics. Here, we review findings from the woodchuck model and discuss the relevant observations made in human occult HBV infection (OBI).

The HCV and HIV coinfected patient: what have we learned about pathophysiology?

PubMed

Talal, Andrew H; Canchis, P Wilfredo; Jacobson, Ira

2002-02-01

Hepatitis C virus (HCV) infection is an important problem in individuals who are also infected with HIV. HCV infection is very common in HIV-infected individuals, occurring in approximately one quarter to one third of this group, presumably as a consequence of shared routes of transmission related to virologic and pathogenic aspects of the viral infections. Although both are single-stranded RNA viruses and share similar epidemiologic properties, there are many important differences. Although the quantity of HIV RNA in plasma is an important prognostic determinant of HIV infection, this has not been shown with HCV. A direct relationship is apparent between HIV-related destruction of CD4 cells and the clinical consequences of the disease resulting from immunodeficiency. The pathogenesis of HCV, which occurs as a consequence of hepatic fibrosis, is much more complex. The hepatic stellate cell, the major producer of the extracellular matrix protein, is the main contributor to hepatic fibrosis, but the mechanism by which HCV induces hepatic fibrosis remains unclear. Treatment of HCV is increasingly important in HIV-infected patients due to improved HIV-associated morbidity and mortality and due to the frequency with which HCV occurs in patients with HIV-HCV coinfection. Timing of treatment initiation, management of side effects, and possible effects of anti-HCV therapy on HIV are among the issues that need consideration. Also, because several issues concerning HCV are unique to coinfected patients, further research is needed to determine optimal management of HCV in this setting.

No difference in sensitivity for occult infection between tropolone- and oxine-labeled indium-111 leukocytes

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

Datz, F.L.; Bedont, R.A.; Baker, W.J.

1985-05-01

There is considerable disagreement as to whether oxine or tropolone is the best labeling agent for indium leukocytes. The authors have previously looked at the sensitivity of oxine-labeled /sup 111/In leukocyte scans for occult infections and now present a similar group of patients imaged with tropolone-labeled /sup 111/In leukocytes. Thirty-four patients (38 studies) with possible occult infection were prospectively studied. Patients were imaged 1-4 hr after injection and again at 24 hr postinjection. The differences in sensitivity between oxine and tropolone when imaged early and at 24 hr were not statistically significant. They conclude that there is not significant differencemore » in the ability to detect infection between oxine- and tropolone-labeled leukocytes, both early at 1-4 hr, and on delayed imaging 24 hr after injection.« less

High Dead-Space Syringes and the Risk of HIV and HCV Infection among Injecting Drug Users

PubMed Central

Zule, William A.; Bobashev, Georgiy; International, RTI

2009-01-01

This study examines the association between using and sharing high dead-space syringes (HDSSs)—which retain over 1,000 times more blood after rinsing than low dead-space syringes (LDSSs)—and prevalent HIV and hepatitis C virus (HCV) infections among injecting drug users (IDUs). A sample of 851 out-of-treatment IDUs was recruited in Raleigh-Durham, North Carolina, between 2003 and 2005. Participants were tested for HIV and HCV antibodies. Demographic, drug use, and injection practice data were collected via interviews. Data were analyzed using multiple logistic regression analysis. Participants had a mean age of 40 years and 74% percent are male, 63% are African American, 29% are non-Hispanic white, and 8% are of other race/ethnicity. Overall, 42% of participants had ever used an HDSS and 12% had shared one. HIV prevalence was 5% among IDUs who had never used an HDSS compared with 16% among IDUs who had shared one. The HIV model used a propensity score approach to adjust for differences between IDUs who had used an HDSS and those who had never used one. The HCV models included all potential confounders as covariates. A history of sharing HDSSs was associated with prevalent HIV (Odds Ratio = 2.50; 95% Confidence Interval = 1.01, 6.15). Use and sharing of HDSSs were also associated with increased odds of HCV infection. Prospective studies are needed to determine if sharing HDSSs is associated with increased HIV and HCV incidence among IDUs. PMID:19004579

HCV associated glomerulopathy in Egyptian patients: clinicopathological analysis

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

Sabry, Alaa; E-Agroudy, Amgd; Sheashaa, Hussein

Background: Hepatitis C virus (HCV) infection in Egypt has reached an epidemic proportion and is associated with many extra hepatic manifestations; Glomerulonephritis (GN) is one of the most consequences of HCV infection often resulting in end stage renal disease in some cases. Detection of viral genome or particles within the kidney biopsies from HCV-infected patients has proven to be difficult. Histological characterization of renal lesions still represents a major challenge. The aim of our work was to describe the histological pattern of HCV-associated nephropathy. Methods: Fifty Patients - out of 233 - presented to Mansoura Urology and Nephrology clinic withmore » manifestations of glomerular disease were screened for HCV antibodies by a 3rd generation ELISA test. Those tested positive for HCV antibodies were confirmed by PCR for HCV-RNA and subjected to more detailed clinical, biochemical and histological study. Kidney biopsies and in appropriate cases liver biopsies were examined by LM and electron microscopy (EM). Results: Histological study of renal biopsies revealed membranoproliferative (MPGN) type 1 to be the most common lesion encountered (54%), followed by focal segmental glomerulosclerosis (FSGS) (24%), mesangioproliferative GN (18%), membranous nephropathy (MN) (4%) in that order. EM examinations of renal biopsies were successful in identifying HCV like particles in frozen renal tissue. Conclusion: HCV-associated glomerulopathy is a distinct category of glomerulonephritis. Results of LM showed some peculiar features. In addition, we were successful in location and detection of HCV particles in renal tissues by EM.« less

SUMO1 depletion prevents lipid droplet accumulation and HCV replication.

PubMed

Akil, Abdellah; Wedeh, Ghaith; Zahid Mustafa, Mohammad; Gassama-Diagne, Ama

2016-01-01

Infection by hepatitis C virus (HCV) is a major public-health problem. Chronic infection often leads to cirrhosis, steatosis, and hepatocellular carcinoma. The life cycle of HCV depends on the host cell machinery and involves intimate interaction between viral and host proteins. However, the role of host proteins in the life cycle of HCV remains poorly understood. Here, we identify the small ubiquitin-related modifier (SUMO1) as a key host factor required for HCV replication. We performed a series of cell biology and biochemistry experiments using the HCV JFH-1 (Japanese fulminate hepatitis 1) genotype 2a strain, which produces infectious particles and recapitulates all the steps of the HCV life cycle. We observed that SUMO1 is upregulated in Huh7.5 infected cells. Reciprocally, SUMO1 was found to regulate the expression of viral core protein. Moreover, knockdown of SUMO1 using specific siRNA influenced the accumulation of lipid droplets and reduced HCV replication as measured by qRT-PCR. Thus, we identify SUMO1 as a key host factor required for HCV replication. To our knowledge, this is the first report showing that SUMO1 regulates lipid droplets in the context of viral infection. Our report provides a meaningful insight into how HCV replicates and interacts with host proteins and is of significant importance for the field of HCV and RNA viruses.

An OPTIMIZE study retrospective analysis for management of telaprevir-treated hepatitis C virus (HCV)-infected patients by use of the Abbott RealTime HCV RNA assay.

PubMed

Sarrazin, Christoph; Dierynck, Inge; Cloherty, Gavin; Ghys, Anne; Janssen, Katrien; Luo, Donghan; Witek, James; Buti, Maria; Picchio, Gaston; De Meyer, Sandra

2015-04-01

Protease inhibitor (PI)-based response-guided triple therapies for hepatitis C virus (HCV) infection are still widely used. Noncirrhotic treatment-naive and prior relapser patients receiving telaprevir-based treatment are eligible for shorter, 24-week total therapy if HCV RNA is undetectable at both weeks 4 and 12. In this study, the concordance in HCV RNA assessments between the Roche High Pure System/Cobas TaqMan and Abbott RealTime HCV RNA assays and the impacts of different HCV RNA cutoffs on treatment outcome were evaluated. A total of 2,629 samples from 663 HCV genotype 1 patients receiving telaprevir/pegylated interferon/ribavirin in OPTIMIZE were analyzed using the High Pure System and reanalyzed using Abbott RealTime (limits of detection, 15.1 IU/ml versus 8.3 IU/ml; limits of quantification, 25 IU/ml versus 12 IU/ml, respectively). Overall, good concordance was observed between the assays. Using undetectable HCV RNA at week 4, 34% of the patients would be eligible for shorter treatment duration with Abbott RealTime versus 72% with the High Pure System. However, using <12 IU/ml for Abbott RealTime, a similar proportion (74%) would be eligible. Of the patients receiving 24-week total therapy, 87% achieved a sustained virologic response with undetectable HCV RNA by the High Pure System or <12 IU/ml by Abbott RealTime; however, 92% of the patients with undetectable HCV RNA by Abbott RealTime achieved a sustained virologic response. Using undetectable HCV RNA as the cutoff, the more sensitive Abbott RealTime assay would identify fewer patients eligible for shorter treatment than the High Pure System. Our data confirm the <12-IU/ml cutoff, as previously established in other studies of the Abbott RealTime assay, to determine eligibility for shortened PI-based HCV treatment. (The study was registered with ClinicalTrials.gov under registration no. NCT01241760.). Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Characterization of occult hepatitis B virus infection among HIV positive patients in Cameroon.

PubMed

Gachara, George; Magoro, Tshifhiwa; Mavhandu, Lufuno; Lum, Emmaculate; Kimbi, Helen K; Ndip, Roland N; Bessong, Pascal O

2017-03-08

Occult hepatitis B infection (OBI) among HIV positive patients varies widely in different geographic regions. We undertook a study to determine the prevalence of occult hepatitis B infection among HIV infected individuals visiting a health facility in South West Cameroon and characterized occult HBV strains based on sequence analyses. Plasma samples (n = 337), which previously tested negative for hepatitis B surface antigen (HBsAg), were screened for antibodies against hepatitis B core (anti-HBc) and surface (anti-HBs) antigens followed by DNA extraction. A 366 bp region covering the overlapping surface/polymerase gene of HBV was then amplified in a nested PCR and the amplicons sequenced using Sanger sequencing. The resulting sequences were then analyzed for genotypes and for escape and drug resistance mutations. Twenty samples were HBV DNA positive and were classified as OBI giving a prevalence of 5.9%. Out of these, 9 (45%) were anti-HBs positive, while 10 (52.6%) were anti-HBc positive. Additionally, 2 had dual anti-HBs and anti-HBc reactivity, while 6 had no detectable HBV antibodies. Out of the ten samples that were successfully sequenced, nine were classified as genotype E and one as genotype A. Three sequences possessed mutations associated with lamivudine resistance. We detected a number of mutations within the major hydrophilic region of the surface gene where most immune escape mutations occur. Findings from this study show the presence of hepatitis B in patients without any of the HBV serological markers. Further prospective studies are required to determine the risk factors and markers of OBI.

Cost-effectiveness of rapid HCV testing and simultaneous rapid HCV and HIV testing in substance abuse treatment programs

PubMed Central

Schackman, Bruce R.; Leff, Jared A.; Barter, Devra M.; DiLorenzo, Madeline A.; Feaster, Daniel J.; Metsch, Lisa R.; Freedberg, Kenneth A.; Linas, Benjamin P.

2014-01-01

Aims To evaluate the cost-effectiveness of rapid hepatitis C virus (HCV) and simultaneous HCV/HIV antibody testing in substance abuse treatment programs. Design We used a decision analytic model to compare the cost-effectiveness of no HCV testing referral or offer, off-site HCV testing referral, on-site rapid HCV testing offer, and on-site rapid HCV and HIV testing offer. Base case inputs included 11% undetected chronic HCV, 0.4% undetected HIV, 35% HCV co-infection among HIV-infected, 53% linked to HCV care after testing antibody positive, and 67% linked to HIV care. Disease outcomes were estimated from established computer simulation models of HCV (HEP-CE) and HIV (CEPAC). Setting and Participants Data on test acceptance and costs were from a national randomized trial of HIV testing strategies conducted at 12 substance abuse treatment programs in the USA. Measurements Lifetime costs (2011 US dollars) and quality-adjusted life years (QALYs) discounted at 3% annually; incremental cost-effectiveness ratios (ICERs) Findings On-site rapid HCV testing had an ICER of $18,300/QALY compared with no testing, and was more efficient than (dominated) off-site HCV testing referral. On-site rapid HCV and HIV testing had an ICER of $64,500/QALY compared with on-site rapid HCV testing alone. In one and two-way sensitivity analyses, the ICER of on-site rapid HCV and HIV testing remained <$100,000/QALY, except when undetected HIV prevalence was <0.1% or when we assumed frequent HIV testing elsewhere. The ICER remained <$100,000/QALY in approximately 90% of probabilistic sensitivity analyses. Conclusions On-site rapid hepatitis C virus and HIV testing in substance abuse treatment programs is cost-effective at a <$100,000/ quality-adjusted life years threshold. PMID:25291977

Anti-HCV immunoblot indeterminate results in blood donors: non-specific reactivity or past exposure to HCV?

PubMed

Kiely, P; Styles, C

2017-08-01

The significance of anti-HCV immunoblot (IB) indeterminate results can be difficult to determine. We analysed results for blood donors tested on the MP Diagnostics HCV Blot 3.0 IB assay to determine whether indeterminate results representing past exposure to HCV could be distinguished from those due to non-specific reactivity. Results for all donors tested by IB during the study period (July 2010 to December 2013) were included in this study. Of 131 donors tested by IB, 34 (26.0%) were negative, 38 (29.0%) were indeterminate, and 59 (45.0%) were positive. There was no significant difference in IB band reactivity strength between indeterminate and positive donors. The PRISM HCV chemiluminescent immunoassay (ChLIA) sample to cut-off (s/co) ratio distribution for the indeterminate donors was significantly higher than for those with biological false reactivity (P = 0·037), but significantly lower than for donors who were IB positive/HCV RNA negative (P < 0·001) or IB not tested/HCV RNA positive (P < 0·001). Of donors available for follow-up, 53.1% of the indeterminate group disclosed a putative risk factor for HCV infection compared to 39.4% (P < 0·001) for the IB-negative group, 76.6% (P = 0·065) for the IB-positive group and 83.4% (P < 0·001) for the HCV RNA-positive group. The results of this study indicate that PRISM ChLIA s/co ratios >2·00 with IB indeterminate results predict exposure to HCV, particularly in the presence of putative risk factors for HCV infection. These findings may be applied to optimizing counselling of donors with indeterminate HCV results. © 2017 International Society of Blood Transfusion.

Exploratory trial of ombitasvir and ABT-450/r with or without ribavirin for HCV genotype 1, 2, and 3 infection.

PubMed

Lawitz, Eric; Sullivan, Greg; Rodriguez-Torres, Maribel; Bennett, Michael; Poordad, Fred; Kapoor, Mudra; Badri, Prajakta; Campbell, Andrew; Rodrigues, Lino; Hu, Yiran; Pilot-Matias, Tami; Vilchez, Regis A

2015-02-01

To examine the safety and efficacy of ombitasvir and ABT-450 with ritonavir (ABT-450/r) ± ribavirin (RBV) in treatment-naïve, non-cirrhotic adults with chronic HCV genotype 1-3 infection. Patients in this open-label, exploratory, phase 2, multicenter study received ombitasvir (25 mg QD) and ABT-450/r (200/100 mg QD) ± RBV for 12 weeks. Primary efficacy endpoint was HCV RNA < lower limit of quantitation (LLOQ) from week 4 through 12. Sustained virologic response 12 weeks post-treatment (SVR12) was a secondary endpoint. Sixty-one patients were enrolled. Among genotype 1-, 2-, and 3-infected patients, respectively, HCV RNA wasinfected patients, respectively, SVR12 was achieved by 10 (100%), 8 (80%), and 5 (50%) receiving the RBV-containing regimen, and 6 (60%), 6 (60%), and 1 (9%) receiving the RBV-free regimen. The most common adverse events were fatigue, nausea, and headache. One patient discontinued due to an adverse event. In this study, ombitasvir and ABT-450/r ± RBV regimens were generally well-tolerated. Sustained virologic response was achieved in most patients with HCV genotype 1 or 2 infection, but low SVR rates were observed in HCV genotype 3-infected patients. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Characterization of Hepatitis C Virus (HCV) Envelope Diversification from Acute to Chronic Infection within a Sexually Transmitted HCV Cluster by Using Single-Molecule, Real-Time Sequencing

PubMed Central

Ho, Cynthia K. Y.; Raghwani, Jayna; Koekkoek, Sylvie; Liang, Richard H.; Van der Meer, Jan T. M.; Van Der Valk, Marc; De Jong, Menno; Pybus, Oliver G.

2016-01-01

ABSTRACT In contrast to other available next-generation sequencing platforms, PacBio single-molecule, real-time (SMRT) sequencing has the advantage of generating long reads albeit with a relatively higher error rate in unprocessed data. Using this platform, we longitudinally sampled and sequenced the hepatitis C virus (HCV) envelope genome region (1,680 nucleotides [nt]) from individuals belonging to a cluster of sexually transmitted cases. All five subjects were coinfected with HIV-1 and a closely related strain of HCV genotype 4d. In total, 50 samples were analyzed by using SMRT sequencing. By using 7 passes of circular consensus sequencing, the error rate was reduced to 0.37%, and the median number of sequences was 612 per sample. A further reduction of insertions was achieved by alignment against a sample-specific reference sequence. However, in vitro recombination during PCR amplification could not be excluded. Phylogenetic analysis supported close relationships among HCV sequences from the four male subjects and subsequent transmission from one subject to his female partner. Transmission was characterized by a strong genetic bottleneck. Viral genetic diversity was low during acute infection and increased upon progression to chronicity but subsequently fluctuated during chronic infection, caused by the alternate detection of distinct coexisting lineages. SMRT sequencing combines long reads with sufficient depth for many phylogenetic analyses and can therefore provide insights into within-host HCV evolutionary dynamics without the need for haplotype reconstruction using statistical algorithms. IMPORTANCE Next-generation sequencing has revolutionized the study of genetically variable RNA virus populations, but for phylogenetic and evolutionary analyses, longer sequences than those generated by most available platforms, while minimizing the intrinsic error rate, are desired. Here, we demonstrate for the first time that PacBio SMRT sequencing technology can be

[Prevalence of occult hepatitis B virus infection and its phylogenetic features among mother-teenager pairs].

PubMed

Dong, Xiao-lian; Yao, Qing-qing; Wang, Xue-cai; Xu, Hai-tao; Wang, Xiao-li; Chen, Sheng-yu; Tang, Zhi-feng; Zheng, Ying-Jie

2013-03-01

Prevalence of occult hepatitis B virus (HBV) infection (OBI) was investigated in a paired mother-teenager population and HBV S gene variation including overt and occult HBV, was determined. A follow-up study based on an initial survey of 135 mother-teenager pairs was carried out through collection of questionnaires and blood samples HBsAg were detected by ELISA method, viral load by PCR amplification and HBV S gene by phylogenetic analysis. 102 pairs of subjects were followed-up. Blood samples from 94 mothers and 101 children were collected. OBI prevalence in mothers was 10.0% (6/60), significantly higher than 2.0% (2/101) in teenagers. Medians of viral load were 399.9 IU/ml and 247.6 IU/ml in overt and occult HBV strains, but without significant difference. 1 occult HBV strain belonged to genotype B with serotype adw while the other 7 were genotype C with serotype adr. 15 of the overt HBV strains belonged to genotype B with serotype adw and the other 8 were genotype C with serotype adr. Proportions of genotype-C strains were significantly higher in occult HBV strains than in overt HBV strains. OBI was seen in teenage-mother population.

Several Human Liver Cell Expressed Apolipoproteins Complement HCV Virus Production with Varying Efficacy Conferring Differential Specific Infectivity to Released Viruses.

PubMed

Hueging, Kathrin; Weller, Romy; Doepke, Mandy; Vieyres, Gabrielle; Todt, Daniel; Wölk, Benno; Vondran, Florian W R; Geffers, Robert; Lauber, Chris; Kaderali, Lars; Penin, François; Pietschmann, Thomas

2015-01-01

Apolipoprotein E (ApoE), an exchangeable apolipoprotein, is necessary for production of infectious Hepatitis C virus (HCV) particles. However, ApoE is not the only liver-expressed apolipoprotein and the role of other apolipoproteins for production of infectious HCV progeny is incompletely defined. Therefore, we quantified mRNA expression of human apolipoproteins in primary human hepatocytes. Subsequently, cDNAs encoding apolipoproteins were expressed in 293T/miR-122 cells to explore if they complement HCV virus production in cells that are non-permissive due to limiting endogenous levels of human apolipoproteins. Primary human hepatocytes expressed high mRNA levels of ApoA1, A2, C1, C3, E, and H. ApoA4, A5, B, D, F, J, L1, L2, L3, L4, L6, M, and O were expressed at intermediate levels, and C2, C4, and L5 were not detected. All members of the ApoA and ApoC family of lipoproteins complemented HCV virus production in HCV transfected 293T/miR-122 cells, albeit with significantly lower efficacy compared with ApoE. In contrast, ApoD expression did not support production of infectious HCV. Specific infectivity of released particles complemented with ApoA family members was significantly lower compared with ApoE. Moreover, the ratio of extracellular to intracellular infectious virus was significantly higher for ApoE compared to ApoA2 and ApoC3. Since apolipoproteins complementing HCV virus production share amphipathic alpha helices as common structural features we altered the two alpha helices of ApoC1. Helix breaking mutations in both ApoC1 helices impaired virus assembly highlighting a critical role of alpha helices in apolipoproteins supporting HCV assembly. In summary, various liver expressed apolipoproteins with amphipathic alpha helices complement HCV virus production in human non liver cells. Differences in the efficiency of virus assembly, the specific infectivity of released particles, and the ratio between extracellular and intracellular infectivity point to

Several Human Liver Cell Expressed Apolipoproteins Complement HCV Virus Production with Varying Efficacy Conferring Differential Specific Infectivity to Released Viruses

PubMed Central

Doepke, Mandy; Vieyres, Gabrielle; Todt, Daniel; Wölk, Benno; Vondran, Florian W. R.; Geffers, Robert; Lauber, Chris; Kaderali, Lars; Penin, François; Pietschmann, Thomas

2015-01-01

Apolipoprotein E (ApoE), an exchangeable apolipoprotein, is necessary for production of infectious Hepatitis C virus (HCV) particles. However, ApoE is not the only liver-expressed apolipoprotein and the role of other apolipoproteins for production of infectious HCV progeny is incompletely defined. Therefore, we quantified mRNA expression of human apolipoproteins in primary human hepatocytes. Subsequently, cDNAs encoding apolipoproteins were expressed in 293T/miR-122 cells to explore if they complement HCV virus production in cells that are non-permissive due to limiting endogenous levels of human apolipoproteins. Primary human hepatocytes expressed high mRNA levels of ApoA1, A2, C1, C3, E, and H. ApoA4, A5, B, D, F, J, L1, L2, L3, L4, L6, M, and O were expressed at intermediate levels, and C2, C4, and L5 were not detected. All members of the ApoA and ApoC family of lipoproteins complemented HCV virus production in HCV transfected 293T/miR-122 cells, albeit with significantly lower efficacy compared with ApoE. In contrast, ApoD expression did not support production of infectious HCV. Specific infectivity of released particles complemented with ApoA family members was significantly lower compared with ApoE. Moreover, the ratio of extracellular to intracellular infectious virus was significantly higher for ApoE compared to ApoA2 and ApoC3. Since apolipoproteins complementing HCV virus production share amphipathic alpha helices as common structural features we altered the two alpha helices of ApoC1. Helix breaking mutations in both ApoC1 helices impaired virus assembly highlighting a critical role of alpha helices in apolipoproteins supporting HCV assembly. In summary, various liver expressed apolipoproteins with amphipathic alpha helices complement HCV virus production in human non liver cells. Differences in the efficiency of virus assembly, the specific infectivity of released particles, and the ratio between extracellular and intracellular infectivity point to

HCV screening in a cohort of HIV infected and uninfected homeless and marginally housed women in San Francisco, California.

PubMed

Page, Kimberly; Yu, Michelle; Cohen, Jennifer; Evans, Jennifer; Shumway, Martha; Riley, Elise D

2017-02-07

Hepatitis C virus (HCV) screening has taken on new importance as a result of updated guidelines and new curative therapies. Relatively few studies have assessed HCV infection in homeless populations, and a minority include women. We assessed prevalence and correlates of HCV exposure in a cohort of homeless and unstably housed women in San Francisco, and estimated the proportion undiagnosed. A probability sample of 246 women were recruited at free meal programs, homeless shelters, and low-cost single room occupancy hotels in San Francisco; women with HIV were oversampled. At baseline, anti-HCV status was assessed using an enzyme immunoassay, and results compared in both HIV-positive and negative women. Exposures were assessed by self-report. Logistic regression was used to assess factors independently associated th HCV exposure. Among 246 women 45.9% were anti-HCV positive, of whom 61.1% were HIV coinfected; 27.4% of positives reported no prior screening. Most (72%) women were in the 'baby-boomer' birth cohort; 19% reported recent injection drug use (IDU). Factors independently associated with anti-HCV positivity were: being born in 1965 or earlier (AOR) 3.94; 95%CI: 1.88, 8.26), IDU history (AOR 4.0; 95%CI: 1.68, 9.55), and number of psychiatric diagnoses (AOR 1.16; 95%CI: 1.08, 1.25). Results fill an important gap in information regarding HCV among homeless women, and confirm the need for enhanced screening in this population where a high proportion are baby-boomers and have a history of drug use and psychiatric problems. Due to their age and risk profile, there is a high probability that women in this study have been infected for decades, and thus have significant liver disease. The association with mental illness and HCV suggests that in addition increased screening, augmenting mental health care and support may enhance treatment success.

Synthetic lipophilic antioxidant BO-653 suppresses HCV replication.

PubMed

Yasui, Fumihiko; Sudoh, Masayuki; Arai, Masaaki; Kohara, Michinori

2013-02-01

The influence of the intracellular redox state on the hepatitis C virus (HCV) life cycle is poorly understood. This study demonstrated the anti-HCV activity of 2,3-dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran (BO-653), a synthetic lipophilic antioxidant, and examined whether BO-653's antioxidant activity is integral to its anti-HCV activity. The anti-HCV activity of BO-653 was investigated in HuH-7 cells bearing an HCV subgenomic replicon (FLR3-1 cells) and in HuH-7 cells infected persistently with HCV (RMT-tri cells). BO-653 inhibition of HCV replication was also compared with that of several hydrophilic and lipophilic antioxidants. BO-653 suppressed HCV replication in FLR3-1 and RMT-tri cells in a concentration-dependent manner. The lipophilic antioxidants had stronger anti-HCV activities than the hydrophilic antioxidants, and BO-653 displayed the strongest anti-HCV activity of all the antioxidants examined. Therefore, the anti-HCV activity of BO-653 was examined in chimeric mice harboring human hepatocytes infected with HCV. The combination treatment of BO-653 and polyethylene glycol-conjugated interferon-α (PEG-IFN) decreased serum HCV RNA titer more than that seen with PEG-IFN alone. These findings suggest that both the lipophilic property and the antioxidant activity of BO-653 play an important role in the inhibition of HCV replication. Copyright © 2012 Wiley Periodicals, Inc.

Lack of Siglec-7 expression identifies a dysfunctional natural killer cell subset associated with liver inflammation and fibrosis in chronic HCV infection.

PubMed

Varchetta, Stefania; Mele, Dalila; Lombardi, Andrea; Oliviero, Barbara; Mantovani, Stefania; Tinelli, Carmine; Spreafico, Marta; Prati, Daniele; Ludovisi, Serena; Ferraioli, Giovanna; Filice, Carlo; Aghemo, Alessio; Lampertico, Pietro; Facchetti, Floriana; Bernuzzi, Francesca; Invernizzi, Pietro; Mondelli, Mario U

2016-12-01

Sialic-acid-binding immunoglobulin-like lectin-7 (Siglec-7) is a natural killer (NK) cell inhibitory receptor associated with NK phenotypic and functional abnormalities in HIV-1 infection. We investigated the significance of NK-expressed and serum soluble Siglec-7 in relation to NK functional ability and parameters of liver necroinflammation and fibrosis in chronic HCV infection. NK-expressed and serum Siglec-7 were evaluated in 130 and 166 HCV-infected individuals by flow cytometry and ELISA, respectively. NK cell degranulation and cytokine secretion were determined by flow cytometry. 65 patients with chronic HBV infection, 84 with chronic biliary disorders and 168 healthy donors served as controls. Expression of Siglec-7 was significantly decreased on NK cells from HCV-infected and HBV-infected patients and, conversely, serum Siglec-7 was significantly increased in these patients compared with controls. The frequency of Siglec-7pos NK cells was significantly higher at baseline in sustained virological responders to pegylated interferon-α/ribavirin treatment than in non-responders. Activating receptor expression was significantly higher in Siglec-7pos NK cells and was associated with increased degranulation and cytokine secretion compared with Siglec-7 neg cells. In chronic HCV infection, there was an inverse correlation between Siglec-7 expression and serum aminotransferases, γ-glutamyl transpeptidase, liver stiffness, aspartate aminotransferase to platelet ratio index and fibrosis-4 scores, and a positive correlation between serum Siglec-7 and the same clinical parameters, including histological staging. These findings identify Siglec-7 neg NK cells as a dysfunctional subpopulation associated with severe liver disease in chronic HCV infection. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Are RA patients from a non-endemic HCV population screened for HCV? A cross-sectional analysis of three different settings.

PubMed

Skinner-Taylor, Cassandra Michelle; Erhard-Ramírez, Alejandro; Garza-Elizondo, Mario Alberto; Esquivel-Valerio, Jorge Antonio; Abud-Mendoza, Carlos; Martínez-Martínez, Marco Ulises; Vega-Morales, David; Arana-Guajardo, Ana

In Mexico, other risk factors are associated with hepatitis C virus (HCV): prior heroin users, living alone, widower, and northern region residence. Rheumatoid arthritis (RA) patients are considered immunosuppressed and HCV testing is recommended before treatment. The aim of the study was to describe the characteristics of HCV testing in RA patients in three different medical care settings in a non-endemic area. A retrospective observational study was performed using medical records from 960 RA patients describing the indications for HCV testing. The test was performed in 28.6% and the HCV overall frequency was 0.36%. Population characteristics were not associated with an increased risk of HCV infection; therefore, anti-HCV positivity was low. The main reason for testing was before starting biological agents. Due to the low pre-test probability, testing for HCV infection should be personalized; i.e., according to disease prevalence in a particular geographical location and the individual risk factors. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

High burden of HCV disease and poor access to HCV services among people who inject drugs in India: A cross-sectional study among 14,481 drug users across India

PubMed Central

Solomon, Sunil Suhas; Mehta, Shruti H; Srikrishnan, Aylur K; Solomon, Suniti; McFall, Allison M.; Laeyendecker, Oliver; Celentano, David D; Iqbal, Syed H; Anand, Santhanam; Vasudevan, Canjeevaram K; Saravanan, Shanmugam; Lucas, Gregory M; Kumar, Muniratnam S; Sulkowski, Mark S; Quinn, Thomas C

2014-01-01

Background Globally, 90% of HCV-infected individuals reside in resource-limited settings (RLS). We characterized the prevalence of HCV, HIV/HCV co-infection, and the HCV care continuum among people who inject drugs (PWID) in India. Methods 14,481 PWID were sampled from 15 cities throughout India using respondent-driven sampling (RDS) from January–December 2013. HCV prevalence was estimated by the presence of anti-HCV antibodies incorporating RDS weights. HCV care continuum outcomes were self-reported except for viral clearance among treatment-experienced participants. Findings Median age was 30 years and 13,608/14,449 (92·4%) were male. Overall weighted HCV prevalence was 37·2% (5,777/14,447); HIV/HCV co-infection prevalence was 13·2% (2,085/14,435). Correlates of HCV infection included higher lifetime injection frequency, HIV positivity, and a higher prevalence of persons with HIV RNA > 1000 copies/ml in the community. Of 5,777 HCV antibody positive PWID, 440 (5·5%) were aware of their status, 225 (3·0%) had seen a doctor for their HCV, 79 (1·4%) had taken HCV treatment, and 18 (0·4%) had undetectable HCV RNA. Overall, 6,138/12,128 (50·5%) did not get tested for HCV because they had never heard of HCV. Among the 5,777 HCV antibody positives, 2,086 (34·4%) reported harmful/hazardous alcohol use of whom 1,082 (50·4%) were dependent; 3,007 (52.9%) reported recent needle sharing. Awareness of HCV positive status was significantly associated with higher education, HIV testing history, awareness of HIV positive status, and higher community antiretroviral therapy coverage. Interpretation The high burden of HCV and HIV/HCV co-infection coupled with low-access to HCV services highlights an urgent need to include RLS in the global HCV agenda. While newer treatments will become available globally in the near future, programs to improve awareness, and reduce disease progression and transmission need to be scaled-up without further delay. Failure to do so could

According to Hepatitis C Virus (HCV) Infection Stage, Interleukin-7 Plus 4-1BB Triggering Alone or Combined with PD-1 Blockade Increases TRAF1low HCV-Specific CD8+ Cell Reactivity.

PubMed

Moreno-Cubero, Elia; Subirá, Dolores; Sanz-de-Villalobos, Eduardo; Parra-Cid, Trinidad; Madejón, Antonio; Miquel, Joaquín; Olveira, Antonio; González-Praetorius, Alejandro; García-Samaniego, Javier; Larrubia, Juan-Ramón

2018-01-15

Hepatitis C virus (HCV)-specific CD8 + T cells suffer a progressive exhaustion during persistent infection (PI) with HCV. This process could involve the positive immune checkpoint 4-1BB/4-1BBL through the loss of its signal transducer, TRAF1. To address this issue, peripheral HCV-specific CD8 + T cells (pentamer-positive [pentamer + ]/CD8 + T cells) from patients with PI and resolved infection (RI) after treatment were studied. The duration of HCV infection and the liver fibrosis progression rate inversely correlated with the likelihood of detection of peripheral pentamer + /CD8 + cells. In PI, pentamer + /CD8 + cells had impaired antigen-specific reactivity that worsened when these cells were not detectable ex vivo Short/midduration PI was characterized by detectable peripheral PD-1 + CD127 low TRAF1 low cells. After triggering of T cell receptors (TCR), the TRAF1 level positively correlated with the levels of CD127, Mcl-1, and CD107a expression and proliferation intensity but negatively with PD-1 expression, linking TRAF1 low to exhaustion. In vitro treatment with interleukin-7 (IL-7) upregulated TRAF1 expression, while treatment with transforming growth factor-β1 (TGF-β1) did the opposite, suggesting that the IL-7/TGF-β1 balance, besides TCR stimulation, could be involved in TRAF1 regulation. In fact, the serum TGF-β1 concentration was higher in patients with PI than in patients with RI, and it negatively correlated with TRAF1 expression. In line with IL-7 increasing the level of TRAF1 expression, IL-7 plus 4-1BBL treatment in vitro enhanced T cell reactivity in patients with short/midduration infection. However, in patients with long-lasting PI, anti-PD-L1, in addition to the combination of IL-7 and 4-1BBL, was necessary to reestablish T cell proliferation in individuals with slowly progressing liver fibrosis (slow fibrosers) but had no effect in rapid fibrosers. In conclusion, a peripheral hyporeactive TRAF1 low HCV-specific CD8 + T cell response

Alcohol and HCV chronic infection are risk cofactors of type 2 diabetes mellitus for hepatocellular carcinoma in Italy.

PubMed

Balbi, Massimiliano; Donadon, Valter; Ghersetti, Michela; Grazioli, Silvia; Valentina, Giovanni Della; Gardenal, Rita; Mas, Maria Dal; Casarin, Pietro; Zanette, Giorgio; Miranda, Cesare; Cimarosti, Paolo

2010-04-01

Type 2 diabetes mellitus (DM2) has been associated with hepatocellular carcinoma (HCC) development. To study this relationship, we enrolled 465 HCC patients compared with 618 Cirrhotic cases and 490 Controls. The prevalence of DM2 is significantly higher in HCC patients with an Odds Ratio of 3.12 versus Controls. In HCC cases with alcohol abuse, the frequency of DM2 is the highest. In our HCC patients, when HCV infection is associated with alcohol abuse, the liver cancer develops earlier. In addition, multivariate analysis shows that alcohol consumption is an independent risk factor for HCC more relevant than HCV infection.

Hepatitis C virus (HCV) induces formation of stress granules whose proteins regulate HCV RNA replication and virus assembly and egress.

PubMed

Garaigorta, Urtzi; Heim, Markus H; Boyd, Bryan; Wieland, Stefan; Chisari, Francis V

2012-10-01

Stress granules (SGs) are cytoplasmic structures that are induced in response to environmental stress, including viral infections. Here we report that hepatitis C virus (HCV) triggers the appearance of SGs in a PKR- and interferon (IFN)-dependent manner. Moreover, we show an inverse correlation between the presence of stress granules and the induction of IFN-stimulated proteins, i.e., MxA and USP18, in HCV-infected cells despite high-level expression of the corresponding MxA and USP18 mRNAs, suggesting that interferon-stimulated gene translation is inhibited in stress granule-containing HCV-infected cells. Finally, in short hairpin RNA (shRNA) knockdown experiments, we found that the stress granule proteins T-cell-restricted intracellular antigen 1 (TIA-1), TIA1-related protein (TIAR), and RasGAP-SH3 domain binding protein 1 (G3BP1) are required for efficient HCV RNA and protein accumulation at early time points in the infection and that G3BP1 and TIA-1 are required for intracellular and extracellular infectious virus production late in the infection, suggesting that they are required for virus assembly. In contrast, TIAR downregulation decreases extracellular infectious virus titers with little effect on intracellular RNA content or infectivity late in the infection, suggesting that it is required for infectious particle release. Collectively, these results illustrate that HCV exploits the stress granule machinery at least two ways: by inducing the formation of SGs by triggering PKR phosphorylation, thereby downregulating the translation of antiviral interferon-stimulated genes, and by co-opting SG proteins for its replication, assembly, and egress.

77 FR 30293 - Recommendations for the Identification of Hepatitis C Virus (HCV) Chronic Infection

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-22

...-2012-0005] Recommendations for the Identification of Hepatitis C Virus (HCV) Chronic Infection AGENCY...: Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers... Morgan, Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB...

Use of HCV+ Donors Does Not Affect HCV Clearance With Directly Acting Antiviral Therapy But Shortens the Wait Time to Kidney Transplantation.

PubMed

Sawinski, Deirdre; Patel, Nikunjkumar; Appolo, Brenda; Bloom, Roy

2017-05-01

Hepatitis C virus (HCV) infection is prevalent in the renal transplant population but direct acting antiviral agents (DAA) provide an effective cure of HCV infection without risk of allograft rejection. We report our experience treating 43 renal transplant recipients with 4 different DAA regimens. One hundred percent achieved a sustained viral response by 12 weeks after therapy, and DAA regimens were well tolerated. Recipients transplanted with a HCV+ donor responded equally well to DAA therapy those transplanted with a kidney from an HCV- donor, but recipients of HCV+ organs experienced significantly shorter wait times to transplantation, 485 days (interquartile range, 228-783) versus 969 days (interquartile range, 452-2008; P = 0.02). On this basis, we advocate for a strategy of early posttransplant HCV eradication to facilitate use of HCV+ organs whenever possible. Additional studies are needed to identify the optimal DAA regimen for kidney transplant recipients, accounting for efficacy, timing relative to transplant, posttransplant clinical outcomes, and cost.

[Contribution of HCV core antigen testing in HCV diagnosis by test from the company Abbott Laboratories].

PubMed

Trbusek, J

2009-11-01

Detection of HCV core antigen as direct marker of hepatitis C infection clearly improves diagnosis of this disease (especially reduction of window period) and brings broad clinical utilization. The company Abbott Laboratories offers fully automated laboratory test for measurement of HCV core antigen on ARCHITECT analyzers.

Geographical distribution of HCV genotypes in Mexico.

PubMed

Sánchez-Avila, Juan Francisco; González, Elizabeth; Vázquez, Victoria; Suárez, Susana; Uribe, Misael

2007-01-01

Chronic hepatitis C (CHC) is the second cause of endstage liver disease in our country and one of the main indications of liver transplantation. Hepatitis C virus (HCV) genotype is the principal prognostic factor and the determinant of the therapeutic scheme. In our country few data exist regarding the prevalence of HCV infection and genotype distribution in the Mexican Republic has not been determined. The aim of this study was to characterize the prevalence of the different HCV genotypes and to explore their geographical distribution. Mexican patients with hepatitis C infection, detected throughout the country between 2003 and 2006, were included. All samples were analyzed by a central laboratory and Hepatitis C genotype was identified by Line Immuno Probe Assay in PCR positive samples (Versant Line Probe Assay Quest Diagnostics Nichols Institute, San Juan Capistrano CA). Data were analyzed according to the four geographical areas in Mexico. One thousand three hundred and ninety CHC patients were included. The most frequent genotype detected was genotype 1 (69%) followed by genotype 2 (21.4%) and genotype 3 (9.2%). Genotype 4 and 5 were infrequent. There was no subject infected with genotype 6. Genotype 1 and 2 exhibit very similar distribution in all geographical areas. Genotype 3 infected patients were more frequent in the North region (52%) compared with other areas:center-western (30%), center (17%), South-South east (1%) (p < 0.001). The most prevalent HCV genotype in Mexico is genotype 1. Geographical distribution of HCV genotypes in the four geographical areas in Mexico is not homogenous with a greater frequency of genotype3 in the north region. This difference could be related to the global changes of risk factors for HCV infection.

[Comparative analysis of viral load by bDNA HCV RNA-2.0 and amplicor HCV monitor in patients with hepatitis C infection].

PubMed

Córdoba, J; Olaso, V; Molina, J M; López Viedma, B; Argüello, L; Ortiz, V; Esteban, R J; Garijo, R; Pastor, M; Gobernado, M

2000-01-01

Two standardized techniques, Quantiplex (bDNA-2.0) and Amplicor Monitor have been evaluated for the quantification of virus load of HCV with these objectives: a) determinate the relationship between virus load and genotype, and b) evaluate the virus load in serial serum samples and in patients with normal or slightly increased liver enzymes in an area with a high prevalence of genotype 1. A significant correlation of 0.7 (p < 0.0001) in virus load has been observed by both methods, but the virus load is smaller by Monitor than by Quantiplex and does not depend on genotype. The relationship Monitor/Quantiplex is smaller in patients with non-1 genotype than in patients with genotype 1a (p = 0.01) and 1b (p = 0.005). Virus characteristics are similar in patients with normal or slightly increased enzymes than in patients with high enzymes. Virus load by both methods is not related to the age, sex, know duration of the infection, transmission manner of the infection neither to the histologic activity index. The virus load not depends on genotype. The determination of virus load in a single serum sample adequately reflects the virus load are in several serum samples in patients with chronic HCV infection. The genotype and the virus load are similar in patients with normal enzymes than in patients with high enzymes.

Osteopontin Regulates Hepatitis C Virus (HCV) Replication and Assembly by Interacting with HCV Proteins and Lipid Droplets and by Binding to Receptors αVβ3 and CD44.

PubMed

Iqbal, Jawed; Sarkar-Dutta, Mehuli; McRae, Steven; Ramachandran, Akshaya; Kumar, Binod; Waris, Gulam

2018-07-01

Hepatitis C virus (HCV) replication and assembly occur at the specialized site of endoplasmic reticulum (ER) membranes and lipid droplets (LDs), respectively. Recently, several host proteins have been shown to be involved in HCV replication and assembly. In the present study, we demonstrated the important relationship among osteopontin (OPN), the ER, and LDs. OPN is a secreted phosphoprotein, and overexpression of OPN in hepatocellular carcinoma (HCC) tissue can lead to invasion and metastasis. OPN expression is also enhanced in HCV-associated HCC. Our recent studies have demonstrated the induction, proteolytic cleavage, and secretion of OPN in response to HCV infection. We also defined the critical role of secreted OPN in human hepatoma cell migration and invasion through binding to receptors integrin αVβ3 and CD44. However, the role of HCV-induced OPN in the HCV life cycle has not been elucidated. In this study, we showed a significant reduction in HCV replication, assembly, and infectivity in HCV-infected cells transfected with small interfering RNA (siRNA) against OPN, αVβ3, and CD44. We also observed the association of endogenous OPN with HCV proteins (NS3, NS5A, NS4A/B, NS5B, and core). Confocal microscopy revealed the colocalization of OPN with HCV NS5A and core in the ER and LDs, indicating a possible role for OPN in HCV replication and assembly. Interestingly, the secreted OPN activated HCV replication, infectivity, and assembly through binding to αVβ3 and CD44. Collectively, these observations provide evidence that HCV-induced OPN is critical for HCV replication and assembly. IMPORTANCE Recently, our studies uncovered the critical role of HCV-induced endogenous and secreted OPN in migration and invasion of hepatocytes. However, the role of OPN in the HCV life cycle has not been elucidated. In this study, we investigated the importance of OPN in HCV replication and assembly. We demonstrated that endogenous OPN associates with HCV NS3, NS5A, NS5B, and

Risk Behaviors for HIV and HCV Infection Among People Who Inject Drugs in Hai Phong, Viet Nam, 2014.

PubMed

Duong, Huong Thi; Jarlais, Don Des; Khuat, Oanh Hai Thi; Arasteh, Kamyar; Feelemyer, Jonathan; Khue, Pham Minh; Giang, Hoang Thi; Laureillard, Didier; Hai, Vinh Vu; Vallo, Roselyne; Michel, Laurent; Moles, Jean Pierre; Nagot, Nicolas

2017-06-13

We examined the potential for HIV and hepatitis C (HCV) transmission across persons who inject drugs (PWID), men-who-have-sex-with-men (MSM) and female commercial sex workers (CSW) PWID and the potential for sexual transmission of HIV from PWID to the general population in Hai Phong, Viet Nam. Using respondent driven and convenience sampling we recruited 603 participants in 2014. All participants used heroin; 24% used non-injected methamphetamine. HIV prevalence was 25%; HCV prevalence was 67%. HIV infection was associated with HCV prevalence and both infections were associated with length of injecting career. Reported injecting risk behaviors were low; unsafe sexual behavior was high among MSM-PWID and CSW-PWID. There is strong possibility of sexual transmission to primary partners facilitated by methamphetamine use. We would suggest future HIV prevention programs utilize multiple interventions including "treatment as prevention" to potential sexual transmission of HIV among MSM and CSW-PWID and from PWID to the general population.

Infection of Hepatocytes With HCV Increases Cell Surface Levels of Heparan Sulfate Proteoglycans, Uptake of Cholesterol and Lipoprotein, and Virus Entry by Up-regulating SMAD6 and SMAD7.

PubMed

Zhang, Fang; Sodroski, Catherine; Cha, Helen; Li, Qisheng; Liang, T Jake

2017-01-01

The signaling molecule and transcriptional regulator SMAD6, which inhibits the transforming growth factor β signaling pathway, is required for infection of hepatocytes by hepatitis C virus (HCV). We investigated the mechanisms by which SMAD6 and another inhibitory SMAD (SMAD7) promote HCV infection in human hepatoma cells and hepatocytes. We infected Huh7 and Huh7.5.1 cells and primary human hepatocytes with Japanese fulminant hepatitis-1 (JFH1) HCV cell culture system (HCVcc). We then measured HCV binding, intracellular levels of HCV RNA, and expression of target genes. We examined HCV entry in HepG2/microRNA (miR) 122/CD81 cells, which support entry and replication of HCV, were transfected these cells with small interfering RNAs targeting inhibitory SMADs to analyze gene expression profiles. Uptake of labeled low-density lipoprotein (LDL) and cholesterol was measured. Cell surface proteins were quantified by flow cytometry. We obtained liver biopsy samples from 69 patients with chronic HCV infection and 19 uninfected individuals (controls) and measured levels of syndecan 1 (SDC1), SMAD7, and SMAD6 messenger RNAs (mRNAs). Small interfering RNA knockdown of SMAD6 blocked the binding and infection of hepatoma cell lines and primary human hepatocytes by HCV, whereas SMAD6 overexpression increased HCV infection. We found levels of mRNAs encoding heparan sulfate proteoglycans (HSPGs), particularly SDC1 mRNA, and cell surface levels of heparan sulfate to be reduced in cells after SMAD6 knockdown. SMAD6 knockdown also reduced transcription of genes encoding lipoprotein and cholesterol uptake receptors, including the LDL receptor (LDLR), the very LDLR, and the scavenger receptor class B member 1 in hepatocytes; knockdown of SMAD6 also inhibited cell uptake of cholesterol and lipoprotein. Overexpression of SMAD6 increased the expression of these genes. Similar effects were observed with knockdown and overexpression of SMAD7. In addition, HCV infection of cells increased

Management of psoriasis patients with hepatitis B or hepatitis C virus infection.

PubMed

Bonifati, Claudio; Lora, Viviana; Graceffa, Dario; Nosotti, Lorenzo

2016-07-28

The systemic therapies available for the management of Psoriasis (PsO) patients who cannot be treated with more conservative options, such as topical agents and/or phototherapy, with the exception of acitretin, can worsen or reactivate a chronic infection. Therefore, before administering immunosuppressive therapies with either conventional disease-modifying drugs (cDMARDs) or biological ones (bDMARDs) it is mandatory to screen patients for some infections, including hepatitis B virus (HBV) and hepatitis C virus (HCV). In particular, the patients eligible to receive an immunosuppressive drug must be screened for the following markers: antibody to hepatitis B core, antibody to hepatitis B surface antigen (anti-HBsAg), HBsAg, and antibody to HCV (anti-HCV). In case HBV or HCV infection is diagnosed, a close collaboration with a consultant hepatologist is needed before and during an immunosuppressive therapy. Concerning therapy with immunosuppressive drugs in PsO patients with HBV or HCV infection, data exist mainly for cyclosporine a (CyA) or bDMARDs (etanercept, adalimumab, infliximab, ustekinumab). The natural history of HBV and HCV infection differs significantly as well as the effect of immunosuppression on the aforementioned infectious diseases. As a rule, in the case of active HBV infection, systemic immunosuppressive antipsoriatic therapies must be deferred until the infection is controlled with an adequate antiviral treatment. Inactive carriers need to receive antiviral prophylaxis 2-4 wk before starting immunosuppressive therapy, to be continued after 6-12 mo from its suspension. Due to the risk of HBV reactivation, these patients should be monitored monthly for the first 3 mo and then every 3 mo for HBV DNA load together with transaminases levels. Concerning the patients who are occult HBV carriers, the risk of HBV reactivation is very low. Therefore, these patients generally do not need antiviral prophylaxis and the sera HBsAg and transaminases dosing can

Alcohol and HCV Chronic Infection Are Risk Cofactors of Type 2 Diabetes Mellitus for Hepatocellular Carcinoma in Italy

PubMed Central

Balbi, Massimiliano; Donadon, Valter; Ghersetti, Michela; Grazioli, Silvia; Valentina, Giovanni Della; Gardenal, Rita; Mas, Maria Dal; Casarin, Pietro; Zanette, Giorgio; Miranda, Cesare; Cimarosti, Paolo

2010-01-01

Type 2 diabetes mellitus (DM2) has been associated with hepatocellular carcinoma (HCC) development. To study this relationship, we enrolled 465 HCC patients compared with 618 Cirrhotic cases and 490 Controls. The prevalence of DM2 is significantly higher in HCC patients with an Odds Ratio of 3.12 versus Controls. In HCC cases with alcohol abuse, the frequency of DM2 is the highest. In our HCC patients, when HCV infection is associated with alcohol abuse, the liver cancer develops earlier. In addition, multivariate analysis shows that alcohol consumption is an independent risk factor for HCC more relevant than HCV infection. PMID:20617035

Entry inhibitors: New advances in HCV treatment

PubMed Central

Qian, Xi-Jing; Zhu, Yong-Zhe; Zhao, Ping; Qi, Zhong-Tian

2016-01-01

Hepatitis C virus (HCV) infection affects approximately 3% of the world's population and causes chronic liver diseases, including liver fibrosis, cirrhosis, and hepatocellular carcinoma. Although current antiviral therapy comprising direct-acting antivirals (DAAs) can achieve a quite satisfying sustained virological response (SVR) rate, it is still limited by viral resistance, long treatment duration, combined adverse reactions, and high costs. Moreover, the currently marketed antivirals fail to prevent graft reinfections in HCV patients who receive liver transplantations, probably due to the cell-to-cell transmission of the virus, which is also one of the main reasons behind treatment failure. HCV entry is a highly orchestrated process involving initial attachment and binding, post-binding interactions with host cell factors, internalization, and fusion between the virion and the host cell membrane. Together, these processes provide multiple novel and promising targets for antiviral therapy. Most entry inhibitors target host cell components with high genetic barriers and eliminate viral infection from the very beginning of the viral life cycle. In future, the addition of entry inhibitors to a combination of treatment regimens might optimize and widen the prevention and treatment of HCV infection. This review summarizes the molecular mechanisms and prospects of the current preclinical and clinical development of antiviral agents targeting HCV entry. PMID:26733381

Shortened therapy of eight weeks with paritaprevir/ritonavir/ombitasvir and dasabuvir is highly effective in people with recent HCV genotype 1 infection.

PubMed

Martinello, M; Bhagani, S; Gane, E; Orkin, C; Cooke, G; Dore, G J; Petoumenos, K; Applegate, T L; Tu, E; Marks, P; Pagani, N; Grebely, J; Nelson, M; Matthews, G V

2018-04-16

Paritaprevir/ritonavir/ombitasvir and dasabuvir with or without ribavirin for 12 weeks are approved for treatment of chronic HCV genotype 1 infection. This study assessed the efficacy of shortened duration paritaprevir/ritonavir/ombitasvir and dasabuvir with or without ribavirin for 8 weeks among people with recent HCV infection. In this open-label single-arm trial conducted in Australia, England and New Zealand, adults with recent HCV (duration of infection <12 months) received paritaprevir/ritonavir/ombitasvir and dasabuvir (with weight-based ribavirin for genotypes 1a and 1, no subtype) for 8 weeks. The primary endpoint was sustained virological response at 12 weeks post-treatment (SVR12) in the intention-to-treat (ITT) population. Thirty people (median age 38 years, male 93%) commenced treatment (with ribavirin, 97%), of whom 77% (n = 23) were HIV-positive, 93% (n = 28) had genotype 1a infection and 53% (n = 16) had ever injected drugs. Median maximum ALT in the preceding 12 months was 433 IU/L (IQR 321, 1012). Acute clinical hepatitis with ALT > 10 x ULN was documented in 83% (n = 25); one participant (3%) had jaundice. At baseline, median estimated duration of infection was 30 weeks (range 11, 51), and median HCV RNA was 5.7 log 10 IU/mL (range 2.7, 7.3). SVR12 was achieved in 97% (29/30; early discontinuation at week 2, n = 1; per protocol 100%, 29/29). No relapse or reinfection was observed. In conclusion, paritaprevir/ritonavir/ombitasvir and dasabuvir (with ribavirin) for eight weeks were highly effective among HIV-positive and HIV-negative individuals with recent HCV infection. These data support the use of this shortened duration direct-acting antiviral regimen in this population. © 2018 John Wiley & Sons Ltd.

[Prevalence of HBV and HCV infection markers in patients with sexually transmitted diseases].

PubMed

Selibórska, Z; Dajek, Z; Stapiński, A

1998-01-01

Sera of 125 patients with sexually transmitted diseases (syphilis, gonorrhoea, chlamydiosis, HPV and HIV infections) were investigated for presence of 3 markers of HBV infection; they were found in 41 (33%) patients. Anti-HBc was present in sera of 35 (28%) patients, in 3 of them antigen HBs was found and in 28 anti-HBs was found as well. Antigen HBs alone was present in sera of 6 other patients but they were not reactive in test for anti-HBc. Moreover in this group of 125 patients anti-HCV were discovered in 4 (3%); in 3 of them occurrence of markers of HBV infection was found.

Hepatitis C virus infection in HIV-infected patients.

PubMed

Sulkowski, Mark S

2007-10-01

The hepatitis C virus (HCV) is a spherical enveloped RNA virus of the Flaviviridae family, classified within the Hepacivirus genus. Since its discovery in 1989, HCV has been recognized as a major cause of chronic hepatitis and hepatic fibrosis that progresses in some patients to cirrhosis and hepatocellular carcinoma. In the United States, approximately 4 million people have been infected with HCV, and 10,000 HCVrelated deaths occur each year. Due to shared routes of transmission, HCV and HIV co-infection are common, affecting approximately one third of all HIV-infected persons in the United States. In addition, HIV co-infection is associated with higher HCV RNA viral load and a more rapid progression of HCV-related liver disease, leading to an increased risk of cirrhosis. HCV infection may also impact the course and management of HIV disease, particularly by increasing the risk of antiretroviral drug-induced hepatotoxicity. Thus, chronic HCV infection acts as an opportunistic disease in HIV-infected persons because the incidence of infection is increased and the natural history of HCV infection is accelerated in co-infected persons. Strategies to prevent primary HCV infection and to modify the progression of HCV-related liver disease are urgently needed among HIV/HCV co-infected individuals.

Role of HCV Core gene of genotype 1a and 3a and host gene Cox-2 in HCV-induced pathogenesis

PubMed Central

2011-01-01

Background Hepatitis C virus (HCV) Core protein is thought to trigger activation of multiple signaling pathways and play a significant role in the alteration of cellular gene expression responsible for HCV pathogenesis leading to hepatocellular carcinoma (HCC). However, the exact molecular mechanism of HCV genome specific pathogenesis remains unclear. We examined the in vitro effects of HCV Core protein of HCV genotype 3a and 1a on the cellular genes involved in oxidative stress and angiogenesis. We also studied the ability of HCV Core and Cox-2 siRNA either alone or in combination to inhibit viral replication and cell proliferation in HCV serum infected Huh-7 cells. Results Over expression of Core gene of HCV 3a genotype showed stronger effect in regulating RNA and protein levels of Cox-2, iNOS, VEGF, p-Akt as compared to HCV-1a Core in hepatocellular carcinoma cell line Huh-7 accompanied by enhanced PGE2 release and cell proliferation. We also observed higher expression levels of above genes in HCV 3a patient's blood and biopsy samples. Interestingly, the Core and Cox-2-specific siRNAs down regulated the Core 3a-enhanced expression of Cox-2, iNOS, VEGF, p-Akt. Furthermore, the combined siRNA treatment also showed a dramatic reduction in viral titer and expression of these genes in HCV serum-infected Huh-7 cells. Taken together, these results demonstrated a differential response by HCV 3a genotype in HCV-induced pathogenesis, which may be due to Core and host factor Cox-2 individually or in combination. Conclusions Collectively, these studies not only suggest a genotype-specific interaction between key players of HCV pathogenesis but also may represent combined viral and host gene silencing as a potential therapeutic strategy. PMID:21457561

Interferon lambda: opportunities, risks, and uncertainties in the fight against HCV.

PubMed

Laidlaw, Stephen M; Dustin, Lynn B

2014-01-01

Innate immunity is key to the fight against the daily onslaught from viruses that our bodies are subjected to. Essential to this response are the interferons (IFNs) that prime our cells to block viral pathogens. Recent evidence suggests that the Type III (λ) IFNs are intimately associated with the immune response to hepatitis C virus (HCV) infection. Genome-wide association studies have identified polymorphisms within the IFN-λ gene locus that correlate with response to IFNα-based antiviral therapy and with spontaneous clearance of HCV infection. The mechanisms for these correlations are incompletely understood. Restricted expression of the IFN-λ receptor, and the ability of IFN-λ to induce IFN-stimulated genes in HCV-infected cells, suggest potential roles for IFN-λ in HCV therapy even in this era of directly acting antivirals. This review summarizes our current understanding of the IFN-λ family and the role of λ IFNs in the natural history of HCV infection.

Characteristics of HCV positive patients in an Italian urban psychiatric unit

PubMed Central

2006-01-01

Objectives 1) to assess the prevalence of hepatitis C virus (HCV) infection in a population of acute psychiatric in-patients; 2) to find out relationships between HCV comorbidity and clinical features of psychiatric patients. Methods Prospective observational study in a 6-year period. Results 2396 cases (1492 patients) were admitted in the considered period. Forty-two patients (2.8%) were affected by HCV infection. HCV infection was more frequent in patients with less years of education, lower social class, lower last year best Global Assessment of Functioning score, more hostile or violent behavior in hospital, with a lifetime history of previous suicide attempt, and with substance-related disorders. Conclusion HCV infection in psychiatric patients constitutes a major threat to the health of psychiatric patients and is related with unfavorable social background, worse global functioning, hostile or violent behavior, substance-related disorders. It appears also to be a significant risk of suicidal behavior. PMID:17010216

Point -of -care testing (POCT) in molecular diagnostics: Performance evaluation of GeneXpert HCV RNA test in diagnosing and monitoring of HCV infection.

PubMed

Gupta, Ekta; Agarwala, Pragya; Kumar, Guresh; Maiwall, Rakhi; Sarin, Shiv Kumar

2017-03-01

Molecular testing at the point-of-care may turn out to be game changer for HCV diagnosis and treatment monitoring, through increased sensitivity, reduced turnaround time, and ease of performance. One such assay GeneXpert ® has recently been released. Comparative analysis between performances of GeneXpert ® and Abbott HCV-RNA was done. 174 HCV infected patients were recruited and, one time plasma samples from 154 patients and repeated samples from 20 patients, obtained at specific treatment time-points (0, 4, 12 and 24) weeks were serially re-tested on Xpert ® . Genotype 3 was the commonest, seen in 80 (66%) of the cases, genotype 1 in 34 (28.3%), genotype 4 in 4 (3.3%) and genotypes 2 and 5 in 1 (0.8%) each. Median HCV RNA load was 4.69 log 10 (range: 0-6.98log 10 ) IU/ml. Overall a very good correlation was seen between the two assays (R 2 =0.985), concordance of the results between the assays was seen in 138 samples (89.6%). High and low positive standards were tested ten times on Xpert ® to evaluate the precision and the coefficient of variation was 0.01 for HPC and 0.07 for the LPC. Monitoring of patients on two different regimes of treatment, pegylated interferon plus ribavirin and sofosbuvir plus ribavirin was done by both the systems at baseline, 4, 12 and 24 weeks. Perfect correlation between the assays in the course of therapy at different treatment time- point in genotypes 3 and 1 was seen. The study demonstrates excellent performance of the Xpert ® HCV assay in viral load assessment and in treatment course monitoring consistency. Copyright © 2017 Elsevier B.V. All rights reserved.

Efficient infectious cell culture systems of the hepatitis C virus (HCV) prototype strains HCV-1 and H77.

PubMed

Li, Yi-Ping; Ramirez, Santseharay; Mikkelsen, Lotte; Bukh, Jens

2015-01-01

The first discovered and sequenced hepatitis C virus (HCV) genome and the first in vivo infectious HCV clones originated from the HCV prototype strains HCV-1 and H77, respectively, both widely used in research of this important human pathogen. In the present study, we developed efficient infectious cell culture systems for these genotype 1a strains by using the HCV-1/SF9_A and H77C in vivo infectious clones. We initially adapted a genome with the HCV-1 5'UTR-NS5A (where UTR stands for untranslated region) and the JFH1 NS5B-3'UTR (5-5A recombinant), including the genotype 2a-derived mutations F1464L/A1672S/D2979G (LSG), to grow efficiently in Huh7.5 cells, thus identifying the E2 mutation S399F. The combination of LSG/S399F and reported TNcc(1a)-adaptive mutations A1226G/Q1773H/N1927T/Y2981F/F2994S promoted adaptation of the full-length HCV-1 clone. An HCV-1 recombinant with 17 mutations (HCV1cc) replicated efficiently in Huh7.5 cells and produced supernatant infectivity titers of 10(4.0) focus-forming units (FFU)/ml. Eight of these mutations were identified from passaged HCV-1 viruses, and the A970T/I1312V/C2419R/A2919T mutations were essential for infectious particle production. Using CD81-deficient Huh7 cells, we further demonstrated the importance of A970T/I1312V/A2919T or A970T/C2419R/A2919T for virus assembly and that the I1312V/C2419R combination played a major role in virus release. Using a similar approach, we found that NS5B mutation F2994R, identified here from culture-adapted full-length TN viruses and a common NS3 helicase mutation (S1368P) derived from viable H77C and HCV-1 5-5A recombinants, initiated replication and culture adaptation of H77C containing LSG and TNcc(1a)-adaptive mutations. An H77C recombinant harboring 19 mutations (H77Ccc) replicated and spread efficiently after transfection and subsequent infection of naive Huh7.5 cells, reaching titers of 10(3.5) and 10(4.4) FFU/ml, respectively. Hepatitis C virus (HCV) was discovered in 1989 with

Acetaminophen-induced acute liver injury in HCV transgenic mice

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

Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle

2013-01-15

The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wildmore » type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.« less

Performance of ARCHITECT HCV core antigen test with specimens from US plasma donors and injecting drug users.

PubMed

Mixson-Hayden, Tonya; Dawson, George J; Teshale, Eyasu; Le, Thao; Cheng, Kevin; Drobeniuc, Jan; Ward, John; Kamili, Saleem

2015-05-01

Hepatitis C virus (HCV) core antigen is a serological marker of current HCV infection. The aim of this study was mainly to evaluate the performance characteristics of the ARCHITECT HCV core antigen assay with specimens from US plasma donors and injecting drug users. A total of 551 serum and plasma samples with known anti-HCV and HCV RNA status were tested for HCV core antigen using the Abbott ARCHITECT HCV core antigen test. HCV core antigen was detectable in 100% of US plasma donor samples collected during the pre-seroconversion phase of infection (anti-HCV negative/HCV RNA positive). Overall sensitivity of the HCV core antigen assay was 88.9-94.3% in samples collected after seroconversion. The correlation between HCV core antigen and HCV RNA titers was 0.959. HCV core antigen testing may be reliably used to identify current HCV infection. Published by Elsevier B.V.

IL-28B Polymorphisms Correlated with Treatment Response in HCV-4 Mono-Infected Patients: A Meta-Analysis

PubMed Central

Liu, Tonggang; Sha, Kaihui; Yang, Luhua; Wang, Yun; Zhang, Liguo; Liu, Xianxian; Yang, Fang

2014-01-01

Background The role of interleukin 28B (IL-28B) polymorphisms played in hepatitis C virus (HCV) infection has been gradually explicit, especially in HCV genotype 1, 2 and 3. However, no confirmative conclusion was acquired in genotype 4 HCV patients. Thus we conducted this meta-analysis. Methods We searched the commonly used databases both in English and Chinese. Meta-analysis was performed in fixed/random effects models using STATA 12.0 or R software. Publication bias was examined through Egger's test and Begg's funnel plot. Results In total, 11 studies were included in this meta-analysis, encompassing 1284 patients who were mono-infected with HCV-4 and received Peg-interferon (Peg-IFN) plus Ribavirin (Rbv). Around 53.0% patients would achieve sustained virologic response (SVR), 36.6% achieve rapid virologic response (RVR) and 62.4% achieve end of treatment response (ETR). Egyptian patients had a higher rate achieving SVR than non-Egyptian patients (56.3% vs. 47.8%). IL-28B rs12979860 CC genotype not only favored SVR (OR = 3.95, 95%CI = 3.03–5.16), regardless of citizenship, but also favored RVR (OR = 3.82, 95%CI = 2.46–5.95) and ETR (OR = 4.22, 95%CI = 2.81–6.34). IL-28B rs8099917 genotype TT also correlated with SVR (OR = 3.41, 95%CI = 1.92–6.07), but might not with RVR. IL-28B rs12980275 might still correlate with SVR, but warrant more studies to validate. Conclusions The favorable IL-28B rs12979860 genotype is a statistically significant predictor of SVR, RVR and ETR in HCV-4 monoinfected patients treated with Peg-IFN plus Rbv. Rs8099917 might predict SVR but not RVR. Egyptian HCV-4 patients would achieve better outcomes than non-Egyptian patients when treated with standard care. PMID:24642705

High false-negative rate of anti-HCV among Egyptian patients on regular hemodialysis.

PubMed

El-Sherif, Assem; Elbahrawy, Ashraf; Aboelfotoh, Atef; Abdelkarim, Magdy; Saied Mohammad, Abdel-Gawad; Abdallah, Abdallah Mahmoud; Mostafa, Sadek; Elmestikawy, Amr; Elwassief, Ahmed; Salah, Mohamed; Abdelbaseer, Mohamed Ali; Abdelwahab, Kouka Saadeldin

2012-07-01

Routine serological testing for hepatitis C virus (HCV) infection among hemodialysis (HD) patients is currently recommended. A dilemma existed on the value of serology because some investigators reported a high rate of false-negative serologic testing. In this study, we aimed to detect the false-negative rate of anti-HCV among Egyptian HD patients. Seventy-eight HD patients, negative for anti-HCV, anti-HIV, and hepatitis B surface antigen, were tested for HCV RNA by reverse transcriptase polymerase chain reaction (RT-PCR). In the next step, the viral load was quantified by real-time PCR in RT-PCR-positive patients. Risk factors for HCV infection, as well as clinical and biochemical indicators of liver disease, were compared between false-negative and true-negative anti-HCV HD patients. The frequency of false-negative anti-HCV was 17.9%. Frequency of blood transfusion, duration of HD, dialysis at multiple centers, and diabetes mellitus were not identified as risk factors for HCV infection. The frequency of false-negative results had a linear relation to the prevalence of HCV infection in the HD units. Timely identification of HCV within dialysis units is needed in order to lower the risk of HCV spread within the HD units. The high false-negative rate of anti-HCV among HD patients in our study justifies testing of a large scale of patients for precious assessment of effectiveness of nucleic acid amplification technology testing in screening HD patient. © 2012 The Authors. Hemodialysis International © 2012 International Society for Hemodialysis.

Correlates of HIV, HBV, HCV and syphilis infections among prison inmates and officers in Ghana: A national multicenter study

PubMed Central

Adjei, Andrew A; Armah, Henry B; Gbagbo, Foster; Ampofo, William K; Boamah, Isaac; Adu-Gyamfi, Clement; Asare, Isaac; Hesse, Ian FA; Mensah, George

2008-01-01

Background Prisons are known to be high-risk environments for the spread of bloodborne and sexually transmitted infections. Prison officers are considered to have an intermittent exposure potential to bloodborne infectious diseases on the job, however there has been no studies on the prevalence of these infections in prison officers in Ghana. Methods A national multicenter cross-sectional study was undertaken on correlates of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis infections in sample of prison inmates and officers from eight of ten regional central prisons in Ghana. A total of 1366 inmates and 445 officers were enrolled between May 2004 and December 2005. Subjects completed personal risk-factor questionnaire and provided blood specimens for unlinked anonymous testing for presence of antibodies to HIV, HCV and Treponema pallidum; and surface antigen of HBV (HBsAg). These data were analyzed using both univariate and multivariate techniques. Results Almost 18% (1336) of 7652 eligible inmates and 21% (445) of 2139 eligible officers in eight study prisons took part. Median ages of inmates and officers were 36.5 years (range 16–84) and 38.1 years (range 25–59), respectively. Among inmates, HIV seroprevalence was 5.9%, syphilis seroprevalence was 16.5%, and 25.5% had HBsAg. Among officers tested, HIV seroprevalence was 4.9%, HCV seroprevalence was 18.7%, syphilis seroprevalence was 7.9%, and 11.7% had HBsAg. Independent determinants for HIV, HBV and syphilis infections among inmates were age between 17–46, being unmarried, being illiterate, female gender, being incarcerated for longer than median time served of 36 months, history of homosexuality, history of intravenous drug use, history of sharing syringes and drug paraphernalia, history of participation in paid sexual activity, and history of sexually transmitted diseases. Independent determinants for HIV, HBV, HCV and syphilis infections among officers

149 HCV AND lymphoma: Genetic and epigenetic factors

PubMed Central

Zignego, AL; Gragnani, L; Fognani, E; Piluso, A

2014-01-01

Over 180 million people worldwide are chronically infected with the hepatitis C virus (HCV). HCV infection is a major cause for hepatocellular carcinoma (HCC), moreover the association with B-cell lymphoproliferative disorders (LPDs) like mixed cryoglobulinemia (MC) or B-cell non-Hodgkin lymphoma (B-NHL) is undisputed. The mechanisms by which HCV contributes to LPD development are still poorly understood. Available data suggest that the viral infection may induce LPDs through a multifactorial and multistep process that involves the sustained activation of B cells, the abnormal and prolonged B cell survival, and genetic and/or epigenetic factors. Concerning genetic factors, different authors reported an association between specific HLA clusters or B-cell activating factor promoter genotype and a higher risk of developing MC and lymphoma. In addition, the results of a large, ongoing genome wide association study (GWAS) will probably allow the identification of specific genetic profile of HCV patients with LPDs. Furthermore, microRNAs (miRNAs) can give a major contribution to the pathogenesis of several neoplastic, lymphoproliferative diseases and it is conceivable their involvement in the pathogenesis of HCV-related LPDs. We recently showed that specific miRNAs were differently modulated in PBMCs from HCV patients who developed MC and/or NHL. In addition, HCV patients who developed HCC, showed a differential miRNAs regulation. In conclusion, available data suggest that the genetic/epigenetic analysis of HCV-related cancerogenesis is of great usefulness in both the pathogenetic and clinical/translational areas possibly allowing the definition of diagnostic/prognostic markers for early detection of lymphatic or hepatic cancer.

Analytical and clinical performance of the Hologic Aptima HCV Quant Dx Assay for the quantification of HCV RNA in plasma samples.

PubMed

Schønning, Kristian; Pedersen, Martin Schou; Johansen, Kim; Landt, Bodil; Nielsen, Lone Gilmor; Weis, Nina; Westh, Henrik

2017-10-01

Chronic hepatitis C virus (HCV) infection can be effectively treated with directly acting antiviral (DAA) therapy. Measurement of HCV RNA is used to evaluate patient compliance and virological response during and after treatment. To compare the analytical performance of the Aptima HCV Quant Dx Assay (Aptima) and the COBAS Ampliprep/COBAS TaqMan HCV Test v2.0 (CAPCTMv2) for the quantification of HCV RNA in plasma samples, and compare the clinical utility of the two tests in patients undergoing treatment with DAA therapy. Analytical performance was evaluated on two sets of plasma samples: 125 genotyped samples and 172 samples referred for quantification of HCV RNA. Furthermore, performance was evaluated using dilutions series of four samples containing HCV genotype 1a, 2b, 3a, and 4a, respectively. Clinical utility was evaluated on 118 plasma samples obtained from 13 patients undergoing treatment with DAAs. Deming regression of results from 187 plasma samples with HCV RNA >2 Log IU/mL indicated that the Aptima assay quantified higher than the CAPCTMv2 test for HCV RNA >4.9 Log IU/mL. The linearity of the Aptima assay was excellent across dilution series of four HCV genotypes (slope of the regression line: 1.00-1.02). The Aptima assay detected significantly more replicates below targeted 2 Log IU/mL than the CAPCTMv2 test, and yielded clearly interpretable results when used to analyze samples from patients treated with DAAs. The analytical performance of the Aptima assay makes it well suited for monitoring patients with chronic HCV infection undergoing antiviral treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Treatment of chronic hepatitis C in patients with HIV/HCV coinfection

PubMed Central

Coppola, Nicola; Martini, Salvatore; Pisaturo, Mariantonietta; Sagnelli, Caterina; Filippini, Pietro; Sagnelli, Evangelista

2015-01-01

Hepatitis C virus (HCV) infection is one of the most frequent causes of comorbidity and mortality in the human immunodeficiency virus (HIV) population, and liver-related mortality is now the second highest cause of death in HIV-positive patients, so HCV infection should be countered with adequate antiviral therapy. In 2011 began the era of directly acting antivirals (DAAs) and the HCV NS3/4A protease inhibitors telaprevir and boceprevir were approved to treat HCV-genotype-1 infection, each one in combination with pegylated interferon alfa (Peg-IFN) + ribavirin (RBV). The addition of the first generation DAAs, strongly improved the efficacy of antiviral therapy in patients with HCV-genotype 1, both for the HCV-monoinfected and HIV/HCV coinfected, and the poor response to Peg-IFN + RBV in HCV/HIV coinfection was enhanced. These treatments showed higher rates of sustained virological response than Peg-IFN + RBV but reduced tolerability and adherence due to the high pill burden and the several pharmacokinetic interactions between HCV NS3/4A protease inhibitors and antiretroviral drugs. Then in 2013 a new wave of DAAs arrived, characterized by high efficacy, good tolerability, a low pill burden and shortened treatment duration. The second and third generation DAAs also comprised IFN-free regimens, which in small recent trials on HIV-positive patients have shown comforting preliminary results in terms of efficacy, tolerability and adherence. PMID:25674512

Interferon-free treatment for HCV-infected patients with decompensated cirrhosis.

PubMed

Kanda, Tatsuo

2017-01-01

Progress in interferon-free treatment against hepatitis C virus (HCV) has remained a challenge in patients with decompensated cirrhosis due to a paucity of information on efficacy and safety profiles. This review illustrates that interferon-free treatment could result in greater than 85 % sustained virological response (SVR) rates in patients with HCV genotype 1 and decompensated cirrhosis. The combination of pangenotypic HCV NS5A inhibitor velpatasvir and HCV NS5B inhibitor sofosbuvir has demonstrated high SVR rates in patients with HCV genotypes 1, 2, 3, 4 or 6 and decompensated cirrhosis. Certain patients discontinued treatment due to adverse events, death or having liver transplantation. Taken together, interferon-free treatment could produce higher SVR rates in decompensated hepatic cirrhosis. However, as adverse events were occasionally observed, liver transplantation should always be considered as well. Further improvements in treatment are called for in patients with decompensated cirrhosis.

[Comparison of eight screening tests for ant-HCV antibody].

PubMed

Deguchi, Matsuo; Kagita, Masanori; Yamashita, Naoko; Nakano, Takasi; Tahara, Kazuko; Asari, Seishi; Iwatani, Yoshinori

2002-09-01

We compared eight HCV screening tests for detection of anti-HCV antibody; Ortho Quick Chaser HCV Ab (QC), Ortho HCV Ab ELISA III (ELISA), Ortho HVC Ab PA test III (PA), Lumipulse II Ortho HCV (LUMI), IMx HCV.DAINAPACKII (IMx), ARCHITECT HCV (ARCH), Immucheck.F-HCV C50 Ab (Immu), RANREAM HCV Ab Ex II (RAN). Sera from six hundred patients were examined by these eight screening tests. The positive rates of the eight screening tests were from 9.0% to 13.2%. Forty-five sera showed discrepant results between the eight screening tests, and about half of them showed weak positive reaction and/or false positive. Twenty-five of the forty-five sera were negative for ant-HCV antibody in the CHIRON RIBA III confirmatory test, and forty-four of them were negative for HCV-RNA in the PCR method. The agreement rates between the two reagents were from 95.5% to 99.2%, but were not always high between the two reagents that used similar antigen. The specificities and sensitivities evaluated by using the RIBA III confirmatory test were excellent in ELISA, LUMI, IMx, ARCH and Immu. Three BBI seroconversion panels were used to compare the positive readings in the initial stage of HCV infection by eight screening tests. ELISA and ARCH showed the earliest positive readings, and then IMx, LUMI = RAN, PA, QC and Immu in this order. These findings indicate that ELISA and ARCH were the most excellent in the sensitivity, specificity and early diagnosis of HCV infection. However, we must pay attention to the weak positive reaction in the screening tests, because there is a possibility of "false positive".

HCV proteins and immunoglobulin variable gene (IgV) subfamilies in HCV-induced type II mixed cryoglobulinemia: a concurrent pathogenetic role.

PubMed

Sautto, Giuseppe; Mancini, Nicasio; Solforosi, Laura; Diotti, Roberta A; Clementi, Massimo; Burioni, Roberto

2012-01-01

The association between hepatitis C virus (HCV) infection and type II mixed cryoglobulinemia (MCII) is well established, but the role played by distinct HCV proteins and by specific components of the anti-HCV humoral immune response remains to be clearly defined. It is widely accepted that HCV drives the expansion of few B-cell clones expressing a restricted pool of selected immunoglobulin variable (IgV) gene subfamilies frequently endowed with rheumatoid factor (RF) activity. Moreover, the same IgV subfamilies are frequently observed in HCV-transformed malignant B-cell clones occasionally complicating MCII. In this paper, we analyze both the humoral and viral counterparts at the basis of cryoglobulins production in HCV-induced MCII, with particular attention reserved to the single IgV subfamilies most frequently involved.

Vitamin D deficiency is a risk factor for infections in patients affected by HCV-related liver cirrhosis.

PubMed

Buonomo, Antonio Riccardo; Zappulo, Emanuela; Scotto, Riccardo; Pinchera, Biagio; Perruolo, Giuseppe; Formisano, Pietro; Borgia, Guglielmo; Gentile, Ivan

2017-10-01

To evaluate the prevalence of vitamin D deficiency and its impact on infections in HCV-related liver cirrhosis. We enrolled 291 patients affected by HCV-related liver cirrhosis. Serum vitamin D levels were dosed at enrolment. The presence of infection was assessed at baseline and during follow-up based on physical examination and laboratory analyses. Vitamin D deficiency (<20ng/mL) was diagnosed in 68.3% of patients, and a total of 102 infections were detected. Urinary tract infections were the most common infections diagnosed (41.2%). Vitamin D deficiency rates were higher in patients with decompensated cirrhosis (Child-Pugh B vs A p=0.008, and Child-Pugh C vs A p=0.024). Infection was significantly associated with vitamin D deficiency (p<0.001), MELD score >15 (p=0.003), Child-Pugh class B/C vs A (p<0.001), and active hepatocellular carcinoma (HCC) (p<0.001). At multivariate analysis, vitamin D deficiency (p<0.01), HCC (p<0.05), hospitalization (p<0.001) and exposure to immunosuppressant agents (p<0.05) were independent risk factors for infection at baseline. Vitamin D may play a role in the development of infections in patients affected by liver cirrhosis, and preventive strategies with vitamin D supplementation are to be evaluated in randomized controlled trials. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Prevalence of HCV among the young male blood donors of Quetta region of Balochistan, Pakistan

PubMed Central

2013-01-01

Background Hepatitis C, caused by hepatitis C virus (HCV) is a contagious disease of the liver which infects more than 170 million people world-wide and around 16 million in Pakistan. HCV associated infection spreads mainly by blood-to-blood contact. In recent years, many studies have been conducted to determine the prevalence of HCV infection in Pakistan; however, no data is available on HCV infection from the largest province of Pakistan. Therefore, the present study focuses on the prevalence of HCV infection in the young male blood donor population of Quetta region of Balochistan, Pakistan. Methods A total of 356 blood samples were collected from blood donors (age range 17–25 years) at Combined Military Hospital (CMH), Quetta, Balochistan, Pakistan. Blood samples were screened for HCV positivity by Immunochromatographic test (ICT) and Enzyme Linked Immunosorbant Assay (ELISA). Results Out of 356 blood samples, the overall HCV prevalence was 20.8%. Among the HCV positive cases, the age group with 25 years was more frequently infected with a prevalence of 26.3%. Conclusions The present study provides the preliminary information about high HCV prevalence among the young male donor population in Balochistan province. This data may be helpful in formulating public health strategy for the prevention of risk factors associated with spreading of the disease. Furthermore, we recommend that in public sector hospitals and health care units ELISA should be preferred for anti-HCV detection over ICT. PMID:23497435

Prevalence of HCV among the young male blood donors of Quetta region of Balochistan, Pakistan.

PubMed

Khan, Ayesha; Tareen, Abdul Malik; Ikram, Aamer; Rahman, Hazir; Wadood, Abdul; Qasim, Muhammad; Khan, Kalimullah

2013-03-13

Hepatitis C, caused by hepatitis C virus (HCV) is a contagious disease of the liver which infects more than 170 million people world-wide and around 16 million in Pakistan. HCV associated infection spreads mainly by blood-to-blood contact. In recent years, many studies have been conducted to determine the prevalence of HCV infection in Pakistan; however, no data is available on HCV infection from the largest province of Pakistan. Therefore, the present study focuses on the prevalence of HCV infection in the young male blood donor population of Quetta region of Balochistan, Pakistan. A total of 356 blood samples were collected from blood donors (age range 17-25 years) at Combined Military Hospital (CMH), Quetta, Balochistan, Pakistan. Blood samples were screened for HCV positivity by Immunochromatographic test (ICT) and Enzyme Linked Immunosorbant Assay (ELISA). Out of 356 blood samples, the overall HCV prevalence was 20.8%. Among the HCV positive cases, the age group with 25 years was more frequently infected with a prevalence of 26.3%. The present study provides the preliminary information about high HCV prevalence among the young male donor population in Balochistan province. This data may be helpful in formulating public health strategy for the prevention of risk factors associated with spreading of the disease. Furthermore, we recommend that in public sector hospitals and health care units ELISA should be preferred for anti-HCV detection over ICT.

Mutations Associated With Occult Hepatitis B in HIV-Positive South Africans

PubMed Central

Powell, Eleanor A.; Gededzha, Maemu P.; Rentz, Michael; Rakgole, Nare J.; Selabe, Selokela G.; Seleise, Tebogo A.; Mphahlele, M. Jeffrey; Blackard, Jason T.

2015-01-01

Occult hepatitis B is characterized by the absence of hepatitis B surface antigen (HBsAg) but the presence of HBV DNA. Because diagnosis of hepatitis B virus (HBV) typically includes HBsAg detection, occult HBV remains largely undiagnosed. Occult HBV is associated with increased risk of hepatocellular carcinoma, reactivation to chronic HBV during immune suppression, and transmission during blood transfusion and liver transplant. The mechanisms leading to occult HBV infection are unclear, although viral mutations are likely a significant factor. In this study, sera from 394 HIV-positive South Africans were tested for HBV DNA and HBsAg. For patients with detectable HBV DNA, the overlapping surface and polymerase open reading frames (ORFs) were sequenced. Occult-associated mutations—those mutations found exclusively in individuals with occult HBV infection but not in individuals with chronic HBV infection from the same cohort or GenBank references—were identified. Ninety patients (22.8%) had detectable HBV DNA. Of these, 37 had detectable HBsAg, while 53 lacked detectable surface antigen. The surface and polymerase ORFs were cloned successfully for 19 patients with chronic HBV and 30 patients with occult HBV. In total, 235 occult-associated mutations were identified. Ten occult-associated mutations were identified in more than one patient. Additionally, 15 amino acid positions had two distinct occult-associated mutations at the same residue. Occult-associated mutations were common and present in all regions of the surface and polymerase ORFs. Further study is underway to determine the effects of these mutations on viral replication and surface antigen expression in vitro. PMID:25164924

Mutations associated with occult hepatitis B in HIV-positive South Africans.

PubMed

Powell, Eleanor A; Gededzha, Maemu P; Rentz, Michael; Rakgole, Nare J; Selabe, Selokela G; Seleise, Tebogo A; Mphahlele, M Jeffrey; Blackard, Jason T

2015-03-01

Occult hepatitis B is characterized by the absence of hepatitis B surface antigen (HBsAg) but the presence of HBV DNA. Because diagnosis of hepatitis B virus (HBV) typically includes HBsAg detection, occult HBV remains largely undiagnosed. Occult HBV is associated with increased risk of hepatocellular carcinoma, reactivation to chronic HBV during immune suppression, and transmission during blood transfusion and liver transplant. The mechanisms leading to occult HBV infection are unclear, although viral mutations are likely a significant factor. In this study, sera from 394 HIV-positive South Africans were tested for HBV DNA and HBsAg. For patients with detectable HBV DNA, the overlapping surface and polymerase open reading frames (ORFs) were sequenced. Occult-associated mutations-those mutations found exclusively in individuals with occult HBV infection but not in individuals with chronic HBV infection from the same cohort or GenBank references-were identified. Ninety patients (22.8%) had detectable HBV DNA. Of these, 37 had detectable HBsAg, while 53 lacked detectable surface antigen. The surface and polymerase ORFs were cloned successfully for 19 patients with chronic HBV and 30 patients with occult HBV. In total, 235 occult-associated mutations were identified. Ten occult-associated mutations were identified in more than one patient. Additionally, 15 amino acid positions had two distinct occult-associated mutations at the same residue. Occult-associated mutations were common and present in all regions of the surface and polymerase ORFs. Further study is underway to determine the effects of these mutations on viral replication and surface antigen expression in vitro. © 2014 Wiley Periodicals, Inc.

HCV core protein induces hepatic lipid accumulation by activating SREBP1 and PPAR{gamma}

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

Kim, Kook Hwan; Hong, Sung Pyo; Kim, KyeongJin

2007-04-20

Hepatic steatosis is a common feature in patients with chronic hepatitis C virus (HCV) infection. HCV core protein plays an important role in the development of hepatic steatosis in HCV infection. Because SREBP1 (sterol regulatory element binding protein 1) and PPAR{gamma} (peroxisome proliferators-activated receptor {gamma}) are involved in the regulation of lipid metabolism of hepatocyte, we sought to determine whether HCV core protein may impair the expression and activity of SREBP1 and PPAR{gamma}. In this study, it was demonstrated that HCV core protein increases the gene expression of SREBP1 not only in Chang liver, Huh7, and HepG2 cells transiently transfectedmore » with HCV core protein expression plasmid, but also in Chang liver-core stable cells. Furthermore, HCV core protein enhanced the transcriptional activity of SREBP1. In addition, HCV core protein elevated PPAR{gamma} transcriptional activity. However, HCV core protein had no effect on PPAR{gamma} gene expression. Finally, we showed that HCV core protein stimulates the genes expression of lipogenic enzyme and fatty acid uptake associated protein. Therefore, our finding provides a new insight into the mechanism of hepatic steatosis by HCV infection.« less

Interferon-free therapy in hepatitis C virus (HCV) monoinfected and HCV/HIV coinfected patients: effect on cognitive function, fatigue, and mental health.

PubMed

Kleefeld, Felix; Heller, Sophie; Ingiliz, Patrick; Jessen, Heiko; Petersen, Anders; Kopp, Ute; Kraft, Antje; Hahn, Katrin

2018-05-21

The efficacy and safety of interferon-free therapies for hepatitis C virus (HCV) infection have been reported. Considering the accumulating evidence for a direct central nervous system infection by HCV, we aim to evaluate the effect of direct acting antivirals (DAA) therapy on cognitive function in HCV patients. We conducted a longitudinal analysis of the cognitive performance of 22 patients (8 HCV+, 14 HCV+/HIV+) who completed neuropsychological testing at baseline and at week 12 after DAA therapy. In 20 patients, we analyzed specific attention parameters derived from an experimental testing based on the Theory of Visual Attention (TVA). Depression, fatigue, and mental health were assessed as patient reported outcomes. At baseline, 54.5% of the patients met the criteria for cognitive impairment and 40% showed impairment in TVA parameters. Follow-up analysis revealed significant improvements in the domains of visual memory/learning, executive functions, verbal fluency, processing speed, and motor skills but not in verbal learning and attention/working memory. We did not observe significant improvement in visual attention measured by TVA. Fatigue and mental health significantly improved at follow-up. Our findings indicate that successful DAA treatment leads to cognitive improvements in several domains measured by standard neuropsychological testing. The absence of improvement in TVA parameters and of significant improvement in the domain of attention/working memory might reflect the persistence of specific cognitive deficits after HCV eradication. In summary, DAA treatment seems to have a positive effect on some cognitive domains and leads to an improvement in mental health and fatigue in HCV-infected patients.

Performance evaluation of the Aptima® HCV Quant Dx assay for hepatitis C virus (HCV) RNA detection and quantification in comparison to the Abbott RealTime HCV assay.

PubMed

Garbuglia, Anna Rosa; Bibbò, Angela; Sciamanna, Roberta; Pisciotta, Marina; Capobianchi, Maria Rosaria

2017-07-01

The Aptima HCV Quant Dx assay (Aptima) is a real-time transcription-mediated amplification assay CE-approved for the diagnosis and monitoring of hepatitis C virus (HCV) infection. Aptima's analytical performance was compared to the Abbott RealTime HCV assay (RealTime) in a clinical routine setting. Overall 295 clinical plasma samples (117 prospective/fresh; 178 retrospective/frozen) from HCV-infected patients were tested in Aptima and RealTime to determine concordance on qualitative and quantitative results. Linearity and precision at low viral loads (VLs; 0.8-3.3LogIU/mL) was tested using dilutions of the 5th WHO standard, in 10 and 20 replicates in the two assays, respectively. The ability to measure different HCV genotypes and accuracy were analyzed using the Seracare EQA panel. Inter-assay agreement for qualitative results (prospective samples) was 88% (kappa=0.78). For the 127 samples with quantitative results in both assays, Aptima yielded on average slightly higher values (by 0.24LogIU/mL; Bland-Altman method) than RealTime. Concordance between assay results was excellent (R=0.98). At low VLs (0.8-3.3LogIU/mL), Aptima demonstrated good linearity and precision, similar to RealTime. Aptima detected and accurately quantified all main HCV genotypes. Aptima demonstrated excellent precision, linearity, and accuracy in all genotypes tested. Good concordance was observed between Aptima and RealTime assays in clinical samples. The performance of the Aptima assay, on the fully automated Panther platform, makes it an excellent candidate for the detection and monitoring of HCV RNA in plasma and serum samples. Copyright © 2017 Elsevier B.V. All rights reserved.

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

[Chronic HCV hepatopathy and cryoglobulinemia. The associated clinical spectrum].

PubMed

Pellicano, R; Leone, N; Maiocco, I A; Modena, V; Arena, V; Marietti, G; Puiatti, P; Palmas, F; Rizzetto, M; Ponzetto, A

1999-01-01

The hepatitis C infection (HCV) has numerous extrahepatic manifestations owing to the systemic nature of the infection itself. HCV infects the cells that carry a CD 81 receptor and show a marked tropism for hepatocytes, bone marrow staminal cells and circulating lymphomonocytes. One consequence of this tropism is the activation of B lymphocyte clones with the consequent production of autoantibodies and cryoglobulins. The secondary event is the formation of circulating immune complexes which, having precipitated at an intravascular level, may cause part of the extrahepatic manifestations associated with these infections. This retrospective study evaluated the manifestations correlated and/or associated with HCV hepatitis and mixed cryoglobulinaemia. This analysis showed that 75% of consecutively studied patients reveal clinically important extrahepatic manifestations. This underlines the "broad spectrum" action played by the hepatitis C virus in the host organism.

HCV Proteins and Immunoglobulin Variable Gene (IgV) Subfamilies in HCV-Induced Type II Mixed Cryoglobulinemia: A Concurrent Pathogenetic Role

PubMed Central

Sautto, Giuseppe; Mancini, Nicasio; Solforosi, Laura; Diotti, Roberta A.; Clementi, Massimo; Burioni, Roberto

2012-01-01

The association between hepatitis C virus (HCV) infection and type II mixed cryoglobulinemia (MCII) is well established, but the role played by distinct HCV proteins and by specific components of the anti-HCV humoral immune response remains to be clearly defined. It is widely accepted that HCV drives the expansion of few B-cell clones expressing a restricted pool of selected immunoglobulin variable (IgV) gene subfamilies frequently endowed with rheumatoid factor (RF) activity. Moreover, the same IgV subfamilies are frequently observed in HCV-transformed malignant B-cell clones occasionally complicating MCII. In this paper, we analyze both the humoral and viral counterparts at the basis of cryoglobulins production in HCV-induced MCII, with particular attention reserved to the single IgV subfamilies most frequently involved. PMID:22690241

Association of TNF-alpha (-308 A/G) and IFN-gamma (+874 A/T) gene polymorphisms in response to spontaneous and treatment induced viral clearance in HCV infected multitransfused thalassemic patients.

PubMed

Biswas, Aritra; Gupta, Nabyendu; Gupta, Debanjali; Datta, Abira; Firdaus, Rushna; Chowdhury, Prosanto; Bhattacharyya, Maitreyee; Sadhukhan, Provash C

2018-06-01

Multitransfused thalassemic individuals are at high risk of developing transfusion transmitted Hepatitis C virus (HCV) infection. The aim of the study was to correlate the effects of host cytokine single nucleotide polymorphisms of TNF-α (-308 A/G) and IFN-γ (+874 A/T) in spontaneous or IFN induced treatment response in the HCV infected thalassemic individuals. A total of 427 HCV sero-reactive thalassemic individuals were processed for HCV viral genomic diversity and host gene polymorphisms analysis of TNF-α (-308 A/G) and IFN-γ (+874 A/T). Out of 427 HCV sero-reactive individuals, 69.09% were found to be HCV RNA positive with genotype 3 as the predominant infecting strain (94.29%). Study highlighted that, A allele was significantly associated with (p < .05) spontaneous clearance of HCV infection and G allele was correlated with viral persistence at TNF-α (-308) gene polymorphism. Whereas in case of IFN-γ (+874) SNPs, A allele was significantly responsible (p < .05) for spontaneous clearance than T allele. Our study also indicated that in relapsed cases, IFN-γ (+874) T allele is more responsible than A allele. Though no significant correlation was found at both TNF-α (-308) and IFN-γ (+874) gene polymorphism among SVR and relapsed thalassemic patients. A allele at both TNF-α (-308) and IFN-γ (+874) were strongly associated with spontaneous clearance among this population. But in case of SVR and relapsed cases no significant association was found. This cytokine gene polymorphisms pattern will help clinicians to take an informed decision about therapeutic management of HCV infected thalassemic individuals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Molecular characterization of occult hepatitis B virus infection in patients with end-stage liver disease in Colombia

PubMed Central

Rendon, Julio Cesar; Cortes-Mancera, Fabian; Restrepo-Gutierrez, Juan Carlos; Hoyos, Sergio

2017-01-01

Background Hepatitis B virus (HBV) occult infection (OBI) is a risk factor to be taken into account in transfusion, hemodialysis and organ transplantation. The aim of this study was to identify and characterize at the molecular level OBI cases in patients with end-stage liver disease. Methods Sixty-six liver samples were obtained from patients with diagnosis of end-stage liver disease submitted to liver transplantation in Medellin (North West, Colombia). Samples obtained from patients who were negative for the surface antigen of HBV (n = 50) were tested for viral DNA detection by nested PCR for ORFs S, C, and X and confirmed by Southern-Blot. OBI cases were analyzed by sequencing the viral genome to determine the genotype and mutations; additionally, viral genome integration events were examined by the Alu-PCR technique. Results In five cases out of 50 patients (10%) the criteria for OBI was confirmed. HBV genotype F (subgenotypes F1 and F3), genotype A and genotype D were characterized in liver samples. Three integration events in chromosomes 5q14.1, 16p13 and 20q12 affecting Receptor-type tyrosine-protein phosphatase T, Ras Protein Specific Guanine Nucleotide Releasing Factor 2, and the zinc finger 263 genes were identified in two OBI cases. Sequence analysis of the viral genome of the 5 OBI cases showed several punctual missense and nonsense mutations affecting ORFs S, P, Core and X. Conclusions This is the first characterization of OBI in patients with end-stage liver disease in Colombia. The OBI cases were identified in patients with HCV infection or cryptogenic cirrhosis. The integration events (5q14.1, 16p13 and 20q12) described in this study have not been previously reported. Further studies are required to validate the role of mutations and integration events in OBI pathogenesis. PMID:28686707

Occult Hepatitis B virus infection in previously screened, blood donors in Ile-Ife, Nigeria: implications for blood transfusion and stem cell transplantation.

PubMed

Olotu, Amadin A; Oyelese, Adesola O; Salawu, Lateef; Audu, Rosemary A; Okwuraiwe, Azuka P; Aboderin, Aaron O

2016-05-05

Hepatitis B virus (HBV) transmission through blood transfusion is reduced by screening for hepatitis B surface antigen (HBsAg). However this method cannot detect the presence of occult hepatitis B virus infection. This study sought to determine the prevalence of occult hepatitis B virus infection among blood donors in Ile-Ife, Nigeria. For the first time in Nigeria we employed an automated real-time PCR- method to investigate the prevalence of occult HBV in blood donors. Blood donors screened with HBsAg immunochromatographic rapid test kits at the blood transfusion units of two hospitals and found to be negative were recruited into the study. Questionnaires to elicit risk factors for HBV infection were administered and then 10 ml of blood was collected from each donor. Plasma samples obtained from these HBsAg negative blood donors were screened again for HBsAg using an enzyme-linked immunosorbent assay (ELISA) method, and those found negative were screened for the presence of total antibody to the HBV core antigen (anti-HBc) using ELISA method. Those positive to anti-HBc were then tested for HBV DNA, using an automated real-time PCR method. Five hundred and seven blood donors found HBsAg negative by immunochromatographic rapid test kits at both blood transfusion units, were tested for HBsAg using ELISA and 5 (1 %) were HBsAg positive. The 502 found negative were tested for anti-HBc and 354 (70.5 %) were found positive implying previous exposure to HBV and 19 (5.4 %) of the 354 anti-HBc positive had HBV DNA signifying occult HBV infection. No risk factors were found to be associated with the presence of HBV DNA among those who tested positive. Occult HBV infection exists in blood donors in Ile-Ife, Nigeria and the use of HBsAg alone for screening prospective donors will not eliminate the risk of HBV transmission in blood transfusion or stem cell transplantation.

HCV Core Residues Critical for Infectivity Are Also Involved in Core-NS5A Complex Formation

PubMed Central

Gawlik, Katarzyna; Baugh, James; Chatterji, Udayan; Lim, Precious J.; Bobardt, Michael D.; Gallay, Philippe A.

2014-01-01

Hepatitis C virus (HCV) infection is a major cause of liver disease. The molecular machinery of HCV assembly and particle release remains obscure. A better understanding of the assembly events might reveal new potential antiviral strategies. It was suggested that the nonstructural protein 5A (NS5A), an attractive recent drug target, participates in the production of infectious particles as a result of its interaction with the HCV core protein. However, prior to the present study, the NS5A-binding site in the viral core remained unknown. We found that the D1 domain of core contains the NS5A-binding site with the strongest interacting capacity in the basic P38-K74 cluster. We also demonstrated that the N-terminal basic residues of core at positions 50, 51, 59 and 62 were required for NS5A binding. Analysis of all substitution combinations of R50A, K51A, R59A, and R62A, in the context of the HCVcc system, showed that single, double, triple, and quadruple mutants were fully competent for viral RNA replication, but deficient in secretion of viral particles. Furthermore, we found that the extracellular and intracellular infectivity of all the mutants was abolished, suggesting a defect in the formation of infectious particles. Importantly, we showed that the interaction between the single and quadruple core mutants and NS5A was impaired in cells expressing full-length HCV genome. Interestingly, mutations of the four basic residues of core did not alter the association of core or NS5A with lipid droplets. This study showed for the first time that basic residues in the D1 domain of core that are critical for the formation of infectious extracellular and intracellular particles also play a role in core-NS5A interactions. PMID:24533158

Seroprevalence of HCV among Cairo University students in Egypt.

PubMed

Esmat, Gamal; Raziky, Maissa El; Nabeel, Mohammed M; Maher, Rabab; Zakaria, Zeinab

2016-08-01

Hepatitis C virus (HCV) is highly prevalent in Egypt. This work aimed at determining the seroprevalence of HCV among Cairo University students. The present study included 3,000 students from Cairo University, Egypt. Blood sample was obtained from each participant to be tested for HCV seromarker. HCV RNA detection by polymerase chain reaction (PCR) was carried out for those with positive anti-HCV. Overall prevalence rate of HCV antibody (anti-HCV) was 4.6%. It showed that the prevalence was relatively higher among females (86/1660; 5.2%) while males (51/1340; 3.8%) with no significant difference. PCR for HCV RNA was detected in 31.4% of the HCV antibody positive subjects (43/137). Which showed statistical significant difference between males (29/51) and females (14/86) at P = 0.001. Despite the prevalence rate reported in the present study was similar to anti-HCV prevalence among persons in the same age group, confirmed that HCV infection is detected among Cairo University students. J. Med. Virol. 88:1384-1387, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Temporal changes in HCV genotype distribution in three different high risk populations in San Francisco, California

PubMed Central

2011-01-01

Background Hepatitis C virus (HCV) genotype (GT) has become an important measure in the diagnosis and monitoring of HCV infection treatment. In the United States (U.S.) HCV GT 1 is reported as the most common infecting GT among chronically infected patients. In Europe, however, recent studies have suggested that the epidemiology of HCV GTs is changing. Methods We assessed HCV GT distribution in 460 patients from three HCV-infected high risk populations in San Francisco, and examined patterns by birth cohort to assess temporal trends. Multiple logistic regression was used to assess factors independently associated with GT 1 infection compared to other GTs (2, 3, and 4). Results Overall, GT 1 was predominant (72.4%), however younger injection drug users (IDU) had a lower proportion of GT 1 infections (54.7%) compared to older IDU and HIV-infected patients (80.5% and 76.6%, respectively). Analysis by birth cohort showed increasing proportions of non-GT 1 infections associated with year of birth: birth before 1970 was independently associated with higher adjusted odds of GT 1: AOR 2.03 (95% CI: 1.23, 3.34). African-Americans as compared to whites also had higher adjusted odds of GT 1 infection (AOR: 3.37; 95% CI: 1.89, 5.99). Conclusions Although, HCV GT 1 remains the most prevalent GT, especially among older groups, changes in GT distribution could have significant implications for how HCV might be controlled on a population level and treated on an individual level. PMID:21810243

The Changing Face of Hepatitis C: Recent Advances on HCV Inhibitors Targeting NS5A

PubMed

Rai, Diwakar; Wang, Liu; Jiang, Xuemei; Zhan, Peng; Jia, Haiyong; De Clercq, Erik; Liu, Xinyong

2015-05-05

Current treatment for HCV infections consists of approved direct acting antivirals (DAAs), viz. the protease inhibitors (boceprevir, telaprevir, and simeprevir), NS5B polymerase inhibitors (sofosbuvir) and NS5A inhibitor (ledipasvir) in combination with pegylated interferon α and ribavirin). These treatments have made a great improvement in the treatment of chronic HCV infections in recent years, but their adverse side effects, emergence of resistant mutants, high cost, and increased pill burden have limited their clinical use. Recently, with the increasing knowledge in understanding the HCV life cycle, more targets have been recognized. NS5A protein plays a critical role in assembly of infectious HCV particles and offering potential for HCV therapies. Therefore, discovery and development of novel DAAs targeting NS5A with novel mechanisms of action, is of great necessity to improve the quality of existing HCV treatments. In the present review, we discuss recent advances with NS5A inhibitors with potent anti-HCV activity, and the potential for the development of HCV NS5A inhibitors to combat HCV infections.

Packaging of HCV-RNA into lentiviral vector

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

Caval, Vincent; Piver, Eric; Service de Biochimie et Biologie Moleculaire, CHRU de Tours

2011-11-04

Highlights: Black-Right-Pointing-Pointer Description of HCV-RNA Core-D1 interactions. Black-Right-Pointing-Pointer In vivo evaluation of the packaging of HCV genome. Black-Right-Pointing-Pointer Determination of the role of the three basic sub-domains of D1. Black-Right-Pointing-Pointer Heterologous system involving HIV-1 vector particles to mobilise HCV genome. Black-Right-Pointing-Pointer Full length mobilisation of HCV genome and HCV-receptor-independent entry. -- Abstract: The advent of infectious molecular clones of Hepatitis C virus (HCV) has unlocked the understanding of HCV life cycle. However, packaging of the genomic RNA, which is crucial to generate infectious viral particles, remains poorly understood. Molecular interactions of the domain 1 (D1) of HCV Core protein andmore » HCV RNA have been described in vitro. Since compaction of genetic information within HCV genome has hampered conventional mutational approach to study packaging in vivo, we developed a novel heterologous system to evaluate the interactions between HCV RNA and Core D1. For this, we took advantage of the recruitment of Vpr fusion-proteins into HIV-1 particles. By fusing HCV Core D1 to Vpr we were able to package and transfer a HCV subgenomic replicon into a HIV-1 based lentiviral vector. We next examined how deletion mutants of basic sub-domains of Core D1 influenced HCV RNA recruitment. The results emphasized the crucial role of the first and third basic regions of D1 in packaging. Interestingly, the system described here allowed us to mobilise full-length JFH1 genome in CD81 defective cells, which are normally refractory to HCV infection. This finding paves the way to an evaluation of the replication capability of HCV in various cell types.« less

Unsolved Puzzles Surrounding HCV Immunity: Heterologous Immunity Adds Another Dimension.

PubMed

Agrawal, Babita; Singh, Shakti; Gupta, Nancy; Li, Wen; Vedi, Satish; Kumar, Rakesh

2017-07-27

Chronic infection with hepatitis C virus (HCV) afflicts 3% of the world's population and can lead to serious and late-stage liver diseases. Developing a vaccine for HCV is challenging because the correlates of protection are uncertain and traditional vaccine approaches do not work. Studies of natural immunity to HCV in humans have resulted in many enigmas. Human beings are not immunologically naïve because they are continually exposed to various environmental microbes and antigens, creating large populations of memory T cells. Heterologous immunity occurs when this pool of memory T cells cross-react against a new pathogen in an individual. Such heterologous immunity could influence the outcome when an individual is infected by a pathogen. We have recently made an unexpected finding that adenoviruses, a common environmental pathogen and an experimental vaccine vector, can induce robust cross-reactive immune responses against multiple antigens of HCV. Our unique finding of previously uncharacterized heterologous immunity against HCV opens new avenues to understand HCV pathogenesis and develop effective vaccines.

Biomarkers of inflammation, coagulation and microbial translocation in HIV/HCV co-infected patients in the SMART study.

PubMed

Peters, Lars; Neuhaus, Jacqueline; Duprez, Daniel; Neaton, James D; Tracy, Russel; Klein, Marina B; Mocroft, Amanda; Rockstroh, Jürgen; Dore, Gregory; Lundgren, Jens D

2014-07-01

Previous results from the SMART study showed that HIV/viral hepatitis co-infected persons with impaired liver function are at increased risk of death following interruption of antiretroviral therapy (ART). To investigate the influence of fibrosis and ART interruption on levels of biomarkers of inflammation, coagulation and microbial translocation in HIV/HCV co-infected persons in the SMART study. All HIV/HCV co-infected persons with stored plasma at study entry and at six months of follow-up were included (N=362). D-dimer, IL-6, sCD14 and hepatic synthesized coagulation markers were measured and compared according to the liver fibrosis marker hyaluronic acid (HA) at study entry. Percent difference in changes in biomarker levels from study entry to month 6 was compared between randomization groups and according to study entry HA levels. At study entry, persons with elevated HA (>75ng/mL vs. ≤75ng/mL) had higher median (IQR) levels of IL-6 [4.14pg/mL (2.60-6.32) vs. 2.74pg/mL (1.88-3.97)] and soluble CD14 [2163ng/mL (1952-2916) vs. 1979ng/mL (1742-2310)] (p<0.001). Elevated HA was also associated with alterations of both pro- and anti-coagulation markers but the overall coagulation profile was not affected. Interruption of ART lead to a particularly pronounced increase in IL-6 levels in persons with elevated HA levels (p=0.01 for interaction between randomization group and continuous HA level). HIV/HCV co-infected persons with impaired liver function are in an enhanced pro-inflammatory state which is further exacerbated upon interruption of ART. Copyright © 2014 Elsevier B.V. All rights reserved.

Treatment of HCV infection in Poland at the beginning of the interferon-free era-the EpiTer-2 study.

PubMed

Flisiak, R; Zarębska-Michaluk, D; Janczewska, E; Staniaszek, A; Gietka, A; Mazur, W; Tudrujek, M; Tomasiewicz, K; Belica-Wdowik, T; Baka-Ćwierz, B; Dybowska, D; Halota, W; Lorenc, B; Sitko, M; Garlicki, A; Berak, H; Horban, A; Orłowska, I; Simon, K; Socha, Ł; Wawrzynowicz-Syczewska, M; Jaroszewicz, J; Deroń, Z; Czauż-Andrzejuk, A; Citko, J; Krygier, R; Piekarska, A; Laurans, Ł; Dobracki, W; Białkowska, J; Tronina, O; Pawłowska, M

2018-01-06

The aim of the EpiTer-2 study was to analyse patient characteristics and their medication for HCV infection in Poland at the beginning of the interferon-free era. Analysis of data of HCV infected patients treated during the initial period of availability of interferon-free regimens in Poland, who started therapy after 1 July 2015 and had available an efficacy evaluation report before 30 June 2017 was undertaken. A total of 2879 patients with chronic hepatitis C were entered, including 46% with liver cirrhosis. The most common was genotype 1b (86.8%). The study population was gender balanced, the majority of patients were overweight or obese and 69% presented comorbidities, with the highest prevalence that for hypertension. More than half of patients were retreated due to failure of previous therapy with pegylated interferon and ribavirin. Almost two-third of patients received current therapy with ombitasvir/paritaprevir/ritonavir±dasabuvir (OPrD) ±ribavirin. Other patients received mostly sofosbuvir-based regimens including combination with ledipasvir and pegylated interferon and ribavirin for genotype 3-infected patients. Efficacy of treatment in the whole study population measured as intent-to-treat analysis was 95%. The most frequent regimen, administered for patients infected with genotype 1b, was 12 weeks of OPrD, resulting in an SVR rate of 98%. At least one adverse event was reported in 38% of patients, and the death rate was 0.8%. In conclusion, data from the EpiTer-2 study confirmed the excellent efficacy and safety profile of the real-world experience with recently introduced therapeutic options for genotype 1 HCV infection, but demonstrated weakness of the current therapeutic programme regarding genotype 3 infections. © 2018 John Wiley & Sons Ltd.

Management of HCV-Related Liver Disease in Hemophilia and Thalassemia.

PubMed

Rumi, Maria Grazia; Di Marco, Vito; Colombo, Massimo

2018-05-01

Chronic infection with the hepatitis C virus (HCV) has long been the dominant complication of substitution therapy in patients with inherited blood disorders and the cause of anticipated death due to end-stage liver disease. In hemophilia, transmission of HCV with clotting factors concentrates started to be curbed in the mid-1980s following the adoption of procedures of virus inactivation of concentrates based on heat, whereas in the 1990s treatment of HCV infection with interferon monotherapy was attempted, however, with little success. The advent of combination therapy of interferon with ribavirin led to a substantial improvement of treatment outcome (40% rate of cure), that however was still of limited efficacy in patients with advanced liver disease, those with high load of HCV genotype 1, and patients coinfected with the human immunodeficiency virus. In this latter population, while the course of hepatitis C was accelerated as a consequence of immunodeficiency, the advent of highly active antiretroviral therapy led acquired immunodeficiency syndrome (AIDS) to decline and hepatitis C to progressively emerge as a dominant cause of mortality, in parallel. In patients with thalassemia, transfusion-related transmission of HCV was efficiently interrupted in 1992 with the advent of sensitive screening tests for testing donors for HCV, whereas treatment with interferon and ribavirin of infected thalassemics was constrained by an increased risk of anemia due to the hemolytic properties of ribavirin coupled with interferon-induced bone marrow suppression. The advent of safe and potent regimens based on the oral administration of direct antiviral agents has revolutionized therapy of HCV in patients with congenital blood diseases, providing substantial clinical benefits and making elimination of infection in these populations, possible. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Utility of the serum C-reactive protein for detection of occult bacterial infection in children.

PubMed

Isaacman, Daniel J; Burke, Bonnie L

2002-09-01

To assess the utility of serum C-reactive protein (CRP) as a screen for occult bacterial infection in children. Febrile children ages 3 to 36 months who visited an urban children's hospital emergency department and received a complete blood cell count and blood culture as part of their evaluation were prospectively enrolled from February 2, 2000, through May 30, 2001. Informed consent was obtained for the withdrawal of an additional 1-mL aliquot of blood for use in CRP evaluation. Logistic regression and receiver operator characteristic (ROC) curves were modeled for each predictor to identify optimal test values, and were compared using likelihood ratio tests. Two hundred fifty-six patients were included in the analysis, with a median age of 15.3 months (range, 3.1-35.2 months) and median temperature at triage 40.0 degrees C (range, 39.0 degrees C-41.3 degrees C). Twenty-nine (11.3%) cases of occult bacterial infection (OBI) were identified, including 17 cases of pneumonia, 9 cases of urinary tract infection, and 3 cases of bacteremia. The median white blood cell count in this data set was 12.9 x 10(3)/ micro L [corrected] (range, 3.6-39.1 x10(3)/ micro L) [corrected], the median absolute neutrophil count (ANC) was 7.12 x 10(3)/L [corrected] (range, 0.56-28.16 x10(3)/L) [corrected], and the median CRP level was 1.7 mg/dL (range, 0.2-43.3 mg/dL). The optimal cut-off point for CRP in this data set (4.4 mg/dL) achieved a sensitivity of 63% and a specificity of 81% for detection of OBI in this population. Comparing models using cut-off values from individual laboratory predictors (ANC, white blood cell count, and CRP) that maximized sensitivity and specificity revealed that a model using an ANC of 10.6 x10(3)/L [corrected] (sensitivity, 69%; specificity, 79%) was the best predictive model. Adding CRP to the model insignificantly increased sensitivity to 79%, while significantly decreasing specificity to 50%. Active monitoring of emergency department blood cultures

Clinical application of the Quantiplex HCV RNA 2.0 and Amplicor HCV Monitor assays for quantifying serum hepatitis C virus RNA.

PubMed

Yu, M L; Chuang, W L; Chen, S C; Lin, Z Y; Hsieh, M Y; Wang, L Y; Chang, W Y

1999-11-01

To compare the performance characteristics and clinical application of two different technologies for quantifying serum hepatitis C virus (HCV) RNA levels. HCV RNA was quantified by Amplicor HCV Monitor assay (Amplicor) and Quantiplex HCV RNA 2.0 assay (bDNA-2) in 119 sera from 107 HCV infected patients. Both assays had similar sensitivity (79.4% for Amplicor; 86.0% for bDNA-2), acceptable coefficients of variation (5.3% in Amplicor; 2.6% in bDNA-2), and good linearity (r2 > or = 0.98). There was a positive correlation between quantification values of both methods (r = 0.683, p < 0.001). The Amplicor values were on an average 1.76 log lower than bDNA-2 results. Male subjects and HCV genotype 1b were significantly associated with higher viral load determined by Amplicor, but not with viral load measured by bDNA-2. In 70 chronic HCV infected patients treated with interferon alfa, mean (SD) pretreatment viral load in 27 complete responders (3.47 (0.84) logs for Amplicor, 5.63 (0.58) for bDNA-2) was significantly lower than in non-responders (4.43 (1.01) logs for Amplicor, 6.10 (0.67) logs for bDNA-2; p < 0.001). Cut off points of 3.9 logs for Amplicor and 5.8 logs for bDNA-2 were determined to be the best for predicting response to interferon alfa, giving acceptable sensitivity (70.4%, 74.1%), specificity (72.1%, 65.1%), and accuracy (71.4%, 68.6%), respectively. Both the Amplicor and bDNA-2 assays are clinically useful methods for HCV RNA quantification and are reliable for predicting the outcome of treatment, despite differences in absolute quantification values and in the correlation between HCV genotypes and viral load.

Retention in buprenorphine treatment is associated with improved HCV care outcomes.

PubMed

Norton, B L; Beitin, A; Glenn, M; DeLuca, J; Litwin, A H; Cunningham, C O

2017-04-01

Persons who inject drugs, most of whom are opioid dependent, comprise the majority of the HCV infected in the United States. As the national opioid epidemic unfolds, increasing numbers of people are entering the medical system to access treatment for opioid use disorder, specifically with buprenorphine. Yet little is known about HCV care in patients accessing buprenorphine-based opioid treatment. We sought to determine the HCV prevalence, cascade of care, and the association between patient characteristics and completion of HCV cascade of care milestones for patients initiating buprenorphine treatment. We reviewed electronic health records of all patients who initiated buprenorphine treatment at a primary-care clinic in the Bronx, NY between January 2009 and January 2014. Of the 390 patients who initiated buprenorphine treatment, 123 were confirmed to have chronic HCV infection. The only patient characteristic associated with achieving HCV care milestones was retention in opioid treatment. Patients retained (vs. not retained) in buprenorphine treatment were more likely to be referred for HCV specialty care (63.1% vs. 34.0%, p<0.01), achieve an HCV-specific evaluation (40.8% vs. 21.3%, p<0.05), be offered HCV treatment (22.4% vs. 8.5%, p<0.05), and initiate HCV treatment (9.2% vs. 6.4%, p=0.6). Given the current opioid epidemic in the US and the growing number of people receiving buprenorphine treatment, there is an unprecedented opportunity to access and treat persons with HCV, reducing HCV transmission, morbidity and mortality. Retention in opioid treatment may improve linkage and retention in HCV care; innovative models of care that integrate opioid drug treatment with HCV treatment are essential. Copyright © 2017 Elsevier Inc. All rights reserved.

Retention in Buprenorphine Treatment is Associated with Improved HCV Care Outcomes

PubMed Central

Norton, BL; Beitin, A; Glenn, M; DeLuca, J; Litwin, AH; Cunningham, CO

2018-01-01

Persons who inject drugs, most of whom are opioid dependent, comprise the majority of the HCV infected in the United States. As the national opioid epidemic unfolds, increasing numbers of people are entering the medical system to access treatment for opioid use disorder, specifically with buprenorphine. Yet little is known about HCV care in patients accessing buprenorphine-based opioid treatment. We sought to determine the HCV prevalence, cascade of care, and the association between patient characteristics and completion of HCV cascade of care milestones for patients initiating buprenorphine treatment. We reviewed electronic health records of all patients who initiated buprenorphine treatment at a primary-care clinic in the Bronx, NY between January 2009-January 2014. Of the 390 patients who initiated buprenorphine treatment, 123 were confirmed to have chronic HCV infection. The only patient characteristic associated with achieving HCV care milestones was retention in opioid treatment. Patients retained (vs. not retained) in buprenorphine treatment were more likely to be referred for HCV specialty care (63.1% vs. 34.0%, p<0.01), achieve an HCV-specific evaluation (40.8% vs. 21.3%, p<0.05), be offered HCV treatment (22.4% vs. 8.5%, p<0.05), and initiate HCV treatment (9.2% vs. 6.4%, p=0.6). Given the current opioid epidemic in the US and the growing number of people receiving buprenorphine treatment, there is an unprecedented opportunity to access and treat persons with HCV, reducing HCV transmission, morbidity and mortality. Retention in opioid treatment may improve linkage and retention in HCV care; innovative models of care that integrate opioid drug treatment with HCV treatment are essential. PMID:28237052

HIV, HBV and HCV Coinfection Prevalence in Iran--A Systematic Review and Meta-Analysis.

PubMed

Bagheri Amiri, Fahimeh; Mostafavi, Ehsan; Mirzazadeh, Ali

2016-01-01

worldwide, hepatitis C and B virus infections (HCV and HCV), are the two most common coinfections with human immunodeficiency virus (HIV) and has become a major threat to the survival of HIV-infected persons. The review aimed to estimate the prevalence of HIV, HBV, HCV, HIV/HCV and HIV/HBV and triple coinfections in different subpopulations in Iran. Following PRISMA guidelines, we conducted a systematic review and meta-analysis of reports on prevalence of HIV, HBV, HCV and HIV coinfections in different subpopulations in Iran. We systematically reviewed the literature to identify eligible studies from January 1996 to March 2012 in English or Persian/Farsi databases. We extracted the prevalence of HIV antibodies (diagnosed by Elisa confirmed with Western Blot test), HCV antibodies and HBsAg (with confirmatory laboratory test) as the main primary outcome. We reported the prevalence of the three infections and coinfections as point and 95% confidence intervals. HIV prevalence varied from %0.00 (95% CI: 0.00-0.003) in the general population to %17.25 (95% CI: 2.94-31.57) in people who inject drugs (PWID). HBV prevalence ranged from % 0.00 (95% CI: 0.00-7.87) in health care workers to % 30.9 (95% CI: 27.88-33.92) in PWID. HCV prevalence ranged from %0.19 (95% CI: 0.00-0.66) in health care workers to %51.46 (95% CI: 34.30-68.62) in PWID. The coinfection of HIV/HBV and also HIV/HCV in the general population and in health care workers was zero, while the most common coinfections were HIV/HCV (10.95%), HIV/HBV (1.88%) and triple infections (1.25%) in PWID. We found that PWID are severely and disproportionately affected by HIV and the other two infections, HCV and HBV. Screenings of such coinfections need to be reinforced to prevent new infections and also reduce further transmission in their community and to others.

HIV, HBV and HCV Coinfection Prevalence in Iran - A Systematic Review and Meta-Analysis

PubMed Central

Bagheri Amiri, Fahimeh; Mostafavi, Ehsan; Mirzazadeh, Ali

2016-01-01

Background worldwide, hepatitis C and B virus infections (HCV and HCV), are the two most common coinfections with human immunodeficiency virus (HIV) and has become a major threat to the survival of HIV-infected persons. The review aimed to estimate the prevalence of HIV, HBV, HCV, HIV/HCV and HIV/HBV and triple coinfections in different subpopulations in Iran. Method Following PRISMA guidelines, we conducted a systematic review and meta-analysis of reports on prevalence of HIV, HBV, HCV and HIV coinfections in different subpopulations in Iran. We systematically reviewed the literature to identify eligible studies from January 1996 to March 2012 in English or Persian/Farsi databases. We extracted the prevalence of HIV antibodies (diagnosed by Elisa confirmed with Western Blot test), HCV antibodies and HBsAg (with confirmatory laboratory test) as the main primary outcome. We reported the prevalence of the three infections and coinfections as point and 95% confidence intervals. Findings HIV prevalence varied from %0.00 (95% CI: 0.00–0.003) in the general population to %17.25 (95% CI: 2.94–31.57) in people who inject drugs (PWID). HBV prevalence ranged from % 0.00 (95% CI: 0.00–7.87) in health care workers to % 30.9 (95% CI: 27.88–33.92) in PWID. HCV prevalence ranged from %0.19 (95% CI: 0.00–0.66) in health care workers to %51.46 (95% CI: 34.30–68.62) in PWID. The coinfection of HIV/HBV and also HIV/HCV in the general population and in health care workers was zero, while the most common coinfections were HIV/HCV (10.95%), HIV/HBV (1.88%) and triple infections (1.25%) in PWID. Conclusions We found that PWID are severely and disproportionately affected by HIV and the other two infections, HCV and HBV. Screenings of such coinfections need to be reinforced to prevent new infections and also reduce further transmission in their community and to others. PMID:27031352

Direct anti-HCV agents

PubMed Central

Zhang, Xingquan

2015-01-01

Unlike human immunodeficiency virus (HIV) and hepatitis B virus (HBV), hepatitis C virus (HCV) infection is a curable disease. Current direct antiviral agent (DAA) targets are focused on HCV NS3/4A protein (protease), NS5B protein (polymerase) and NS5A protein. The first generation of DAAs includes boceprevir and telaprevir, which are protease inhibitors and were approved for clinical use in 2011. The cure rate for genotype 1 patients increased from 45% to 70% when boceprevir or telaprevir was added to standard PEG-IFN/ribavirin. More effective and less toxic second generation DAAs supplanted these drugs by 2013. The second generation of DAAs includes sofosbuvir (Sovaldi), simeprevir (Olysio), and fixed combination medicines Harvoni and Viekira Pak. These drugs increase cure rates to over 90% without the need for interferon and effectively treat all HCV genotypes. With these drugs the “cure HCV” goal has become a reality. Concerns remain about drug resistance mutations and the high cost of these drugs. The investigation of new HCV drugs is progressing rapidly; fixed dose combination medicines in phase III clinical trials include Viekirax, asunaprevir+daclatasvir+beclabuvir, grazoprevir+elbasvir and others. PMID:26904396

Detection of HBV genome in the plasma and peripheral blood mononuclear cells of Iranian HBsAg negative patients with HIV infection: occult HBV infection.

PubMed

Tajik, Zahra; Bokharaei-Salim, Farah; Ghorbani, Saied; Keyvani, Hossein; Esghaei, Maryam; Monavari, Seyed Hamidreza; Ataei-Pirkooh, Angila; Garshasbi, Saba; Donyavi, Tahereh; Fakhim, Atousa

2018-06-01

The presence of hepatitis B virus (HBV) DNA in the absence of traceable hepatitis B surface antigen (HBsAg) in the plasma specimen of patients is defined as occult HBV infection (OBI). This study aimed to detect HBV-DNA in the plasma and peripheral blood mononuclear cells (PBMCs) of Iranian HBsAg negative patients with human immunodeficiency virus (HIV) infection. This cross-sectional study was conducted on 172 patients with HIV infection from September 2015 to August 2017. The patients were tested for serological parameters (HBsAg, HBcAb, HBeAg and HBeAb) against HBV infection. Moreover, they were tested for HBV viral load (using COBAS TaqMan 48 Kit, Roche, USA) in plasma and the presence of the HBV genome in PBMC specimens using real-time PCR. The mean age of the patients was 35.4 ± 13.4 years. Of the 172 studied patients, 109 (63.4%) were male. In this study, 151 (87.8%) patients were negative for HBsAg, 111 (64.5%) patients were negative for all HBV infection serological markers, 9 (5.2%) patients were only positive for HBsAg and 29 (16.9%) patients were only positive for HBcAb. Moreover, five (3.3%) patients with HBsAg negative had OBI (in the plasma sample of four patients and PBMC specimens of all five patients, HBV-DNA was detected). The present study revealed that 3.3% of the patients with HIV infection had occult HBV infection. Presumably, designing prospective studies to identify this infection in patients with HIV infection is informative and valuable.

Chimeric antigen receptor (CAR)-engineered T cells redirected against hepatitis C virus (HCV) E2 glycoprotein

PubMed Central

Sautto, Giuseppe A; Wisskirchen, Karin; Clementi, Nicola; Castelli, Matteo; Diotti, Roberta A; Graf, Julia; Clementi, Massimo; Burioni, Roberto; Protzer, Ulrike; Mancini, Nicasio

2016-01-01

Objective The recent availability of novel antiviral drugs has raised new hope for a more effective treatment of hepatitis C virus (HCV) infection and its severe sequelae. However, in the case of non-responding or relapsing patients, alternative strategies are needed. To this end we have used chimeric antigen receptors (CARs), a very promising approach recently used in several clinical trials to redirect primary human T cells against different tumours. In particular, we designed the first CARs against HCV targeting the HCV/E2 glycoprotein (HCV/E2). Design Anti-HCV/E2 CARs were composed of single-chain variable fragments (scFvs) obtained from a broadly cross-reactive and cross-neutralising human monoclonal antibody (mAb), e137, fused to the intracellular signalling motif of the costimulatory CD28 molecule and the CD3ζ domain. Activity of CAR-grafted T cells was evaluated in vitro against HCV/E2-transfected cells as well as hepatocytes infected with cell culture-derived HCV (HCVcc). Results In this proof-of-concept study, retrovirus-transduced human T cells expressing anti-HCV/E2 CARs were endowed with specific antigen recognition accompanied by degranulation and secretion of proinflammatory and antiviral cytokines, such as interferon γ, interleukin 2 and tumour necrosis factor α. Moreover, CAR-grafted T cells were capable of lysing target cells of both hepatic and non-hepatic origin expressing on their surface the HCV/E2 glycoproteins of the most clinically relevant genotypes, including 1a, 1b, 2a, 3a, 4 and 5. Finally, and more importantly, they were capable of lysing HCVcc-infected hepatocytes. Conclusions Clearance of HCV-infected cells is a major therapeutic goal in chronic HCV infection, and adoptive transfer of anti-HCV/E2 CARs-grafted T cells represents a promising new therapeutic tool. PMID:25661083

Update on epidemiology of HCV in Italy: focus on the Calabria Region

PubMed Central

2014-01-01

The epidemiological profile of HCV infection is evolving in Europe, as well as in Italy. We have previously showed genotype distributions and their dynamics in 2,153 HCV RNA positive patients living in Calabria, Southern Italy, over 11 years. In this study, we extend and update this information by evaluating a hospital-based cohort of 945 HCV RNA positive patients attending five hospitals in the Calabria Region from January 2011 to August 2013. We assessed rates of HCV genotypes according to age and gender and the dynamics of HCV genotype distribution over the 3-year period studied. Data showed that genotype 1b is the most prevalent, followed by subtypes 2a/2c and genotype 3. Genotype 4 exhibited an increase between 2011 and 2013. Also, we found a significant decrease in the median age of subjects infected with HCV genotype 3 and 4 during the period studied. Since HCV genotypes are important in epidemiology, pathogenesis and response to antiviral therapy, a continuous epidemiological surveillance is needed. PMID:25236184

Co-Infection of the Hepatitis C Virus With Other Blood-Borne and Hepatotropic Viruses Among Hemophilia Patients in Poland.

PubMed

Kucharska, Marta; Inglot, Malgorzata; Szymczak, Aleksandra; Rymer, Weronika; Zalewska, Malgorzata; Malyszczak, Krzysztof; Zaleska-Dorobisz, Urszula; Kuliszkiewicz-Janus, Malgorzata

2016-09-01

The prevalence of HCV infection in people with hemophilia is substantially higher than that in the general population (63% - 98%). Multiple transfusions and substitutive therapy have also been linked to a high risk of HBV and HIV transmission. However, the prevalence of other blood-borne viral infections in this population is less well known. This study aimed to assess the prevalence of co-infection with HBV and other blood-borne viruses in Polish HCV-infected hemophiliacs. Seventy-one individuals, the majority of whom were male (94.36%), who had congenital bleeding disorders (60 had hemophilia A, five had hemophilia B, and six had other factor deficiencies) and HCV infection, which was defined as the presence of positive anti-HCV antibodies, were included in this study. The study group was divided into two subgroups according to the year in which blood donors were first tested for HBsAg in Poland. The serological markers were screened using commercially available enzyme immunoassays according to the manufacturer's instructions. The molecular tests were performed using real-time PCR technology with commercial assays according to the manufacturer's instructions. The spontaneous elimination rate of HCV RNA was 29.6%. The HCV genotype 1 was detected in 28 patients (65.1%), genotype 2 in one patient (2.3%), genotype 3 in 11 patients (25.6%), genotype 4 in two patients (4.7%), and a mixed infection with genotypes 1 and 4 was detected in one person (2.3%). Fifty-three patients (74.6%) were anti-HBc positive. Among the seven HBsAg(+) patients, three individuals were HBV-DNA positive. No occult hepatitis B was detected. In six HBsAg positive patients, the HCV RNA was positive, while one patient was also infected with HIV. The prevalence rate of past infection with HAV in the study group was 30.9%, with a tendency for a higher prevalence in older patients. The prevalence of CMV and EBV infection was high and similar to that seen in the general population. All the patients

Co-Infection of the Hepatitis C Virus With Other Blood-Borne and Hepatotropic Viruses Among Hemophilia Patients in Poland

PubMed Central

Kucharska, Marta; Inglot, Malgorzata; Szymczak, Aleksandra; Rymer, Weronika; Zalewska, Malgorzata; Malyszczak, Krzysztof; Zaleska-Dorobisz, Urszula; Kuliszkiewicz-Janus, Malgorzata

2016-01-01

Background The prevalence of HCV infection in people with hemophilia is substantially higher than that in the general population (63% - 98%). Multiple transfusions and substitutive therapy have also been linked to a high risk of HBV and HIV transmission. However, the prevalence of other blood-borne viral infections in this population is less well known. Objectives This study aimed to assess the prevalence of co-infection with HBV and other blood-borne viruses in Polish HCV-infected hemophiliacs. Methods Seventy-one individuals, the majority of whom were male (94.36%), who had congenital bleeding disorders (60 had hemophilia A, five had hemophilia B, and six had other factor deficiencies) and HCV infection, which was defined as the presence of positive anti-HCV antibodies, were included in this study. The study group was divided into two subgroups according to the year in which blood donors were first tested for HBsAg in Poland. The serological markers were screened using commercially available enzyme immunoassays according to the manufacturer’s instructions. The molecular tests were performed using real-time PCR technology with commercial assays according to the manufacturer’s instructions. Results The spontaneous elimination rate of HCV RNA was 29.6%. The HCV genotype 1 was detected in 28 patients (65.1%), genotype 2 in one patient (2.3%), genotype 3 in 11 patients (25.6%), genotype 4 in two patients (4.7%), and a mixed infection with genotypes 1 and 4 was detected in one person (2.3%). Fifty-three patients (74.6%) were anti-HBc positive. Among the seven HBsAg(+) patients, three individuals were HBV-DNA positive. No occult hepatitis B was detected. In six HBsAg positive patients, the HCV RNA was positive, while one patient was also infected with HIV. The prevalence rate of past infection with HAV in the study group was 30.9%, with a tendency for a higher prevalence in older patients. The prevalence of CMV and EBV infection was high and similar to that seen in

Bystander hyperactivation of preimmune CD8+ T cells in chronic HCV patients

PubMed Central

Alanio, Cécile; Nicoli, Francesco; Sultanik, Philippe; Flecken, Tobias; Perot, Brieuc; Duffy, Darragh; Bianchi, Elisabetta; Lim, Annick; Clave, Emmanuel; van Buuren, Marit M; Schnuriger, Aurélie; Johnsson, Kerstin; Boussier, Jeremy; Garbarg-Chenon, Antoine; Bousquet, Laurence; Mottez, Estelle; Schumacher, Ton N; Toubert, Antoine; Appay, Victor; Heshmati, Farhad; Thimme, Robert; Pol, Stanislas; Mallet, Vincent; Albert, Matthew L

2015-01-01

Chronic infection perturbs immune homeostasis. While prior studies have reported dysregulation of effector and memory cells, little is known about the effects on naïve T cell populations. We performed a cross-sectional study of chronic hepatitis C (cHCV) patients using tetramer-associated magnetic enrichment to study antigen-specific inexperienced CD8+ T cells (i.e., tumor or unrelated virus-specific populations in tumor-free and sero-negative individuals). cHCV showed normal precursor frequencies, but increased proportions of memory-phenotype inexperienced cells, as compared to healthy donors or cured HCV patients. These observations could be explained by low surface expression of CD5, a negative regulator of TCR signaling. Accordingly, we demonstrated TCR hyperactivation and generation of potent CD8+ T cell responses from the altered T cell repertoire of cHCV patients. In sum, we provide the first evidence that naïve CD8+ T cells are dysregulated during cHCV infection, and establish a new mechanism of immune perturbation secondary to chronic infection. DOI: http://dx.doi.org/10.7554/eLife.07916.001 PMID:26568315

Characterization of vaniprevir, a hepatitis C virus NS3/4A protease inhibitor, in patients with HCV genotype 1 infection: safety, antiviral activity, resistance, and pharmacokinetics.

PubMed

Lawitz, Eric; Sulkowski, Mark; Jacobson, Ira; Kraft, Walter K; Maliakkal, Benedict; Al-Ibrahim, Mohamed; Gordon, Stuart C; Kwo, Paul; Rockstroh, Juergen Kurt; Panorchan, Paul; Miller, Michelle; Caro, Luzelena; Barnard, Richard; Hwang, Peggy May; Gress, Jacqueline; Quirk, Erin; Mobashery, Niloufar

2013-09-01

Vaniprevir is a competitive inhibitor of the hepatitis C virus (HCV) NS3/4A protease that has potent anti-HCV activity in preclinical models. This placebo-controlled dose-ranging study assessed the safety, tolerability, and antiviral efficacy of vaniprevir monotherapy in patients with genotype 1 chronic HCV infection. Treatment-naive and treatment-experienced non-cirrhotic adult patients with baseline HCV RNA >10(6)IU/ml were randomized to receive placebo or vaniprevir at doses of 125 mg qd, 600 mg qd, 25mg bid, 75 mg bid, 250 mg bid, 500 mg bid, and 700 mg bid for 8 days. Forty patients (82.5% male, 75% genotype 1a) received at least one dose of placebo or vaniprevir. After 1 week of vaniprevir, the decrease in HCV RNA from baseline ranged from 1.8 to 4.6 log₁₀IU/ml across all treatment groups, and there was a greater than dose-proportional increase in vaniprevir exposure at doses above 75 mg bid. The most commonly reported drug-related adverse events (AEs) were diarrhea (n=5) and nausea (n=5). No pattern of laboratory or ECG abnormalities was observed, all AEs resolved during the study, and there were no discontinuations due to AEs. No serious AEs were reported. Resistance-associated amino acid variants were identified at positions R155 and D168 in patients infected with genotype 1a virus. Vaniprevir monotherapy demonstrated potent antiviral activity in patients with chronic genotype 1 HCV infection, and was generally well tolerated with no serious AEs or discontinuations due to AEs. Further development of vaniprevir, including studies in combination with other anti-HCV agents, is ongoing. Copyright © 2013 Elsevier B.V. All rights reserved.

Seroprevalence of HIV, HBV, HCV, and HTLV among Pregnant Women in Southwestern Nigeria.

PubMed

Opaleye, Oluyinka Oladele; Igboama, Magdalene C; Ojo, Johnson Adeyemi; Odewale, Gbolabo

2016-01-01

Sexually transmitted infections (STIs) are major public health challenge especially in developing countries. This study was designed to determine the prevalence of Hepatitis B virus (HBV), Hepatitis C Virus (HCV), Human immunodeficiency virus (HIV), and Human T-cell lymphotropic Virus type I (HTLV-I) among pregnant women attending antenatal clinic, in Ladoke Akintola University Teaching Hospital, Osogbo, and South-Western Nigeria. One hundred and eighty two randomly selected pregnant women were screened for HBsAg, anti-HCV, anti-HIV and HTLV-1 IgM antibodies using commercially available ELISA kit. Of the 182 blood samples of pregnant women screened whose age ranged from 15-49 years, 13 (7.1%), 5 (2.7%), 9 (4.9%), and 44 (24.2%) were positive for HBsAg, anti-HCV, anti-HIV, and HTLV-1 IgM antibodies, respectively. The co-infection rate of 0.5% was obtained for HBV/HCV, HBV/HIV, HIV/HTLV-1, and HCV/HTLV-1 while 1.1% and 0% was recorded for HBV/HTLV-1 and HCV/HIV co-infections, respectively. Expected risk factors such as history of surgery, circumcision, tattooing and incision showed no significant association with any of the viral STIs (P > 0.05). This study shows that there is the need for a comprehensive screening of all pregnant women for HBsAg, anti-HCV, anti-HIV and HTLV-1 to prevent mother to child transmission of these viral infections and its attending consequences.

Patient-to-patient transmission of hepatitis C virus (HCV) during colonoscopy diagnosis

PubMed Central

2010-01-01

Background No recognized risk factors can be identified in 10-40% of hepatitis C virus (HCV)-infected patients suggesting that the modes of transmission involved could be underestimated or unidentified. Invasive diagnostic procedures, such as endoscopy, have been considered as a potential HCV transmission route; although the actual extent of transmission in endoscopy procedures remains controversial. Most reported HCV outbreaks related to nosocomial acquisition have been attributed to unsafe injection practices and use of multi-dose vials. Only a few cases of likely patient-to-patient HCV transmission via a contaminated colonoscope have been reported to date. Nosocomial HCV infection may have important medical and legal implications and, therefore, possible transmission routes should be investigated. In this study, a case of nosocomial transmission of HCV from a common source to two patients who underwent colonoscopy in an endoscopy unit is reported. Results A retrospective epidemiological search after detection of index cases revealed several potentially infective procedures: sample blood collection, use of a peripheral catheter, anesthesia and colonoscopy procedures. The epidemiological investigation showed breaches in colonoscope reprocessing and deficiencies in the recording of valuable tracing data. Direct sequences from the NS5B region were obtained to determine the extent of the outbreak and cloned sequences from the E1-E2 region were used to establish the relationships among intrapatient viral populations. Phylogenetic analyses of individual sequences from viral populations infecting the three patients involved in the outbreak confirmed the patient pointed out by the epidemiological search as the source of the outbreak. Furthermore, the sequential order in which the patients underwent colonoscopy correlates with viral genetic variability estimates. Conclusions Patient-to-patient transmission of HCV could be demonstrated although the precise route of

HCV upregulates Bim through the ROS/JNK signalling pathway, leading to Bax-mediated apoptosis.

PubMed

Deng, Lin; Chen, Ming; Tanaka, Motofumi; Ku, Yonson; Itoh, Tomoo; Shoji, Ikuo; Hotta, Hak

2015-09-01

We previously reported that hepatitis C virus (HCV) infection induces Bax-triggered, mitochondrion-mediated apoptosis by using the HCV J6/JFH1 strain and Huh-7.5 cells. However, it was still unclear how HCV-induced Bax activation. In this study, we showed that the HCV-induced activation and mitochondrial accumulation of Bax were significantly attenuated by treatment with a general antioxidant, N-acetyl cysteine (NAC), or a specific c-Jun N-terminal kinase (JNK) inhibitor, SP600125, with the result suggesting that the reactive oxygen species (ROS)/JNK signalling pathway is upstream of Bax activation in HCV-induced apoptosis. We also demonstrated that HCV infection transcriptionally activated the gene for the pro-apoptotic protein Bim and the protein expression of three major splice variants of Bim (BimEL, BimL and BimS). The HCV-induced increase in the Bim mRNA and protein levels was significantly counteracted by treatment with NAC or SP600125, suggesting that the ROS/JNK signalling pathway is involved in Bim upregulation. Moreover, HCV infection led to a marked accumulation of Bim on the mitochondria to facilitate its interaction with Bax. On the other hand, downregulation of Bim by siRNA (small interfering RNA) significantly prevented HCV-mediated activation of Bax and caspase 3. Taken together, these observations suggest that HCV-induced ROS/JNK signalling transcriptionally activates Bim expression, which leads to Bax activation and apoptosis induction.

21 CFR 610.47 - Hepatitis C virus (HCV) “lookback” requirements.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Hepatitis C virus (HCV) âlookbackâ requirements... Disease Agents § 610.47 Hepatitis C virus (HCV) “lookback” requirements. (a) If you are an establishment... after a donor tests reactive for evidence of hepatitis C virus (HCV) infection when tested under § 610...

21 CFR 610.47 - Hepatitis C virus (HCV) “lookback” requirements.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Hepatitis C virus (HCV) âlookbackâ requirements... Disease Agents § 610.47 Hepatitis C virus (HCV) “lookback” requirements. (a) If you are an establishment... after a donor tests reactive for evidence of hepatitis C virus (HCV) infection when tested under § 610...

21 CFR 610.47 - Hepatitis C virus (HCV) “lookback” requirements.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Hepatitis C virus (HCV) âlookbackâ requirements... Disease Agents § 610.47 Hepatitis C virus (HCV) “lookback” requirements. (a) If you are an establishment... after a donor tests reactive for evidence of hepatitis C virus (HCV) infection when tested under § 610...

21 CFR 610.47 - Hepatitis C virus (HCV) “lookback” requirements.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Hepatitis C virus (HCV) âlookbackâ requirements... Disease Agents § 610.47 Hepatitis C virus (HCV) “lookback” requirements. (a) If you are an establishment... after a donor tests reactive for evidence of hepatitis C virus (HCV) infection when tested under § 610...

21 CFR 610.47 - Hepatitis C virus (HCV) “lookback” requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Hepatitis C virus (HCV) âlookbackâ requirements... Disease Agents § 610.47 Hepatitis C virus (HCV) “lookback” requirements. (a) If you are an establishment... after a donor tests reactive for evidence of hepatitis C virus (HCV) infection when tested under § 610...

HCV IRES-Mediated Core Expression in Zebrafish

PubMed Central

Zhang, Jing-Pu; Hu, Zhan-Ying; Tong, Jun-Wei; Ding, Cun-Bao; Peng, Zong-Gen; Zhao, Li-Xun; Song, Dan-Qing; Jiang, Jian-Dong

2013-01-01

The lack of small animal models for hepatitis C virus has impeded the discovery and development of anti-HCV drugs. HCV-IRES plays an important role in HCV gene expression, and is an attractive target for antiviral therapy. In this study, we report a zebrafish model with a biscistron expression construct that can co-transcribe GFP and HCV-core genes by human hepatic lipase promoter and zebrafish liver fatty acid binding protein enhancer. HCV core translation was designed mediated by HCV-IRES sequence and gfp was by a canonical cap-dependent mechanism. Results of fluorescence image and in situ hybridization indicate that expression of HCV core and GFP is liver-specific; RT-PCR and Western blotting show that both core and gfp expression are elevated in a time-dependent manner for both transcription and translation. It means that the HCV-IRES exerted its role in this zebrafish model. Furthermore, the liver-pathological impact associated with HCV-infection was detected by examination of gene markers and some of them were elevated, such as adiponectin receptor, heparanase, TGF-β, PDGF-α, etc. The model was used to evaluate three clinical drugs, ribavirin, IFNα-2b and vitamin B12. The results show that vitamin B12 inhibited core expression in mRNA and protein levels in dose-dependent manner, but failed to impact gfp expression. Also VB12 down-regulated some gene transcriptions involved in fat liver, liver fibrosis and HCV-associated pathological process in the larvae. It reveals that HCV-IRES responds to vitamin B12 sensitively in the zebrafish model. Ribavirin did not disturb core expression, hinting that HCV-IRES is not a target site of ribavirin. IFNα-2b was not active, which maybe resulted from its degradation in vivo for the long time. These findings demonstrate the feasibility of the zebrafish model for screening of anti-HCV drugs targeting to HCV-IRES. The zebrafish system provides a novel evidence of using zebrafish as a HCV model organism. PMID:23469178

Update on occult hepatitis B virus infection

PubMed Central

Makvandi, Manoochehr

2016-01-01

The event of mutations in the surface antigen gene of hepatitis B virus (HBV) results in undetectable hepatitis B surface antigen with positive/negative anti-hepatitis B core (anti-HBc) antibody status in serum and this phenomenon is named occult hepatitis B infection (OBI). The presence of anti-HBc antibody in serum is an important key for OBI tracking, although about 20% of OBI cases are negative for anti-HBc antibody. The diagnosis of OBI is mainly based on polymerase chain reaction (PCR) and real-time PCR assays. However, real-time PCR is a more reliable method than PCR. OBI is a great issue for the public health problem and a challenge for the clinical entity worldwide. The persistence of OBI may lead to the development of cirrhosis and hepatocellular carcinoma. With regard to OBI complications, the screening of HBV DNA by the highly sensitive molecular means should be implemented for: (1) patients with a previous history of chronic or acute HBV infection; (2) patients co-infected with hepatitis C virus/human immunodeficiency virus; (3) patients undergoing chemotherapy or anti-CD20 therapy; (4) recipients of organ transplant; (5) blood donors; (6) organ transplant donors; (7) thalassemia and hemophilia patients; (8) health care workers; (9) patients with liver related disease (cryptogenic); (10) hemodialysis patients; (11) patients undergoing lamivudine or interferon therapy; and (12) children in time of HBV vaccination especially in highly endemic areas of HBV. Active HBV vaccination should be implemented for the close relatives of patients who are negative for OBI markers. Thus, the goal of this review is to evaluate the rate of OBI with a focus on status of high risk groups in different regions of the world. PMID:27818588

Evaluation of the Abbott Real Time HCV genotype II assay for Hepatitis C virus genotyping.

PubMed

Sariguzel, Fatma Mutlu; Berk, Elife; Gokahmetoglu, Selma; Ercal, Baris Derya; Celik, Ilhami

2015-01-01

The determination of HCV genotypes and subtypes is very important for the selection of antiviral therapy and epidemiological studies. The aim of this study was to evaluate the performance of Abbott Real Time HCV Genotype II assay in HCV genotyping of HCV infected patients in Kayseri, Turkey. One hundred patients with chronic hepatitis C admitted to our hospital were evaluated between June 2012 and December 2012, HCV RNA levels were determined by the COBAS® AmpliPrep/COBAS® TaqMan® 48 HCV test. HCV genotyping was investigated by the Abbott Real Time HCV Genotype II assay. With the exception of genotype 1, subtypes of HCV genotypes could not be determined by Abbott assay. Sequencing analysis was used as the reference method. Genotypes 1, 2, 3 and 4 were observed in 70, 4, 2 and 24 of the 100 patients, respectively, by two methods. The concordance between the two systems to determine HCV major genotypes was 100%. Of 70 patients with genotype 1, 66 showed infection with subtype 1b and 4 with subtype 1a by Abbott Real Time HCV Genotype II assay. Using sequence analysis, 61 showed infection with subtype 1b and 9 with subtype 1a. In determining of HCV genotype 1 subtypes, the difference between the two methods was not statistically significant (P>0.05). HCV genotype 4 and 3 samples were found to be subtype 4d and 3a, respectively, by sequence analysis. There were four patients with genotype 2. Sequence analysis revealed that two of these patients had type 2a and the other two had type 2b. The Abbott Real Time HCV Genotype II assay yielded results consistent with sequence analysis. However, further optimization of the Abbott Real Time HCV Genotype II assay for subtype identification of HCV is required.

Immune Responses to HCV and Other Hepatitis Viruses

PubMed Central

Park, Su-Hyung; Rehermann, Barbara

2014-01-01

Summary Five human hepatitis viruses cause most acute and chronic liver disease worldwide. Over the past 25 years hepatitis C virus (HCV) in particular has received much interest because of its ability to persist in most immunocompetent adults and the lack of a protective vaccine. Here we examine innate and adaptive immune responses to HCV infection. Although HCV activates an innate immune response, it employs an elaborate set of mechanisms to evade interferon (IFN)-based antiviral immunity. By comparing innate and adaptive immune responses to HCV with those to hepatitis A and B viruses, we suggest that prolonged innate immune activation impairs the development of successful adaptive immune responses. Comparative immunology furthermore provides insights into the maintenance of immune protection. We conclude by discussing prospects for an HCV vaccine and future research needs for the hepatitis viruses. PMID:24439265

Costs and absence of HCV-infected employees by disease stage.

PubMed

Baran, Robert W; Samp, Jennifer C; Walker, David R; Smeeding, James E; Young, Jacob W; Kleinman, Nathan L; Brook, Richard A

2015-01-01

Quantify the costs and absenteeism associated with stages of the Hepatitis C virus (HCV). Retrospective analysis of the HCMS integrated database from multiple geographically diverse, US-based employers with employee information on medical, prescription, and absenteeism claims. Employee data were extracted from July 2001-March 2013. Employees with HCV were identified by ICD-9-CM codes and classified into disease severity cohorts using diagnosis/procedure codes assigning the first date of most severe claim as the index date. Non-HCV employees (controls) were assigned random index dates. Inclusion required 6-month pre-/post-index eligibility. Medical, prescription, and absenteeism cost and time were analyzed using two-part regression (logistic/generalized linear) models, controlling for potentially confounding factors. Costs were inflation adjusted to September 2013. All direct costs comparisons were statistically significant (p ≤ 0.05) with mean medical costs of $1813 [SE = $3] for controls (n = 727,588), $4611 [SE = $211] for non-cirrhotic (n = 1007), $4646 [SE = $721] for compensated cirrhosis (CC, n = 87), $12,384 [SE = $1122] for decompensated cirrhosis (DCC, n = 256), $33,494 [SE = $11,753] for hepatocellular carcinoma (HCC, n = 17) and $97,724 [SE = $32,437] for liver transplant (LT, n = 19) cohorts. Mean short-term disability days/costs were significantly greater for the non-cirrhotic (days = 2.03 [SE = 0.36]; $299 [SE = $53]), DCC (days = 6.20 [SE = 1.36]; $763 [SE = $169]), and LT cohorts (days = 21.98 [SE = 8.21]; $2537 [SE = $972]) compared to controls (days = 1.19 [SE = 0.01]; $155 [SE = $1]). Mean sick leave costs were significantly greater for non-cirrhotic ($373 [SE = $22]) and DCC ($460 [SE = $54]) compared to controls ($327 [SE = $1]). Employees with HCV were shown to have greater direct and indirect costs compared to non-HCV employee

Clinical presentation and course of acute hepatitis C infection in HIV-infected patients.

PubMed

Luetkemeyer, Annie; Hare, C Bradley; Stansell, John; Tien, Phyllis C; Charlesbois, Edwin; Lum, Paula; Havlir, Diane; Peters, Marion

2006-01-01

Hepatitis C virus (HCV) has become a significant source of morbidity and mortality in HIV-infected patients. However, little is known about the clinical presentation and course of acute HCV infection in this population. This study reports the outcomes of acute HCV infection in 9 HIV-infected men. Sex with men was the only reported risk factor for HCV infection in 6 of the subjects. Clinical presentation of acute HCV ranged from incidentally discovered elevated transaminases to severe liver dysfunction requiring hospitalization. At the time of HCV diagnosis, 8 of 9 patients had CD4+ counts >250 cells/mm(3), and 6 had HIV viral loads of < or =5000 copies/mL. Eight patients were receiving antiretroviral therapy. Outcome of these acute HCV infections varied. Five patients experienced virologic clearance, 2 in whom virus cleared spontaneously and 3 who were treated with pegylated interferon and ribavirin. Four patients developed chronic infection, one of whom had a relapse during HCV treatment and 3 of whom were untreated. All 4 patients to whom HCV therapy was administered experienced significant anemia or neutropenia, necessitating dose reduction or support with growth factors. Prompt recognition of acute HCV infection may minimize antiretroviral treatment interruption and will allow early treatment, which may improve virologic clearance. Unexplained transaminase elevations in HIV-infected patients, including men who have sex with men, should trigger an evaluation for acute HCV infection.

Real-World Experiences with the Combination Treatment of Ledipasvir plus Sofosbuvir for 12 Weeks in HCV Genotype 1-Infected Japanese Patients: Achievement of a Sustained Virological Response in Previous Users of Peginterferon plus Ribavirin with HCV NS3/4A Inhibitors.

PubMed

Kanda, Tatsuo; Yasui, Shin; Nakamura, Masato; Suzuki, Eiichiro; Arai, Makoto; Ooka, Yoshihiko; Ogasawara, Sadahisa; Chiba, Tetsuhiro; Saito, Tomoko; Haga, Yuki; Takahashi, Koji; Sasaki, Reina; Wu, Shuang; Nakamoto, Shingo; Tawada, Akinobu; Maruyama, Hitoshi; Imazeki, Fumio; Kato, Naoya; Yokosuka, Osamu

2017-04-25

The aim of this study was to characterize the treatment response and serious adverse events of ledipasvir plus sofosbuvir therapies in Japanese patients infected with hepatitis C virus (HCV) genotype 1 (GT1). This retrospective study analyzed 240 Japanese HCV GT1 patients treated for 12 weeks with 90 mg of ledipasvir plus 400 mg of sofosbuvir daily. Sustained virological response at 12 weeks post-treatment (SVR12) was achieved in 236 of 240 (98.3%) patients. Among treatment-naïve patients, SVR12 was achieved in 136 of 138 (98.6%) patients, and among treatment-experienced patients, SVR12 was achieved in 100 of 102 (98.0%) patients. In patients previously treated with peginterferon plus ribavirin with various HCV NS3/4A inhibitors, 100% SVR rates (25/25) were achieved. Two relapsers had HCV NS5A resistance-associated variants (RAVs), but no HCV NS5B-S282 was observed after they relapsed. We experienced two patients with cardiac events during treatment. In conclusion, combination of ledipasvir plus sofosbuvir for 12 weeks is a potential therapy for HCV GT1 patients. Caution is needed for HCV NS5A RAVs, which were selected by HCV NS5A inhibitors and cardiac adverse events.

Quantification of HCV RNA in Clinical Specimens by Branched DNA (bDNA) Technology.

PubMed

Wilber, J C; Urdea, M S

1999-01-01

The diagnosis and monitoring of hepatitis C virus (HCV) infection have been aided by the development of HCV RNA quantification assays A direct measure of viral load, HCV RNA quantification has the advantage of providing information on viral kinetics and provides unique insight into the disease process. Branched DNA (bDNA) signal amplification technology provides a novel approach for the direct quantification of HCV RNA in patient specimens. The bDNA assay measures HCV RNA at physiological levels by boosting the reporter signal, rather than by replicating target sequences as the means of detection, and thus avoids the errors inherent in the extraction and amplification of target sequences. Inherently quantitative and nonradioactive, the bDNA assay is amenable to routine use in a clinical research setting, and has been used by several groups to explore the natural history, pathogenesis, and treatment of HCV infection.

Effect of genotypes on the quantification of hepatitis C virus (HCV) RNA in clinical samples using the Amplicor HCV Monitor Test and the Quantiplex HCV RNA 2.0 assay (bDNA).

PubMed

Tong, C Y; Hollingsworth, R C; Williams, H; Irving, W L; Gilmore, I T

1998-07-01

The Amplicor HCV Monitor test and the Quantiplex HCV RNA 2.0 (bDNA) assay are two commercially available assays for the quantification of hepatitis C virus (HCV) RNA in clinical samples. A direct comparison of the two assays was carried out using sera frozen previously from patients known to be chronically infected with HCV. Overall, 61 samples from 51 patients were tested simultaneously by the two methods: 67% (28/42) of the patients were infected by HCV genotype/serotype 1, 10% (4/42) with type 2, and 24% (10/42) with type 3. When the absolute value from each assay was examined, the Quantiplex assay gave a consistently higher reading and the mean logarithmic difference between the two assays was 1.4 (1.0 in type 1, 2.0 in type 2, and 2.2 in type 3). When analyzed according to genotype, strong correlation was observed between the two assays for type 1 (r = 0.83, 95% CI 0.63-0.93, P < 0.01), but not for nontype 1 samples. Despite the difference in absolute level reported by the two assays, there was a consistent trend of change in HCV RNA concentration by both assays in patients whose consecutive samples were analyzed and the differences between the two assays in consecutive samples were within 0.4 log of each other. The results suggested that with samples containing genotype 1, the Amplicor assay was more sensitive than the Quantiplex assay by about one log. However, the sensitivities of the two assays with nontype 1 samples were much closer probably due to the failure of the Amplicor assay to quantify nontype 1 genotypes effectively.

Impact of old Schistosomiasis infection on the use of transient elastography (Fibroscan) for staging of fibrosis in chronic HCV patients.

PubMed

Ramzy, Iman; Elsharkawy, Aisha; Fouad, Rabab; Hafez, Hanan Abdel; El Raziky, Maissa; El Akel, Wafaa; El-Sayed, Mohammad; Khattab, Hany; Shehata, Mohamed; Elsharkawy, Marwa; Radwan, Amr; Esmat, Gamal

2017-12-01

In tropical regions, Hepatitis C virus (HCV) - Schistosomiasis coinfection remains one of the health problems. With the new era of HCV treatment and the variety of methods of assessment of liver fibrosis so we aimed to evaluate the effectiveness of FibroScan for staging hepatic fibrosis in HCV-Schistosomiasis coinfected patients. Three groups of patients were enrolled. Group 1: chronic HCV with out antischistosomal antibody (122 patients), Group 2: chronic HCV with positive antischistosomal antibodies and without periportal tract thickening (122 patients), Group 3: chronic HCV with positive antischistosomal antibodies and ultrasonographic picture of periportal tract thickening (108 patients). Routine laboratory workup, serum Antischistosomal antibody, and Schistosomal antigen in serum were performed. Ultrasound guided liver biopsy with histopathological examination; abdominal ultrasound and fibroscan examination were done for all patients. The agreement between results of liver biopsy and results of fibroscan in the staging of fibrosis was the best in group 1 (55.7%), Although the agreement was higher among those with no periportal tract thickening (70.7%) and the disagreement was higher among those with positive schistosomal serology (66.5%), yet this relation was not statistically significant. Multivariate logistic regression analysis showed that disagreement is significantly associated with older age, higher BMI (≥30), and increase in anti Schistosomal antibody titer. Fibroscan is a reliable, non-invasive tool for staging hepatic fibrosis among HCV-schistosomiasis co-infected patients with no effect of the induced periportal tract thickening on the readings. Only higher antischistosomal antibody titres may cause disagreement between liver biopsy and fibroscan. Copyright © 2017 Elsevier B.V. All rights reserved.

New insights into HCV replication in original cells from Aedes mosquitoes.

PubMed

Fallecker, Catherine; Caporossi, Alban; Rechoum, Yassine; Garzoni, Frederic; Larrat, Sylvie; François, Olivier; Fender, Pascal; Morand, Patrice; Berger, Imre; Petit, Marie-Anne; Drouet, Emmanuel

2017-08-22

The existing literature about HCV association with, and replication in mosquitoes is extremely poor. To fill this gap, we performed cellular investigations aimed at exploring (i) the capacity of HCV E1E2 glycoproteins to bind on Aedes mosquito cells and (ii) the ability of HCV serum particles (HCVsp) to replicate in these cell lines. First, we used purified E1E2 expressing baculovirus-derived HCV pseudo particles (bacHCVpp) so we could investigate their association with mosquito cell lines from Aedes aegypti (Aag-2) and Aedes albopictus (C6/36). We initiated a series of infections of both mosquito cells (Ae aegypti and Ae albopictus) with the HCVsp (Lat strain - genotype 3) and we observed the evolution dynamics of viral populations within cells over the course of infection via next-generation sequencing (NGS) experiments. Our binding assays revealed bacHCVpp an association with the mosquito cells, at comparable levels obtained with human hepatocytes (HepaRG cells) used as a control. In our infection experiments, the HCV RNA (+) were detectable by RT-PCR in the cells between 21 and 28 days post-infection (p.i.). In human hepatocytes HepaRG and Ae aegypti insect cells, NGS experiments revealed an increase of global viral diversity with a selection for a quasi-species, suggesting a structuration of the population with elimination of deleterious mutations. The evolutionary pattern in Ae albopictus insect cells is different (stability of viral diversity and polymorphism). These results demonstrate for the first time that natural HCV could really replicate within Aedes mosquitoes, a discovery which may have major consequences for public health as well as in vaccine development.

HBV Bypasses the Innate Immune Response and Does Not Protect HCV From Antiviral Activity of Interferon.

PubMed

Mutz, Pascal; Metz, Philippe; Lempp, Florian A; Bender, Silke; Qu, Bingqian; Schöneweis, Katrin; Seitz, Stefan; Tu, Thomas; Restuccia, Agnese; Frankish, Jamie; Dächert, Christopher; Schusser, Benjamin; Koschny, Ronald; Polychronidis, Georgios; Schemmer, Peter; Hoffmann, Katrin; Baumert, Thomas F; Binder, Marco; Urban, Stephan; Bartenschlager, Ralf

2018-05-01

Hepatitis C virus (HCV) infection is sensitive to interferon (IFN)-based therapy, whereas hepatitis B virus (HBV) infection is not. It is unclear whether HBV escapes detection by the IFN-mediated immune response or actively suppresses it. Moreover, little is known on how HBV and HCV influence each other in coinfected cells. We investigated interactions between HBV and the IFN-mediated immune response using HepaRG cells and primary human hepatocytes (PHHs). We analyzed the effects of HBV on HCV replication, and vice versa, at the single-cell level. PHHs were isolated from liver resection tissues from HBV-, HCV-, and human immunodeficiency virus-negative patients. Differentiated HepaRG cells overexpressing the HBV receptor sodium taurocholate cotransporting polypeptide (dHepaRGNTCP) and PHHs were infected with HBV. Huh7.5 cells were transfected with circular HBV DNA genomes resembling viral covalently closed circular DNA (cccDNA), and subsequently infected with HCV; this served as a model of HBV and HCV coinfection. Cells were incubated with IFN inducers, or IFNs, and antiviral response and viral replication were analyzed by immune fluorescence, reverse-transcription quantitative polymerase chain reaction, enzyme-linked immunosorbent assays, and flow cytometry. HBV infection of dHepaRGNTCP cells and PHHs neither activated nor inhibited signaling via pattern recognition receptors. Incubation of dHepaRGNTCP cells and PHHs with IFN had little effect on HBV replication or levels of cccDNA. HBV infection of these cells did not inhibit JAK-STAT signaling or up-regulation of IFN-stimulated genes. In coinfected cells, HBV did not prevent IFN-induced suppression of HCV replication. In dHepaRGNTCP cells and PHHs, HBV evades the induction of IFN and IFN-induced antiviral effects. HBV infection does not rescue HCV from the IFN-mediated response. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Sofosbuvir and Velpatasvir Combination Improves Patient-reported Outcomes for Patients With HCV Infection, Without or With Compensated or Decompensated Cirrhosis.

PubMed

Younossi, Zobair M; Stepanova, Maria; Feld, Jordan; Zeuzem, Stefan; Sulkowski, Mark; Foster, Graham R; Mangia, Alessandra; Charlton, Michael; O'Leary, Jacqueline G; Curry, Michael P; Nader, Fatema; Henry, Linda; Hunt, Sharon

2017-03-01

The combination of sofosbuvir and velpatasvir is used to treat patients with hepatitis C virus (HCV) infection of different genotypes. We compared the effects of this treatment regimen, with and without ribavirin, on outcomes reported by patients (patient-reported outcomes [PROs]) with HCV infection, with or without cirrhosis. We performed a post hoc analysis of data collected from phase 3 clinical trials (ASTRAL-1, -2, -3, and -4) of 1701 patients infected with HCV of different genotypes treated with sofosbuvir and velpatasvir with ribavirin for 12 weeks (n = 87), sofosbuvir with ribavirin for 12 or 24 weeks (n = 401), and ribavirin-free sofosbuvir and velpatasvir for 12 or 24 weeks (n = 1213). In all trials, participants completed 4 PRO questionnaires (while blinded to their HCV RNA levels): the Short Form-36, the Functional Assessment of Chronic Illness Therapy-Fatigue, the Chronic Liver Disease Questionnaire-HCV Version, and the Work Productivity and Activity Impairment: Specific Health Problem, at multiple time points. We compared baseline PROs and changes in PROs following treatment in patients without cirrhosis (n = 1112), with compensated cirrhosis (n = 338), and with decompensated cirrhosis (n = 251). Baseline PRO scores were as much as 33.5% lower in patients with decompensated cirrhosis than in patients without cirrhosis (P < .05). Following treatment with ribavirin-containing regimens, changes in PRO scores were similar among patients with compensated and decompensated cirrhosis (all P > .01). Treatment with these regimens increased some PRO scores by as much as 11.8% from baseline (P < .05) and reduced others, by as much as 7.1% (P < .05). Despite this, by 12 weeks after cessation of treatment with ribavirin-containing regimens, all PRO decrements resolved; PRO scores increased by as much as 14.2%, and as much as 17.1% at 24 weeks after treatment, regardless of cirrhosis status (all P > .01 between cirrhosis groups). In contrast, treatment with

Limiting the access to direct-acting antivirals against HCV: an ethical dilemma.

PubMed

Gentile, Ivan; Maraolo, Alberto E; Niola, Massimo; Graziano, Vincenzo; Borgia, Guglielmo; Paternoster, Mariano

2016-11-01

Hepatitis C virus (HCV) infection affects about 200 million people worldwide and represents a leading cause of liver-related mortality. Eradication of HCV infection, achieved mainly through direct-acting antivirals (DAA), results in a decrease of mortality and an improvement of quality of life. These drugs have a maximal efficacy and an optimal tolerability. However, their high cost precludes a universal access even in wealthy countries. Areas covered: This article deals with the policies adopted for the use of the new anti-HCV drugs, especially in Europe and most of all in Italy, supposedly the developed country with the highest HCV prevalence. The literature search was performed using Pubmed and Web of Science. Moreover, national regulatory institutional websites were consulted. Expert commentary: The current policy of limitation to the access of the DAA presents a series of ethical issues that makes it non-applicable. A 'treat-all' strategy should resolve all ethical dilemmas, by virtue of the wide benefits of anti-HCV treatment not only for the advanced stage of infection, but also for the initial stages. A reduction in price of the drugs is the actual condition to achieve such a change.

Successful treatment of HCV/HBV/HDV-coinfection with pegylated interferon and ribavirin

PubMed Central

Hartl, Janine; Ott, Claudia; Kirchner, Gabriele; Salzberger, Bernd; Wiest, Reiner

2012-01-01

Dual and triple infections with hepatitis virus C (HCV), B (HBV) and D (HDV) frequently lead to severe liver damage. Hereby we describe a 38-year-old Caucasian male coinfected with HCV (genotype 3a), HBV [positive hepatitis B surface antigen (HbsAg) and antibody to hepatitis B core antigen; negative hepatitis B e antigen (HbeAg) and antibody to hepatitis B e antigen (anti-HBe)] and HDV. Laboratory diagnostics revealed increased liver enzymes and histological examination of the liver showed signs of fibrosis with moderate inflammation. On therapy with pegIFN-α2b and ribavirin HCV-RNA was undetectable at week 8. After week 24 the antiviral therapy was stopped because of a HBs-seroconversion, the loss of HbeAg and the detection of anti-HBe. Furthermore the HCV-RNA was negative. Six months after successful treatment of the triple-infection, HCV- and HDV-RNA and HbsAg remained negative and the liver enzymes had been completely normalized. In conclusion, pegylated-interferon plus ribavirin may be an effective therapy for HCV, HBV and HDV-coinfected patients. PMID:24765463

Progression of Liver Fibrosis in HIV/HCV Co-Infection: A Comparison between Non-Invasive Assessment Methods and Liver Biopsy

PubMed Central

Schmid, Patrick; Bregenzer, Andrea; Huber, Milo; Rauch, Andri; Jochum, Wolfram; Müllhaupt, Beat; Vernazza, Pietro; Opravil, Milos; Weber, Rainer

2015-01-01

Objectives To evaluate the diagnostic performance of seven non-invasive tests (NITs) of liver fibrosis and to assess fibrosis progression over time in HIV/HCV co-infected patients. Methods Transient elastography (TE) and six blood tests were compared to histopathological fibrosis stage (METAVIR). Participants were followed over three years with NITs at yearly intervals. Results Area under the receiver operating characteristic curve (AUROC) for significant fibrosis (> = F2) in 105 participants was highest for TE (0.85), followed by FIB-4 (0.77), ELF-Test (0.77), APRI (0.76), Fibrotest (0.75), hyaluronic acid (0.70), and Hepascore (0.68). AUROC for cirrhosis (F4) was 0.97 for TE followed by FIB-4 (0.91), APRI (0.89), Fibrotest (0.84), Hepascore (0.82), ELF-Test (0.82), and hyaluronic acid (0.79). A three year follow-up was completed by 87 participants, all on antiretroviral therapy and in 20 patients who completed HCV treatment (9 with sustained virologic response). TE, APRI and Fibrotest did not significantly change during follow-up. There was weak evidence for an increase of FIB-4 (mean increase: 0.22, p = 0.07). 42 participants had a second liver biopsy: Among 38 participants with F0-F3 at baseline, 10 were progessors (1-stage increase in fibrosis, 8 participants; 2-stage, 1; 3-stage, 1). Among progressors, mean increase in TE was 3.35 kPa, in APRI 0.36, and in FIB-4 0.75. Fibrotest results did not change over 3 years. Conclusion TE was the best NIT for liver fibrosis staging in HIV/HCV co-infected patients. APRI-Score, FIB-4 Index, Fibrotest, and ELF-Test were less reliable. Routinely available APRI and FIB-4 performed as good as more expensive tests. NITs did not change significantly during a follow-up of three years, suggesting slow liver disease progression in a majority of HIV/HCV co-infected persons on antiretroviral therapy. PMID:26418061

Progression of Liver Fibrosis in HIV/HCV Co-Infection: A Comparison between Non-Invasive Assessment Methods and Liver Biopsy.

PubMed

Schmid, Patrick; Bregenzer, Andrea; Huber, Milo; Rauch, Andri; Jochum, Wolfram; Müllhaupt, Beat; Vernazza, Pietro; Opravil, Milos; Weber, Rainer

2015-01-01

To evaluate the diagnostic performance of seven non-invasive tests (NITs) of liver fibrosis and to assess fibrosis progression over time in HIV/HCV co-infected patients. Transient elastography (TE) and six blood tests were compared to histopathological fibrosis stage (METAVIR). Participants were followed over three years with NITs at yearly intervals. Area under the receiver operating characteristic curve (AUROC) for significant fibrosis (> = F2) in 105 participants was highest for TE (0.85), followed by FIB-4 (0.77), ELF-Test (0.77), APRI (0.76), Fibrotest (0.75), hyaluronic acid (0.70), and Hepascore (0.68). AUROC for cirrhosis (F4) was 0.97 for TE followed by FIB-4 (0.91), APRI (0.89), Fibrotest (0.84), Hepascore (0.82), ELF-Test (0.82), and hyaluronic acid (0.79). A three year follow-up was completed by 87 participants, all on antiretroviral therapy and in 20 patients who completed HCV treatment (9 with sustained virologic response). TE, APRI and Fibrotest did not significantly change during follow-up. There was weak evidence for an increase of FIB-4 (mean increase: 0.22, p = 0.07). 42 participants had a second liver biopsy: Among 38 participants with F0-F3 at baseline, 10 were progessors (1-stage increase in fibrosis, 8 participants; 2-stage, 1; 3-stage, 1). Among progressors, mean increase in TE was 3.35 kPa, in APRI 0.36, and in FIB-4 0.75. Fibrotest results did not change over 3 years. TE was the best NIT for liver fibrosis staging in HIV/HCV co-infected patients. APRI-Score, FIB-4 Index, Fibrotest, and ELF-Test were less reliable. Routinely available APRI and FIB-4 performed as good as more expensive tests. NITs did not change significantly during a follow-up of three years, suggesting slow liver disease progression in a majority of HIV/HCV co-infected persons on antiretroviral therapy.

[The velocity of HCV subtype 6a transmission in southwest China].

PubMed

Hong, Guo-hu; Tan, Zhao-xia; Guo, Yan; Mao, Qing

2011-07-01

To estimate the velocity of HCV subtype 6a transmission in Southwest China. The HCV CE1 region from 61 patients infected with HCV genotype 6 were amplificated by RT-PCR and sequenced. The subtypes were identified, and the period of HCV 6a strains originated in southwest china was estimated by using molecular clock phylogenetic analysis. The velocity of HCV subtype 6a transmission in southwest China was estimated by BEAST v1.6.1 and Tracer v1.5 software theoretically. Most of HCV 6a strains distributed in Southwest China origine around the year 1968 and at last 4 epidemic strains existed. The earlier origine strains could be isolated both in intravenous drug users (IDU) and non-IDU patients. After 1997, the HCV 6a strains transmission in southwest China accelerated and the trend intensified in 2007. HCV 6a strains spread fastly both in IDU and non-IDU patients, which might be the main HCV subtype distributed in Southwest China in the future.

Characterization of miR-122-independent propagation of HCV

PubMed Central

Motooka, Daisuke; Nakamura, Shota; Yamamoto, Satomi; Mori, Hiroyuki; Sato, Asuka; Uemura, Kentaro; Fauzyah, Yuzy; Suda, Takahiro; Nishio, Akira; Hmwe, Su Su; Okamoto, Toru; Tatsumi, Tomohide; Takehara, Tetsuo; Chayama, Kazuaki; Wakita, Takaji; Koike, Kazuhiko

2017-01-01

miR-122, a liver-specific microRNA, is one of the determinants for liver tropism of hepatitis C virus (HCV) infection. Although miR-122 is required for efficient propagation of HCV, we have previously shown that HCV replicates at a low rate in miR-122-deficient cells, suggesting that HCV-RNA is capable of propagating in an miR-122-independent manner. We herein investigated the roles of miR-122 in both the replication of HCV-RNA and the production of infectious particles by using miR-122-knockout Huh7 (Huh7-122KO) cells. A slight increase of intracellular HCV-RNA levels and infectious titers in the culture supernatants was observed in Huh7-122KO cells upon infection with HCV. Moreover, after serial passages of HCV in miR-122-knockout Huh7.5.1 cells, we obtained an adaptive mutant, HCV122KO, possessing G28A substitution in the 5’UTR of the HCV genotype 2a JFH1 genome, and this mutant may help to enhance replication complex formation, a possibility supported by polysome analysis. We also found the introduction of adaptive mutation around miR-122 binding site in the genotype 1b/2a chimeric virus, which originally had an adenine at the nucleotide position 29. HCV122KO exhibited efficient RNA replication in miR-122-knockout cells and non-hepatic cells without exogenous expression of miR-122. Competition assay revealed that the G28A mutant was dominant in the absence of miR-122, but its effects were equivalent to those of the wild type in the presence of miR-122, suggesting that the G28A mutation does not confer an advantage for propagation in miR-122-rich hepatocytes. These observations may explain the clinical finding that the positive rate of G28A mutation was higher in miR-122-deficient PBMCs than in the patient serum, which mainly included the hepatocyte-derived virus from HCV-genotype-2a patients. These results suggest that the emergence of HCV mutants that can propagate in non-hepatic cells in an miR-122-independent manner may participate in the induction of

The impact of HCV co-infection status on healthcare-related utilization among people living with HIV in British Columbia, Canada: a retrospective cohort study.

PubMed

Ma, Huiting; Villalobos, Conrado Franco; St-Jean, Martin; Eyawo, Oghenowede; Lavergne, Miriam Ruth; Ti, Lianping; Hull, Mark W; Yip, Benita; Wu, Lang; Hogg, Robert S; Barrios, Rolando; Shoveller, Jean A; Montaner, Julio S G; Lima, Viviane D

2018-05-02

The burden of HCV among those living with HIV remains a major public health challenge. We aimed to characterize trends in healthcare-related visits (HRV) of people living with HIV (PLW-HIV) and those living with HIV and HCV (PLW-HIV/HCV), in British Columbia (BC), and to identify risk factors associated with the highest HRV rates over time. Eligible individuals, recruited from the BC Seek and Treat for Optimal Prevention of HIV/AIDS population-based retrospective cohort (N = 3955), were ≥ 18 years old, first started combination antiretroviral therapy (ART) between 01/01/2000-31/12/2013, and were followed for ≥6 months until 31/12/2014. The main outcome was HRV rate. The main exposure was HIV/HCV co-infection status. We built a confounder non-linear mixed effects model, adjusting for several demographic and time-dependent factors. HRV rates have decreased since 2000 in both groups. The overall age-sex standardized HRV rate (per person-year) among PLW-HIV and PLW-HIV/HCV was 21.11 (95% CI 20.96-21.25) and 41.69 (95% CI 41.51-41.88), respectively. The excess in HRV in the co-infected group was associated with late presentation for ART, history of injection drug use, sub-optimal ART adherence and a higher number of comorbidities. The adjusted HRV rate ratio for PLW-HIV/HCV in comparison to PLW-HIV was 1.18 (95% CI 1.13-1.24). Although HRV rates have decreased over time in both groups, PLW-HIV/HCV had 18% higher HRV than those only living with HIV. Our results highlight several modifiable risk factors that could be targeted as potential means to minimize the disease burden of this population and of the healthcare system.

Spatial distribution of HIV, HCV, and co-infections among drug users in the southwestern border areas of China (2004-2014): a cohort study of a national methadone maintenance treatment program.

PubMed

Li, Mingli; Li, Rongjian; Shen, Zhiyong; Li, Chunying; Liang, Nengxiu; Peng, Zhenren; Huang, Wenbo; He, Chongwei; Zhong, Feng; Tang, Xianyan; Lan, Guanghua

2017-09-30

A methadone maintenance treatment (MMT) program to curb the dual epidemics of HIV/AIDS and drug use has been administered by China since 2004. Little is known regarding the geographic heterogeneity of HIV and hepatitis C virus (HCV) infections among MMT clients in the resource-constrained context of Chinese provinces, such as Guangxi. This study aimed to characterize the geographic distribution patterns and co-clustered epidemic factors of HIV, HCV and co-infections at the county level among drug users receiving MMT in Guangxi Zhuang Autonomous Region, located in the southwestern border area of China. Baseline data on drug users' demographic, behavioral and biological characteristics in the MMT clinics of Guangxi Zhuang Autonomous Region during the period of March 2004 to December 2014 were obtained from national HIV databases. Residential addresses were entered into a geographical information system (GIS) program and analyzed for spatial clustering of HIV, HCV and co-infections among MMT clients at the county level using geographic autocorrelation analysis and geographic scan statistics. A total of 31,015 MMT clients were analyzed, and the prevalence of HIV, HCV and co-infections were 13.05%, 72.51% and 11.96% respectively. Both the geographic autocorrelation analysis and geographic scan statistics showed that HIV, HCV and co-infections in Guangxi Zhuang Autonomous Region exhibited significant geographic clustering at the county level, and the Moran's I values were 0.33, 0.41 and 0.30, respectively (P < 0.05). The most significant high-risk overlapping clusters for these infections were restricted to within a 10.95 km 2 radius of each of the 13 locations where P county was the cluster center. These infections also co-clustered with certain characteristics, such as being unmarried, having a primary level of education or below, having used drugs for more than 10 years, and receptive sharing of syringes with others. The high-risk clusters for these

Impact of HCV treatment and depressive symptoms on adherence to HAART among coinfected HIV-HCV patients: results from the ANRS-CO13-HEPAVIH cohort

PubMed Central

Roux, Perrine; Lions, Caroline; Cohen, Julien; Winnock, Maria; Salmon-Céron, Dominique; Bani-Sadr, Firouzé; Sogni, Philippe; Spire, Bruno; Dabis, François; Carrieri, Maria Patrizia

2014-01-01

Background The additional burden of HCV infection in HIV-HCV coinfected individuals may have some consequences on adherence to highly active antiretroviral therapy (HAART). Few studies have explored the pattern of correlates of non-adherence to HAART while simultaneously considering the impact of HCV treatment and depressive symptoms on adherence to HAART. We used longitudinal data to assess factors associated with non-adherence to HAART. Methods The French national prospective cohort ANRS-CO-13-HEPAVIH is a multi-center cohort which recruited 1175 HIV-HCV coinfected patients in 17 hospital outpatient units delivering HIV and HCV care in France between October 2006 and June 2008. For this analysis, we selected participants on HAART with self-reported data for adherence to HAART (n = 727 patients, 1190 visits). Data were collected using self-administered questionnaires and medical records. A mixed logistic regression model based on an exchangeable correlation matrix was used to identify factors associated with non-adherence to HAART. Results Patients reported non-adherence to HAART in 808 (68%) of the 1190 visits. Four variables remained associated with non-adherence to HAART after multivariate analysis: hazardous alcohol consumption, cocaine use and depressive symptoms, regardless of whether treatment for depression was being received. Finally, patients being treated for HCV infection were less likely to be non-adherent to HAART. Conclusions Besides the problem of polydrug use, two other dimensions deserve special attention when considering adherence to HAART in HIV-HCV coinfected patients. Access to HCV treatment should be encouraged as well adequate treatment for depression in this population to improve adherence and response to HAART. PMID:24166726

Estimating the number of injecting drug users in Scotland's HCV-diagnosed population using capture-recapture methods.

PubMed