MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Journal of Viral Hepatitis' source. Wed, 08 Feb 2012 18:15:48 +0100 http://www.medworm.com/index.php?rid=5668169&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01576.x This study confirmed on a nationwide representative sample the very high HCV antibody prevalence in Egypt. It stresses the urgent need for strengthening prevention efforts, and bringing down the costs of antiviral drugs for countries like Egypt, where the people in the most precarious situations are also those most likely to be infected by the virus. (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5668169 Wed, 01 Feb 2012 05:00:00 +0100 5668169 http://www.medworm.com/index.php?rid=5649375&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2012.01583.x Summary.  To explore the impact of the differences in baseline characteristics between immigrants with chronic hepatitis C (CHC) and native‐born patients on the prognosis of advanced fibrosis. A retrospective cohort study was conducted in 318 patients (including 128 immigrants) with CHC and advanced fibrosis attending a tertiary referral clinic. Patients’ medical records were reviewed to collect data describing immigrant status, baseline characteristics, and liver‐related clinical outcomes. Kaplan–Meier (KM) analyses and Cox proportional‐hazards regression analyses were performed to explore the differences between the two groups with respect to clinical outcomes. Relative to native‐born patients, immigrant patients were older, more likely to be female, and more likely to be A... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5649375 Wed, 01 Feb 2012 05:00:00 +0100 5649375 http://www.medworm.com/index.php?rid=5639144&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01581.x In conclusion, through NF‐κB activation, HBV induced Mig expression in vivo, which recruited peripheral inflammatory cells to the liver and resulted in liver damage. Phosphorylation of phosphoinositide 3‐kinase/Akt, ERK and JNK but not p38 might involved in the molecular mechanisms underlying HBV induced Mig expression in vivo. (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5639144 Sun, 29 Jan 2012 22:39:21 +0100 5639144 http://www.medworm.com/index.php?rid=5639147&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01575.x Summary.  Information on the impact of maternal hepatitis B virus (HBV) infection on pregnancy outcome is conflicting. Some studies reported an association with increased infant birthweight, which could be interpreted as advantageous to pregnancy. A retrospective study was performed to compare birthweight outcome between 6261 and 55 817 singleton pregnancies in mothers screened positive and negative for hepatitis B surface antigen (HBsAg), respectively. The HBsAg positive women were younger, had higher body mass index (BMI) and incidence of overweight, but less gestational weight gain, and were associated with increased macrosomia (birthweight ≥4000 g) in mothers <35 years (odds ratio, OR, 1.28), BMI ≥25 kg/m2 (OR 1.24), without gestational diabetes mellitus (GDM, OR 1.19)... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5639147 Sat, 28 Jan 2012 05:00:00 +0100 5639147 http://www.medworm.com/index.php?rid=5639146&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01577.x Summary.  Asians Americans have a high burden of hepatitis B virus (HBV) associated hepatocellular carcinoma (HCC). HCC screening practices in this population are unknown. We aimed to investigate predictors and patterns of HCC screening and its impact on survival in HBV‐infected Asian Americans. Clinical data were obtained from a retrospective cohort of 1870 HBsAg‐positive Asians in San Francisco’s safety net clinics. In 824 patients at‐risk for HCC, screening (≥1 imaging and/or AFP per year) decreased from 67% to 47% to 24% from the 1st to 2nd to 10th year after HBV diagnosis, respectively. AFP, imaging, and imaging plus AFP were used in 37%, 14%, and 49% during the first year after diagnosis, and imaging plus AFP increased to 64% by the 10th year. Among 1431 patients followed... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5639146 Sat, 28 Jan 2012 05:00:00 +0100 5639146 http://www.medworm.com/index.php?rid=5639145&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01580.x In conclusion, the ‐1195GG genotype in COX‐2 is a genetic marker for liver disease progression, while the PNPLA3 genotypes are not associated with disease progression in Japanese patients with chronic hepatitis C. (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5639145 Sat, 28 Jan 2012 05:00:00 +0100 5639145 http://www.medworm.com/index.php?rid=5629965&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01578.x Summary.  Liver kidney microsomal type 1 (LKM‐1) antibodies have been shown to decrease the CYP2D6 activity in vitro and are present in a minority of patients with chronic hepatitis C infection. We investigated whether LKM‐1 antibodies might reduce the CYP2D6 activity in vivo. All patients enrolled in the Swiss Hepatitis C Cohort Study and tested for LKM‐1 antibodies were assessed (n = 1723): 10 eligible patients were matched with patients without LKM‐1 antibodies. Patients were genotyped for CYP2D6 variants to exclude individuals with a poor metabolizer genotype. CYP2D6 activity was measured by a specific substrate using the dextromethorphan/dextrorphan metabolic ratio to classify patients into four activity phenotypes. All patients had a CYP2D6 extensive metabolizer genotyp... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5629965 Thu, 26 Jan 2012 22:59:28 +0100 5629965 http://www.medworm.com/index.php?rid=5598866&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01565.x Summary.  Recipients of haemodialysis for end‐stage renal disease (ESRD) have a higher prevalence of hepatitis C virus (HCV) infection relative to the general US population. However, the natural course of HCV infection in patients with renal failure, including African Americans (AAs) and Caucasian Americans (CAs), is not well known. We compared the degree of liver inflammation and fibrosis in AA and CA patients with HCV infection, with and without ESRD. This was a cross‐sectional study of 156 HCV patients with ESRD (130 AAs and 26 CAs) with a liver biopsy between 1992 and 2005. The control group consisted of 138 patients (50 AAs; 88 CAs) with HCV infections and a serum creatinine <1.5 mg/dL with a liver biopsy between 1995 and 1998. Specimens were graded for inflammation and fib... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5598866 Tue, 17 Jan 2012 23:28:46 +0100 5598866 http://www.medworm.com/index.php?rid=5561356&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01574.x Summary.  A cohort of injection drug users (IDU) have been identified who despite a long history of IDU and sharing of injecting equipment remain seronegative and aviraemic for hepatitis C virus (HCV). They have been termed HCV exposed uninfected (EU). The study of potential innate or adaptive immune mechanisms of resistance to HCV infection in this group is of interest. The aim of this study was to determine the levels of a broad range of cytokines in serum of exposed, uninfected individuals to ascertain whether there is a specific cytokine profile associated with apparent resistance to HCV. Sera from 22 EU individuals were analysed for a range of cytokines and chemokines, and compared to 16 treatment‐naive chronic HCV cases (HCV Ab+ RNA+), 16 individuals with spontaneous resolution o... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5561356 Wed, 04 Jan 2012 05:00:00 +0100 5561356 http://www.medworm.com/index.php?rid=5561357&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01571.x Summary.  Therapeutic options in hepatitis C virus (HCV)‐related vasculitis may target the viral trigger using antiviral therapy [pegylated interferon plus ribavirin (PEG‐IFN/RBV)], and/or the downstream B‐cell arm of autoimmunity with rituximab (RTX). To date, no study has compared the efficacy of RTX combined with PEG‐IFN/RBV on biomarkers of liver insufficiency in patients with severe liver fibrosis. Twenty‐eight untreated HCV‐related vasculitis patients with severe liver fibrosis (Metavir F3–F4) were included: 14 patients received RTX plus PEG‐IFN/RBV and 14 patients PEG‐IFN/RBV. The main clinical and biological data were recorded and compared at baseline, month 3 (M3), M12 and M24 of follow‐up. Baseline epidemiological, clinical, virological and immunological fea... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5561357 Tue, 03 Jan 2012 05:00:00 +0100 5561357 http://www.medworm.com/index.php?rid=5561355&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01570.x Summary.  Chronic hepatitis C is an independent risk factor for severe drug hepatotoxicity. Successful treatment of chronic hepatitis C may modulate drug hepatotoxicity, as it is associated with a decline in hepatic enzyme release and halts fibrosis progression in HIV/HCV‐coinfected patients. The aim of this study was to determine biological and/or clinical determinants of alanine aminotransferase and/or aspartate aminotransferase elevation (>five‐fold above the upper limit of normal in patients with normal baseline levels or >3.5‐fold increase from baseline in those with increased baseline levels) in a large prospective cohort of HIV/HCV‐coinfected patients on HAART who had previously been treated for HCV infection. Median follow‐up exceeded five years. Cox proportional ... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5561355 Sun, 01 Jan 2012 05:00:00 +0100 5561355 http://www.medworm.com/index.php?rid=5553089&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01572.x Summary.  Incomplete suppression of hepatitis C virus (HCV) replication with persistence of minimal viremia (partial virologic response) leading to treatment failure can be observed in a significant proportion of HCV type 1‐infected patients during antiviral therapy. Recently, high‐dose intravenous silibinin has demonstrated strong antiviral activity against HCV. We were therefore interested in whether patients with partial virologic response can be rescued by the on‐treatment addition of a short‐term course of high‐dose intravenous silibinin infusions. Twenty patients who failed to achieve a complete virologic response to different interferon‐based regimens qualified for the rescue strategy and received 1400 mg/day silibinin infusions on two consecutive days. Complete vira... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5553089 Sat, 31 Dec 2011 21:15:24 +0100 5553089 http://www.medworm.com/index.php?rid=5553090&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01567.x In this study, we searched for association between H. pylori and HCV‐related liver disease. Liver specimens were collected from eighty‐five patients; they were divided into five different groups according to liver pathology (METAVIR system). Group I (the 1st control group) consisted of 16 patients with chronic hepatitis C without histological activity. Group II consisted of 25 patients with chronic active hepatitis C, Group III, 17 patients with HCV‐related cirrhosis and Group IV, 16 patients with HCV‐related cirrhosis and HCC. Group V (2nd control group) consisted of 11 patients suffering from gastro duodenal and gall bladder diseases but negative for HCV. All cases were tested by polymerase chain reaction on liver samples for the presence of H. pylori DNA Cag A gene. Routine bi... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5553090 Wed, 28 Dec 2011 05:00:00 +0100 5553090 http://www.medworm.com/index.php?rid=5526316&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01569.x In this study, associations between histology status and early viral kinetics were assessed in 149 HCV genotype 1–infected patients treated with pegylated interferon alfa‐2a and ribavirin (DITTO trial). In multivariate analyses adjusted for critical factors such as IL28B genotype and baseline viral load, presence of significant fibrosis (Ishak stage > 2) was found to independently reduce the odds of achieving an initial reduction (calculated from day 0 to day 4) in HCV RNA of ≥2 logIU/mL (adjusted OR 0.03, P = 0.004) but was not associated with the second‐phase slope of viral decline (calculated from day 8 to day 29). On the contrary, presence of liver steatosis was an independent risk factor for not having a rapid second‐phase slope, that is, ≥0.3 logIU/mL/week ... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5526316 Thu, 22 Dec 2011 11:02:02 +0100 5526316 http://www.medworm.com/index.php?rid=5526317&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01560.x Summary.  Long‐term safety of treatment with hepatitis B virus (HBV) polymerase inhibitors is a concern. Adefovir dipivoxil (ADV) therapy has previously been associated with impairment of renal function. Limited data are available on the safety of combination therapy with nucleos(t)ide analogues and interferon alfa (IFNα). The aim of this analysis was to assess the renal function during combination therapy with peginterferon alfa‐2a (PegIFNα‐2a) plus ADV vs either drug alone in patients with hepatitis B/D co‐infection. We performed a retrospective analysis of renal function data of patients treated in the Hep‐Net/International Delta Hepatitis Intervention Trial 1(HIDIT‐1‐trial), a European multicenter study to investigate the efficacy of 48 weeks of therapy with PegIFN�... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5526317 Mon, 19 Dec 2011 05:00:00 +0100 5526317 http://www.medworm.com/index.php?rid=5516085&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01563.x The objective of this study was to assess the economic burden data sources for hepatitis C in the United States. A systematic literature search was conducted to identify studies reporting the costs of hepatitis C sequelae in the United States. Over 400 references were identified, of which 50 were pertinent. The costs were compiled and adjusted to 2010 constant US dollars using the medical component of the consumer price index (CPI). The cost of liver transplants was estimated at $201 110 ($178 760–$223 460), hepatocellular carcinoma (HCC) at $23 755–$44 200, variceal haemorrhage at $25 595, compensated cirrhosis at $585–$1110, refractory ascites at $24 755, hepatic encephalopathy at $16 430, sensitive ascites at $2450, moderate chronic hepatitis C at $155, and mild ch... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5516085 Sun, 18 Dec 2011 05:00:00 +0100 5516085 http://www.medworm.com/index.php?rid=5506180&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01562.x Summary.  To evaluate T cell immunity in advanced liver disease, antigen‐specific lymphoproliferative (LP) responses were prospectively studied in the context of the Hepatitis C Antiviral Long‐term Treatment against Cirrhosis trial. Peripheral blood responses to hepatitis C virus (HCV), tetanus and Candida protein antigens were measured at baseline, month 12 (M12), M24, M36 and M48 in 186 patients randomized to either low‐dose peginterferon‐alfa‐2a (PEG‐IFN) only or observation. Liver histology was evaluated at baseline, M24 and M48. Patients with cirrhosis (Ishak 5–6) were less likely to have positive LP responses to HCV at baseline than patients with fibrosis (15%vs 29%, P = 0.03) and had lower levels of HCV c100 responses at baseline, M24 and M48 (P = 0.11, P =... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5506180 Fri, 16 Dec 2011 05:00:00 +0100 5506180 http://www.medworm.com/index.php?rid=5477473&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01547.x Summary.  A mammalian expression vector comprised of the PreS2‐TLM (translocation motif), a single‐chain variable fragment (ScFv) that binds to hepatitis B surface antigen (HBsAg) and the EGFP gene was constructed. A stably transformed cell line that could express and secrete the fusion protein (PreS2‐TLM‐ScFv‐EGFP) was established. HBsAg‐positive HepG2.2.15 cells and HepG2 and HeLa cells were incubated with the supernatant of the transformed cell line cultures for evaluating the cellular permeability of PreS2‐TLM‐ScFv‐EGFP. The location of the fusion protein PreS2‐TLM‐ScFv‐EGFP in HepG2.2.15 cells was observed with immunofluorescence staining. EGFP was next replaced by a dominant negative mutant of the hepatitis B virus core gene (HBcDN) for producing fusion prot... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5477473 Sun, 04 Dec 2011 05:00:00 +0100 5477473 http://www.medworm.com/index.php?rid=5469868&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01529.x This study assessed the association of HIV RNA with indirect markers of liver injury including FIB‐4 index, liver enzymes and platelet counts in a high‐risk Hispanic population. The data were derived from a prospective study that included 138 HIV/hepatitis C (HCV)‐coinfected and 68 HIV‐infected participants without hepatitis C or B co‐infection (mono‐infected). In unadjusted analyses, detectable HIV viral load (vs undetectable, <400 copies/mL) was associated with a 40% greater odds (OR 1.4, 95% CI: 1.1–1.9, P = 0.016) of FIB‐4 > 1.45 in the HIV/HCV‐coinfected group and 70% greater odds of FIB‐4 > 1.45 (OR 1.7, 95% CI: 1.0–2.8; P = 0.046) in the HIV‐mono‐infected group. In multivariable analyses, a 1 log10 increase in HIV RNA was associated... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5469868 Fri, 02 Dec 2011 05:00:00 +0100 5469868 http://www.medworm.com/index.php?rid=5469867&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01552.x Summary.  The treatment paradigm for hepatitis C virus (HCV) infection is at a critical point in its evolution. The addition of a protease inhibitor to peginterferon plus ribavirin has become the new standard‐of‐care treatment for most patients. Data from clinical trials of new antivirals have been difficult to interpret and compare, partly because of heterogeneity in trial design, and partly because of inconsistencies in terminology used to define viral responses and the populations evaluated. Present definitions of viral responses for treatment with peginterferon and ribavirin are insufficient for novel treatment paradigms. Further, categorization of prior patient treatment experience in clinical trials, particularly of nonresponders to prior therapy, is inconsistent. Existing term... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5469867 Fri, 02 Dec 2011 05:00:00 +0100 5469867 http://www.medworm.com/index.php?rid=5516084&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01568.x Summary.  Although hepatitis C (HCV) is associated with diabetes, few studies have examined pre‐diabetes in this population. We aimed to evaluate factors associated with pre‐diabetes in HCV‐infected patients, including direct measurement of insulin action. Ninety‐seven non‐cirrhotic, non‐diabetic and HCV‐infected patients underwent clinical evaluation and oral glucose tolerance testing (OGTT). Insulin sensitivity was measured directly by steady‐state plasma glucose (SSPG) concentration during insulin suppression test. Early phase and total insulin secretion were determined using OGTT. Rates of pre‐diabetes were as follows: 21% impaired fasting glucose (IFG), 7% impaired glucose tolerance (IGT) and 9% combined IFG/IGT. Twelve percent of Caucasians, 50% of African America... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5516084 Thu, 01 Dec 2011 05:00:00 +0100 5516084 http://www.medworm.com/index.php?rid=5506179&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01566.x This study was aimed at determining treatment response on the basis of rapid virological response (RVR) of HCV genotype 6 in comparison with genotypes 1 and 3. Sixty‐six treatment naïve patients were treated with PEG‐IFN‐α2a (180 μg/week) plus weight‐based RBV (1000–1200 mg/day). Patients with genotype 1 n = 16) and genotype 3 (n = 16) were treated for a fixed duration of 48 and 24 weeks, respectively. Patients with genotype 6 (n = 34) who achieved RVR were treated for 24 weeks (response‐guided therapy) and the remaining patients were treated for 48 weeks (standard therapy). The mean baseline HCV RNA levels were not statistically different between groups (6.4 ± 0.8, 6.0 ± 1.0 and 6.5 ± 0.8 Log10 IU/mL for genotypes 1, 3 and 6, respect... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5506179 Thu, 01 Dec 2011 05:00:00 +0100 5506179 http://www.medworm.com/index.php?rid=5477472&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01564.x Summary.  Anaemia is a common side effect of ribavirin (RBV) which is used for the treatment of hepatitis C. Inosine triphosphatase gene polymorphism (C to A) protects against RBV‐induced anaemia. The aim of our study was to genotype patients for inosine triphosphatase gene polymorphism rs1127354 SNP (CC or CA) and associate treatment‐induced anaemia with gene expression profile and genotypes. We used 67 hepatitis C patients with available gene expression, clinical, laboratory data and whole‐blood samples. Whole blood was used to determine inosine triphosphatase gene polymorphism rs1127354 genotypes (CC or CA). The cohort with inosine triphosphatase gene polymorphism CA genotype revealed a distinct pattern of protection against anaemia and a lower drop in haemoglobin. A variation i... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5477472 Thu, 01 Dec 2011 05:00:00 +0100 5477472 http://www.medworm.com/index.php?rid=5469866&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01559.x Summary.  We investigated the virus–host interaction for hepatitis E virus (HEV) by performing competitive binding assays using in vitro assembled virus‐like particles (VLPs). We used Escherichia coli expressed native capsid protein (pORF2) and its mutants with an attached Gly(5)‐Ala (linker) reporter [enhanced green fluorescent protein (EGFP)/firefly luciferase (Fluc)]. Transmission electron microscopy and nanoparticle tracking showed near uniform particles of approximately 30–35 nm in diameter for pORF2 VLPs and 60–100 nm for reporter‐linked VLPs. Binding of reporter‐linked full‐length (1–660aa) and N‐terminal truncated (Δ1–112aa) pORF2 VLPs to Huh7 cell surfaces was found to be specific with 1.92 ± 0.065 × 105 sites per cell. Saturation binding indic... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5469866 Thu, 01 Dec 2011 05:00:00 +0100 5469866 http://www.medworm.com/index.php?rid=5450112&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01557.x Summary.  Methylenetetrahydrofolate reductase status, homocysteine and lipoproteins levels have been associated with severity of disease and both rapid and sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C (CHC). We aimed to assess the association of homocysteine and MTHFR status with serum cholesterol levels and their potential links to both histological findings and virological response, in patients with genotype 1 hepatitis C virus (HCV). A total of 119 consecutive patients were evaluated by biopsy and metabolic measurements. A total of 103 healthy blood donors were used as controls. Serum homocysteine and MTHFR C677T mutation were also evaluated. All patients underwent antiviral therapy with PEG‐IFN alfa‐2a plus ribavirin. HCV‐RNA was assessed... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5450112 Mon, 28 Nov 2011 11:10:22 +0100 5450112 http://www.medworm.com/index.php?rid=5442249&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01558.x In this report, we demonstrated that 3‐hydroxy caruilignan C (3‐HCL‐C) isolated from Swietenia macrophylla stems exhibited high anti‐HCV activity at both protein and RNA levels at nontoxic concentrations, with an EC50 value of 10.5 ± 1.2 μm. Combinations of 3‐HCL‐C and interferon‐α (IFN‐α), an HCV NS5B polymerase inhibitor (2′‐C‐methylcytidine; NM‐107) or an HCV NS3/4A protease inhibitor (Telaprevir; VX‐950) increased the suppression of HCV RNA replication. The results suggested that 3‐HCL‐C may be a potential anti‐viral agent. We then demonstrated that 3‐HCL‐C interfered with HCV replication by inducing IFN‐stimulated response element transcription and IFN‐dependent anti‐viral gene expression. (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5442249 Fri, 25 Nov 2011 11:00:16 +0100 5442249 http://www.medworm.com/index.php?rid=5442252&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01546.x Summary.  Cytokeratin‐18 (CK‐18) is a major intermediate filament protein in liver cells. The M30 fragment of CK‐18 has been identified as a useful marker of apoptosis associated with fibrosis and steatosis in nonalcoholic steatohepatitis (NASH). We sought to assess the relationship of this marker and steatosis in a cohort of adult patients with chronic hepatitis C. The study cohort included sera from 267 treatment‐naïve chronic hepatitis C (CHC) patients and 100 healthy controls with normal alanine aminotransferase (ALT). Biopsies from CHC patients were assessed for METAVIR fibrosis stage, Histology Activity Index (HAI) inflammation score and steatosis grade by expert histopathologists. The M30 fragment of CK‐18 was quantified by ELISA. Wilcoxon Rank Sum, Spearman Correlation... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5442252 Thu, 24 Nov 2011 05:00:00 +0100 5442252 http://www.medworm.com/index.php?rid=5442251&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01549.x Summary.  Hepatitis C virus (HCV)‐specific T cell responses are essential for HCV control, and chronic infection is characterized by functionally altered antigen‐specific T cells. It has been proposed that the early inactivation of specific CD4+ T cell responses may be involved in establishment of HCV persistence. We have investigated whether HCV‐specific CD4+ T cells dysfunction can be reversed in vitro. Nonstructural protein 3 (NS3) and core‐specific CD4+ T cells from eight chronically infected and eight spontaneously resolved HCV individuals were selected through transient CD154 (CD40 ligand) expression, and their functional profile (IFN‐γ, IL‐2, TNF‐α, IL‐10 and IL‐4 production by enzyme‐linked immunospot assay, cytometric bead array and intracellular cytokine s... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5442251 Thu, 24 Nov 2011 05:00:00 +0100 5442251 http://www.medworm.com/index.php?rid=5442250&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01550.x Summary.  Self‐efficacy or confidence in one’s ability to successfully engage in goal‐directed behaviour has been shown to influence medication adherence across many chronic illnesses. In the present study, we investigated the psychometric properties of a self‐efficacy instrument used during treatment for chronic hepatitis C viral infection (HCV). Baseline (n = 394) and treatment week 24 (n = 254) data from the prospective, longitudinal Viral Resistance to Antiviral Therapy of Chronic Hepatitis C study were examined. Baseline participants were randomly split into two equal‐sized subsamples (S1 and S2). Initial exploratory and confirmatory factor analyses (EFA/CFA) were performed on S1, while S2 was used to validate the factor structure of the S1 results using CFA. An ad... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5442250 Thu, 24 Nov 2011 05:00:00 +0100 5442250 http://www.medworm.com/index.php?rid=5432493&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01556.x Summary.  We identified heat shock protein 72 (Hsp72) as a host factor that was differentially expressed in cells expressing nonstructural 5A (NS5A) protein. To investigate how NS5A modulates Hsp72 in hepatitis C virus (HCV) life cycle, we examined the role of Hsp72 in HCV replication and virus production. NS5A specifically interacted with Hsp72. Both Hsp72 and nuclear factor of activated T cells 5 (NFAT5) levels were increased in cells expressing NS5A protein. Treatments of N‐acetylcysteine and glutathione markedly reduced protein levels of both NFAT5 and Hsp72. Knockdown of NFAT5 resulted in decrease in Hsp72 level in cells expressing NS5A. Importantly, silencing of Hsp72 expression resulted in decrease in both RNA replication and virus production in HCV‐infected cells. These data ... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5432493 Tue, 22 Nov 2011 10:59:39 +0100 5432493 http://www.medworm.com/index.php?rid=5432494&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01503.x In conclusion, we identified novel, reliable biomarkers for EF and exposed functional properties of the molecular network regulating CCL5 biosynthesis in peripheral or hepatic cell types with key roles in cHCV‐related liver and/or immune pathogenesis. (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5432494 Mon, 21 Nov 2011 05:00:00 +0100 5432494 http://www.medworm.com/index.php?rid=5432495&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01509.x Summary.  There are few reports on hepatitis B e antigen (HBeAg) titres during nucleos(t)ide analogues treatment. We investigated the changes in HBeAg levels in patients treated with entecavir and the usefulness of HBeAg quantification for predicting antiviral response. Ninety‐five consecutive HBeAg‐positive patients treated with entecavir for more than 48 weeks were enrolled. Serum levels of hepatitis B surface antigen (HBsAg), HBeAg and HBV DNA were assessed at 4‐week intervals to week 24 and thereafter at 12‐week intervals. Virologic response (Y1VR) was defined as an undetectable HBV DNA level at week 48 of therapy. During 48 weeks, HBeAg and HBV DNA level decreased significantly in a biphasic manner and HBsAg level tended to decease. Fifty‐three patients (55.8%) attai... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5432495 Sun, 20 Nov 2011 05:00:00 +0100 5432495 http://www.medworm.com/index.php?rid=5423282&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01551.x In conclusion, the combined analysis of NT‐proBNP and echocardiography showed a possible subclinical left ventricular diastolic dysfunction as evidence of a pathogenic link between HCV and CVD. (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5423282 Sat, 19 Nov 2011 11:16:36 +0100 5423282 http://www.medworm.com/index.php?rid=5423285&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01544.x This study evaluated durability of virologic response over 5 years in children previously treated with interferon alfa‐2b plus ribavirin (IFN/R). Ninety‐seven of 147 children with CHC, who were treated with IFN/R and completed the 6‐month follow‐up in two previous clinical trials, participated in this long‐term follow‐up study. All were assessed annually for up to 5 years; patients with SVR were assessed for durability of virologic response. Children with SVR (n = 56) and those with detectable hepatitis C virus (HCV) RNA 24‐week post‐treatment (n = 41) were followed for a median of 284 weeks. Overall, 70% (68/97) of patients completed the 5‐year follow‐up. One patient with genotype 1a CHC had SVR and relapsed at year 1 of follow‐up with the same genotype... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5423285 Thu, 17 Nov 2011 05:00:00 +0100 5423285 http://www.medworm.com/index.php?rid=5423284&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01539.x Summary.  Prior studies found that hepatitis C virus (HCV) risk assessment and testing in primary care clinics were suboptimal. We aimed to determine the actual HCV testing rate among patients with HCV risk factors and to identify variables predictive of testing. In order to do so, we performed a prospective cohort study among patients seen in four urban primary care clinics. At the initial visit, patients were given a questionnaire that listed HCV risk factors and they were instructed to check ‘yes’ or ‘no’ if they did or did not have a risk factor, respectively. Patients then handed this questionnaire to their physician during their initial visit. Among those who acknowledged having a HCV risk factor via the questionnaire, we determined the subsequent HCV testing rate and calcu... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5423284 Thu, 17 Nov 2011 05:00:00 +0100 5423284 http://www.medworm.com/index.php?rid=5423283&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01540.x Summary.  Tumour necrosis factor‐α (TNF‐α) plays a pivotal role in hepatitis B virus (HBV) clearance and host immune response determining the chronicity of HBV infection. However, studies of the association between TNF‐α‐857 polymorphism and chronic HBV infection have reported conflicting results. So a meta‐analysis was carried out to draw a more precise conclusion. Pubmed (January, 1966–March, 2011) and the China Biological Medicine Database (January, 1978–March, 2011) were searched using the keywords TNF‐α gene polymorphism in combination with HBV infection without language restriction. Fourteen studies including 4929 chronic HBV infection cases and 2702 controls describing the C857T genotype were included in the meta‐analysis. All fourteen studies focussed on an ... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5423283 Thu, 17 Nov 2011 05:00:00 +0100 5423283 http://www.medworm.com/index.php?rid=5388958&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01554.x Summary.  Studies from tertiary care medical centres have linked hepatitis C virus (HCV) to the development of insulin resistance (IR) and type 2 diabetes. The aim of the study is to assess the relationship between HCV positivity and insulin resistance/diabetes in the US population. Three cycles of the National Health and Nutrition Examination Survey (NHANES) conducted between 1988 and 2008 were used. HCV infection was diagnosed using a positive serologic anti‐HCV test. Additionally, diabetes was diagnosed as fasting blood glucose ≥126 mg/dL and/or the use of hypoglycaemic medications. Insulin resistance was defined as a homeostasis of model assessment (HOMA) score of >3.0. Logistic regression was used to estimate the odds ratios (ORs) of each of the potential risk factors for d... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5388958 Wed, 09 Nov 2011 05:00:00 +0100 5388958 http://www.medworm.com/index.php?rid=5388959&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01528.x Summary.  The aims of this phase III study were to assess the efficacy and safety of telaprevir in combination with peginterferon alfa‐2b (PEG‐IFN) and ribavirin (RBV) for difficult‐to‐treat patients who had not achieved sustained virological response (SVR) to prior regimens in Japan. The subjects were 109 relapsers (median age of 57.0 years) and 32 nonresponders (median age of 57.5 years) with hepatitis C virus genotype 1. Patients received telaprevir (750 mg every 8 h) for 12 weeks and PEG‐IFN/RBV for 24 weeks. The SVR rates for relapsers and nonresponders were 88.1% (96/109) and 34.4% (11/32), respectively. Specified dose modifications of RBV that differed from that for the standard of care were introduced to alleviate anaemia. RBV dose reductions were used for 1... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5388959 Tue, 08 Nov 2011 05:00:00 +0100 5388959 http://www.medworm.com/index.php?rid=5388960&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01548.x Summary.  Hepatitis C virus (HCV) infection is a major cause for liver transplantation worldwide. Still, HCV re‐infection of the graft occurs in almost all cases. Most liver transplant recipients experience episodes of graft hepatitis associated with fibrosis progression and graft failure. Clinical management of graft hepatitis can be challenging as in addition to rejection and HCV‐induced hepatitis various other factors might be involved including toxic liver injury, steatohepatitis, ischaemic bile duct lesions or infections with other pathogens. Treatment options are often contradictory for different causes of graft hepatitis, and the role of distinct immunosuppressive drugs has been discussed controversially. Corticosteroids increase the infectivity of HCV by altering expression l... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5388960 Mon, 07 Nov 2011 05:00:00 +0100 5388960 http://www.medworm.com/index.php?rid=5409718&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01545.x In conclusion, HCV infection was not associated with an increased risk of incident MI. (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5409718 Tue, 01 Nov 2011 04:00:00 +0100 5409718 http://www.medworm.com/index.php?rid=5388957&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01555.x In conclusion, a 12‐week course of therapy is sufficient for patients without cirrhosis, not obese and infected with HCV genotype 2 achieve a RVR. This is not the case for genotype 3. Steatosis is the independent predictor of relapse. New therapeutic strategies are necessary for this subgroup of HCV genotype 3. (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5388957 Tue, 01 Nov 2011 04:00:00 +0100 5388957 http://www.medworm.com/index.php?rid=5362773&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01537.x Summary.  Acoustic Radiation Force Impulse (ARFI) imaging is a novel ultrasound‐based elastography method that is integrated in a conventional ultrasound machine enabling the exact localization of measurement site. It might present an alternative method to transient elastography for the noninvasive assessment of liver fibrosis. At present, studies with small patient population have shown promising results. A systematic review and meta‐analysis of pooled patient data were performed to evaluate the overall performance of ARFI for the staging of liver fibrosis. Literature databases were searched up to 10/2010. The authors of the original publication were contacted, and the original patient data were requested. A meta‐analysis was performed using a random effect meta‐analytic method f... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5362773 Tue, 01 Nov 2011 04:00:00 +0100 5362773 http://www.medworm.com/index.php?rid=5362775&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01531.x Summary.  We evaluated whether quantitative measurements of liver fibrosis with recently developed diagnostics outperform histological staging in detecting natural or interferon‐induced changes. We compared Metavir staging, morphometry (area and fractal dimension) and six blood tests in 157 patients with chronic hepatitis C from two trials testing maintenance interferon for 96 weeks. Paired liver biopsies and blood tests were available for 101 patients, and there was a significant improvement in Metavir activity and a significant increase in blood tests reflecting fibrosis quantity in patients treated with interferon when compared with controls – all per cent changes in histological fibrosis measures were significantly increased in F1 vs F2–4 stages only in the interferon group. ... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5362775 Sun, 30 Oct 2011 04:00:00 +0100 5362775 http://www.medworm.com/index.php?rid=5362774&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01532.x Summary.  Anaemia is a common complication of antiviral therapy for chronic hepatitis C virus (HCV) infection that necessitates dose reductions or therapy discontinuation. Administration of erythropoietin (EPO) is an alternative to ribavirin (RBV) dose reduction, but its advantage in terms of sustained virological response (SVR) has not been determined yet. In a systematic way, randomized studies were identified that evaluated the effect of EPO administration vs RBV dose reduction on virological response in patients who developed anaemia during anti‐HCV therapy. The random‐effects model was employed to run meta‐analysis. SVR was set as the end point of interest. Data were abstracted from four studies containing 257 patients who developed anaemia during therapy. One hundred and twen... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5362774 Sun, 30 Oct 2011 04:00:00 +0100 5362774 http://www.medworm.com/index.php?rid=5349125&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01471.x Summary.  Interferon alpha (IFN‐α) therapy is widely used to treat patients with chronic hepatitis B (CHB) but the sustained response rate is low, and the molecular mechanisms for the ineffectiveness of IFN‐α treatments are not known. We screened differentially expressed genes between responders (Rs) and nonresponders (NRs) in patients with CHB treated with IFN‐α to explore the molecular basis for treatment failure. Expression profiling was performed on percutaneous needle liver biopsy specimens taken before therapy. Gene expression levels were compared between seven patients who did not respond to therapy (NR) and six who did respond (R). Gene ontology category and KEGG pathway were analysed for differentially expressed genes, and the selected differentially expressed genes wer... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5349125 Wed, 26 Oct 2011 22:27:15 +0100 5349125 http://www.medworm.com/index.php?rid=5337356&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01543.x Summary.  The study aims were to describe a case series of occupationally acquired hepatitis C (HCV) infections in UK healthcare workers and examine factors associated with transmission using exposure data reported to the Health Protection Agency between July 1997 and December 2007. Fifteen reported cases of documented HCV seroconversion occurred after percutaneous exposure, the majority from hollow‐bore needles used in the source patient’s vein or artery and contaminated with blood or blood‐stained fluid. The seroconversion rate was 2.2% (14/626). In multivariable analysis of healthcare workers with percutaneous exposure to blood or blood‐stained fluid, we demonstrate that blood sampling procedures (odds ratio [OR], 5.75; 95% CI, 1.33–24.91; P = 0.01) and depth of injury (... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5337356 Sat, 22 Oct 2011 23:50:47 +0100 5337356 http://www.medworm.com/index.php?rid=5324721&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01541.x The objective of this study was to analyse the effects of HCV infection of B cells on the efficacy of interferon (IFN)‐based therapy. The study enrolled 102 patients with chronic hepatitis C who were treated with pegylated IFN plus ribavirin. HCV RNA titres in B cells were compared in patients with rapid viral responder (RVR) vs non‐RVR, sustained viral responder (SVR) vs non‐SVR and null viral responder (NVR) vs VR. The levels of HCV RNA in B cells were significantly higher in non‐RVR, non‐SVR and NVR groups. Association between the therapy outcome and the positive B‐cell HCV RNA was also investigated in relation to other known viral and host factors. Multivariable analyses showed that the positive B‐cell HCV RNA and the minor single‐nucleotide polymorphism near the IL28B ... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5324721 Tue, 18 Oct 2011 12:13:56 +0100 5324721 http://www.medworm.com/index.php?rid=5337358&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01527.x Summary.  Combined pegylated interferon (PegIFN) and ribavirin represents the standard therapy for patients with chronic hepatitis C (CHC), which allows for sustained viral response (SVR) in up to 90% of patients depending on certain viral and host factors. Clinical studies have demonstrated the importance of adherence to therapy, that is, the ability of patients to tolerate and sustain a fully dosed therapy regimen. Adherence is markedly impaired by treatment‐related adverse effects. In particular, haemolytic anaemia often requires dose reduction or termination of ribavirin treatment, which compromises treatment efficacy. Recent evidence points to a beneficial role of recombinant erythropoietin (EPO) in alleviating ribavirin‐induced anaemia thereby improving quality of life, enablin... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5337358 Tue, 18 Oct 2011 04:00:00 +0100 5337358 http://www.medworm.com/index.php?rid=5337357&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01542.x Summary.  The aims of this study were to assess hepatitis B surface antigen (HBsAg) seroconversion and to determine its impact on the natural course of the disease in patients with HBeAg‐negative chronic hepatitis B (CHB) during lamivudine (LMV) treatment. A total of 183 consecutive patients with HBeAg‐negative CHB who were treated with LMV were included in the study. Data were retrospectively collected from outpatient visit charts. The primary endpoint was HBsAg seroconversion to anti‐HBs. The secondary endpoint was to determine the development of cirrhosis. Loss of HBsAg was confirmed in 10 patients and seroconversion to anti‐HBs in nine patients during LMV treatment or after its discontinuation. HBsAg seroconversion was achieved on‐treatment in four patients after a median t... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5337357 Tue, 18 Oct 2011 04:00:00 +0100 5337357 http://www.medworm.com/index.php?rid=5324724&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01510.x Summary.  Patients with chronic hepatitis C infection may exhibit neuropsychological symptoms and cognitive impairment. Post‐mortem studies of hepatitis C virus HCV quasispecies and replicative intermediates indicate that the brain might act as a separate compartment for viral replication and microglia may be the locus for infection and subsequent neuroinflammatory activity. We sought to use two independent in vivo imaging techniques to determine evidence of neuroinflammation in patients with histologically mild chronic hepatitis C. Using positron emission tomography (PET) with a ligand for microglial/brain macrophage activation, 11C‐(R)‐PK11195 (PK11195) and cerebral proton magnetic resonance spectroscopy, we determined whether there was evidence of neuroinflammation in a pilot st... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5324724 Mon, 17 Oct 2011 04:00:00 +0100 5324724 http://www.medworm.com/index.php?rid=5324723&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01533.x In conclusion, suboptimal response to ETV is rare (approximately 3%). TDF monotherapy is safe and very effective in the management of HBV patients with SOR to ETV. (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5324723 Mon, 17 Oct 2011 04:00:00 +0100 5324723 http://www.medworm.com/index.php?rid=5324722&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01536.x Summary.  miR‐122 is a liver‐specific microRNA, which also circulates in the blood. The levels of miR‐122 in serum and plasma correlate with hepatic necroinflammation in patients with hepatitis B virus (HBV) infection. Here, we investigated whether miR‐122 levels correlate with surrogate markers for viral replication and translation. Furthermore, we examined whether miR‐122 levels differ in the different groups of HBV‐infected patients and whether miR‐122 levels may be useful to identify patients with higher or lower risk for liver disease progression. Therefore, RNA was extracted from sera of therapy‐naïve patients with HBV infection (n = 89) and from healthy volunteers (n = 19). The concentration of miR‐122 was assessed by quantitative real‐time reverse‐t... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5324722 Mon, 17 Oct 2011 04:00:00 +0100 5324722 http://www.medworm.com/index.php?rid=5316440&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01534.x Summary.  A novel controlled attenuation parameter (CAP) has been developed for Fibroscan® to assess liver steatosis, simultaneously with liver stiffness measurement (LSM). We assessed CAP diagnostic accuracy in a large cohort of patients with chronic hepatitis C (CHC) virus. A total of 615 patients with CHC, who underwent both Fibroscan® and liver biopsy, were analysed. Fibrosis was graded using METAVIR score. Steatosis was categorized by visual assessment as S0: steatosis in <10% of hepatocytes, S1: 11–33%, S2: 34–66% and S3: 67–100%. Performances of CAP and liver stiffness were determined using receiver operating characteristic (ROC) curve analysis and cross‐validated using the bootstrap method. The Obuchowski measure was used to assess overall accuracy of CAP and to diff... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5316440 Sat, 15 Oct 2011 12:54:12 +0100 5316440 http://www.medworm.com/index.php?rid=5316441&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01530.x Summary.  Autophagy is a very tightly regulated process that is important in many cellular processes including development, differentiation, survival and homoeostasis. The importance of this process has already been proven in numerous common diseases such as cancer and neurodegenerative disorders. Emerging data indicate that autophagy plays an important role in some liver diseases including liver injury induced by ischaemia reperfusion and alpha‐1 antitrypsin Z allele‐dependent liver disease. Autophagy may also occur in viral infection, and it may play a crucial role in antimicrobial host defence against pathogens, while supporting cellular homoeostasis processes. Here, the latest findings on the role of autophagy in viral hepatitis B and C infection, which are both serious health th... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5316441 Wed, 12 Oct 2011 04:00:00 +0100 5316441 http://www.medworm.com/index.php?rid=5297791&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01513.x Summary.  Commonly known risk factors for infection with hepatitis C virus (HCV) include blood transfusion, injection drug use, intranasal cocaine use, and body tattoos. We hypothesized that Asian Americans infected with HCV may not identify with these established risk factors present in Caucasians and Hispanics, and our aim was to conduct a survey of risk factors in HCV‐infected patients in these ethnic groups. In this prospective study, 494 patients infected with HCV completed a detailed risk assessment questionnaire at a liver centre in Northern California from 2001 to 2008. Among subjects participating in this study, 55% identified themselves as Caucasian, 20% as Hispanic, and 25% as Asian. Asian Americans were older, less likely to smoke or consume alcohol, and have a family histo... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5297791 Fri, 07 Oct 2011 04:00:00 +0100 5297791 http://www.medworm.com/index.php?rid=5297789&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01514.x Conclusion: Telaprevir alone was well tolerated at 750 mg q8h for up to 12 weeks. The safety profile and emergence of resistant variants of genotype 1b under telaprevir monotherapy for 12 weeks will become increasingly important in evaluating an oral combination of telaprevir with other direct‐acting antiviral agents. (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5297789 Fri, 07 Oct 2011 04:00:00 +0100 5297789 http://www.medworm.com/index.php?rid=5297788&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01498.x We describe here an immunohistochemical method for the detection of HEV antigens (pORF2 and pORF3) in formalin‐fixed, paraffin‐embedded liver tissues using monoclonal antibodies raised against two of the virus proteins (pORF2 and pORF3). We analysed their specificity and sensitivity in comparison with serology and nucleic acid detection in cases of acute liver failure (ALF). We used this test on 30 liver biopsies collected post‐mortem from the patients of ALF caused by HEV infection. These cases were selected on the basis of positive results for enzyme immunoassay (IgM anti‐HEV). Of the 30 cases taken from the archives of the Department of Pathology, the antibodies successfully stained all. However, only 25 serum samples (83.3%) of these were positive for HEV RNA. Fifteen controls ... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5297788 Fri, 07 Oct 2011 04:00:00 +0100 5297788 http://www.medworm.com/index.php?rid=5286784&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01502.x Summary.  Hepatitis C virus (HCV) infection is a major cause for chronic liver disease and hepatocellular carcinoma. The HCV‐ARF/core+1 protein is an alternative product of HCV core‐encoding sequence of unknown biological function. Highly purified HCV core and ARF/core+1 recombinant proteins from HCV genotype 1a and HCV‐ARF/core+1 recombinant protein from HCV genotype 3a were expressed in Escherichia coli. Using an enzyme‐linked immunosorbent assay, we assessed the prevalence of anti‐ARF/core+1 antibodies in 90 chronic hepatitis C patients infected with HCV genotypes 1a/1b or 3a, treated with pegylated interferon (Peg‐IFN‐a‐2a) plus ribavirin. Samples derived from 92 healthy blood donors were used as negative controls. All HCV‐RNA‐positive serum samples reacted with c... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5286784 Tue, 04 Oct 2011 04:00:00 +0100 5286784 http://www.medworm.com/index.php?rid=5297787&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01538.x In conclusion, hepatic MxA and OAS1 expression predicted, respectively, the end of therapeutic and sustained virological responses in interferon‐based treatment of chronic hepatitis C. (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5297787 Sat, 01 Oct 2011 04:00:00 +0100 5297787 http://www.medworm.com/index.php?rid=5286783&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01512.x Summary.  There is no study that follows up longitudinal changes in laboratory data of patients with C‐viral chronic liver disease (C‐CLD) who achieved sustained virological esponse (SVR) with interferon treatment in a long‐term study. We investigated the laboratory data in a long‐term retrospective cohort study of 581 patients with C‐CLD who underwent liver biopsy between January 1986 and December 2005. 467 were treated with interferon and 207 of these patients achieved SVR with follow‐up periods of 8.36 ± 5.13 years. Alanine aminotransferase (ALT) levels, albumin levels, platelet counts, and the aspartate aminotransferase (AST)‐to‐platelet ratio index (APRI) values were serially examined during the follow‐up period. None of the 207 patients with SVR exhibited h... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5286783 Sat, 01 Oct 2011 04:00:00 +0100 5286783 http://www.medworm.com/index.php?rid=5261912&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01535.x Summary.  The metabolic syndrome may cause disease progression in patients with chronic hepatitis B (CHB). However, the interactions between hepatitis B virus (HBV) infection and metabolic factors remain unknown. We investigated the association of HBV infection with metabolic profiles in HBV‐infected and noninfected subjects. In addition, the impacts of serum HBV DNA level on metabolic profiles were studied. Initially, a case–control analysis of patients with and without chronic HBV infection was performed. The HBV group consisted of 322 patients with chronic HBV infection, and the control group consisted of 870 matched subjects without HBV infection. Fasting blood glucose, lipid profiles and adiponectin levels were compared. The results were then confirmed in a second retrospective ... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5261912 Thu, 29 Sep 2011 11:34:00 +0100 5261912 http://www.medworm.com/index.php?rid=5251610&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01515.x This study further demonstrates that peginterferon alfa‐2b plus weight‐based ribavirin for 24 weeks is an effective treatment strategy for treatment‐naive patients with G1 CHC and low viral load who attain RVR. (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5251610 Sun, 25 Sep 2011 22:55:25 +0100 5251610 http://www.medworm.com/index.php?rid=5227317&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01464.x Summary.  It is unknown whether hepatitis C virus (HCV)‐specific cellular immune responses can develop in seronegative sexual partners of chronically HCV‐infected patients and whether they have occult infection. Thirty‐one heterosexual partners of patients with chronic HCV were studied, fifteen of them with HCV transmission risks. Ten healthy individuals and 17 anti‐HCV seropositive patients, without viremia, were used as controls. Virus‐specific CD4+ and CD8+ T‐cell responses were measured by flow cytometry against six HCV peptides, situated within the nonstructural (NS) proteins NS3, NS4 and NS5, through intracellular detection of gamma interferon (IFN‐γ) or interleukin 4 (IL‐4) production and CD69 expression. Sexual partners had a higher production of IFN‐γ and IL�... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5227317 Mon, 19 Sep 2011 03:04:20 +0100 5227317 http://www.medworm.com/index.php?rid=5227316&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01441.x Summary.  Liver steatosis is a main histopathological feature of Hepatitis C (HCV) infection because of genotype 3. Steatosis and/or mechanisms underlying steatogenesis can contribute to hepatocarcinogenesis. The aim of this retrospective study was to assess the impact of infection with HCV genotype 3 on hepatocellular carcinoma (HCC) occurrence in patients with ongoing HCV cirrhosis. Three hundred and fifty‐three consecutive patients (193 men, mean age 58 ± 13 years), with histologically proven HCV cirrhosis and persistent viral replication prospectively followed and screened for HCC between 1994 and 2007. Log‐rank test and Cox model were used to compare the actuarial incidence of HCC between genotype subgroups. The patients infected with a genotype 3 (n = 25) as compared... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5227316 Mon, 19 Sep 2011 03:04:14 +0100 5227316 http://www.medworm.com/index.php?rid=5227315&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01500.x (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5227315 Mon, 19 Sep 2011 03:03:36 +0100 5227315 http://www.medworm.com/index.php?rid=5227312&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01516.x We examined pretreatment serum levels of 14 cytokines among 190 patients who were treated with pegylated interferon‐α‐2b plus ribavirin for chronic HCV‐1b infection with high viral load (≥5 log IU/mL) and analyzed their contribution to treatment response. Plasminogen activator inhibitor‐1 (PAI‐1), vascular endothelial growth factor, and 11 clinical factors showed significant association with SVR in univariate logistic regression analysis. Four significant factors in multivariate analysis; serum PAI‐1 (odds ratio [OR] = 15.42), body mass index (OR = 4.56), rs8099917 (OR = 4.95) and fibrosis stage (OR = 5.18) were identified as independent predictors. We constructed a simple and minimally invasive prediction score for SVR based on the presence of these fact... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5227312 Mon, 19 Sep 2011 03:02:13 +0100 5227312 http://www.medworm.com/index.php?rid=5227313&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01508.x In conclusion, in well‐compensated chronic hepatitis B infection, hepatic iron deposits and elevation of serum iron indices are common, especially in male gender and in patients coinfected with HDV. As HBV/HDV liver disease is generally more rapidly progressive than that caused by HBV monoinfection, we speculate that iron overload may be one of the factors contributing to the severity of liver disease. (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5227313 Wed, 14 Sep 2011 04:00:00 +0100 5227313 http://www.medworm.com/index.php?rid=5227314&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01511.x Summary.  Experts from seven countries convened as a Specialist Panel for the Middle East to share information on practical issues relating to the epidemiology, diagnosis and management of chronic hepatitis B (CHB) infection. The Middle East is regarded as a region of high‐to‐intermediate epidemicity; however, infant vaccination programmes have successfully lowered the prevalence of hepatitis B infection in most countries to that of low‐to‐intermediate endemicity. Vaccine issues still to be addressed included improving coverage in some rural/poor communities, instituting hepatitis B vaccine at birth and providing vaccines for high‐risk population groups. Hepatitis B infection in the Middle East primarily occurs as a result of perinatal infection, horizontal transmission between... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5227314 Tue, 13 Sep 2011 04:00:00 +0100 5227314 http://www.medworm.com/index.php?rid=5185004&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01496.x Summary.  Natural killer cells (NK) are one of the key players in the eradication and control of viral infections. Infections with the hepatitis B virus (HBV) may lead to persistence in a subgroup of patients, and impaired NK cell functions have been observed in these patients. Crosstalk with other immune cells has been shown to modulate the function of NK cells. We studied the functional crosstalk between NK cells and plasmacytoid dendritic cell (pDC) and its modulation by HBV. Healthy human peripheral blood–derived NK cells and pDC were purified and cocultured in the presence or absence of HepG2.2.15‐derived HBV under various in vitro conditions. The functionality of NK cells was assessed by evaluation of activation markers, cytokine production and cytotoxicity of carboxyfluorescei... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5185004 Wed, 31 Aug 2011 23:00:00 +0100 5185004 http://www.medworm.com/index.php?rid=5185005&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01504.x This study identified residues at the NS2Pro dimer interface that modulate NS2Pro homodimerization and demonstrated that abrogation of NS2Pro homodimerization results in defects in HCV replication and release of infectious virus. (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5185005 Mon, 29 Aug 2011 23:00:00 +0100 5185005 http://www.medworm.com/index.php?rid=5145086&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01484.x Summary.  Previous clinical studies have demonstrated an association between the hepatitis B e antigen and Toll‐like receptor (TLR) expression and signalling. Therefore, the aim of this study was to develop an in vitro assay to measure the effect of hepatitis B virus proteins, including the precore protein, on signalling mediated by members of the Toll‐like/interleukin 1 (TIR) superfamily, by measuring NF‐κB promoter activity. The basal level of NF‐κB reporter activity was measured in three hepatocyte cell lines (Huh7, HepG2 and PH5CH8) and one kidney cell line (HEK293) using a luciferase assay. All cell lines were virtually refractory to stimulation with lipopolysaccharide; however, PH5CH8 cells had a robust activation of NF‐κB in response to IL‐1β stimulation, with ∼4... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5145086 Sat, 20 Aug 2011 17:10:00 +0100 5145086 http://www.medworm.com/index.php?rid=5133026&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01507.x Summary.  Phytochemicals exert antiviral activity and may play a potential therapeutic role in hepatitis C virus (HCV) infection. In this work, we aimed to isolate NS3 inhibitors from traditional Indian medicinal plants that were found, in our earlier study, to inhibit HCV NS3 protease activity and to evaluate their potential to inhibit HCV replication. A potent inhibitory effect of NS3 catalytic activity was obtained with Embelia ribes plant extracts. Quercetin, a ubiquitous plant flavonoid, was identified as the active substance in the fractioned extract. It was found to inhibit NS3 activity in a specific dose‐dependent manner in an in vitro catalysis assay. Quercetin inhibited HCV RNA replication as analysed in the subgenomic HCV RNA replicon system. It also inhibited HCV infectious... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5133026 Tue, 16 Aug 2011 23:46:07 +0100 5133026 http://www.medworm.com/index.php?rid=5133028&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01505.x In conclusion, HCV RNA replication was significantly augmented by the inhibition of IKK activation and subsequent NF‐κB signalling, whereas a restoration of NF‐κB activity by the addition of NF‐κB/RelA markedly reduced HCV replication. This study lends added importance to the role of the NF‐κB signalling pathway in controlling HCV replication. (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5133028 Mon, 15 Aug 2011 23:00:00 +0100 5133028 http://www.medworm.com/index.php?rid=5133027&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01506.x Summary.  For phylogenetic comparison of hepatitis B virus (HBV) isolates, often a region of the HBV surface gene is analysed. Because the surface gene completely overlaps the polymerase gene, its evolution is constrained, and it may not be the best choice for genetic comparison of HBV isolates. Analysing serial sample pairs of 33 chronically HBV‐infected, untreated patients, with a cumulative follow‐up of 184 years, the synonymous and nonsynonymous substitution rates of a part of the overlapping HBV surface and polymerase genes were compared to those of a nonoverlapping part of the HBV core gene. The substitution rate of the HBV core gene was higher (8.15 × 10−4vs 4.57 × 10−4 substitutions/site/year) than that of the surface gene. The difference was mainly due to a... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5133027 Mon, 15 Aug 2011 23:00:00 +0100 5133027 http://www.medworm.com/index.php?rid=5098756&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01497.x Summary.  Single nucleotide polymorphisms (SNPs) near the IL28B gene have been shown to be associated with response to treatment for chronic hepatitis C and also with spontaneous clearance of hepatitis C virus (HCV) infection. We analysed the association between IL28B genetic variants and spontaneous clearance of HCV infection in 376 HCV‐infected Chinese paid plasma donors. Genotyping of eight SNPs near the IL28B region was performed by the iPLEX system (MassARRAY® SNP Genotyping; Sequenom) in all donors, and sequencing was performed on all 80 donors who cleared HCV and on 160 of 296 donors who did not clear HCV to validate the genotypes. Eighty (21.3%) donors spontaneously cleared HCV. Four SNPs were significantly associated with spontaneous HCV clearance: rs8099917 TT (vs GT), rs810... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5098756 Sat, 06 Aug 2011 17:09:10 +0100 5098756 http://www.medworm.com/index.php?rid=5098758&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01495.x Summary.  The presence of coagulopathy in acute viral hepatitis (AVH) in children raises issues about prognosis and need for liver transplantation. We evaluated factors predicting outcome in such patients and determined the applicability of the paediatric acute liver failure study group (PALFSG) definition of acute liver failure (ALF) of coagulopathy alone in comparison with coagulopathy and encephalopathy. Children with AVH (clinical features, raised transaminases and positive viral serology) with uncorrectable coagulopathy [prothrombin time (PT) > 15 s] with or without hepatic encephalopathy (HE) were enrolled. Comparative analysis was based on (i) outcome: survivors/nonsurvivors and (ii) ALF criteria: group A coagulopathy (PT > 15 s) and encephalopathy and group B co... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5098758 Wed, 03 Aug 2011 23:00:00 +0100 5098758 http://www.medworm.com/index.php?rid=5098757&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01501.x In this report, we also summarize the findings of 11 cases of IFN‐associated ischaemic colitis (nine previously published cases plus our two cases) and review the clinical characteristics of ischaemic colitis during IFN therapy in patients with chronic hepatitis C. (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5098757 Wed, 03 Aug 2011 23:00:00 +0100 5098757 http://www.medworm.com/index.php?rid=5089190&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01492.x This study retrospectively evaluated virologic and other risk factors associated with immunoprophylaxis failure in infants born to HBsAg‐positive mothers. Between January 2007 and March 2010, we reviewed the clinical and virologic tests in 869 mother–infant pairs. All infants received the identical passive–active immunization schedule after birth. The failure infants (HBsAg positive at 7–12 months of age) were compared to infants who were HBsAg negative when tested during this time period. Among 869 infants, 27 (3.1%) infants were immunoprophylaxis failures and the other 842 (96.9%) infants remained HBsAg negative. When mothers’ pre‐delivery HBV DNA levels were stratified to <6, 6–6.99, 7–7.99 and ≥8 log10 copies/mL, the corresponding rates of immunoprophylaxis f... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5089190 Wed, 03 Aug 2011 18:24:23 +0100 5089190 http://www.medworm.com/index.php?rid=5053749&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01491.x Summary.  Tumour necrosis factor‐α (TNF‐α) plays a pivotal role in viral clearance and host immune response to hepatitis B virus (HBV) infection, of which the production capacity in individuals is demonstrated to be influenced by a single nucleotide polymorphism within the promoter region of TNF‐α genes. However, there have been conflicting results reported in previous studies on TNF‐α‐238 and TNF‐α‐863 gene promoter polymorphisms in chronic HBV infection. To derive a more precise estimation of their relationship, we searched Pubmed (January, 1966–August, 2010) and China Biological Medicine Database (January, 1978–August, 2010) and carried out a meta‐analysis involving nineteen studies that included 5245 chronic HBV infection cases and 3181 controls describing G2... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5053749 Sat, 23 Jul 2011 17:26:33 +0100 5053749 http://www.medworm.com/index.php?rid=5053750&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01486.x Summary.  Quantitative serology for hepatitis B surface antigen (HBsAg) is a new candidate marker for prediction of clinical outcome. The aim of this study was to investigate the clinical significance of quantifying HBsAg in patients with hepatitis B virus (HBV) infection. A total of 424 patients who tested positive for HBsAg and were referred to Chiba University Hospital between January 1985 and April 2008 were included in the study, and the following characteristics were analyzed: age, gender, status of hepatitis B e antigen (HBeAg), alanine aminotransferase level (ALT), HBV DNA level, number of platelets and development of hepatocellular carcinoma. Measurement of HBsAg was performed using the chemiluminescent enzyme immunoassay method. The study group consisted of 239 men and 185 wome... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5053750 Thu, 21 Jul 2011 23:00:00 +0100 5053750 http://www.medworm.com/index.php?rid=5000091&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01469.x Summary.  The focus of this study was to evaluate the safety and efficacy of sequential peginterferon α‐2a (Pegasys) therapy for chronic hepatitis B with acute exacerbation [ALT > 10 × upper limit of normal (ULN), bilirubin <2.0 mg/dL]. Four groups of patients categorized by HBeAg status and treatment regimens were studied since May 2007. Nineteen HBeAg‐positive patients (Group 1) had received entecavir  pretreatment  (when ALT > 10 × ULN) plus Pegasys (180 μg/kg/week, when ALT was 5–10 × ULN) for 24 weeks. Thirteen HBeAg‐negative patients (Group 2) had the same protocol for 48 weeks. In both groups, entecavir was then discontinued 14 days after the initiation of Pegasys. The results were compared, respectively, to 35 HBeAg‐positive... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5000091 Sun, 03 Jul 2011 23:00:00 +0100 5000091 http://www.medworm.com/index.php?rid=5000090&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01480.x Summary.  Hepatitis B virus (HBV) genotypes/mutants are known to affect natural outcomes. The virologic differences among HBV genotype, precore and basal core promoter (BCP) mutations were investigated. HBV strains were isolated from 18 hepatitis B e antigen (HBeAg)‐positive patients (nine genotype B and nine genotype C). All had precore and BCP wild‐type sequences. After cloning of full‐length HBV genome, the effects of viral genotype, precore and BCP mutations singly or additively on the expression of viral DNA and antigens were investigated by mutagenesis and transfection assays in Huh7 cells. Significant findings included the following: (i) expression of intracellular core protein increased when precore or BCP mutation was introduced in genotype C strains; (ii) expression of in... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5000090 Sun, 03 Jul 2011 23:00:00 +0100 5000090 http://www.medworm.com/index.php?rid=5031379&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01494.x In conclusion, adherence to NUC therapy in our patients with chronic hepatitis B was high but self‐reporting of adherence to healthcare providers may be inflated. Patients with chronic hepatitis B with better adherence to NUC therapy had a trend towards a lower rate of viral breakthroughs. (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5031379 Thu, 30 Jun 2011 23:00:00 +0100 5031379 http://www.medworm.com/index.php?rid=5021813&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01489.x Summary.  Hepatitis E virus (HEV) is a leading cause of acute viral hepatitis in several developing countries. Information on cellular immune responses during acute hepatitis E is limited. We therefore studied peripheral blood mononuclear cells (PBMCs) from patients with acute hepatitis E and healthy adult subjects who lacked anti‐HEV antibodies for enumeration of various T‐cell subsets using flow cytometry and to assess HEV‐specific T effector cell responses using interferon‐gamma ELISPOT assays. The patients showed increased numbers of CD8+ cells and CD4+CD8+ cells compared with healthy controls. In addition, the proportion of PBMCs that produced interferon‐gamma in response to recombinant HEV open reading frame (ORF) 2 and ORF 3 proteins were found to be higher in patients t... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5021813 Thu, 30 Jun 2011 23:00:00 +0100 5021813 http://www.medworm.com/index.php?rid=5010622&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01483.x In this study, we applied ASP‐RNAi into two long‐term eukaryotic cell lines of full‐length HBV containing either lamivudine‐resistant mutants (HBV‐YIDD) or wild type (HBV–WT) which we generated in previously. The designed siRNAs were also used in this eukaryotic expression system together with lamivudine. ELISA and real‐time PCR were performed to monitor virus‐specific protein synthesis and viral DNA replication. The results showed that the base substitutions conferring marked ASP‐RNAi appeared to be largely present in positions 1, 3, 6, 11, 12, 15 and 19 of the sense strand of siRNAs which were different from the most sensitive positions of this application in eukaryotes. In addition, siRNA–lamivudine combinations did not possess the prominent anti‐HBV activity we ex... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5010622 Thu, 30 Jun 2011 23:00:00 +0100 5010622 http://www.medworm.com/index.php?rid=5000089&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01485.x Summary.  Approximately 30% of patients with chronic HCV infection have persistently normal ALT levels. Although formerly referred to as ‘healthy’ or ‘asymptomatic’ HCV carriers, and thus historically excluded from antiviral treatment, it has now become clear that the majority of these patients have some degree of histological liver damage that may be significant in up to 20% of cases and might progress towards a more severe degree of liver fibrosis. A significant proportion of patients experience periods of increased serum ALT associated with enhanced disease progression. However, controversies still exist in clinical practice regarding the definition of ‘persistent’ ALT normality, the virological and histological features of these subjects, the need for liver biopsy, the ro... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=5000089 Thu, 30 Jun 2011 23:00:00 +0100 5000089 http://www.medworm.com/index.php?rid=4986998&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01481.x In conclusion, viral genotype 3 was associated with faster fibrosis progression in single‐biopsy studies. This observation may have important consequences on the clinical management of genotype 3‐infected patients. The association was not significant in paired biopsies studies, although the latter may be limited by important indication bias, short observation time and small sample size. (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4986998 Thu, 30 Jun 2011 23:00:00 +0100 4986998 http://www.medworm.com/index.php?rid=4986997&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01488.x Summary.  Hepatitis E, which is endemic to resource‐poor regions of the world, is largely an acute and self‐limiting disease, but some patients have an increased susceptibility to develop fulminant hepatitis. The pathogenesis of hepatitis E in humans is poorly characterized. To understand the metabolic pathways involved in the pathophysiology of hepatitis E, we have used 1H nuclear magnetic resonance spectroscopy to quantify various metabolites in the plasma and urine of the patients with hepatitis E. These were compared with specimens from patients with acute hepatitis B as disease controls and healthy volunteers. Data were analysed using chemometric statistical methods and metabolite databases. The main metabonomic changes found in patients with hepatitis E, but not in those with h... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4986997 Thu, 30 Jun 2011 23:00:00 +0100 4986997 http://www.medworm.com/index.php?rid=4986996&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01487.x This study demonstrates and signifies that changes occur in the expression of CS proteins in HCV‐infected hepatocytes and, for the first time, shows the up‐regulation and interaction of fila with HCV proteins. Association between CS and HCV proteins may have implications in future design of CS protein‐targeted therapy for the treatment for HCV infection. (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4986996 Thu, 30 Jun 2011 23:00:00 +0100 4986996 http://www.medworm.com/index.php?rid=4986995&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01493.x Summary.  There is increasing interest in developing noninvasive means to evaluate liver fibrosis in patients with chronic liver disease to determine disease severity, prognosis and optimal treatment. Transient elastography (TE) has previously been demonstrated to predict the presence or absence of advanced fibrosis. The current study was conducted to determine whether TE can identify patients with chronic liver disease at risk of clinical decompensation. A total of 667 patients underwent TE and were followed for a median of 861 days and 57 patients achieved the primary outcome, a composite of clinical endpoints including death, ascites, encephalopathy, increased Child Score ≥2, variceal bleed, hepatocellular carcinoma or listing for transplant. Overall, TE had an area under the rece... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4986995 Thu, 30 Jun 2011 23:00:00 +0100 4986995 http://www.medworm.com/index.php?rid=4987000&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01482.x In conclusion, ‘anti‐HBc alone’ should be considered a risk marker for a so‐called ‘false occult’ HBV infection with significant viraemia. Indeed, results in this hospital population indicate that a small proportion of patients with ‘anti‐HBc alone’ have high viral loads, revealing the occurrence of infection with HBV mutants that escape detection even by multivalent HBsAg assays. (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4987000 Wed, 29 Jun 2011 23:00:00 +0100 4987000 http://www.medworm.com/index.php?rid=4986999&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01490.x Summary.  Minority drug‐resistant hepatitis C virus (HCV) variants may go undetected yet be clinically important. NS3/4A protease resistance substitutions V36A and A156S/T/V were selected in patients treated with protease inhibitors. The aim of this study was to investigate whether these substitutions pre‐existed in HCV infected patients. An allele‐specific PCR protocol that detected the NS3/4A protease resistance substitutions V36A and A156S/T/V was used to determine the prevalence of naturally occurring variants in 45 patients. All patient samples were infected with HCV of genotype 1b and were naïve for pegIFNα/ribavirin treatment. Thirty samples (67%) had at least one HCV PI‐resistant variant. A156T (23, 51%) was detected more frequently than A156V (13, 29%) or A156S (1, 2%)... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4986999 Wed, 29 Jun 2011 23:00:00 +0100 4986999 http://www.medworm.com/index.php?rid=4962117&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01128.x Summary.  Despite the introduction of blood donor screening, worldwide, children continue to become infected with hepatitis C virus (HCV) via un‐sterile medical injections, receipt of unscreened blood and isolated hospital contamination outbreaks. It is plausible that the natural history and disease progression in these children might differ from that of their vertically infected counterparts. Vertically and parenterally HCV‐infected children were prospectively followed within the European Paediatric HCV Network and the UK National HCV Register, respectively. Biological profiles were compared. Vertically and parenterally HCV‐infected children differed in terms of some key characteristics including the male to female ratio and the proportion of children receiving therapy. Parenteral... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4962117 Fri, 24 Jun 2011 15:00:21 +0100 4962117 http://www.medworm.com/index.php?rid=4886342&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01470.x We examined the effect of dendritic cells engineered to express an HBV S antigen CD40L fusion gene (HBV S‐ecdCD40L). The DNA of HBV S gene and the cDNA of the extracellular domain of human CD40 ligand were linked by cloning. Peripheral blood mononuclear cells (PBMC) from healthy adults were incubated and induced into dendritic cells (DC) in presence of granulocyte/macrophage colony‐stimulating factor (GM‐CSF) and interleukin‐4(IL‐4). The DCs were transfected the novel construct, and the impact of the expressed clone assessed. We find that, compared with control groups, modification of DCs with HBV S‐ecdCD40L fusion gene resulted in the activation of DCs with upregulated expression of immunologically important cell surface molecules (CD80, CD86 and HLA‐DR) and proinflammatory ... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4886342 Tue, 31 May 2011 23:00:00 +0100 4886342 http://www.medworm.com/index.php?rid=4886341&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01473.x Summary.  Serum hepatitis B virus surface antigen (HBsAg) levels have been suggested to predict interferon response in chronic hepatitis B. A few data are available on the role of HBsAg measurement in nucleos(t)ide analogues (NA) treatment. We retrospectively investigated the relation between HBsAg changes and main treatment outcomes during long‐term lamivudine treatment in hepatitis e antigen (HBeAg)‐negative chronic hepatitis B. A total of 42 HBeAg‐negative patients were consecutively enrolled in an open‐label study on long‐term lamivudine monotherapy (150 mg/die). Serum HBsAg levels were quantified every 6 months by Architect assay (Abbott Diagnostics). HBV‐DNA was quantified quarterly by real‐time PCR (Roche Diagnostics). The median duration of lamivudine treatment ... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4886341 Tue, 31 May 2011 23:00:00 +0100 4886341 http://www.medworm.com/index.php?rid=4886340&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01475.x Summary.  The immune mechanism(s) that lead to hepatitis B‐related acute‐on‐chronic liver failure (HB‐ACLF) are poorly understood. Interleukin‐21 is a newly discovered cytokine that is involved in autoimmune and inflammatory diseases. Its potential role in HB‐ACLF remains unknown. The serum levels of 12 immune cytokines measured by cytometric bead arrays and the frequency of IL‐21‐secreting CD4+ T cells in peripheral blood mononuclear cells (PBMC) measured by intracellular cytokine staining were compared in moderate chronic hepatitis B (M‐CHB, n = 20), severe chronic hepatitis B (S‐CHB, n = 20), HB‐ACLF (n = 39) and healthy controls (n = 10). PBMC from M‐CHB patients or healthy subjects were stimulated with rhIL‐21 in vitro, and cytokines in supe... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4886340 Tue, 31 May 2011 23:00:00 +0100 4886340 http://www.medworm.com/index.php?rid=4886339&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01477.x This study investigated the clinical, serological and molecular characteristics of coexistence of both immunoglobulin M (IgM) antihepatitis A virus (HAV) and IgM antihepatitis E virus (HEV) in acute viral hepatitis using a prospective, multicentre design. Among a total of 771 symptomatic cases with acute viral hepatitis enrolled in a Korean city from September 2006 to August 2008, coexistence of IgM anti‐HAV and IgM anti‐HEV was found in 43 patients (A+E group; 6%), while the existence of IgM anti‐HAV alone was found in 595 patients (A group; 77%) and that of IgM anti‐HEV alone in 14 patients (E group; 2%). Clinical data analysis and measurement of IgM and IgG anti‐HEV were performed using two different commercial kits, and HAV RNA and HEV RNA were detected in available serum or ... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4886339 Tue, 31 May 2011 23:00:00 +0100 4886339 http://www.medworm.com/index.php?rid=4886338&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01479.x This study aimed to evaluate the long‐term efficacy of entecavir (ETV) in adefovir (ADV)‐refractory chronic hepatitis B (CHB) patients with prior lamivudine (LMV) resistance. A total of 55 ADV‐refractory CHB patients with prior LMV resistance, who received rescue therapy with ETV 1 mg daily for at least 12 months, were consecutively enrolled and analysed. Forty‐four patients were men, and their median age was 47 (25–69). Ten patients had liver cirrhosis and 46 patients were positive for hepatitis B e antigen (HBeAg). Median hepatitis B virus DNA levels were 6.6 (4.3–8.0) log10 copies/mL, and the median duration of ETV therapy was 24 (12–47) months. Cumulative virologic response rates at 6, 12, 24 and 36 months were 18%, 29%, 58% and 75%, respectively. HBeAg loss occur... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4886338 Tue, 31 May 2011 23:00:00 +0100 4886338 http://www.medworm.com/index.php?rid=4886337&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01467.x Summary.  Most previous studies of burden of disease (BoD) in the area of transmissible diseases have assessed the burden of hepatitis C and B without including the end stages of the disease and using an incident approach. We aimed to assess the disability‐adjusted life years (DALYs) related to hepatitis C and B in Spain in 2006 taking into account related cirrhosis and liver cancer. A prevalence approach was used to estimate current years lived with disability (YLD) because of viral hepatitis contracted years/decades before. We added years of life lost (YLL) to obtain DALYs. Around 76 000 DALYs were attributed to hepatitis C virus (HCV) and 15 323 to hepatitis B virus (HBV) when calculated without applying social values. Applying the discount rate and age‐weighting used in the G... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4886337 Tue, 31 May 2011 23:00:00 +0100 4886337 http://www.medworm.com/index.php?rid=4873742&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01476.x Summary.  This population‐based study aimed to assess the determinants of the outcome of chronic hepatitis C with analysis of the impact of antiviral therapy with or without sustained virological response (SVR) on cirrhosis decompensation, hepatocellular carcinoma, liver‐related and non‐liver‐related mortality. A total of 1159 HCV‐positive patients newly detected between 1994 and 2001 were included. For each outcome, the prognostic effect of patients’ baseline characteristics was estimated by time‐dependent Cox models using age as the time‐scale and adjusting for treatment received during follow‐up. The impact of antiviral therapy was assessed by using a propensity score in a sample including 184 patients treated in the first 24 months following diagnosis who were mat... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4873742 Sat, 28 May 2011 18:37:46 +0100 4873742 http://www.medworm.com/index.php?rid=4873743&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01463.x Summary.  It is widely believed that hepatocellular cancer (HCC), especially HBV associated HCC, is highly resistant to chemotherapy. To investigate the molecular influence of HBx protein on multidrug resistance (MDR) in HCC and the potential role of the NF‐κB pathway in this process. We established HBx‐expressing cells by liposome‐mediated transfection of the HBx into the HepG2 cell line. We found that HBx expression in HCC cells induces drug resistance against multiple drugs, a significantly lower apoptosis ratio in HepG2‐HBx and HepG2.2.15 cells, compared with HepG2 and HepG2‐3.1 cells (P < 0.05) after treating with 5‐FU or adriamycin. And compared with the control group, the HBx‐transfected cells showed a higher expression of MDR‐associated and anti‐apoptoti... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4873743 Thu, 26 May 2011 23:00:00 +0100 4873743 http://www.medworm.com/index.php?rid=4865179&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01478.x In conclusion, both host factors and viral factors may be involved in the generation of hyporesponsiveness to TLR ligands in patients with chronic HCV infection. (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4865179 Thu, 26 May 2011 17:32:01 +0100 4865179 http://www.medworm.com/index.php?rid=4865180&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01474.x Summary.  Chronic infection with hepatitis C virus (HCV) can induce insulin resistance (IR) in a genotype‐dependent manner and contributes to steatosis, progression of fibrosis and resistance to interferon plus ribavirin therapy. Our understanding of HCV‐induced IR has improved considerably over the years, but certain aspects concerning its evaluation still remain elusive to clinical researchers. One of the most important issues is elucidating the ideal method for assessment of IR in the setting of hepatitis C. The hyperinsulinaemic euglycaemic clamp is the gold standard method for determining insulin sensitivity, but is impractical as it is labour intensive and time‐consuming. To date, all human studies except for four where IR was evaluated in the HCV setting, an estimation of IR... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4865180 Tue, 24 May 2011 23:00:00 +0100 4865180 http://www.medworm.com/index.php?rid=4855017&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01468.x Summary.  The present study was designed to determine the predictive factors for the viral response to pegylated interferon‐alpha plus ribavirin combination therapy (PEGIFN/RBV) administered after curative treatment for hepatitis C virus (HCV)‐related hepatocellular carcinoma (HCC). The study group was 78 patients treated between January 2005 and January 2009. The sustained viral response (SVR) rate was 25.8% (15/58) in patients infected with HCV‐genotype 1 and 55.0% (11/20) in those with genotype 2. Among the 78 patients, 32 (41.0%) could not complete the treatment protocol, and this was because of HCC recurrence in 17 (53%) of them. Multivariate analysis identified partial early viral response (pEVR) as the only independent determinant of SVR [odds ratio (OR) 14.73, P = 0.013... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4855017 Tue, 24 May 2011 17:41:33 +0100 4855017 http://www.medworm.com/index.php?rid=4855019&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01465.x Summary.  Serum hepatitis B surface antigen (HBsAg) levels reflect intrahepatic hepatitis B virus (HBV) covalently closed circular DNA and may be a valuable addition to HBV DNA in the management of patients with chronic hepatitis B (CHB). Among HBeAg‐negative CHB patients with low HBV DNA levels, HBsAg quantification may help distinguish those with active CHB from true inactive carriers with a very favourable prognosis, thus limiting the need for long‐term intensive monitoring of ALT and HBV DNA levels. In patients treated with peginterferon (PEG‐IFN), achievement of a decline in HBsAg during therapy appears to be an important marker for treatment outcome, and several groups have proposed stopping rules based on HBsAg thresholds. A recently described stopping rule incorporating a c... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4855019 Sun, 22 May 2011 23:00:00 +0100 4855019 http://www.medworm.com/index.php?rid=4855018&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01472.x Summary.  The aim of this study was to further investigate the prevalence of infection and genotype of hepatitis E virus (HEV) among different species of animals, people whose works are related to pigs and the general population in the suburb of Beijing, China. Serum and faecal samples were collected from 10 animal species and humans. Anti‐HEV was detected by enzyme immunoassays (EIA); HEV RNA was amplified by reverse transcription–nested polymerase chain reaction (RT‐nPCR) method. PCR products were cloned and sequenced. The isolated swine HEV sequences were analysed phylogenetically. The positive rates of serum anti‐HEV in swine, cattle, milk cow, horse, sheep, donkey, dog, duck, chicken, pig farm workers and slaughterhouse workers, and general population were 81.17% (802/988), ... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4855018 Sun, 22 May 2011 23:00:00 +0100 4855018 http://www.medworm.com/index.php?rid=4832746&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01457.x Summary.  An explosive outbreak of Hepatitis B with high mortality was reported in 2009, in Modasa, Gujarat, India. Mortality was associated with basal core promoter and precore mutant hepatitis B virus (HBV). The current study addresses the role of immunological parameters in the progression to fulminant hepatitis. The study population comprised of 22 acute HBV patients, 13 fulminant HBV liver failure patients and 54 healthy controls. Hepatitis B surface antigen‐induced CTL responses by enzyme‐linked immunosorbent spot (ELISPOT), cytokine and chemokine quantitation by Bioplex assay, peripheral NK, natural killer T (NKT), CD4 and CD8 T‐cell frequencies by flow cytometry were carried out. The median percentage of NK cells in the lymphocytes of the acute and fulminant liver failure p... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4832746 Wed, 18 May 2011 18:51:09 +0100 4832746 http://www.medworm.com/index.php?rid=4822829&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01466.x Summary.  Widespread use of lamivudine in antiretroviral therapy may lead to hepatitis B virus resistance in HIV–HBV coinfected patients from endemic settings where tenofovir is not readily available. We evaluated 389 Kenyan HIV‐infected adults before and for 18 months after starting highly active antiretroviral therapy with stavudine, lamivudine and nevirapine. Twenty‐seven (6.9%) were HBsAg positive and anti‐HBs negative, 24 were HBeAg negative, and 18 had HBV DNA levels ≤10 000 IU/mL. Sustained HBV suppression to <100 IU/mL occurred in 89% of 19 evaluable patients. Resistance occurred in only two subjects, both with high baseline HBV DNA levels. Lamivudine resistance can emerge in the setting of incomplete HBV suppression but was infrequently observed among HIV–... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4822829 Sat, 14 May 2011 20:54:57 +0100 4822829 http://www.medworm.com/index.php?rid=4822830&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01461.x Summary.  No studies have reported the long‐term effects of entecavir switching in patients with multidrug resistance who developed resistance after lamivudine/adefovir sequential therapy. We evaluated the efficacy of 96 weeks of entecavir therapy in patients with resistance to lamivudine/adefovir sequential therapy. In total, 33 patients with chronic hepatitis B virus (HBV) infection with evidence of active viral replication (HBV DNA levels ≥105 copies/mL) or a history of treatment failure to lamivudine/adefovir sequential therapy between April 2007 and July 2009 were treated with entecavir (1.0 mg daily) for at least 48 weeks. The rates of alanine transaminase (ALT) normalization and HBV DNA negativity were 66.7% (14/21) and 24.2% (8/33) at 48 weeks, respectively. The ini... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4822830 Thu, 12 May 2011 23:00:00 +0100 4822830 http://www.medworm.com/index.php?rid=4806925&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01447.x Summary.  Chronic infection with hepatitis C virus (HCV), mainly genotype 1, has been shown to be associated with insulin resistance and type 2 diabetes. The mechanisms underlying this association are partly understood. Increased levels of tumor necrosis factor (TNF)‐α occurring in HCV infection have an important role in HCV‐mediated insulin resistance; however, other direct effects of HCV core protein on disrupting insulin signalling have been suggested. The insulin receptor substrate (IRS) proteins are key players in insulin signal transduction and are the major substrates of the insulin receptor. To further elucidate the direct effect of HCV core protein on insulin signalling. We studied the direct effects of HCV core protein in two cell lines transfected with HCV core protein. W... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4806925 Wed, 11 May 2011 18:00:10 +0100 4806925 http://www.medworm.com/index.php?rid=4806926&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01446.x Summary.  Hepatitis C virus (HCV) is commonly transmitted by intravenous drug use (IDU) but drug users are under represented in many treatment cohorts, this is because of the assumption of lowered treatment success. We assessed HCV treatment outcomes in active intravenous drug users and patients on opiate substitution therapy. The Tayside HCV treatment database was retrospectively analysed for consecutively treated patients based on risk factor for acquisition of HCV. Primary end point was sustained virological response (SVR). Two hundred and ninety‐one consecutively treated patients were assessed. The overall SVR rate was 55.3%. The SVR rates by risk factor were; Non‐IDU 61.4%, Ex‐IDU 54.8% and Active IDU 47.1% (P = n/s). In the groups G1 patients SVR was; Non‐IDU 52.7%, Ex�... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4806926 Sun, 08 May 2011 23:00:00 +0100 4806926 http://www.medworm.com/index.php?rid=4783434&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01462.x In conclusion, the hepatitis B stigma instrument showed reliability and construct validity. The relationship identified between familiarity and knowledge regarding HBV with lower stigma scores provides the basis for the development of interventions to reduce HBV stigma. (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4783434 Thu, 05 May 2011 17:15:31 +0100 4783434 http://www.medworm.com/index.php?rid=4783436&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01456.x Summary.  The natural history of hepatitis C virus (HCV) infection in adults has been established, but less is known about outcome in children. We conducted a retrospective review of patients referred to Birmingham Children’s Hospital Liver Unit, from 1991 till 2008, with the diagnosis of HCV was undertaken. Only children with documented positive HCV RNA and a minimum duration of follow‐up of 6 months were included. One hundred and thirty‐three children were identified. The route of transmission was transfusion acquired in 47%, vertically acquired in 49% and transplantation in 2%. Since 2000, most children were infected vertically. The overall rate of spontaneous viral clearance was 17.5% with higher clearance (27%) in the transfusion group compared to the vertically acquired gro... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4783436 Mon, 02 May 2011 23:00:00 +0100 4783436 http://www.medworm.com/index.php?rid=4687317&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01460.x (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4687317 Fri, 08 Apr 2011 17:09:47 +0100 4687317 http://www.medworm.com/index.php?rid=4687315&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2010.01429.x Summary.  Approximately 20% of hepatitis C virus (HCV) infected individuals clear the virus. Host factors that influence the course of HCV infection are still under investigation, and the data on the association of human leukocyte antigen (HLA) alleles and HCV clearance are scarce and controversial. The aims of this study were to investigate whether HLA alleles are associated with clearance of HCV infection in a highly admixed Brazilian population and whether these associations could be influenced by ethnicity and route of infection. HLA‐A, ‐B, ‐C, ‐DRB1 and ‐DQB1 genotyping were performed in 135 HCV‐infected Brazilian patients among which 45 cleared HCV infection (cases) and 90 had persistent viral infection (controls). Controls were matched by sex, ethnicity (withes and non... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4687315 Fri, 08 Apr 2011 17:08:49 +0100 4687315 http://www.medworm.com/index.php?rid=4687316&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01454.x Summary.  Hepatitis A is a widespread infectious disease. The prevalence of the disease is closely related to socioeconomic status (SES) and environmental factors. Understanding its prevalence is essential for instituting appropriate precautions. The aim of this study was to determine the prevalence of hepatitis A and evaluate the associated demographic features in children and young adults in Istanbul. In total, 630 individuals between the ages of 5–24 were included in the study. They were classified into four age groups (5–9, 10–14, 15–19 and 20–24 years). The seropositivity of hepatitis A in the whole study population was 40%. Age‐specific prevalence was 11.4% in children 5–9 years old, 29% in those 10–14 years old, 49.7% in those 15–19 years old and 69% in tho... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4687316 Wed, 06 Apr 2011 23:00:00 +0100 4687316 http://www.medworm.com/index.php?rid=4672294&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01455.x Summary.  We compared in vivo hepatic 31P magnetic resonance spectroscopy (31P MRS) and hepatic vein transit times (HVTT) using contrast‐enhanced ultrasound with a microbubble agent to assess the severity of hepatitis C virus (HCV)‐related liver disease. Forty‐six patients with biopsy‐proven HCV‐related liver disease and nine healthy volunteers had 31P MRS and HVTT performed on the same day. 31P MR spectra were obtained at 1.5 T. Peak areas were calculated for metabolites, including phosphomonoesters (PME) and phosphodiesters (PDE). Patients also had the microbubble ultrasound contrast agent, Levovist (2 g), injected into an antecubital vein, and time‐intensity Doppler ultrasound signals of the right and middle hepatic veins were measured. The HVTT was calculated as the t... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4672294 Sun, 03 Apr 2011 23:00:00 +0100 4672294 http://www.medworm.com/index.php?rid=4672293&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01458.x Summary.  The aim of the study was to investigate the prevalence of mutations of basal core promoter (BCP) and precore (PreC) region of hepatitis B virus (HBV) and their association with hepatocellular carcinoma. A total of 341 untreated older HBV patients were divided into three groups: chronic hepatitis B (CHB, 185), cirrhotic hepatocellular carcinoma (LC‐HCC, 113) and non‐cirrhotic hepatocellular carcinoma (non‐LC‐HCC, 43). HBV BCP and PreC mutations and genotypes were determined by direct sequencing. Using univariate analysis, age (≥45 years), single mutations including A1896 and A1899 and multiple mutations T1762/A1764 + A1896, T1762/A1764 + A1899 and T1762/A1764 + A1896 + A1899 were more frequently detected in LC‐HCC and non‐LC‐HCC patients than in C... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4672293 Sun, 03 Apr 2011 23:00:00 +0100 4672293 http://www.medworm.com/index.php?rid=4672292&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01459.x Summary.  It is well known that the seroconversion rate of patients following hepatitis B virus (HBV) vaccination is lower in uraemic than healthy subjects. A variety of inherited or acquired factors have been implicated in this diminished response, and the high prevalence of hepatitis C virus (HCV) infection among patients on maintenance dialysis has been suggested to play a role. However, the impact of HCV on the immune response to HB vaccine in patients receiving long‐term dialysis is not entirely understood. Here, we evaluate the influence of HCV infection on the immunological response to HBV vaccine in dialysis population by performing a systematic review of the literature with a meta‐analysis of clinical studies.We used the random‐effects model of DerSimonian and Laird with h... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4672292 Thu, 31 Mar 2011 23:00:00 +0100 4672292 http://www.medworm.com/index.php?rid=4645654&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2010.01421.x In this study, we detected abundant soluble B7‐H3 (sB7‐H3) in the plasma of patients with chronic HBV infections. The increase of the plasma B7‐H3 was associated with the progression of liver cirrhosis and accompanied by decreased expression of B7‐H3 on hepatocytes. The identification analysis suggests that the plasma B7‐H3 might be derived from the membrane‐bound B7‐H3 on hepatocytes. A functional study showed that immobilized (4Ig) B7‐H3Ig fusion protein could inhibit TCR‐induced proliferation and IFN‐γ secretion of T cells, which could be partially blocked by soluble B7‐H3flag fusion protein. These results suggest that the reduced expression of B7‐H3 in the livers might temper the inhibition of T‐cell responses mediated by B7‐H3 expressed on hepatocytes and ... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4645654 Tue, 29 Mar 2011 17:04:06 +0100 4645654 http://www.medworm.com/index.php?rid=4628101&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01444.x Summary.  Hepatitis B virus (HBV) DNA levels and liver histological necroinflammation grades are correlated with the antiviral efficacy. It is necessary to clarify the relationship between HBV replication levels apportioned by the same hepatic parenchyma cell volume and severity of liver histological necroinflammation grades in both hepatitis B e antigen (HBeAg)‐positive and HBeAg‐negative chronic hepatitis B. The serum HBV DNA levels apportioned by the same hepatic parenchyma cell volume were compared between HBeAg‐positive and HBeAg‐negative chronic hepatitis B as well as among liver histological necroinflammation grades 1, 2, 3 and 4, respectively. There were no differences in the serum HBV DNA levels between HBeAg‐positive and HBeAg‐negative chronic hepatitis B as well as... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4628101 Thu, 24 Mar 2011 00:00:00 +0100 4628101 http://www.medworm.com/index.php?rid=4623441&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01451.x Summary.  Hepatitis C virus (HCV) nonstructural protein 3‐4A (NS3‐4A) is a complex composed of NS3 and its cofactor NS4A. It harbours serine protease as well as NTPase/RNA helicase activities and is essential for viral polyprotein processing, RNA replication and virion formation. Specific inhibitors of the NS3‐4A protease significantly improve sustained virological response rates in patients with chronic hepatitis C when combined with pegylated interferon‐α and ribavirin. The NS3‐4A protease can also target selected cellular proteins, thereby blocking innate immune pathways and modulating growth factor signalling. Hence, NS3‐4A is not only an essential component of the viral replication complex and prime target for antiviral intervention but also a key player in the persiste... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4623441 Wed, 23 Mar 2011 00:00:00 +0100 4623441 http://www.medworm.com/index.php?rid=4596611&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01452.x Summary.  To investigate the functions of signal transducers and activators of transcription 1 (STAT1)‐induced anti‐hepatitis C viral (HCV) effects, a stable Huh7.5 cell line (Huh7.5‐STAT1ER) was established that constitutively expresses a fusion protein (STAT1ER) of STAT1 and the mouse oestrogen receptor (ER), which forms STAT1ER homodimers after 4‐hydroxytamoxifen (4‐HT) treatment. This inducible and cytokine/receptor‐independent STAT1 activation system allowed us to investigate the anti‐HCV effects of STAT1ER activation after inducing IFN‐stimulated gene (ISG) expression. The anti‐HCV effects of dimerized STAT1ER fusion protein were determined by real‐time PCR in a time‐dependent fashion post‐HCV (JFH‐1) infection. HCV (JFH‐1) RNA decreased 48% at 72 h af... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4596611 Tue, 15 Mar 2011 00:00:00 +0100 4596611 http://www.medworm.com/index.php?rid=4582017&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2010.01384.x Summary.  Dendritic cells (DCs) are likely to play a key role in the compromised T‐cell function associated with hepatitis C Virus (HCV) infection. However, studies of DC function in HCV‐infected patients to date have yielded conflicting findings possibly because of patient and virus heterogeneity. Here, we report the characterization of monocyte‐derived DCs obtained from a homogenous cohort of women who were infected with HCV genotype 1b following exposure to contaminated anti‐D immunoglobulin from a single donor source. Patients included in the study had not received anti‐viral therapy and all had mild liver disease. We show that phenotypically normal monocyte‐derived dendritic cells (MDDCs) (CD11c+HLA−DR+CD1a+CD14lo) can be obtained from these patients. These cells respo... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4582017 Mon, 14 Mar 2011 00:00:00 +0100 4582017 http://www.medworm.com/index.php?rid=4582016&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01450.x This study was conducted to address this issue using serial HBV DNA assays in patients with persistently normal ALT (PNALT) over 10 years following spontaneous hepatitis B e antigen (HBeAg) seroconversion. Serial serum specimens (mean 9 samples per patient) of 62 patients with PNALT and no disease progression over 10 years (median 18.1 years) after spontaneous HBeAg seroconversion were assayed for HBV DNA. Excluding assays within 1 year after HBeAg seroconversion, 21% and 82.3% of the patients with PNALT had HBV DNA levels persistently lower than 4 log10 and 5 log10 copies/mL, respectively, and only 8% had a level ≥5 log10 copies/mL in at least two assays. Of the 27 patients with PNALT defined by ALT <30 U/L for male and <19 U/L for female, only 33% had serum HBV DNA le... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4582016 Mon, 14 Mar 2011 00:00:00 +0100 4582016 http://www.medworm.com/index.php?rid=4582015&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01453.x Summary.  Chronic hepatitis C virus (HCV) infection occurs in patients who fail to mount an effective T‐cell response against the virus. One hypothesis for poor anti‐viral immunity in these patients is that the virus impedes the immune response by disabling dendritic cells (DCs), cells that play a key role in pathogen recognition and initiation of adaptive immunity. Initial studies in the 1990s supported this hypothesis, as they clearly demonstrated that monocyte‐derived DCs obtained from patients with chronic HCV infection displayed a reduced ability to stimulate lymphocyte proliferation. However, over the last 20 years, the situation has become more ambiguous. Many studies support the initial observation of a DC defect, while others using different patient cohorts or technologi... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4582015 Mon, 14 Mar 2011 00:00:00 +0100 4582015 http://www.medworm.com/index.php?rid=4562230&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01443.x Summary.  MicroRNAs (miRNAs) are stably present in human serum. The relationship between circulating miRNAs and hepatitis B virus (HBV) infected liver disease has not been previously reported. Applied Biosystems array‐based miRNA expression profiling was performed on pooled sera obtained from identified groups of chronic asymptomatic carriers (ASC), patients with chronic hepatitis B (CHB) and HBV‐associated acute‐on‐chronic liver failure (ACLF), as well as healthy controls (HC). Nine miRNAs were verified in more clinical samples by RT‐PCR. The correlation between miRNAs expression and the relationship between miRNA levels and clinical characteristics was analysed. Results showed that circulating miRNAs were detected in all disease and control samples, and their numbers increase... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4562230 Mon, 07 Mar 2011 00:00:00 +0100 4562230 http://www.medworm.com/index.php?rid=4537145&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01449.x Summary.  Treatment with hepatitis C virus (HCV)‐NS3‐protease inhibitors lead to the selection of resistant variants. Viral kinetics and resistance profiles in patients who are re‐treated with the same protease inhibitor are unknown. Viral kinetics and NS3‐resistance mutations obtained by clonal sequencing of the NS3‐protease were analyzed in nine HCV‐genotype‐1‐infected nonresponder patients who were sequentially treated with boceprevir (400 mg t.i.d.) for 1 week, peginterferon‐alfa‐2b for 2 weeks and combination of the two for 2 weeks in varying order. In addition to predominant wild‐type isolates, previously described boceprevir‐resistant mutations (V36, T54, R155, A156, V170) were observed. Furthermore, two resistant mutations (Q41, F43) were detected ... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4537145 Tue, 01 Mar 2011 00:00:00 +0100 4537145 http://www.medworm.com/index.php?rid=4537144&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01437.x Summary.  Current guidelines recommend antiviral therapy in chronic hepatitis B (HBV) patients with significant histological disease. We aimed to compare histological fibrosis (METAVIR, ≥F2) in patients with HBV DNA ≥20 000 IU/mL vs≥2000 IU/mL and identify predictors of fibrosis. We performed prospective liver biopsies on 203 HBeAg‐negative patients in four groups: Group I (n = 55): HBV DNA ≥20 000 IU/mL and persistently elevated alanine aminotransferase (ALT) levels (PEALT; >40 U/L); Group II (n = 34): HBV DNA ≥20 000 IU/mL and persistently normal ALT (PNALT); Group III (n = 40): HBV DNA <20 000 IU/mL and PEALT; and Group IV (n = 74): HBV DNA <20 000 IU/mL, and PNALT. We reanalysed all groups in relation to updated cut‐off for... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4537144 Tue, 01 Mar 2011 00:00:00 +0100 4537144 http://www.medworm.com/index.php?rid=4537143&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01442.x In conclusion, the prevalence of OCI after SVR is comparable in individuals with or without past exposure to HBV. HCV loads and liver alterations in OCI appear to be unaffected by low‐level HBV DNA carriage. (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4537143 Tue, 01 Mar 2011 00:00:00 +0100 4537143 http://www.medworm.com/index.php?rid=4537142&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01448.x In this study, flares related to NA therapy never led to immune control and sustained disease remission, and sometimes resulted in decompensated liver disease. (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4537142 Tue, 01 Mar 2011 00:00:00 +0100 4537142 http://www.medworm.com/index.php?rid=4513801&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01445.x Summary.  Hepatitis C virus (HCV) treatment requires maximal adherence to pegylated interferon (Peg‐IFN) and ribavirin to achieve a sustained virologic response (SVR). Neutropenia is the most common cause for Peg‐IFN dose reduction. Our objectives were to evaluate the effectiveness, safety and cost‐effectiveness of granulocyte colony‐stimulating factor (G‐CSF) versus Peg‐IFN dose reduction for HCV therapy‐associated neutropenia in treatment naïve adults. We conducted a systematic review to identify controlled trials and observational studies. Study selection, quality assessment and data extraction were completed independently by two investigators. Cost‐effectiveness and cost‐utility analyses compared G‐CSF with dose reduction. Nineteen studies were included. In one t... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4513801 Thu, 24 Feb 2011 00:00:00 +0100 4513801 http://www.medworm.com/index.php?rid=4508558&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01439.x Summary.  The triglycerides × glucose (TyG) index is a recently proposed surrogate marker of insulin resistance (IR), calculated from fasting plasma triglyceride and glucose concentrations. We tested the host and viral factors associated with Tyg and homeostasis model assessment (HOMA) scores, comparing their associations with histological features and with sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C(G1CHC). Three hundred and forty consecutive patients with G1CHC were considered. All had a liver biopsy scored by one pathologist for staging and grading (Scheuer), and graded for steatosis, which was considered moderate–severe if ≥30%. Anthropometric and metabolic measurements, including IR measured by both HOMA and TyG, were registered. By ... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4508558 Tue, 22 Feb 2011 00:00:00 +0100 4508558 http://www.medworm.com/index.php?rid=4491143&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01440.x We examined trends in the incidence of HCC among a population‐based cohort of people infected with HBV or HCV. HBV and HCV cases notified to the New South Wales Health Department between 1992 and 2007 were linked to the Central Cancer Registry, Registry of Births, Deaths and Marriages, and National HIV/AIDS Registries. Crude HCC incidence rates were estimated using person‐time methodology. Age‐standardized incidence rates were calculated using the 2001 Australian population. Trends in incidence were examined using join point regression models. Between 1992 and 2007, 1201 people had a linked HCC record: 556 of those with HBV; 592 with HCV; 45 with HBV/HCV co‐infection; and 8 with HIV co‐infection. The overall age‐standardized HCC incidence rates declined non‐significantly from... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4491143 Thu, 17 Feb 2011 00:00:00 +0100 4491143 http://www.medworm.com/index.php?rid=4478776&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01438.x This study aimed to explore GSTP1 promoter methylation status and oxidative stress in such patients. DNA was extracted from peripheral blood mononuclear cells (PBMCs) of patients with acute‐on‐chronic liver hepatitis B‐induced liver failure, chronic hepatitis B (CHB) and normal controls, followed by sodium‐bisulfite treatment and methylation‐specific PCR (MSP) analysis. Plasma malondialdehyde (MDA) adducts levels were detected by enzyme‐linked immunosorbent assay as oxidative stress marker. Model for end‐stage liver disease (MELD) score was employed to estimate the severity of the liver failure. Eleven of 35 patients with acute‐on‐chronic liver failure and 3 of 35 patients with stab le hepatitis B displayed GSTP1 promoter methylation, and the difference was significant (�... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4478776 Tue, 15 Feb 2011 00:00:00 +0100 4478776 http://www.medworm.com/index.php?rid=4447022&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01434.x Summary.  Chronic hepatitis C infection is associated with hypolipidaemia that resolves with viral clearance. Lipid levels in a subgroup of patients rebound to levels that may increase the risk of coronary heart disease. The impact of acute hepatitis C infection and its clearance on lipid levels is unknown. We undertook a retrospective evaluation of subjects with acute hepatitis C infection evaluating lipid levels before, during and following acute infection. Thirty‐eight subjects with acute hepatitis C infection had lipid levels available. Twelve patients had pre‐infection and intra‐infection lipid levels available. Cholesterol (197.8–152.4 mg/dL, P = 0.025), low‐density lipoprotein (LDL) (116.1–76.3 mg/dL, P = 0.001) and non‐high‐density lipoprotein (non‐H... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4447022 Tue, 08 Feb 2011 00:00:00 +0100 4447022 http://www.medworm.com/index.php?rid=4447021&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01436.x Summary.  The aim of this study was to examine the contribution of hepatitis B virus (HBV) and hepatitis C virus (HCV) to pregnancy‐related complications including gestational diabetes mellitus (GDM), preterm birth (PTB), intrauterine growth restriction (IUGR), pre‐eclampsia, antepartum haemorrhage and cholestasis. The Nationwide Inpatient Sample was queried for all pregnancy‐related discharges, pregnancy complications and viral hepatitis from 1995 to 2005. Logistic regression was used to examine the association between HBV, HCV, HBV + HCV and pregnancy‐related complications including GDM, PTB, IUGR, pre‐eclampsia, antepartum haemorrhage, cholestasis and caesarean delivery. Model covariates included maternal age, race, insurance status, substance use and medical complicatio... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4447021 Tue, 08 Feb 2011 00:00:00 +0100 4447021 http://www.medworm.com/index.php?rid=4420440&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2010.01426.x This study explores family physicians’ knowledge, attitudes and practices associated with providing care for HCV infection. Seven hundred and forty‐nine members of the College of Family Physicians of Canada (CFPC) completed a self‐administered survey examining knowledge, attitudes and behaviours regarding HCV infection screening and care. Multivariate analyses were performed using the outcome, HCV care provision, and variables based on a conceptual model of practice guideline adherence. Family physicians providing basic–advanced HCV care were more likely to be older, practice in a rural setting, have injection drug users (IDU) in their practice and have higher levels of knowledge about the initial assessment (OR = 1.77; 95% CI = 1.23–2.54) and treatment of HCV (OR = 1... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4420440 Tue, 01 Feb 2011 00:00:00 +0100 4420440 http://www.medworm.com/index.php?rid=4395538&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2010.01381.x Summary.  The aim of this study was to estimate the prevalence and identify the risk factors of hepatitis C virus (HCV) infection among healthy Egyptian children. A representative random sample of 500 children, age between 6 and 15 years, was selected from 10 schools in Alexandria, Egypt. A questionnaire was used to collect demographic data and potential risk factors, while blood samples were collected and analyzed for antibodies to HCV (anti‐HCV). Positive sera were further confirmed by HCV‐RNA. HCV seroprevalence of 5.8% was found, with HCV viraemia in 75% of the studied children. The prevalence of anti‐HCV increased with age from 0% in children aged 6–7 years to 16% in those of 15 years old. It was also shown that history of previous blood transfusion (odds ratio[OR] =... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4395538 Mon, 24 Jan 2011 00:00:00 +0100 4395538 http://www.medworm.com/index.php?rid=4395537&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2010.01433.x Summary.  Elastometry has demonstrated good accuracy, but little is known about its reproducibility. The aim of this study was to assess the intra‐ and inter‐operator reproducibility of liver stiffness measurement among hepatitis C virus (HCV)‐infected patients in Egypt. The study was conducted among HCV‐infected patients referred for treatment evaluation in two hepatitis treatment centres of Cairo. Two operators took liver stiffness measurement two times per patient the same day. Intra‐ and inter‐reproducibility were estimated by different methods: Bland and Altman graphics, variation coefficient, intraclass correlation coefficient and Kappa coefficient; 7.1 kPa was used as the threshold of significant (≥F2) fibrosis whenever needed. Fifty‐eight patients were included ... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4395537 Mon, 24 Jan 2011 00:00:00 +0100 4395537 http://www.medworm.com/index.php?rid=4378983&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2011.01435.x Summary.  Drug resistance is a major limitation for the long‐term efficacy of antiviral therapy with nucleos(t)ide analogues (NAs) in chronic hepatitis B (CHB). Antiviral resistance mutations may pre‐exist in the overall viral population of untreated patients. We aimed to assess the prevalence of such hepatitis B virus (HBV) variants in a large cohort of NAs‐naïve patients with CHB and to explore possible association with viral and host variables. Serum samples from 286 NAs‐naïve consecutive patients with CHB were tested for serum HBV‐DNA, and 255 of them having HBV‐DNA > 1000 IU/mL were further analysed for drug resistance mutations by INNO‐LiPA HBV DRv2/v3. NAs‐naïve patients analysed were mainly men (73%), Caucasians (85%), hepatitis B e Antigen (HBeAg) neg... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4378983 Fri, 21 Jan 2011 00:00:00 +0100 4378983 http://www.medworm.com/index.php?rid=4373815&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2010.01424.x Summary.  Chronic hepatitis C virus (HCV) infection is associated with chronic inflammation of liver, which leads to the development of cirrhosis and hepatocellular carcinoma (HCC). Because of severe side effects and only a 50–70% cure rate in genotype 1 HCV‐infected patients upon current standard treatment with pegylated interferon‐α plus ribavirin, new therapeutic regimens are still needed. San‐Huang‐Xie‐Xin‐Tang (SHXT) is a transitional Chinese herbal formula, composed of Rhei rhizoma, Scutellaria radix and Coptidis rhizome, and possesses anti‐inflammatory effect. Here, we describe a (+)‐catechin‐containing fraction extracted from SHXT, referred as SHXT‐frC, exhibited effective inhibition of HCV replication, with selectivity index value (SI; CC50/EC50) of 84, an... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4373815 Thu, 20 Jan 2011 00:00:00 +0100 4373815 http://www.medworm.com/index.php?rid=4373816&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2010.01432.x Summary.  Hepatitis B virus (HBV) infection may run undetected. Unawareness of an ongoing infection delays the diagnosis of HBV‐related liver disease and favours the spread of the virus. We have evaluated among hepatitis B surface antigen–positive (HBsAg) inpatients admitted to a Southern Italian hospital the proportion of those aware of their carrier status and correlated the status to signs of liver disease. All patients admitted to the San Giovanni Rotondo Hospital from March 2008 to July 2009 were tested for HBV and hepatitis C virus (HCV) markers, and those positive for HBsAg were interviewed and underwent examinations for liver function and abdominal ultrasound. Overall, of 25 000 patients admitted during the observation period 311 (1.2%) were positive for HBsAg, most of them... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4373816 Wed, 19 Jan 2011 00:00:00 +0100 4373816 http://www.medworm.com/index.php?rid=4356950&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2010.01420.x (Source: Journal of Viral Hepatitis) Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4356950 Tue, 18 Jan 2011 13:41:35 +0100 4356950 http://www.medworm.com/index.php?rid=4363980&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2010.01430.x Summary.  CD4 T‐cell function is crucial for the eradication of HCV, and insufficient function is observed in chronic carriers. The monitoring of T‐cell responses is complicated by the scarcity of antigen‐specific T cells and the relative inefficiency of virus‐specific T cells to produce effector cytokines. CD154 is a marker of activation expressed on T cells induced through their T‐cell receptor. We analysed CD4 T‐cell responses in 72 patients with chronic or resolved HCV infection (23 treatment naïve, 49 treatment experienced, including 16 who had achieved a sustained response). In an additional prospective protocol, 20 of the chronically infected patients were analysed before and after 8–12 weeks of combination therapy with peg‐interferon‐α and ribavirin. T‐cel... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4363980 Tue, 18 Jan 2011 00:00:00 +0100 4363980 http://www.medworm.com/index.php?rid=4363979&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2010.01431.x Summary.  Whether HIV controllers, patients who spontaneously control HIV viraemia, are able to control hepatitis C virus (HCV) infection, in terms of spontaneous clearance or lower HCV replication, is not well understood. To assess to what extent Caucasian HIV controllers are able to control HCV replication and potential associated factors, plasma HIV‐1 and HCV RNA levels, anti‐HCV antibodies, HCV genotype and human leucocyte antigens (HLA) typing were determined in samples from 75 HIV controllers (33 viraemic controllers, <1000 HIV‐1 RNA copies/mL, and 42 elite controllers, <40 HIV‐1 RNA copies/mL) and compared with 261 HIV‐infected noncontrollers. We did not find differences in the HCV spontaneous clearance rates between groups. However, we interestingly found a lo... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4363979 Tue, 18 Jan 2011 00:00:00 +0100 4363979 http://www.medworm.com/index.php?rid=4339447&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2010.01423.x Summary.  Quantification of HBeAg levels has been found to be useful in monitoring and predicting the outcomes of interferon and lamivudine treatment in HBeAg‐positive patients. The aim of this study was to determine whether quantification of HBeAg at baseline and on treatment could predict which patients would achieve HBeAg seroconversion after 96 weeks of entecavir therapy. Sixty‐five HBeAg‐positive naïve chronic hepatitis B patients who were treated with entecavir at a dose of 0.5 mg once daily for 96 weeks were evaluated. Serum HBV DNA levels were assessed at baseline, week 24, 48 and 96; serum HBeAg levels were assessed at baseline, week 12, 24, 48, 72 and 96. Serum HBeAg levels were associated with a higher likelihood of HBeAg seroconversion to entecavir at weeks 96 th... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4339447 Thu, 13 Jan 2011 00:00:00 +0100 4339447 http://www.medworm.com/index.php?rid=4339446&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2010.01425.x Summary.  Single nucleotide polymorphisms (SNPs) upstream of IL28B predict the outcome of treatment in chronic hepatitis C virus (HCV) infection, but their impact on viral kinetics and relation to other predictors are not well known. Here, two SNPs, rs12979860 and rs8099917, were analysed and related to early viral kinetics during treatment in 110 patients with HCV genotype 1 infection. The reduction of HCV RNA after 7 days of therapy was more pronounced (P < 0.0001) in patients with CCrs12979860 or TTrs8099917 than in patients carrying TTrs12979860 or GGrs8099917, respectively. The two SNPs were in linkage disequilibrium (d’ = 1, r2 = 0.44), but CCrs12979860 was less common (43%vs 71%) than TTrs8099917. Patients carrying both CCrs12979860 and TTrs8099917 genotypes ach... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4339446 Thu, 13 Jan 2011 00:00:00 +0100 4339446 http://www.medworm.com/index.php?rid=4339448&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2010.01422.x The objective of this analysis was to develop a model to identify nonrapid virologic response (non‐RVR) patients who may be candidates for intensified therapy that would increase treatment response. The retrospective analysis included non‐RVR patients from four trials of 48‐week peginterferon alfa‐2a/ribavirin treatment. Patients were grouped into those who cleared virus between weeks 5 and 12 (complete early virologic responders, cEVR) or between weeks 13 and 24 (slow responders). A model was developed to predict relapse at the end of follow‐up (week 72). An optimal model was evaluated and compared with current practice by using receiver operating characteristic curves, sensitivity and specificity. In total, 539 non‐RVR patients were eligible for analysis of which 72% experien... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4339448 Wed, 12 Jan 2011 00:00:00 +0100 4339448 http://www.medworm.com/index.php?rid=4332867&cid=s_33105_20_f&fid=33105&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2893.2010.01417.x Summary.  The impact of antiretroviral drug exposure and associated lipodystrophy and/or insulin resistance (IR) on advanced liver fibrosis in HIV/HCV‐coinfected patients is not fully documented. We determined the prevalence of advanced liver fibrosis (defined by hepatic stiffness ≥9.5 kPa) and associated factors, focusing on the impact of highly active antiretroviral therapy and its major adverse effects (lipodystrophy and IR), in 671 HIV/HCV‐coinfected patients included in the ANRS CO13 HEPAVIH cohort. One hundred ninety patients (28.3%) had advanced liver fibrosis. In univariate analysis, advanced liver fibrosis was significantly associated with male sex, higher body mass index, HCV infection through intravenous drug use, a lower absolute CD4 cell count, a longer history of an... Journal of Viral Hepatitis journals http://www.medworm.com/rss/comments.php?id=4332867 Tue, 11 Jan 2011 00:00:00 +0100 4332867