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Despite the availability of highly effective and well-tolerated direct-acting antivirals, not all patients with chronic hepatitis C virus infection receive treatment. This retrospective, multi-centre, noninterventional, case-control study identified patients with chronic hepatitis C virus infection initiating (control) or not initiating (case) treatment at 43 sites in Germany from September 2017 to June 2018. It aimed to compare characteristics of the two patient populations and to identify factors involved in patient/physician decision to initiate/not initiate chronic hepatitis C virus treatment, with a particular focus on historical barriers. Overall, 793 patients were identified: 573 (72%) who received treatment and 220 (28%) who did not. In 42% of patients, the reason for not initiating treatment was patient wish, particularly due to fear of treatment (17%) or adverse events (13%). Other frequently observed reasons for not initiating treatment were in accordance with known historical barriers for physicians to initiate therapy, including perceived or expected lack of compliance (14.5%), high patient age (10.9%), comorbidities (15.0%), alcohol abuse (9.1%), hard drug use (7.7%), and opioid substitution therapy (4.5%). Patient wish against therapy was also a frequently reported reason for not initiating treatment in the postponed (35.2%) and not planned (47.0%) subgroups; of note, known historical factors were also common reasons for postponing treatment. Real-world and clinical trial evidence is accumulating, which suggests that such historical barriers do not negatively impact treatment effectiveness. Improved education is key to facilitate progress towards the World Health Organization target of eliminating viral hepatitis as a major public health threat by 2030., Competing Interests: PB has served as a speaker, a consultant and an advisory board member for AbbVie, Falk, Gilead, Intercept, Merck/MSD, and Norgine, and has received research funding from AbbVie, Falk, Gilead, Intercept, Merck/MSD, and Norgine. HH has served as a speaker and an advisory board member for AbbVie, Gilead, Janssen, MSD, and ViiV Healthcare. SM has served as a speaker and an advisory board member for AbbVie, Gilead, Janssen, and MSD. HG has served as a speaker and a consultant for AbbVie, Gilead, and Sanofi-Aventis; he has served as a speaker and an advisory board member for AbbVie, Gilead, and MSD. DH is an employee of AbbVie Inc and may own stocks and shares in AbbVie Inc. BK is an employee of AbbVie Inc and may own stocks and shares in AbbVie Inc. AGPS is an employee of AbbVie Inc and may own stocks and shares in AbbVie Inc. CN has served as a speaker, a consultant and an advisory board member for AbbVie, Alexion, Biogen, Bristol-Myers Squibb, Falk, Gilead, Janssen, MSD, Sanofi-Genzyme, and Shire-Takeda and has received research funding from AbbVie, Alexion, Biogen, Bristol-Myers Squibb, Falk, Gilead, Janssen, MSD, Sanofi-Genzyme, and Shire-Takeda. TB has served as a speaker and a consultant for AbbVie, Alexion, Bayer, Bristol-Myers Squibb, Eisai, Gilead, Humedics, Intercept, Ipsen, Janssen, Merck/MSD, Novartis, and Sequana Medical, and has received research funding from AbbVie, Alexion, Bayer, Bristol-Myers Squibb, Eisai, Gilead, Humedics, Intercept, Ipsen, Janssen, Merck/MSD, Novartis, and Sequana Medical. AbbVie sponsored the study, and also contributed to its design, and participated in the collection, analysis, and interpretation of the data and in the writing, reviewing, and approval of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

Background: For treatment of genotype 1a (GT1a) infection with elbasvir/grazoprevir, the German guidelines recommend a differentiated approach depending on baseline viral load (BVL). For low BVL ≤800 000 IU/mL, treatment with 12 weeks elbasvir/grazoprevir should be considered, whereas for high BVL >800 000 IU/mL, this regimen is only recommended in nonstructural protein 5A (NS5A) resistance-associated substitutions (RAS) absence. With present NS5A RAS or when RAS-testing is not available, 16 weeks elbasvir/grazoprevir + ribavirin is preferred. Here, we investigated the adherence to these recommendations and the effectiveness of elbasvir/grazoprevir in a large German Hepatitis C-Registry GT1a cohort., Methods: From September 2016 until July 2018, 195 GT1a-infected patients were treated with elbasvir/grazoprevir ± ribavirin for 12-16 weeks. The primary outcome was per protocol SVR12 or SVR24., Results: Mean age was 50 years, 89% were male, 19% had cirrhosis, 72% were treatment-naïve. Forty-five percent had low BVL ≤800 000 IU/mL, 55% high BVL >800 000 IU/mL, of whom 49 vs. 42% were baseline RAS-tested. Four patients with high (7.7%) and two with low BVL (5%) had NS5A RAS of whom 50% received elbasvir/grazoprevir+ribavirin, respectively. Ninety-four percent of patients with low and 65% with high BVL received elbasvir/grazoprevir without ribavirin. Thirty-five percent of patients with high BVL received ribavirin, mostly without prior RAS-testing. Per protocol sustained virologic response (SVR) by low vs. high BVL was 98.8 and 95.1%. All patients with NS5A RAS achieved SVR., Conclusions: In German, real-world most patients received elbasvir/grazoprevir without ribavirin. Ribavirin was mainly added in GT1a patients >800 000 IU/mL, who were not NS5A RAS tested. SVR rates were consistently high and comparable to clinical trial results., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Hepatitis C virus infection is causing chronic liver disease, cirrhosis, and hepatocellular carcinoma. By combining direct-acting antivirals (DAAs), high sustained virologic response rates (SVRs) can be achieved. Resistance-associated substitutions (RASs) are commonly observed after DAA failure, and especially nonstructural protein 5A (NS5A) RASs may impact retreatment options. 1-3 Data on retreatment of DAA failure patients using first-generation DAAs are limited. 4-7 Recently, a second-generation protease- and NS5A-inhibitor plus sofosbuvir (voxilaprevir/velpatasvir/sofosbuvir [VOX/VEL/SOF]) was approved for retreatment after DAA failure. 8 However, this and other second-generation regimens are not available in many resource-limited countries or are not reimbursed by regular insurance, and recommendations regarding the selection of retreatment regimens using first-generation DAAs are very important. This study aimed to analyze patients who were re-treated with first-generation DAAs after failure of a DAA combination therapy., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: The once-daily, ribavirin-free, pangenotypic, direct-acting antiviral regimen, glecaprevir coformulated with pibrentasvir, has shown high rates of sustained virological response in phase 2 and 3 studies. We aimed to assess the efficacy and safety of 12 weeks of coformulated glecaprevir and pibrentasvir in patients with hepatitis C virus (HCV) infection and compensated cirrhosis., Methods: We did this single-arm, open-label, multicentre phase 3 study at 40 sites in Belgium, Canada, Germany, South Africa, Spain, and the USA. We enrolled patients aged 18 years or older with HCV genotype 1, 2, 4, 5, or 6 infection and compensated cirrhosis. Patients were either HCV treatment-naive or had not responded to treatment with interferon or pegylated interferon with or without ribavirin, or sofosbuvir plus ribavirin with or without pegylated interferon. Oral glecaprevir (300 mg) coformulated with pibrentasvir (120 mg) was administered once daily for 12 weeks. The primary efficacy endpoint was sustained virological response at post-treatment week 12 (HCV RNA <15 IU/mL). We assessed efficacy and safety in all patients who received at least one dose of study drug (intention-to-treat population). This study is registered with ClinicalTrials.gov, number NCT02642432., Findings: Between Dec 7, 2015, and May 4, 2016, we enrolled 146 patients with compensated cirrhosis, of whom 48 (33%) had genotype 1a HCV infection, 39 (27%) had genotype 1b infection, 34 (23%) had genotype 2 infection, 16 (11%) had genotype 4 infection, two (1%) had genotype 5 infection, and seven (5%) had genotype 6 infection. 12 weeks after treatment, 145 patients (99%, 95% CI 98-100) achieved sustained virological response, with one (1%) relapse at post-treatment week 8. We recorded 101 (69%) adverse events, of which 65 (64%) were mild. The most common adverse events were fatigue (n=28 [19%]) and headache (n=20 [14%]). 11 (8%) patients had serious adverse events, none of which were deemed related to study drugs. No patients had elevations in alanine aminotransferase and no patients prematurely discontinued treatment because of adverse events., Interpretation: Our results show that 99% of patients treated with once-daily glecaprevir plus pibrentasvir achieved a sustained virological response at 12 weeks. Furthermore, this drug regimen had a favourable safety profile in previously treated or untreated patients with chronic HCV genotype 1, 2, 4, 5, or 6 infection and compensated cirrhosis. These findings could help simplify treatment algorithms and reduce treatment burden., Funding: AbbVie., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: Neuropsychiatric symptoms of hepatitis C virus (HCV) infection and during peginterferon α therapy have been investigated in the chronic stage of the infection, but have not been described during the acute phase of the disease so far. We therefore evaluated anxiety and depression in patients with acute hepatitis C by the Hospital Anxiety and Depression Scale (HADS) within a clinical trial., Methods: Data were analysed from the German Hep-Net Acute HCV-III study. Anxiety and depression were characterized by an anxiety (HADS-A) and a depression subscale (HADS-D). More than eight points in each subscale were considered clinically relevant. Data were prospectively collected at baseline, end of treatment and at the end of the study., Results: At baseline, a HADS-A above eight points was observed significantly more frequently than a HADS-D above eight points [n=23/103 (22%) vs. n=12/103 (12%); P=0.041].A pathological HADS-A or HADS-D score did not correlate with age, sex, IL28B genotype, the probable mode of infection, HCV genotype or severity of disease as investigated by alanine aminotransferase and bilirubin levels.Antiviral therapy did not influence anxiety as 12/50 (24%) of patients had HADS-A above 8 at the end of therapy. The proportion of patients with HADS-D above eight points increased from 12% at baseline to 24% (n=12/50) at the end of therapy (P=0.06). HADS results were not associated with lost to follow-up or sustained virological response rates., Conclusion: HADS data in acute HCV infection indicate that anxiety and depression do not correlate with severity of the disease, mode of acquisition, lost to follow-up and sustained virological response rates.

Background: Early treatment of acute hepatitis C virus (HCV) infection with interferon alfa monotherapy is very effective, with cure rates of greater than 85%. However, spontaneous clearance of HCV occurs in 10-50% of cases. We aimed to assess an alternative treatment strategy of delayed antiviral therapy in patients who do not eliminate the virus spontaneously compared with immediate treatment., Methods: In our open-label phase 3 non-inferiority trial, we enrolled adults (≥18 years) with acute hepatitis C but no HIV or hepatitis B co-infection at 72 centres in Germany. We randomly allocated patients with symptomatic acute hepatitis C (1:1) to receive immediate pegylated interferon alfa-2b treatment for 24 weeks or delayed treatment with pegylated interferon alfa-2b plus ribavirin (for 24 weeks) starting 12 weeks after randomisation if HCV RNA remained positive. We used a computer-generated randomisation sequence and block sizes of eight, stratified by bilirubin concentration. We assigned all asymptomatic patients to immediate treatment with pegylated interferon alfa-2b for 24 weeks. The primary endpoint was sustained HCV RNA negativity in all randomly allocated participants who completed screening (intention-to-treat analysis), with a non-inferiority margin of 10%. For the primary analysis, we calculated the virological response of patients in the immediate and delayed treatment groups and an absolute risk difference stratified by bilirubin status. The trial was stopped early on advice from the study advisory committee because of slow recruitment of participants. This study is registered, number ISRCTN88729946., Findings: Between April, 2004, and February, 2010, we recruited 107 symptomatic and 25 asymptomatic patients. 37 (67%) of 55 symptomatic patients randomly allocated to receive immediate treatment and 28 (54%) of 52 symptomatic patients randomly allocated to receive delayed treatment had a sustained virological response (difference 13·7%, 95% CI -4·6 to 32·0; p=0·071). 18 (72%) of 25 asymptomatic patients had a sustained virological response. 22 (42%) of 52 symptomatic patients allocated to receive delayed treatment did not complete follow-up compared with 20 (25%) of 80 symptomatic or asymptomatic patients assigned immediate treatment (p=0·037). 11 symptomatic patients (21%) assigned delayed treatment had spontaneous HCV clearance. 14 patients who received delayed pegylated interferon alfa-2b plus ribavirin treatment and completed follow-up achieved sustained virological response., Interpretation: Delayed treatment is effective although not of equal efficacy to immediate treatment; coupled with the rate of spontaneous clearance it can reduce unnecessary treatment in closely monitored populations. Immediate treatment seems preferable in populations where loss to follow-up is great., Funding: German Network of Competence on Viral Hepatitis (HepNet, funded by the German Federal Ministry of Education and Research, grants 01KI0102, 01KI0401, and 01KI0601), MSD, Schering-Plough., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Unlabelled: Individualized treatment on the basis of early viral kinetics has been discussed to optimize antiviral therapy in chronic hepatitis C virus (HCV) infection. Individually tailored reduction in treatment duration in HCV type 1-infected patients represents one possible strategy. Four hundred thirty-three patients were randomly assigned to receive either 1.5 microg/kg peginterferon alfa-2b weekly plus 800-1,400 mg ribavirin daily for 48 weeks (n = 225, group A) or an individually tailored treatment duration (18-48 weeks; n = 208, group B). In the latter group, treatment duration was calculated using the time required to induce HCV RNA negativity (branched DNA [bDNA] assay; sensitivity limit, 615 IU/mL) multiplied by the factor 6. All bDNA negative samples were retested with the more sensitive transcription-mediated amplification (TMA) assay (sensitivity limit, 5.3 IU/mL). Sustained virologic response (SVR) rates were significantly lower in group B (34.6% versus 48.0% [P = 0.005]) due to higher relapse rates (32.7% versus 14.2% [P< 0.0005]). Important predictors of response were the levels of baseline viremia as well as the time to TMA negativity on treatment. Taking the simultaneous presence of low baseline viral load (<800,000 IU/mL) and a negative TMA test within the first 4 weeks as predictors for treatment response, SVR rates were comparable between both treatment schedules with an SVR probability of >80% obtained in patients treated for only 18 or 24 weeks., Conclusion: The individualized treatment strategy according to time to bDNA negativity failed to provide comparable efficacy compared with the standard of care. The inferiority of the individualized protocol may be explained by the use of a less sensitive HCV RNA assay, and also by underestimation of the importance of baseline viremia.

Early treatment of acute hepatitis C infection with interferon alfa-2b (IFN-alpha-2b) prevents chronicity in almost all patients. So far, no data are available on the long-term outcome after interferon (IFN) therapy of acute hepatitis C. The aim of this study was to assess the clinical, virological, and immunological long-term outcome of 31 successfully treated patients with acute hepatitis C infection who were followed for a median of 135 weeks (52-224 weeks) after end of therapy. None of the individuals had clinical evidence of liver disease. Alanine aminotransferase (ALT) levels were normal in all but 1 patient. Serum hepatitis C virus (HCV) RNA was negative throughout follow-up, even when investigated with the highly sensitive transcription-mediated amplification (TMA) assay (cutoff 5-10 IU/mL). In addition, no HCV RNA was detected in peripheral blood mononuclear cells (PBMC) of 15 cases tested. The patients' overall quality-of-life scores as determined by the SF-36 questionnaire did not differ from the German reference control cohort. Ex vivo interferon gamma (IFN-gamma) ELISPOT analysis detected HCV-specific CD4(+) T-helper cell reactivity in only 35% of cases, whereas HCV-specific CD8(+) T-cell responses were found in 4 of 5 HLA-A2-positive individuals. Anti-HCV antibody levels decreased significantly during and after therapy in all individuals. In conclusion, early treatment of symptomatic acute hepatitis C with IFN-alpha-2b leads to a long-term virological, biochemical, and clinical response. Waning of anti-HCV humoral immunity and presence of HCV-specific CD8(+) (but not CD4(+)) T cells highlights the complexity of T-cell and B-cell memory to HCV, which might be significantly altered by IFN treatment.

Evidence based clinical guidelines are implemented to treat patients efficiently that include efficacy, tolerability but also health economic considerations. This is of particular relevance to the new direct acting antiviral agents that have revolutionized treatment of chronic hepatitis C. For hepatitis C genotypes 2/3 interferon free treatment is already available with sofosbuvir plus ribavirin. However, treatment with sofosbuvir-based regimens is 10–20 times more expensive compared to pegylated interferon alfa and ribavirin (PegIFN/RBV). It has to be discussed if PegIFN/RBV is still an option for easy to treat patients. We assessed the treatment of patients with chronic hepatitis C genotypes 2/3 with PegIFN/RBV in a real world setting according to the latest German guidelines. Overall, 1006 patients were recruited into a prospective patient registry with 959 having started treatment. The intention-to-treat analysis showed poor SVR (GT2 61%, GT3 47%) while patients with adherence had excellent SVR in the per protocol analysis (GT2 96%, GT3 90%). According to guidelines, 283 patients were candidates for shorter treatment duration, namely a treatment of 16 weeks (baseline HCV-RNA <800.000 IU/mL, no cirrhosis and RVR). However, 65% of these easy to treat patients have been treated longer than recommended that resulted in higher costs but not higher SVR rates. In conclusion, treatment with PegIFN/RBV in a real world setting can be highly effective yet similar effective than PegIFN± sofosbuvir/RBV in well-selected naïve G2/3 patients. Full adherence to guidelines could be further improved, because it would be important in the new era with DAA, especially to safe resources. [ABSTRACT FROM AUTHOR]

This study demonstrates that a more precise prediction of the individual relapse risk in chronic hepatitis C virus genotype 1 infection can be obtained by kinetics of minimal residual viremia at weeks 4, 8, and 12 in combination with levels of baseline viremia. These data may also help to further individualize new protease inhibitor-based triple therapy regimens. [ABSTRACT FROM AUTHOR]

Background & Aims: IC41 is a synthetic peptide vaccine containing 7 relevant hepatitis C virus (HCV) T-cell epitopes and the T helper cell (Th)1/Tc1 adjuvant poly-L-arginine. IC41 has been shown to be safe and to induce HCV-specific interferon (IFN)-γ-secreting CD4+ and CD8+ T cells in healthy volunteers. We aimed to investigate whether IC41 is able to induce HCV-specific T-cell responses also in chronic hepatitis C patients. Methods: Sixty HLA-A2-positive chronic HCV patients not responding to or relapsing from standard therapy were randomized in a double-blind phase II study into 5 groups to receive 6 vaccinations of IC41 (3 different dose groups), HCV peptides alone, or poly-L-arginine alone. Results: IC41 was well tolerated, and no drug-related serious adverse events or induction of hepatitis were observed. T-cell proliferation was recorded in up to 67% of patients in the 3 IC41 vaccine groups but only in 17% of patients treated with peptides alone. IFN-γ enzyme-linked immunospot assay responses were observed exclusively in the IC41 groups with response rates up to 42%. There were 3 RNA responders with transient >1-log declines of HCV serum RNA associated with the strongest IFN-γ enzyme-linked immunospot assay values within all 60 patients. Conclusions: This study showed that the HCV peptide vaccine IC41 can induce HCV-specific Th1/Tc1 responses in a subset of difficult to treat HCV nonresponder patients despite persisting viremia. However, changes in HCV RNA occurred only in single patients. Because strongest T-cell responses were associated with HCV RNA decline, further studies with optimized vaccine regimens and combination therapies have been initiated. [Copyright &y& Elsevier]

Background & Aims: Standard therapy of patients with chronic hepatitis C virus (HCV) infected with HCV genotype-2 or -3 is the combination of pegylated interferon-α and ribavirin for 24 weeks. Whether shorter treatment durations are possible for these patients without compromising sustained virologic response rates is unknown. Methods: Patients chronically infected with HCV-2 (n = 39), HCV-2/3 (n = 1), or HCV-3 (n = 113) were treated with peginterferon-α-2a (180 μg/wk) plus ribavirin 800–1200 mg/day. HCV RNA was quantitatively assessed after 4 weeks. Patients with a rapid virologic response (HCV RNA below 600 IU/mL) were randomized for a total treatment duration of 16 (group A) or 24 weeks (group B). All patients with HCV RNA ≥600 IU/mL at week 4 (group C) were treated for 24 weeks. End-of-treatment and sustained virologic response were assessed by qualitative RT-PCR (sensitivity 50 IU/mL). Results: Only 11 of 153 patients (7%) were allocated to group C. End-of-treatment and sustained virologic response rates were 94% and 82%, (group A), 85% and 80% (group B), and 73% and 36% (group C), respectively. In patients infected with genotype HCV-3 and high viral load (>800,000 IU/mL), a significant lower sustained virologic response rate was found than in patients infected with HCV-3 and a viral load lower or equal to 800,000 IU/mL (59% vs 85%, respectively; P = .003). Conclusions: In HCV-2 and -3 (low viral load)-infected patients who have a rapid virologic response, treatment for 16 weeks with peginterferon-α-2a and ribavirin is sufficient. In patients infected by HCV-3 (high viral load), longer treatment may be necessary. [Copyright &y& Elsevier]

Background/Aims: A vigorous T-cell response is essential for the resolution of HCV infection. It is modified by co-stimulatory molecules that attenuate T-lymphocyte responses by binding to CTLA4. We investigated whether CTLA4 single nucleotide polymorphisms are associated with the resolution of infection or with the course of disease. Methods: We enrolled 127 individuals with self-limited and 947 patients with chronic HCV infection, of whom 560 were treated with interferon-α-based therapies, and 200 healthy controls. We analyzed CTLA4 polymorphisms −318C>T and +49A>G by melting curve analysis and reconstructed haplotypes. Results: CTLA4 haplotypes were distributed differently between men but not women with self-limited and chronic infection (p =0.043) but were not predictive of the stage of fibrosis in chronic carriers. Haplotypes were distributed differently between male but not female end-of-treatment responders and non-responders (p =0.025). The influence of CTLA4 haplotypes was more pronounced in “hard-to-treat” situations, i.e., treatment with interferon-α monotherapy or infection with HCV genotypes 1/4. Logistic regression analysis confirmed gender-specific risk factors for a virological non-response. Conclusions: CTLA4 polymorphisms are associated with the resolution of HCV infection. This study underlines the role of an efficient T-cell response in the clearance of HCV and sheds light on a gender-dependent difference of immune regulation. [Copyright &y& Elsevier]

Background & Aims: There is increasing interest in identifying patients with chronic hepatitis C genotype 2 or 3 infection in whom it is possible to lower the burden of therapy while retaining high levels of efficacy. Methods: Treatment-naive patients with chronic hepatitis C genotype 2/3 infection were randomized to receive peginterferon alfa-2b (1.5μg/kg/wk) for 24weeks (group A); peginterferon alfa-2b (1.0μg/kg/wk) for 24weeks (group B); or peginterferon alfa-2b (1.5μg/kg/wk) for 16weeks (group C), each in combination with weight-based ribavirin (800–1200mg/d). The study population comprised two cohorts: the Hep-Net cohort enrolled in Germany and an International cohort enrolled at study sites throughout Europe and Asia. The primary end point was sustained virological response (SVR). Results: The study included 682 patients; 80.2% had genotype 3 infection. In the intent-to-treat population, SVR rates were 66.5%, 64.3%, and 56.6% in groups A, B, and C, and were similar in Asian and white patients. Treatment differences (A vs. B and A vs. C) failed to reach the predefined margin for noninferiority of -10%; and thus groups B and C failed to show noninferiority relative to group A. Among patients with undetectable HCV RNA at week 4, SVR rates were 75.3%, 75.9%, and 72.4%, respectively. Relapse rates were 17.8%, 16.3%, and 29.3%, respectively. Treatment-emergent serious adverse events were highest in group A and lowest in group C, and adverse events leading to discontinuation were similar across treatment arms. Conclusions: For patients with chronic hepatitis C genotype 2/3 infection, 24weeks of peginterferon alfa-2b (1.5μg/kg/wk) plus weight-based ribavirin remains a standard-of-care therapy; however, treatment for 16weeks may be considered for patients with undetectable HCV RNA at week 4 of the treatment. [ABSTRACT FROM AUTHOR]

Abstract: We examined the effect of the hepatitis C virus (HCV) peptide vaccine IC41 on HCV-specific T-cell responses and virological relapse rates in patients with chronic HCV genotype 1 infection when added to pegylated interferon plus ribavirin standard therapy. 35 patients received 6 vaccinations with IC41 from weeks 28 to 48 of standard antiviral treatment and were followed-up for another 6 months. IC41 vaccination did not prevent HCV-RNA relapse in patients with ongoing interferon standard treatment but HCV-specific T-cell responses were inducible and were associated with lower relapse rates. An increase of HCV-specific T-cell responses occurred in 73% of patients, responses were more frequent and stronger in patients with sustained virologic response than in patients who relapsed. Optimized vaccine responses may enhance sustained virologic response rates obtained with standard treatment of chronic hepatitis C. [Copyright &y& Elsevier]

Background/Aims: Intercross studies in inbred mice susceptible or resistant to liver fibrosis revealed complement factor 5 as a quantitative trait gene associated with the development of fibrosis. In 277 patients with hepatitis C, two C5 SNPs, rs17611 and rs2300929, have been associated with advanced fibrosis. Methods: We investigated the association of these C5 SNPs with advanced fibrosis in 1435 HCV infected patients and in 1003 patients with other liver diseases. We performed genotyping with melting curve analysis using fluorescence resonance energy transfer probes in the LightCycler. Results: The defined high-risk genotypes (AA and TT) and alleles (A and T) were not associated with advanced fibrosis in HCV patients when Chi square testing and logistic regression analysis were applied (rs17611A 0.45 in F0-1 vs. 0.43 in F2-4, P =0.31; rs2300929T 0.91 F0-1 and 0.91 in F2-4, P =0.82). In the group of patients with liver diseases other than HCV we neither found an association of the C5 SNPs with advanced fibrosis nor an overrepresentation of the SNPs in patients with cirrhosis. Conclusions: We found no evidence that these C5 SNPs are genetic risk factors for the development of advanced fibrosis in chronic HCV infection or other chronic liver diseases. [Copyright &y& Elsevier]