Correlations of CTLA-4 gene polymorphisms and hepatitis C chronic infection

Background: Cytotoxic T lymphocyte-associated factor 4 (CTLA-4) functions as a negative regulator of T cell-mediated immune response. Molecular changes associated to CTLA-4 gene polymorphisms could reduce its ability to suppress and control lymphocyte proliferation. Aims: To evaluate the frequency of CTLA-4 gene polymorphisms in chronic hepatitis C virus (HCV) infected patients and correlate to clinical and histological findings. Methods: We evaluated 112 HCV-infected subjects prospectively selected and 183 healthy controls. Clinical and liver histological data were analysed. - 318C > T, A49G and CT60 CTLA-4 single-nucleotide polymorphisms (SNPs) were studied by PCR-RFLP and AT(n) polymorphism by DNA fragment analysis by capillary electrophoresis in automatic sequencer. Results: Eight AT repetitions in 3' UTR region were more frequent in HCV-infected subjects. We found a positive association of -318C and + 49G with HCV genotype 3 (P = 0.008, OR 9.13, P = 0.004, OR 2.49 respectively) and an inverse association of both alleles with HCV genotype 1 (P = 0.020, OR 0.19, P = 0.002, OR 0.38 respectively). Allele + 49G was also associated to aminotransferases quotients > 3 (qALT, P = 0.034, qAST, P = 0.041). Allele G of CT60 SNP was also associated with qAST > 3 (P = 0.012). Increased number of AT repetitions was positively associated to severe necroinflammatory activity scores in liver biopsies (P = 0.045, OR 4.62). Conclusion: CTLA-4 gene polymorphisms were associated to HCVinfection. Eight AT repetitions were more prevalent in HCV-infected subjects. - 318C and + 49G alleles were associated to genotypes 1 and 3 infections and increased number of AT repetitions in 3' UTR region favoured severe necroinflammatory activity scores in liver biopsies.

Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study.

BACKGROUND & AIMS: Hepatitis C virus (HCV) induces chronic infection in 50% to 80% of infected persons; approximately 50% of these do not respond to therapy. We performed a genome-wide association study to screen for host genetic determinants of HCV persistence and response to therapy. METHODS: The analysis included 1362 individuals: 1015 with chronic hepatitis C and 347 who spontaneously cleared the virus (448 were coinfected with human immunodeficiency virus [HIV]). Responses to pegylated interferon alfa and ribavirin were assessed in 465 individuals. Associations between more than 500,000 single nucleotide polymorphisms (SNPs) and outcomes were assessed by multivariate logistic regression. RESULTS: Chronic hepatitis C was associated with SNPs in the IL28B locus, which encodes the antiviral cytokine interferon lambda. The rs8099917 minor allele was associated with progression to chronic HCV infection (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.74-3.06; P = 6.07 x 10(-9)). The association was observed in HCV mono-infected (OR, 2.49; 95% CI, 1.64-3.79; P = 1.96 x 10(-5)) and HCV/HIV coinfected individuals (OR, 2.16; 95% CI, 1.47-3.18; P = 8.24 x 10(-5)). rs8099917 was also associated with failure to respond to therapy (OR, 5.19; 95% CI, 2.90-9.30; P = 3.11 x 10(-8)), with the strongest effects in patients with HCV genotype 1 or 4. This risk allele was identified in 24% of individuals with spontaneous HCV clearance, 32% of chronically infected patients who responded to therapy, and 58% who did not respond (P = 3.2 x 10(-10)). Resequencing of IL28B identified distinct haplotypes that were associated with the clinical phenotype. CONCLUSIONS: The association of the IL28B locus with natural and treatment-associated control of HCV indicates the importance of innate immunity and interferon lambda in the pathogenesis of HCV infection.

Vaniprevir with pegylated interferon alpha-2a and ribavirin in treatment-naïve patients with chronic hepatitis C: a randomized phase II study.

Vaniprevir (MK-7009) is a macrocyclic hepatitis C virus (HCV) nonstructural protein 3/4A protease inhibitor. The aim of the present phase II study was to examine virologic response rates with vaniprevir in combination with pegylated interferon alpha-2a (Peg-IFN-α-2a) plus ribavirin (RBV). In this double-blind, placebo-controlled, dose-ranging study, treatment-naïve patients with HCV genotype 1 infection (n = 94) were randomized to receive open-label Peg-IFN-α-2a (180 μg/week) and RBV (1,000-1,200 mg/day) in combination with blinded placebo or vaniprevir (300 mg twice-daily [BID], 600 mg BID, 600 mg once-daily [QD], or 800 mg QD) for 28 days, then open-label Peg-IFN-α-2a and RBV for an additional 44 weeks. The primary efficacy endpoint was rapid viral response (RVR), defined as undetectable plasma HCV RNA at week 4. Across all doses, vaniprevir was associated with a rapid two-phase decline in viral load, with HCV RNA levels approximately 3 log(10) IU/mL lower in vaniprevir-treated patients, compared to placebo recipients. Rates of RVR were significantly higher in each of the vaniprevir dose groups, compared to the control regimen (68.8%-83.3% versus 5.6%; P < 0.001 for all comparisons). There were numerically higher, but not statistically significant, early and sustained virologic response rates with vaniprevir, as compared to placebo. Resistance profile was predictable, with variants at R155 and D168 detected in a small number of patients. No relationship between interleukin-28B genotype and treatment outcomes was demonstrated in this study. The incidence of adverse events was generally comparable between vaniprevir and placebo recipients; however, vomiting appeared to be more common at higher vaniprevir doses. CONCLUSION: Vaniprevir is a potent HCV protease inhibitor with a predictable resistance profile and favorable safety profile that is suitable for QD or BID administration.

An integrated alcohol abuse and medical treatment model for patients with hepatitis C.

BACKGROUND: Patients with chronic hepatitis C virus (HCV) infection have high rates of alcohol consumption, which is associated with progression of fibrosis and lower response rates to HCV treatment. AIMS: This prospective cohort study examined the feasibility of a 24-week integrated alcohol and medical treatment to HCV-infected patients. METHODS: Patients were recruited from a hepatology clinic if they had an Alcohol Use Disorders Identification Test score >4 for women and >8 for men, suggesting hazardous alcohol consumption. The integrated model included patients receiving medical care and alcohol treatment within the same clinic. Alcohol treatment consisted of 6 months of group and individual therapy from an addictions specialist and consultation from a study team psychiatrist as needed. RESULTS: Sixty patients were initially enrolled, and 53 patients participated in treatment. The primary endpoint was the Addiction Severity Index (ASI) alcohol composite scores, which significantly decreased by 0.105 (41.7% reduction) between 0 and 3 months (P < 0.01) and by 0.128 (50.6% reduction) between 0 and 6 months (P < 0.01) after adjusting for covariates. Alcohol abstinence was reported by 40% of patients at 3 months and 44% at 6 months. Patients who did not become alcohol abstinent had reductions in their ASI alcohol composite scores from 0.298 at baseline to 0.219 (26.8% reduction) at 6 months (P = 0.08). CONCLUSION: This study demonstrated that an integrated model of alcohol treatment and medical care could be successfully implemented in a hepatology clinic with significant favorable impact on alcohol use and abstinence among patients with chronic HCV.

Estimating the net contribution of interleukin-28B variation to spontaneous hepatitis C virus clearance.

The identification of associations between interleukin-28B (IL-28B) variants and the spontaneous clearance of hepatitis C virus (HCV) raises the issues of causality and the net contribution of host genetics to the trait. To estimate more precisely the net effect of IL-28B genetic variation on HCV clearance, we optimized genotyping and compared the host contributions in multiple- and single-source cohorts to control for viral and demographic effects. The analysis included individuals with chronic or spontaneously cleared HCV infections from a multiple-source cohort (n = 389) and a single-source cohort (n = 71). We performed detailed genotyping in the coding region of IL-28B and searched for copy number variations to identify the genetic variant or haplotype carrying the strongest association with viral clearance. This analysis was used to compare the effects of IL-28B variation in the two cohorts. Haplotypes characterized by carriage of the major alleles at IL-28B single-nucleotide polymorphisms (SNPs) were highly overrepresented in individuals with spontaneous clearance versus those with chronic HCV infections (66.1% versus 38.6%, P = 6 × 10(-9) ). The odds ratios for clearance were 2.1 [95% confidence interval (CI) = 1.6-3.0] and 3.9 (95% CI = 1.5-10.2) in the multiple- and single-source cohorts, respectively. Protective haplotypes were in perfect linkage (r(2) = 1.0) with a nonsynonymous coding variant (rs8103142). Copy number variants were not detected. We identified IL-28B haplotypes highly predictive of spontaneous HCV clearance. The high linkage disequilibrium between IL-28B SNPs indicates that association studies need to be complemented by functional experiments to identify single causal variants. The point estimate for the genetic effect was higher in the single-source cohort, which was used to effectively control for viral diversity, sex, and coinfections and, therefore, offered a precise estimate of the net host genetic contribution.

Progression of liver fibrosis in blood donors infected with hepatitis C virus

Background/Aims. Chronic hepatitis by HCV is progressive towards cirrhosis, with variable rate. We evaluated the rate of fibrosis progression (RFP), risk factors associated with advanced fibrosis (F3 and F4), and estimated the evolution time to cirrhosis. Methods. We transversely selected 142 blood donors infected only with HCV, with a known route of infection, submitted to liver biopsy at admission. RFP= ratio between stage of fibrosis (METAVIR)/estimated duration of infection in years. Non-parametric tests and logistic regression analysis, with significance level of 5% were used. Results. Median RFP was 0.086 U/year (0.05 - 0.142). Ten patients had F4 and 25 had F3. Median RFP values were significantly different (p=0.001) from one age group at contamination to the others and ALT and AST levels. There were no differences in the expected evolution to cirrhosis between intermediate fibrosers (F2) and the rapid fibrosers (F3 and F4). The independent variables associated with advanced fibrosis were ALT (OR 7.2) and GGT (OR 6.4) and age at inclusion (OR 1.12). Conclusion. This study suggests that RFP is extremely variable, it is exponential with age, and mainly influenced by host characteristics, especially age at contamination and possibly ethnical group. These asymptomatic patients had high percentage of fibrosis F2, F3 and F4.

Hepatitis C infection: challenges in dental management and diagnosis of extrahepatic manifestations

Hepatitis C is associated with autoimmune diseases, hepatocellular carcinoma,and extrahepatic manifestations that, in conjunction, may seriously compromise the patient's quality of life. We herein describe a case of chronic hepatitis C with oral manifestations and discuss some implications for diagnosis and treatment. A 63-year-old woman complaining of spontaneous bleeding of the oral mucosa presented with bilateral asymmetric ulcers surrounded by white papules and striae on the buccal mucosa. Her medical history revealed leucopenia, thrombocytopenia, and skin lesions associated with chronic hepatitis C. Propranolol and ranitidine had recently been prescribed. Lichen planus, lichenoid reaction, and erythema multiforme were considered in the differential diagnosis. Histopathological analysis revealed lymphocytic infiltrate in a lichenoid pattern. The lesions partially healed after 1 week and completely regressed after 6 months, despite the maintenance of all medications; no recurrence was observed. The final diagnosis was oral lichen planus associated with hepatitis C. Chronic hepatitis C may present oral manifestations, which demand adjustments in dental treatment planning. Medication side effects may interfere with the clinical presentation and course of the disease and should be accounted for in the differential diagnosis. The possibility of spontaneous remission of oral lichen planus should always be considered, especially when putative etiological factors of a lichenoid lesion are withdrawn in an attempt to differentiate oral lichen planus from lichenoid lesions. This case emphasizes the importance of recognizing the extrahepatic manifestations of hepatitis C as a cause of increased morbidity.

Prevalence and risk factors of Hepatitis C virus infection in Brazil, 2005 through 2009: a cross-sectional study

Abstract Background Hepatitis C chronic liver disease is a major cause of liver transplant in developed countries. This article reports the first nationwide population-based survey conducted to estimate the seroprevalence of HCV antibodies and associated risk factors in the urban population of Brazil. Methods The cross sectional study was conducted in all Brazilian macro-regions from 2005 to 2009, as a stratified multistage cluster sample of 19,503 inhabitants aged between 10 and 69 years, representing individuals living in all 26 State capitals and the Federal District. Hepatitis C antibodies were detected by a third-generation enzyme immunoassay. Seropositive individuals were retested by Polymerase Chain Reaction and genotyped. Adjusted prevalence was estimated by macro-regions. Potential risk factors associated with HCV infection were assessed by calculating the crude and adjusted odds ratios, 95% confidence intervals (95% CI) and p values. Population attributable risk was estimated for multiple factors using a case–control approach. Results The overall weighted prevalence of hepatitis C antibodies was 1.38% (95% CI: 1.12%–1.64%). Prevalence of infection increased in older groups but was similar for both sexes. The multivariate model showed the following to be predictors of HCV infection: age, injected drug use (OR = 6.65), sniffed drug use (OR = 2.59), hospitalization (OR = 1.90), groups socially deprived by the lack of sewage disposal (OR = 2.53), and injection with glass syringe (OR = 1.52, with a borderline p value). The genotypes 1 (subtypes 1a, 1b), 2b and 3a were identified. The estimated population attributable risk for the ensemble of risk factors was 40%. Approximately 1.3 million individuals would be expected to be anti-HCV-positive in the country. Conclusions The large estimated absolute numbers of infected individuals reveals the burden of the disease in the near future, giving rise to costs for the health care system and society at large. The known risk factors explain less than 50% of the infected cases, limiting the prevention strategies. Our findings regarding risk behaviors associated with HCV infection showed that there is still room for improving strategies for reducing transmission among drug users and nosocomial infection, as well as a need for specific prevention and control strategies targeting individuals living in poverty.

The influence of viral genotypes and rejection episodes on the recurrence of hepatitis C after liver transplantation

Purpose. The aim of this study was to report the influence of hepatitis C virus (HCV) genotype and rejection episodes on the outcome of orthotopic liver transplantation (OLT), hepatitis recurrence, and progression to graft cirrhosis after OLT. Methods. Fifty-three patients who all had undergone OLT for end-stage liver cirrhosis were selected for this study. Hepatitis C genotype was determined. Recurrent hepatitis and rejection were diagnosed based on elevated liver function tests and a liver biopsy. Results. The patients were followed up for a mean of 51.9 +/- 34.3 months. The cumulative survival rate was no different in OLT for hepatitis C and OLT for all other liver diseases. After OLT, serum HCV RNA was detected in 93%. Histological recurrence occurred in 85% of all patients. The 1-, 3-, and 5-year recurrence rates were 48%, 77%, and 85%, respectively. Of the 41 patients with recurrent hepatitis C, 4 (10%) had cirrhosis, 18 (44%) had hepatitis with fibrosis, and 91 (46%) had hepatitis without fibrosis at the end of follow-up. A total of 32% of the patients were infected by HCV genotype 1b and 68% by other HCV genotypes. The recurrence rates were significantly higher in patients infected with genotype 1b than in those with other genotypes (p = 0.04). Twenty of 48 patients (42%) experienced acute rejection. There was a strong association between the number of rejection episodes and the incidence of HCV-related cirrhosis (p < 0.01). Conclusion. Our findings showed the genotype 1b to result in a higher recurrence rate after OLT. On the other hand, rejection episodes were associated with a more rapid progression to graft cirrhosis.

Safety and efficacy of ledipasvir-sofosbuvir in black patients with hepatitis C virus infection: A retrospective analysis of phase 3 data.

UNLABELLED: Black patients chronically infected with genotype 1 hepatitis C virus (HCV) have historically had lower rates of response to interferon-based treatment than patients of other races. In the phase 3 ION program, the single-tablet regimen of the NS5A inhibitor ledipasvir and NS5B nucleotide polymerase inhibitor sofosbuvir was shown to be safe and highly effective in the general population. The aim of this study was to evaluate the safety and efficacy of ledipasvir/sofosbuvir in black patients using data from the three open-label ION clinical trials, which evaluated the safety and efficacy of 8, 12, and 24 weeks of ledipasvir/sofosbuvir with or without ribavirin for the treatment of treatment-naïve and treatment-experienced patients with genotype 1 HCV, including those with compensated cirrhosis. The primary endpoint was sustained virologic response at 12 weeks after the end of therapy (SVR12). For our analysis, rates of SVR12, treatment-emergent adverse events, and graded laboratory abnormalities were analyzed in black versus non-black patients. Of the 1949 patients evaluated, 308 (16%) were black. On average, black patients were older, had higher body mass index, were more likely to be IL28B non-CC, and had a lower serum alanine aminotransferase at baseline than non-black patients. Overall, 95% of black and 97% of non-black patients achieved SVR12. The rate of relapse was 3% in black patients as compared with 2% in non-black patients. The most common adverse events included fatigue, headache, nausea, and insomnia. The majority of adverse events occurred more frequently in the ribavirin-containing arms of the studies. No differences were observed in overall safety by race. CONCLUSION: A once-daily dosage of ledipasvir/sofosbuvir was similarly effective in black and non-black patients with genotype 1 HCV infection. The addition of ribavirin did not appear to increase SVR12 but was associated with higher rates of adverse events.

A smoking cessation intervention for people with chronic Hepatitis C : a randomised controlled trial

Purpose The purpose of this study was to examine the validity of current practice in smoking cessation for the general population i.e., a telephone counselling and nicotine replacement therapy (NRT) intervention and its applicability to people with chronic hepatitis-C. Methods A randomised controlled trial was conducted over twelve weeks. Following consent, ninety-two smokers (outpatients) with chronic hepatitis-C were recruited by the Nurse Practitioner hepatology, randomly assigned and stratified by number of cigarettes smoked (i.e., 15 and greater; <15) into the intervention group (telephone counselling and NRT) and control group (telephone counselling). Outcomes measured included socio-demographics, nicotine dependence, depression, anxiety and stress and quality of life (QOL). All statistical data were analysed using SPSS. Results After 12 weeks, the intervention group showed a sustained reduction of smoking i.e., 5.8(CI: 2.4,9.3) cigarettes less per day, whereas the control group showed 1.6(CI:-1.9,5.2) cigarette reduction. Although not statistically significantly different (F=2.9, p=0.090) the intervention group on average smoked 4.2 fewer cigarettes compared to the control group. After twelve weeks, seven patients in the intervention group and three patients in the control group reported quitting. Whilst not statistically significant (Fisher’s Exact, p=0.311) this was a clinically significant result. No differences were found for nicotine dependence or depression, anxiety and stress. The intervention group experienced no change in QOL (-0.1,CI:-0.9, 0.6), however, the environmental score for the control group decreased by 1.8(CI:1.0, 2.6,p= 0.001). This was statistically significant. Conclusion A telephone counselling and nicotine replacement therapy intervention from the nurse practitioner, hepatology reduced smoking in patients with chronic hepatitis-C. The intervention group showed a sustained reduction over the 12 weeks. A total of 10 patients quit smoking at the end of the study. QOL deteriorated in the environmental subscale for the control group. These results informed a nurse practitioner model of care for approaches to smoking cessation.

Telaprevir or boceprevir based therapy for chronic hepatitis C infection: Development of resistance-associated variants in treatment failure

The use of triple-therapy, pegylated-interferon, ribavirin and either of the first generation hepatitis C virus (HCV) protease inhibitors telaprevir or boceprevir, is the new standard of care for treating genotype 1 chronic HCV. Clinical trials have shown response rates of around 70–80%, but there is limited data from the use of this combination outside this setting. Through an expanded access programme, we treated 59 patients, treatment naïve and experienced, with triple therapy. Baseline factors predicting treatment response or failure during triple therapy phase were identified in 58 patients. Thirty seven (63.8%) of 58 patients had undetectable HCV RNA 12 weeks after the end of treatment. Genotype 1a (p = 0.053), null-response to previous treatment (p = 0.034), the rate of viral load decline after 12 weeks of previous interferon-based treatment (p = 0.033) were all associated with triple-therapy failure. The most common cause of on-treatment failure for telaprevir-based regimens was the development of resistance-associated variants (RAVs) at amino acids 36 and/or 155 of HCV protease (p = 0.027) whereas in boceprevir-based regimens mutations at amino acid 54 were significant (p = 0.015). SVR12 rates approaching 64% were achieved using triple therapy outside the clinical trial setting, in a patient cohort that included cirrhotics.

IFN stimulated gene expression in the liver is a better predictor of treatment response in chronic hepatitis c than the IL28b (IFN lambda 3) genotype

Background: Therapy of chronic hepatitis C (CHC) with pegIFNa/ribavirin achieves sustained virologic response (SVR) in ~55%. Pre-activation of the endogenous interferon system in the liver is associated non-response (NR). Recently, genome-wide association studies described associations of allelic variants near the IL28B (IFNλ3) gene with treatment response and with spontaneous clearance of the virus. We investigated if the IL28B genotype determines the constitutive expression of IFN stimulated genes (ISGs) in the liver of patients with CHC. Methods: We genotyped 93 patients with CHC for 3 IL28B single nucleotide polymorphisms (SNPs, rs12979860, rs8099917, rs12980275), extracted RNA from their liver biopsies and quantified the expression of IL28B and of 8 previously identified classifier genes which discriminate between SVR and NR (IFI44L, RSAD2, ISG15, IFI22, LAMP3, OAS3, LGALS3BP and HTATIP2). Decision tree ensembles in the form of a random forest classifier were used to calculate the relative predictive power of these different variables in a multivariate analysis. Results: The minor IL28B allele (bad risk for treatment response) was significantly associated with increased expression of ISGs, and, unexpectedly, with decreased expression of IL28B. Stratification of the patients into SVR and NR revealed that ISG expression was conditionally independent from the IL28B genotype, i.e. there was an increased expression of ISGs in NR compared to SVR irrespective of the IL28B genotype. The random forest feature score (RFFS) identified IFI27 (RFFS = 2.93), RSAD2 (1.88) and HTATIP2 (1.50) expression and the HCV genotype (1.62) as the strongest predictors of treatment response. ROC curves of the IL28B SNPs showed an AUC of 0.66 with an error rate (ERR) of 0.38. A classifier with the 3 best classifying genes showed an excellent test performance with an AUC of 0.94 and ERR of 0.15. The addition of IL28B genotype information did not improve the predictive power of the 3-gene classifier. Conclusions: IL28B genotype and hepatic ISG expression are conditionally independent predictors of treatment response in CHC. There is no direct link between altered IFNλ3 expression and pre-activation of the endogenous system in the liver. Hepatic ISG expression is by far the better predictor for treatment response than IL28B genotype.

Vitamin D deficiency and a CYP27B1-1260 promoter polymorphism are associated with chronic hepatitis C and poor response to interferon-alfa based therapy

BACKGROUND: Vitamin D is an important immune modulator and preliminary data indicated an association between vitamin D deficiency and sustained virologic response (SVR) rates in patients with chronic hepatitis C. We therefore performed a comprehensive analysis on the impact of vitamin D serum levels and of genetic polymorphisms within the vitamin D cascade on chronic hepatitis C and its treatment. METHODS: Vitamin D serum levels, genetic polymorphisms within the vitamin D receptor and the 1α- hydroxylase were determined in a cohort of 468 HCV genotype 1, 2 and 3 infected patients who were treated with interferon-alfa based regimens. RESULTS: Chronic hepatitis C was associated with a high incidence of severe vitamin D deficiency compared to controls (25(OH)D3<10 ng/mL in 25% versus 12%, p<0.00001), which was in part reversible after HCV eradication. 25(OH)D3 deficiency correlated with SVR in HCV genotype 2 and 3 patients (63% and 83% SVR for patients with and without severe vitamin D deficiency, respectively, p<0.001). In addition, the CYPB27-1260 promoter polymorphism rs10877012 had substantial impact on 1-25- dihydroxyvitamin D serum levels and SVR rates in HCV genotype 1, 2 and 3 infected patients. CONCLUSIONS: Chronic hepatitis C virus infection is associated with vitamin D deficiency. Reduced 25- hydroxyvitamin D levels and CYPB27-1260 promoter polymorphism are associated with failure to achieve SVR in HCV genotype 1, 2, 3 infected patients.

Impact of international consensus guidelines on antiviral therapy of chronic hepatitis C patients in Switzerland.

To assess the impact of international consensus conference guidelines on the attitude of Swiss specialists when facing the decision to treat chronic hepatitis C patients. Questionnaires focusing on the personal situation and treatment decisions were mailed to 165 patients who were newly diagnosed with hepatitis C virus (HCV) infection and enrolled into the Swiss Hepatitis C Cohort Study during the years 2002-2004. Survey respondents (n = 86, 52.1%) were comparable to non-respondents with respect to severity of liver disease, history of substance abuse and psychiatric co-morbidities. Seventy percent of survey respondents reported having been offered antiviral treatment. Patients deferred from treatment had less advanced liver fibrosis, were more frequently infected with HCV genotypes 1 or 4 and presented more often with a history of depression. There were no differences regarding age, socio-economic background, alcohol abuse, intravenous drug abuse or methadone treatment when compared with patients to whom treatment was proposed. Ninety percent of eligible patients agreed to undergo treatment. Overall, 54.6% of respondents and 78.3% of those considered eligible had actually received antiviral therapy by 2007. Ninety-five percent of patients reported high satisfaction with their own hepatitis C management. Consistent with latest international consensus guidelines, patients enrolled in the Swiss Hepatitis C Cohort with a history of substance abuse were not withheld antiviral treatment. A multidisciplinary approach is warranted to provide antiviral treatment to patients suffering from depression.