Liver stiffness diminishes with antiviral response in chronic hepatitis C.: Liver Stiffness Kinetics on HCV Therapy

International audienceAliment Pharmacol Ther 2011; 34: 656-663 SUMMARY: Background Transient elastography measures liver stiffness, which correlates with the hepatic fibrosis stage and has excellent accuracy for the diagnosis of cirrhosis in patients with chronic hepatitis C. Aim To assess prospectively the kinetics of liver stiffness in treated patients with chronic hepatitis C and compare them with the viral kinetics on treatment and with the final outcome of therapy. Methods 91 patients with chronic hepatitis C with significant fibrosis (>7.0 kPa) at baseline were included. They received therapy with pegylated interferon-α and ribavirin. The kinetics of liver stiffness were characterized during therapy and thereafter by means of Fibroscan, and compared with the virological responses at weeks 4, 12, 24, end of treatment and 12 and 24 weeks after. Results A significant liver stiffness decrease was observed during therapy, which continued after treatment only in patients who achieved a sustained virological response. In this group, the median intra-patient decrease relative to baseline at the end of follow-up was -3.4 kPa, vs-1.8 kPa in the patients who did not achieve an SVR. Similar dynamics were observed in cirrhotic and non-cirrhotic patients. In multivariate analysis, only the SVR was associated with long-term improvement of liver stiffness (odds ratio: 3.10; 95% confidence interval: 1.20-8.02, P = 0.019). Conclusions In patients with advanced fibrosis at the start of therapy, liver stiffness is significantly reduced during treatment, but improvement continues off treatment only in patients who achieve a sustained virological response. Liver stiffness assessment earlier than 6 months after the end of therapy does not appear to be clinically meaningful

Efficacy and safety of treatment of chronic hepatitis C with sofosbuvir and ribavirin with or without peginterferon

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High-Dose Pegylated Interferon-α and Ribavirin in Nonresponder Hepatitis C Patients and Relationship With IL-28B Genotype (SYREN Trial).: High-Dose peg-IFN and Ribavirin and IL28B in HCV nonresponders

International audienceBACKGROUND & AIMS: In patients with chronic hepatitis C who failed to respond to standard therapy, high-dose pegylated interferon (IFN)-α and/or ribavirin could induce a stronger antiviral response and prevent treatment failure and HCV resistance when combined with direct-acting antivirals. The influence of genetic determinants in this context remains unknown. METHODS: Eighty-three patients infected with HCV genotype 1 who were nonresponsive to standard therapy received pegylated IFN-α2a (360 μg once per week or 180 μg twice per week) with ribavirin (1.0-1.2 or 1.2-1.6 g/d) for up to 72 weeks. Virological responses were assessed at different time points, and the influence of the IL-28B genotype was studied. RESULTS: At weeks 12 and 24, respectively, 47 (56.6%) and 50 (60.2%) patients achieved a ≥2-Log(10) decrease of HCV RNA levels; 8 (9.6%) and 21 (25.3%) patients had undetectable HCV RNA after 12 and 24 weeks of treatment, respectively. Patients with a CT IL-28B genotype responded significantly better and earlier than those with a TT genotype. In multivariate analysis, the IL-28B genotype was an independent predictor of the virological responses at weeks 4, 12, and 24. CONCLUSIONS: High-dose pegylated IFN-α with standard or high doses of ribavirin induces a potent antiviral response in a substantial number of patients who did not respond to standard therapy. The IL-28B genotype is an independent predictor of the antiviral response. High-dose pegylated IFN-α in combination with ribavirin and protease inhibitors appears as an attractive option for future study in this population

Daclatasvir plus sofosbuvir with or without ribavirin in genotype 3 patients from a large French multicenter compassionate use program

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Apolipoprotein H expression is associated with IL28B genotype and viral clearance in hepatitis C virus infection

International audienceBACKGROUND & AIMS:HCV requires host lipid metabolism for replication, and apolipoproteins have been implicated in the response to treatment.METHODS:We examined plasma apolipoprotein concentrations in three cohorts of patients: mono-infected patients with symptomatic acute hepatitis C (aHCV); those undergoing treatment for chronic hepatitis C (cHCV); and HIV/HCV co-infected patients being treated for their chronic hepatitis C. We also evaluated associations between apolipoproteins and IL28B polymorphisms, a defined genetic determinant of viral clearance.RESULTS:Plasma apolipoprotein H (ApoH) levels were significantly higher in patients who achieved spontaneous clearance or responded to pegylated-interferon/ribavirin therapy. Strikingly, patients carrying the IL28B rs12979860 CC SNP correlated with the plasma concentration of ApoH in all three cohorts. Both ApoH and IL28B CC SNP were associated with HCV clearance in univariate analysis. Additional multivariate analysis revealed that the association between IL28B and HCV clearance was closely linked to that of Apo H and HCV clearance, suggesting that both belong to the same biological pathway to clearance. The association between IL28B CC SNP and ApoH was not observed in healthy individuals, suggesting that early post-infection events trigger differential ApoH expression in an IL28B allele dependent manner.CONCLUSIONS:This relationship identifies ApoH as the first induced protein quantitative trait associated with IL28B, and characterises a novel host factor implicated in HCV clearanc

Effectiveness of telaprevir or boceprevir in treatment-experienced patients with HCV genotype 1 infection and cirrhosis.: Triple therapy in HCV genotype 1 cirrhotics

International audienceBACKGROUND & AIMS: We investigated the effectiveness of the protease inhibitors peginterferon and ribavirin in treatment-experienced patients with hepatitis C virus (HCV) genotype 1 infection and cirrhosis. METHODS: In the Compassionate Use of Protease Inhibitors in Viral C Cirrhosis study, 511 patients with HCV genotype 1 infection and compensated cirrhosis who did not respond to a prior course of peginterferon and ribavirin (44.3% relapsers or patients with viral breakthrough, 44.8% partial responders, and 8.0% null responders) were given either telaprevir (n = 299) or boceprevir (n = 212) for 48 weeks. We assessed percentages of patients with sustained viral responses 12 weeks after therapy and safety. This observational study did not allow for direct comparison of the 2 regimens. RESULTS: Among patients given telaprevir, 74.2% of relapsers, 40.0% of partial responders, and 19.4% of null responders achieved SVR12. Among those given boceprevir, 53.9% of relapsers, 38.3% of partial responders, and none of the null responders achieved SVR12. In multivariate analysis, factors associated with SVR12 included prior response to treatment response, no lead-in phase, HCV subtype 1b (vs 1a), and baseline platelet count greater than 100,000/mm(3). Severe adverse events occurred in 49.9% of cases, including liver decompensation, severe infections in 10.4%, and death in 2.2%. In multivariate analysis, baseline serum albumin level less than 35 g/L and baseline platelet counts of 100,000/mm(3) or less predicted severe side effects or death. CONCLUSIONS: Relatively high percentages of real-life, treatment-experienced patients with HCV genotype 1 infection and cirrhosis respond to the combination of peginterferon and ribavirin with telaprevir or boceprevir. However, side effects are frequent and often severe. Baseline levels of albumin and platelet counts can be used to guide treatment decisions. ClinicalTrials.gov number: NCT01514890

Triple therapy in treatment-experienced patients with HCV-cirrhosis in a multicentre cohort of the French Early Access Programme (ANRS CO20-CUPIC) – NCT01514890

International audienceBackground & AimsIn phase III trials, the safety profile of triple therapy (pegylated interferon/ribavirin with boceprevir or telaprevir) seems to be similar in HCV treatment-experienced cirrhotic and non-cirrhotic patients, but few cirrhotics were included. We report the week 16 safety and efficacy analysis in a cohort of compensated cirrhotics treated in the French Early Access Programme.Methods674 genotype 1 patients, prospectively included, received 48 weeks of triple therapy. The analysis is restricted to 497 patients reaching week 16.ResultsA high incidence of serious adverse events (40.0%), and of death and severe complications (severe infection or hepatic decompensation) (6.4%), and a difficult management of anaemia (erythropoietin and transfusion use in 50.7% and 12.1%) were observed. Independent predictors of anaemia <8 g/dl or blood transfusion were: female gender (OR 2.19, 95% CI 1.11–4.33, p = 0.024), no lead-in phase (OR 2.25, 95% CI 1.15–4.39, p = 0.018), age ⩾65 years (OR 3.04, 95% CI 1.54–6.02, p = 0.0014), haemoglobin level (⩽12 g/dl for females, ⩽13 g/dl for males) (OR 5.30, 95% CI 2.49–11.5, p = 0.0001). Death or severe complications were related to platelets count ⩽100,000/mm3 (OR 3.11, 95% CI 1.30–7.41, p = 0.0105) and albumin <35 g/dl (OR 6.33, 95% CI 2.66–15.07, p = 0.0001), with a risk of 44.1% in patients with both. However, the on-treatment virological response was high.ConclusionsThe safety profile was poor and patients with platelet count ⩽100,000/mm3 and serum albumin <35 g/L should not be treated with the triple therapy