Usefulness of viral kinetics for early prediction of a sustained virological response in HCV-1 non-responders re-treated with pegylated interferon and ribavirin.

BACKGROUND & AIMS: Undetectable HCV RNA at 12 weeks is the stopping rule recommended in HCV patients in whom previous treatment has failed. Whether earlier virological criteria may be useful for deciding treatment discontinuation remains subject of debate. The aim of this study was to identify, in HCV-1 non-responders and relapsers to IFN or Peg-IFN and ribavirin, the earliest and most accurate predictor of failure to respond to a new treatment combining Peg-IFN and ribavirin. METHODS: Prediction of SVR was assessed using the area under the ROC (AUROC) curve of reduction in viral load at different time points. RESULTS: This study included 151 patients (32% with extensive fibrosis or cirrhosis). A SVR was reached in 34% (21% in non-responders and 59% in relapsers). In non-responders, 1 month was the most accurate time point for predicting SVR (AUROC: 0.787 ± 0.075, p = 0.0001). Thirty-seven percent of non-responders did not have a 1-log drop in viral load at 1 month. All these patients had detectable HCV RNA at 3 months (p < 0.0001) and only 4% attained a SVR (p = 0.004). The same high negative predictive value for SVR was found in sensitivity analysis restricted to non-responders to Peg-IFN and ribavirin. In contrast, in relapsers, undetectable HCV RNA at 3 months was the earliest criterion with high negative predictive value (92%, p < 0.0001). CONCLUSIONS: All HCV-1 non-responders who did not have a 1-log drop in viral load at 1 month remained HCV-RNA-detectable at 3 months, and only 4% attained a SVR. This new criterion can be used early on as a first stopping rule.

Impact of insulin resistance on sustained response in HCV patients treated with pegylated interferon and ribavirin: a meta-analysis.

BACKGROUND & AIMS: Recent studies suggested that SVR rates might be lower in HCV patients with insulin resistance (IR) than in patients without IR, but the extent of the impact of IR on treatment response has not been established. We aimed to confirm the role of IR assessed by the homoeostasis model assessment (HOMA-IR) on SVR and to determine its magnitude. METHODS: We performed meta-analysis of studies evaluating the impact of IR in HCV patients treated with pegylated interferon and ribavirin. RESULTS: Fourteen studies involving 2732 patients were included. SVR was less frequent in patients with IR than in patients without IR (mean difference: -19.6%, 95% CI: -29.9% to -9.4%, p<0.001). In sensitivity analyses according to HCV-1 patients, patients with IR also less frequently attained a SVR than patients without IR (mean difference: -13.0%, 95% CI: -22.6% to -3.4%, p=0.008). In addition, the baseline HOMA-IR index was lower in responders than in non-responders (mean difference: -0.92, 95% CI: -1.53 to -0.32, p<0.001). In sensitivity analyses restricted to HCV-1 patients, the baseline HOMA-IR index remained lower in responders than in non-responders (mean difference: -0.63, 95% CI: -1.13 to -0.14, p<0.001). CONCLUSIONS: HCV patients with IR have a 20% lower SVR than patients without IR. The baseline HOMA-IR index is a major determinant of SVR.

Impact of pegylated interferon and ribavirin on morbidity and mortality in patients with chronic hepatitis C and normal aminotransferases in France.

UNLABELLED: Clinicians continue to raise questions concerning the necessity of treating chronic hepatitis C virus (HCV)-infected patients with normal alanine aminotransferase (N-ALT), in light of their slower progression to cirrhosis than patients with elevated alanine aminotraferase (E-ALT). This study was undertaken to predict the impact of pegylated interferon (IFN) and ribavirin on HCV-related morbidity and mortality in patients with N-ALT. A previous Markov model was adapted to separately simulate patients with N-ALT (30%) and those with E-ALT (70%). The model estimates fibrosis progression rates according to age, sex, and whether ALT levels are normal or elevated, assuming that patients with E-ALT have a 2.6 times higher progression than those with N-ALT. It takes into account improvement in HCV screening and treatment and competitive mortality. We assumed that N-ALT patients were treated 80% less frequently between 2002 and 2004 and 70% less frequently from 2005 on, as obtained in real life from three multicentric cohorts (Hepatys, Adequation, Persee). Antiviral treatment of HCV-infected populations might reduce 2008-2025 HCV-related morbidity and mortality by 34,200 cases of cirrhosis (36%, 33,000-35,000), 22,400 complications (28%, 21,000-23,000) and 17,500 deaths (25%, 17,000-18,000), including 3000 cases of cirrhosis (22%, 2000-5000), 1200 complications (15%, 1000-1700), and 1000 deaths (14%, 900-1300) in the N-ALT population, despite a probability of receiving treatment that is three to five times less in this population. If N-ALT patients are treated at the same proportions as those with E-ALT, morbidity and mortality could be further reduced by 1400 cases of cirrhosis (13%, 1200-2200), 600 complications (9%, 600-1000), and 500 deaths (9%, 500-800). CONCLUSION: Treatment of N-ALT patients would decrease HCV morbidity and mortality. These patients should be considered candidates for treatment just as others are.