Insulin resistance predicts rapid virological response in non-diabetic, non-cirrhotic genotype 1 HCV patients treated with peginterferon alpha-2b plus ribavirin.

BACKGROUND/AIMS: The rapid decline in hepatitis C virus RNA is crucial for determining the outcome of therapy in patients with genotype 1 chronic hepatitis C. However, the variables influencing the early phase of viral decay are still largely unexplored. We aimed to assess which pre-treatment variable may predict rapid virologic response (RVR) and sustained virologic response (SVR). METHODS: We evaluated 90 consecutive non-diabetic patients with genotype 1 chronic hepatitis C without cirrhosis, treated with peginterferon alpha-2b plus ribavirin. Viral load (COBAS Amplicore, Roche) was measured at 1, 4 and 12 weeks after starting treatment, and then 24 weeks after the end of treatment. RESULTS: The overall SVR was 47%. The SVR in patients with RVR was 100%. Age, GGT levels, viral load, steatosis, fibrosis and HOMA-IR were significantly associated with RVR in univariate analysis. After logistic regression, HOMA-IR proved to be the strongest independent predictor of RVR (OR 0.37, 95% CI: 0.16-0.89; p=0.027), whereas fibrosis had a weaker independent association with RVR (OR 0.32, 95% CI: 0.1-1.04; p=0.057). Among the eight pre-treatment variables, both BMI and steatosis were significantly associated with HOMA-IR, either in univariate or in multivariate analyses. CONCLUSIONS: Our data suggest that insulin resistance is strongly associated with RVR, thus reflecting the important role played by metabolic factors in the early phase of viral kinetics. HOMA-IR would appear to be a useful tool in predicting RVR and should be evaluated at baseline in all chronic hepatitis C patients before initiating antiviral treatment.

Durability of the response to peginterferon-α2b and ribavirin in patients with chronic hepatitis C: a cohort study in the routine clinical setting.

OBJECTIVES: To evaluate whether, in chronic hepatitis C-positive naive patients recruited in the routine clinical setting and treated with pegylated-interferon-α2b (Peg-IFN) and ribavirin (RBV), the sustained virologic response (SVR) is durable over the long term and whether it is associated with a decrease in liver complications and incidence of glucose abnormalities. PATIENTS AND METHODS: This was a prospective long-term follow-up study of 182 naive patients enrolled in 2001-2002 and treated with Peg-IFN and RBV and followed up to December 2010, with clinical, biochemical, and virological evaluations every 6-12 months. RESULTS: None of the 115 (63.2%) sustained responders showed late viremic relapse during the follow-up. SVR was better defined at 24 weeks (16/16 relapsers, 100%) than at 12 weeks after the end of therapy (14/16 relapsers, 87.5%). On multivariable analysis, viral genotype (odds ratio 0.16, 95% confidence interval 0.07-0.36, P=0.0001) and a greater than 20% RBV reduction (odds ratio 5.21, 95% confidence interval 1.54-17.67, P=0.008) predicted long-term response (LTR) independently. The incidence of cirrhosis was significantly higher among nonresponders (21.3%) compared with long-term responders (0.9%, P≤0.0001), but the risk of developing glucose abnormalities was not significantly reduced in long-term responders (hazard ratio 1.36, P=0.363). Hepatocellular carcinoma occurred only in three cases. CONCLUSION: SVR achieved in patients treated in the routine clinical setting with Peg-IFN and RBV is durable over the long term and LTR significantly reduces the risk of progression to cirrhosis; however, in a population with mild liver fibrosis, the clinical impact of LTR on the risk of glucose abnormalities seems negligible.

Therapy of chronic hepatitis C with PEG-IFN α-2b plus ribavirin in patients with genotype 2 or 3: 16 versus 24 weeks, clinical outcome and direct cost analyses.

INTRODUCTION: Short antiviral therapy has been proposed for patients with chronic hepatitis C, easy genotypes, low fibrosis score, low viral load at baseline, and rapid virological response (RVR). However, this approach is not completely accepted. OBJECTIVES: The aims of this study were (a) to evaluate the sustained virological response (SVR) in noncirrhotic patients with genotype 2 or 3, achieving an RVR, randomized to receive pegylated-interferon (IFN) α-2b plus ribavirin for either 16 or 24 weeks and (b) to carry out direct cost analysis comparing patients treated for 16 versus 24 weeks. RESULTS: Of the 142 initially evaluated patients, 130 were enrolled according to the selection criteria, but independent of the viral load. According to the intention-to-treat analysis, SVR was achieved in 104 patients (80%). Logistic regression analysis showed that RVR (P<0.001) and genotype 2 (P<0.03) were the most important factors independently associated with SVR. Among patients with RVR, SVR was comparable between patients treated for 16 weeks and those treated for 24 weeks (86.2 vs. 89.7%, P=NS). The mean direct costs were €4003.7 for patients treated for 16 weeks and €5676.7 for those treated for 24 weeks, with a 30% difference between the two arms. CONCLUSION: In patients achieving an RVR, a 16-week treatment with pegylated-interferon plus ribavirin was comparable to a 24-week treatment. Short treatment in patients with RVR allows us to save 30% of the direct costs, independent of the viral load at baseline.