Insulin resistance and response to telaprevir plus peginterferon α and ribavirin in treatment-naïve patients infected with HCV genotype 1. Issue 10 (2nd March 2012)

• Record Type: Journal Article
• Authors: Serfaty, Lawrence; Forns, Xavier; Goeser, Tobias; Ferenci, Peter; Nevens, Frederik; Carosi, Giampiero; Drenth, Joost P; Lonjon-Domanec, Isabelle; DeMasi, Ralph; Picchio, Gaston; Beumont, Maria; Marcellin, Patrick
• Is Part Of: Gut. Volume 61:Issue 10(2012)
• Page Start: 1473
• Page End: 1480
• Publication Date: 2012-03-02
• Subjects: Vx-950 -- homeostatis model assessment -- LDL-cholesterol -- fibrosis -- direct-acting antiviral agent -- hepatitis C -- liver transplantation -- chronic hepatitis -- chronic liver disease -- hepatic encephalopathy -- Wilson's disease -- haemochromatosis -- haemodynamics in cirrhosis -- hepatocellular carcinoma -- hepatitis B -- hepatic haemodynamics -- portal hypertension -- cirrhosis -- liver failure -- liver transplantation -- chronic viral hepatitis -- autoimmune hepatitis -- hepatitis D -- cirrhosis; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2011-300749
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Objective: Insulin resistance is a predictor of poor response to peginterferon/ribavirin in patients infected with the chronic hepatitis C virus (HCV). There are no data on direct-acting antivirals. This exploratory analysis assessed the effect of metabolic factors and insulin resistance, measured by homoeostatic model assessment (HOMA), on virological response to telaprevir in Study C208. Design: Overall, 161 HCV genotype 1-infected, treatment-naïve patients received 12 weeks of telaprevir plus peginterferon/ribavirin, then 12/36 weeks of peginterferon/ribavirin depending on on-treatment response criteria. The prognostic significance of several factors, including HOMA-insulin resistance (HOMA-IR), on virological response at weeks 4 and 12, end of treatment and 24 weeks after treatment was explored by multiple regression analysis. Results: Baseline HOMA-IR data were available for 147 patients; baseline characteristics were consistent with the overall population. Baseline HOMA-IR <2, 2–4 and >4 was seen in 54%, 30% and 16% of patients, respectively. Neither response rates (any time point) nor week 4 viral load decline were significantly influenced by baseline HOMA-IR. In multivariate analyses, fibrosis stage and low-density lipoprotein cholesterol level were predictive of sustained virological response (OR 0.47 and 1.02, respectively). After the end of treatment, HOMA-IR was significantly lower in patients with sustained virological response than in those without (0.61 vs 1.34 for relapsers and 1.15 for non-responders; p<0.05). Conclusion: In this study, baseline HOMA-IR was not predictive of virological response to telaprevir in HCV genotype 1-infected, treatment-naïve patients, while sustained virological response was associated with improved HOMA-IR. These results suggest that metabolic factors and insulin resistance do not have a significant effect on telaprevir-based treatment efficacy.