May 7, 2012

Insulin resistance and response to telaprevir plus peginterferon α and ribavirin in treatment-naïve patients infected with HCV genotype 1

Gut doi:10.1136/gutjnl-2011-300749

Viral hepatitis

Original article

Lawrence Serfaty1, Xavier Forns2, Tobias Goeser3, Peter Ferenci4, Frederik Nevens5, Giampiero Carosi6, Joost P Drenth7, Isabelle Lonjon-Domanec8, Ralph DeMasi9, Gaston Picchio9, Maria Beumont10, Patrick Marcellin11

+ Author Affiliations

Correspondence to Dr Lawrence Serfaty, Hôpital St Antoine, 184 Rue du Faubourg Saint-Antoine, 75571 Paris Cedex 12, France;

Contributors LS, XF, TG, PF, FN, GC, JPD and PM were study investigators and participated in the recruitment of patients and reporting of data for the patients they enrolled. IL-D, RDeM, GP and MB contributed to the design, conduct and analysis of the C208 clinical trial. LS wrote the first draft of the manuscript and had full access to the data. RDeM provided statistical analysis support. All authors were involved in the interpretation of the data, reviewed and revised the manuscript for intellectual content, and approved the final version for submission.

Revised 11 November 2011

Accepted 28 November 2011

Published Online First 2 March 2012


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.


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