Insulin resistance and response to therapy in patients infected with chronic hepatitis C virus genotypes 2 and 3☆
Section snippets
Background and aims
Chronic hepatitis C (CHC) is a potentially curable disease. Combination therapy with pegylated interferon alpha and ribavirin results in overall sustained virological response (SVR) rates of 54–66% [1], [2], [3], [4]. Evidence accumulated from clinical trials over the last decade suggests that CHC resulting from genotype 3, and particularly genotype 2, has a high likelihood of a cure. SVR rates in this group of subjects is typically >75%, [1], [2], [3], [5] with rates as high as 93% reported in
Patient selection
The study population comprised 82 subjects who underwent combination therapy for CHC. Fifteen (18.3%) were infected with genotype 2 and 67 (81.7%) with genotype 3. The consecutive patients were enrolled and the data were collected prospectively from 1999 at two university teaching hospitals (59 from Westmead Hospital, University of Sydney, Australia, and 23 from University Hospital, Geneva, Switzerland). These patients were part of a larger cohort that has been the subject of previous reports
Results
The baseline demographic characteristics of the patient cohort are summarised in Table 1. Most of the subjects were male (72%) and Caucasian (87%), with 82% undergoing treatment for genotype 3 CHC infection. The treatment regimen for 59 patients (72%) was standard interferon and ribavirin, while the remaining 23 (28%) received pegylated-interferon in combination with ribavirin. In the overall cohort, a SVR was achieved in 63 (77%) patients, including 43 (73%) treated with standard interferon
Discussion
In this study, performed exclusively in patients with the treatment responsive genotype 2 and 3, we sought to clarify the inter-relationships between the BMI, hepatic steatosis, insulin resistance and fibrosis stage, and the response to anti-viral therapy. Our major finding was that as with genotype 1 CHC, there is a close and inverse relationship between insulin resistance and SVR, even in subjects traditionally considered to respond very well to treatment. We identified a threshold
Acknowledgement
The authors thank Dr. Karen Byth for assistance in statistical analysis.
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The authors declared that Schering Plough and Roche have provided unrestricted grants to support the units. This study is supported in part by Grants 219282 and 358398 from the National Health and Medical Research Council of Australia, Grant DK98017 from the National Institutes of Health, USA, Grant No. 3200B0-103727/1 from the Swiss National Science Foundation and by a research award from the Leenaards Foundation (Lausanne, Switzerland). They did not receive any funding from Roche or Schering Plough to undertake this research study.