Gastroenterology

Gastroenterology

Volume 140, Issue 2, February 2011, Pages 469-477
Gastroenterology

Clinical Advances in Liver, Pancreas, and Biliary Tract
Changes in Insulin Sensitivity and Body Weight During and After Peginterferon and Ribavirin Therapy for Hepatitis C

https://doi.org/10.1053/j.gastro.2010.11.002Get rights and content

Background & Aims

Chronic hepatitis C is associated with an increased prevalence of insulin resistance, which might result from liver disease, metabolic factors, or the hepatitis C virus (HCV) itself. The effect of antiviral treatment on insulin sensitivity is not well-known. We evaluated changes in insulin resistance and weight in patients with hepatitis C during and after peginterferon and ribavirin therapy.

Methods

Virahep-C was a prospective, multicenter study of a 48-week course of combination antiviral therapy in patients infected with HCV genotype 1. Insulin resistance (IR) was estimated by the homeostasis model assessment index (HOMA2-IR) based on fasting glucose and insulin levels.

Results

Among 341 patients, 40% had insulin resistance (HOMA2-IR > 2.0). The presence of insulin resistance was associated with increasing age, body mass index (BMI), and fibrosis stage. Among patients with insulin resistance at the start of the trial, median decreases in HOMA2-IR values during treatment were 0.74 at 24 weeks and 0.89 at 48 weeks, whereas BMI decreased by 1.2 and 2.2 at the same time points (P < .001 for all). At follow-up, HOMA2-IR and BMI levels returned toward baseline values in patients who did not respond or relapsed, but HOMA2-IR values remained significantly lower in patients with sustained virologic response (SVR) (P < .001), despite increases in BMI.

Conclusions

In patients with HCV genotype 1 infections, therapy with peginterferon and ribavirin is associated with decreases in body weight and insulin resistance. Among patients with insulin resistance before treatment, resolution of HCV infection results in sustained improvements in the HOMA-IR index, suggesting that HCV could have a direct role in the pathogenesis of insulin resistance.

Section snippets

Patient Population

The Virahep-C study was a multicenter study of combination peginterferon and ribavirin therapy of chronic hepatitis C designed to assess the rates and predictors of response among African American and white American patients with HCV genotype 1 infection and to identify reasons for nonresponse to therapy. The design and primary outcomes of the Virahep-C trial have been reported.15, 18 Adult patients who were 18 years and older, who had not been previously treated, who were infected with HCV

Baseline Features Associated With Insulin Resistance

Among the 401 patients enrolled into the Virahep-C study, 341 (168 African Americans and 173 white Americans) had calculable HOMA values at baseline. Of these, 135 (40%) had insulin resistance as defined by a HOMA2-IR value of greater than 2.0. The frequency of insulin resistance was 46% among African Americans compared with 34% in white Americans (P = .026). Other factors that were significantly (P < .05) associated with the presence of insulin resistance at baseline included history of

Discussion

In this prospective study of therapy of chronic hepatitis C genotype 1, 40% of patients were found to have insulin resistance at baseline. The presence of insulin resistance correlated with higher body weight, higher serum triglycerides, and greater degrees of fibrosis and steatosis on liver biopsy, all of which are well-known risk factors for diabetes and insulin resistance. Because of the lack of a suitable control group, it is not clear whether this rate of insulin resistance was higher than

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    Conflicts of interest The authors disclose no conflicts.

    Funding Supported by a cooperative agreement by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) with cosupport from the National Center on Minority Health and Health Disparities (NCMHD) and the Intramural Research Program of the National Cancer Institute (NCI) with further support under a Cooperative Research and Development Agreement (CRADA) with Roche Laboratories, Inc. Clinical trial number: NCT00038974 (URL: http://www.virahepc.org). Grant numbers: U01 DK60329, U01 DK60340, U01 DK60324, U01 DK60344, U01 DK60327, U01 DK60335, U01 DK60352, U01 DK60342, U01 DK60345, U01 DK60309, U01 DK60346, U01 DK60349, U01 DK60341. Other support includes the National Center for Research Resources (NCRR) General Clinical Research Centers Program grants: M01 RR00645 (New York Presbyterian), M02 RR000079 (University of California, San Francisco), M01 RR16500 (University of Maryland), M01 RR000042 (University of Michigan), M01 RR00046 (University of North Carolina).

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