Insulin resistance means a poorer response to anti-hepatitis C treatment in HIV/hepatitis C coinfected patients, according to a French study presented to the Fourth International Workshop on HIV and Hepatitis C Coinfection in Madrid on June 19th. Measures to improve insulin resistance, such as exercise or weight loss could, the investigators suggest, improve the chances of hepatitis C therapy achieving good results.
HIV/hepatitis C coinfected patients have a poorer response to hepatitis C therapy than patients who are only infected with hepatitis C. A number of factors have been associated with response to treatment for hepatitis C including patient characteristics. Some patient characteristics, such as age, gender and race, cannot be changed. But others, such as body mass index (BMI) and, importantly for the purposes of this study, insulin resistance, are potentially modifiable.
Investigators from the prospective French HOMAVIC-ANRS HC-02 study wished to gain a better understanding of the impact of insulin resistance on the outcome of hepatitis C therapy in coinfected patients.
Their study involved 238 patients, 74% of whom were male. The patients had a liver biopsy on entry to the study to assess their degree of fibrosis, and were then provided with 48 weeks of hepatitis C therapy consisting of pegylated interferon Alpha-2b plus ribavirin. Tests were also undertaken to see how many patients had insulin resistance, which was defined as a homeostasis model assessment (HOMA) score above 2.5. After the completion of therapy, the investigators performed statistical analysis to see which factors, including insulin resistance, were associated with a poorer treatment outcome.
Insulin resistance was present in just under a third of patients, and significant fibrosis (defined as a fibrosis score of two [F2] or above), was present in three-quarters of individuals.
A sustained virological response was achieved by 40% of patients. Statistical analysis showed that insulin resistance was associated with a significantly poorer response to hepatitis C therapy (32% vs. 40%, p = 0.05), severity of fibrosis (p = 0.04), infection with hepatitis C genotypes 1 and 4 (p
The association between a poorer insulin resistance and a poorer response to therapy was confirmed when the investigators restricted their analysis to patients infected with hepatitis genotype 1 – the hardest to treat of all hepatitis C genotypes – with only 18% of patients with insulin resistance clearing infection with hepatitis C compared to 54% of patients without insulin resistance.
Coinfected patients with insulin resistance could, the investigators conclude, increase the chances of achieving a good response to hepatitis C therapy by taking simple measures shown to be effective against insulin resistance such as exercise and weight loss. Therapy with drugs such as metformin could also be a useful intervention, they suggest. They note that such action could be taken before or during hepatitis C therapy.
P Cacoub et al. Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in HIV-HCV co-infected patients: HOMAVIC-ANRS HC-02 study. Fourth International Workshop on HIV and Hepatitis Coinfection, Madrid, abstract 2, 2008.