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Treating obesity may improve the efficacy of therapy for hepatitis C

lic abnormalities, Michael R. Charlton, M.D. of the Division of Gastroenterology and Hepatology at the Mayo Clinic and Foundation in Rochester, MN and coauthors reviewed several mechanisms by which obesity may interfere with the treatment of chronic HCV and recommend management strategies for obese patients.

The authors identify three possible ways by which obesity may interfere with peginterferon alpha and ribavirin activity. First, fat tissue actively secretes hormones that can modulate the immune system. Increases in fat tissue may disregulate immune pathways peginterferon targets, rendering the drug ineffective. Second, obesity causes insulin resistance which itself leads to the accumulation of fat in the liver. The greater the accumulation of fat in the liver, the greater the risk of fibrosis, or scar tissue formation, that alters liver function and blood flow, often permanently. Because HCV also causes liver cells to not respond to insulin, obesity may simply compound the problem and worsen liver disease. Third, fat tissue reduces the amount of peginterferon circulating in the body. The decreased circulation of the drug may also weaken peginterferon's stimulation of the immune system against HCV.

To address all of these mechanisms, the authors make three treatment recommendations. First, weight loss to reduce fat tissue would address all three hypothesized mechanisms. Weight loss in obese HCV patients is already associated with improved liver biopsy results and liver enzyme levels. Second, treatment with drugs that improve cellular sensitivity to insulin, such as the diabetes drugs metformin or pioglitazone, would lead to reduced fat accumulation in liver cells and might reverse disease progression. Third, increasing the dosages or the duration of combination therapy may increase circulating drug levels and improve drug efficacy.

"Treatment strategies that focus on improving underlying metabolic factors associated with poor response to
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Contact: David Greenberg
dgreenbe@wiley.com
201-748-6484
John Wiley & Sons, Inc.
2-Jun-2006


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