Effect of Obesity on Pharmacokinetics and Biologic Effect of Interferon-alpha in Hepatitis C

Abstract
To examine potential adverse effects of obesityin reducing the response to interferon-alpha (IFN-alpha)in chronic hepatitis C (HCV), IFN-alpha and HCV RNAlevels in serum and the 2′,5′-oligoadenylatesynthetase (2-5 OAS) levels in peripheral bloodmononuclear cells (PBMC) were compared between six obeseand five nonobese patients before and after a single, 10mIU dose of IFN-alpha2b. There were nodifferences in the mean histologic activity index between thetwo groups. The maximal IFN concentration and the areaunder the serum IFN concentration-time curve were higherin nonobese patients. These two parameters were inversely correlated with body weight andbody surface area. No differences were found in the meanreduction in HCV RNA levels between the two groupsfollowing IFN-alpha. The maximal 2-5 OAS level after treatment divided by the pretreatment 2-5OAS level (2-5 OAS response ratio) was greater in thenonobese patients, suggesting stronger biologic responseupon exposure to exogenous IFN-alpha in nonobese patients.