Short-term therapy is associated with improved liver histology.
Nonalcoholic steatohepatitis (NASH) is recognized increasingly not just as a histologic curiosity but as a clinically important condition. Thiazoladinediones (e.g., pioglitazone, rosiglitazone), which are approved to treat diabetes, improve liver histology in diabetic patients with NASH (JW Dec 13 2006). But, do nondiabetic patients also show improvement?
U.K. researchers randomized 74 nondiabetic patients with biopsy-proven NASH to receive either pioglitazone (30 mg daily) or placebo; 61 completed the study. At 1 year, when all patients underwent follow-up liver biopsies, patients in the pioglitazone group had significantly lower hepatocyte injury scores than did patients in the placebo group. In the placebo group (30 patients), hepatic fibrosis increased in 6 patients and decreased in 6 patients; in the pioglitazone group (31 patients), fibrosis increased in no patients and decreased in 9 patients. Modest, but statistically significant, mean weight gain was noted in the pioglitazone group.
Comment: In this small short-term study, pioglitazone conferred improvement in histologic parameters in nondiabetic patients with NASH. The researchers discuss plausible cellular mechanisms to explain the hepatic effects of this drug class. Now, the task is to determine whether long-term drug therapy improves clinical outcomes — without untoward side effects — in these patients.
— Allan S. Brett, MD
Published in Journal Watch General Medicine October 30, 2008
Aithal GP et al. Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis. Gastroenterology 2008 Oct; 135:1176.