Clinical

Rosiglitazone improves transaminase levels in nonalcoholic steatohepatitis

Last Updated: 2008-08-21 8:30:01 -0400 (Reuters Health)

By Will Boggs, MD

NEW YORK (Reuters Health) - Rosiglitazone, by improving insulin sensitivity, improves steatosis and transaminase levels in patients with nonalcoholic steatohepatitis (NASH), according to French researchers.

"Pharmacological therapy is necessary in many patients in whom diet and lifestyle modification have failed, because of the possibility of progression of liver injury," Dr. Vlad Ratziu from Universite Pierre et Marie Curie, Paris, told Reuters Health. "Insulin-sensitizing agents such as glitazones are a promising treatment in this condition because insulin resistance is key to the pathogenesis of this disease."

Dr. Ratziu and colleagues assessed the effects of rosiglitazone versus placebo for 1 year on liver disease in 63 patients with NASH, and investigated whether the changes were associated with a reduction in insulin resistance. The 32 patients in the treatment arm were started on 4 mg/d rosiglitazone for 1 month, then increased to 8 mg/d.

The results are reported in the July issue of Gastroenterology. More patients treated with rosiglitazone (47%) than placebo (16%) experienced more than a 30% reduction in steatosis (p = 0.014), the team reports, and more patients treated with rosiglitazone (38%) than placebo (7%) achieved normal ALT levels after treatment (p = 0.005).

Rosiglitazone treatment also resulted in an improvement in insulin sensitivity that correlated with the decrease in steatosis, the researchers note.

In a logistic regression analysis, treatment with rosiglitazone, absence of diabetes, and a high histologic score of steatosis were independent predictors of histologic response to treatment.

Four months after discontinuation of rosiglitazone, most variables had returned to baseline levels, the investigators say, but there was still a significant improvement in insulin levels and insulin sensitivity at that point.

"We planned an extension open label study where all patients, regardless of what they received in the first year, were given open label rosiglitazone for two additional years," Dr. Ratziu said. "This is intended to determine the long-term efficacy of rosiglitazone in NASH patients, mainly in order to see whether there is an additional improvement with longer therapy in responders. The results will be presented at the American Association for the Study of Liver Diseases (AASLD) meeting in November 2008 in San Francisco."

Gastroenterology 2008;135:100-110.