(NEJM, May 2010) In this study, 80 patients received pioglitazone 30 mg/day, vitamin E 800 IU/day or placebo for two years. Nobody had diabetes mellitus, though insulin resistance was present. Biopsies were performed before and after. Major side effect included an average weight gain of 12 lbs. in the pioglitazone group, and the study was not powered to detect any cardiovascular outcomes.
Aminotransferase levels fell in each drug arm, but returned to an elevated level after drug discontinuation. There were histologic benefits of each study drug, including hepatitis and ballooning degeneration; however, there was NO significant decrease in fibrosis (which was, on average, stage 1.5/4 at the outset). Quality of life did not change.
Although it is nice to see the reversal of histologic components of NASH, this study does not evidence any important clinical outcomes, like the progression of fibrosis or development of cirrhosis. After all, in liver disease, that is what really matters. The study does, however, reconfirm our belief that there are multiple pathways involved in NASH (insulin resistance and free-radical oxidation, for example).
Due to cardiovascular risk, I would not recommend vitamin E 800 IU, and due to weight gain and potential cardiovascular risk, I would not recommend pioglitazone unless the patient was a diabetic and needed an insulin sensitizer.
For a look at this article, see the link below: