Drug & Device Development

Thiazolidinediones minor help in non-alcoholic steatohepatitis

Last Updated: 2011-05-03 9:00:53 -0400 (Reuters Health)

By David Douglas

NEW YORK (Reuters Health) - Pooled data suggest that thiazolidinediones may be of some help in patients with non-alcoholic steatohepatitis (NASH), Australian and U.S. researchers report in an April 15th online paper in the Journal of Hepatology.

Lead researcher Dr. Suzanne Mahady said, however, "We do not currently have sufficient data to recommend these drugs for widespread use in patients with NASH."

"NASH represents a silent epidemic of liver disease and the lack of an effective pharmacological treatment is concerning. Our study suggests that thiazolidinediones at best confer a small benefit in reducing liver fibrosis; none of the individual studies were powered to examine fibrosis as an end point," Dr. Mahady told Reuters Health by email.

Dr. Mahady of Westmead Hospital, Wentworthville, New South Wales, and colleagues examined data from seven randomized trials involving 489 patients. Pioglitazone was the intervention in four trials and rosiglitazone in the other three.

Rosiglitazone, widely used to lower blood glucose levels, has been associated with an increased risk of adverse cardiovascular events, particularly in those over 65 years of age, and is under FDA scrutiny (see Reuters Health Report 2010-06-28).

In the current study, patients were relatively young with an age range of 46 to 54 years. Treatment from 6 to 24 months prompted an improvement in fibrosis (risk ratio 1.38). However, compared with placebo, the improvement was significant with pioglitazone but not with rosiglitazone.

In fact, say the investigators, although no difference in cardiovascular events was observed, "Our data in the context of current evidence cannot support the use of rosiglitazone."

The risk ratio for improvement in steatosis was 2.03. There was a greater improvement for diabetics than non-diabetics (RR 2.41 versus 1.93).

Overall, risk ratios for inflammation (1.71) and hepatocellular ballooning (1.62) were reduced.

Despite these modest improvements, treatment increased weight by an average of 4.4 kg. The researchers also point out that "adverse event reporting was inconsistent and only one trial assessed quality of life."

"What is urgently required is to perform more trials in patients at the highest risk of progressing to liver cirrhosis and liver related-outcomes. Importantly, the studies should include a long follow-up and also assess patient-relevant outcomes," Dr. Mahady added.

One of the researchers has received consulting fees from Takeda Pharmaceuticals.

SOURCE: http://bit.ly/ldOwtZ

J Hepatol 2011.