No pharmacologic therapy has conclusively proved to be effective for the treatment of nonalcoholic steatohepatitis.
This is characterized by insulin resistance, steatosis, and necroinflammation with or without centrilobular fibrosis.
Pioglitazone is a thiazolidinedione that ameliorates insulin resistance and improves glucose and lipid metabolism in type 2 diabetes mellitus.
Dr Kenneth Cusi and colleagues from Texas evaluated assigned 55 patients with impaired glucose tolerance or type 2 diabetes.
The patients also had liver biopsy-confirmed nonalcoholic steatohepatitis.
The patients were randomly assigned to 6 months of treatment with a hypocaloric diet plus pioglitazone or a hypocaloric diet plus placebo.
|Pioglitazone reduced necroinflammation|
|New England Journal of Medicine|
Before and after treatment, the researchers assessed hepatic histologic features, and hepatic fat content by means of magnetic resonance spectroscopy.
The team also evaluated glucose turnover during an oral glucose tolerance test given with the oral glucose load, and glucose given by intravenous infusion.
Diet plus pioglitazone, as compared with diet plus placebo, improved glycemic control and glucose tolerance.
The researchers noted that normalized liver aminotransferase levels decreased plasma aspartate aminotransferase levels.
The team also found that normalized liver aminotransferase levels decreased alanine aminotransferase levels.
Normalized liver aminotransferase levels decreased hepatic fat content, and increased hepatic insulin sensitivity.
Administration of pioglitazone, as compared with placebo, was associated with improvement in histologic findings with regard to steatosis.
The researchers noted that pioglitazone was associated with improved ballooning necrosis, and inflammation.
Subjects in the pioglitazone group had a greater reduction in necroinflammation.
However, the team noted that the reduction in fibrosis did not differ significantly from that in the placebo group.
The researchers noted that fatigue and mild lower-extremity edema developed in 1 subject who received pioglitazone.
No other adverse events were observed.
Dr Cusi's team concludes, “In this proof-of-concept study, the administration of pioglitazone led to metabolic and histologic improvement in subjects with nonalcoholic steatohepatitis.”
“Larger controlled trials of longer duration are warranted to assess the long-term clinical benefit of pioglitazone.”