SAN ANTONIO – Fifty percent of adults with nonalcoholic steatohepatitis improved their disease scores by at least two points with pentoxifylline therapy, compared with 15% of the placebo group, in a randomized, double-blind trial of 55 patients.
Pentoxifylline is known to increase the flexibility of red blood cells and reduce platelet aggregation. Preliminary work in mice and rats has prompted studies of pentoxifylline in patients with nonalcoholic steatohepatitis (NASH), but most of these studies have been small and lacking in control groups or histologic follow-up, said Dr. Claudia Zein, who presented the results at the annual scientific meeting of the American College of Gastroenterology.
Effective therapies are important because a significant number of patients with NASH will go on to develop cirrhosis, said Dr. Zein of the Cleveland Clinic. One recent study showed some benefits of vitamin E in some patients, but "there is still a great need for effective and safe therapies for NASH," Dr. Zein said.
In this study, 55 adults who were recruited from two medical centers in Cleveland were randomized to receive either 400-mg pentoxifylline three times daily (26 patients) or placebo (29 patients) for 1 year. The baseline histologic characteristics were similar between the two groups. The mean age of the patients was 50 years, and most were men.
Treatment success was defined as an improvement of 2 or more points in the NAS (NAFLD [Nonalcoholic Fatty Liver Disease] Activity Score), a validated scoring system that combines several histologic features, namely steatosis, lobular inflammation, and intracellular ballooning.
In the per protocol analysis of 49 patients, 50% of the pentoxifylline group improved their NAS scores by at least 2 points after 1 year, compared with 15% of the placebo group; this difference was statistically significant. Three patients in each group dropped out because of reasons unrelated to the study drug.
Patients in the pentoxifylline group were significantly more likely than the placebo patients to have improved steatosis (80% vs. 20%) and inflammation (55% vs. 23%). However, hepatocellular ballooning results did not differ significantly between the two groups.
In addition, no differences in progression of fibrosis were seen between the two groups. "But in future studies, we think we will see a lack of progression of fibrosis," Dr. Zein said.
In addition, 57% of the pentoxifylline patients met the secondary end point of an improvement of 30% or more in ALT (alanine aminotransferase) levels, compared with 25% of the placebo patients.
No serious adverse events were reported in either group, and the incidence of adverse events was similar between the two groups. Nausea and vomiting appeared to be more prominent in the pentoxifylline group, but the difference fell short of statistical significance.
"Pentoxifylline appeared to be safe and well tolerated in patients with NASH," said Dr. Zein. "We feel that further trials with larger numbers of patients are warranted."
This study was a 2010 Governor’s Award Recipient for Excellence in Clinical Research from the American College of Gastroenterology, which involved a monetary grant.