Clinical

Combination therapy fails to boost survival in alcoholic hepatitis

Last Updated: 2013-09-10 17:52:15 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Contrary to expectations, adding pentoxifylline to prednisolone for four weeks did not improve six-month survival in patients with severe alcoholic hepatitis, in a randomized trial.

Pentoxifylline or prednisolone is recommended for severe alcoholic hepatitis and some doctors prescribe both. Because they are thought to work differently (prednisolone by dampening hepatic inflammation and pentoxifylline by protecting against hepatorenal syndrome), researchers hoped to confirm that combining them yields additive benefit.

But that didn't pan out in the new study.

Dr. Philippe Mathurin from Hopital Hurlez, Lille, France, and colleagues studied 270 heavy drinkers with severe biopsy-proven alcoholic hepatitis. Half were assigned to take 40 mg of prednisolone once a day and 400 mg of pentoxifylline three times a day for 28 days. The others took 40 mg of prednisolone plus placebo for 28 days.

Over six months of follow-up, 82 patients died. Sixty-seven deaths (82%) were due to complications from liver failure and other causes, including gastrointestinal bleeding in 15 cases (18%).

Both the pentoxifylline-prednisolone and placebo-prednisolone groups had a six-month survival rate of approximately 69%, the authors reported in a paper released online September 10 in JAMA. There were 40 deaths in the pentoxifylline-prednisolone group and 42 in the placebo-prednisolone group.

"Our study does not support the use of a combination of pentoxifylline and prednisolone for severe alcoholic hepatitis," the authors say.

They did find a trend toward a lower rate of hepatorenal syndrome at six months in the pentoxifylline group (8.4% vs 15.3%, p=0.07); they say the study may have been underpowered to detect a significant difference.

The authors say their results don't prove that pentoxifylline is ineffective for severe alcoholic hepatitis. They cite the placebo-controlled study by Akriviadis et al published in Gastroenterology in 2000, which found that pentoxifylline improves short-term survival in severe acute alcoholic hepatitis.

In editorial published with the Mathurin et al study, Dr. Dina L. Halegoua-De Marzio and Dr. Jonathan M. Fenkel of Thomas Jefferson University Hospital in Philadelphia note that corticosteroids and pentoxifylline are currently "the only and most successful medical treatments available for severe alcoholic hepatitis despite providing only modest improvements in mortality."

However, they add, "the results reported by Mathurin and colleagues demonstrate that the sum (corticosteroids and pentoxifylline) is no greater than the individual parts for preventing mortality in well-characterized patients with severe alcoholic hepatitis."

"Pentoxifylline may remain a useful option for patients who have contraindications to receiving corticosteroids; however, this group was not studied by Mathurin and colleagues," the editorialists noted.

The study was supported by a Hospital-Based Clinical Research Program, a grant from the French Minister of Health. Pentoxifylline and its matching placebo were both supplied by Sanofi-Aventis Pharmaceuticals. The authors and editorial writers have declared no conflicts of interest.

SOURCE: http://bit.ly/15hGJho

JAMA 2013;310:1029-1041.