Prednisolone or pentoxifylline is recommended for severe alcoholic hepatitis, a life-threatening disease.
The benefit of their combination is unknown.
Dr Philippe Mathurin and colleagues from France determined whether the addition of pentoxifylline to prednisolone is more effective than prednisolone alone.
The team performed a multicenter, randomized, double-blind clinical trial conducted between 2007 and 2010 in 1 Belgian and 23 French hospitals of 270 patients aged 18 to 70 years.
The patients were heavy drinkers with severe biopsy-proven alcoholic hepatitis, as indicated by recent onset of jaundice in the prior 3 months and a Maddrey score of at least 32. Duration of follow-up was 6 months.
The last included patient completed the study in 2010.
None of the patients were lost to follow-up for the main outcome.
|The Model for End-Stage Liver Disease score was independently associated with 6-month survival|
|Journal of the American Medical Association|
Patients were randomly assigned to receive either a combination of 40 mg of prednisolone once a day and 400 mg of pentoxifylline 3 times a day for 28 days, or 40 mg of prednisolone and matching placebo for 28 days.
The team's main outcomes and measures included 6-month survival, with secondary end points of development of hepatorenal syndrome and response to therapy based on the Lille model, which defines treatment nonresponders after 7 days of initiation of treatment.
In intention-to-treat analysis, 6-month survival was not different in the pentoxifylline-prednisolone and placebo-prednisolone groups, corresponding to 40 vs 42 deaths, respectively.
In multivariable analysis, only the Lille model and the Model for End-Stage Liver Disease score were independently associated with 6-month survival.
The team found that at 7 days, response to therapy assessed by the Lille model was not significantly different between the 2 groups.
The researchers observed that the probability of being a responder was not different in both groups.
The cumulative incidence of hepatorenal syndrome at 6 months was not significantly different in the pentoxifylline-prednisolone, and the placebo-prednisolone groups.
Dr Mathurin's team concludes, "In patients with alcoholic hepatitis, 4-week treatment with pentoxifylline and prednisolone, compared with prednisolone alone, did not result in improved 6-month survival."
"The study may have been underpowered to detect a significant difference in incidence of hepatorenal syndrome, which was less frequent in the group receiving pentoxifylline."