Clinical Inquiries

How does pentoxifylline affect survival of patients with alcoholic hepatitis?

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References

In a recently published abstract, 50 patients with severe alcoholic hepatitis (defined as DF >32) were enrolled in a randomized, double-blind, placebo-controlled trial of oral pentoxifylline, 400 mg twice a day or placebo for 4 weeks.2 Short-term survival and changes in laboratory values (TNF, creatinine, and DF) were the primary outcome measures.

Survival was 76% in the pentoxifylline group compared with 60% in the placebo group (P not given). In the sub-group of patients who died, however, hepatorenal syndrome was the cause of death in 83% of the pentoxifylline group and 60% of the placebo group (P not given).

In a 1991 pilot study, also published only in abstract form, 22 patients admitted to the hospital with severe alcoholic hepatitis were randomized to receive oral pentoxifylline (1200 mg daily) or placebo for 10 days. Serum creatinine dropped 0.3 mg/dL in the treatment group and rose 2.1 mg/dL in the control group (P<.05). At 30 days, 3 patients in the control group had died compared with 1 in the treatment group (P=not significant).3

It’s not effective for patients who don’t respond to steroids

A cohort study evaluated the effect of switching to pentoxifylline in hospitalized patients with severe alcoholic hepatitis who didn’t respond to initial therapy with steroids. Researchers identified 121 patients who were treated initially with 40 mg oral prednisolone daily. The 36 patients who failed to show a drop in bilirubin levels within 7 days were switched to oral pentoxifylline, 400 mg twice a day.

In the pentoxifylline group, 69% of patients died within 2 months, 27.6% of whom had some form of renal insufficiency. This outcome wasn’t statistically different from that of 58 matched historical controls with severe alcoholic hepatitis who were maintained on oral prednisolone despite failure to respond within the first week of therapy (65% mortality, 20% with renal insufficiency).4

Recommendations

The American College of Gastroenterology doesn’t recommend giving pentoxifylline to patients with severe alcoholic hepatitis, citing lack of evidence for improvement of patient-oriented outcomes.5 However, a group of French hepatologists consider pentoxifylline a reasonable alternative to corticosteroids for severe acute alcoholic hepatitis based on the studies cited here.6

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