Prednisolone or Pentoxifylline Show No Mortality Benefit in Alcoholic Hepatitis

Clinical question: Does administration of prednisolone or pentoxifylline reduce mortality in patients hospitalized with severe alcoholic hepatitis?

Background: Alcoholic hepatitis is associated with high mortality. Studies have shown unclear mortality benefit with prednisolone and pentoxifylline. Despite multiple studies and meta-analyses, controversy about the use of these medications persists.

Study Design: Multicenter, double-blind, randomized trial with 2-by-2 design.

Setting: Sixty-five hospitals across the United Kingdom.

Synopsis: Approximately 1,100 patients with a clinical diagnosis of alcoholic hepatitis were randomized to four groups: placebo + placebo; prednisolone + pentoxifylline-matched placebo; prednisolone-matched placebo + pentoxifylline; or prednisolone + pentoxifylline. Groups received 28 days of treatment. The primary endpoint was 28-day mortality. Secondary endpoints were mortality or liver transplantation at 90 days and one year.

Neither intervention showed a significant reduction in 28-day mortality. Secondary analysis with adjustments for risk showed a reduction in 28-day mortality in the prednisolone groups. There was no difference between groups for mortality or liver transplantation at 90 days or one year.

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Adverse events of death, infection, and acute kidney injury were reported in 42% of patients. Infection rates were higher in the prednisolone groups; however, attributable deaths were no different between groups.

Patients in this trial were younger, with a lower incidence of encephalopathy, infection, and acute kidney injury than those seen in similar trials, which could affect the rates of mortality seen here. Also, liver biopsy was not used, so patients may have been incorrectly included.

Bottom line: No difference was found in mortality or liver transplantation at 90 days and one year for prednisolone or pentoxifylline, although subanalysis showed there may be short-term benefit with prednisolone.

Citation: Thursz MR, Richardson P, Allison M, et al. Prednisolone or pentoxifylline for alcoholic hepatitis. New Engl J Med. 2015;372(17):1619-1628.