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STOPAH

Clinical Question

Does pentoxifylline or prednisolone improve survival rates in patients with severe alcoholic hepatitis?

Bottom Line

Pentoxifylline did not improve survival rates in patients with alcoholic hepatitis. Prednisolone was associated with a reduction in 28-day mortality that did not reach significance and with no improvement in outcomes at 90 days or 1 year.

Major Points

Guidelines

Design

Multicenter, double-blind, randomized controlled trial with a 2-by-2 factorial design evaluating pentoxifylline and prednisolone as treatments.

Population

- 1,103 patients were enrolled initially, with 1,053 available for the final analysis.
- Inclusion criteria:
- Age ≥18 years
- Clinical diagnosis of alcoholic hepatitis
- Severe disease (discriminant function ≥32 or bilirubin >80 μmol/L)
- History of heavy and prolonged alcohol use
- Exclusion criteria:
- Jaundice for more than 3 months
- Cessation of alcohol consumption for more than 2 months prior to randomization
- Other causes of liver disease present

Interventions

Patients were randomized into four groups:
- Placebo for both pentoxifylline and prednisolone
- Prednisolone alone
- Pentoxifylline alone
- Both prednisolone and pentoxifylline

Outcomes

Primary Outcome:
- Mortality at 28 days:
- Placebo–placebo: 17%
- Prednisolone–placebo: 14%
- Pentoxifylline–placebo: 19%
- Prednisolone–pentoxifylline: 13%

Secondary Outcomes:
- Death or liver transplantation at 90 days and at 1 year, with no significant differences observed between groups.
- Serious infections occurred in 13% of prednisolone patients versus 7% who did not receive prednisolone (P=0.002).

Criticisms

The accuracy of diagnosing alcoholic hepatitis without liver biopsy could be questioned, potentially impacting the power of the study to detect a treatment effect. The study was stopped early due to funding limitations, limiting the follow-up data available for some participants.

Funding

Funded by the National Institute for Health Research Health Technology Assessment program.