Network Meta-Analysis: Treatments for Acute Alcohol-Associated Hepatitis

Alcohol-related hepatitis (AH) is an acute form of liver disease with a high short-term mortality. A variety of treatments have been explored in randomised studies. Recent consensus on study outcomes has identified 90-day survival as the primary outcome metric.

This systematic review and network meta-analysis is to update understanding of the comparative efficacy of treatments for AH, based on 90-day survival, to inform future Phase III studies.

PubMed, Ovid-Medline and Embase were searched for randomised studies of treatments of AH. The risk of bias in included papers was measured using the Cochrane risk of bias 2 tool. Data were synthesised with network meta-analysis to estimate risk ratio (RR) of survival at 90 days after randomisation. Heterogeneity was assessed with the magnitude of the between-study variance (tau²).

Thirty five studies including 5045 participants were identified that examined 24 treatments for AH. Twenty-three studies were considered to be at low risk of bias. In network meta-analysis considering placebo as the reference treatment, only granulocyte colony stimulating factor (GCSF) showed a statistically significant benefit on 90-day mortality (RR 0.49, 95% CI 0.28-0.84; p = 0.009). In subgroup analysis of studies at low risk of bias, no treatments showed a significant effect on mortality at 90 days.

Individual studies are small and heterogeneity is marked; however, some agents show promise to improve survival at 90 days in people with AH. This information should inform adequately powered studies to explore potential treatments for AH.