Pharmacological Strategies for the Management of Severe Alcohol-associated Hepatitis: A Systematic Review and Meta-analysis

Abstract

Background & aims: Alcohol-associated hepatitis (AH) is a severe form of alcohol-associated liver disease, with a short-term mortality of up to 50% within 3 months. The aim of this systematic review was to determine the optimal pharmacological treatment for severe AH that results in better survival outcomes.

Methods: MEDLINE, EMBASE, and CENTRAL were searched through February 16, 2025, for randomized controlled trials (RCTs) of medical therapy for adults with severe AH. The primary outcome was mortality at 28 days. Secondary outcomes included mortality at 90 days, adverse events, the incidence of hepatorenal syndrome, acute kidney injury or infections, and liver transplantation rates. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for each outcome. GRADE was used to assess certainty of evidence.

Results: Fifty-two RCTs (5121 participants) were included in the review. A survival benefit at 28 days was observed for corticosteroids over placebo (RR, 0.62; 95% CI, 0.41‒0.95), for corticosteroids plus N-acetylcysteine over corticosteroids alone (RR, 0.35; 95% CI, 0.16‒0.78), for granulocyte colony-stimulating factor combined plus pentoxifylline over pentoxifylline alone (RR, 0.27; 95% CI, 0.13‒0.54), and metadoxine combined with corticosteroids over corticosteroids alone (RR, 0.47; 95% CI, 0.25‒0.90) or pentoxifylline (RR, 0.50; 95% CI, 0.26‒0.96). The certainty of evidence ranged from very low to moderate.

Conclusions: Low certainty evidence supports the efficacy of corticosteroids as first line therapy for eligible patients with severe AH. The certainty of the evidence supporting other therapies ranges from low to moderate. Further studies are needed to confirm these benefits.

Keywords: Alcohol; Alcoholic Hepatitis; Management of AH; Meta-analysis; Systematic Review.