Current Clinical Trials for Alcohol-Associated Hepatitis.

Abstract

Alcohol-associated hepatitis (AH) is a severe form of alcohol-associated liver disease characterized by acute-onset jaundice and liver failure. AH carries a high mortality risk, particularly in severe cases. Although glucocorticoids have been the primary pharmacologic intervention for decades, their use is limited by a lack of long-term efficacy and significant side effects and relative contraindications. For patients who do not respond to glucocorticoids, early liver transplantation is a life-saving option; only a few patients qualify for this intervention, however. In recent years, advances in translational medicine have uncovered key mechanisms in AH pathophysiology, including microbiome interactions, proinflammatory signaling, and disruptions in hepatocyte function. These insights have led to the exploration of innovative pharmacologic treatments, targeting pathways such as the gut-liver axis, oxidative stress, inflammation, and liver regeneration. Despite promising results from ongoing clinical trials, several challenges persist, including low patient recruitment and retention rates, heterogeneity in trial design, and the lack of standardized endpoints. This review assesses the current pharmacologic landscape of AH, emphasizing emerging therapies and the ongoing challenges in AH clinical trials.