Controversies in clinical trials for alcoholic hepatitis.

Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease, contributing to significant morbidity and mortality. Yet, the only available therapies that improve survival are corticosteroids and liver transplantation, with no new drugs successfully developed for decades. This article briefly describes the current state of affairs in AH therapy and examines the practical and ethical challenges of conducting controlled trials in patients with severe AH. While prednisolone is considered standard of care in severe AH, this recommendation remains controversial given the marginal benefits and questionable long-term safety of steroids. Placebo-controlled trials without steroids may be necessary and ethically justified in certain populations with AH who have not been adequately investigated. Ultimately, we suggest that the field will advance with the development of a plausible animal model of true AH, a consensus on a composite clinical endpoint that does not rely solely on mortality, as well as the adoption of the NIAAA Alcoholic Hepatitis Consortia recommendations regarding standard definitions and when to request a liver biopsy prior to study entry.