Prospective clinical trials and novel therapies in the medical management of severe alcohol‐associated hepatitis

Within the spectrum of alcoholassociated liver disease (ALD), severe alcoholassociated hepatitis (sAH) represents the most acute and severe manifestation. This clinical syndrome is characterized by jaundice, abdominal pain, and a systemic inflammatory response that carries significant morbidity and mortality. Rates of alcoholassociated hepatitis (AH) have been increasing, particularly during the coronavirus disease 2019 pandemic, which saw online sales of alcohol increase by 477% in 1 year.1 Few effective therapeutic options for AH exist. Corticosteroids have persisted as the mainstay of treatment for sAH despite considerable limitations, highlighting an unmet need for effective pharmacological therapies. Agents targeting the underlying pathogenic pathways implicated in AH provide new hope for therapeutic advances. Activation of cytokine signaling and inflammatory cascades, altered mechanisms of hepatic regeneration in response to oxidative stress, and increased gastrointestinal tract permeability facilitating systemic bacterial translocation have all been implicated in the complex pathophysiology of AH2 (Figure 1). This review highlights novel therapeutic agents for sAH currently under study through the lens of their proposed mechanism of action.