Alcohol-associated liver disease (ALD) is a major driver of morbidity and mortality globally, especially in its most severe phenotypes, including alcohol-associated hepatitis (AH), decompensated cirrhosis, and hepatocellular carcinoma. With no US Food and Drug Administration-approved therapies to improve ALD, there is an unmet clinical need to better define the pathophysiology of early and severe liver disease. Recent improvements in preclinical models have furthered our understanding of the mechanisms of disease in advanced ALD. In this review, our focus is on current progress in identifying therapeutic targets utilizing preclinical models and reporting the rationale for and current status of ongoing clinical trials that aim to develop effective therapies to slow the progression of earlier stages of ALD and especially improve survival in severe AH.
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