Alcohol-induced steatohepatitis (ASH) increases the risk for both clinically-severe acute alcoholic hepatitis and eventual cirrhosis. The mechanisms that control ASH pathogenesis and progression are unclear but processes that regulate liver cell plasticity seem to be critically involved. In injured adult livers, morphogenic signaling pathways that modulate cell fate decisions during fetal development and in adult liver progenitors become reactivated. Overly-exuberant activation of such morphogenic signaling causes dysregulated liver repair and increases short- and long-term mortality by promoting acute liver failure, as well as progressive fibrosis. Hence, these pathways may be novel therapeutic targets to optimize liver cell reprogramming and prevent defective regenerative responses that cause acute liver failure and cirrhosis.