Acute-on-chronic liver failure in metabolic dysfunction-associated fatty liver disease patients: a disease multiplier

Acute-on-chronic liver failure (ACLF) is a syndrome of liver failure due to an acute hepatic insult leading to liver failure with or without extra-hepatic organ failure in a patient of chronic liver disease (CLD) with or without cirrhosis presenting for the first time. The definition is still with controversy; hence, homogeneity and clarity of the case is an unmet need. There is a paradigm shift noted as far as the etiology of CLD is concerned with rise in metabolic dysfunction-associated fatty liver disease (MAFLD) and ethanol as the dominant cause even in developing countries. MAFLD is the change in nomenclature from NAFLD to justify the metabolic derangement in these group of patients. The shift from an exclusion-based criteria to one that has evolved to a diagnosis that requires positive criteria has profound significance. Clearly there is a difference in terms of its prevalence, disease progression, and liver-related events, as well as management of metabolic risk factors and MAFLD itself which requires further understanding. In tandem with the global rise in MAFLD, the incidence of MAFLD-ACLF is increasing. Excessive alcohol consumption causes metabolic and toxic injury to the liver resulting in nearly similar pathway of fatty liver, hepatitis, and cirrhosis. The interaction of MAFLD as an additional underlying chronic liver injury in ACLF patients is complex due to the presence of metabolic risk factors that are unique to MAFLD. There is lack of clarity on how MAFLD affects the clinical course of ACLF due to scarcity of this specific data. This narrative review aims to understand the unique effects, consequences, and management of MAFLD as the chronic liver injury component in ACLF.