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Acute-on-chronic liver failure(ACLF) results from an acute insult that occurs in patients with chronic liver disease,ultimately leading to liver failure.The underlying chronic liver dysfunction can be characterized into three categories:chronic liver disease with no cirrhosis;compensated liver cirrhosis;decompensated cirrhosis.The underlying chronic liver diseases are numerous and include alcoholic liver disease,viral hepatitis(types B and C),nonalcoholic fatty liver disease,and other underlying etiologies.1 Acute liver injury can arise from viral hepatitis infections(types A,B,and E),acetaminophen toxicity,drug-induced liver injury,toxin exposure,and numerous other hepatic and extrahepatic causes including heat stroke.2 Due to the numerous aspects of pathology that can generate both the chronic and acute components of ACLF,these patients can have significantly different pathology profiles.This makes ACLF difficult to clas-sify,and this is evident by the different ACLF definitions being used by the Asian Pacific Association for the Study of the Liver,the European Association for the Study of the Liver–Chronic Liver Failure Consortium,and the North American Consortium for the Study of End-Stage Liver Disease with regards to mor-tality,presence of organ failure,inclusion/exclusion criteria,and other disease characteristics.3,4 In addition,these differ-ent definitions of ACLF,depending on which definition is used,could potentially influence the outcomes of studies depending upon the metric investigated.