Anthony C Breu, Vilas R Patwardhan, Jennifer Nayor, Jalpan N Ringwala, Zachary G Devore, Rahul B Ganatra, Kelly E Hathorn, Laura Horton, Sentia Iriana, Elliot B Tapper

The differential diagnosis of an increase in alanine aminotransferase (ALT) level and/or aspartate aminotransferase (AST) level of ≥1000 IU/L often is stated to include 3 main etiologies: ischemic hepatitis, acute viral hepatitis (typically hepatitis A and hepatitis B), and drug-induced (more specifically, acetaminophen/paracetamol) liver injury (DILI).1 Unfortunately, there are a paucity of studies examining the most common causes of acute liver injury (ALI) and those that have been published have been small,2 single-center,2 or examined less severe increases in ALT or AST levels.3,4 We conducted a multicenter study of all patients with an ALT and/or AST level ≥1000 IU/L. Our study had 3 main goals: (1) to determine the most common causes of an ALT and/or AST level ≥1000 IU/L, along with their relative frequencies; (2) to determine differences in etiology based on hospital type (liver transplant center, community hospital, Veterans Affairs hospital); and (3) to confirm or disprove the differential heuristic that ischemic hepatitis, acute viral hepatitis, and acetaminophen toxicity are the most common etiologies.