Acute Liver Failure Etiology Is an Independent Predictor of Waitlist Outcome but Not Posttransplantation Survival in a National Cohort

The impact of acute liver failure (ALF) etiology on waitlist (WL) and posttransplantation outcomes, independent of severity of illness, is incompletely characterized. All adults (n = 1691) listed for primary liver transplantation (LT) between 2002 and 2019 with ALF due to acetaminophen toxicity (APAP), drug-induced liver injury (DILI), autoimmune hepatitis (AIH), and hepatitis B virus (HBV) were identified in the United Network for Organ Sharing database. ALF etiology was evaluated as an independent predictor of WL mortality and spontaneous survival (SS; versus outcome of LT), as well as post-LT overall survival, graft survival, and in-hospital mortality using multivariable models accounting for differences in clinical parameters at listing. Accounting for severity of illness at listing, WL mortality and SS for DILI, AIH, and HBV were each lower than those for APAP toxicity (adjusted relative risk ratio <1 in all analyses with P < 0.001 for both outcomes). ALF etiology was not associated with adjusted overall survival after LT (P = 0.09) or graft survival (P = 0.13). Inpatient mortality rate after LT was high at 9.0%. While ALF etiology was also not associated with adjusted inpatient mortality (P = 0.42), cause of death (COD) was different. For example, the rate of post-LT brain death was 5.3% for APAP toxicity, 3.0% for other DILI, 1.1% for AIH, and 3.0% for HBV (P = 0.02). ALF etiology is an independent predictor of WL outcome, even after adjusting for severity of illness, but is not associated with post-LT outcomes with the exception of COD. The majority of post-LT deaths for all ALF etiologies studied occurred during the index hospital stay, suggesting a continued need for enhanced prognostic tools to ensure efficient organ utilization and ALF- and etiology-specific post-LT care to prevent brain death.