Hayashi, Paul H.Rockey, DonFontana, Robert J.Tillmann, Hans L.Kaplowitz, NeilBarnhart, HuimanGu, JiezhanChalasani, NagaReddy, K. RajenderSherker, Averell H.Hoofnagle, Jay H.2017-07-132017-07-132017Hayashi, P. H., Rockey, D., Fontana, R. J., Tillmann, H. L., Kaplowitz, N., Barnhart, H., Gu, J., Chalasani, N. P., Reddy, K. R., Sherker, A. H., Hoofnagle, J. H. and for the Drug Induced Liver Injury Network (DILIN) Investigators. (2017), Death and Liver Transplantation within Two Years of Onset of Drug-Induced Liver Injury. Hepatology. Accepted Author Manuscript. doi:10.1002/hep.29283https://hdl.handle.net/1805/13438Drug-induced liver injury (DILI) is an important cause of death and indication for liver transplantation (fatality). The role of DILI in these fatalities ispoorly characterized particularly when fatalities occur > 26 weeks after DILI onset. We analyzed patients in the U.S. Drug-Induced Liver Injury Network prospective study having a fatal outcome within 2 years of onset. Each case was reviewed by 8 Network investigators and categorized as DILI having a primary, contributory or no role in the fatality. We subcategorized primary role cases as acute, chronic, acute-on-chronic or acute cholestatic liver failure. For contributory and no role cases, we assigned a primary cause of death. Among 1089 patients, 107 (9.8%) fatalities occurred within 2 years. DILI had a primary role in 68 (64%), a contributory role in 15 (14%) and no role in 22 (21%); 2 had insufficient data. Among primary role cases, 74% had acute, 13% chronic, 7% acute-on-chronic and 6% acute cholestatic failure. For the 15 contributory role cases, common causes of death included sepsis, malignancy and severe cutaneous reactions with multi-organ failure. For the 22 no role cases, malignancies accounted for most fatalities. Higher bilirubin, coagulopathy, leukocytosis and thrombocytopenia were independently associated with DILI fatalities. nR Hy's Law had a higher positive predictive value for overall fatality (14% vs. 10%) and stronger independent association with DILI fatalities within 26 weeks compared to the original version of Hy's Law (HR: 6.2, CI 3.4 – 11.1 vs. 2.2, CI 1.3-3.7). DILI leads directly or indirectly to fatality in 7.6% of cases; 40% of these have non-acute liver failure courses. nR Hy's Law better identifies risk for death compared to the original Hy's Law.enPublisher Policyacute liver failureliver transplantationhepatoxicityArticle