Liver transplantation for acute liver failure from drug induced liver injury in the United States

Studies of acute liver failure from drugs have included cases mostly attributed to acetaminophen (APAP) but have reported limited data on other drugs. We used the United Network for Organ Sharing (UNOS) liver transplant database from 1990 to 2002 to identify recipients and estimate a U.S. population-based rate of liver transplantation due to acute liver failure from drugs. Patients were identified if their diagnosis was acute hepatic necrosis from an implicated drug at the time of transplant. Liver transplantation for drug hepatotoxicity accounted for 15% of liver transplants for acute liver failure over the study period. In our cohort (n = 270), 206 (76%) recipients were female. APAP alone, or in combination with another drug, accounted for 133 (49%) cases. In the non-acetaminophen (non-APAP) group (n = 137), the most frequently implicated drugs were: isoniazid, n = 24 (17.5%); propylthiouracil, n = 13 (9.5%); and phenytoin and valproate in 10 (7.3%) cases each. One-year patient and graft survival for the entire cohort was 77 and 71%, respectively. Among Caucasians (n = 206) and African-Americans (n = 48), APAP only was implicated in 110 (53%) patients and 12 (25%) patients, respectively, and non-APAP drugs were implicated in 96 (47%) patients and 36 (75%) patients, respectively (P =.0004). Among African-Americans in the non-APAP group, 28 (78%) were women. In conclusion four drugs were implicated in 42% of patients undergoing liver transplantation for acute liver failure due to drugs other than APAP. The increased frequency of African-American women undergoing liver transplantation for non-APAP drug induced liver injury warrants further study.