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 β«Ψβ¬ 270), 206 (76%) recipients were female. APAP alone, or in combination with another drug, accounted for 133 (49%) cases. In the nonacetaminophen (non-APAP) group (n β«Ψβ¬ 137), the most frequently implicated drugs were: isoniazid, n β«Ψβ¬ 24 (17.5%); propylthiouracil, n β«Ψβ¬ 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 β«Ψβ¬ 206) and African-Americans (n β«Ψβ¬ 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 β«Ψβ¬ .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. (Liver Transpl 2004; 10:1018-1023.) D rug induced liver injury is an important medical problem in the United States. Serious drug induced liver injury may lead to hospitalization, and it is the most common identifiable cause of acute liver failure in the United States. 1,2 Drug induced liver injury has also been the most common single adverse event causing major regulatory problems during drug development and marketing, including failure to obtain FDA approval and the withdrawal of drugs from the market place. 3 In recognition of the need for more investigation of drug induced liver injury, the National Institutes of Diabetes, Digestive and Kidney Diseases recently established the Drug Induced Liver Injury Network. Prior population-based studies from Europe suggest that severe drug induced liver injury is underestimated in single or multicenter studies. 4,5 Population based data on drug induced liver injury in the United States are limited. Reporting of adverse drug reactions through MedWatch is voluntary, and cases of serious drug induced liver injury may not be captured. A study that was conducted in Boston area hospitals in 1974 reported that 3 to 5% of patients are hospitalized for drug induced liver injury. 6 More recently, in a study of acute liver failure from 17 centers in the United States, 308 cases of acute liver failure were captured of which 160 (52%) were due to drugs. 2 Acetaminophen (APAP) accounted for 75% of the drug induced liver injury cases. Details of the other drugs implicated in causing acute liver failure were not reported.
Studies of drug induced liver failure in the United States have been small single center studies or large multicenter studies that have not provided details on the types of drugs, other than APAP, that led to acute liver failure and liver transplantation. 1,2,8 -10 All liver transplants performed in the United States should be entered into the United Network for Organ Sharing (UNOS) liver transplant database. This database, therefore, provides the opportunity to estimate a populationbased incidence of liver transplantation for acute liver failure from drugs in the United States, including drugs other than APAP, and to identify characteristics of liver transplant recipients who developed acute liver failure from drugs.