6 Estimates of the burden Pirfenidone of DILI vary according to criteria for cohort selection.8, 9 In a population-based study from a rural area in France,10 the crude global incidence of DILI was 13.9 cases/100,000 population—a rate 16-fold higher than reported to regulatory authorities. Four of 34 (11.8%) patients in that study were hospitalized, and two (5.9%) died.10 In a 1990s United Kingdom-based survey,11 DILI requiring specialist referral affected 2.4 cases/100,000

person-years (similar to the 1980s DILI incidence in Denmark12), of whom 36/128 (28.2%) were hospitalized, but only one required liver transplantation. DILI is a frequent cause of hepatitis13 and hospitalization,11, 12 and is implicated in 5%-10% of all patients hospitalized for jaundice,14, 15 accounting for 95% of Everolimus research buy adverse drug reactions and 14.6% of drug fatalities

in Denmark.12 Case series of severe idiosyncratic DILI and DILI-induced acute liver failure (ALF) leading to death or liver transplantation have been described16-19 and reviewed.20 Since our initial report of ALF in the United States,21 there has been no overview of ALF caused by nonacetaminophen DILI. The aim of the present study is to identify presenting features, suspect agents, and predictors of outcome in a consecutive cohort of adult idiosyncratic DILI ALF patients. ALF, acute liver failure; ALT, alanine aminotransferase; ANA, antinuclear antibody; BMI, body mass index; CAM, complementary and alternative medication; CI, confidence interval; DILI, drug-induced liver injury; FDA, U.S. Federal Drug Administration; INR, international normalized ratio; IQR, interquartile range; MELD, Model for End-Stage Liver Disease; NAC, N-acetylcysteine; NSAID, nonsteroidal anti-inflammatory drug; OR, odds ratio; SD, standard deviation; TMP-S, trimethoprim-sulfamethoxazole; UTSW, University of Texas, Southwestern. From January 20, 1998 through Pregnenolone July 5, 2007, demographic, clinical, and laboratory results were recorded prospectively at enrollment, and imaging, histology, and outcome data were obtained from 1198 subjects meeting entry criteria

for ALF at 23 academic centers participating in the National Institutes of Health (NIH)-funded Acute Liver Failure Study Group.21 All centers had liver transplant services. By definition, ALF patients had coagulopathy (international normalized ratio [INR] ≥ 1.5), hepatic encephalopathy (hepatic coma), and <26 weeks of illness without apparent chronic liver disease.21 Written informed consent was obtained from legal next-of-kin. Outcomes within 3 weeks of enrollment were defined as transplant-free (i.e., spontaneous) survival and discharge, liver transplantation, or death.21 All centers complied with their local Institutional Review Boards’ requirements and the Health Insurance Portability and Accountability Act (HIPAA).