We also examined

the relationship between illness duration and survival, because outcome has been inversely related to the tempo of development of ALF.25 The intervals between onset of symptoms and stage 1 coma (or stage 2 coma; data not shown), or between jaundice and stage 1 coma, respectively, were shorter in transplant-free survivors than in those who BGJ398 ic50 underwent transplantation, those who died, and those who underwent transplantation or died, respectively (Table 4 and 5), but not statistically significant by univariate (Table 4) or multivariate (Table 5) analysis. Severity of coma, MELD score, and NAC use were entered into a multivariable logistic regression model. MELD met the requirements for linearity in the log odds for rate of transplant-free survival, and neither colinearity I-BET-762 chemical structure nor interaction was present among the covariates. Both MELD score (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.89-0.99; P = 0.01) and coma severity (OR, 0.33; 95%CI, 0.14-0.79; P = 0.01) predicted poor outcomes; however, NAC use was no longer predictive (OR, 1.89; 95%CI, 0.79-4.51; P = 0.15); the model fit was adequate by the Hosmer-Lemeshow goodness-of-fit test

(P = 0.88). This study prospectively explores the causes and consequences of the most serious form of DILI, namely ALF. DILI ALF is characterized by deep jaundice, fluid retention, advanced coagulopathy, and coma (but only moderate elevations of aminotransferases), indicating a slowly evolving or “subacute” condition. This biochemical profile of DILI ALF contrasts with acetaminophen-induced and most other identifiable causes of ALF, which show much higher aminotransferases21, 26, 27 and, in the case of acetaminophen, much less hyperbilirubinemia.26 One-quarter of DILI ALF subjects exhibited an immunoallergic reaction, i.e., rash, Fluorometholone Acetate eosinophilia, or autoantibody positivity. Despite polypharmacy, it was relatively easy to decide which drug or group of drugs was the likely culprit. The most common causes of DILI ALF were antimicrobials, but neuroactive drugs, various CAMs, illicit substances, and statins were frequently

implicated. The outcome of DILI ALF is predicted by the degree of liver dysfunction—as judged by the severity of coma, hyperbilirubinemia, and coagulopathy—but not by the class of drugs, drug injury pattern, age, gender, obesity, or timing of cessation of drug use. When transplant-free recovery from DILI ALF is combined with the excellent results of liver transplantation, overall survival approaches 70%. In the current study, the high female predominance is similar to the gender imbalance seen in DILI ALF in Spain,28 in acetaminophen-induced ALF in Sweden,29 and in U.S. ALF patients of any cause,21, 30, 31 including DILI transplant recipients,17 suggesting that women with acute liver injury are either more predisposed to develop ALF or use more prescription drugs than men.