24 High mortality from idiosyncratic DILI ALF,
has been observed.21, 30 In our study transplant-free survival was only 27.1% (Tables 4 and 5). Fortunately, 56 of the 73 listed remained eligible for liver transplantation, from which all but 4 (92.8%) survived, giving an overall survival of 66.2%. The 23.3% wait-list deaths attest to the urgent need for donor organs in this setting.21 In multivariate analysis, coma grade, jaundice, coagulopathy, and MELD score all predicted transplant-free survival (Table 5). Most striking was the 43.2% lower bilirubin IWR-1 supplier level (12.6 mg/dL) in transplant-free survivors, compared to those with severe outcomes (22.2 mg/dL; P < 0.001). Age,16, 18, 30 duration of drug use,19 ascites,54 drug class,16 and pattern of DILI reaction16, 18 were predictive of outcome in other studies but not here. Neither was the axiom upheld that cholestatic DILI is less life-threatening than hepatocellular DILI.5 BMI did not affect outcome in DILI ALF, as was seen in a larger study of all-cause ALF.54 The trend to better outcomes when coma supervened soon after the onset of symptoms or jaundice
has been observed elsewhere.25, this website 33 Intuitively, one would expect a good result if the offending drug were discontinued promptly when symptoms or liver test abnormalities occur, but that was not the case in our study, presumably because established ALF was the inclusion criterion. Although NAC use appeared to be associated with improved transplant-free survival (Table 5), the result of multivariable
logistic regression analysis did not confirm NAC efficacy independent of MELD score and coma. It should be noted that the current study was not a randomized trial designed to test the effect of NAC on DILI ALF outcome, as reported elsewhere.22 In conclusion, DILI ALF disproportionately affects women and minorities and is most frequently caused by antimicrobials and to a lesser extent by antiepileptics, antimetabolites, statins, and herbal products. Presentations are subacute and though spontaneous survival is infrequent, for many patients liver transplantation is often feasible and highly medchemexpress successful. Survival in DILI ALF is determined by the degree of liver dysfunction. The selection bias of referral to highly specialized tertiary care centers, the imprecision of history in terms of duration of drug use, alcohol habit, and the effects of diabetes (which appear to reduce or facilitate DILI, respectively19), offer study opportunities that may permit future application of quantitative causality testing. We thank Linda S. Hynan, Ph.D., and Corron Sanders, Ph.D., at UTSW for providing ALF data, and Drs. Robert Fontana (University of Michigan), Timothy Davern (California Pacific Medical Center), and Michael Schilsky (Yale University) for insightful comments and corrections to the manuscript. Members and institutions participating in the Acute Liver Failure Study Group 1998-2007: W.M. Lee, M.D. (Principal Investigator), George A.