For practitioners seeing patients with unexplained acute liver disease, comprehensive catalogs of DILI ALF agents are useful, but these NVP-LDE225 cost lists are only “snapshots” because prescribing practices vary geographically and temporarily.3, 24, 34 Few biologicals were implicated here, but DILI from these compounds is emerging,

including fatalities.44 Within the broad spectrum of causative agents, antimicrobials dominate.13, 16, 18, 21 Isoniazid, as monotherapy or in combination, commonly causes hepatoxicity leading to liver transplantation,17 followed by sulfur drugs, nitrofurantoin, other antibiotics, and antifungals. Amoxicillin-clavulanic and NSAIDs often cause DILI,19, 28, 45 but less commonly ALF. Perhaps the inflammation caused by the infection for which antibiotics are prescribed, predisposes the patients to develop DILI.46 Antiepileptics, antimetabolites, herbal mixtures and their derivatives, slimming potions, and illicit drugs,

have strong reputations as hepatotoxins7, 47, 48 and were well represented in our study. Statin prevalence (n ≥ 6) was unexpected, as was the occasionally long duration of exposure (median 3-6 months; range, <1 month to 36 months; see also the footnote to Table 1C). Statin hepatotoxicity is generally benign,49 but statins have been responsible for a few DILI-associated fatalities,18, 19 and atorvastatin-to-simvastatin substitution hepatitis has been reported.50 In six subjects, a statin was the only potential DILI agent—albeit sometimes with a long latency (6-36 months in three of them)—and JAK inhibitor this increases confidence in our provocative observation that awaits confirmation by others. The latency between drug use and DILI onset varies, but is usually up to 3 months although delays of up to 12 months are considered compatible.6, 16, 19, 25, 40, 45 Extended latency is the norm for nitrofurantoin51 and some other drugs,

like diclofenac. In the current study, when the cause of DILI ALF was certain, the median exposure was 2 months, but even here six cases had 6 to 10 months of latency. For isoniazid median latency was 5 months; 6-8 months in one-third of the cases. As anticipated,10, 15, 19, 21 DILI in ALF was mostly hepatocellular (77.8%) compared Ribose-5-phosphate isomerase to cholestatic and mixed reactions (19.2%) Conventional causes of cholestatic and mixed reactions (phenothiazines, macrolides, NSAIDs, carbamazepine, and phenytoin34, 52, 53) were rare. We confirmed that many drugs can cause cholestatic and mixed hepatotoxic reactions16, 19 (Table 3). Three drugs in this study have been withdrawn (bromfenac and troglitazone because of hepatotoxicity, and cerivastatin because of rhabdomyolysis), and development of the hypoglycemic agent, TAK 559, was halted. Many drugs carry warnings of hepatotoxicity (isoniazid, rifampin, ketaconazole, diclofenac, valproic acid, telithromycin, and interferon-β).