impairment of bile flow and cases are predominated by itching and jaundice. histology may show inflammation (cholestatic hepatitis) or it can be bland (without any parenchymal inflammation). on rare occasions, it can produce features similar to primary biliary cirrhosis due to progressive destruction of small bile ducts (vanishing duct syndrome). causes: (a) bland: oral contraceptive pills, anabolic steroid, androgens (b) inflammatory: allopurinol, co-amoxiclav, carbamazepine (c) ductal: chlorpromazine, flucloxacillin steatosis hepatotoxicity may manifest as triglyceride accumulation, which leads to either small-droplet (microvesicular) or large-droplet (macrovesicular) fatty liver. there is a separate type of steatosis by which phospholipid accumulation leads to a pattern similar to the diseases with inherited phospholipid metabolism defects (e.g., tay–sachs disease) causes: (a) microvesicular: aspirin (reye's syndrome), ketoprofen, tetracycline (especially if expired) (b) macrovesicular: acetaminophen, methotrexate (c) phospholipidosis: amiodarone, total parenteral nutrition (d) antiviral: nucleoside analogues (e) corticosteroid (f) hormonal: tamoxifen granuloma drug-induced hepatic granulomas are usually associated with granulomas in other tissues and patients typically have features of systemic vasculitis and hypersensitivity. more than 50 drugs have been implicated. causes: allopurinol, phenytoin, isoniazid, quinine, penicillin, quinidine vascular lesions these result from injury to the vascular endothelium. causes: venoocclusive disease: chemotherapeutic agents, bush tea peliosis hepatis: anabolic steroids hepatic vein thrombosis: oral contraceptives neoplasm neoplasms have been described with prolonged exposure to some medications or toxins. hepatocellular carcinoma, angiosarcoma, and liver adenomas are the ones usually reported. causes: vinyl chloride, combined oral contraceptive pill, anabolic steroid, arsenic, thorotrast diagnosis algorithm for suspected drug-induced hepatic toxicity this remains a challenge in clinical practice due to a lack of reliable markers. many other conditions lead to similar clinical as well as pathological pictures. to diagnose hepatotoxicity, a causal relationship between the use of the toxin or drug and subsequent liver damage has to be established, but might be difficult, especially when idiosyncratic reaction is suspected. simultaneous use of multiple drugs may add to the complexity. as in acetaminophen toxicity, well established, dose-dependent, pharmacological hepatotoxicity is easier to spot. several clinical scales such as cioms/rucam scale and maria and victorino criteria have been proposed to establish causal relationship between offending drug and liver damage. cioms/rucam scale involves a scoring system that categorizes the suspicion into "definite or highly probable" (score > 8), "probable" (score 6–8), "possible" (score 3–5), "unlikely" (score 1–2) and "excluded" (score ≤ 0). in clinical practice, physicians put more emphasis on the presence or absence of similarity between the biochemical profile of the patient and known biochemical profile of the suspected toxicity (e.g., cholestatic damage in amoxycillin-clauvonic acid ). treatment in most cases, liver function will return to normal if the offending drug is stopped early. additionally, the patient may require supportive treatment. in acetaminophen toxicity, however, the initial insult can be fatal. fulminant hepatic failure from drug-induced hepatotoxicity may require liver transplantation. in the past, glucocorticoids in allergic features and ursodeoxycholic acid in cholestatic cases had been used, but there is no good evidence to support their effectiveness. prognosis an elevation in serum bilirubin level of more than 2 times uln with associated transaminase rise is an ominous sign. this indicates severe hepatotoxicity and is likely to lead to mortality in 10% to 15% of patients, especially if the offending drug is not stopped (hy's law). this is because it requires significant damage to the liver to impair bilirubin excretion, hence minor impairment (in the absence of biliary obstruction or gilbert syndrome) would not lead to jaundice. other poor predictors of outcome are old age, female sex, high ast. drugs withdrawn the following therapeutic drugs were withdrawn from the market primarily because of hepatotoxicity: troglitazone, bromfenac, trovafloxacin, ebrotidine, nimesulide, nefazodone, ximelagatran and pemoline.