Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A severe and prolonged form of biopsy-proved cholestatic hepatitis occurred in a 45-year-old man who had received floxacillin for two weeks preceding the episode of drug-related cholestatic injury. Immunologic tests revealed evidence of in vitro sensitization to the drug as well as to the serum of a normal subject collected after ingestion of floxacillin. Floxacillin should be added to the list of drugs causing cholestatic hepatitis, most likely by an immunologic mechanism.
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PMID:Floxacillin-induced cholestatic hepatitis with evidence of lymphocyte sensitization. 357 50

The histological appearances of liver biopsies of 13 patients who developed cholestasis following courses of flucloxacillin are presented. In most of the cases jaundice and pruritus were protracted and in nearly all cases liver function tests are yet to return to normal after mean follow-up of 18 mths. One patient died after 7 mths of jaundice and another shows clinical evidence of secondary biliary cirrhosis. Biopsies typically showed hepatocellular and canalicular bile stasis with minimal or no hepatitis. Mild portal fibrosis and a patchy portal lymphocytic infiltrate were usually present. In 4 cases bile ducts were reduced in number and in 6 cases reduced in size. Bile duct epithelium showed degenerative changes but only occasional infiltration by inflammatory cells. Ductular proliferation was quite variable and in some cases--most noticeably the fatal case--was inconspicuous despite depletion of bile ducts. The appearances suggested damage not only of hepatocytes but also of bile ducts and proliferating ductules. This may explain the prolonged and occasionally irreversible hepatic disease associated with the use of flucloxacillin. Flucloxacillin should be included amongst the causes of vanishing bile duct syndrome.
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PMID:Flucloxacillin induced liver disease: histopathological findings at biopsy and autopsy. 826 36

Drugs and other chemical toxins account for less than 5% of cases of jaundice or acute hepatitis and fewer cases of chronic liver disease, but they are an important cause of more severe types of hepatic injury. Drug reactions produce an array of hepatic lesions that mimic all known hepatobiliary diseases; this poses a diagnostic challenge for physicians and pathologists. Diagnosis of drug-induced hepatic injury is circumstantial, with positive rechallenge being the only factor that unequivocally implicates a particular agent. Nonetheless, other aspects of the temporal relationship between drug ingestion and adverse reaction, exclusion of other diseases, the presence of extrahepatic features of drug hypersensitivity and some findings on liver biopsy can lend support to the diagnosis. Some of these issues will be explored in this review by considering contemporary paradigms of drug-induced hepatic injury. Factors that predispose to dose-dependent hepatic injury will be considered in relation to acetaminophen, an example of acute hepatotoxicity, and methotrexate, an agent that can produce hepatic fibrosis. Flucloxacillin will be discussed as an example of drug-induced cholestatic hepatitis often associated with prolonged cholestasis and the vanishing bile duct syndrome. Minocycline and diclofenac will be mentioned as two drugs for which drug hepatitis is an exceedingly rare complication. Finally, the evidence that Chinese herbal medicines can be hepatotoxic will be reviewed.
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PMID:Drug-induced hepatic injury. 940 44

Flucloxacillin is a semi-synthetic penicillin widely used in the prophylaxis and treatment of staphylococcal infections. Severe liver reactions, characterised by delayed cholestatic hepatitis and a prolonged course of recovery, are associated with flucloxacillin therapy. Clinical findings are suggestive of an immune mediated reaction but there exists little supporting experimental evidence. The formation of drug modified hepatic protein adducts has been proposed to play an important role in the hepatotoxicity of many drugs. The aim of the present study was to investigate whether flucloxacillin treatment results in adduct formation in vivo. Flucloxacillin was conjugated to rabbit serum albumin by formation of a penicilloyl determinant and used as an immunogen to raise a polyclonal antiserum specific for flucloxacillin-modified proteins. Antibody specificity was confirmed by competitive enzyme-linked immunosorbent assay (ELISA) with free drug. The antiserum was used in combination with western blotting to detect adduct formation in the livers of flucloxacillin treated rats. Western blot analysis of rat liver subcellular fractions revealed the formation of six flucloxacillin adducts in various subcellular fractions. These studies demonstrate for the first time that treatment with flucloxacillin results in the formation of hepatic protein adducts.
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PMID:Immunochemical detection of flucloxacillin adduct formation in livers of treated rats. 1611 90

Antibiotics are the therapeutic agents most often associated with hepatotoxicity. However, this is mainly due to the widespread prescription of these drugs. The relative risk of antibiotic-related hepatotoxicity is low. Causality assessment of suspected drug-induced liver injury (DILI) related to antibiotics can be difficult, particularly because some cases occur long after the drug has been stopped. Among the penicillins, amoxicillin clavulanate is the most associated with hepatotoxicity and is the most frequent cause of DILI-related hospitalisations. Flucloxacillin ranks as the second highest cause of DILI in many countries. The severity of antibiotic-induced DILI varies widely, with the hepatitis-like (hepatocellular) damage tending to be more severe that than cholestatic/mixed type. The pattern is strongly influenced by age. Recently telithromycin (a new generation macrolide) has been linked with DILI, with a typical pattern, which includes abrupt commencement of fever, abdominal pain, jaundice and, in some cases, ascites. Antibiotic-induced DILI appears, in most instances, to be idiosyncratic. Genetic-association studies have recently identified genotypes related to flucloxacillin and possibly to amoxicillin-clavulanate hepatotoxicity.
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PMID:Antibiotic-induced liver toxicity: mechanisms, clinical features and causality assessment. 2021 Jul 29