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)

Antituberculosis drug-induced hepatitis is one of the most prevalent drug-induced liver injuries. Isoniazid is the major drug incriminated in this hepatotoxicity. Isoniazid is mainly metabolized to hepatotoxic intermediates by N-acetyltransferase (NAT). However, the association of polymorphic NAT acetylator status and antituberculosis drug-induced hepatitis is debatable. To determine whether acetylator status is a risk factor for antituberculosis drug-induced hepatitis, we genotyped NAT2 in 224 incident tuberculosis patients who received antituberculosis treatment. Antituberculosis drug-induced hepatitis was diagnosed based on a positive isoniazid rechallenge test and exclusion of viral hepatitis. Acetylator status was determined by genotyping NAT2 in patients using a polymerase chain reaction with restriction fragment length polymorphism. Univariate analysis and logistic regression analysis were used to evaluate the risk factors of isoniazid-induced hepatitis. Thirty-three patients (14.7%) were diagnosed with antituberculosis drug-induced hepatitis. Slow acetylators had a higher risk of hepatotoxicity than rapid acetylators (26.4% vs. 11.1%, P =.013). Among patients with hepatotoxicity, slow acetylators had significantly higher serum aminotransferase levels than rapid acetylators. Logistic regression showed that slow-acetylator status (odds ratio [OR], 3.66; 95% CI, 1.58-8.49; P =.003) and age (OR, 1.09; 95% CI, 1.04-1.14; P <.001) were the only 2 independent risk factors for antituberculosis drug-induced hepatitis. In conclusion, slow-acetylator status of NAT2 is a significant susceptibility risk factor for antituberculosis drug-induced hepatitis. Additionally, slow acetylators are prone to develop more severe hepatotoxicity than rapid acetylators. Regular monitoring of serum aminotransferase levels is mandatory in patients receiving antituberculosis treatment, especially in slow acetylators.
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PMID:Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug-induced hepatitis. 1191 35

The literature was reviewed to study cases of intoxication with systemic dermatitis associated with exposure to trichloroethylene. The average age of patients in the reports reviewed to date was twenty-nine; these diseases were found in relatively young persons and no difference was found according to gender. Many cases occurred within one month after the onset of exposure to trichloroethylene, and were accompanied by hepatitis, jaundice, hepatomegaly or hepatosplenomegaly. Most of the patients had no history of drug abuse or herpes infection. The level of exposure to trichloroethylene was not recorded in many cases, but ranged from less than 9 ppm to 800 ppm. In the severest cases, the lesions involved mucous membranes such as the conjunctiva and oral cavity, and the patients were diagnosed with Stevens-Johnson syndrome, but the etiology of the disease after trichloroethylene exposure remains unclear. Since several drugs have also been shown to cause systemic dermatitis with hepatitis, susceptibility factors are discussed. Many patients were found to have the slow acetylator genotype of N-acetyltransferase (NAT) 2, suggesting that the NAT2 genotype is a susceptibility factor. This hypothesis may also be applicable to trichloroethylene because NAT is involved in the glutathione-mediated metabolism.
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PMID:Generalized skin reactions in relation to trichloroethylene exposure: a review from the viewpoint of drug-metabolizing enzymes. 1460 23

Isoniazid (INH) treatment can cause serious liver injury and autoimmunity. There are now several lines of evidence that INH-induced liver injury is immune mediated, but this type of liver injury has not been reproduced in animals, possibly because immune tolerance is the dominant response of the liver. In this study, we immunized mice with isonicotinic acid (INA)-modified proteins and Freund's adjuvant, which led to mild experimental autoimmune hepatitis (EAH) with an increase in cells staining positive for F4/80, CD11b, CD8, CD4, CD45R, and KI67. We expected that subsequent treatment of mice with oral INH would lead to more serious immune-mediated liver injury, but paradoxically it markedly attenuated the EAH caused by immunization with INA-modified hepatic proteins. In addition, patients of the slow acetylator phenotype are at increased risk of INH-induced liver injury. Treatment of arylamine N-acetyltransferase-deficient Nat1/2(-/-) mice with INH for up to 5 weeks produced mild increases in glutamate and sorbitol dehydrogenase activities, but not severe liver injury. Female Nat1/2(-/-) mice treated with INH for 1, 3, or 7 days developed steatosis, an increase in Oil Red O staining, and abnormal mitochondrial morphology in the liver. A decrease in M1 and an increase in M2a and M2b macrophages was observed in female Nat1/2(-/-) mice treated with INH for 1, 3, or 7 days; these changes returned to baseline levels by day 35. These data indicate that INH has immunosuppressive effects, even though it is also known to induce autoantibody production and a lupus-like autoimmune syndrome in humans.
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PMID:Paradoxical attenuation of autoimmune hepatitis by oral isoniazid in wild-type and N-acetyltransferase-deficient mice. 2462 63