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)

Approximately 10% to 20% of isoniazid recipients manifest biochemical evidence of liver injury. A smaller number of patients develop clinically overt hepatitis. Isoniazid is metabolized in man at extremely variable rates, and the rate is under genetic control. Two separate clinical studies have noted a possible relation between susceptibility of patients to isoniazid liver injury and rapid metabolism (acetylation) of the drug. For this reason, 21 patients who had recovered from probable isoniazid hepatitis and 5 patients who previously had manifested biochemical evidence of mild isoniazid liver injury were genetically phenotyped as rapid or slow isoniazid acetylators by the sulfamethazine method. The rapid phenotype was found in 86% of patients with probable hepatitis and in 60% of the possible ones, whereas the expected frequency was 45%. Eximination of isoniazid metabolites revealed that rapid acetylators hydrolze much more isoniazid to isonic otinic hydrazine moiety than do slow acetylators. The hydrazine moiety liberated from isoniazed is primarily acetylhydrazine, and studies in animals show this metabolite to be converted to a potent acylating agent that produces liver necrosis. We suggest that release of the hepatotoxic hydrazino moiety of isoniazid in man is responsible for isoniazid liver injury.
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PMID:Increased incidence of isoniazid hepatitis in rapid acetylators: possible relation to hydranize metabolites. 114 65

The incidence of tuberculosis in the United States, after decreasing for many years, has recently begun to climb at an alarming rate. This rise is due mainly to excess cases in high-risk groups including human immunodeficiency virus-infected patients, the elderly, the foreign born, and the homeless. In the United States tuberculosis has been associated with a 10% mortality despite adequate treatment. The tuberculin skin test is a safe and inexpensive test for detecting tuberculous infection. To improve its predictive value the diagnostic criteria for classifying a positive reaction have recently been revised. High-risk populations should be screened to identify those persons who would most benefit from preventive treatment. Isoniazid therapy taken for 6 to 12 months is a safe and highly effective means of preventing tuberculous infection from developing into active disease. The most worrisome toxicity of isoniazid, fatal hepatitis, is extremely rare; when patients are monitored closely the incidence of death from hepatotoxicity is less than 0.01%.
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PMID:Tuberculosis chemoprophylaxis. 146 52

Hepatotoxicity to different combinations of anti-tuberculosis drugs containing, Rifampicin (R), Streptomycin (S), Isoniazid (H), Pyrazinamide (Z) and Myambutol (E) is described in 47 patients who completed 6 to 9 months therapy. Seven cases (15%) showed signs of toxicity and in 4 patients (8.5%) the drugs had to be withdrawn. Two patients developed hepatitis, one with jaundice and the other with fever and deranged liver functions, while others 2 developed severe hypersensitivity reactions. Burning palms, difficulty in micturition, itching and giddiness were complained of by one patient each, which settled in due course without recourse to withdrawal of drugs.
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PMID:Hepatotoxicity to different antituberculosis drug combinations. 212 69

Among 169 patients treated for superficial bladder tumors with intravesical instillations of 150 mg BCG-Pasteur, five developed BCG-itis--a severe systemic infection with bronchopulmonary lesions and granulomatous hepatitis. In four cases, the complication appeared early during treatment (after three, six, six and eight instillations respectively). In one case, BCG-itis appeared 6 months after completion of 2 years monthly maintenance therapy. In addition to pulmonary basal infiltration and granulomatous hepatitis, intramedullary granulomatosis was observed. In three patients, the role of trauma has to be considered, as BCG-itis appeared after a traumatic instillation with bleeding. All patients were cured by combined treatment with Rifampicin, Isoniazid and Prednisolone.
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PMID:Systemic bacillus Calmette-Guerin infection in patients treated by intravesical BCG therapy for superficial bladder cancer. 267 20

A 10-year-old girl with cervical tuberculosis was treated with Isoniazid, Rimfampicin and Ethambutol. After 2 weeks of treatment a hepatotoxic reaction developed. Withdrawal of therapy resulted in complete clinical improvement and in normalization of all laboratory measurements. Treatment was restarted with Rifampicin, Pyrazinamid and Ethambutol. Liver enzyme levels were monitored weekly. Seven weeks after this three-drug regiment was started, all therapy was discontinued because of elevated liver enzyme levels. However, the patient died 2 weeks later of progressive fulminant hepatitis.
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PMID:Fulminant hepatitis during treatment with rifampicin, pyrazinamid and ethambutol. 359 48

Isoniazid chemoprophylaxis recommendations include its use in persons who have positive tuberculin reactions, but neither recent conversion nor other activation risk factors, only if they are under age 35 years. Above this threshold, the isoniazid hepatitis risk is said to outweigh the benefit of preventing activation. Because this policy is controversial, we performed a decision analysis contrasting those who take with those who decline isoniazid therapy according to three outcome measures: life expectancy, likelihood of illness (isoniazid hepatitis and active tuberculosis), and likelihood of fatal illness. We found no threshold between ages 10 and 80 years by the measures of life expectancy and likelihood of fatal illness; isoniazid benefits outweigh risks for all, though the margin is small for the elderly. A threshold exists only in the likelihood of illness: isoniazid risks outweigh benefits for those aged 50 to 65 years. Only extreme variations of assumptions affect these findings. Chemoprophylaxis recommendations should include low-risk tuberculin reactors over age 35 years.
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PMID:The age threshold for isoniazid chemoprophylaxis. A decision analysis for low-risk tuberculin reactors. 377 78

Hepatitis developed in two patients treated with high doses (1000 mg/day) of isoniazid for severe tuberculous meningitis. Isoniazid was discontinued and later readministered in gradually increasing intrathecal and subsequently oral doses, up to the final dose of 400 mg/day. Transaminases remained normal, during 12 months on this dose, suggesting dose dependence of hepatotoxicity or a metabolic adaptation to the injury. Continued isoniazid treatment can be important in similar cases and it may become possible, if oral or intrathecal doses significantly lower than the initial hepatotoxic ones, are used.
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PMID:Hepatitis on high dose isoniazid: reintroduction of the drug in severe tuberculous meningitis. 685 18

Enzyme induction during an antituberculous treatment with Rifampin, Isoniazid and Ethambutol was studied in 21 patients with tuberculosis. Two tests were used: increase in urinary excretion of D-saccharic acid and decrease of the half-life of antipyrineee. Induction is constant with D-saccharic acid. On the other hand there is a significant decrease in the half-life of antipyrin in only 10 patients. There is an increase in the 11 other patients: all of them are slow acetylators for isoniazid. We suggest that INH has an inhibitor effect on the hydroxylation of antipyrin. This study allows us to discuss the interactions of drugs with INH and Rifampin, as well the predominance of rapid acetylators among subjects suffering of isoniazid hepatitis, recently questioned.
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PMID:[Simultaneous study of the induction effect of rifampicin and the phenotype for acetylation of isoniazid in 21 patients with tuberculosis undergoing a combination treatment]. 718 65

Isoniazid and pyrazinamide are well-known hepatotoxic drugs, often used in combination. The aim of this study was to assess the prognostic influence of pyrazinamide on the outcome of fulminant or subfulminant liver failure caused by antituberculous therapy. Eighteen patients with fulminant or subfulminant liver failure due to antituberculous therapy were studied. Nine patients received isoniazid and rifampicin without pyrazinamide (group 1), and nine patients received isoniazid and rifampicin together with pyrazinamide (group 2). The severity of fulminant and subfulminant liver failure, as judged by the prevalence of coma and the lowest level of factor V, was similar in the two groups. Spontaneous survival was greater in group 1 (eight of nine) than in group 2 (two of nine) (P < .02). The authors conclude that pyrazinamide co-administration was associated with an increased mortality in patients with fulminant or subfulminant hepatitis occurring during antituberculous therapy. In these patients, pyrazinamide administration and an interval of more than 15 days between the onset of antituberculous treatment and jaundice, combined with grade III encephalopathy and factor V below 20%, predicted death without liver transplantation.
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PMID:Deleterious influence of pyrazinamide on the outcome of patients with fulminant or subfulminant liver failure during antituberculous treatment including isoniazid. 770 2

Isoniazid chemoprophylaxis has long been known to be a highly effective means of preventing silent tuberculous infections from spreading to active disease. There has been much controversy, however, about the risk it carries for fatal hepatotoxicity. In this article I review the rate of fatal isoniazid-induced hepatitis during chemoprophylaxis that is done according to current monitoring guidelines. Information was obtained from a MEDLINE literature search and a survey of tuberculosis control officers in large metropolitan areas throughout the country. Data were included of patients who were monitored according to the American Thoracic Society's guidelines or who were treated after 1983 when the guidelines were published. The pooled results of the published studies showed no hepatotoxic deaths in 20,212 patients in whom prophylaxis was started. The unpublished data showed 2 deaths in 182,285 patients, for a combined rate of 0.001% (2 of 202,497). The death rate for those older than 35 years was estimated to be 0.002% (1 of 43,334). This rate is significantly lower than was previously estimated and should be used to reevaluate the benefit of preventive therapy for tuberculin-reactive patients older than 35. The risk of fatal isoniazid-induced hepatitis is negligible for all ages when patients are routinely monitored for liver toxicity.
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PMID:Fatal isoniazid-induced hepatitis. Its risk during chemoprophylaxis. 827 52


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