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)

Drug hepatitis occurred in 0-32 per cent of 7492 patients receiving antituberculous therapy, while the overall incidence of drug reactions was estimated at 9 per cent. PAS was the most common cause of drug hepatitis among the 38 patients analysed. The clinical, biochemical and haematological picture of antituberculous drug hepatitis was found to be fairly uniform. However, the patients with definite PAS hepatitis had lower SGOT values than those in whom there was uncertainty whether PAS or INH was implicated. Premonitory symptoms were present in all but four patients before the onset of jaundice. One or more of the features associated with dry hypersensitivity reactions, such as fever, rashes, lymphadenopathy, arthralgia, leucocytosis, eosinophilia and atypical monocytes were present in 89 per cent of cases so that confusion with viral hepatitis seldom arose. Sensitization time was less than three months in all except three patients, who were considered to be suffering from viral hepatitis. While no patients with PAS hepatitis died, the overall mortality was 17 per cent. A review of the literature stresses the frequency of asymptomatic elevations of SGOT, the value of clinical surveillance during the early months of therapy and the importance of stopping all therapy immediately warning symptoms appear.
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PMID:Hepatic complications of antituberculous therapy. 5 Jun 5

A patient with acute hepatitis associated with isoniazid therapy is described. The relevance fo isoniazid hepatotoxicity in Melanesian populations is discussed. Guidelines for recognition and management of INH-induced hepatitis are suggested.
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PMID:Isoniazid-associated hepatitis in a Melanesian. 27

The release of lymphotoxin (LT) from peripheral blood lymphocytes of patients with isoniazid (INH)-induced hepatitis was studied, using L929 fibroblast target cells, as was the cytotoxic effect of these lymphocytes on murine hepatoma cells (L1469) and L929 fibroblasts, using a 3H-proline cytotoxicity assay. Evidence for LT release was found in five out of six patients, following stimulation of the peripheral blood lymphocytes with INH or isonicotinic acid (INA) conjugated to human serum albumin. In the direct cytotoxicity assay, cytotoxic effects on the hepatoma cells were enhanced by preincubation of the target cells with INH in five out of six patients tested. Although specificity with regard to the drug was demonstrable, tissue specificity was less certain in that enhanced killing of the fibroblast cell line was also found to occur following preincubation of the L929 cells with INH.
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PMID:Lymphocyte-mediated cytotoxicity in isoniazid-associated hepatitis. 31 34

It is generally accepted that hepatitis occurring during treatment with INH and rifampicine results from the hepatotoxicity of INH metabolites. A case is reported of cholestatic hepatitis occurring during such treatment, in which there was a previous history of an isolated hepatic affection. The administration of INH and rifampicin caused cholestasis alone, which reoccurred after rifampicin administration only. No immuno-allergic phenomenon has been shown to be involved in rifampicin toxicity. This observation suggests that rifampicin may be hepatotoxic itself, especially in patients with previous hepatic affections.
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PMID:[Cholestatic hepatitis during treatment with I.N.H. and rifampicin: arguments in favour of the hepatotoxicity of rifampicin (author's transl)]. 49 38

The complications of isoniazid (INH) were studied in 1033 patients, who had received INH for at least 18 months, with or without other drugs. Hepatitis developed in 25 patients; this was attributed to rifampicin, (15 cases); infectious hepatitis (three cases); INH alone, (three cases); IHN possibly exacerbating chronic liver disease, (two cases); and multiple drug treatment, (two cases). Central nervous system disorders (mainly peripheral neuropathy) due to INH occurred in 12 patients, all of whom were over the age of 40 years. Hypersensitivity to INH developed in 12 patients. Some difficulties in distinguishing hepatitis due to rifampicin from that due to INH are discussed. When the risk of hepatitis was compared with the risks of developing, or dying from, tuberculosis, it was found that the benefits of INH chemoprophylaxis outweighed the risks, particularly in patients who were less than 50 years of age.
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PMID:How safe is isoniazid? 65 34

Seventy-five patients who developed mild hepatic reactions (serum transaminase concentrations of 45 to 149 units per liter) and 50 patients who showed more serious liver damage (serum transaminase values greater than 150 units per liter) were compared with 261 consecutive patients who had no liver reactions during treatment with rifampin and isoniazid. Generally, liver toxicity occurred in 18 per cent of patients receiving combined anti-tuberculous drug therapy. Small increases in transaminase occurred in 14 per cent of the patients; large increases occurred in 4 per cent. Elderly women comprised a risk group. Among patients exhibiting a more serious hepatic lesion (transaminase values greater than 150 units per liter), alcoholics, mostly men, formed another risk group, together with other patients with a history of previous liver or biliary disease. Of 261 patients who did not develop a liver reaction, 57 per cent were slow INH acetylators. In this study, the groups with small and large increases in transaminase were clearly separated; in the former group there was no preponderance of phenotype, whereas in the latter group, slow acetylators clearly dominated among early (first 4 weeks of treatment) hepatic reactions (P less than 0.01). Studies of single-drug regimens of isoniazid have shown that neither slow nor rapid acetylation has any causal influence on isoniazid-induced hepatitis. Because the metabolism of rifampin is independent of the acetylation process, rifampin and isoniazid in combination seem to cause a toxic hepatitis that differs from the hepatitis induced by either drug separately.
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PMID:Predisposing factors in hepatitis induced by isoniazid-rifampin treatment of tuberculosis. 70 74

A three-year prospective study during the entire course of preventive therapy with isoniazid (INH) for recently infected hospital employees was undertaken to evaluate the risk of developing INH-related hepatic injury. Results of clinical and laboratory tests at 1, 2, 6, and 12 months were correlated to ascertain the significance and value of monitoring procedures. Thirty-two (32%) of 100 employees developed elevated SGOT levels: one (1%) patient developed clinical hepatitis in the first month of therapy; four (4%) subjects with SGOT elevations (82-378 units) became clinically symptomatic at one to four months and INH was discontinued; one (1%) individual with minimal increases in serum bilirubin and SGOT levels was symptomatic at eight months and the drug was stopped. Twenty-four (24%) otherwise asymptomatic subjects who developed SGOT elevations (70-480 units) were followed at closer intervals to complete INH therapy without further progression of liver function abnormality. The intervals between the beginning of treatment and the elevation of SGOT levels varied widely, with elevations occurring throughout the 12-month course of isoniazid therapy.
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PMID:Close monitoring is essential during isoniazid prophylaxis. 84 90

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

The preventive use of isoniazid (INH) has been controversial since 1975, but official agencies continue to advocate the procedure. Cost-effectiveness and risk benefit studies of preventive INH use have come to conflicting conclusions. A review of eight such studies indicates an increasing tendency to minimize INH hepatotoxicity and to disregard the declining tuberculosis morbidity and mortality in countries in which INH prophylaxis has not been widely adopted. We report three cases of fatal INH-associated hepatitis that illustrate that this complication of preventive INH use remains a serious problem. Current recommendations that encourage wide use of preventive INH therapy are unwise because they inflict a risk of fatal hepatitis on compliant adults and older children who have little danger of tuberculosis while being difficult to deliver to the alcohol- and drug-addicted persons whose risk is high. Health departments and physicians should severely restrict preventive INH therapy.
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PMID:Perspective: preventive isoniazid therapy and the liver. 158 87


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