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)

We examined prospectively risk factors which might contribute to INH-induced liver damage in 113 patients taking preventive INH for at least 8 weeks. Twelve who had abnormal initial liver tests did not get worse with INH, while 19/101 with normal initial tests developed significant liver dysfunction, mostly hepatocellular, three having overt hepatitis. When 12 other patients who drank alcohol were excluded from analysis, there were still 15/89 with significant liver dysfunction, 12 of whom were slow acetylators (p less than 0.05). The only other risk factor was age. By combining acetylator phenotype with age, but excluding alcohol, we calculated the risk of INH-induced liver enzyme elevation as follows: under 35 years--fast acetylators, 3.7%, slow acetylators, 13%; over 35--fast acetylators, 13.2%, slow acetylators, 37% (p less than 0.02). Fast acetylation is thus not a risk factor for developing INH-induced liver dysfunction; indeed, the contrary seems to be the case.
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PMID:Risk factors for isoniazid (NIH)-induced liver dysfunction. 728 21

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

In order to determine the efficacy of short course chemotherapy (SCC) for tuberculosis in children, 83 newly diagnosed cases in children < 12 years old were given SCC and were prospectively followed for 1-3 years. Seventy-one cases were treated for 6-9 months as they had mild to moderate involvement. Twelve cases were treated for 12 months as they had meningitis (7), disseminated tuberculosis (2), or miliary tuberculosis (3). The results showed that none of the children, at the end of follow up, showed evidence of active tuberculosis. All children tolerated the drugs well, with side effects noticed being mild, namely transient hepatitis (4), vomiting (1), and skin rash (1). It is suggested that SCC for 6-9 months using isoniazid (INH) and rifampicin along with other drugs when necessary is highly effective in most cases of tuberculosis in children and has several advantages over conventional chemotherapy of 18 months or longer duration.
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PMID:Short course chemotherapy for tuberculosis in children. 813 59

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

In November 1992, the New York State Department of Health was notified of a patient who underwent liver transplantation because of severe hepatitis that developed during the use of isoniazid (INH) preventive therapy (IPT) for latent tuberculous infection. Inquiry at liver transplant centers in New York revealed other patients who had hepatitis attributed to INH. This report summarizes findings of the ongoing investigation into the extent and causes of this problem.
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PMID:Severe isoniazid-associated hepatitis--New York, 1991-1993. 832 47

Tuberculosis occurs at higher rates in renal transplant recipients than in the general population. It would be desirable to use isoniazid prophylaxis in renal transplant recipients at risk for reactivation of tuberculosis; yet many transplant centers do not routinely employ INH prophylaxis because they perceive transplant recipients to be an enhanced risk of hepatotoxicity from isoniazid. Data on the risk of isoniazid in renal transplant patients receiving cyclosporine-based immunosuppression are limited. We retrospectively studied 83 renal transplant recipients (mean age 39.1 +/- 11.7 yr) who had received INH prophylaxis between 1985 and 1994. Eight patients had laboratory evidence of chronic hepatitis B or chronic hepatitis C infection. The mean duration of INH therapy was 344 +/- 163 d. The mean serum glutamate oxalacetic transferase (SGOT) at the start of INH therapy was 24.1 +/- 10.9 I.U., and 10% of patients had mildly elevated SGOTs. Mean peak SGOT during therapy was 36.4 +/- 15.3 I.U. (p < 0.001 compared to start (SGOT). In follow up, 31% of patients had an abnormal SGOT (> 40 I.U.); however, the elevations were small (the highest SGOT was 88.I.U.) and never necessitated discontinuation of INH. No patient had jaundice or other evidence of clinical hepatotoxicity. The 95% confidence interval for the observed frequency of clinical hepatitis was 0% to 4.3%. At the end of INH therapy the mean SGOT was 22.7 +/- 6.2 I.U. (p > 0.2, compared with start SGOT) and only one patient had an abnormal SGOT. In conclusion, it appears that the risk of renal transplant recipients developing serious hepatotoxicity with the administration of INH is low and not different from normal individuals.
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PMID:Isoniazid hepatotoxicity in renal transplant recipients. 906 92

The current practice of using INH for tuberculosis prevention is limited by the necessity for at least 6 months of therapy and the problem of INH-induced hepatitis, particularly in older individuals and those with chronic liver disease. Bacteriologic models suggest that, in their persistent form, tubercle bacilli are relatively resistant to INH but become more sensitive to other drugs. Similarly, animal models of latent tuberculosis have suggested that alternative, short-course combinations such as RIF/PZA may be effective, and clinical trials of that two-drug regimen are continuing. At the present time, 3 months of daily RIF, 2 months of RIF/PZA, and 3 months of rifabutin can be considered reasonable alternatives to INH in selected patients. Routine use of these agents in preference to INH cannot yet be endorsed, however, as the standard of care. Without highly effective vaccines for tuberculosis, an important strategy for breaking the cycle of tuberculosis transmission lies in inexpensive, convenient, and effective preventive therapy.
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PMID:Short-course chemoprophylaxis for tuberculosis. 909 15

Management of tuberculosis in a hospital environment is well systematized and may include chemoprophylaxis, which may be hazardous when used in psychiatric impairments. We examined retrospectively adverse events occurring during a 6-month period of antituberculosis treatment. Besides patients initially treated for active pulmonary tuberculosis, 16 other patients have benefited from chemoprophylaxis with isoniazid (INH) and/or rifampicin (RFP). All these patients (mean age 53 years) had been institutionalized for several years. Fifteen of them still received a mean of 5.4 +/- 2.2 drugs including 3.3 +/- 1.4 psychotropic agents. During antituberculous treatment, 5 patients (29 per cent) presented side effects: hyperuricaemia with pyrazinamide, neutropenia, dysphagia and anorexia, dizziness and falls, diabetes and fatal fulminant hepatitis associated with INH. Drug interactions were systemically searched for. Three probably led to clinical manifestations: they implicated INH with carbamazepine, RFP with theophylline and RFP with haloperidol. Our results suggest a greater sensitivity for adverse effects and drug interactions in psychiatric institutionalized patients. They pose the problem of the appropriateness of antituberculous chemoprophylaxis in such patients, particularly because of communication difficulties and polytherapy. The INH-RFP regimen should be avoided and the clinical and biological follow-up reinforced.
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PMID:[Adverse effects related to the use of antitubercular drugs in psychiatric centers: retrospective study at the Philippe Pinel CH in Amiens 1994]. 913 90

Conclusive evidence of isoniazid (INH)-related hepatotoxicity ranging from asymptomatic elevation of liver enzymes to fulminant hepatic failure resulting in liver transplantation and/or death has been firmly established. Anticipation of the widespread usage of INH in the prevention and treatment of tuberculosis is expected due to the recent increasing incidence of tuberculosis. The aim of this article is to review the current concepts of pathogenesis, histopathology, risk factors and clinical features of INH-related hepatitis, emphasizing the need for vigilance.
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PMID:Isoniazid-related hepatitis. 943

The incidence of tuberculosis in Japan, 33.7 per 100,000 in 1997, is very high compared with USA or Western European countries. The decrease in the incidence has slowed down from the early 1980s, and the average annual rate of decrease has been 3.8% in the last 5 years. About 9 percent of tuberculosis patients defaulted from the nine-month regimen (6HRS or E/3HR) in urban areas. Regimens shorter than nine-month are needed to achieve high effectiveness of tuberculous chemotherapy. Out of 1128 new pulmonary tuberculosis patients, six-hundred twenty started treatment with six-month (2HRZS or E/4HRE) in Fukujuji Hospital, JATA, in Tokyo from January 1991 to December 1996. Out of 620, four-hundred twenty eight were both smear and culture positive, 136 were smear negative and culture positive and 56 were bacilli negative. Out of 564 bacilli positive cases, 530 were susceptible to INH and RFP. Out of 530 drug susceptible cases three hundred ninety-three patients completed the regimen. Ninety-three percent of these patients had converted to negative at two months of chemotherapy and all of them at five months. Out of 450, two-hundred ninety five completed 6-month regimen, one-hundred fifty-five were changed their regimen or prolonged duration of chemotherapy. Out of 295, nine patients (3.1%) relapsed after the completion of 6-month chemotherapy. Mean follow-up period was 17.2 months and the median was 15.5 months. The relapse rate was 2.2 per 100 person-years. Six of the relapsed cases were complicated with Diabetes Mellitus. Relapse rate was higher in patients with Diabetes Mellitus than in patients without (6/54, 7.9 per 100 person-years vs 3/237, 0.8 per 100 person-years) (p < 0.001). Drug-induced hepatotoxicity was defined as elevated serum transaminase level with clinical symptoms of hepatitis or elevated serum transaminase level more than 5 times of upper limit of normal range with or without symptoms. Drug-induced hepatotoxicity developed in 43 (8.0%) of 535 with initial normal liver function test results, this rate was similar to that in patients treated with nine-month regimen (34/420, 8.1%). But the frequency of hepatotoxicity of more than 400 IU/ml of serum transaminase level was higher in patients treated with PZA-containing regimen than with nine-month regimen (16/536, 3.0% vs 4/420, 1.0%), but this deference was not statistically significant. Hepatotoxicity developed in 13/85 (15.3%) of patients treated with PZA-containing regimen with abnormal liver function tests at the beginning of chemotherapy, and this frequency was similar to 7/65 (10.8%) in patients with nine-month regimen. The relapse rate in patients with Diabetes Mellitus was statistically higher than in without Diabetes Mellitus (7.9 vs 0.8 per 100 person-years). We concluded that the six-month regimen was highly effective, but the frequency of severe hepatotoxicity was relatively higher than in nine-month regimen and the duration of chemotherapy was not enough for patients complicated with Diabetes Mellitus. Further study is needed for sufficient chemotherapy in patients with Diabetes Mellitus.
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PMID:[Six-months chemotherapy (2HRZS or E/4HRE) of new cases of pulmonary tuberculosis--six year experiences on its effectiveness, toxicity, and acceptability]. 1035 21


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