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)

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 Seven cases (15%) showed signs of toxicity and in 4 patients (8.5%) the drugs had to be withdrawn.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

We report on the first trial in the Republic of Ireland to look at chemotherapy for TB. This management trial, carried out in single unit, which treats a third of all TB cases in the Republic of Ireland compared to effectiveness of a three drug/nine month regimen (Rifampicin (R), Isoniazed (R), supplemented with Ethambutol (E) for the first two months = RHE9) with a four drug six months regimen (R, H supplemented with E and Pyrazinamide (Z) for the first two months = RHEZ6). Two hundred and eighty eight patients (288) were entered into the study. A total of 143, (76 were in the RHE9 group and 67 in the RHEZ6 group) completed the trial as planned. At the end of the third month, significantly more patients in the RHEZ6 regimen (98%) were culture negative compared to the RHE9 regimen (88%). All were culture negative at the end of chemotherapy. Drug intolerance was seen in 35 (12%) patients with no significant difference in hepatitis between the two regimens. Toxicity from Pyrazinamide was minimal. One hundred and forty five (145) patients were invalid for analysis for the following reason:- bacteriologically negative TB (41), drug intolerance (35), death (23), non-compliance (19), diagnosis not TB (10), drug resistance (7), extrapulmonary disease (4), consent withdrawn (3), Mycobacteria other than tuberculosis (3). All patients are being followed to monitor relapse rates.
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PMID:Short course chemotherapy for pulmonary tuberculosis. A randomised controlled trial of a six month versus a nine month oral regimen. 266 39

The early and late results of 6 months' chemotherapy (2/INH, RMP, PZA and 4/INH, RMP) of newly detected, bacteriologically positive pulmonary tuberculosis are presented. In the initial period during hospitalisation in nonselected 290 patients 100% conversion of sputum was obtained while in the continuous out-patients' treatment 1.3% of patients were again found to have sputum positive for acid fast bacilli. Toxic reactions on drugs were found in 5.8% of patients: in 3.4% the hepatitis developed yet in all in mild course. The narrowing of medical contraindications for 6 months' regimen is suggested especially in chronic alcoholics since in 15.2% of them the therapy with 9 months' regimen had to be introduced (INH, RMP, EMB/SM). In more than 2 yrs' follow up after the end of chemotherapy in 2.4% of patients--mostly noncooperative alcoholics--the recidivation was found already a few months after discontinuation of the therapy. The problem of chronic alcoholics and noncooperative patients for short course chemotherapy is discussed. The special measures are suggested: obligatory hospitalisation during initial therapy, supervising chemotherapy in out-patients' departments as well as intermittent regimen and prolongation of 6 months' therapy.
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PMID:[Clinical study of a 6-month chemotherapy regimen in the treatment of pulmonary tuberculosis. Results approximately 2 years after completion of chemotherapy]. 279 72

Antituberculosis drug-induced hepatotoxicity is quite common. However, factors predicting its development are still controversial. The objective of the present study was to evaluate the role of certain factors (age and sex of the patient, alcoholism, chronic liver disease, hepatitis B virus carrier status, acetylator status, nutritional status and antituberculosis treatment (ATT) regimen) in predicting the development of ATT-induced hepatitis. In a case-control study, 60 consecutive patients with evidence of ATT-induced hepatitis were studied to assess the possible association of the above-mentioned factors with ATT-induced hepatitis. Body mass index was found to be significantly lower in ATT-induced hepatitis patients (17.2 +/- 2.7) than in controls (19.5 +/- 3.3) (p < 0.05). Pyrazinamide was used in addition to isoniazid and rifampicin in a significantly higher percentage of patients in the ATT-induced hepatitis group (70%) as compared with those in the control group (42%). No significant differences were observed between the two groups with regard to the rest of the parameters.
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PMID:Antituberculosis treatment-induced hepatotoxicity: role of predictive factors. 764 98

Pyrazinamide hepatotoxicity is considered secondary to a direct and dose-related toxic effect. At currently used doses, pyrazinamide provides effective short-term treatment and is free from serious side effects. We report a case of pyrazinamide-induced hepatitis for which the rechallenge data strongly suggest a hypersensitivity mechanism.
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PMID:Hypersensitivity hepatitis due to pyrazinamide. 778 27

The aim of this study was to determine the current incidence of side-effects severe enough to cause intolerance of standard antituberculosis therapy with isoniazid, rifampin and pyrazinamide in patients hospitalized as a result of pulmonary tuberculosis. Five hundred and nineteen patients with proven pulmonary tuberculosis, who initially received standard antituberculosis therapy, were retrospectively studied in the department of infectious diseases in a teaching chest hospital. The incidence of severe side-effects related to the therapy, which led to the definitive termination of one of the three standard drugs, was measured and the risk factors for intolerance were analysed. Final termination of either isoniazid, rifampin or pyrazinamide because of severe side-effects was necessary in 121 of the 519 patients (23%). The most severe side-effects leading to final termination of one drug were hepatotoxicity (11%), exanthema (6%), and arthralgia (2%). Pyrazinamide showed more severe side-effects (15%) than isoniazid (7%) and rifampin (1.5%). Significant risk factors for intolerance of the standard therapy following a multivariate analysis were a history of hepatitis (odds ratio (OR) 3.4; 95% confidence interval (95% CI) 1.6-7.6; p = 0.0026) and an age > or = 60 yrs (OR 1.9; 95% CI 1.2-3.2; p = 0.017). Both of these risk factors were also significantly associated with the intolerance of pyrazinamide (history of hepatitis: OR 2.5; 95% CI 1.4-4.3; p = 0.0045; age > or = 60 yrs: OR 2.1, 95% CI 1.3-3.5; p = 0.0029) but not of isoniazid and rifampin. The side-effects of standard antituberculosis therapy are frequent in hospitalized patients aged > or = 60 yrs or with a history of previous hepatitis, and are probably due to pyrazinamide rather than to isoniazid or rifampin.
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PMID:Risk factors for side-effects of isoniazid, rifampin and pyrazinamide in patients hospitalized for pulmonary tuberculosis. 890 62

The standard antitubercular regimen currently includes a combination of 3 antitubercular agents: isoniazid, rifampicin (rifampin) and pyrazinamide. Administration of a fourth agent, ethambutol, is recommended when isoniazid resistance is suspected. Two of these 4 agents (isoniazid and pyrazinamide) are major hepatotoxins. The remaining 2 agents (rifampicin and ethambutol) are rarely or not hepatotoxic. However, rifampicin, which is a powerful enzyme inducer, may enhance the hepatotoxicity of isoniazid. In patients receiving a combination of isoniazid, rifampicin and pyrazinamide, 2 patterns of fulminant liver injury can be observed. The first pattern is characterised by an increase in serum transaminase activity that occurs soon (usually within the first 15 days) after initiation of treatment. This pattern is likely to be caused by rifampicin-induced isoniazid hepatotoxicity. The prognosis is good in most cases. The second pattern is characterised by an increase in serum transaminase activity that occurs late (usually more than 1 month) after the initiation of treatment. It has been suggested that this pattern may be related to pyrazinamide hepatotoxicity. The prognosis of this type of hepatitis is generally poor. In order to reduce the risk of severe hepatic adverse effects during antitubercular treatment, several measures are proposed. First, patients with underlying liver test abnormalities should not be given pyrazinamide. Second, isoniazid and pyrazinamide should be administered at the lowest dosage within their respective therapeutic ranges. Third, serum transaminase levels should be determined twice weekly during the first 2 weeks of treatment, every 2 weeks during the rest of the first 2 months, and every month thereafter. When serum transaminase levels increase to greater than 3 times the upper limit of normal, therapy with isoniazid, rifampicin and pyrazinamide should be stopped. After serum transaminase levels have returned to normal, isoniazid can be re-introduced at a low daily dose, without rifampicin. Pyrazinamide may not be re-introduced because of the risk of recurrence and the poor prognosis of pyrazinamide-induced hepatitis. Although it is nephrotoxic, streptomycin is an alternative in patients with liver test abnormalities during antitubercular treatment.
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PMID:Hepatotoxicity of antitubercular treatments. Rationale for monitoring liver status. 896 94

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

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

The incidence of tuberculosis has grown seriously in the last ten years and so have the risks due to drug toxicity of Ethambutol, Isoniazid, Pyrazinamide, Rifampicin. One of the questions is whether a careful monitoring of liver function during anti-tubercular chemotherapy could be useful, given that once severe organ toxicity initiates the survival rate remains under 10% if organ transplant is not available. International literature shows a clear prevalence of this event in Asiatic populations which are now well represented in Italy owing to incoming migrations. A case of fulminant hepatitis in a young Chinese man under treatment for TBC arrived at our ICU with a drug-induced acute hepatitis is reported.
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PMID:[Fulminant liver failure caused by antitubercular drugs. Report of a clinical case]. 1083 75


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