Hepatotoxicity of Pyrazinamide
| Autor: | Chi C. Leung, Wing Wai Yew, Cheuk Ming Tam, Tat Y. Lau, Kwok Chiu Chang |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Pulmonary and Respiratory Medicine medicine.medical_specialty Tuberculosis Matched-Pair Analysis Antitubercular Agents Critical Care and Intensive Care Medicine Internal medicine Intensive care Isoniazid Humans Medicine Aged Antibacterial agent biology business.industry Case-control study Middle Aged Pyrazinamide medicine.disease Surgery Logistic Models Alanine transaminase Case-Control Studies Multivariate Analysis Cohort biology.protein Drug Therapy Combination Female Chemical and Drug Induced Liver Injury Rifampin business medicine.drug |
| Zdroj: | American Journal of Respiratory and Critical Care Medicine. 177:1391-1396 |
| ISSN: | 1535-4970 1073-449X |
| DOI: | 10.1164/rccm.200802-355oc |
| Popis: | Relatively little is known about the hepatotoxicity of pyrazinamide.We compared continuation-phase regimens incorporating pyrazinamide, isoniazid, and/or rifampin with those containing isoniazid and rifampin to evaluate the hepatotoxicity of pyrazinamide.Cohort and nested case-control analyses were conducted on a cohort of 3,007 patients with active tuberculosis (TB) managed at government chest clinics under a TB control program with treatment started from January 1 through June 30, 2001. Cases included all patients with probable hepatotoxicity from 12 or more weeks after starting treatment. Hepatotoxicity was considered probable when serum alanine transaminase exceeded three times the upper limit of normal. Each case was matched by sex and age with three control subjects selected randomly from the rest of the cohort. Treatment regimens of cases within 4 weeks preceding hepatotoxicity were compared with those of matched control subjects in comparable periods relative to the date of commencing treatment.Hepatotoxicity occurred in 150 (5.0%) patients at any time including 48 (1.6%) cases. From 12 or more weeks after starting treatment, the estimated risk of hepatotoxicity was 2.6% for regimens incorporating pyrazinamide, isoniazid, and/or rifampin, and 0.8% for standard regimens containing isoniazid and rifampin. Multivariable conditional logistic analysis showed a significant association between hepatotoxicity and, respectively, hepatitis B, previous hepatotoxicity, and treatment regimens. The adjusted odds ratio (95% confidence interval) of hepatotoxicity for regimens incorporating pyrazinamide, isoniazid, and/or rifampin relative to standard regimens was 2.8 (1.4-5.9).Adding pyrazinamide to isoniazid and rifampin increases the risk of hepatotoxicity appreciably. |
| Databáze: | OpenAIRE |
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