Isoniazid hepatotoxicity associated with treatment of latent tuberculosis infection - A 7-year evaluation from a public health tuberculosis clinic
Isoniazid hepatotoxicity associated with treatment of latent tuberculosis infection - A 7-year evaluation from a public health tuberculosis clinic
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DOI：
10.1378/chest.128.1.116
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发表时间：
2005-07-01
期刊：
影响因子：
9.6
通讯作者：
Self, TH
中科院分区：
文献类型：
--
作者：
Fountain, FF;Tolley, E;Self, TH
目的：确定一家公共卫生结核病诊所7年来异烟肼（INH）肝毒性的总发生率，并确定系统的、有限的天冬氨酸转氨酶（AST）监测是否有助于检测INH肝毒性。方法：从1996年秋季至2003年秋季在公共卫生部门诊所维护的数据库中评估年龄bb0 = 25岁成人的INH肝毒性。肝毒性定义为AST水平超过正常上限（ULN）的5倍。结果：在3377例开始接受INH治疗的患者中，19例患者的AST水平超过ULN的5倍，即每1000例患者中有5.6例。19例患者中仅有1例出现与肝毒性相关的前驱症状。治疗1个月、3个月和6个月后，每1000名患者发生肝毒性事件的次数分别为2.75、7.20和4.10。在25 - 34岁年龄组中，每1000名患者中肝毒性事件的年龄特异性数字为4.40；35至49岁（含）的8.54元；50岁的人是20.83。年龄bb0 ~ 49岁（p < 0.02）和基线AST大于ULN （p < 0.0003）是肝毒性的危险因素。结论：与早期试验一致，INH肝毒性与年龄有关。我们的研究结果表明，肝毒性也与基线AST大于ULN有关。中重度肝毒性经常无症状发生，提示更广泛的AST监测的价值。
Objectives: To determine the overall incidence of isoniazid (INH) hepatotoxicity in a public health tuberculosis clinic over a 7-year period, and to determine if systematic, limited aspartate aminotransferase (AST) monitoring would be of benefit in detecting INH hepatotoxicity.Methods: Evaluation of INH hepatotoxicity in adults aged >= 25 years from a database maintained from fall 1996 to 2003 in a public health department clinic. Hepatotoxicity was defined as AST levels more than five times the upper limit of normal (ULN).Results: Among 3,377 patients started on INH therapy, 19 patients had AST levels more than five times the ULN, or a rate of 5.6 per 1,000 patients. Only 1 of 19 patients had prodromal symptoms associated with hepatotoxicity. After 1 month, 3 months, and 6 months of therapy, the numbers of hepatotoxic events per 1,000 patients were 2.75, 7.20, and 4.10. The age-specific numbers of hepatotoxic events per 1,000 patients were 4.40 for those from 25 to 34 years of age, inclusive; 8.54 for those between 35 to 49 years of age, inclusive; and 20.83 for those >= 50 years old. Age > 49 years (p < 0.02) and baseline AST greater than ULN (p < 0.0003) were risk factors for hepatotoxicity.Conclusions: Consistent with earlier trials, INH hepatoxicity is age related. Our results suggest hepatotoxicity is also related to baseline AST greater than ULN. Moderate-to-severe hepatotoxicity frequently occurs without symptoms, suggesting the value of more widespread AST monitoring.