Ho Chao-Chi, Chen Yee-Chun, Hu Fu-Chang, Yu Chong-Jen, Yang Pan-Chyr, Luh Kwen-Tay
Departments of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Clin Infect Dis. 2009 Jun 1;48(11):1526-33. doi: 10.1086/598929.
Fluoroquinolones are frequently used to replace agents in first-line anti-tuberculosis (anti-TB) regimens in patients with TB who have drug-induced hepatic dysfunction. We investigated the safety of using fluoroquinolone in an area where TB is endemic and where there is a high incidence of drug-induced liver injury.
From September 2003 through August 2006, patients who had aspartate aminotransferase and/or alanine aminotransferase levels >3 times the upper limit of normal in the presence of hepatitis symptoms or who had aspartate aminotransferase and/or alanine aminotransferase levels >5 times the upper limit of normal after receipt of anti-TB treatment were enrolled. The control group received ethambutol, with or without streptomycin; study groups received either (1) ethambutol plus levofloxacin, with or without streptomycin; or (2) ethambutol plus moxifloxacin, with or without streptomycin. The outcome measurement was the time from onset of hepatitis to normalization of liver functions.
One hundred thirty-four (11.3%) of 1191 patients received a diagnosis of hepatotoxicity and needed to stop anti-TB treatment. The risk factor was abnormal baseline transaminase levels. Twenty-two of the 134 patients received the control medication, 40 received levofloxacin, and 45 received moxifloxacin; the remaining patients were excluded from the study. There were no significant prestudy differences between groups. Time to liver function normalization was almost the same for all groups (mean +/- standard deviation, 29.1+/-21.4, 25.5+/-17.6, and 29.7+/-14.3 days, respectively).
Abnormal baseline transaminase levels are the independent risk factors for anti-TB therapy-induced hepatitis. Levofloxacin and moxifloxacin caused no additional hepatotoxicity when they were used by patients with hepatitis induced by first-line anti-TB drugs.
在患有药物性肝功能障碍的结核病患者中，氟喹诺酮类药物常被用于替代一线抗结核（抗痨）治疗方案中的药物。我们在结核病流行且药物性肝损伤高发的地区，对使用氟喹诺酮类药物的安全性进行了调查。
从2003年9月至2006年8月，纳入出现肝炎症状时天门冬氨酸氨基转移酶和/或丙氨酸氨基转移酶水平高于正常上限3倍，或接受抗结核治疗后天门冬氨酸氨基转移酶和/或丙氨酸氨基转移酶水平高于正常上限5倍的患者。对照组接受乙胺丁醇，可加用或不加用链霉素；研究组分别接受：（1）乙胺丁醇加左氧氟沙星，可加用或不加用链霉素；或（2）乙胺丁醇加莫西沙星，可加用或不加用链霉素。观察指标为从肝炎发作到肝功能恢复正常的时间。
1191例患者中有134例（11.3%）被诊断为肝毒性，需要停止抗结核治疗。危险因素为基线转氨酶水平异常。134例患者中，22例接受对照药物治疗，40例接受左氧氟沙星治疗，45例接受莫西沙星治疗；其余患者被排除在研究之外。各组在研究前无显著差异。所有组肝功能恢复正常的时间几乎相同（分别为平均±标准差，29.1±21.4天、25.5±17.6天和29.7±14.3天）。
基线转氨酶水平异常是抗结核治疗所致肝炎的独立危险因素。对于一线抗结核药物所致肝炎患者，使用左氧氟沙星和莫西沙星不会引起额外的肝毒性。
