Sun Qin, Zhang Qing, Gu Jin, Sun Wen-Wen, Wang Peng, Bai Chong, Xiao He-Ping, Sha Wei
Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Respiratory and Critical Care Medicine, Changhai Hospital, the Second Military Medical University, Shanghai, China.
Pharmacoepidemiol Drug Saf. 2016 Aug;25(8):908-17. doi: 10.1002/pds.3988. Epub 2016 Mar 2.
Antituberculosis drug-induced liver injury (ATDILI) is one of the most deleterious side effects associated with chemotherapy against tuberculosis (TB). In this study, our objective was to determine the incidence, risk factors, and management of ATDILI and analyze its impact on the treatment outcome in patients receiving standard anti-TB chemotherapy.
A prospective cohort study of ATDILI prevalence was conducted in 938 enrolled patients of the 1426 TB cases in Shanghai from March 2011 to September 2012. Patients were followed up until February 2014. Univariate and multivariate logistic regression analyses were used to determine the risk factors of ATDILI. Successful therapeutic outcome, rates of drug resistance conversion, sputum smear/culture conversion, and lung cavity closure were analyzed.
Hepatitis B surface antigen/hepatitis B e antigen-positive hepatitis B carriers, complicated with systemic lupus erythematosus, albumin ≤ 25 g/L, and chronic alcoholism were independent risk factors for ATDILI. Of the 121 cases with ATDILI (incidence rate of 12.9%), 84 (69.4%) used modified anti-TB therapy after recovery of liver function. Compared with the non-ATDILI group, patients with ATDILI exhibited remarkably decreased lung cavity closure rate (84.6% vs. 93.0%, P < 0.001) along with significantly reduced sputum smear/culture conversion rate (85.4% vs. 94.0%, P < 0.001).
Our findings indicated that 12.9% patients developed ATDILI during standard anti-TB therapy, resulting in poor therapeutic outcome. Hepatitis B carriers with systemic lupus erythematosus, albumin ≤ 25 g/L, and chronic alcoholism manifested increased risks for ATDILI. Copyright © 2016 John Wiley & Sons, Ltd.
抗结核药物性肝损伤(ATDILI)是抗结核化疗最有害的副作用之一。在本研究中,我们的目的是确定ATDILI的发病率、危险因素及管理措施,并分析其对接受标准抗结核化疗患者治疗结局的影响。
对2011年3月至2012年9月在上海1426例结核病患者中登记入组的938例患者进行ATDILI患病率的前瞻性队列研究。对患者随访至2014年2月。采用单因素和多因素logistic回归分析确定ATDILI的危险因素。分析成功的治疗结局、耐药转换率、痰涂片/培养转阴率及肺空洞闭合率。
乙肝表面抗原/乙肝e抗原阳性的乙肝携带者、合并系统性红斑狼疮、白蛋白≤25 g/L及慢性酒精中毒是ATDILI的独立危险因素。121例发生ATDILI的患者(发病率为12.9%)中,84例(69.4%)在肝功能恢复后采用了改良抗结核治疗。与非ATDILI组相比,ATDILI患者的肺空洞闭合率显著降低(84.6%对93.0%,P<0.001),痰涂片/培养转阴率也显著降低(85.4%对94.0%,P<0.001)。
我们的研究结果表明,12.9%的患者在标准抗结核治疗期间发生ATDILI,导致治疗结局不佳。合并系统性红斑狼疮的乙肝携带者、白蛋白≤25 g/L及慢性酒精中毒患者发生ATDILI的风险增加。版权所有©2016约翰威立父子有限公司。