School of Pharmacy, Jimma University, Jimma, Ethiopia.
PLoS One. 2013 May 16;8(5):e64622. doi: 10.1371/journal.pone.0064622. Print 2013.
This study was carried out to determine the incidence and predictors of anti-tuberculosis drug induced hepatotoxicity among TB/HIV co-infected patients at Jimma University Hospital, Ethiopia.
METHODS/PRINCIPAL FINDINGS: A nested case-control study was conducted by reviewing charts of all TB/HIV co-infected patients who commenced anti-TB treatment from January 2008 to December 2011 at Jimma University Hospital. Patients who had developed hepatotoxicity after at least 5 days of standard doses of anti-TB drug therapy were labeled as "cases" and those without hepatotoxicity were "controls". Each case with anti-TB drug induced hepatotoxicity was compared with 3 controls selected randomly from the cohort. From a cohort of 296 TB/HIV co-infected patients 8 were excluded from the study as the causality between anti-TB drugs and hepatotoxicity was not confirmed, 33 had developed hepatotoxicity. On bivariate logistic regression analysis, body mass index (BMI) <18.5 Kg/m(2) [P = 0.01; OR (95%CI): 3.6 (1.4-9.5)], disseminated pulmonary TB [P = 0.00; OR (95%CI): 5.6 (2.2-14.6)], CD4 count ≤50 [P = 0.016; OR (95%CI): 3.6(1.27-10.23)] and WHO stage 4 [P = 0.004, OR (95%CI): 3.8 (1.68-8.77)] were significantly associated with anti-TB drug induced hepatotoxicity. Predictor variables with p-value <0.05 by bivariate analysis were analyzed using multivariable logistic regression analysis and identified disseminated pulmonary TB [P = 0.001; AOR (95%CI) = 5.6 (2.1-15.0)] and BMI <18.5 [P = 0.014; AOR (95%CI)= 3.6 (1.3-10.1)] as independent predictors of anti-TB drug induced hepatotoxicity.
The incidence of anti-TB drug induced hepatotoxicity was 11.5%. The results suggest that in the presence of disseminated pulmonary TB and/or BMI <18.5 Kg/m(2), TB/HIV co-infected patients should be closely followed for the occurrence of hepatotoxicity during the intensive phase of TB treatment to prevent morbidity and mortality.
本研究旨在确定在埃塞俄比亚 Jimma 大学医院接受抗结核药物治疗的结核/艾滋病毒合并感染患者中抗结核药物引起肝毒性的发生率和预测因素。
方法/主要发现:对 2008 年 1 月至 2011 年 12 月期间在 Jimma 大学医院接受抗结核治疗的所有结核/艾滋病毒合并感染患者的图表进行了嵌套病例对照研究。在至少 5 天标准剂量抗结核药物治疗后出现肝毒性的患者被标记为“病例”,而无肝毒性的患者为“对照”。每例抗结核药物引起的肝毒性与从队列中随机选择的 3 例对照进行比较。在 296 例结核/艾滋病毒合并感染患者中,有 8 例因抗结核药物与肝毒性之间的因果关系未得到确认而被排除在研究之外,有 33 例发生了肝毒性。在单变量逻辑回归分析中,体重指数(BMI)<18.5 Kg/m(2) [P=0.01;比值比(95%CI):3.6(1.4-9.5)]、播散性肺结核[P=0.00;比值比(95%CI):5.6(2.2-14.6)]、CD4 计数≤50 [P=0.016;比值比(95%CI):3.6(1.27-10.23)]和世界卫生组织(WHO)第 4 期[P=0.004,比值比(95%CI):3.8(1.68-8.77)]与抗结核药物引起的肝毒性显著相关。通过单变量分析得出的 p 值<0.05 的预测变量通过多变量逻辑回归分析进行分析,并确定播散性肺结核[P=0.001;比值比(95%CI)=5.6(2.1-15.0)]和 BMI<18.5 [P=0.014;比值比(95%CI)=3.6(1.3-10.1)]为抗结核药物引起的肝毒性的独立预测因素。
抗结核药物引起肝毒性的发生率为 11.5%。结果表明,在存在播散性肺结核和/或 BMI<18.5 Kg/m(2)的情况下,结核/艾滋病毒合并感染患者在结核强化期治疗期间应密切注意肝毒性的发生,以预防发病率和死亡率。