Hoffmann Christopher J, Charalambous Salome, Thio Chloe L, Martin Desmond J, Pemba Lindiwe, Fielding Katherine L, Churchyard Gavin J, Chaisson Richard E, Grant Alison D
Aurum Institute for Health Research, Johannesburg, South Africa.
AIDS. 2007 Jun 19;21(10):1301-8. doi: 10.1097/QAD.0b013e32814e6b08.
Hepatotoxicity is a significant complication of antiretroviral therapy (ART). We assessed the incidence of and risk factors for hepatotoxicity among HIV-infected individuals on ART in South Africa.
We conducted a retrospective cohort study in a workplace HIV care program in South Africa which uses a first-line regimen of efavirenz, zidovudine, and lamivudine and provides routine clinical and laboratory monitoring.
We included subjects with baseline and follow-up alanine transaminase and aspartate aminotransferase tests. Severe hepatotoxicity cases were identified during the first 12 months of ART. Potential risk factors, including concomitant medication use, tuberculosis, and hepatitis B and C, were determined from clinical records, database queries, and serological testing. Associations with hepatotoxicity were investigated using Cox proportional hazards modeling.
Of the 868 subjects (94% male, median age 41 years), the median nadir CD4 cell count was 136/microl, 25% received concomitant tuberculosis treatment during ART, and 17% of a randomly selected subset were positive for hepatitis B surface antigen (HBsAg). We identified 7.7 episodes of severe hepatotoxicity per 100 person-years. Tuberculosis treatment increased risk 8.5 fold, positive HBsAg 3.0 fold, and nadir CD4 cells count < 100/microl 1.9 fold. Importantly, the fraction of patients with severe hepatotoxicity on ART (4.6%) was similar to the fraction with liver enzyme elevations > 5 times the upper limit of normal before starting ART (4%).
In this African ART cohort, we found a low incidence of and minimal morbidity due to hepatotoxicity. HBsAg and concomitant tuberculosis therapy significantly increased the risk of hepatotoxicity.
肝毒性是抗逆转录病毒疗法（ART）的一个重要并发症。我们评估了南非接受ART治疗的HIV感染者中肝毒性的发生率及危险因素。
我们在南非一个职场HIV护理项目中开展了一项回顾性队列研究，该项目采用依非韦伦、齐多夫定和拉米夫定的一线治疗方案，并提供常规临床和实验室监测。
纳入有基线及随访时丙氨酸转氨酶和天冬氨酸转氨酶检测结果的受试者。在ART治疗的前12个月内确定严重肝毒性病例。通过临床记录、数据库查询和血清学检测确定潜在危险因素，包括合并用药、结核病以及乙型和丙型肝炎。使用Cox比例风险模型研究与肝毒性的关联。
868名受试者（94%为男性，中位年龄41岁）中，CD4细胞计数最低点的中位数为136/微升，25%在ART治疗期间接受了合并结核病治疗，随机抽取的一个亚组中有17%的人乙型肝炎表面抗原（HBsAg）呈阳性。我们确定每100人年有7.7例严重肝毒性发作。结核病治疗使风险增加8.5倍，HBsAg阳性使风险增加3.0倍，CD4细胞计数最低点<100/微升使风险增加1.9倍。重要的是，接受ART治疗的严重肝毒性患者比例（4.6%）与开始ART治疗前肝酶升高超过正常上限5倍的患者比例（4%）相似。
在这个非洲ART队列中，我们发现肝毒性的发生率较低且发病率最小。HBsAg和合并结核病治疗显著增加了肝毒性风险。
