Aranzabal Lidia, Casado José L, Moya Javier, Quereda Carmen, Diz Sergio, Moreno Ana, Moreno Leonor, Antela Antonio, Perez-Elias Maria J, Dronda Fernando, Marín Ana, Hernandez-Ranz Felix, Moreno Alberto, Moreno Santiago
Department of Infectious Diseases, Hospital Ramón y Cajal, Madrid, Spain.
Clin Infect Dis. 2005 Feb 15;40(4):588-93. doi: 10.1086/427216. Epub 2005 Jan 21.
Coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) is a known risk factor for hepatotoxicity in patients receiving highly active antiretroviral therapy (HAART). The aim of this study was to evaluate the role of HCV-related liver fibrosis in HAART-associated hepatotoxicity.
In a prospective study involving 107 patients who underwent liver biopsy, fibrosis was graded according 5 stages, from F0 (no fibrosis) to F4 (cirrhosis). Hepatotoxicity was defined as an increase in levels of aspartate aminotransferase and alanine aminotransferase to >5 times the upper limit of normal, or a >3.5-fold increase if baseline levels were abnormal. The incidence of hepatotoxicity was compared with liver fibrosis stage and with time and composition of HAART.
Overall, 27 patients (25%) had hepatotoxic events (5.1 events/100 person-years of therapy). The incidence was greater for patients with stage F3 or F4 fibrosis (38%) than for those with stage F1 or F2 fibrosis (15%; 7.6 vs. 3 events/100 person-years; relative risk, 2.75; 95% confidence interval, 1.08-6.97; P=.013). Duration of HCV infection, duration of HAART, diagnosis of acquired immunodeficiency syndrome, HCV load, HCV genotype, and nadir CD4(+) cell count did not affect the risk of hepatotoxicity. Of the 86 patients who received nonnucleoside reverse-transcriptase inhibitors (NNRTIs), 11 (13%) developed liver toxicity. In these patients, fibrosis stages F1 and F2 were associated with similar rates of toxicity (3 events/100 person-years for patients who received nevirapine, 3.3 events/100 person-years for those who received efavirenz, and 3.4 events/100 person-years for those who received non-NNRTIs). There was a greater incidence among patients with F3 or F4 fibrosis who received NNRTIs (11.7 events/100 person-years for patients who received nevirapine, and 8.6 events/100 person-years for those who received efavirenz), compared with those who received non-NNRTIs (4 events/100 person-years).
HAART-associated hepatotoxicity correlates with liver histological stage in patients coinfected with HIV and HCV. There was no difference in hepatotoxicity risk for different antiretroviral therapies in patients with mild-to-moderate fibrosis.
丙型肝炎病毒（HCV）与人类免疫缺陷病毒（HIV）合并感染是接受高效抗逆转录病毒治疗（HAART）患者发生肝毒性的已知危险因素。本研究旨在评估HCV相关肝纤维化在HAART相关肝毒性中的作用。
在一项涉及107例行肝活检患者的前瞻性研究中，纤维化根据5个阶段进行分级，从F0（无纤维化）到F4（肝硬化）。肝毒性定义为天冬氨酸转氨酶和丙氨酸转氨酶水平升高至正常上限的5倍以上，或如果基线水平异常则升高3.5倍以上。将肝毒性的发生率与肝纤维化阶段以及HAART的时间和组成进行比较。
总体而言，27例患者（25%）发生了肝毒性事件（5.1次事件/100人年治疗）。F3或F4期纤维化患者的发生率（38%）高于F1或F2期纤维化患者（15%；7.6次对3次事件/100人年；相对风险，2.75；95%置信区间，1.08 - 6.97；P = 0.013）。HCV感染持续时间、HAART持续时间、获得性免疫缺陷综合征诊断、HCV载量、HCV基因型和最低点CD4(+)细胞计数均不影响肝毒性风险。在86例接受非核苷类逆转录酶抑制剂（NNRTIs）治疗的患者中，11例（13%）发生了肝毒性。在这些患者中，F1和F2期纤维化与相似的毒性发生率相关（接受奈韦拉平的患者为3次事件/100人年，接受依非韦伦的患者为3.3次事件/100人年，接受非NNRTIs的患者为3.4次事件/100人年）。接受NNRTIs的F3或F4期纤维化患者的发生率更高（接受奈韦拉平的患者为11.7次事件/100人年，接受依非韦伦的患者为8.6次事件/100人年），与接受非NNRTIs的患者（4次事件/100人年）相比。
HAART相关肝毒性与HIV和HCV合并感染患者的肝脏组织学阶段相关。轻度至中度纤维化患者中，不同抗逆转录病毒疗法的肝毒性风险无差异。
