Walker Ulrich A
Department of Rheumatology and Clinical Immunology, Freiburg University Hospital, D-79106 Freiburg, Germany.
Curr Opin HIV AIDS. 2007 Jul;2(4):293-8. doi: 10.1097/COH.0b013e328122dbaa.
Antiretroviral drugs are associated with hepatotoxicity. Progress in our knowledge on the prevalence, contributory factors and mechanisms is reviewed.
Liver toxicity is highly prevalent and a major cause of hospitalization among HIV-infected individuals. Liver steatosis is probably more frequent in the setting of hepatitis C virus coinfection but is also seen in noncoinfected patients. Among the individual drugs, severe liver toxicity is more strongly associated with nevirapine, and the mitochondrial toxicity of some nucleoside analogues. Mitochondrial toxicity can also induce or contribute to steatohepatitis, with dietary uridine supplementation as a possible strategy of prevention. Atazanavir inhibits UDP-glucuronosyltransferase, which in Gilberts' syndrome has been associated with breast cancer. A UDP-glucuronosyltransferase gene promoter variant predisposes to hyperbilirubinemia. Tipranavir induces elevated transaminases more frequently than boosted comparator protease inhibitors. CCR5 inhibitors may predispose to hepatotoxic events by causing an imbalance in the cytokine response.
Hepatotoxicity is associated with all classes of antiretroviral agents and continues to contribute to hospitalization.
抗逆转录病毒药物与肝毒性相关。本文综述了我们在肝毒性的患病率、促成因素及机制方面的认知进展。
肝毒性在HIV感染者中非常普遍,是导致住院的主要原因。在丙型肝炎病毒合并感染的情况下,肝脂肪变性可能更为常见,但在未合并感染的患者中也可见到。在各类药物中,严重肝毒性与奈韦拉平以及某些核苷类似物的线粒体毒性关联更为紧密。线粒体毒性还可诱发或导致脂肪性肝炎,补充膳食尿苷可能是一种预防策略。阿扎那韦抑制尿苷二磷酸葡萄糖醛酸转移酶,在吉尔伯特综合征中,这与乳腺癌有关。尿苷二磷酸葡萄糖醛酸转移酶基因启动子变异易导致高胆红素血症。与增强型对照蛋白酶抑制剂相比,替拉那韦更常导致转氨酶升高。CCR5抑制剂可能通过引起细胞因子反应失衡而导致肝毒性事件。
肝毒性与所有类别抗逆转录病毒药物相关,且仍是导致住院的原因之一。