Guillaume M P, De Prez C, Cogan E
Department of Internal Medicine, Hôpital Universitaire Brugmann, Belgium.
Am J Gastroenterol. 1996 Jan;91(1):165-8.
Azole-derived antifungal medications are particularly involved in drug-induced hepatic injury encountered in patients with AIDS. Fluconazole may induce multiple hepatic abnormalities usually characterized by asymptomatic and reversible mild hepatic necrosis. We here describe severe subacute liver damage occurring in a patient with AIDS who was receiving fluconazole maintenance therapy for a cryptococcosis. Hepatotoxicity was essentially characterized by mixed cytolytic and cholestatic liver tests abnormalities which improved after fluconazole discontinuation and worsened on fluconazole rechallenge. Optical microscopy demonstrated nonspecific abnormalities including granular aspect of the cytoplasm of the hepatocytes. In contrast, analysis of electron microscopy revealed unusual unreported features characterized by giant mitochondria with paracrystalline inclusions and enlarged smooth endoplasmic reticulum. All microscopic abnormalities were reversed after discontinuation of fluconazole. We suggest that persistent increased hepatic enzymes in HIV-infected patient taking fluconazole should prompt suspension of the treatment. Prospective studies are needed to determine whether careful monitoring of hepatic tests should be recommended in AIDS patients on prolonged fluconazole maintenance therapy.
唑类抗真菌药物尤其与艾滋病患者出现的药物性肝损伤有关。氟康唑可能诱发多种肝脏异常，通常表现为无症状且可逆的轻度肝坏死。我们在此描述了一名艾滋病患者在接受氟康唑维持治疗隐球菌病时发生的严重亚急性肝损伤。肝毒性主要表现为混合性细胞溶解性和胆汁淤积性肝功能检查异常，在停用氟康唑后有所改善，而在重新使用氟康唑时病情恶化。光学显微镜显示非特异性异常，包括肝细胞胞质呈颗粒状。相比之下，电子显微镜分析揭示了不寻常的未报告特征，其特点是含有副晶状包涵体的巨大线粒体和扩大的滑面内质网。停用氟康唑后，所有显微镜下的异常均消失。我们建议，服用氟康唑的HIV感染患者若肝酶持续升高，应暂停治疗。需要进行前瞻性研究以确定对于接受长期氟康唑维持治疗的艾滋病患者，是否应建议仔细监测肝功能检查。
