Cornejo-Juárez Patricia, Sierra-Madero Juan, Volkow-Fernández Patricia
Departamento de Enfermedades Infecciosas, Instituto Nacional de Cancerología, Mexico City, Mexico.
Arch Med Res. 2003 Jan-Feb;34(1):64-9. doi: 10.1016/s0188-4409(02)00454-x.
Nucleoside analog reverse transcriptase inhibitors (NRTI) have been used to treat HIV-infected patients for >10 years. Some severe adverse events have been attributed to mitochondrial dysfunction. Since 1991, cases of severe lactic acidosis have been reported in association with nucleoside therapy. Our objective was to report two cases of metabolic acidosis and hepatic steatosis in patients receiving stavudine (d4T) and to review the literature. A male and a female, 47 and 45 years of age, respectively, presented with abdominal pain, nausea, vomiting, and weakness after 9 and 6 months, respectively, of treatment with stavudine. At presentation, both patients had severe metabolic acidosis and liver failure. Ultrasonography showed hepatic steatosis (confirmed by biopsy in one case). All antiretroviral drugs were withdrawn and patients were treated with bicarbonate. Both patients developed fulminant liver dysfunction and multiple organ failure. We reviewed the literature and found 75 cases of lactic acidosis and hepatic steatosis associated with use of NRTI; 57 of these patients received d4T (76%). Of all cases reported in association with nucleoside therapy, 63% were females and mortality was 47%. General weakness, hepatic enzyme elevation, and liver steatosis are data that should alert physicians to this serious adverse event and to respond with prompt interruption of antiretroviral drugs and measurement of lactic acid in plasma. It is important to report serious adverse events in commercially released drugs to know prevalence in an exposed population. Physicians should be aware of risk and early signs of this serious adverse event.
核苷类似物逆转录酶抑制剂（NRTI）已用于治疗HIV感染患者超过10年。一些严重不良事件被归因于线粒体功能障碍。自1991年以来，已有与核苷治疗相关的严重乳酸酸中毒病例报告。我们的目的是报告2例接受司他夫定（d4T）治疗的患者发生代谢性酸中毒和肝脂肪变性的病例，并复习相关文献。一名47岁男性和一名45岁女性，分别在接受司他夫定治疗9个月和6个月后出现腹痛、恶心、呕吐及乏力。就诊时，两名患者均有严重代谢性酸中毒和肝衰竭。超声检查显示肝脂肪变性（1例经活检证实）。所有抗逆转录病毒药物均被停用，患者接受碳酸氢盐治疗。两名患者均出现暴发性肝功能障碍和多器官功能衰竭。我们复习文献发现75例与使用NRTI相关的乳酸酸中毒和肝脂肪变性病例；其中57例患者接受d4T治疗（76%）。在所有与核苷治疗相关的报告病例中，63%为女性，死亡率为47%。全身乏力、肝酶升高和肝脂肪变性等情况应提醒医生注意这一严重不良事件，并及时中断抗逆转录病毒药物治疗并检测血浆乳酸水平。报告市售药物中的严重不良事件对于了解暴露人群中的患病率很重要。医生应意识到这一严重不良事件的风险和早期迹象。
