Indinavir-associated hepatitis in patients with advanced HIV infection
Indinavir-associated hepatitis in patients with advanced HIV infection
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晚期 HIV 感染患者中的茚地那韦相关性肝炎
DOI：
10.1258/0956462981920883
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发表时间：
1998
影响因子：
1.4
通讯作者：
Nina Singh
中科院分区：
文献类型：
--
作者：
E. Vergis;D. Paterson;Nina Singh
包括依地那韦在内的蛋白水解酶抑制剂已被广泛应用于HIV感染患者的治疗。虽然肾结石和无症状胆红素血症常与依地那韦相关，但急性肝炎并不是依地那韦公认的不良反应。我们报告了一例艾滋病患者与吲哚那韦相关的重症急性肝炎。据我们所知，以前只报告了3例这种严重不良反应1。1例患者，46岁，CD4细胞数为10个/毫升，在加入吲哚那韦(800毫克，一天三次)之前，曾接受甲氧嘧啶-磺胺甲恶唑、齐多夫定、二磷酸核苷和地西米帕明治疗7个月。乙型和丙型肝炎病毒血清学检查均为阴性。服药3周后，肝功能检查正常。服用依地那韦治疗46天后，患者出现上腹部中段疼痛和恶心，持续一周。检查时，记录右上腹压痛和肝肿大。总胆红素3.7 mg/dl，丙氨酸氨基转移酶123IU/L，丙氨酸氨基转移酶520IU/L，碱性磷酸酶136IU/L。所有药物都被停用。内窥镜逆行胰胆管造影术(ERCP)检查结果并不明显。肝活检(经颈静脉入路)显示脂肪变性、嗜酸性粒细胞变性和嗜酸性粒细胞变性；这些结果与先前活检证实的吲哚那韦肝炎病例相似。在接下来的几天里，患者出现了大量腹水和需要利尿剂的腹痛。他的血清胆红素峰值为12.2 mg/dl，然后逐渐恢复正常。我们的患者出现了急性起病的肝炎，伴有严重的肝细胞损伤、低凝血酶原血症、腹水和腹水，这与依地那韦的启动时间有关。肝脏活检没有发现病毒性或酒精性肝炎的证据，包括ERCP在内的广泛检查也未能揭示他急性肝炎的替代病因。在遇到这一病例时，唯一报告的与黄疸相关的吲哚那韦的不良反应是记录在案的高达10%的患者出现无症状的间接高胆红素血症2，3；在这类患者中不推荐停用吲哚那韦。我们的患者和之前的3例一样，CD4计数低于50/ml，提示为晚期艾滋病。因此，对于晚期HIV感染患者，在服用吲哚那韦后出现急性高胆红素血症并出现转氨酶异常的患者，应考虑与吲地那韦相关的肝炎。对于此类患者，应立即停止使用吲哚那韦治疗。
Protease inhibitors including indinavir have gained widespread use in the management of HIVinfected patients. Although nephrolithiasis and asymptomatic bilirubinaemia occur commonly in association with indinavir, acute hepatitis is not a well recognized adverse effect of indinavir. We report a case of indinavir-associated severe acute hepatitis in a patient with AIDS. To our knowledge, only 3 cases of this serious adverse effect have been reported previously1. A 46-year-old man with CD4 count of 10 cells/ml had been on treatment with trimethoprim-sulfamethoxazole, zidovudine, didanosine, and desimipramine for 7 months prior to the addition of indinavir (800 mg, thrice a day). Serology for hepatitis B and C virus was negative. Liver function tests 3 weeks after the institution of indinavir were normal. Forty-six days after treatment with indinavir, the patient presented with mid-epigastric pain and nausea of one week’s duration. On examination, right upper quadrant tenderness and hepatomegaly were documented. Total bilirubin was 3.7 mg/dl, alanine aminotransferase was 123 IU/l, gamma glutamyl transpeptidase was 520 IU/l and the alkaline phosphatase was 136 IU/l. An ultrasound and CT scan of the abdomen revealed hepatomegaly with no evidence of duct dilatation. All medications were discontinued. An endoscopic retrograde cholangiopancreatogram (ERCP) was unremarkable. A liver biopsy (performed via transjugular approach) revealed steatosis, eosinophilic degeneration, and ® brosis; these ® ndings were similar to a previous biopsy proven case of indinavir hepatitis1. Over the ensuing several days, the patient developed massive ascites and anasarca requiring diuretics. His serum bilirubin peaked at 12.2 mg/dl before gradually returning to normal. Our patient developed acute onset hepatitis with severe hepatocellular injury, hypoprothrombinaemia, ascites, and anasarca that was temporally related to the initiation of indinavir. There was no evidence of viral or alcoholic hepatitis on liver biopsy and extensive workup including ERCP failed to reveal an alternative aetiology of his acute hepatitis. At the time when this case was encountered, the only reported adverse effect of indinavir associated with jaundice was asymptomatic indirect hyperbilirubinaemia documented in up to 10% of the patients2,3; discontinuation of indinavir is not recommended in such patients. Our patient, as in the 3 previous cases, had advanced AIDS as indicated by CD4 counts of less than 50/ml. Thus, indinavir-associated hepatitis should be a consideration in patients with advanced HIV infection who develop acute hyperbilirubinaemia in conjunction with abnormal transaminases upon institution of indinavir. Indinavir treatment should be promptly withheld in such patients.