Ingiliz Patrick, Valantin Marc-Antoine, Duvivier Claudine, Medja Fadia, Dominguez Stephanie, Charlotte Frédéric, Tubiana Roland, Poynard Thierry, Katlama Christine, Lombès Anne, Benhamou Yves
Hepatology Department, AP-HP, GH Pitié-Salpêtrière, Paris, France.
Hepatology. 2009 Feb;49(2):436-42. doi: 10.1002/hep.22665.
Liver damage associated with chronic unexplained high serum transaminases in human immunodeficiency virus (HIV)-infected patients under combined antiretroviral therapy is unknown. Liver histology was prospectively investigated in patients presenting serum transaminase elevation for more than 6 months, after exclusion of alcohol abuse, hepatitis C virus (HCV) or hepatitis B virus (HBV) infection, autoimmune, and genetic liver diseases. In a subgroup of patients, liver mitochondrial activities were measured by spectrophotometry and mitochondrial DNA (mtDNA) by real-time polymerase chain reaction (PCR). Thirty patients were included with median values of alanine aminotransferase (ALT) levels: 80 U/L, age: 46 years, body mass index: 23 kg/m(2), HIV RNA: 200 copies/mL, CD4 count: 365/mm(3), duration of HIV infection: 13 years, and duration of treatment exposure: 118, 41, and 53 months for nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors, respectively. Histological anomalies were found in 22 of 30 patients. Steatosis was present in 18 patients, severe in nine patients, and associated with inflammation in 16 patients with a diagnosis of non-alcoholic steatohepatitis (NASH). Fibrosis was found in 18 patients, severe in six patients and associated with steatosis in 13 patients. Significant liver respiratory complex I defect, contrasting with high complex IV activity and normal mitochondrial DNA content, was observed in the group of patients compared with controls. The presence of NASH was correlated with high fasting glycemia and insulin levels, not with liver mitochondrial function or mitochondrial DNA content.
HIV-infected patients on combined antiretroviral therapy with chronic transaminase elevation of unknown origin have a high rate of liver lesions, mostly consistent with NASH related to insulin resistance.
在接受联合抗逆转录病毒治疗的人类免疫缺陷病毒（HIV）感染患者中，与慢性不明原因高血清转氨酶相关的肝损伤情况尚不清楚。在排除酒精滥用、丙型肝炎病毒（HCV）或乙型肝炎病毒（HBV）感染、自身免疫性和遗传性肝病后，对血清转氨酶升高超过6个月的患者进行了肝脏组织学的前瞻性研究。在一组患者中，通过分光光度法测量肝脏线粒体活性，并通过实时聚合酶链反应（PCR）检测线粒体DNA（mtDNA）。纳入了30名患者，丙氨酸氨基转移酶（ALT）水平中位数为80 U/L，年龄46岁，体重指数23 kg/m²，HIV RNA为200拷贝/mL，CD4细胞计数为365/mm³，HIV感染持续时间为13年，核苷类逆转录酶抑制剂、非核苷类逆转录酶抑制剂和蛋白酶抑制剂的治疗暴露持续时间分别为118、41和53个月。30名患者中有22名发现组织学异常。18名患者存在脂肪变性，其中9名严重，16名诊断为非酒精性脂肪性肝炎（NASH）的患者伴有炎症。18名患者发现纤维化，其中6名严重，13名与脂肪变性相关。与对照组相比，在患者组中观察到显著的肝脏呼吸链复合体I缺陷，而复合体IV活性高且线粒体DNA含量正常。NASH的存在与高空腹血糖和胰岛素水平相关，与肝脏线粒体功能或线粒体DNA含量无关。
接受联合抗逆转录病毒治疗且慢性转氨酶升高原因不明的HIV感染患者肝损伤发生率高，大多与胰岛素抵抗相关的NASH一致。
