Hepatic Steatosis in Human Immunodeficiency Virus A Prospective Study in Patients Without Viral Hepatitis, Diabetes, or Alcohol Abuse
Hepatic Steatosis in Human Immunodeficiency Virus A Prospective Study in Patients Without Viral Hepatitis, Diabetes, or Alcohol Abuse
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DOI：
10.1097/mcg.0b013e318264181d
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发表时间：
2013-02-01
影响因子：
2.9
通讯作者：
Brunt, Elizabeth M.
中科院分区：
文献类型：
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作者：
Sterling, Richard K.;Smith, Paula G.;Brunt, Elizabeth M.
背景与目的：肝酶（LEs）异常在人类免疫缺陷病毒（HIV）感染者中很常见。没有病毒性肝炎的LE异常患者的组织学资料缺乏。方法：hiv阳性，无丙型肝炎病毒、乙型肝炎病毒、酗酒、糖尿病，le1以上异常（定义为天门冬氨酸转氨酶、丙氨酸转氨酶或碱性磷酸酶1.25ULN）超过6个月。受试者接受2小时口服葡萄糖耐量试验、空腹血脂、胰岛素和葡萄糖的胰岛素抵抗（IR），通过胰岛素抵抗稳态模型评估（HOMA-IR）和双能x线吸收仪测量脂肪分布。根据临床资料盲目阅读活检，并根据炎症和纤维化的Ishak组织学活性指数和NAFLD活性评分进行评分。结果：14例患者行活检。所有患者都接受了高活性抗逆转录病毒治疗，HIV RNA检测不到，平均CD4为614。炎症和纤维化的组织学活动指数评分分别为3.43（1.4）和1.71(1.26)，2例患者出现晚期纤维化（桥接纤维化/肝硬化）。大多数（65%）患者有脂肪变性：1级21%，2级28%，3级14%。7例（40%）出现肝细胞球囊，但仅4例（26%）诊断为非酒精性脂肪性肝炎（NASH）。所有活组织检查的NAFLD活动性评分为3.07（2.2，范围0 ~ 5）。脂肪变性患者的HOMA-IR高于非脂肪变性患者（3.52 vs. 1.91; P = 0.11）， NASH患者的HOMA-IR最高（4.89）。使用多变量logistic回归，只有γ -谷氨酰转肽酶升高（P = 0.0009）预测脂肪变性，而HOMA-IR （P = 0.0046）预测NASH。结论：虽然脂肪变性在无糖尿病、酒精或病毒性肝炎合并感染的LE异常HIV患者中很常见，但NASH仅占26%。与活检证实的脂肪变性和NASH相关的唯一临床或实验室特征分别是γ -谷氨酰转肽酶和胰岛素抵抗的计算测量。需要在该人群中进一步研究以确定长期临床意义。
Background and Aims: Abnormal liver enzymes (LEs) are common in those infected with human immunodeficiency virus (HIV). Histologic data on those with abnormal LE without viral hepatitis are lacking.Methods: HIV-positive subjects without hepatitis C virus, hepatitis B virus, alcohol abuse, and diabetes mellitus with more than 1 abnormal LE, defined as 1.25ULN in aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase, over 6 months were included. Subjects underwent a 2-hour oral glucose tolerance test, fasting lipids, insulin and glucose for insulin resistance (IR) by homeostasis model assessment for insulin resistance (HOMA-IR) and dual-energy X-ray absorptiometry for fat distribution. Biopsies were read blindly to clinical data, and scored by Ishak histologic activity index for inflammation and fibrosis and NAFLD activity score.Results: Fourteen patients underwent biopsy. All were on highly active antiretroviral therapy with undetectable HIV RNA and mean CD4 614. The histologic activity index scores for inflammation and fibrosis were 3.43(1.4) and 1.71(1.26), respectively, and 2 patients had advanced fibrosis (bridging fibrosis/cirrhosis). The majority (65%) of patients had steatosis: grade 1: 21%, grade 2: 28%, and grade 3: 14%. Hepatocyte ballooning was seen in 7 (40%) but nonalcoholic steatohepatitis (NASH) was diagnosed only in 4 (26%). NAFLD activity score of all biopsies of 3.07 (2.2; range, 0 to 5). HOMA-IR was higher in those with compared with those without steatosis (3.52 vs. 1.91; P = 0.11) and highest in those with NASH (4.89). Using multivariate logistic regression, only increased gamma-glutamyl transpeptidase (P = 0.0009) predicted steatosis whereas HOMA-IR (P = 0.0046) predicted NASH.Conclusions: Although steatosis is common in HIV patients with abnormal LE without diabetes mellitus, alcohol, or viral hepatitis coinfection, NASH was observed in only 26%. The only clinical or laboratory feature associated with biopsy proven steatosis and NASH were gamma-glutamyl transpeptidase and a calculated measure of insulin resistance, respectively. Further studies are needed in this population to determine the long-term clinical significance.