Division of Gastroenterology, Hepatology, and Nutrition, Infectious Diseases, Virginia Commonwealth University Health System, Richmond, VA, USA.
J Clin Gastroenterol. 2013 Feb;47(2):182-7. doi: 10.1097/MCG.0b013e318264181d.
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.
HIV-positive subjects without hepatitis C virus, hepatitis B virus, alcohol abuse, and diabetes mellitus with more than 1 abnormal LE, defined as 1.25 ULN 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.
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 γ-glutamyl transpeptidase (P = 0.0009) predicted steatosis whereas HOMA-IR (P = 0.0046) predicted NASH.
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 γ-glutamyl transpeptidase and a calculated measure of insulin resistance, respectively. Further studies are needed in this population to determine the long-term clinical significance.
人类免疫缺陷病毒（HIV）感染者常出现肝功能异常（LE）。目前缺乏关于无病毒性肝炎但 LE 异常者的组织学数据。
纳入 HIV 阳性、无丙型肝炎病毒、乙型肝炎病毒、酗酒和糖尿病，且 LE 异常超过 1 项（天门冬氨酸氨基转移酶、丙氨酸氨基转移酶或碱性磷酸酶超过正常值上限 1.25 倍，持续超过 6 个月）者。所有患者均接受口服葡萄糖耐量试验、空腹血脂、胰岛素和血糖检查，以稳态模型评估胰岛素抵抗（HOMA-IR）评估胰岛素抵抗（IR），采用双能 X 线吸收法评估脂肪分布。根据临床资料进行肝组织学盲法阅片，采用 Ishak 炎症活动度和纤维化评分系统以及非酒精性脂肪性肝病活动度评分（NAFLD-activity score）进行评分。
14 例患者接受了肝活检。所有患者均接受高效抗逆转录病毒治疗，HIV RNA 检测不到，平均 CD4 计数为 614。炎症和纤维化的 Ishak 组织学活动指数评分分别为 3.43（1.4）和 1.71（1.26），2 例患者存在晚期纤维化（桥接纤维化/肝硬化）。大多数（65%）患者存在脂肪变性：1 级 21%，2 级 28%，3 级 14%。7 例（40%）患者存在肝细胞气球样变，但仅 4 例（26%）诊断为非酒精性脂肪性肝炎（NASH）。所有活检的 NAFLD-activity score 为 3.07（2.2；范围 0 至 5）。与无脂肪变性者相比，有脂肪变性者的 HOMA-IR 更高（3.52 比 1.91；P = 0.11），NASH 患者的 HOMA-IR 最高（4.89）。采用多变量逻辑回归分析，仅 γ-谷氨酰转肽酶升高（P = 0.0009）可预测脂肪变性，而 HOMA-IR（P = 0.0046）可预测 NASH。
尽管 HIV 感染者 LE 异常且无糖尿病、酒精或病毒性肝炎合并感染时，常出现脂肪变性，但仅 26% 的患者诊断为 NASH。与肝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指标。需要对这一人群进行进一步研究，以确定其长期临床意义。
