Regional Institute of Gastroenterology and Hepatology, 3rd Medical Clinic, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
J Physiol Pharmacol. 2012 Aug;63(4):347-53.
Non-invasive biochemical markers are useful to distinguish between nonalcoholic steatohepatitis (NASH) and simple steatosis. The aim of this study was to test the diagnostic value of a panel of biomarkers derived from the pathophysiological events involved in the development of NASH. A total of 79 patients: 20 not-NASH and 59 NASH were included in the study. Definitive NASH was defined according to Kleiner's classification. In all subjects, parameters of the metabolic syndrome, insulin resistance (HOMA-IR), adiponectin, interleukin-6 (IL-6) and total cytokeratin-18 (M65 antigen) were determined. Univariate and multivariate analysis were used to identify independent predictors of NASH. In multivariate analysis three markers were independently predictors of NASH: adiponectin, IL-6 and M65 levels. In decreasing order, the independent predictors of NASH (NAS≥5) were M65 with an AUROC of 0.791, IL-6 with an AUROC of 0.727 and adiponectin with an AUROC of 0.709. The combination of two biomarkers yelded an AUROC of 0.828 for M65 and IL-6, 0.841 for adiponectin and M65 and 0.852 for adiponectin and IL-6. The best value was obtained by triple combination: adiponectin, M65 and IL-6 with and AUROC of 0.903, Sp=85.7% (PPV=94.2%) and Se=84.5% (NPV=66.7%). In conclusion, a novel pathophysiological - based panel of biomarkers combining total CK-18, IL-6 and adiponectin may be useful to predict NASH.
非侵入性生化标志物有助于鉴别非酒精性脂肪性肝炎（NASH）和单纯性脂肪变性。本研究旨在检验源自 NASH 发生过程中病理生理事件的一组生物标志物的诊断价值。共纳入 79 例患者：20 例非 NASH 和 59 例 NASH。根据 Kleiner 分类，明确诊断为 NASH。所有患者均测定代谢综合征参数、胰岛素抵抗（HOMA-IR）、脂联素、白细胞介素 6（IL-6）和总细胞角蛋白 18（M65 抗原）。采用单变量和多变量分析确定 NASH 的独立预测因子。多变量分析显示，脂联素、IL-6 和 M65 水平是 NASH 的独立预测因子。按降序排列，NASH 的独立预测因子（NAS≥5）依次为 M65，AUROC 为 0.791；IL-6，AUROC 为 0.727；脂联素，AUROC 为 0.709。两种生物标志物联合，M65 和 IL-6 的 AUROC 为 0.828，脂联素和 M65 的 AUROC 为 0.841，脂联素和 IL-6 的 AUROC 为 0.852。最佳值通过三联组合获得：脂联素、M65 和 IL-6，AUROC 为 0.903，Sp=85.7%（PPV=94.2%），Se=84.5%（NPV=66.7%）。总之，基于病理生理的总 CK-18、IL-6 和脂联素的新型生物标志物组合可能有助于预测 NASH。
