血清骨保护素对非酒精性脂肪性肝炎无创性诊断的价值

Value of serum osteoprotegerin in noninvasive diagnosis of nonalcoholic steatohepatitis

目的 探究骨保护素（OPG）与NAFLD进展的相关性,无创性预测诊断非酒精性脂肪性肝炎（NASH）. 方法 筛选136例配套肝穿刺活组织标本及其肝穿刺1周血清标本的非酒精性脂肪肝患者、83例经B型超声检查无脂肪肝症状的正常健康人群作为对照.测量身高、体质量、腰围等生理指标,计算体质量指数;检测丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、AST/ALT、碱性磷酸酶、γ-谷氨酰转移酶、总胆固醇、甘油三酯（TG）、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇等生物化学指标;酶联免疫吸附试验双抗夹心法测定血清中OPG浓度水平.据资料不同采用秩和检验、x2检验、t检验分析、单因素方差分析、Spearman相关分析、LSD检验或受试者工作特征曲线进行统计分析. 结果 血清OPG与AST及TG具有相关性（P＜0.05）,与肝细胞脂肪变性、气球样变、小叶内炎症、汇管区炎症及纤维化程度呈高度相关（P＜ 0.01）;随NAS评分增高其浓度降低,呈高度负相关（r=-0.928,P＜0.01）;NASH患者血清中OPG明显低于无NASH患者,经ROC曲线分析,曲线下面积AUROC=0.963,利用Youden指数确定最佳敏感性为96.1％,特异性为97.4％,最佳截断值为242.96 ng/L,具有较高的诊断能力.结论 NASH患者血清OPG水平显著降低,血清OPG可作为评价NASH及其严重程度的独立预测因子,可以作为一个无创性诊断指标对NASH进行诊断.

Objective To investigate the correlation of serum osteoprotegerin （OPG） with the progression of nonalcoholic fatty liver disease （NAFLD） and the noninvasive prediction and diagnosis of nonalcoholic steatohepatitis （NASH）.Methods A total of 136 patients with NAFLD were enrolled,and their tissue samples for liver biopsy and serum samples obtained at 1 week after liver biopsy were collected;83 healthy subjects without the symptoms of fatty liver disease proved by ultrasound examination were enrolled as controls.The physiological indicators including height,body weight,and waist circumference were measured,and body mass index was calculated.The biochemical parameters including alanine aminotransferase （ALT）,aspartate aminotransferase （AST）,AST/ALT,alkaline phosphatase,gamma-glutamyl transferase,total cholesterol,triglyceride （TG）,high-density lipoprotein cholesterol,and low-density lipoprotein cholesterol were measured.Double-antibody sandwich enzymelinked immunosorbent assay was used to determine the serum level of OPG.The rank sum test,chi-square test,t-test,one-way analysis of variance,Spearman correlation analysis,least significant difference test,and receiver operating characteristic （ROC） curve were applied for statistical analysis of various data.Results Serum OPG level was correlated with AST and TG （P ＜ 0.05）,and was highly correlated with hepatocyte fatty degeneration,ballooning degeneration,intralobular inflammation,portal inflammation,and fibrosis degree （P ＜ 0.01）.With the increasing NAFLD activity score （NAS）,serum OPG level decreased,and there was a highly negative correlation between them （r =-0.928,P ＜ 0.01）.Serum OPG level was significantly lower in NASH patients than non-NASH patients.The area under the ROC curve of serum OPG level was 0.963,and according to the Youden index,its optimal sensitivity and specificity were 96.1％ and 97.4％,respectively,at an optimal cut-offvalue of 242.96 ng/L,which suggested a high diagnostic power.Conclusion In NASH patients,serum OPG level decreases significantly.Serum OPG level can be used as an independent predictive factor to evaluate NASH and its severity,as well as a noninvasive diagnostic index for NASH.