乙型肝炎肝硬化患者血清miR-25-3p 和IBSP 表达及临床意义

目的 研究乙型肝炎肝硬化患者血清微小核糖核酸（miRNA，miR）-25-3p 和整合素结合唾液蛋白(integrinbinding sialoprotein，IBSP) 表达及临床意义。方法 选取2018 年5 月～ 2019 年5 月南通市第六人民医院诊治的乙型肝炎肝硬化患者120 例为肝硬化组，并将其分为肝硬化失代偿并发腹腔积液组（47 例）和非肝硬化失代偿并发腹腔积液组（73例），以同期诊治的慢性乙型肝炎患者80 例为肝炎组，健康体检者60 例为对照组。应用酶联免疫吸附法检测各组血清IBSP 表达，荧光定量PCR 检测各组血清miR-25-3p 的表达。比较肝硬化组不同临床特征患者血清miR-25-3p 和IBSP 水平差异。Pearson 线性相关分析血清miR-25-3p 和IBSP 与肝功能评分的相关性。多因素Logistic 回归分析影响肝硬化失代偿并发腹腔积液的危险因素。受试者工作曲线（ROC）分析miR-25-3p 和IBSP 及联合检测对肝硬化失代偿并发腹腔积液的诊断价值。结果 肝硬化组、肝炎组及对照组血清miR-25-3p 水平分别为5.22±0.41，1.16±0.34 和0.92±0.32，IBSP 蛋白水平分别为9.34±1.28ng/ml, 3.15±0.37ng/ml 和1.02±0.30ng/ml。肝硬化组血清miR-25-3p 和IBSP 蛋白明显高于肝炎组（t=73.327, 42.067）及对照组（t=4.238, 34.486），差异均有统计学意义（均P ＜ 0.05）。肝硬化组患者血清miR-25-3p 和IBSP 蛋白表达水平与肝纤维化、消化道出血及腹腔积液有关（t=10.194 ～ 34.744, 均P ＜ 0.05）。肝硬化组患者血清miR-25-3p 和IBSP 蛋白表达与清蛋白-胆红素评分（albumin-bilirubin, ALBI）、终末期肝病模型评分（modelfor end-stage liver disease, MELD）、肝硬化Child -Pugh 评分均呈明显正相关（r=0.457 ～ 0.584，均P ＜ 0.05）。多因素Logistic 回归分析结果血清miR-25-3p 升高（OR:1.202,95%CI:1.059 ～ 1.642）,IBSP 升高（OR:1.229, 95%CI:1.081 ～ 1.719）是肝硬化失代偿并发腹腔积液的独立危险因素。ROC 曲线显示，miR-25-3p 和IBSP 联合诊断肝硬化失代偿及并发腹腔积液的曲线下面积（AUC）大于miR-25-3p 和IBSP 单独诊断(Z=3.727，4.163，均P=0.000)。结论 乙型肝炎肝硬化患者血清中miR-25-3p 和IBSP 蛋白水平升高，二者联合检测对乙型肝炎肝硬化失代偿并发腹腔积液具有较高诊断价值。

Expression and Clinical Significance of Serum miR-25-3p and IBSP in Patients with Hepatitis B Cirrhosis

Objective To study the expression and clinical significance of serum microRNA (miR) -25-3p and integrin binding salivary protein (IBSP) in patients with hepatitis B cirrhosis. Methods 120 patients with hepatitis B cirrhosis treated in the Sixth People’s Hospital of Nantong from May 2018 to May 2019 were selected as the cirrhosis group, and they were divided into decompensated cirrhosis complicated with peritoneal effusion group (47 cases) and non decompensated cirrhosis complicated with peritoneal effusion group (73 cases),80 patients with chronic hepatitis B diagnosed and treated at the same time were taken as the hepatitis group and 60 healthy persons as the control group.The expression of serum IBSP was detected by enzyme-linked immunosorbent assay, and the expression of serum miR-25-3p was detected by fluorescence quantitative PCR.The levels of serum miR-25-3p and IBSP in patients with different clinical characteristics in cirrhosis group were compared.Pearson linear correlation analysis was used to analyze the correlation between serum miR-25-3p, IBSP and liver function score.Multivariate logistic regression analysis was used to analyze the risk factors of decompensated liver cirrhosis complicated with peritoneal effusion.Receiver operating curve (ROC) was used to analyze the diagnostic value of miR-25-3p,IBSP and combined detection in decompensated liver cirrhosis complicated with peritoneal effusion. Results The levels of serum miR-25-3p in liver cirrhosis group, hepatitis group and control group were 5.22±0.41,1.16±0.34, 0.92±0.32, and the levels of IBSP protein were 9.34 ±1.28ng/ml, 3.15±0.37ng/ml and 1.02±0.30ng/ml, respectively.Serum miR-25-3p and IBSP protein in liver cirrhosis group were significantly higher than those in hepatitis group（t=73.327, 42.067） and control group(t=4.238, 34.486), the differences were statistically significant(all P ＜ 0.05). The expression levels of serum miR-25-3p and IBSP protein in patients with liver cirrhosis were related to liver fibrosis, gastrointestinal bleeding and peritoneal effusion (t=10.194 ~ 34.744, all P ＜ 0.05).The expression of serum miR-25-3p and IBSP protein in patients with liver cirrhosis was positively correlated with albumin bilirubin （ALBI）score, model for end-stage liver disease(MELD) score and child Pugh score of liver cirrhosis (r= 0.457 ~ 0.584, all P ＜ 0.05). Multivariate logistic regression analysis showed that the increase of serum miR-25-3p(OR: 1.202, 95% CI: 1.059 ~ 1.642) and IBSP (OR: 1.229,95% CI: 1.081 ~ 1.719) were independent risk factors of decompensated liver cirrhosis complicated with peritoneal effusion.ROC curve showed that the area under the curve (AUC) of miR-25-3p and IBSP in the combined diagnosis of decompensated liver cirrhosis and concurrent peritoneal effusion was greater than that of miR-25-3p and IBSP alone (Z = 3.727, 4.163, all P = 0.000). Conclusion The serum levels of miR-25-3p and IBSP protein in patients with hepatitis B cirrhosis increased. The combined detection of miR-25-3p and IBSP protein has high diagnostic value for decompensated hepatitis B cirrhosis complicated with peritoneal effusion.