GP73预测慢性乙型肝炎患者肝硬化进展研究

 

目的 探讨血清高尔基体蛋白73(golgi protein 73,GP73)浓度对慢性乙型肝炎(chronic hepatitis B,CHB)是否发展为肝硬化的诊断价值。方法 收集2018年1-12月武警特色医学中心就诊的CHB患者107名,根据《慢性乙型肝炎防治指南(2015年版)》同时参考临床表现、影像学、实验室检查等综合考虑,将入组患者分为慢性乙肝组(59例)和乙肝肝硬化组(48例),此为实验队列。同时选取2018年8-11月就诊于天津市第二人民医院CHB患者133例,分为慢性乙肝组(97例)和慢性乙肝肝硬化组(36例),此为验证队列。收集患者人口学资料和实验室资料,并收集患者血清通过ELISA方法检测GP73浓度,计算无创血清学诊断方法GPR得分。正态分布的计量资料选择t检验比较,计数资料组间差异采用χ²检验比较,非正态分布采用四分位数间距表示,两组间选择Mann-Whitney U检验。采用Pearson相关性分析比较血清GP73浓度与肝脏炎症程度相关性、采用Spearman相关性分析其与是否发生肝硬化的相关性。建立ROC曲线,计算血清GP73含量在诊断肝硬化中的cut-off值。结果 两队列中慢性乙肝肝硬化组年龄(P₁=0.012,P₂=0.000)、总胆红素(P₁=0.015,P₂=0.000)、碱性磷酸酶(P₁=0.013,P₂=0.000)、血小板计数(P₁=0.012,P₂=0.001)、肝硬度值(liver stiffness measurement,LSM)(P₁=0.000,P₂=0.000)、GPR(P₁=0.000,P₂=0.000)、GP73(P₁=0.000,P₂=0.026)数值明显高于慢性乙肝组,两组数据比较差异有统计学意义。GP73浓度与谷丙转氨酶(P₁=0.012,P₂=0.010)、谷草转氨酶(P₁=0.000,P₂=0.000)、总胆红素(P₁=0.000,P₂=0.000)具有相关性,与是否发生肝硬化密切相关(r₁=0.846,P₁=0.000;r₂=0.591,P₂=0.000)。ROC曲线显示三种无创指标诊断乙肝肝硬化的曲线下面积分别为LSM(AUC₁=0.844,AUC₂=0.730)、GPR(AUC₁=0.922,AUC₂=0.724)、GP73(AUC₁=0.991,AUC₂=0.870),相较而言GP73诊断价值最高。结论 血清中GP73浓度与抗病毒治疗CHB肝脏疾病严重程度相关,具有提示肝硬化发生的临床价值。

Prediction of cirrhosis progression by GP73 in patients with chronic hepatitis B

Objective To investigate the potential of serum Golgi protein 73 (GP73) concentrations to predict the chance of chronic hepatitis B cirrhosis(CHB) developing into cirrhosis.Methods The clinical data on 107 patients with chronic hepatitis B who were treated in the Characteristic Medical Center of the Chinese People’s Armed Police Force between January and December 2018 was collected. According to the Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2015 edition), these patients (the experimental group) were divided into the chronic hepatitis B group (59 cases) and cirrhosis group (48 cases) with reference to their clinical manifestations, imaging and laboratory examinations. Meanwhile, 133 CHB patients (the validation group) treated at Tianjin Second People’s Hospital between August and November 2018 were selected and divided into the chronic hepatitis B group (97 cases) and cirrhosis group (36 cases). The demographic data and laboratory data of all these patients were collected, and the serum GP73 concentrations were detected by ELISA, and the GPR score of the non-invasive serological diagnostic method was calculated. The normally-distributed measurement data was compared via t-test, while chi-square test was used to compare the differences of the data between groups. Abnormal distribution was represented by the quartile range, and Mann Whitney U test was used to make a comparison between the two groups. Pearson correlation analysis was used to compare the correlation between serum GP73concentrations and liver inflammation, while Spearman correlation analysis was used to analyze the correlation between serum GP73 concentrations and liver cirrhosis. The ROC curve was established to calculate the cut-off value of serum GP73 in the diagnosis of chronic hepatitis B cirrhosis.Results The age(P₁=0.012,P₂=0.000), total bilirubin(P₁=0.015,P₂=0.000),alkaline phosphatase(P₁=0.013,P₂=0.000), platelet count (P₁=0.012,P₂=0.001), liver stiffness measurement(LSM) (P₁=0.000,P₂=0.000), GPR(P₁=0.000,P₂=0.000), GP73(P₁=0.000,P₂=0.026)of the two cirrhosis groups were significantly above those of the two hepatitis B groups, and the difference was statistically significant.GP73 concentrations were correlated with alanine aminotransferase (P₁=0.012,P₂=0.010), glutamic oxaloacetic aminotransferase (P₁=0.000,P₂=0.000), total bilirubin (P₁=0.000,P₂=0.000), and were closely related to the occurrence of cirrhosis (r₁=0.846, P₁=0.000; r₂=0.591, P₂=0.000). the ROC curve showed that the areas under the curve of three non-invasive indicators were LSM(AUC₁=0.844,AUC₂=0.730),GPR(AUC₁=0.922,AUC₂=0.724) and GP73 (AUC₁=0.991,AUC₂=0.870), respectively. GP73 had the highest diagnostic value.Conclusions The concentration of GP73 in serum is closely related to the severity of chronic hepatitis B, which is of clinical value.