慢性乙型肝炎肝纤维化患者血清Copeptin和PCT表达水平及其临床价值研究

Serum Copeptin and PCT Expression Levels and Their Diagnostic Value in Patients with Hepatitis B Liver Fibrosis

目的探讨慢性乙型肝炎肝纤维化患者血清和肽素(Copeptin)和降钙素原(procalcitonin,PCT)表达水平,并分析其在肝纤维化诊断中的价值。方法共纳入2019年2月~2021年12月在广西医科大学第四附属医院就诊的195例慢性肝病单感染HBV患者作为HBV组,并选择同一期间在该院进行健康体检的志愿者作为对照组。其中HBV组中慢性乙型肝炎(CHB)患者117例(CHB组),CHB相关肝硬化(LC)患者78例(LC组),对所有参与患者进行临床指标分析,采用ELISA方法检测患者血清Copeptin和PCT表达水平。METAVIR评分系统评估CHB组中接受肝活检的患者的肝纤维化程度;Child-Pugh分级评估LC患者的肝功能障碍程度。比较Copeptin,PCT表达水平与肝纤维化和肝功能的关系。ROC曲线评估肝纤维化诊断生物标志物。结果HBV组血清Copeptin(2.39±0.73 ng/ml vs 1.19±0.39ng/ml)和PCT(2.11±0.69 ng/ml vs 0.97±0.31 ng/ml)水平明显高于对照组(t=11.912,12.108,均P<0.05),并且与CHB组比较,LC组血清Copeptin(3.18±0.96 ng/ml vs 1.87±0.58 ng/ml)和PCT(2.87±0.92 ng/ml vs 1.61±0.53 ng/ml)表达水平增加(t=11.871,12.111,均P<0.05),差异具有统计学意义。血清Copeptin和PCT表达水平随着肝纤维化程度和Child-Pugh分级的增加而升高,差异有统计学意义(t=2.887~9.116,均P<0.05)。血清Copeptin和PCT表达水平及其他无创方法[肝脏硬度(LSM),AST与血小板比率指数(APRI)和纤维化-4(FIB-4)指数]区分CHB患者发生F0~F1期与F2~F3期肝纤维化的ROC曲线下面积分别为0.910,0.889,0.790,0.765和0.672,而以上五项指标联合的曲线下面积为0.962。Copeptin和PCT区分CHB患者肝纤维化程度的曲线下面积及总有效率高于肝纤维化指标(Ⅳ型胶原、Ⅲ型前胶原、透明质酸酶、层黏连蛋白)。结论血清Copeptin和PCT在慢性乙型肝炎肝纤维化患者中高表达,能够用于诊断肝纤维化程度。

Objective To determine the expression characteristics of serum Copeptin and procalcitonin(PCT)in patients with hepatitis B virus(HBV),and analyze their diagnostic value in liver fibrosis.Methods A total of 195 patients with chronic liver disease single-infected with HBV who were treated in the Fourth Affiliated Hospital of Guangxi Medical University from February 2019 to December 2021 were included as the HBV group,and volunteers who underwent physical examination in the hospital during the same period were selected as the control group.Among them,there were 117 patients with chronic hepatitis B(CHB)in the HBV group(CHB group),and 78 patients with CHB-related liver cirrhosis(LC)(LC group).The clinical indicators of all the participating patients were analyzed,and the serum Copeptin and PCT expression levels of the patients in each group were detected by ELISA.The METAVIR scoring system assessed the degree of liver fibrosis in patients in the CHB group who underwent liver biopsy.The Child-Pugh classification assessed the degree of liver dysfunction in patients with LC.The relationship between Copeptin and PCT expression levels and liver fibrosis and liver function were compared,and ROC curve evaluation of diagnostic biomarkers of liver fibrosis.Results The levels of serum Copeptin(2.39±0.73 ng/ml vs 1.19±0.39 ng/ml)and PCT(2.11±0.69 ng/ml vs 0.97±0.31 ng/ml)in the HBV group were significantly higher than those in the control group(t=11.912,12.108,all P<0.05),and compared with the CHB group,the expression levels of serum Copeptin and PCT in the LC group increased(3.18±0.96 ng/ml vs 1.87±0.58 ng/ml,2.87±0.92 ng/ml vs 1.61±0.53 ng/ml,t=11.871,12.111,all P<0.05),and the difference were statistically significant.Serum Copeptin and PCT expression levels increased with the degree of liver fibrosis and Child-Pugh grade(t=3.666,2.887,9.116,3.755,all P<0.05).Serum Copeptin,PCT expression levels and other non-invasive methods[liver stiffness(LSM),AST to platelet ratio index(APRI)and fibrosis-4(FIB-4)index]to differentiate CHB patients with F0~F1 and F2~F3 stages the areas under the ROC curve of liver fibrosis were 0.910,0.889,0.790,0.765 and 0.672,respectively,and the combined area under the curve of the above five indicators was 0.962.The area under the curve and total effective rate of Copeptin and PCT in differentiating the degree of liver fibrosis in CHB patients were higher than those of liver fibrosis indicators(type Ⅳ collagen,type Ⅲ procollagen,hyaluronidase,laminin).Conclusion Serum Copeptin and PCT were highly expressed in patients with chronic hepatitis B liver fibrosis and can be used to diagnose the degree of liver fibrosis.