慢性乙型肝炎患者血清sVAP-1、DNMT1、Tim-3水平与肝功能指标及炎症因子的相关性

Correlation analysis of serum levels of soluble vascular adhesion protein-1,DNA methyltransferase-1,T lymphocyte immunoglobulin mucin-3 with liver function indexes and inflammatory factors in patients with chronic hepatitis B.

目的观察慢性乙型肝炎(CHB)患者血清DNA甲基化转移酶1(DNMT1)、T淋巴细胞免疫球蛋白黏蛋白分子3(Tim-3)、可溶性血管黏附蛋白-1(sVAP-1)水平变化,并分析sVAP-1、DNMT1、Tim-3与肝功能指标及炎症因子的相关性。方法选取2018年4月至2020年7月期间西安市第八医院肝病科收治的93例CHB患者为研究对象,将患者分为乙型肝炎病毒(HBV)DNA阳性组(HBV DNA>1.0×10^(3)copy/mL,n=53)和HBV DNA阴性组(HBV DNA≤1.0×10^(3)copy/mL,n=40),另选取同期来我院体检的50例健康志愿者为对照组。比较三组受检者的血清sVAP-1、DNMT1、Tim-3水平及肝功能指标及炎症因子水平,采用Pearson线性相关性分析患者血清sVAP-1、DNMT1、Tim-3水平与肝功能指标及炎症因子的相关性。结果HBV DNA阳性组患者的血清sVAP-1、DNMT1、Tim-3水平分别为(762.75±102.05)ng/mL、(51.37±5.29)μg/L、(24.58±4.39)%,HBV DNA阴性组分别为(493.13±93.11)ng/mL、(38.59±4.24)μg/L、(13.28±2.35)%,两组均明显高于对照组的(184.64±54.19)ng/mL、(25.66±3.18)μg/L、(5.16±0.93)%,且HBV DNA阳性组的上述各项指标明显高于HBV DNA阴性组,差异均有统计学意义(P<0.05);HBV DNA阳性组患者的肿瘤坏死因子-α(TNF-α)、白介素-4(IL-4)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)水平分别为(31.53±2.87)pg/mL、(21.29±4.43)ng/L、(52.96±9.32)U/L、(49.31±6.06)U/L、(37.29±3.25)μmol/L,HBV DNA阴性组分别为(23.24±2.68)pg/mL、(13.56±3.41)ng/L、(38.25±5.26)U/L、(35.68±5.17)U/L、(19.71±4.36)μmol/L,两组均明显高于对照组的(15.18±2.77)pg/mL、(4.72±0.93)ng/L、(18.38±3.09)U/L、(16.19±3.23)U/L、(9.23±2.25)μmol/L,且HBV DNA阳性组的上述各项指标明显高于HBV DNA阴性组,差异均有统计学意义(P<0.05);HBV DNA阳性组和HBV DNA阴性组患者的白蛋白(Alb)水平分别为(39.43±4.05)g/L,(51.57±5.25)g/L,明显低于对照组的(66.89±6.12)g/L,且HBV DNA阳性组明显低于HBV DNA阴性组,差异均有统计学意义(P<0.05);经Pearson线性相关性分析结果显示,sVAP-1、DNMT1、Tim-3与TNF-α、IL-4、ALT、AST、TBIL呈正相关(P<0.05),而与Alb呈负相关(P<0.05)。结论CHB患者中的sVAP-1、DNMT1、Tim-3水平存在异常升高,且与肝功能指标及炎症因子指标存在一定的相关性,可考虑作为CHB诊断的血清学指标之一。

Objective To observe the changes of levels of serum DNA methyltransferase 1(DNMT1),T lymphocyte immunoglobulin mucin 3(Tim-3)and soluble vascular adhesion protein-1(sVAP-1)in patients with chronic hepatitis B(CHB),and to analyze the correlation between sVAP-1,DNMT1,Tim-3 and liver function indexes and inflammatory factors.Methods A total of 93 patients with CHB,who admitted to Department of Hepatology,Xi’an Eighth Hospital from April 2018 to July 2020,were selected as the observation group,and they were divided into hepatitis B virus(HBV)DNA positive group(HBV DNA>1.0×10^(3)copy/mL,n=53)and HBV DNA negative group(HBV DNA≤1.0×10^(3)copy/mL,n=40).Another 50 healthy volunteers who came to Xi’an Eighth Hospital for physical examination during the same period were selected as the control group.The serum levels of s VAP-1,DNMT1,Tim-3,liver function indexes and inflammatory factors in the three groups were compared.The correlation between serum levels of sVAP-1,DNMT1,Tim-3 and liver function indexes and inflammatory factors in the observation group was analyzed by Pearson linear correlation.Results The levels of serum sVAP-1,DNMT1,and Tim-3 in HBV DNA positive group were(762.75±102.05)ng/mL,(51.37±5.29)μg/L,(24.58±4.39)%,respectively,and(493.13±93.11)ng/mL,(38.59±4.24)μg/L,(13.28±2.35)%in HBV DNA negative group,which were significantly higher than corresponding(184.64±54.19)ng/mL,(25.66±3.18)μg/L,(5.16±0.93)%in the control group;and above indexes in HBV DNA positive group those significantly higher than tthose in the HBV DNA negative group(all P<0.05).Tumor necrosis factor-α(TNF-α),interleukin-4(IL-4),alanine aminotransferase(ALT),aspartate aminotransferase(AST),and total bilirubin(TBIL)in HBV DNA positive group were(31.53±2.87)pg/mL,(21.29±4.43)ng/L,(52.96±9.32)U/L,(49.31±6.06)U/L,and(37.29±3.25)μmol/L,respectively,and(23.24±2.68)pg/mL,(13.56±3.41)ng/L,(38.25±5.26)U/L,(35.68±5.17)U/L,(19.71±4.36)μmol/L in HBV DNA negative group,which were higher than corresponding(15.18±2.77)pg/mL,(4.72±0.93)ng/L,(18.38±3.09)U/L,(16.19±3.23)U/L,(9.23±2.25)μmol/L in the control group,and above indexes in HBV DNA positive group were significantly those in higher than tthose in HBV DNA negative group(all P<0.05).The albumin(Alb)levels in HBV DNA positive group and HBV DNA negative group were(39.43±4.05)g/L,(51.57±5.25)g/L,which were significantly lower than(66.89±6.12)g/L of the control group,and the HBV DNA positive group was significantly lower than that of HBV DNA negative group(all P<0.05).Pearson linear correlation analysis showed that,sVAP-1,DNMT1 and Tim-3 were positively correlated with TNF-α,IL-4,ALT,AST and TBIL(all P<0.05),but negatively correlated with ALB(P<0.05).Conclusion The levels of sVAP-1,DNMT1 and Tim-3 in patients with CHB are abnormally increased,and there is a certain correlation with liver function indexes and inflammatory factors,which can be considered as one of the serological indexes for the diagnosis of CHB.