基于HBV感染自然病程的慢性乙型肝炎患者外周血白细胞 介素-35表达水平及与病毒载量和转氨酶的相关性

Interleukin-35 expression in peripheral blood and its correlation with viral load and transaminase in patients with chronic hepatitis B based on the natural course of HBV infection

目的探究白细胞介素-35(IL-35)在慢性HBV感染自然病程中的表达及与病毒载量和肝脏生化指标的相关性,评估其在HBV慢性感染管理中的作用,为动态监测慢性乙型肝炎(简称乙肝)病程并降低重症化提供证据。方法选取2015年1月至2020年11月上海长海医院感染科就诊的慢性HBV感染者83例,依据慢性HBV感染的自然病程分为免疫耐受期22例、免疫清除期29例及重型肝炎32例。选取健康对照20例。空腹采取患者静脉血,应用酶联免疫吸附试验(ELISA)检测外周血IL-35表达水平,同时检测HBV DNA及转氨酶水平。统计学方法采用两组间Mann-Whitney U检验、多组间Kruskal-Wallis H检验以及相关性分析。结果慢性HBV感染者与健康对照者的IL-35分别为51.75(9.9,96.5)pg/ml和7.33(3.35,8.76)pg/ml,差异有统计学意义(Z=-5.69,P<0.01)。慢性HBV感染后各自然病程中IL-35表达水平均高于健康对照组,其中在重型肝炎患者中表达最高,为121.46(68.98,213.44)pg/ml。IL-35指标变化与HBV DNA无明显相关性(r分别为0.385、0.392、-0.168,P均>0.05)。重型肝炎患者的IL-35与ALT呈正相关(ρ=0.543,P=0.045),慢性HBV感染后整体IL-35与ALT和AST均呈较好的正相关(ALT:r=0.684,P=0.001;AST:r=0.618,P=0.001)。血清IL-35每增加1个单位,进展至重型肝炎的可能性增加7.2%。血清IL-35水平的ROC曲线显示AUC为0.9491(95%CI:0.9078~0.9905,P<0.01),cut off值<50.95pg/ml。结论①HBV慢性感染病程中外周血高表达IL-35,IL-35水平同肝脏炎症程度呈正相关;②IL-35在临床评估乙肝患者病情方面有重要应用价值,可动态监测外周血IL-35水平辅助评估患者免疫状态,及早抗病毒治疗以降低重型肝炎的发生率。

Objective To investigate the expression of interleukin-35(IL-35)in the natural course of chronic HBV infection and its correlation with viral load and liver biochemical parameters,and to evaluate its role in the management of chronic HBV infection so as to provide evidence for dynamic monitoring of the course of disease and reducing severity.Method 83 patients with chronic HBV infection were selected from the Department of Infectious Diseases of Shanghai Changhai Hospital from January 2015 to November 2020,including immune tolerance group(n=22),immune clearance group(n=29)and severe hepatitis group(n=32)according to the natural course of chronic HBV infection.20 healthy people were chosen as control.The expression level of IL-35 in peripheral blood was detected by ELISA(enzyme linked immunosorbent assay),HBV DNA and transaminase were also detected meanwhile.Statistical analysis was performed using the Mann-Whitney U test between two groups,Kruskal-Wallis H test between multiple groups and correlation analysis.Result The IL-35 levels of chronic HBV infection and healthy people were 51.75(9.9,96.5)pg/ml and 7.33(3.35,8.76)pg/ml respectively,the difference was statistically significant(Z=-5.69,P<0.01).The natural course of chronic HBV infection was higher than that in healthy controls,and IL-35 expression was highest in severe hepatitis group[121.46(68.98,213.44)pg/ml].There was no significant correlation between IL-35 and HBV DNA(r=0.385,0.392,-0.168,P>0.05).There was positive correlation between IL-35 and ALT in patients with severe hepatitis(ρ=0.543,P=0.045),and a good positive correlation between IL-35 and ALT or AST in patients with chronic HBV infection(ALT:r=0.684,P=0.001;AST:r=0.618,P=0.001).For each unit increase in serum IL-35,the likelihood of progression to severe hepatitis increased by 7.2%.The ROC curve of serum IL-35 level showed AUC was 0.9491(95%CI:0.9078-0.9905,P<0.01),cut off<50.95 pg/ml.Conclusion①IL-35 is highly expressed in peripheral blood in the course of HBV chronic infection and is positively correlated with the degree of liver inflammation;②IL-35 has important application value in clinical evaluation of hepatitis B patients.Dynamic monitoring of IL-35 level in peripheral blood can assist in evaluating patients’immune status,and early antiviral treatment can reduce the incidence of severe hepatitis.