乙型肝炎病毒核心抗体水平与慢性乙型肝炎患者肝脏炎症、纤维化程度及抗病毒疗效关系的Meta分析

Meta-analysis of the relationship between hepatitis B virus core antibody levels and liver inflammation,fibrosis degree and antiviral efficacy in patients with chronic hepatitis B

目的系统评估乙型肝炎病毒核心抗体(hepatitis B virus core antibody,HBcAb)水平与慢性乙型肝炎(chronic hepatitis B,CHB)患者肝脏炎症及纤维化程度的相关性,以及HBcAb能否作为CHB患者抗病毒疗效的预测指标。方法检索PubMed、Embase、Web of Science、The Cochrane Library、中国知网、万方、维普数据库建库至2022年10月发表的有关HBcAb的文献。使用R4.2.1软件进行Meta分析,横断面研究文献质量评价参照美国卫生保健质量和研究机构(the Agency for Healthcare Research and Quality,AHRQ)提出的文献质量评价标准,队列研究质量评价参照纽卡斯尔-渥太华量表(Newcastle-Ottawa Scale,NOS)。采用剔除异质性最大或权重最大的文献进行敏感性分析。采用漏斗图和Egger检验进行发表偏倚评估。结果纳入30篇文献进行系统评价,其中21篇文献纳入Meta分析。结果表明HBcAb水平越高,CHB患者肝脏炎症程度(Summary r=0.39,95%CI:0.30~0.48,P<0.05)和肝脏纤维化程度(Summary r=0.33,95%CI:0.22~0.43,P<0.05)均越高。ALT基本正常的CHB患者中HBcAb较低的患者发生肝脏炎症(G2~G4)的风险较高(OR=2.02,95%CI:0.64~6.38,P<0.05)。干扰素(interferon,IFN)治疗的CHB患者基线HBcAb水平越高,HBsAg阴转率越高(MD=0.34,95%CI:-0.12~0.80,P<0.05)。核苷(酸)类似物[nucleos(t)ide analogues,NAs]和IFN治疗的CHB患者基线HBcAb水平越高,HBeAg血清学转换率(MD=0.37,95%CI:0.26~0.49,P<0.05)和HBV DNA病毒学应答率(MD=0.30,95%CI:0.16~0.44,P<0.05)均越高。IFN治疗的CHB患者停药时HBcAb水平越高,临床治愈后复发率越低(MD=-0.74,95%CI:-1.00~-0.48,P<0.05)。结论HBcAb水平越高,CHB患者肝脏炎症程度及纤维化程度越高。较高的HBcAb水平可作为预测NAs或IFN抗病毒疗效的指标之一。

Objective To systematically evaluate the correlation between hepatitis B virus core antibody(HBcAb)level and the degree of liver inflammation and fibrosis in patients with chronic hepatitis B(CHB),and whether HBcAb can be used as a predictor of antiviral effect in patients with CHB.Methods Literatures on HBcAb published in PubMed,Embase,Web of Science,The Cochrane Library,CNKI,Wanfang and Weipu databases were searched until October 2022.Meta-analysis was performed by R4.2.1 software.The quality evaluation of cross-sectional studies was based on the quality evaluation criteria of The Agency for Healthcare Research and Quality(AHRQ),and the quality evaluation of cohort studies was based on the Newcastle-Ottawa scale.The literatures with the greatest heterogeneity or the greatest weight were excluded for sensitivity analysis.Funnel plot and Egger test were used to assess publication bias.Results Total of thirty literatures were included for systematic review,and twenty-one of which were included in Meta-analysis.The results showed that the higher the HBcAb level,the higher the degree of liver inflammation(Summary r=0.39,95%CI:0.30~0.48,P<0.05)and fibrosis(Summary r=0.33,95%CI:0.22~0.43,P<0.05)in patients with CHB.The risk of liver inflammation(G2~G4)increased in CHB patients with substantially normal ALT who had higher levels of HBcAb(OR=2.02,95%CI:0.64~6.38,P<0.05).The higher the baseline HBcAb level,the higher the HBsAg conversion rate in CHB patients treated with interferon(IFN)(MD=0.34,95%CI:-0.12~0.80,P<0.05).The higher the baseline HBcAb levels in CHB patients treated with nucleos(t)ide analogues(NAs)and IFN,the higher the HBeAg serological conversion rate(MD=0.37,95%CI:0.26~0.49,P<0.05)and HBV DNA virological response rate(MD=0.30,95%CI:0.16~0.44,P<0.05).The higher the HBcAb level at drug withdrawal in CHB patients treated with IFN,the lower the recurrence rate after clinical cure(MD=-0.74,95%CI:-1.00~-0.48,P<0.05).Conclusions The higher level of HBcAb,the higher degree of liver inflammation and fibrosis in patients with CHB.Higher HBcAb level can be used as one of the indicators to predict the effects of NAs or IFN antiviral therapy.