Role Of Quantitative Hepatitis B Core Antibody In Children With Chronic HBV Infection

Objectives:Approximately 257 million people worldwide are chronically infected with hepatitis B virus(HBV),which can progress to liver cirrhosis and hepatocellular carcinoma(HCC),resulting in 887000 deaths per year.Quantitative hepatitis B core antibody(qAnti-HBc)is a new biomarker that reflects anti-HBV immune activation,which plays a predictive role in hepatitis activity and hepatitis B virus envelope antigen(HBeAg)seroconversion in adult patients.Until now,the role of qAnti-HBc in children with chronic HBV infection is still unclear.The relationship between qAnti-HBc level in children with chronic HBV infection and liver inflammation and immunity,and the predictive value of baseline qAnti-HBc levels for HBeAg seroconversion in children receiving entecavir(ETV)treatment were studied.Methods: qAnti-HBc levels were detected in 91 children with chronic HBV infection using a newly developed double-sandwich immunoassay.The activation phenotype and intracellular cytokine expression of natural killer cells(NK)were detected by flow cytometry.one-way ANOVA or Kruskal-Wallis test were used to compare the levels of qAnti-HBc and other serological parameters in children in different phases of chronic HBV infection.Correlations between variables were calculated by Spearman method.Univariate and multivariate logistic regression was performed to analyze the factors related to advanced liver inflammation in 57 HBeAg-positive children under liver biopsy.Receiver operating characteristic(ROC)curves and areas under the ROC(AUROC)curves were calculated to evaluate the diagnostic accuracy of qAnti-HBc and other variables for moderate-to-severe liver inflammation(G2-3).And ROC analysis was used to analyze the predictive value of baseline qAnti-HBc level in HBeAg seroconversion in 18 HBeAg-positive children receiving ETV treatment with regular follow-up for 52 weeks.Results:qAnti-HBc levels in children in different phases of chronic HBV infection were statistically different.qAnti-HBc level in the immune clearance phase(IC)was significantly higher than that in the immune tolerance phase(IT)and the low replication phase(LR)(P=0.000),while no significant difference was observed between IT and LR(P>0.05).There were significant correlation between qAnti-HBc level and ALT and NK cell function activation(P<0.05).qAnti-HBc(P = 0.044,OR =67.059)and GGT(P = 0.035,OR = 1.059)were independent predictors of advanced liver inflammation(G2-3).With the area under the ROC curve(AUC)0.81(95%CI: 0.70-0.93),the combination index of qAnti-HBc,AST and GGT played a good predictive value in moderate-to-severe liver inflammation(G2-3).Baseline qAnti-HBc level in children receiving ETV treatment for 52 weeks with HBeAg seroconversion was significantly higher than children without HBeAg seroconversion(P<0.05).The AUC of baseline qAnti-HBc for predicting HBeAg seroconversion was 0.778(95%CI: 0.557-0.999).Conclusions: Elevated qAnti-HBc was closely related to immune activation and hepatitis activity and may play a predictive value in HBeAg seroconversion in children receiving ETV treatment.Serum qAnti-HBc is a promising non-invasive immune biomarker in children with chronic HBV infection.