| BackgroundHepatitis B virus(HBV)infection is still an important public health problem in the world,which is the main cause of liver cirrhosis and liver cancer,and seriously endangers the health of the people.while oral nucleoside(nucleotide)analogues(NAs)have been shown to treat HBV related liver diseases such as chronic Hepatitis B(CHB),there is no direct effect on covalent closed circular DNA(cccDNA),which can cause viral rebound and disease recurrence after dis-continuation,so long-term treatment is recommended.The elimination of cccDNA is the ultimate goal of treatment for chronic HBV infections,as persistent cccDNA in infected hepatocytes can hinder cure.liver biopsy for quantitative in trahepatic cccDNA is the most accurate method for virus library measurement,but it is limited by its invasive nature and can not be widely used in clinic.a-lso considering that traditional serological indicators(such as HBsAg、HBeAg、HBV DNA,etc.)are not satisfactory in evaluating antiviral efficacy.to this end,some novel HBV serological markers[e.g HBV RNA,Hepatitis B core anti-body(Anti-HBc)]quantitative data have emerged in recent years.these studies sug-gest that serum HBV RNA can be used as a new marker to monitor the eff-icacy of NA s and interferon therapy in patients receiving NAs treatment.Mean-while,the whole quantitative Anti-HBc level is also an important HBV relat-ed index related to liver inflammatory activity and therapeutic effect,which can be used to evaluate the degree of liver inflammation,predict the antiviral effect and the continuous response after withdrawal.New HBV related indexes such as HBV RNA and quantitative Anti-HBc have opened up new directions for individualized treatment of patients with HBV infectionObjectiveThe existing studies are still insufficient for the dynamic monitoring of serum quantitative Anti-HBc levels in the initial stage of antiviral therapy,and whether the HBV RNA combined quantitative Anti-HBc can better predict the antiviral efficacy is still unclear.Therefore,in this study,the clinical significance of the nucleoside drug entecavir(ETV)was investigated by dynamically observing the regular Anti-HBc level of the first antiviral therapy,analyzing its trend and correlation with the antiviral efficacyResearch methodsThis study included patients with chronic hepatitis B(CHB)treated with entecavir(ETV)in the second hospital of shandong university from october 2016 to december 2019 to establish a prospective cohort of chronic CHB studies.all patients regularly came to the outpatient follow-up according to the standard diagnosis and treatment procedure,and at the same time detected HBV DNA、HBsAg、HBeAg、alanine aminotransferase(ALT)and other indicators.At the same time,blood samples were left at 5 time points of antiviral therapy,such as 0 months,1 months,3 months,6 months and 12 months,and serological indexes such as serum HBV RNA、Anti-HBc quantitative level were detected.we used non-parametric tests to compare quantitative data,cox regression to analyze influencing factors,and diagnostic tests using ROC curves.Results1.The total of 48 CHB patients in this study were divided into two groups according to whether the HBeAg was positive or not,including 32 HBeAg positive group,23 men and 9 women.HBeAg negative group total 16,male 6,female 10.The HBeAg positive group was divided into HBeAg disappearance group and HBeAg disappearance group according to the occurrence of serum disappearance;the HBeAg disappearance group had 15 people and the HBeAg disappearance group had 17 people.2.Serum indexes such as HBV RNA、HBV DNA、HBsAg and quantitative Anti-HBc of all CHB patients showed a decreasing trend with the treatment time.Meanwhile,the HBV RNA、HBsAg、HBV DNA and quantitative Anti-HBc index of patients in HBeAg disappearance group showed a more obvious downward trend in the course of treatment than that in the non-occurrence group.3.The level of HBV RNA、HBsAg、HBV DNA in the HBeAg positive group was significantly higher in the baseline data than in the HBeAg negative group.On the contrary,the level of quantitative Anti-HBc in HBeAg positive patients was significantly lower than that in HBeAg negative patients[4.12(2.84,4.44)vs.4.33(4.09,4.61))10IU/mL,P＜0.05].4.HBeAg baseline clinical data of the positive group were associated with HBeAg disappearance,the baseline HBV RNA level of the disappeared patients was significantly lower than that of the non-occurring patients[7.42(3.97,9.59)log10copies/mLvs.8.59(5.24,9.89)log10 copies/mL,P＜0.05].nevertheless,the baseline quantitative Anti-HBc level of patients with HBeAg disappearance was significantly higher than that of patients without occurrence Anti-HBc disappearance,with a median of[4.25(4.07,4.44)vs.4.02(2.84,4.39)log10IU/mL].5.The baseline quantitative Anti-HBc level and baseline HBV RNA were both influencing factors to predict the disappearance of serum HBeAg by regression analysis(P＜0.05).we subsequently performed C ox multivariate analysis and found that baseline quantitative Anti-HB c levels were independent factors in predicting serum HBeAg disappearance at 96 weeks[HR 21.653,95%Cl(1.207～387.71),P＜0.05].6.The baseline quantitative Anti-HBc、HBV RNA and the combination of the two indexes were analyzed AUC curve.baseline quantitative Anti-HBc、quantitative Anti-HBc and HBV RNA combined prediction of serum HBeAg disappearance at 96 weeks were 0.761 and 0.80,respectively.The comparison of each ROC curve showed that there was no significant statistical difference between the diagnostic efficacy Anti-HBc baseline quantification alone and the HBV RNA、quantitative Ani-HBc combined diagnostic performance(P＞0.05).When baseline quantification Anti-HBc threshold 4.09 log10IU/mL,its sensitivity to serum HBeAg disappearance at predicted 96 weeks reached 93.8%and the specificity was 64.7%.7.The critical value of quantitative Anti-HBc in HBeAg positive group was 4.09 log10IU/mL were divided into two groups for the boundary to carry out survival analysis.Quantitative Anti-HBc quantitative level＞4.09 Iog10IU/mL,the cumulative disappearance rate of serum HBeAg increased more significantly in the IU/mL group than in the other group with prolonged ETV treatment time.Conclusions1.The HBV RNA、HBV DNA、HBsAg and quantitative Anti-HBc of all CHB patients showed a decreasing trend with the treatment time.The HBV RNA、HBsAg、HBV DNA and quantitative Anti-HBc indexes of the patients in the group of occurrence HBeAg disappearance showed a more obvious downward trend in the course of ETV treatment than those in the group without occurrence and disappearance.2.The quantitative Anti-HBc level in HBeAg negative group was significantly higher than that in HBeAg positive group,and the baseline quantitative Anti-HBc level in patients with serum HBeAg disappearance group was significantly higher than that in patients without serum disappearance group3.The baseline quantitative of Anti-HBc level is an independent predictor of serum HBeAg disappearance in ETV antiviral treatment patients.HBV RNA、quantitative Anti-HBc combined diagnostic efficacy had no significant advantage over the individual baseline quantitative Anti-HBc level4.Baseline quantitative of Anti-HBc level 4.09 log10IU/mL is the best critical value for predicting the disappearance of serum HBeAg.Baseline quantitative Anti-HBc level＞4.09 log10IU/mL patients have a higher antiviral response rate as ETV treatment time is prolonged. |
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