Response Prediction After The Addition Of Pegylated Interferon Therapy For 48 Weeks In Chronic Hepatitis B Patients With Low-Level HBsAg Previously Treated With Nucleos(t)ide Analogues

Objective:To explore the clinical cure and the influencing factors in HBeAg-negative chronic hepatitis B patients with low HBsAg levels previously treated with nucleos(t)ide analogues(NAs)after 48 weeks of pegylated interferon a-2b(Peg-IFNa-2b)therapyMethods:The study retrospectively included 123 HBeAg-negative chronic hepatitis B(CHB)patients who achieved HBV DNA<25IU/ml and HBsAg quantification between 0.05 IU/ml and 3000 IU/ml after treatment with NAs in the first affiliated Hospital of Zhengzhou University from August 2019 to March 2021.Patients were entered into the treatment group and the control group,according to their will.The patients in the treatment group were treated with pegylated interferon a-2b antiviral therapy for 48 weeks,based on the original NAs treatment.The control group continued the NAs treatment for 48 weeks.The primary endpoint was HBsAg loss or seroconversion.The blood routine,liver function,HBV serum markers and HBV DNA quantification were collected in patients.According to whether the HBsAg was cleared after pegylated interferona-2b treatment for 48 weeks,the patients of treatment group were divided into response group and non-response group.The Independent Samples t-test was used to compare normally distributed continuous data between the two groups.The Mann-Whitney U test was used to compare non-normally distributed continuous data between the two groups.The chi-squared test or Fisher exact test were used to compare categorical data between the two groups.Binary logistic regression analysis was used to investigate the factors affecting HBsAg clearance.Furthermore,a receiver operating characteristic(ROC)curve was used to analyze the value of the influencing factors in predicting HBsAg clearance at week 48 of treatment.Results:1.There were no significant differences in the baseline HBsAg quantification,gender,age,types of NAs,ALT,AST,GGT,ALP,ALB,TBIL,WBC and PLT between the treatment group and the control group,All P>0.05.2.There were no significant differences in gender,age,types of NAs,ALT,AST,GGT,ALP,ALB,TBIL,WBC and PLT between the response group and the non-response group,all P>0.05.The baseline HBsAg quantification in the response group was lower than that in the non-response group,and the difference was statistically significant,P<0.05.3.After 48 weeks of Peg-INF α-2b treatment,there were 25 cases of HBsAg clearance(34.2%)and 14 cases of HBsAg seroconversion(19.2%)in the treatment group.HBsAg clearance and HBsAg seroconversion were not achieved in the control group at 48 weeks.The HBsAg clearance and HBsAg seroconversion rates were significantly higher in the treatment group than in the control group(P<0.05).4.Multivariate logistic regression analysis of HBsAg clearance in the treatment group showed that the baseline HBsAg quantification and the HBsAg decline at week 24 were independent factors affecting HBsAg clearance(odds ratio[OR]=0.437,4.515;95%CI:0.206～0.926,1.548～13.174;P=0.031,0.006).5.The results of the ROC curve analysis showed that the baseline HBsAg quantification could predict the clearance rate of HBsAg,with a cutoff value of 2.8831gIU/mL.The area under the ROC curve was 0.715(95%CI:0.597～0.814),while the sensitivity and specificity were 92.00%and 43.75%,respectively.The HBsAg decline at week 24 predicted that the cutoff value for HBsAg clearance was 1.662gIU/ml,the area under the ROC curve was 0.885(95%CI:0.789-0.948),and the sensitivity and specificity were 84.00%and 77.08%,respectively.Conclusion:1.CHB patients with low HBsAg levels(HBsAg<3000IU/ml),previously treated with nucleos(t)ide analogues can achieve higher HBsAg clearance and seroconversion rates after the sequential combination of Peg-INFα-2b treatment.2.Baseline HBsAg level can predict the HBsAg clearance at week 48 of pegylated interferon a-2b treatment to a certain extent,its optimal cutoff value is 2.883lgIU/ml.3.Week 24 HBsAg decline can predict the HBsAg clearance at week 48 of pegylated interferon a-2b treatment to a certain extent,its optimal cutoff value is 1.6621gIU/ml.4.Patients with low baseline HBsAg levels and markedly decreased HBsAg during treatment are more likely to obtain clinical cure.