| Backgroud:Chronic hepatitis B(CHB)is an infectious disease mainly involveing the liver caused by chronic hepatitis B virus(HBV)infection,which affects about 250 million people worldwide.Nucleos(t)ide analogues(NAs)play an effective role in controlling HBV replication by directly inhibiting HBV DNA polymerase,thus delaying CHB disease progression.With the widespread application of NAs clinically,the exploration of a reasonable course of treatment and the problems of management and retreatment after discontinuance in patients have attracted much attention.In recent years,advances have been made in exporing predicting factors for relapse after drug withdrawal,however,few studies have focused on the dynamic changes of HBsAg and the response effects of clinical recurrence with retreatment after discontinuance.Purpose and Significance:The purpose of this study was to explore the chance of HBsAg clearance and the change of HBsAg after NAs discontinuance,and to explore HBsAg changes,virological response,and the incidence of HBeAg serological conversion after retreatment due to off-treatment clinical relapse among HBeAg-positive non-cirrhotic CHB patients.Methods:The subjects of the study were mainly from a prospective observational discontinuation cohort(ChiCTR-OOCO17013970)established at the early stage and some HBeAg-positive patients receiving NAs treatment and visiting regularly in the outpatient department.Patients were divided into four groups according to their treatment strategy:A Discontinuation group:in the discontinuation cohort,129 HBeAg-positive patients who achieved complete response before discontinuation and maintained the response after discontinuation were included;B Retreatment group:39 patients in the discontinuation cohort had clinical recurrence and received retreatment;C Maintained treatment group:214 HBeAg-positive patients from outpatient department continued to receive treatment after achieving sustained response;D Naive treatment group:291 HBeAg positive patients fromoutpatient department received antiviral therapy for the first time.Results:1.Compared with the patients in the maintained treatment group,the patients in the discontinuation group achieved HBsAg clearance more frequently and had a greater HBsAg decline:(1)The 5-year cumulative rate of HBsAg clearance in the discontinuation group was significantly higher than that in the maintained treatment group(22.3%vs.1.6%,p<0.001;after 1:1 propensity score matching,20.9%vs.2.2%,p=0.007);(2)HBsAg decreased 0.2 log10 IU/mL per year in the discontinued group,significantly higher than 0.1 log10 IU/mL in the the maintained treatment group(P=0.002);The quantitative level of HBsAg in the discontinuation group was significantly lower than that in the maintained treatment group at the 4th(2.0 vs.2.6 log10 IU/mL,p=0.019;after 1:1 propensity score matching,2.0 vs.2.6 log10IU/mL,p=0.032)and 5th years(1.7 vs.2.8 log10 IU/mL,p=0.002;after 1:1 propensity score matching,1.7 vs.2.8 log 10IU/mL,p=0.004).2.Cox regression analysis showed that NAs withdrawal and baseline HBsAg level of discontinuation independently influenced HBsAg clearance.(1)Univariate regression analysis showed baseline HBsAg level of discontinuation([HR],0.27;95%[CI],0.15-0.46;P<0.001)and NAs withdrawal([HR],5.45;95%[CI],1.06-28.01;P=0.042)was significantly correlated with the occurrence of HBsAg clearance.(2)Multivariate regression analysis showed that baseline HBsAg level of discontinuation([HR],0.34;95%[CI],0.23-0.50;P<0.001)and NAs withdrawal([HR],5.33;95%[CI],1.12-25.39;P=0.035)were independent predictors of HBsAg clearance.3.Compared with the maintained treatment group and the naive treatment group,the retreatment group showed a greater decline in HBsAg,higher HBsAg clearance rate,virological response rate and HBeAg serological conversion rate:(1)The 5-year cumulative rate of HBsAg clearance in the retreatment group was significantly higher than that in the maintained treatment group(9.0%vs.1.6%,P=0.040;After 1:2 propensity score matching,9.0%vs.0%,P=0.047);(2)Compared with the naive treatment group,HBV DNA(-6.99 vs.-6.19 log10 ILV/mL,P=0.007)and HBsAg levels(-0.85 vs.-0.56 log10 IU/mL,P=0.039)decreased more rapidly in the first year with treatment after relapse in the retreatment group.(3)The 5-year cumulative virological response rate(100%vs.98.8%,P<0.001),HBeAg serological conversion rate(92.6%vs.69.8%,P<0.001)and HBsAg clearance rate(9.0%vs.0.66%,P<0.001)in the retreatment group were significantly higher than those in the naive treatment group,and the results were consistent after 1:2 propensity score matching analysis.Conclusions:1.HBeAg-positive patients who discontinued NAs achieved HBsAg clearance more frequently and had a greater HBsAg decline than patients who maintained NAs treatment.2.Compared with the patients in the maintained treatment group or the naive treatment group,the rate of HBsAg decline and clearance,the rate of virological response and the rate of HBeAg serum conversion were increased significantly in the retreatment patients. |
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