Efficacy And Safety Analysis Of Peginterferon Combined With Nucleoside Drugs In The Treatment Of Chronic Hepatitis B In Indeterminate Period And Post-treatment

Part Ⅰ:the efficacy and safety analysis of initial treatment of chronic HBV infection combined with antiviral therapy with E antigen negative indeterminate periodBackground and aims:In addition to the traditional four stages,a considerable proportion of patients with chronic hepatitis B(CHB)are in an "indeterminate period".Previous studies have confirmed that patients with uncertain CHB have the risk of liver disease progression.Therefore,we included the patients with hepatitis B E antigen(HBeAg)negative and uncertain initial treatment of HBV infection in this study,and evaluated the efficacy and safety of the combination therapy of peginterferonα-2b(Peg-IFN α-2b)and nucleoside analogues(NAs),aiming at exploring the clinical treatment methods for functional cure of patients with indeterminate periodMethods:This is a prospective,multicenter cohort study,We selected the outpatients from June 2020 to February 2023,and screened out the patients with HBeAg-negative indeterminate period,and treated them with Peg-IFN α-2b combined with NAs.Peg-IFN α-2b was treated for 48 weeks,and the people whose HBsAg turned negative within 48 weeks continued to consolidate treatment for 3 months.All patients were followed up for more than 72 weeks,and the main end points of treatment were HBsAg serum clearance rate and HBsAg serum conversion rate at the end of treatment(EOT).Results:67 patients were included in the study,and 51 patients finally met the research requirements.At EOT,17 patients achieved HBsAg seroclearance,13 patients achieved HBsAg seroconversion,and at the end of follow-up(EOF),2 patients with HBsAg seroclearance showed HBsAg relapse.The baseline HBsAg level in the response group was lower than that in the non-response group.In addition,patients with HBeAg negative uncertainty whose baseline HBV DNA is less than 1000 IU/ml are more likely to get a response.During the follow-up period,the patients in the uncertain period were well tolerated by the combination therapy,and no patients had serious adverse reactions.Baseline HBsAg<118.455 IU/mL,HBsAg<9.935 IU/mL in 12th week and HBsAg<0.236 IU/mL in 24th week can predict the response after combined therapy.Conclusion:The initial treatment of HBV patients with HBeAg-negative can achieve a response rate of 33.3%by using NAs combined with PEG-IFN α-2b.Patients with HBeAg negative indeterminate period with low baseline HBsAg level and baseline HBV DNA<1000 IU/mL are more likely to get a response.Baseline HBsAg<118.455 IU/mL,HBsAg<15.975 IU/mL in 12th week and HBsAg<0.229 IU/mL in 24th week can predict the response after combined therapy.Patients in indeterminate period are well tolerated by combined therapy.Part Ⅱ:Analysis of the efficacy and safety of nucleoside drugs alone or combined with interferon in the treatment of chronic hepatitis BBackground and aims:The serum clearance rate of hepatitis B surface antigen(HBsAg)in patients with chronic hepatitis B(CHB)using nucleoside analogues(NAs)is low,while the combination of interferon will increase the serum clearance rate of HBsAg.Our research aims to explore the efficacy and safety of PEG-IFN α-2b combined with NAs.Methods:This is a prospective,randomized and controlled cohort study.We selected patients from June 2020 to February 2023.and screened out the patients who were treated with NAs for more than one year,HBsAg≤1500 IU/mL,HBeAg negative and obtained virological inhibition,and randomly assigned them to group A and group B according to the ratio of 1:2(group A was single drug of NAs),Peg-IFN α-2b was treated for 48 weeks,and the people whose HBsAg turned negative within 48 weeks continued to consolidate treatment for 3 months.All patients were followed up for more than 72 weeks,and the main end points of treatment were HBsAg serum clearance rate and HBsAg serum conversion rate at the end of treatment(EOT).Results:49 patients in group A finally met the research requirements,and 84 patients in group B met the research requirements.At EOT.34 patients in the combined treatment group achieved HBsAg seroclearance and 26 patients achieved HBsAg seroconversion.At the end of follow-up(EOF).only one patient in NAs group achieved HBsAg seroclearance,and no patient had HBsAg seroconversion,while 39 patients in combination therapy group achieved HBsAg seroclearance and 27 patients achieved HBsAg seroconversion.Patients with low baseline HBsAg level and fluctuating ALT at 12 weeks are more likely to realize HBsAg negative conversion.Baseline HBsAg<204.71 IU/mL and HBsAg<0.978 IU/mL at the 24th week can predict the response after combined treatment.During the follow-up.only one patient stopped taking drugs because of adverse reactions,and most of the treated CHB patients were well tolerated by the combined treatment.Patients with HBsAg below 10 IU/mL and negative HBV RNA still maintain virological response after stopping taking drugs.Conclusion:Patients with chronic hepatitis B who have been treated for more than one year,HBsAg<1500 IU/mL,HBeAg negative and obtained virological inhibition,on the basis of NAs treatment,combined with PEG-IFN α-2b treatment will improve the response rate.CHB patients with low baseline HBsAg level and ALT fluctuation at week 12 are more likely to get a response.Baseline HBsAg<204.71 IU/mL and HBsAg<0.978 IU/mL at the 24th week can predict the response after combined treatment.The treated CHB patients are well tolerated by combined therapy.After combined treatment,patients whose HBsAg is continuously below 10 IU/mL and whose HBV RNA is negative are the best candidates for drug withdrawal except HBsAg turns negative.