Analysis Of The Clinical Efficacy Of Sequential Combined Peg-IFN Treatment After NAs Treatment In CHB Patients

Objective:Preliminary analysis of the clinical efficacy of sequential combination of Peg-IFN after NAs treatment in CHB patients will provide real data for more CHB patients to pursue clinical cure.Methods:From January 2018 to March 2020,CHB patients who were treated at Yan’an University Affiliated Hospital and treated with NAs for ≥1 year were collected.According to the inclusion and exclusion criteria,60 patients were finally enrolled.When enrolling 30 patients in the sequential combination group,30 NAs monotherapy patients were enrolled in a 1:1 ratio as a control.The sequential combination group continued the NAs treatment while sequentially combined with Peg-IFN α-2b;The NAs single-drug group continued to take NAs.Among them,NAs(ETV/TDF)was taken orally,once a day;Peg-IFN α-2b(Pegabine)180ug,subcutaneously injected,once a week,observed for 48 weeks.The demographic and baseline characteristics of the two groups were collected and rechecked every 12 weeks.Follow up and record the hs HBV DNA,HBV serological indicators,liver function and four items of liver fiber,LSM of the two groups of patients,the occurrence of adverse reactions,and the corresponding measures for adverse reactions.SPSS22.0 was used for data analysis to observe the HBsAg level and the negative conversion rate,the negative status of HBeAg and HBV DNA,and the adverse reactions of the NAs treated CHB patients with sequential combined Peg-IFN treatment for 48 weeks,and the change trend of liver function,liver fiber four items,and LSM.Results:1.After 48 weeks of treatment,the HBsAg clearance rate,HBeAg conversion rate,and HBV DNA conversion rate in the sequential combination group were higher than those in the NAs single-agent group.Comparing the HBsAg levels of the two groups after 48 weeks of treatment,the sequential combination group had a high degree of HBsAg decline.Finally,7 patients in the sequential combination group achieved HBsAg clearance,and the NAs single-drug group did not show HBsAg clearance.The HBsAg clearance rates of the two groups were respectively 23.3%,0%,the former is significantly higher(P=0.016);There were more HBeAg negative patients in the sequential combination group,accounting for 93.3%,while the NAs single-drug group only accounted for 53.3%,(P<0.001);30 patients in the sequential combination group had hs HBV DNA lower than the detection limit,and 6 patients in the NAs single-agent group had hs HBV DNA not lower than the detection limit the lower limit,HBV DNA negative patients accounted for 80%,Among them,2 patients had a virological breakthrough during the observation process,the negative rate of HBV DNA in the sequential combination group was high.2.According to the baseline HBsAg level,patients with ≤1500IU/mL are considered as dominant patients,and patients with >1500IU/mL are considered as non-dominant patients.At 48 weeks of treatment,the number of dominant patients in the NAs single-agent group was 43.3%,and the dominant patients did not increase or decrease;The number of dominant patients in the sequential combination group was 83.3%,an increase of 8 cases from baseline,and the number of dominant patients in the sequential combination group increased significantly.3.At 48 weeks of treatment,for the comparison of four items of liver fiber between the two groups,the sequential combination group and the NAs single-drug group compared the four liver fibrosis indicators,P>0.05,and there was no difference between the two groups after treatment.Comparing the two groups of LSM,P=0.439,the difference was not statistically significant.4.Starting from the baseline,the ALT and AST levels of the sequential combination group gradually increased,reached a peak at 12-24 weeks,and then gradually decreased.There was no significant fluctuation in the NAs single-drug group.The ALT and AST levels of the two groups were different at 12 weeks,24 weeks,36 weeks,and 48 weeks(P<0.05).The ALT and AST levels of the sequential combination group were higher than those of the NAs single Medicine group.5.In the sequential combination group,90% of patients developed influenza-like syndrome,bone marrow suppression and other manifestations.Patients in the NAs single-agent group did not complain of special discomfort.Compared with the NAs single-agent group,the incidence of adverse reactions in the sequential combination group was P<0.001,and the sequential combination group was higher than the NAs single-agent group.6.For patients in the sequential combination group,groupings were compared according to their gender,age,family history,NAs type,baseline HBsAg and HBeAg levels,and baseline hs HBV DNA levels.The results showed that the baseline HBsAg level would have a significant effect on the clearance rate of HBsAg.7.The patients in the sequential combination group were divided into dominant and non-dominant groups based on their baseline HBsAg levels.At 48 weeks,the HBsAg clearance rates of the dominant group and the non-dominant group were 41.2% and 0%,and the dominant group was significantly higher;The HBsAg decline during the observation period between the two groups is compared(P<0.05),the non-dominant group has a greater decline than the dominant group.Conclusion:1.For NAs treated CHB patients with sequential combination of Peg-IFN treatment,the HBsAg decline level and the rate of negative conversion,the rate of negative conversion of HBeAg,and the rate of HBV DNA conversion are better than those of continuing NAs monotherapy.2.NAs sequential combined Peg-IFN therapy is also applicable to non-dominant CHB patients,and its 48-week HBsAg reduction is better than that of dominant patients,which can effectively increase the proportion of dominant patients in the CHB population and create conditions for the pursuit of clinical cure.3.For NAs treated CHB patients with sequential combination of Peg-IFN treatment,have a high incidence of adverse reactions,but they can be tolerated after symptomatic treatment.4.Sequential combination of Peg-IFN therapy for NAs treated CHB patients is a high-quality choice for pursuing clinical cure and improving long-term outcomes.