Efficacy Of Sequential Pegylated Interferon Alpha-2a Treatments In Patients With Nucleoside-treated Chronic Hepatitis B And Its Early Prediction Of HBsAg Loss

BACKGROUNDThe elimination of the hepatitis B surface antigen(HBsAg)is an important index of the clinical cure of chronic hepatitis B.Currently,a large number of nucleoside analogues(NAs)with limited effects on reducing HBsAg levels are being used in clinical practice.In addition,the recurrence rate after drug withdrawal is high,although these drugs effectively inhibit hepatitis B virus(HBV)DNA replication.The search for novel methods to improve the therapeutic efficacy of nucleosides in patients with chronic hepatitis B(CHB)and effectively reduce the HBsAg levels to achieve the ultimate goal of a clinical cure for this disease has intensified in clinical research.Compared with the continuous application of nucleoside drugs,patients with nucleoside-treated CHB who are administered sequential pegylated interferon alpha-2a(PEG-IFN?-2a)treatments display a higher rate of hepatitis B e-antigen(HBeAg)seroconversion,which continues to increase after 48 weeks.Furthermore,the sequential treatment reduced the HBsAg levels to a significantly greater extent than the continuous NA treatment,and HBsAg clearance.OBJECTIVEThis study was designed to assess the feasibility and safety of a switch to a pegylated interferon(PEG-IFN)treatment after long-term entecavir(ETV)administration and to explore the factors associated with the loss of HBsAg.METHODSOne hundred and forty-four patients with CHB who were treated with entecavir were included.Forty-eight patients who received 48 weeks of sequential PEG-IFN?-2a therapy were included in the sequential group;96 patients who continued to take entecavir(ETV)and were matched for baseline characteristics were included in the ETV group.The virological and biochemical indexes were measured at 0,12,24,36,and 48 weeks during therapy and at 24 weeks after the cessation of treatment.Primary efficacy was defined as a virological response(VR)for HBV DNA <1000 IU/mL and a reduction in HBsAg levels ?1.97 log10 IU/mL at the end of the PEG-IFN treatment.HBsAg loss(with or without HBsAg seroconversion)is defined as a complete response(CR).Secondary efficacy was defined as HBeAg seroconversion.RESULTS 1.The decrease of HBsAg level in the sequential group was significantly higher than that of the ETV group:The reduction in HBsAg levels observed at 48 weeks was 1.26±1.38 log10 IU/mL in the sequential group,which was significantly higher than the reduction observed in the ETV group(0.16±0.39 log10 IU/mL,P<0.001)2.The virological response rate in the sequential group is higher than that in the ETV group:The VR rates of the sequential and ETV groups were 25.00% and 2.08%(P<0.001),respectively.The odds ratio(OR)of the sequential group was 15.67(95% confidence interval(CI): 3.34-73.48)which was statistically significant(P<0.001)3.The HBsAg clearance rate in the sequential group is higher than that in the ETV group: At the end of the treatment,9 patients in the sequential group achieved a CR;HBsAg loss and seroconversion rates were 18.75% and 12.50%,but no HBsAg loss or HBsAg seroconversion was observed in the ETV group(P<0.001).4.Among the HBeAg-positive patients,HBeAg seroconversion was higher in the sequential group(45.45% vs 13.24%,P<0.001).Among patients with HBeAg-negative CHB,only the sequential treatment group achieved a CR.5.Baseline HBsAg levels were significantly predictive of HBsAg loss during early treatment(weeks 12 and 24).CONCLUSIONSequential therapy with PEG-IFN after long-term NA enhances the reduction of HBsAg and may represent a treatment option to promote HBsAg loss.The baseline HBsAg levels and changes observed during the early period of treatment(at weeks 12 and 24)were strong predictors of HBsAg clearance in patients treated with PEG-IFNa-2a.