Efficacy Of 48-week Sequential Therapy With Telbivudine Or Entecavir In HBeAg-positive Chronic Hepatitis B Patients With Suboptimal Responses To 24-week Therapy With Pegylated Interferon-α-2b

Objective To research the efficacy,safety and resistance mustations of 48-week sequential therapy with telbivudine or entercavir in HBe Ag-positive chronic hepatitis B(CHB)patients with suboptimal response to24 week pegylated interferon-α-2b therapy.Analyze relevant factors that affect efficacy.Methods Establish a prospective and open research cohort.A total of 100 patients were included in the study.They all received 80 μ g of PEG-IFN-α-2b by subcutaneous injection once weekly for 24 weeks.Patients with HBV-DNA≥2×104IU/ml or HBV-DNA reduction<2lg IU/ml compared with baseline stop IFN to sequential therapy with telbivudine 600 mg or entercavir 0.5mg once daily for 48 weeks.HBV DNA,HBs Ag,HBe Ag,and HBe Ab levels were detected per 12 weeks.The HBV-DNA undetectable rate,HBe Ag clearance/seroconversion rate,HBs Ag clearance/seroconversion rate,and ALT normalization rate at 48 weeks were observed.Use intent-to treat(ITT)analysisand per-protocol(PP)analysis to compare the efficacy indicators between the two groups.The difference in baseline indicators between the HBe Ag transition group and the untransformed group was compared.Baseline indices with differences were analyzed by logistic regression analysis to explore which baseline measures were related to the 48-week HBe Ag transition.Drawing ROC curves to explore the predictive value and cutoff of these factors for HBe Ag seroconversion.Results A total of 62 patients enrolled sequential therapy.31 in telbivudine group and 2 of them were lost(lost rate 6.45%),31 in entercacvir group,and 5 of them were lost(lost rate16.12%).Although the loss rate of entecavir group was higher than that of telbivudine group but There was no significant difference in the rate of loss between the twogroups(χ2=0.64,P=0.42).At the end of therapy HBe Ag seroconversion rate of telbivudine group and entercavir group were 45.16% and 16.13%(ITT analysis,χ2=6.14,P =0.026< 0.05)、51.72% and 19.23%(PP analysis,χ2=5.12,P =0.045< 0.05),telbivudine group were higher than entercavir group,the difference had statistical significance.HBV-DNA undetectable rates were64.52% and 74.19%(ITT analysis,χ2=0.68,P=0.41>0.05)、68.97%和88.46%(PP analysis,χ2=3.06,P=0.081>0.05),the difference had no statistical significance;normalization rates of ALT were 58.06% and 80.65%(ITT analysis,χ2=3.72,P=0.054>0.05)、62.07% and96.15%(PP analysis,χ2=9.34,P=0.002<0.05),the difference had no statistical significance.There were no patients get HBs Ag clearance in two sequential groups.Multivariate logistic regression analyses showed that the present or absence of HBe Ag seroconversion at week 48 was significantly associated with baseline HBe Ag quantitative(P=0.005,OR=2.895)and telbivudine therpay(P=0.036,OR=4.219).No resistance mutations occurred during treatment.In term of predicting HBe Ag seroconversion at 48-week ROC analysis,the area under the curve(AUC)is 0.73(95%CI 0.575~0.884,P=0.005),The sensitivity is 0.917 and the specificity is 0.612 when the Cut off value is 1.75.No resistance mutations occurred in all cases during treatment..Conclusion 1.Sequential therapy with telbivudine has a higher HBe Ag seroconversion rate than entecavir at 48 weeks for patients had suboptimal response to pegylated interferon-α-2b,the virologic response rate is not inferior to that of entecavir,and with satisfactory safety,This may be the optimal treatment regimen for this patients.2.Baseline HBe Ag levels below 1.73(lg s/co)can be effective in predicting HBe Ag conversion at 48 weeks.