| Objective: To explore the changes in HBs Ag and LSM of different interferon(IFN) combination with nucleos(t)ide analogues(NUC) in a long-term treatment(96 weeks and 156 weeks).Methods: This was an observational case-control study conducted in Sichuan Provincial People’s Hospital, China. Adults with chronic hepatitis B and compensated liver disease and received antiviral therapy from Jan 2008 to Oct 2015 were enrolled. According to the treatments, patients were assigned to 3 groups(Group A: simultaneous combination therapy with IFN alpha and NUC, Group B: sequential combination therapy with IFN alpha combined treatment after NUC treatment for at least 12 weeks, Group C: NUC monotherapy for 3 years). Of the 187 patients included,40 patients were in Group A. In group B,47 patients were received NUC for 2.8±2.4 years followed by IFN plus NUC treatment. 100 patients with NUC monotherapy for 3 years were included in group C. To observe HBs Ag curved line, loss, seroconversion and LSM at week 48,96 and 156.T-test, one-way ANOVA(normal distribution), Rank sum test analyze(abnormal distribution) and Mixed effects linear model analyzed the quantitative data, and chi-square test analyzed qualitative data.Results: Curved line of quantitative HBs Ag showed that quantitation of serum HBs Ag gradually declined with the extension of treatment in group A and group B. After mixed effects linear model analyzing the changes of quantitative HBs Ag in different time and groups, patients in imported reagent detection, according to weeks’ variance, the changes in HBs Ag level had statistical significance(P<0.05). The same result existed in method*week which indicated that HBs Ag level changed when weeks and therapies changed(P=0.005). However, patients in domestic reagent, method*week didn’t have statistical significance(P=0.294).The results of qualitative HBs Ag were below: The three groups showed statistical significance in HBs Ag seroconversion in week 48(5.0%(2/40) vs. 14.9%(7/47) vs. 3%(3/100), respectively, χ2=6.668,P=0.025),and the seroconversion rate of group B was higher than group C(P<0.016),but HBs Ag loss didn’t have statistical significance(7.5%(3/40) vs. 12.8(6/47) vs. 4.0%(4/100),respectively, χ2=3.900,P=0.138). The HBs Ag loss and seroconversion in week 96 were 10.3%(3/29) vs. 38.7%(12/31) vs. 4.0%(4/100), 10.3%(3/29) vs. 38.7%(12/31) vs. 3.0%(3/100), respectively, and 58.3%(7/12) vs. 65.4%(17/26) vs. 4.0%(4/100), 50.0%(6/12) vs. 61.5%(16/26) vs. 3.0%(3/100) in week 156.Statistical significance were found both in HBs Ag loss and seroconversion in week 96,156(both P<0.001).Patients in group B showed a higher HBs Ag loss and HBs Ag seroconversion than those in group A only in week 96(P<0.016). But group B always showed a higher HBs Ag loss and HBs Ag seroconversion than group C(both P<0.016). Furthermore, in IFN-treated patients(A+B), HBs Ag loss and HBs Ag seroconversion were higher in patients received Peg IFN alpha-2a than that in patients received c IFN alpha-2b(50.0%(21/42) vs. 16.7%(3/18), χ2=5.833, P=0.016,45.2% vs. 16.7%,χ2=4.429, P=0.035, respectively) in a long-term treatment(96 weeks and 156 weeks). After treatment for 48 weeks,96 weeks, and 156 weeks, the LSM in three groups were lower than prior treatment. However, the differences in group C in week 48 were obvious than group B(P=0.02) only. And the differences couldn’t find in other weeks and groups(P>0.05).Conclusion: Patients with sequential combination therapy with NUC and IFN might achieve higher rates of HBs Ag loss, HBs Ag seroconversion and downward trends, especially in patients with Peg IFN alpha-2a and a long-term treatment. Antiviral therapy could decline the LSM in different degree. |
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