Comparison Of Nucleos(t)ide Analogues And Interferon Sequential Therapy With Nucleos(t)ide Analogues Monotherapy For Chronic Hepatitis B: A Systematic Review And A Meta-analysis

Objective:To evaluate the efficacy of nucleos(t)ide analogues(NAs)and interferon(IFN)sequential therapy versus NAs monotherapy for CHB,and to further explore the better therapeutic schedule of the three-phase treatment(NAs pre-treatment,NAs and IFN shortly combinational treatment in the period of transition,IFN treatment).Methods:The meta-analysis of the included 24 articles was used by Review Manager Software 5.3.Alanine aminotransferase(ALT)normalization rate,hepatitis B virus(HBV)DNA undetectable rate,hepatitis B e antigen(HBeAg)and hepatitis B surface antigen(HBsAg)loss rate,HBeAg and HBsAg seroconversion rate were measured.Results:1.At the end of the treatment,patients who had received sequential therapy have higher rates of ALT normalization,HBV DNA undetectable,HBeAg and HBsAg loss,HBe Ag and HBsAg seroconversion respectively is 83.9%,78.4%,47.2%,9.1%,41.6% and 5.6% than those in NAs monotherapy group 68.6%,67.3%,26.8%,0%,17.3% and 0%(P<0.05).2.According to the different medicine of NAs therapy(ETV or LAM),we made analysis in the two subgroup,the results showed that there is a statistical difference at the ALT normalization and HBV DNA undetectable rate in the two subgroup(P<0.05),the rate of ALT normalization in ETV group is higher than that in LAM group(92.1% vs 85.7%,P<0.05),but the HBV DNA undetectable rate is lower than LAM group(78.9% vs 79.0%,P<0.05).3.According to the different medicine of INF therapy(COM IFN or PEG IFN),the results showed that there is a statistical difference at the ALT normalization rate in the two subgroup(P<0.05),the rate of ALT normalization in PEG IFN group is lower than LAM group(64.7% vs 86.5%).Further,according to the different duration of IFN therapy(≥48 weeks and<48 weeks),it showed that there is not a statistical difference in the two subgroup(P<0.05).4.The other clinical indexes’ in the different subgroup showed that the rate of HBe Ag loss and HBe Ag seroconversion have more beneficial in the sequential group.5.The clinical indexes in the comparison of the end-of-treatment with the end-of-follow-up showed that the rates of ALT normalization,HBV DNA undetectable,HBe Ag loss at the end of treatment respectively is 84.4%,81.9% and 85.0%,which is higher than those at the end of follow-up 74.1%,63.1% and 50%(P<0.05),the HBeAg seroconversion rate at the former(48.8%)is higher than that at the later(47.4%),but there is no significant statistical difference(P>0.05).At the end-of-treatment has a lower HBsAg loss rate and HBsAg seroconversion rate(10.6%,8.3%)than that at the end-of-follow-up [(12.3%,10.3%),P>0.05].6.According to the different duration of IFN therapy(≥48 weeks and<48 weeks),the results showed that the rates of ALT normalization and HBV DNA undetectable is higher at the end of treatment than the end of follow-up(84.4% vs 73.1%,81.0% vs 63.4%)in IFN therapy <48 weeks group,and there is a significantly different(P<0.05),the other clinical indexes in the two subgroup have no statistical difference(P>0.05).Conclusion:1.At the end of treatment,sequential therapy have higher rates of ALT normalization,HBV DNA undetectable,HBeAg and HBsAg loss,HBeAg and HBsAg seroconversion than NAs monotherapy.2.At the end of follow-up,the IFN therapeutic duration <48 weeks received lower ALT normalization rate and HBV DNA undetectable rate than that at the end of treatment,so the HBV may relapse after long-term drug withdrawal.3.The IFN therapeutic duration ≥48 weeks is relatively safety after 24 weeks drug withdrawal,but the long-term of follow-up is required.