Abstract:ObjectiveTo systematically evaluate the efficacy and safety of nucleo(s)tide analogues (NAs) sequential/NAs sequential combined with pegylated interferon (PegIFN) for the treatment of HBeAgpositive chronic hepatitis B（CHB）. MethodsPubMed, Cochrane Library, Embase, and Chinese Medical databases (CNKI, Wanfang and VIP) from database establishment to March 25, 2017 were retrieved, randomized controlled trials of NAs sequential/sequential combined with PegIFN for the treatment of CHB after application of NAs to achieve virologic response were included in study, Meta analysis was performed by RevMan 5.3 software, HBeAg seroconversion rate and HBsAg negative conversion rate at the end of treatment were compared. ResultsNine studies were eventually included, 4 were about NAs sequential PegIFN,5 about NAs sequential combined with PegIFN. At the end of treatment, compared with using NAs monotherapy for antiviral treatment, NAs sequential/sequential combined with PegIFN therapy can improve HBeAg seroconversion rate(31.2％ vs 11.7％；OR, 3.69 ［95％CI, 2.43-5.60］；P＜0.01) and HBsAg negative conversion rate(11.5％ vs 0.5％；OR, 9.31［95％CI, 2.72-31.89］；P＜0.01). According to the results of subgroup analysis, HBeAg seroconversion rate in NAs sequential PegIFN therapy group was higher than control group (25.3％［42/166］ vs 10.0％［17/170］; OR,3.1［95％CI, 1.66-5.79］；P＜0.01)；HBeAg seroconversion rate in NAs sequential combined with PegIFN therapy was higher than control group (36.8％［63/171］ vs 13.5％［23/171］；OR,4.24［95％CI, 2.41-7.46］；P＜0.01). Sequential/sequential combination therapy showed more adverse reaction, most of which can be tolerated or improved after symptomatic treatment. ConclusionFor the treatment of HBeAgpositive CHB, after application of NAs to achieve virologic response, NAs sequential/sequential combined with PegIFN therapy for 48 weeks can significantly increase HBeAg seroconversion rate and HBsAg negative conversion rate.

Abstract:ObjectiveTo study the correlation between expression of natural killer T (NKT) cells and virological response to treatment with peginterferon alfa2a （PegINFα2a）in patients with HBeAgpositive chronic hepatitis B(CHB).MethodsA cohort of 63 HBeAgpositive CHB inpatients and outpatients in a hospital between January and December 2010 were treated with 18MIU PegIFNα2a once a week for 48 weeks. The percentage of NKT cells in T lymphocytes,five serological markers of hepatitis B and HBV DNA load were assessed by flow cytometry and quantitative real time PCR.ResultsAt the end of 48week treatment, 26 cases achieved complete virological response, 21 achieved partial response, and 16 didn’t achieve response. The percentage of NKT cells in T lymphocytes in complete virological response group before treatment and after 4, 8, 12, 16 and 24 weeks of treatment all increased markedly compared with partial and non response group(all P<0.01); At the end of 48week treatment and 24 weeks after withdrawing from the treatment, the expression level of NKT cells of complete response group was also higher than partial response group(t=32.0，P＜0.01；t=27.6，P＜0.01）. Within 4 weeks after the start of treatment, the expression level of NKT cells in complete response group increased fastest and reached highest at week 12, then decreased slowly, and at week 24-48 was slightly higher than pretreatment; the expression level of NKT cells in partial response group reached highest at week 12, which was much higher than that before treatment (t=12.83，P＜0.05）.Liver function in complete response group returned to normal at week 12, and continued to remain normal, HBV DNA level also decreased gradually, but in partial and nonresponse groups, the liver function fluctuated at（1-2）×ULN. Followup to 24 weeks after stopping treatment, 27 cases appeared HBeAg seroconversion.ConclusionThe expression of NKT cells in HBeAgpositive CHB patients’ peripheral blood can help predict response to PegIFNα2a therapy.

Abstract:ObjectiveTo explore the influence of adefovir dipivoxil (ADV) therapy on the cellular immunity by observing the levels of interferonγ(IFNγ), interleukin4 (IL4) and their relationship with HBV DNA loads in patients with HBeAgpositive chronic hepatitis B at different time before and after treatment. MethodsSera of 30 patients before ADV therapy and 16 weeks ,52 weeks and 132 weeks after ADV therapy respectively were collected in this study. There were 14 complete response cases(group A),16 incomplete response cases(group B). Sera of 10 healthy people were chosen as control group(group C). Levels of IFNγ and IL4 were detected with enzymelinked immunosorbent assay; HBV DNA loads were detected by ROCHE COBAS AMPLICOR HBV MONITOR, lower limit was 103 copy/mL.ResultsThe average IFNγ level in group A was significantly higher than that of group B（P<0.05）and C（P<0.05）, there was no significant difference between group B and C(P>0.05);The level of IL4 of group A decreased after treatment while group B didn’t. HBV DNA loads of all groups had no significant correlation with IFNγ and IL4 levels before treatment, but dropped obviously at 16th week after treatment; and the increased level of IFNγ in group A was significantly higher than that of group B(P<0.05); IL4 levels in group A decreased gradually, but didn’t decreased obviously in group B.ConclusionCellular immune response of patients with hepatitis B was resumed to some extent after ADV treatment. The resumption level was positively related with the decreased level of HBV DNA load.