系列分享 | 重磅！一图纵览十年慢乙肝临床治愈研究结果

编者按：

随着慢乙肝临床治愈从早期的探索阶段，逐渐到快速发展阶段，再到如今的全面深入探索阶段，临床治愈的研究也逐渐丰富和深入，越来越多的肝病医生加入到临床治愈的探索研究中来，也取得了很多令人振奋的结果。

为了更系统地了解慢乙肝临床治愈这十余年来的进展情况，雨露肝霖将推出4篇临床治愈系列文章。第1篇与大家分享了慢乙肝临床治愈的发展史，第2篇带大家从三大国际会议见证临床治愈的发展，今天第3篇将带大家一览近十年慢乙肝临床治愈研究结果。

概况

最具代表性的OSST和NEW SWITCH研究，打开了慢乙肝临床治愈探索的大门，核苷（NA）经治患者序贯聚乙二醇干扰素α(PEG IFNα)治疗可大幅度提高其临床治愈率，其中优势患者HBsAg清除率可高达20%-80%。

后续NA序贯PEG IFNα提高临床治愈率的研究陆续发表，如浙江省人民医院的相关研究、香港研究、和S-Collate研究等。同时，NA联合PEG IFNα的探索研究发现了与序贯研究同样较高的临床治愈率，如S-C研究、Anchor研究、Icure研究等。近年来多项研究开始探索NA序贯或联合PEG IFNα的疗效差异，欲寻求最佳的临床治愈方式。

对特殊人群，如儿童、非活动性HBsAg携带者等的临床治愈的探索研究发现了高于普通人群的临床治愈机会，还需要更多的研究去积累证据。

详情

（长图内容请横屏观看）

注：序贯或联合治疗是指核苷类药物序贯或联合聚乙二醇干扰素α治疗。

参考文献：（可上下滑动查看）

[1] Ning Q, Han M, Sun Y, et al. Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: a randomised open-label trial (OSST trial)[J]. J Hepatol, 2014, 61(4): 777-784.

[2] Han M, Jiang J, Hou J, et al. Sustained immune control in HBeAg-positive patients who switched from entecavir therapy to pegylated interferon-alpha2a: 1 year follow-up of the OSST study[J]. Antivir Ther, 2016, 21(4): 337-344.

[3] Lu J, Zhang S, Liu Y, et al. Effect of Peg-interferon alpha-2a combined with Adefovir in HBV postpartum women with normal levels of ALT and high levels of HBV DNA[J]. Liver Int, 2015, 35(6): 1692-1699.

[4] Cao ZH, Ma LN, Zhang HW, et al. Extended treatment with peginterferon alpha-2a in combination with lamivudine or adefovir for 96 weeks yields high rates of HBeAg and HBsAg seroconversion[J]. J Dig Dis, 2013, 14(8): 446-450.

[5] Li GJ, Yu YQ, Chen SL, et al. Sequential combination therapy with pegylated interferon leads to loss of hepatitis B surface antigen and hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive chronic hepatitis B patients receiving long-term entecavir treatment[J]. Antimicrob Agents Chemother, 2015, 59(7): 4121-4128.

[6] Li MH, Xie Y, Zhang L, et al. Hepatitis B surface antigen clearance in inactive hepatitis B surface antigen carriers treated with peginterferon alfa-2a[J]. World J Hepatol, 2016, 8(15): 637-643.

[7] Hu P, Shang J, Zhang W, et al. HBsAg Loss with Peg-interferon Alfa-2a in Hepatitis B Patients with Partial Response to Nucleos(t)ide Analog: New Switch Study[J]. J Clin Transl Hepatol, 2018, 6(1): 25-34.

[8] Wu D, Yan WM, Tan DM. COMBINATION OF NA, PEG-IFN ALPHA-2b AND GMCSF ENHANCED HBSAB PRODUCTION IN NA SUPPRESSED CHB PATIENTS (THE ANCHOR A STUDY): AN INTERIM ANALYSIS[J]. Hepatology, 2018, Abstract(oral) 157.

[9] Wu D, Yan W, Tan D. COMBINATION OF NA, PEG-IFN ALPHA-2b AND GMCSF ENHANCED HBSAB PRODUCTION IN NA SUPPRESSED CHB PATIENTS (THE ANCHOR A STUDY): AN INTERIM ANALYSIS[J]. Hepatology, 2019, 2019AASLD, abstract( oral 157 ).

[10] Xie Q, Cai W, Ouyang L. Effectiveness of Response-Guided Peginterferon Alfa-2a Therapy in Nucleos(t)Ide Analogues Treated Patients with Hbeag-Positive Chronic Hepatitis B: Interim Analysis of a Prospective, Multicenter, Randomized Study[J]. Hepatology, 2018, 2018AASLD, abstract( poster 389).

[11] Zhou Y, Yan R, Ru GQ, et al. Pegylated-interferon consolidation treatment versus nucleos(t)ide analogue consolidation treatment in non-cirrhotic hepatitis B patients with hepatitis B e antigen seroconversion: an open-label pilot trial[J]. Hepatol Int, 2019, 13(4): 422-430.

[12] Yan L, Zhu C, Li J, et al. Entecavir add-on or switch-to pegylated interferon improves HBsAg clearance in HBe antigen negative chronic hepatitis B patients[J]. Infect Drug Resist, 2018, 11: 2001-2009.

[13] Gao Z, Zhu X, Lin B. The Optimizing Treatment of Peg Interferon Alfa in Hbeag Negative Chronic Hepatitis B Patients with Low Level HBsAg: A Multicenter Real World Study (Interferon Cure Study, I CURE Study)[J]. J Hepatol, 2018, Abstract 413.

[14] Cao Z, Liu Y, Ma L, et al. A potent hepatitis B surface antigen response in subjects with inactive hepatitis B surface antigen carrier treated with pegylated-interferon alpha[J]. Hepatology, 2017, 66(4): 1058-1066.

[15] Chan HLY, Chan FWS, Hui AJ, et al. Switching to peginterferon for chronic hepatitis B patients with hepatitis B e antigen seroconversion on entecavir - A prospective study[J]. J Viral Hepat, 2019, 26(1): 126-135.

[16] Chen Q, Zhang J, Huang J, et al. Early Serum HBsAg Drop Is a Strong Predictor of HBeAg Seroconversion and HBsAg Loss to Pegylated Interferon Alfa-2a in Chronic Hepatitis B Patients with Prior Nucleos(t)ide Analogue Exposure[J]. Med Sci Monit, 2019, 25: 4665-4674.

[17] Lim SG, Yang WL, Chang JPE. Switch or add-on PEGINTEREERON to chronic hepatitis B patients already on nucleos(t)ide analogue ( SWAP study ): final results.[J]. J Hepatol, 2019, AASLD2019. Abstracts (oral193).

[18] Ren PP, Li H, Gao ZJ, et al. The effects and predictors of PEG-interferon based antiviral therapy optimization on functional cure in NAs-treated CHB patients[J]. Hepatology, 2019, AASLD2019(Abstracts (poster 466)).

[19] Wu D, Wang P, Han M, et al. Sequential combination therapy with interferon, interleukin-2 and therapeutic vaccine in entecavir-suppressed chronic hepatitis B patients: the Endeavor study[J]. Hepatol Int, 2019, 13(5): 573-586.

[20] Zheng C, Yan H, Zeng J, et al. Comparison of pegylated interferon monotherapy and de novo pegylated interferon plus tenofovir combination therapy in patients with chronic hepatitis B[J]. Infect Drug Resist, 2019, 12: 845-854.

[21] Liu Y, Li H, Yan X, et al. Long-term efficacy and safety of peginterferon in the treatment of children with HBeAg-positive chronic hepatitis B[J]. J Viral Hepat, 2019, 26 Suppl 1: 69-76.

[22] Fan H, Lin L, Jia S, et al. Interferon alpha treatment leads to a high rate of hepatitis B surface antigen seroconversion in Chinese children with chronic hepatitis B[J]. J Viral Hepat, 2019, 26 Suppl 1: 77-84.

[23] Lim SG, Lee GH, DAN YY, et al. HBsAg loss in inactive chronic hepatitis B carriers is dependent on level of qHBsAg and interferon response: a randomised control trial[J]. Hepatology, 2019, AASLD2019(Abstracts (oral196)).

[24] Wu FP, Yang Y, Li M, et al. Add-on pegylated interferon augments hepatitis B surface antigen clearance vs continuous nucleos(t)ide analog monotherapy in Chinese patients with chronic hepatitis B and hepatitis B surface antigen≤1500 IU/mL: An observational study[J]. World J Gastroenterol, 2020, 26(13): 1525-1539.

[25] Lee JH, Lee YB, Cho EJ, et al. Entecavir Plus Pegylated Interferon and Sequential HBV Vaccination Increases HBsAg Seroclearance: A Randomized Controlled Proof-of-Concept Study[J]. Clin Infect Dis, 2020.

[26] Bazinet M, Pantea V, Placinta G, et al. Safety and Efficacy of 48 Weeks REP 2139 or REP 2165, Tenofovir Disoproxil, and Pegylated Interferon Alfa-2a in Patients With Chronic HBV Infection Naive to Nucleos(t)ide Therapy[J]. Gastroenterology, 2020, 158(8): 2180-2194.

[27] Pang X, Zhang L, Liu N, et al. Combination of pegylated-interferon-alpha and nucleos(t)ide analogue treatment enhances the activity of natural killer cells in nucleos(t)ide analogue experienced chronic hepatitis B patients[J]. Clin Exp Immunol, 2020.

[28] Marcellin P, Xie Q, Woon Paik S, et al. Final analysis of the international observational S-Collate study of peginterferon alfa-2a in patients with chronic hepatitis B[J]. PLoS One, 2020, 15(4): e0230893.

[29] Zeng QL, Yu ZJ, Shang J. High functional cure rate in inactive HBV carriers with extremely low HBsAg levels receiving a short duration of peginterferon α-2b therapy[J]. Open Forum Infect Dis, 2020.

[30] Zhu SS, Dong Y, Xu ZQ. Antiviral effect and Clinical Predictors of HBsAg seroconversion in Children aged 1-6 years old with Chronic Hepatitis B Virus Infection[J]. Liver Int, 2020, APASL2020, Abstract #1564.