Turn off MathJax
Article Contents
Article Navigation >  ORGAN TRANSPLANTATION  > 2024  > 
Wu Feng, Duan Binwei, Ouyang Yabo, et al. Long-term safety and effectiveness of withdrawal of HBIG and/or nucleos(t)ide analogues in recipients undergoing hepatitis B immune reconstitution after liver transplantation[J]. ORGAN TRANSPLANTATION. doi: 10.3969/j.issn.1674-7445.2023253
Citation: Wu Feng, Duan Binwei, Ouyang Yabo, et al. Long-term safety and effectiveness of withdrawal of HBIG and/or nucleos(t)ide analogues in recipients undergoing hepatitis B immune reconstitution after liver transplantation[J]. ORGAN TRANSPLANTATION. doi: 10.3969/j.issn.1674-7445.2023253
shu

Long-term safety and effectiveness of withdrawal of HBIG and/or nucleos(t)ide analogues in recipients undergoing hepatitis B immune reconstitution after liver transplantation

doi: 10.3969/j.issn.1674-7445.2023253

  • Department of General Surgery Center, Beijing You'an Hospital Affiliated to Capital Medical University, Beijing 100069, China

More Information
  • Corresponding author: Li Guangming, Email: liguangming@ccmu.edu.cn
  • Received Date: 2023-12-18
    Available Online: 2024-03-07
    Abstract
  •   Objective   To investigate the long-term safety and effectiveness of withdrawal of hepatitis B immuneglobulin (HBIG) and nucleos(t)ide analogues (NAs) to prevent hepatitis B virus (HBV) reinfection in liver transplant recipients with hepatitis B-related diseases after successful vaccination.   Methods  Baseline data of 76 liver transplant recipients undergoing hepatitis B immune reconstitution after receiving hepatitis B vaccines were retrospectively analyzed. The vaccination and response, the follow-up results of respondents with HBIG and/or NAs withdrawal, and the reinfection of HBV after withdrawal of HBIG and/or NAs were analyzed.   Results  The time interval from liver transplantation to hepatitis B vaccination was 26 (20, 40) months. The time interval from vaccination to response was 15 (8,27) months. Initially, 76 recipients withdrew HBIG, and 36 recipients withdrew HBIG and NAs. During the follow-up, 12 of 76 recipients who withdrew HBIG resumed use of HBIG, and 16 of 36 recipients who withdrew HBIG and NAs resumed use of NAs. The withdrawal time of HBIG and NAs was 135 (98,150) and 133 (34,149) months, respectively. Sixteen respondents did not receive booster, and 36 respondents received boosters on a regular basis. The time interval between the first boosters and HBIG withdrawal was 44 (11,87) months. No significant differences were observed in baseline data between the respondents with and without boosters (all P>0.05). During the follow-up, 9 recipients were lost to follow-up, 5 were re-infected with HBV, 3 died, and 1 recipient developed graft loss and underwent secondary liver transplantation. Among 5 recipients re-infected with HBV, 4 cases had virus mutation. Significant differences were found between re-infected and uninfected patients regarding withdrawal of NAs and hepatitis B e antigen (HBeAg) positive before transplantation (both P<0.05).   Conclusions  Long-term withdrawal of HBIG is feasible and safe for recipients with successful hepatitis B immune reconstitution after liver transplantation for hepatitis B-related diseases. Nevertheless, whether antiviral drugs can be simultaneously withdrawn remains to be validated.

     

    • FullText(HTML)
  • loading
    • References(38)
  • [1]
    ZHANG D, FENG D, REN M, et al. Preoperative serum hepatitis B virus DNA was a risk factor for hepatocellular carcinoma recurrence after liver transplantation[J]. Ann Med, 2022, 54(1): 2213-2221. DOI: 10.1080/07853890.2022.2107233.
    [2]
    SHENG LP, ZHANG JC, ZHONG ZQ, et al. High-potency nucleos(t)ide analogues alone or plus immunoglobulin for HBV prophylaxis after liver transplantation: a meta-analysis[J]. Hepatol Int, 2023, 17(5): 1113-1124. DOI: 10.1007/s12072-022-10466-w.
    [3]
    ROCHE B, BAUHOFER A, GOMEZ BRAVO MÃ, et al. Long-term effectiveness, safety, and patient-reported outcomes of self-administered subcutaneous hepatitis b immunoglobulin in liver post-transplant hepatitis B prophylaxis: a prospective non-interventional study[J]. Ann Transplant, 2022, 27: e936162. DOI: 10.12659/AOT.936162.
    [4]
    PAPATHEODORIDIS GV, LEKAKIS V, VOULGARIS T, et al. Hepatitis B virus reactivation associated with new classes of immunosuppressants and immunomodulators: a systematic review, meta-analysis, and expert opinion[J]. J Hepatol, 2022, 77(6): 1670-1689. DOI: 10.1016/j.jhep.2022.07.003.
    [5]
    LI J, MA M, WANG X, et al. Prevention and treatment of new hepatitis B after living donor liver transplantation in children[J]. Transl Pediatr, 2021, 10(6): 1610-1617. DOI: 10.21037/tp-20-485.
    [6]
    FERENCI P, REIBERGER T, STADLBAUER V, et al. Transplantation of hepatitis D virus patients: lifelong hepatitis B immunoglobulins?[J]. Liver Int, 2023, 43(Suppl 1): 96-100. DOI: 10.1111/liv.15352.
    [7]
    LAI Q, MENNINI G, GIOVANARDI F, et al. Immunoglobulin, nucleos(t)ide analogues and hepatitis B virus recurrence after liver transplant: a meta-analysis[J]. Eur J Clin Invest, 2021, 51(8): e13575. DOI: 10.1111/eci.13575.
    [8]
    MUT SURMELI D, TURAN I, AKAY S, et al. Significance of detectable hepatitis B virus DNA in liver allograft tissue in long-term follow-up of liver transplant recipients[J]. Hepatol Forum, 2021, 2(2): 43-48. DOI: 10.14744/hf.2021.2021.0003.
    [9]
    WANG G, DUAN Z. Guidelines for prevention and treatment of chronic hepatitis B[J]. J Clin Transl Hepatol, 2021, 9(5): 769-791. DOI: 10.14218/JCTH.2021.00209.
    [10]
    中华医学会肝病学分会, 中华医学会感染病学分会. 慢性乙型肝炎防治指南(2022年版)[J]. 中华肝脏病杂志, 2022, 30(12): 1309-1331. DOI: 10.3760/cma.j.cn501113-20221204-00607.

    Branch of Hepatology of Chinese Medical Association, Branch of Infectious Diseases, Chinese of Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B (version 2022)[J]. Chin J Hepatol, 2022, 30(12): 1309-1331. DOI: 10.3760/cma.j.cn501113- 20221204-00607.
    [11]
    张静娴. 乙肝疫苗免疫规划对降低乙肝病毒感染的效果[J]. 中国医药指南, 2023, 21(25): 111-113,117.

    ZHANG JX. Effect of hepatitis B vaccine immunization program on reducing hepatitis B virus infection[J]. Guide China Med, 2023, 21(25): 111-113,117.
    [12]
    YANG A, GUO Z, REN Q, et al. Active immunization in patients transplanted for hepatitis B virus related liver diseases: a prospective study[J]. PLoS One, 2017, 12(11): e0188190. DOI: 10.1371/journal.pone.0188190.
    [13]
    BALLESTER MP, JALAN R, MEHTA G. Vaccination in liver diseases and liver Transplantation: Recommendations, implications and opportunities in the post-COVID era[J]. JHEP Rep, 2023, 5(8): 100776. DOI: 10.1016/j.jhepr.2023.100776.
    [14]
    KRAMVIS A, CHANG KM, DANDRI M, et al. A roadmap for serum biomarkers for hepatitis B virus: current status and future outlook[J]. Nat Rev Gastroenterol Hepatol, 2022, 19(11): 727-745. DOI: 10.1038/s41575-022-00649-z.
    [15]
    VALOUR F, CONRAD A, ADER F, et al. Vaccination in adult liver transplantation candidates and recipients[J]. Clin Res Hepatol Gastroenterol, 2020, 44(2): 126-134. DOI: 10.1016/j.clinre.2019.08.007.
    [16]
    中华医学会器官移植学分会, 中华医学会肝病学分会. 中国肝移植乙型肝炎防治指南(2016版)[J/CD]. 实用器官移植电子杂志, 2017, 5(4): 241-248. DOI: 10.3969/j.issn.2095-5332.2017.04.001.

    Branch of Organ Transplantation of Chinese Medical Association, Branch of Hepatology of Chinese Medical Association. Chinese liver transplantation Hepatitis B prevention and treatment guidelines (2016 Edit) [J/CD]. Pract J Organ Transplant (Electr Vers), 2017, 5(4): 241-248. DOI: 10.3969/j.issn.2095-5332.2017.04.001.
    [17]
    郑卫萍. 《2018年英国移植学会乙型肝炎与实体器官移植指南(第1版)》摘译[J]. 临床肝胆病杂志, 2018, 34(8): 1649-1653. DOI: 10.3969/j.issn.1001-5256.2018.08.011.

    ZHENG WP. An excerpt of 2018 BTS guidelines for hepatitis B & solid organ transplantation (first edition)[J]. J Clin Hepatol, 2018, 34(8): 1649-1653. DOI: 10.3969/j.issn.1001-5256.2018.08.011.
    [18]
    段斌炜, 卢实春, 武聚山, 等. 肝移植术后乙肝主动免疫重建受体停用乙肝免疫球蛋白和(或)抗病毒药物的可行性[J]. 北京医学, 2015, 37(12): 1139-1141. DOI: 10.15932/j.0253-9713.2015.12.003.

    DUAN BW, LU SC, WU JS, et al. The feasibility of HBIG and (or) antiviral agents withdrawing in liver transplant recipients with hepatitis B immune reconstitution[J]. Beijing Med J, 2015, 37(12): 1139-1141. DOI: 10.15932/j.0253-9713.2015.12.003.
    [19]
    LENCI I, TARICIOTTI L, ANGELICO R, et al. Successful clinical and virological outcomes of liver transplantation for HDV/HBV-related disease after long-term discontinuation of hepatitis B immunoglobulins[J]. Clin Transplant, 2023, 37(6): e14971. DOI: 10.1111/ctr.14971.
    [20]
    ROLAK S, SAID A, GERMAN R, et al. Optimizing immunization strategies in adult patients with chronic liver disease and liver transplant recipients[J]. Gastroenterol Hepatol (N Y), 2022, 18(4): 196-206.
    [21]
    LU SC, JIANG T, LAI W, et al. Reestablishment of active immunity against HBV graft reinfection after liver transplantation for HBV-related end stage liver disease[J]. J Immunol Res, 2014: 764234. DOI: 10.1155/2014/764234.
    [22]
    SINTUSEK P, BURANAPRADITKUN S, WANAWONGSAWAD P, et al. Safety and immunogenicity of standard and double doses of hepatitis B vaccine in children after liver transplantation: an open-label, randomised controlled trial[J]. Vaccines (Basel), 2022, 10(1): 92. DOI: 10.3390/vaccines10010092.
    [23]
    SONG Z, DONG C, MENG X, et al. Prophylactic strategy against de novo hepatitis B virus infection for pediatric recipients who receive hepatitis b core antibody-positive liver grafts[J]. Liver Transpl, 2021, 27(1): 96-105. DOI: 10.1002/lt.25813.
    [24]
    STÄRKEL P, STOFFEL M, LERUT J, et al. Response to an experimental HBV vaccine permits withdrawal of HBIg prophylaxis in fulminant and selected chronic HBV-infected liver graft recipients[J]. Liver Transpl, 2005, 11(10): 1228-1234. DOI: 10.1002/lt.20464.
    [25]
    WONG TC, FUNG JY, LO CM. Prevention of recurrent hepatitis B infection after liver transplantation[J]. Hepatobiliary Pancreat Dis Int, 2013, 12(5): 465-472. DOI: 10.1016/s1499-3872(13)60074-0.
    [26]
    GÜNTHER M, NEUHAUS R, BAUER T, et al. Immunization with an adjuvant hepatitis B vaccine in liver transplant recipients: antibody decline and booster vaccination with conventional vaccine[J]. Liver Transpl, 2006, 12(2): 316-319. DOI: 10.1002/lt.20674.
    [27]
    颜丙玉, 吕静静, 刘甲野, 等. 成年人乙型肝炎疫苗低应答者加强免疫后24个月免疫持久性研究[J]. 中华预防医学杂志, 2014, 48(12): 1043-1047. DOI: 10.3760/cma.j.issn.0253-9624.2014.12.005.

    YAN B, LYU J, LIU J, et al. Antibody persistence following booster vaccination with three doses of hepatitis B vaccines among low-response adults in Zhangqiu county of Shandong province: 24-month of follow-up from 2009[J]. Chin J Prevent Med, 2014, 48(12): 1043-1047. DOI: 10.3760/cma.j.issn.0253-9624.2014.12.005.
    [28]
    SINTUSEK P, BURANAPRADITKUN S, KHUNSRI S, et al. Safety and efficacy of a third dose of the BNT162b2 vaccine in liver-transplanted and healthy adolescents[J]. JPGN Rep, 2023, 4(4): e373. DOI: 10.1097/PG9.0000000000000373.
    [29]
    CHAI Y, TANG J, SU Y, et al. Hepatitis B antibody levels after different doses of hepatitis B vaccination: a retrospective study based on hospitalized children[J]. Epidemiol Infect, 2023, 151: e186. DOI: 10.1017/S0950268823001747.
    [30]
    朱晓霞, 李彦蓉, 徐俊涵. 预防接种管理模式在乙肝疫苗接种中的管理效果及对接种成功率的影响研究[J]. 中国卫生产业, 2023, 20(4): 209-212. DOI: 10.16659/j.cnki.1672-5654.2023.04.209.

    ZHU XX, LI YR, XU JH. a study on the management effectiveness of preventive vaccination management model in hepatitis b vaccine vaccination and its impact on vaccination success rate[J]. China Health Ind, 2023, 20(4): 209-212. DOI: 10.16659/j.cnki.1672-5654.2023.04.209.
    [31]
    MAKAN N, SONG E, KINGE CW, et al. Hepatitis B virus immunity prior to and after administration of a 'booster' dose of vaccine among health-care students at a South African university[J]. Vaccine X, 2023, 14: 100284. DOI: 10.1016/j.jvacx.2023.100284.
    [32]
    RANGEL MC, CORONADO VG, EULER GL, et al. Vaccine recommendations for patients on chronic dialysis. the Advisory Committee on Immunization Practices and the American Academy of Pediatrics[J]. Semin Dial, 2000, 13(2): 101-107. DOI: 10.1046/j.1525-139x.2000.00029.x.
    [33]
    CONTRERAS GA, RODRIGUEZ G, DEL BIANCO G, et al. Durability of cellular and humoral immunity after primary and booster hepatitis b vaccination of individuals living with perinatally acquired HIV[J]. Open Forum Infect Dis, 2023, 10(2): ofad070. DOI: 10.1093/ofid/ofad070.
    [34]
    ISHIGAMI M, HONDA T, ISHIZU Y, et al. Frequent incidence of escape mutants after successful hepatitis B vaccine response and stopping of nucleos(t)ide analogues in liver transplant recipients[J]. Liver Transpl, 2014, 20(10): 1211-1220. DOI: 10.1002/lt.23935.
    [35]
    VILLERET F, LEBOSSÉ F, RADENNE S, et al. Early intrahepatic recurrence of HBV infection in liver transplant recipients despite antiviral prophylaxis[J]. JHEP Rep, 2023, 5(6): 100728. DOI: 10.1016/j.jhepr.2023.100728.
    [36]
    WONG GLH, GANE E, LOK ASF. How to achieve functional cure of HBV: stopping NUCs, adding interferon or new drug development?[J]. J Hepatol, 2022, 76(6): 1249-1262. DOI: 10.1016/j.jhep.2021.11.024.
    [37]
    BAE SK, ARITA J, AKAMATSU N, et al. The impact of the covalently closed circular DNA level on recurrence of hepatocellular carcinoma after initial hepatectomy: an analysis of patients with resolved hepatitis B virus infection[J]. HPB (Oxford), 2022, 24(10): 1780-1788. DOI: 10.1016/j.hpb.2022.06.013.
    [38]
    DUAN BW, LU SC, LAI W, et al. The detection of (total and ccc) HBV DNA in liver transplant recipients with hepatitis B vaccine against HBV reinfection[J]. Hum Vaccin Immunother, 2015, 11(10): 2490-2494. DOI: 10.1080/21645515.2015.1063755.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Tables(3)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (34) PDF downloads(6) Cited by()
    Proportional views
    Related

    WeChat Subscription Account

    Wechat Service Account

    Contact Us
    • Tel：020-38736410
    • Email: organtranspl@163.com
    • Address：The Third Affiliated Hospital of Sun Yat-sen University, No. 600, Tianhe Road, Tianhe District, Guangzhou
    • Editorial Office of Organ Transplantation  粤ICP备2021030844号
    Links

    Supported by: Beijing Renhe Information Technology Co. Ltd    

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return