切换至 "中华医学电子期刊资源库"

中华移植杂志(电子版) ›› 2026, Vol. 20 ›› Issue (04) : 326 -332. doi: 10.3877/cma.j.issn.1674-3903.2026.04.018

综述

乙肝肝移植受者术后完全停用抗HBV药物的研究进展
王丽君1, 饶伟2,†()   
  1. 1266071 青岛,青岛大学青岛医学院
    2266035 青岛,青岛大学附属医院器官移植中心肝脏病中心
  • 收稿日期:2025-09-29 出版日期:2026-08-25
  • 通信作者: 饶伟

Progress in complete withdrawal of anti-hepatitis B drugs among HBV related liver transplantation recipients

Lijun Wang1, Wei Rao2,†()   

  1. 1Qingdao Medical College of Qingdao University, Qingdao 266071, China
    2Liver Disease Centre, Organ Transplant Center of Affiliated Hospital of Qingdao University, Qingdao 266035, China
  • Received:2025-09-29 Published:2026-08-25
  • Corresponding author: Wei Rao
引用本文:

王丽君, 饶伟. 乙肝肝移植受者术后完全停用抗HBV药物的研究进展[J/OL]. 中华移植杂志(电子版), 2026, 20(04): 326-332.

Lijun Wang, Wei Rao. Progress in complete withdrawal of anti-hepatitis B drugs among HBV related liver transplantation recipients[J/OL]. Chinese Journal of Transplantation(Electronic Edition), 2026, 20(04): 326-332.

现有研究表明,在严谨、科学的监测下,对特定的HBV相关肝移植受者完全停用抗HBV药物(乙肝免疫球蛋白+核苷类似物)是安全可行的。目前临床上可用于肝移植术后完全停用抗HBV药物的预测及评价指标,主要包括HBV DNA、HBsAg、HBV共价闭合环状DNA、HBV RNA、HBcrAg及HBcAb等。新型标志物的出现和检测方式的改进,有助于识别或筛选出肝移植术后能够完全停用抗HBV药物的适宜人群,为肝移植术后科学管理提供进一步支持。本文综述HBV相关肝移植受者完全停用抗HBV药物的研究进展以及相关预测和评价指标,为术后个体化治疗提供临床参考。

Recent studies have demonstrated that complete discontinuation anti-HBV therapy (hepatitis B immunoglobulin + nucleoside analogues) may be safe and feasible in selected HBV-related liver transplantation recipients under rigorous scientific monitoring. Currently, clinically available predictive and evaluative markers mainly include HBV DNA, HBsAg, HBV cccDNA, HBV RNA, HBcrAg and HBcAb. The advent of novel markers and advances in detection assays may facilitate the identification and screening of candidates eligible for complete discontinuation of anti-HBV drugs after liver transplantation, further supporting scientific management after liver transplantation. This review elaborates on research progress regarding complete withdrawal of anti-hepatitis-B agents among HBV-related liver transplantation recipients, as well as relevant predictive and evaluative biomarkers to inform individualized postoperative clinical management.

表1 HBV相关肝移植受者术后完全停用抗HBV药物的相关研究
1
Terrault NA, Bzowej NH, Chang KM, et al; American Association for the Study of Liver Diseases. AASLD guidelines for treatment of chronic hepatitis B[J]. Hepatology, 2016, 63(1): 261-283.
2
中国肝移植注册中心. 2018年中国肝脏移植医疗质量报告[R]. 杭州:中国肝移植注册中心,2019.
3
Yuen MF, Chen DS, Dusheiko GM, et al. Hepatitis B virus infection[J]. Nat Rev Dis Primers, 2018, 4: 18035.
4
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.
5
Lenci I, Milana M, Grassi G, et al. Hepatitis B virus recurrence after liver transplantation: an old tale or a clear and present danger? [J]. World J Gastroenterol, 2020, 26(18): 2166-2176.
6
Cholongitas E, Papatheodoridis GV. High genetic barrier nucleos(t)ide analogue(s) for prophylaxis from hepatitis B virus recurrence after liver transplantation: a systematic review [J]. Am J Transplant, 2013, 13(2): 353-362.
7
Roche B, Samuel D. HBV prophylaxis after liver transplantation: close to the full success but at the price of long-term prophylaxis adapted to the risk of HBV recurrence [J]. Hepatol Int, 2023, 17(5): 1072-1074.
8
Fung J, Cheung C, Chan SC, et al. Entecavir monotherapy is effective in suppressing hepatitis B virus after liver transplantation [J]. Gastroenterology, 2011, 141(4): 1212-1219.
9
Fung J, Chan SC, Cheung C, et al. Oral nucleoside/nucleotide analogs without hepatitis B immune globulin after liver transplantation for hepatitis B [J]. Am J Gastroenterol, 2013, 108(6): 942-928.
10
Fung J, Wong T, Chok K, et al. Long-term outcomes of entecavir monotherapy for chronic hepatitis B after liver transplantation: results up to 8 years [J]. Hepatology, 2017, 66(4): 1036-1044.
11
Muthiah MD, Tan EY, Chua SHM, et al. Nucleoside analog monotherapy for prophylaxis in hepatitis B liver transplant patients is safe and efficacious [J]. Hepatol Int, 2020, 14(1): 57-69.
12
姜晓青,解曼,张群,等. 替诺福韦单一用药预防肝移植术后乙肝复发的疗效分析 [J/CD]. 实用器官移植电子杂志,2021, 9(2): 139-145.
13
Lenci I, Tisone G, Di Paolo D, et al. Safety of complete and sustained prophylaxis withdrawal in patients liver-transplanted for HBV-related cirrhosis at low risk of HBV recurrence [J]. J Hepatol, 2011, 55(3): 587-593.
14
Lenci I, Baiocchi L, Tariciotti L, et al. Complete hepatitis B virus prophylaxis withdrawal in hepatitis B surface antigen-positive liver transplant recipients after longterm minimal immunosuppression [J]. Liver Transpl, 2016, 22(9): 1205-1213.
15
Duan BW, Tian LT, Lin DD, et al. Long-term consequences of stopping HBIG and/or nucleotide analogues in liver transplant recipients administered hepatitis B vaccination to prevent HBV reinfection [J]. J Viral Hepat, 2019, 26(Suppl 1): 85-89.
16
Xie M, Zang YJ, Zhang B, et al. Successful withdrawal of antiviral treatment in two HBV-related liver transplant recipients after hepatitis B vaccination with long-term follow-up [J]. Hepatobiliary Pancreat Dis Int, 2021, 20(6): 595-597.
17
Geng L, Lin BY, Shen T, et al. Anti-virus prophylaxis withdrawal may be feasible in liver transplant recipients whose serum HBeAg and HBV DNA are negative [J]. Hepatobiliary Pancreat Dis Int, 2016, 15(3): 316-318.
18
Duvoux C, Belli LS, Fung J, et al. 2020 position statement and recommendations of the European Liver and Intestine Transplantation Association (ELITA): management of hepatitis B virus-related infection before and after liver transplantation [J]. Aliment Pharmacol Ther, 2021, 54(5): 583-605.
19
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.
20
刘明琛,杨兴雯,彭思雯,等. 核苷(酸)类药物对慢性乙型肝炎患者血清HBV DNA和RNA定量检测的影响 [J]. 中华实验和临床病毒学杂志,2021, 35(3): 305-311.
21
Otsuka M, Koike K. Should level of HBV RNA be used to determine when patients should stop treatment with nucleos(t)ide analogues [J]. Clin Gastroenterol Hepatol, 2020, 18(3): 551-552.
22
Wong DK, Yuen MF, Ngai VW, et al. One-year entecavir or lamivudine therapy results in reduction of hepatitis B virus intrahepatic covalently closed circular DNA levels [J]. Antivir Ther, 2006, 11(7): 909-916.
23
张长坤,高杰,汪洋,等. 乙型肝炎病毒背景肝移植患者术后长期抗乙型肝炎病毒治疗的策略研究[J]. 中华普通外科杂志,2023, 38(6): 435-440.
24
Izumi T, Toshima T, Itoh S, et al. Novel protocol for prevention from hepatitis B reactivation following living-donor liver transplantation[J]. Hepatol Res, 2024. [Epub ahead of print]
25
Yuen MF, Lim SG, Plesniak R, et al. Efficacy and safety of bepirovirsen in chronic hepatitis B infection [J]. N Engl J Med, 2022, 387(21): 1957-1968.
26
Nasir M, Wu GY. Prevention of HBV recurrence after liver transplant: a review [J]. J Clin Transl Hepatol, 2020, 8(2): 150-160.
27
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]. 中华肝脏病杂志,2016, 12(24): 885-891.
28
Orfanidou A, Papatheodoridis GV, Cholongitas E. Antiviral prophylaxis against hepatitis B recurrence after liver transplantation: current concepts[J]. Liver Int, 2021, 41(7): 1448-1461.
29
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.
30
鲁凤民,于乐成,高林,等. HBeAg阴性慢性乙型肝炎患者停药后HBsAg可阴转:停药-治愈策略或许正在来临[J]. 中华医学杂志,2022, 102(40): 3160-3166.
31
Lau KCK, Osiowy C, Giles E, et al. Deep sequencing shows low-level oncogenic hepatitis B virus variants persists post-liver transplant despite potent anti-HBV prophylaxis [J]. J Viral Hepat, 2018, 25(6): 724-732.
32
Faria LC, Gigou M, Roque-Afonso AM, et al. Hepatocellular carcinoma is associated with an increased risk of hepatitis B virus recurrence after liver transplantation[J]. Gastroenterology, 2008, 134(7):1890-1899; quiz 2155.
33
Yuen MF, Chen DS, Dusheiko GM, et al. Hepatitis B virus infection[J]. Nat Rev Dis Primers, 2018, 4: 18035.
34
Leung RH, Hui RW, Mak LY, et al. ALT to qHBsAg ratio predicts long-term HBsAg seroclearance after entecavir cessation in Chinese patients with chronic hepatitis B[J]. J Hepatol, 2024, 81(2): 218-226.
35
Roche B, Roque-Afonso AM, Nevens F, et al. Rational basis for optimizing short and long-term hepatitis B virus prophylaxis post liver transplantation: role of hepatitis B immune globulin [J]. Transplantation, 2015, 99(7): 1321-1334.
36
Roche B, Samuel D. Withdrawal of posttransplant hepatitis B virus prophylaxis: a blind test [J]. Liver Transpl, 2016, 22(9): 1183-1185.
37
Matsuzaki T, Tatsuki I, Otani M, et al. Significance of hepatitis B virus core-related antigen and covalently closed circular DNA levels as markers of hepatitis B virus re-infection after liver transplantation [J]. J Gastroenterol Hepatol, 2013, 28(7): 1217-1222.
38
中华医学会肝病学分会基础医学与实验诊断协作组. 乙型肝炎病毒标志物临床应用专家共识[J]. 中华肝脏病杂志,2023, 31(4): 389-400.
39
中华医学会感染病学分会,中华医学会肝病学分会. 慢性乙型肝炎防治指南(2019年版)[J]. 中华肝脏病杂志,2019, 27(12): 938-961.
40
Cornberg M, Lok A SF, Terrault NA, et al. Guidance for design and endpoints of clinical trials in chronic hepatitis B - Report from the 2019 EASL-AASLD HBV Treatment Endpoints Conference[J]. Hepatol, 2020, 72(3):539-557.
41
European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection[J]. J Hepatol, 2017, 67(2):370-398.
42
Xia M, Chi H, Wu Y, et al. Serum hepatitis B virus RNA level is associated with biochemical relapse in patients with chronic hepatitis B infection who discontinue nucleos(t)ide analogue treatment [J]. Aliment Pharmacol Ther, 2021, 54(5): 709-714.
43
Papatheodoridi M, Papachristou E, Moschidis Z, et al. Significance of serum HBV RNA in non-cirrhotic HBeAg-negative chronic hepatitis B patients who discontinue effective antiviral therapy [J]. J Viral Hepat, 2022, 29(11): 948-957.
44
Seto WK, Liu KS, Mak LY, et al. Role of serum HBV RNA and hepatitis B surface antigen levels in identifying Asian patients with chronic hepatitis B suitable for entecavir cessation [J]. Gut, 2021, 70(4): 775-783.
45
Liu Y, Xue J, Liao W, et al. Serum HBV RNA dynamic and drug withdrawal predictor value in patients with chronic HBV infection on long-term nucleos(t)ide analogue (NA) therapy [J]. J Clin Gastroenterol, 2020, 54(8): e73-e82.
46
Fan R, Zhou B, Xu M, et al. Association between negative results from tests for HBV DNA and RNA and durability of response after discontinuation of nucles(t)ide analogue therapy [J]. Clin Gastroenterol Hepatol, 2020, 18(3): 719-727.e7.
47
Inoue T, Matsui T, Tanaka Y. Novel strategies for the early diagnosis of hepatitis B virus reactivation [J]. Hepatol Res, 2021, 51(10): 1033-1043.
48
Testoni B, Lebosse F, Scholtes C, et al. Serum hepatitis B core-related antigen (HBcrAg) correlates with covalently closed circular DNA transcriptional activity in chronic hepatitis B patients [J]. J Hepatol, 2019, 70(4): 615-625.
49
Hagiwara S, Kusumoto S, Inoue T, et al. Management of hepatitis B virus (HBV) reactivation in patients with resolved HBV infection based on a highly sensitive HB core-related antigen assay [J]. Hepatol Res, 2022, 52(9): 745-753.
50
中华医学会感染病学分会,中华医学会肝病学分会. 慢性乙型肝炎临床治愈(功能性治愈)专家共识[J]. 中华肝脏病杂志,2019, 27(8): 594-603.
51
Caviglia GP, Abate ML, Tandoi F, et al. Quantitation of HBV cccDNA in anti-HBc-positive liver donors by droplet digital PCR: a new tool to detect occult infection [J]. J Hepatol, 2018, 69(2): 301-307.
52
Fan R, Sun J, Yuan Q, et al. Baseline quantitative hepatitis B core antibody titre alone strongly predicts HBeAg seroconversion across chronic hepatitis B patients treated with peginterferon or nucleos(t)ide analogues [J]. Gut, 2016, 65(2): 313-320.
53
Lou B, Ma G, Lv F, et al. Baseline quantitative hepatitis B core antibody titer is a predictor for hepatitis B virus infection recurrence after orthotopic liver transplantation [J]. Front Immunol, 2021, 12: 710528.
54
Chi H, Li Z, Hansen BE, et al. Serum level of antibodies against hepatitis B core protein is associated with clinical relapse after discontinuation of nucleos(t)ide analogue therapy [J]. Clin Gastroenterol Hepatol, 2019, 17(1): 182-191.e1.
55
Lazarevic I, Banko A, Miljanovic D, et al. Clinical utility of quantitative HBV core antibodies for solving diagnostic dilemmas [J]. Viruses, 2023, 15(2):373.
[1] 陈昌贤, 罗钟玢, 李力. 血管生成抑制剂治疗铂耐药复发性卵巢癌患者的研究现状[J/OL]. 中华妇幼临床医学杂志(电子版), 2026, 22(04): 290-297.
[2] 钟婷婷, 陈梓锋, 杨金鑫, 张少冰, 吴文震. 益生菌水凝胶在龋病防治中的研究进展[J/OL]. 中华口腔医学研究杂志(电子版), 2026, 20(05): 372-382.
[3] 王中尧, 李敬东. 肝细胞癌术后早期复发危险因素研究进展[J/OL]. 中华普外科手术学杂志(电子版), 2026, 20(05): 495-500.
[4] 张浩然, 王实现, 王凯, 缪骥. SSLA治疗复发性阑尾炎的疗效与手术时间因素研究[J/OL]. 中华普外科手术学杂志(电子版), 2026, 20(04): 379-383.
[5] 周燕, 周春霞, 雷佳玉, 陈晓娟. 腹腔镜胃癌根治术后消化道重建技术与吻合口漏防治策略研究进展[J/OL]. 中华普外科手术学杂志(电子版), 2026, 20(04): 394-397.
[6] 童翾, 赵洪强, 吴广东, 于里涵, 侯昱丞, 卢倩, 徐光勋, 宋继勇, 林景熠, 郝华媛, 李昂, 汤睿. 胆道系统恶性肿瘤肝移植单中心经验[J/OL]. 中华移植杂志(电子版), 2026, 20(04): 254-259.
[7] 冯嘉耀, 曾翔宇, 赖文杰, 赵忠祥, 唐柯, 赖洪燊, 钟碧玲, 邱晓拂. 广东省医学会泌尿外科疑难病例多学科会诊(第35期)——转移性复发性嗜铬细胞瘤[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2026, 20(05): 601-608.
[8] 李茂林, 杨骏波, 江志鹏, 徐金桥. 腹腔镜下巴西尼原理腹股沟管后壁重建短期可行性分析[J/OL]. 中华疝和腹壁外科杂志(电子版), 2026, 20(04): 386-389.
[9] 谢吉艳, 江志鹏, 何立锐. 复发性腹壁疝的危险因素及治疗策略[J/OL]. 中华疝和腹壁外科杂志(电子版), 2026, 20(04): 471-476.
[10] 汪祖宇, 刘笑安, 王汉譞, 吕少诚, 郎韧. 终末期良性肝病肝移植术后顽固性脾亢影响因素及预测模型构建[J/OL]. 中华肝脏外科手术学电子杂志, 2026, 15(04): 606-611.
[11] 林婉琪, 任芳菲, 钟伟航, 杨卿, 马玲, 陈海丽, 向莎, 陈孟娇, 朱丽萍, 何心念, 张献玲. 基于多维度评估的前瞻性干预策略在肝癌肝移植围手术期的应用及效果[J/OL]. 中华肝脏外科手术学电子杂志, 2026, 15(04): 612-618.
[12] 丁育, 林倩, 王志, 吴文睿, 张克林, 赵海璇. 肝移植术后早期感染风险简易评分模型构建及分级护理策略[J/OL]. 中华肝脏外科手术学电子杂志, 2026, 15(04): 619-626.
[13] 董雯, 张小春, 金黑鹰, 金超. 结直肠息肉生长速率预测模型建立及其在结直肠腺瘤性息肉筛查中的应用价值[J/OL]. 中华结直肠疾病电子杂志, 2026, 15(04): 331-339.
[14] 许丹, 孙现新, 于海丽. 幽门螺杆菌感染与早期胃癌CYP2C19、CD14基因多态性的关系及对内镜黏膜下剥离术后短期复发的影响[J/OL]. 中华消化病与影像杂志(电子版), 2026, 16(04): 302-307.
[15] 何承远, 徐晓, 陈琴, 吴义军. 脑膜中动脉栓塞治疗非急性硬膜下血肿的研究进展[J/OL]. 中华脑血管病杂志(电子版), 2026, 20(05): 585-589.
阅读次数
全文


摘要


AI
小
编
AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?