乙肝抗病毒与长期管理：病毒抑制、停药边界与肝癌监测

先看懂四件事：谁需要治疗、风险为什么不同、一线药怎么选、停药后怎么办Hepatitis B: Antiviral Therapy & Long-term Management

乙肝管理是一条长期链条：确认感染状态（HBsAg／HBeAg／HBV DNA）→ 评估纤维化与肝癌风险 → 决定是否启动抗病毒治疗 → 长期用药并每 6 个月筛查肝癌 → 谨慎评估停药与随访。任何一环缺失，都可能让「可控的慢性病」走向肝硬化或肝癌。

发病机理：病毒、免疫与纤维化：乙肝为什么要长期管理Pathogenesis

乙肝的损害并不是病毒直接「吃掉」肝细胞，而是持续复制引发免疫攻击、反复修复形成纤维化，最终走向肝硬化与肝癌。抗病毒治疗切断的是这条链条的前半段，因此开始得越早、坚持得越久，收获越大。

哪些因素增加肝硬化与肝癌风险

两个容易被忽略的问题

怎么检查：病毒、肝功与影像Assessment

怎么治疗：一线药物、联合方案与停药边界Treatment

治疗与监测一览

日常管理：复查、筛查与生活Daily Management

十个常见误区Ten Common Misconceptions

参考文献与证据来源References & Evidence

本页共 24 条文献，来自国际共识与指南、随机对照试验、荟萃分析与机制研究，链接指向 PubMed。每条结论后的编号对应下方文献；证据不足或结论不一致之处已在正文标注。

1. EASL 临床实践指南（慢性乙肝病毒感染的管理）European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2025;83(2):502-583. pubmed.ncbi.nlm.nih.gov/40348683
2. AASLD 与 IDSA 实践指南（慢性乙肝的治疗）Ghany MG, Pan CQ, Lok AS, Feld JJ, Lim JK, Wang SH, Kim AY, Tang AS, Nguyen MH, Naggie S, Sulkowski MS, Norberto RB, Chen J, Murad MH, Mohammad KS, Terrault NA. AASLD ISDA Practice Guideline on treatment of chronic hepatitis B. Hepatology. 2026;83(4):974-997. pubmed.ncbi.nlm.nih.gov/41186418
3. 指南解读（WHO 2024 年慢性乙肝预防与管理指南更新及影响）Wong GL, Lemoine M. The 2024 updated WHO guidelines for the prevention and management of chronic hepatitis B: Main changes and potential implications for the next major liver society clinical practice guidelines. J Hepatol. 2025;82(5):918-925. pubmed.ncbi.nlm.nih.gov/39647534
4. 社区前瞻队列研究（血清 HBV DNA 水平与肝癌风险的剂量反应：REVEAL-HBV）Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH, REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295(1):65-73. pubmed.ncbi.nlm.nih.gov/16391218
5. 社区队列研究（HBeAg 与肝癌风险）Yang HI, Lu SN, Liaw YF, You SL, Sun CA, Wang LY, Hsiao CK, Chen PJ, Chen DS, Chen CJ, Taiwan Community-Based Cancer Screening Project Group. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med. 2002;347(3):168-174. pubmed.ncbi.nlm.nih.gov/12124405
6. 风险评分开发与验证（REACH-B 肝癌风险预测评分）Yang HI, Yuen MF, Chan HL, Han KH, Chen PJ, Kim DY, Ahn SH, Chen CJ, Wong VW, Seto WK, REACH-B Working Group. Risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B): development and validation of a predictive score. Lancet Oncol. 2011;12(6):568-574. pubmed.ncbi.nlm.nih.gov/21497551
7. 人群研究（台湾新生儿普种乙肝疫苗与儿童肝癌发生率）Chang MH, Chen CJ, Lai MS, Hsu HM, Wu TC, Kong MS, Liang DC, Shau WY, Chen DS. Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group. N Engl J Med. 1997;336(26):1855-1859. pubmed.ncbi.nlm.nih.gov/9197213
8. 随机对照试验（恩替卡韦与拉米夫定治疗 HBeAg 阳性慢性乙肝）Chang TT, Gish RG, de Man R, Gadano A, Sollano J, Chao YC, Lok AS, Han KH, Goodman Z, Zhu J, Cross A, DeHertogh D, Wilber R, Colonno R, Apelian D, BEHoLD AI463022 Study Group. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med. 2006;354(10):1001-1010. pubmed.ncbi.nlm.nih.gov/16525137
9. 随机对照试验（替诺福韦与阿德福韦治疗慢性乙肝）Marcellin P, Heathcote EJ, Buti M, Gane E, de Man RA, Krastev Z, Germanidis G, Lee SS, Flisiak R, Kaita K, Manns M, Kotzev I, Tchernev K, Buggisch P, Weilert F, Kurdas OO, Shiffman ML, Trinh H, Washington MK, Sorbel J, Anderson J, Snow-Lampart A, Mondou E, Quinn J, Rousseau F. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med. 2008;359(23):2442-2455. pubmed.ncbi.nlm.nih.gov/19052126
10. 三期非劣效随机试验（TAF 与 TDF 治疗 HBeAg 阳性慢性乙肝）Chan HL, Fung S, Seto WK, Chuang WL, Chen CY, Kim HJ, Hui AJ, Janssen HL, Chowdhury A, Tsang TY, Mehta R, Gane E, Flaherty JF, Massetto B, Gaggar A, Kitrinos KM, Lin L, Subramanian GM, McHutchison JG, Lim YS, Acharya SK, Agarwal K, GS-US-320-0110 Investigators. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-positive chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol. 2016;1(3):185-195. pubmed.ncbi.nlm.nih.gov/28404091
11. 三期非劣效随机试验（TAF 与 TDF 治疗 HBeAg 阴性慢性乙肝）Buti M, Gane E, Seto WK, Chan HL, Chuang WL, Stepanova T, Hui AJ, Lim YS, Mehta R, Janssen HL, Acharya SK, Flaherty JF, Massetto B, Cathcart AL, Kim K, Gaggar A, Subramanian GM, McHutchison JG, Pan CQ, Brunetto M, Izumi N, Marcellin P, GS-US-320-0108 Investigators. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol. 2016;1(3):196-206. pubmed.ncbi.nlm.nih.gov/28404092
12. 随机对照试验（恩替卡韦与替诺福韦治疗慢性乙肝的疗效与安全性）Sriprayoon T, Mahidol C, Ungtrakul T, Chun-On P, Soonklang K, Pongpun W, Laohapand C, Dechma J, Pothijaroen C, Auewarakul C, Tanwandee T. Efficacy and safety of entecavir versus tenofovir treatment in chronic hepatitis B patients: A randomized controlled trial. Hepatol Res. 2017;47(3):E161-E168. pubmed.ncbi.nlm.nih.gov/27176630
13. 系统评价与荟萃分析（替诺福韦与恩替卡韦的肝癌发生率比较）Tseng CH, Hsu YC, Chen TH, Ji F, Chen IS, Tsai YN, Hai H, Thuy LTT, Hosaka T, Sezaki H, Borghi JA, Cheung R, Enomoto M, Nguyen MH. Hepatocellular carcinoma incidence with tenofovir versus entecavir in chronic hepatitis B: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2020;5(12):1039-1052. pubmed.ncbi.nlm.nih.gov/33007228
14. 双盲随机试验（替诺福韦预防乙肝母婴传播）Jourdain G, Ngo-Giang-Huong N, Harrison L, Decker L, Khamduang W, Tierney C, Salvadori N, Cressey TR, Sirirungsi W, Achalapong J, Yuthavisuthi P, Kanjanavikai P, Na Ayudhaya OP, Siriwachirachai T, Prommas S, Sabsanong P, Limtrakul A, Varadisai S, Putiyanun C, Suriyachai P, Liampongsabuddhi P, Sangsawang S, Matanasarawut W, Buranabanjasatean S, Puernngooluerm P, Bowonwatanuwong C, Puthanakit T, Klinbuayaem V, Thongsawat S, Thanprasertsuk S, Siberry GK, Watts DH, Chakhtoura N, Murphy TV, Nelson NP, Chung RT, Pol S, Chotivanich N. Tenofovir versus Placebo to Prevent Perinatal Transmission of Hepatitis B. N Engl J Med. 2018;378(10):911-923. pubmed.ncbi.nlm.nih.gov/29514030
15. 随机临床试验（替诺福韦与孕期乙肝病毒传播）Pan CQ, Dai E, Mo Z, Zhang H, Zheng TQ, Wang Y, Liu Y, Chen T, Li S, Yang C, Wu J, Chen X, Zou H, Mei S, Zhu L. Tenofovir and Hepatitis B Virus Transmission During Pregnancy: A Randomized Clinical Trial. JAMA. 2025;333(5):390-399. pubmed.ncbi.nlm.nih.gov/39540799
16. 随机试验（替诺福韦联合聚乙二醇干扰素提高 HBsAg 清除率）Marcellin P, Ahn SH, Ma X, Caruntu FA, Tak WY, Elkashab M, Chuang WL, Lim SG, Tabak F, Mehta R, Petersen J, Foster GR, Lou L, Martins EB, Dinh P, Lin L, Corsa A, Charuworn P, Subramanian GM, Reiser H, Reesink HW, Fung S, Strasser SI, Trinh H, Buti M, Gaeta GB, Hui AJ, Papatheodoridis G, Flisiak R, Chan HL, Study 149 Investigators. Combination of Tenofovir Disoproxil Fumarate and Peginterferon α-2a Increases Loss of Hepatitis B Surface Antigen in Patients With Chronic Hepatitis B. Gastroenterology. 2016;150(1):134-144.e10. pubmed.ncbi.nlm.nih.gov/26453773
17. 队列研究（停药后 HBsAg 清除的发生率与预测因素）Jeng WJ, Chen YC, Chien RN, Sheen IS, Liaw YF. Incidence and predictors of hepatitis B surface antigen seroclearance after cessation of nucleos(t)ide analogue therapy in hepatitis B e antigen-negative chronic hepatitis B. Hepatology. 2018;68(2):425-434. pubmed.ncbi.nlm.nih.gov/29108132
18. 队列研究（HBsAg 清除进一步降低完全病毒抑制者的肝癌风险）Yip TC, Wong GL, Chan HL, Tse YK, Lam KL, Lui GC, Wong VW. HBsAg seroclearance further reduces hepatocellular carcinoma risk after complete viral suppression with nucleos(t)ide analogues. J Hepatol. 2019;70(3):361-370. pubmed.ncbi.nlm.nih.gov/30367899
19. 系统评价（HBeAg 阴性患者停用长期核苷（酸）类似物治疗）Chang ML, Liaw YF, Hadziyannis SJ. Systematic review: cessation of long-term nucleos(t)ide analogue therapy in patients with hepatitis B e antigen-negative chronic hepatitis B. Aliment Pharmacol Ther. 2015;42(3):243-257. pubmed.ncbi.nlm.nih.gov/26151841
20. 国际多中心队列研究（核苷（酸）类似物停药后的应答：RETRACT-B）Hirode G, Choi HSJ, Chen CH, Su TH, Seto WK, Van Hees S, Papatheodoridi M, Lens S, Wong G, Brakenhoff SM, Chien RN, Feld J, Sonneveld MJ, Chan HLY, Forns X, Papatheodoridis GV, Vanwolleghem T, Yuen MF, Hsu YC, Kao JH, Cornberg M, Hansen BE, Jeng WJ, Janssen HLA, RETRACT-B Study Group. Off-Therapy Response After Nucleos(t)ide Analogue Withdrawal in Patients With Chronic Hepatitis B: An International, Multicenter, Multiethnic Cohort (RETRACT-B Study). Gastroenterology. 2022;162(3):757-771.e4. pubmed.ncbi.nlm.nih.gov/34762906
21. 2b 期随机试验（bepirovirsen 治疗慢性乙肝的疗效与安全性）Yuen MF, Lim SG, Plesniak R, Tsuji K, Janssen HLA, Pojoga C, Gadano A, Popescu CP, Stepanova T, Asselah T, Diaconescu G, Yim HJ, Heo J, Janczewska E, Wong A, Idriz N, Imamura M, Rizzardini G, Takaguchi K, Andreone P, Arbune M, Hou J, Park SJ, Vata A, Cremer J, Elston R, Lukić T, Quinn G, Maynard L, Kendrick S, Plein H, Campbell F, Paff M, Theodore D, B-Clear Study Group. Efficacy and Safety of Bepirovirsen in Chronic Hepatitis B Infection. N Engl J Med. 2022;387(21):1957-1968. pubmed.ncbi.nlm.nih.gov/36346079
22. 随机对照试验（肝癌筛查：每 6 个月 AFP 联合超声）Zhang BH, Yang BH, Tang ZY. Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol. 2004;130(7):417-422. pubmed.ncbi.nlm.nih.gov/15042359
23. 系统评价与荟萃分析（1973 至 2021 年中国慢性乙肝流行率变化）Liu Z, Lin C, Mao X, Guo C, Suo C, Zhu D, Jiang W, Li Y, Fan J, Song C, Zhang T, Jin L, De Martel C, Clifford GM, Chen X. Changing prevalence of chronic hepatitis B virus infection in China between 1973 and 2021: a systematic literature review and meta-analysis of 3740 studies and 231 million people. Gut. 2023;72(12):2354-2363. pubmed.ncbi.nlm.nih.gov/37798085
24. 开放标签随访研究（替诺福韦治疗 5 年的肝硬化逆转）Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson IM, Washington MK, Germanidis G, Flaherty JF, Aguilar Schall R, Bornstein JD, Kitrinos KM, Subramanian GM, McHutchison JG, Heathcote EJ. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013;381(9865):468-475. pubmed.ncbi.nlm.nih.gov/23234725