肝硬化病因治疗联合抗纤维化治疗（双抗治疗）的现状与展望

韩一凡; 徐小元

doi:10.12449/JCH260601

肝硬化病因治疗联合抗纤维化治疗（双抗治疗）的现状与展望

DOI: 10.12449/JCH260601

韩一凡,
徐小元^, ,

北京大学第一医院消化内科，北京 100034

基金项目:

新发突发与重大传染病防控国家科技重大专项 (2025ZD01906300);

新发突发与重大传染病防控国家科技重大专项 (2025ZD01906303)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：韩一凡负责查阅资料，撰写稿件；徐小元负责指导，修改稿件及最终定稿。

详细信息

通信作者:
徐小元， xiaoyuanxu6@163.com （0000-0002-1759-4330）

计量
- 文章访问数: 10
- HTML全文浏览量: 1
- PDF下载量: 2
- 被引次数: 0
出版历程
- 收稿日期: 2026-03-01
- 录用日期: 2026-04-02
- 出版日期: 2026-06-25

Etiological treatment combined with antifibrotic therapy （dual therapy） for liver cirrhosis： Current status and future perspectives

Yifan HAN,
Xiaoyuan XU^{,
,}

Department of Gastroenterology，Peking University First Hospital，Beijing 100034，China

Research funding:

Prevention and Control of Emerging and Major Infectious Diseases-National Science and Technology Major Project (2025ZD01906300);

Prevention and Control of Emerging and Major Infectious Diseases-National Science and Technology Major Project (2025ZD01906303)

More Information

Corresponding author: XU Xiaoyuan， xiaoyuanxu6@163.com （ORCID： 0000-0002-1759-4330）

摘要

摘要: 肝硬化是多种慢性肝病的终末阶段，持续炎症导致的肝纤维化是其发生发展的核心机制。随着疾病谱演变和对肝纤维化逆转认识的不断深入，源于乙型肝炎肝硬化治疗中抗病毒联合抗肝纤维化的“双抗治疗”，逐渐演变为肝硬化治疗中病因治疗联合抗肝纤维化和/或抗炎的广义“双抗治疗”。本文旨在系统综述肝硬化“双抗治疗”的概念演变及研究进展。
- 肝纤维化 /
- 肝硬化 /
- 双抗治疗
Abstract: Liver cirrhosis is the end-stage of various chronic liver diseases， and hepatic fibrosis caused by persistent inflammation is the core mechanism of the development and progression of liver cirrhosis. With the evolution of disease spectrum and a deeper understanding of the reversal of hepatic fibrosis， dual antiviral-antifibrotic therapy initially applied in the treatment of hepatitis B cirrhosis has gradually evolved into a broad-sense dual therapy for liver cirrhosis， which integrates etiological treatment with antifibrotic and/or anti-inflammatory interventions. This article systematically reviews the conceptual evolution of dual therapy for liver cirrhosis and related research advances.
- Hepatic Fibrosis /
- Liver Cirrhosis /
- Dual-anti Therapy

HTML全文

参考文献(47)

[1]	THAM EKJ, TAN DJH, DANPANICHKUL P, et al. The global burden of cirrhosis and other chronic liver diseases in 2021[J]. Liver Int, 2025, 45( 3): e70001. DOI: 10.1111/liv.70001.
[2]	TAN Z, SUN HB, XUE TX, et al. Liver fibrosis: Therapeutic targets and advances in drug therapy[J]. Front Cell Dev Biol, 2021, 9: 730176. DOI: 10.3389/fcell.2021.730176.
[3]	Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Gastroenterology, Chinese Medical Association; Chinese Society of Infectious Diseases, Chinese Medical Association. Consensus on the diagnosis and therapy of hepatic fibrosis(2019)[J]. J Clin Hepatol, 2019, 35( 10): 2163- 2172. DOI: 10.3969/j.issn.1001-5256.2019.10.007. 中华医学会肝病学分会, 中华医学会消化病学分会, 中华医学会感染病学分会. 肝纤维化诊断及治疗共识(2019年)[J]. 临床肝胆病杂志, 2019, 35( 10): 2163- 2172. DOI: 10.3969/j.issn.1001-5256.2019.10.007.
[4]	LIN J. Virus-related liver cirrhosis: Molecular basis and therapeutic options[J]. World J Gastroenterol, 2014, 20( 21): 6457. DOI: 10.3748/wjg.v20.i21.6457.
[5]	de ZAWADZKI A, LEEMING DJ, SANYAL AJ, et al. Hot and cold fibrosis: The role of serum biomarkers to assess immune mechanisms and ECM-cell interactions in human fibrosis[J]. J Hepatol, 2025, 83( 1): 239- 257. DOI: 10.1016/j.jhep.2025.02.039.
[6]	LIAW YF, SUNG JJY, CHOW WC, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease[J]. N Engl J Med, 2004, 351( 15): 1521- 1531. DOI: 10.1056/nejmoa033364.
[7]	LAI CL, CHIEN RN, LEUNG NWY, et al. A one-year trial of lamivudine for chronic hepatitis B[J]. N Engl J Med, 1998, 339( 2): 61- 68. DOI: 10.1056/nejm199807093390201.
[8]	MARCELLIN P, CHANG TT, LIM SG, et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B[J]. N Engl J Med, 2003, 348( 9): 808- 816. DOI: 10.1056/nejmoa020681.
[9]	HADZIYANNIS SJ, TASSOPOULOS NC, HEATHCOTE EJ, et al. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years[J]. Gastroenterology, 2006, 131( 6): 1743- 1751. DOI: 10.1053/j.gastro.2006.09.020.
[10]	LAI CL, SHOUVAL D, LOK AS, et al. Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B[J]. N Engl J Med, 2006, 354( 10): 1011- 1020. DOI: 10.1056/NEJMoa051287.
[11]	LAI CL, GANE E, LIAW YF, et al. Telbivudine versus lamivudine in patients with chronic hepatitis B[J]. N Engl J Med, 2007, 357( 25): 2576- 2588. DOI: 10.1056/nejmoa066422.
[12]	MARCELLIN P, HEATHCOTE EJ, BUTI M, et al. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B[J]. N Engl J Med, 2008, 359( 23): 2442- 2455. DOI: 10.1056/NEJMoa0802878.
[13]	MARCELLIN P, GANE E, BUTI M, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: A 5-year open-label follow-up study[J]. Lancet, 2013, 381( 9865): 468- 475. DOI: 10.1016/S0140-6736(12)61425-1.
[14]	XU B, XU GG, GUO Q, et al. Long term treatment of lamivudine in chronic hepatitis B patients with severe liver fibrosis: Ten-year follow-up outcomes of NUCB 4006 trial[J]. Chin J Infect Dis, 2010, 28( 11): 656- 661. DOI: 10.3760/cma.j.issn.1000-6680.2010.11.004 许蓓, 徐国光, 郭清, 等. 拉米夫定对慢性乙型肝炎伴重度肝纤维化患者的长期应用疗效: NUCB 4006十年随访研究[J]. 中华传染病杂志, 2010, 28( 11): 656- 661. DOI: 10.3760/cma.j.issn.1000-6680.2010.11.004
[15]	TIAN FX, XIA HZ, DING WC. Observation on therapeutic effect of adefovir dipivoxil tablets combined with Anluohuaxian pills on early cirrhosis after hepatitis B.[J]. Chin J Exp Clin Virol, 2008, 22( 4): 315. DOI: 10.3760/cma.j.issn.1003-9279.2008.04.026. 田发勋, 夏和中, 丁伟村. 阿德福韦脂片联合安络化纤丸治疗乙肝后早期肝硬化疗效观察[J]. 中华实验和临床病毒学杂志, 2008, 22( 4): 315. DOI: 10.3760/cma.j.issn.1003-9279.2008.04.026.
[16]	WANG L, LU W, GAO YH, et al. Effect of Anluohuaxianwan on the expression of matrix metalloproteinases and their inhibitors in rat liver with fibrosis[J]. Chin J Hepatol, 2019, 27( 4): 267- 273. 王林, 卢玮, 高玉华, 等. 安络化纤丸对肝纤维化大鼠肝组织基质金属蛋白酶及其抑制物表达的影响[J]. 中华肝脏病杂志, 2019, 27( 4): 267- 273.
[17]	FAN Y, HAO KY, LI P, et al. Meta-analysis of the efficacy of the Fuzheng Huayu formula in the treatment of hepatitis B-associated liver fibrosis or cirrhosis[J]. Chin J Hepatol, 2024, 32( 12): 1141- 1152. DOI: 10.3760/cma.j.cn501113-20240612-00293. 范晔, 郝坤艳, 李平, 等. 扶正化瘀组方治疗乙型肝炎肝纤维化或肝硬化疗效的荟萃分析[J]. 中华肝脏病杂志, 2024, 32( 12): 1141- 1152. DOI: 10.3760/cma.j.cn501113-20240612-00293.
[18]	JI D, CHEN Y, BI JF, et al. Entecavir plus Biejia-Ruangan compound reduces the risk of hepatocellular carcinoma in Chinese patients with chronic hepatitis B[J]. J Hepatol, 2022, 77( 6): 1515- 1524. DOI: 10.1016/j.jhep.2022.07.018.
[19]	RONG GH, CHEN YP, YU ZJ, et al. Synergistic effect of Biejia-Ruangan on fibrosis regression in patients with chronic hepatitis B treated with entecavir: A multicenter, randomized, double-blind, placebo-controlled trial[J]. J Infect Dis, 2022, 225( 6): 1091- 1099. DOI: 10.1093/infdis/jiaa266.
[20]	Chinese Society of Hepatology, Chinese Society of Gastroenterology, and Chinese Society of Digestive Endoscopology of Chinese Medical Association. Guidelines on the management of esophagogastric variceal bleeding in cirrhotic portal hypertension[J]. J Clin Hepatol, 2023, 39( 3): 527- 538. DOI: 10.3969/j.issn.1001-5256.2023.03.znygf. 中华医学会肝病学分会, 中华医学会消化病学分会, 中华医学会消化内镜学分会. 肝硬化门静脉高压食管胃静脉曲张出血的防治指南[J]. 临床肝胆病杂志, 2023, 39( 3): 527- 538. DOI: 10.3969/j.issn.1001-5256.2023.03.znygf.
[21]	DENG X, LIANG J, LIU ZW, et al. Treatment of posthepatitic cirrhosis by Fuzheng Huayu Tablet for reinforcing qi and resolving stasis[J]. Chin J Integr Med, 2013, 19( 4): 289- 296. DOI: 10.1007/s11655-013-1433-7.
[22]	ZHAO ZM, ZHU CW, HUANG JQ, et al. Efficacy and safety of Fuzheng Huayu tablet on persistent advanced liver fibrosis following 2 years entecavir treatment: A single arm clinical objective performance criteria trial[J]. J Ethnopharmacol, 2022, 298: 115599. DOI: 10.1016/j.jep.2022.115599.
[23]	SHI K, LIU Y, WANG XJ, et al. Adjuvant fuzheng Huayu capsule reduces the incidence of hepatocellular carcinoma in patients with hepatitis B-caused cirrhosis[J]. Evid Based Complement Alternat Med, 2020, 2020: 8826091. DOI: 10.1155/2020/8826091.
[24]	FAN HN, LEI SJ, ZHAO ZM, et al. Beneficial effects of traditional Chinese medicine fuzheng Huayu on the occurrence of hepatocellular carcinoma in patients with compensated chronic hepatitis B cirrhosis receiving entecavir: A multicenter retrospective cohort study[J]. J Clin Transl Hepatol, 2024, 12( 5): 505- 515. DOI: 10.14218/jcth.2023.00521.
[25]	FAN HN, HUANG K, DAI YK, et al. Effect and mechanism of Fuzheng Huayu Decoction on carcinogenesis in mice with liver fibrosis[J]. Chin J Integr Tradit West Med Dig, 2023, 31( 2): 110- 117. 范海纳, 黄恺, 代云凯, 等. 扶正化瘀方对肝纤维化小鼠肝癌发生的影响与机制[J]. 中国中西医结合消化杂志, 2023, 31( 2): 110- 117.
[26]	LIU YD, MAO X, MA ZC, et al. Aberrant regulation of LncRNA TUG1-microRNA-328-3p-SRSF9 mRNA Axis in hepatocellular carcinoma: A promising target for prognosis and therapy[J]. Mol Cancer, 2022, 21( 1): 36. DOI: 10.1186/s12943-021-01493-6.
[27]	CHENG Q, LI N, CHEN MQ, et al. Fuzheng Huayu inhibits carbon tetrachloride-induced liver fibrosis in mice through activating hepatic NK cells[J]. J Ethnopharmacol, 2013, 145( 1): 175- 181. DOI: 10.1016/j.jep.2012.10.047.
[28]	LU KQ, SUI JJ, YU WH, et al. An analysis of the burden of liver cirrhosis: Differences between the global, China, the United States and India[J]. Liver Int, 2024, 44( 12): 3183- 3203. DOI: 10.1111/liv.16087.
[29]	HUANG DQ, TERRAULT NA, TACKE F, et al. Global epidemiology of cirrhosis: Aetiology, trends and predictions[J]. Nat Rev Gastroenterol Hepatol, 2023, 20( 6): 388- 398. DOI: 10.1038/s41575-023-00759-2.
[30]	Chinese Society of Hepatology, Chinese Medical Association. Chinese guidelines for clinical diagnosis, treatment, and management of cirrhosis(2025)[J]. Chin J Hepatol, 2025, 33( 10): 958- 976. DOI: 10.3760/cma.j.cn501113-20250728-00298. 中华医学会肝病学分会. 肝硬化临床诊治管理指南(2025版)[J]. 中华肝脏病杂志, 2025, 33( 10): 958- 976. DOI: 10.3760/cma.j.cn501113-20250728-00298.
[31]	XU XY, DING HG, YOU H, et al. Chinese guidelines for clinical diagnosis, treatment, and management of cirrhosis(2025)[J]. J Clin Transl Hepatol, 2026, 14( 1): 96- 115. DOI: 10.14218/JCTH.2025.00517.
[32]	Chinese Society of Hepatology, Chinese Medical Association. Guidelines for the prevention and treatment of metabolic dysfunction-associated( non-alcoholic) fatty liver disease(Version 2024)[J]. J Prac Hepatol, 2024, 27( 4): 494- 510. DOI: 10.3760/cma.j.cn501113-20240327-00163. 中华医学会肝病学分会. 代谢相关(非酒精性)脂肪性肝病防治指南(2024年版)[J]. 实用肝脏病杂志, 2024, 27( 4): 494- 510. DOI: 10.3760/cma.j.cn501113-20240327-00163.
[33]	ARMANDI A, BUGIANESI E. Dietary and pharmacological treatment in patients with metabolic-dysfunction associated steatotic liver disease[J]. Eur J Intern Med, 2024, 122: 20- 27. DOI: 10.1016/j.ejim.2024.01.005.
[34]	RINELLA ME, NEUSCHWANDER-TETRI BA, SIDDIQUI MS, et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease[J]. Hepatology, 2023, 77( 5): 1797- 1835. DOI: 10.1097/hep.0000000000000323.
[35]	VILAR-GOMEZ E, MARTINEZ-PEREZ Y, CALZADILLA-BERTOT L, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis[J]. Gastroenterology, 2015, 149( 2): 367- 378.e5. DOI: 10.1053/j.gastro.2015.04.005.
[36]	FRANCQUE SM, MARCHESINI G, KAUTZ A, et al. Non-alcoholic fatty liver disease: A patient guideline[J]. JHEP Rep, 2021, 3( 5): 100322. DOI: 10.1016/j.jhepr.2021.100322.
[37]	CUSI K, ISAACS S, BARB D, et al. American association of clinical endocrinology clinical practice guideline for the diagnosis and management of nonalcoholic fatty liver disease in primary care and endocrinology clinical settings[J]. Endocr Pract, 2022, 28( 5): 528- 562. DOI: 10.1016/j.eprac.2022.03.010.
[38]	YOUNOSSI ZM, COREY KE, LIM JK. AGA clinical practice update on lifestyle modification using diet and exercise to achieve weight loss in the management of nonalcoholic fatty liver disease: Expert review[J]. Gastroenterology, 2021, 160( 3): 912- 918. DOI: 10.1053/j.gastro.2020.11.051.
[39]	SANYAL AJ, NEWSOME PN, KLIERS I, et al. Phase 3 trial of semaglutide in metabolic dysfunction-associated steatohepatitis[J]. N Engl J Med, 2025, 392( 21): 2089- 2099. DOI: 10.1056/nejmoa2413258.
[40]	BANSAL MB, PATTON H, MORGAN TR, sl et. Semaglutide therapy for metabolic dysfunction-associated steatohepatitis: November 2025 updates to AASLD Practice Guidance[J]. Hepatology, 2026, 83( 5): 1326- 1340. DOI: 10.1097/HEP.0000000000001608.
[41]	SUN K, PARK J, GUPTA OT, et al. Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction[J]. Nat Commun, 2014, 5: 3485. DOI: 10.1038/ncomms4485.
[42]	FRANCQUE SM, BEDOSSA P, RATZIU V, et al. A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH[J]. N Engl J Med, 2021, 385( 17): 1547- 1558. DOI: 10.1056/nejmoa2036205.
[43]	CHEAH MCC, CRANE H, GEORGE J. Global prevalence, metabolic characteristics, and outcomes of lean-MAFLD: A systematic review and meta-analysis[J]. Hepatol Int, 2025, 19( 3): 607- 618. DOI: 10.1007/s12072-025-10801-x.
[44]	Fatty Liver Expert Committee, Chinese Medical Doctor Association, National Workshop on Fatty Liver and Alcoholic Liver Disease, Chinese Society of Hepatology, Chinese Medical Association. Guidelines of prevention and treatment for alcoholic liver disease: A 2018 update[J]. J Clin Hepatol, 2018, 34( 5): 939- 946. DOI: 10.3969/j.issn.1001-5256.2018.05.006. 中华医学会肝病学分会脂肪肝和酒精性肝病学组, 中国医师协会脂肪性肝病专家委员会. 酒精性肝病防治指南(2018年更新版)[J]. 临床肝胆病杂志, 2018, 34( 5): 939- 946. DOI: 10.3969/j.issn.1001-5256.2018.05.006.
[45]	HARRISON SA, BEDOSSA P, GUY CD, et al. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis[J]. N Engl J Med, 2024, 390( 6): 497- 509. DOI: 10.1056/nejmoa2309000.
[46]	Two-Year Time Course of Biomarker and Imaging Responses in Patients With Well-Compensated MASH Cirrhosis Treated With Resmetirom[J]. Gastroenterol Hepatol(N Y), 2025, 21(12 Suppl 11): 6- 7.
[47]	ZHOU R, YANG LP, ZHANG BB, et al. Clinical impact of hepatic steatosis on chronic hepatitis B patients in Asia: A systematic review and meta-analysis[J]. J Viral Hepat, 2023, 30( 10): 793- 802. DOI: 10.1111/jvh.13872.