复方中药阻断逆转肝纤维化：超越已知的前沿

柏兆方; 湛小燕; 吕桂基; 杨永平

doi:10.3969/j.issn.1001-5256.2023.02.004

复方中药阻断逆转肝纤维化：超越已知的前沿

DOI: 10.3969/j.issn.1001-5256.2023.02.004

柏兆方^{1, 2},
湛小燕^{1, 2},
吕桂基^{1, 2},
杨永平^1, , ,

1.
中国人民解放军总医院第五医学中心肝病医学部，北京 100039
2.
中国人民解放军总医院第五医学中心全军中医药研究所，北京 100039

基金项目:

国家科技重大专项 (2018ZX10725506);

国家“重大新药创制”科技重大专项 (2017ZX09301022)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：杨永平负责设计论文框架，起草、修订和终审论文；柏兆方、湛小燕负责起草论文，修订论文；吕桂基负责文献数据整理，起草论文。

详细信息

通信作者:
杨永平，yongpingyang@hotmail.com (ORCID: 0000-0002-8307-1095)

计量
- 文章访问数: 916
- HTML全文浏览量: 383
- PDF下载量: 149
- 被引次数: 0
出版历程
- 收稿日期: 2022-12-10
- 录用日期: 2023-01-12
- 出版日期: 2023-02-20

Blocking and reversing liver fibrosis with traditional Chinese medicine compound prescriptions: Beyond the known frontiers

Zhaofang BAI^{1, 2},
Xiaoyan ZHAN^{1, 2},
Guiji LYU^{1, 2},
Yongping YANG^{1
, ,
,}

1.
Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
2.
China Military Institute of Chinese Medicine, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China

Research funding:

National Science and Technology Key Project (2018ZX10725506);

National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program" (2017ZX09301022)

More Information

Corresponding author: YANG Yongping, yongpingyang@hotmail.com (ORCID: 0000-0002-8307-1095)

摘要

摘要: 肝纤维化是慢性乙型肝炎进展为肝硬化的必由之路，也是肝癌发生最重要的危险因素，因此阻断逆转肝纤维化是有效降低慢性乙型肝炎肝硬化和肝癌发生的重要策略。西医目前尚无治疗肝纤维化的有效药物和手段，在我国中药抗肝纤维化具有独特优势，但是由于缺乏严格规范的临床研究，导致缺少高质量循证医学证据支持。笔者团队在“十二·五”“十三·五”国家科技重大专项的资助下，开展了中药复方鳖甲软肝片联合恩替卡韦阻断逆转慢性乙型肝炎肝纤维化的多中心、随机、双盲、安慰剂对照临床研究，以肝活组织检查为标准，纳入1000例患者，确证复方鳖甲软肝片联合恩替卡韦阻断、逆转肝纤维化和肝硬化的确切疗效，并成为首个具有高质量循证医学证据支持的中医药抗肝纤维化研究成果，为全球慢性肝病患者带来巨大希望，助力中医药走向世界。本文重点就这一研究成果进行介绍并对中医药阻断逆转肝纤维化研究的现状和面临问题进行评述。
- 乙型肝炎, 慢性 /
- 肝纤维化 /
- 中草药 /
- 复方鳖甲软肝片
Abstract: Liver fibrosis is the inevitable course for the progression of chronic hepatitis B to liver cirrhosis and is also the most important risk factor for hepatocarcinogenesis, and therefore, blocking and reversing liver fibrosis is an important strategy to effectively reduce the development of chronic hepatitis B cirrhosis and liver cancer. There are currently no effective drugs and measures for the treatment of liver fibrosis in Western medicine, and traditional Chinese medicine (TCM) has unique advantages in the treatment of liver fibrosis; however, due to a lack of strict and standardized clinical research, there is still no high-quality evidence for support from the aspect of evidence-based medicine (EBM). With subsidies from National Science and Technology Major Project in the 12th and 13th five-year plans, the authors conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial on compound Biejia Ruangan tablets combined with entecavir in blocking and reversing chronic hepatitis B liver fibrosis. With liver biopsy as the gold standard, 1000 patients were enrolled to confirm the efficacy of compound Biejia Ruangan tablets combined with entecavir in blocking and reversing liver fibrosis and cirrhosis, and this study has become the first clinical trial investigating the anti-liver fibrosis effect of TCM supported by high-quality EBM evidence, bringing great hope to patients with chronic liver diseases and helping TCM move towards the world. This article introduces these research findings and reviews the current status and challenges of TCM in blocking and reversing liver fibrosis.
- Hepatitis B, Chronic /
- Liver Fibrosis /
- Drugs, Chinese Herbal /
- Biejia-Ruangan compound

HTML全文

参考文献(20)

[1]	YIN C, EVASON KJ, ASAHINA K, et al. Hepatic stellate cells in liver development, regeneration, and cancer[J]. J Clin Invest, 2013, 123(5): 1902-1910. DOI: 10.1172/JCI66369.
[2]	FRIEDMAN SL. Liver fibrosis - from bench to bedside[J]. J Hepatol, 2003, 38 Suppl 1: S38-S53. DOI: 10.1016/s0168-8278(02)00429-4.
[3]	Liver Disease Committee, Chinese Association of Integrative Medicine. Guidelines for the diagnosis and treatment of liver fibrosis in integrative medicine practice (2019)[J]. J Clin Hepatol, 2019, 35(7): 1444-1449. DOI: 10.3969/j.issn.1001-5256.2019.07.007. 中国中西医结合学会肝病专业委员会. 肝纤维化中西医结合诊疗指南(2019年版)[J]. 临床肝胆病杂志, 2019, 35(7): 1444-1449. DOI: 10.3969/j.issn.1001-5256.2019.07.007.
[4]	RONG G, CHEN Y, YU Z, 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.
[5]	JI D, CHEN Y, BI J, 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.
[6]	WU YY. Effect of compound Biejia Ruangan Tablet on HBV DNA replication and hepatic fibrosis in patients with hepatitis B cirrhosis[J]. J North Pharm, 2018, 15(3): 22-23. DOI: 10.3969/j.issn.1672-8351.2018.03.013. 吴玉叶. 复方鳖甲软肝片对乙肝肝硬化患者HBV-DNA复制及肝纤维化的影响[J]. 北方药学, 2018, 15(3): 22-23. DOI: 10.3969/j.issn.1672-8351.2018.03.013.
[7]	ZHANG L, SCHUPPAN D. Traditional Chinese Medicine (TCM) for fibrotic liver disease: hope and hype[J]. J Hepatol, 2014, 61(1): 166-168. DOI: 10.1016/j.jhep.2014.03.009.
[8]	CHEN WJ, MAO X, GUO XD, et al. Investigation on anti-liver cancer potential and compatibility characteristics of Fufang Biejia Ruangan Pian from network perspective[J]. Chin J Exp Med Formul, 2020, 26(24): 11-22. DOI: 10.13422/j.cnki.syfjx.20202352. 陈文佳, 毛霞, 郭晓东, 等. 从网络视角探讨复方鳖甲软肝片的抗肝癌潜能及其组方功效配伍特点[J]. 中国实验方剂学杂志, 2020, 26(24): 11-22. DOI: 10.13422/j.cnki.syfjx.20202352.
[9]	SU ZB. Effect analysis of Compound Biejia Ruangan Tablet and Entecavir on Cirrhosis after hepatitis B[J]. Clin Res, 2018, 26(2): 170-172. DOI: 10.3969/j.issn.1004-8650.2018.02.094. 苏志波. 复方鳖甲软肝片与恩替卡韦治疗乙肝后肝硬化的效果分析[J]. 临床研究, 2018, 26(2): 170-172. DOI: 10.3969/j.issn.1004-8650.2018.02.094.
[10]	ZHOU J, CHEN XM, LIU SW, et al. Effects of Biejia Ruangan Tablet-containing serum on matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in cultured renal interstitial fibroblasts[J]. Chin J Integr Med, 2015, 21(2): 152-156. DOI: 10.1007/s11655-014-1784-0.
[11]	YANG FR, FANG BW, LOU JS. Effects of Fufang Biejia Ruangan pills on hepatic fibrosis in vivo and in vitro[J]. World J Gastroenterol, 2013, 19(32): 5326-5333. DOI: 10.3748/wjg.v19.i32.5326.
[12]	GUO SG, ZHANG W, JIANG T, et al. Influence of serum collected from rat perfused with compound Biejiaruangan drug on hepatic stellate cells[J]. World J Gastroenterol, 2004, 10(10): 1487-1494. DOI: 10.3748/wjg.v10.i10.1487.
[13]	ZHAO ZJ, ZHANG XX, YANG MJ, et al. Effects of Fufangbiejiaruangan Tablets on expression of TGF-β1 and mRNA in rat renal cortex after unilateral ureteral obstraction[J]. J Beijing Univ Chin Med, 2005, 28(2): 23-25. DOI: 10.3321/j.issn:1006-2157.2005.02.010. 赵宗江, 张新雪, 杨美娟, 等. 复方鳖甲软肝片对输尿管结扎大鼠肾组织TGF-β1蛋白及其mRNA表达的影响[J]. 北京中医药大学学报, 2005, 28(2): 23-25. DOI: 10.3321/j.issn:1006-2157.2005.02.010.
[14]	ZHANG DW, WANG JF, NIU JZ, et al. Influence of compound biejia ruangan prescription on extracelluar matrix in bleomycin induced pulmonary fibrosis rats[J]. China J Chin Mater Med, 2004, 29(1): 62-66. DOI: 10.3321/j.issn:1001-5302.2004.01.019. 张东伟, 王继峰, 牛建昭, 等. 复方鳖甲软肝方对肺纤维化大鼠细胞外基质的影响[J]. 中国中药杂志, 2004, 29(1): 62-66. DOI: 10.3321/j.issn:1001-5302.2004.01.019.
[15]	ZHAO JM, ZHOU GD, LI WS, et al. An experimental study on the mechanism of anti-hepatic fibrosis with Chinese medicinal herbs Fufangbiejiaruanganpian[J]. Med J Chin PLA, 2004, 29(7): 560-562. DOI: 10.3321/j.issn:0577-7402.2004.07.002. 赵景民, 周光德, 李文淑, 等. 复方鳖甲软肝片抗肝纤维化机制的实验研究[J]. 解放军医学杂志, 2004, 29(7): 560-562. DOI: 10.3321/j.issn:0577-7402.2004.07.002.
[16]	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.
[17]	HASSANEIN T, TAI D, LIU C, et al. Efficacy and safety of a botanical formula fuzheng huayu for hepatic fibrosis in patients with CHC: Results of a phase 2 clinical trial[J]. Evid Based Complement Alternat Med, 2022, 2022: 4494099. DOI: 10.1155/2022/4494099.
[18]	SHI K, LIU Y, WANG X, 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.
[19]	MIAO L, YANG WN, DONG XQ, et al. Combined anluohuaxianwan and entecavir treatment significantly improve the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection[J]. Chin J Hepatol, 2019, 27(7): 521-526. DOI: 10.3760/cma.j.issn.1007-3418.2019.07.009. 苗亮, 杨婉娜, 董晓琴, 等. 安络化纤丸联合恩替卡韦治疗可显著提高慢性乙型肝炎病毒感染者肝纤维化的改善率[J]. 中华肝脏病杂志, 2019, 27(7): 521-526. DOI: 10.3760/cma.j.issn.1007-3418.2019.07.009.
[20]	WANG GQ. The latest research progress of Anluo Chemical Fiber in reversing liver fibrosis/cirrhosis during the 13th Five-Year Plan[R]. Beijing: The 15th Beijing Forum on Infectious Diseases and Liver Diseases, 2022. 王贵强. 安络化纤逆转肝纤维化/肝硬化十三五重大专项最新研究进展[R]. 北京: 第十五届北京感染病和肝病论坛, 2022.