PDF下载 ( 749 KB)
慢性乙型肝炎中医临床疗效评价体系的构建与思考
DOI: 10.12449/JCH260502
利益冲突声明：本文不存在任何利益冲突。
作者贡献声明：赵孝良负责撰写论文；雒琳负责相关文献的检索、筛选与整理；何丽云负责拟定写作思路，指导文章框架结构，修改论文。何丽云和赵孝良对本文贡献等同，同为第一作者。
Construction of a clinical efficacy evaluation system for traditional Chinese medicine treatment of chronic hepatitis B and related reflections
-
摘要: 中医药在我国慢性乙型肝炎的临床实践中应用广泛，在改善症状、调节机体状态及辅助干预疾病进展等方面具有一定优势。但是，慢性乙型肝炎中医临床疗效评价尚存在评价体系不完整，评价指标选择不一致，证候与症状评价的客观化和标准化程度有限，制约了中医药疗效证据的系统积累及其在临床指南和专家共识中的应用。本文系统梳理慢性乙型肝炎中医临床疗效评价的研究现状，分析了国家科技计划“十一五”至“十三五”期间，我国重大传染病专项的中医、中西医结合治疗慢性肝病领域取得的成就，以及目前仍然需要解决的评价体系相关问题，从评价目标、指标构成和应用场景等方面提出构建中医临床疗效评价体系的思路与具体内容，以期为相关标准制定、临床研究及中西医结合诊疗规范提供参考。Abstract: Traditional Chinese medicine （TCM） is widely used in the clinical management of chronic hepatitis B in China and has exhibited certain advantages in alleviating symptoms， regulating overall physiological status， and assisting in the intervention against disease progression. However， there is still a lack of a comprehensive clinical efficacy evaluation system for TCM treatment of chronic hepatitis B， with inconsistencies in the selection of evaluation indicators and limited objectivity and standardization in the assessment of syndromes and symptoms， which have limited the systematic accumulation of evidence regarding TCM efficacy and the incorporation of TCM into clinical guidelines and expert consensus statements. This article systematically reviews the current status of research on the clinical efficacy evaluation of TCM for chronic hepatitis B and analyzes the achievements made in the field of TCM therapy and integrated traditional Chinese and Western medicine therapy for chronic liver diseases in China’s national major infectious disease research programs during the periods of the Eleventh to Thirteenth Five-Year Plans. It also points out related issues that remain to be addressed and proposes a conceptual framework and specific components for constructing a TCM clinical efficacy evaluation system from the perspectives of evaluation objectives， indicator composition， and application scenarios， in order to provide a reference for the development of related standards， clinical research， and the standardization of integrated traditional Chinese and Western medicine diagnosis and treatment.
-
注： PRO，患者报告结局；ALT，丙氨酸氨基转移酶；AST，天冬氨酸氨基转移酶；TBil，总胆红素；LSM，肝硬度值；HBV，乙型肝炎病毒；HCC，肝细胞癌。
图 1 慢性乙型肝炎中医临床疗效评价体系构建思路图
Figure 1. Diagram of the construction framework for the traditional Chinese medicine clinical efficacy evaluation system in chronic hepatitis B
表 1 中医药参与CHB 治疗的历程分析
Table 1. Analysis of the participation of traditional Chinese medicine in the treatment of chronic hepatitis B
阶段 主要背景与政策环境 中医药参与方式 评价与研究关注重点 阶段性意义 国际指南主导阶段
（2007年至今）WHO［14］、EASL［15］、AASLD［16］ 等
发布CHB诊疗指南中医药仅作为补充
或替代医学被提及HBV DNA、ALT、肝纤维
化分期及并发症风险确立以抗病毒治疗为
核心的国际诊疗范式国内中西医并行探索
期（1990—2018年）我国CHB防治需求突出［17］ 中医药作为协同干
预参与临床实践症状改善、肝功能变化 形成中西医并行治疗
的实践基础国家指南纳入阶段
（2019年至今）《慢性乙型肝炎防治指南（2019
年版）》［4］和《慢性乙型肝炎防治
指南（2022年版）》［5］发布部分中成药以“可考
虑”形式纳入抗纤维
化治疗抗纤维化治疗证据与辅
助干预疗效中医药首次以循证形
式进入国家级CHB指
南体系中医/中西医结合指南
细化阶段（2018年
至今）中医及中西医结合诊疗指南、专
家共识发布基于疾病分期引入
证候分型，形成分阶
段干预策略病程分期+证候分层+分
阶段干预构建“病程分期-证候
分层”的中西医结合诊
疗路径国家科研系统推进阶
段（约2006年至今）“十一五”以来国家重大专项与
重点研发计划中医药系统介入
CHB全病程治疗和
管理症状、生活质量、血清学
应答、纤维化及重症
结局构建覆盖早期-活动
期-重症-肿瘤预防的
研究体系结局导向与长期管理
阶段（2019年至今）大样本、多中心与长期随访研究
开展中医/中西医结合用
于重症及长期管理病死率、纤维化逆转、远
期预后疗效评价由症状导向
延伸至关键临床结局评价方法学规范化阶
段（2020年至今）核心结局指标集研究推进 建立标准化结局指
标体系患者报告结局、客观指
标与现代终点对接提升中医证据的可重
复性与国际可对话性注：CHB，慢性乙型肝炎；WHO，世界卫生组织；EASL，欧洲肝病学会；AASLD，美国肝病学会；HBV，乙型肝炎病毒；ALT，丙氨酸氨基转移酶。
下载: 导出CSV
-
[1] World Health Organization. Hepatitis B[EB/OL].( 2025-07-23)[ 2026-02-02]. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b [2] European Association for The Study of The Liver. EASL Clinical Practice Guidelines on the management of hepatitis B virus infection[J]. J Hepatol, 2025, 83( 2): 502- 583. DOI: 10.1016/j.jhep.2025.03.018. [3] TERRAULT NA, LOK ASF, MCMAHON BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance[J]. Hepatology, 2018, 67( 4): 1560- 1599. DOI: 10.1002/hep.29800. [4] Chinese Society of Infectious Diseases, Chinese Medical Association; Chinese Society of Hepatology, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B(version 2019)[J]. J Clin Hepatol, 2019, 35( 12): 2648- 2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007.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]. 临床肝胆病杂志, 2019, 35( 12): 2648- 2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007. [5] Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Infectious Diseases, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B[J]. Infect Dis Inf, 2023, 36( 1): 1- 17. DOI: 10.3969/j.issn.1007-8134.2023.01.01.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]. 传染病信息, 2023, 36( 1): 1- 17. DOI: 10.3969/j.issn.1007-8134.2023.01.01. [6] Hepatobiliary Specialized Committee of China Association of Chinese Medicine, Liver Diseases Specialized Committee of China Medical Associa- tion of Minorities. The clinical guidelines of diagnosis and treatment of chronic hepatitis B with traditional Chinese medicine(2018)[J]. J Clin Hepatol, 2018, 34( 12): 2520- 2525. DOI: 10.3969/j.issn.1001-5256.2018.12.007.中华中医药学会肝胆病专业委员会, 中国民族医药学会肝病专业委员会. 慢性乙型肝炎中医诊疗指南(2018年版)[J]. 临床肝胆病杂志, 2018, 34( 12): 2520- 2525. DOI: 10.3969/j.issn.1001-5256.2018.12.007. [7] Expert Committee on Hepatology, Doctor Society of Integrative Medicine, Chinese Medical Doctor Association. Expert consensus on integrated traditional Chinese and Western medicine diagnosis and treatment of chronic hepatitis B[J]. J Clin Hepatol, 2024, 40( 5): 884- 892. DOI: 10.12449/JCH240507.中国医师协会中西医结合医师分会肝病学专家委员会. 慢性乙型肝炎中西医结合诊疗专家共识[J]. 临床肝胆病杂志, 2024, 40( 5): 884- 892. DOI: 10.12449/JCH240507. [8] The Digestive System Diseases Professional Committee of the Chinese Society of Integrated Traditional Chinese and Western Medicine. Expert Consensus on Diagnosis and Treatment of chronic hepatitis B with the Integrated Traditional Chinese and Western Medicine(2025)[J]. J Clin Hepatol, 2026, 42( 1): 33- 46. DOI: 10.12449/JCH260106.中国中西医结合学会消化系统疾病专业委员会. 慢性乙型肝炎中西医结合诊疗专家共识(2025年)[J]. 临床肝胆病杂志, 2026, 42( 1): 33- 46. DOI: 10.12449/JCH260106. [9] YE YA. An integrated traditional Chinese and Western Medicine study on the comprehensive prevention and treatment of chronic hepatitis B and its related diseases[J]. J Clin Hepatol, 2023, 39( 6): 1257- 1266. DOI: 10.3969/j.issn.1001-5256.2023.06.001.叶永安. 慢性乙型肝炎及其相关疾病一体化治疗的中西医结合研究[J]. 临床肝胆病杂志, 2023, 39( 6): 1257- 1266. DOI: 10.3969/j.issn.1001-5256.2023.06.001. [10] GAO YQ. Clinical practice of traditional chinese medicine in the management of chronic hepatitis B[Z]. Shanghai, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 2021-08-31.高月求. 中医药防治慢性乙型肝炎的临床实践[Z]. 上海, 上海中医药大学附属曙光医院, 2021-08-31. [11] ZHU XJ, ZHANG JH, SUN XH, et al. Clinical efficacy and mechanism of action of kidney-tonifying, spleen-strengthening, and diuresis-promoting therapy in treatment of chronic hepatitis B[J]. J Clin Hepatol, 2023, 39( 6): 1274- 1279. DOI: 10.3969/j.issn.1001-5256.2023.06.003.朱晓骏, 张景豪, 孙学华, 等. 补肾健脾利湿法治疗慢性乙型肝炎临床效果及相关机制研究[J]. 临床肝胆病杂志, 2023, 39( 6): 1274- 1279. DOI: 10.3969/j.issn.1001-5256.2023.06.003. [12] ZHOU C, GONG M, ZHANG N, et al. Study on the intervention of integrated traditional Chinese and Western medicine therapy in patients with hepatitis B virus-related acute-on-chronic liver failure[J]. Chin J Integr Tradit West Med Liver Dis, 2019, 29( 3): 203- 207. DOI: 10.3969/j.issn.1005-0264.2019.03.004.周超, 宫嫚, 张宁, 等. 中西医结合治疗方案干预乙型肝炎病毒相关慢加急性肝衰竭的疗效分析[J]. 中西医结合肝病杂志, 2019, 29( 3): 203- 207. DOI: 10.3969/j.issn.1005-0264.2019.03.004. [13] SUN YN, HE LY, LUO L, et al. Core outcome sets of traditional Chinese medicine on the treatments of chronic hepatitis B clinical trails[J]. China J Tradit Chin Med Pharm, 2020, 35( 9): 4684- 4688.孙亚男, 何丽云, 雒琳, 等. 中医药治疗慢性乙型肝炎临床试验的核心结局指标集研究[J]. 中华中医药杂志, 2020, 35( 9): 4684- 4688. [14] World Health Organization. Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection[R]. Geneva: World Health Organization, 2015-03-01. https://www.who.int/publications/i/item/9789241549059. [15] European Association for The Study of The Liver. EASL Clinical Practice Guidelines: Management of chronic hepatitis B[J]. J Hepatol, 2009, 50( 2): 227- 242. DOI: 10.1016/j.jhep.2008.10.001. [16] LOK ASF, MCMAHON BJ. Chronic hepatitis B[J]. Hepatology, 2007, 45( 2): 507- 539. DOI: 10.1002/hep.21513. [17] ZHOU N. Discussion on syndrome differentiation and treatment of chronic hepatitis B[J]. J Pract Tradit Chin Intern Med, 1990, 4( 2): 20.周宁. 慢性乙型肝炎证治刍议[J]. 实用中医内科杂志, 1990, 4( 2): 20. [18] FENG YK, LIU YM, CHEN QL. Research progress on traditional Chinese medicine and western medicine in treatment of cirrhosis due to hepatitis B[J]. China Med Her, 2016, 13( 29): 28- 31.冯因克, 刘亚敏, 陈启龙. 慢性乙型肝炎后肝硬化中西医治疗研究进展[J]. 中国医药导报, 2016, 13( 29): 28- 31. [19] DONG YY, XIANG Y. Clinical observation of Hugan tablet combined with entecavir on elderly patients with chronic hepatitis B and its influence on endothelial function and liver fibrosis[J]. Chin J Gerontol, 2019, 39( 20): 4990- 4992.董亚云, 向阳. 护肝片联合恩替卡韦对老年慢性乙型肝炎患者疗效观察及对内皮功能和肝纤维化的影响[J]. 中国老年学杂志, 2019, 39( 20): 4990- 4992. [20] LIN H, WU Y, MO Q, et al. Clinical observation on compound Huanggen Granules combined with entecavir tablets in treating chronic hepatitis B with syndrome of collateral retardation due to blood stasis[J]. Chin J Exp Tradit Med Formulae, 2020, 26( 21): 142- 148.林海, 吴悠, 莫琼, 等. 复方黄根颗粒联合恩替卡韦治疗慢性乙肝瘀血阻络证临床观察[J]. 中国实验方剂学杂志, 2020, 26( 21): 142- 148. [21] ZHANG CL, LI J, HUO RJ, et al. Effects of modified Chaihu Shugan Powder combined with antiviral drugs on prognosis of patients with chronic hepatitis B[J]. Eval Anal Drug Use Hosp China, 2023, 23( 2): 203- 207. DOI: 10.14009/j.issn.1672-2124.2023.02.016.张翠丽, 李静, 霍瑞静, 等. 柴胡疏肝散加减联合抗病毒药对慢性乙型肝炎患者预后的影响[J]. 中国医院用药评价与分析, 2023, 23( 2): 203- 207. DOI: 10.14009/j.issn.1672-2124.2023.02.016. [22] WU YF. Clinical study on the effect of warming meridian and removing depression on the quality of life and immune function of patients with chronic hepatitis B complicated with anxiety disorder[J]. Heilongjiang Med Pharm, 2019, 42( 5): 235- 236.吴艺锋. 温经开郁法对慢性乙型肝炎合并焦虑障碍患者生存质量及免疫功能影响的临床研究[J]. 黑龙江医药科学, 2019, 42( 5): 235- 236. [23] XU Q, XIONG ZF, MA L, et al. Meta-analysis of traditional Chinese medicine combined with entecavir in the treatment of chronic hepatitis B with liver depression and spleen deficiency[J]. Lishizhen Med Mater Med Res, 2018, 29( 2): 495- 500.徐倩, 熊振芳, 马利, 等. 中药联合恩替卡韦治疗肝郁脾虚型慢性乙型肝炎的Meta分析[J]. 时珍国医国药, 2018, 29( 2): 495- 500. [24] LIU HM, GUO YM, WANG RL, et al. Systematic evaluation of Liuweiwuling Tablets for treatment of liver fibrosis resulting from chronic hepatitis B[J]. Chin Tradit Herb Drugs, 2016, 47( 17): 3133- 3142. DOI: 10.7501/j.issn.0253-2670.2016.17.029.刘慧敏, 郭玉明, 王睿林, 等. 六味五灵片联合核苷(酸)类药物治疗慢性乙型肝炎肝纤维化的系统评价[J]. 中草药, 2016, 47( 17): 3133- 3142. DOI: 10.7501/j.issn.0253-2670.2016.17.029. [25] YOUNOSSI ZM, GUYATT G, KIWI M, et al. Development of a disease specific questionnaire to measure health related quality of life in patients with chronic liver disease[J]. Gut, 1999, 45( 2): 295- 300. DOI: 10.1136/gut.45.2.295. [26] TAO JX, LI XD, GAO XL, et al. Application of Omni-directional follow-up management in traditional Chinese medicine clinical research for chronic hepatitis B patients[J]. Chin Nurs Res, 2018, 32( 17): 2767- 2769. DOI: 10.12102/j.issn.1009-6493.2018.17.032.陶军秀, 李晓东, 高小莲, 等. 全方位随访管理在慢性乙型肝炎病人中医药临床研究中的应用[J]. 护理研究, 2018, 32( 17): 2767- 2769. DOI: 10.12102/j.issn.1009-6493.2018.17.032. [27] REN S, ZHANG H, HU XC, et al. Meta-analysis of the clinical efficacy of combination therapy with traditional Chinese medicine and nucleoside analogue antiviral drugs for chronic hepatitis B[J]. J Clin Hepatol, 2013, 29( 4): 264- 269, 275.任爽, 张华, 胡鑫才, 等. 中药联合核苷和核苷酸类药物治疗慢性乙型肝炎的系统评价[J]. 临床肝胆病杂志, 2013, 29( 4): 264- 269, 275. [28] GUI HL, ZHAO CQ, WANG Y, et al. Histological outcome of fuzheng Huayu plus entecavir combination therapy in chronic hepatitis B patients with significant liver fibrosis[J]. J Clin Transl Hepatol, 2020, 8( 3): 277- 284. DOI: 10.14218/JCTH.2020.00004. [29] 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. [30] WU XQ, LU XZ. Research on methods of traditional Chinese medicine for evaluating objective efficacy in treating chronic hepatitis B[J]. J Tianjin Univ Tradit Chin Med, 2014, 33( 4): 199- 203. DOI: 10.11656/j.issn.1673-9043.2014.03.03.吴喜庆, 陆小左. 慢性乙型肝炎中医客观化疗效评价方法研究[J]. 天津中医药大学学报, 2014, 33( 4): 199- 203. DOI: 10.11656/j.issn.1673-9043.2014.03.03. [31] ZHANG LY, WANG GQ, HOU WH, et al. Contemporary clinical research of traditional Chinese medicines for chronic hepatitis B in China: An analytical review[J]. Hepatology, 2010, 51( 2): 690- 698. DOI: 10.1002/hep.23384. [32] ZHANG QY, LI Y, MIAO L, et al. Syndrome representation biology and research on traditional Chinese medicine[J]. Chin Sci Bull, 2025, 70( 35): 6010- 6026.张秋艳, 李瑛, 苗兰, 等. 证候表征生物学与中医药研究[J]. 科学通报, 2025, 70( 35): 6010- 6026. [33] TU A, ZHU XN, DASTJERDI PZ, et al. Evaluate the clinical efficacy of traditional Chinese Medicine as the neoadjuvant treatment in reducing the incidence of hepatocellular carcinoma in patients with hepatitis B-related cirrhosis: A systematic review and meta-analysis[J]. Heliyon, 2024, 10( 3): e24437. DOI: 10.1016/j.heliyon.2024.e24437. [34] TSAI TY, LIVNEH H, HUNG TH, et al. Associations between prescribed Chinese herbal medicine and risk of hepatocellular carcinoma in patients with chronic hepatitis B: A nationwide population-based cohort study[J]. BMJ Open, 2017, 7( 1): e014571. DOI: 10.1136/bmjopen-2016-014571. [35] ZHOU ZH, SUN XH, ZHU XJ, et al. The clinical research of Bushenjianpi formulae combined entecavir in treating hepatitis HBeAg positive chronic hepatitis B[J]. Chin J Integr Tradit West Med Liver Dis, 2021, 31( 7): 590- 592. DOI: 10.3969/j.issn.1005-0264.2021.07.004.周振华, 孙学华, 朱晓骏, 等. 补肾健脾方联合恩替卡韦治疗HBeAg阳性慢性乙型肝炎患者的临床研究[J]. 中西医结合肝病杂志, 2021, 31( 7): 590- 592. DOI: 10.3969/j.issn.1005-0264.2021.07.004. [36] YE YA, LI XK, ZHOU DQ, et al. Chinese herbal medicine combined with entecavir for HBeAg positive chronic hepatitis B: Study protocol for a multi-center, double-blind randomized-controlled trial[J]. Chin J Integr Med, 2018, 24( 9): 653- 660. DOI: 10.1007/s11655-018-3011-5. [37] PENG DT, XING YF, WEI CS, et al. Clinic study of the method of invigorating the kidney and detoxification on the immune resistance in chronic HBV carriers[J]. Lishizhen Med Mater Med Res, 2016, 27( 12): 2949- 2951. DOI: 10.3969/j.issn.1008-0805.2016.12.044.彭得倜, 邢宇锋, 魏春山, 等. 补肾解毒方对慢性HBV携带者免疫耐受的临床研究[J]. 时珍国医国药, 2016, 27( 12): 2949- 2951. DOI: 10.3969/j.issn.1008-0805.2016.12.044. [38] LI FY, MAO DW, WANG LF, et al. Construction of retrospective syndrome survey database of CSHB[J]. Chin Arch Tradit Chin Med, 2011, 29( 7): 1494- 1497.李丰衣, 毛德文, 王立福, 等. 慢性乙型重型肝炎回顾性证候研究数据库的建立[J]. 中华中医药学刊, 2011, 29( 7): 1494- 1497. [39] JIANG H, YU HS, HU C, et al. Liver stiffness measurement trajectory analysis for prognosis in patients with chronic hepatitis B and compensated advanced chronic liver disease[J]. Ann Hepatol, 2025, 30( 1): 101788. DOI: 10.1016/j.aohep.2025.101788. [40] VUTIEN P, BARNARD GIUSTINI A, KIM NJ, et al. Validation and expansion of Baveno VII criteria for cACLD and CSPH based on liver stiffness and platelet count: Correlation with risk of hepatic decompensation and death[J]. Hepatology, 2025, 82( 2): 422- 437. DOI: 10.1097/HEP.0000000000001183. [41] KONG DZ, LIANG N, YANG GL, et al. Acupuncture for chronic hepatitis B[J]. Cochrane Database Syst Rev, 2019, 8( 8): CD013107. DOI: 10.1002/14651858.cd013107.pub2. [42] LAZAR A, SPOREA I, POPA A, et al. Dynamic changes in liver stiffness in patients with chronic hepatitis B undergoing antiviral therapy[J]. Diagnostics(Basel), 2022, 12( 11): 2646. DOI: 10.3390/diagnostics12112646. [43] World Health Organization. WHO international standard terminologies on traditional Chinese medicine[R]. Geneva: World Health Organization, 2022-03-03. https://www.who.int/publications/i/item/9789240042322. [44] LUO Y, ZHAO X, WANG RL, et al. Integrated evidence chain-based effectiveness evaluation of traditional Chinese medicines(Eff-iEC): A demonstration study[J]. Acta Pharm Sin B, 2025, 15( 2): 909- 918. DOI: 10.1016/j.apsb.2024.12.024. -
本文二维码
图(1) / 表(1)
计量
- 文章访问数: 13
- HTML全文浏览量: 3
- PDF下载量: 2
- 被引次数: 0
