酒精性肝病(ALD)是中国主要的肝脏疾病之一,多由长期大量饮酒引起,初起多表现为脂肪肝、肝炎,随着肝脏纤维化加重,有可能会发展为肝硬化甚至肝癌。西医治疗ALD缺乏特效药物,目前临床上治疗原则以保肝为主,但疗效并不十分显著。近年来,中医药治疗ALD的研究进展不断更新,单味中药及复方的研究证实中医药在治疗ALD的显著成效。本文总结了ALD的危险因素、发病机制以及目前中西药治疗ALD的现有数据,以期为临床应用提供参考。
Alcoholic liver disease (ALD) is one type of the main liver disorders in China caused by chronic heavy alcoholic drinking, appearing as fatty liver, hepatitis in the first stage, with the aggravation of liver fibrosis, then may develop into cirrhosis, or even liver cancer. At present, the western clinical treating principle of alcoholic liver disease is mainly protecting the liver, which doesn’t attain an obvious curative effect resulted from the lack of specific medicine. Recently, the research focused on single herb and formulations affirms the remarkable effect of treating ALD by TCM, leading to the advances update. The article is expected to be available for clinical consultation by summarizing ALD’s risk factors, pathogenesis, as well as treatment based on TCM and western medicine of ALD.
酒精性肝病,中医,西医,研究进展, Alcoholic Liver Disease Traditional Chinese Medicine Western Medicine Recent Advances摘要
Alcoholic liver disease (ALD) is one type of the main liver disorders in China caused by chronic heavy alcoholic drinking, appearing as fatty liver, hepatitis in the first stage, with the aggravation of liver fibrosis, then may develop into cirrhosis, or even liver cancer. At present, the western clinical treating principle of alcoholic liver disease is mainly protecting the liver, which doesn’t attain an obvious curative effect resulted from the lack of specific medicine. Recently, the research focused on single herb and formulations affirms the remarkable effect of treating ALD by TCM, leading to the advances update. The article is expected to be available for clinical consultation by summarizing ALD’s risk factors, pathogenesis, as well as treatment based on TCM and western medicine of ALD.
Keywords:Alcoholic Liver Disease, Traditional Chinese Medicine, Western Medicine, Recent Advances
房雨晨,沈 楠,喻 晓,潘洁露,缪虹雨,王睿清,张海燕,邢练军. 中西医治疗酒精性肝病的研究进展Research Progress of TCM and Western Medicine Treatment of Alcoholic Liver Disease[J]. 中医学, 2022, 11(04): 604-613. https://doi.org/10.12677/TCM.2022.114085
参考文献ReferencesCollaborators, G.A. and Rahman, M.A. (2018) Alcohol Use and Burden for 195 Countries and Territories, 1990-2016: A Systematic Analysis for the Global Burden of Disease Study 2016. The Lancet, 392, 1015-1035.
<br>https://doi.org/10.1016/S0140-6736(18)31310-2黄颖. 刺梨解酒口服液研发及功能性评价[D]: [硕士学位论文]. 贵阳: 贵州大学, 2020.Axley, P.D., Richardson, C.T. and Singal, A.K. (2019) Epidemiology of Alcohol Consumption and Societal Burden of Alcoholism and Alcoholic Liver Disease. Clinics in Liver Disease, 23, 39-50. <br>https://doi.org/10.1016/j.cld.2018.09.011孟文文, 刘慧茹, 张文光, 马智慧, 邓志鹏, 赵东升, 等. 中药防治酒精性肝病作用机制的研究进展[J]. 中草药, 2022, 53(3): 868-881.Dunn, W. and Shah Vijay, H. (2016) Pathogenesis of Alcoholic Liver Disease. Clinics in Liver Disease, 20, 445-456.
<br>https://doi.org/10.1016/j.cld.2016.02.004中华医学会, 中华医学会杂志社, 中华医学会消化病学分会, 中华医学会全科医学分会, 中华医学会《中华全科医师杂志》编辑委员会, 消化系统疾病基层诊疗指南编写专家组. 酒精性肝病基层诊疗指南(2019年) [J]. 临床肝胆病杂志, 2021, 36(1): 36-40.何志勇, 黄先菊. 不同种类酒精饮料与小鼠酒精性肝病的关系研究[J]. 绿色科技, 2019(14): 214-215+220.Delacôte, C., Bauvin, P., Louvet, A., Dautrecque, F., Ntandja Wandji, L.C., Lassailly, G., et al. (2020) A Model Toidentify Heavy Drinkers at High Risk for Liver Diseaseprogression. Clinical Gastroenterology and Hepatology, 18, 2315-2323, e6. <br>https://doi.org/10.1016/j.cgh.2019.12.041Choudhary, N.S. and Duseja, A. (2021) Genetic and Epigenetic Disease Modifiers: Non-Alcoholic Fatty Liver Disease (NAFLD) and Alcoholic Liver Disease (ALD). Translational Gastroenterology and Hepatology, 6, 1-17.
<br>https://doi.org/10.21037/tgh.2019.09.06Méndez, C. and Rey, M. (2015) Characterization of Polymorphisms of Genes ADH2, ADH3, ALDH2 and CYP2E1 and Relationship to the Alcoholism in a Colombian Population. Colombia Médica, 46, 176-182.
<br>https://doi.org/10.25100/cm.v46i4.1668姚锦慧, 赵秋冬, 熊鹏芬, 何冬梅, 姚丽仙, 朱艳平, 等. 云南元江少数民族酒精性肝病流行病学调查[J]. 胃肠病学和肝病学杂志, 2011, 20(12): 1137-1139.Singal, A.K., Bataller, R., Ahn, J., Kamath, P.S. and Shah, V.H. (2018) ACG Clinical Guideline: Alcoholic Liver Disease. American Journal of Gastroenterology, 113, 175-194. <br>https://doi.org/10.1038/ajg.2017.469Hart, C.L., Morrison, D., Batty, G.D., Mitchell, R.J. and Davey Smith, G. (2010) Effect of Body Mass Index and Alcohol Consumption on Liver Disease: Analysis of Data from Two Prospective Cohort Studies. BMJ, 340, Article No. c1240. <br>https://doi.org/10.1136/bmj.c1240Seitz, H.K., Bataller, R., Cortez-Pinto, H., Gao, B., Gual, A., Lackner, C., et al. (2018) Alcoholic Liver Disease. Nature Reviews Disease Primers, 4, Article No. 16. <br>https://doi.org/10.1038/s41572-018-0014-7Nahon, P., Nuraldeen, R., Rufat, P., Sutton, A., Trautwein, C. and Strnad, P. (2016) In Alcoholic Cirrhosis, Low-Serum Hepcidin Levels Associate with Poor Long-Term Survival. Liver International, 36, 185-188.
<br>https://doi.org/10.1111/liv.13007Styskel, B., Natarajan, Y. and Kanwal, F. (2019) Nutrition in Alcoholic Liver Disease: An Update. Clinics in Liver Disease, 23, 99-114. <br>https://doi.org/10.1016/j.cld.2018.09.012许蓬娟, 蔡青, 谭俊珍. 酒精性肝病发生机制的研究进展[J]. 海南医学, 2021, 32(12): 1600-1604.Ceni, E., Mello, T. and Galli, A. (2014) Pathogenesis of Alcoholic Liver Disease: Role of Oxidative Metabolism. World Journal of Gastroenterology, 20, 17756-17772. <br>https://doi.org/10.3748/wjg.v20.i47.17756Hyun, J., Han, J., Lee, C., Yoon, M. and Jung, Y. (2021) Pathophysiological Aspects of Alcohol Metabolism in the Liver. International Journal of Molecular Sciences, 22, Article No. 5717. <br>https://doi.org/10.3390/ijms22115717Kourkoumpetis, T. and Sood, G. (2019) Pathogenesis of Alcoholic Liver Disease: An Update. Clinics in Liver Disease, 23, 71-80. <br>https://doi.org/10.1016/j.cld.2018.09.006Kong, L.Z., Chandimali, N., Han, Y.H., Lee, D.-H., Kim, J.-S., Kim, S.-U., et al. (2019) Pathogenesis, Early Diagnosis, and Therapeutic Management of Alcoholic Liver Disease. International Journal of Molecular Sciences, 20, Article No. 2712. <br>https://doi.org/10.3390/ijms20112712Woodhouse, C.A., Patel, V.C., Singanayagam, A. and Shawcross, D.L. (2018) Review Article: The Gut Microbiome as a Therapeutic Target in the Pathogenesis and Treatment of Chronic Liver Disease. Alimentary Pharmacology & Therapeutics, 47, 192-202. <br>https://doi.org/10.1111/apt.14397Colakoglu, M., Xue, J. and Trajkovski, M. (2020) Bacteriophage Prevents Alcoholic Liver Disease. Cell, 180, 218-220.
<br>https://doi.org/10.1016/j.cell.2019.12.034Albhaisi, S.A.M., Bajaj, J.S. and Sanyal, A.J. (2020) Role of Gut Microbiota Inliver Disease. American Journal of Physiology-Gastrointestinal and Liver Physiology, 318, G84-G98. <br>https://doi.org/10.1152/ajpgi.00118.2019Gao, B., Ahmad, M.F., Nagy, L.E. and Tsukamoto, H. (2019) Inflammatory Pathways in Alcoholic Steatohepatitis. Journal of Hepatology, 70, 249-259. <br>https://doi.org/10.1016/j.jhep.2018.10.023Kawaratani, H., Moriya, K., Namisaki, T., Uejima, M., Kitade, M., Takeda, K., et al. (2017) Therapeutic Strategies for Alcoholic Liver Disease: Focusing on Inflammation and Fibrosis (Review). International Journal of Molecular Medicine, 40, 263-270. <br>https://doi.org/10.3892/ijmm.2017.3015Shim, Y.R. and Jeong, W.I. (2020) Recent Advances of Sterile Inflammation and Inter-Organ Cross-Talk in Alcoholic Liver Disease. Experimental & Molecular Medicine, 52, 772-780. <br>https://doi.org/10.1038/s12276-020-0438-5Li, L.X., Guo, F.F., Liu, H. and Zeng, T. (2022) Iron Overload in Alcoholic Liver Disease: Underlying Mechanisms, Detrimental Effects, and Potential Therapeutic Targets. Cellular and Molecular Life Sciences, 79, Article No. 201.
<br>https://doi.org/10.1007/s00018-022-04239-9Salehi, E., Mashayekh, M., Taheri, F., Gholami, M., Motaghinejad, M., Safari, S., et al. (2021) Curcumin Can Be Acts as Effective agent for Prevent or Treatment of Alcohol-Induced Toxicity in Hepatocytes: An Illustrated Mechanistic Review. Iranian Journal of Pharmaceutical Research, 20, 418-436.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.Meroni, M., Longo, M. and Dongiovanni, P. (2019) Alcohol or Gut Microbiota: Who Is the Guilty? International Journal of Molecular Sciences, 20, Article No. 4568. <br>https://doi.org/10.3390/ijms20184568Arnedt, J.T., Cardoni, M.E., Conroy, D.A., Graham, M., Amin, S., Bohnert, K.M., et al. (2022) Telemedicine-Delivered Cognitive-Behavioral Therapy for Insomnia in Alcohol Use Disorder (AUD): Study Protocol for a Randomized Controlled Trial. Trials, 23, Article No. 59. <br>https://doi.org/10.1186/s13063-021-05898-y张志雄, 刘春芳, 孔庆辉. 酒精性肝病的中西医治疗进展[J]. 光明中医, 2020, 35(19): 3137-3138+封3-封4.Yan, J., Nie, Y., Luo, M., Chen, Z. and He, B. (2021) Natural Compounds: A Potential Treatment for Alcoholic Liver Disease? Frontiers in Pharmacology, 12, Article ID: 694475. <br>https://doi.org/10.3389/fphar.2021.694475Yang, Y.M., Cho, Y.E. and Hwang, S. (2022) Crosstalk between Oxidative Stress and Inflammatory Liver Injury in the Pathogenesis of Alcoholic Liver Disease. International Journal of Molecular Sciences, 23, Article No.774.
<br>https://doi.org/10.3390/ijms23020774Morley, K.C., Baillie, A., Van Den Brink, W., Chitty, K.E., Brady, K., Back, S.E., et al. (2018) N-Acetyl Cysteine in the Treatment of Alcohol Use Disorder in Patients with Liver Disease: Rationale for Further Research. Expert Opinion on Investigational Drugs, 27, 667-675. <br>https://doi.org/10.1080/13543784.2018.1501471Singal, A.K. and Mathurin, P. (2021) Diagnosis and Treatment of Alcohol-Associated Liver Disease: A Review. JAMA, 326, 165-176. <br>https://doi.org/10.1001/jama.2021.7683庞树朝, 郭卉. 中医药治疗酒精性肝病研究述评[J]. 世界中西医结合杂志, 2016, 11(1): 140-142+145.周文伟, 王邦才. 中医药治疗酒精性肝病研究进展[J]. 辽宁中医药大学学报, 2017, 19(2): 118-121.张慧珍, 卢秉久. 卢秉久辨治酒精性肝病经验[J]. 长春中医药大学学报, 2018, 34(4): 692-695.刘江凯. 赵文霞分期辨治酒精性肝病经验介绍[J]. 新中医, 2021, 53(18): 201-204.白钰. 陈永灿治疗慢性肝病临证治法举要[J]. 中华中医药杂志, 2018, 33(4): 1409-1411.方子燕, 王邦才. 王邦才辨治酒精性肝硬化经验[J]. 浙江中西医结合杂志, 2019, 29(9): 703-705.吴黎艳, 陈芝芸, 严茂祥, 何蓓晖. 三七对酒精性肝病大鼠肝组织CYP2E1表达的影响[J]. 中华中医药杂志, 2011, 26(6): 1395-1398.庾少梅, 周伟青, 林锐珊, 苏宁, 刘坤东. 三七总皂苷对实验性酒精性肝硬化大鼠的保护作用研究[J]. 世界中西医结合杂志, 2015, 10(6): 779-781.庾少梅, 周伟青, 林锐珊, 苏宁. 三七总皂苷对酒精性肝硬变大鼠肝星状细胞蛋白组学的影响[J]. 中医学报, 2016, 31(7): 1004-1007.赵月蓉, 侯碧玉, 张莉, 杜冠华, 管淑玉. 葛根素对实验性肝损伤的治疗作用研究进展[J]. 中国新药杂志, 2017, 26(9): 1005-1010.Zhao, Y.-Z., Zhang, L., Gupta Pardeep, K., Tian, F.R., Mao, K.L., Qiu, K.Y., et al. (2016) Using PG-Liposome-Based System to Enhance Puerarin Liver-Targeted Therapy for Alcohol-Induced Liver Disease. AAPS PharmSciTech, 17, 1376-1382. <br>https://doi.org/10.1208/s12249-015-0427-5余选良, 朱肖鸿, 冯舒婷. 枳椇子治疗酒精性肝病现状[J]. 浙江中西医结合杂志, 2017, 27(4): 342-344.张楠, 杨欢欢, 严秀莺, 赵婧陶, 陈飞, 赵云丽, 等. 枳椇子预防大鼠酒精性肝损伤的肝脏代谢组学[J]. 沈阳药科大学学报, 2020, 37(11): 1003-1008.许皖. 葛花、枳椇子及其配伍对急性酒精性肝损伤小鼠保护作用的实验研究[D]: [博士学位论文]. 北京: 北京中医药大学, 2020.都梦帆, 向汝, 胥冰, 郭东艳, 李涛, 史晓燕, 等. 五味子及其活性成分治疗酒精性肝损伤研究进展[J]. 现代中西医结合杂志, 2022, 31(3): 429-433.Jang, H.I., Do, G.-M., Lee, H.M., Ok, H.M., Shin, J.H., Kwon, O., et al. (2014) Schisandra Chinensis Baillon Regulates the Gene Expression of Phase II Antioxidant/Detoxifying Enzymes in Hepatic Damage Induced Rats. Nutrition Research and Practice, 8, 272-277. <br>https://doi.org/10.4162/nrp.2014.8.3.272Guo, C., Ma, J., Zhong, Q., Zhao, M., Hu, T., Chen, T., et al. (2017) Curcumin Improves Alcoholic Fatty Liver by Inhibiting Fatty Acid Biosynthesis. Toxicology and Applied Pharmacology, 328, 1-9.
<br>https://doi.org/10.1016/j.taap.2017.05.001陆春风. 姜黄素逆转酒精性肝纤维化的作用及机理研究[D]: [博士学位论文]. 南京: 南京中医药大学, 2017.尹可欢, 罗晓敏, 丁翼, 阙涵韵, 谭睿, 李大鹏, 等. 余甘子及其活性成分肝保护作用及机制的研究进展[J]. 中草药, 2022, 53(1): 295-307.刘晓丽, 杨冰鑫, 陈柳青, 范宇婷, 吴克刚, 于泓鹏. 余甘子多酚对体外酒精性肝损伤的保护作用[J]. 中国食品学报, 2021, 21(10): 108-115.翁卫东. 葛花解酲汤治疗酒精性肝病的临床疗效观察[J]. 中华中医药学刊, 2010, 28(6): 1226-1227.邹尚亮. 葛花解酲汤及其拆方对酒精性肝损伤模型鼠的实验研究[D]: [硕士学位论文]. 黑龙江中医药大学, 2017.关瑜. 茵陈蒿汤主要体内直接作用物质联合治疗酒精性肝损伤作用的机制研究[D]: [硕士学位论文]. 黑龙江中医药大学, 2015.杨焘, 宋厚盼, 陈哲, 刘恒铭, 李佳妮, 冯瑶, 等. 基于SIRT1/AMPK信号通路探讨茵陈蒿汤治疗急性酒精性肝损伤的效应及机制[J]. 中药药理与临床, 2022, 38(1): 36-40.魏媛媛, 张贵贤, 李木松, 陈晖, 秦维. 蒿汤对酒精性肝纤维化大鼠肝功能和pERK/eI F2a信号通路的影响[J]. 海南医学院学报, 2019, 25(19): 1461-1465+1470.李木松, 张贵贤, 陈晖, 秦维, 魏媛媛. 茵陈蒿汤对酒精性肝纤维化模型大鼠内质网应激介导肝细胞凋亡相关分子的影响[J]. 上海中医药杂志, 2019, 52(6): 75-79.李木松, 张贵贤, 魏媛媛, 秦维, 陈晖. 茵陈蒿汤对酒精性肝纤维化大鼠肝组织Caspase-12通路的影响[J]. 现代中西医结合杂志, 2019, 28(6): 571-574+617.王磊, 王惠娟, 吴凯, 胡冬青. 茵陈蒿汤改善酒精性肝病大鼠肝脏及小肠病变的组织病理学研究[J]. 环球中医药, 2015, 8(11): 1329-1332.季光, 王育群, 曹承楼, 姜鲁峰, 张玮, 邢练军, 等. 清肝活血方治疗酒精性肝病的临床研究[J]. 中国中西医结合杂志, 2004, 24(1): 13-16.Wu, T., Liu, T., Zhang, L., Xing, L.J., Zheng, P.Y. and Ji, G. (2014) Chinese Medicinal Formula, Qinggan Huoxue Recipe Protects Rats from Alcoholic Liver Disease via the Lipopolysaccharide-Kupffer Cell Signal Conduction Pathway. Experimental and Therapeutic Medicine, 8, 363-370. <br>https://doi.org/10.3892/etm.2014.1740潘洁露, 邢练军, 张济, 喻晓, 张海燕. 清肝活血方治疗酒精性肝硬化湿热瘀结证的随机对照临床试验[J]. 海南医学院学报, 2022, 28(8): 579-584.陈珺明, 王磊, 邢练军, 郑培永, 季光. 清肝活血方对酒精性肝纤维化大鼠基质金属蛋白酶的调控作用[J]. 中国中西医结合杂志, 2011, 31(11): 1538-1544.张欢, 孙劲晖. 基于肠道微生态探索“调肝理脾”法治疗酒精性肝病的新思路[J]. 中国医药导报, 2020, 17(9): 123-126.成扬, 汪海慧, 胡义扬, 彭景华, 平键, 陈高峰. 健脾活血方对Lieber-DeCarli酒精性脂肪肝大鼠肠道菌群的影响[J]. 中国中西医结合杂志, 2011, 31(1): 73-79.周梅月. 健脾活血方修复酒精性肝病小鼠肠粘膜损伤的机制研究[D]: [硕士学位论文]. 北京: 北京中医药大学, 2021.叶松. 王氏保赤丸预防酒精性肝病的作用及机制研究[D]: [硕士学位论文]. 南京: 南京中医药大学, 2021.何义华, 罗建君, 文安怡, 程志生, 余志映, 吴舒婷. 二至解酲汤治疗酒精性肝病临床研究[J]. 中医学报, 2018, 33(6): 1099-1102.王春吉. 茵柴汤治疗肝胆湿热型酒精性肝炎疗效观察[D]: [硕士学位论文]. 沈阳: 辽宁中医药大学, 2020.王映林, 肖明中, 李青叶. 牛黄参胶囊联合多烯磷脂酰胆碱治疗酒精性肝炎40例[J]. 中西医结合肝病杂志, 2017, 27(4): 241-242.