中医药诊治乙肝后肝硬化–肝癌恶性转化的研究进展
Research Progress of Traditional Chinese Medicine in Diagnosis and Treatment of Malignant Transformation from Hepatitis B Cirrhosis to Hepatocellular Carcinoma

DOI: 10.12677/TCM.2019.86058, PP. 359-366

Keywords: 乙肝后肝硬化，肝癌，恶性转化，证候，中医药诊治
Hepatitis B Cirrhosis, Hepatocellular Carcinoma, Malignant Transformation, TCM Zheng, Diagnosis and Treatment of TCM

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Abstract:

乙型肝炎病毒感染性肝硬化是肝脏慢性炎症坏死性疾病。肝癌在2018年成为全球第六大最常见的癌症和第四大癌症死亡原因。乙肝后肝硬化–肝癌的恶性转化是一个多阶段的从癌前病变演变到肝癌的长期过程。中医药在防治乙肝后肝硬化–肝癌恶性转化方面具有特色和优势。本文就乙肝后肝硬化–肝癌癌前病变的中医病因病机、证候分类及其物质基础研究以及中医药防治肝癌前病变机制研究等方面进行综述，为中医诊断和治疗乙肝后肝硬化–肝癌恶性转化提供参考。
Hepatitis B virus (HBV)-infected cirrhosis is a chronic inflammatory liver disease. HBV induced hepatocellular carcinoma (HCC) has become the sixth most commonly diagnosed cancer and the fourth leading cause of cancer death worldwide in 2018. The malignant evolution HBV induced cirrhosis to HCC is a multi-stage and long process with precancerous lesions. Traditional Chinese medicine (TCM) has great advantages and effectiveness in the prevention and treatment of malignant transformation from HBV induced cirrhosis to HCC. In this paper, we reviewed etiology, pathogenesis, classification and biological basis of TCM Zheng of malignant transformation from Hepatitis B cirrhosis to HCC, and mechanisms of TCM treating liver precancerosis were also reviewed to provide references for prevention and treatment in TCM treating malignant transformation from Hepatitis B cirrhosis to HCC.

References

[1]	付修文, 徐春军. HBV所致肝癌前病变的中医辨证分型与AFP-L3及AFPmRNA相关性研究[J]. 中国中医基础医学杂志, 2012, 18(12):1363-1365.
[2]	Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A. and Jemal, A. (2018) Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 68, 394-424. https://doi.org/10.3322/caac.21492
[3]	Di Tommaso, L., Sangiovanni, A., Borzio, M., Park, Y.N., Farinati, F. and Roncalli, M. (2013) Advanced Precancerous Lesions in the Liver. Best Practice & Research Clinical Gastroenterology, 27, 269-284. https://doi.org/10.1016/j.bpg.2013.03.015
[4]	王轲, 李京涛, 闫曙光, 魏海梁, 鞠迪, 冯飞雪, 等. 肠道微生态对肝硬化–肝癌癌前病变恶性转变的影响[J]. 胃肠病学和肝病学杂志, 2018, 27(1): 111-114.
[5]	赵宾宾. 地五养肝胶囊抑制2-AAF/PH大鼠肝癌前病变的作用及机制[D]: [博士学位论文]. 武汉: 湖北中医药大学, 2015.
[6]	陈晓婷, 何超, 李京涛, 闫曙光, 魏海梁, 宋艺君, 等. 中医药防治肝癌癌前病变的研究现状[J]. 中西医结合肝病杂志, 2016, 26(5): 314-316.
[7]	赵立甫. 谢英彪教授应用药膳治疗肝癌癌前病变经验[J]. 时珍国医国药, 2000, 11(12): 1153-1154.
[8]	张琴, 刘平, 王磊, 都广礼, 章浩伟, 陈慧芬, 等. 900例肝炎后肝硬化中医证候判别模式的研究[C]//第十五次全国中西医结合肝病学术会议论文汇编. 全国中西医结合肝病学术会议, 2006.
[9]	袁虹, 曹廷智, 刘红, 李晓良, 王东, 吴其恺, 等. 302例乙型肝炎肝硬化患者中医证候学探讨[J]. 中西医结合肝病杂志, 2009, 19(6): 346-349.
[10]	Zeng, X.X., Bian, Z.X., Wu, T.X., Fu, S.F., Ziea, E. and Woon, W.T. (2011) Traditional Chinese Medicine Syndrome Distribution in Chronic Hepatitis B Populations: A Systematic Review. The American Journal of Chinese Medicine, 39, 1061-1074. https://doi.org/10.1142/S0192415X11009408
[11]	袁继丽, 张华, 王磊, 林彦, 胡鑫才, 张琴, 等. 乙型肝炎后肝硬化患者中医证候要素的生物化学特征[J]. 中西医结合学报, 2011, 9(4): 374-381.
[12]	李永健, 方肇勤, 唐辰龙, 马骏, 管冬元, 等. 2060例原发性肝癌中医证候分布规律的临床流行病学调查研究[J]. 中华中医药杂志, 2003, 18(3): 144-146.
[13]	郎庆波, 翟东霞, 黄枫, 陈建国, 张永辉, 刘群, 等. 江苏启东地区4618例乙型肝炎病毒感染者证候调查[J]. 中西医结合学报, 2012, 10(5): 525-531.
[14]	方肇勤, 李永健, 唐辰龙, 马骏, 管冬元, 陈德溯. 2060例原发性肝癌患者证候特点分析[J]. 中医杂志, 2004, 45(1): 53-54.
[15]	刘平. 乙型肝炎肝硬化、肝癌的中医发病学及其基本病机演变规律的探讨[J]. 中西医结合肝病杂志, 1998(s1): 6-10.
[16]	付修文, 徐春军. HBV所致肝癌前病变的中医辨证分型与AFP-L3及AFPmRNA相关性研究[J]. 中国中医基础医学杂志, 2012, 18(12): 1363-1365.
[17]	Ji, Q, Wang, W., Luo, Y., Cai, F., Lu, Y., Deng, W., et al. (2017) Characteristic Proteins in the Plasma of Postoperative Colorectal and Liver Cancer Patients with Yin Deficiency of Liver-Kidney Syndrome. Oncotarget, 8, 103223-103235. https://doi.org/10.18632/oncotarget.21735
[18]	Du, J., Zhong, M., Liu, D., Liang, S., Liu, X., Cheng, B., et al. (2017) Reduced MLH3 Expression in the Syndrome of Gan-Shen Yin Deficiency in Patients with Different Diseases. Evidence-Based Complementary and Alternative Medicine, 2017, Article ID: 4109828. https://doi.org/10.1155/2017/4109828
[19]	Lu, Y.Y., Chen, Q.L., Guan, Y., Guo, Z.Z., Zhang, H., Zhang, W., et al. (2014) Study of ZHENG Differentiation in Hepatitis B-Caused Cirrhosis: A Transcriptional Profiling Analysis. BMC Complementary and Alternative Medicine, 14, 371. https://doi.org/10.1186/1472-6882-14-371
[20]	Wan, D.F., Gong, Y., Qin, W.X., Zhang, P.P., Li, J.J., Wei, L., et al. (2004) Large-Scale cDNA Transfection Screening for Genes Related to Cancer Development and Progression. Proceedings of the National Academy of Sciences of the United States of America, 101, 15724-15729. https://doi.org/10.1073/pnas.0404089101
[21]	Janne, L. (2014) Metabolic Impact of the Glycerol Channels AQP7 and AQP9 in Adipose Tissue and Liver. Journal of Molecular Endocrinology, 52, 165-178. https://doi.org/10.1530/JME-13-0268
[22]	Li, Q.Y., Guo, Z.Z., Liang, J., Zhang, W., Xu, L.M., Gao, Y.Q., et al. (2012) Interleukin-10 Genotype Correlated to Deficiency Syndrome in Hepatitis B Cirrhosis. Evidence-Based Complementary and Alternative Medicine, 2012, Article ID: 298925. https://doi.org/10.1155/2012/298925
[23]	叶永安, 田德录, 赵凤志, 朱陵群, 王晓静, 等. 肝癌前病变发生机理及中药干预作用的研究探讨[J]. 中国中医基础医学杂志, 2003, 9(2): 22-24.
[24]	张希. 复方叶下珠对乙肝相关癌的癌前病变治疗的临床研究[D]: [硕士学位论文]. 广州: 广州中医药大学, 2008.
[25]	马素平. 赵文霞教授基于“毒瘀痰虚”理论治疗肝炎肝硬化经验[J]. 中医研究, 2015, 28(11): 43-46.
[26]	王倩, 杨柱, 龙奉玺, 罗莉, 王镜辉, 郭斌, 等. 肝癌癌前病变动物模型研究进展[J]. 湖南中医杂志, 2017, 33(8): 212-214.
[27]	刘蕊洁, 杨先照, 焦云涛, 李莹, 张鹏, 叶永安. 二乙基亚硝胺诱导肝细胞癌癌前病变动物模型研究[J]. 中西医结合肝病杂志, 2015, 25(3): 162-164+95.
[28]	Newell, P., Villanueva, A., Friedman, S.L., Koike, K. and Llovet, J.M. (2008) Experimental Models of Hepatocellular Carcinoma. Journal of Hepatology, 48, 858-879. https://doi.org/10.1016/j.jhep.2008.01.008
[29]	唐东昕. 建立乙醇、HBV双因素所致肝癌癌前病变小鼠模型的探讨[J]. 中国中医基础医学杂志, 2015, 21(11): 1374-1376+1472.
[30]	刘莹, 廖芝玲, 向邦德. 磷脂酰肌醇蛋白聚糖-3及热休克蛋白70在肝细胞结节性病变中的表达及意义[J]. 广西医学, 2016, 38(3): 297-300+307.
[31]	杨大国, 邓欣, 吴其恺, 等. 正肝方对大鼠癌前病变肝组织细胞周期蛋白D1及依赖性激酶4的影响[J]. 中国中西医结合消化杂志, 2011, 19(3): 145-148.
[32]	杨大国, 李知玉, 邓欣, 李晓良, 聂广, 等. 正肝方治疗肝硬化伴高甲胎蛋白血症的近期疗效观察[J]. 中国中西医结合杂志, 2005, 25(10): 931-933.
[33]	蒿艳蓉, 杨芳, 曹骥, 欧超, 张晶晶, 杨春, 等. 银杏叶提取物(EGb761)阻断AFB1致大鼠肝癌及其机制研究[J]. 中药材, 2009, 32(1): 92-96.
[34]	尹宗柱, 金海玲, 李天洙, 李晶俊, 金荣镐, 李哲浩, 等. 草苁蓉甲醇提取物对二乙基亚硝胺诱发大鼠肝脏癌前病变的抑制作用[J]. 中国中药杂志, 1998, 23(7): 424-426.
[35]	郭辉. 益脾养肝方对大鼠肝癌癌前病变炎症微环境形成机制的影响[D]: [硕士学位论文]. 咸阳: 陕西中医药大学, 2017.
[36]	胡利荣, 陈闯, 欧超, 黎汉忠, 黄智芬, 陈军. 健脾消积汤抑制二乙基亚硝胺致大鼠肝癌前病变的作用[J]. 广西医学, 2014, 36(1): 62-65.
[37]	郭斌. 葛花解酲方对乙醇性HBV转基因小鼠肝癌癌前病变相关因子的影响[D]: [硕士学位论文]. 贵阳: 贵阳中医学院, 2015.
[38]	鲁玉辉. 叶下珠复方抗HBV、人肝癌裸鼠移植瘤及其分子生物学机制探讨[D]: [博士学位论文]. 广州: 广州中医药大学, 2006.
[39]	邓欣. 正肝方对大鼠肝癌前病变及人肝癌细胞分化和端粒酶的影响[D]: [博士学位论文]. 武汉: 湖北中医学院, 2008.
[40]	季光, 曹承楼, 刘平, 胡义扬, 顾宏图. 扶正化瘀方预防大鼠肝癌形成机制的研究[J]. 中国中西医结合消化杂志, 2001, 9(1): 20-22.
[41]	陈滨, 郭洁文, 何素, 李常青, 杜欣芸, 李俏敏, 等. 叶下珠复方Ⅱ号对肝癌细胞增殖和胰岛素样生长因子-1受体信号通路转录的作用[J]. 中国实验方剂学杂志, 2018, 24(14): 108-114.
[42]	Yu, Z., Feng, H., Sun, X., Zhuo, Y., Li, M., Zhou, Z., et al. (2018) Bufalin Suppresses Hepatocarcinogenesis by Targeting Beta-Catenin/TCF Signaling via Cell Cycle-Related Kinase. Scientific Reports, 8, 3891. https://doi.org/10.1038/s41598-018-22113-2
[43]	魏海梁, 李京涛, 闫曙光, 郭辉, 鞠迪, 冯飞雪, 等. 基于TLR4/NF-κB信号通路研究益脾养肝方对大鼠肝癌前病变的影响[J]. 四川中医, 2017, 35(10): 54-57.
[44]	廖国志. 银杏叶多糖抗氧化活性及对肝癌HepG2细胞诱导凋亡作用的研究[D]: [硕士学位论文]: 泰安: 山东农业大学, 2017.
[45]	Cleary, S.P., Jeck, W.R., Zhao, X., Chen, K., Selitsky, S.R., Savich, G.L., et al. (2013) Identification of Driver Genes in Hepatocellular Carcinoma by Exome Sequencing. Hepatology, 58, 1693-1702. https://doi.org/10.1002/hep.26540
[46]	Hunecke, D., Spanel, R., Langer, F., Nam, S.W. and Borlak, J. (2012) MYC-Regulated Genes Involved in Liver Cell Dysplasia Identified in a Transgenic Model of Liver Cancer. The Journal of Pathology, 228, 520-533. https://doi.org/10.1002/path.4059
[47]	Kolquist, K.A., Ellisen, L.W., Counter, C.M., Meyerson, M., Tan, L.K., Weinberg, R.A., et al. (1998) Expression of TERT in Early Premalignant Lesions and a Subset of Cells in Normal Tissues. Nature Genetics, 19, 182-186. https://doi.org/10.1038/554
[48]	Longerich, T., Endris, V., Neumann, O., Rempel, E., Kirchner, M., Abadi, Z., et al. (2019) RSPO2 Gene Rearrangement: A Powerful Driver of Beta-Catenin Activation in Liver Tumours. Gut, 68, 1287-1296. https://doi.org/10.1136/gutjnl-2018-317632
[49]	Howell, J., Atkinson, S.R., Pinato, D.J., Knapp, S., Ward, C., Minisini, R., et al. (2019) Identification of Mutations in Circulating Cell-Free Tumour DNA as a Biomarker in Hepatocellular Carcinoma. European Journal of Cancer, 116, 56-66. https://doi.org/10.1016/j.ejca.2019.04.014
[50]	Li, T., Zheng, Q., An, J., Wu, M., Li, H., Gui, X., et al. (2016) SET1A Cooperates With CUDR to Promote Liver Cancer Growth and Hepatocyte-Like Stem Cell Malignant Trans-formation Epigenetically. Molecular Therapy: The Journal of the American Society of Gene Therapy, 24, 261-275. https://doi.org/10.1038/mt.2015.208
[51]	Jain, S., Singhal, S., Lee, P. and Xu, R. (2010) Molecular Genetics of Hepatocellular neoplasia. American Journal of Translational Research, 2, 105-118.
[52]	Charni, M., Aloni-Grinstein, R., Molchadsky, A. and Rotter, V. (2017) p53 on the Crossroad between Regeneration and Cancer. Cell Death and Differentiation, 24, 8-14. https://doi.org/10.1038/cdd.2016.117
[53]	Zucman-Rossi, J., Villanueva, A., Nault, J.C. and Llovet, J.M. (2015) Genetic Landscape and Biomarkers of Hepatocellular Carcinoma. Gastroenterology, 149, 1226-39.e4. https://doi.org/10.1053/j.gastro.2015.05.061
[54]	磨炼, 杨林浩, 严格, 刘小美. 黄连大黄肉桂复方及其有效组分配伍对人肝癌细胞株SMMC-7721端粒酶的影响[J]. 中西医结合肝病杂志, 2019, 29(2): 152-154+201.

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