中西医结合有效逆转乙肝肝纤维化的目标人群特征和作用机制

Characteristics of Target Population and Action Mechanisms of the Integrative Medicine on Regression of HBV Induced Hepatic Fibrosis Relating to Liver Immune Microenvironment

抗病毒西药具有病因治疗优势,中药具有抗肝纤维化优势,中西药联用优势互补可提高乙肝肝纤维化逆转率。从中西药物联用疗效提高的关键机制和其治疗应答的目标人群特征出发,围绕肝脏区域免疫微环境在肝病中的作用,提出"调节肝脏免疫微环境、恢复自然杀伤细胞对活化肝星形细胞的免疫杀伤功能是中药扶正化瘀方联合西药恩替卡韦有效逆转乙肝高度肝纤维化的主要机制"的科学假说。首先,采用传染病重大科技专项乙肝肝硬化临床生物样本,基于疗效分层与回归分析,发现中西医结合治疗有效人群主要生物学与中医证候特征,并通过组内、组间比较分析阐明该治疗方案的主要作用机制;其次,复制乙肝背景的肝纤维化动物模型,体内给药,检测肝内细胞表型功能及相互关系,探讨中西药联用对肝脏免疫病理调控机制;最后,复制肝硬化动物模型,分离培养人肝脏细胞,阐明中药影响活化肝星形细胞对自然杀伤细胞负调控等细胞联系的作用特点,从而验证以上科学假说,最终发现有效方案目标人群特征,阐明其主要治疗机制与中药作用特点,促进中西医结合肝病的精准医疗与基础研究发展。

Antiviral drugs （western medicine） have advantages of etiological treatment, and traditional Chinese medicine have advantages of anti hepatic fibrosis. The combination of Chinese and western medicine can improve the reversal rate of hepatitis B cir- rhosis. What is the key mechanism to improve the efficacy of integrative medicine？ What are characteristics of target population for effective response？ Starting from these questions, based on features of intrahepatie inmmne nfieroenvironment, we made hypothesis that ＂regulating liver fibrosis immune microenvironment and restoring immune killing function of NK cells to activated HSC are main mechanisms of FZHY combined with ETV to effectively reverse HBV advanced liver fibrosis＂. Firstly, we will utilize bio- chemical samples from two cohort of HBV cirrhosis established by national key grant, and analyze the characteristics of target population with hepatic immune mieroenvironment and TCM pattern. Then curative effect will be compared before and after treatment, and between two groups, to understand the main action mechanisms of combined therapy. The cirrhosis animal models with HBV will be established, treated with ETV and FZHY, intrahepatie cells and their relationship were assayed to investigate the regulation of integrative medicine on liver immunological disorder. Lastly, cirrhosis mice and human liver cells will be isolated, and then treated with FZHY, to study the FZHY effect on retinoid metabolism and liver immune cells interaction. These work will find the effective target population characteristics and the main therapeutic mechanism of TCM, promote development of precision medicine and basic research in the field of liver disease with integrative medicine.