山西地区基因C型慢性乙型肝炎中医证候特点研究

【作者】 郭晓霞；

【导师】 叶永安；

【作者基本信息】 北京中医药大学 ， 中医内科学， 2014， 博士

【摘要】 目的乙型肝炎病毒(Hepatitis B virus,HBV)感染是世界性的健康问题,乙肝病毒特性及宿主免疫机制紊乱等因素导致HBV感染慢性化,乙型肝炎慢性迁延而最终导致肝硬化、肝细胞癌。全球约有100万人每年死于乙型肝炎后肝硬化、肝细胞癌。慢性乙型肝炎已成为严重威胁人类健康的传染性疾病,因此慢性乙型肝炎的防治问题变得尤为重要。HBV感染后,机体对病毒的清除能力以及感染后疾病的转归,在很大程度上取决于个体间基因组的差异和病毒基因型的差异。我国最常见的是基因型B和C。不同的HBV基因型所导致的慢性乙型肝炎(Chronic Hepatitis B,CHB)患者的发病率也不同。流行病调查显示,与B基因型相比,C基因型慢性HBV感染者的病毒载量较高,HBV活动性复制的持续时间较长,HBeAg血清学转换时间较晚,抗病毒疗效较差,是肝细胞肝癌与肝硬化发展的高危因素之一。山西地区是我国HBV感染的高发区,基因C型为其主要基因型,因此确定合理的CHB的治疗方案是当前急需解决的问题。慢性乙型肝炎在中医医学中属于“胁痛”、“黄疸”、“肝着”等范畴。近年来中医辨证论治在CHB的治疗中发挥着重要的作用。辨证论治是中医诊断疾病和治疗疾病的基本原则,其中辨证起着关键的指导作用,是论治的基础。而相同的疾病,可由于疾病的不同阶段、患者所在地区以及患者的体质、季节等因素,出现不同的临床表现。大量的临床观察和基础研究表明,中医药具有抗病毒、调节免疫、改善临床症状以及防治肝纤维化等综合作用,但目前仍有许多关键问题有待解决。由于慢性乙型肝炎病机复杂,且由于各地地域及优势基因型的差异,辨证标准至今尚未统一,疗效评价体系尚不完善,尤其是慢性乙型肝炎的中医证候及辨证规律缺乏规范化研究,不利于指导临床。考虑到山西地区气候、地域及宿主因素等对慢性乙型肝炎中医证型的影响,为此本研究借鉴中医证候量表和多元统计方法,以大样本的山西地区慢性乙型肝炎患者为研究对象,从中提取相应的证素,应用因子分析、主成分分析等多元统计方法明确山西地区慢性乙型肝炎患者中医证型特点,同时借助双脱氧核酸法检测山西地区HBV基因型。在此基础上,分析山西地区基因C型慢性乙型肝炎患者患者的中医证候学特点,为优化山西地区慢性乙型肝炎患者治疗方案提供一定的依据。方法在广泛查阅相关文献的基础上,收集山西地区慢性乙型肝炎患者的中医症状,建立临床流调问卷条目池,咨询相关专家并根据相关标准,确定所需调查的中医症状条目池以及相应的症状分级量化标准,最终形成中医证侯临床调查问卷表。按统一问卷表收集慢性乙型肝炎患者的临床证候资料,应用主成分分析及因子分析等多元统计方法分析研究山西地区慢性乙型肝炎中医证候特点。同时,应用双脱氧核酸法检测山西地区慢性乙型肝炎患者HBV基因型。在此基础上,探讨山西地区慢性乙型肝炎患者的优势基因型,以及HBV基因型与所得出的中医证型及临床指标之间的关系。结果1对所收集到的420例山西地区慢性乙型肝炎患者的中医症状进行多元统计学方法分析,结果显示山西地区慢性乙型肝炎患者的中医证候可归纳为无证可辨型、肝郁脾虚型、肝胆湿热型、肝肾阴虚型及肝血瘀阻型五种证型。2经双脱氧核酸法分析山西地区HBV基因型,结果提示山西地区以C型为优势基因型。其次为B/C和B型。进一步分析显示,基因C型患者中医证型以肝郁脾虚和肝胆湿热型为主,不同中医证型的舌象、苔质及脉象具有各自的特点,中医证型与肝炎分型关系密切。3把基因C型的慢性乙型肝炎患者按轻、中、重度分为三组,结果显示不同的中医证型在肝炎分型中的分布不同。轻度主要见于无证可辨型、肝郁脾虚型和肝胆湿热型,慢性乙型肝炎重度主要见于肝肾阴虚型和肝血瘀阻型。肝郁脾虚型和肝胆湿热型在各个阶段均有分布,但随着病情的加重,其比例有逐渐递减的趋向；肝血瘀阻型主要见于慢性乙型肝炎中度、重度,轻度也有小比例的涉及；肝肾阴虚型则仅见于中、重度,未见于轻度。4基因C型慢性乙型肝炎患者各中医证型间HBVDNA定量无明显相关性。5基因C型的轻度慢性乙型肝炎患者肝组织炎症活动度和纤维化程度与中医证型有明显相关性,其中肝血瘀阻型患者肝组织损伤最为严重。结论山西地区慢性乙型肝炎患者以基因C型为主要优势,中医证候类型有无证可辨、肝郁脾虚型、肝胆湿热型、肝肾阴虚型及肝血瘀阻型五种,其中以肝郁脾虚和肝胆湿热型为主,肝血瘀阻型次之。基因C型慢性乙型肝炎患者中医证型与肝炎分度、肝组织病理关系密切,与HBVDNA数值无明显相关性。更多还原

【Abstract】 Objective:Hepatitis B virus (HBV) infection is a worldwide health problems. HBV factors such as the characteristics and mechanism of host immune disorder lead to chronic HBV infection, and eventually lead to cirrhosis and hepatocellular carcinoma (HCC). There are about1million people worldwide died of liver cirrhosis and HCC each year. The problem of prevention and control about HBV is particularly important because HBV infectious diseases has become a serious threat to human health.After HBV infection, It depends on the difference between the genomes of individual and virus genotype difference to a large extent that the body’s ability to clear the virus and the outcome after infection. The genotype B and C are the most common in our countiy. The Chronic Hepatitis B (CHB) caused by different HBV genotypes have the different incidence for patients. Compared with genotype B, the viral load of the patients with C genotype is higher, the duration of active HBV replication is longer, HBeAg seroconversion time is later, and antiviral effect is poorer by Epidemic survey. Genotype C is one of the high-risk factors for the development of hepatocellular carcinoma and liver cirrhosis. HBV genotype C is main genotype of Shanxi region, which has the high incidence of infection.So it is an urgent need to solve the problem for the reasonable treatment of CHB currently.Chronic hepatitis B belongs to the "Hypochondriac","Jaundice" in the Traditional Chinese Medcine(TCM) category. In recent years, Chinese medicine syndrome differentiation and treatment in the treatment of CHB plays a vital role. Treatment based on syndrome differentiation of TCM is the basic principle of diagnosis and treatment of diseases. The differentiation plays a key role in guiding, and is the foundation of treatment. The same disease appears different clinical manifestations, due to the different stages of disease, patients region, and the patient’s constitution, seasonal factors, and so on.A large number of clinical observation and basic research shows that Chinese medicine has antiviral action, immune regulation, the prevention and treatment of liver fibrosis combination, and improving the clinical symptoms.But there are still many key problems should be solved at present. Due to the complexity of pathogenesis of CHB, and because the advantages of genotype differences around the region, syndrome differentiation standard has not been unity, and curative effect evaluation system is not perfect, especially the TCM syndromes of CHB is not conducive to guide clinicalbecause the lack of standardization research.Considering the shanxi region climate, geography, and host factors impact on the TCM syndrome types of CHB, we will extract the corresponding syndrome elements and carry out the syndrome of Shanxi region by cluster analysis, factor analysis, principal component analysis of multivariate statistical methods, and detect HBV genotype by Sanger nuceic acid method. Finally,we will study the corresponding relationship between TCM syndrome and HBV genotype with clinical indicators. Methods:Based on extensively reviewing the relevant literature, collected the clinical symptoms of TCM of the ascites with CHB, then established an initially clinical epidemiological survey questionnaire. At last, determined the required clinical symptoms of the survey questionnaire item pool in TCM, and made the corresponding classification of quantitative criteria symptoms by relevant expert advice and feasibility analysis, repeated discussions and seminars and clinical research guidelines. Used uniform questionnaire to collect clinical syndromes data of the ascites with CHB. We use the method of factor analysis to investigate its characteristics of TCM syndrome, and to discuss the relationship between the objective indexes with the characteristics of TCM.Results:1The results show that the TCM syndrome in patients with CHB in shanxi region can be summarized five types by multivariate statistical analysis with collected clinical data of420cases,including Unlicensed discernible type, liver stagnation and spleen deficiency, wetness-Heat of Liver and Gallbladder deficiency of liver-yin and kidney-yin and obstruction of collaterals by blood stasis.2HBV genotypes in shanxi region is analyzed by Dideoxy method of nucleic acid suggests genotype C is the most prevalent followed by B/C and B in Shanxi Province.Further analysis showed that patients with genotype C syndrome type of traditional Chinese medicine is given priority to with dampness heat resistance, blood stasis resistance type winding times, TCM syndrome type and hepatitis, is close to the parting and HBVDNA quantitative no significant correlation.3The genotype C in patients with CHB are divided into three groups with light, medium and heavy, the results showed different distribution of TCM syndrome in hepatitis is different. The mild is mainly seen in Unlicensed discernible type, liver stagnation and spleen deficiency, wetness-Heat of Liver and Gallbladder,the severe is mainly seen in deficiency of liver-yin and kidney-yin and obstruction of collaterals by blood stasis, iver stagnation and spleen deficiency,detness-Heat of Liver and Gallbladder can be distributed in each stage, however, as the illness is aggravating, its ratio have gradually decreasing trend. The obstruction of collaterals by blood stasis can be seen mainly in moderate and severe CHB, mild and there’s a small proportion of the involved.Deficiency of liver-yin and kidney-yin is restricted to medium, heavy, not in light.4The TCM syndrome of CHB has no significant correlation with the quantity of HBVDNA.5Genotype C of mild CHB patients with liver tissue inflammation activity and fibrosis degree has obvious correlation with TCM syndrome types, while the syndrome of obstruction of collaterals by blood stasis is most severe in patients with liver injury.Conclusion: Genotype C is the most prevalent followed by B/C and B in Shanxi Province. The syndrome in patients with CHB in shanxi region can be summarized five types by multivariate statistical analysis,including Unlicensed discernible type, liver stagnation and spleen deficiency, wetness-Heat of Liver and Gallbladder,deficiency of liver-yin and kidney-yin and obstruction of collaterals by blood stasis. The syndromes of liver stagnation and spleen deficiency, wetness-Heat of Liver and Gallbladder are the most types of all, The syndromes are closely related to disease and liver tissue pathology,but no significant correlation with te quantity of HBVDNA.更多还原