基于流行病学调查的乙型肝炎肝硬化证候及病机研究
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摘要
HBV慢性感染是重要的全球性公共卫生问题,肝硬化是其重要的发展阶段之一。近年来提高乙型肝炎肝硬化的诊疗水平一直是国内外研究的热点,但目前尚缺乏疗效肯定的治疗手段,而中医采用辨病与辨证相结合,多途径、多靶点整体调节的治疗方法,临床治疗取得了一些可喜的进展,有一定的特色和优势,显示出了较广阔的前景。
本研究在以往研究的基础上,受国家自然科学基金支持,采用流行病学调查方法收集临床资料,借助现代统计学方法,对乙型肝炎肝硬化的发病因素、中医证候规律以及病因病机方面进行了探讨,全文分理论探讨和临床研究。第一部分理论探讨——乙型肝炎肝硬化中医病因病机探讨
多年来,以导师为首的课题组经过长期的临床实践、反复的基础及临床研究,认为乙型肝炎肝硬化的病因为“疫毒“和”内生之毒”,病位在“肝络”；指出“肝脾不调”是乙型肝炎肝硬化基本的脏腑病变。本研究分析乙型肝炎肝硬化的发生、发展特点,提出了“毒损肝络、肝脾不调”的基本病机,并进行了初步探讨。
肝络作为络脉系统的重要组成部分,布散于肝脏,又是肝脏结构和功能体系的基本构成。它既有络脉的基本属性,又有其特殊的生理、病理特征。肝络生理上既是肝脏与其他脏腑及组织联络的纽带,又是肝脏气血津液生化贮藏的场所和输布贯通的要道；病理上肝络则可能成为外邪入侵肝脏和气血邪浊郁滞的场所。肝能通过肝之经络系统对相关脏腑组织进行生理功能的调节,其中尤以“肝脾”关系最为密切,二者是调节“升降出入”的枢纽。同样肝脏病变也可通过肝之经络系统影响到这些脏腑组织器官的功能(以肝脾不调最为常见),而产生病变。因此,湿热疫毒外袭、内生之毒为患,极易入肝脏血分,深入肝络,犯肝累脾,发生传变,导致一系列变证。
本研究在前期临床及实验研究基础上,结合文献研究及导师经验,对乙型肝炎肝硬化的病因、病机,特别是基本病机和证候特点进行深入探讨,认为：①“疫毒内伏”是乙型肝炎肝硬化发生、发展的启动子和关键因素；②“肝脾不调、正气不足”则是影响乙型肝炎肝硬化病情发展的基本脏腑病变；③“水湿痰瘀浊阻滞”是乙型肝炎肝硬化的临床病理变化；④“毒损肝络,肝脾不调”是贯穿乙型肝炎肝硬化始终的基本病机。治疗上遵“扶正祛邪”的原则,采用“解毒和络、调和肝脾”的治疗大法,随证加减论治。
第二部分临床研究——乙型肝炎肝硬化证候特点及病机的临床研究
本研究对2007年9月-2009年10月间,分别于中国中医科学院广安门医院、解放军302医院、北京佑安医院、北京地坛医院,河南安阳市第五人民医院、河南省中医院、芜湖市第五人民医院、公主岭市人民医院等多家传染病医院或中医院传染科的住院或门诊搜集到的650份合格病例进行相关分析探讨。
1.一般资料研究
乙型肝炎肝硬化的发生、进展是多种因素共同综合作用的结果。本课题研究表明,性别、病程、年龄、季节以及情绪因素都是引起乙型肝炎肝硬化发病、进展的相关因素。尤其季节因素的研究符合中医传统四时医学理论,研究发现季节对乙型肝炎肝硬化病情的进展和／或加重有一定影响(202／650,31.1%),占52.0%(105／202),其中涉及春季者占52.0%(105／202)；涉及冬季者亦不在少数,占33.7%(68／202)。尤以春季明显,是否与春季气候变化无常或乙肝病毒的活性增强有关,值得进一步探讨。这印证了中医四时五脏相应,而肝病易发于春的认识。为从中医时间医学的角度,研究乙型肝炎肝硬化的发作和加重提供了依据。
2.乙型肝炎肝硬化证候特点研究
本研究应用频次统计对乙型肝炎肝硬化不同发展阶段的中医证候分布特点进行了分析。研究表明：肝胆湿热、脾胃湿热、湿困中焦、肝胃不和、肝肾阴虚等证型可以发生于肝硬化病变发展的整个过程中,在代偿和失代偿不同阶段均有表现；而肝脾不调、肝郁脾虚、肝气郁结主要反映在代偿性肝硬化阶段；气滞血瘀、脾肾阳虚、寒湿中阻多见于失代偿性肝硬化阶段,这表明乙型肝炎肝硬化的证候特点涉及湿热、气滞、血瘀、痰湿、肝脾(胃)肾、阴虚、阳虚等相关因素,且随着病情的发展,在湿热疫毒及内生之毒的作用下,出现肝脾不调,致使气滞血瘀逐渐加重,病变脏腑由肝脾而及肾,终至阴虚、阳虚叠现。
3.乙型肝炎肝硬化病机及临床特点研究
本研究通过对乙型肝炎肝硬化患者的“四诊”信息进行因子分析及聚类分析,并结合中医学理论对结果进行分析,具体结论如下：
(1)因子分析表明乙型肝炎肝硬化的病机涉及湿热、脾胃虚、肝气郁、肝脾不和、痰湿、水停、血瘀伤络及肾虚等相关因素。其特点为“虚实夹杂”。结合前面证候特点的研究结果可以初步认为其病机演变规律基本为：疫毒湿热内侵,耗气伤津,导致脾胃虚弱、肝气郁结、致使肝脾不调,后期兼及于肾,变生水湿痰瘀等病理产物,后者又可再伤肝脾肾,导致恶性循环,终成肝硬化之疾。
(2)聚类分析表明乙型肝炎肝硬化“毒损肝络、肝脾不调”基本病机相关证候类别为脾虚湿困类证,肝郁脾虚类证,湿热内蕴、肝脾肾俱虚类证,肝胆湿热类证。
(3)通过对聚类所得证候类别的相关指标计算权重,初步探讨乙型肝炎肝硬化“毒损肝络、肝脾不调”基本病机相关证候类别的诊断标准。
脾虚湿困类证：倦怠乏力、食欲差、腹胀、肝掌、腹胀大、目黄、红丝赤缕、胃脘胀、气短懒言、下肢浮肿、身黄、身困重、大便溏、胁肋胀、口淡乏味、舌淡、苔白厚腻、脉沉细。
肝郁脾虚类证：倦怠乏力、肝掌、面色萎黄、腹胀、食欲差、胁肋胀、小便黄赤、精神情绪异常、口淡乏味、胃脘胀、口渴、舌淡暗红、苔白厚腻、舌下系脉紫暗、脉沉弦细。
湿热内蕴、肝脾肾俱虚类证：倦怠乏力、小便黄赤、身体困重、腹胀、身黄、胃脘胀、肝掌、目黄、精神情绪异常、气短懒言、口渴、腰膝酸软、食欲差、眠差多梦、善太息、下肢浮肿、面色晦暗、胁肋胀、双目干涩、腹胀大、口苦、健忘、异常出血、烦躁、舌暗红、苔黄厚腻、脉弦。
肝胆湿热类证：目黄、身黄、肝掌、口渴、小便黄赤、口苦、倦怠乏力、面色晦暗、腹胀、大便不畅、色暗红、苔黄厚腻、舌下系脉紫暗迂曲、脉弦滑数。
4.“毒损肝络、肝脾不调”相关证候与临床检验指标关系的探讨
本研究对乙型肝炎肝硬化聚类后的各证候类别与常见临床指标进行比较,分析认为胆红素代谢异常在一定程度上似能反映湿热疫毒为患的病机及证候特点；ALP、PT反映的肝细胞损害及肝细胞合成功能障碍是基本病机演进的生化基础；血浆蛋白的下降是在疫毒与肝脾不调的双重作用下随着病情的发展逐渐出现的；ALT、AST和γ-GT体现了乙型肝炎肝硬化“毒损肝络、肝脾不调”病机的基本理化表现。
总之,本研究从理论和临床两方面入手,对乙型肝炎肝硬化的基本病机和证候特征进行了一定程度的探讨,发现了一定规律,今后尚需通过广泛收集临床信息,进一步探讨本病的病机及证候特征,为临床提供参考。
Hepatitis B virus (HBV) infection is a important of global public problem hepatic cirrhosis is its important of one of the development stage.In recent years, it becomes the hot pot to improve the diagnosis and treatment level of hepatitis B cirrhosis. To date, the therapy with satisfying therapeutic effect is absent, but traditional Chinese Medicine (TCM) exerts a promising future for clinical treatment, with combination of disease and syndrome differentiation, entirely regulation from multiple pathway and mufti-strata.
On support of National Natural Science Foundation of China, this research explores the etiological factors, discipline of the syndrome and pathogenesis of the hepatitis B cirrhosis, employing epidemiological method, by means of statistical methods,on the basis of past researches. The paper can be divided into two parts: theory and clinical research.
Part I:Theory study:the exploration of the hepatitis B cirrhosis s etiology and pathogenesis of TCM.
For many years, after long-time clinical practice and researches, my advisor and researching group postulate that the etiology of hepatitis B cirrhosis is "epidemic toxin" and "endogenous toxicity", the location of disease is "liver meridian", "the discord of the spleen and the liver" is basic pathological changes of the hepatitis B cirrhosis.This research proposes and expounds basic pathogenesis of "toxin damaging the liver meridian and the discord of the spleen and the liver", analyzes the characteristics of the occurrence and development of hepatitis B cirrhosis.
liver meridian is the important part of the whole collateral and meridian system, which distributes in liver, and constitutes the basic structural and functional unit. It processes not only the characteristics of meridian but also its special physiological and pathological features. Pathologically, liver meridian is the pathway of evil invasion, transmission and stagnating location. Liver can regulate the physiological function of related organs through its collateral and meridian system, in which the relationship of the liver and the spleen is most osculating,they are key points of ascending-descending。Vise visa, the diseases of the liver can affect other organs by the collaterals and meridians. So that, damp-heat epidemic toxin" and "endogenous toxicity" easily invade into the liver-blood, liver meridian, offenseing liver and tired spleen, transmission along and change, then inducing a series of diseases.
In terms of the literature study, combined with advisor's clinical practice and experimental studies, we concluded the etiological factors and major pathogenesis as following①Inhiding epidemic toxin is the promoter and the key of the hepatitis B cirrhosis.②They which are "the discord of the spleen and the liver、the deficiency of vital qi" effect the disease development, which is basic pathological changes of the hepatitis B cirrhosis.③Blocking stasis、wet、sputum and water are clinic pathological changes of the hepatitis B cirrhosis.④"toxin damaging the liver meridian and the discord of the spleen and the liver" are hepatitis B cirrhosis's basic pathogenesis. The therapeutic principle suggested to be resolveing toxin and dredging merdian, harmonizing liver and spleen.
PartⅡ:clinical research:Clinical research on the pathogenesis and the syndrome characteristics of hepatitis B cirrhosis.
This research analyzes of 650 eligible case of illness from 2007 to 2009, which come from several infectious diseases hospital of Guang'anmen Hospital、302 Military Hospital of China、Beijing YouAn Hospital、Beijing DiTan Hospita、The fifth Anyang People's hospital、The fifth People's hospital of WuHu、The People's hospital of GongZuLing、HeNan Provincial hospital of TCM.
1.Research on the baseline material.
The occurrence and activation of the hepatitis B cirrhosis is caused by multiple factors. Our research suggests that sex, age, duration, season and emotional factors participated in the pathogenesis, especially the season. The research has discovered that seasons have a certain influences on the development and(or) activation of the hepatitis B cirrhosis(202/650,31.1%), accounting for 52.0%(105/202) in the spring; accounting for 33.7%(68/202)in the winter.especially the spring.It is worth to further study that whether the development and/or activation of the hepatitis B cirrhosis are related to the enhanced
2 The study on the syndrome distributing laws of hepatitis B cirrhosis.
We applied frequency analysis, studied the syndrome distributing laws difference of hepatitis B cirrhosis different stages. It is suggested that liver and gallbladder dampness-heat, spleen-stomach dampness heat, dampness obstructing middle-jiao, Yin deficiency of liver and kidney appeared in Cirrhosis of the Liver, they are not different in the hepatitis B cirrhosis different stages; the discord of the spleen and the liver, liver depression and spleen deficiency, liver qi stagnation syndromemainly reflects in compensatory phase cirrhosis; qi stagnation and blood stasis, spleen-kidney yang deficiency, internal retention of cold wetness, mainly reflects in loss compensatory phase cirrhosis,which are syndrome characteristic or principal contradiction of loss compensatory phase cirrhosis.This indicates that syndrome characteristics of hepatitis B cirrhosis involves in dampness-heat, qi stagnation, blood stasis, phlegm-dampness, liver, spleen, kidney, yang deficiency,yin deficiency. With the disease development, damp-heat epidemic toxin and endogenous of toxicity lead to the discord of the spleen and the liver, qi stagnation and blood stasis aggravated gradually, disease of zang and fu is from liver-spleen to kidney, then gradually from yin deficiency to yang deficiency.
3. The study on pathogenesis and Clinical Characteristics of the hepatitis B cirrhosis.
We study on the "information from the TCM four diagnostic methods" by factor analysis and cluster analysis, combining with traditional chinese medicine theory,we analyze the results.
(1) Factor analysis shows that the pathogenesis of the hepatitis B cirrhosis involves in dampness-heat, weakness of spleen-stomach, liver qi stagnation, disharmony of liver-spleen, phlegm-dampness, water retention, blood stasis, kidney deficiency ect, which reflects in the pathogenesis evolution process of the hepatitis B cirrhosis, its character is group insufficiency and excess.It reveals as damp-heat epidemic toxin HBV latending in liver, which damages the liver meridian, results in the discord of the spleen and the liver and vital qi deficiency, qi blood and body fluid disorder, producing blood stasis and phlegm-dampness ect, that finally causes damp-heat brewing internally, discord of the spleen and the liver, stagnation of damp turbidity and static blood,that blocks merdian, forms of disease of hepatic cirrhosis.
(2) Cluster analysis shows that syndrome category which is "toxin damaging the liver meridian and the discord of the spleen and the liver"of the hepatitis B cirrhosis is stagnation of dampness due to splenic asthenia classified syndrome, liver depression and spleen deficiency classified syndrome, damp-heat brewing internally and liver-spleen-kideny deficiency classified syndrome, liver and gallbladder dampness-heat classified syndrome.
(3) We calculate weight of related indexes that have obtained by using cluster analysis and preliminary study on diagnostic criteria of related syndrome category,which are related with "toxin damaging the liver meridian and the discord of the spleen and the liver"of the hepatitis B cirrhosis's basic pathogenesis.
Stagnation of dampness due to splenic asthenia classified syndrome:burnout and hypodynamia, poor appetite, abdominal distension, liver palms,yellowish eyes, spider telangiectasia, bloating great, weiwan expansion, reluctant to speak, short of breath, low extremity edema, body huang, heaviness sensation of body, stool pond, xielei expansion, mouth pale dull, pale tongue, thick white greasy fur, deep and fine pulse.
Liver depression and spleen deficiency classified syndrome:burnout and hypodynamia, liver palms, Looking chlorosis, abdominal distension, poor appetite, xielei expansion, dark purple veins under the tongue, yellow red of Urine, mental or emotional abnormalities, pale dark red tongue, thick white greasy fur, mouth pale dull, weiwan expansion, thirsty, deep fine string pulse.
Damp-heat brewing internally and liver-spleen-kideny deficiency classified syndrome:burnout and hypodynamia, yellow red of Urine, heaviness sensation of body, abdominal distension, body huang, weiwan expansion, liver palms, yellowish eyes, mental or emotional abnormalities, reluctant to speak, short of breath, thirsty,sour and feeble of the lion and knees, poor appetite, Poor sleep,more dream,easy to sign, low extremity edema, complexion dark and gloomy, xielei expansion, Dry eyes, abdominal distension, mouth pain, having a bad memory, abnormal bleeding, irritable, dark red tongue, thick yellow greasy moss, string pulse.
Liver and gallbladder dampness-heat classified syndrome:yellowish eyes, body huang, liver palms, thirsty, yellow of Urine, mouth pain, burnout weak, abdominal distension, complexion dark and gloomy, poor stool, dark red tongue, thick yellow greasy moss, dark purple veins under the tongue, tortuous sublingual veins, string slip su pulse.
4. Exploring the relation of the "toxin damaging the liver meridian and the discord of the spleen and the liver" related syndrome and the clinical investigating indexes.
After clustering analysis, this research compared the common clinical indexes related to various syndromes of hepatitis B cirrhosis of the liver, we consider that disordered bilirubin and bile acid (BA) metabolism may be the pathogenesis and Syndromes of the hot and humid Immunotoxin; ALP, PT reflects the hepatocellular lesions and synthesis dysfunction may be the physical and chemical basis of the evolution of the basic pathogenesis; The decline of plasma protein in the Immunotoxin with the liver and spleen are not transferred under the action of pairs of heavy development as the gradual emergence of the disease; ALT, AST and y-GT embodies the basic pathogenesis of the biochemical appearances of the hepatitis B cirrhosis of the liver, that is " toxin damaging the liver meridian and the discord of the spleen and the liver". in this aspect we made a preliminary exploration and found some tendency, which still need to be verified by more intensive and extensive researches, we try to find the relation between the syndrome and the micro-index by collecting clinical material, provide references for the clinical practice.'
本研究在以往研究的基础上,受国家自然科学基金支持,采用流行病学调查方法收集临床资料,借助现代统计学方法,对乙型肝炎肝硬化的发病因素、中医证候规律以及病因病机方面进行了探讨,全文分理论探讨和临床研究。第一部分理论探讨——乙型肝炎肝硬化中医病因病机探讨
多年来,以导师为首的课题组经过长期的临床实践、反复的基础及临床研究,认为乙型肝炎肝硬化的病因为“疫毒“和”内生之毒”,病位在“肝络”；指出“肝脾不调”是乙型肝炎肝硬化基本的脏腑病变。本研究分析乙型肝炎肝硬化的发生、发展特点,提出了“毒损肝络、肝脾不调”的基本病机,并进行了初步探讨。
肝络作为络脉系统的重要组成部分,布散于肝脏,又是肝脏结构和功能体系的基本构成。它既有络脉的基本属性,又有其特殊的生理、病理特征。肝络生理上既是肝脏与其他脏腑及组织联络的纽带,又是肝脏气血津液生化贮藏的场所和输布贯通的要道；病理上肝络则可能成为外邪入侵肝脏和气血邪浊郁滞的场所。肝能通过肝之经络系统对相关脏腑组织进行生理功能的调节,其中尤以“肝脾”关系最为密切,二者是调节“升降出入”的枢纽。同样肝脏病变也可通过肝之经络系统影响到这些脏腑组织器官的功能(以肝脾不调最为常见),而产生病变。因此,湿热疫毒外袭、内生之毒为患,极易入肝脏血分,深入肝络,犯肝累脾,发生传变,导致一系列变证。
本研究在前期临床及实验研究基础上,结合文献研究及导师经验,对乙型肝炎肝硬化的病因、病机,特别是基本病机和证候特点进行深入探讨,认为：①“疫毒内伏”是乙型肝炎肝硬化发生、发展的启动子和关键因素；②“肝脾不调、正气不足”则是影响乙型肝炎肝硬化病情发展的基本脏腑病变；③“水湿痰瘀浊阻滞”是乙型肝炎肝硬化的临床病理变化；④“毒损肝络,肝脾不调”是贯穿乙型肝炎肝硬化始终的基本病机。治疗上遵“扶正祛邪”的原则,采用“解毒和络、调和肝脾”的治疗大法,随证加减论治。
第二部分临床研究——乙型肝炎肝硬化证候特点及病机的临床研究
本研究对2007年9月-2009年10月间,分别于中国中医科学院广安门医院、解放军302医院、北京佑安医院、北京地坛医院,河南安阳市第五人民医院、河南省中医院、芜湖市第五人民医院、公主岭市人民医院等多家传染病医院或中医院传染科的住院或门诊搜集到的650份合格病例进行相关分析探讨。
1.一般资料研究
乙型肝炎肝硬化的发生、进展是多种因素共同综合作用的结果。本课题研究表明,性别、病程、年龄、季节以及情绪因素都是引起乙型肝炎肝硬化发病、进展的相关因素。尤其季节因素的研究符合中医传统四时医学理论,研究发现季节对乙型肝炎肝硬化病情的进展和／或加重有一定影响(202／650,31.1%),占52.0%(105／202),其中涉及春季者占52.0%(105／202)；涉及冬季者亦不在少数,占33.7%(68／202)。尤以春季明显,是否与春季气候变化无常或乙肝病毒的活性增强有关,值得进一步探讨。这印证了中医四时五脏相应,而肝病易发于春的认识。为从中医时间医学的角度,研究乙型肝炎肝硬化的发作和加重提供了依据。
2.乙型肝炎肝硬化证候特点研究
本研究应用频次统计对乙型肝炎肝硬化不同发展阶段的中医证候分布特点进行了分析。研究表明：肝胆湿热、脾胃湿热、湿困中焦、肝胃不和、肝肾阴虚等证型可以发生于肝硬化病变发展的整个过程中,在代偿和失代偿不同阶段均有表现；而肝脾不调、肝郁脾虚、肝气郁结主要反映在代偿性肝硬化阶段；气滞血瘀、脾肾阳虚、寒湿中阻多见于失代偿性肝硬化阶段,这表明乙型肝炎肝硬化的证候特点涉及湿热、气滞、血瘀、痰湿、肝脾(胃)肾、阴虚、阳虚等相关因素,且随着病情的发展,在湿热疫毒及内生之毒的作用下,出现肝脾不调,致使气滞血瘀逐渐加重,病变脏腑由肝脾而及肾,终至阴虚、阳虚叠现。
3.乙型肝炎肝硬化病机及临床特点研究
本研究通过对乙型肝炎肝硬化患者的“四诊”信息进行因子分析及聚类分析,并结合中医学理论对结果进行分析,具体结论如下：
(1)因子分析表明乙型肝炎肝硬化的病机涉及湿热、脾胃虚、肝气郁、肝脾不和、痰湿、水停、血瘀伤络及肾虚等相关因素。其特点为“虚实夹杂”。结合前面证候特点的研究结果可以初步认为其病机演变规律基本为：疫毒湿热内侵,耗气伤津,导致脾胃虚弱、肝气郁结、致使肝脾不调,后期兼及于肾,变生水湿痰瘀等病理产物,后者又可再伤肝脾肾,导致恶性循环,终成肝硬化之疾。
(2)聚类分析表明乙型肝炎肝硬化“毒损肝络、肝脾不调”基本病机相关证候类别为脾虚湿困类证,肝郁脾虚类证,湿热内蕴、肝脾肾俱虚类证,肝胆湿热类证。
(3)通过对聚类所得证候类别的相关指标计算权重,初步探讨乙型肝炎肝硬化“毒损肝络、肝脾不调”基本病机相关证候类别的诊断标准。
脾虚湿困类证：倦怠乏力、食欲差、腹胀、肝掌、腹胀大、目黄、红丝赤缕、胃脘胀、气短懒言、下肢浮肿、身黄、身困重、大便溏、胁肋胀、口淡乏味、舌淡、苔白厚腻、脉沉细。
肝郁脾虚类证：倦怠乏力、肝掌、面色萎黄、腹胀、食欲差、胁肋胀、小便黄赤、精神情绪异常、口淡乏味、胃脘胀、口渴、舌淡暗红、苔白厚腻、舌下系脉紫暗、脉沉弦细。
湿热内蕴、肝脾肾俱虚类证：倦怠乏力、小便黄赤、身体困重、腹胀、身黄、胃脘胀、肝掌、目黄、精神情绪异常、气短懒言、口渴、腰膝酸软、食欲差、眠差多梦、善太息、下肢浮肿、面色晦暗、胁肋胀、双目干涩、腹胀大、口苦、健忘、异常出血、烦躁、舌暗红、苔黄厚腻、脉弦。
肝胆湿热类证：目黄、身黄、肝掌、口渴、小便黄赤、口苦、倦怠乏力、面色晦暗、腹胀、大便不畅、色暗红、苔黄厚腻、舌下系脉紫暗迂曲、脉弦滑数。
4.“毒损肝络、肝脾不调”相关证候与临床检验指标关系的探讨
本研究对乙型肝炎肝硬化聚类后的各证候类别与常见临床指标进行比较,分析认为胆红素代谢异常在一定程度上似能反映湿热疫毒为患的病机及证候特点；ALP、PT反映的肝细胞损害及肝细胞合成功能障碍是基本病机演进的生化基础；血浆蛋白的下降是在疫毒与肝脾不调的双重作用下随着病情的发展逐渐出现的；ALT、AST和γ-GT体现了乙型肝炎肝硬化“毒损肝络、肝脾不调”病机的基本理化表现。
总之,本研究从理论和临床两方面入手,对乙型肝炎肝硬化的基本病机和证候特征进行了一定程度的探讨,发现了一定规律,今后尚需通过广泛收集临床信息,进一步探讨本病的病机及证候特征,为临床提供参考。
Hepatitis B virus (HBV) infection is a important of global public problem hepatic cirrhosis is its important of one of the development stage.In recent years, it becomes the hot pot to improve the diagnosis and treatment level of hepatitis B cirrhosis. To date, the therapy with satisfying therapeutic effect is absent, but traditional Chinese Medicine (TCM) exerts a promising future for clinical treatment, with combination of disease and syndrome differentiation, entirely regulation from multiple pathway and mufti-strata.
On support of National Natural Science Foundation of China, this research explores the etiological factors, discipline of the syndrome and pathogenesis of the hepatitis B cirrhosis, employing epidemiological method, by means of statistical methods,on the basis of past researches. The paper can be divided into two parts: theory and clinical research.
Part I:Theory study:the exploration of the hepatitis B cirrhosis s etiology and pathogenesis of TCM.
For many years, after long-time clinical practice and researches, my advisor and researching group postulate that the etiology of hepatitis B cirrhosis is "epidemic toxin" and "endogenous toxicity", the location of disease is "liver meridian", "the discord of the spleen and the liver" is basic pathological changes of the hepatitis B cirrhosis.This research proposes and expounds basic pathogenesis of "toxin damaging the liver meridian and the discord of the spleen and the liver", analyzes the characteristics of the occurrence and development of hepatitis B cirrhosis.
liver meridian is the important part of the whole collateral and meridian system, which distributes in liver, and constitutes the basic structural and functional unit. It processes not only the characteristics of meridian but also its special physiological and pathological features. Pathologically, liver meridian is the pathway of evil invasion, transmission and stagnating location. Liver can regulate the physiological function of related organs through its collateral and meridian system, in which the relationship of the liver and the spleen is most osculating,they are key points of ascending-descending。Vise visa, the diseases of the liver can affect other organs by the collaterals and meridians. So that, damp-heat epidemic toxin" and "endogenous toxicity" easily invade into the liver-blood, liver meridian, offenseing liver and tired spleen, transmission along and change, then inducing a series of diseases.
In terms of the literature study, combined with advisor's clinical practice and experimental studies, we concluded the etiological factors and major pathogenesis as following①Inhiding epidemic toxin is the promoter and the key of the hepatitis B cirrhosis.②They which are "the discord of the spleen and the liver、the deficiency of vital qi" effect the disease development, which is basic pathological changes of the hepatitis B cirrhosis.③Blocking stasis、wet、sputum and water are clinic pathological changes of the hepatitis B cirrhosis.④"toxin damaging the liver meridian and the discord of the spleen and the liver" are hepatitis B cirrhosis's basic pathogenesis. The therapeutic principle suggested to be resolveing toxin and dredging merdian, harmonizing liver and spleen.
PartⅡ:clinical research:Clinical research on the pathogenesis and the syndrome characteristics of hepatitis B cirrhosis.
This research analyzes of 650 eligible case of illness from 2007 to 2009, which come from several infectious diseases hospital of Guang'anmen Hospital、302 Military Hospital of China、Beijing YouAn Hospital、Beijing DiTan Hospita、The fifth Anyang People's hospital、The fifth People's hospital of WuHu、The People's hospital of GongZuLing、HeNan Provincial hospital of TCM.
1.Research on the baseline material.
The occurrence and activation of the hepatitis B cirrhosis is caused by multiple factors. Our research suggests that sex, age, duration, season and emotional factors participated in the pathogenesis, especially the season. The research has discovered that seasons have a certain influences on the development and(or) activation of the hepatitis B cirrhosis(202/650,31.1%), accounting for 52.0%(105/202) in the spring; accounting for 33.7%(68/202)in the winter.especially the spring.It is worth to further study that whether the development and/or activation of the hepatitis B cirrhosis are related to the enhanced
2 The study on the syndrome distributing laws of hepatitis B cirrhosis.
We applied frequency analysis, studied the syndrome distributing laws difference of hepatitis B cirrhosis different stages. It is suggested that liver and gallbladder dampness-heat, spleen-stomach dampness heat, dampness obstructing middle-jiao, Yin deficiency of liver and kidney appeared in Cirrhosis of the Liver, they are not different in the hepatitis B cirrhosis different stages; the discord of the spleen and the liver, liver depression and spleen deficiency, liver qi stagnation syndromemainly reflects in compensatory phase cirrhosis; qi stagnation and blood stasis, spleen-kidney yang deficiency, internal retention of cold wetness, mainly reflects in loss compensatory phase cirrhosis,which are syndrome characteristic or principal contradiction of loss compensatory phase cirrhosis.This indicates that syndrome characteristics of hepatitis B cirrhosis involves in dampness-heat, qi stagnation, blood stasis, phlegm-dampness, liver, spleen, kidney, yang deficiency,yin deficiency. With the disease development, damp-heat epidemic toxin and endogenous of toxicity lead to the discord of the spleen and the liver, qi stagnation and blood stasis aggravated gradually, disease of zang and fu is from liver-spleen to kidney, then gradually from yin deficiency to yang deficiency.
3. The study on pathogenesis and Clinical Characteristics of the hepatitis B cirrhosis.
We study on the "information from the TCM four diagnostic methods" by factor analysis and cluster analysis, combining with traditional chinese medicine theory,we analyze the results.
(1) Factor analysis shows that the pathogenesis of the hepatitis B cirrhosis involves in dampness-heat, weakness of spleen-stomach, liver qi stagnation, disharmony of liver-spleen, phlegm-dampness, water retention, blood stasis, kidney deficiency ect, which reflects in the pathogenesis evolution process of the hepatitis B cirrhosis, its character is group insufficiency and excess.It reveals as damp-heat epidemic toxin HBV latending in liver, which damages the liver meridian, results in the discord of the spleen and the liver and vital qi deficiency, qi blood and body fluid disorder, producing blood stasis and phlegm-dampness ect, that finally causes damp-heat brewing internally, discord of the spleen and the liver, stagnation of damp turbidity and static blood,that blocks merdian, forms of disease of hepatic cirrhosis.
(2) Cluster analysis shows that syndrome category which is "toxin damaging the liver meridian and the discord of the spleen and the liver"of the hepatitis B cirrhosis is stagnation of dampness due to splenic asthenia classified syndrome, liver depression and spleen deficiency classified syndrome, damp-heat brewing internally and liver-spleen-kideny deficiency classified syndrome, liver and gallbladder dampness-heat classified syndrome.
(3) We calculate weight of related indexes that have obtained by using cluster analysis and preliminary study on diagnostic criteria of related syndrome category,which are related with "toxin damaging the liver meridian and the discord of the spleen and the liver"of the hepatitis B cirrhosis's basic pathogenesis.
Stagnation of dampness due to splenic asthenia classified syndrome:burnout and hypodynamia, poor appetite, abdominal distension, liver palms,yellowish eyes, spider telangiectasia, bloating great, weiwan expansion, reluctant to speak, short of breath, low extremity edema, body huang, heaviness sensation of body, stool pond, xielei expansion, mouth pale dull, pale tongue, thick white greasy fur, deep and fine pulse.
Liver depression and spleen deficiency classified syndrome:burnout and hypodynamia, liver palms, Looking chlorosis, abdominal distension, poor appetite, xielei expansion, dark purple veins under the tongue, yellow red of Urine, mental or emotional abnormalities, pale dark red tongue, thick white greasy fur, mouth pale dull, weiwan expansion, thirsty, deep fine string pulse.
Damp-heat brewing internally and liver-spleen-kideny deficiency classified syndrome:burnout and hypodynamia, yellow red of Urine, heaviness sensation of body, abdominal distension, body huang, weiwan expansion, liver palms, yellowish eyes, mental or emotional abnormalities, reluctant to speak, short of breath, thirsty,sour and feeble of the lion and knees, poor appetite, Poor sleep,more dream,easy to sign, low extremity edema, complexion dark and gloomy, xielei expansion, Dry eyes, abdominal distension, mouth pain, having a bad memory, abnormal bleeding, irritable, dark red tongue, thick yellow greasy moss, string pulse.
Liver and gallbladder dampness-heat classified syndrome:yellowish eyes, body huang, liver palms, thirsty, yellow of Urine, mouth pain, burnout weak, abdominal distension, complexion dark and gloomy, poor stool, dark red tongue, thick yellow greasy moss, dark purple veins under the tongue, tortuous sublingual veins, string slip su pulse.
4. Exploring the relation of the "toxin damaging the liver meridian and the discord of the spleen and the liver" related syndrome and the clinical investigating indexes.
After clustering analysis, this research compared the common clinical indexes related to various syndromes of hepatitis B cirrhosis of the liver, we consider that disordered bilirubin and bile acid (BA) metabolism may be the pathogenesis and Syndromes of the hot and humid Immunotoxin; ALP, PT reflects the hepatocellular lesions and synthesis dysfunction may be the physical and chemical basis of the evolution of the basic pathogenesis; The decline of plasma protein in the Immunotoxin with the liver and spleen are not transferred under the action of pairs of heavy development as the gradual emergence of the disease; ALT, AST and y-GT embodies the basic pathogenesis of the biochemical appearances of the hepatitis B cirrhosis of the liver, that is " toxin damaging the liver meridian and the discord of the spleen and the liver". in this aspect we made a preliminary exploration and found some tendency, which still need to be verified by more intensive and extensive researches, we try to find the relation between the syndrome and the micro-index by collecting clinical material, provide references for the clinical practice.'
引文
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