慢性肝病不同病程阶段病机证素分布特点临床调查研究
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摘要
“慢性肝炎一肝纤维化一肝硬化／肝癌”是许多慢性肝病患者最为恐惧的“三部曲”!如何阻断或延缓慢性肝病的进程,是中西医慢性肝病领域最为重要的科学问题。此前,30多年来,人们更多地开展了各种慢性肝病证候的标准化、客观化和规范化研究,或采用一方一药开展疗效评价及作用机制研究,而对制约提高中医药防治肝病临床疗效的瓶颈问题-—慢性肝病进程中的病机演变规律,尚缺乏深入研究,更没有形成切实能够指导临床应用的慢性肝病辨证论治思路与方法。为此,本项研究针对这一在江苏省科技厅自然科学基金项目(BK2010563)和南京中医药大学基础研究与重点培育专项基金项目(09XJC03)资助下完成以下研究。
研究目的
通过多中心、大样本临床流行病学调查,探讨湿、热、瘀、毒、郁和肝脾肾等脏腑虚实病机证素在慢性肝病进程中不同阶段的分布特点,及其之间的相关性,从而阐明慢性肝炎病机证素之间的兼夹、组合、转化规律,从而证明“湿热瘀毒互结”复合病机是慢性肝病的基本病机特征。
研究方法
(1)理论研究：
分别对中西医有关慢性肝病进程中相关研究的文献综述,基于中医整体观和辨证论治思想,对慢性肝病湿、热、瘀、毒、郁和气虚、阴虚、阳虚等主要病机证素的基本内涵、临床特征,在理论上阐明不同病机证素兼夹、转化和复合为患的发病学机制。
(2)临床研究：
①在参照《病毒性肝炎中医辨证标准》、《中药新药临床研究指导原则》和朱文峰教授《证素辨证学》及专家经验的基础上,通过预调查,确立肝病主要病机证素的辨识方法。
②采用多中心、大样本临床流行病学调查研究,选择慢性肝炎轻度、中度、重度,慢性重症肝炎、代偿期肝硬化和失代偿期肝硬化等慢性肝病的6个不同病程阶段患者,收集四诊信息、实验室检查等资料,采用Epidata数据库软件建立“慢性肝病脏腑病机证素临床调查信息采集系统”,采用State9、 SPSS17.0统计软件进行分析,探讨慢性肝病不同阶段的病机证素分布特点,及其间的相关性。
研究结果
(1)总计调查各型慢性肝病患者1003例,男女之比1.8：1,年龄以青壮年35～65岁为主,病程以1-5年为最多,其次是5-10年；(2)慢性肝病不同病程阶段中皆存在慢性肝病共性证候为倦怠乏力、纳差、口干、胁肋胀痛及溲黄；(3)湿、热、瘀、毒、郁临床证候表征的客观存在,随着病程的延长,或病情的加重,瘀热病机和肝肾阴虚证素所占比例逐渐升高；与年龄、性别无关。(4)涉及病机证素以湿、热、气滞、气虚为主,出现频次依次是热>脾胃气虚>肝肾阴虚>湿>肝郁气滞>脾肾阳虚>血瘀。其中,湿、热、瘀在所占比例分别为80.86%、88.63%和66.30%；湿热瘀三者互结并见所占比例为53.24%,慢性肝病轻度时为33.88%,中度时58.70%，重度时71.43%，肝硬化代偿期时62.93%,肝硬化失代偿期时88.70%。(5)脾胃气虚证素在年龄小于65岁的患者中始终处于前三位,但在65岁以后血瘀、脾胃气虚、肝肾阴虚及肝郁各病机证素所占比例相似。(6)理化检查指标、抗病毒疗法等与病机证素之间没有显著相关性。
结论
(1)慢性肝病男性多发于女性,多见于青壮年,病程长,短则1-5年,长则5-10年甚至更久。(2)慢性肝病共性证候信息表征依次是：倦怠乏力、纳差、口干、胁肋胀痛、溲黄、烦躁、失眠、多梦、口苦、胁肋隐痛、腹胀、面色晦暗、肢体困重、易怒、胃脘胀痛、腰膝酸软等。(3)病程越长,面色晦暗、胁肋隐痛等血瘀表现,或视物疲劳、腰酸膝软等肝肾阴虚表象所占比例越多；(4)口干、口苦、烦躁等火热证候存在于全部病程中,与病情严重程度有关：(5)病机证素中“热”及“脾胃气虚”占首要地位,其次是“湿”,湿热存在于整个肝病过程中,瘀热病机则与病情严重程度和病程密切相关。(6)本研究发现理化检查指标与慢性肝病病机证素之间存在一定相关性,但不具备特异性。(7)慢性肝病临床特点是：主要证候繁杂、集中,难以用单一证型来解释其全部临床表现,符合“湿热瘀毒互结”,多因复合为患,肝脾肾功能失调。(8)慢性肝病不同病程阶段的基本病机演变特点是：本虚标实,虚实夹杂,病情由邪盛为主,发展到邪盛与正虚并见,多因夹杂,湿热瘀毒互结复合病机贯穿始终。
总之,本研究证明了慢性肝病病情进展是由多种因素共同综合作用导致,湿热瘀毒互结复合病机贯穿慢性肝病发生发展始终,是各型慢性肝病的基本病机特征。
"Chronic liver disease(CLD),liver fibrosis,liver cirrhosis or hepatocellular carcinoma" is many patients with chronic liver disease most fear.How to block or delay the process of the CLD,is the most important scientific problems of the CLD in TCM and western medicine.After30years,people more had studied on the objective and the standardization of the CLD syndrome,or on a medicine effect assessment and mechanism research.The researches on the CLD in the process of evolution law are the lack of depth.lt is not able to guide formed more clinical application of the syndrome differentiation and treatment of the CLD ideas and methods.Therefore,this study is aimed at these problems,which is supported by the nature science fund project of Jiangsu Province(BK2010563) and Nanjing University of TCM basic research and cultivate special fund project(09XJC03).
Objective:Through the prospective, large sample clinical epidemiology investigation, this paper discusses the pathogenesis syndrome factors of the dampness,heat,blood stasis,toxin,depression and liver and spleen and kidney in the process of the distribution characteristics of the CLD different stages, and the correlation between them,thus the combination and transformation law of CLD pathogenesis factors.So as to prove the "dampness-heat-blood-stasis-toxin"composite pathogenesis is the CLD pathogenesis of basic features.
Methods:
(1)Theory study:Of TCM and western medicine were about the CLD in the process of the research literature review,based on the overall concept of TCM and syndrome differentiation idea.This research expatiate on the dampness,heat,blood stasis,toxin,depression and deficiency of qi and ying and yang of the CLD,such as main pathogenesis factors' transformation and compound of a precise definition of learning mechanism.
(2)Clinical research:①In reference to the,, writed by Zhu Wenfeng Professor,and expert experience.On the basis of the survey through,this research establishes the main pathogenesis factors identification method of the CLD.②Employing the multi-center,large sample,the prospective clinical epidemiological study,this research chooses six different course stage patients of the CLD,investigating the four diagnostic informations and laboratory indicators,etc.By the Epidata database software basing on the "chronic liver disease pathogenesis syndrome factor and clinical investigation information collection system", the Stata9and SPSS17.0statistical analyzing software, this paper discusses the different stages of the CLD pathogenesis factor distribution characteristics and relevance.
Results:(1)The survey each model in1003patients with CLD, the men and women than1.8:1, with young age35to65years mainly, the course of1～5years to for the most, followed by5～10years;(2)Chronic liver disease of different stage has the common syndromes:such as fatigues,anorexia,dry mouth,chest hypochondriac pain and yellow urine;(3)The clinical syndrome characteristics of dampness,heat,blood stasis,toxin,depression exist objectively,as the extension of course or the deterioration of the illness,blood stasis-heat pathogenesis and kidney yin deficiency syndrome factor proportion are increasing gradually,and they have nothing to do with age and sex.(4)Involving pathogenesis factors,as dampness,heat,qi depression,qi deficiency are given priority to, appearing frequency in turn is heat>qi deficiency>yin deficiency>dampness> qi depression>yang deficiency>blood stasis. Among them,the dampness,heat, blood stasis in proportion of80.86%, 88.63%and66.30%respectively;(5)spleen-stomach qi deficiency syndrome factors in the age of less than65-year-old patients is always in the top three, but in65after the age of spleen-stomach qi deficiency, blood stasis, liver-kidney Yin deficiency the pathogenesis syndrome factors are similar proportion.(6) by physical and chemical index, anti-retroviral therapy and pathogenesis, syndrome factor are no significant correlation among them.
Conclusions:(1)Among the CLD patients,men are more than women,more common in young and middle-aged.The CLD has a long course.(2)The common informations of the CLD syndrome characteristics in order:fatigues,anorexia,dry mouth,hypochondriac pain in stomach and chest,yellow urine,irritable,irritability,insomnia,bitter taste,chest dull pain,abdominal distension,looking gloomy,etc.(3)The longer the duration,the performances of blood stasis and liver-kidney yin deficiency are the more proportion.(4)The heat syndrome such as dry mouth,bitter taste,irritable,exists in the course of the whole,and in serious condition levels.(5)In the pathogenesis syndrome factor "heat" and "qi deficiency" accounting for primary status, the second is "dampness", dampness-heat exists in the whole process of the CLD.Blood stasis-heat pathogenesis and severe disease degree and course are closely related.(6)The study found that CLD pathogenesis syndrome factor and physical and chemical examination index has some correlations between, but are not specific.(7)The CLD clinical features are:main syndrome is multifarious, it is difficult to use a single factor to explain all of its clinical manifestations.(8)The CLD of different stages of the basic pathogenesis evolution features are: dampness-heat-blood-stasis-toxin composite pathogenesis is always existed throughout.
All in all, this study proves that the activation of the CLD is caused by multiple factors.Dampness-heat-blood-stasis-toxin composite pathogenesis is always existed throughout,and it is each CLD pathogenesis basic characteristics.
研究目的
通过多中心、大样本临床流行病学调查,探讨湿、热、瘀、毒、郁和肝脾肾等脏腑虚实病机证素在慢性肝病进程中不同阶段的分布特点,及其之间的相关性,从而阐明慢性肝炎病机证素之间的兼夹、组合、转化规律,从而证明“湿热瘀毒互结”复合病机是慢性肝病的基本病机特征。
研究方法
(1)理论研究：
分别对中西医有关慢性肝病进程中相关研究的文献综述,基于中医整体观和辨证论治思想,对慢性肝病湿、热、瘀、毒、郁和气虚、阴虚、阳虚等主要病机证素的基本内涵、临床特征,在理论上阐明不同病机证素兼夹、转化和复合为患的发病学机制。
(2)临床研究：
①在参照《病毒性肝炎中医辨证标准》、《中药新药临床研究指导原则》和朱文峰教授《证素辨证学》及专家经验的基础上,通过预调查,确立肝病主要病机证素的辨识方法。
②采用多中心、大样本临床流行病学调查研究,选择慢性肝炎轻度、中度、重度,慢性重症肝炎、代偿期肝硬化和失代偿期肝硬化等慢性肝病的6个不同病程阶段患者,收集四诊信息、实验室检查等资料,采用Epidata数据库软件建立“慢性肝病脏腑病机证素临床调查信息采集系统”,采用State9、 SPSS17.0统计软件进行分析,探讨慢性肝病不同阶段的病机证素分布特点,及其间的相关性。
研究结果
(1)总计调查各型慢性肝病患者1003例,男女之比1.8：1,年龄以青壮年35～65岁为主,病程以1-5年为最多,其次是5-10年；(2)慢性肝病不同病程阶段中皆存在慢性肝病共性证候为倦怠乏力、纳差、口干、胁肋胀痛及溲黄；(3)湿、热、瘀、毒、郁临床证候表征的客观存在,随着病程的延长,或病情的加重,瘀热病机和肝肾阴虚证素所占比例逐渐升高；与年龄、性别无关。(4)涉及病机证素以湿、热、气滞、气虚为主,出现频次依次是热>脾胃气虚>肝肾阴虚>湿>肝郁气滞>脾肾阳虚>血瘀。其中,湿、热、瘀在所占比例分别为80.86%、88.63%和66.30%；湿热瘀三者互结并见所占比例为53.24%,慢性肝病轻度时为33.88%,中度时58.70%，重度时71.43%，肝硬化代偿期时62.93%,肝硬化失代偿期时88.70%。(5)脾胃气虚证素在年龄小于65岁的患者中始终处于前三位,但在65岁以后血瘀、脾胃气虚、肝肾阴虚及肝郁各病机证素所占比例相似。(6)理化检查指标、抗病毒疗法等与病机证素之间没有显著相关性。
结论
(1)慢性肝病男性多发于女性,多见于青壮年,病程长,短则1-5年,长则5-10年甚至更久。(2)慢性肝病共性证候信息表征依次是：倦怠乏力、纳差、口干、胁肋胀痛、溲黄、烦躁、失眠、多梦、口苦、胁肋隐痛、腹胀、面色晦暗、肢体困重、易怒、胃脘胀痛、腰膝酸软等。(3)病程越长,面色晦暗、胁肋隐痛等血瘀表现,或视物疲劳、腰酸膝软等肝肾阴虚表象所占比例越多；(4)口干、口苦、烦躁等火热证候存在于全部病程中,与病情严重程度有关：(5)病机证素中“热”及“脾胃气虚”占首要地位,其次是“湿”,湿热存在于整个肝病过程中,瘀热病机则与病情严重程度和病程密切相关。(6)本研究发现理化检查指标与慢性肝病病机证素之间存在一定相关性,但不具备特异性。(7)慢性肝病临床特点是：主要证候繁杂、集中,难以用单一证型来解释其全部临床表现,符合“湿热瘀毒互结”,多因复合为患,肝脾肾功能失调。(8)慢性肝病不同病程阶段的基本病机演变特点是：本虚标实,虚实夹杂,病情由邪盛为主,发展到邪盛与正虚并见,多因夹杂,湿热瘀毒互结复合病机贯穿始终。
总之,本研究证明了慢性肝病病情进展是由多种因素共同综合作用导致,湿热瘀毒互结复合病机贯穿慢性肝病发生发展始终,是各型慢性肝病的基本病机特征。
"Chronic liver disease(CLD),liver fibrosis,liver cirrhosis or hepatocellular carcinoma" is many patients with chronic liver disease most fear.How to block or delay the process of the CLD,is the most important scientific problems of the CLD in TCM and western medicine.After30years,people more had studied on the objective and the standardization of the CLD syndrome,or on a medicine effect assessment and mechanism research.The researches on the CLD in the process of evolution law are the lack of depth.lt is not able to guide formed more clinical application of the syndrome differentiation and treatment of the CLD ideas and methods.Therefore,this study is aimed at these problems,which is supported by the nature science fund project of Jiangsu Province(BK2010563) and Nanjing University of TCM basic research and cultivate special fund project(09XJC03).
Objective:Through the prospective, large sample clinical epidemiology investigation, this paper discusses the pathogenesis syndrome factors of the dampness,heat,blood stasis,toxin,depression and liver and spleen and kidney in the process of the distribution characteristics of the CLD different stages, and the correlation between them,thus the combination and transformation law of CLD pathogenesis factors.So as to prove the "dampness-heat-blood-stasis-toxin"composite pathogenesis is the CLD pathogenesis of basic features.
Methods:
(1)Theory study:Of TCM and western medicine were about the CLD in the process of the research literature review,based on the overall concept of TCM and syndrome differentiation idea.This research expatiate on the dampness,heat,blood stasis,toxin,depression and deficiency of qi and ying and yang of the CLD,such as main pathogenesis factors' transformation and compound of a precise definition of learning mechanism.
(2)Clinical research:①In reference to the
Results:(1)The survey each model in1003patients with CLD, the men and women than1.8:1, with young age35to65years mainly, the course of1～5years to for the most, followed by5～10years;(2)Chronic liver disease of different stage has the common syndromes:such as fatigues,anorexia,dry mouth,chest hypochondriac pain and yellow urine;(3)The clinical syndrome characteristics of dampness,heat,blood stasis,toxin,depression exist objectively,as the extension of course or the deterioration of the illness,blood stasis-heat pathogenesis and kidney yin deficiency syndrome factor proportion are increasing gradually,and they have nothing to do with age and sex.(4)Involving pathogenesis factors,as dampness,heat,qi depression,qi deficiency are given priority to, appearing frequency in turn is heat>qi deficiency>yin deficiency>dampness> qi depression>yang deficiency>blood stasis. Among them,the dampness,heat, blood stasis in proportion of80.86%, 88.63%and66.30%respectively;(5)spleen-stomach qi deficiency syndrome factors in the age of less than65-year-old patients is always in the top three, but in65after the age of spleen-stomach qi deficiency, blood stasis, liver-kidney Yin deficiency the pathogenesis syndrome factors are similar proportion.(6) by physical and chemical index, anti-retroviral therapy and pathogenesis, syndrome factor are no significant correlation among them.
Conclusions:(1)Among the CLD patients,men are more than women,more common in young and middle-aged.The CLD has a long course.(2)The common informations of the CLD syndrome characteristics in order:fatigues,anorexia,dry mouth,hypochondriac pain in stomach and chest,yellow urine,irritable,irritability,insomnia,bitter taste,chest dull pain,abdominal distension,looking gloomy,etc.(3)The longer the duration,the performances of blood stasis and liver-kidney yin deficiency are the more proportion.(4)The heat syndrome such as dry mouth,bitter taste,irritable,exists in the course of the whole,and in serious condition levels.(5)In the pathogenesis syndrome factor "heat" and "qi deficiency" accounting for primary status, the second is "dampness", dampness-heat exists in the whole process of the CLD.Blood stasis-heat pathogenesis and severe disease degree and course are closely related.(6)The study found that CLD pathogenesis syndrome factor and physical and chemical examination index has some correlations between, but are not specific.(7)The CLD clinical features are:main syndrome is multifarious, it is difficult to use a single factor to explain all of its clinical manifestations.(8)The CLD of different stages of the basic pathogenesis evolution features are: dampness-heat-blood-stasis-toxin composite pathogenesis is always existed throughout.
All in all, this study proves that the activation of the CLD is caused by multiple factors.Dampness-heat-blood-stasis-toxin composite pathogenesis is always existed throughout,and it is each CLD pathogenesis basic characteristics.
引文
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