肝硬化辨证分型与辅助性检查指标及PGA指数的相关性研究
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摘要
背景:肝炎后肝硬化是慢性肝炎逐渐发展而成,严重影响人们生活质量,给家庭和社会带来了沉重的负担。然而目前西医对于本病的治疗都缺乏有效的手段,但中医对于本病的治疗具有一定的特色。然而由于本病临床表现错综复杂,常常影响辨证施治,并直接影响本病的治疗效果。中医认为,疾病是在病因作用下内在反应与外在表现的全部演变过程,同一种疾病由于发病时间、地点以及患者机体反应性不同或处于不同的发展阶段,可以表现出不同的证。且诊疗过程中对肝脏的形态、大小、门脉的管径及侧支循环,胆囊的情况,脾脏的厚度及少量腹水的部位及量都不得而知。超声能够在活体上观察到肝脏的形态大小及其内部的异常改变,作为肝硬化的首选诊断方法。为了使中医“证”和西医的“病”相互结合及统一,使中医辨证得以规范化,客观化,做到有证可循,进一步提高治疗效果,我们进行了肝硬化中医“证”与现代医学客观指标关系的研究。这对于我们探索中医“证”与现代医学客观指标关系,搞清他们之间的内在联系,指导临床辨证,将具有重要的实际意义。目前有研究以系统聚类分析法,在判明的三类证候为基础,运用逐步判别法和方差分析的多元统计法分析三类证候与其相关实验室指标是否有相关性。结果显示,肝炎后肝硬化患者的血清AST活性、Fn、FV、TNF-α等含量与各类证候存在一定相关性。此外,部分实验室指标在三类证候间亦有显著性差异,可从这些相关指标的病理生理意义方面发现肝炎后肝硬化部分中医病机的病理特点。但作为证候类型的判别,尚有待于进一步深入细致的分析探讨。
     目的:通过调查肝硬化患者症状体征、中医证候特点和证型分布,探讨辨证分型与肝硬化患者血清肝功能、肝纤维化指标、PGA指数、Child-pugh分级和影像学变化的关系,进一步为临床证候辨证标准规范化研究提供思路和方法。
     方法:本研究参照2000年9月西安全国肝病学术会议由中华医学会传染病与寄生虫病学会、肝病学分会联合修订的肝炎后肝硬化诊断标准,选取2006年10月~2008年10月江苏省中医院感染科、南通市第三人民医院中西医结合专科、常州市第三人民医院中西医结合专科门诊和病房300例患者,调查患者的临床表现、证候特征、辨证分型,按中国中西医结合学会消化系统疾病专业委员会于1993年11月在洛阳召开的第五届学术交流会上制定的肝硬化临床诊断、中医辨证和疗效标准修订方案进行证候识别,收集患者的血清肝功能指标、肝纤维化指标、计算出PGA指数、Child-pugh分级,运用彩色Doppler观察患者的肝脏的血流并对其血流动力学进行测定。并努力找出这些证候与肝功能、肝纤维化指标、PGA指数及影像学改变的关系。
     结果:本研究调查了300例肝炎后肝硬化患者,其中男性190例(占63.3%),女性110例(占36.4%),患者最小年龄22岁,最大年龄70岁,平均年龄50.4岁,肝硬化患者多集中分布在40~60岁阶段。乙型肝炎病毒感染者215例,丙型肝炎病毒感染82例,3例为乙肝合并感染丙肝;有明确的家族史者204例,有明确输血史者51例,感染途径不明者45例。代偿期患者174例,失代偿期患者126例;Child A级患者98例,Child B级92例,C级110例;有43例患者行过脾切除;有108例病人首诊即为肝硬化,其中58例处于失代偿期;明确为肝硬化腹水者153例。
     本研究观察临床症状以乏力最为多见,有91.0%的患者有不同程度的表现,较为明显的占51%;腰膝酸软或腰痛占83.7%;脉弦237例,占75%;口苦占67.7%。其他出现较多的有目黄身黄尿黄66.0%;胁隐痛劳累加重61.3%;苔黄腻54.7%,小便短赤54.0%;舌苔薄白48.3%;两目干涩40.7%;舌红少苔34%;脉弦滑或滑数95例,占31.7%;脉细数占31.3%;尿少占31.0%;脘闷腹胀占30%;五心烦热或低热占29%;胁部灼痛占28.7%。有55.7%的病人出现大便性状的改变,其中便溏84例,占28%,便干结难下或粘滞不爽83例,占27.7%;其余的症状还有下肢浮肿、恶心恶吐、面晦黎黑、舌紫暗或瘀点、脉细涩或芤、胁下痞胀疼痛等。中医诊断共分六个证型,其分布如下:肝气郁结证24例,占8%:脾虚湿盛证42例,占14%;湿热内蕴证66例,占22%;肝肾阴虚证70例,占23.3%;脾肾阳虚证36例,占12%;血瘀证62例,占20.7%。
     比较中医辨证分型与Child-pugh的关系发现,肝气郁结以A级为主,占88.9%,与其它差异显著(P<0.05),未见有C级病人;而肝肾阴虚、脾肾阳虚、血瘀证则以C级为主,分别占61.52%、83.3%、75%,与另三种证型有显著差异(P<0.05)。湿热内蕴证患者的ALT、AST较其他证型明显升高,与血瘀证患者比较,差异有统计学意义(P<0.01);肝气郁结证患者的Alb较正常值减少不明显,而其他各证型Alb下降较多,尤以肝肾阴虚证、脾肾阳虚证患者为著。HA以血瘀证与湿热内蕴证为最高,与其它证候比较有显著差异(P<0.05),但此两组相比,无显著差异(P>0.05),脾肾阳虚与肝肾阴虚也无明显差异,而肝气郁结为最低。PⅢP、C-Ⅳ与HA有类似特点,但不成平行关系。PGA数值各证候间有显著差异,尤以肝肾阴虚证为最高,血瘀证为其次,而湿热内蕴证并不是最高的,这和肝纤维化指标在各症候中的分布是不同的。
     结论:湿热内蕴证患者多处于病毒清除期,机体免疫反应活跃,肝脏细胞受损程度较重,致使转氨酶较其他证型升高明显。肝肾阴虚证和脾肾阳虚证多见于肝病终末期,因病情缠绵,迁延日久,肝脏合成功能受损,长期的消化吸收功能障碍,也妨碍了人体正常的营养供应,致使该两型患者白蛋白较其他证型降低明显,而肝气郁结证多见于病程较短,病情较轻的患者,肝脏代偿功能仍然较好,白蛋白水平较正常值无明显下降。肝硬化中医辨证分型与实验室指标和影像学变化有着内在的联系,将肝功能、肝纤维化指标、PGA指数和B超联合检测可明显提高对肝炎后肝硬化中医辨证分型客观依据的敏感性和特异性,能指导我们临床辨证用药。
Project:Aim to explore the relationship between TCM Syndromes classification and serum liver function,hepatic fibrosis,PGA index,Child-pugh classification and the changes in imaging in patients with liver cirrhosis,and provide further clinical syndrome differentiation criteria standardization of research ideas and methods.
     Methods:In this study,with reference to the diagnostic criteria of liver cirrhosis revised in the National Symposium on liver disease by the Chinese Medical Association Society of infectious and parasitic diseases and liver disease.this investigation selected 300 cases of patients from the inpatient and out-patient of infectious disease dept of Jiangsu provincial hospital of TCM in October 2006 October 2008,investigating the clinical performance characteristics syndrome, syndrome type,according to traditional Chinese and western medicine in China Institute of Professional Committee of digestive diseases in the November 1993 meeting of the fifth in Luoyang academic exchange at the development of clinical diagnosis of livuuuuuuer cirrhosis,and efficacy of TCM program standards amended Syndrome identification,collection of serum indicators of liver function,hepatic fibrosis,PGA index calculated,Child-pugh classification,the use of color Doppler Observation of blood flow in patients with liver and hemodynamics were measured. And efforts to identify these relationship among syndromes,the liver function,hepatic fibrosis,PGA index and image changes.
     Result:This study investigated 300 cases of patients with liver cirrhosis, including 190 cases of men(or 63.3%),female 110 cases(36.4%),patients with 22-year-old minimum age,maximum age 70 years old,the average age of 50.4 years old,patients with liver cirrhosis more concentrated in 40 to 60-year-old stage.215 cases of HBV,hepatitis C virus infection in 82 cases,three cases of hepatitis C infection and hepatitis B;a clear family history of the 204 cases,a clear history of 51 cases of blood transfusion,infection 45 cases of unknown.174 cases of decompensated patients,patients with decompensated 126 cases;Child A class patients with 98 cases,Child B class 92 cases,C-class 110 cases;there have been 43 cases of patients with splenectomy;108 patients the first attending was diagnosed cirrhosis,which in 58 cases of decompensation period;those 153 cases of ascites due to cirrhosis is definite.
     The most often clinical symptoms observed in this study was weak,with 91.0%of patients with different levels of performance,perhaps even more evident in 51%;knee flabby or low back pain accounted for 83.7%;237 cases of pulse string,accounting for 75%;pain accounted for 67.7%.Occuring more frequently with yellow skin and yellow urine accout for 66.0%;flank exertion pain 61.3%;yellow greasy moss 54.7%, 54.0%short urine;tongue thin white 48.3%;the 40.7%of eyes dry;mamillata less cover on the tongue 34%;pulse slip or slide string account for 95 cases,accounting for 31.7%;thin and fast pulse accounted for 31.3%;oliguria accounted for 31.0%;upper abdomen bloating and nausea 30%;hot or low fever 29%;flank burning sore accounted for 28.7%.There are 55.7%of patients change in stool traits,of which 84 cases have pond,accounting for 28%,then dry and hard or sticky 83 cases of discrepancy,accounting for 27.7%;the rest have symptoms of lower extremity edema, nausea,vomiting evil face Leahey dark,dark purple tongue or blockage point, Shibuya or hollow fine veins,swelling of the liver swell flank pain.Chinese medicine diagnosis is divided into six types,and its distribution is as follows:24 cases of liver pent-up syndrome,accounting for 8%;42 cases of spleen deficiency wet syndrome, accounting for 14%;66 cases of intrinsic heat and damp,accounting for 22%; liver-yin and kidney-yin deficiency 70 cases,accounting for 23.3%;36 cases of Spleen-Yang and Kidney-Yang Deficiency 12%;62 cases of blood stasis syndrome, accounting for 20.7%.
     Comparison of TCM Syndrome Types with the Child-pugh suggested that liver pent-up lied in A class,accounting for 88.9%,with other significant difference(P<0.05),no C-class patients;and liver-yin and kidney-yin deficiency,spleen and kidney yang deficiency,blood stasis mainly concluded to C-grade,accounted for 61.52%,83.3%,75%,respectively,with another three syndromes were significantly different(P<0.05).ALT,AST of patients with intrinsic heat increased than those of other significantly,compared with patients with blood stasis syndrome,the difference was statistically significant(P<0.01);Alb of liver pent-up had no reduction in the normal,while Alb of the others decrease,particularly of liver-yin kidney-yin deficiency and syndorme of spleen-yang and kidney yang deficiency.HA binding to blood stasis and syndrome of heat and damp were significantly different(P<0.05) compared with other symptoms,but the two groups had no significant difference(P>0.05),there was no difference between spleen-yang and kidney-yang deficiency, liver-yin and kidney yin deficiency.PⅢP,C-Ⅳand HA have similar features,there is no parallel relationship.PGA index between the various syndromes were significaatly different,particularly supremly in the liver-yin and kidney-yin deficiency,blood stasis is followed,and the heat is not the highest intrinsic evidence,this is different between the indicator of liver fibrosis.
     Conclusion:The syndrome of intrinsic heat and damp in hepatic cirrhosis patients mostly get along with clear multi-period,active immune response,severe liver cell damage,resulting in transaminase increased significantly.Liver-yin and kidney-yin deficiency and syndrome of spleen-yang and kidney-Yang deficiency are often found in end-stage liver disease due to prolonged,lingering illness,liver synthetic function, digestion and absorption dysfunction also prevented the supply of human normal nutrition,resulting in the albumin in patients with two types of syndromes than the other types,and the syndrome of pent-up liver disease was particularly prevalent in shorter in patients with less severe diseases,decompensated liver function is still better than the normal albumin levels,and had no significant decline.Syndrome Types of cirrhosis of TCM with laboratory indicators,liver function,hepatic fibrosis, PGA index and the changes in imaging is intrinsically linked to each other.Those values can significantly increase the detection of objective sensitivity and specificity of liver cirrhosis syndrome differentiation,it also can use to guide our clinical differentiation.
引文
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