| Hepatitis cirrhosis is the end-stage of chronic, progressive and diffuse liver disease due to the long-term effects of hepatitis virus on the liver. Liver fibrous tissue proliferated, normal lobular structures was disrupted and replaced with regenerative nodules and false lobules, resulting in normal blood supply to the liver was damaged, and its clinical menifestation included liver dysfunction and portal hypertension,etc. According to traditioanal Chinese medicine(TCM), the occurrence and development of hepatitis cirrhosis was affected by the dysfunction of liver controlling dispersion and housing blood. The specific contents of dysfunction of liver housing blood included blood stasis, yin deficiency, etc. The study focused on analyzing the correlation between dysfunction of liver housing blood and indicators from lab findings and imaging of hepatitis cirrhosis, supplying evidence for interpreting the modern scientific connotation of liver housing blood by inferring physiology from pathology.Objective1To build the working hypothesis by combing the theory of hepatitis cirrhosis and liver housing blood.2To understand the distribution features of common syndrome elements of hepatitis cirrhosis, and then understand the manifestation featres of blood stasis, yin deficiency, etc. based on the clinical cross-sectional survey data.3To understand the manifestation features of indicators when liver housing blood was dysfunction based on the clinical cross-sectional survey data and supply evidence for further analysis.4To supply evidence for interpreting the modern scientific connotation of dysfunction of liver housing blood by analyzing the correlation between the dysfunction manifestation of liver housing blood and indicators from lab findings and imaging based on the clinical cross-sectional survey data.Methods1Building the working hypothesisThe traditional Chinese medicine(TCM) theory of the dysfunction manifestation of liver housing blood and hepatitis cirrhosis pathogenesis and the western medicine theory of liver physiology and hepatitis cirrhosis pathophysiology was combed. The syndrome elements of the dysfunction manifestation of liver housing blood was established. The working hypothesis was built.2Data collectionNationwide multi-center cross-sectional epidemiological survey was conducted. TCM symptoms, signs and indicators from lab findings and imaging were collected by using the unified "hepatitis cirrhosis case survey form" formulated by research group.3"Standards of hepatitis cirrhosis syndrome elements differentiation"The standards were formulated based on current multiple clinic consensus, literature review, clinical survey data and experts evaluation.4"Quantization form of hepatitis cirrhosis symptoms and syndrome elements"The form was formulated based on the quantitative classification of symptoms and signs in the "hepatitis cirrhosis case survey form".5Data processingIncluding data entry, data cleaning and data type conversion.6Statistical methodsSPSS13.0statistical package was adopted.6.1Analyzing the distribution features(1) Independent sample t test or Mann-Whitney rank sum test was used to compare the difference between two groups and one-way ANOVA or Kruskal-Wallis H test was used to compare the differences among three groups when the data was measurement.(2)The chi-square test was used to compare the difference between two groups when the data was count.Statistical inference took0.05as the significance level.6.2Analyzing the correlation(1)Linear trend:a linear trend was used to observe the liner trend between syndrome elements quantized score of blood stasis or yin deficiency and indicators’average level.(2) Simple correlation analysis:pearson and spearman correlation analysis were respectively used to analyze continuous and categorical variables.(3)Multiple linear regression:syndrome elements quantized score of blood stasis or yin deficiency as the dependent variable, the indicators level as independent variable, the variable selection using stepwise regression method. (4) Binary Logistic Regression Analysis:whether blood stasis or yin deficiency combined with bleeding syndrome being diagnosed as the dependent variable, whether indicators being abnormal as independent variables, single independent variable in fitting the model were respectively conducted using the enter method.(5) Stepwise Bayes discriminant analysis:whether blood stasis or yin deficiency being diagnosed, and whether blood stasis or yin deficiency combined with bleeding syndrome being diagnosed as the dependent variables, indicators as the independent variables, variables selection using Wilks’Lambda method.Results1Building the working hypothesis of the studyThe occurrence and development of hepatitis cirrhosis was affected by blood stasis and yin deficiency, which were the dysfunction manifestation of liver housing blood. The correlation between the syndrome elements of blood stasis, yin deficiency(or combined with bleeding syndrome) and indicators(routine blood test, clotting function, liver function, portal hemodynamics, liver ultrasound, endoscopy, liver reserve function, vasoactive substances, etc.) were explored by using statistical methods as the tools.2The distribution features of syndrome elements of hepatitis cirrhosis(1) The distribution of syndrome elements:503cases of patients were diagnosed blood stasis,448case of yin deficiency,257cases of damp heat,438cases of qi stagnation,517cases of qi deficiency,428cases of yang deficiency,462cases of water retention during all the801cases of hepatitis cirrhosis patients.(2)The distribution of blood stasis and yin deficiency:In the compensated and decompensated stages, patients with blood stasis accounted for52.50%and69.60%and quantified score were4.97±2.41and5.96±2.61respectively (P<0.05); patients with yin deficiency accounted for55.40%and56.30%and quantified score were5.33±2.05and5.55±2.15respectively (P>0.05)(3) The distribution of bleeding syndrome:In the compensated&decompensated stage, patients with hematemesis, melena, ecchymosis, gum bleeding and epistaxis accounted for5&38,5&33,7&16,72&78and43&70cases respectively. In addition, gum bleeding usually combined with epistaxis, which was most distributed in the two stages. Hematemesis combined with melena, which was distributed in the decompensated stage.(4) The distribution of combination of blood stasis or yin deficiency with bleeding syndrome:67.4%of hematemesis patients,71%of melena patients,91.3%of ecchymosis patients,92%of gum bleeding patients and96.4%of epistaxis patients combined with blood stasis or(and) yin deficiency. The quantified score of blood stasis and yin deficiency exists difference among the three groups of blood stasis, yin deficiency and their combination and both the score was much higher when combined with ecchymosis, hematemesis or melena than other bleeding syndrome.3The manifestation features of indicators when liver housing blood dysfunction3.1The manifestation features of indicators when blood stasis existed or aggravatedWhen blood stasis existed or aggravated, the changes of indicators contained:(1) reduced erythrocytes, hemoglobin, hematocrit, platelets, mean platelet volume, etc.;(2)prolonged prothrombin time, reduced prothrombin time activity percentage, increased international normalized ratio;(3) reduced albumin, albumin/globulin and prealbumin, elevated globulin;(4) increased MELD, Child-Pugh score;(5)growed spleen diameter and thickness;(6)widened portal vein, reduced portal vein average flow velocity, etc. through comparing the difference of indicator level between blood stasis and not blood stasis groups, blood stasis in the compensated and decompensated stages, and the difference of blood stasis’s distribution and quantified score between the normal and abnormal indicators groups.When blood stasis combined with bleeding syndrome existed, the changes of indicators contained:(1) reduced erythrocytes, hemoglobin, hematocrit and platelets;(2) reduced prothrombin time activity percentage, increased international normalized ratio;(3) reduced total protein, albumin, and albumin/globulin;(4) elevated hepatic artery peak velocity, etc. through comparing the difference of distribution of blood stasis combined with hematemesis, melena, ecchymosis, gum bleeding and epistaxis respectively between the normal and abnormal indicators groups.The above differences were statistically significant (P<0.05)3.2The manifestation features of indicators when yin deficiency existed or aggravatedWhen yin deficiency existed or aggravated, the changes of indicators contained:(1) reduced prothrombin time activity percentage, increased international normalized ratio, elevated fibrinogen;(2) elevated globulin, reduced albumin/globulin;(3) reduced erythrocytes, hemoglobin, hematocrit, and mean platelet volume, etc.(4)growed spleen thickness;(5)elevated hepatic artery peak velocity, reduced portal vein average flow velocity;(6) reduced NO level, etc. through comparing the difference of indicator level between yin deficiency and not yin deficiency groups, yin deficiency in the compensated and decompensated stages, and the difference of yin deficiency’s distribution and quantified score between the normal and abnormal indicators groups.When yin deficiency combined with bleeding syndrome existed, the changes of indicators contained:(1) reduced percentage of neutrophils, erythrocytes, hemoglobin, hematocrit, platelets, mean platelet volume;(2) reduced prothrombin time activity percentage, increased international normalized ratio;(3)increased MELD score;(4)widened hepatic artery, etc. through comparing the difference of distribution of yin deficiency combined with hematemesis, melena, ecchymosis, gum bleeding and epistaxis respectively between the normal and abnormal indicators groups.The above differences were statistically significant (P<0.05)3.3The manifestation features of indicators among the three groups of blood stasis, yin deficiency and their combination(1) albumin, albumin/globulin and total protein reduced, MELD, Child-Pugh score increased, portal vein and spleen vein average flow velocity reduced when blood stasis or their combination compared with yin deficiency group;(2) erythrocytes reduced, prothrombin time prolonged, prothrombin time activity percentage reduced, international normalized ratio increased when their combination compared with yin deficiency group;(3)5-HT, NO level reduced when yin deficiency or their combination compared with blood stasis group;(4) portal vein narrowed, percentage of neutrophils reduced when yin deficiency compared with blood stasis group. The above differences were statistically significant (P<0.05)4The correlation between dysfunction manifestation of liver housing blood and indicators of hepatitis cirrhosis patients 4.1The correlation between blood stasis and indicators of hepatitis cirrhosis patientsThe indicators that positively related with blood stasis included:(l)reduced platelets, mean platelet volume;(2) prolonged prothrombin time, reduced prothrombin time activity percentage, increased international normalized ratio;(3) reduced albumin, albumin/globulin, elevated globulin;(4) growed spleen thickness;(5)widened portal vein, reduced portal vein average flow velocity;(6) elevated AT-II level;(7) increased MELD, Child-Pugh score;(8) reduced erythrocytes, hemoglobin, hematocrit, etc. based on linear trend, simple correlation analysis and multiple linear regression.The indicators that positively related with blood stasis combined with bleeding syndrome included:(1)reduced prothrombin time activity percentage, increased international normalized ratio;(2)reduced erythrocytes, hemoglobin, hematocrit;(3)elevated hepatic artery peak velocity, etc. based on the simple correlation analysis and binary logistic regression analysis between indicators and blood stasis combined with bleeding syndrome.The above results were statistically significant (P<0.05)4.2The correlation between yin deficiency and indicators of hepatitis cirrhosis patientsThe indicators that positively related with yin deficiency included:(1)reduced prothrombin time activity percentage, increased international normalized ratio, elevated fibrinogen;(2) reduced albumin/globulin and prealbumin, elevated globulin;(3) narrowed portal vein, elevated hepatic artery peak velocity, widened hepatic artery;(4)reduced percentage of neutrophils;(5)reduced5-HT, TNF-a, NO level, etc. based on linear trend, simple correlation analysis and multiple linear regression.The indicators that positively related with yin deficiency combined with bleeding syndrome included:(1)reduced erythrocytes, hemoglobin, hematocrit;(2) reduced prothrombin time activity percentage, increased international normalized ratio;(3)widened hepatic artery, etc. based on the simple correlation analysis and binary logistic regression analysis between indicators and yin deficiency combined with bleeding syndrome.The above results were statistically significant (P<0.05)4.3Discriminant analysis among the three groups of blood stasis, yin deficiency and their combination of hepatitis cirrhosis patients The indicators that contributed to discriminate blood stasis, yin deficiency and their combination were erythrocytes, albumin, portal vein,5-HT and TNF-a.The indicators that contributed to discriminate blood stasis, yin deficiency and their combination accompanied with5bleeding syndrome respectively were erythrocytes, leukocytes, prothrombin time activity percentage, fibrinogen, Child-Pugh score and NO level.Conclusion1With the severity of blood stasis in hepatitis cirrhosis patients, portal hypertension and splenomegaly/hypersplenism aggravated, liver reserve function decreased, liver coagulation dysfunctioned, etc.2With the severity of yin deficiency in hepatitis cirrhosis patients, liver’s synthesis of prothrombin dysfunctioned, liver’s synthesis of plasma protein dysfunctioned, portal hypertension aggravated, etc.3Inferring physiology from pathology of hepatitis corrihosis, the correlation preliminarily indicated that liver housing blood might associated with portal hemodynamics, spleen function, liver’s synthesis function of plasma protein, liver’s synthesis function of prothrombin, liver reserve function, etc. |
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