| ObjectiveIn this study,the clinical cases of hepatitis B liver fibrosis were retrospectively analyzed to explore the distribution of TCM syndromes,TCM constitution and the five movements and six climates in embryonic period in patients with hepatitis B liver fibrosis.We further analyzed the correlation between the above factors and liver pathology and other objective indicators,so that we can summarized the differences in pathological liver fibrosis staging and serological indicators among patients with hepatitis B liver fibrosis who had different TCM syndromes,TCM constitutions and five movements and six climates in embryonic period.On this basis,we established a non-invasive significant prediction model of liver fibrosis,which was composed of TCM constitution,five movements and six climates in embryonic period and serological indexes,so as to identify patients with high risk of moderate and severe liver fibrosis in clinical diagnosis and treatment..We hoped that this study will provide a scientific basis for the clinical diagnosis and treatment of hepatitis B liver fibrosis and a new idea for the further study of traditional Chinese medicine.MethodsIn this study,a retrospective study was conducted to collect the clinical data of the patients with hepatitis B liver fibrosis who underwent liver biopsy in Department of Hepatology,Guangdong Provincial Hospital of Traditional Chinese Medicine in the past 10 years,including gender,age,TCM syndrome differentiation,TCM constitution type,date of birth,pathological results of liver tissue,ALT,AST,PLT,PCIII,LV,IV-C,HA,IgA,IgM,IgG,C3,C4 and CH50.After the establishment of the database,statistical analysis was carried out to analyze the correlation between TCM syndrome type,constitution,five movements and six climates in embryonic period and liver pathology and other objective indicators in patients with hepatitis B liver fibrosis.On this basis,some influencing factors with statistical differences were preliminarily screened as independent predictors into binary logistics regression analysis.The regression model was established according to its parameters and regression coefficients,and the diagnostic value was tested by ROC curve,use DCA curve to test the clinical value of the predictive model.Result1 Analysis of correlation between TCM Syndromes and objective Indexes of Hepatitis B Hepatic Fibrosis:1.1 General informationA total of 1145 patients with hepatitis B liver fibrosis were included,with an average age of 39.69±10.68 years.Most of the patients were male(71.97%),of which patients aged 26-55 accounted for 82.45%of the total cases.1.2 Distribution characteristics of TCM syndromes:It is divided into five TCM syndrome types:liver depression and spleen deficiency type,liver and gallbladder damp-heat type,blood stasis type,liver and kidney yin deficiency type and spleen and kidney yang deficiency type.Among them,the top three were liver stagnation and spleen deficiency(62.10%),damp-heat of liver and gallbladder(21.48%),and blood stasis blocking collaterals(14.41%).1.3 Correlation between TCM Syndrome types and stages of pathological Hepatic Fibrosis:The distribution of pathological liver fibrosis stages was different among patients with different TCM syndrome types(P<0.01).The proportion of patients with liver stagnation and spleen deficiency type in S1-S2 stage of liver fibrosis was significantly higher than that of other TCM syndrome types,and the proportion of patients with blood stasis blocking collaterals type in S3-S4 stage was significantly higher than that of other TCM syndrome types(P<0.05).1.4 Correlation between TCM syndrome types and serological indexes:There were differences in ALT and AST levels of liver function in patients with different TCM syndrome types.The levels of ALT and AST in patients with damp-heat in liver and gallbladder were significantly higher than those in patients with liver stagnation and spleen deficiency(51 vs.33,37 vs.27,P<0.05),but there was no significant difference between them and other syndrome types(P>0.05).The levels of PCIII,LN,IV-C and HA in patients with blood stasis blocking collaterals were significantly higher than those in patients with liver stagnation and spleen deficiency(9.8 vs.8.4,55.6 vs.41.1,54.8 vs.44.6,48.9 vs.30.4,P<0.05),and the levels of LN and HA in patients with blood stasis blocking collaterals were significantly higher than those in patients with damp-heat of liver and gallbladder(55.6 vs.43.9,48.9 vs.38.8,P<0.05).There was no significant difference in the level of 6 immune items among patients with different TCM syndrome types(P>0.05).2 Analysis of correlation between TCM Constitution and objective Indexes of Hepatitis B Hepatic Fibrosis:2.1 Distribution characteristics of TCM constitution types:the top five TCM constitutions ranked in descending order:qi deficiency constitution>qi stagnation constitution>phlegm dampness constitution>blood stasis constitution>damp heat constitution,accounting for 94.79%in total.2.2 Correlation between TCM constitution and pathological liver fibrosis stage:The distribution of pathological liver fibrosis stage in patients with different TCM constitutions is different.The proportion of patients with qi deficiency in S1-S2 stage of liver fibrosis(31.12%)was significantly higher than that of other TCM constitutions,and the proportion of patients with blood stasis in S3-S4 stage(35.29%)was significantly higher than that of other TCM constitutions(P<0.05).2.3 Correlation between TCM constitution and serological indexes:ALT and AST levels in patients with different TCM constitutions are different.The level of ALT in patients with damp-heat and blood stasis was significantly higher than that in patients with qi deficiency(40.0 vs.31.0,39.0 vs.31.0,P<0.05),and the level of AST in patients with damp-heat was significantly higher than that in patients with qi deficiency and phlegm-dampness(31.5 vs.27.0,31.5 vs.27.0,P<0.05).There are differences in PCIII,LN,IV-C,HA in patients with different TCM constitutions.Among them,the levels of PCⅢ and IV-C in patients with blood stasis were significantly higher than those in patients with phlegm-dampness(9.11 vs.7.90,51.96 vs.42.50,P<0.05),and the levels of LN in patients with blood stasis were significantly higher than those in patients with qi deficiency and phlegm-dampness(52.55 vs.42.68 52.55 vs.38.90,P<0.05).The level of HA in patients with blood stasis was significantly higher than that in patients with qi deficiency(43.46 vs.32.60,43.49 vs.30.22,P<0.05),and the level of HA in patients with yin deficiency was significantly higher than that in patients with qi deficiency and qi depression(45.80 vs.32.60,45.80 vs.30.22,P<0.05).Patients with different TCM constitutions have statistical differences in the distribution of IgA,IgG and CH50 levels,while there are no statistical differences in the distribution of IgM,C3 and C4 levels.The level of IgA in patients with yang deficiency was significantly lower than that in patients with qi deficiency(0.6vs.2.5,24.0 vs.35.0,P<0.05).The levels of IgG and CH50 in patients with yang deficiency were significantly lower than those in other physique types(P<0.05).There are differences in the levels of IgG,IgM,C4 and CH50 in patients with different TCM constitutions,but there is no statistical difference in the levels of IgA and C3.The level of IgA in patients with yang deficiency was significantly lower than that in patients with qi deficiency(0.6 vs.2.5,24.0 vs.35.0,P<0.05).The levels of IgG and CH50 in patients with yang deficiency were significantly lower than those in other TCM constitutions(P<0.05).3 Analysis of the correlation between the five movements and six climates in embryonic period and the objective Indexes of Hepatitis B Hepatic Fibrosis3.1 Distribution characteristics of five movements and six climates in embryonic period:In terms of yearly luck,the distribution of five yearly luck more to less is as follows:earth luck>gold luck>fire luck>wood luck>water luck,of which the earth luck taiguo is the most(11.53%),and the water luck buji is the least(8.30%).In the aspect of Sitian during pregnancy,the distribution of six types of Sitian from more to less was as follows:Shaoyang Xianghuo Sitian>Shaoyin Junhuo Sitian>Taiyin Shitu Sitian>Sun Hanshui Sitian>Yangming Zaojin Sitian>Jueyin Fengmu Sitian.Shaoyang Xianghuo Sitian is the most(18.34%)and Jueyin Fengmu Sitian is the least(15.46%).3.2 The correlation between the characteristics of five movements and six climates in embryonic period and the stage of pathological Hepatic Fibrosis:There was no significant difference in the distribution of pathological liver fibrosis among patients with different yearly luck in embryonic period,and there was no significant difference in the distribution of pathological liver fibrosis among patients with different types of Sitian in embryonic period(P>0.05).However,in the S3-S4 stage of liver fibrosis,the proportion of Taiyin Shitu Sitian in embryonic period(22.75%)was significantly higher than that of other Sitian types(P<0.05).3.3 The correlation between the five movements and six climates in embryonic period and serological indexes:There was no significant difference in the distribution of ALT,AST,PCⅢ,LN,IV-C,HA,IgA,IgG,IgM,C3,C4 and CH50 among patients with different yearly luck in embryonic period.The correlation between the characteristics of five movements and six climates in embryonic period and serological indexes:There was no significant difference in the distribution of ALT,AST,PCIII,LN,IV-C,HA,IgA,IgG,IgM,C3,C4 and CH50 among patients with different Sitian types in embryonic period.4 Establishment of non-invasive predictive model of progressive Hepatic Fibrosis.4.1 A total of 1064 patients with hepatitis B liver fibrosis were included,with an average age of 39.88±10.66 years old,mostly male patients(70.87%).The serological indexes of patients with progressive hepatic fibrosis were significantly higher than those of non-progressive hepatic fibrosis.The most of TCM constitution is blood stasis(34.68%),in the related part of five movements and six climates,and the number of patients in fire luck buji in embryonic period is the most(22.52%),and the number of patients in Taiyin Shitu Sitian in embryonic period is the most(22.52%).4.2 Logistic univariate analysis showed that 10 factors such as ALT,AST,PLT,PCIII,LN,IV-C,HA,blood stasis,yin deficiency and Taiyin dampness might be associated with progressive liver fibrosis.Logistic multivariate analysis showed that low level of PLT,high level of IV-C,high level of HA,physical type of blood stasis and Taiyin wet soil of Sitian type were independent risk factors of progressive liver fibrosis.4.3 Based on the above five independent risk factors related to progressive liver fibrosis,the regression model was constructed and finally the following prediction model,W:ln(W/1-W)=-2.403+0.016*(Si Tian=Shaoyin Junhuo Sitian)+0.723*(Si Tian=Taiyin wet toast)+0.045*(Si Tian=Shaoyang phase fire Si Tian)+0.142*(Si Tian=Yangming dry Jin Si Tian)+0.061*(Si Tian)was established.Days=Sun,cold and water)-0.261*(physique=qi depression)+0.428*(physique=damp-heat)+0.529*(physique = phlegm-dampness)+1.618*(physique=blood stasis)+1.989*(physique=yang deficiency)+2.384*(constitution=yin deficiency)+0.010*IV-C+0.010*HA-0.005*PLT.The AUC value of predictive model W for the diagnosis of progressive liver fibrosis was 0.803,the sensitivity was 0.698,the specificity was 0.761,and the best cutoff value was 0.459.The AUC value of model W was significantly higher than that of APRI and FIB-4(0.803 vs.0.619,0.803 vs.0.623).Conclusion1.The TCM syndrome types of patients with hepatitis B liver fibrosis are mainly liver depression and spleen deficiency type,liver and gallbladder damp-heat type and blood stasis type,which indirectly reflects the importance of qi depression,spleen deficiency,dampness,heat and blood stasis in the occurrence and development of hepatic fibrosis.2.There are some differences in pathological liver fibrosis stages and serological indexes among patients with different TCM syndrome types of hepatitis B liver fibrosis,in which patients in stage S1-S2 of liver fibrosis are mainly patients with liver depression and spleen deficiency,and patients with liver fibrosis in S3-S4 stage are mainly patients with blood stasis blocking collaterals,suggesting that patients with blood stasis blocking collaterals are seriously ill and need timely monitoring and vigilance against their progression to liver cirrhosis.3.There are some differences in pathological liver fibrosis stages and serological indexes among patients with hepatitis B liver fibrosis with different TCM constitution.Among them,patients with liver qi deficiency in S1-S2 stage of liver fibrosis and blood stasis in S3-S4 stage of liver fibrosis were mainly in stage S1-S2 and blood stasis in stage S3-S4 of liver fibrosis.It can be seen that the degree of liver fibrosis in patients with blood stasis is serious,and special attention should be paid to timely treatment to prevent the progression of the disease.4.There was no significant difference in liver fibrosis stage and serological indexes among patients with different gestational age types of hepatitis B liver fibrosis.In the S3-S4 stage of liver fibrosis,the proportion of Taiyin wet toast days during pregnancy was significantly higher than that of other Sitian types.There was no significant difference in serological indexes among patients with different types of hepatitis B liver fibrosis during pregnancy.Therefore,patients with hepatitis B liver fibrosis of Taiyin wet toast type during pregnancy should pay special attention to the changes of their condition in order to prevent aggravation.5.Five factors,such as low level of PLT,high level of IV-C,high level of HA,physical type of blood stasis and Taiyin wet soil,are independent risk factors of progressive liver fibrosis. |