The Association Of Hepatic T Lymphocyte Subsets And The Expression Of HBcAg In The Liver Tissue With Different Syndrome Types Of Chronic Hepatitis B Patients

Objective:To investigate the differences in the patients gender, age, liver biopsy for histological activity index in liver(grading, G), serum alanine aminotransferase(ALT) levels, serum HBV DNA loads, the expression of HBcAg in the liver, the expression of CD4+T cells in the liver and the expression CD8+T cells in the liver among TCM syndrome types of CHB, and to reveal the immune state entailed in different patterns of TCM syndrome types, in order to explore suitable solution and breakthrough point for high-performance integrated traditional Chinese medicine and Western medicine therapy for CHB.Methods:A total of 600 consecutive patients with CHB proven by liver biopsy in this study. Syndrome types were zheng differentiation-classified as syndrome of stagnation of syndrome of dampness-heat of liver and gallbladder, syndrome of liver depression and qi stagnation, syndrome of stagnation of liver qi and spleen deficiency, syndrome of yin deficiency of liver and kidney, syndrome of static blood blocking collaterals according to criteria of zheng differentiation-classification of viral hepatitis, and as occult syndrome in case of slight syndromes or lack of syndrome, by two separate associate chief physicians of TCM. Blood tests for serum ALT levels and serum HBVDNA loads were performed within two weeks after enrollment. Histological activity index in liver(grading, G), the expression of HBcAg in the liver, the expression of CD4+T cells in the liver and the expression CD8+T cells in the liver were analyzed with pathological methods and immunochemistry separately. Significance of the constituent ratio of all the six syndrome types was analyzed by Chi-square test. For multinomial logistic regression used in this paper, gender, age[by^40years, and<40 years, respectively.], serum ALT levels by [>5×upper limit of normal (ULN) and≤5×ULN, respectively.], serum HBV DNA loads[by≤ 6log10 copies/ML and>61og10 copies/ML, respectively], the expression of HBcAg[by negative (-), positive (+),positive (++), positive (+++)/(++++), respectively.], the ratio of CD4+T cells and CD8+T cells[by≥1.5, and<1.5, respectively.] and G(by≥G3) were categorized, respectively. Statistical analysis of data was performed by using the SPSS v.13.0 program.Results:Multinomial logistic regression indicated that significant differences were found in between gender and age and among ALT levels, G, HBcAg, CD4+T and CD8+T while not among HBV DNA loads (x2=14.385, p=0.132). The independent predictive factor(s), by multinomial logistic regression if the occult syndrome served as reference category, for syndrome of yin deficiency of liver and kidney was≥G3 of grading[B=0.603, Wald=5.408, p=0.021, Exp(B)=1.826,95%CI for Exp(B):1.102,3.035.], of stagnation of liver qi and spleen deficiency were ≥G3 of grading[B=0.513, Wald=5.964, p=0.020, Exp(B)=3.896, 95%CI for Exp(B):1.302,3.985.], the positive expression of HBcAg(+++/++++)[B=-0.361, Wald=6.589,p=0.037,Exp(B)=0.655,95%CI for Exp(B):1.023,3.462.], of liver depression and qi stagnation were ≥G3 of grading[B=1.413, Wald=5.124, p=0.024, Exp(B)=3.896, 95%CI for Exp(B):1.306,3.685.], the positive expression of HBcAg(+++/++++)[B=-1.561, Wald=4.589, p=0.031, Exp(B)=3.655,95%CI for Exp(B):1.063,3.647.], the ratio of CD4+T /CD8+T>1.5[B=1.656, Wald=9.647, p=0.001, Exp(B)=5.026,95%CI for Exp(B):0.998, 6.987.], of dampness-heat of liver and gallbladder were>5 X ULN of ALT levels[B=-1.769, Wald=11.987, p=0.001, Exp(B)=4.324,95%CI for Exp(B):0.465,3.699.], G≥G3 of grading[B=1.713,Wald=10.924,p=0.001,Exp(B)=6.896,95%CI for Exp(B):1.306,3.685.], the positive expression of HBcAg(+++/++++)[B=-1.861, Wald=5.589, p=0.002 Exp(B)=4.655,95%CI for Exp(B):2.063,5.647.]. the ratio of CD4+T/CD8+T> 1.5[B=2.636, Wald=31.647, p=0.000, Exp(B)=6.687,95%CI for Exp(B):3.298,7.935.], of static blood blocking collaterals were>5×ULN of ALT levels[B= 1.069, Wald=4.693, p=0.025, Exp(B)=2.124,95%CI for Exp(B):0.981,3.668.], G≥G3 of grading[B=1.313, Wald=8.924, p=0.011, Exp(B)=5.986,95%CI for Exp(B):0.956,3.785.], the positive expression of HBcAg(+++/++++)[B=-1.548, Wald=4.593, p=0.025, Exp(B)=3.231,95%CI for Exp(B):1.123,4.638.], the ratio of CD4+T/CD8+T>1.5[B=1.432, Wald=10.647, p=0.001, Exp(B)=6.112,95%CI for Exp(B):0.358,8.987.], respectively. Independent predictive factor screening applied to syndrome of yang deficiency of spleen and kidney due to smaller sample.Conclusions:.1.Diverse demographic and biological bases are attributable to variable syndrome types of CHB.2.A definite syndrome type implies a certain immune state, and immune activity increasingly more active in order in CHB patients with occult syndrome, yin deficiency of liver and kidney, syndrome of stagnation of liver qi and spleen deficiency, syndrome of static blood blocking collaterals, syndrome of liver depression and qi stagnation, syndrome of and syndrome of dampness-heat of liver and gallbladder.3. The immune state entailed in different patterns of TCM syndrome types is relevant directly to the histological activity index in liver, the positive expression of HBcAg in the liver, the expression of CD4+T cells in the liver and the expression CD8+T cells in the liver, in which CD4+, CD8+T cells may be the most able to react the immune state of TCM syndrome types of CHB.4. Further study with larger sample is necessary on syndrome of yang deficiency of spleen and kidney.