| Objective:Observe the clinical effect of HZKXF on liver fibrosisin patients of chronic hepatitis B.Detect the serum level of Th1/Th2,CD4~+CD25~+Foxp3~+Treg, TGF-β1,T lymphocyte subsets and HBV specificCTL.Probe into the immunologic mechanism of HZKXF on fibrosis.Methods:1、122patients of chronic hepatitis B were divided into3groupsrandomly.The treatment group was treated by HZKXF(everyday1agent,3times a day).The control group1was treated by Anluohuaxianpills (6grams evevy time,3times a day). Control group2wastreated by reduced glutathione tablets(0.4grams evevy time,3times a day).The courses of treatment were all24weeks in everygroup.Detect the level of liver function,HBVDNA quantity andHA,LN,PCⅢ,C-Ⅳ,liver elasticity number before and after thetreatment.Observe the clinical effect of HZKXF on liver fibrosis.2、60patients of chronic hepatitis B were divided into2groupswith random.The treatment group was treated by HZKXF(everyday1agent,3times a day).The control group was treated by reducedglutathione tablets(0.4grams evevy time,3times a day). Thecourses of treatment were both24weeks.30healthy people were thehealthy control group.There are40times liver puncture among60patients. Detect the level of HA,LN,PCⅢ,C-Ⅳ, the serum level ofIFN-,IL-4,Th1/Th2before and after the treatment.Analyse the correlativity relations between Th1/Th2, serum hepatic fibrosisindexes and the stage of liver fibrosis. Observe the effect of HZKXFon Th1/Th2.3、Based on the second experiment,using the flow cytometryintracellular cytokine staining method to dectect the level ofCD4~+CD25~+Foxp3~+Treg in serum before and after the treatment.Usingthe ELISA double antibody sandwich method to dectect the level ofTGF-β1in serum before and after the treatment. Analyse the corr-elativity relations between CD4~+CD25~+Foxp3~+Treg,TGF-β1, serumhepatic fibrosis indexes and the stage of liver fibrosis. Observethe effect of HZKXF on CD4~+CD25~+Foxp3~+Treg and TGF-β1.4、Application of HLA-A2as a screening index，62patients ofHLA-A2antibody(+) were divided into2groups randomly in patientswith chronic hepatitis B. There were32patients in the treatmentgroup.The treatment group was treated by HZKXF (everyday1agent,3times a day). There were30patients in the control group.Thecontrol group was treated by reduced glutathione tablets(0.4gramsevevy time,3times a day).The courses of treatment were all24weeksin every group.Using flow cytometry to dectect the level of CD4~+,CD8+and CD4~+/CD8+in serum before and after treatment.Using MHC-HBVcore18-27-pentmer to dectect the level of HBV specific CTL and the itsfunction of secreting IFN-γin serum before and after the treatment.Analyse the correlativity relations between T lymphocyte subsets,HBV specific CTL,HBVDNA quantity serum hepatic fibrosis indexes andthe stage of liver fibrosis.Results:1、The level of liver function was improved obviously after HXKXF treatment(P＜0.05). The level of ALT and AST were improvedmore obviously in the treatment group than in the control group1.There were no significant differences on the level of ALT and ASTbetween the treatment group and the control group2after thetreatment(P＞0.05).The level of A/G was improved more obviously inthe treatment group than in the control group1and control group.2、The level of HBVDNA quantity was decreased more obviouslyin the treatment group than in the countrol group1and countrolgroup2. There were no significant differences on the level ofHBVDNA quantity both in the control group1and control group2afterthe treatment(P＞0.05). The level of liver fibrosis indexes inserum and liver elasticity numbers detecting with Fibroscan weredecreased obviously after HXKXF and Anluohuaxian pills treatment(P＜0.05).There were no significant differences between the2groupson the level of liver fibrosis indexes in serum and liver elasticitynumbers(P＞0.05).There were no significant differences on thelevel of liver fibrosis indexes in serum and liver elasticitynumbers after the treatment in the control group2(P＞0.05).3、The level of Th1、Th2and Th1/Th2decreased obviously comparedwith the healthy control group(P＜0.05).The level of Th1decreasedmore obviously than the level of Th2. The level of Th1negativelycorrelated with the liver fibrosis indexes in serum（r=－0.71，P＜0.05）,it declined with the stage of liver fibrosis rised.Th2positively correlated with the liver fibrosis indexes in serum（r=0.58，P＜0.05）,it elevated the stage of liver fibrosis rised.Th1/Th2negatively correlated with the liver fibrosis indexes inserum（r=－0.82，P＜0.05） and the stage of liver fibrosis(r=－0.84，P＜0.05).The level of Th1and Th1/Th2elevated after HZKXF treatment（P＜0.05）.The level of Th2decreased after HZKXFtreatment（P＜0.05）. There were no significant differences on thelevel of Th1, Th2and Th1/Th2after the treatment in the controlgroup (P＞0.05).4、 The level of the liver fibrosis indexes,TGF-β1andCD4~+CD25~+Foxp3~+Treg in serum rised obviously compared with thehealthy control group(P＜0.05). The level of the liver fibrosisindexes,TGF-β1and CD4~+CD25~+Foxp3~+Treg in serum decreased afterHZKXF treatment(P＜0.05). There were no significant differences onthe level of the liver fibrosis indexes,TGF-β1andCD4~+CD25~+Foxp3~+Treg in serum after the treatment in the control group(P＞0.05).The level of TGF-β1positively correlated with the liverfibrosis indexes in serum（rHA=0.56, P＜0.05；rLN=0.58, P＜0.05；rPC Ⅲ=0.56,P＜0.05；rC-Ⅳ=0.48, P＜0.05）. The level of TGF-β1positively correlated with the stage of liver fibrosis（r=0.51，P＜0.05）.The level of CD4~+CD25~+Foxp3~+Treg positively correlatedwith the level of TGF-β1in serum.5、The level of CD4~+T and CD4~+/CD8+in serum decreased,the levelof CD8+rised obviously compared with the healthy control groupbefore the treatment(P＜0.05).The level of CD4~+T and CD4~+/CD8+negatively correlated with the stage of liver fibrosis(rCD4~+=－0.53，P＜0.05；rCD4~+/CD8+=－0.59，P＜0.05）. The level of CD8+positivelycorrelated with the stage of liver fibrosis（rCD8+=0.55，P＜0.05）.Thelevel of CD4~+, CD4~+/CD8+, HBVcore18-27specific CTL and seretingIFN-γ improved after HXKXF treatment（P＜0.05）.The level of CD8+and HBVDNA quantity decreased after HXKXF treatment（P＜0.05）.There were no significant differences on the level of T lymphocyte subsets, HBVcore18-27specific CTL and sereting IFN-γin serumafter the treatment in the control group (P＞0.05).Conclusion:1、HZKXF can improved the liver function,decrease the levelof HBVDNA quantity,liver fibrosis indexes, liver elasticitynumbers. There were no significant differences on anti-hepaticfibrosis effects(P＞0.05).Itis superior to Anluohuaxian pills oninhibition of virus replication and improving the liver function.2、HZKXF can elevate the levels of Th1and Th1/Th2, justify theimbalance of Th1/Th2,make the immune function develop towords Th1cell subsets dominant direction. Reduced glutathione tablets hasno effect on correcting the imbalance of Th1/Th2,3、HZKXF can decrease the level of CD4~+CD25~+Foxp3~+Treg andTGF-β1, obstruct the bad circle of CD4~+CD25~+Foxp3~+Treg,TGF-β1andHSC, reverse the immune microenvironment in patients with liverfibrosis,promote the recovery of liver fibrosis.4、HZKXF can elevate the levels of CD4~+, CD4~+/CD8+, decreasethe level of CD8+T lymphocyte.It can reduce the injury of livercells, promote the recovery of liver fibrosis in patients withchronic hepatitis B.At the same time,it can elevate the levels ofHBVcore18-27specific CTL and the function of sereting IFN-γ.Through correcting the imbalance of immune, HZKXF can controlthe HBV replication and improve the liver fibrosis causing by HBV. |
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