Study On The Effectiveness Evaluation And Mechanism Of The Chronic Hepatitis B Traditional Chinese Medicine Card For The Anti-viral Therapy Of Lamivudine

Treatment according to card differentiation is the characteristic for Traditional Chinese medicine(TCM) to treat chronic hepatitis B, anti-viral therapy is the advantages for modern medicine to treat chronic hepatitis B. The thesis researched the effectiveness evaluation and mechanism on the Chronic Hepatitis B TCM card for the anti-viral curative effect of Lamivudine by combine the advantages of TCM and modern medicine. There were three Parts in the thesis,one was The relationship between Traditional Chinese Medicine card and cellular immune function of chronic hepatitis B,two was The effectiveness evaluation on the Chronic Hepatitis B Traditional Chinese Medicine card for the anti-viral curative effect of Lamivudine,three was the effect of Lamivudine anti-viral therapy on celluar immune function in chronic hepatitis B patients with damp-heat blocking the middle cardPart one The relationship between Traditional Chinese Medicinecard and cellular immune function of chronic hepatitis BObjeetive: To examine and analyze the distribution of T lymphocyte subsets(CD3+、CD4+、CD8+)、 IL-2 or IFN-γsecreted by Th1 cells and IL-6 or IL-10 secreted by Th2 cells in Peripheral blood of the chronic hepatitis B(CHB) traditional Chinese Medicine(TCM) card patients,To provide some objective evidence for the clinical card differentiation and diagnosis.Methods:In accordance with the diagnosis dialectical standards of Western medicine, 150 patients of CHB were divided into five groups,which were damp-heat blocking the middle group(A),depressed liver and deficient spleen group(B), Yin deficiency of liver and kidney group(C), Yang deficiency of spleen and kidney group(D) and blood stasis blocking collaterals group(E). T lymphocyte subsets(CD3+ 、 CD4+ 、 CD8+) were detected by flow cytometry.The concentrations of IL-2 or IFN-γsecreted by Th1 cells and IL-6 or IL-10 secreted by Th2 cells were detected by enzyme-linked immunosorbent assay(ELISA).Results:1. Distribution laws of traditional Chinese Medicine card of Chronic Hepatitis B:Five types of A、B、C、D and E card were respectively 44.67%、30%、10.67%、8% and 6.67%.2. The relationship between clinical degree with traditional Chinese Medicine card of Chronic Hepatitis B:The clinical degree of A、B、C、D and E card were significantly different(P<0.05) by rank sum test of statistics.3.The serum CD3+T lymphocyte level was highest in the Damp-heat blocking the middle group(A), compared with Yang deficiency of spleen and kidney group(D)with statistical significance(P<0.05),compared with other TCM card with no statistical significance(P>0.05).The serum CD4+ T lymphocyte level was highest in the Damp-heat blocking the middle group(A), compared with Yang deficiency of spleen and kidney group(D) with statistical significance(P<0.05),compared with other TCM card with no statistical significance(P > 0.05). The serum CD8+ T lymphocyte level was highest in the Yang deficiency of spleen and kidney group(D), compared with Damp-heat blocking the middle group(A) with statistical significance(P<0.05).4.The IL-2 level was highest in the Damp-heat blocking the middle group(A), compared with D and C group with statistical significance(P<0.05),compared with B and E with no statistical significance(P > 0.05). The IFN- γ level was highest in the Damp-heat blocking the middle group(A) too, compared with D group with statistical significance(P<0.01), compared with B and C group with statistical significance(P<0.05),compared with E group with no statistical significance(P>0.05).5.The IL-6 level was highest in the Yang deficiency of spleen and kidney group(D),compared with A group with statistical significance(P<0.01),compared with B and C with no statistical significance(P>0.05). The IL-10 level was highest in the Yang deficiency of spleen and kidney group too, compared with A group with statistical significance(P<0.05), compared with B and C group with no statistical significance(P>0.05).Conclusions:The serum CD3+ and CD4+ T lymphocyte level was highest in the Damp-heat blocking the middle group(A), arranged from high to low order in the traditional Chinese Medicine card of Chronic Hepatitis B were as follows: A>E>B>C>D. The serum CD8+ T lymphocyte level was highest in the Yang deficiency of spleen and kidney group(D), arranged from high to low order in the traditional Chinese Medicine card of Chronic Hepatitis B were as follows: D>E>C>A>B.The level of IL-2 and IFN-γ was highest in the Damp-heat blocking the middle group(A), arranged from high to low order in the traditional Chinese Medicine card of Chronic Hepatitis B were as follows: A>E>B>C>D. The IL-6 level was highest in the Yang deficiency of spleen and kidney group(D), arranged from low to high order in the traditional Chinese Medicine card of Chronic Hepatitis B were as follows: A<E<C<B<D. The IL-10 level was highest in the Yang deficiency of spleen and kidney group(D), arranged from low to high order in the traditional Chinese Medicine card of Chronic Hepatitis B were as follows: A<E<B<C<D.They provided the evidence for the objectivity of TCM card in Chronic Hepatitis B. Part two The effectiveness evaluation on the Chronic Hepatitis B Traditional Chinese Medicine card for the anti-viral curativeeffect of LamivudineObjective: To evaluate the relationship between the chronic hepatitis B Traditional Chinese Medicine card and the anti-viral curative effect of Lamivudine so as to provide the theoretical basis for the choice opportunity and enthance the curative effect from the Traditional Chinese Medicine dialectical aspect.Methods: In accordance with the diagnosis dialectical standards of Western medicine, 150 patients of CHB were divided into five groups,which were damp-heat blocking the middle group(A),depressed liver and deficient spleen group(B), Yin deficiency of liver and kidney group(C), Yang deficiency of spleen and kidney group(D) and blood stasis blocking collaterals group(E).All patients were treated with Lamivudine for three years.HBV-DNA and HBV makers were detected for every 3 month.If part patients have developed virologic resistance,they were treated with Lamivudine and Adefovir dipivoxil(ADV),they were detected with YMDD mutant.We kept closely investigate the relationship between the rate of ALT normalization、HBV-DNA negative conversion、drug resistance and YMDD mutant and different TCM card.Results:1. The relationship between state of HBe Ag Distribution laws、HBV-DNA replication and ALT baseline value in traditional Chinese Medicine card of Chronic Hepatitis B:In the HBe Ag Distribution laws, there were no significantly different(P>0.05).In the HBV-DNA replication value,arranged from high to low order in the traditional Chinese Medicine card of Chronic Hepatitis B were as follows:D>B>C>E>A,there were no significantly different(P>0.05).In the ALT baseline value,arranged from high to 1ow order in the traditional Chinese Medicine card of Chronic Hepatitis B were as follows:A>E>C>B>D.Damp-heat blocking the middle group(A) compared with other TCM card with statistical significance(P<0.05).2. The rate of ALT normalization: After 1 year of treatment,The rate of ALT normalization of A、B、C、D and E was 94.0%、73.3%、62.5%、50% and 50%,Damp-heat blocking the middle group(A) were higher than other TCM card,compared with other TCM card with statistical significance(P<0.05).3. The rate of HBV-DNA negative conversion: After 1 year of treatment, The rate of HBV-DNA negative conversion of A、B、C、D and E was 95.5%、80%、68.8%、58.3% and 50%, Damp-heat blocking the middle group(A) were higher than other TCM card,compared with other TCM card with statistical significance(P<0.05). After 3 year of treatment, The rate of HBV-DNA negative conversion of A、B、C、D and E was 80.6%、62.2%、50%、41.7% and 30%, Damp-heat blocking the middle group(A) were higher than other TCM card,compared with other TCM card with statistical significance(P<0.05).4. The rate of drug resistance:After 3 year of treatment, The rate of drug resistance of A、B、C、D and E was 19.4%、37.8%、50%、58.3% and 70%, Damp-heat blocking the middle group(A) were lower than other TCM card,compared with other TCM card with statistical significance(P<0.05).5. The rate of YMDD mutant:After 3 year of treatment, The rate of YMDD mutant of A、B、C、D and E was 10.4%、26.7%、37.5%、41.7% and 40%, Damp-heat blocking the middle group(A) were lower than other TCM card,compared with other TCM card with statistical significance(P<0.05).Conclusion: The rate of ALT normalization and HBV-DNA negative conversion in the different TCM card were treated by Lamivudine on chronic hepatitis B, Damp-heat blocking the middle group(A) were higher than other TCM card, arranged from high to low order in the traditional Chinese Medicine card of Chronic Hepatitis B were as follows: A>B>C>D>E.The rate of drug resistance and YMDD mutant in the different TCM card were treated by Lamivudine on chronic hepatitis B Patients, Damp-heat blocking the middle group(A) were lower than other TCM card, arranged from high to low order in the traditional Chinese Medicine card of Chronic Hepatitis B were as follows: A<B<C<D<E. We may choose sensibly lamivudine to resistant hepatitis B virus for different TCM card of chronic hepatitis B Patients. There are best effect of Lamivudine treating chronic hepatitis B in the Damp-heat blocking the middle group(A).Part three The effect of Lamivudine anti-viral therapy oncelluar immune function in chronic hepatitis B patients withdamp-heat blocking the middle cardObjective: To observe the changes of T lymphocyte subsets and Thl/Th2 cell related cytokines of chronic hepatitis B patients with damp-heat blocking the middle card after Lamivudine therapy and to explore the effect of Lamivudine anti-viral therapy on celluar immune function. Try to predict effectiveness of Lamivudine anti-viral therapy.Methods: 67 chronic hepatitis B patients with damp-heat blocking the middle card were treated with Lamivudine. Sera were collected before treatment and in third month, sixth month and first year after treatment.T lymphocyte subsets(CD3+、CD4+、CD8+) were detected by flow cytometry.The concentrations of IL-2 or IFN-γsecreted by Th1 cells and IL-6 or IL-10 secreted by Th2 cells were detected by enzyme-linked immunosorbent assay(ELISA).Results:1.The changes of T lymphocyte subsets of chronic hepatitis B patients with damp-heat blocking the middle card after Lamivudine therapy: The serum CD3+ and CD4+ T lymphocyte level was highest in the sixth month,compared with before treatment with statistical significance(P<0.05),compared with first year with no statistical significance(P>0.05). The levels of CD8+T lymphocyte had no significant changes after treatment.2. The changes of IL-2 and IFN-γof chronic hepatitis B patients with damp-heat blocking the middle card after Lamivudine therapy: The levels of IL-2 and IFN-γwas highest in the sixth month,compared with before treatment with statistical significance,compared with first year with no statistical significance(P>0.05), compared with third month with no statistical significance(P>0.05).3.The changes of IL-6 and IL-10 of chronic hepatitis B patients with damp-heat blocking the middle card after Lamivudine therapy: The levels of IL-6 had no significant changes after treatment, compared with before treatment with no statistical significance(P>0.05).The levels of IL-10 was lowest in the sixth month,compared with before treatment with statistical significance(P<0.05),compared with first year with no statistical significance(P>0.05).Conclusion:1.The levels of CD3+ and CD4+ T lymphocyte increased gradually after Lamivudine treated chronic hepatitis B patients with damp-heat blocking the middle card for 1 year and was highest in the sixth month, the levels of CD8+T lymphocyte had no significant changes after treatment.2.The levels of IL-2 and IFN- γ increased gradually after Lamivudine treated chronic hepatitis B patients with damp-heat blocking the middle card for 1 year and was highest in the sixth month.3. The levels of IL-10 decreased gradually after Lamivudine treated chronic hepatitis B patients with damp-heat blocking the middle card for 1 year and was lowest in the sixth month, the levels of IL-6 had no significant changes after treatment.Lamivudine treatment leads to high effectiveness which may be related to its immunoregulation for chronic hepatitis B patients with damp-heat blocking the middle card.