The Effectiveness Evaluation On Traditional Chinese Medicine And Lamivudine For The Treatment Of Chronic Hepatitis B

The advantages and characteristic for traditional Chinese medicine(TCM) to treat chronic hepatitis B(CHB) is the use of pathogenesis obtained through differentiation of symptoms and signs.The thesis researched on the evaluation methodology of the effectiveness on CHB by TCM in the view of clinical decision analysis in evidence-based medicine.And the simulation of the disease progress and changes in the quality of the life was made with the different interventions,and the clinical decision analysis was made from the point of view of the doctors based on the data of literatures and clinical trials.There were two parts in the thesis;one was the effectiveness evaluation in the short-time,and the other was the one in the long-term.Part one:The evaluation of the short-time effectiveness of TCM for CHB.1.The evaluation of the effectiveness of TCM on CHB based on the data from literatureObjective:To evaluate the effectiveness of TCM compared with nucleoside antivirus drugs for CHB and offer source data for the effectiveness evaluation of TCM in the long-term based on the literature,.Methods:Via the method of Cochrane systematic review,the authors searched the databases of the Cochrane Hepato-Biliary Group Controlled Trials Register(March, 2006),the Cochrane Central Register of Controlled Trials(CENTRAL)(Issue 1, 2006),Pubmed(from year 1966 to year 2007),EMBASE(from year1966 to year 2007),OVID(from year 1965 to year 2006),the Chinese Biomedical Database(CBM) (from year 1978 to year 2007) and CNKI(from year 1979 to year 2007).And there was no limitation to the language.All the comparison trials and systematic reviews were included that compared the effectiveness between TCM(Or TCM plus nucleoside antivirus drugs) and nucleoside antivirus drugs applied to the CHB patients. The qualities of the included researches in the literature were assessed and the subgroup analysis was performed according to the measurement objectives, interventions and the courses of treatment.Meta-analyses were performed for homogeneous studies by the software of RevMan4.2.Results:A total of 44 studies involving 3974 patients met the inclusion criteria. And there was no study on TCM compared with other nucleoside antivirus drugs except Lamivudine.The Meta-analysis results with the statistical significance were as follows.(1) Compared with Lamivudine,the HBeAg recurrence rate of TCM group decreased absolutely 37%in the follow-up 6-month visit after the treatment of 12 months.(2) After 6 months' treatment,and in the follow-up 6-month visit after the treatment of 12 months,the DNA recurrence rate of TCM group absolutely decreased 23%and 44%respectively.(3) By the end of treatment of 3 months,6 months and 24 months,decreases in HA levels of TCM group were all more than those of Lamivudine group.(4) By the end of 24 months' treatment the reduction in LN of TCM was greater than that of Lamivudine.(5)The changes in PCⅢfrom baseline level to 3 months and to 24 months were both better in TCM group than thosc in Lamivudine group.(6) Decreases inⅣ-C of TCM group were more than that of Lamivudine group after 3-month treatment.(7) The risk difference of ALT response rate in TCM group were absolutely larger by 29%and 49%at the end of 6-month treatment and in the 6-month follow-up visit after 6-month treatment respectively than those in Lamivudine group.(8) Remission rate on cardinal symptoms and objective signs in TCM group was larger by 22%than that in Lamivudine group.(9) But for DNA suppression rate,it was less by 14%and 21%after 3-month and 6-month TCM treatment than that in Lamivudine group.(10) There was no evidence in the literature that the effectiveness by Lamivudine treatment was better than that by TCM plus Lamivudine. Conclusions:At first,TCM was effective in normalizing ALT levels/decreasing ALT levels,improving hepatic fibrosis,clearing HBV DNA,achieving virus loss and seroconversion(HBsAg and HBeAg),preventing DNA relapse,preventing HBeAg reconversion,and recovering symptoms and objective signs.Second,TCM plus Lamivudine were more effective than Lamivudine monotherapy.Finally,the overall effectiveness,however,didn't be pooled for analysis in the systematic review due to the different terms of treatment.More evidence was needed to support the overall effectiveness of TCM treatment.2.The evaluation of the effectiveness of TCM on CHB based on the data from clinical trialObjective:To evaluate the effectiveness of TCM compared with Lamivudine on CHB and to offer source data for the effectiveness evaluation of TCM in the long-term based on the clinical trials.Methods:The two-center prospective cohort approach was used.The 84 patients with CHB at the clinic of Guang-an-men hospital were assigned to receive TCM treatment as the exposure group based on the pathogenesis obtained through differentiation of symptoms and signs,one dose once daily,while the other 40 patients at the You-an hospital were received 100mg of Lamivudine once daily as the comparison group.Patients were treated for 6 months and followed for an additional 3 months.Results:ALT normalization rate:In the patients whose DNA levels were more than(or equal) 1.00e+04copies/ml at baseline,48.8%,58.1%and 88.4%of the patients received TCM treatment had normalized ALT levels at the end of treatment of 3 months,6 months and at the 3-month follow-up respectively,compared with 42.5%, 65%and 87.5%of the patients with Lamivudine treatment,respectively.It was not significantly different at 5%significance level.In the patients whose DNA levels were less than 1.00e+04copies/ml at baseline,61.5%,79.5%and 97.4%of patients received TCM treatment had normalized ALT levels respectively.HBV DNA clearance rate:In the patients whose DNA levels were more than(or equal) 1.00e+04copies/ml at baseline with HBeAg-positive CHB,33.3%and 66.7% of TCM treated patients had undetectable DNA levels at the end of treatment of 6 months and at the follow-up visit respectively in comparison with 32.1%and 51.5% of Lamivudine treated patients(p＞0.05).In the patients whose DNA levels were less than 1.00e+04copies/ml at baseline with HBeAg-positive CHB,57.1%patients who received TCM treatment had undetectable DNA levels both after 6-month treatment and at the 3-month follow-up visit,while 71.4%and 42.9%of the patients who received Lamivudine had undetectable DNA levels respectively(p＞0.05).For the patients with HBeAg-negative CHB and DNA levels more than(or equal) 1.00e+04copies/ml at baseline,at month 6,75.0%of patients who received TCM had undetectable DNA levels compared with 40.0%of patients who received Lamivudine (p=0.280).At the end of follow-up visit,the proportion of patients treated with TCM with undetectable DNA levels was 81.3%compared with 20.0%for Lamivudine treated patients,the difference between the TCM group and the Lamivudine group was statistically significant(p=0.025).Rate of HBeAg loss and seroconversion:By the end of treatment of 6 month,the rates of HBeAg loss and seroconversion of the TCM patients were both 6.81% compared with both 8.57%of the Lamivudine group(p＞0.05).Four patients in the TCM patients lost HBsAg and one had HBsAg seroconversion,but no patients in the Lamivudine group did so.Effectiveness of syndromes:After 3-month TCM treatment,the remarkably effective rate,the effective rate and the total effective rate of syndromes were absolutely higher by 27.3%,20.6%and 47.9%than those of the patients in the Lamivudine group respectively.Besides,after 6-month TCM treatment,the remarkably effective rate and the total effective rate of syndromes were absolutely higher by 70.9%and 21.6%%than those of the patients in the Lamivudine group respectively.At the 3-month follow-up visit,the cure rate,remarkably effective rate and the total effective rate in the patients treated with TCM were absolutely higher by 25.6%,50.8%and 20.1%than those of the patients treated with Lamivudine,respectively.Conclusions:At first,it is effective in TCM group in achieving virus loss and seroconversion,normalizing ALT levels and clearing HBV DNA.Second,TCM offered superior efficacy over lamivudine on the basis of HBsAg loss and seroconversion.Third,TCM offered better HBV DNA clearance result at the follow-up visit in the HBeAg-negative patients.However,more evidence is needed to support the above conclusions due to limited sample amount.Part two:The evaluation of the long-term effectiveness of TCM on CHB by Markov modelObjective:To estimate the effectiveness of TCM and Lamivudine for adult patients with CHB.Design:Two 5-health state Markov models were developed for HBeAg-positive and HBeAg-negative CHB patients respectively.The models followed cohorts of HBeAg-positive and HBeAg-negative CHB patients respectively over a period of 40 years,during which the majority of the cohorts would have died if left untreated. Annual transition probabilities of disease progression and the magnitude of treatment effects were obtained from the literature,with a focus on data obtained from Asian patients and meeting the criteria of therapy as described in internationally recognized management guidelines.The potential effect of uncertainty in the model assumptions was tested by using sensitivity analyses.Monte Carlo micro-simulation was used to perform clinical decision analysis on the basis of quality-adjusted life expectancy.Results:Among the patients with HBeAg-positive CHB received TCM treatment, 18.48%to 62.49%of the patients occurred HBeAg seroconversion,and 1.4%to 36.6%of the patients progressed to compensated cirrhosis in the course of 40 years treatments,and average per patient had gained 28.18 accumulated QALYs in the end of 40 years treatments,compared with 2.90%to 23.89%,3.06%to 82.33%and 16.17 QALYs respectively for the patients treated with Lamivudine.The patients who received TCM had gained more than 12.11 accumulated QALYs per patient than the ones who received Lamivudine.Among the patients with HBeAg-negative CHB treated with TCM,there were 22.98%to 46.74%of patients who had combined response,and 2.92%to 57.06%of patients who progressed to compensated cirrhosis in the course of 40 years,and average per patient had gained 23.36 accumulated QALYs in the end of 40 years treatments,in comparison with 5.83%to 29.43%, 2.35%to 80.21%and 16.84 QALYs of the patients treated with Lamivudine respectively.There were 6.52 accumulated QALYs per patient average gained in the TCM group more than those of the Lamivudine group.By monte carlo microsimulation for 10000 times,among the HBeAg-positive CHB patients that received TCM,the P0 of QALYs that they would gain average per patient in the end of 40 years treatments was 1,P100 was 37,and P50 was 35, compared with 1,35 and 14 QALYs respectively for the patients who received Lamivudine.The difference of the optimal clinical intervention between TCM and Lamivudine was 0.134.Among the HBeAg-negative CHB patients treated with TCM, the P0 of QALYs that they would gain average per patient in the end of 40 years treatments was 1,P100 was 36,and P50 was 30,compared with 1,35 and 15 QALYs respectively for the patients who received Lamivudine.And the difference of the optimal clinical intervention between TCM and Lamivudine was 0.003.Conclusions:First,TCM was the optimal intervention compared with Lamivudine for the patients with HBeAg-positive CHB in the long-term at the 0.05 tolerance level, while for the ones with HBeAg-negative,there was no statistical difference between TCM intervention and Lamivudine intervention at the 0.05 tolerance level.Second, Markov model could be used to simulate the progression of CHB and it was feasible for Markov model to assess the long-time outcomes of chronic diseases with the treatment of TCM.However,more researches were needed to make it better in the future work.