Efficency And Safety Of Tenofovir Disoproxil Fumarate Based Rescue Therapy After A Failed Rescue Treatment In Lamivudine-resistant Chronic Hepatitis B Virus Patients

PurposeThis thesis aims to assess the efficiency and safety of tenofovir disoproxil fumarate based on treatment in Lamnivudine-resistant chronic hepatitis B virus patients with poor response after rescue therapy failed,discovering the best treatment by comparison between TDF combination therapy and Monotherapy.Method1.Selecting 51 patients among the people with lamivudine resistance received a treatment in combination of lamivudine and adefovir dipivoxil,retrospectively studying for96 weeks and observing treatment with efficiency and drug resistance mutation.2.Screening 132 patients and divided them into four groups at random.Each group includes 33 people.Not only collecting baseline information,hematology sample data,and virology sample data.But also measuring the level of HBV DNA,core antigen e and alanine aminotransferase(ALT)when the patients entered the therapeutic group on12 th week,24 th week,36 th week,48 th week.We divided groups into two parts according to the HBeAg result about whether positive or not and evaluate the efficency based on the Virologic response rate and horizontal directional of HBV DNA.Multivariate regression analysis was also conducted to investigate the relative factor effecting the outcome of therapy.All adverse reactions during the clinical research period were analysised together with Laboratory test results to evaluate the drug safety.Result1.The combination of LAM and ADV as a rescue therapy of LAM resistant patients achieved the negative conversion rate was 51.0%,while 19.6% patients showed drug resistance.2.Within 48 weeks,it is observed that there is a significant difference on HBV DNA negative conversion rate conversion between four groups.The negative conservation ratein Combination of ADV and LAM group,TDF group,combination of LAM and TDF group,combination of ETV and TDF is 24.24%?83.87%?71.43%?80.00% respectively.The negative turning rate of TDF,TDF plus ETV,TDF plus LAM were much higher than ETV,no more difference was found in the comparison between inner groups.3.Over the period of 48 weeks,among the HBeAg positive patients,negative conversion rate in LAM+ADV was 17.39%: 70.59% in the TDF monotherapy group,64,71% in the ETV plus TDF combination therapy group and 68.75% in the LAM plus TDF combination group.Efficacy difference was found between the groups.The HBV DNA conservation rate was lower in ADV-intaken patients than the other there groups,while the difference was not found among them.Among the HBeAg negative patients,The overall probability of complete virologic suppression in ADV+LAM was 40.0%: 100.0%in the TDF monotherapy group,100.0% in the ETV plus TDF combination therapy group and 75.0% in the LAM plus TDF combination group.The HBeAg negative patients achieved better virologic suppression than that in HBeAg positive patients.Moreover,HBV DNA conservation rate was higher in TEV group,TDF group,TDF plus ETV combination therapy group when it termed to HBeAg negative patients than HBeAg positive patient.However,no more difference was not found beside these.4.After 48 weeks' treatment,HBV DNA levels fell by an average 3.64±1.00 log10copies/ml.HBV DNA level decreased by 2.89±0.72 log10 copies/ml in combination ADV and LAM group,3.96±1.16 log10 copies/ml in TDF group,3.98±1.11 log10 copies/ml in ETV plus TDF group,3.41±0.82 log10 copies/ml in LAM plus TDF group,respectively.Comparison was conducted between inner groups.The declination range were found higher in TDF monotherapy and TDF plus ETV combination therapy than that in combination ADV and LAM group(p<0.05).No more difference was found in the other comparisons.5.After the 48 weeks of treatment,The HBeAg conservation rate was 13.04% in combination ADV and LAM group among HBe Ag positive patients,15.76% in TDF group,23.53% in ETV plus TDF group and 18.75% in LAM plus TDF group.No statistic difference was found between groups.Among the ALT patients with abnormality,ALT recovery rate was 52.63% in ETV group,94.27% in TDF group,87.51% in LAM plus TDF group,100% in ETV plus TDF group,respectively.Significant difference was also not found.6.Multivariate regression analysis was conducted In order to figure out factorsrelative to the prognosis.The outcome showed that HBV DNA level,HBeAg,age,therapy stratepy were correlative with the prognosis while the alcohol Consuming,smoking,gender,showed no associations in statistics.7.Notable Adverse effect was reported in four patients,two patients showed the ALT level increasing by two folds compared with baseline.Insomnia and phosphorus levels decreasing were reported in the other two patients.Conclusion1.Patients with lamivudine resistance who received a treatment in combination of lamivudine and adefovir dipvoxil showed a poor response to antiviral therapy.2.There is a possibility of multiple drug resistance in the process of salvage therapy in LAM resistance of combination ADV with LAM.3.The TDF showed strong antiviral activities and the ability to lower the virus level both in monotherapy and combination therapy.4.Tenofovir used in HBeAg negative patients' HBV-DNA negative turning rate is higher than that of HBeAg positive patients.5.Regression analysis of logistics with multiple factor showed the effect of NUCs treatment is correlative with age,HBV DNA level,HBeAg and therapeutic regimen.