The biosensor based microarray signal can be easily record by digital camera or even by the naked eyes And the detection signal for positive discriminated from negative were sharply contrasted as whole yes or no and it looks be significantly superior to classical microarray technique; 2. The sensitivity of the detection limitation of sera HBV load is 2X10E3 copies/ml with 95% reproducibility. The concordance index of 50 times negative and mutated plasmids were 98%(Kappa=0.932). 3. 30 sera samples of HBV>10E4 load and 20 sera of HBV negative tested by PCR fragment sequencing were showing very good agreement between sequencing with our biosensor based microarray and the concordance index kappa was 0.7619. Conclusion: Our biosensor-based microarray for Pre-C/BCP mutation assay were a both sensitive and accurate method. And its advantages of equipment free, sharply contracted signal of positive vs negative and easily be perform in testing were make it be a promised assay for clinical application. Objective: To investigate the frequencies of CD4 + CD25 + regulatory T cells in the cord blood of fetuses whose mothers are patients with chronic hepatitis B, we assayed the differences among HBsAg-positive and healthy subjects by flow cytometry. The results might offer some experimental evidence to explain the high rates of HBV persistent infection in vertical transmission of HBV from HBV-infected mothers. Methods: 12 newborns born from HBsAg positive mothers were recruited , 10 healthy subjects being used as a control group. The cord blood and peripheral blood of mothers were collected respectively .Frequencies of CD4 + CD25 + regulatory T cells in the cord blood of fetuses whose mothers are patients with chronic hepatitis B were analyzed by flow cytometric analysis. Result: The number of CD4 + CD25 + regulatory T cells/PBMCs in the cord blood of newborns born from HBsAg positive mothers 4.49 ±1.18 significantly exceeded that in normal controls 2.26 ±0.97 ,P 0.001 ;And newborns born from HBsAg positive mothers presented a much higher fraction of cord blood CD4 + CD25 + /CD4 + 9.62 ±2.34 than those in normal controls 7.93 ±1.43 ,P P=0.0025 P 0.05 . Conclusions: The results indicate that the proportion of CD4 + CD25 + regulatory T cells in HBsAg positive mother cord blood was higher than those of healthy cord blood. Objective: To study the clinical features of chronic severe hepatitis B with negative hepatitis B e-antigen (HBeAg) and positive hepatitis B e-antigen (HBeAg) Methods: A total of 353 in-patients with chronic severe hepatitis B were recruited into the study and divided into two groups according to the HBeAg status. The serological chemistry data, hepatitis B virus (HBV) DNA quantification data were detected, and morbility of cirrhosis, its complications and prognosis were also studied. Results: Of the 353 in-patients, 236(66.8%) patients were HBeAg-negative. 117(33.2%) patients were HBeAg-positive. The ratio of HBeAg-positive patients was significantly higher than that of HBeAg-positive patients (p<0.05).The average age of HBeAg-negative patients was older than that of HBeAg-positive patients (P=0.048). The serum HBV DNA level of HBeAg-negative patients was significantly lower than that of HBeAg-positive patients (5.49±2.02) vs(6.64±1.41) log copies/ml (p<0.01).The ratio of patients who had a serum HBV DNA level less than 5log copies/ml in HBeAg-negative patients was significantly higher than that in HBeAg-positive patients (41.8% vs 11.9% ,p=0.000). There was no significant difference in serological chemistry data, morbility of cirrhosis and its complications on infections, ascites, hepatoencephalopathy, gastrointestinal hemorrhage, as well as prognosis of the patients between those two groups. Conclusions: The study suggested that serological chemistry data, morbility of complications and prognosis of the disease of HBeAg-negative patients mimics that of HBeAg-positive patients. The HBeAg-negative patients had a higher level of age, while a lower level of serum HBV DNA. To reduce the incidence of liver failure, more frequent monitoring and earlier antiviral therapy prone to be reasonable for chronic hepatitis B patients with negative hepatitis B e-antigen. Background: The emergence of LAM-resistant virus greatly limits the efficacy of therapy and induces the liver injury. The aims of this study were to assess the related factors of LAM-resistant mutation in HBeAg positive CHB patients. Methods: Thirty-five patients carrying LAM-resistant with HBeAg positive were enrolled in this study. All of them underwent percutaneous liver biopsy, histological findings and had detectable viral load. Age, viral load, levels of ALT, types of mutation and HBV genotype was monitored. Result: The median year of mutation found was 23months. 85.71% were genotype C and 14.29% were genotype B. The mutation of L80I, L80V, G173L, L180M, M204V and M204I were detected. The emergence rates were 34.3%(12/35), 25.7%(9/35), 17.1%(6/35), 60%(21/35), 57.1%(20/35), 54.3%(19/35) respectively. The rate of patients with two or three mutation were much more than one or four mutation. 62.9% patients were found to have significant histological findings, even 5 had established cirrhosis. Two had no histological finding. One had rtL80I and rtM204I. The other had rtL80V, rtL180M and rtM204V. The number of resistant mutation has no significant finding with histological finding, basic ALT level and basic viral load. Conclusions: The emergence rate of L180M, M204V and M204I were higher than that of L80I, L80V, G173L in HBeAg positive CHB patients with LAM-resistance. Most of them have two or three LAM-resistant mutation regardless of histological finding severity, level of basic ALT and viral load. We must select the efficacious method to treat the patients with LAM-resistant. Objective: To investigate the therapeutic efficacy of foscarnet sodium in the treatment of patients with severe chronic hepatitis B. Methods: Forty four patients were randomly divided into foscarnet sodium treatment and placebo groups.Each group consisted of 22 patients, 22 patients in foscarnet sodium group were treated with foscarnet sodium twice daily 3.0g given by intravenous infusions ,in addition to general therapy for 28 days.The other 22 cases were treated without any form of antiviral therapy as control.All patients were followed up for 6 months.The HBV markers, quantification of HBV-DNA, serological chemistry data were measured at baseline , during therapy period and the end of follow-up period . Results: Clinical symptoms were improved in Two groups patients, meanwhile alanine aminotransferase (ALT) and total serum bilirubin (TBiL) decreased. Compare ALT and TBiL at the end of trentment, there were no significant differences between the two groups (p>0.05). In foscarnet sodium treatment group, the level of serum HBV-DNA descreased from (6.993±0.898) log copies/ml to( 4.033±1.286) log copies/ml (p<0.05), the rate of HBV-DNA descrease of more than two log was 81.1% 18/22 . In the control group, the level of serum HBV-DNA descreased from( 7.068±0.938) log copies/ml to (5.188±1.926 )log copies/ml, the rate of HBV-DNA descrease of more than two log was 45.4% 10/22 .A comparison of serum HBV-DNA showed significant differences between the two groups(p<0.05) Conclusion: foscarnet sodium administered can inhibit HBV replication in treating severe chronic hepatitis B.It can rapid lower the level of serum HBV-DNA obviously.But the relapse rate was 47.0% in foscarnet sodium treated at the end of follow up period Objective: Evaluation of efficacy and safety of five years trail of entecavir for chronic hepatitis Bpatients failed with lamivudine therapy in the Chongqing area. Methods: Thirty-two eligible patients were enrolled who had documented LVD failure.In the double-blind phase,patients were randomized(4:1)to ETV1.0mg/d (n=28)and placebo (n=4) for 12 weeks.In the open-lable phase ,patients received ETV 1.0mg/d for 240 weeks.HBV-DNA level,liver function tests,HBV serology and safety assessments were conducted. Results: The mean reduction in HBV DNA levels at week 12 was 4 05 logl0 copies ml in ETV group compared to 0.08logl0 copies ml in placebo group(P< 0 05). The mean of HBV DNA levels after 240 weeks of ETV treatment decreased to 2.58logl0 copies m1 The proportion of HBV DNA<3log10copy/ml raised from 0 at baseline to 6.25% at week 8,to 15.6% at week 24,to 50% at week 96,and raised to 57.14% at week 240.There were two patients with HBsAg seroconversion and four patients with HBeAg seroconversion at the end of study. The mean of ALT became normal at week 12 and remained normal throughout week 240.There was one patient who had a severe adverse event during the trail. Conclusion: The findings from this study demonstrated the antiviral activity and safety of ETV in adults with CHB who have failed LVD PE198 showing delayed response on T cells as increased on day 7.The mRNA expression of IL-5 and IL-2 showed no response to HBV vaccine but highly regulated in TT after day 7(p=0.00,0.001).MyD88andTRAF 6(p=0.042)upregulated in HBV vaccine group followed by of IFN-(0.012)no change of IFN found in TT Conclusions: i) HBV vaccine stimulates innate response by day 3 which potentiates further cascade,peripheral dendritic cells plays significant role in generating immune flare follows MYD88 pathway and releases IFN-.ii) Whereas T cells Marjory involved in TT showed delayed immune response.iii) Identification of key factors at different time points may prove to be a novel model to study the initial events after vaccination. Objective: To Compare TH1/TH2 cytokines' dynamic change and its clinical significance in hepatitis B e antigen-positive patients treated with Telbivudine. Methods: Twelve hepatitis B e antigen-positive patients treated with telbivudine.The blood sample was collected at baseline, week 4, week 8, week 12, week 24 and week 48 and stored at -70C; serum IL-2, IL-4, IL-6, IL-10, TNF-and IFN-were tested at each time point by Cytometric Bead Array (CBA), Compare TH1/TH2 cytokines' dynamic change at different time point in each group and Compare TH1/TH2 cytokines' dynamic change cross four different groups: complete response, partial response, non-response and break through . Results:The level of Th1 type cytokines in complete response group are Obviously higher than the group of partial response non-response and breakthrough,but the level of Th2 type cytokines are lower than the group of partial response, non-response and breakthrough. Conclusions: Th1/Th2 cytokines is essential for the regulation of the immune function of the body. After treated with Telbivudine, the level of Th1-type cytokines in the complete response group increased significantly, while the level of Th2 cytokines declined trend.