Results: Compared with the control down regulation of 44 proteins and up regulation of 38 proteins were found in HepG2-S-G2 cell. All these regulated proteins were identified by MS/MS and could be fell into several categories including metabolism-associated, immune-response-related, protein modification, signal transduction and others. Among them, a group of proteins in putative pathways associated with apoptosis were found out and discussed, including glucose-regulated protein 78kD (GRP78/Bip), heterogeneous nuclear ribonucleoprotein (hnRNP), Far upstream element-binding protein (FUSEbp), Rho GDP Dissociation Inhibitor (GDI), cystatin B and some scaffold proteins. GRP78, an important chaperone protein involved in multiple functions in host cells, was consistently decreased in HepG2-S-G2 and in Huh7 cell transiently transfected with HBsAg expression plasmid. Decreased CRP78 inducing by HBsAg or blockage of RNAi consistently led to the less resistance to staurosporine-induced cell death. Conclusions: These results revealed a possible pathogenesis induced by HBsAg via GRP78. Background/Aim: To evaluate the efficacy of adefovir dipivoxil alone and in combination with lamivudine in treating patients with lamivudine-refractory HBeAg-positive chronic hepatitis B. Methods: Eighty-five HBeAg-positive patients who had received lamivudine treatment for various periods and had a lamivudine-resistant liver function abnormality, documented YMDD mutations and persistent viremia were randomized to adefovir dipivoxil 10 mg, lamivudine 100 mg, or addition of adefovir dipivoxil to ongoing lamivudine daily. The primary efficacy measure was virological response. The secondary efficacy measure was serological response (HBeAg loss rate and HBeAg seroconversion rate) and ALT normalization rate. Results: After 24 weeks of therapy, mean reduction of HBV-DNA level, the percentage of patients with HBV-DNA lower than 5 log10 copies/ml and the percentage of patients with HBV-DNA level decrease of more than 2 log10 copies/ml in patients of adefovir dipivoxil/lamivudine and adefovir dipivoxil monotherapy groups were significantly higher than those in patients of lamivudine group (2.58, 2.21 log copies/ml vs. 1.02 log copies/ml, 92.3%, 88.5% vs. 33.6%, 76.9%, 75.8% vs. 28.8%; P < 0.001, respectively). At the end of 52 weeks, mean reduction from baseline in serum HBV-DNA level at was 0.08, 4.25, and 4.12 log10 copies/mL in the lamivudine, adefovir dipivoxil/lamivudine, and adefovir dipivoxil groups, respectively. ALT normalization rates were significant hihger in adefovir dipivoxil/lamivudine and adefovir dipivoxil recipients than those in lamivudine recipients (62%, 55% vs. 8%, P < 0.001, respectively). A similar pattern was observed in HBeAg loss among three groups. Conclusions: Adefovir dipivoxil is an effective treatment option for patients with lamivudine-refractory HBeAg-positive chronic hepatitis B. Aim: To find the prevalence of HBV virologic flare as defined by HBV DNA viral load of > 2,000 IU/mL in inactive chronic hepatitis B (HBV DNA less than 2,000 IU/mL), HBeAg-negative patients who have not received any treatment and to identify if there are any predictors that can predict virologic flare. Methods: We retrospectively analyzed medical records of the patients who have attended Hepatitis Clinic, Siriraj Hospital from January 1, 2002 to February 28, 2008 . The patients were eligible if they were naïve to any treatment and HBV DNA less than 2000 IU/mL at entry. Co-infection with HIV and/or hepatitis C virus were excluded. HBV DNA measurement determine by Roche Amplicor ® (detection limit of 60 IU/mL). HBV virologic flare was defined as HBV DNA more than 2000 IU/mL during follow up period. Result: There were 84 patients with mean follow up time was 598 days with annual prevalence of HBV virologic flare of 12.8, 4.8, and 4.2% for the first, second and third year of follow up, respectively. Initial HBV DNA level was the only predictor that can predict reactivation. No patients with HBV DNA at entry below detection limit developed flare and the patients with HBV DNA above 740 IU/mL had 22 times higher chance to develop flare during follow up. Conclusion: HBV DNA flare is not uncommon in inactive chronic hepatitis B patients. Most of the virologic flares occur in the first year. The most important predictor or virologic flare is higher HBV DNA at beginning. Background: Multi-drug resistant HBV developed with multiple antiviral agents. There existed difficulty in dealing with Multi-drug resistant HBV. Methods: Retrospective analysis of 23 consecutive patients who exhibited chronic hepatitis B associated with multiple drug-resistant mutations to lamivudine and adefovir during antiviral treatment. Multiple drug-resistant mutations were detected in those patients by DNA direct sequencing. Result: Before multiple drug-resistant HBV emerged, 20 patients accept sequential antiviral therapy, 3 patients accept NA monotherapies. There were 16 cases of rtA181T/V rtM204V/I mutation, 2 cases of M204V/I +N236T mutation, 4 cases of A181T/V+M204V/I +N236T mutation, 1 case of L180M+A181T/V mutation. 14 cases received rescue therapy of Interfronand HBV DNA level of 8 cases decreased; Other 9 cases received combination treatment and HBV DNA level of 4 cases decreased. Conclusion: The main reason of multiple drug-resistant mutations was sequential antiviral therapy. Another reason may be pre-exist drug-resistant mutation before nucleoside or nucleotide analogue treatment. De novo combination of antiviral agents should be recommended. Combination therapy directed against mutants resistant to each treatment may not be adequate in suppressing multi-drug resistant HBV. Interfron may be one choice for HBV of multiple drug-resistant mutations. Background: To furnish basis for an accurate evaluation of HBeAg negative chronic hepatitis B (e CHB), the present study studies the clinical features and hepatic pathology, and analyzes the relation between the data and the grade and stage of hepatic pathology in e CHB. Methods: A study is performed in 120 Chinese e CHB patients (106 men and 14 women; mean age SD, 34.3 9.4 years). The relationship between the clinical features and the grade and stage of hepatic pathology was analyzed by Spearman's rank correlation test or Kruskal-Wallis test by applying STATA 7.0 software. Result: Negative correlation is shown between the grade and leucocyte count Methods: 80 patients with HBeAg-positive compensated CHB with HBV DNA >6 log10 copies/ml, serum ALT 2 x ULN were divided two groups:one treated with Telbivudine and the other treated with Entecavir. Results: Baseline characteristics were well balanced between treatment groups. At 12wk of the treatment the HBV DNA undetectable rates of HBeAg-poitive patients in the Telbivudine group and the Entecavir were respectively 50 52.5 (p 0.05), the rates of HBeAg negative were 10 0 respectively, the rates of HBeAg seroconversion were 20 5 respectively; At 24wk of the treatment the HBV DNA undetectable rates of HBeAg-poitive patients in the Telbivudine group and the Entecavir were respectively 80 70 (p 0.05), the total rates of HBeAg negative were 20 15 respectively, the total rates of HBeAg seroconversion were 27.5 17.5 respectively(p 0.05).No adverse reactions were found in both groups Conclusion: There was no significant difference in HBV DNA undetectable rates between two nucleotide analogs in short-term (24 weeks).The Telbivudine group has better effect in HBeAg seroconversion rate than the Entecavir group in early stage,but no statistical significance.