Hepatitis B virus (HBV) infection is a global public health problem, which plays a crucial role in the pathogenesis of chronic hepatitis, cirrhosis and hepatocellular carcinoma. Although considerable progress has been made, the pathogenesis of HBV infection is still elusive. There's an urgent need to elucidate the mechanisms of HBV-host interactions, to discover novel biomarkers for diagnosis and prognosis and to develop therapeutic targets for anti-HBV treatment. Herein, we applied a two-dimensional gel electrophoresis and MALDI-TOF/MS based comparative proteomics approach to globally analyze the host response to HBV by using an inducible HBV-producing cell line HepAD38. Of the 23 differentially expressed proteins identified, glucose regulated protein 78 (GRP78) was one of the most striking proteins elevated by HBV replication, which was confirmed by real-time PCR and western blotting. Knockdown of GRP78 expression by RNA interference resulted in a significant increase of both intracellular and extracellular HBV virions in HBV-transfected HepG2 cells. Reversely, GRP78 overexpression led to HBV suppression. The expression levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were determined by enzyme linked immunosorbent assay (ELISA). Immunofluoresce further revealed a positive correlation between the expression levels of GRP78 and HBsAg in both HBV-transfected HepG2 cells and HBV-infected human liver tissues. Altogether, these data demonstrate for the first time that GRP78 is an endogenous anti-viral factor in HBV-transfected HepG2 cells and may serve as a potential prognostic indicator of viral status in anti-HBV therapies. Background/Aims: To evaluate the predictors of response to long-term treatment of adefovir dipivoxil (ADV) in patients with emerging lamivudine (LAM)-resistant hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. Methods: One-hundred-thirty-four LAM-resistant HBeAg-positive CHB patients were treated with ADV for a median of 28.0 months (range, 18 -54 months), following LAM therapy for a median of 25.5 months (range, 5 -66 months). 65 patients (48.5%) were switched from LAM to ADV monotherapy, 43 (32.1%) were switched to ADV with 1 month of LAM overlap therapy, and 26 (19.4%) were switched to ADV with 3 months of LAM overlap therapy. The influence of baseline parameters on treatment response to ADV in patients with LAM-resistant HBeAg positive CHB was analyzed. Result: During the follow-up period, 28 (20.9%) of 134 patients achieved complete response, defined as normalization of ALT level, negative HBV DNA by a Digene hybrid capture assay and achievement of HBeAg loss. Sixteen (11.9%) patients achieved HBeAg seroconversion. Twenty-eight (20.9%) patients developed ADV-related mutations during ADV treatment. In multivariate analysis, virological response at 3 months (OR=9.70, 95% CI: 32.63-35.78, p=0.001), defined as serum HBV DNA levels less than 5 log10 copies/mL or a reduction in serum HBV DNA levels greater than 2 log10 copies/mL after 3 months of ADV therapy, independently predicted complete response. Conclusions: Virological response at 3 months was the strongest predictor of ADV response in LAM-resistant HBeAg-positive CHB patients. Background/Aims: To explore the effects of HBV DNA level HBV genotype/subgenotype on the pathogenesis of severe liver diseases in Chongqing. Methods HBV DNA level was analyzed in patients with severe liver diseases in retrospect,and HBV genotype/subgenotype HBV DNA level and HBeAg were determined in patients with hepatocellular carcinoma (HCC,n=78 ), Liver cirrhosis(LC, n=58),chronic hepatitis B(CHB, n=20) and acute on chronic liver failure(ACLF, n=42). Results HBV level from high to low with CHB were LC, ACLF and HCC in turn(P 0.05). HBV genotype was mainly genotype B.The rate of genotype B and C were 51. 3% and 47.4 respectively in HCC patients, 60.3% and 39.7 in LC patients, 55% and 40 in CHB patients, 55% and 40 in ACLF patients. The percentage of genotype B/C in ACLF patients was higher in compared with other groups. But the distribution of HBV genotype among groups was not statistically different(P 0.05).Subgenotypes of genotype B were almost Ba but one. Subgenotypes of genotype C were mainly Ce in Chongqing area, and there was no statistical difference among the 4 groups (P 0.05). Conclusion: HBV DNA level seems not to be a determining factor at end point of severe liver disease. Both genotype B and C of HBV can lead to severe liver diseases, and there are more mixed infections by different genotypes in ACLF.