J. Chen 1 , X.J.. Wu 1 , Y. Wang 1 , G.Q. Wang 1 1 Department of Infectious Diseases, Peking University First Hospital, Beijing, China Background: The dysfunction of T cells may represent a mechanism of hepatitis B virus (HBV) persistence. Programmed death-1 (PD-1) and its ligands, PD-L1/PD-L2, are new members of CD28/B7 family, as co-stimulatory molecules expressing on T cells and Antigen Present Cells (APCs). Their engaging can downregulate the T cells function, including proliferation, cytokines secretion and cytotoxicity. In periphery blood, PD-1 was upreguated on virus specific-T cells, leading to the impairment of T cells. Blocking the PD-1/PD-L can improve the function of T cells. Methods and Patients: 21 patients with chronic hepatitis B (CHB) were treated by pegylated IFN -2b (PegIntron from Schering-Plough, once a week, 0.5 or 1 g/kg/weight). The periphery blood were taken at 0 weeks, 4 weeks, 8 weeks, and 12 weeks. Periphery blood mononuclear cells (PBMC) were isolated from fresh heparinized blood by Ficoll-Hypaque (density: 1.077g/L) density gradient centrifugation. Then the cells were incubated with APC-conjugated anti-PD-1 antibodies. The PD-1 expression on lymphocytes was detected by flow cytometry (FCM). Results: The PD-1 expression on lymphocytes at 0 weeks was 14.47±5.8%, at 4 weeks was 9.68±3.75%, at 8 weeks was 6.95±2.39%, at 12 weeks was 6.08±1.31% (p<0.05). Conclusion: Treatment with IFN -2b can downregulate the PD-1 expression on lymphocytes and may partially restore the function of T cells. To investigate the effects of nucleoside analogs therapy in hepatitis B related acute-on-chronic liver failure, we treated 55 HBV related acute-on-chronic liver failure patients with entecavir. as control, the remaining 74 were not treated with nucleoside analogues. Results show the survival rate of entecavir therapy group has no significantly difference with none-treated group (P>0.05). Although entecavir greatly reduced HBV replication during different therapy times (P<0.001), the MELD score and liver function (ALT, albumin, bilirubin, prothrombin time) had no significant changes (P>0.05). Further more, we analyzed the MELD score and liver function in different HBV-DNA level patients .No significantly difference was observed (P>0.05). There is no significant correlation between HBV-DNA level and MELD score in different therapy times (P>0.05).The HBV-DNA level between patients with over 3 months and less than 3 months survival patients showed no significant difference either (P>0.05). However, MELD score and some parameters of liver function (albumin, bilirubin, prothrombin time) showed significant difference (P<0.05). These results suggest HBV-DNA loading may not be a direct factor to increased liver injury and suppression of HBV replication may not reduce the severity of liver failure in HBV related acute-on-chronic hepatitis.