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Chronic hepatitis B ( CHB) is characterized by an impaired immune response to hepatitis B virus. Among the nucleos(t)ides used in CHB treatment, telbivudine is associated with the highest rates of hepatitis B e antigen ( HBeAg) seroconversion rates, which are similar to those observed with pegylated interferon (Peg IFN). Besides direct antiviral effect, modulation of the immune system may be an additional benefit for telbivudine-treated patients. Indeed, there is much clinical data indicating an IFN-like behaviour for telbivudine in contrast to other oral nucleos(t)ides, such as high HBeAg seroconversion, similar hepatitis B surface antigen ( HBsAg) decline and biphasic viral kinetics. Clinical studies, animal models and in vitro studies suggest that both the innate and adaptive immune system responses contribute to high HBeAg seroconversion during telbivudine treatment through modulation of the function and/or expression of CD4+/ CD8+ T cells, Th1/Th2, Treg, PD-1/ PD-L1, Th17, IL-21 and TFH. The results described in this review suggest that the antiviral effect of telbivudine may be attributable not only to direct suppression of hepatitis B virus, but also to immunoregulatory effects. Hypothetically, telbivudine shares some common signal pathways with IFN. [ABSTRACT FROM AUTHOR]

The dynamics of programmed death-1 ( PD-1) as well as cytokine/chemokine expression and its correlation with virological response in patients with chronic hepatitis B ( CHB) is unclear. This study was conducted in 29 treatment-naïve patients undergoing telbivudine treatment for 52 weeks. The results showed that PD-1 expression on both CD4+ and CD8+ T cells was positively correlated with hepatitis B virus ( HBV) DNA levels ( r = 0.621, P < 0.0001; r = 0.548, P = 0.002, respectively), and in virological responders, this decrease was directly correlated with a decrease in HBV DNA levels ( r = 0.664, P = 0.002; r = 0.572, P = 0.01, respectively). Furthermore, at the end of 52 weeks, in virological responders, the decreased rate in the frequency of PD-1+ CD8+ T cells was significantly higher than in non-virological responders (58.3% vs 25.7%, P = 0.001), and at weeks 24 and 52, in virological responders, PD-1 expression on CD4+ and CD8+ T cells was lower than in non-virological responders ( P = 0.01 and P = 0.035; P < 0.0001 and P < 0.0001, respectively). In 34 cytokines/chemokines detected in serum, IP-10 expression was positively correlated with viral load, level of ALT and PD-1 expression on CD8+ and CD4+ T cells at baseline ( r = 0.36, P = 0.055, r = 0.635, P < 0.0001, r = 0.414, P = 0.026, and r = 0.402, P = 0.030, respectively). Moreover, the decrease in IP-10 in serum directly correlated with a decrease in ALT levels ( r = 0.751, P < 0.0001). At weeks 24 and 25, IP-10 expression was significantly lower than baseline in virological responders (both P = 0.005); however, this was not observed in nonresponders. Based on the above findings, PD-1 and IP-10 may be used as predictors for virological response, and blockade of their pathway may improve the outcome of patients with CHB. [ABSTRACT FROM AUTHOR]

. A DNA vaccine against the hepatitis B virus (HBV), enhanced by IL-2/IFN-γ fusion protein expression from a plasmid construct and mediated by in vivo electroporation, was evaluated in a total of 39 HBeAg-positive patients with chronic hepatitis B (CHB). The six of 39 patients with a serum alanine aminotransferase (ALT) value of 1-2 times upper limit of normal (ULN) were assigned to the open-label arm (Group01) receiving vaccine monotherapy; the remaining 33 patients with an ALT of more than two times ULN were enroled to the randomized and controlled arm (Group02) receiving lamivudine (LAM) monotherapy (LAM+placebo) or combined therapy (LAM+DNA vaccine) in 1:2 ratio. In Group01, a significant elevation of HBV-specific IFN-γ-secreting T-cell counts in comparison with baseline was observed. In Group02, the proportion of patients with HBV DNA suppression was higher with LAM+DNA vaccine than with LAM monotherapy at each visit time point after the final injection of DNA vaccine at week 36, revealing a significant difference between the two groups ( P = 0.03) at week 60. The incidence of dual-site mutations of rtM204/I/S+rtL180M was significantly lower ( P = 0.03) with an identified lower virological breakthrough (VBT) rate ( P = 0.03) in patients receiving LAM+DNA vaccine than LAM monotherapy, accompanied with a significant higher positive T-cell response rate in patients receiving LAM+DNA vaccine ( P = 0.03). In conclusion, this study provides evidence that HBV DNA vaccination is safe and immunologically effective, and that the HBV-specific T-cell responses induced by DNA vaccination under LAM chemotherapy showed a correlation with the suppression of viral replication in patients with CHB. [ABSTRACT FROM AUTHOR]