Rapid downregulation of programmed death-1 and interferon-γ-inducible protein-10 expression is associated with favourable outcome during antiviral treatment of chronic hepatitis B

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-naivepatients undergoing telbivudine treatment for 52weeks. 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 52weeks, 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.