title: 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.
abstract: 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.
authors: Department of Infectious Diseases, Center for Liver Diseases, Peking University First Hospital, Beijing, China.
authors: F-Q
authors: FQ
authors: Hou
authors: X-J
authors: XJ
authors: Wu
authors: Y
authors: Y
authors: Wang
authors: J
authors: J
authors: Chen
authors: Y-Z
authors: YZ
authors: Liu
authors: Y-Y
authors: YY
authors: Ren
authors: G
authors: G
authors: Song
authors: Y-P
authors: YP
authors: Ding
authors: M
authors: M
authors: Yu
authors: G-Q
authors: GQ
authors: Wang
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism*; D002681:China; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism*; D000077712:Telbivudine; D013936:Thymidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D016207:Cytokines; D004279:DNA, Viral; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000077712:Telbivudine; D007371:Interferon-gamma; D013936:Thymidine