{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:26:49Z","timestamp":1787023609229,"version":"build-2736575974"},"reference-count":49,"publisher":"Impact Journals, LLC","issue":"28","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oncotarget"],"published-print":{"date-parts":[[2017,7,11]]},"DOI":"10.18632\/oncotarget.17546","type":"journal-article","created":{"date-parts":[[2017,5,2]],"date-time":"2017-05-02T07:23:56Z","timestamp":1493709836000},"page":"46020-46033","source":"Crossref","is-referenced-by-count":34,"title":["Circulating soluble programmed death-1 levels may differentiate immune-tolerant phase from other phases and hepatocellular carcinoma from other clinical diseases in chronic hepatitis B virus infection"],"prefix":"10.18632","volume":"8","author":[{"given":"Na","family":"Li","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Sang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qunying","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China"},{"name":"Institute of Advanced Surgical Technology and Engineering, Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengwen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China"},{"name":"Institute of Advanced Surgical Technology and Engineering, Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"7892","published-online":{"date-parts":[[2017,5,2]]},"reference":[{"issue":"30","key":"1","first-page":"2212","article-title":"Global epidemiology of hepatitis B virus infection: new estimates of agespecific HBsAg seroprevalence and endemicity","volume":"2012","author":"Wiersma","journal-title":"Vaccine"},{"issue":"10","key":"2","first-page":"1","article-title":"Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update","volume":"2016","author":"Hou","journal-title":"Hepatol Int"},{"issue":"51","key":"3","first-page":"403","article-title":"Antiviral therapy of chronic hepatitis B: opportunities and challenges in Asia","volume":"2009","author":"Liaw","journal-title":"J Hepatol"},{"issue":"31","key":"4","first-page":"J21","article-title":"Reprint of: epidemiological serosurvey of Hepatitis B in China--declining HBV prevalence due to Hepatitis B vaccination","volume":"2013","author":"Wang","journal-title":"Vaccine"},{"issue":"6","key":"5","doi-asserted-by":"publisher","first-page":"4440","DOI":"10.18632\/oncotarget.2913","article-title":"Hepatocellular carcinoma in a large medical center of China over a 10-year period: evolving therapeutic option and improving survival","volume":"2015","author":"Liu","journal-title":"Oncotarget"},{"issue":"57","key":"6","first-page":"167","article-title":"EASL clinical practice guidelines: management of chronic hepatitis B virus infection","volume":"2012","author":"European Association For The Study Of The Liver","journal-title":"J Hepatol"},{"issue":"77","key":"7","first-page":"68","article-title":"CD8(+) T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection","volume":"2003","author":"Chisari","journal-title":"J Virol"},{"issue":"81","key":"8","first-page":"4215","article-title":"Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection","volume":"2007","author":"Ferrari","journal-title":"J Virol"},{"issue":"184","key":"9","first-page":"287","article-title":"CD8(+) T cell control of hepatitis B virus replication: direct comparison between cytolytic and noncytolytic functions","volume":"2010","author":"Naoumov","journal-title":"J Immunol"},{"issue":"150","key":"10","first-page":"684","article-title":"Hepatitis B virus--specific and global T-cell dysfunction in chronic hepatitis B","volume":"2016","author":"Smith","journal-title":"Gastroenterology"},{"issue":"17","key":"11","first-page":"34","article-title":"Regulatory T cells in chronic hepatitis B patients affect the immunopathogenesis of hepatocellular carcinoma by suppressing the anti-tumour immune responses","volume":"2010","author":"Chen","journal-title":"J Viral Hepat"},{"issue":"53","key":"12","first-page":"718","article-title":"Regulation of HBV-specific CD8(+) T cell-mediated inflammation is diversified in different clinical presentations of HBV infection","volume":"2015","author":"Fauceglia","journal-title":"J Microbiol"},{"issue":"6","key":"13","first-page":"e1694","article-title":"T-cell exhaustion in chronic hepatitis B infection: current knowledge and clinical significance","volume":"2015","author":"Chen","journal-title":"Cell Death Dis"},{"issue":"8","key":"14","first-page":"239","article-title":"The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection","volume":"2007","author":"Freeman","journal-title":"Nat Immunol"},{"issue":"56","key":"15","first-page":"739","article-title":"Contribution of the PD-L1\/PD-1 pathway to T-cell exhaustion: an update on implications for chronic infections and tumor evasion","volume":"2007","author":"Mackensen","journal-title":"Cancer Immunol Immunother"},{"issue":"45","key":"16","first-page":"963","article-title":"PD-1 upregulation is associated with HBV-specific T cell dysfunction in chronic hepatitis B patients","volume":"2008","author":"Chen","journal-title":"Mol Immunol"},{"issue":"128","key":"17","first-page":"887","article-title":"PD-1 and PD-L1 upregulation promotes CD8(+) T-cell apoptosis and postoperative recurrence in hepatocellular carcinoma patients","volume":"2011","author":"Wang","journal-title":"Int J Cancer"},{"issue":"12","key":"18","first-page":"394","article-title":"Programmed death 1 and programmed death ligand 1 expressions in patients with chronic hepatitis B","volume":"2013","author":"Zheng","journal-title":"Hepatobiliary Pancreat Dis Int"},{"issue":"8","key":"19","first-page":"186","article-title":"The expression of programmed death-1 in circulating CD4+ and CD8+ T cells during hepatitis B virus infection progression and its correlation with clinical baseline characteristics","volume":"2014","author":"Wang","journal-title":"Gut Liver"},{"issue":"61","key":"20","first-page":"1212","article-title":"Restoration of HBV-specific CD8+ T cell function by PD-1 blockade in inactive carrier patients is linked to T cell differentiation","volume":"2014","author":"Thimme","journal-title":"J Hepatol"},{"issue":"6","key":"21","doi-asserted-by":"publisher","first-page":"18933","DOI":"10.18632\/oncotarget.3662","article-title":"microRNA-4717 differentially interacts with its polymorphic target in the PD1 3\u2032 untranslated region: a mechanism for regulating PD-1 expression and function in HBV-associated liver diseases","volume":"2015","author":"Liu","journal-title":"Oncotarget"},{"issue":"30","key":"22","first-page":"1379","article-title":"Increased PD-1 and decreased CD28 expression in chronic hepatitis B patients with advanced hepatocellular carcinoma","volume":"2010","author":"Wu","journal-title":"Liver Int"},{"issue":"17","key":"23","first-page":"3322","article-title":"Immunostaining of PD-1\/PD-Ls in liver tissues of patients with hepatitis and hepatocellular carcinoma","volume":"2011","author":"Yang","journal-title":"World J Gastroenterol"},{"issue":"8","key":"24","first-page":"55","article-title":"The co-inhibitory pathway and cellular immune imbalance in the progress of HBV infection","volume":"2014","author":"Liao","journal-title":"Hepatol Int"},{"issue":"8","key":"25","first-page":"2926","article-title":"Follicular helper T cell exhaustion induced by PD-L1 expression in hepatocellular carcinoma results in impaired cytokine expression and B cell help, and is associated with advanced tumor stages","volume":"2016","author":"Zhang","journal-title":"Am J Transl Res"},{"issue":"95","key":"26","first-page":"e5749","article-title":"Immune checkpoint proteins PD-1 and TIM-3 are both highly expressed in liver tissues and correlate with their gene polymorphisms in patients with HBV-related hepatocellular carcinoma","volume":"2016","author":"Liu","journal-title":"Medicine (Baltimore)"},{"issue":"138","key":"27","article-title":"Antiviral intrahepatic T-cell responses can be restored by blocking programmed death-1 pathway in chronic hepatitis B","volume":"2010","author":"Ferrari","journal-title":"Gastroenterology"},{"issue":"235","key":"28","first-page":"109","article-title":"Alternative splice variants of the human PD-1 gene","volume":"2005","author":"Lillevang","journal-title":"Cell Immunol"},{"issue":"177","key":"29","first-page":"8844","article-title":"Aberrant regulation of synovial T cell activation by soluble costimulatory molecules in rheumatoid arthritis","volume":"2006","author":"Zhang","journal-title":"J Immunol"},{"issue":"38","key":"30","first-page":"408","article-title":"Soluble PD-1 is associated with aberrant regulation of T cells activation in aplastic anemia","volume":"2009","author":"Zhang","journal-title":"Immunol Invest"},{"issue":"34","key":"31","first-page":"297","article-title":"Enhancement of vaccine-induced primary and memory CD8(+) T-cell responses by soluble PD-1","volume":"2011","author":"Sung","journal-title":"J Immunother"},{"issue":"124","key":"32","first-page":"277","article-title":"Soluble PD-1 rescues the proliferative response of simian immunodeficiency virus-specific CD4 and CD8 T cells during chronic infection","volume":"2008","author":"Ansari","journal-title":"Immunology"},{"issue":"191","key":"33","first-page":"6060","article-title":"In vivo blockade of the programmed cell death-1 pathway using soluble recombinant PD-1-Fc enhances CD4+ and CD8+ T cell responses but has limited clinical benefit","volume":"2013","author":"Villinger","journal-title":"J Immunol"},{"issue":"13","key":"34","first-page":"1823","article-title":"Soluble PD-1 facilitates 4-1BBL-triggered antitumor immunity against murine H22 hepatocarcinoma in vivo","volume":"2007","author":"Feng","journal-title":"Clin Cancer Res"},{"issue":"21","key":"35","first-page":"688","article-title":"Adenovirus expressing both thymidine kinase and soluble PD1 enhances antitumor immunity by strengthening CD8 T-cell response","volume":"2013","author":"Lee","journal-title":"Mol Ther"},{"issue":"9","key":"36","first-page":"e95870","article-title":"Circulating programmed death-1 as a marker for sustained high hepatitis B viral load and risk of hepatocellular carcinoma","volume":"2014","author":"Yu","journal-title":"PLoS One"},{"issue":"15","key":"37","first-page":"25","article-title":"The natural history of chronic HBV infection and geographical differences","volume":"2010","author":"Hadziyannis","journal-title":"Antivir Ther"},{"issue":"75","key":"38","first-page":"5","article-title":"Cancer immunotherapy and breaking immune tolerance: new approaches to an old challenge","volume":"2015","author":"Weiner","journal-title":"Cancer Res"},{"issue":"36","key":"39","first-page":"93","article-title":"HBV: do I treat my immunotolerant patients?","volume":"2016","author":"Papatheodoridis","journal-title":"Liver Int"},{"issue":"12","key":"40","first-page":"568","article-title":"Risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B): development and validation of a predictive score","volume":"2011","author":"Seto","journal-title":"Lancet Oncol"},{"issue":"50","key":"41","first-page":"80","article-title":"Independent risk factors and predictive score for the development of hepatocellular carcinoma in chronic hepatitis B","volume":"2009","author":"Lai","journal-title":"J Hepatol"},{"issue":"28","key":"42","first-page":"1660","article-title":"Clinical scoring system to predict hepatocellular carcinoma in chronic hepatitis B carriers","volume":"2010","author":"Mok","journal-title":"J Clin Oncol"},{"key":"43","first-page":"1124A","article-title":"Nivolumab (Nivo) in patients (Pts) with advanced hepatocellular carcinoma (HCC): the CheckMate 040 study","volume":"64","author":"Chopra","year":"2016","journal-title":"Hepatology"},{"issue":"122","key":"44","first-page":"367","article-title":"Immunotherapy in hepatocellular carcinoma: primed to make a difference?","volume":"2016","author":"Abou-Alfa","journal-title":"Cancer"},{"issue":"28","key":"45","first-page":"39","article-title":"Prognostic and predictive markers for the new immunotherapies","volume":"2014","author":"Atkins","journal-title":"Oncology (Williston Park)"},{"issue":"41","key":"46","first-page":"868","article-title":"Predictive biomarkers in PD-1\/PD-L1 checkpoint blockade immunotherapy","volume":"2015","author":"Yu","journal-title":"Cancer Treat Rev"},{"issue":"16","key":"47","first-page":"e542","article-title":"Predictive biomarkers for checkpoint inhibitor-based immunotherapy","volume":"2016","author":"Atkins","journal-title":"Lancet Oncol"},{"issue":"14","key":"48","first-page":"35","article-title":"Association of serum soluble human leukocyte antigen-G levels with chronic hepatitis B virus infection","volume":"2014","author":"Hao","journal-title":"Clin Exp Med"},{"issue":"38","key":"49","first-page":"5125","article-title":"CTLA-4 exon 1 +49 polymorphism alone and in a haplotype with -318 promoter polymorphism may confer susceptibility to chronic HBV infection in Chinese Han patients","volume":"2011","author":"Zhu","journal-title":"Mol Biol Rep"}],"container-title":["Oncotarget"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.oncotarget.com\/lookup\/doi\/10.18632\/oncotarget.17546","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,10]],"date-time":"2020-05-10T16:27:51Z","timestamp":1589128071000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.oncotarget.com\/lookup\/doi\/10.18632\/oncotarget.17546"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,2]]},"references-count":49,"journal-issue":{"issue":"28","published-print":{"date-parts":[[2017,7,11]]}},"alternative-id":["17546","28545019"],"URL":"https:\/\/doi.org\/10.18632\/oncotarget.17546","relation":{},"ISSN":["1949-2553"],"issn-type":[{"value":"1949-2553","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,2]]}}}