{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T06:20:12Z","timestamp":1783146012189,"version":"3.54.6"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hepatol Int"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1007\/s12072-026-11075-7","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T15:20:10Z","timestamp":1775575210000},"page":"619-631","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum soluble PD-L1 predicts hepatocellular carcinoma development across distinct virological cohorts of chronic hepatitis C"],"prefix":"10.1007","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8876-4440","authenticated-orcid":false,"given":"Kazumi","family":"Yamasaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Mizokami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumi","family":"Goto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Nagaoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Saeki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhide","family":"Motoyoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Suehiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kugiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsumasa","family":"Komori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ohashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Yatsuhashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"11075_CR1","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/S1473-3099(15)70099-X","volume":"15","author":"M Mizokami","year":"2015","unstructured":"Mizokami M, Yokosuka O, Takehara T, Sakamoto N, Korenaga M, et al. Ledipasvir and sofosbuvir fixed-dose combination with and without ribavirin for 12 weeks in treatment-naive and previously treated Japanese patients with genotype 1 hepatitis C: an open-label, randomised, phase 3 trial. Lancet Infect Dis. 2015;15:645\u2013653","journal-title":"Lancet Infect Dis"},{"key":"11075_CR2","doi-asserted-by":"crossref","unstructured":"EASL recommendations on treatment of hepatitis C: Final update of the series(\u2606). J Hepatol. 2020;73:1170\u20131218","DOI":"10.1016\/j.jhep.2020.08.018"},{"key":"11075_CR3","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/j.jhep.2016.06.015","volume":"65","author":"F Conti","year":"2016","unstructured":"Conti F, Buonfiglioli F, Scuteri A, Crespi C, Bolondi L, et al. Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals. J Hepatol. 2016;65:727\u2013733","journal-title":"J Hepatol"},{"key":"11075_CR4","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1002\/hep.30823","volume":"71","author":"F Kanwal","year":"2020","unstructured":"Kanwal F, Kramer JR, Asch SM, Cao Y, Li L, El-Serag HB. Long-term risk of hepatocellular carcinoma in HCV patients treated with direct acting antiviral agents. Hepatology. 2020;71:44\u201355","journal-title":"Hepatology"},{"key":"11075_CR5","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1016\/j.jhep.2016.04.008","volume":"65","author":"M Reig","year":"2016","unstructured":"Reig M, Mari\u00f1o Z, Perell\u00f3 C, I\u00f1arrairaegui M, Ribeiro A, et al. Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy. J Hepatol. 2016;65:719\u2013726","journal-title":"J Hepatol"},{"key":"11075_CR6","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1002\/hep.21178","volume":"43","author":"RK Sterling","year":"2006","unstructured":"Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV\/HCV coinfection. Hepatology. 2006;43:1317\u20131325","journal-title":"Hepatology"},{"key":"11075_CR7","doi-asserted-by":"publisher","first-page":"1368","DOI":"10.1016\/j.jhep.2020.07.025","volume":"73","author":"R Fan","year":"2020","unstructured":"Fan R, Papatheodoridis G, Sun J, Innes H, Toyoda H, et al. aMAP risk score predicts hepatocellular carcinoma development in patients with chronic hepatitis. J Hepatol. 2020;73:1368\u20131378","journal-title":"J Hepatol"},{"key":"11075_CR8","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1002\/hep.27305","volume":"60","author":"K Yamasaki","year":"2014","unstructured":"Yamasaki K, Tateyama M, Abiru S, Komori A, Nagaoka S, et al. Elevated serum levels of Wisteria floribunda agglutinin-positive human Mac-2 binding protein predict the development of hepatocellular carcinoma in hepatitis C patients. Hepatology. 2014;60:1563\u20131570","journal-title":"Hepatology"},{"key":"11075_CR9","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1158\/2326-6066.CIR-16-0329","volume":"5","author":"J Zhou","year":"2017","unstructured":"Zhou J, Mahoney KM, Giobbie-Hurder A, Zhao F, Lee S, et al. Soluble PD-L1 as a biomarker in malignant melanoma treated with checkpoint blockade. Cancer Immunol Res. 2017;5:480\u2013492","journal-title":"Cancer Immunol Res"},{"key":"11075_CR10","doi-asserted-by":"publisher","first-page":"62490","DOI":"10.18632\/oncotarget.11519","volume":"7","author":"SY Huang","year":"2016","unstructured":"Huang SY, Lin HH, Lin CW, Li CC, Yao M, et al. Soluble PD-L1: a biomarker to predict progression of autologous transplantation in patients with multiple myeloma. Oncotarget. 2016;7:62490\u201362502","journal-title":"Oncotarget"},{"key":"11075_CR11","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-99311-y","volume":"11","author":"SY Oh","year":"2021","unstructured":"Oh SY, Kim S, Keam B, Kim TM, Kim DW, Heo DS. Soluble PD-L1 is a predictive and prognostic biomarker in advanced cancer patients who receive immune checkpoint blockade treatment. Sci Rep. 2021;11: 19712","journal-title":"Sci Rep"},{"key":"11075_CR12","doi-asserted-by":"publisher","first-page":"261","DOI":"10.2217\/fon-2021-0641","volume":"18","author":"Y Cheng","year":"2022","unstructured":"Cheng Y, Wang C, Wang Y, Dai L. Soluble PD-L1 as a predictive biomarker in lung cancer: a systematic review and meta-analysis. Future Oncol. 2022;18:261\u2013273","journal-title":"Future Oncol"},{"key":"11075_CR13","doi-asserted-by":"publisher","first-page":"403","DOI":"10.7150\/ijms.18784","volume":"14","author":"S Yamagiwa","year":"2017","unstructured":"Yamagiwa S, Ishikawa T, Waguri N, Sugitani S, Kamimura K, et al. Increase of soluble programmed cell death ligand 1 in patients with chronic Hepatitis C. Int J Med Sci. 2017;14:403\u2013411","journal-title":"Int J Med Sci"},{"key":"11075_CR14","doi-asserted-by":"publisher","first-page":"2248","DOI":"10.1515\/cclm-2023-0232","volume":"61","author":"L Loacker","year":"2023","unstructured":"Loacker L, Egger A, Fux V, Bellmann-Weiler R, Weiss G, et al. Serum sPD-L1 levels are elevated in patients with viral diseases, bacterial sepsis or in patients with impaired renal function compared to healthy blood donors. Clin Chem Lab Med. 2023;61:2248\u20132255","journal-title":"Clin Chem Lab Med"},{"key":"11075_CR15","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics12112650","author":"CH Liu","year":"2022","unstructured":"Liu CH, Liu CJ, Su TH, Huang SC, Tseng TC, et al. Serum Mac-2 binding protein glycosylation isomer to predict the severity of hepatic fibrosis in patients with Hepatitis C Virus infection. Diagnostics. 2022. https:\/\/doi.org\/10.3390\/diagnostics12112650","journal-title":"Diagnostics"},{"key":"11075_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-46548-3","volume":"9","author":"M Goto","year":"2019","unstructured":"Goto M, Chamoto K, Higuchi K, Yamashita S, Noda K, et al. Analytical performance of a new automated chemiluminescent magnetic immunoassays for soluble PD-1, PD-L1, and CTLA-4 in human plasma. Sci Rep. 2019;9: 10144","journal-title":"Sci Rep"},{"key":"11075_CR17","doi-asserted-by":"publisher","DOI":"10.1172\/JCI168318","author":"H Hayashi","year":"2024","unstructured":"Hayashi H, Chamoto K, Hatae R, Kurosaki T, Togashi Y, et al. Soluble immune checkpoint factors reflect exhaustion of antitumor immunity and response to PD-1 blockade. J Clin Invest. 2024. https:\/\/doi.org\/10.1172\/JCI168318","journal-title":"J Clin Invest"},{"key":"11075_CR18","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1111\/j.1365-2893.2009.01172.x","volume":"17","author":"T Watanabe","year":"2010","unstructured":"Watanabe T, Bertoletti A, Tanoto TA. PD-1\/PD-L1 pathway and T-cell exhaustion in chronic hepatitis virus infection. J Viral Hepat. 2010;17:453\u2013458","journal-title":"J Viral Hepat"},{"key":"11075_CR19","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1145682","volume":"14","author":"Y Zhao","year":"2023","unstructured":"Zhao Y, Qu Y, Hao C, Yao W. PD-1\/PD-L1 axis in organ fibrosis. Front Immunol. 2023;14: 1145682","journal-title":"Front Immunol"},{"key":"11075_CR20","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-03706-w","volume":"12","author":"R Kozuka","year":"2022","unstructured":"Kozuka R, Enomoto M, Dong MP, Hai H, Thuy LTT, et al. Soluble programmed cell death-1 predicts hepatocellular carcinoma development during nucleoside analogue treatment. Sci Rep. 2022;12: 105","journal-title":"Sci Rep"},{"key":"11075_CR21","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110349","volume":"38","author":"L Sun","year":"2022","unstructured":"Sun L, Wang Y, Wang X, Navarro-Corcuera A, Ilyas S, et al. PD-L1 promotes myofibroblastic activation of hepatic stellate cells by distinct mechanisms selective for TGF-\u03b2 receptor I versus II. Cell Rep. 2022;38: 110349","journal-title":"Cell Rep"},{"key":"11075_CR22","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1016\/j.jhep.2006.05.007","volume":"45","author":"M M\u00fchlbauer","year":"2006","unstructured":"M\u00fchlbauer M, Fleck M, Sch\u00fctz C, Weiss T, Froh M, Blank C, et al. PD-L1 is induced in hepatocytes by viral infection and by interferon-alpha and -gamma and mediates T cell apoptosis. J Hepatol. 2006;45:520\u2013528","journal-title":"J Hepatol"},{"key":"11075_CR23","doi-asserted-by":"publisher","first-page":"97671","DOI":"10.18632\/oncotarget.18311","volume":"8","author":"X Zhu","year":"2017","unstructured":"Zhu X, Lang J. Soluble PD-1 and PD-L1: predictive and prognostic significance in cancer. Oncotarget. 2017;8:97671\u201397682","journal-title":"Oncotarget"}],"container-title":["Hepatology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12072-026-11075-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12072-026-11075-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12072-026-11075-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T05:57:43Z","timestamp":1783144663000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12072-026-11075-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,7]]},"references-count":23,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["11075"],"URL":"https:\/\/doi.org\/10.1007\/s12072-026-11075-7","relation":{},"ISSN":["1936-0533","1936-0541"],"issn-type":[{"value":"1936-0533","type":"print"},{"value":"1936-0541","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,7]]},"assertion":[{"value":"30 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Dr. Yamasaki received speaker fees from Sysmex Co., Abbvie, and Gilead Sciences. Dr. Suehiro received speaker fees from Gilead Sciences. Dr. Yatsuhashi received speaker fees from Sysmex Co., Abbvie, and Gilead Sciences. Dr. Mizokami received speaker fees from Sysmex Co. and Gilead Sciences and received research funds from Sysmex Co.  The remaining authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interests"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Informed consent for access to medical records and specimens was obtained from each patient. Written informed consent was obtained from all participants at the time of serum collection. The processes and research protocols were approved by the Ethics Committee of the National Hospital Organization Nagasaki Medical Center (Approval Number: 2021133) and adhered to the Helsinki Declaration of 1975, as revised in 2008, and the Ethics Guidelines for Clinical Research in Japan (Ministry of Health, Labor and Welfare, Clinical Research Ethics, 2008).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"During the preparation of this manuscript, the authors used ChatGPT by OpenAI to assist with language editing and refinement. This technology was used strictly for manuscript proofreading and to enhance the clarity and coherence of our written communication. After using this tool, the authors reviewed and edited the content as needed and took full responsibility for the content of the publication.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declaration of generative AI and AI-assisted technologies in the writing process"}}]}}