{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:05:33Z","timestamp":1787321133075,"version":"build-2736575974"},"reference-count":117,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Clinical Hospital Merkur"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Virus-associated hepatocellular carcinoma (HCC) remains a major global health burden despite effective antiviral therapies. Chronic infection with hepatitis B (HBV), hepatitis C (HCV), and hepatitis D (HDV) promotes malignant transformation through overlapping pathways of fibrosis, immune dysregulation, and microenvironmental remodeling. YKL-40, a glycoprotein secreted by hepatic stellate cells, hepatocytes under stress, macrophages, and endothelial cells, has emerged as a marker that reflects stromal activation rather than direct hepatocyte injury. Its expression is reinforced by profibrotic and angiogenic circuits, and circulating concentrations correlate with advanced fibrosis, residual risk after viral suppression, and oncologic outcomes. This review synthesizes current evidence on YKL-40 across HBV, HCV, and HDV cohorts, with emphasis on its role in bridging molecular mechanisms to clinical applications. We examine its utility in non-invasive fibrosis assessment, longitudinal monitoring after antiviral therapy, and prognostic modeling in HCC. Particular attention is given to its potential in the liver transplant pathway, where YKL-40 may refine eligibility beyond morphology, inform bridging therapy response, and predict post-transplant recurrence or graft fibrosis. Remaining challenges include its lack of disease specificity, assay variability, and limited multicenter validation. Future integration of YKL-40 into multimarker, algorithm-based frameworks could enable risk-adaptive strategies that align surveillance and transplant decisions with the evolving biology of virus-associated liver disease.<\/jats:p>","DOI":"10.3390\/ijms26199584","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T11:06:02Z","timestamp":1759316762000},"page":"9584","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["YKL-40 in Virus-Associated Liver Disease: A Translational Biomarker Linking Fibrosis, Hepatocarcinogenesis, and Liver Transplantation"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4124-8056","authenticated-orcid":false,"given":"Jadranka","family":"Pavicic Saric","sequence":"first","affiliation":[{"name":"Solid Organ Transplant Unit, Department of Anesthesiology, Intensive Care and Pain Medicine, Clinical Hospital Merkur, Zajceva 19, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinka","family":"Lulic","sequence":"additional","affiliation":[{"name":"Immediate Medical Care Unit, Saint James Hospital, SLM-1030 Sliema, Malta"},{"name":"Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, A. Kovacica 1, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7097-276X","authenticated-orcid":false,"given":"Dunja","family":"Rogic","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, A. Kovacica 1, 10000 Zagreb, Croatia"},{"name":"Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stipislav","family":"Jadrijevic","sequence":"additional","affiliation":[{"name":"Solid Organ Transplant Unit, Department of Surgery, Clinical Hospital Merkur, Zajceva 19, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danko","family":"Mikulic","sequence":"additional","affiliation":[{"name":"Solid Organ Transplant Unit, Department of Surgery, Clinical Hospital Merkur, Zajceva 19, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9828-8916","authenticated-orcid":false,"given":"Tajana","family":"Filipec Kanizaj","sequence":"additional","affiliation":[{"name":"Solid Organ Transplant Unit, Department of Gastroenterology, Clinical Hospital Merkur, Zajceva 19, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0170-8858","authenticated-orcid":false,"given":"Nikola","family":"Prpic","sequence":"additional","affiliation":[{"name":"Solid Organ Transplant Unit, Department of Anesthesiology, Intensive Care and Pain Medicine, Clinical Hospital Merkur, Zajceva 19, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Karla","family":"Bozic","sequence":"additional","affiliation":[{"name":"Solid Organ Transplant Unit, Department of Anesthesiology, Intensive Care and Pain Medicine, Clinical Hospital Merkur, Zajceva 19, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivona","family":"Adamovic","sequence":"additional","affiliation":[{"name":"Solid Organ Transplant Unit, Department of Anesthesiology, Intensive Care and Pain Medicine, Clinical Hospital Merkur, Zajceva 19, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iva","family":"Bacak Kocman","sequence":"additional","affiliation":[{"name":"Solid Organ Transplant Unit, Department of Anesthesiology, Intensive Care and Pain Medicine, Clinical Hospital Merkur, Zajceva 19, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zrinka","family":"Sarec","sequence":"additional","affiliation":[{"name":"Solid Organ Transplant Unit, Department of Anesthesiology, Intensive Care and Pain Medicine, Clinical Hospital Merkur, Zajceva 19, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gorjana","family":"Erceg","sequence":"additional","affiliation":[{"name":"Solid Organ Transplant Unit, Department of Anesthesiology, Intensive Care and Pain Medicine, Clinical Hospital Merkur, Zajceva 19, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirta","family":"Adanic","sequence":"additional","affiliation":[{"name":"Solid Organ Transplant Unit, Department of Anesthesiology, Intensive Care and Pain Medicine, Clinical Hospital Merkur, Zajceva 19, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Ozegovic Zuljan","sequence":"additional","affiliation":[{"name":"Solid Organ Transplant Unit, Department of Anesthesiology, Intensive Care and Pain Medicine, Clinical Hospital Merkur, Zajceva 19, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip","family":"Jadrijevic","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Mostar, Zrinskog Frankopana 34, 88000 Mostar, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8828-9176","authenticated-orcid":false,"given":"Ileana","family":"Lulic","sequence":"additional","affiliation":[{"name":"Solid Organ Transplant Unit, Department of Anesthesiology, Intensive Care and Pain Medicine, Clinical Hospital Merkur, Zajceva 19, 10000 Zagreb, Croatia"},{"name":"Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, A. 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