{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:10:23Z","timestamp":1787069423007,"version":"build-2736575974"},"reference-count":106,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,8]],"date-time":"2020-09-08T00:00:00Z","timestamp":1599523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["106-2320-B-006-048-MY3, 108-2622-B-006-007-CC2, 107-2320-B-006-032-MY3, and 108-2320-B-041 -002"],"award-info":[{"award-number":["106-2320-B-006-048-MY3, 108-2622-B-006-007-CC2, 107-2320-B-006-032-MY3, and 108-2320-B-041 -002"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Hepatitis B is the most prevalent viral hepatitis worldwide, affecting approximately one-third of the world\u2019s population. Among HBV factors, the surface protein is the most sensitive biomarker for viral infection, given that it is expressed at high levels in all viral infection phases. The large HBV surface protein (LHBs) contains the integral pre-S1 domain, which binds to the HBV receptor sodium taurocholate co transporting polypeptide on the hepatocyte to facilitate viral entry. The accumulation of viral LHBs and its prevalent pre-S mutants in chronic HBV carriers triggers a sustained endoplasmic reticulum (ER) overload response, leading to ER stress-mediated cell proliferation, metabolic switching and genomic instability, which are associated with pro-oncogenic effects. Ground glass hepatocytes identified in HBV-related hepatocellular carcinoma (HCC) patients harbor pre-S deletion variants that largely accumulate in the ER lumen due to mutation-induced protein misfolding and are associated with increased risks of cancer recurrence and metastasis. Moreover, in contrast to the major HBs, which is decreased in tumors to a greater extent than it is in peritumorous regions, LHBs is continuously expressed during tumorigenesis, indicating that LHBs serves as a promising biomarker for HCC in people with CHB. Continuing efforts to delineate the molecular mechanisms by which LHBs regulates pathological changes in CHB patients are important for establishing a correlation between LHBs biomarkers and HCC development.<\/jats:p>","DOI":"10.3390\/cells9092052","type":"journal-article","created":{"date-parts":[[2020,9,8]],"date-time":"2020-09-08T09:03:48Z","timestamp":1599555828000},"page":"2052","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Association of the Hepatitis B Virus Large Surface Protein with Viral Infectivity and Endoplasmic Reticulum Stress-mediated Liver Carcinogenesis"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2139-3099","authenticated-orcid":false,"given":"Wei-Ling","family":"Lin","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Biochemistry, Department of Pathology, National Cheng Kung University Hospital, 138 Sheng Li Rd, Tainan 704, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jui-Hsiang","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chia Nan University of Pharmacy &amp; Science, 60 Sec. 1, Erren Rd, Rende Dist., Tainan 717, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenya","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, 1 University Rd, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,8]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (WHO) (2018, August 01). 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