{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T10:32:19Z","timestamp":1780050739666,"version":"3.53.1"},"reference-count":47,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"2021 APEF\/MSD Research Grant","award":["CENTRO-01-0145-FEDER-000008"],"award-info":[{"award-number":["CENTRO-01-0145-FEDER-000008"]}]},{"name":"2021 APEF\/MSD Research Grant","award":["POCI-01-0145-FEDER-030331"],"award-info":[{"award-number":["POCI-01-0145-FEDER-030331"]}]},{"name":"2021 APEF\/MSD Research Grant","award":["UIDB\/04539\/2020"],"award-info":[{"award-number":["UIDB\/04539\/2020"]}]},{"name":"2021 APEF\/MSD Research Grant","award":["UIDP\/04539\/2020"],"award-info":[{"award-number":["UIDP\/04539\/2020"]}]},{"name":"2021 APEF\/MSD Research Grant","award":["LA\/P\/0058\/2020"],"award-info":[{"award-number":["LA\/P\/0058\/2020"]}]},{"name":"2021 APEF\/MSD Research Grant","award":["2020.10043.BD"],"award-info":[{"award-number":["2020.10043.BD"]}]},{"name":"2021 APEF\/MSD Research Grant","award":["SFRH\/BD\/139142\/2018"],"award-info":[{"award-number":["SFRH\/BD\/139142\/2018"]}]},{"name":"Internationalisation and Portuguese national funds via FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["CENTRO-01-0145-FEDER-000008"],"award-info":[{"award-number":["CENTRO-01-0145-FEDER-000008"]}]},{"name":"Internationalisation and Portuguese national funds via FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["POCI-01-0145-FEDER-030331"],"award-info":[{"award-number":["POCI-01-0145-FEDER-030331"]}]},{"name":"Internationalisation and Portuguese national funds via FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["UIDB\/04539\/2020"],"award-info":[{"award-number":["UIDB\/04539\/2020"]}]},{"name":"Internationalisation and Portuguese national funds via FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["UIDP\/04539\/2020"],"award-info":[{"award-number":["UIDP\/04539\/2020"]}]},{"name":"Internationalisation and Portuguese national funds via FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["LA\/P\/0058\/2020"],"award-info":[{"award-number":["LA\/P\/0058\/2020"]}]},{"name":"Internationalisation and Portuguese national funds via FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["2020.10043.BD"],"award-info":[{"award-number":["2020.10043.BD"]}]},{"name":"Internationalisation and Portuguese national funds via FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["SFRH\/BD\/139142\/2018"],"award-info":[{"award-number":["SFRH\/BD\/139142\/2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Chronic hepatitis B (CHB) remains a significant global health concern due to complications like cirrhosis and liver cancer. Immune cell exhaustion, characterized by increased suppressive molecules and inhibitory receptors, represents a critical feature of CHB. Understanding the mechanisms of hepatic immune exhaustion in CHB patients is imperative for the development of effective therapeutic interventions. In this study, we investigated the expression levels and histological distribution of various immune checkpoint receptors and ligands in liver biopsies obtained from CHB patients. Additionally, we aimed to evaluate potential concurrent overexpression of specific receptors and their association with clinical parameters such as ALT levels. Our analysis revealed that PD-1, PD-L1, CTLA-4, TIM-3, GAL-9, CD272, TIGIT, and 2B4 exhibited predominant localization in portal tracts and sinusoids. Furthermore, we observed a correlation between the expression of PD-1, TIM-3, and GAL-9 with ALT levels in CHB patients. Additionally, a strong relationship was identified between the expression of CD272 and TIGIT, as well as between GAL-9 and CTLA-4 within the studied population. Our findings underscore the significance of the TIM-3:GAL-9 pathway in the immunopathogenesis of CHB. This detailed analysis sets the stage for future combined immunotherapy strategies aimed at leveraging checkpoint receptors to enhance clinical outcomes.<\/jats:p>","DOI":"10.3390\/pathogens14060596","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T07:38:15Z","timestamp":1750232295000},"page":"596","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Immunohistochemical Profiling of Immune Checkpoints in Chronic Hepatitis B Liver Tissue"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2414-8945","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Pan\u00e3o-Costa","sequence":"first","affiliation":[{"name":"CNC-UC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CIBB\u2014Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7202-8059","authenticated-orcid":false,"given":"Rui Caetano","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Pathology, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3000-075 Coimbra, Portugal"},{"name":"Institute of Histology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Institute for Clinical and Biomedical Research (iCBR): Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6812-7305","authenticated-orcid":false,"given":"Paulo","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Department of Pathology, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3000-075 Coimbra, Portugal"},{"name":"Coimbra Health School, Polytechnic University of Coimbra, 3045-093 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0015-8604","authenticated-orcid":false,"given":"Francisco","family":"Caramelo","sequence":"additional","affiliation":[{"name":"CIBB\u2014Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Institute for Clinical and Biomedical Research (iCBR): Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Augusta","family":"Cipriano","sequence":"additional","affiliation":[{"name":"Department of Pathology, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3000-075 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2215-5121","authenticated-orcid":false,"given":"Olga","family":"Borges","sequence":"additional","affiliation":[{"name":"CNC-UC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CIBB\u2014Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2455-8781","authenticated-orcid":false,"given":"Armando","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Centro Hospitalar e Universit\u00e1rio de Coimbra, 3004-561 Coimbra, Portugal"},{"name":"Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1016\/j.jhep.2016.01.027","article-title":"Overview of hepatitis B viral replication and genetic variability","volume":"64","author":"Tong","year":"2016","journal-title":"J. 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