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Our aim was to investigate the impact of viral suppression on PD\u20101 expression on intrahepatic versus circulating lymphocyte populations from chronic hepatitis B (CHB) patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Twenty\u2010two CHB patients, nine of them on nucleos(t)ide analogues (NUCs), had paired blood, liver fine needle aspirations (FNAs) and biopsies. A subset had a follow\u2010up FNA after treatment initiation (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20094) or discontinuation (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20094). Intrahepatic (iHBV\u2010DNA and cccDNA) and serum (HBV\u2010DNA, HBsAg, HBcrAg and cirB\u2010RNA) viral markers were quantified. Flow cytometry was used for immunophenotyping PBMCs and intrahepatic lymphocytes. An independent liver FNA scRNAseq dataset was used to consolidate our results.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PD\u20101 expression on tissue\u2010resident memory CD8 T cells (T\n                      <jats:sub>RM<\/jats:sub>\n                      ) correlated with both iHBV\u2010DNA and cccDNA, as well as surrogate markers of cccDNA transcriptional activity (cirB\u2010RNA and HBcrAg) in CHB patients with mild hepatitis. These associations were not reflected in circulating T cells. PD\u20101 expression intensity on CD8 T\n                      <jats:sub>RM<\/jats:sub>\n                      was lower in NUC\u2010treated than in naive patients, changes that were again not detectable in the circulation. Longitudinal analysis showed that viral load rebound induced by NUC discontinuation had the potential to drive re\u2010expression of high levels of PD\u20101 on CD8 T\n                      <jats:sub>RM<\/jats:sub>\n                      . Conversely, therapy initiation and subsequent viral suppression reversed these changes. scRNAseq results further extended the profiling of these PD\u20101\u2009+\u2009CD8 T\n                      <jats:sub>RM<\/jats:sub>\n                      , showing a phenotype consistent with bystander activation in response to subclinical liver damage.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Intrahepatic viral markers correlate with PD\u20101 expression on global liver\u2010resident T cells of CHB patients with mild hepatitis, with a reduction after prolonged NUC therapy and re\u2010expression following treatment withdrawal.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70338","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T16:10:02Z","timestamp":1759507802000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<scp>HBV<\/scp>\n                    Suppression by Nucleos(t)ide Analogues Reduces\n                    <scp>PD<\/scp>\n                    \u20101 Expression on Liver\u2010Resident T Cells"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9643-7172","authenticated-orcid":false,"given":"Mireia","family":"Garc\u00eda\u2010L\u00f3pez","sequence":"first","affiliation":[{"name":"Liver Unit Hospital Cl\u00ednic, University of Barcelona, IDIBAPS, CIBEREHD  Barcelona 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