{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T23:38:25Z","timestamp":1787701105441,"version":"build-2784847793"},"reference-count":37,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,2,27]],"date-time":"2022-02-27T00:00:00Z","timestamp":1645920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/00206"],"award-info":[{"award-number":["PI19\/00206"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Hepatitis B virus (HBV)\u2010specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      cell response restoration during nucleos(t)ide analogue (NUC) treatment could lead to off\u2010treatment HBV control in e\u2010antigen\u2010negative chronic hepatitis B (CHBe(\u2212)).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To predict this response with variables involved in T\u2010cell exhaustion for use as a treatment stopping tool.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In NUC\u2010treated CHBe(\u2212) patients, we considered a functional response in cases with HBV\u2010specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      cells against core and polymerase HBV epitopes able to proliferate and secrete type I cytokines after antigen encounter. We performed a logistic regression model (LRM) to predict the likelihood of developing this response, based on patient age (subrogate of infection length), HBsAg level, NUC therapy starting point and duration (antigenic pressure). We discontinued treatment and assessed HBV DNA dynamics, HBsAg decline and loss during off\u2010treatment follow\u2010up according to LRM likelihood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We developed an LRM that predicted the presence of a proliferative type I cytokine\u2010secreting CD8\n                      <jats:sup>+<\/jats:sup>\n                      cell response, which correlated positively with treatment duration and negatively with treatment initiation after the age of 40 years and with age adjusted by HBsAg level. We observed a positive correlation between LRM probability and intensity of proliferation, number of epitopes with the functional proliferating response and type I cytokine secretion level. Off\u2010treatment, HBsAg loss, HBsAg decline &gt;50% and HBV control were more frequent in the group with &gt;90% LRM probability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Short\u2010term low\u2010level antigen exposure and early long\u2010term NUC treatment influence the restoration of a functional HBV\u2010specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      cell response. Based on these predictors, a high likelihood of detecting this response at treatment withdrawal is associated with off\u2010treatment HBV control and HBsAg decline and loss.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apt.16850","type":"journal-article","created":{"date-parts":[[2022,2,27]],"date-time":"2022-02-27T22:20:00Z","timestamp":1646000400000},"page":"1545-1559","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Model to predict on\u2010treatment restoration of functional\n                    <scp>HBV<\/scp>\n                    \u2010specific\n                    <scp>CD8<\/scp>\n                    <sup>+<\/sup>\n                    cell response foresees off\u2010treatment\n                    <scp>HBV<\/scp>\n                    control in\n                    <scp>eAg<\/scp>\n                    \u2010negative chronic hepatitis B"],"prefix":"10.1111","volume":"55","author":[{"given":"Julia","family":"Pe\u00f1a\u2010Asensio","sequence":"first","affiliation":[{"name":"Department of Biology of Systems University of Alcal\u00e1  Alcal\u00e1 de Henares Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henar","family":"Calvo","sequence":"additional","affiliation":[{"name":"Section of Gastroenterology Guadalajara University Hospital  Guadalajara Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaqu\u00edn","family":"Miquel","sequence":"additional","affiliation":[{"name":"Section of Gastroenterology Guadalajara University Hospital  Guadalajara Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Sanz\u2010de\u2010Villalobos","sequence":"additional","affiliation":[{"name":"Section of Gastroenterology Guadalajara University Hospital  Guadalajara Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Gonz\u00e1lez\u2010Praetorius","sequence":"additional","affiliation":[{"name":"Section of Microbiology Guadalajara University Hospital  Guadalajara Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Torralba","sequence":"additional","affiliation":[{"name":"Service of Internal Medicine Guadalajara University Hospital  Guadalajara Spain"},{"name":"Department of Medicine &amp; 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