{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:52:54Z","timestamp":1791247974604,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Durvalumab plus tremelimumab (Dur\/Tre) has shown promising efficacy in advanced hepatocellular carcinoma (HCC), but predictive biomarkers remain unclear. This study aimed to determine whether early changes in peripheral blood lymphocyte counts during Dur\/Tre therapy can predict clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this multicenter retrospective study, we evaluated 299 patients with advanced HCC to assess whether early changes in peripheral blood lymphocyte counts predict clinical outcomes during Dur\/Tre therapy. Changes in lymphocyte counts at 2\u2009weeks after treatment initiation (2w\u2010\u0394lymphocyte) were analyzed in relation to objective response rate (ORR), progression\u2010free survival (PFS), and overall survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients with a high\u20102w\u2010\u0394lymphocyte (&gt;\u2009+107\/\u03bcL) demonstrated a significantly higher ORR (29.6% vs. 14.0%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and longer PFS (4.3 vs. 2.8\u2009months,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.035) compared with those with a low\u20102w\u2010\u0394lymphocyte (\u2264\u2009+107\/\u03bcL). Subgroup analyses showed that higher 2w\u2010\u0394lymphocyte values were associated with better PFS across modified albumin\u2013bilirubin grades (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.011), Barcelona Clinic Liver Cancer stages (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.007), and baseline lymphocyte\u2010to\u2010monocyte ratio (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Early increases in peripheral blood lymphocyte counts, particularly 2w\u2010\u0394lymphocyte, may be associated with treatment response to Dur\/Tre and provide complementary dynamic information to established prognostic factors. Although a favorable association with PFS was observed, this association was attenuated after propensity score matching. Further prospective studies are warranted to validate the clinical utility of 2w\u2010\u0394lymphocyte.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jgh.70793","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:07:06Z","timestamp":1791245226000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Early Changes in Lymphocyte Counts Predict Clinical Outcomes in Hepatocellular Carcinoma Treated With Durvalumab Plus Tremelimumab"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7112-3479","authenticated-orcid":false,"given":"Yuichi","family":"Honma","sequence":"first","affiliation":[{"name":"Third Department of Internal Medicine, School of Medicine University of Occupational and Environmental Health  Kitakyushu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2068-8386","authenticated-orcid":false,"given":"Shigeo","family":"Shimose","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine Kurume University School of Medicine  Kurume Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2594-0854","authenticated-orcid":false,"given":"Takanori","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5885-5042","authenticated-orcid":false,"given":"Issei","family":"Saeki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Yamaguchi University Graduate School of Medicine  Yamaguchi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8801-2505","authenticated-orcid":false,"given":"Joji","family":"Tani","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Neurology, Faculty of Medicine Kagawa University  Kagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7361-881X","authenticated-orcid":false,"given":"Takanori","family":"Matsuura","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine Kobe University Graduate School of Medicine  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8484-9866","authenticated-orcid":false,"given":"Tetsu","family":"Tomonari","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Oncology, Institute of Biomedical Sciences Tokushima University Graduate School of Medicine  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3261-0842","authenticated-orcid":false,"given":"Yasuto","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Okayama University Hospital  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3627-5412","authenticated-orcid":false,"given":"Nobuhito","family":"Taniki","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyo","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Kawasaki Medical School  Kurashiki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0001-7377","authenticated-orcid":false,"given":"Ryu","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3656-285X","authenticated-orcid":false,"given":"Takeshi","family":"Hatanaka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Gunma Saiseikai Maebashi Hospital  Maebashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0224-7093","authenticated-orcid":false,"given":"Satoru","family":"Kakizaki","sequence":"additional","affiliation":[{"name":"Department of Clinical Research NHO Takasaki General Medical Center  Takasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Yoshioka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehito","family":"Naito","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Toyohashi Municipal Hospital  Toyohashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamiko","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Anjo Kosei Hospital  Anjo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Yasunaka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Fukuyama City Hospital  Fukuyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Sakata","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Fukuyama Medical Center  Fukuyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5688-1335","authenticated-orcid":false,"given":"Hideki","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine Kurume University School of Medicine  Kurume Japan"},{"name":"Iwamoto Internal Medical Clinic  Kitakyushu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2662-6779","authenticated-orcid":false,"given":"Tomotake","family":"Shirono","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine Kurume University School of Medicine  Kurume Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Itano","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Kurume Central Hospital  Kurume Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9502-8886","authenticated-orcid":false,"given":"Norikazu","family":"Tanabe","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Yamaguchi University Graduate School of Medicine  Yamaguchi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9904-1894","authenticated-orcid":false,"given":"Takafumi","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Toyohashi Municipal Hospital  Toyohashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0663-0102","authenticated-orcid":false,"given":"Atsushi","family":"Naganuma","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology NHO Takasaki General Medical Center  Takasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kanayama","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Gunma Saiseikai Maebashi Hospital  Maebashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8067-4376","authenticated-orcid":false,"given":"Hisamitsu","family":"Miyaaki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5803-4986","authenticated-orcid":false,"given":"Sohji","family":"Nishina","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Kawasaki Medical School  Kurashiki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5203-7444","authenticated-orcid":false,"given":"Nobuhiro","family":"Nakamoto","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2869-2881","authenticated-orcid":false,"given":"Motoyuki","family":"Otsuka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Okayama University Hospital  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0175-1573","authenticated-orcid":false,"given":"Tetsuji","family":"Takayama","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Oncology, Institute of Biomedical Sciences Tokushima University Graduate School of Medicine  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1223-7147","authenticated-orcid":false,"given":"Yuzo","family":"Kodama","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine Kobe University Graduate School of Medicine  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8508-827X","authenticated-orcid":false,"given":"Hideki","family":"Kobara","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Neurology, Faculty of Medicine Kagawa University  Kagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6689-4989","authenticated-orcid":false,"given":"Taro","family":"Takami","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Yamaguchi University Graduate School of Medicine  Yamaguchi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3720-781X","authenticated-orcid":false,"given":"Hiroki","family":"Kawashima","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7064-4325","authenticated-orcid":false,"given":"Takumi","family":"Kawaguchi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine Kurume University School of Medicine  Kurume Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9891-3526","authenticated-orcid":false,"given":"Masaru","family":"Harada","sequence":"additional","affiliation":[{"name":"Third Department of Internal Medicine, School of Medicine University of Occupational and Environmental Health  Kitakyushu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1915745"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.11.030"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/EVIDoa2100070"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.02.005"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(25)00403-9"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0311084"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol31080315"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.14189"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.14224"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.70570"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.70192"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.03555"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000466"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.11.018"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.57.9151"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.EJ23-0593"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2012.244"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2025.03.033"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.14212"},{"key":"e_1_2_13_23_1","first-page":"119","article-title":"Treatment Decision\u2010Making in Unresectable Hepatocellular Carcinoma: Importance of Understanding the Different Response Patterns Between IO Plus Anti\u2010VEGF and IO Plus IO Regimens","volume":"14","author":"Kudo M.","year":"2025","journal-title":"Liver Cancer"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-25-1592"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17081274"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.70023"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2992"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13071607"}],"container-title":["Journal of Gastroenterology and Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jgh.70793","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jgh.70793","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jgh.70793","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:07:06Z","timestamp":1791245226000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jgh.70793"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,5]]},"references-count":27,"alternative-id":["10.1111\/jgh.70793"],"URL":"https:\/\/doi.org\/10.1111\/jgh.70793","archive":["Portico"],"relation":{},"ISSN":["0815-9319","1440-1746"],"issn-type":[{"value":"0815-9319","type":"print"},{"value":"1440-1746","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,5]]},"assertion":[{"value":"2026-05-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"jgh.70793"}}