{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:53:48Z","timestamp":1791557628988,"version":"4.3.4"},"reference-count":27,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"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":["Liver International"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>The optimal sequencing of programmed cell death protein 1 (PD\u20101) inhibitors relative to locoregional therapy (LRT) in unresectable hepatocellular carcinoma (uHCC) remains undefined. This study evaluated the impact of PD\u20101 inhibitor timing on outcomes in patients receiving hepatic arterial infusion chemotherapy (HAIC) or transarterial chemoembolisation (TACE) plus lenvatinib and PD\u20101 inhibitors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with initially uHCC who received LRT in combination with lenvatinib and PD\u20101 inhibitors across six academic centres were stratified by LRT modality (HAIC vs. TACE) and categorised into two groups based on PD\u20101 inhibitor timing (Pre\u2010LRT PD\u20101 and Post\u2010LRT PD\u20101 group). Overall survival (OS) and progression\u2010free survival (PFS) were estimated using the Kaplan\u2013Meier method; propensity score matching (PSM) and landmark analyses were applied to mitigate potential biases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 350 patients were included, with 185 in the HAIC cohort and 165 in the TACE cohort. Pre\u2010LRT PD\u20101 group was associated with significantly improved OS in the overall population, driven primarily by the HAIC cohort rather than the TACE cohort (34.03\u2009m vs. 30.6\u2009m,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.032); these findings remained consistent after PSM and landmark analyses. Subgroup analyses further supported the survival benefit of Pre\u2010LRT PD\u20101 initiation. After PSM, Pre\u2010LRT PD\u20101 was also associated with significantly prolonged PFS in the HAIC cohort. According to RECIST 1.1 criteria, the Pre\u2010LRT PD\u20101 group showed a higher objective response rate (ORR) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In patients with uHCC receiving HAIC combined with lenvatinib and PD\u20101 inhibitors, initiation of PD\u20101 inhibitors prior to HAIC is associated with superior survival outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70847","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T06:17:23Z","timestamp":1787897843000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Impact of\n                    <scp>PD<\/scp>\n                    \u20101 Inhibitor Timing Relative to Locoregional Therapy on Outcomes in\n                    <scp>uHCC<\/scp>\n                    Treated With Lenvatinib\u2010Based Triple Therapy"],"prefix":"10.1111","volume":"46","author":[{"given":"Jian","family":"He","sequence":"first","affiliation":[{"name":"Department of Interventional Radiology Mengchao Hepatobiliary Hospital of Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, The First Affiliated Hospital Fujian Medical University  Fuzhou China"},{"name":"Department of Interventional Radiology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bohua","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Nanping First Hospital Affiliated to Fujian Medical University  Nanping China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7611-7529","authenticated-orcid":false,"given":"Fuqun","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, The First Affiliated Hospital Fujian Medical University  Fuzhou China"},{"name":"Department of Interventional Radiology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weifu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oncology and Vascular Interventional Therapy Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peishu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Radiology Jinjiang Municipal Hospital (Shanghai Sixth People's Hospital Fujian Campus)  Jinjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songhui","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology Zhangzhou Affiliated Hospital of Fujian Medical University  Zhangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"You","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, The First Affiliated Hospital Fujian Medical University  Fuzhou China"},{"name":"Department of Interventional Radiology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhisheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, The First Affiliated Hospital Fujian Medical University  Fuzhou 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