{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:34:31Z","timestamp":1791304471806,"version":"4.3.1"},"reference-count":69,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515010537"],"award-info":[{"award-number":["2022A1515010537"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515012531"],"award-info":[{"award-number":["2023A1515012531"]}],"id":[{"id":"10.13039\/501100021171","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":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>While immune\u2010related adverse events (irAEs) have been linked to improved outcomes in melanoma and non\u2010small cell lung cancer (NSCLC), their prognostic role in hepatocellular carcinoma (HCC), a malignancy arising in a unique immune microenvironment shaped by chronic inflammation and cirrhosis, remains unexplored. This meta\u2010analysis investigated the relationship between irAEs and the effectiveness of immune checkpoint inhibitors (ICIs) in HCC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Following PRISMA guidelines, we systematically reviewed studies from PubMed, Embase and the Cochrane Library (through December 2024) that evaluated the association between irAEs and ICIs' effectiveness in HCC. The primary outcomes were progression\u2010free survival (PFS) and overall survival (OS), and the secondary outcomes were objective response rate (ORR) and disease control rate (DCR). Subgroup analyses assessed irAEs' types, severity and corticosteroid impact.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 24 retrospective studies (4798 patients), irAEs occurrence correlated with superior ORR (OR, 2.18; 95% CI, 1.64\u20132.89), DCR (OR, 3.09; 95% CI, 1.81\u20135.27), PFS (HR, 0.62; 95% CI, 0.51\u20130.75) and OS (HR, 0.76; 95% CI, 0.61\u20130.95). Dermatologic and endocrine irAEs were associated with improved survival (PFS: HR, 0.45 and 0.50; OS: HR, 0.51 and 0.59, respectively), while pulmonary, gastrointestinal and hepatobiliary irAEs did not show such relations. Low\u2010grade irAEs (Grades 1 and 2) were linked to better survival (PFS: HR, 0.47; OS: HR, 0.48), unlike high\u2010grade events. Corticosteroid use for irAEs management did not impair survival (PFS: HR, 0.97; OS: HR, 0.91).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>irAEs, particularly dermatologic, endocrine and low\u2010grade events, were associated with improved ICIs' effectiveness in HCC. Early irAEs detection and corticosteroid management preserve survival benefits. However, more large\u2010scale prospective studies are needed to verify our findings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apt.70427","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T07:29:54Z","timestamp":1761031794000},"page":"188-202","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Meta\u2010Analysis: Immune\u2010Related Adverse Events Are Associated With Improved Effectiveness of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma"],"prefix":"10.1111","volume":"63","author":[{"given":"Shijia","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Center The First Affiliated Hospital, Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhichao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Center The First Affiliated Hospital, Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junlong","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Center The First Affiliated Hospital, Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixin","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Center The First Affiliated Hospital, Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4814-9392","authenticated-orcid":false,"given":"Yunpeng","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Center The First Affiliated Hospital, Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575\u2010019\u20100186\u2010y"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.12.276"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.11.018"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29086"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/cm9.0000000000003060"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3405"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0910341107"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1703481"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010019\u20100218\u20100"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.11.030"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.12.008"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432\u2010018\u20102819\u2010x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2019.03.003"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.19.00318"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13643\u2010021\u201001626\u20104"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654\u2010010\u20109491\u2010z"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003\u20104819\u2010158\u20104\u2010201302190\u201000009"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12874\u2010021\u201001308\u20108"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12010182"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2021.08.020"},{"issue":"12","key":"e_1_2_7_23_1","first-page":"4547","article-title":"Predictors of Response and Survival in Patients With Unresectable Hepatocellular Carcinoma Treated With Nivolumab: Real\u2010World Experience","volume":"10","author":"Hsu W. 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