{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T19:16:10Z","timestamp":1785352570107,"version":"3.55.0"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T00:00:00Z","timestamp":1721606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>There is a lack of precision in the immunotherapy strategy tailored for patients exhibiting diverse clinical characteristics. This study aims to employ a rigorous network meta-analysis (NMA) approach to systematically evaluate the effectiveness of immune-combination therapies among patients with advanced hepatocellular carcinoma, taking into account their varying clinico-characteristics.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Studies were retrieved from PubMed, Embase, Cochrane Library, and Web of Science databases. The included first-line phase III studies were categorized into three types: immunotherapy combined with anti-angiogenetic agents, immunotherapy combined with tyrosine kinase inhibitors, and dual immunotherapy, with sorafenib serving as the control group. The primary endpoint used to assess efficacy was overall survival (OS), facilitating a comparative analysis among the three treatment modalities. Furthermore, subgroup analyses were conducted to evaluate the varying effectiveness for patients with diverse clinico-characteristics. Secondary outcome measures included progression-free survival, objective response rate, and toxicity assessment.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>A total of 6 studies were included in the NMA, encompassing a cohort of 3840 patients. The results revealed that immunotherapy combined with anti-angiogenetic agents exhibited a significantly enhanced therapeutic effect in terms of improving OS compared to sorafenib (HR = 0.61, 95% CrI, 0.42\u20130.90). Furthermore, based on various clinicopathological features, this combination therapy demonstrated superior OS responses in specific patient subgroups: BCLC C (HR = 0.63, 95% CrI, 0.42\u20130.93), ECOG 1 (HR = 0.57, 95% CrI, 0.36\u20130.91), with extrahepatic spread (EHS) (HR = 0.59, 95% CrI, 0.37\u20130.92), alpha fetoprotein (AFP)&lt;400ng\/ml (HR = 0.56, 95% CrI, 0.33\u20130.94) and viral hepatitis positivity (HR = 0.56, 95% CrI, 0.39\u20130.77) (especially HBV (HR = 0.58, 95% CrI, 0.40\u20130.85)). Importantly, the advantage of this combination therapy was even more pronounced in patients with viral hepatitis positivity. Also, the adverse events associated with immunotherapy combined with antiangiogenic drugs were moderate.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Immunotherapy combined with anti-angiogenetic agents could represent the most effective first-line intervention for achieving improved OS, particularly in patients with viral hepatitis positivity.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0306869","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T17:30:37Z","timestamp":1721669437000},"page":"e0306869","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy comparison of immune combination therapies in subgroups for advanced hepatocellular carcinoma patients: Systematic review and network meta-analysis"],"prefix":"10.1371","volume":"19","author":[{"given":"Yani","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanyee","family":"Lau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yafei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yichen","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongrong","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0459-7145","authenticated-orcid":true,"given":"Jianhua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,7,22]]},"reference":[{"issue":"3","key":"pone.0306869.ref001","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global 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