{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T16:22:38Z","timestamp":1789402958395,"version":"build-2803163510"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Management of patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh class B liver function is challenging owing to compromised hepatic functional reserve, affecting treatment selection and outcomes, as many systemic therapies demonstrate altered pharmacokinetics and increased toxicity in this population. Current treatment guidelines predominantly focus on patients with preserved liver function (Child-Pugh A), creating a critical evidence gap for the optimal management of patients with Child-Pugh B liver function. This network meta-analysis (NMA) evaluated first-line therapies for patients with advanced HCC and Child-Pugh B cirrhosis, addressing current evidence gaps to guide optimal treatment selection for this high-risk population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The PubMed, Embase, and Cochrane Library databases were searched until 31 October 2024. Randomized controlled trials and prospective cohort studies were included if they involved patients with advanced HCC and Child-Pugh class B liver function, evaluated first-line therapeutic agents, and reported overall survival (OS) and\/or progression-free survival (PFS) with 95% confidence intervals. Bayesian NMA was employed to evaluate treatment efficacy and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eleven studies comprising 2,536 patients were included in the NMA. Lenvatinib exhibited the greatest probability of ideal efficacy for OS, while atezolizumab and bevacizumab combination therapy demonstrated the highest likelihood of optimal performance in terms of PFS. The overall incidence of adverse events (AEs) was 68.58%. The predominant grade 3\u20134 AEs included hypertension, proteinuria, hand-foot syndrome, and abnormal liver function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Atezolizumab and bevacizumab combination therapy demonstrated the optimal net benefit regarding PFS and reduced toxicity, whereas lenvatinib monotherapy exhibited the greatest net benefit in OS but with increased toxicity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1705502","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T05:23:38Z","timestamp":1767331418000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["A network meta-analysis of first-line treatment options for patients with Child-Pugh class B functional hepatocellular carcinoma: comparison of efficacy and safety"],"prefix":"10.3389","volume":"16","author":[{"given":"Yu-Xuan","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Yi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Yi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Xin","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong-Jian","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-Ye","family":"Ou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Nan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao-Lin","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1007\/s40265-019-01116-x","article-title":"Lenvatinib: a review in hepatocellular carcinoma","volume":"79","author":"Al-Salama","year":"2019","journal-title":"Drugs"},{"key":"B2","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/s12072-020-10120-3","article-title":"Phase 2 trial comparing sorafenib, pravastatin, their combination or supportive care in HCC with child-pugh B cirrhosis","volume":"15","author":"Blanc","year":"2021","journal-title":"Hepatol. Int."},{"key":"B3","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1002\/cam4.4906","article-title":"Comparison of nivolumab and sorafenib for first systemic therapy in patients with hepatocellular carcinoma and child-pugh B cirrhosis","volume":"12","author":"Chapin","year":"2023","journal-title":"Cancer Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1016\/j.jhep.2021.11.030","article-title":"Updated efficacy and safety data from IMbrave150: atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma","volume":"76","author":"Cheng","year":"2022","journal-title":"J. Hepatol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"112","DOI":"10.3760\/cma.j.issn.1007-3418.2020.02.004","article-title":"Guidelines for diagnosis and guidelines for diagnosis and treatment of primary liver cancer in China (2019 edition)","volume":"28","year":"2020","journal-title":"Zhonghua Gan Zang Bing Za Zhi"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2492","DOI":"10.1016\/S0140-6736(17)31046-2","article-title":"Nivolumab in patients with advanced hepatocellular carcinoma (checkMate 040): an open-label, non comparative, phase 1\/2 dose escalation and expansion trial","volume":"389","author":"El-Khoueiry","year":"2017","journal-title":"Lancet"},{"key":"B7","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1186\/s12885-022-09453-z","article-title":"Safety and efficacy of cabozantinib for patients with advanced hepatocellular carcinoma who advanced to child-pugh B liver function at study week 8: a retrospective analysis of the CELESTIAL randomised controlled trial","volume":"22","author":"El-Khoueiry","year":"2022","journal-title":"BMC Cancer"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1894","DOI":"10.1056\/NEJMoa1915745","article-title":"Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma","volume":"382","author":"Finn","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1016\/S0140-6736(18)30010-2","article-title":"Hepatocellular carcinoma","volume":"391","author":"Forner","year":"2018","journal-title":"Lancet"},{"key":"B10","doi-asserted-by":"publisher","first-page":"S7","DOI":"10.1016\/j.annonc.2023.04.043","article-title":"PD-16 atezolizumab plus bevacizumab is associated with improved survival outcomes in HCC patients with child-pugh B dysfunction compared to best supportive therapy","volume":"34","author":"Fulgenzi","year":"2023","journal-title":"Ann. Oncol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1001\/jamaoncol.2024.2166","article-title":"Immunotherapy vs best supportive care for patients with hepatocellular cancer with child-pugh B dysfunction","volume":"10","author":"Fulgenzi","year":"2024","journal-title":"JAMA Oncol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"d5928","DOI":"10.1136\/bmj.d5928","article-title":"The cochrane Collaboration's tool for assessing risk of bias in randomised trials","volume":"343","author":"Higgins","year":"2011","journal-title":"Bmj"},{"key":"B13","doi-asserted-by":"publisher","first-page":"777","DOI":"10.7326\/M14-2385","article-title":"The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations","volume":"162","author":"Hutton","year":"2015","journal-title":"Ann. Intern Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"17588359221116608","DOI":"10.1177\/17588359221116608","article-title":"Lenvatinib in patients with unresectable hepatocellular carcinoma who progressed to child-Pugh B liver function","volume":"14","author":"Huynh","year":"2022","journal-title":"Ther. Adv. Med. Oncol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1200\/JCO.2014.57.9151","article-title":"Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade","volume":"33","author":"Johnson","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1159\/000533859","article-title":"Outcomes of patients with child-pugh B and unresectable hepatocellular carcinoma undergoing first-line systemic treatment with sorafenib, lenvatinib, or atezolizumab plus bevacizumab","volume":"102","author":"Kikugawa","year":"2024","journal-title":"Oncology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1016\/S0140-6736(18)30207-1","article-title":"Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial","volume":"391","author":"Kudo","year":"2018","journal-title":"Lancet"},{"key":"B18","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1056\/NEJMoa0708857","article-title":"Sorafenib in advanced hepatocellular carcinoma","volume":"359","author":"Llovet","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/s41572-020-00240-3","article-title":"Hepatocellular carcinoma","volume":"7","author":"Llovet","year":"2021","journal-title":"Nat. Rev. Dis. Prim."},{"key":"B20","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1159\/000530028","article-title":"Comparison between atezolizumab plus bevacizumab and lenvatinib for hepatocellular carcinoma in patients with child-pugh class B in real-world clinical settings","volume":"101","author":"Ohama","year":"2023","journal-title":"Oncology"},{"key":"B21","doi-asserted-by":"publisher","first-page":"4939","DOI":"10.1007\/s10620-021-07365-9","article-title":"Effectiveness of lenvatinib versus sorafenib for unresectable hepatocellular carcinoma in patients with hepatic decompensation","volume":"67","author":"Park","year":"2022","journal-title":"Dig. Dis. Sci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"7565","DOI":"10.1007\/s00432-023-04678-2","article-title":"Survival outcomes from atezolizumab plus bevacizumab versus lenvatinib in child pugh B unresectable hepatocellular carcinoma patients","volume":"149","author":"Rimini","year":"2023","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1016\/j.dld.2024.01.199","article-title":"Sorafenib and metronomic capecitabine in child-pugh B patients with advanced HCC: a real-life comparison with best supportive care","volume":"56","author":"Stefanini","year":"2024","journal-title":"Dig. Liver Dis."},{"key":"B24","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"B25","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/S1470-2045(21)00604-5","article-title":"Nivolumab versus sorafenib in advanced hepatocellular carcinoma (checkMate 459): a randomised, multicentre, open-label, phase 3 trial","volume":"23","author":"Yau","year":"2022","journal-title":"Lancet Oncol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1016\/S1470-2045(18)30351-6","article-title":"Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial","volume":"19","author":"Zhu","year":"2018","journal-title":"Lancet Oncol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1705502\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T05:23:40Z","timestamp":1767331420000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1705502\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,2]]},"references-count":26,"alternative-id":["10.3389\/fphar.2025.1705502"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1705502","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,2]]},"article-number":"1705502"}}