{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T13:58:09Z","timestamp":1793973489775,"version":"4.8.0"},"reference-count":46,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2023,10,1]]},"abstract":"<jats:sec id=\"ab-coi230042-4\"><jats:title>Importance<\/jats:title><jats:p>Immune checkpoint inhibitors (ICIs) are increasingly used in patients with advanced hepatocellular carcinoma (HCC). However, data on ICI therapy in patients with advanced HCC and impaired liver function are scarce.<\/jats:p><\/jats:sec><jats:sec id=\"ab-coi230042-5\"><jats:title>Objective<\/jats:title><jats:p>To conduct a systematic review and meta-analysis to determine the efficacy and safety of ICI treatment for advanced HCC with Child-Pugh B liver function.<\/jats:p><\/jats:sec><jats:sec id=\"ab-coi230042-6\"><jats:title>Data Sources<\/jats:title><jats:p>PubMed, Embase, Web of Science, and Cochrane Library were searched for relevant studies from inception through June 15, 2022.<\/jats:p><\/jats:sec><jats:sec id=\"ab-coi230042-7\"><jats:title>Study Selection<\/jats:title><jats:p>Randomized clinical trials, cohort studies, or single-group studies that investigated the efficacy or safety of ICI therapy for Child-Pugh B advanced HCC were included.<\/jats:p><\/jats:sec><jats:sec id=\"ab-coi230042-8\"><jats:title>Data Extraction and Synthesis<\/jats:title><jats:p>The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline was followed to extract data. A random-effects model was adopted if the heterogeneity was significant (<jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u2009&amp;amp;gt;\u200950%); otherwise, a fixed-effect model was used.<\/jats:p><\/jats:sec><jats:sec id=\"ab-coi230042-9\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>The objective response rate (ORR) and overall survival (OS) were considered to be the primary efficacy outcomes of ICI treatment for Child-Pugh B advanced HCC, and the incidence of treatment-related adverse events (trAEs) was set as the primary measure for the safety outcome.<\/jats:p><\/jats:sec><jats:sec id=\"ab-coi230042-10\"><jats:title>Results<\/jats:title><jats:p>A total of 22 studies including 699 patients with Child-Pugh B and 2114 with Child-Pugh A advanced HCC comprised the analytic sample (median age range, 53-73 years). Upon pooled analysis, patients treated with ICIs in the Child-Pugh B group had an ORR of 14% (95% CI, 11%-17%) and disease control rate (DCR) of 46% (95% CI, 36%-56%), with a median OS of 5.49 (95% CI, 3.57-7.42) months and median progression-free survival of 2.68 (95% CI, 1.85-3.52) months. The rate of any grade trAEs in the Child-Pugh B group was 40% (95% CI, 34%-47%) and of grade 3 or higher trAEs was 12% (95% CI, 6%-23%). Compared with the Child-Pugh A group, the ORR (odds ratio, 0.59; 95% CI, 0.43-0.81; <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001) and DCR (odds ratio, 0.64; 95% CI, 0.50-0.81; <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001) were lower in the Child-Pugh B group. Child-Pugh B was independently associated with worse OS in patients with advanced HCC treated with ICIs (hazard ratio, 2.72 [95% CI, 2.34-3.16]; adjusted hazard ratio, 2.33 [95% CI, 1.81-2.99]). However, ICIs were not associated with increased trAEs in the Child-Pugh B group.<\/jats:p><\/jats:sec><jats:sec id=\"ab-coi230042-11\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>The findings of this systematic review and meta-analysis suggest that although the safety of ICI treatment was comparable between patients with HCC with vs without advanced liver disease and the treatment resulted in a significant number of radiologic responses, survival outcomes are still inferior in patients with worse liver function. More study is needed to determine the effectiveness of ICI treatment in this population.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaoncol.2023.3284","type":"journal-article","created":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T15:38:26Z","timestamp":1692891506000},"page":"1423","source":"Crossref","is-referenced-by-count":93,"title":["Immune Checkpoint Inhibitors for Child-Pugh Class B Advanced Hepatocellular Carcinoma"],"prefix":"10.1001","volume":"9","author":[{"given":"Enrui","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, The Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee Hui","family":"Yeo","sequence":"additional","affiliation":[{"name":"Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Scheiner","sequence":"additional","affiliation":[{"name":"Department of Surgery and Cancer, Imperial College London, United Kingdom"},{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an, China"},{"name":"The Eighth Hospital of Xi\u2019an City, Xi\u2019an Jiaotong University, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Hiraoka","sequence":"additional","affiliation":[{"name":"Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxing","family":"Tantai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petros","family":"Fessas","sequence":"additional","affiliation":[{"name":"Department of Surgery and Cancer, Imperial College London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiago","family":"de Castro","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"D\u2019Alessio","sequence":"additional","affiliation":[{"name":"Department of Surgery and Cancer, Imperial College London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia Angela Maria","family":"Fulgenzi","sequence":"additional","affiliation":[{"name":"Department of Surgery and Cancer, Imperial College London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Ming","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swetha Kambhampati","family":"Thiruvengadam","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hematopoietic Stem Cell Transplantation, City of Hope National Medical Center, Duarte, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget P.","family":"Keenan","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an, China"},{"name":"Department of Gastroenterology, The Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixuan","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Pinter","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yih-Jyh","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanjun","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arndt","family":"Vogel","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaaki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Yu","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan"},{"name":"Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin K.","family":"Kelley","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoshi","family":"Kudo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju Dong","family":"Yang","sequence":"additional","affiliation":[{"name":"Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California"},{"name":"Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Pinato","sequence":"additional","affiliation":[{"name":"Department of Surgery and Cancer, Imperial College London, United Kingdom"},{"name":"Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale \u201cA Avogadro,\u201d Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanpu","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an, China"},{"name":"National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an, China"},{"name":"Shaanxi Provincial Clinical Medical Research Center of Infectious Diseases, Xi\u2019an, China"},{"name":"Key Laboratory of Surgical Critical Care and Life Support (Xi\u2019an Jiaotong University), Ministry of Education, Xi\u2019an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"3","key":"coi230042r1","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"},{"issue":"1","key":"coi230042r2","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1053\/j.gastro.2020.02.068","article-title":"Global burden of 5 major types of gastrointestinal cancer.","volume":"159","author":"Arnold","year":"2020","journal-title":"Gastroenterology"},{"issue":"1","key":"coi230042r3","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.jhep.2018.03.019","article-title":"Management of hepatocellular carcinoma.","volume":"69","author":"European Association for the Study of the Liver","year":"2018","journal-title":"J Hepatol"},{"issue":"9972","key":"coi230042r4","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1016\/S0140-6736(14)62038-9","article-title":"Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2).","volume":"385","author":"Allemani","year":"2015","journal-title":"Lancet"},{"issue":"2","key":"coi230042r5","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.suronc.2016.03.002","article-title":"Hepatocellular carcinoma: from diagnosis to treatment.","volume":"25","author":"Grandhi","year":"2016","journal-title":"Surg Oncol"},{"issue":"3","key":"coi230042r6","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1002\/hep.24199","article-title":"Management of hepatocellular carcinoma: an update.","volume":"53","author":"Bruix","year":"2011","journal-title":"Hepatology"},{"issue":"6","key":"coi230042r7","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1016\/j.jhep.2016.07.020","article-title":"Observational registry of sorafenib use in clinical practice across Child-Pugh subgroups: the GIDEON study.","volume":"65","author":"Marrero","year":"2016","journal-title":"J Hepatol"},{"issue":"4","key":"coi230042r8","doi-asserted-by":"publisher","first-page":"793","DOI":"10.3892\/mco.2015.536","article-title":"Safety and efficacy of sorafenib in patients with Child-Pugh B advanced hepatocellular carcinoma.","volume":"3","author":"da Fonseca","year":"2015","journal-title":"Mol Clin Oncol"},{"issue":"21","key":"coi230042r9","doi-asserted-by":"publisher","first-page":"5293","DOI":"10.1002\/cncr.27543","article-title":"The use of single-agent sorafenib in the treatment of advanced hepatocellular carcinoma patients with underlying Child-Pugh B liver cirrhosis: a retrospective analysis of efficacy, safety, and survival benefits.","volume":"118","author":"Chiu","year":"2012","journal-title":"Cancer"},{"key":"coi230042r10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ejca.2018.09.031","article-title":"Sorafenib as first-line therapy in patients with advanced Child-Pugh B hepatocellular carcinoma-a meta-analysis.","volume":"105","author":"McNamara","year":"2018","journal-title":"Eur J Cancer"},{"issue":"4","key":"coi230042r11","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1097\/MEG.0b013e328333df23","article-title":"Consensus on the current use of sorafenib for the treatment of hepatocellular carcinoma.","volume":"22","author":"Peck-Radosavljevic","year":"2010","journal-title":"Eur J Gastroenterol Hepatol"},{"issue":"3","key":"coi230042r12","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/j.jhep.2019.05.014","article-title":"Nivolumab in advanced hepatocellular carcinoma: sorafenib-experienced Asian cohort analysis.","volume":"71","author":"Yau","year":"2019","journal-title":"J Hepatol"},{"issue":"4","key":"coi230042r13","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1158\/1078-0432.CCR-20-2571","article-title":"Camrelizumab in Combination with Apatinib in Patients with Advanced Hepatocellular Carcinoma (RESCUE): a nonrandomized, open-label, phase II trial.","volume":"27","author":"Xu","year":"2021","journal-title":"Clin Cancer Res"},{"issue":"1","key":"coi230042r14","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"},{"issue":"3","key":"coi230042r15","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1016\/j.jhep.2021.04.047","article-title":"CheckMate 040 cohort 5: a phase I\/II study of nivolumab in patients with advanced hepatocellular carcinoma and Child-Pugh B cirrhosis.","volume":"75","author":"Kudo","year":"2021","journal-title":"J Hepatol"},{"issue":"7","key":"coi230042r16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000097","article-title":"Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.","volume":"6","author":"Moher","year":"2009","journal-title":"PLoS Med"},{"issue":"1","key":"coi230042r19","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1186\/s12874-021-01308-8","article-title":"IPDfromKM: reconstruct individual patient data from published Kaplan-Meier survival curves.","volume":"21","author":"Liu","year":"2021","journal-title":"BMC Med Res Methodol"},{"issue":"5","key":"coi230042r20","doi-asserted-by":"publisher","first-page":"e249","DOI":"10.1111\/ajco.13454","article-title":"Real-world efficacy and safety of immune checkpoint inhibitors in advanced hepatocellular carcinoma: experience of a tertiary Asian center.","volume":"17","author":"Ng","year":"2021","journal-title":"Asia Pac J Clin Oncol"},{"issue":"7","key":"coi230042r21","doi-asserted-by":"publisher","first-page":"1968","DOI":"10.3390\/cancers12071968","article-title":"Effectiveness and safety of nivolumab in Child-Pugh B patients with hepatocellular carcinoma: a real-world cohort study.","volume":"12","author":"Choi","year":"2020","journal-title":"Cancers (Basel)"},{"issue":"1","key":"coi230042r22","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1007\/s00432-018-2780-8","article-title":"Feasibility and safety of nivolumab in advanced hepatocellular carcinoma: real-life experience from three German centers.","volume":"145","author":"Finkelmeier","year":"2019","journal-title":"J Cancer Res Clin Oncol"},{"issue":"18","key":"coi230042r23","doi-asserted-by":"publisher","first-page":"3234","DOI":"10.1002\/cncr.32206","article-title":"Nivolumab in patients with advanced hepatocellular carcinoma and Child-Pugh class B cirrhosis: safety and clinical outcomes in a retrospective case series.","volume":"125","author":"Kambhampati","year":"2019","journal-title":"Cancer"},{"issue":"10","key":"coi230042r24","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1111\/apt.15245","article-title":"Programmed cell death protein-1 (PD-1)-targeted immunotherapy in advanced hepatocellular carcinoma: efficacy and safety data from an international multicentre real-world cohort.","volume":"49","author":"Scheiner","year":"2019","journal-title":"Aliment Pharmacol Ther"},{"key":"coi230042r25","doi-asserted-by":"publisher","first-page":"143","DOI":"10.2147\/OTT.S234868","article-title":"Programmed cell death protein-1 (PD-1)-targeted immunotherapy for advanced hepatocellular carcinoma in real world.","volume":"13","author":"Cui","year":"2020","journal-title":"Onco Targets Ther"},{"issue":"2","key":"coi230042r26","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001033","article-title":"Post-registration experience of nivolumab in advanced hepatocellular carcinoma: an international study.","volume":"8","author":"Fessas","year":"2020","journal-title":"J Immunother Cancer"},{"issue":"5","key":"coi230042r27","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1159\/000505933","article-title":"Impact of immune checkpoint inhibitors with or without a combination of tyrosine kinase inhibitors on organ-specific efficacy and macrovascular invasion in advanced hepatocellular carcinoma.","volume":"43","author":"Kuo","year":"2020","journal-title":"Oncol Res Treat"},{"issue":"1","key":"coi230042r28","doi-asserted-by":"publisher","first-page":"182","DOI":"10.3390\/cancers12010182","article-title":"Predictors of response and survival in immune checkpoint inhibitor-treated unresectable hepatocellular carcinoma.","volume":"12","author":"Lee","year":"2020","journal-title":"Cancers (Basel)"},{"key":"coi230042r29","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.835889","article-title":"Apatinib plus camrelizumab with\/without chemoembolization for hepatocellular carcinoma: a real-world experience of a single center.","volume":"11","author":"Ju","year":"2022","journal-title":"Front Oncol"},{"key":"coi230042r30","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.794099","article-title":"Correlation between immune-related adverse events and prognosis in hepatocellular carcinoma patients treated with immune checkpoint inhibitors.","volume":"12","author":"Xu","year":"2021","journal-title":"Front Immunol"},{"issue":"3","key":"coi230042r31","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1111\/hepr.13732","article-title":"Safety and efficacy of atezolizumab plus bevacizumab in patients with unresectable hepatocellular carcinoma in early clinical practice: a multicenter analysis.","volume":"52","author":"Chuma","year":"2022","journal-title":"Hepatol Res"},{"issue":"4","key":"coi230042r32","doi-asserted-by":"publisher","first-page":"1000","DOI":"10.1002\/hep.32468","article-title":"Preliminary evidence of safety and tolerability of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child-Pugh A and B cirrhosis: a real-world study.","volume":"76","author":"D\u2019Alessio","year":"2022","journal-title":"Hepatology"},{"key":"coi230042r33","doi-asserted-by":"publisher","DOI":"10.1177\/17588359221080298","article-title":"Atezolizumab and bevacizumab in patients with advanced hepatocellular carcinoma with impaired liver function and prior systemic therapy: a real-world experience.","author":"de Castro","year":"2022","journal-title":"Ther Adv Med Oncol"},{"issue":"7","key":"coi230042r34","doi-asserted-by":"publisher","first-page":"1722","DOI":"10.3390\/cancers14071722","article-title":"Efficacy and safety of atezolizumab and bevacizumab in the real-world treatment of advanced hepatocellular carcinoma: experience from four tertiary centers.","volume":"14","author":"Himmelsbach","year":"2022","journal-title":"Cancers (Basel)"},{"issue":"9","key":"coi230042r35","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1111\/hepr.13797","article-title":"Therapeutic efficacy of atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma in patients with Child-Pugh class A or B liver function in real-world clinical practice.","volume":"52","author":"Tanaka","year":"2022","journal-title":"Hepatol Res"},{"issue":"1","key":"coi230042r36","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1159\/000518619","article-title":"Impact of immune-related adverse events on efficacy of immune checkpoint inhibitors in patients with advanced hepatocellular carcinoma.","volume":"11","author":"Ng","year":"2021","journal-title":"Liver Cancer"},{"issue":"19","key":"coi230042r37","doi-asserted-by":"publisher","first-page":"3612","DOI":"10.1002\/cam4.4747","article-title":"Efficacy and safety of PD-1 inhibitor combined with antiangiogenic therapy for unresectable hepatocellular carcinoma: a multicenter retrospective study.","volume":"11","author":"Yao","year":"2022","journal-title":"Cancer Med"},{"issue":"1","key":"coi230042r38","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1186\/s12885-022-09405-7","article-title":"Real-world efficiency of lenvatinib plus PD-1 blockades in advanced hepatocellular carcinoma: an exploration for expanded indications.","volume":"22","author":"Sun","year":"2022","journal-title":"BMC Cancer"},{"issue":"11","key":"coi230042r39","doi-asserted-by":"publisher","first-page":"2631","DOI":"10.1007\/s00262-022-03185-6","article-title":"Lenvatinib plus pembrolizumab for systemic therapy-na\u00efve and -experienced unresectable hepatocellular carcinoma.","volume":"71","author":"Wu","year":"2022","journal-title":"Cancer Immunol Immunother"},{"issue":"4","key":"coi230042r40","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1097\/HEP.0000000000000030","article-title":"Outcome of patients with HCC and liver dysfunction under immunotherapy: a systematic review and meta-analysis.","volume":"77","author":"El Hajra","year":"2023","journal-title":"Hepatology"},{"issue":"2","key":"coi230042r41","first-page":"40","article-title":"Safety and efficacy of sorafenib in patients with hepatocellular carcinoma (HCC) and Child-Pugh A versus B cirrhosis.","volume":"4","author":"Abou-Alfa","year":"2011","journal-title":"Gastrointest Cancer Res"},{"issue":"2","key":"coi230042r42","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1093\/annonc\/mds343","article-title":"Sorafenib in patients with Child-Pugh class A and B advanced hepatocellular carcinoma: a prospective feasibility analysis.","volume":"24","author":"Pressiani","year":"2013","journal-title":"Ann Oncol"},{"issue":"6","key":"coi230042r43","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1016\/j.jhep.2014.08.010","article-title":"Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance.","volume":"61","author":"Albillos","year":"2014","journal-title":"J Hepatol"},{"issue":"3","key":"coi230042r44","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1159\/000507370","article-title":"A changing paradigm for the treatment of intermediate-stage hepatocellular carcinoma: Asia-Pacific primary liver cancer expert consensus statements.","volume":"9","author":"Kudo","year":"2020","journal-title":"Liver Cancer"},{"issue":"1","key":"coi230042r45","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.jhep.2017.01.033","article-title":"Hepatic decompensation is the major driver of death in HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma.","volume":"67","author":"Cabibbo","year":"2017","journal-title":"J Hepatol"},{"issue":"3","key":"coi230042r46","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1002\/hep.27729","article-title":"Predictors of survival in patients with advanced hepatocellular carcinoma who permanently discontinued sorafenib.","volume":"62","author":"Iavarone","year":"2015","journal-title":"Hepatology"},{"key":"coi230042r17","unstructured":"Wells? GA, Shea? B, O\u2019Connell? D, . The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. The Ottawa Hospital Research Institute. 2019. Accessed May 24, 2023. https:\/\/www.ohri.ca\/programs\/clinical_epidemiology\/oxford.asp"},{"key":"coi230042r18","unstructured":"Case series studies quality appraisal tool. Institute of Health Economics. 2014. Accessed May 24, 2023. https:\/\/www.ihe.ca\/research-programs\/rmd\/cssqac\/cssqac-about"}],"container-title":["JAMA Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaoncology\/articlepdf\/2808728\/jamaoncology_xie_2023_oi_230042_1750880199.75471.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T15:00:32Z","timestamp":1751554832000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaoncology\/fullarticle\/2808728"}},"subtitle":["A Systematic Review and Meta-Analysis"],"short-title":[],"issued":{"date-parts":[[2023,10,1]]},"references-count":46,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2023,10,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaoncol.2023.3284","relation":{},"ISSN":["2374-2437"],"issn-type":[{"value":"2374-2437","type":"print"}],"subject":[],"published":{"date-parts":[[2023,10,1]]}}}