{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T05:04:55Z","timestamp":1783919095997,"version":"3.55.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"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. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Digestive system malignant tumors (DSMTs) represent a major contributor to global cancer-related morbidity and mortality. With improving cancer survival, coexisting conditions and complications, including liver failure, have become increasingly relevant in mortality patterns among patients with DSMTs. However, population-level evidence on temporal trends and disparities in liver failure-related mortality remains limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This population-based retrospective repeated cross-sectional study used data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database. Death records from 1999 to 2023 were analyzed among patients aged \u226545 years with DSMTs, defined by ICD-10 codes C15-C26. Liver failure was identified using ICD-10 code K72 under a multiple cause-of-death framework. Age-adjusted mortality rates (AAMRs) were calculated using the 2000 U.S. standard population. Temporal trends were assessed using Joinpoint regression to estimate annual percent change (APC) and average annual percent change (AAPC). Analyses were stratified by sex, age group, race and ethnicity, urbanization level, Census region, and Health and Human Services (HHS) region.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>From 1999 to 2023, a total of 82,796 liver failure-related deaths occurred among patients aged \u226545 years with DSMTs in the United States. Annual deaths declined from 4,131 in 1999 to 3,250 in 2023 (\u221221.33%). The AAMR decreased from 4.34 per 100,000 population (95% CI: 4.21\u20134.47) to 2.08 per 100,000 (95% CI: 2.01\u20132.15), corresponding to a significant overall decline (AAPC = \u22122.94%, 95% CI: \u22123.18 to \u22122.69). Although mortality declined across most subgroups, substantial heterogeneity persisted. Males consistently exhibited higher mortality than females, deaths were concentrated among older age groups, and liver failure-related deaths increased markedly among Hispanic individuals. Geographic analyses revealed pronounced regional variation, with attenuated declines or increasing trends in selected Census and HHS regions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Liver failure-related mortality among middle-aged and older patients with DSMTs in the United States has declined substantially over the past two decades. However, this improvement has slowed in recent years and remains uneven across populations and regions. These findings support continued attention to liver function monitoring, liver disease risk assessment, and targeted surveillance in high-risk populations and regions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1825036","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T04:23:53Z","timestamp":1783916633000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Trends in liver failure-related mortality among middle-aged and older adults with digestive system malignant tumors in the United States, 1999\u20132023"],"prefix":"10.3389","volume":"16","author":[{"given":"Ling","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of General Surgery, The Second People\u2019s Hospital of Jiulongpo District","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengjun","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The Second People\u2019s Hospital of Jiulongpo District","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ao","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-02097-4","article-title":"Digestive cancers: mechanisms, therapeutics and management","volume":"10","author":"Zhan","year":"2025","journal-title":"Signal Transduct Tgt Ther"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/btm2.70006","article-title":"Biomembrane-coated nanosystems as next-generation delivery systems for the treatment of gastrointestinal cancers","volume":"10","author":"Lopes","year":"2025","journal-title":"Bioeng Transl Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41417-020-00272-7","article-title":"Autophagy and gastrointestinal cancers: the behind the scenes role of long non-coding RNAs in initiation, progression, and treatment resistance","volume":"28","author":"Shafabakhsh","year":"2021","journal-title":"Cancer Gene Ther"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.70017","article-title":"Global trends and epidemiological shifts in gastrointestinal cancers: insights from the past four decades","volume":"45","author":"Li","year":"2025","journal-title":"Cancer Commun (Lond)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12220","article-title":"A global assessment of recent trends in gastrointestinal cancer and lifestyle-associated risk factors","volume":"41","author":"Lu","year":"2021","journal-title":"Cancer Commun (Lond)"},{"key":"B6","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1136\/gutjnl-2024-333227","article-title":"Epidemiology of gastrointestinal cancers: a systematic analysis from the Global Burden of Disease Study 2021","volume":"74","author":"Danpanichkul","year":"2024","journal-title":"Gut"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2025.1674621","article-title":"Attributable burden of high BMI-related gastrointestinal tract cancers among middle-aged and elderly populations globally, 1990-2021 and projected to 2050: analysis of GBD 2021","volume":"12","author":"Yilihaer","year":"2025","journal-title":"Front Nutr"},{"key":"B8","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1016\/j.amjmed.2024.12.019","article-title":"Mortality of gastrointestinal cancers attributable to smoking, alcohol, and metabolic risk factors, and its association with socioeconomic development status 2000-2021","volume":"138","author":"Danpanichkul","year":"2025","journal-title":"Am J Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/srep29655","article-title":"Sex, race, and age disparities in the improvement of survival for gastrointestinal cancer over time","volume":"6","author":"Wan","year":"2016","journal-title":"Sci Rep"},{"key":"B10","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1053\/j.gastro.2022.04.019","article-title":"Factors associated with geographic disparities in gastrointestinal cancer mortality in the United States","volume":"163","author":"Ma","year":"2022","journal-title":"Gastroenterology"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.canep.2025.102973","article-title":"Population-based trends in gastrointestinal cancer incidence and mortality in New Zealand: a 11-year analysis","volume":"100","author":"Shanika","year":"2026","journal-title":"Cancer Epidemiol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.705999","article-title":"Targeted immunotherapies in gastrointestinal cancer: from molecular mechanisms to implications","volume":"12","author":"Wang","year":"2021","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.12049","article-title":"Population-based long-term cardiac-specific mortality among patients with major gastrointestinal cancers","volume":"4","author":"Ramai","year":"2021","journal-title":"JAMA Netw Open"},{"key":"B14","doi-asserted-by":"publisher","first-page":"69","DOI":"10.21037\/hbsn-22-238","article-title":"Surgery for metastatic pancreatic neuroendocrine tumors: a narrative review","volume":"12","author":"Williams","year":"2023","journal-title":"Hepatobiliary Surg Nutr"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15813","article-title":"Conventional cytotoxic chemotherapy for gastrointestinal cancer in patients with cirrhosis: a multicentre case-control study","volume":"44","author":"Ningarhari","year":"2024","journal-title":"Liver Int"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2025.105001","article-title":"Tumor microenvironment and metabolic reprogramming: unraveling the complex interplay in gastrointestinal tumor liver metastasis","volume":"216","author":"Wang","year":"2025","journal-title":"Crit Rev Oncol Hematol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2020.06.003","article-title":"The unique immune microenvironment of liver metastases: challenges and opportunities","volume":"71","author":"Ciner","year":"2021","journal-title":"Semin Cancer Biol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/s41421-020-0145-3","article-title":"Identification of primordial germ cell-like cells as liver metastasis initiating cells in mouse tumour models","volume":"6","author":"Liu","year":"2020","journal-title":"Cell Discov"},{"key":"B19","article-title":"Management of hepatotoxicity of chemotherapy and targeted agents","volume":"11","author":"Mudd","year":"2021","journal-title":"Am J Cancer Res"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-024-01019-7","article-title":"Immune-mediated liver injury from checkpoint inhibitors: mechanisms, clinical characteristics and management","volume":"22","author":"Triantafyllou","year":"2025","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/liv.70002","article-title":"Drug-induced liver injury associated with emerging cancer therapies","volume":"45","author":"Chodup","year":"2025","journal-title":"Liver Int"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1542328","article-title":"Metabolic syndrome is associated with worse prognosis in elderly patients with hepatocellular carcinoma","volume":"15","author":"Huang","year":"2025","journal-title":"Front Oncol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.70071","article-title":"The Fibrosis-4 score is associated with overall mortality and severe haematological toxicity in older patients with cancer: analysis of two prospective cohort studies","volume":"157","author":"de Salins","year":"2025","journal-title":"Int J Cancer"},{"key":"B24","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1111\/jcpe.13304","article-title":"Oral health and gastrointestinal cancer: a nationwide cohort study","volume":"47","author":"Lee","year":"2020","journal-title":"J Clin Periodontol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2024.118439","article-title":"Short-term impact of air pollution, noise and temperature on emergency hospital admissions in Madrid (Spain) due to liver and gallbladder diseases","volume":"249","author":"L\u00f3pez-Bueno","year":"2024","journal-title":"Environ Res"},{"key":"B26","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s12872-025-05417-w","article-title":"Temporal trends and disparities in cardiovascular disease-related mortality among adults with multiple myeloma in the United States, 1999-2023","volume":"26","author":"Tian","year":"2025","journal-title":"BMC Cardiovasc Disord"},{"key":"B27","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1186\/s12931-025-03336-0","article-title":"Trends in influenza- and pneumonia-related mortality in lung cancer patients from 1999 to 2022: a retrospective CDC WONDER analysis","volume":"26","author":"Woods","year":"2025","journal-title":"Respir Res"},{"key":"B28","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1186\/s12876-025-04354-4","article-title":"Trends in pancreatic cancer mortality among US adults, 1999-2023","volume":"25","author":"Wu","year":"2025","journal-title":"BMC Gastroenterol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2025.104063","article-title":"Trends and disparities in acute myocardial infarction and type 2 diabetes mellitus-related mortality in the United States from 1999-2022","volume":"35","author":"Akhtar","year":"2025","journal-title":"Nutr Metab Cardiovasc Dis"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3390\/jcm14072190","article-title":"Acute myocardial infarction mortality in the older population of the United States: an analysis of demographic and regional trends and disparities from 1999 to 2022","volume":"14","author":"Abdul Jabbar","year":"2025","journal-title":"J Clin Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2025.1715729","article-title":"Shifting mortality patterns of primary liver cancer in the United States: a 20-year analysis of disparities","volume":"13","author":"Zhao","year":"2025","journal-title":"Front Public Health"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2025.112112","article-title":"Trends and disparities in diabetes mellitus and atrial fibrillation related mortality in the United States: 1999-2020","volume":"223","author":"Sohail","year":"2025","journal-title":"Diabetes Res Clin Pract"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1002\/clc.70129","article-title":"Trends and disparities in acute myocardial infarction-related mortality among U.S. adults with hypertension, 2000-2023","volume":"48","author":"Sajid","year":"2025","journal-title":"Clin Cardiol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.hoc.2024.01.007","article-title":"The role of screening and early detection in upper gastrointestinal cancers","volume":"38","author":"Yoo","year":"2024","journal-title":"Hematol Oncol Clin North Am"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2019-320200","article-title":"Effectiveness of one-time endoscopic screening programme in prevention of upper gastrointestinal cancer in China: a multicentre population-based cohort study","volume":"70","author":"Chen","year":"2021","journal-title":"Gut"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1097\/JS9.0000000000003495","article-title":"Impact of Child-Pugh score on surgical outcomes after distal gastrectomy and right hemicolectomy: a retrospective study from the Japanese National Clinical Database","volume":"112","author":"Shimada","year":"2026","journal-title":"Int J Surg"},{"key":"B37","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.ctrv.2018.05.010","article-title":"Long-term survival after liver metastasectomy in gastric cancer: systematic review and meta-analysis of prognostic factors","volume":"69","author":"Montagnani","year":"2018","journal-title":"Cancer Treat Rev"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1111\/apt.18280","article-title":"The association between alcohol consumption and cardiometabolic factors and liver fibrosis in metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction and alcohol-associated liver disease","volume":"60","author":"Sogabe","year":"2024","journal-title":"Aliment Pharmacol Ther"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3390\/jcm14176158","article-title":"Sex differences in patients with MASLD and their association with cardiometabolic risk factors: insights from the Polish Gallstone Surgery Registry","volume":"14","author":"Gorczyca-G\u0142owacka","year":"2025","journal-title":"J Clin Med"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1001823","article-title":"Application of artificial liver in immune-related liver injury induced by immune checkpoint inhibitor: case reports and review of the literature","volume":"13","author":"Li","year":"2022","journal-title":"Front Immunol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.ypmed.2020.106146","article-title":"Colorectal cancer screening among Hispanics in the United States: disparities, modalities, predictors, and regional variation","volume":"138","author":"Viramontes","year":"2020","journal-title":"Prev Med"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.gassur.2024.05.010","article-title":"Esophageal cancer in Hispanics: a demographic analysis of the National Cancer Database","volume":"28","author":"Ricardo","year":"2024","journal-title":"J Gastrointest Surg"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.ssmph.2022.101213","article-title":"Trends in lifespan variation across the spectrum of rural and urban places in the United States, 1990-2017","volume":"19","author":"Walker","year":"2022","journal-title":"SSM Popul Health"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2024.107762","article-title":"Rural-urban stroke mortality gaps in the United States","volume":"33","author":"Chang","year":"2024","journal-title":"J Stroke Cerebrovasc Dis"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1111\/jrh.12658","article-title":"Trends in rural-urban disparities among surgical specialties treating cancer, 2004-2017","volume":"38","author":"Herb","year":"2022","journal-title":"J Rural Health"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1825036\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T04:23:54Z","timestamp":1783916634000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1825036\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,13]]},"references-count":45,"alternative-id":["10.3389\/fonc.2026.1825036"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1825036","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,13]]},"article-number":"1825036"}}