{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T08:00:41Z","timestamp":1771920041456,"version":"3.50.1"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"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>The global burden of liver cancer is undergoing an etiological shift, driven by population aging and the increasing complexity of pharmacological management. While Drug-Induced Liver Injury (DILI) is a recognized carcinogenic mechanism, the population-level impact remains under-quantified. This study aims to quantify the spatiotemporal trends of liver cancer burden attributable to drug use in the elderly population (aged 55+) and elucidate the drivers behind regional disparities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Leveraging data from the Global Burden of Disease (GBD) Study 2021, we analyzed incidence, mortality, and disability-adjusted life years (DALYs) across 204 countries and territories from 1990 to 2021. Adopting the Comparative Risk Assessment (CRA) framework, we estimated the specific burden by calculating the Population Attributable Fraction (PAF) relative to a theoretical minimum risk exposure level (TMREL) of zero drug use. Temporal trends were assessed using Estimated Annual Percentage Change (EAPC), and associations with the Socio-demographic Index (SDI) were evaluated to delineate developmental disparities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Globally, the absolute number of deaths has steadily increased despite stable age-standardized rates. A distinct \u201cSDI Divergence\u201d was observed: High-SDI regions exhibited the most rapid escalation in burden (highest EAPC), driven by the \u201cOpioid-Polypharmacy Nexus,\u201d whereas Low-SDI regions sustained a persistently high baseline burden due to unmet diagnostic needs. Demographic analysis revealed a stark male predominance and identified the 55\u201374 age group as the \u201cactive intervention window,\u201d accounting for the largest proportion of the global burden in terms of both mortality and DALYs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The escalating burden of liver cancer attributable to drug use in the elderly underscores the \u201cCumulative Impact of Prolonged Exposure,\u201d where the intersection of physiological aging and complex drug use patterns amplifies hepatic risk. Mitigating this crisis requires stratified strategies: prioritizing \u201cCapacity Building\u201d (integrating screening into infectious disease programs) in resource-limited settings, and implementing strict \u201cStewardship\u201d (pharmacovigilance and active deprescribing) in developed nations to curb this trajectory.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1678700","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T05:18:51Z","timestamp":1771910331000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Global and regional burden of liver cancer attributable to drug use in elderly patients: a 1990\u20132021 analysis from the GBD study"],"prefix":"10.3389","volume":"16","author":[{"given":"Chengchi","family":"Xia","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianshu","family":"Rong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baoqing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA: Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1016\/j.cmet.2022.05.003","article-title":"Changing global epidemiology of liver cancer from 2010 to 2019: NASH is the fastest growing cause of liver cancer","volume":"34","author":"Huang","year":"2022","journal-title":"Cell Metab"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.09.011","article-title":"Primary liver cancer: worldwide incidence and trends","volume":"127","author":"Bosch","year":"2004","journal-title":"Gastroenterology"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0457-8","article-title":"Facing up to the global challenge of ageing","volume":"561","author":"Partridge","year":"2018","journal-title":"Nature"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1080\/10937404.2023.2261848","article-title":"Drug induced liver injury \u2013 a 2023 update","volume":"26","author":"Allison","year":"2023","journal-title":"J Toxicol Environ Health B"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c00524","article-title":"Drug induced liver injury (DILI). 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