The metabolic transition of liver cancer: a 34-year analysis of global burden across the 10 most populous countries, 1990–2023

Background:The global burden of liver cancer continues to rise, yet comprehensive assessments of trends in behavioral and metabolic risk factor-attributable mortality and disability-adjusted life years (DALYs) remain limited. We aimed to quantify these trends across the world's 10 most populous countries from 1990 to 2023.MethodsUsing data from the Global Burden of Disease Study 2023, we extracted age-standardized mortality rates (ASMRs) and disability-adjusted life years (DALYs) for primary liver cancer attributable to seven risk factors—two composite exposures (behavioral risks and metabolic risks) and five component exposures (alcohol use, tobacco, drug use, high body mass index, and high fasting plasma glucose)—globally and across the 10 most populous nations. All burden estimates are reported with 95% uncertainty intervals (UIs). Joinpoint regression analysis identified temporal trend changes by sex and country, with annual percentage changes (APCs) and average annual percentage changes (AAPCs) reported with 95% confidence intervals (CIs).FindingsGlobally, alcohol remained the predominant behavioral risk, although alcohol use-attributable ASMRs changed little across the study period [1.08 [95% UI 0.83–1.46] to 1.13 [0.87–1.46] per 100,000; AAPC 0.06% [95% CI −0.01 to 0.14], p = 0.07]. Concerningly, drug use-related ASMRs rose by 79% [0.40 [0.28–0.59] to 0.73 [0.56–0.92] per 100,000; AAPC 1.78% [1.68–1.87]], while metabolic risk-attributable mortality increased 71% [0.42 [0.24–0.64] to 0.73 [0.40–1.05] per 100,000; AAPC 1.67% [1.60–1.73]] and high body mass index-related DALYs nearly doubled [8.96 [3.90–14.82] to 16.26 [7.50–25.62] per 100,000]. Marked heterogeneity existed across countries: by 2023 Nigeria exhibited male metabolic risk-related DALYs nearly four times the global average [95.17 [34.23–204.38] vs. 25.13 [13.61–38.01] per 100,000]. Among women, behavioral and metabolic risk burdens increased in most countries, with the United States showing 2–3-fold higher rates than global averages.InterpretationWhile traditional behavioral risk factors stabilized, metabolic risks and drug use now account for a growing share of liver cancer burden globally, with an apparent acceleration after 2020. These findings are restricted to the 10 most populous countries and therefore do not represent Europe, the Middle East, or most of Africa, and the ecological design precludes individual-level causal inference. Integrated prevention strategies targeting obesity, diabetes, and substance use disorders are nonetheless likely to be important, particularly in rapidly developing nations and among women.