# Global and regional burden of liver cancer attributable to drug use in elderly patients: a 1990–2021 analysis from the GBD study

## TL;DR

This paper shows that drug use in elderly people is increasingly causing liver cancer worldwide, with different patterns in high- and low-income regions.

## Contribution

The study quantifies for the first time the liver cancer burden in elderly populations attributable to drug use using global data from 1990 to 2021.

## Key findings

- High-SDI regions saw the fastest rise in liver cancer burden due to opioid-polypharmacy, while low-SDI regions had persistently high baseline rates.
- The 55–74 age group bears the largest share of liver cancer mortality and disability from drug use.
- Male predominance and prolonged drug exposure in aging populations are key drivers of the observed trends.

## Abstract

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.

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.

Globally, the absolute number of deaths has steadily increased despite stable age-standardized rates. A distinct “SDI Divergence” was observed: High-SDI regions exhibited the most rapid escalation in burden (highest EAPC), driven by the “Opioid-Polypharmacy Nexus,” 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 55–74 age group as the “active intervention window,” accounting for the largest proportion of the global burden in terms of both mortality and DALYs.

The escalating burden of liver cancer attributable to drug use in the elderly underscores the “Cumulative Impact of Prolonged Exposure,” where the intersection of physiological aging and complex drug use patterns amplifies hepatic risk. Mitigating this crisis requires stratified strategies: prioritizing “Capacity Building” (integrating screening into infectious disease programs) in resource-limited settings, and implementing strict “Stewardship” (pharmacovigilance and active deprescribing) in developed nations to curb this trajectory.