Letter: Global Burden of Metabolic Dysfunction-Associated Steatotic Liver Disease-Related Liver Cancer—Results From the Global Burden of Disease Study 2021. Authors' Reply

Abstract

We deeply appreciate the insightful letter from Liu and He et al., which highlights their analysis of the global burden of metabolic dysfunction-associated steatotic liver disease (MASLD)-related liver cancer using the Global Burden of Disease Study (GBD) 2021 database [1]. The similarities between their findings and our observations on the rising burden of MASLD-related liver cancer in the United States underscore the global importance of this issue [2].

The data on global trends in MASLD-related liver cancer, particularly the notable increases in incidence and mortality, are highly significant. Prior studies using the same database also emphasised the rising burden of steatotic liver disease-related liver cancer, with increasing age-standardised incidence rates for both alcohol-associated liver disease (ALD) (APC: 0.26%, 95% CI 0.22%–0.30%) and MASLD (APC: 0.62%, 95% CI 0.58%–0.67%) [3, 4]. The non-overlapping confidence intervals support the assertion, as noted by Liu and He et al., that MASLD is a primary driver of the global burden of steatotic liver disease, as evidenced by projections through 2050 [1]. However, several limitations to the GBD methodology warrant consideration [5]. For example, alcohol use is frequently underreported, which could result in some MASLD cases being reclassified as metabolic dysfunction and alcohol-associated liver disease (MetALD) or ALD [6, 7]. A comprehensive alcohol history, including recent and lifetime intake, is essential to ensure accurate prognosis and management. Consideration of alcohol's impact on metabolic syndrome criteria, reassessing alcohol use and metabolic dysfunction over time, and addressing challenges with underreporting through biomarkers, validated questionnaires and collateral information are essential [6]. Furthermore, since 2024, Resmetirom has received conditional approval for treating MASH, while treatment advancements for ALD have lagged behind, suggesting the future burden of ALD may increase more than MASLD [8, 9].

The letter further underscores the critical need to incorporate demographic factors, particularly population aging, into strategies for preventing and managing MASLD-related liver cancer. This consideration extends to ALD-associated liver cancer, as alcohol use disorder shows similar age-standardised prevalence rates as the general population [10]. Such demographic insights can guide the development of tailored public health strategies and resource allocation to effectively address these populations' unique needs, which will translate into primary prevention of ALD-associated liver cancer.

Further refinement of large-scale databases to accurately quantify aetiology-specific contributions, both in the United States and globally, is essential for informing prevention efforts, including target populations, to effectively reduce liver cancer incidence and mortality.