Letter: Towards Better Intervention Strategies for MASLD and MetALD—What Are We Missing?

Abstract

We have carefully reviewed the recent study by Park et al., which examines the relationship between metabolic dysfunction-associated steatotic liver disease (MASLD), its alcohol-associated subtype (MetALD) and cancer risk [1]. The study provides valuable data, highlighting the increased risk of liver and gastrointestinal cancers in patients with MASLD and MetALD. While this is a noteworthy contribution, we believe that several key issues warrant further exploration to enhance the clinical applicability of this new disease classification.

First, although the new nomenclature offers a more detailed classification of MASLD and MetALD, it remains unclear whether this distinction will significantly improve patient management in clinical practice. The study mentions the association between alcohol consumption and cancer risk, but the definition of alcohol intake (e.g., moderate consumption of 30–60 g per day) may be interpreted and followed differently by individual patients, especially those with pre-existing metabolic dysfunction. Future research should consider developing more precise tools to evaluate the specific impact of alcohol consumption on cancer risk and provide clearer guidance for clinicians when managing MASLD and MetALD patients [2].

Second, we suggest that future studies focus on optimising intervention strategies. While the study demonstrates a clear link between MASLD, MetALD and increased cancer risk, it does not provide specific recommendations for interventions targeting this high-risk population. Some research has shown that a multidisciplinary approach integrating metabolic control and alcohol management can be an effective strategy for reducing cancer risk in such patients [3]. Prospective intervention studies will be essential in shaping preventive strategies.

Third, we question the global applicability of this new classification. Although the study is based on a national cohort in South Korea, the generalisability of MASLD and MetALD classifications on a global scale remains uncertain, given the diverse metabolic profiles, lifestyle habits and alcohol consumption patterns across different regions. Significant differences in cancer risk between Western and Asian populations highlight the need for cross-national cohort studies to verify the universality of these classifications across diverse populations [4, 5].

Lastly, although the study accounts for multiple known confounders (e.g., age, sex, BMI, diabetes and blood pressure), the role of unmeasured confounders cannot be entirely ruled out. Genetic factors, in particular, play a significant role in the development of MASLD and MetALD. Recent studies have shown that genetic variants such as PNPLA3 substantially increase the risk of alcohol-related and metabolic liver diseases [3]. While Park et al. emphasise metabolic and lifestyle factors, the interplay between genetic and metabolic pathways may further exacerbate cancer risk. We recommend that future research incorporates genetic factors to provide a more comprehensive assessment of the carcinogenic mechanisms underlying MASLD and MetALD.

In conclusion, while Park et al.'s study lays an important foundation for understanding the cancer risks associated with MASLD and MetALD, further research is needed to clarify its clinical implications and global relevance. Addressing these issues in depth will help refine prevention and intervention strategies to reduce the cancer burden associated with these newly defined conditions.

Qiang Hu: writing – review and editing, writing – original draft. Xiyin Yang: writing – review and editing.

The authors declare no conflicts of interest.

This article is linked to Park et al papers. To view these articles, visit https://doi.org/10.1111/apt.18286 and https://doi.org/10.1111/apt.18412.