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ADDRESSING THE COEXISTENCE OF LIVER DISEASES: MAFLD VS. MASLD
FRAMEWORKS
Two definitions for liver disease due to metabolic dysfunction are currently utilized, namely MAFLD and
MASLD. One of the fundamental differences between the two approaches is how they address the
coexistence of liver diseases when metabolic dysfunction-associated liver disease coexists with another liver
condition.

The MASLD framework introduces a distinct term called MetALD to address this issue. In this model, cases
in which metabolic dysfunction and significant alcohol consumption occur simultaneously at one time
point in the patient’s course are classified as MetALD. In contrast, the MAFLD framework espoused the
concept of dual etiology encompassing the coexistence of MAFLD with any other liver disease, including,
but not limited to, alcohol consumption. This approach refrains from complicating the classification with
the introduction of new terms. To better understand the implications of these differing approaches, the next
section will provide a focused comparison based on key aspects such as clinical applicability, global
suitability, research implications, and scalability.

FRAMEWORK ADAPTABILITY AND SCALABILITY
The frameworks for MAFLD and MASLD would have different implications for classification and
adaptability.

MASLD, by introducing MetALD, describes cases involving alcohol consumption above specified
thresholds with metabolic dysfunction. This differentiation emphasizes the role of alcohol but applies this
[44]
logic selectively, overlooking other common liver diseases, such as viral hepatitis . Following this logic of
introducing various terms, should we also consider the role of viruses and develop new terms such as
“MetHBVLD” (Metabolic dysfunction-related and Hepatitis B-Related Liver Disease) or “MetHCVLD”
(Metabolic dysfunction-related and Hepatitis C-Related Liver Disease)? Furthermore, how should we
manage patients who qualify for MetALD while also being positive for hepatitis viruses? The precedent for
creating additional categories risks an overcomplication of classification systems, which could ultimately
undermine their scalability and utility in clinical and research contexts.

In contrast, MAFLD integrates dual etiology within a unified framework, accommodating the coexistence of
metabolic dysfunction alongside contributors like alcohol or viral hepatitis without creating separate
terminology. This inclusive approach prevents fragmentation and ensures consistency in diagnosis and
[14]
management across various clinical situations . By treating overlapping contributors as coexisting factors
within a single framework, MAFLD supports broader applicability and aligns with the evolving
understanding of liver disease. Its cohesive structure avoids the complexity introduced by MASLD’s
segmentation, facilitating scalability and adaptability for both global clinical practice and research
initiatives .
[45]
BEYOND THRESHOLDS: ADDRESSING ALCOHOL AND METABOLIC SYNERGY IN LIVER
DISEASE
MASLD definition employs predefined alcohol thresholds to differentiate alcohol-driven liver disease,
categorizing cases with significant alcohol consumption into separate MetALD classifications. While this
approach aims to delineate alcohol’s role as a primary contributor, it has substantial limitations.