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Iruzubieta et al. Metab Target Organ Damage. 2025;5:10 https://dx.doi.org/10.20517/mtod.2024.143 Page 7 of 16

[40]
and chemokines . These cytokines not only contribute to hepatic insulin resistance and fibrosis but also
act systemically, exacerbating low-grade chronic inflammation, which is a key driver of atherosclerosis and
cardiovascular complications.

Several studies showed that MASLD is associated with a higher prevalence of arterial stiffness and
atherosclerotic plaques [41,42] . Arterial stiffness is an early marker of vascular damage, while the presence of
atherosclerotic plaques is a strong predictor of adverse cardiovascular events. The elevated prevalence of
these markers in MASLD patients, particularly those with advanced liver fibrosis, highlights an elevated
cardiovascular risk profile. Regarding MAFLD, a recent comparative analysis evaluating the relationship
between MASLD and MAFLD with coronary artery calcification (CAC) highlighted a distinct association
between MASLD and the severity of CAC, with MASLD being uniquely linked to the advanced stage of
[43]
CAC . However, another recent study found that MAFLD predicted CVD risk more effectively than
MASLD . The authors reported that the proportion of patients with high CVD risk was higher in the
[44]
MAFLD-only group (51.1%) compared to the MASLD-only group (35.0%). This finding aligns with
expectations, as patients in the MASLD-only group typically have normal weight and no more than one
feature of MetS. This reinforces the concept that, in cardiovascular medicine, the overall risk is largely
determined by the number of concurrent metabolic abnormalities in each patient . Additionally, including
[45]
patients with MetALD alongside those with MASLD is likely to identify a population with a similar CVD
risk profile. In fact, while current data are preliminary, a recent meta-analysis of five studies involving
nearly 10 million individuals found that MetALD was associated with worse outcomes compared to
[46]
MASLD, primarily due to an increase in CVD- and cancer-related mortality .
In conclusion, MASLD offers a significant advantage in cardiovascular risk management by more accurately
linking metabolic dysfunction with increased cardiovascular risk. This improvement facilitates better
stratification and clinical management of these patients, optimizing outcomes and reducing the burden of
cardiovascular complications.

SIMPLIFYING DIAGNOSIS AND EXPANDING PRIMARY CARE INVOLVEMENT
The new classification of MASLD has proven to be an invaluable tool for the early identification of at-risk
patients, particularly in primary care settings. This nomenclature facilitates the implementation of early
intervention strategies, aiding in the prevention of liver fibrosis progression and the effective management
of cardiovascular risk, offering a significant advantage over previous classifications .
[47]

One of MASLD’s key strengths is its simplicity and practicality in daily clinical practice. Unlike the MAFLD
classification, which includes the less commonly used metabolic markers, such as the HOMA-IR index and
high-sensitivity C-reactive protein (hs-CRP), MASLD relies on more accessible and routinely assessed
criteria . The metabolic markers required by MAFLD, while valuable in specific contexts, are not widely
[48]
employed in many clinical settings due to limited availability, making their broad application challenging.
MASLD, in contrast, employs commonly used clinical parameters such as central obesity, hypertension, and
blood glucose levels, factors that are readily available and integral to routine patient management in primary
care. This approach streamlines the identification of at-risk patients of liver disease progression, enabling
earlier intervention and improved management of liver disease from the primary care level.

The introduction of MASLD in place of NAFLD marks a paradigm shift in the approach to diagnosing this
liver disease. One of the most significant changes is the reduced reliance on liver biopsy as a diagnostic
standard, reflecting a transition toward more accessible, non-invasive diagnostic methods based on clinical
criteria. This shift not only addresses the need for greater diagnostic accessibility but also aligns with