To the Editor:
We read with great interest the study by Song et al.,1 which evaluated the predictive value of the SPISE and METS-IR indices for identifying metabolic dysfunction-associated steatotic liver disease (MASLD) in children and adolescents. While the authors emphasized the practical advantages of using surrogate markers of insulin resistance, we would like to raise several important issues that were not addressed in the article.
First, it is important to note that due to privacy and ethical considerations, NHANES does not publicly release alcohol use data for participants under the age of 18.2 However, according to the 2022 National Survey on Drug Use and Health (NSDUH), 15% of US adolescents reported drinking alcohol in the past month, and 8% reported binge drinking.3 Without individual-level data on alcohol consumption, it is not possible to differentiate MASLD from early alcohol-related liver disease (ALD), nor to rule out mixed etiologies. Future research is needed to better describe patterns of alcohol use among adolescents and their relationships with cardiometabolic risk factors and hepatic steatosis.4 Moreover, the study did not account for rare but clinically important monogenic diseases that can mimic MASLD, such as lysosomal acid lipase deficiency and familial partial lipodystrophy. Although uncommon, these genetic disorders are often associated with hepatic steatosis, insulin resistance, and dyslipidemia, features that overlap with the diagnostic profile of MASLD.5 In pediatric patients with severe or atypical metabolic features, such conditions may be misclassified as MASLD, potentially confounding the observed associations between SPISE/METS-IR and liver fat.
Another key limitation lies in the limited sensitivity of these surrogate markers in clinical practice, despite promising AUC values reported in the NHANES cohort. For example, when a SPISE threshold of <7.004 was applied in a real-world Korean pediatric cohort, sensitivity was only 79%, meaning that approximately one in five children with MASLD would be missed. This level of underdiagnosis limits the utility of SPISE as a reliable screening tool in diverse pediatric populations. By contrast, MRI-proton density fat fraction (MRI-PDFF) remains the only validated non-invasive method capable of accurately quantifying liver fat content in children.6 MRI-PDFF can detect hepatic steatosis with >95% sensitivity at fat fractions as low as 5% and is considered the non-invasive gold standard for pediatric liver fat quantification.6 Without confirmation by MRI-PDFF or liver biopsy, the diagnostic performance of SPISE and METS-IR in identifying MASLD remains uncertain and may be limited, particularly in early-stage MASLD, where sensitivity is crucial to initiate timely lifestyle interventions and prevent fibrosis progression.
In conclusion, we commend Song et al. for their work.1 Their study provides valuable insight, but further in-depth research and validation are necessary to ensure that non-invasive screening tools for MASLD are applied accurately and meaningfully in pediatric clinical practice.
Financial support
The authors did not receive any financial support to produce this manuscript.
Authors’ contributions
Sheng Li: Writing – original draft. Qianqian Mao– review & editing.
Conflict of interest
The authors declare that they have no conflict of interest.
Please refer to the accompanying ICMJE disclosure forms for further details.
Footnotes
Author names in bold designate shared co-first authorship
Supplementary data to this article can be found online at https://doi.org/10.1016/j.jhepr.2025.101522.
Appendix A. Supplementary data
The following are the Supplementary data to this article:
References
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