A proposal to simplify the definition of metabolic dysfunction-associated steatotic liver disease in youths

In parallel with the childhood obesity epidemic, non-alcoholic fatty liver disease (NAFLD) has become the most widespread liver disease in youths, affecting approximately 15% of the general pediatric population and up to 40% of those with obesity (1). Youths with NAFLD have increased risks of early morbidity and mortality than their healthy peers (2). It is therefore crucial to identify youths with NAFLD early to mitigate adverse complications across their life spans.

However, there is increasing recognition that the term NAFLD is limited by its reliance on exclusionary criteria and the use of stigmatizing language, such as “alcoholic” or “fatty”. In 2023, a multisociety Delphi consensus statement was released on the nomenclature transition from NAFLD to metabolic dysfunction-associated steatotic liver disease (MASLD) (3). Unlike NAFLD, MASLD is defined as the presence of hepatic steatosis together with at least one cardiometabolic risk factor, including excessive adiposity, high blood pressure (BP), prediabetes/type 2 diabetes, or dyslipidemia. Notably, pediatric MASLD criteria involve numerous cut-offs for certain components, which can be cumbersome for clinical practice. For example, overweight (including obesity) is defined as body mass index (BMI) ≥ age- and sex-specific 85^th percentile cut-offs; central obesity is defined as waist circumference (WC) >95^th percentile values; and high BP is defined as systolic BP (SBP)/diastolic BP (DBP) ≥ age-, sex- and height-specific 95^th percentile values or ≥130/80 mmHg (age <13 years) or ≥130/85 mmHg (age ≥13 years). Studies have shown that high BP in youths often goes undiagnosed, even when measured (4). Despite electronic medical records being increasingly used, they are not always available in primary pediatric care or large-scale screening programs. Moreover, these complex thresholds are difficult to understand for youths and their parents/guardians, impeding self-monitoring or self-management. A simplified and precise definition of pediatric MASLD is deemed necessary, as underscored by the multisociety Delphi consensus statement.

We therefore proposed a simplified definition of pediatric MASLD. First, we recommended adopting static waist-to-height ratio (WHtR) cut-offs for assessing adiposity instead of the complex BMI 85^th or WC 95^th percentile-based definition (Figure S1). Consistent evidence has shown that WHtR performs comparably or better than BMI and WC in predicting cardiometabolic risk and MASLD in youths. A recent international study, involving 34,224 youths aged 6–18 years, has established static WHtR cut-offs of 0.50 for European and United States youths and 0.46 for Asian, South American, and African youths (5). These two cut-offs have been proven to be robust in identifying youths at increased cardiometabolic risk (5), and they have been endorsed by the recently proposed simplified definition of pediatric metabolic syndrome. Second, we proposed simplified SBP/DBP thresholds of 120/80 mmHg for youths aged 6–12 years and 130/80 mmHg for youths aged 13–17 years to define high BP (Figure S1). Likewise, international collaborative studies have confirmed that the simplified definition of high BP performs as well as the complex 95^th percentile-based definition in predicting subclinical cardiovascular damage in both youths and adults (6,7). Static BP cut-offs have been adopted in the Canadian and Japanese pediatric hypertension guidelines. The remaining three MASLD components were retained from the existing definition (Figure S1), as they were already simple and convenient to use.

Next, we validated the performance of our proposed simplified definition for screening MASLD and subclinical cardiovascular damage among Chinese youths, in comparison with the original consensus-based (“complex”) definition. Data were drawn from the Huantai Childhood Cardiovascular Health Cohort study, an ongoing longitudinal survey conducted in Zibo City, China. Wave 1 (baseline) of the study was carried out in 2017, enrolling 1,515 youths aged 6–11 years from one primary school. Subsequent data were collected every 2 years. At each wave, participants underwent standardized questionnaires, physical examinations, fasting blood tests, and ultrasound screenings. Participants with complete data on MASLD diagnosis at each wave were included to assess the performance of the simplified definition in identifying MASLD: 1,417 at Wave 1, 1,232 at Wave 2, 1,329 at Wave 3, and 1,154 at Wave 4. In addition, a prospective cohort design (baseline: 2021; follow-up: 2023; n=1,128, after further excluding participants with missing data on subclinical cardiovascular measures and covariates) was used to evaluate its association with subclinical cardiovascular damage [high carotid intima-media thickness (cIMT) and left ventricular hypertrophy (LVH)]. Hepatic steatosis and subclinical cardiovascular parameters were assessed in all four surveys by an experienced sonographer, who was blinded to participants’ clinical data, to ensure consistency in image acquisition and interpretation and to minimize interobserver variability using a portable ultrasound device (CX30, Philips, Bothell, WA, USA). MASLD was defined using either simplified or complex criteria in the absence of viral infection. Detailed information on anthropometric and biochemical assessments, ultrasonography examinations, covariates, and statistical analysis is provided in Appendix 1.

According to the complex definition, the prevalence of MASLD increased from 1.3% (n=18) at Wave 1 to 2.2% (n=27) at Wave 2, 3.9% (n=52) at Wave 3, and 7.9% (n=91) at Wave 4 (Figure 1). At each wave, the prevalence of MASLD based on the simplified definition was entirely consistent (100% agreement) with that estimated from the complex definition. Moreover, the two definitions identified an identical set of individuals (Cohen’s kappa =1.00). Similar patterns were observed across different sex and age groups (Table S1). Besides, MASLD defined by simplified criteria at baseline predicted subclinical cardiovascular damage at follow-up [high cIMT: adjusted odds ratio (OR) =5.60, 95% confidence interval (CI): 2.84–11.04; LVH: adjusted OR =6.28, 95% CI: 3.12–12.63] entirely consistent with the disease defined by complex criteria.

Figure 1 Prevalence of MASLD based on simplified definition vs. complex definition in four cross-sectional surveys (Wave 1 to Wave 4) of the Huantai Childhood Cardiovascular Health Cohort study. BP, blood pressure; HDL-C, high-density lipoprotein cholesterol; MASLD, metabolic dysfunction-associated steatotic liver disease; TG, triglycerides.

In summary, we proposed a simplified, evidence-based definition of MASLD for youths with the inclusion of simplified static cut-offs for adiposity and high BP, which showed perfect agreement with the complex definition in identifying MASLD and predicting subclinical cardiovascular damage among Chinese youths. We believe this simplified definition of pediatric MASLD will facilitate early identification and management of MASLD in clinical practice. Further studies are needed to validate whether this simplified definition performs as effectively as the complex definition in predicting long-term outcomes of pediatric MASLD when diagnosed using liver biopsy or proton density fat fraction.

Acknowledgments

The authors acknowledge all participants and research staff for their contributions to the study.

Footnote

Provenance and Peer Review: This article was a standard submission to the journal. The article has undergone external peer review.

Peer Review File: Available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-2025-599/prf

Funding: This work was supported by the National Natural Science Foundation of China (Nos. 82173538, 82473653, and 81673195 to B.X., and No. 82504436 to L.Y.), the Distinguished Professor of Changjiang Scholar Awards Program (No. T2023116 to B.X.), and the China Postdoctoral Science Foundation (No. 2023M742061 to L.Y.).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-2025-599/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was approved by the Ethics Committees of the School of Public Health, Shandong University (approval No. 20160308), and written informed consent was obtained from each participant and his/her guardians. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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