Editorial: Prevalence of Suspected Metabolic Dysfunction-Associated Steatotic Liver Disease in Adolescents in the United States Using Updated Diagnostic Criteria

Abstract

In 2023, diagnostic criteria for metabolic dysfunction-associated steatotic liver disease (MASLD) were updated to require hepatic steatosis with one or more cardiometabolic risk factors, including overweight, obesity, dysglycaemia, dyslipidaemia or hypertension [1]. Prior diagnosis of nonalcoholic fatty liver disease (NAFLD) focused primarily on excluding other aetiologies and did not require cardiometabolic risk factors. Among US adolescents in the National Health Examination and Nutrition Surveys (NHANES) 2011–2018, an estimated 16.5% had NAFLD [2]; however, the prevalence of MASLD under the new diagnostic criteria remained uncertain.

To estimate the prevalence of MASLD among US adolescents, Noon et al. [3] evaluated the association of elevated ALT level, a validated biomarker for hepatic steatosis [4], with cardiometabolic risk factors in a 2011–2020 NHANES sample of youth, ages 12–19 years. Among the 14.6% with elevated ALT (Figure 1), 77% met cardiometabolic criteria for MASLD (11% overall), defined as paediatric overweight/obesity, elevated waist circumference, triglyceride, fasting glucose, haemoglobin A1C levels and/or low high-density lipoprotein. Body mass index had the strongest association with elevated ALT. Among those without cardiometabolic risks, 0.7% had viral hepatitis, 1.9% had potential medication hepatotoxicity, and 20.2% had cryptogenic hepatitis.

The 11% prevalence of MASLD was one third lower than the recent estimate of NAFLD in adolescents (16.5%) [2], although concordance could not be fully assessed without imaging or biopsy confirmation of hepatic steatosis. Notably, a substantial proportion with elevated ALT (23%) lacked any cardiometabolic risk factors, with 88% of these having cryptogenic elevation. Overall, 7% of adolescents with healthy weight and no other cardiometabolic risk factors had elevated ALT. Conversely, 50% of adolescents with normal ALT had at least one cardiometabolic risk factor. Without validated liver imaging (MRI proton-density fat fraction in children [5]), abnormal hepatic steatosis could not be assessed. One open question is whether childhood onset of hepatic steatosis may precede the later development of hepatitis or cardiometabolic risk factors. The lack of longitudinal follow-up and precise magnetic resonance liver imaging precludes answering this question in NHANES.

Another key limitation is the lack of information on alcohol use in this publicly available NHANES dataset. In a 2022 national survey of US adolescents, 15% reported drinking alcohol in the past month, and 8% reported binge drinking [6]. Further research is needed to fully characterise patterns of alcohol use and associations with ALT elevation, cardiometabolic risk factors and hepatic steatosis in adolescents [7]. This study could also not ascertain monogenic metabolic disorders that can mimic MASLD. While rare, several monogenic disorders associated with hepatic steatosis, such as lysosomal acid lipase deficiency or partial lipodystrophy syndromes, often have concurrent dyslipidaemia and/or insulin resistance, so they may be misclassified as MASLD [8].

Under current diagnostic criteria, MASLD remains the most common liver disease in US adolescents in NHANES, affecting an estimated 11%. Notably, however, another one in five adolescents with cryptogenic hepatitis did not meet the criteria for MASLD. Additional research is needed to identify potential causes, including the potential for injury from endocrine-modifying chemical exposures and toxins, including alcohol [9]. Ideally, future studies should include validated imaging measures to more precisely estimate the population prevalence of youth-onset MASLD.

Julie Bonn: writing – review and editing. Stavra A. Xanthakos: writing – original draft, writing – review and editing, conceptualization.

Julie Bonn has served as a speaker for Ipsen and as an advisory board member for Echosens. Stavra Xanthakos has served as a consultant for Madrigal Pharmaceuticals and receives research funding to her institution from Target RWE.

This article is linked to Noon et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70022 and https://doi.org/10.1111/apt.70092.