Reclassifying pediatric NAFLD using the steatotic liver disease framework: A multicenter retrospective study from the NASH CRN

Abstract

Background and aims: The terminology for hepatic steatosis and NAFLD was revised under the umbrella of steatotic liver disease, with metabolic dysfunction-associated steatotic liver disease (MASLD) as the primary subtype. MASLD is defined by hepatic steatosis plus at least 1 cardiometabolic risk factor. A new category, Met-ALD, describes MASLD with alcohol consumption below the defined thresholds for alcohol-associated liver disease (ALD). While adult studies have demonstrated strong concordance between NAFLD and MASLD, the applicability of this framework in children remains unclear.

Approach and results: We assessed children clinically diagnosed with NAFLD and enrolled in the NASH CRN who had available liver histology. Clinical and demographic data, including body mass index, hepatotoxic medication use, and alcohol intake, were analyzed. Liver biopsies were centrally reviewed to confirm hepatic steatosis and evaluate for alternative etiologies. Participants were reclassified using the steatotic liver disease framework. Among 1019 children diagnosed with NAFLD, 858 (84%) met MASLD criteria. The average number of cardiometabolic risk factors per participant was 2.7±1.1; 41 (4.7%) met all five. Thirty-three participants (3.2%) were reclassified as Met-ALD, a prevalence that rose to 5.4% among adolescents. Sixty-six children (6.5%) were reclassified as drug-induced steatotic liver disease.

Conclusions: Most children with NAFLD met MASLD criteria, but nearly 1 in 6 were reclassified based on alcohol use or medication exposure. These findings highlight the need for a systematic diagnostic approach accounting for metabolic risk factors, alcohol use, and medication-related liver injury.

Keywords: DILI; adolescent health; alcohol consumption; cardiometabolic risk; metabolic dysfunction–associated steatotic liver disease.