ALT/HDL May Improve Pediatric MASLD Screening

Key Takeaways

• In a U.S. adolescent cohort paired with a Korean real-world pediatric cohort, ALT, ALT/AST, and ALT/HDL were associated with MASLD after adjustment.
• The derived ratios were similar to or slightly better than ALT alone, with ALT/HDL often performing best, although the NHANES total-population AUC was slightly higher for ALT/AST (0.77 vs 0.76).
• Study-derived ALT thresholds were lower than commonly used pediatric ALT cutoffs and were reported as more sensitive across subgroups.
• MASLD was more common above the study cutoffs across cohorts and sex strata.

Pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) often has to be detected with routine laboratory testing rather than biopsy or imaging, which may be less practical in children. Alanine aminotransferase (ALT) is widely available, but whether ALT alone or simple ratios such as ALT/aspartate aminotransferase (AST) and ALT/high-density lipoprotein cholesterol (HDL) can better flag hepatic steatosis with metabolic risk remains a common screening question. Investigators compared those markers across a U.S. adolescent sample and a Korean pediatric clinical cohort.

In a pediatric MASLD ALT-derived marker analysis, investigators performed a retrospective cross-sectional evaluation of 1,158 adolescents aged 12-18 years from the National Health and Nutrition Examination Survey (NHANES) 2017-2020 and 263 children and adolescents aged 18 years or younger from two Korean clinical centers. MASLD was defined as hepatic steatosis plus at least one metabolic risk factor. Steatosis was identified with vibration-controlled transient elastography using controlled attenuation parameter (CAP) >248 dB/m in NHANES and with abdominal ultrasonography in the clinical cohort. Cutoffs were derived in NHANES and then applied to the clinical cohort, with logistic regression and receiver operating characteristic (ROC) analyses used to assess association and discrimination.

After adjustment, ALT, ALT/AST, and ALT/HDL remained associated with MASLD in both datasets, with all p<0.001. All three ALT-based markers also showed discriminatory value in both settings.

Among U.S. adolescents in NHANES, the areas under the ROC curves (AUCs) were 0.73 for ALT, 0.77 for ALT/AST, and 0.76 for ALT/HDL. The derived ratios slightly exceeded ALT alone in this population-based dataset.

In the Korean clinical cohort, ALT and ALT/AST each had an AUC of 0.84, ALT/HDL had an AUC of 0.86, and the female subgroup reached 0.92 for ALT/HDL. Within these ALT-based comparisons, ALT/HDL showed the strongest discrimination. ROC and cutoff results for ALT, ALT/AST, and ALT/HDL identified total-population thresholds of ALT >14.50, ALT/AST >0.74, and ALT/HDL >0.29. In males, the thresholds were ALT >17.50, ALT/AST >0.86, and ALT/HDL >0.43. In females, the thresholds were ALT >13.50, ALT/AST >0.75, and ALT/HDL >0.26. The study-derived ALT thresholds were lower than commonly used pediatric ALT cutoffs, and the authors reported that the ALT, ALT/AST, and ALT/HDL thresholds showed higher sensitivity across subgroups. MASLD was more common above them in both cohorts and sex strata.

Interpretation of those findings remains bounded by a retrospective, cross-sectional design, a smaller clinical cohort, and steatosis definitions that differed between datasets. The authors described the sex-stratified clinical-cohort findings as exploratory. They also reported that hepatic steatosis index (HSI) was numerically higher than the ALT-based markers in both cohorts, so the results do not place ALT/HDL ahead of every comparator. Five-fold cross-validation was directionally consistent, and the clinical-cohort sex-stratified analyses were supported by high power, but those checks did not remove the underlying between-cohort differences.

According to the authors, ALT and ALT-derived markers provided practical prediction signals for pediatric MASLD across a population-based U.S. dataset and a Korean clinical cohort. Among the three ALT-based markers, ALT/HDL often showed the strongest discrimination, although the NHANES total-population AUC was slightly higher for ALT/AST. Prospective validation in larger and more diverse pediatric cohorts remains needed.

Clinician Questions

Why can’t the NHANES and Korean clinical-cohort AUCs be treated as directly interchangeable for pediatric MASLD?

Pediatric MASLD was defined with different steatosis reference methods in the two cohorts: CAP-based vibration-controlled transient elastography in NHANES and abdominal ultrasonography in the Korean clinical cohort. One dataset was population-based and the other was a smaller real-world clinic cohort, so cross-cohort performance is comparable in direction but not identical against the same reference standard.

Which pediatric patients do these ALT and ratio cutoffs apply to most directly?

These cutoffs map most directly to the populations that were studied: U.S. adolescents aged 12-18 years in NHANES and children and adolescents aged 18 years or younger from two Korean clinical centers. The thresholds were derived from NHANES and then applied to the clinical cohort, and the authors characterized the sex-stratified clinical-cohort findings as exploratory rather than definitive.

How did ALT-derived markers compare with TG/HDL and HSI for pediatric MASLD prediction?

ALT-derived markers generally outperformed triglyceride/high-density lipoprotein cholesterol (TG/HDL) across both cohorts, while hepatic steatosis index (HSI) showed numerically higher discrimination than the ALT-based markers. The authors nonetheless framed ALT, ALT/AST, and ALT/HDL as simpler routine-laboratory measures, which separates ease of use from highest overall discrimination.