Non-invasive biomarkers in pediatric MASLD: utility of gamma-glutamyltransferase for steatohepatitis and the FIB-4 index for fibrosis.

BACKGROUND

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly nonalcoholic fatty liver disease (NAFLD), is a growing pediatric health concern. Liver biopsy remains the gold standard for grading steatohepatitis and staging fibrosis, but its invasive nature necessitates reliable non-invasive alternatives, particularly for children. While adult-derived scoring systems like the FIB-4 index are widely used, their validity in pediatric populations is not well established. This study aimed to evaluate the diagnostic utility of the FIB-4 index for detecting advanced fibrosis and to assess the performance of other biomarkers, including gamma-glutamyltransferase (GGT), for differentiating metabolic dysfunction-associated steatohepatitis (MASH) from simple steatosis in children with biopsy-proven MASLD.

METHODS

This single-center, retrospective diagnostic accuracy study included 27 children (aged 5-18) with liver biopsy-confirmed MASLD. Histological staging was performed using the FLIP/SAF scoring system, with advanced fibrosis defined as stage ≥ 2. The diagnostic performance of non-invasive markers, including the FIB-4 index, AST to Platelet Ratio Index (APRI), and GGT, was evaluated using receiver operating characteristic (ROC) curve analysis to determine the area under the curve (AUC), sensitivity, and specificity for predicting advanced fibrosis and identifying MASH.

RESULTS

The cohort had a mean age of 11.7 years and was predominantly male (96.2%). A high prevalence of advanced fibrosis was observed, with 14 of 27 patients (51.9%) having fibrosis stage ≥ 2. The FIB-4 index demonstrated fair discriminatory ability for detecting advanced fibrosis (AUC = 0.725; 95% CI: 0.530-0.921), with an optimal cut-off of 0.215 yielding a sensitivity of 57.1% and specificity of 84.6%. In contrast, GGT emerged as an excellent marker for differentiating MASH from MASLD (AUC = 0.914; 95% CI: 0.804-0.980). A GGT cut-off value of 20 IU/L provided a sensitivity of 77.3% and a specificity of 100% for identifying MASH.

CONCLUSION

The findings of this study suggest that the FIB-4 index may have some utility in identifying advanced fibrosis in pediatric MASLD, although its performance might be limited compared to adult cohorts. Furthermore, GGT shows promise as a simple and non-invasive biomarker for distinguishing MASH from simple steatosis in children. Integrating GGT into future screening protocols could contribute to improved risk stratification, potentially aiding in the identification of high-risk patients who may benefit from earlier, more intensive clinical interventions or prioritized consideration for liver biopsy.