This prospective, single-center, two-group observational study evaluates a non-invasive multi-parameter diagnostic panel for metabolic dysfunction-associated steatotic liver disease (MASLD) in children with obesity. A total of 180 children aged 8 to 18 years with a body mass index at or above the 85th percentile for age and sex are planned for enrollment at a single tertiary pediatric center.
Each participant attends a single study visit comprising a fasting venous blood sample for serum biomarkers (cytokeratin-18 M30 and M65, fibroblast growth factor 21, retinol-binding protein 4, insulin-like growth factor binding protein 7, adiponectin, leptin, insulin, and routine biochemistry), abdominal ultrasonography with two-dimensional shear wave elastography, and genotyping of three MASLD-associated variants (PNPLA3 rs738409, TM6SF2 rs58542926, HSD17B13 rs72613567).
Participants are classified as MASLD-positive or MASLD-negative according to a guideline-based composite reference standard consisting of ultrasonographic steatosis grading and cardiometabolic risk factor criteria, assessed independently of the candidate index tests. The primary objective is to determine the discriminative performance, expressed as the area under the receiver operating characteristic curve, of a LASSO-regularized logistic regression model combining biomarker, elastography, and genetic predictors. No therapeutic intervention is assigned by the study protocol. Reporting will follow the STARD 2015 statement.
Age 8 to 18 years.
Body mass index at or above the 85th percentile for age and sex according to Turkish national growth references.
Hepatic steatosis of grade 1 or higher on abdominal ultrasonography and/or alanine aminotransferase at or above the biology-based upper limit of normal (26 U/L for boys; 22 U/L for girls), or persistent alanine aminotransferase elevation at or above twice the upper limit of normal (50 U/L for boys; 44 U/L for girls).
At least one cardiometabolic risk factor.
Viral hepatitis.
Autoimmune liver disease.
Wilson disease, alpha-1 antitrypsin deficiency, or hereditary hemochromatosis.
Use of hepatotoxic medication, including corticosteroids, methotrexate, valproate, amiodarone, or tamoxifen.
Children aged 8 to 18 years with a body mass index at or above the 85th percentile for age and sex, screened consecutively in the pediatric endocrinology outpatient clinic of a single tertiary center in Kayseri, Türkiye. Participants are enrolled prospectively using consecutive non-probability sampling and are classified as MASLD-positive or MASLD-negative according to a composite reference standard.
Cohort
Prospective
Non-Invasive Multi-Parameter Diagnostic Panel
Diagnostic testAll participants undergo the same set of index tests at a single study visit: a fasting venous blood sample for serum cytokeratin-18 M30 and M65, fibroblast growth factor 21, retinol-binding protein 4, insulin-like growth factor binding protein 7, adiponectin, leptin, insulin and routine biochemistry measured by enzyme-linked immunosorbent assay and standard laboratory methods; abdominal ultrasonography with two-dimensional shear wave elastography for liver stiffness; and genotyping of PNPLA3 rs738409, TM6SF2 rs58542926 and HSD17B13 rs72613567 for derivation of a three-variant polygenic risk score. These are observational measurements; no therapeutic intervention is administered.
Diagnostic Performance of the LASSO-Regularized Multi-Parameter Panel for MASLD
Discriminative performance of a LASSO-regularized logistic regression model combining serum biomarkers (cytokeratin-18 M30, cytokeratin-18 M65, fibroblast growth factor 21, retinol-binding protein 4, insulin-like growth factor binding protein 7), homeostatic model assessment of insulin resistance, liver stiffness measured by two-dimensional shear wave elastography, and a three-variant polygenic risk score, for classifying participants against the composite reference standard for MASLD. Metric: area under the receiver operating characteristic curve with bootstrap-derived 95% confidence interval.
Comparative Discrimination of the Panel Versus Alanine Aminotransferase Alone and Ultrasonography Alone
Comparison of the area under the receiver operating characteristic curve of the multi-parameter panel with that of alanine aminotransferase alone and of ultrasonography alone for classification against the composite reference standard, using the DeLong test for correlated curves.
Serum Biomarker Concentrations in MASLD-Positive Versus MASLD-Negative Children With Obesity
Comparison of serum concentrations of cytokeratin-18 M30 and M65, fibroblast growth factor 21, retinol-binding protein 4, insulin-like growth factor binding protein 7, adiponectin and leptin between participants classified as MASLD-positive and MASLD-negative. Units of measure as reported by the respective enzyme-linked immunosorbent assays.
Incremental Discriminative Value of Serum IGFBP7
Incremental contribution of serum insulin-like growth factor binding protein 7 to the classification model, evaluated by change in the area under the receiver operating characteristic curve, the net reclassification improvement, and the integrated discrimination improvement.
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Kayseri City Hospital
Lead sponsor
Presidency of the Health Institutes of Türkiye
Collaborator
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