Non-Invasive Diagnostic Panel for MASLD in Children With Obesity (PedMASLD-Pilot)

July 29, 2026 updated by: Agah Bahadır Öztürk,MD, Kayseri City Hospital

A Non-Invasive Diagnostic Panel for MASLD in Children With Obesity: Evaluation of a Multiparametric Biomarker Panel and Genetic Risk Score Using LASSO-Regularized Logistic Regression - The PedMASLD-MultiOmics Pilot Study

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease of childhood and is closely associated with obesity. Liver biopsy, the histological reference standard, is not ethically acceptable as a routine screening tool in children because it requires general anaesthesia and carries procedural risk and sampling error. The currently used non-invasive screening tools, alanine aminotransferase and ultrasonography, have limited diagnostic accuracy when used alone. An accurate, non-invasive diagnostic approach for pediatric MASLD is therefore needed.

This single-center, prospective, two-group, exploratory pilot diagnostic classification study is conducted at Kayseri City Hospital, Kayseri, Türkiye. Children aged 8 to 18 years with a body mass index at or above the 85th percentile for age and sex, according to Turkish national growth references, are screened consecutively in the pediatric endocrinology outpatient clinic. Enrollment of 180 participants is planned, balanced by sex.

Each participant attends a single study visit of approximately three hours. After a 12-hour fast, a single venous blood sample is obtained for routine biochemistry, insulin, and the serum biomarker panel; serum and plasma aliquots are stored at -80 °C until batched analysis by enzyme-linked immunosorbent assay in duplicate with blinded internal controls. Abdominal ultrasonography is performed for hepatic steatosis grading, and liver stiffness is measured by two-dimensional shear wave elastography. A separate whole-blood sample is used for DNA isolation and genotyping of three MASLD-associated variants, from which a three-variant polygenic risk score is derived. Anthropometric measurements including waist circumference percentile, blood pressure, pubertal staging, and questionnaire-based nutritional and physical activity assessment are recorded at the same visit. No therapeutic intervention is assigned by the study protocol.

Participants are classified as MASLD-positive or MASLD-negative using a composite reference standard based on ultrasonographic steatosis grading together with cardiometabolic risk factor criteria, in accordance with current pediatric guidelines. To avoid incorporation bias, two-dimensional shear wave elastography is used only as a candidate predictor and does not contribute to the reference standard; reference standard assessment is performed blinded to biomarker and genotype results.

The analysis develops a LASSO-regularized logistic regression model combining serum biomarkers, liver stiffness, and the polygenic risk score, with internal validation by bootstrap resampling. Model discrimination is compared with alanine aminotransferase alone and with ultrasonography alone. Reporting will follow the STARD 2015 statement.

Study Type

Observational

Enrollment (Estimated)

180

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

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.

Description

Inclusion Criteria:

  • 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.
  • Written informed consent provided by a parent or legal guardian, with simplified assent for children aged 8 to 11 years and standard assent for children aged 12 years and older.

Exclusion Criteria:

  • 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.
  • Fasting duration shorter than 12 hours.
  • Active infection, defined as C-reactive protein above 10 mg/L.
  • Untreated thyroid disorder, defined as thyroid-stimulating hormone below 0.5 or above 5.
  • Total parenteral nutrition.
  • Diabetic ketoacidosis.
  • Inability to obtain informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Group 1 MASLD-Positive
MASLD-Positive - Children with obesity classified as having MASLD by the composite reference standard (ultrasonographic steatosis grading plus cardiometabolic risk factor criteria). All candidate index tests are performed.
Diagnostic test: Non-Invasive Multi-Parameter Diagnostic Panel
All 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.
Group 2 MASLD-Negative
MASLD-Negative - Children with obesity not meeting the composite reference standard for MASLD. All candidate index tests are performed.
Diagnostic test: Non-Invasive Multi-Parameter Diagnostic Panel
All 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diagnostic Performance of the LASSO-Regularized Multi-Parameter Panel for MASLD
Time Frame: Through study completion, an average of 12 months
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.
Through study completion, an average of 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparative Discrimination of the Panel Versus Alanine Aminotransferase Alone and Ultrasonography Alone
Time Frame: Through study completion, an average of 12 months
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.
Through study completion, an average of 12 months
Serum Biomarker Concentrations in MASLD-Positive Versus MASLD-Negative Children With Obesity
Time Frame: Day 1 (single study visit)
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.
Day 1 (single study visit)
Incremental Discriminative Value of Serum IGFBP7
Time Frame: Through study completion, an average of 12 months
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.
Through study completion, an average of 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kayseri City Hospital

Collaborators

Presidency of the Health Institutes of Türkiye

Investigators

  • Principal Investigator: Agah B ÖZTÜRK, MD, Kayseri City Hospital, Kayseri, Türkiye

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2026

Primary Completion (Estimated)

April 1, 2027

Study Completion (Estimated)

June 1, 2027

Study Registration Dates

First Submitted

July 22, 2026

First Submitted That Met QC Criteria

July 24, 2026

First Posted (Actual)

July 28, 2026

Study Record Updates

Last Update Posted (Actual)

July 30, 2026

Last Update Submitted That Met QC Criteria

July 29, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Etik C.D.No:1009(Kayseri CH)
  • TUSEB-2026-A4-U-55859 (Other Identifier: Health Institutes of Türkiye (TÜSEB))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified individual participant data underlying the published results, including serum biomarker concentrations, anthropometric, clinical and laboratory variables, and derived index values, will be available from the principal investigator upon reasonable request. Individual genotype data will be shared only in aggregate or as derived polygenic risk scores, in accordance with the ethics approval and applicable data protection legislation. Data will be shared with qualified researchers whose proposed use has been approved and is consistent with the original ethics approval. A data-use agreement will be required.

IPD Sharing Time Frame

Data will become available after publication of the main results and will remain available for 5 years thereafter, upon reasonable request to the principal investigator

IPD Sharing Access Criteria

Qualified researchers may request access by contacting the principal investigator. Requests will be evaluated for scientific merit and for consistency with the original ethics approval and the scope of participant consent. A data-use agreement must be executed before de-identified data are released.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe