Metabolic Dysfunction-Associated Steatotic Liver DiseasePedMASLD-PilotNCT07731360
Non-Invasive Diagnostic Panel for MASLD in Children With Obesity
An observational study of Metabolic Dysfunction-Associated Steatotic Liver Disease and Pediatric Obesity, run by Kayseri City Hospital at 1 site in Turkey (Türkiye).
Trial summary
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. Read more about this study
- Who is it for?
- Ages 8 to 18 years
- Conditions the study is for
- Metabolic Dysfunction-Associated Steatotic Liver Disease, Pediatric Obesity, Insulin Resistance Syndrome
- What is being tested?
- Non-Invasive Multi-Parameter Diagnostic Panel
- How many people
- 180 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 1 Jul 2026to 1 Jun 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
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- Untreated thyroid disorder, defined as thyroid-stimulating hormone below 0.5 or above 5.
- Total parenteral nutrition.
- Diabetic ketoacidosis.
- Inability to obtain informed consent.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Turkey (Türkiye)1 site
Kayseri City Hospital
Kayseri, 38080
Agah B ÖZTÜRK, Principal Investigator, Department of Pediatrics, MD, +90 352 315 77 00, agahbahadir.ozturk@sbu.edu.tr
About this study
Official title: 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.
Read the 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.
- Conditions
- Metabolic Dysfunction-Associated Steatotic Liver Disease, Pediatric Obesity, Insulin Resistance Syndrome
- Being tested
- Non-Invasive Multi-Parameter Diagnostic Panel
- Keywords
- MASLD, NAFLD, Pediatric Obesity, Non-Invasive Diagnosis, Cytokeratin-18, FGF21, RBP4, IGFBP7, Shear Wave Elastography, PNPLA3, Polygenic Risk Score, LASSO, Diagnostic Accuracy
- Medical subject headings
- Pediatric Obesity, Metabolic Syndrome, Non-alcoholic Fatty Liver Disease, Genetic Risk Score
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Non-Invasive Multi-Parameter Diagnostic PanelDiagnostic test
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Diagnostic Test: Non-Invasive Multi-Parameter Diagnostic Panel | |
| Group 2 MASLD-Negative | MASLD-Negative - Children with obesity not meeting the composite reference standard for MASLD. All candidate index tests are performed. Receives: Diagnostic Test: Non-Invasive Multi-Parameter Diagnostic Panel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Through study completion, an average of 12 months
Secondary outcomes (3)
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.
Measured: Through study completion, an average of 12 months
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.
Measured: Day 1 (single study visit)
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.
Measured: Through study completion, an average of 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2026
- Study start1 Jul 2026 (estimated)
- Primary completion1 Apr 2027 (estimated)
- Study completion1 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (40)Papers the sponsor has linked to this study.
- Other trials for Metabolic Dysfunction-Associated Steatotic Liver DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kayseri City Hospital
- Sponsor type
- Other government
- Collaborators
- Presidency of the Health Institutes of Türkiye
- Responsible party
- Principal investigator, Agah Bahadır Öztürk,MD, Kayseri City Hospital
- Investigators
- Agah B ÖZTÜRK, MD, Principal investigator, Kayseri City Hospital, Kayseri, Türkiye
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07731360
- Sponsor's protocol ID
- Etik C.D.No:1009(Kayseri CH)
- Other IDs
- TUSEB-2026-A4-U-55859
- Acronym
- PedMASLD-Pilot
- Status last verified
- Jul 2026
- First submitted
- 22 Jul 2026
- Last updated
- 30 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
McTeer M, Applegate D, Mesenbrink P, Ratziu V, Schattenberg JM, Bugianesi E, Geier A, Romero Gomez M, Dufour JF, Ekstedt M, Francque S, Yki-Jarvinen H, Allison M, Valenti L, Miele L, Pavlides M, Cobbold J, Papatheodoridis G, Holleboom AG, Tiniakos D, Brass C, Anstee QM, Missier P; LITMUS Consortium investigators. Machine learning approaches to enhance diagnosis and staging of patients with MASLD using routinely available clinical information. PLoS One. 2024 Feb 29;19(2):e0299487. doi: 10.1371/journal.pone.0299487. eCollection 2024.
PubMed 38421999Riley RD, Ensor J, Snell KIE, Harrell FE Jr, Martin GP, Reitsma JB, Moons KGM, Collins G, van Smeden M. Calculating the sample size required for developing a clinical prediction model. BMJ. 2020 Mar 18;368:m441. doi: 10.1136/bmj.m441. No abstract available.
PubMed 32188600Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig L, Lijmer JG, Moher D, Rennie D, de Vet HC, Kressel HY, Rifai N, Golub RM, Altman DG, Hooft L, Korevaar DA, Cohen JF; STARD Group. STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. BMJ. 2015 Oct 28;351:h5527. doi: 10.1136/bmj.h5527.
PubMed 26511519Lahtinen L, Hiltunen P, Vuorela N, Huhtala H, Kurppa K, Aitokari L. Screening and diagnosis of metabolic dysfunction-associated steatotic liver disease in children within public healthcare. Pediatr Res. 2025 Oct 30. doi: 10.1038/s41390-025-04540-w. Online ahead of print.
PubMed 41168404Schwimmer JB, Johnson JS, Angeles JE, Behling C, Belt PH, Borecki I, Bross C, Durelle J, Goyal NP, Hamilton G, Holtz ML, Lavine JE, Mitreva M, Newton KP, Pan A, Simpson PM, Sirlin CB, Sodergren E, Tyagi R, Yates KP, Weinstock GM, Salzman NH. Microbiome Signatures Associated With Steatohepatitis and Moderate to Severe Fibrosis in Children With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2019 Oct;157(4):1109-1122. doi: 10.1053/j.gastro.2019.06.028. Epub 2019 Jun 27.
PubMed 31255652Hahn JW, Lim JG, Lee KJ, Moon JS, Kim TH, Son Y, Yon DK, Lee YJ, Seo Y, Park J, Lee S, Kim D, Ko JS. Clinical and microbial correlates of response to lifestyle intervention in pediatric metabolic dysfunction-associated steatotic liver disease. Gut Pathog. 2026 Jan 18;18(1):6. doi: 10.1186/s13099-026-00798-5.
PubMed 41549262Yaser S, Yaser H, Mohammed HE, Nasser M, Darwish MK, Haseeb ME, Heiba AH, Ghonaim MM, Aboeldahab H, Bady Z. Efficacy of pharmacotherapies on pediatric patients with metabolic dysfunction-associated steatotic liver disease: a systematic review and network meta-analysis. BMC Gastroenterol. 2025 Dec 8;25(1):853. doi: 10.1186/s12876-025-04393-x.
PubMed 41361375Omana-Guzman I, Rosas-Diaz M, Martinez-Lopez YE, Perez-Navarro LM, Diaz-Badillo A, Alanis A, Bustamante A, Castillo-Ruiz O, Del Toro-Cisneros N, Esquivel-Hernandez DA, Garcia-Villalobos G, Garibay-Nieto N, Garcia-Oropesa EM, Hernandez-Martinez JC, Lopez-Sosa EB, Maldonado C, Martinez D, Membreno J, Moctezuma-Chavez OO, Munguia-Cisneros CX, Nava-Gonzalez EJ, Perales-Torres AL, Perez-Garcia A, Rivera-Marrero H, Valdez A, Vazquez-Chavez AA, Ramirez-Pfeiffer C, Carter KV, Tapia B, Vela L, Lopez-Alvarenga JC. Strategic interventions in clinical randomized trials for metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity in the pediatric population: a systematic review with meta-analysis and bibliometric analysis. BMC Med. 2024 Nov 21;22(1):548. doi: 10.1186/s12916-024-03744-x.
PubMed 39574069Song K, Lee E, Youn YH, Baik SJ, Shin HJ, Lee JW, Chae HW, Lee HS, Kwon YJ. Prediction Model for Insulin Resistance and Implications for MASLD in Youth: A Novel Marker, the Pediatric Insulin Resistance Assessment Score. Yonsei Med J. 2025 Aug;66(8):464-472. doi: 10.3349/ymj.2024.0442.
PubMed 40709676Keskin M, Kurtoglu S, Kendirci M, Atabek ME, Yazici C. Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics. 2005 Apr;115(4):e500-3. doi: 10.1542/peds.2004-1921. Epub 2005 Mar 1.
PubMed 15741351Kurtoglu S, Hatipoglu N, Mazicioglu M, Kendirici M, Keskin M, Kondolot M. Insulin resistance in obese children and adolescents: HOMA-IR cut-off levels in the prepubertal and pubertal periods. J Clin Res Pediatr Endocrinol. 2010;2(3):100-6. doi: 10.4274/jcrpe.v2i3.100. Epub 2010 Aug 2.
PubMed 21274322Yao K, Tarabra E, Sia D, Morotti R, Fawaz R, Valentino P, Santoro N, Caprio S, Liu S, Yimlamai D. Transcriptomic profiling of a multiethnic pediatric NAFLD cohort reveals genes and pathways associated with disease. Hepatol Commun. 2022 Jul;6(7):1598-1610. doi: 10.1002/hep4.1940. Epub 2022 Mar 21.
PubMed 35312185Jegodzinski L, Rudolph L, Castven D, Sayk F, Rout AK, Foh B, Holzen L, Meyhofer S, Schenk A, Weber SN, Rau M, Meyhofer SM, Schattenberg JM, Krawczyk M, Geier A, Mallagaray A, Gunther UL, Marquardt JU. PNPLA3 I148M variant links to adverse metabolic traits in MASLD during fasting and feeding. JHEP Rep. 2025 May 10;7(8):101450. doi: 10.1016/j.jhepr.2025.101450. eCollection 2025 Aug.
PubMed 40677694Gellert-Kristensen H, Richardson TG, Davey Smith G, Nordestgaard BG, Tybjaerg-Hansen A, Stender S. Combined Effect of PNPLA3, TM6SF2, and HSD17B13 Variants on Risk of Cirrhosis and Hepatocellular Carcinoma in the General Population. Hepatology. 2020 Sep;72(3):845-856. doi: 10.1002/hep.31238.
PubMed 32190914Li J, Hua W, Ji C, Rui J, Zhao Y, Xie C, Shi B, Yang X. Effect of the patatin-like phospholipase domain containing 3 gene (PNPLA3) I148M polymorphism on the risk and severity of nonalcoholic fatty liver disease and metabolic syndromes: A meta-analysis of paediatric and adolescent individuals. Pediatr Obes. 2020 Jun;15(6):e12615. doi: 10.1111/ijpo.12615. Epub 2020 Feb 5.
PubMed 32020770
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07731360
- Acronym / sponsor ID
- PedMASLD-Pilot / Etik C.D.No:1009(Kayseri CH)
- Conditions
- Metabolic Dysfunction-Associated Steatotic Liver Disease, Pediatric Obesity, Insulin Resistance Syndrome
- Keywords
- MASLD, NAFLD, Pediatric Obesity, Non-Invasive Diagnosis, Cytokeratin-18, FGF21, RBP4, IGFBP7
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- Kayseri City HospitalOther government
- Collaborators
- Presidency of the Health Institutes of Türkiye
- Study start
- 1 Jul 2026 (estimated)
- Primary completion
- 1 Apr 2027 (estimated)
- Study completion
- 1 Jun 2027 (estimated)
- First posted
- 28 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 MASLD-Positive | – | Diagnostic Test: Non-Invasive Multi-Parameter Diagnostic PanelMASLD-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. |
| Group 2 MASLD-Negative | – | Diagnostic Test: Non-Invasive Multi-Parameter Diagnostic PanelMASLD-Negative - Children with obesity not meeting the composite reference standard for MASLD. All candidate index tests are performed. |
Who may qualify
- Ages
- 8 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- 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.
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Non-Invasive Multi-Parameter Diagnostic PanelAll 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 test | Group 1 MASLD-Positive, Group 2 MASLD-Negative |
Primary outcome
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.
3 secondary outcomes
Comparative Discrimination of the Panel Versus Alanine Aminotransferase Alone and Ultrasonography Alone
Time frame: 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)
Incremental Discriminative Value of Serum IGFBP7
Time frame: Through study completion, an average of 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2026.
- Results publication: PubMed 38421999McTeer M, Applegate D, Mesenbrink P, Ratziu V, Schattenberg JM, Bugianesi E, Geier A, Romero Gomez M, Dufour JF, Ekstedt M, Francque S, Yki-Jarvinen H, Allison M, Valenti L, Miele L, Pavlides M, Cobbold J, Papatheodoridis G, Holleboom AG, Tiniakos D, Brass C, Anstee QM, Missier P; LITMUS Consortium investigators. Machine learning approaches to enhance diagnosis and staging of patients with MASLD using routinely available clinical information. PLoS One. 2024 Feb 29;19(2):e0299487. doi: 10.1371/journal.pone.0299487. eCollection 2024.
- Results publication: PubMed 32188600Riley RD, Ensor J, Snell KIE, Harrell FE Jr, Martin GP, Reitsma JB, Moons KGM, Collins G, van Smeden M. Calculating the sample size required for developing a clinical prediction model. BMJ. 2020 Mar 18;368:m441. doi: 10.1136/bmj.m441. No abstract available.
- Results publication: PubMed 26511519Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig L, Lijmer JG, Moher D, Rennie D, de Vet HC, Kressel HY, Rifai N, Golub RM, Altman DG, Hooft L, Korevaar DA, Cohen JF; STARD Group. STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. BMJ. 2015 Oct 28;351:h5527. doi: 10.1136/bmj.h5527.
- Results publication: PubMed 41168404Lahtinen L, Hiltunen P, Vuorela N, Huhtala H, Kurppa K, Aitokari L. Screening and diagnosis of metabolic dysfunction-associated steatotic liver disease in children within public healthcare. Pediatr Res. 2025 Oct 30. doi: 10.1038/s41390-025-04540-w. Online ahead of print.
- Results publication: PubMed 31255652Schwimmer JB, Johnson JS, Angeles JE, Behling C, Belt PH, Borecki I, Bross C, Durelle J, Goyal NP, Hamilton G, Holtz ML, Lavine JE, Mitreva M, Newton KP, Pan A, Simpson PM, Sirlin CB, Sodergren E, Tyagi R, Yates KP, Weinstock GM, Salzman NH. Microbiome Signatures Associated With Steatohepatitis and Moderate to Severe Fibrosis in Children With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2019 Oct;157(4):1109-1122. doi: 10.1053/j.gastro.2019.06.028. Epub 2019 Jun 27.
- Results publication: PubMed 41549262Hahn JW, Lim JG, Lee KJ, Moon JS, Kim TH, Son Y, Yon DK, Lee YJ, Seo Y, Park J, Lee S, Kim D, Ko JS. Clinical and microbial correlates of response to lifestyle intervention in pediatric metabolic dysfunction-associated steatotic liver disease. Gut Pathog. 2026 Jan 18;18(1):6. doi: 10.1186/s13099-026-00798-5.
- Results publication: PubMed 41361375Yaser S, Yaser H, Mohammed HE, Nasser M, Darwish MK, Haseeb ME, Heiba AH, Ghonaim MM, Aboeldahab H, Bady Z. Efficacy of pharmacotherapies on pediatric patients with metabolic dysfunction-associated steatotic liver disease: a systematic review and network meta-analysis. BMC Gastroenterol. 2025 Dec 8;25(1):853. doi: 10.1186/s12876-025-04393-x.
- Results publication: PubMed 39574069Omana-Guzman I, Rosas-Diaz M, Martinez-Lopez YE, Perez-Navarro LM, Diaz-Badillo A, Alanis A, Bustamante A, Castillo-Ruiz O, Del Toro-Cisneros N, Esquivel-Hernandez DA, Garcia-Villalobos G, Garibay-Nieto N, Garcia-Oropesa EM, Hernandez-Martinez JC, Lopez-Sosa EB, Maldonado C, Martinez D, Membreno J, Moctezuma-Chavez OO, Munguia-Cisneros CX, Nava-Gonzalez EJ, Perales-Torres AL, Perez-Garcia A, Rivera-Marrero H, Valdez A, Vazquez-Chavez AA, Ramirez-Pfeiffer C, Carter KV, Tapia B, Vela L, Lopez-Alvarenga JC. Strategic interventions in clinical randomized trials for metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity in the pediatric population: a systematic review with meta-analysis and bibliometric analysis. BMC Med. 2024 Nov 21;22(1):548. doi: 10.1186/s12916-024-03744-x.
- Results publication: PubMed 40709676Song K, Lee E, Youn YH, Baik SJ, Shin HJ, Lee JW, Chae HW, Lee HS, Kwon YJ. Prediction Model for Insulin Resistance and Implications for MASLD in Youth: A Novel Marker, the Pediatric Insulin Resistance Assessment Score. Yonsei Med J. 2025 Aug;66(8):464-472. doi: 10.3349/ymj.2024.0442.
- Results publication: PubMed 15741351Keskin M, Kurtoglu S, Kendirci M, Atabek ME, Yazici C. Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics. 2005 Apr;115(4):e500-3. doi: 10.1542/peds.2004-1921. Epub 2005 Mar 1.
- Results publication: PubMed 21274322Kurtoglu S, Hatipoglu N, Mazicioglu M, Kendirici M, Keskin M, Kondolot M. Insulin resistance in obese children and adolescents: HOMA-IR cut-off levels in the prepubertal and pubertal periods. J Clin Res Pediatr Endocrinol. 2010;2(3):100-6. doi: 10.4274/jcrpe.v2i3.100. Epub 2010 Aug 2.
- Results publication: PubMed 35312185Yao K, Tarabra E, Sia D, Morotti R, Fawaz R, Valentino P, Santoro N, Caprio S, Liu S, Yimlamai D. Transcriptomic profiling of a multiethnic pediatric NAFLD cohort reveals genes and pathways associated with disease. Hepatol Commun. 2022 Jul;6(7):1598-1610. doi: 10.1002/hep4.1940. Epub 2022 Mar 21.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Agah B ÖZTÜRK, MD principal investigator
Kayseri City Hospital, Kayseri, Türkiye
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Metabolic Dysfunction-Associated Steatotic Liver Disease and Pediatric Obesity, run by Kayseri City Hospital at 1 site in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 30 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Agah Bahadır Öztürk, MD (Türkiye ext. 05058116762, dr-agahoz@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diagnostic Performance of the LASSO-Regularized Multi-Parameter Panel for MASLD (time frame: Through study completion, an average of 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07731360, which also lists 40 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2026; AzTrials last refreshed its copy on 26 Oct 2026.