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
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- Diagnostic Performance of the LASSO-Regularized Multi-Parameter Panel for MASLD
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 8 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
- •Total parenteral nutrition.
- •Diabetic ketoacidosis.
- •Inability to obtain informed consent.
研究组 & 干预措施
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.
干预措施: Non-Invasive Multi-Parameter Diagnostic Panel (Diagnostic Test)
Group 2 MASLD-Negative
MASLD-Negative - Children with obesity not meeting the composite reference standard for MASLD. All candidate index tests are performed.
干预措施: Non-Invasive Multi-Parameter Diagnostic Panel (Diagnostic Test)
结局指标
主要结局
Diagnostic Performance of the LASSO-Regularized Multi-Parameter Panel for MASLD
时间窗: 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.
次要结局
- Comparative Discrimination of the Panel Versus Alanine Aminotransferase Alone and Ultrasonography Alone(Through study completion, an average of 12 months)
- Serum Biomarker Concentrations in MASLD-Positive Versus MASLD-Negative Children With Obesity(Day 1 (single study visit))
- Incremental Discriminative Value of Serum IGFBP7(Through study completion, an average of 12 months)
研究者
Agah Bahadır Öztürk,MD
Principal Investigator, Department of Pediatrics
Kayseri City Hospital