COMPASS-PedPCOS: BMI-Independent Mechanistic Dissection of PCOS-Associated MASLD in Adolescent Girls With Obesity Using an Expanded Biomarker Panel - A Single-Center Pre-Pilot Clinical Study

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition of childhood and is closely linked to obesity and insulin resistance. Polycystic ovary syndrome (PCOS) frequently co-occurs with obesity in adolescent girls, and hyperandrogenism has been proposed as an additional hepatic insult. Because obesity is a powerful confounder, the independent contribution of hyperandrogenism to hepatic steatosis in adolescents remains poorly defined.

This study will be conducted at the Departments of Pediatric, Departments of Pediatric Endocrinology, Pediatric Gastroenterology and Hepatology, Medical Biochemistry, Medical Genetics, and Pediatric Radiology of Kayseri City Hospital, Kayseri, Türkiye. Participants will be allocated to three predefined groups. Group 1 comprises girls with PCOS and obesity, diagnosed according to adolescent-adapted Rotterdam criteria requiring both hyperandrogenism and oligo-anovulation, with a body mass index at or above the 95th percentile. Group 2 comprises girls with obesity without features of PCOS, matched to Group 1 for age and body mass index. Group 3 comprises healthy normal-weight girls between the 5th and 84th body mass index percentiles.

The central comparison is Group 1 versus Group 2, which equalises adiposity and therefore isolates the contribution of hyperandrogenism. Hierarchical regression models will additionally adjust for body mass index z-score, homeostatic model assessment of insulin resistance, and free androgen index. Hepatic steatosis will be quantified by the controlled attenuation parameter obtained during vibration-controlled transient elastography; liver stiffness will be assessed by vibration-controlled transient elastography and two-dimensional shear wave elastography.

A single venous blood sample will be obtained at the study visit. Serum will be separated and stored at minus 80 degrees Celsius until batch analysis, and genomic DNA will be isolated for TaqMan single nucleotide polymorphism genotyping of PNPLA3 rs738409 and HSD17B13 rs72613567. All enzyme-linked immunosorbent assay kits will be procured as a single lot, and intra-assay and inter-assay coefficients of variation together with spike-recovery validation will be documented for each kit.

Data will be recorded in a REDCap electronic case report form in accordance with ALCOA+ principles. The study is exploratory and is designed to generate effect-size and variance estimates for a subsequent validation study. Reporting will follow the STROBE statement, and non-invasive diagnostic performance analyses will follow the STARD 2015 statement. The study is also referred to as COMPASS-PedPCOS in institutional, ethics committee and funding documents.