Collaborative Study from UPMC Children’s Pediatric Endocrinology and Gastroenterology Divisions Examines MASLD Risk in Adolescents with Obesity

A collaborative research study from the Divisions of Pediatric Endocrinology and Pediatric Gastroenterology, Hepatology and Nutrition at UPMC Children’s Hospital of Pittsburgh investigated how features of metabolic dysfunction-associated steatotic liver disease (MASLD) in adolescents with obesity relate to circulating androgens, insulin sensitivity, and inflammatory markers.

The study, published in Hormone Research in Paediatrics, was led Mary Ellen Vajravelu, MD, MSHP, assistant professor of Pediatrics in the Division of Pediatric Endocrinology, and Silva Arslanian, MD, scientific director and principal investigator of the Center for Pediatric Research in Obesity and Metabolism, and the Richard L. Day Professor of Pediatrics and Clinical and Translational Science. The research was funded by a medical research grant from The Pittsburgh Foundation.

Summary of Findings and Clinical Insights

MASLD has become increasingly prevalent in adolescents with obesity and is commonly seen in girls with polycystic ovary syndrome (PCOS). While MASLD has traditionally been viewed through the lens of metabolic dysfunction, accumulating data suggests that hormonal and inflammatory pathways may also play an important role in hepatic fat accumulation and the progression to liver fibrosis. This study was designed to see how androgenemia, insulin resistance, and inflammation intersect with hepatic imaging biomarkers of MASLD in this population.

The study cohort included adolescents aged 12 to 18 years with obesity, comparing girls with and without PCOS and a group of boys. Dr. Vajravelu and colleagues measured hepatic fat fraction (HFF) and liver stiffness with MRI scans, along with glucose metabolism and circulating markers of inflammation.

The study found that hepatic fat accumulation was more pronounced in girls with PCOS compared to those without it, but hepatic fat levels were similar between girls without PCOS and boys. Measurements of liver stiffness did not vary in a statistically significant way across each of the study’s groups. However, hepatic fat and stiffness were associated with markers of reduced insulin sensitivity and with elevated glucose levels after an oral glucose challenge. Also, liver stiffness correlated with testosterone levels in girls without PCOS and with markers of inflammation in all of the cohorts.

The findings from Dr. Vajravelu and colleague’s research preliminarily show that MASLD risk in adolescents with obesity may be influenced by insulin resistance and systemic inflammation, and also by androgen exposure even in girls without a formal diagnosis of PCOS. The results point to the potential importance of evaluating hormonal and inflammatory markers when assessing hepatic risk in this population, but larger studies and additional research will need to be conducted to further validate these results.

Reference
Vajravelu ME, Shahid N, Chebli M, Stauffer T, Squires JE, Tadros S, Witchel SF, Arslanian S. Hepatic Steatosis and Stiffness in Adolescent Obesity are Linked to Androgenemia, Insulin Sensitivity, and Inflammation. Horm Res Paediatr. May 23, 2025: 1–11. Online ahead of print.