Fibrosis and Perinatal Features Correlated with Telomere Shortening in Pediatric Metabolic Dysfunction-Associated Steatotic Liver Disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly prevalent condition in both adults and children. Dysregulated telomere maintenance has been proposed as a mechanism underlying disease progression, although pediatric evidence remains limited and controversial. This study aimed to investigate the relationship between telomere length (TL) and hepato-metabolic features in children with MASLD. A total of 212 pediatric patients with biopsy-proven MASLD and 40 controls were enrolled. Telomere length in leukocytes (LTL) and liver tissue (HTL) was measured using quantitative polymerase chain reaction, and telomerase reverse transcriptase (TERT) mRNA and protein expression were also evaluated. Associations between TL and clinical, metabolic, and perinatal variables were analyzed. Children with MASLD showed significantly shorter LTL and HTL compared to controls. Shorter LTL was observed in more advanced steatohepatitis (MASH) and was associated with fibrosis severity. TERT expression was reduced in patients. LTL was also associated with perinatal factors, including preterm birth and low birthweight. Multivariable analysis identified MASH, fibrosis, and small-for-gestational-age status as independently associated with shorter LTL. In conclusion, LTL is associated with disease severity in pediatric MASLD, particularly fibrosis. These findings support a potential role of telomere dynamics in disease progression, although causal relationships require confirmation in longitudinal studies.