Fibrosis and birthweight correlated with telomere shortening in paediatric metabolic dysfunction-associated steatotic liver disease

Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging health concern in both children and adults. A few studies have suggested that dysregulation of telomere-maintaining processes may be a molecular mechanism involved in the disease; however, data in paediatric patients are controversial. This study aimed to evaluate the relationship between telomere length (TL) and hepato-metabolic features in a cohort of children with MASLD. Methods In all, 212 paediatric patients with biopsy-proven MASLD and 31 controls were enrolled in the Hepatology Unit of Bambino Gesù Children's Hospital. TL of leukocytes (LTL) and hepatic cells (HTL) was measured by quantitative polymerase chain reaction (qPCR). Telomerase reverse transcriptase (TERT) mRNA and protein levels were evaluated in a subgroup of liver samples using qPCR and immunofluorescence analyses. TL data association with hepato-metabolic and perinatal features was evaluated using different approaches. Results Our results revealed that children with MASLD had significantly lower LTL and HTL than the control children. TL shortening worsened in more advanced phases of the disease (MASH) and was associated with fibrosis grade. TERT expression was lower in the liver of patients than in controls. LTL was significantly associated with preterm birth and birthweight, and a general linear model highlighted the impact of MASH, fibrosis, and being born small for gestational age on LTL decrease. Conclusion In conclusion, our study demonstrated for the first time a strong relationship between TL and pediatric MASLD-related features, mainly fibrosis. Further studies are needed to clarify the causal relationship between MASH, fibrosis, birthweight and TL.