학술논문

Shorter leukocyte telomere length protects against NAFLD progression in children
Document Type
article
Source
Scientific Reports. 13(1)
Subject
Biomedical and Clinical Sciences
Clinical Sciences
Clinical Research
Chronic Liver Disease and Cirrhosis
Hepatitis
Digestive Diseases
Liver Disease
Prevention
Clinical Trials and Supportive Activities
2.1 Biological and endogenous factors
Aetiology
Oral and gastrointestinal
Inflammatory and immune system
Adult
Child
Humans
Disease Progression
Inflammation
Leukocytes
Liver Cirrhosis
Non-alcoholic Fatty Liver Disease
Telomere
Language
Abstract
Leukocyte telomere length (LTL) gets shorter with each cell division and is also sensitive to reactive oxygen species damage and inflammatory processes. Studies in adults with non-alcoholic fatty liver disease (NAFLD) have found that increased fibrosis but not ALT levels are associated with shorter LTL. Few pediatric studies have been conducted; as such, we sought to evaluate potential associations between LTL and liver disease and liver disease progression in pediatric patients. Using data from the Treatment of NAFLD in Children (TONIC) randomized controlled trial, we assessed the potential predictive relationship between LTL and liver disease progression based on two successive liver biopsies over 96 weeks. We assessed the potential relationship between LTL and child age, sex, and race/ethnicity and features of liver disease including components of histology. We subsequently evaluated predictors for improvement in non-alcoholic steatohepatitis (NASH) at 96 weeks including LTL. We also assessed predictors of lobular inflammation improvement at 96 weeks using multivariable models. Mean LTL at baseline was 1.33 ± 0.23 T/S. Increasing lobular and portal inflammation were associated with longer LTL. In multivariable models, greater lobular inflammation at baseline was associated with longer LTL (Coeff 0.03, 95% CI 0.006-0.13; p = 0.03). Longer LTL at baseline was associated with worsening lobular inflammation at 96 weeks (Coeff 2.41, 95% CI 0.78-4.04; p