Abstract

Telomere length has been linked to the prevalence and progression of metabolic disease. However, clinical implications of telomere length in biopsy-proven non-alcoholic fatty liver disease (NAFLD) patients remain unclear. Therefore, this study aimed to investigate the association of telomere length with the histological severity of NAFLD. The cross-sectional data derived from the prospectively enrolled Boramae NAFLD registry (n = 91) were analyzed. The liver tissues and clinical information were obtained from both NAFLD patients and non-NAFLD subjects. Binary logistic regression was performed to identify the independent association between telomere length and the histological severity of NAFLD. A total of 83 subjects with or without biopsy-proven NAFLD were included for analysis: non-NAFLD in 23 (27.7%), non-alcoholic fatty liver in 15 (18.1%), and non-alcoholic steatohepatitis (NASH) in 45 (54.2%). Telomere length measured from liver tissues showed a strong negative correlation (p < 0.001) with age, regardless of NAFLD status. Therefore, telomere length was corrected for age. Age-adjusted telomere length than decreased gradually with an increasing severity of fibrosis in patients with NAFLD (p < 0.028). In multivariate analysis, age-adjusted telomere length (odds ratio [OR] 0.59; 95% CI 0.37–0.92; p = 0.019) and high-density lipoprotein cholesterol (OR 0.94; 95% CI 0.80–0.99; p = 0.039) were independently associated with significant fibrosis. The age-adjusted telomere length tends to decrease along with the fibrosis stage of NAFLD. In particular, among the histological components of NAFLD, fibrosis severity seems to be related to telomere length in the liver.

Highlights

  • Telomere length has been linked to the prevalence and progression of metabolic disease

  • The prevalence of gender and type 2 diabetes mellitus (DM), body mass index (BMI), liver stiffness, controlled attenuation parameter, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gammaglutamyl transferase, glucose, triglycerides, and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly different between the two groups

  • This study investigated the relationship between non-alcoholic fatty liver disease (NAFLD) and telomere length using the liver tissue samples obtained from study subjects with biopsy-proven NAFLD

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Summary

Introduction

Telomere length has been linked to the prevalence and progression of metabolic disease. Clinical implications of telomere length in biopsy-proven non-alcoholic fatty liver disease (NAFLD) patients remain unclear. Age-adjusted telomere length than decreased gradually with an increasing severity of fibrosis in patients with NAFLD (p < 0.028). Age-adjusted telomere length (odds ratio [OR] 0.59; 95% CI 0.37–0.92; p = 0.019) and high-density lipoprotein cholesterol (OR 0.94; 95% CI 0.80–0.99; p = 0.039) were independently associated with significant fibrosis. Among the histological components of NAFLD, fibrosis severity seems to be related to telomere length in the liver. The dysfunction and mutation of telomerase involved in telomere length are closely related to various chronic diseases, including non-alcoholic fatty liver disease (NAFLD)[1]. Since NAFLD involves multiple environmental and genetic factors, various approaches and studies to understand the pathophysiology of NAFLD progression are needed (e.g., telomere shortening)

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