Leucocyte telomere shortening is associated with nonalcoholic fatty liver disease-related advanced fibrosis

Telomere length and telomerase have been linked with cirrhosis and hepatocellular carcinoma. However, the impact of telomere length on nonalcoholic fatty liver disease and advanced fibrosis in a large national population sample is not well understood.

Cross-sectional data from the National Health and Nutrition Examination Survey 1999-2002 were utilized. Suspected nonalcoholic fatty liver disease was diagnosed if serum alanine aminotransferase was >30 IU/L for men and >19 IU/L for women in the absence of other causes of chronic liver disease. Presence of advanced fibrosis was determined by the nonalcoholic fatty liver disease fibrosis score, aspartate aminotransferase to platelet ratio index and FIB-4 score.

Of the 6738 participants (mean age 46.3 years, 48.4% male), suspected nonalcoholic fatty liver disease prevalence was inversely associated with leucocyte telomere length in young adults aged 20-39 years, though this was not seen in the overall population. Percentage of participants with advanced fibrosis increased corresponding with leucocyte telomere length (longest to shortest). The shortest quartile of leucocyte telomere length was associated with a significantly higher odds ratio (95% confidence interval) of advanced fibrosis of 2.36 (1.32-4.24) in a univariate model compared to the longest quartile, and 2.01 (1.13-3.58) in a multivariate model adjusted for age, gender, ethnicity, waist circumference, smoking, diabetes, hypertension, total cholesterol and high-density lipoprotein cholesterol (P for trend <.05 respectively).

In this large nationally representative sample of American adults, leucocyte telomere shortening was associated with increased risk of advanced fibrosis in the setting of suspected nonalcoholic fatty liver disease independent of other known risk factors.