Inverse Association of Telomere Length With Liver Disease and Mortality in the US Population.

Physiologic aging leads to attrition of telomeres and replicative senescence. An acceleration of this process has been hypothesized in the progression of chronic liver disease. We sought to examine the association of telomere length (TL) with liver disease and its impact on mortality risk. A cohort of 7,072 adults with leukocyte TL measurements from the National Health and Nutrition Examination Survey 1999‐2002 with mortality follow‐up through 2015 was analyzed. Liver disease was defined by aminotransferase levels and classified into etiology‐based and advanced fibrosis categories. Multivariable‐adjusted linear regression models estimated effect sizes, with 95% confidence intervals (CIs), of the presence of liver disease on TL. Cox regression models evaluated associations between TL and all‐cause mortality risk using adjusted hazard ratios (HRs). The cohort was representative of the US population with mean age 46.1 years and mean TL 5.79 kilobase pairs. No overall association between TL and liver disease was found; however, there was a significant negative association of TL and advanced liver fibrosis in individuals aged 65 and above. The liver disease cohort (HR 1.22, 95% CI 0.99‐1.51) and those with metabolic syndrome (HR 1.26, 95% CI 0.96‐1.67) had increased mortality risk with shorter TL. The relationship between TL and all‐cause mortality was stronger in women (HR 1.51, 95% CI 1.02‐2.23) and in non‐Hispanic Whites (HR 1.37, 95% CI 1.02‐1.84). Conclusion: Shortened leukocyte TL is independently associated with advanced liver disease at older ages, and with a higher risk of all‐cause mortality in those with liver disease. These associations reaffirm the need to better understand the role of telomeres in the progression of liver disease. We examined the association of peripheral telomere length with liver disease and assessed its impact on mortality using data from the National Health and Nutrition Examination Survey (NHANES). We discovered that shortened leukocyte telomere length is independently associated with advanced liver disease at older ages, and also with a higher risk of all‐cause mortality in those with liver disease.

生理衰老导致端粒损耗和复制性衰老。据推测，在慢性肝病的进展过程中，这一过程会加速。我们试图研究端粒长度（TL）与肝病的关联及其对死亡风险的影响。对1999 - 2002年美国国家健康与营养检查调查中7072名进行了白细胞端粒长度测量且随访至2015年的成年人队列进行了分析。肝病通过转氨酶水平定义，并分为基于病因和晚期纤维化类别。多变量调整线性回归模型估计了肝病存在对端粒长度影响的效应大小及95%置信区间（CIs）。考克斯回归模型使用调整后的风险比（HRs）评估了端粒长度与全因死亡风险之间的关联。该队列代表了美国人群，平均年龄为46.1岁，平均端粒长度为5.79千碱基对。未发现端粒长度与肝病之间存在总体关联；然而，在65岁及以上个体中，端粒长度与晚期肝纤维化呈显著负相关。肝病队列（风险比1.22，95%置信区间0.99 - 1.51）和患有代谢综合征的人群（风险比1.26，95%置信区间0.96 - 1.67）端粒长度较短时死亡风险增加。端粒长度与全因死亡之间的关系在女性（风险比1.51，95%置信区间1.02 - 2.23）和非西班牙裔白人（风险比1.37，95%置信区间1.02 - 1.84）中更强。结论：白细胞端粒长度缩短在老年时与晚期肝病独立相关，且在肝病患者中与全因死亡风险较高相关。这些关联再次表明需要更好地理解端粒在肝病进展中的作用。 我们利用美国国家健康与营养检查调查（NHANES）的数据研究了外周端粒长度与肝病的关联，并评估了其对死亡率的影响。我们发现白细胞端粒长度缩短在老年时与晚期肝病独立相关，并且在肝病患者中也与全因死亡风险较高相关。