遗传性短端粒与肝病的风险存在关联，而较长的端粒则更易于癌症发生。端粒长度与肝细胞癌和胆管癌的风险关联尚不明确。我们在63,272名丹麦普通人群中使用多重PCR测量了白细胞端粒长度。在线性回归模型中，端粒长度与血浆丙氨酸转氨酶浓度无关（β = 4 ×10⁻⁶，p值 = 0.06），且没有非线性关系的迹象。我们使用Cox回归分析测试了端粒长度与肝硬化、肝细胞癌和胆管癌的风险关联。在中位随访时间为11年的期间，出现了241例肝硬化、76例肝细胞癌和112例胆管癌。端粒长度与肝硬化的风险呈反向线性关联（p值 = 0.004，非线性关联p值 = 0.27）。与端粒最长四分位数相比，端粒最短四分位数的个体患肝硬化的风险增加2.25倍。端粒长度与肝细胞癌的风险呈非线性关联（p值 = 0.009，非线性关联p值 = 0.01）。这种关系呈倒J型，端粒长度越短，风险越高。与端粒最长四分位数相比，端粒最短四分位数的个体患肝细胞癌的风险增加2.29倍。端粒长度与胆管癌的风险呈线性反向关联。与端粒最长四分位数相比，端粒最短四分位数的个体患胆管癌的风险增加1.86倍。端粒长度较短与肝硬化、肝细胞癌和胆管癌的风险增加有关。版权所有©2023年美国肝病研究协会。

Inherited short telomeres are associated with risk of liver disease, whereas longer telomeres predispose to cancer. The association between telomere length and risk of hepatocellular carcinoma and cholangiocarcinoma remains unknown.We measured leukocyte telomere length using multiplex PCR in 63,272 individuals from the Danish general population. Telomere length and plasma alanine transaminase concentration were not associated (β = 4 ×10⁻⁶, p-value = 0.06) in a linear regression model, without any signs of a non-linear relationship. We tested the association between telomere length and risk of cirrhosis, hepatocellular carcinoma, and cholangiocarcinoma using Cox regression. During a median follow-up of 11 years, 241, 76, and 112 individuals developed cirrhosis, hepatocellular carcinoma, and cholangiocarcinoma, respectively. Telomere length and risk of cirrhosis were inversely and linearly associated (p-value = 0.004, p for nonlinearity = 0.27). Individuals with telomeres in the shortest vs. longest quartile had a 2.25-fold higher risk of cirrhosis. Telomere length and risk of hepatocellular carcinoma were nonlinearly associated (p-value = 0.009, p-value for nonlinearity = 0.01). This relationship resembled an inverted J-shape, with the highest risk observed in individuals with short telomeres. Individuals with telomeres in the shortest vs. longest quartile had a 2.29-fold higher risk of hepatocellular carcinoma. Telomere length was inversely and linearly associated with the risk of cholangiocarcinoma. Individuals with telomeres in the shortest vs. longest quartile had a 1.86-fold higher risk of cholangiocarcinoma.Shorter telomere length is associated with a higher risk of cirrhosis, hepatocellular carcinoma, and cholangiocarcinoma.Copyright © 2023 American Association for the Study of Liver Diseases.