Liver Aging Index: A Noninvasive Score for Liver Biological Aging and Liver‐Related Outcomes in Multicohorts

作者：Zhiyu Wu, Shanshan Wu, Shuyao Song, Yating Huang, C Q Yu, D J Y Sun, P Pei, Ling Yang, Yiping Chen, H D Du, Robin Walters, Iona Millwood, Hao Xu, Xiaoming Yang, J S Chen, Seung Up Kim, Salvatore Petta, Atsushi Nakajima, Emmanuel A. Tsochatzis, Jérôme Boursier, Elisabetta Bugianesi, W K Chan, Manuel Romero‐Gomez, José Luis Calleja, Victor de Lédinghen, Laurent Castéra, Arun J. Sanyal, George Boon‐Bee Goh, Philip Noel Newsome, Jian‐Gao Fan, Michelle Lai, X Y Zhou, Z M Chen, Jun Lv, Liming Li, Vincent Wai‐Sun Wong, Ming‐Hua Zheng, Y J Pang, the China Kadoorie Biobank Collaborative Group and VCTE‐Prognosis Study Group · 发表于：Aging Cell · 年份：2026 · DOI：10.1111/acel.70565 · 研究领域：Liver Disease Diagnosis and Treatment、Metabolomics and Mass Spectrometry Studies、Nutritional Studies and Diet

Biological aging is a key determinant of liver disease and mortality, but there is little evidence on noninvasive index for assessment of liver biological aging. We developed the Liver Aging Index (LAI) in the China Kadoorie Biobank (CKB, N = 21,629) using Cox-Gompertz proportional hazards model. The LAI incorporated three clinical factors (body mass index, systolic and diastolic blood pressure), eight plasma biomarkers (glucose, total cholesterol, triglycerides, high- and low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase), and two imaging biomarkers (fat attenuation parameter and liver stiffness measurement). External validation was conducted in the National Health and Nutrition Examination Survey (NHANES; N = 3412) and the VCTE-Prognosis cohort (N = 12,170, 16 global centers). Across all cohorts, the LAI demonstrated strong discrimination for all-cause mortality (AUROC: 0.764 in NHANES; 0.759 in VCTE-Prognosis), outperforming chronological age (p < 0.05). Liver aging acceleration (LAA), defined as the difference between LAI and chronological age, was associated with substantially elevated risks: each 1-SD increase in LAA conferred a 22%-85% higher risk of all-cause mortality and a 34%-170% higher risk of liver-related event or mortality. Using genetic instruments identified in CKB, we found genetic predisposition to accelerated liver aging was associated with higher risks of cirrhosis and liver cancer (H...