Liver Aging Index: A Noninvasive Score for Liver Biological Aging and Liver‐Related Outcomes in Multicohorts
Abstract
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 (HR = 3.94 [3.20-4.86] and 7.82 [2.05-29.80]), further validated in Biobank Japan. Integrating genetics and proteomics revealed novel pathophysiological involvement of amyloid-beta clearance pathway and amyloid precursor protein in liver aging. These findings demonstrate the feasibility of a noninvasive, liver-specific biological aging index and provide new insights into mechanisms underlying liver aging.
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BibTeX
@article{wu2026liver,
title = {{Liver Aging Index: A Noninvasive Score for Liver Biological Aging and Liver‐Related Outcomes in Multicohorts}},
author = {Zhiyu Wu and Shanshan Wu and Shuyao Song and Yating Huang and Canqing Yu and Dianjianyi Sun and Pei Pei and Ling Yang and Yiping Chen and Huaidong Du and Robin Walters and Iona Millwood and Hao Xu and Xiaoming Yang and Junshi Chen and Seung Up Kim and Salvatore Petta and Atsushi Nakajima and Emmanuel Tsochatzis and Jérôme Boursier and Elisabetta Bugianesi and Wah‐kheong Chan and Manuel Romero-Gomez and José Luis Calleja and Victor de Lédinghen and Laurent Castéra and Arun Sanyal and George Boon‐bee Goh and Philip Noel Newsome and Jian‐gao Fan and Michelle Lai and Xiao‐dong Zhou and Zhengming Chen and Jun Lv and Liming Li and Vincent Wai‐sun Wong and Ming‐hua Zheng and Yuanjie Pang},
journal = {Aging Cell},
year = {2026},
month = may,
doi = {10.1111/acel.70565},
url = {https://hal.science/hal-05840395v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Liver Aging Index: A Noninvasive Score for Liver Biological Aging and Liver‐Related Outcomes in Multicohorts
AU - Zhiyu Wu
AU - Shanshan Wu
AU - Shuyao Song
AU - Yating Huang
AU - Canqing Yu
AU - Dianjianyi Sun
AU - Pei Pei
AU - Ling Yang
AU - Yiping Chen
AU - Huaidong Du
AU - Robin Walters
AU - Iona Millwood
AU - Hao Xu
AU - Xiaoming Yang
AU - Junshi Chen
AU - Seung Up Kim
AU - Salvatore Petta
AU - Atsushi Nakajima
AU - Emmanuel Tsochatzis
AU - Jérôme Boursier
AU - Elisabetta Bugianesi
AU - Wah‐kheong Chan
AU - Manuel Romero-Gomez
AU - José Luis Calleja
AU - Victor de Lédinghen
AU - Laurent Castéra
AU - Arun Sanyal
AU - George Boon‐bee Goh
AU - Philip Noel Newsome
AU - Jian‐gao Fan
AU - Michelle Lai
AU - Xiao‐dong Zhou
AU - Zhengming Chen
AU - Jun Lv
AU - Liming Li
AU - Vincent Wai‐sun Wong
AU - Ming‐hua Zheng
AU - Yuanjie Pang
PY - 2026
DA - 2026/05/31
JO - Aging Cell
DO - 10.1111/acel.70565
UR - https://hal.science/hal-05840395v1
AB - 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 (HR = 3.94 [3.20-4.86] and 7.82 [2.05-29.80]), further validated in Biobank Japan. Integrating genetics and proteomics revealed novel pathophysiological involvement of amyloid-beta clearance pathway and amyloid precursor protein in liver aging. These findings demonstrate the feasibility of a noninvasive, liver-specific biological aging index and provide new insights into mechanisms underlying liver aging.
SN - 1474-9718
SN - 1474-9728
ER -