Browse by author
Lookup NU author(s): Professor Quentin AnsteeORCiD, Emerita Professor Ann Daly, Dr Olivier Govaere
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
© 2025 The Author(s). Background & Aims: Liver-related mortality represents a growing public health concern, disproportionately affecting younger subjects. Because there are no established tools for early detection of individuals at risk for liver-related death (LRD), we analyzed LRD predictors in the UK Biobank (UKB) data and validated the usefulness of serum insulin-like growth factor-1 (IGF-1). Methods: The UKB dataset encompassing 325,981 participants, a median follow-up of 13.5 years, and 846 LRDs was used as a training cohort. IGF-1 was validated in several independent cohorts of different liver disease etiologies and fibrosis stages. A Cox proportional hazard model was used to develop the gamma-glutamyl transferase (GGT)-IGF-1 score that was validated in an independent UKB cohort with 83,528 subjects and 237 LRDs. Results: Among 59 variables in the UKB training cohort, GGT and IGF-1 were identified as the LRD predictors with time-dependent area under the curve (AUROC) >80%. Phenome-wide association study demonstrated the higher liver specificity of IGF-1 compared with GGT. In validation cohorts, IGF-1 levels: (1) increased in subjects with alcohol misuse after alcohol detoxification; (2) were reduced in individuals with alcohol-related/steatotic liver disease or severe alpha-1 antitrypsin deficiency and higher fibrosis stages; and (3) were diminished in participants with more advanced liver cirrhosis and lower levels associated with higher mortality. In the UKB training and validation cohorts, the novel GGT-IGF-1 score achieved an AUROC of 0.87 for LRD and was significantly better than established risk scores (AUROC = 0.77–0.81). Conclusions: The study highlights the usefulness of IGF-1 as a reliable predictor of LRD and identifies a novel, population-based screening tool outperforming the currently used scores.
Author(s): Schneider CV, Gross S, Balasubramani S, Tomanova P, Schrader C, Fromme M, Mandorfer M, Guldiken N, Schneider KM, Lurje G, Raptis A, Huang HYR, Mueller S, Reiberger T, Nahon P, Anstee QM, Daly AK, Govaere O, Strnad P
Publication type: Article
Publication status: Published
Journal: Clinical Gastroenterology and Hepatology
Year: 2025
Pages: Epub ahead of print
Online publication date: 14/05/2025
Acceptance date: 02/04/2018
Date deposited: 26/06/2025
ISSN (print): 1542-3565
ISSN (electronic): 1542-7714
Publisher: W.B. Saunders
URL: https://doi.org/10.1016/j.cgh.2025.02.030
DOI: 10.1016/j.cgh.2025.02.030
PubMed id: 40378984
Altmetrics provided by Altmetric
