| Title: | Insulin-like Growth Factor-1 reflects liver disease stage and improves prediction of liver-related mortality |
| Journal: | Clinical Gastroenterology and Hepatology |
| Published: | 14 May 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40378984/ |
| DOI: | https://doi.org/10.1016/j.cgh.2025.02.030 |
Publication 15343
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Abstract
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).</p>
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.</p>
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).</p>
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.</p>
19 Authors
- Carolin V Schneider
- Stefan Gross
- Sriram Balasubramani
- Petra Tomanová
- Christina Schrader
- Malin Fromme
- Mattias Mandorfer
- Nurdan Guldiken
- Kai Markus Schneider
- Georg Lurje
- Anastasia Raptis
- Helen Ye Rim Huang
- Sebastian Mueller
- Thomas Reiberger
- Pierre Nahon
- Quentin M Anstee
- Ann K Daly
- Olivier Govaere
- Pavel Strnad
1 Application
| Application ID | Title |
|---|---|
| 71300 | Elucidating host-environment interactions in gastrointestinal diseases |
Enabling scientific discoveries that improve human health