Insulin-like Growth Factor-1 Reflects Liver Disease Stage and Improves Prediction of Liver-related Mortality

作者：Carolin V. Schneider, Stefan Groß, Sriram Balasubramani, Petra Tomanová, Christina Schrader, Malin Fromme, Mattias Mandorfer, Nurdan Güldiken, Kai Markus Schneider, Georg Lurje, Anastasia Raptis, Helen Huang, Sebastian Mueller, Thomas Reiberger, Pierre Nahon, Quentin M. Anstee, Ann K. Daly, Olivier Govaere, Pavel Strnad · 发表于：Clinical Gastroenterology and Hepatology · 年份：2025 · DOI：10.1016/j.cgh.2025.02.030 · 被引用次数：9 · 研究领域：Growth Hormone and Insulin-like Growth Factors、Liver Disease Diagnosis and Treatment、Alcohol Consumption and Health Effects

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 cohor...