Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2025
Insulin-like Growth Factor-1 Reflects Liver Disease Stage and Improves Prediction of Liver-related Mortality.
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Schneider Carolin V, Gross Stefan, Balasubramani Sriram, Tomanová Petra, Schrader Christina, Fromme Malin, Mandorfer Mattias, Guldiken Nurdan, Schneider Kai Markus, Lurje Georg, Raptis Anastasia, Huang Helen Ye Rim, Mueller Sebastian, Reiberger Thomas, Nahon Pierre, Anstee Quentin M, Daly Ann K, Govaere Olivier, Strnad Pavel
Аннотация
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.
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.