Hepatic Fibro-inflammation Measured by MRI Iron-Corrected T1 Predicts Extrahepatic Cancer Risk: A UK Biobank Study

Background/Aims: Iron-corrected T1 (cT1) is a magnetic resonance imaging (MRI)-derived biomarker of hepatic fibro-inflammation. This study aimed to investigate whether high cT1 values are associated with an increased risk of extrahepatic malignancy in a large prospective cohort. Methods: We included 24,003 cancer-free participants from the United Kingdom (UK) Biobank with liver MRI and complete covariate data. Incident extrahepatic malignancy was assessed over a median follow-up of 4.28 years. Multivariable Fine-Gray subdistribution hazard models were used to evaluate the association between cT1 and extrahepatic cancer risk, accounting for competing risks and adjusting for demographic, metabolic, and liver-related factors. Results: During follow-up, 1,144 participants developed extrahepatic malignancies. In the multivariable analysis, higher cT1 was independently associated with increased extrahepatic cancer risk (hazard ratio [HR], 1.116; 95% confidence interval [CI], 1.033-1.205, per standard deviation increase; P=0.005). Older age (HR, 1.512; 95% CI, 1.402-1.631) and male sex (HR, 1.388; 95% CI, 1.220-1.578) were also significant predictors (P<0.001). The fibrosis-4 score showed a modest positive association (HR, 1.032; 95% CI, 1.004-1.062; P=0.026), whereas MRI-proton density fat fraction demonstrated an inverse association (HR, 0.906; 95% CI, 0.832-0.987; P=0.024). When dichotomized at 771 ms, elevated cT1 was associated with a higher cumulative incidence of extrahepatic malignancy (6.1% vs. 4.6%, P=0.002). Conclusions: Elevated cT1 is independently associated with an increased risk of future extrahepatic malignancy, suggesting that it may reflect systemic disease processes related to cancer risk. These findings highlight the potential relevance of cT1 beyond liver-specific outcomes; however, further validation is required before clinical implementation.