Background: Steatotic liver disease (SLD) is a potentially reversible condition but often goes unnoticed with the risk for end-stage liver disease.
Purpose: To opportunistically estimate SLD on lung screening chest computed tomography (CT) and investigate its prognostic value in heavy smokers participating in the National Lung Screening Trial (NLST).
Material and methods: We used a deep learning model to segment the liver on non-contrast-enhanced chest CT scans of 19,774 NLST participants (age 61.4 ± 5.0 years; 41.2% female) at baseline and on the 1-year follow-up scan if no cancer was detected. SLD was defined as hepatic fat fraction (HFF) ≥5% derived from Hounsfield unit measures of the segmented liver. Participants with SLD were categorized as lean (body mass index [BMI] < 25 kg/m2) and overweight (BMI ≥ 25 kg/m2). The primary outcome was all-cause mortality. Cox proportional hazard regression assessed the association between (1) SLD and mortality at baseline and (2) the association between a change in HFF and mortality within 1 year.
Results: There were 5.1% (1000/19,760) all-cause deaths over a median follow-up of 6 (range, 0.8-6) years. At baseline, SLD was associated with increased mortality in lean but not in overweight/obese participants as compared to participants without SLD (hazard ratio [HR] adjusted for risk factors: 1.93 [95% confidence interval 1.52-2.45]; p = 0.001). Individuals with an increase in HFF within 1 year had a significantly worse outcome than participants with stable HFF (HR adjusted for risk factors: 1.29 [1.01-1.65]; p = 0.04).
Conclusion: SLD is an independent predictor for long-term mortality in heavy smokers beyond known clinical risk factors.
Keywords: CT imaging; artificial intelligence; lung cancer screening; opportunistic; risk assessment; steatotic liver disease.
© 2025 The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.