• Artificial Intelligence in Medicine (AIM) Program, Mass General Brigham, Harvard Medical School, Harvard Institutes of Medicine (HIM), Boston, Massachusetts, USA.
• Department of Radiology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.

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.