AI-based Hepatic Steatosis Detection and Integrated Hepatic Assessment from Cardiac CT Attenuation Scans Enhances All-cause Mortality Risk Stratification: A Multi-center Study

Summary Background Hepatic steatosis (HS) is a common cardiometabolic risk factor frequently present but under-diagnosed in patients with suspected or known coronary artery disease. We used artificial intelligence (AI) to automatically quantify hepatic tissue measures for identifying HS from CT attenuation correction (CTAC) scans during myocardial perfusion imaging (MPI) and evaluate their added prognostic value for all-cause mortality prediction. Methods This study included 27039 consecutive patients [57% male] with MPI scans from nine sites. We used an AI model to segment liver and spleen on low dose CTAC scans and quantify the liver measures, and the difference of liver minus spleen (LmS) measures. HS was defined as mean liver attenuation < 40 Hounsfield units (HU) or LmS attenuation < −10 HU. Additionally, we used seven sites to develop an AI liver risk index (LIRI) for comprehensive hepatic assessment by integrating the hepatic measures and two external sites to validate its improved prognostic value and generalizability for all-cause mortality prediction over HS. Findings Median (interquartile range [IQR]) age was 67 [58, 75] years and body mass index (BMI) was 29.5 [25.5, 34.7] kg/m 2 , with diabetes in 8950 (33%) patients. The algorithm identified HS in 6579 (24%) patients. During median [IQR] follow-up of 3.58 [1.86, 5.15] years, 4836 (18%) patients died. HS was associated with increased mortality risk overall (adjusted hazard ratio (HR): 1.14 [1.05, 1.24], p=0.0016) and in subpopulations. LIRI provided higher prognostic value than HS after adjustments overall (adjusted HR 1.5 [1.32, 1.69], p<0.0001 vs HR 1.16 [1.02, 1.31], p=0.0204) and in subpopulations. Interpretations AI-based hepatic measures automatically identify HS from CTAC scans in patients undergoing MPI without additional radiation dose or physician interaction. Integrated liver assessment combining multiple hepatic imaging measures improved risk stratification for all-cause mortality. Funding National Heart, Lung, and Blood Institute/National Institutes of Health. Research in context Evidence before this study Existing studies show that fully automated hepatic quantification analysis from chest computed tomography (CT) scans is feasible. While hepatic measures show significant potential for improving risk stratification and patient management, CT attenuation correction (CTAC) scans from patients undergoing myocardial perfusion imaging (MPI) have rarely been utilized for concurrent and automated volumetric hepatic analysis beyond its current utilization for attenuation correction and coronary artery calcium burden assessment. We conducted a literature review on PubMed and Google Scholar on April 1 st , 2025, using the following keywords: (“liver” OR “hepatic”) AND (“quantification” OR “measure”) AND (“risk stratification” OR “survival analysis” OR “prognosis” OR “prognostic prediction”) AND (“CT” OR “computed tomography”). Previous studies have established approaches for the identification of hepatic steatosis (HS) and its prognostic value in various small-scale cohorts using either invasive biopsy or non-invasive imaging approaches. However, CT-based non-invasive imaging, existing research predominantly focuses on manual region-of-interest (ROI)-based hepatic quantification from selected CT slices or on identifying hepatic steatosis without comprehensive prognostic assessment in large-scale and multi-site cohorts, which hinders the association evaluation of hepatic steatosis for risk stratification in clinical routine with less precise estimates, weak statistical reliability, and limited subgroup analysis to assess bias effects. No existing studies investigated the prognostic value of hepatic steatosis measured in consecutive patients undergoing MPI. These patients usually present with multiple cardiovascular risk factors such as hypertension, dyslipidemia, diabetes and family history of coronary disease. Whether hepatic measures could provide added prognostic value over existing cardiometabolic factors is unknown. Furthermore, despite the diverse hepatic measures on CT in existing literature, integrated AI-based assessment has not been investigated before though it may improve the risk stratification further over HS. Lastly, previous research relied on dedicated CT scans performed for screening purposes. CTAC scans obtained routinely with MPI had never been utilized for automated HS detection and prognostic evaluation, despite being readily available at no additional cost or radiation exposure. Added value of this study In this multi-center (nine sites) international (three countries) study of 27039 consecutive patients undergoing myocardial perfusion imaging (MPI) with PET or SPECT, we used an innovative artificial intelligence (AI)-based approach for automatically segmenting the entire liver and spleen volumes from low-dose ungated CT attenuation correction (CTAC) scans acquired during MPI, followed by the identification of hepatic steatosis. We evaluated the added prognostic value of several key hepatic metrics—liver measures (mean attenuation, coefficient of variation (CoV), entropy, and standard deviation), and similar measures for the difference of liver minus spleen (LmS)—derived from volumetric quantification of CTAC scans with adjustment for existing clinical and MPI variables. A HS imaging criterion (HSIC: a patient has moderate or severe hepatic steatosis if the mean liver attenuation is < 40 Hounsfield unit (HU) or the difference of liver mean attenuation and spleen mean attenuation is < −10 HU) was used to detect HS. These hepatic metrics were assessed for their ability to predict all-cause mortality in a large-scale and multi-center patient cohort. Additionally, we developed and validated an eXtreme Gradient Boosting decision tree model for integrated liver assessment and risk stratification by combining the hepatic metrics with the demographic variables to derive a liver risk index (LIRI). Our results demonstrated strong associations between the hepatic metrics and all-cause mortality, even after adjustment for clinical variables, myocardial perfusion, and atherosclerosis biomarkers. Our results revealed significant differences in the association of HS with mortality in different sex, age, and race subpopulations. Similar differences were also observed in various chronic disease subpopulations such as obese and diabetic subpopulations. These results highlighted the modifying effects of various patient characteristics, partially accounting for the inconsistent association observed in existing studies. Compared with individual hepatic measures, LIRI showed significant improvement compared to HSIC-based HS in mortality prediction in external testing. All these demonstrate the feasibility of HS detection and integrated liver assessment from cardiac low-dose CT scans from MPI, which is also expected to apply for generic chest CT scans which have coverage of liver and spleen while prior studies used dedicated abdominal CT scans for such purposes. Implications of all the available evidence Routine point-of-care analysis of hepatic quantification can be seamlessly integrated into all MPI using CTAC scans to noninvasively identify HS at no additional cost or radiation exposure. The automatically derived hepatic metrics enhance risk stratification by providing additional prognostic value beyond existing clinical and imaging factors, and the LIRI enables comprehensive assessment of liver and further improves risk stratification and patient management.

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