Non-alcoholic fatty liver disease (NAFLD) has emerged as one of the most common chronic liver conditions, with growing recognition of its links to cardiovascular complications. Beyond hepatic dysfunction, NAFLD significantly increases the risk of coronary artery disease (CAD) and, more critically, the development of high-risk coronary plaques (HRP). These plaques are known to rupture and cause acute cardiac events. Traditional diagnostic approaches, including liver biopsy and ultrasound, are limited in scope, especially for early or mild disease. In this context, the liver fat volume fraction (FVF), measured using spectral CT and the multi-material decomposition (MMD) algorithm, has shown promise as a non-invasive biomarker that may bridge hepatology and cardiology. A recent study explored the association between hepatic FVF and coronary HRP in NAFLD patients, assessing its diagnostic utility and potential role in cardiovascular risk stratification.
Spectral CT and FVF Quantification
Spectral CT with MMD offers a novel method for directly quantifying hepatic fat as a percentage of liver volume. Unlike conventional CT or MRI, spectral CT distinguishes fat, iodine and soft tissue based on atomic number and energy spectrum, enabling accurate liver fat mapping, even post-contrast. This overcomes the limitations of ultrasound and single-energy CT, which struggle with early-stage or mild steatosis and the contraindications and high cost associated with MRI. In this study, 159 patients undergoing coronary CT angiography and abdominal spectral CT were classified into three groups: those with no plaque, non-HRP and HRP. The FVF was significantly higher in the HRP group (13.2%) compared to non-HRP (9.2%) and no plaque (6.5%) patients. These findings indicate a graded increase in liver fat with plaque vulnerability.
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Multivariate logistic regression confirmed FVF as an independent risk factor for HRP, with an odds ratio (OR) of 2.55. In addition, diabetes mellitus (OR: 9.83) and high-sensitivity C-reactive protein (hs-CRP) (OR: 1.94) also emerged as significant predictors. Among the three, FVF demonstrated superior diagnostic accuracy, with an area under the ROC curve (AUC) of 0.931, outperforming both diabetes (AUC: 0.688) and hs-CRP (AUC: 0.788). A combined model incorporating FVF, hs-CRP and diabetes achieved an AUC of 0.968, suggesting synergistic value in multimodal risk assessment.
Ectopic Fat and Cardiovascular Risk
Ectopic fat deposition is central to the progression of NAFLD and its systemic effects. Fat accumulation in epicardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT), both of which are in proximity to coronary vessels, plays a key role in promoting inflammation and destabilising atherosclerotic plaques. This study confirmed a positive correlation between hepatic FVF and EAT/PCAT volumes and CT attenuation values, suggesting a systemic pattern of ectopic fat deposition. Higher FVF was associated with elevated EAT volume and CT attenuation, indicating more inflamed and metabolically active fat tissue. Similarly, increased PCAT volume and attenuation were observed in HRP patients.
These findings support the notion that hepatic, epicardial and pericoronary fat collectively contribute to coronary plaque vulnerability through inflammatory mediators and paracrine signalling. Elevated liver fat may therefore serve as a proxy for broader metabolic dysfunction, reinforcing the rationale for integrating hepatic fat measurements into cardiovascular risk models.
Clinical Implications and Future Directions
The implications of these findings are substantial. As spectral CT becomes more accessible, routine FVF assessment could offer a non-invasive, reproducible tool for identifying NAFLD patients at elevated cardiovascular risk. By enabling early detection of HRP, clinicians could implement targeted interventions—ranging from lifestyle modifications to pharmacotherapy—before adverse cardiac events occur. Furthermore, FVF monitoring may provide a valuable metric for assessing treatment response, particularly in integrated strategies aiming to reduce both liver fat and cardiovascular burden.
Nevertheless, limitations exist. This study was retrospective and single-centre, with a relatively small HRP sample. Histological validation of FVF was not performed, and the confounding impact of hepatic iron deposition on CT readings was not assessed. Future research should focus on prospective multicentre trials, longitudinal tracking of FVF changes and comparative imaging studies incorporating MRI to confirm measurement accuracy. Additional attention should be given to stratifying patients by fibrosis stage, as advanced liver disease may independently elevate cardiovascular risk regardless of FVF levels.
Spectral CT-derived liver fat volume fraction emerges as a promising biomarker in linking hepatic and cardiovascular risk. Its independent association with high-risk coronary plaque formation highlights its potential clinical value in managing NAFLD patients with suspected CAD. By combining FVF with traditional markers such as hs-CRP and diabetes status, clinicians may better stratify risk and personalise care pathways. Ultimately, integrating FVF into routine evaluation could advance NAFLD management from a liver-centric to a systemic, prevention-focused approach, potentially mitigating the burden of cardiometabolic diseases.
Source: Clinical Radiology
Image Credit: iStock
