Noninvasive Diagnosis of Hepatocellular Carcinoma Outside Guideline-Defined High-Risk Populations: Evolving Perspectives in the Era of MASLD.
Authors
Affiliations (2)
Affiliations (2)
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. [email protected].
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Abstract
Noninvasive imaging-based diagnosis of hepatocellular carcinoma (HCC) in high-risk patients currently relies on the radiological hallmark of arterial-phase hyperenhancement followed by delayed washout. These criteria were designed to achieve both a high positive predictive value and sufficient specificity when applied to well-defined target populations. However, the incidence of HCC is rising globally among individuals outside the traditional high-risk groups, including those with metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as non-alcoholic fatty liver disease) and genetic predispositions. This shifting epidemiology poses challenges to the current noninvasive diagnostic strategies and the binary classification of patients as either "at high-risk" or "not at high-risk," which heavily depends on established risk factors such as chronic hepatitis B, chronic hepatitis C, and liver cirrhosis. Consequently, HCC in non-high-risk individuals is often diagnosed at more advanced stages, underscoring the urgent need for reliable and noninvasive diagnostic tools tailored to this demographic population. These challenges present opportunities for the radiology community to play a proactive role in addressing them. Given the heterogeneous risk factors among low- and intermediate-risk populations, integrated strategies incorporating imaging features, fibrosis stage, serum biomarkers, individualized risk models, and artificial intelligence-assisted cross-sectional imaging may help improve the noninvasive diagnosis of non-cirrhotic or metabolically driven HCC. This review summarizes the current performance and limitations of noninvasive diagnosis outside the conventional high-risk populations in the era of MASLD and highlights emerging diagnostic strategies that warrant further investigation as evidence continues to accumulate.