Hepatobiliary phase imaging in HCC: revisiting diagnostic algorithms and clinical utility of gadoxetic acid-enhanced MRI across international guidelines

Abstract Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide. In at-risk populations, noninvasive imaging diagnosis relies primarily on the vascular hallmarks of arterial phase hyperenhancement and washout appearance. However, these features are often absent in early hepatocarcinogenesis, thereby limiting timely detection. Gadoxetic acid-enhanced MRI has expanded the role of imaging in HCC, yet its clinical value is often oversimplified as a comparison of diagnostic performance with CT or extracellular contrast MRI. A critical issue is that the same imaging feature, particularly hepatobiliary phase (HBP) hypointensity, carries different diagnostic consequences across international frameworks. Because HBP signal loss reflects early hepatocellular dysfunction that may precede typical vascular hallmarks, gadoxetic acid-enhanced MRI provides a biologically driven sensitivity advantage for detecting small and early-stage HCC. However, its apparent performance varies largely according to diagnostic intent: sensitivity-oriented Asian guidelines incorporate HBP hypointensity as a major feature to enable earlier detection, whereas Western guidelines prioritize specificity in high-stakes decision contexts, such as liver transplantation, and therefore restrict its diagnostic weight. This intent-dependent interpretation explains much of the inconsistency reported in the literature and underscores the limitations of pooled, guideline-agnostic performance estimates. Beyond diagnosis, HBP imaging also offers complementary information for assessing treatment response, although it remains underutilized in current criteria. Overall, the clinical value of gadoxetic acid-enhanced MRI lies not in universal superiority but in context-aligned application, shifting the focus from modality comparison to optimization according to downstream clinical consequences. Key Points Question Gadoxetic acid-enhanced MRI is interpreted differently across international hepatocellular carcinoma diagnostic guidelines, resulting in uncertainty regarding optimal imaging criteria and clinical decision-making. Findings Hepatobiliary phase hypointensity reflects early hepatocellular dysfunction and improves sensitivity for small and early-stage HCC, but its impact varies according to diagnostic intent. Critical Relevance Statement An intent-aligned interpretation strategy may help reconcile guideline heterogeneity and optimize the use of gadoxetic acid-enhanced MRI, particularly in the evaluation of small HCC.