ObjectiveThis study proposes a novel reference standard for hypervascular hepatocellular carcinomas (HCCs), established by cone-beam computed tomography-hepatic arteriography (CBCT-HA) and two-year imaging follow-up, and discusses its clinical implication on tumor staging and understanding the intrahepatic distant recurrence (IDR) in relation to dynamic computed tomography (CT).Materials and MethodsIn this retrospective study, 99 patients were enrolled, who underwent CBCT-HA during initial chemoembolization for HCC suspected on CT. All patients underwent chemoembolization and regular clinical and imaging follow-up for two years. If IDR appeared on follow-up imaging, initial CBCT-HA images were reviewed to determine if a hypervascular focus pre-existed at the site of recurrence. Pre-existing hypervascular foci on CBCT-HA were regarded as HCCs in initial presentation. Initial HCCs were classified into three groups according to their mode of detection (Group I, detected on CT and CBCT-HA; Group II, additionally detected on CBCT-HA; Group III, confirmed by interval growth). We assessed the influence of CBCT-HA and two-year follow-up on initial tumor stage and calculated the proportion of IDR that pre-existed in initial CBCT-HA.ResultsA total of 405 nodules were confirmed as HCCs, and 297 nodules initially pre-existed. Of the initial 297 HCCs, 149 (50.2%) lesions were in Group I, 74 (24.9%) lesions were in Group II, and the remaining 74 (24.9%) lesions were in Group III. After applying CBCT-HA findings, 11 patients upstaged in T stage, and 4 patients had a change in Milan criteria. Our reference standard for HCC indicated that 120 of 148 (81.1%) one-year IDR and 148 of 256 (57.8%) two-year IDR existed on initial CBCT-HA.ConclusionThe proposed method enabled the confirmation of many sub-centimeter-sized, faintly vascularized HCC nodules that pre-existed initially but clinically manifested as IDR. Our reference standard for HCC helped in understanding the nature of IDR and the early development of HCC as well as the clinical impact of tumor staging and treatment decision.