1 3 Int J Clin Oncol DOI 10.1007/s10147-016-1066-x ORIGINAL ARTICLE Simplified HCC-ART score for highly sensitive detection of small-sized and early-stage hepatocellular carcinoma in the widely used Okuda, CLIP, and BCLC staging systems Abdelfattah M. Attallah 1 · Mohamed M. Omran 2 · Ahmed A. Attallah 1 · Mohamed A. Abdelrazek 1 · Khaled Farid 3 · Ibrahim El-Dosoky 4 Received: 16 June 2016 / Accepted: 7 November 2016 © Japan Society of Clinical Oncology 2016 CLIP (0.945 AUC, 84% sensitivity, 99% specificity), and BCLC (1.000 AUC, 100% sensitivity, 99% specificity) staging systems. The simplified HCC-ART score was more strongly correlated than AFP and other staging systems with HCC tumor size (P < 0.0001; r = 0.8). Conclusion The HCC-ART is superior to AFP for diag- nosing early-stage HCC. Due to its advantages of minimal variability and a wide continuous scale for assessing HCC severity, the simplified HCC-ART has the potential to be more widely used than the original HCC-ART. Keywords Hepatocellular carcinoma · Early stage · Diagnosis · Blood biomarkers · HCC-ART score Introduction Liver cancer is generally associated with less-developed regions. Indeed, 83% of the estimated 782,000 new liver cancer cases that occurred worldwide in 2012 were in less- developed regions [1]. Early diagnosis is important for successful treatment by means of ablation, resection, and/ or transplant [2]. While effective HCC treatment is usually curative surgery, about 80% of patients are inoperable at presentation and die early due to late diagnosis [3]. Thus, identifying effective screening strategies to detect early- stage HCC is of the utmost importance as it could result in more effective treatment and extend patient survival [4]. Although α-fetoprotein (AFP) is routinely used for screening and has been widely applied in HCC surveillance programs, it often gives normal or indeterminate results in early cancer cases. AFP is a low-sensitivity biomarker that is normal in up to 50% of patients with HCC, particu- larly during the early stages of the disease (HCC ≤ 3 cm) [5]. Other modalities such as ultrasonography (US) and Abstract Background Small-sized HCC can be effectively cured by surgery with good clinical outcomes. A highly sensi- tive HCC α-fetoprotein routine test (HCC-ART) for HCC diagnosis as well as a simplied form of the HCC-ART were reported in the British Journal of Cancer. Here, we verified and studied the applicability of the HCC-ART to the detec- tion of early-stage HCC. Methods 341 cirrhotic patients and 318 HCC patients were included in this study. For each, the HCC-ART score was calculated, and then the sensitivity, specificity, and results of an ROC curve analysis were compared between the HCC-ART and AFP when these biomarkers were used to detect small-sized HCC. Results Different HCC-ART cutoffs were set for the detection of different tumor sizes. The HCC-ART (AUC = 0.871, 70% sensitivity, 97% specificity) and the simplified HCC-ART (AUC = 0.934, 82% sensitivity, 100% specificity) were found to have high predictive power when attempting to separate cirrhotic patients from those with small-sized HCC. The simplified HCC-ART score was superior to AFP for determining stages according to the early Okuda (0.950 AUC, 84% sensitivity, 99% specificity), * Abdelfattah M. Attallah amattallah@hotmail.com 1 R&D Department, Biotechnology Research Center, PO Box (14), 23 July Street, Industrial Zone, New Damietta 34517, Egypt 2 Faculty of Science, Helwan University, Cairo, Egypt 3 Tropical Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt 4 Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt