European Radiology

, Volume 29, Issue 2, pp 1022–1031 | Cite as

Optimal criteria for hepatocellular carcinoma diagnosis using CT in patients undergoing liver transplantation

  • Nieun Seo
  • Myoung Soo Kim
  • Mi-Suk ParkEmail author
  • Jin-Young Choi
  • Chansik An
  • Kyunghwa Han
  • Seung Up Kim
  • Dong Jin Joo
  • Myeong-Jin Kim



To compare the diagnostic performance of various guidelines for hepatocellular carcinoma (HCC) diagnosis using computed tomography (CT) in patients undergoing liver transplantation (LT).


In total, 216 patients who underwent preoperative CT and subsequent LT were included. Two radiologists retrospectively evaluated focal hepatic lesions independently according to various guidelines and allocated patients according to the Milan criteria. The diagnostic performance of the guidelines was compared using alternative free-response receiver-operating characteristics (AFROC) analysis with bootstrapping. Comparisons of sensitivity, specificity, and accuracy of patient allocation based on the Milan criteria between guidelines were performed using logistic regression with generalized estimating equations (GEE).


Fifty-two of 216 patients had 87 HCCs. The reader-averaged figure of merit obtained using AFROC analysis was 0.738 for the AASLD/EASL or KLCSG-NCC guidelines and 0.728 for the LI-RADS v2014 or OPTN/UNOS (bootstrapping, p = 0.005). The per-lesion sensitivity for HCCs (all and 1–2-cm lesions) was significantly higher with the AASLD/EASL (37.9–41.4% and 30.8–41.0%) than with LI-RADS (28.7% and 15.4–18.0%) (logistic regression with GEE, p = 0.008 and 0.030 for reader 1 and p = 0.005 for reader 2). The per-patient specificity (98.8–99.4%) was the same for all guidelines. The accuracy of the Milan criteria was 81.5–83.3% without significant differences among the four guidelines (logistic regression with GEE, p > 0.05).


AASLD/EASL showed higher diagnostic performance and sensitivity, particularly for 1–2-cm HCCs, and the same specificity with LI-RADS. All guidelines are comparable for patient allocation based on the Milan criteria for LT.

Key Points

• The overall diagnostic performance of CT for HCC diagnosis was highest with AASLD/EASL.

• AASLD/EASL showed higher sensitivity for diagnosis of 1–2-cm HCCs than LI-RADS.

• The accuracy of the Milan criteria using CT was comparable among the four guidelines.


Carcinoma, hepatocellular Liver transplantation ROC curve Sensitivity and specificity Tomography, X-ray computed 



American Association for the Study of Liver Diseases


Alternative free-response receiver operating characteristics


Computed tomography


European Association for the Study of the Liver


European Organization for Research and Treatment of Cancer


Figure of merit


Generalized estimating equation


Hepatocellular carcinoma


Korean Liver Cancer Study Group and the National Cancer Center


Liver Imaging Reporting and Data System


Liver transplantation


Milan criteria


Magnetic resonance imaging


Organ Procurement and Transplant Network


United Network for Organ Sharing



The authors state that this work has not received any funding.

Compliance with ethical standards


The scientific guarantor of this publication is Mi-Suk Park.

Conflict of interest

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

Kyunghwa Han from Yonsei Biomedical Research Institute, who is one of the coauthors, performed statistical analysis.

Informed consent

Written informed consent was waived by the Institutional Review Board.

Ethical approval

Institutional Review Board approval was obtained.


• retrospective

• diagnostic study

• performed at one institution

Supplementary material

330_2018_5557_MOESM1_ESM.docx (27 kb)
ESM 1 (DOCX 27.3 kb)


  1. 1.
    Clavien PA, Lesurtel M, Bossuyt PM, Gores GJ, Langer B, Perrier A (2012) Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol 13:e11–e22CrossRefGoogle Scholar
  2. 2.
    Yu SJ (2016) A concise review of updated guidelines regarding the management of hepatocellular carcinoma around the world: 2010-2016. Clin Mol Hepatol 22:7–17CrossRefGoogle Scholar
  3. 3.
    Mazzaferro V, Regalia E, Doci R et al (1996) Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 334:693–699CrossRefGoogle Scholar
  4. 4.
    Befeler AS, Hayashi PH, Di Bisceglie AM (2005) Liver transplantation for hepatocellular carcinoma. Gastroenterology 128:1752–1764CrossRefGoogle Scholar
  5. 5.
    Wald C, Russo MW, Heimbach JK, Hussain HK, Pomfret EA, Bruix J (2013) New OPTN/UNOS policy for liver transplant allocation: standardization of liver imaging, diagnosis, classification, and reporting of hepatocellular carcinoma. Radiology 266:376–382CrossRefGoogle Scholar
  6. 6.
    Mitchell DG, Bruix J, Sherman M, Sirlin CB (2015) LI-RADS (Liver Imaging Reporting and Data System): summary, discussion, and consensus of the LI-RADS Management Working Group and future directions. Hepatology 61:1056–1065CrossRefGoogle Scholar
  7. 7.
    American College of Radiology. Liver imaging reporting and data system (LI-RADS). American College of Radiology. Web site. Accessed June 1, 2017
  8. 8.
    Bruix J, Sherman M (2011) Management of hepatocellular carcinoma: an update. Hepatology 53:1020–1022CrossRefGoogle Scholar
  9. 9.
    European Association for the Study of the Liver, European Organisation for Research and Treatment of Cancer (2012) EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 56:908–943CrossRefGoogle Scholar
  10. 10.
    Lee JM, Park JW, Choi BI (2014) 2014 KLCSG-NCC Korea Practice Guidelines for the management of hepatocellular carcinoma: HCC diagnostic algorithm. Dig Dis 32:764–777CrossRefGoogle Scholar
  11. 11.
    Korean Liver Cancer Study Group (KLCSG) and National Cancer Center, Korea (NCC) (2015) 2014 Korean Liver Cancer Study Group-National Cancer Center Korea practice guideline for the management of hepatocellular carcinoma. Korean J Radiol 16:465–522CrossRefGoogle Scholar
  12. 12.
    Korean Society of Abdominal Radiology (2017) Diagnosis of Hepatocellular Carcinoma with Gadoxetic Acid-Enhanced MRI: 2016 Consensus Recommendations of the Korean Society of Abdominal Radiology. Korean J Radiol 18:427–443CrossRefGoogle Scholar
  13. 13.
    Kokudo N, Hasegawa K, Akahane M et al (2015) Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma: The Japan Society of Hepatology 2013 update (3rd JSH-HCC Guidelines). Hepatol Res 45Google Scholar
  14. 14.
    Omata M, Lesmana LA, Tateishi R et al (2010) Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int 4:439–474CrossRefGoogle Scholar
  15. 15.
    Tang A, Fowler KJ, Chernyak V, Chapman WC, Sirlin CB (2017) LI-RADS and transplantation for hepatocellular carcinoma. Abdom Radiol (NY).
  16. 16.
    Lee DH, Lee JM, Baek JH, Shin CI, Han JK, Choi BI (2015) Diagnostic performance of gadoxetic acid-enhanced liver MR imaging in the detection of HCCs and allocation of transplant recipients on the basis of the Milan criteria and UNOS guidelines: correlation with histopathologic findings. Radiology 274:149–160CrossRefGoogle Scholar
  17. 17.
    Edmondson HA, Steiner PE (1954) Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer 7:462–503CrossRefGoogle Scholar
  18. 18.
    Chakraborty DP, Berbaum KS (2004) Observer studies involving detection and localization: modeling, analysis, and validation. Med Phys 31:2313–2330CrossRefGoogle Scholar
  19. 19.
    Zhai X, Chakraborty DP (2015). RJafroc: Analysis of data acquired using the receiver operating characteristic paradigm and its extensions. R package version 0.1.1.
  20. 20.
    Ronot M, Fouque O, Esvan M, Lebigot J, Aube C, Vilgrain V (2017) Comparison of the accuracy of AASLD and LI-RADS criteria for the non-invasive diagnosis of HCC smaller than 3cm. J Hepatol.
  21. 21.
    Manini MA, Sangiovanni A, Fornari F et al (2014) Clinical and economical impact of 2010 AASLD guidelines for the diagnosis of hepatocellular carcinoma. J Hepatol 60:995–1001CrossRefGoogle Scholar
  22. 22.
    Kim TK, Lee KH, Jang HJ et al (2011) Analysis of gadobenate dimeglumine-enhanced MR findings for characterizing small (1-2-cm) hepatic nodules in patients at high risk for hepatocellular carcinoma. Radiology 259:730–738CrossRefGoogle Scholar
  23. 23.
    Aube C, Oberti F, Lonjon J et al (2017) EASL and AASLD recommendations for the diagnosis of HCC to the test of daily practice. Liver Int 37:1515–1525CrossRefGoogle Scholar
  24. 24.
    Pahwa A, Beckett K, Channual S, Tan N, Lu DS, Raman SS (2014) Efficacy of the American Association for the Study of Liver Disease and Barcelona criteria for the diagnosis of hepatocellular carcinoma. Abdom Imaging 39:753–760CrossRefGoogle Scholar
  25. 25.
    Lee YJ, Lee JM, Lee JS et al (2015) Hepatocellular carcinoma: diagnostic performance of multidetector CT and MR imaging-a systematic review and meta-analysis. Radiology 275:97–109CrossRefGoogle Scholar
  26. 26.
    Ronzoni A, Artioli D, Scardina R et al (2007) Role of MDCT in the diagnosis of hepatocellular carcinoma in patients with cirrhosis undergoing orthotopic liver transplantation. AJR Am J Roentgenol 189:792–798CrossRefGoogle Scholar
  27. 27.
    Luca A, Caruso S, Milazzo M et al (2010) Multidetector-row computed tomography (MDCT) for the diagnosis of hepatocellular carcinoma in cirrhotic candidates for liver transplantation: prevalence of radiological vascular patterns and histological correlation with liver explants. Eur Radiol 20:898–907CrossRefGoogle Scholar
  28. 28.
    Rimola J, Forner A, Tremosini S et al (2012) Non-invasive diagnosis of hepatocellular carcinoma </= 2 cm in cirrhosis. Diagnostic accuracy assessing fat, capsule and signal intensity at dynamic MRI. J Hepatol 56:1317–1323CrossRefGoogle Scholar
  29. 29.
    Forner A, Vilana R, Ayuso C et al (2008) Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: Prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma. Hepatology 47:97–104CrossRefGoogle Scholar
  30. 30.
    Rostambeigi N, Taylor AJ, Golzarian J et al (2016) Effect of MRI Versus MDCT on Milan Criteria Scores and Liver Transplantation Eligibility. AJR Am J Roentgenol 206:726–733CrossRefGoogle Scholar
  31. 31.
    Addley HC, Griffin N, Shaw AS et al (2011) Accuracy of hepatocellular carcinoma detection on multidetector CT in a transplant liver population with explant liver correlation. Clin Radiol 66:349–356CrossRefGoogle Scholar
  32. 32.
    Park MS, Kim S, Patel J et al (2012) Hepatocellular carcinoma: detection with diffusion-weighted versus contrast-enhanced magnetic resonance imaging in pretransplant patients. Hepatology 56:140–148CrossRefGoogle Scholar
  33. 33.
    Heimbach J, Kulik LM, Finn R et al (2017) Aasld guidelines for the treatment of hepatocellular carcinoma. Hepatology.
  34. 34.
    Roberts LR, Sirlin CB, Zaiem F et al (2017) Imaging for the Diagnosis of Hepatocellular Carcinoma: a Systematic Review and Meta-analysis. Hepatology.

Copyright information

© European Society of Radiology 2018

Authors and Affiliations

  1. 1.Department of Radiology, Severance HospitalYonsei University College of MedicineSeoulKorea
  2. 2.Department of SurgeryYonsei University College of MedicineSeoulKorea
  3. 3.Department of RadiologyYonsei Biomedical Research Institute, Research Institute of Radiological ScienceSeoulKorea
  4. 4.Department of Internal Medicine, Institute of GastroenterologyYonsei University College of MedicineSeoulKorea

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