Current status of imaging biomarkers predicting the biological nature of hepatocellular carcinoma

  • Norihide YonedaEmail author
  • Osamu Matsui
  • Satoshi Kobayashi
  • Azusa Kitao
  • Kazuto Kozaka
  • Dai Inoue
  • Kotaro Yoshida
  • Tetsuya Minami
  • Wataru Koda
  • Toshifumi Gabata
Invited Review


Hepatocellular carcinoma (HCC) is heterogeneous in terms of its biological nature. Various factors related to its biological nature, including size, multifocality, macroscopic morphology, grade of differentiation, macro/microvascular invasion, bile duct invasion, intra-tumoral fat and molecular factors, and their value as prognostic imaging biomarkers have been reported. And recently, genome-based molecular HCC classification correlated with clinical outcome has been elucidated. The imaging biomarkers suggesting a less aggressive nature of HCC are smaller size, solitary tumor, smooth margin suggesting small nodular type with indistinct margin and simple nodular type with distinct margin, capsule, imaging biomarkers predicting early or well-differentiated grade, intra-tumoral fat detection, and low fluorodeoxyglucose (FDG) accumulation. The imaging biomarkers suggesting an aggressive HCC nature are larger size, multifocality, non-smooth margin suggesting simple nodular type with extranodular growth, confluent multinodular, and infiltrative type, imaging biomarkers predicting poor differentiation, macrovascular tumor thrombus, predicting microvascular invasion imaging biomarkers, bile duct dilatation or tumor thrombus, and high FDG accumulation. In the genome-based molecular classification, CTNNB-1 mutated HCC shows a less aggressive nature, while CK19/EpCAM positive HCC and macrotrabecular massive HCC show an aggressive one. Better understanding of these imaging biomarkers can contribute to devising more appropriate treatment plans for HCC.


Hepatocellular carcinoma Biological nature Imaging biomarkers Genome-based molecular HCC classification 



Hepatocellular carcinoma


T1 weighted image


Magnetic resonance imaging


 T2 weighted image


Intrahepatic metastases


Small nodular type with indistinct margin


Simple nodular type with distinct margin


Simple nodular type with extranodular growth


Confluent multinodular type

HB phase

Hepatobiliary phase


Dysplastic nodule


Apparent diffusion coefficient


Diffusion weighted image


Fluorodeoxyglucose positron emission tomography


Organic anion-transporting polypeptide


Superparamagnetic iron oxide




Glucose transporter 1




Positive predictive value


Negative predictive value


Standardized uptake values




Protein induced by Vitamin K absence or antagonists-II


Hepatocyte nuclear factor (HNF)


Epithelial–mesenchymal transformation




Epithelial cell adhesion molecule


Catenin beta 1


Macrotrabecular massive HCC


Steatohepatitic HCC



This work received no grant funding.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest to disclose with respect to this article.

Ethical statement

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© Japan Radiological Society 2019

Authors and Affiliations

  • Norihide Yoneda
    • 1
    Email author
  • Osamu Matsui
    • 1
  • Satoshi Kobayashi
    • 2
  • Azusa Kitao
    • 1
  • Kazuto Kozaka
    • 1
  • Dai Inoue
    • 1
  • Kotaro Yoshida
    • 1
  • Tetsuya Minami
    • 3
  • Wataru Koda
    • 1
  • Toshifumi Gabata
    • 1
  1. 1.Department of RadiologyKanazawa University Graduate School of Medical SciencesKanazawaJapan
  2. 2.Department of Quantum Medical ImagingKanazawa University Graduate School of Medical SciencesKanazawaJapan
  3. 3.Department of RadiologyKanazawa Medical UniversityUchinadaJapan

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