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Magnetic resonance elastography and proton density fat fraction predict adverse outcomes in hepatocellular carcinoma



Magnetic resonance (MR) elastography and proton density fat fraction (PDFF) are emerging techniques for non-invasive assessment of liver stiffness and steatosis, respectively. We investigated the role of MR metrics in pre-treatment prognostication of hepatocellular carcinoma (HCC).


Patients with newly diagnosed HCC were prospectively recruited. Pre-treatment MR elastography and PDFF were performed on tumor and non-tumor regions. HCC treatment was categorized as potentially curative (resection/ablation) or non-curative (locoregional/systemic therapy). HCC recurrence, liver-related complications (ascites/ variceal bleeding/ hepatic encephalopathy) and mortality were monitored.


Of the 158 recruited patients (mean age 62.9 years, 84.2% male, 82.9% viral hepatitis), 58.2% (n = 92) and 41.8% (n = 66) received potentially curative and non-curative therapy, respectively. Pre-treatment non-tumor liver stiffness independently predicted liver-related complications, regardless of treatment type (HR 1.384, 95% CI 1.067–1.796, p = 0.014). In the potentially curative therapy group, non-tumor stiffness and non-tumor PDFF were independently associated with HCC recurrence (HR 1.308, 95% CI 1.022–1.673 & HR 1.080, 95% CI 1.009–1.156 respectively, both p < 0.05); and non-tumor PDFF predicted mortality (HR 1.160, 95% CI 1.038–1.296, p = 0.009). In the non-curative group, tumor stiffness independently predicted liver-related complications (HR 1.299, 95% CI 1.023–1.651, p = 0.032), and a combination of tumor stiffness ≥ 5.7 kPa plus non-tumor stiffness ≥ 3.7 kPa was associated with a two-fold risk of liver-related complications (86.7% vs 40.0%, p < 0.001).


Pre-treatment MR elastography and PDFF over tumor and non-tumor regions demonstrated prognosticating roles in HCC. Simultaneous measurements of both metrics during conventional MR liver should be considered in the diagnostic workup of HCC.

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Data availability

The data from this study is available from the corresponding author upon reasonable request.

Code availability

Not applicable.



Alpha fetoprotein


Barcelona clinic liver cancer


Body mass index


Hepatocellular carcinoma


Hazard ratio


Model for end-stage liver disease


Magnetic resonance


Non-alcoholic fatty liver disease


Proton density fat fraction


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The authors thank Ms. Carol Yin Yu Chu, Ms. Carmen Chan and Ms. Crystal Kwan at The University of Hong Kong for the logistical arrangements for recruited patients; and Dr Andrew Siu Ho Lai, Dr Kin Wah Li, Dr Solomon Yig Joon Ka, Mr Benny Wing Hung Ho, Ms. Wendy Sau Yee Yu and Ms. Sophia Yuen Shan Lee at the Hong Kong Sanatorium Hospital for their collaboration and support of this project.


This study was supported by the Li Shu Pui Medical Foundation Research Grant, Li Ka Shing Faculty of Medicine, The University of Hong Kong. The study was performed independent of the sponsors.

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Authors and Affiliations



RWHH was involved in study concept and design, acquisition of data, analysis and interpretation of data and drafting of the manuscript. ACYC, GL, RL, CC, CNK, LYM, WHS, KPA, VA and JF were involved in the acquisition of data and interpretation of data. MFY was involved in the study concept and design and critical revision of the manuscript. WKS was involved in study concept and design, securing research funding, analysis and interpretation of data, critical revision of the manuscript and overall study supervision. All authors declare that they have participated in the preparation of the manuscript and have seen and approved the final version.

Corresponding authors

Correspondence to Man-Fung Yuen or Wai-Kay Seto.

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Conflict of interest

MF Yuen is an advisory board member and/or received research funding from AbbVie, Arbutus Biopharma, Assembly Biosciences, Bristol Myer Squibb, Dicerna Pharmaceuticals, GlaxoSmithKline, Gilead Sciences, Janssen, Merck Sharp and Dohme, Clear B Therapeutics, Springbank Pharmaceuticals; and received research funding from Arrowhead Pharmaceuticals, Fujirebio Incorporation and Sysmex Corporation. WK Seto received speaker’s fees from AstraZeneca and Mylan, is an advisory board member of CSL Behring, is an advisory board member and received speaker’s fees from AbbVie, and is an advisory board member, received speaker’s fees and researching funding from Gilead Sciences. The other authors have no conflict of interests.

Animal research (ethics)

This article does not contain any studies with animals.

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All procedures were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients for being included in the study.

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Informed consent was obtained from all individual participants included in this study. No identifiable personal data from recruited patients were included in this article.

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Not applicable.

Registration and ethical approval

This study was registered and approved by the Institutional Review Board, University of Hong Kong/ Hospital Authority West Cluster; and the Research Ethics Committee, Hong Kong Sanatorium and Hospital.

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Hui, R.WH., Chan, A.CY., Lo, G. et al. Magnetic resonance elastography and proton density fat fraction predict adverse outcomes in hepatocellular carcinoma. Hepatol Int 16, 371–380 (2022).

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