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MRI features associated with HCC histologic subtypes: a western American and European bicenter study

  • Gastrointestinal
  • Published:
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Abstract

Objectives

To evaluate if preoperative MRI can predict the most frequent HCC subtypes in North American and European patients treated with surgical resection.

Methods

A total of 119 HCCs in 97 patients were included in the North American group and 191 HCCs in 176 patients were included in the European group. Lesion subtyping was based on morphologic features and immuno-histopathological analysis. Two radiologists reviewed preoperative MRI and evaluated the presence of imaging features including LI-RADS major and ancillary features to identify clinical, biologic, and imaging features associated with the main HCC subtypes.

Results

Sixty-four percent of HCCs were conventional. The most frequent subtypes were macrotrabecular-massive (MTM—15%) and steatohepatitic (13%). Necrosis (OR = 3.32; 95% CI: 1.39, 7.89; p = .0064) and observation size (OR = 1.011; 95% CI: 1.0022, 1.019; p = .014) were independent predictors of MTM-HCC. Fat in mass (OR = 15.07; 95% CI: 6.57, 34.57; p < .0001), tumor size (OR = 0.97; 95% CI: 0.96, 0.99; p = .0037), and absence of chronic HCV infection (OR = 0.24; 95% CI: 0.084, 0.67; p = .0068) were independent predictors of steatohepatitic HCC. Independent predictors of conventional HCCs were viral C hepatitis (OR = 3.20; 95% CI: 1.62, 6.34; p = .0008), absence of fat (OR = 0.25; 95% CI: 0.12, 0.52; p = .0002), absence of tumor in vein (OR = 0.34; 95% CI: 0.13, 0.84; p = .020), and higher tumor-to-liver ADC ratio (OR = 1.96; 95% CI: 1.14, 3.35; p = .014)

Conclusion

MRI is useful in predicting the most frequent HCC subtypes even in cohorts with different distributions of liver disease etiologies and tumor subtypes which might have future treatment and management implications.

Key Points

• Representation of both liver disease etiologies and HCC subtypes differed between the North American and European cohorts of patients.

• Retrospective two-center study showed that liver MRI is useful in predicting the most frequent HCC subtypes.

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Abbreviations

ADC:

Apparent diffusion coefficient

AFP:

Alpha-fetoprotein

APHE:

Arterial phase hyperenhancement

Cis:

Confidence intervals

DWI:

Diffusion-weighted image

EPI:

Echo-planar imaging

H&E:

Hematoxylin and eosin

HASTE:

Half-Fourier acquisition single-shot turbo spin echo

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

LASSO:

Least absolute shrinkage and selection operator

Li-RADS:

Liver Imaging Reporting and Data System

MTM:

Macrotrabecular massive

NAFLD:

Nonalcoholic fatty liver disease

NASH:

Nonalcoholic steatohepatitis

OR:

Odds ratio

SPAIR:

Spectral pre-saturation attenuated inversion-recovery

TIV:

Tumor in vein

TSE:

Turbo spin echo

US:

United States

VIBE:

Volumetric interpolated breath-hold examination

WHO:

World Health Organization

References

  1. Sung H, Ferlay J, Siegel RL et al (2021) Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209–249. https://doi.org/10.3322/caac.21660

    Article  Google Scholar 

  2. Choo SP, Tan WL, Goh BKP et al (2016) Comparison of hepatocellular carcinoma in Eastern versus Western populations. Cancer 122:3430–3446. https://doi.org/10.1002/cncr.30237

    Article  Google Scholar 

  3. Younossi Z, Stepanova M, Ong JP et al (2019) Nonalcoholic steatohepatitis is the fastest growing cause of hepatocellular carcinoma in liver transplant candidates. Clin Gastroenterol Hepatol 17:748–755.e3. https://doi.org/10.1016/j.cgh.2018.05.057

  4. Petrick JL, Florio AA, Znaor A et al (2020) International trends in hepatocellular carcinoma incidence, 1978-2012. Int J Cancer 147:317–330. https://doi.org/10.1002/ijc.32723

    Article  CAS  Google Scholar 

  5. El Jabbour T, Lagana SM, Lee H (2019) Update on hepatocellular carcinoma: pathologists’ review. World J Gastroenterol 25:1653–1665. https://doi.org/10.3748/wjg.v25.i14.1653

    Article  CAS  Google Scholar 

  6. Hoshida Y, Nijman SMB, Kobayashi M et al (2009) Integrative transcriptome analysis reveals common molecular subclasses of human hepatocellular carcinoma. Cancer Res 69:7385–7392. https://doi.org/10.1158/0008-5472.CAN-09-1089

    Article  CAS  Google Scholar 

  7. Lee J-S, Chu I-S, Heo J et al (2004) Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling. Hepatology 40:667–676. https://doi.org/10.1002/hep.20375

  8. Boyault S, Rickman DS, de Reyniès A et al (2007) Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets. Hepatology 45:42–52. https://doi.org/10.1002/hep.21467

  9. Chiang DY, Villanueva A, Hoshida Y et al (2008) Focal gains of VEGFA and molecular classification of hepatocellular carcinoma. Cancer Res 68:6779–6788. https://doi.org/10.1158/0008-5472.CAN-08-0742

    Article  CAS  Google Scholar 

  10. WHO Classification of Tumours Editorial Board (2019) Digestive system tumours, 5th edn, Lyon

  11. Zucman-Rossi J, Villanueva A, Nault J-C, Llovet JM (2015) Genetic landscape and biomarkers of hepatocellular carcinoma. Gastroenterology 149:1226–1239.e4. https://doi.org/10.1053/j.gastro.2015.05.061

    Article  CAS  Google Scholar 

  12. Calderaro J, Couchy G, Imbeaud S et al (2017) Histological subtypes of hepatocellular carcinoma are related to gene mutations and molecular tumour classification. J Hepatol 67:727–738. https://doi.org/10.1016/j.jhep.2017.05.014

    Article  CAS  Google Scholar 

  13. Reig M, Forner A, Rimola J et al (2022) BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol 76:681–693. https://doi.org/10.1016/j.jhep.2021.11.018

    Article  Google Scholar 

  14. Llovet JM, Brú C, Bruix J (1999) Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 19:329–338. https://doi.org/10.1055/s-2007-1007122

    Article  CAS  Google Scholar 

  15. Lee S, Kim SH, Lee JE et al (2017) Preoperative gadoxetic acid-enhanced MRI for predicting microvascular invasion in patients with single hepatocellular carcinoma. J Hepatol 67:526–534. https://doi.org/10.1016/j.jhep.2017.04.024

    Article  CAS  Google Scholar 

  16. Xu X, Zhang H-L, Liu Q-P et al (2019) Radiomic analysis of contrast-enhanced CT predicts microvascular invasion and outcome in hepatocellular carcinoma. J Hepatol 70:1133–1144. https://doi.org/10.1016/j.jhep.2019.02.023

    Article  Google Scholar 

  17. Renzulli M, Brocchi S, Cucchetti A et al (2016) Can current preoperative imaging be used to detect microvascular invasion of hepatocellular carcinoma? Radiology 279:432–442. https://doi.org/10.1148/radiol.2015150998

    Article  Google Scholar 

  18. Choi S-Y, Kim SH, Park CK et al (2018) Imaging features of gadoxetic acid-enhanced and diffusion-weighted MR imaging for identifying cytokeratin 19-positive hepatocellular carcinoma: a retrospective observational study. Radiology 286:897–908. https://doi.org/10.1148/radiol.2017162846

    Article  Google Scholar 

  19. European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu, European Association for the Study of the Liver (2018) EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 69:182–236. https://doi.org/10.1016/j.jhep.2018.03.019

  20. Marrero JA, Kulik LM, Sirlin CB et al (2018) Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology 68:723–750. https://doi.org/10.1002/hep.29913

  21. Loy LM, Low HM, Choi J-Y et al (2022) Variant hepatocellular carcinoma subtypes according to the 2019 WHO classification: an imaging-focused review. AJR Am J Roentgenol:1–12. https://doi.org/10.2214/AJR.21.26982

  22. Ziol M, Poté N, Amaddeo G et al (2018) Macrotrabecular-massive hepatocellular carcinoma: a distinctive histological subtype with clinical relevance. Hepatology 68:103–112. https://doi.org/10.1002/hep.29762

  23. Mulé S, Galletto Pregliasco A, Tenenhaus A et al (2020) Multiphase liver MRI for identifying the macrotrabecular-massive subtype of hepatocellular carcinoma. Radiology 295:562–571. https://doi.org/10.1148/radiol.2020192230

    Article  Google Scholar 

  24. Chen J, Xia C, Duan T et al (2021) Macrotrabecular-massive hepatocellular carcinoma: imaging identification and prediction based on gadoxetic acid-enhanced magnetic resonance imaging. Eur Radiol 31:7696–7704. https://doi.org/10.1007/s00330-021-07898-7

    Article  CAS  Google Scholar 

  25. Calderaro J, Meunier L, Nguyen CT et al (2019) ESM1 as a marker of macrotrabecular-massive hepatocellular carcinoma. Clin Cancer Res 25:5859–5865. https://doi.org/10.1158/1078-0432.CCR-19-0859

  26. Inui S, Kondo H, Tanahashi Y et al (2021) Steatohepatitic hepatocellular carcinoma: imaging findings with clinicopathological correlation. Clin Radiol 76:160.e15–160.e25. https://doi.org/10.1016/j.crad.2020.09.011

    Article  CAS  Google Scholar 

  27. Salomao M, Yu WM, Brown RS et al (2010) Steatohepatitic hepatocellular carcinoma (SH-HCC): a distinctive histological variant of HCC in hepatitis C virus-related cirrhosis with associated NAFLD/NASH. Am J Surg Pathol 34:1630–1636. https://doi.org/10.1097/PAS.0b013e3181f31caa

    Article  Google Scholar 

  28. Salomao M, Remotti H, Vaughan R et al (2012) The steatohepatitic variant of hepatocellular carcinoma and its association with underlying steatohepatitis. Hum Pathol 43:737–746. https://doi.org/10.1016/j.humpath.2011.07.005

    Article  Google Scholar 

  29. Cannella R, Dioguardi Burgio M, Beaufrère A et al (2021) Imaging features of histological subtypes of hepatocellular carcinoma: implication for LI-RADS. JHEP Rep 3:100380. https://doi.org/10.1016/j.jhepr.2021.100380

  30. Jain D, Nayak NC, Kumaran V, Saigal S (2013) Steatohepatitic hepatocellular carcinoma, a morphologic indicator of associated metabolic risk factors: a study from India. Arch Pathol Lab Med 137:961–966. https://doi.org/10.5858/arpa.2012-0048-OA

    Article  Google Scholar 

  31. Shibahara J, Ando S, Sakamoto Y et al (2014) Hepatocellular carcinoma with steatohepatitic features: a clinicopathological study of Japanese patients. Histopathology 64:951–962. https://doi.org/10.1111/his.12343

    Article  Google Scholar 

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Funding

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

Author information

Author notes

  1. Sébastien Mulé and Ali Serhal equally contributed as first authors.

  2. Frank H. Miller and Alain Luciani equally contributed as senior/last authors.

Authors and Affiliations

  1. Medical Imaging Department, AP-HP, Henri Mondor University Hospital, 51 Avenue du Maréchal de Lattre de Tassigny, 94010, Créteil, France

    Sébastien Mulé, Athena Galletto Pregliasco, Edouard Reizine & Alain Luciani

  2. Faculté de Médecine, Université Paris Est Créteil, Créteil, France

    Sébastien Mulé, Julien Calderaro, Giuliana Amaddeo & Alain Luciani

  3. Department of Radiology, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA

    Ali Serhal, Camila Lopes Vendrami & Frank H. Miller

  4. Department of Pathology, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA

    Jessica Nguyen & Guang-Yu Yang

  5. Pathology Department, AP-HP, Henri Mondor University Hospital, Créteil, France

    Julien Calderaro

  6. Hepatology Department, AP-HP, Henri Mondor University Hospital, Créteil, France

    Giuliana Amaddeo

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  1. Sébastien Mulé
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Corresponding authors

Correspondence to Sébastien Mulé or Ali Serhal.

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Guarantor

The scientific guarantor of this publication is Frank H. Miller.

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

One of the authors has significant statistical expertise.

Informed consent

Written informed consent was waived by the Institutional Review Board.

Ethical approval

Institutional Review Board approval was obtained.

Study subjects or cohorts overlap

Some study subjects or cohorts have been previously reported in a previously published study (Mulé et al, Radiology, 2020. 295(3):562–571. doi: 10.1148/radiol.2020192230).

Methodology

• retrospective

• observational

• multicenter study

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Mulé, S., Serhal, A., Pregliasco, A.G. et al. MRI features associated with HCC histologic subtypes: a western American and European bicenter study. Eur Radiol 33, 1342–1352 (2023). https://doi.org/10.1007/s00330-022-09085-8

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