European Radiology

, Volume 28, Issue 2, pp 506–513 | Cite as

Imaging features of microvascular invasion in hepatocellular carcinoma developed after direct-acting antiviral therapy in HCV-related cirrhosis

  • Matteo Renzulli
  • Federica Buonfiglioli
  • Fabio Conti
  • Stefano Brocchi
  • Ilaria Serio
  • Francesco Giuseppe Foschi
  • Paolo Caraceni
  • Giuseppe Mazzella
  • Gabriella Verucchi
  • Rita Golfieri
  • Pietro Andreone
  • Stefano Brillanti
Gastrointestinal

Abstract

Objectives

To evaluate imaging features of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) developed after direct-acting antiviral (DAA) therapy in HCV-related cirrhosis.

Methods

Retrospective cohort study on 344 consecutive patients with HCV-related cirrhosis treated with DAA and followed for 48–74 weeks. Using established imaging criteria for MVI, HCC features were analysed and compared with those in nodules not occurring after DAA.

Results

After DAA, HCC developed in 29 patients (single nodule, 18 and multinodular, 11). Median interval between therapy end and HCC diagnosis was 82 days (0–318). Forty-one HCC nodules were detected (14 de novo, 27 recurrent): maximum diameter was 10–20 mm in 27, 20–50 mm in 13, and > 50 mm in 1. Imaging features of MVI were present in 29/41 nodules (70.7%, CI: 54–84), even in 17/29 nodules with 10–20 mm diameter (58.6%, CI: 39–76). MVI was present in only 17/51 HCC nodules that occurred before DAA treatment (33.3%, CI: 22–47) (p= 0.0007). MVI did not correlate with history of previous HCC.

Conclusions

HCC occurs rapidly after DAA therapy, and aggressive features of MVI characterise most neoplastic nodules. Close imaging evaluations are needed after DAA in cirrhotic patients.

Key Points

In HCV cirrhosis, hepatocellular carcinoma develops soon after direct-acting antiviral therapy.

HCC presents imaging features of microvascular invasion, predictive of more aggressive progression.

Cirrhotic patients need aggressive and close monitoring after direct-acting antiviral therapy.

Keywords

Hepatitis C Liver neoplasms Computed tomography Magnetic resonance imaging Drug side effects 

Abbreviations

BCLC

Barcelona clinic liver cancer

CI

Confidence interval

CT

Computed tomography

DAA

Direct-acting antiviral

HBV

Hepatitis B virus

HCC

Hepatocellular carcinoma

HCV

Hepatitis C virus

MRI

Magnetic resonance imaging

MVI

Microvascular invasion

NSTM

Non-smooth tumour margins

OR

Odds ratio

PEI

Percutaneous ethanol injection

PTE

Peritumoral enhancement

RFA

Radiofrequency ablation

SVR

Sustained virological response

TACE

Transarterial chemoembolisation

TTPVI

Two-trait predictor of venous invasion

Notes

Funding

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

Compliance with ethical standards

Guarantor

The scientific guarantor of this publication is Stefano Brillanti, M.D., Department of Medical and Surgical Sciences, University of Bologna, Italy.

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

No complex statistical methods were necessary for this paper.

Ethical approval

Institutional Review Board approval was obtained.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Methodology

• retrospective

• case-control study

• performed at one institution

References

  1. 1.
    AASLD-IDSA (2017) Recommendations for testing, managing, and treating hepatitis C. Available via http://www.hcvguidelines.org. Accessed on 31 Jul 2017
  2. 2.
    EASL (2017) Recommendations on Treatment of Hepatitis C 2016. J Hepatol 66:153–194CrossRefGoogle Scholar
  3. 3.
    Morgan TR, Ghany MG, Kim HY et al (2010) Outcome of sustained virological responders with histologically advanced chronic hepatitis C. Hepatology 52:833–844CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    van der Meer AJ, Feld JJ, Hofer H et al (2017) Risk of cirrhosis-related complications in patients with advanced fibrosis following hepatitis C virus eradication. J Hepatol 66:485–493CrossRefPubMedGoogle Scholar
  5. 5.
    Morgan RL, Baack B, Smith BD, Yartel A, Pitasi M, Yet F-Y (2013) Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies. Ann Intern Med 158:329–337CrossRefPubMedGoogle Scholar
  6. 6.
    Huang CF, Yeh ML, Tsai PC et al (2014) Baseline gamma-glutamyl transferase levels strongly correlate with hepatocellular carcinoma development in non-cirrhotic patients with successful hepatitis C virus eradication. J Hepatol 61:67–74CrossRefPubMedGoogle Scholar
  7. 7.
    El-Serag HB, Kanwal F, Richardson P, Kramer J (2016) Risk of hepatocellular carcinoma after sustained virological response in Veterans with hepatitis C virus infection. Hepatology 64:130–137CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Nault JC, Colombo M (2016) Hepatocellular carcinoma and direct acting antiviral treatments: Controversy after the revolution. J Hepatol 65:663–665CrossRefPubMedGoogle Scholar
  9. 9.
    Conti F, Buonfiglioli F, Scuteri A et al (2016) Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals. J Hepatol 65:727–733CrossRefPubMedGoogle Scholar
  10. 10.
    Reig M, Mariño Z, Perelló C et al (2016) Unexpected high rate of early tumour recurrence in patients with HCV-related HCC undergoing interferon-free therapy. J Hepatol 65:719–726CrossRefPubMedGoogle Scholar
  11. 11.
    Roayaie S, Blume IN, Thung SN et al (2009) A system of classifying microvascular invasion to predict outcome after resection in patients with hepatocellular carcinoma. Gastroenterology 137:850–855CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Lencioni R, Llovet JM (2010) Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 30:52–60CrossRefPubMedGoogle Scholar
  13. 13.
    Kim H, Park MS, Choi JY et al (2009) Can microvessel invasion of hepatocellular carcinoma be predicted by pre-operative MRI? Eur Radiol 19:1744–1751CrossRefPubMedGoogle Scholar
  14. 14.
    Banerjee S, Wang DS, Kim HJ et al (2015) A computed tomography radiogenomic biomarker predicts microvascular invasion and clinical outcomes in hepatocellular carcinoma. Hepatology 62:792–800CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Renzulli M, Brocchi S, Cucchetti A et al (2016) Can Current Preoperative Imaging Be Used to Detect Microvascular Invasion of Hepatocellular Carcinoma? Radiology 279:432–442CrossRefPubMedGoogle Scholar
  16. 16.
    Lee S, Kim SH, Lee JE, Sinn DH, Park CK (2017) Preoperative gadoxetic acid-enhanced MRI for predicting microvascular invasion in patients with single hepatocellular carcinoma. J Hepatol.  https://doi.org/10.1016/j.jhep.2017.04.024
  17. 17.
    Kozbial K, Moser S, Schwarzer R et al (2016) Unexpected high incidence of hepatocellular carcinoma in cirrhotic patients with sustained virologic response following interferon-free direct-acting antiviral treatment. J Hepatol 65:856–858CrossRefPubMedGoogle Scholar
  18. 18.
    Romano A, Capra F, Piovesan S et al (2016) Incidence and pattern of "de novo" hepatocellular carcinoma in HCV patients treated with oral DAAs. Hepatology 63:10AGoogle Scholar
  19. 19.
    Reig M, Mariño Z, Perelló C et al (2017) Tumour recurrence after Interferon-free treatment for hepatitis C in patients with previously treated hepatocellular carcinoma discloses a more aggressive pattern and faster tumour growth. J Hepatol 66:PS-031Google Scholar
  20. 20.
    Lim KC, Chow PK, Allen JC et al (2011) Microvascular invasion is a better predictor of tumour recurrence and overall survival following surgical resection for hepatocellular carcinoma compared to the Milan criteria. Ann Surg 254:108–113CrossRefPubMedGoogle Scholar
  21. 21.
    Werner JM, Adenugba A, Protzer U (2017) Immune Reconstitution After HCV Clearance With Direct Antiviral Agents: Potential Consequences for Patients With HCC? Transplantation 101:904–909CrossRefPubMedGoogle Scholar
  22. 22.
    EASL-EORTC (2012) Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 56:908–943CrossRefGoogle Scholar
  23. 23.
    Belli LS, Berenguer M, Cortesi PA et al (2016) Delisting of liver transplant candidates with chronic hepatitis C after viral eradication: A European study. J Hepatol 65:524–531CrossRefPubMedGoogle Scholar
  24. 24.
    Yang JD, Aqel BA, Pungpapong S, Gores GJ, Roberts LR, Leise MD (2016) Direct acting antiviral therapy and tumor recurrence after liver transplantation for hepatitis C-associated hepatocellular carcinoma. J Hepatol 65:859–860CrossRefPubMedGoogle Scholar

Copyright information

© European Society of Radiology 2017

Authors and Affiliations

  • Matteo Renzulli
    • 1
  • Federica Buonfiglioli
    • 2
  • Fabio Conti
    • 2
  • Stefano Brocchi
    • 1
  • Ilaria Serio
    • 3
  • Francesco Giuseppe Foschi
    • 4
  • Paolo Caraceni
    • 5
  • Giuseppe Mazzella
    • 5
  • Gabriella Verucchi
    • 2
  • Rita Golfieri
    • 1
  • Pietro Andreone
    • 2
  • Stefano Brillanti
    • 2
    • 6
  1. 1.Department of Diagnostic Medicine and PreventionSant’Orsola-Malpighi HospitalBolognaItaly
  2. 2.Research Centre for the Study of Hepatitis, Department of Medical and Surgical Sciences DIMECUniversity of BolognaBolognaItaly
  3. 3.Department of Digestive DiseasesSant’Orsola-Malpighi HospitalBolognaItaly
  4. 4.Division of Internal MedicineOspedale di FaenzaFaenzaItaly
  5. 5.Department of Medical and Surgical Sciences (DIMEC)University of BolognaBolognaItaly
  6. 6.U.O. di GastroenterologiaBolognaItaly

Personalised recommendations