Hepatocellular metastasis recurrence in liver transplant after treatment with direct antiviral agents

Abstract

Chronic HCV liver infection is considered one of the main causes of liver cirrhosis and hepatocellular carcinoma (HCC). For a selected group of patients, orthotopic liver transplantation (OLTx) is the most effective option to cure both liver diseases. After liver transplantation, patients may be at risk of viral infection reactivation and HCC recurrence. HCV recurrence on the transplanted organ can lead to graft cirrhosis and therefore the clearance of virus with antiviral therapies has a pivotal role on the prevention of graft damage. Nowadays, direct antiviral agents (DAAs) represent the choice treatment for HCV recurrence in liver transplanted patients, ensuring high eradication rates. We present the case of a liver transplant recipient who developed, 7 years after OLTx and immediately after a DAAs treatment, a subcutaneous abdominal mass with histological characteristics of HCC.

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References

  1. 1.

    European Association For The Study Of The Liver. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56:908–43.

    Article  Google Scholar 

  2. 2.

    Heimbach JK, Kulik LM, Finn RS, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2017;67:358–80.

    Article  Google Scholar 

  3. 3.

    Zamor PJ, deLemos AS, Russo MW. Viral hepatitis and hepatocellular carcinoma: etiology and management. J Gastrointest Oncol. 2017;8:229–42.

    Article  Google Scholar 

  4. 4.

    Mazzaferro V, Llovet JM, Miceli R, et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol. 2009;10:35–43.

    Article  Google Scholar 

  5. 5.

    Roayaie S, Blume IN, Thung SN, et al. A system of classifying microvascular invasion to predict outcome after resection in patients with hepatocellular carcinoma. Gastroenterology. 2009;137:850–5.

    Article  Google Scholar 

  6. 6.

    Kneuertz PJ, Cosgrove DP, Cameron AM, et al. Multidisciplinary management of recurrent hepatocellular carcinoma following liver transplantation. J Gastrointest Surg. 2012;16:874–81.

    Article  Google Scholar 

  7. 7.

    Llovet JM, Brú C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19:329–38.

    CAS  Article  Google Scholar 

  8. 8.

    D’Amico F, Schwartz M, Vitale A, et al. Predicting recurrence after liver transplantation in patients with hepatocellular carcinoma exceeding the up-to-seven criteria. Liver Transpl. 2009;15:1278–87.

    Article  Google Scholar 

  9. 9.

    Duseja A. Staging of hepatocellular carcinoma. J Clin Exp Hepatol. 2014;4(Suppl 3):74–9.

    Article  Google Scholar 

  10. 10.

    Onen A, Sanli A, Karacam V, et al. Chest-wall metastasis in a patient who underwent liver transplantation due to hepatocellular carcinoma. Heart Lung Circ. 2008;17:156–8.

    Article  Google Scholar 

  11. 11.

    Katyal S, Oliver JH, Peterson MS, et al. Extrahepatic metastases of hepatocellular carcinoma. Radiology. 2000;216:698–703.

    CAS  Article  Google Scholar 

  12. 12.

    Strazzulla A, Iemolo RMR, Carbone E, et al. The risk of hepatocellular carcinoma after directly acting antivirals for hepatitis C virus treatment in liver transplanted patients: Is it real? Hepat Mon. 2016;16:e41933.

    Article  Google Scholar 

  13. 13.

    Reig M, Marino M, Perello C, et al. Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy. J Hepatol. 2016;65:719–26.

    CAS  Article  Google Scholar 

  14. 14.

    Reig M, Boix L, Bruix J. The impact of direct antiviral agents on the development and recurrence of hepatocellular carcinoma. Liver Int. 2017;37(Suppl 1):136–9.

    Article  Google Scholar 

  15. 15.

    Grandhe S, Frenette CT. Occurrence and recurrence of hepatocellular carcinoma after successful direct-acting antiviral therapy for patients with chronic hepatitis C virus infection. Gastroenterol Hepatol (N Y). 2017;13:421–5.

    Google Scholar 

  16. 16.

    Cucchetti A, D’Amico G, Trevisani F, et al. Effect of direct-acting antivirals on future occurrence of hepatocellular carcinoma in compensated cirrhotic patients. Dig Liver Dis. 2018;50:156–62.

    CAS  Article  Google Scholar 

  17. 17.

    Nagaoki Y, Aikata H, Nakano N, et al. Development of hepatocellular carcinoma in patients with hepatitis C virus infection who achieved sustained virological response following interferon therapy: a large-scale, long-term cohort study. J Gastroenterol Hepatol. 2016;31:1009–15.

    CAS  Article  Google Scholar 

  18. 18.

    The ANRS. Lack of evidence of an effect of direct-acting antivirals on the recurrence of hepatocellular carcinoma: Data from three ANRS cohorts. J Hepatol. 2016;65:734–40.

    Article  Google Scholar 

  19. 19.

    Yang JD, Leise MD. Damned if you do, damned if you don’t: the evolving story of de novo and recurrent hepatocellular carcinoma amongst those treated with direct-acting antivirals for hepatitis C virus. Liver Int. 2017;37:809–11.

    Article  Google Scholar 

  20. 20.

    Yang JD, Aqel BA, Pungpapong S, et al. Direct acting antiviral therapy and tumor recurrence after liver transplantation for hepatitis C-associated hepatocellular carcinoma. J Hepatol. 2016;65:859–60.

    Article  Google Scholar 

  21. 21.

    Reig M, Boix L, Marino Z, et al. Liver cancer emergence associated with antiviral treatment: an immune surveillance failure? Semin Liver Dis. 2017;37:109–18.

    Article  Google Scholar 

  22. 22.

    Muller L, Aigner P, Stoiber D. Type I interferons and natural killer cell regulation in cancer. Front Immunol. 2017;8:304.

    PubMed  PubMed Central  Google Scholar 

  23. 23.

    Hengst J, Strunz B, Deterding K, et al. Nonreversible MAIT cell-dysfunction in chronic hepatitis C virus infection despite successful interferon-free therapy. Eur J Immunol. 2016;46:2204–10.

    CAS  Article  Google Scholar 

  24. 24.

    Walker NF, Scriven J, Meintjes G, et al. Immune reconstitution inflammatory syndrome in HIV-infected patients. HIV AIDS (Auckl). 2015;7:49–64.

    Google Scholar 

  25. 25.

    de’Angelis N, Landi F, Carra MC, et al. Managements of recurrent hepatocellular carcinoma after liver transplantation: a systematic review. World J Gastroenterol. 2015;21:11185–98.

    Article  Google Scholar 

  26. 26.

    Clavien PA, Lesurtel M, Bossuyt PM, et al. Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol. 2012;13:e11–22.

    Article  Google Scholar 

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Correspondence to Giorgio Soardo.

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Maier, S., Donnini, D., De Luca, L. et al. Hepatocellular metastasis recurrence in liver transplant after treatment with direct antiviral agents. Clin J Gastroenterol 13, 260–266 (2020). https://doi.org/10.1007/s12328-019-01031-4

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Keywords

  • Hepatocellular carcinoma metastasis
  • Orthotopic liver transplantation
  • Hepatitis C infection
  • Direct antiviral agents