Advertisement

The influence of direct-acting antivirals in hepatitis C virus related hepatocellular carcinoma after curative treatment

  • Yuan-Hung Kuo
  • Jing-Houng Wang
  • Kuo-Chin Chang
  • Chao-Hung Hung
  • Sheng-Nan Lu
  • Tsung-Hui Hu
  • Yi-Hao Yen
  • Kwong-Ming Kee
  • Chien-Hung ChenEmail author
PHASE III STUDIES

Summary

This study was done to elucidate the influence of direct-acting antiviral (DAA) agents on the recurrence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related HCC (HCV-HCC) after curative therapies. HCV-HCC patients who received curative therapies and obtained a complete response were analyzed. From January 2017 to September 2017, 112 HCV-HCC patients received DAA and obtained a sustained virological response (SVR). From January 2006 to December 2014, another 345 HCV-HCC patients received peg-interferon-based treatment and 118 obtained SVR. From January 2012 to December 2016, 248 HCV-HCC patients had complete HCC response and did not receive antiviral treatment. Patients were divided into DAA, IFN, and Untreated groups based on what antiviral treatment they received. There were 82 patients in the DAA group, 80 patients in the IFN group, and 160 patients in the Untreated group. During the follow-up period, the DAA group had 22 (26.8%) recurrent cases, whereas the IFN group had 46 (56.8%) cases after antiviral treatment. Among the 22 recurrent cases in the DAA group, 19 (86.9%) experienced HCC recurrence during 1 year after DAA initiation. Compared with the IFN group, the DAA group had poorer one-year recurrence-free survival (75.4% vs. 95%, p < 0.001), even after adjustment with propensity score matching (81.4% vs. 93.9%, p = 0.034). However, DAA was an improving factor for HCC recurrence compared with the Untreated group in the multivariate analysis. Among HCV-HCC patients with complete treatment, those with DAA-induced SVR had a higher one-year recurrence rate than those who received IFN-based antiviral therapy, but DAA did not seem to increase HCC recurrence compared to untreated patients.

Keywords

Direct-acting antiviral agent Hepatocellular carcinoma Hepatitis C virus Interferon-based therapy Recurrence 

Notes

Acknowledgements

We thank Miss Nien-Tzu Hsu and the biostatistics center of Kaohsiung Chang Gung Memorial Hospital for excellent statistics works.

Funding

This study was supported by a grant from Chang Gung Memorial Hospital (CMRPG:8F0443).

Compliance with ethical standards

Conflict of interest

Yuan-Hung Kuo declares that he has no conflict of interest. Jing-Houng Wang declares that he has no conflict of interest. Kuo-Chin Chang declares that he has no conflict of interest. Chao-Hung Hung declares that he has no conflict of interest. Sheng-Nan Lu declares that he has no conflict of interest. Tsung-Hui Hu declares that he has no conflict of interest. Yi-Hao Yen declares that he has no conflict of interest. Kwong-Ming Kee declares that he has no conflict of interest. Chien-Hung Chen declares that he has no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. And this study was also approved by the Institutional Review Board of our institute: Kaohsiung Chang Gung Memorial Hospital.

Informed consent

For this type of retrospective study, informed consent is not required.

References

  1. 1.
    El-Serag HB (2012) Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 142:1264–1273CrossRefGoogle Scholar
  2. 2.
    Hoshida Y, Fuchs BC, Bardeesy N, Baumert TF, Chung RT (2014) Pathogenesis and prevention of hepatitis C virus- induced hepatocellular carcinoma. J Hepatol 61:S79–S90CrossRefGoogle Scholar
  3. 3.
    Fried MW, Shiffman ML, Reddy KR et al (2002) Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 347:975–982CrossRefGoogle Scholar
  4. 4.
    Veldt BJ, Heathcote EJ, Wedemeyer H et al (2007) Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Ann Intern Med 147:677–864CrossRefGoogle Scholar
  5. 5.
    Morgan RL, Baack B, Smith BD et al (2013) Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies. Ann Intern Med 158:329–337CrossRefGoogle Scholar
  6. 6.
    van der Meer AJ, Veldt BJ, Feld JJ, Wedemeyer H, Dufour JF, Lammert F et al (2012) Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA 308:2584–2593CrossRefGoogle Scholar
  7. 7.
    Afdhal N, Zeuzem S, Kwo P et al (2014) Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med 370:1889–1898CrossRefGoogle Scholar
  8. 8.
    Charlton M, Everson GT, Flamm SL et al (2015) Ledipasvir and sofosbuvir plus ribavirin for treatment of HCV infection in patients with advanced liver disease. Gastroenterology 149:649–659CrossRefGoogle Scholar
  9. 9.
    Leroy V, Angus P, Bronowicki JP et al (2016) Daclatasvir, sofosbuvir, and ribavirin for hepatitis C virus genotype 3 and advanced liver disease: a randomized phase III study (ALLY-3+). Hepatology 63:1430–1441CrossRefGoogle Scholar
  10. 10.
    Reig M, Mariño Z, Perelló C et al (2016) Unexpected high rate of early tumor recurrence in patients with HCVrelated HCC undergoing interferon-free therapy. J Hepatol 65:719–726CrossRefGoogle Scholar
  11. 11.
    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 65:727–733CrossRefGoogle Scholar
  12. 12.
    Kanwal F, Kramer J, Asch SM et al (2017) Risk of hepatocellular cancer in HCV patients treated with direct-acting antiviral agents. Gastroenterology 153:996–1005CrossRefGoogle Scholar
  13. 13.
    Ioannou G, Green P, Berry K (2018) HCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma. J Hepatol 68:25–32CrossRefGoogle Scholar
  14. 14.
    Manthravadi S, Paleti S, Pandya P (2017) Impact of sustained viral response postcurative therapy of hepatitis C-related hepatocellular carcinoma: a systematic review and meta-analysis. Int J Cancer 140(5):1042–1049CrossRefGoogle Scholar
  15. 15.
    Forner A, Llovet JM, Bruix J (2012) Hepatocellular carcinoma. Lancet 379(9822):1245–1255CrossRefGoogle Scholar
  16. 16.
    European Association for the Study of the Liver (2018) EASL recommnedations on tretment of hepatitis C 2018. J Hepatol 69(2):461–511CrossRefGoogle Scholar
  17. 17.
    Omata M, Kanda T, Wei L et al (2016) APASL consensus statements and recommendation on treatment of hepatitis C. Hepatol Int 10(5):702–726CrossRefGoogle Scholar
  18. 18.
    The reimbursement criteria of anti-HCV treatment (2017) The National Health Insurance Administration, Ministry of Health and Welfare, ROCGoogle Scholar
  19. 19.
    Nault JC, Colombo M (2016) Hepatocellular carcinoma and direct acting antiviral treatments: controversy after the revolution. J Hepatol 65:663–665CrossRefGoogle Scholar
  20. 20.
    Llovet JM, Villanueva A (2016) Liver cancer: effect of HCV clearance with direct- acting antiviral agents on HCC. Nat Rev Gastroenterol Hepatol 13:561–562CrossRefGoogle Scholar
  21. 21.
    Serti E, Chepa-Lotrea X, Kim YJ et al (2015) Successful interferon- free therapy of chronic hepatitis C virus infection normalizes natural killer cell function. Gastroenterology. 149:190–200CrossRefGoogle Scholar
  22. 22.
    Portolani N, Coniglio A, Ghidoni S et al (2006) Early and late recurrence after liver resection for hepatocellular carcinoma: prognostic and therapeutic implications. Ann Surg 243:229–235CrossRefGoogle Scholar
  23. 23.
    Waziry R, Grebely J, Amin J et al (2016) Trends in hepatocellular carcinoma among people with HBV or HCV notification in Australia (2000–2014). J Hepatol 65:1086–1093CrossRefGoogle Scholar
  24. 24.
    Hagihara H, Nouso K, Kobayashi Y et al (2011) Effect of pegylated interferon therapy on intrahepatic recurrence after curative treatment of hepatitis C virus-related hepatocellular carcinoma. Int J Clin Oncol 16:210–220CrossRefGoogle Scholar
  25. 25.
    ANRS collaborative study group on hepatocellular carcinoma (ANRS CO22 HEPATHER, CO12 CirVir and CO23 CUPILT cohorts) (2016) Lack of evidence of an effect of direct-acting antivirals on the recurrence of hepatocellular carcinoma: Data from three ANRS cohorts. J Hepatol 65:734–740CrossRefGoogle Scholar
  26. 26.
    Ikeda K, Kawamura Y, Kobayashi M et al (2017) Direct-acting antivirals decreased tumor recurrence after initial treatment of hepatitis C virus-related hepatocellular carcinoma. Dig Dis Sci 62:2932–2942CrossRefGoogle Scholar
  27. 27.
    Cabibbo G, Petta S, Barbàra M et al (2017) A metaanalysis of single HCV-untreated arm of studies evaluating outcomes after curative treatments of HCV-related hepatocellular carcinoma. Liver Int 37:1157–1166CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Hepatogastroenterology, Department of Internal MedicineKaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineKaohsiung CityTaiwan
  2. 2.Division of Hepatogastroenterology, Department of Internal MedicineChiayi Chang Gung Memorial HospitalChiayiTaiwan

Personalised recommendations