Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy

J Hepatol. 2016 Oct;65(4):719-726. doi: 10.1016/j.jhep.2016.04.008. Epub 2016 Apr 13.


Background & aims: The success of direct-acting antivirals (DAA) against hepatitis C is a major breakthrough in hepatology. Until now, however, there are very few data on the effect of hepatitis C virus (HCV) eradication in patients who have already developed hepatocellular carcinoma.

Methods: The study included patients with HCV infection and prior history of treated hepatocellular carcinoma who achieved complete response and lacked 'non-characterized nodules' at the time they underwent anti-HCV treatment with all-oral DAAs in 4 hospitals. Patients receiving interferon as part of the antiviral regimen were excluded. The baseline characteristics, laboratory and radiologic tumor response were registered in all patients before starting antiviral therapy and during the follow-up according to the clinical practice policy.

Results: Between 2014 and 2015, 103 patients with prior hepatocellular carcinoma received DAA, 58 of them met the inclusion criteria. After a median follow-up of 5.7months, 3 patients died and 16 developed radiologic tumor recurrence (27.6%). The pattern of recurrence was: intrahepatic growth (3 patients), new intrahepatic lesion (1 nodule in 5 patients, up to 3 nodules less or equal to 3cm in 4 cases and multifocal in one patient) and infiltrative ill-defined hepatocellular carcinoma and/or extra-hepatic lesions in 3 patients.

Conclusions: Our data show an unexpected high rate and pattern of tumor recurrence coinciding with HCV clearance and, although based in a very small cohort of patients, should be taken as a note of caution and prime a large scale assessment that exceeds the individual investigators capacity.

Lay summary: High rate of cancer recurrence after DAA treatment in patients with prior hepatocellular carcinoma. Disruption of immune surveillance may facilitate the emergence of metastatic clones.

Keywords: Direct-acting antivirals; HCV viral kinetics; Hepatocellular carcinoma; Immune responses; Interferon-free regimen; Tumor recurrence.

MeSH terms

  • Antiviral Agents
  • Carcinoma, Hepatocellular*
  • Hepacivirus
  • Hepatitis C
  • Hepatitis C, Chronic
  • Humans
  • Interferons
  • Liver Neoplasms*
  • Neoplasm Recurrence, Local
  • Recurrence


  • Antiviral Agents
  • Interferons