title: Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Reig
authors.affiliation: Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona, CIBERehd, Barcelona, Spain.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Mariño
authors.affiliation: Liver Unit, Hospital Universitario Puerta de Hierro, CIBERehd, IDIPHIM, Madrid, Spain.
authors.forename: Christie
authors.initials: C
authors.lastname: Perelló
authors.affiliation: Unidad de Hepatología, Clínica Universidad de Navarra, IDISNA, CIBERehd, Pamplona, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Iñarrairaegui
authors.affiliation: Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ribeiro
authors.affiliation: Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona, CIBERehd, Barcelona, Spain.
authors.forename: Sabela
authors.initials: S
authors.lastname: Lens
authors.affiliation: Department of Pathology, BCLC Group, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Díaz
authors.affiliation: Department of Radiology, BCLC Group, Hospital Clinic Barcelona, University of Barcelona, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Vilana
authors.affiliation: Department of Radiology, BCLC Group, Hospital Clinic Barcelona, University of Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Darnell
authors.affiliation: Liver Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Varela
authors.affiliation: Unidad de Hepatología, Clínica Universidad de Navarra, IDISNA, CIBERehd, Pamplona, Spain.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sangro
authors.affiliation: Liver Unit, Hospital Universitario Puerta de Hierro, CIBERehd, IDIPHIM, Madrid, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Calleja
authors.affiliation: Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona, CIBERehd, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Forns
authors.affiliation: Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain. Electronic address: jbruix@clinic.ub.es.
authors.forename: Jordi
authors.initials: J
authors.lastname: Bruix
mesh_terms: D000998:Antiviral Agents; D006528:Carcinoma, Hepatocellular; D016174:Hepacivirus; D006526:Hepatitis C; D019698:Hepatitis C, Chronic; D006801:Humans; D007372:Interferons; D008113:Liver Neoplasms; D009364:Neoplasm Recurrence, Local; D012008:Recurrence
chemical_list: D000998:Antiviral Agents; D007372:Interferons
keywords: Direct-acting antivirals; HCV viral kinetics; Hepatocellular carcinoma; Immune responses; Interferon-free regimen; Tumor recurrence