title: Incidental hepatocellular carcinoma after liver transplantation: Prevalence, histopathological features and prognostic impact.
abstract: BACKGROUND
  Incidental hepatocellular carcinoma (iHCC) is a histological finding after liver transplantation (LT) which relevance has been scarcely studied.
  
  
  OBJECTIVE
  to describe the histopathological features of iHCC and to determine its prognostic impact in terms of tumor recurrence and overall survival.
  
  
  METHODS
  Observational study including 451 consecutive adult LT patients (2000-2013). Patients aged<18, retransplanted or with early postoperative death were excluded. Median follow-up after LT was 58 months. Multiple Cox's regression was used to assess the prognostic impact of iHCC on tumor recurrence and mortality while controlling for potential confounders.
  
  
  RESULTS
  141 patients had known HCC before LT (31.3%). Among the remaining 310 patients, the prevalence of iHCC was 8.7% (n = 27). In the explanted liver, 36.2% of patients with known HCC and 25.9% of patients with iHCC trespassed Milan criteria (p = 0.30). Patients with known and iHCC had similar rates of multinodular disease (50.4% vs 55.6%; p = 0.62), macrovascular invasion (6.5% vs 3.7%; p = 0.58), microvascular invasion (12.9% vs 14.8%; p = 0.76) and moderate-poor tumor differentiation (53.9% vs 70.4%; p = 0.09). In the multivariate analysis, iHCC and known HCC had identical recurrence-free survival after controlling for histological features (RR = 1.06, 95%CI 0.36-3.14; p = 0.90). Cumulative 5-year overall survival rates were similar between patients with known and iHCC (65% vs 52.8% respectively; log rank p = 0.44), but significantly inferior as compared with patients without HCC (77.8%) (p = 0.002 and p = 0.007 respectively). Indeed, in the overall cohort, iHCC was an independent predictor of mortality (RR = 3.02; 95%CI 1.62-5.65; p = 0.001).
  
  
  CONCLUSIONS
  The risk of tumor recurrence after LT is similar in patients with iHCC and known HCC. A close imaging surveillance is strongly recommended for patients awaiting LT in order to detect HCC prior to LT, thus allowing for an adequate selection of candidates, prioritization and indication of bridging therapies.
authors.affiliation: Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Córdoba, Spain.
authors.forename: Pablo
authors.identifier: http://orcid.org/0000-0002-4182-0254
authors.initials: P
authors.lastname: Pérez
authors.affiliation: Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Córdoba, Spain.|Maimónides Institute of Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain.|CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Manuel
authors.identifier: http://orcid.org/0000-0002-1795-2919
authors.initials: M
authors.lastname: Rodríguez-Perálvarez
authors.affiliation: Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Córdoba, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Guerrero
authors.affiliation: Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Córdoba, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: González
authors.affiliation: Department of Pathology, Reina Sofía University Hospital, Córdoba, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Sánchez
authors.affiliation: Department of Pathology, Reina Sofía University Hospital, Córdoba, Spain.
authors.forename: Macarena
authors.initials: M
authors.lastname: Centeno
authors.affiliation: Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Córdoba, Spain.|Maimónides Institute of Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain.|CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Poyato
authors.affiliation: Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Córdoba, Spain.|Maimónides Institute of Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Briceño
authors.affiliation: Department of Pathology, Reina Sofía University Hospital, Córdoba, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Sánchez-Frías
authors.affiliation: Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Córdoba, Spain.|Maimónides Institute of Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain.|CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Montero
authors.affiliation: Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Córdoba, Spain.|Maimónides Institute of Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain.|CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: De la Mata
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000401:mortality* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000473:pathology / Q000601:surgery; D008113:Liver Neoplasms / Q000209:etiology / Q000401:mortality* / Q000473:pathology; D016031:Liver Transplantation / Q000009:adverse effects* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies