Incidental hepatocellular carcinoma after liver transplantation: Prevalence, histopathological features and prognostic impact

PLoS One. 2017 Apr 12;12(4):e0175010. doi: 10.1371/journal.pone.0175010. eCollection 2017.

Abstract

Background: Incidental hepatocellular carcinoma (iHCC) is a histological finding after liver transplantation (LT) which relevance has been scarcely studied.

Aims: 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).

Conclusion: 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.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Carcinoma, Hepatocellular / etiology
  • Carcinoma, Hepatocellular / mortality*
  • Carcinoma, Hepatocellular / pathology
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Liver / pathology
  • Liver / surgery
  • Liver Neoplasms / etiology
  • Liver Neoplasms / mortality*
  • Liver Neoplasms / pathology
  • Liver Transplantation / adverse effects*
  • Liver Transplantation / mortality
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prevalence
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies

Grants and funding

The present project has been partially supported by the Instituto de Salud Carlos III (FIS PI14/01469) and co-funded by FEDER. M. Rodríguez-Perálvarez is a recipient of the EASL physician scientist Fellowship awarded by the European Association for the Study of the Liver (EASL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.