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

Pablo Pérez,Marina Sánchez-Frías,Lourdes Guerrero,Jose Luis Montero,Macarena Centeno,Víctor González,Antonio Poyato,Manuel Rodríguez-Perálvarez,Manuel De La Mata,Javier Briceño,Rafael Sánchez,William B Coleman

doi:10.1371/journal.pone.0175010

Abstract

BackgroundIncidental hepatocellular carcinoma (iHCC) is a histological finding after liver transplantation (LT) which relevance has been scarcely studied.Aimsto describe the histopathological features of iHCC and to determine its prognostic impact in terms of tumor recurrence and overall survival.MethodsObservational 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.Results141 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).ConclusionThe 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.

Highlights

Hepatocellular carcinoma (HCC) is the main cause of death among patients with end-stage liver disease, and the second leading indication for liver transplantation (LT) in Europe and US [1, 2]
The risk of tumor recurrence after LT is similar in patients with incidental hepatocellular carcinoma” (iHCC) and known HCC
A close imaging surveillance is strongly recommended for patients awaiting LT in order to detect HCC prior to LT, allowing for an adequate selection of candidates, prioritization and indication of bridging therapies

Summary

Introduction

Hepatocellular carcinoma (HCC) is the main cause of death among patients with end-stage liver disease, and the second leading indication for liver transplantation (LT) in Europe and US [1, 2]. It has been suggested that an intensive imaging surveillance by using high resolution dynamic techniques Despite the technologic development observed in recent years, HCC remains elusive in some patients before LT, and it is sometimes unexpectedly diagnosed in the histopathologic examination of the explanted liver, in what has been termed as “incidental hepatocellular carcinoma” (iHCC). This subset of patients with iHCC may not benefit from any of the above referred strategies to prevent tumor recurrence [11]. Incidental hepatocellular carcinoma (iHCC) is a histological finding after liver transplantation (LT) which relevance has been scarcely studied

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