Immunosuppression exposes recipients of liver transplant to de novo malignancies.1 However, few data are available regarding de novo primary liver cancer (PLC) and especially hepatocellular carcinoma (HCC). Indeed, interpretation of data is challenging as most PLCs after liver transplant are mainly recurrence of pretransplant cancer.2 As a result, only 14 cases of de novo HCC have been reported so far in the literature; 9/12 patients had recurrence of the initial liver disease associated with cirrhosis at time of HCC diagnosis and 8 patients died. In these 14 cases, 5 patients had hepatitis B virus, 3 had hepatitis C virus (HCV), 3 had HCV + alcoholism, 2 had alcoholic liver disease, and 1 had Budd-Chiari syndrome.3-14 De novo cholangiocarcinoma is rare and mostly related to primary sclerosing cholangitis (PSC) recurrence.15,16
We had the opportunity to analyze the data of a cohort of 15 803 liver transplant recipients (trans-planted between 1993 and 2012, with median follow-up of 6.00 ± 5.33 y), obtained from the French national database Cristal (Agence de la Biomédecine). All liver transplant recipients with PLC before (2984) or at the time of transplant (112) were excluded. From this group, 5 patients (5/12 707; 0.04%) presented with de novo PLC (3 with HCC, 1 with intrahepatic cholangio-carcinoma peripheral, and 1 with hepato-cellular cholangiocarcinoma, all histologically proven) after a median time of 6.8 ± 2.1 years posttransplant (Table 1). An exhaustive examination of explanted livers had been performed, and no nodules with dysplasia were observed. Donor biopsies had been performed on the day of liver transplant, and no nodules with dysplasia, no significant fibrosis, no steatosis, and no iron overload were observed.
At the time of PLC diagnosis, none of the 5 patients had metabolic features, chronic alcohol intake, tobacco consumption, or hepatitis B virus infection. On liver biopsy, cirrhosis was observed only for the patient with HCV. The 2 patients transplanted for PSC and primary biliary cirrhosis (PBC) presented with posttransplant HCC and not cholangiocarcinoma (1 patient presented with PSC recurrence). De novo HCC were all grade 3 according to Edmondson classification with a median alpha-fetoprotein level of 9.3 ± 10.9 ng/mL. Treatment consisted of surgical resection in 2 patients who presented with a single nodule with a median size of 33 ± 18 mm; microvascular invasion was diagnosed for both of these patients on pathologic analysis. The third patient with HCC presented with extrahepatic metastases and was treated with sorafenib. The 2 patients with intrahepatic cholangiocarcinoma and hepatocellular cholangiocarcinoma also underwent surgical resection, and microvascular invasion was observed. During follow-up, 4 patients died (80%) with a median survival after diagnosis of 23.1 ± 23.4 months for all PLC and 14.9 ± 23.4 months for HCC.
We report here the first description of de novo PLC after liver transplant in France based on a large cohort. Prevalence was extremely low and could have been underestimated since liver transplant recipients with history of pretransplant PLC were excluded. Molecular profiling could have differentiated de novo PLC from recurrence. Moreover, this technique could also have distinguished recipient origin from donor origin.17 Unlike the previous cases described in the literature, de novo HCC incidences in our series were not usually associated with cirrhosis and occurred in patients with PSC, PBC and Budd-Chiari syndrome and not viral hepatitis. Only 1 patient presented with recurrence of cirrhosis associated with hepatocellular cholangiocarcinoma in case of HCV.
To conclude, de novo PLC after liver transplant is a rare event (0.04%), can occur in patients without significant liver fibrosis, and present with high degree of severity.
Volume : 16
Issue : 6
Pages : 779 - 780
DOI : 10.6002/ect.2018.0222
From the 1Hôpital Côte de Nacre, Service d'Hépato-Gastroentérologie, Nutrition
et Oncologie Digestive, Caen, France; the 2Unité Inserm-U1149, Centre de
recherche sur l'inflammation, Paris, France; the 3Réseau Régional de
Cancérologie OncoBasseNormandie, Hérouville Saint Clair, France; the 4UFR Santé
Caen France: U1086 INSERM- “ANTICIPE,” Caen, France; the 5AP-HP, Hôpital Paul
Brousse, Centre Hépato-Biliaire, INSERM, Unité 1193, Villejuif, France; the
6Hôpital Universitaire de Pontchaillou, Service d’Hépatologie et Transplantation
Hépatique, Rennes, France; the 7CHU de Bordeaux, Hôpital Haut Lévêque, Service
de Chirurgie Hépatobiliaire et de Transplantation Hépatique, Bordeaux, France;
the 8CHU Saint Eloi, Département d’Hépatologie et Transplantation Hépatique,
Montpellier, France; and the 9Hospices civils de Lyon, Hôpital Edouard Herriot,
Unité de Transplantation Hépatique, et Université Claude Bernard, Lyon, France
Acknowledgements: The authors have no sources of funding for this study and have no conflicts of interest to declare. The authors thank all French liver transplant centers and the Agence de la Biomédecine for having authorized access to the data.
Corresponding author: Mario Altieri, Service d'Hépato-Gastroentérologie, Nutrition et Oncologie Digestive, Hôpital Côte de Nacre, 14033 Caen, France
Phone: +33 2 31 06 45 43
Table 1. Main Characteristics of the 5 French Patients With De Novo Primary Liver Cancer