Objective: The objective of this study from the International Registry of Hepatic Tumors in Liver Transplantation is to analyze the impact of tumor characteristics on tumor recurrence and patient survival.
Summary background data: Many attempts have been made to identify patients with hepatocellular carcinoma who can be treated successfully with liver transplantation. Studies presented to date lack enough patients to make reported findings universally accepted. In lieu of a prospective, randomized multicenter trial, in 1992 an International Registry of Hepatic Tumors in Liver Transplantation was established to collect data on these patients, their tumors, and their treatment.
Methods: The registry mails out new patient registration forms and patient follow-up forms twice yearly to all known liver transplant programs. Fifty-three programs in 21 countries have supplied information on 553 patients with tumors. Four hundred ten patients had hepatocellular carcinoma (HCC), and 12 had the fibrolamellar variant of HCC (FLL-HCC). These 422 patients were investigated for this study. One hundred sixty-nine of these (40.0%) were classified as "incidental tumors." For the remaining patients, the tumor was known before the transplant. Twenty-six and eight tenths percent of the patients had a history of hepatitis B and 32.7% had a history of hepatitis C.
Results: One hundred ninety patients (46.7%) have died, 99 free of tumor and 91 with tumor. Death was tumor related in 90 patients. Of the 232 patients now living, 215 are free of tumor and 17 have tumor. The most common sites for recurrence are the transplanted liver (41.7%) and the lungs (28.7%). The overall patient survival was 72.2% at 1 year, 63.4% at 2 years, 47.4% at 4 years, and 44.4% at 5 years. Using univariate analysis, incidental tumors (p = 0.3107), FLL-HCC (p = 0.0704), multifocal tumor (p = 0.5464), and bilobar tumor (p = 0.1024) were not found to have an influence on patient survival. Four factors, tumor size greater than 5 cm (p = 0.0221), vascular invasion (p = 0.0005), positive nodes (p = 0.0014), and histologic grade (p = 0.0001) had a profound impact on patient survival. Using Cox multiple regression analysis, only histologic grade had a negative impact on overall patient survival (p = 0.0009) and for patients with known tumors (p = 0.0003). For incidental tumors, patient survival was negatively influenced by multifocality (p = 0.0021) and an age older than 60 years (p = 0.0008). Tumor histologic grade (p = 0.0134) and size (>5 cm) (p = 0.0133) were significantly linked to recurrence-free patient survival.
Conclusions: This analysis has documented three tumor characteristics that strongly impact patient survival after transplantation for HCC. In addition to tumor size greater than 5 cm and the presence of vascular invasion (which confirm several, single-center studies), this registry notes that a poorly differentiated HCC may be a contraindication for transplantation. A liver tumor's histologic grade may be important information to have when these patients are considered for liver transplantation.