Clinical and Pathological Analysis of Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma

Abstract

Introduction: Hepatocellular carcinoma (HCC) is an aggressive tumor with raising incidence worldwide and represents a major global health problem. Liver transplant (LT) is an optimal therapeutical option with potential to cure HCC and subjacent liver disease. However, HCC recurrence is a major problem and hepatocarcinogenesis and tumor biological behavior is still poorly understood. The aim of this study was to identify clinical, analytical and histological prognostic factors with impact in post-LT overall survival (OS) and disease free survival (DFS) and to determine post-LT prognostic and tumor recurrence value of immunohistochemical markers such as cytokeratin 19 (CK19), glypican-3 (GPC3) and podoplanin (D2-40), on patients that underwent LT for HCC. Patients and Methods: Retrospective study of clinical and outcome data of 80 patients who underwent LT for HCC in our center from 1st January of 2010 to 31st December of 2015. Results: Follow-up was at least 1 year and the mean period was 33.6±21.9 (0-84) months. One and 5-year OS was 88.6% and 85.2%, respectively and DFS was 87.4% and 83.6%, respectively. Ninety-day post-LT morbidity was 63.7% and mortality 5%. Recurrence of HCC was observed in 10%. In univariate analysis (p<0.05) presence of 4-5 nodules (p=0.017), alpha-fetoprotein (AFP) serum levels ≥ 200ng/ml (p=0.027), microvascular invasion (MVI) (p=0.018) and HCC recurrence (p<0.001) were predictors of worse OS. Presence of 4-5 nodules (p=0.022) and MVI (p=0.006) were predictors of worse DFS (p<0.05). There was no statistical difference on OS (p=0.717) and DFS (p=0.794) of patients with BCLC (Barcelona Clinic Liver Cancer) 0-C stages when compared to stage D. In patients beyond Milan Criteria (MC), 3-year OS when MVI was observed was 50%, whereas without MVI was 93.8% (p=0.026). On multivariate analysis, we found that AFP serum levels ≥200ng/ml (p=0.035) and MVI (p=0.021) were independent predictor factors of worse OS and MVI was also a predictor of worse DFS (p=0.027).Conclusion: LT is an optimal therapeutical option for patients with severe liver diseasecomplicated with HCC, even in those with end-stage liver disease. Further work must be doneto assess and identify predictive factors that clarify biological tumor behavior of HCC, that can be applied in a better selection of patients for LT.

Introduction: Hepatocellular carcinoma (HCC) is an aggressive tumor with raising incidence worldwide and represents a major global health problem. Liver transplant (LT) is an optimal therapeutical option with potential to cure HCC and subjacent liver disease. However, HCC recurrence is a major problem and hepatocarcinogenesis and tumor biological behavior is still poorly understood. The aim of this study was to identify clinical, analytical and histological prognostic factors with impact in post-LT overall survival (OS) and disease free survival (DFS) and to determine post-LT prognostic and tumor recurrence value of immunohistochemical markers such as cytokeratin 19 (CK19), glypican-3 (GPC3) and podoplanin (D2-40), on patients that underwent LT for HCC. Patients and Methods: Retrospective study of clinical and outcome data of 80 patients who underwent LT for HCC in our center from 1st January of 2010 to 31st December of 2015. Results: Follow-up was at least 1 year and the mean period was 33.6±21.9 (0-84) months. One and 5-year OS was 88.6% and 85.2%, respectively and DFS was 87.4% and 83.6%, respectively. Ninety-day post-LT morbidity was 63.7% and mortality 5%. Recurrence of HCC was observed in 10%. In univariate analysis (p<0.05) presence of 4-5 nodules (p=0.017), alpha-fetoprotein (AFP) serum levels ≥ 200ng/ml (p=0.027), microvascular invasion (MVI) (p=0.018) and HCC recurrence (p<0.001) were predictors of worse OS. Presence of 4-5 nodules (p=0.022) and MVI (p=0.006) were predictors of worse DFS (p<0.05). There was no statistical difference on OS (p=0.717) and DFS (p=0.794) of patients with BCLC (Barcelona Clinic Liver Cancer) 0-C stages when compared to stage D. In patients beyond Milan Criteria (MC), 3-year OS when MVI was observed was 50%, whereas without MVI was 93.8% (p=0.026). On multivariate analysis, we found that AFP serum levels ≥200ng/ml (p=0.035) and MVI (p=0.021) were independent predictor factors of worse OS and MVI was also a predictor of worse DFS (p=0.027).Conclusion: LT is an optimal therapeutical option for patients with severe liver diseasecomplicated with HCC, even in those with end-stage liver disease. Further work must be doneto assess and identify predictive factors that clarify biological tumor behavior of HCC, that can be applied in a better selection of patients for LT.