Prognostic Significance of the DNA-Index in Liver Transplantation for Hepatocellular Carcinoma in Cirrhosis

Abstract

This study was conducted to evaluate the prognostic significance of the tumor DNA index in patients receiving liver transplantation for hepatocellular carcinoma (HCC) in cirrhosis. In patients suffering from HCC in cirrhosis, the current selection for liver transplantation does not optimally achieve the goal to simultaneously maximize the number of viable transplant candidates and reject the smallest number of those who could have benefited. This is the first report on the prognostic significance of the tumor DNA index. From 1988 to 2007, liver transplantation for HCC in cirrhosis was performed in 246 consecutive patients. The DNA-index was determined by Feulgen staining and semiautomatical image analysis. Interpretation of DNA histograms followed the recommendations outlined in the European Society for Analytical Cellular Pathology consensus report on diagnostic DNA image cytometry. A DNA-index <or=1.5 was detected in the HCC of 159 patients (65%). Five- and 10-year post-transplant survival rates in this group were 86% and 80%, respectively. The DNA-index exceeded 1.5 in 87 patients (35%). These patients had 5- and 10-year survival rates of 27% and 6%, respectively, which were significantly lower than in the DNA-index <or=1.5 group (P < 0.0001). On univariate analysis, DNA-index, vascular invasion, fulfillment of the Milan criteria, and histopathological grading were prognostic parameters. In the multivariate analysis, only DNA-index (odds ratio: 11.9; 95% confidence interval: 7.1-20.0; P < 0.0001) and vascular infiltration (odds ratio: 1.7; 95% confidence interval: 1.1-2.6; P < 0.01) were identified as prognostic variables. This is the first study to describe the DNA-index as a strong prognostic indicator after liver transplantation for HCC in cirrhosis. At this time, determination of the DNA-index is likely to be the most promising diagnostic tool in the selection of transplant candidates.