Role of allelic imbalance in predicting the risk of hepatocellular carcinoma recurrence after liver transplantation

Abstract

Background: Hepatocellular carcinoma (HCC) recurrence (HR) after liver transplantation (LT) remains a challenging issue, because HCC size and number tell only a partial tale of the characteristics that predict post-transplant outcomes. We aimed to analyze the allelic imbalance (or loss of heterozygosity) in specific microsatellites, and to assess the risk of HR. Methods: Seventy-one (71) patients who underwent LT for HCC at ISMETT were included in this retrospective study, 18 of whom developed HR at 5-years post-transplant. Molecular analysis, using 19 microsatellites, was done on whole blood and on the corresponding native liver. The presence of allelic imbalance for a specific locus (presence of loss of heterozygosity) was determined for values outside the normal range (0.66-1.50). Results: We found a statistically significant association between allelic imbalance and tumor recurrence only in 3 loci (D3S2303, D9S251, and D9S254). The evaluation of fractional allelic imbalance (FAI) cut-point index is associated with HR. ROC analysis indicated that this diagnostic test has good accuracy in terms of HR after LT. FAI index has correctly classified on average 74% of patients, predicted HR within 2 years of LT for 69% of patients, and confirmed the high predictive role of allelic imbalance in D9S251. Conclusion: Our data suggest that the information obtained by allelic imbalance analysis could have a prognostic application in risk management of HR in patients who have undergone LT, particularly for early HR.