Biological markers of hepatocellular carcinoma for use as selection criteria in liver transplantation

The Milan criteria (MC) have been widely accepted as an effective way of selecting patients with early-stage hepatocellular carcinoma (HCC) for curative liver transplantation (LT). However, since a substantial subset of HCC patients exists that is beyond the MC but with the potential for good outcomes after LT, several institutions have recently proposed new extended criteria. To explore optimal criteria that can reasonably predict the risk of recurrence, it is considered that new markers of biological behavior are needed in addition to morphological tumor size and number. Several promising candidates for such biological markers have been reported, including serum tumor markers such as alpha-fetoprotein and des-gamma-carboxy prothrombin, inflammatory markers such as C-reactive protein and neutrophil-to-lymphocyte ratio, response to pre-transplant treatments for bridging therapy or down-staging, and fluorine-18-fluorodeoxyglucose positron emission tomography. However, the role of these biological markers in patient selection criteria for LT has yet to be clarified. This review article aims to summarize the results of recent reported studies and to display perspectives for the establishment of optimal criteria that incorporate such biological markers.