Background and aims:
Selection criteria for liver transplant allocation are crucial for benefit-risk assessment of every patient evaluated for liver transplantation (LTx). Currently, Milan criteria are the key decision tool in several countries to assess whether a patient with hepatocellular carcinoma (HCC) is eligible for LTx. In this post-hoc analysis of the SiLVER Study, we analysed the performance of Milan criteria compared to the broader criteria UCSF, Up-to-7 and MT 2.0 to assess whether there is need to reform the selection process of HCC patients evaluated for LTx.

Methods:
Outcomes of 485 patients of the multicentre and randomized SiLVER Study were analysed determined by recurrence-free survival (RFS), overall survival (OS) and freedom of tumor (FoT).

Results:
Discrimination was modest for all four criteria and showed no statistically significant differences across OS (C-index 0.55–0.57), RFS (0.57–0.59) or FoT (0.62–0.64), with Metroticket 2.0 numerically highest. In the competing-risks analysis, being outside any criterion was associated with an increased subdistribution hazard of recurrence (sHR 2.7–3.6, all p < 0.001). The broader criteria classified substantially more patients as eligible (Up-to-7 83.9% vs Milan 65.6%).

Conclusions:
Our data based on explant histopathology suggest that Milan criteria exclude patients with HCC evaluated for LTx without demonstrable benefit, questioning Milan criteria as sole selection tool in many regions doing liver transplants.