*Review* **Liver Transplantation in Patients with Hepatocellular Carcinoma beyond the Milan Criteria: A Comprehensive Review**

**Pierluigi Toniutto \*, Elisa Fumolo, Ezio Fornasiere and Davide Bitetto**

Hepatology and Liver Transplantation Unit, Azienda Sanitaria Universitaria Integrata, 33100 Udine, Italy; elisa.fumolo@asufc.sanita.fvg.it (E.F.); ezio.fornasiere@asufc.sanita.fvg.it (E.F.); davide.bitetto@asufc.sanita.fvg.it (D.B.)

**\*** Correspondence: pierluigi.toniutto@uniud.it; Tel.: +39-0432-552636; Fax: +39-0432-559487

**Abstract:** The Milan criteria (MC) were developed more than 20 years ago and are still considered the benchmark for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). However, the strict application of MC might exclude some patients who may receive a clinical benefit of LT. Several expanded criteria have been proposed. Some of these consider pretransplant morphological and biological variables of the tumor, others consider post-LT variables such as the histology of the tumor, and others combine pre- and post-LT variables. More recently, the HCC response to locoregional treatments before transplantation emerged as a surrogate marker of the biological aggressiveness of the tumor to be used as a better selection criterion for LT in patients beyond the MC at presentation. This essential review aims to present the current data on the pretransplant selection criteria for LT in patients with HCC exceeding the MC at presentation based on morphological and histological characteristics of the tumor and to critically discuss those that have been validated in clinical practice. Moreover, the role of HCC biological markers and the tumor response to downstaging procedures as new tools for selecting patients with a tumor burden outside of the MC for LT is evaluated.

**Keywords:** hepatocellular carcinoma; liver transplantation; Milan criteria; alpha-fetoprotein
