Review Article: Liver Transplantation for Hepatocellular Carcinoma in the Era of Immune Checkpoint Inhibitors

Abstract

Background

Ablation, surgical resection and liver transplantation (LT) are curative therapies for patients with hepatocellular carcinoma (HCC). Milan Criteria and University of California San Francisco Criteria are traditionally accepted for liver transplantation, with the expectation of favourable outcomes. In recent years, immune checkpoint inhibitors (ICI) have revolutionised the management of unresectable HCC (uHCC) and are now considered first-line systemic therapy.

Aims

In this narrative review, we aimed to comprehensively discuss the role of ICIs in the peri-transplant period, with the goal of enhancing the chances of a successful LT for advanced HCC while also decreasing the risk of recurrence post-LT.

Methods

A search of PubMed and manual screening of references was performed to identify studies evaluating ICIs in the context of LT, and relevant articles were included.

Results

ICIs can achieve complete response and ultimately provide long-term survival in a subset of patients. There has been an exponential increase in the use of these drugs, and increasing interest in the use of combination locoregional therapies plus ICIs as a strategy for downstaging or bridging to LT. While there can be objective responses with ICI therapy, there are potentially serious adverse events, including immune-mediated liver injury and enhanced risk of infections in the pre-LT period. Rejections and recurrence post-LT are relevant in the context of ICIs, while endeavouring to downstage or bridge HCC pre-transplant.

Conclusions

ICI therapy is nuanced during the peri-transplant period and should therefore be selectively used in specific patients rather than being used ubiquitously.