Abstract

Simple SummaryImmune checkpoint inhibitors (ICI) have revolutionized the treatment of hepatocellular carcinoma (HCC). In addition to their role in advanced HCC, there is considerable interest in using ICIs in the neoadjuvant setting, either as a downstaging or bridging therapy, prior to potentially curative liver transplantation. In this article, we reviewed all the available literature on ICI use in this context. We postulate that ICIs may be utilized safely prior to liver transplant; however, further research is needed in this area.Liver transplantation offers excellent outcomes for patients with HCC. For those who initially present within the Milan criteria, bridging therapy is essential to control disease while awaiting liver transplant. For those who present beyond the Milan criteria, a liver transplant may still be considered following successful downstaging. Since the introduction of atezolizumab as part of the first-line treatment for HCC in 2020, there has been increasing interest in the use of ICIs as bridging or downstaging therapies prior to liver transplant. A total of six case reports/series have been published on this topic, with mixed outcomes. Overall, liver transplantation can be performed safely following prolonged ICI use, though ICIs may increase the risk of fulminant acute rejection early in the post-operative period. A minimal washout period between the last dose of ICI and liver transplantation has been identified as an important factor predicting transplant outcomes; however, further research is needed.

Highlights

  • Liver cancer is the sixth most common cancer worldwide, with hepatocellular carcinoma (HCC) accounting for 90% of cases [1]

  • We present the available literature on the clinical experience with Immune checkpoint inhibitors (ICIs) in the neoadjuvant setting, either as a bridging or downstaging therapy for HCC before liver transplantation

  • In additional to Locoregional therapy (LRT), ICIs have recently emerged as a potential option for either bridging or downstaging therapy for those with intermediate- or advancedstage HCC

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Summary

Introduction

Liver cancer is the sixth most common cancer worldwide, with hepatocellular carcinoma (HCC) accounting for 90% of cases [1]. For patients with tumors within the Milan criteria, liver transplantation offers excellent short-term and long-term outcomes, with a 5-year overall survival over 70% and recurrence rate around 10–15% [4,5]. For patients with tumors beyond the Milan criteria, or beyond the intermediate stage based on the Barcelona Clinic Liver Cancer (BCLC) system, locoregional and systemic therapy have become the mainstay treatment options. In 2020, atezolizumab, a PD-L1 monoclonal antibody, plus bevacizumab, an anti-VEGF monoclonal antibody, have been shown to improve progression-free survival compared to sorafenib [9]. We present the available literature on the clinical experience with ICIs in the neoadjuvant setting, either as a bridging or downstaging therapy for HCC before liver transplantation. This review highlights potential directions for future research regarding the use of ICIs in HCC treatment

Current Bridging and Downstaging Strategies Prior to Liver Transplantation
Immune Checkpoint Inhibitors for HCC
Downstaging HCC with Neoadjuvant Immune Checkpoint Inhibitors
30 U intra-op transfusion 15 U intra-op transfusion
Findings
Conclusions
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