Hepatocellular Carcinoma and the Role of Liver Transplantation: An Update and Review

Abstract

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. Multiple treatment modalities are available for the management of HCC, depending on its stage as determined by the Barcelona Clinic Liver Cancer staging system. Because liver transplantation (LT) theoretically removes the cancer and replaces the organ at risk for future malignancy, LT is often considered the most definitive and one of the most efficacious treatment options for HCC. Nevertheless, the success and efficacy of liver transplantation depend on various tumor characteristics. As a result, multiple criteria have been developed to assess the appropriateness of a case of HCC for LT, with the pioneering Milan Criteria established in 1996. Over the past 20 to 30 years, these criteria have been critically evaluated, expanded, and often liberalized to make LT for patients with HCC a more universally applicable option. Furthermore, the development of other treatment modalities has enabled downstaging and bridging strategies for HCC prior to LT. In this narrative and comprehensive review, we provided an update on recent trends in the epidemiology of HCC, selection criteria for LT, implementation of LT across different regions, treatment modalities available as bridges, downstaging strategies, alternatives to LT, and, finally, post-LT surveillance.

Keywords: Alpha-fetoproteins; Deceased donor liver transplant; Hepatocellular carcinoma diagnosis; Hepatocellular carcinoma therapy; Immunotherapy; Liver neoplasms; Liver transplantation; Living donor liver transplant; Milan Criteria; Model for end-stage liver disease score; Molecular targeted therapy; Radiofrequency ablation; Sorafenib; Transarterial chemoembolization (TACE); Waiting lists.

Fig. 1. Representation of treatment options for HCC.

*If eligible for surgical resection or liver transplantation according to the guidelines. HCC, Hepatocellular carcinoma.

Fig. 2. Systemic treatment options for HCC.

HCC, hepatocellular carcinoma; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; CTLA-4, cytotoxic T-lymphocyte associated protein 4.

Fig. 3. Schematic of treatment recommendations for HCC not eligible for LT.

*If patients not eligible for clinical trial. ICI, immunotherapy; AFP, alpha-fetoprotein; HCC, hepatocellular carcinoma; LT, liver transplant.