Liver Transplantation for Hepatocellular Carcinoma after Downstaging or Bridging Therapy with Immune Checkpoint Inhibitors

Abstract

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.

G Protein Subunit Gamma 5 Is a Prognostic Biomarker and Correlated with Immune Infiltrates in Hepatocellular Carcinoma

“…According to the theory of immune microenvironment, tumor cells do not grow in isolation but interact with other cells such as surrounding endothelial cells and fibroblast immune cells, leading to macrophage infiltration and fibroblast proliferation and angiogenesis, which together determine the progression of the tumor [ 9 ]. Immunotherapy for liver cancer, represented by immune checkpoint inhibitors, is being used in conjunction with traditional HCC treatments to further improve patient prognosis [ 10 ].…”

Conversion therapy with an immune checkpoint inhibitor and an antiangiogenic drug for advanced hepatocellular carcinoma: A review

“…Conversion therapies also present the unique possibility of expanding the population eligible for liver transplantation. Studies on conversion therapies prior to liver transplantation for patients with HCC outside the Milan criteria are still limited and have mixed outcomes (68)(69)(70)(71)(72)(73)(74). Despite the concern that an ICI might increase the possibility of acute rejection and graft loss in the early post-transplantation period, transplantation can be performed safely with a sufficient washout period between ICI administration and transplantation (71).…”

Immunotherapy Use Prior to Liver Transplant in Patients with Hepatocellular Carcinoma

“…According to AASLD guidelines, patients beyond Milan criteria should be considered for liver transplant after downstaging therapy to meet the criteria [ 13 ]. Bridging therapies are recommended for patients who spend prolonged periods on the waitlist and to decrease progression of disease [ 14 ]. The AASLD does not favor one bridging strategy over another in patients awaiting transplant who are within Milan criteria [ 13 ].…”

“…Among the fourcases that resulted in graft loss, concomitant use of steroids and anti-thymocyte globulin were used in three of the cases. Gao et al proposed plasmapheresis as a potential treatment modality to wash out remaining effects of immunotherapy agents given the reversibility of target-binding [ 14 ]. In three of the four cases, plasma exchange was employed in addition to these medical therapies along with the implementation of IV Immunoglobulin therapy in two cases.…”