Abstract
Immune checkpoint inhibitors (ICI) have been used to treat hepatocellular carcinoma (HCC) since 2017. The safety of ICIs in the setting of solid organ transplantation remains controversial. When used in the post-transplant setting, ICIs have been associated with high allograft rejection rates, but there are few published reports on the use of ICIs prior to transplant. We present the first reported case of rescue liver re-transplantation after loss of the first allograft due to severe acute rejection with extensive hepatic necrosis in the setting of pre-transplant ICI therapy with the PD-1 inhibitor nivolumab. It is likely that the durable immune response triggered by nivolumab contributes to graft rejection, therefore extreme caution should be taken when using ICIs before transplant until further investigation has been conducted on their safety in the pre-transplant setting.
Highlights
Systemic therapy options for advanced hepatocellular carcinoma (HCC) have expanded substantially with the advent of immune checkpoint inhibitors (ICIs)
We present a patient who was successfully re-transplanted after demonstrating severe acute rejection with massive hepatic necrosis and loss of the first allograft, which we attribute to immune-mediated damage from nivolumab use prior to initial transplant
Other studies have demonstrated an association between acute rejection and positive protein-ligand 1 (PD-L1) staining in allografts of patients who experienced acute rejection after nivolumab therapy [11, 12]
Summary
Systemic therapy options for advanced hepatocellular carcinoma (HCC) have expanded substantially with the advent of immune checkpoint inhibitors (ICIs). The programmed cell death protein-ligand 1 (PD-L1) inhibitor atezolizumab is approved as first-line treatment (in combination with bevacizumab), and the PD-1 inhibitors such as nivolumab are approved for second-line treatment [1, 2] Given their efficacy, there is growing interest in using ICIs as neoadjuvant or adjuvant therapy. Most transplant centers employ pre-transplant locoregional therapies to prevent tumor progression and keep patients within transplant-eligible criteria or to down-stage tumors to gain transplant eligibility Older systemic therapies such as the multikinase inhibitor sorafenib failed to show efficacy as a neoadjuvant therapy before liver transplantation, with minimal response rates and associated intolerability [3]. Previous reviews have found that ICI therapy was associated with high allograft rejection rates when used in patients with prior solid organ transplants [4, 5]. We present the first reported case of a successful re-transplantation after the initial allograft was lost due to severe acute rejection with subtotal necrosis in a patient who had received nivolumab prior to transplantation
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