What is the role of immunotherapy in hepatocellular carcinoma (HCC) before and after liver transplantation?

From the Guidelines

Immunotherapy should be used with caution in patients with hepatocellular carcinoma (HCC) before and after liver transplantation, considering the potential benefits and risks, including the risk of rejection and the need for careful monitoring and multidisciplinary management. When considering immunotherapy for HCC, both before and after liver transplantation, it is crucial to weigh the potential benefits against the risks, particularly the risk of triggering rejection of the transplanted organ 1.

Pre-Transplant Considerations

Before transplantation, immunotherapies like checkpoint inhibitors (e.g., nivolumab or pembrolizumab) may be considered as bridging therapy to downstage tumors and maintain transplant eligibility in selected patients with advanced HCC.

• The choice of immunotherapy should be based on individual patient factors and the specific characteristics of their HCC.
• Close monitoring and regular assessments are necessary to evaluate the response to therapy and adjust the treatment plan as needed.

Post-Transplant Considerations

After liver transplantation, the use of immunotherapy is generally avoided due to concerns about triggering rejection of the transplanted organ 1.

• However, in cases of post-transplant HCC recurrence that is unresponsive to traditional treatments, immunotherapy may be considered as a last resort, with extremely careful monitoring and intensified immunosuppression.
• The decision to use immunotherapy post-transplant should be made through a multidisciplinary discussion involving transplant hepatologists, oncologists, and transplant surgeons, taking into account the individual patient's risk-benefit profile.

Key Considerations

• The use of immunotherapy in HCC, both pre and post liver transplant, requires a comprehensive and multidisciplinary approach, considering the patient's perspective and individual risks and benefits 1.
• Regular liver function testing and close monitoring for signs of rejection are crucial when using immunotherapy in the post-transplant setting.
• The integration of new diagnostic and therapeutic tools, including immunotherapy, into clinical practice for HCC management presents challenges and necessitates guidance from recent and high-quality evidence, such as the EASL clinical practice guidelines 1.

From the Research

Immunotherapy in HCC Pre and Post Liver Transplant

• The use of immune checkpoint inhibitors (ICIs) in the setting of liver transplant (LT) poses a risk of rejection and has unclear benefits in both the neoadjuvant (pre-transplant) and post-transplant salvage setting 2.
• Neoadjuvant ICIs may serve as a bridge to LT by downstaging disease burden to fit within transplant criteria, but may also pose a risk for acute cellular rejection 2.
• In the post-LT setting, there are few treatment options if there is a recurrence of disease, and the use of ICIs may be reconsidered, but with a higher risk of rejection 2, 3.
• A longer period of time between transplant and checkpoint inhibition may reduce the risk of rejection 2.
• The combination of atezolizumab/bevacizumab is a relatively new treatment option for unresectable hepatocellular carcinoma (HCC), but its use in the post-LT setting is limited, with only three reported cases, all of which had progression of disease 2.
• Fatal rejection remains a significant risk even 4 years after LT, and graft versus host disease (GVHD) may be an additional risk of ICIs in the setting of LT 2, 4.
• The safety of ICIs in the setting of solid organ transplantation remains controversial, and extreme caution should be taken when using ICIs before transplant until further investigation has been conducted on their safety in the pre-transplant setting 4.
• A systematic review of 2,402 patients with HCC treated with ICIs found an overall objective response rate of 22.7% and a disease control rate of 60.7%, but also found a high rate of graft rejection (40.0%) and mortality (80.0%) in patients who received ICIs in the LT setting 5.

Risks and Benefits of Immunotherapy in HCC Pre and Post Liver Transplant

• The benefits of immunotherapy in HCC pre and post liver transplant include the potential to downstage disease burden and improve overall survival 2, 6.
• The risks of immunotherapy in HCC pre and post liver transplant include the risk of rejection, graft versus host disease, and fatal complications 2, 4, 5.
• The use of ICIs in the LT setting requires careful consideration of the potential risks and benefits, and further research is needed to understand the safety and efficacy of ICIs in this setting 2, 3, 5.