From the Guidelines
Immunotherapy should be used with caution in patients with hepatocellular carcinoma (HCC) before and after liver transplantation, considering the potential risks and benefits, as outlined in the latest EASL clinical practice guidelines 1. When considering immunotherapy for HCC in the context of liver transplantation, several key points must be taken into account:
- Before transplantation, immunotherapy may be considered as a bridging therapy in selected patients with advanced HCC, particularly when conventional locoregional therapies have failed, as suggested by the updated guidelines 1.
- The use of checkpoint inhibitors like nivolumab or pembrolizumab may be beneficial in this setting, but it is crucial to discontinue these treatments at least 6 weeks before surgery to minimize the risk of rejection.
- After transplantation, the use of immunotherapy is generally avoided due to concerns about triggering graft rejection, as these agents can enhance immune responses against both tumor and transplanted liver antigens, highlighting the need for a multiparametric assessment of individual risks and benefits 1.
- For HCC recurrence post-transplant, conventional treatments like surgical resection, ablation, or targeted therapies are preferred first-line options, with immunotherapy considered only in specific cases and with close monitoring of liver function and graft status.
- The latest guidelines emphasize the importance of personalized surveillance, standardized liver imaging procedures, and diagnostic criteria, as well as the integrated role of liver transplantation and transitions between surgical, locoregional, and systemic therapies 1.
From the Research
Immunotherapy in HCC Pre and Post Liver Transplant
- The use of immunotherapy in patients with hepatocellular carcinoma (HCC) before and after liver transplant is a topic of increasing interest, with studies suggesting its potential in downstaging tumor burden and preventing recurrence 2, 3.
- However, the use of immunotherapy in the setting of liver transplantation is limited due to the potentially increasing risk of graft rejection, with reported incidence of rejection ranging from 18.5% to 25.0% pre-transplant and post-transplant 2, 4, 5.
- The safety, availability, and costs of immunotherapy are other challenges that need to be addressed, with some studies reporting high rates of treatment discontinuation due to adverse events and fatal graft rejection 5.
- Several immune checkpoint inhibitors (ICIs), including nivolumab, pembrolizumab, and atezolizumab plus bevacizumab, have been approved for the management of advanced-stage HCC, with overall objective response rates and disease control rates ranging from 19.7% to 30% and 51.1% to 77%, respectively 5.
- The role of PD-1 and PD-L1 in risk stratification for rejection is of special interest to researchers, with ongoing randomized clinical trials aiming to provide insight into their role in liver transplant management 3.
Challenges and Future Directions
- The use of immunotherapy before or after liver transplant is not yet standardized, with most clinical experience coming from individual case studies and small-scale trials 2, 6, 4.
- Further research is needed to investigate the safety and efficacy of immunotherapy in the setting of liver transplantation, including the identification of novel immunotherapy targets and the development of strategies to minimize the risk of graft rejection 2, 6, 5.
- Ongoing and future clinical trials, such as PLENTY and Dulect 2020-1, will provide valuable insights into the role of immunotherapy in liver transplant management and help to address the current gaps in knowledge 3.