Pretransplant Immunotherapy for Hepatocellular Carcinoma, with Parissa Tabrizian, MD

Immunotherapy has reshaped the treatment of hepatocellular carcinoma (HCC), offering survival benefits once thought unattainable. While its success in advanced disease is well established, its potential in surgical and transplant settings remains a subject of debate.

The use of immunotherapy before liver transplantation presents both promise and risk, raising hopes for improved outcomes while also sparking concerns about immune-mediated rejection. With limited long-term data and no formal guidelines supporting its use in this setting, ongoing research is necessary to determine which patients may benefit, how to mitigate risks, and whether this approach could become a viable strategy for bridging patients to transplant.

“The role of immunotherapy in surgery and in the neoadjuvant setting really started with the experience that we had with resection cases,” Parissa Tabrizian, MD, MSc, a surgeon who specializes in hepatobiliary and liver transplantation at the Recanati/Miller Transplantation Institute and an associate professor of surgery at Mount Sinai School of Medicine, explained to HCPLive. “As a high-volume center here at Sinai and many others, we explored the use of the neoadjuvant therapy in resectable HCC cases and we've shown excellent outcomes in a small group of patients.”

However, she notes current guidelines do not support the use of pretransplant immunotherapy, and she says this is “rightfully so” due to concerns about immune-mediated rejection, adverse events, and a lack of positive long-term data.

Tabrizian cites key studies in the field, including a large retrospective study from China and a meta-analysis showing that shorter washout periods correlate with higher rejection rates. Her own multi-center study, the VITALITY study, demonstrated the feasibility of immunotherapy in 117 consecutive patients with HCC assessed for liver transplantation and treated preoperatively with immune checkpoint inhibitors, reporting no severe adverse effects and promising survival outcomes.

“Unfortunately, we have a lot of unanswered questions because we don't do not have robust data or level one evidence,” Tabrizian said.

Specifically, she outlines lingering unanswered questions about optimal patient selection, the best timing for discontinuation before transplant, and the management of immunosuppression post-transplant, although she suggests that patients at high risk of disease progression or those with long waitlist times may benefit most from a neoadjuvant approach.

While preliminary data is encouraging, Tabrizian stresses that more research is necessary to define the role of immunotherapy in transplantation and ensure its safe integration into clinical practice.

Editors’ note: Tabrizian has relevant disclosures with Boston Scientific and AstaZeneca.

References

1. Tabrizian P, Abdelrahim M, Schwartz M, et al. Immunotherapy and transplantation for hepatocellular carcinoma. Journal of Hepatology. doi:10.1016/j.jhep.2024.09.003

2. Tabrizian P, Holzner ML, Ajmera V, et al. Intention-to-treat outcomes of patients with hepatocellular carcinoma receiving immunotherapy before liver transplant: The multicenter VITALITY study. Journal of Hepatology. doi:10.1016/j.jhep.2024.09.003