Identifying Which Patients With HCC Need Immunotherapy Before Liver Transplant

In an interview with CancerNetwork® at The Liver Meeting® 2026, Neil Mehta, MD, professor of medicine and director of the Liver Cancer Multidisciplinary Program at the University of California, San Francisco, and Laura M. Kulik, MD, professor of medicine in the Division of Gastroenterology and Hepatology at Northwestern Medicine, discussed the evidence still needed before immune checkpoint inhibitors could become a standard bridging strategy for patients with hepatocellular carcinoma (HCC) awaiting liver transplant.

Mehta said immunotherapy is unlikely to become standard for all patients on the waitlist, because many patients with limited disease, such as a single small tumor treated with yttrium-90 (Y-90) radiation segmentectomy, reach transplant without it. Instead, the goal is to identify higher-risk cohorts, including patients with elevated α-fetoprotein (AFP), multifocal disease requiring downstaging, or portal venous invasion, in whom adding immunotherapy may reduce waitlist dropout and improve intention-to-treat survival. Data from the multicenter VITALITY study have suggested that immunotherapy before transplant appears safe. Kulik said prior trials of transarterial chemoembolization (TACE) plus immunotherapy did not account for patients proceeding to transplant, and that ongoing Y-90 plus immunotherapy studies, including 1 randomized trial, should clarify listing, transplant, and dropout outcomes.

Transcript:

CancerNetwork: What evidence do we still need before immunotherapy becomes a standard bridging strategy, and how should transplant centers track waitlist dropout, rejection, and recurrence to guide practice in the interim?

Mehta: I am not sure we will ever get to a place where immunotherapy is standard for all patients with HCC who are awaiting transplant. There are adverse effects, it is expensive, and many patients do not need it. If you have a patient with a single HCC that is, say, 2.5 or 3 cm, and you perform a radiation segmentectomy with Y-90, by and large, that patient will have an excellent response, a high chance of making it to transplant, and a low risk of waitlist dropout.

Our goal is to understand who benefits from additional immunotherapy during the waiting period. As Laura mentioned earlier, those are patients with higher-risk features: a higher AFP multifocal disease requiring downstaging, or perhaps portal venous invasion. We have to identify the higher-risk cohorts that face a high risk of waitlist dropout unless we add immunotherapy. That is where the field has moved, to try to improve intention-to-treat survival for those patients, because a whole group of patients will probably make it to transplant without immunotherapy.

Kulik: That is a good point, because it brings up the studies we have had thus far of TACE plus immunotherapy, which did not build in patients going to transplant. Future studies have taken this into account. We are waiting on several Y-90 plus immunotherapy studies. Two are single arm, and 1 is randomized, so we will get more data from that. We will see which patients go on to be listed, who makes it to transplant, who drops out, and so on.

In terms of whether it will ever become standard of care, I do not think we will necessarily see it as standard of care in guidelines or guidance, but I do think it will become more of a center-level standard of care, and that may be different for each center.

Reference

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. J Hepatol. 2025;82(3):512-522. doi:10.1016/j.jhep.2024.09.003