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IMMUNE checkpoint inhibitor (ICI)-based therapy before liver transplantation may improve survival and reduce cancer recurrence in patients with hepatocellular carcinoma (HCC), according to a multicentre study involving 416 transplant recipients.
Researchers found that patients receiving ICI-based multimodal treatment before transplantation experienced significantly longer overall survival (OS) and recurrence-free survival (RFS) than those receiving treatment without ICIs. However, these benefits were accompanied by a higher incidence of acute transplant rejection, highlighting the importance of balancing oncological outcomes against transplant-related risks.
Evaluating Immunotherapy Before Liver Transplantation
Liver transplantation offers a potentially curative treatment option for selected patients with HCC. However, patients whose tumours initially exceed the Milan criteria, which are used to assess transplant eligibility based on tumour burden, may require downstaging treatment before transplantation.
ICI-based regimens have emerged as a potential component of downstaging strategies, often alongside locoregional or targeted therapies. Nevertheless, their association with long-term outcomes following transplantation has remained uncertain.
Researchers conducted a retrospective, propensity score-matched cohort study across eight high-volume liver transplantation centres in China. The analysis included adults with HCC initially beyond the Milan criteria who underwent transplantation between January 2019 and December 2024.
A total of 416 recipients were included in the matched analysis, with 208 receiving ICI-based multimodal therapy and 208 receiving treatment without ICIs. Median age was 53 years, and 90.6% of participants were male.
Immunotherapy Associated With Longer Survival
Patients who received ICI-based treatment demonstrated significantly improved survival outcomes following transplantation.
Median OS was 4.57 years in the ICI group compared with 2.53 years among patients who did not receive ICIs (p<0.001). Median RFS was also longer, reaching 1.47 years versus 0.89 years, respectively (p=0.02).
After adjustment for relevant clinical factors, ICI-based treatment was associated with a 37% lower hazard of death (hazard ratio [HR]: 0.63; 95% CI: 0.43–0.92) and a 41% lower hazard of recurrence or death (HR: 0.59; 95% CI: 0.44–0.80).
The strategy was also associated with a significantly lower risk of posttransplant cancer recurrence, with a subdistribution HR of 0.54 (95% CI: 0.40–0.72), representing a 46% lower recurrence hazard.
Increased Risk of Acute Transplant Rejection
Despite the favourable survival outcomes, acute rejection within 90 days of transplantation was significantly more common among patients who received ICI-based therapy.
Rejection occurred in 16.3% of ICI-treated recipients compared with 8.2% of those receiving treatment without ICIs (p=0.01).
This finding highlights an important safety consideration, as immune checkpoint inhibitors enhance immune responses that may also increase the likelihood of transplant rejection.
The researchers concluded that ICI-based multimodal downstaging therapy was associated with improved posttransplant survival and oncological outcomes in selected patients with HCC initially beyond the Milan criteria.
However, the retrospective design means that a causal treatment benefit cannot be established. Further prospective research is needed to clarify patient selection, optimal treatment strategies, and approaches to minimising rejection risk.
Reference
Ong M et al. Immune Checkpoint Inhibitor–Based Downstaging Therapy for Hepatocellular Carcinoma. JAMA Oncol. Published online October 01, 2026;DOI :10.1001/jamaoncol.2026.3901.
