Liver transplantation remains one of the most powerful curative options for hepatocellular carcinoma (HCC) because it removes both the tumor and the diseased liver. Yet many patients are excluded because their tumors exceed the Milan criteria (MC), while others progress during long waiting periods caused by organ shortage. Locoregional treatment (LRT), including transarterial chemoembolization (TACE), radioembolization, and ablation, has improved downstaging and bridging, but responses vary. Meanwhile, Immune checkpoint inhibitors (ICIs) have changed the treatment landscape for advanced HCC, raising the possibility that immunotherapy could be moved earlier into the transplant pathway. Based on these challenges, in-depth research is needed to define how immunotherapy can expand transplant access without compromising graft safety.
Researchers from the Liver Transplant and Hepatobiliary Surgery Program, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, USA, reviewed current evidence on neoadjuvant and adjuvant immunotherapy for HCC in the liver transplantation (LT) setting. The review article was published (DOI: 10.1016/j.hbpd.2025.10.004) online on October 19, 2025, in Hepatobiliary & Pancreatic Diseases International. The article synthesizes clinical trials, cohort studies, meta-analyses, and case series published up to August 2025, focusing on therapeutic potential, rejection risk, washout timing, and ongoing clinical trials.
The review shows that neoadjuvant ICI therapy—given before transplantation—has produced encouraging results in selected candidates. Across early-phase trials and multicenter cohorts, pre-LT ICIs achieved downstaging in about 75%–82% of patients, with radiologic responses up to 94% and pathologic responses ranging from 35% to 88%. One- and three-year survival after ICI bridging reached about 95% and 70%–80%, respectively, while post-LT survival remained above 85% at three years. However, the safety signal is equally important. Rejection occurred in 16%–28% of large series, and an individual patient data meta-analysis reported a 26.4% rejection rate. The review identifies washout duration—the interval between the last ICI dose and transplantation—as a key determinant of risk, with shorter intervals, especially under 30–90 days, linked to higher rejection rates. Evidence for adjuvant ICI use after LT remains much weaker and is largely limited to case reports.
The authors said the field is moving from asking whether immunotherapy can work before transplant to defining how it can be used safely. They said ICIs may become a valuable bridge for patients whose tumors respond well and who can observe an adequate washout period before surgery. At the same time, they emphasized that this approach should not be treated as routine care. The safest strategy, they said, requires experienced transplant centers, multidisciplinary decision-making, close monitoring of alpha-fetoprotein (AFP) trends and imaging response, and careful adjustment of immunosuppression around transplantation.
The implications are significant for both cancer control and transplant access. If validated in prospective randomized trials, neoadjuvant immunotherapy could help more patients with HCC reach curative LT and reduce waitlist dropout. Post-transplant immunotherapy remains more uncertain: adjuvant ICI use has shown rejection in about 25% of reported cases and mortality of roughly 10%–12%. Alternative immune-based approaches, including natural killer (NK) cell therapy and cytokine-induced killer (CIK) cells, may offer safer ways to reduce recurrence while preserving graft tolerance. For now, the review supports a cautious, individualized model in which immunotherapy is used only when oncologic benefit and immunologic risk can be carefully balanced.
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References
DOI
10.1016/j.hbpd.2025.10.004
Original Source URL
https://doi.org/10.1016/j.hbpd.2025.10.004
About Hepatobiliary & Pancreatic Diseases International
Hepatobiliary & Pancreatic Diseases International (HBPD INT) (ISSN 1499-3872 / CN 33-1391/R), owned by the First Affiliated Hospital, Zhejiang University School of Medicine in China, publishes peer-reviewed original papers, reviews and editorials concerned with clinical practice and research in the fields of hepatobiliary and pancreatic diseases.