ICI-Based Downstaging Before Liver Transplant: JAMA Oncology | October 2026

What Did the Study Find?

This study examined whether immune checkpoint inhibitor (ICI)-based multimodal therapy before liver transplantation can improve outcomes in selected patients with HCC initially beyond Milan criteria. The analysis included 416 matched transplant recipients from 8 high-volume Chinese centres.

• 208 patients received ICI-based therapy, usually combined with locoregional and/or targeted treatment, and 208 received non-ICI downstaging therapy.
• Median overall survival after LT was 4.57 years with ICI vs 2.53 years without ICI.
• ICI-based therapy was independently associated with 37% lower mortality (HR 0.63).
• Median recurrence-free survival was 1.47 vs 0.89 years, with a 41% lower risk of recurrence or death (HR 0.59).
• Post-transplant HCC recurrence was also lower with ICI-based treatment (subdistribution HR 0.54).
• However, acute rejection within 90 days doubled: 16.3% with ICI vs 8.2% without ICI.

Why Does It Matter?

ICI therapy before transplantation has traditionally raised concern because persistent immune activation may precipitate allograft rejection. Yet ICIs are increasingly effective components of advanced-HCC therapy and may achieve deeper tumor responses during downstaging.

This study suggests that, in carefully selected patients initially outside Milan criteria, the oncological benefit may potentially outweigh the increased rejection risk.

GastroAGI Takeaway

Prior immune checkpoint inhibition should no longer be viewed simply as an automatic barrier to liver transplantation—but neither is it ready to become routine pre-LT therapy.

In selected successfully downstaged HCC patients, an ICI-based multimodal strategy was associated with better post-transplant survival and substantially lower recurrence, but at the cost of approximately doubling early acute rejection.

The critical unanswered questions are now who should receive ICI before LT, which agent/regimen is safest, what washout interval is required, and how post-transplant immunosuppression should be modified.