Downstaging of advanced hepatocellular carcinoma followed by liver transplantation using immune checkpoint inhibitors: Where do we stand?

Table 2 Recommendations

Aspect	Recommendation
Indications	HCC: Patients requiring downstaging therapy before liver transplantation. PVTT: Patients with HCC complicated by PVTT who are candidates for liver transplantation
Contraindications	Autoimmune diseases: History of severe autoimmune diseases that could be exacerbated by ICIs. Infections: Ongoing significant infections that may be worsened by immunotherapy. Liver disease: Decompensated liver disease where the risks of ICIs outweigh potential benefits
Timing of ICI initiation	Pre-transplant downstaging: Start ICIs as part of a structured downstaging protocol for HCC to shrink tumors to within transplant criteria. Advanced HCC management: Initiate ICIs in patients with advanced HCC and PVTT to control disease progression pre-transplant
Timing of ICI cessation	Before liver transplantation: Stop ICIs at least 4-6 weeks prior to planned liver transplantation to reduce the risk of graft rejection. Immune resolution: Ensure resolution of immune activation and monitoring for potential adverse effects post-ICI cessation before proceeding to LT
Monitoring and follow-up	Regular assessment: Frequent monitoring of liver function and immune response during ICI treatment. Post-ICI cessation: Close follow-up after stopping ICIs to detect and manage any late-onset immune-related adverse events and ensure patient readiness for transplantation
Immunosuppressive strategy post-LT	Standardized protocols: Implement standardized immunosuppressive regimens tailored to the patient's condition and prior ICI therapy to prevent graft rejection. Adaptive management: Adjust immunosuppression based on patient response and any emerging complications post-transplant

ICI: Immune checkpoint inhibitors; HCC: Hepatocellular carcinoma; PVTT: Portal vein tumor thrombosis; LT: Liver transplantation.