Fatal graft-versus-host disease in recipient with pretransplant exposure to immune checkpoint inhibitors and donor-dominant one-way HLA matching after liver transplantation: A case report

Introduction and importance: Graft-versus-host disease (GvHD) is a rare but severe complication following liver transplantation (LT), occurring in 1-2 % of cases with a mortality rate exceeding 80 %. Immune checkpoint inhibitors (ICIs) used pretransplant are associated with increased allograft rejection risk, but their impact on GvHD in LT remains unclear. Dominant one-way donor-recipient human leukocyte antigen (HLA) matching is a known risk factor for GvHD. This report presents a rare case of fatal GvHD in a hepatocellular carcinoma (HCC) patient treated with PD-1 inhibitors before LT and transplanted with a liver graft from a deceased donor with donor-dominant one-way HLA matching.

Case presentation: A 59-year-old male with a 30-year history of hepatitis B and unresectable HCC underwent LT after receiving the last dose of PD-1 inhibitors 7 days prior to the transplant. On post-operative day (POD) 12, the patient developed a skin rash, fever, and vomiting, and was diagnosed with GvHD. Despite aggressive treatment, including high-dose corticosteroids and extracorporeal membrane oxygenation (ECMO), the patient succumbed to gastrointestinal bleeding and multi-organ failure on POD 30. HLA genotyping revealed typical donor-dominant one-way HLA matching.

Clinical discussion: This case highlights a potential link between pretransplant exposure to ICIs and GvHD, particularly with donor-dominant one-way HLA matching. Residual anti-PD-1 antibodies may activate graft-resident immune cells, precipitating GvHD. Further research with larger cohorts and animal models is required to clarify this relationship and understand the underlying mechanisms.

Conclusion: Besides allograft rejection, caution should also be exercised regarding GvHD in patients with prior exposure to ICIs before LT.