The development of Graft-Versus-Host Disease (GVHD) post-liver transplantation (LT) is an uncommon complication. GVHD occurs when immunocompetent donor lymphocytes originating from the transplanted liver mount a destructive immune response against the immunocompromised recipient. Diagnosis of post-LT GVHD represents a major challenge due to lack of standard criteria a rarity of the condition. Therefore, diagnosis and initiation of therapy are often delayed.

Here, we report a case of a one-year old child who developed GVHD two months post-LT. A full investigation with histocompatibility testing was performed post-LT demonstrated many risk factors of developing post-LT GVHD. The chimerism analysis showed 39% mixed chimerism in the recipient's peripheral blood. The mother was homozygous donor with broad sensitization against the patient's mismatched antigens. Reverse flow crossmatch exhibited strong positive T and B cells crossmatches. This case was missed because unlike other solid organ transplants, routine histocompatibility testing is not often required before liver transplantation.

In conclusion, although post-LT GVHD is a rare complication, proper histocompatibility testing prior LT is critical to prevent post-LT GVHD incidence. Additionally, it can be useful as a diagnostic tool post-LT to exclude competing etiology and begin treatment regimen.