Humoral Response in Liver Allograft Transplantation: A Review of the Role of Anti-Human Leukocyte Antigen (HLA) Antibodies

Antibody-mediated rejection (AMR) is relatively uncommon in AB0-compatible liver grafts; however, recent data suggest that antibody-mediated mechanisms may play a role in the differential pathogenesis of liver graft rejection. In this sense, it has been shown that staining for diffuse C4d deposition (in endothelium or stroma of portal tracts or sinusoids) could be used as a tissue biomarker of humoral allograft rejection and fibrosis in biopsies obtained in post-transplantation period, in addition to the determination of donor specific antibodies (DSA). Therefore, more stringer criteria have to be established in order to define real antibody-mediated injury (acute rejection, chronic rejection or fibrosis development) in liver graft transplant. These criteria should intend to correlate allograft dysfunction associated with compatible histological findings, presence of DSAs and C4d positivity and should be clarified with respect to rejection injury frequency, its severity and its response to antibody-depleting immunosuppression in the future. This could improve our progressive understanding of the clinical-pathological characteristic and diagnostic approaches of AMR and fibrosis.