Antibody-mediated rejection in post-liver transplant clinical care: Are we there yet for timely diagnosis and treatment?

Abstract

With improvements in medical management and surgical technique in the field of solid organ transplantation, many historically prominent causes of liver allograft injury have been ameliorated or, in the case of Hepatitis C virus, eliminated altogether. In this transformed clinical landscape, antibody-mediated rejection (AMR) has emerged as a defining barrier to maintenance of long-term liver allograft function. The liver's unique anatomy, high regenerative capacity, and tolerogenic immunological environment tend to mitigate the severest AMR manifestations. Consequently, the clinical importance of AMR in the liver has been recognized more slowly than for other solid organ allografts. Significant strides have been made in elucidating clinical and histopathologic features of acute and chronic liver AMR, with the Banff 2016 criteria among the most notable. However, current histopathologic definitions of AMR are lacking in sensitivity and specificity. C4d staining is an imperfect biological surrogate for antibody-mediated injury, and suffers from significant technical limitations. The frequent co-occurrence of T cell mediated rejection and non-immunologic allograft damage (including recurrence of primary disease) also hinders definitive identification of AMR and results in misattribution of its effects. The goal of this review is to summarize the current understanding of AMR in the context of liver transplantation, including risk factors, pathogenesis, and current diagnostic and treatment strategies. Potential directions of future research are also addressed.