Serum and tissue biomarkers of plasma-cell rich rejection in liver transplant recipients

The distinction between autoimmune and alloimmune reactions in liver transplant recipients can be challenging. Plasma cell-rich rejection (PCRR), previously known as "de novo autoimmune hepatitis" or "plasma cell hepatitis", is an atypical and under-recognized form of allograft rejection observed post-liver transplantation, often in conjunction with features of T-cell-mediated and antibody-mediated rejection. If PCRR is not recognized and treated with prompt immunosuppressive augmentation, patients can develop advanced hepatic fibrosis, necro-inflammation, and allograft failure. Given the significant morbidity and mortality associated with PCRR, there exists a need to develop noninvasive biomarkers which can be used in screening, diagnosis, and treatment monitoring of PCRR. Herein is a literature review of candidate serum and tissue-based biomarkers in adult and pediatric liver transplant PCRR. We also discuss biomarkers from plasma-cell rich processes observed in other disease states and other organ transplant recipients that might be tested in liver transplant PCRR. We conclude with proposed future directions in which biomarker implementation into clinical practice could lead to advances in personalized management of PCRR.