Recurrent Idiopathic Liver Allograft Failure: The Role of Antibody-Mediated Rejection

• Published in: American journal of clinical pathology 2019-09, Vol.152 (3), p.369-376
• Main Authors: Schiano, Thomas D, Florman, Sander, Fiel, M. Isabel
• Format: Article
• Language: English
• Subjects: Allografts; Antibodies; Biopsy; Causes of; Development and progression; Etiology; Explants; Graft rejection; Health aspects; Liver; Liver diseases; Liver transplantation; Liver transplants; Physiological aspects; Transplantation; Transplants & implants; Viral antibodies
• ISSN: 0002-9173; 1943-7722
• DOI: 10.1093/AJCP/AQZ044

Objectives: Many transplant programs have had patients who develop idiopathic recurrent liver allograft failure, necessitating serial transplants, and are deemed to have refractory or recurrent rejection. The frequency and the etiology of this immunologic dysfunction have not been well characterized. Methods: Herein, we illustrate the case of a patient who required three retransplants over a period of 20 years for recurrent liver allograft failure. By extensively compiling the patient's many liver biopsy specimens and explants over time, we demonstrate that antibody-mediated rejection (AMR) was a major contributing factor from the outset. We conducted a review of the Scientific Registry for Transplant Recipients database to estimate the potential frequency of AMR. Results: As illustrated by this case, AMR has varied histologic findings in the setting of elevated donor-specific antibody titers. Conclusions: The cause of recurrent allograft failure in this patient was likely a combination of acute cellular rejection and AMR, manifestations of likely underlying immune dysregulation. Pathologists and transplant physicians should recognize the variable histologic presentations of AMR, which is imperative for its timely intervention. This case demonstrates how difficult the diagnosis of AMR can be to make, highlighting the need for strong clinical suspicion in patients having difficult-to-treat rejection and recurrent allograft failure. Key Words: Allograft failure; Rejection; Liver transplantation; Retransplantation