S5403 An Unexpected Trigger: Atypical Infectious Hepatitis Inducing Antibody-Mediated Rejection in a Liver Transplant Recipient

Introduction: Antibody-mediated rejection (AMR) of a liver allograft is a rare complication following liver transplantation, especially when compared to other major organ transplants such as the heart or kidney. We report a novel case of AMR 7 months post-orthotopic liver transplant due to suspected infection. Case Description/Methods: A 58-year-old woman, 7-months-post orthotopic liver transplant due to Hepatitis C-associated liver cirrhosis, was admitted with elevated liver function tests (LFTs), fever, and flank pain. Endoscopic ultrasound-guided liver biopsy revealed active hepatitis and fibrin ring granulomas. Polymerase chain reaction (PCR) detection of infectious organisms on the biopsy revealed positive bacterial DNA on 16s rDNA analysis. Laboratory evaluation identified positive Bartonella IgG (1:512) with a negative PCR and positive Brucella IgM. Calculated panel-reactive antibodies (cPRA) increased from 0% to 93%, with de novo donor-specific antibodies (DSA). Her LFTs remained elevated despite a course of intravenous solumedrol 500 mg once a day and doxycycline. A second and third biopsy demonstrated resolution of the fibrin rings but the new appearance of biliary-related changes, ductopenia, and a positive C4d. Discussion: Our patient’s initial findings of fever, leukocytosis, and elevated LFTs suggested acute infectious hepatitis, further supported by her first biopsy findings demonstrating a positive bacterial PCR and fibrin ring granulomas of which bacterial infections, namely Coxiella burnetii and Bartonella, are some of the most common causes. Moreover, the patient’s infectious workup indicated a possible Bartonella infection, although Q-fever is a possible alternative etiology given the known cross-reactivity between antibodies. Regardless, empiric treatment with doxycycline successfully resolved the patient’s fevers and led to resolution of her fibrin ring granulomas on follow-up biopsies, implicating an atypical infectious hepatitis as the likely precipitant. Despite the resolution of her infection, her LFTs did not improve in the following weeks. Her second and third biopsy findings as well as her new DSAs were consistent with a new development of AMR. Therefore, we propose that this case represents a novel mechanism of AMR of an allogeneic liver transplant due to an atypical infectious trigger, as evidenced by the evolution of our patient’s liver biopsies, with fibrin ring granulomas subsequently transitioning to characteristic chronic rejection histology, as AMR developed following the initial insult.