P0831 - Antibody-Mediated Rejection in Hepatitis C Discordant Allograft Leading to Re-Transplantation Despite Early Antiviral Therapy

Anna Archbold, MD, Christopher Nguyen, DO, Ravi Pavurala, MD, Heather L. Stevenson, MD, PhD, Rupak Kulkarni, MD, Sheharyar Merwat, MD, Shehzad Merwat, MD
University of Texas Medical Branch, Galveston, TX

Introduction: The advent of direct acting antivirals (DAAs) has expanded the pool of HCV positive (HCV+) donor livers. Studies revealed early treatment of HCV with DAA after orthotopic liver transplantation (OLT) resulted in sustained virological response (SVR). Here, we present an HCV-negative (HCV-) recipient who underwent OLT from an HCV+ donor, developed antibody-mediated rejection (AMR) despite early treatment with DAA and required re-transplantation.

Case Description/Methods: A 47-year-old HCV- female with diabetes, obesity, and cirrhosis due to nonalcoholic steatohepatitis received OLT from HCV+ donor and was managed with prednisone, mycophenolate and tacrolimus. On post-operative day (POD) 4, patient had a rise in aminotransferases and bilirubin in context of HCV+ polymerase chain reaction. Arterial ultrasound and hepatobiliary scintigraphy were within normal limits. Liver biopsy revealed active hepatitis with lobular lymphoplasmacytic inflammation and frequent apoptosis. The patient was started on glecaprevir/pibrentasvir on POD 9, with improvement in aminotransferases. The medical course was complicated by profound conjugated hyperbilirubinemia and renal failure. Repeat biopsy on POD 25 revealed morphologic features of AMR (Fig. 1), with de novo donor specific antibodies, and C4d positivity. The patient was treated with plasma exchange, intravenous IgG and steroids. Her clinical course deteriorated, leading to a MELD-Na of 40. The patient underwent re-transplantation on POD 49, due to primary graft non-function and explanted liver histology exhibited cholangitis lenta, perivenular necrosis and centrilobular fibrosis. The patient completed 12 weeks of DAA therapy, with confirmed SVR and stable allograft function.

Discussion: Use of DAAs has led to successful eradication of post-OLT HCV infections allowing for HCV discordant liver transplantations. Studies demonstrate similar short-term graft-survival outcomes in both concordant and discordant HCV+ transplantations. Graft failure requiring transplantation is not common. One study, with a median DAA initiation of 43 days post OLT, showed a 30% incidence of rejection during or following DAA therapy though all patients achieved SVR and no graft failure or deaths were noted. Another study showed a 7% incidence of rejection when DAAs were started within 5 days of OLT and all patients achieved SVR. We present a severe complication of discordant HCV OLT despite early recognition and initiation of DAAs requiring re-transplantation.


Figure: Figure 1. AMR with C4d positive in portal tract capillary plexus.


Disclosures:
Anna Archbold indicated no relevant financial relationships.
Christopher Nguyen indicated no relevant financial relationships.
Ravi Pavurala indicated no relevant financial relationships.
Heather Stevenson indicated no relevant financial relationships.
Rupak Kulkarni indicated no relevant financial relationships.
Sheharyar Merwat indicated no relevant financial relationships.
Shehzad Merwat indicated no relevant financial relationships.


Anna Archbold, MD, Christopher Nguyen, DO, Ravi Pavurala, MD, Heather L. Stevenson, MD, PhD, Rupak Kulkarni, MD, Sheharyar Merwat, MD, Shehzad Merwat, MD. P0831 - Antibody-Mediated Rejection in Hepatitis C Discordant Allograft Leading to Re-Transplantation Despite Early Antiviral Therapy, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.