University of Iowa Hospitals & Clinics Iowa City, IA, United States
Xiaoping He, MD1, Arvind R. Murali, MD1, Alan Gunderson, MD1, Tomohiro Tanaka, MD2 1University of Iowa Hospitals & Clinics, Iowa City, IA; 2University of Iowa Carver College of Medicine, Iowa City, IA
Introduction: Late onset of acute antibody-mediated rejection (AMR) remains uncommon in liver transplant (LT), often associated with graft dysfunction and loss. The management is challenging. Here, we report a rare case with late acute AMR refractory to traditional therapy but successfully rescued with belatacept.
Case Description/Methods: A 52-year-old male with alcoholic liver cirrhosis received an ABO-identical graft LT in April 2015. Maintenance immunosuppression consisted of MMF and tacrolimus. Post-transplant complications included acute cellular rejection (ACR) in May 2015 that responded to steroids and biliary anastomotic stricture remedied with stent placement. He developed jaundice in June 2018 three months after stopping immunosuppression. Notable tests included: total bilirubin (TB) 24 mg/dl, direct bilirubin (DB) 18.7 mg/dl, AST 180 U/L, ALT 135 U/L, ALP 435U/L, GGT 94 U/L. Abdominal ultrasound with Doppler was normal. Liver biopsy revealed moderate ACR with bile duct epithelial injury, multifocal endothelialitis, and severe bile stasis. C4d immunostain was negative, but he had de novo high-risk donor-specific antibodies (DSA) to HLA class II (MFI ~22K). His liver enzymes worsened despite IV Methylprednisolone treatment: AST 351, ALT 171 U/L, TB 25.8 mg/dl. He partially responded plasmapheresis (4 sessions) with IVIG and continued to have high-risk DSA (MFI ~20K). Repeat liver biopsy showed improved but ongoing ACR and negative C4d immunostain. Thymoglobulin was started but dose limited to 4 mg/kg due to developing CMV viremia. Liver enzymes continued to worsen. He received another course of IV Methylprednisolone and thymoglobulin (6 mg/kg) with only transient and partial response. Liver tests in Nov showed TB 18.5 mg/dl, ALT 685, AST 337 U/L. Repeat liver biopsy was similar to his previous. DSA MFI was 15,000. Plasmapheresis (6 sessions) with IVIG followed by rituximab (2 doses) showed modest improvement: TB 8.7 mg/dl, ALT 223 , AST 227 , ALP 182 U/L. Belatacept was started in Dec 2018 and continued for 12 months. He had good response with subsequent disappearance of DSA and substantive improvement in liver enzymes: TB 1.5 mg/dl, ALT 42, AST 50, ALP 310 U/L. He was maintained on tacrolimus, MMF, and ursodiol. Transaminases were completely normal 6 months after.
Discussion: Belatacept is a novel agent approved for immunosuppression in renal transplants, but its data in LTx are limited. The efficacy of Belatacept in this refractory late AMR is encouraging and worth further investigations.
Disclosures: Xiaoping He indicated no relevant financial relationships. Arvind Murali indicated no relevant financial relationships. Alan Gunderson indicated no relevant financial relationships. Tomohiro Tanaka indicated no relevant financial relationships.
Xiaoping He, MD1, Arvind R. Murali, MD1, Alan Gunderson, MD1, Tomohiro Tanaka, MD2. P0782 - Belatacept Rescue for Late Onset Acute Antibody-Mediated Rejection in a Liver Transplant Recipient, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.