Wayne State University School of Medicine & Henry Ford Health System Novi, Michigan
Introduction: We present a unique case of chronic rejection due to HLA-antibody formation during pregnancy.
Case Description/Methods: A 51-year-old female with a history of autoimmune hepatitis received a live donor liver transplant (LDLT) with her husband as the donor in January 2008. HLA crossmatch testing was performed prior to transplant with a negative result. Patient was well overall for 8 years following liver transplant. Moderate elevation of liver enzymes during this period lead to liver biopsies consistent with autoimmune hepatitis but no evidence of acute rejection.
Patient became pregnant 8 years after LDLT. She developed moderate-chronic elevation of liver enzymes during pregnancy with the most prominent peaks being 731 IU/L alkaline phosphatase (N: 40-140 IU/L), 200 IU/L aspartate aminotransferase (N: < 35 IU/L), and 160 IU/L alanine aminotransferase (N: < 52 IU/L). In December 2016, the patient had a liver biopsy displaying microvesicular steatosis, endotheliitis, and bile duct damage representative of acute cellular rejection. The patient was placed on quadruple immunosuppression therapy: everolimus, tacrolimus, prednisone, and mycophenolate mofetil.
HLA antibody testing was performed at that time to check for donor specific antibodies (DSA). DSA was identified against HLA DQ6, suggesting sensitization to her husband’s HLA antigens that occurred during pregnancy/delivery.
Despite extensive treatment, chronic rejection of the liver transplant prevailed with bile duct damage progressing to ductopenia.
Additional treatments for her condition included intravenous immunoglobulin (IVIG) therapy every 28 days, with photopheresis and plasmapheresis to reduce leukocytes and immunoglobulins attacking the transplanted liver respectively. However, even with multi-modal therapy, the patient’s condition worsened indicated by a rising MELD (model of end-stage liver disease) score and bilirubin concentration to 8 mg/dL.
Discussion: We present a unique case of acute (antibody-mediated) rejection progressing to chronic rejection in a LDLT patient following pregnancy due to sensitization to donor HLA DQ6. Consistent post-transplant HLA antibody testing should be a consideration for LDLT patients for early detection and treatment of DSA before memory B-cell production allows rejection to become chronic. Testing is especially important for monitoring female patients with LDLTs from spouse due to risk of blood exposure during pregnancy.
