Delayed T-cell Mediated Liver Transplant Rejection

Introduction: Liver transplant is the only curative treatment for acute and chronic liver failure. Complications of transplant include infection from long term immunosuppression, biliary complications, disease recurrence and organ donor rejection. Acute rejection is one of the most common complications with incidence rates up to 40%. Risk of acute liver rejection is highest within the first 4 to 6 weeks and typically does not occur after 6 months. The following case is about a patient who experienced acute T cell mediated liver transplant rejection years after transplant. Case Description/Methods: A 54 year old female with a history of Hepatitis C and cirrhosis status post liver transplant ten years prior presented to the hospital for anxiety associated with palpitations and dyspnea for three days. Home medications included Buspar, gemfibrozil, metformin, metoprolol, pantoprazole and tacrolimus. Lab work demonstrated a total bilirubin 1.0, direct bilirubin 0.2, alkaline phosphatase 400, ALT 759, AST 514, PT 12.2 and INR 1.0. Tacrolimus level was 8.5. Liver ultrasound with doppler showed normal architecture, biliary ducts, and patent vasculature with a RI 0.72. Viral hepatitis panel and CMV tests were negative. EBV testing demonstrated positive IgG and negative IgM. Liver biopsy demonstrated moderate acute cellular rejection. She was started on pulse dose methylprednisolone for three days with improvement in her hepatic panel to a total bilirubin 0.4, direct bilirubin 0.1, alkaline phosphatase 205, ALT 157, and AST 46. She was discharged on an oral prednisone taper and interval follow up with hepatology. Discussion: Acute liver rejection can be divided into T cell-mediated and antibody-mediated rejection, with T cell-mediated being more common. Immunosuppression is integral to preventing rejection. The initial regimen usually involves prednisone, tacrolimus, and/or mycophenolate mofetil. If the patient remains free of rejection for six months, monotherapy, typically a calcineurin inhibitor such as tacrolimus, is sufficient. During literature review, data could not be found on T cell mediated liver transplant rejection beyond 6 months. Our patient presented with transaminitis 10 years following transplant with a liver biopsy demonstrating moderate acute cellular rejection. The patient was negative for acute viral infection and noted compliance with immunosuppressive regimen. The etiology of her rejection is not known at this time and further investigation is warranted for future prevention of acute rejection.Figure 1.: Portal tracts demonstrating moderate lympho-plasmacytic inflammation, endothelialitis and bile duct damage resulting in a rejection activity index of 6.