S3207 Vanishing Tacrolimus Syndrome

Abstract

Introduction: Cellular rejection is common and therapeutic IS levels are needed to minimize this risk. This case stresses the need to fully explore, and potentially reexplore common causes of subtherapeutic IS levels. Case Description/Methods: A 38-year-old man with history of alcohol related cirrhosis and liver transplant in 2019. followed by 2 episodes of acute rejection, presented with significantly abnormal liver tests. Tacrolimus levels were undetectable and liver biopsy showed moderate rejection. After a course of IV steroid, he was started on prednisone, sirolimus, and increased doses of tacrolimus. Tacrolimus levels remained undetectable despite escalating doses, and addition of fluconazole– used for cytochrome (CYP) inhibition. Liver tests worsened after initial improvements, and repeat biopsy showed changes of chronic rejection. He was treated with a 5-day course of anti-thymocyte globulin, steroids, and maintained on increased immunosuppression (IS). Drug levels for tacrolimus, sirolimus, and mycophenolate were undetectable. He reported medication adherence, and undetectable tacrolimus levels were thought to be due to CYP metabolism. With this concern, he was started on azathioprine and belatacept infusions for IS. He was readmitted with abdominal pain and chronic 10-15 stools daily. Physical exam was notable for abdominal pain, no jaundice or asterixis. Labs showed WBC 5.7, INR 1.03, total bilirubin 11.9, AST 784, ALT 714, Alkaline phosphatase 538, albumin 3.5, negative serology for EBV, CMV, and HSV, and tacrolimus level < 1.0. Lab testing for diarrhea was negative for viral and bacterial causes. With concern for malabsorption, IV tacrolimus was started. EGD and colonoscopy with biopsies were negative for malabsorptive pathology. He was started on pancreatic enzymes for concerns of pancreatic insufficiency, and fecal elastase obtained after was elevated. After 24 hours of IV tacrolimus, serum level was 22.7, and continued to rise even after reduction of dosing suggesting malabsorption as cause of subtherapeutic IS. Discussion: Therapeutic IS levels are vital for transplant success, with an understanding that this needs effective absorption and metabolism. Our patient failed to have therapeutic levels since shortly after his transplant– despite previous negative lab and endoscopic evaluations for malabsorption. We used tactics focused on abnormal metabolism, however, resultant drug levels after IV tacrolimus shows the importance of considering malabsorption as barriers to achieving therapeutic IS.