The Long and Short of It: A Case of Long-term Teduglutide for the Treatment of Intestinal Rejection in Small Bowel Transplant: 2016 ACG Presidential Poster Award

Abstract

Small bowel transplantation (SBT) is a therapeutic option for those patients who suffer from short bowel syndrome, intestinal failure, and life-threatening complications related to total parental nutrition (TPN). Post-small bowel transplant rejection continues to be a major cause of morbidity and mortality. Endoscopically, graft rejection is characterized by hemorrhage, blunting, and sloughing of the intestinal villi while histologically, it is characterized by increased apoptotic bodies and decreased mitotic bodies per crypt. Teduglutide, a glucagon-like peptide 2 analogue, has been shown to improve intestinal absorption by promoting villous hypertrophy and crypt proliferation. We hypothesized that teduglutide 5 mg subcutaneously daily can promote small bowel villous growth and attenuate small bowel transplant rejection by increasing crypt division while decreasing the apoptotic rate. This novel application of teduglutide may facilitate recovery from rejection and improve nutritional absorption. We present an interesting case of a 22-year-old woman with a myofibroblastic tumor of the mesentery who underwent extensive small bowel resection and subsequent living related small bowel transplantation. She presented with fever and abdominal pain post-operative day 14 after SBT. She underwent ileoscopy revealing ulcerated and extensively denuded intestinal mucosal villi. Histology demonstrated inflammatory changes extending through the muscularis mucosa that was consistent with severe acute graft rejection. She was subsequently placed on teduglutide while continuing immunosuppressive therapy and underwent serial endoscopic evaluations with random small bowel biopsies. Endoscopically, there was serial improvement in the health of the small bowel graft, as histologically demonstrated by an increase in villous growth, overall decrease in the apoptotic rate, and overall increase mitotic rate over 9 months. Furthermore, we conducted novel fluorescent in-situ hybridization (FISH) analysis which confirmed an XY karyotype in the regenerating stem cells of the small bowel graft, indicating that her father's stem cells from the donated small bowel were indeed regenerating. In conclusion, we present a novel application of teduglutide to mitigate small bowel transplant rejection and promote villous growth. Teduglutide should be considered in these patients to help improve nutritional status, allow them to wean off TPN, and ultimately improve quality of life.