Department of surgery
Cholestatic Liver Injury after Biliary Reconstruction Impairs Transplanted Islet Viability and Function due to Oxidative Stress
Naoaki Sakata1, Fuyuhiko Motoi1, Hiroki Hayashi1, Gumpei Yoshimatsu1, Haruyuki Tsuchiya1, Shojiro Sawada3, Takeshi Naitoh1, Yu Katayose1, Masafumi Goto2, Michiaki Unno1.
1Department of Surgery, Tohoku University, Sendai, Japan; 2New Industry Creation Hatchery Center, Tohoku University, Sendai, Japan; 3Division of Molecular Metabolism and Diabetes, Tohoku University, Sendai, Japan
Total pancreatectomy (TP) with islet autotransplantation (IAT) is a good therapeutic option for benign pancreatic diseases that require TP. In general, TP requires resection and reconstruction of the common bile duct by choledochojejunostomy. Therefore, postoperative cholangitis may occur after reconstruction of the biliary tract. We examined the influence of postoperative cholangitis on transplanted islets using case report and experimental study.
We encountered a patient who had episodes of postoperative cholangitis after TP with IAT. A 59-year-old man who had pancreatic arteriovenous malformation (AVM) received TP with IAT, and has a good control in blood glucose with daily insulin use at 5 years after transplantation. But cholangitis attacks were seen at 6 and 13 months after transplantation. After the initial episode of cholangitis, his hemoglobin A1c (HbA1c) gradually increased and temporal elevation of C-peptide was detected. After the second attack, his daily insulin use and HbA1c level increased (Figure 1).
We considered that postoperative cholangitis after biliary reconstruction might be harmful to autotransplanted islets, and attempted to clarify the mechanism using an animal model.
We developed a murine model of postoperative cholestatic liver injury after biliary reconstruction with IAT that involved syngeneic intraportal islet transplantation into chemically induced diabetic mice and common bile duct ligation. We assessed the viability and function of the transplanted islets. The impaired viability of transplanted islets and increased blood glucose levels indicated restoration of the diabetic state after common bile duct ligation in this murine model. Furthermore, impaired islet viability and function occurred earlier in the transplanted islets than in the surrounding liver tissues, which was consistent with the faster and higher expression of oxidative stress markers in the transplanted islets. Transplanted islets may be more vulnerable to oxidative stress caused by cholestatic liver injury than the surrounding liver tissue (Figure 2).
In conclusion, cholestatic liver injury after biliary reconstruction impairs transplanted islet viability and function due to oxidative stress. Therefore, patients should be intensively managed after TP with IAT to preserve viability and function of the transplanted islets.
 Hata T, Sakata N, Aoki T, et al. Transplantation. 2013;96:e40-3
 Hata T, Sakata N, Yoshimatsu, et al. Am J Transplant. 2015 (in press)
07:00 - 08:00
|Mini-Orals: Clinical Pancreas and Islet Transplantation||Cholestatic Liver Injury after Biliary Reconstruction Impairs Transplanted Islet Viability and Function due to Oxidative Stress||Room 110|