Immune Tolerance After Pediatric Liver Transplantation

Background: Immune tolerance after liver transplantation is defined as the status that recipients no longer taking any immunosuppressive agents with normal liver function and intrahepatic pathology. For pediatric liver transplantation recipients, immune tolerance is easier to reach than adult liver transplantation recipients. It is reported that spontaneous immune tolerance ratio in pediatric liver transplantation recipients is between 15%-60%, varying among different centers. Some recipients could develop into spontaneous immune tolerance due to refractory infections or side effects of IS. Some recipients could also reach immune tolerance by gradually weaning off the IS if liver function maintained normal and stable in the long-term follow-up. What's more, immune tolerance could reduce the long-term side effects of IS in pediatric recipients. However, how the immune status was modulated, or which factors contribute to the development of immune tolerance is unknown. Besides, the long-term safety of immune tolerance also needs more research. This study is designed to figure out the ratio and safety of immune tolerance in pediatric liver transplantation recipients. Assessment before enrollment: In this study, enrolled population should have received living donor liver transplantation (LDLT) in Ren Ji Hospital affiliated to Shanghai Jiao Tong University School of Medicine for more than one year and liver function maintains stable and normal for more than 3 months. No severe complication including vessel complications, biliary complications or renal dysfunction should occur before enrollment. Liver biopsy should indicate no signs of acute rejection or chronic rejection, and no obvious fibrosis (Ishak\<2). Protocol after enrollment: After enrollment, the recipients will be evaluated for virus infection and side effects of IS. For patients with refractory EBV or CMV infections, or obvious side effects of IS, IS minimization should be applied. The dosage of IS will be weaned off as the 3/4 dosage of last dosage every 4 weeks. During the process of weaning off, liver function will be monitored every two weeks and liver biopsy should be conducted every six months. If liver dysfunction or acute rejection is detected during follow-up, steroid bolus and increased IS will be applied. For patients who have stop taking any IS, liver biopsy will be conducted to exclude potential liver injury in liver biopsy. For patients who have stop taking IS for more than one year with normal liver function and liver pathology, immune tolerance is considered as reached. At the endpoint of study, the ratio of immune tolerance, ratio of acute rejection and safety of immune tolerance will be assessed.