Immune Tolerance After Pediatric Liver Transplantation

NCT05501301 | Unknown

• 1 other identifier: IIT-2022-0004
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Immunosuppressive (IS) agents are effective treatment to avoid acute or chronic rejection after pediatric liver transplantation. However, long-term side effect of IS intaking, like infection, kidney dysfunction, metabolic disorders and developmental retardation, should be aware, especially in pediatric recipients. Spontaneous immune tolerance is defined as recipients who cease to taking IS agents due to multiple reasons and the liver function maintained normal. However, the real ratio and safety of immune tolerance in pediatric liver transplantation recipients are rarely known. We would like to investigate the ratio and safety of spontaneous immune tolerance in pediatric liver transplantation recipients during long-term follow-up by constructing an immune tolerance cohort. In this cohort, long-term pediatric liver transplantation recipients with normal liver function and taking monotherapy of IS would be involved. The IS strategy would be monitored and adjusted according to the "Clinical guidelines for pediatric liver transplantation in China(2015)". For recipients suffering refractory virus infection, such as EBV or CMV infection, IS will be minimized to assist the clearance of virus until IS was weaned off. Since most of pediatric liver transplantation recipients may encounter chronic EBV or CMV infection within one year after transplantation, they may need IS minimization during follow-up. During the process of IS weaning off, liver function, immunological status and intrahepatic pathology will be closely monitored. If acute rejection or other complications were found, increase of IS dosage or other related treatments will be applied. Immune tolerance is defined as liver function and intrahepatic pathology maintain normal for more than one year after stop taking IS. At the end of study, the ratio of immune tolerance, acute rejection and all types of complications will be assessed.

Conditions

Immune Tolerance; Liver Transplant; Complications

Keywords

immune tolerance, pediatric liver transplantation

Outcome Measures

Primary Outcomes (1)

• Ratio of immune tolerance

  The ratio of spontaneous immune tolerance in pediatric liver transplantation recipients, which is free of IS for more than one year with normal liver function

  One year after withdraw of IS

Secondary Outcomes (1)

• Ratio of acute rejection

  6 months, 1 year, 2 years and 3 years after enrolled into the study

Study Arms (1)

Immune tolerance cohort

Patients that are enrolled into this cohort will receive IS minimization if virus infection or side effects of IS was found. The strategy of IS minimization will follow the "Clinical guidelines for pediatric liver transplantation in China(2015)". Blood test and liver biopsy will be conducted to monitor liver function and intrahepatic pathological conditions. If IS is ceased for more than one year without liver dysfunction or signs of acute rejection in liver biopsy, immune tolerance was considered reached.

Other: IS weaning off

Interventions

IS weaning off OTHER

IS weaning off will be conducted in recipients with chronic virus infection or side effects of IS

Immune tolerance cohort

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

The study population is pediatric liver transplantation recipient that received living donor liver transplantation (LDLT) in Ren Ji Hospital affiliated to Shanghai Jiao Tong University School of Medicine. The enrolled recipients should have received LDLT 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. As for most recipient, monotherapy of IS will be applied three months after transplantation, so the enrolled recipients should taking only one type of IS. Since most of pediatric liver transplantation recipients may encounter chronic EBV or CMV infection with one year after transplantation, they may need IS minimization during follow-up. For those patients, IS weaning off will be applied. During the process of IS weaning off, liver function, immunological status and intrahepatic pathology will be closely monitored.

You may qualify if:

• Age at liver transplantation: 4 months to 18 years;
• Original disease before liver transplantation: End-stage liver diseases including cholestatic diseases or metabolic diseases;
• Type of liver transplantation: living donor liver transplantation, with donors of recipient's parents
• Follow-up time after liver transplantation: more than one year
• Liver function: liver function maintains normal and stable 3 months before enrollment
• IS strategy: monotherapy of IS (FK or cyclosporine) or no longer taking any IS
• Liver biopsy: No signs of acute rejection or chronic rejection, and no obvious fibrosis (Ishak\<2)
• Written consents are required

You may not qualify if:

• Original disease before liver transplantation: Tumor, hepatitis virus infection, autoimmune hepatitis, liver failure, secondary liver transplantation
• Type of liver transplantation: ABO incompatible liver transplantation, donors are not recipient's parents or multiple organ transplantation
• Hepatitis virus infection during follow-up
• Severe compilations, including bleeding complication, biliary complication, vessel complication or renal dysfunction -

Sponsors & Collaborators

• RenJi Hospital: lead

Study Sites (1)

Ren Ji Hospital affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200127, China

RECRUITING

Related Publications (1)

• Wang B, Zhou A, Wu Y, Pan Q, Wei X, Gao Y, Xiao W, Jin J, Zhou T, Luo Y, Zhan Z, Liu Y, Gao W, Liu Y, Xia Q. Establishment and validation of a predictive model of immune tolerance after pediatric liver transplantation: a multicenter cohort study. Int J Surg. 2024 Sep 1;110(9):5615-5626. doi: 10.1097/JS9.0000000000001671.

  PMID: 38833360 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

The peripheral blood samples and liver biopsy will be stored during study. Blood samples will be used for blood tests including liver function, IS level and immunological factors. Liver biopsy will be used for pathological evaluation.

Study Officials

• Qiang Xia, MD

  Ren Ji Hospital affiliated to Shanghai Jiao Tong University School of Medicine

  STUDY DIRECTOR

Central Study Contacts

Yuan Liu, MD

CONTACT

13651733680; liuyuanbird@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant professor

Study Record Dates

• First Submitted: August 7, 2022
• First Posted: August 15, 2022
• Study Start: August 1, 2022
• Primary Completion: July 31, 2025
• Study Completion: July 31, 2025
• Last Updated: December 19, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)