Pediatric Liver Transplantation-Liver Fibrosis Evaluation by Using Fibrosis Panel (PT-LiFE)

Shanghai Jiao Tong University

Status: Enrolling

Conditions: Liver Transplant; Complications; Pediatric Disorder; Liver Fibrosis

Treatments: Diagnostic Test: Liver Allograft Fibrosis by Using Fibrosis Panel(PRO-C3, PIIINP, TIMP-1, HA etc.)

Study type: Interventional

Funder types: Other

Identifiers

NCT05308628

Renji-IIT-2022-0002

Details and patient eligibility

About

Liver transplantation in children is highly successful with >80% having 20 years survival. Most pediatric liver diseases are potentially curable with liver transplantation and it is important to establish whether children who have undergone successful transplantation can expect a normal life expectancy or whether there will be a gradual decline in liver function and eventual graft loss. The most common reasons in late graft loss in children are unexplained graft inflammation ("idiopathic" post-transplant hepatitis) and graft fibrosis. PRO-C3, a disintegrin and metalloproteinase with thrombospondin motifs-generated neo-epitope marker of type III collagen formation, has been proved to be a marker of fibrosis in patients with NAFLD. The aim of this study is to explore the role of Fibrosis Panel(PRO-C3, PIIINP, TIMP-1, HA) in children received liver transplantation.

Full description

The cross-section study will be performed in pediatric patients who underwent liver transplantation from year 2016-2021. Patients will be enrolled after collecting their informed consent from their parents. As soon as the patient is included, arrangements will be made for the liver biopsy according to the schedule.

Liver biopsies will be performed at 3 months, 6 months and 12 months post-transplant. For the purpose of this study, each section was independently and blindly reassessed by expert pathologists. Fibrosis was evaluated using the liver allograft fibrosis score (LAFSc) staging system [Fibrosis deposition was classified in three main areas of the liver parenchyma: portal tracts, sinusoids (zones 1 and 2) and centrolobular veins (zone 3); in each area, fibrosis was staged from 0 to 3 (0 = absent, 1 = mild, 2 = moderate and 3 = severe fibrosis), with a total score of 9. Equal score weight was assigned to each area] and the Ishak staging system (0 = no fibrosis; 1 = fibrous expansion of some portal area; 2 = fibrous expansion of most portal areas; 3 = fibrous expansion of most portal areas with occasional bridging; 4 = fibrous expansion of most portal areas with marked bridging; 5 = marked bridging occasional nodules; and 6 = cirrhosis).

At the time of biopsy, a fasting blood sample was obtained and routine biochemical tests were performed using standard methods and assays. Additional blood samples were drawn and frozen at -80℃ for future research. Type III collagen formation was assessed in serum using the Fibrosis Panel(PRO-C3, PIIINP, TIMP-1, HA) competitive enzyme-linked immunosorbent assay.

Enrollment: 1,200 estimated patients

Sex: All

Ages: 2 months to 18 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female participant must be between 8 weeks and 18 years of age.
• Participant is a recipient of a first liver allograft from cadaveric or living donors.
• Participant is a single-organ recipient (liver only).
• Participants' parent/guardian is capable of understanding the purposes and risks of the study and must sign an informed consent for the study.

Exclusion criteria

• Participants older than 18 years of age
• Pregnant or breastfeeding
• Active systemic infections
• Receiving any form of solid organ retransplantation
• Multiorgan transplantation
• Multi organ failure
• Congenital sufferers from heart, lung, kidney, nervous system or blood disease
• Refused to participate the study

Trial design

Primary purpose: Screening

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

---

1,200 participants in 2 patient groups

Post-Transplant-Liver Allograft Fibrosis

Active Comparator group

Description:

Pediatric patients who have undergone liver transplantation , the occurrence of graft fibrosis necessitates hospitalization for biopsy and treatment to assess the degree of fibrosis and its underlying causes.

Treatment:

Diagnostic Test: Liver Allograft Fibrosis by Using Fibrosis Panel(PRO-C3, PIIINP, TIMP-1, HA etc.)

Post-Transplant-Liver Allograft regular recovery

Sham Comparator group

Description:

Pediatric patients who have undergone liver transplantation and have recovered normally typically undergo liver biopsy around 3 to 5 years postoperatively and around 10 years postoperatively to evaluate the presence of potential subclinical rejection. This assessment guides the long-term application of immunosuppressive medications.

Treatment:

Diagnostic Test: Liver Allograft Fibrosis by Using Fibrosis Panel(PRO-C3, PIIINP, TIMP-1, HA etc.)