NAtural Course and Prognosis of PFIC and Effect of Biliary Diversion

Study Overview
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Brief Summary
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The natural course of PFIC syndromes and the effect of diversion techniques, have so far not been characterized in a rigorous manner within a larger population of patients. In fact, the clinical or biochemical parameters which most directly define and/or predict the success of reduced enterohepatic circulation (either by surgical diversion or medically) are still unclear. The present project aims to: Define the natural course of disease in genetically defined PFIC1, and PFIC2 patients, with respect to relevant biochemical and clinical parameters (and if available, histological). Included will be patients homozygous for a known, disease-causing mutation, patients compound homozygous for two disease-causing mutations or heterozygous for one disease-causing mutation in combination with the clinical phenotype of Bsep-deficiency or FIC1-deficiency. Define the change in the natural course of disease in response to biliary diversion surgery and or liver transplantation, based on short- and long(er)-term changes in biochemical (if available, histological) and clinical parameters, including outcome measures. Follow up after transplantation will be limited to max 3 months after transplant surgery, follow up after surgical biliary diversion will be as long as possible. Assessment of biochemical variables as possible surrogate endpoints for clinical hard endpoints. If possible this allows for identification of low-risk to high-risk patients early during follow-up. If patient numbers permit, to establish genotype-phenotype relationships for the most common genetic mutations causing Bsep-deficiency or FIC1-deficiency. Based on this project it is anticipated that the investigators are able: to characterize the variation in natural course of disease (whether or not genotype dependent) to allow clinicians to rationally select a target population for assessing the effect of medical intervention, rather than surgical biliary diversion); to identify and qualify one or more biomarkers that independently predict either improved or poor clinical outcomes of surgical biliary diversion; to investigate if the identified biomarker(s) can be used as surrogate end point(s) for assessing and predicting outcomes with novel interventional strategies.

Official Title
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NAtural Course and Prognosis of PFIC and Effect of Biliary Diversion (NAPPED Study), Meta-analysis of Individual Patient Data of PFIC Before and After Surgery (Bile Diversion or Liver Transplantation)

Conditions
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Progressive Familial Intrahepatic Cholestasis

Intervention / Treatment
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* Procedure: Surgical biliary diversion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical suspicion for Bsep- or FIC1-deficiency

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| FIC1-deficiency and Bsep-deficiency<br> | Procedure: Surgical biliary diversion<br>* Surgical interruption of enterohepatic circulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with liver transplantation | Underwent liver transplant | at 18 years of age | 
| Number of participants that succumbed | Succumbed | at 18 years of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participant undergoing a surgical biliary diversion | Underwent surgical biliary diversion | at 5, 10, 15 and 18 years of age |