Progressive Familial Intrahepatic Cholestasis in Indian Children - Establishing an Indian PFIC Registry

Study Overview
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Brief Summary
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The project will amalgamate data from several large Indian centers to describe the genotype, clinical spectrum, natural course, genotype-phenotype correlation, outcome, and response to medical therapy in Indian children with progressive familial intrahepatic cholestasis (PFIC). This will be the first such Indian registry of children with PFIC. There are currently limited single-center studies describing the genotype, natural course, and outcome of Indian children with PFIC. Data will be collected retrospectively from the participating centers across the country. Only genetically confirmed cases would be included.

Detailed Description
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There is a lack of robust literature from India on PFIC. The study would be the first to extensively describe the genotype of Indian children with PFIC and their natural course. Being a multicentric study, the results generated would therefore be applicable to the whole of the country. Understanding the prevalent genotypes in the Indian population and their related phenotype would help both the individual management decisions of these patients and further policy-making for their diagnosis and treatment. With the advent of genetic diagnosis through sequencing techniques and these tests becoming more affordable, every Indian center is now diagnosing a fair number of these cases which used to go undiagnosed previously. This has changed the landscape of cholestatic liver disease in children where PFICs are now the most prevalent pediatric cholestatic disorder. European studies have demonstrated 2 common mutations where patients respond very well to surgical biliary diversion and have good native liver survival. These mutations have rarely been reported in India. Results from this study could thus guide appropriate decision-making based on outcome and help choose the modality of treatment for the individual patient - medical, surgical biliary diversion, or liver transplantation.

Official Title
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Progressive Familial Intrahepatic Cholestasis in Indian Children - Establishing an Indian PFIC Registry

Conditions
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Progressive Familial Intrahepatic Cholestasis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Genetically proven homozygous or compound heterozygous mutations of ATP8B1/ ABCB11/ ABCB4/ TJP2/ NR1H4/ MYO5B/ USP53/ KIF12 AND Clinical and biochemical evidence of chronic cholestatic disease AND / OR Histological features of intrahepatic cholestasis with suggestive immunohistochemistry Exclusion Criteria: Genetic analysis showing mutations unrelated to intrahepatic cholestasis according to database Clinical, biochemical, and histological evidence of progressive familial intrahepatic cholestasis without a genetic sequencing report

Ages Eligible for Study
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Maximum Age: 18 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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Native liver survival (in percentage) at the latest follow up in different types of PFIC | The proportion of patients of each subtype of PFIC who have survived with their own with their native liver till the time of last follow up | Through study completion - average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Describe the spectrum of genetic mutations in Indian children with familial intrahepatic cholestasis | This objective would be assessed by studying the frequency of each of these subtypes of PFIC and describing the various genotypes under each subtype. | Through study completion - average of 1 year | 
| Genotype-phenotype correlation in Indian children with various types of progressive familial intrahepatic cholestasis | Well defined clinical parameters (jaundice, pruritus, presentation, presence of cirrhosis) and clinical end points (death, liver transplantation, native liver survival) would be used to describe the genotype-phenotype correlation. We will try to club various mutations into categories based on the type of mutations to better assess the genotype-phenotype correlation. | Through study completion - average of 1 year | 
| Analyse the natural course after surgical biliary diversion in Indian children with various types of progressive familial intrahepatic cholestasis | We will analyze the response to surgical biliary diversion in various types of PFIC with emphasis on identifying the genotypes likely to gain maximum benefit through this procedure. Biochemical parameters to assess/ predict the response would be evaluated by regression analysis. | Through study completion - average of 1 year | 
| Complications after liver transplantation in children with various types of progressive familial intrahepatic cholestasis till the time of last follow up | The proportion of children going for liver transplantation at various time points would be assessed. Genetic, clinical or biochemical parameters predicting need for imminent/ future liver transplantation would be determined by regression analysis. | Through study completion - average of 1 year | 
| Proportion of patients surviving with native liver in uncommon variants of progressive familial intrahepatic cholestasis | Describe the prevalence, natural course and outcome of uncommon variants of progressive familial intrahepatic cholestasis in Indian children | Through study completion - average of 1 year | 
| Develop and maintain a registry of Indian patients with progressive familial intrahepatic cholestasis (Indian PFIC registry) | A registry (Indian PFIC registry) would be maintained with use of appropriate data managing software. | Through study completion - average of 2 years |