Literature DB >> 35535061

Progressive Familial Intrahepatic Cholestasis: A Study in Children From a Liver Transplant Center in India.

Sagar Mehta1, Karunesh Kumar1, Ravi Bhardwaj1, Smita Malhotra1, Neerav Goyal2, Anupam Sibal1.   

Abstract

Background/Aims: This study aimed to delineate the clinical profile of children diagnosed with progressive familial intrahepatic cholestasis (PFIC).
Methods: This study was a retrospective analysis of case records of children in the tertiary care hospital, with the diagnosis of PFIC from January 2017 to January 2020. The diagnosis was made using clinical and laboratory parameters and with genetic testing when available. Medical and surgical management was according to the departmental protocol. Liver transplant was offered to children with end-stage liver disease, intractable pruritus, or severe growth failure. Result: There were 13 identified PFIC cases (familial intrahepatic cholestasis 1 [FIC1] deficiency-4, bile salt export pump (BSEP) deficiency-3, tight junction protein [TJP2] deficiency 3, multidrug-resistant protein 3 [MDR3] deficiency 2 and farnesoid X receptor deficiency-1). PFIC subtypes 1, 2, and 5 presented in infancy, whereas MDR3 presented in childhood. TJP2 deficiency had varied age of presentation from infancy to adolescence. Jaundice with or without pruritus was present in most cases. Genetic testing was carried out in 10 children, of which five had a homozygous mutation, three had a compound heterozygous mutation, and two had a heterozygous mutation. Three children (FIC1-2 and TJP2-1) underwent biliary diversion, of which clinical improvement was seen in two. Six children underwent liver transplantation, which was successful in four.
Conclusion: Byler's disease was the most common subtype. A clinicopathologic correlation with molecular diagnosis leads to early diagnosis and management. Liver transplantation provides good outcomes in children with end-stage liver disease.
© 2021 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.

Entities:  

Keywords:  BD, biliary diversion; BSEP, bile salt export pump; Byler's disease; ESLD, end stage liver disease; FIC 1, Familial Intrahepatic Cholestasis 1; FXR, Farnesoid X receptor; GGT, gamma glutamyl transferase; LFT, liver functions test; LRLT, living related liver transplant; LT, liver transplantation; MDR3, multi drug resistant protein 3; NGS, Next generation sequencing; PEBD, partial external biliary diversion; PELD, Pediatric end-stage liver disease; PFIC, progressive familial intrahepatic cholestasis; PIBD, partial internal biliary diversion; TJP 2, Tight junction protein 2; UDCA, ursodeoxycholic acid; cirrhosis; liver transplantation; neonatal cholestasis; next-generation sequencing

Year:  2021        PMID: 35535061      PMCID: PMC9077189          DOI: 10.1016/j.jceh.2021.06.006

Source DB:  PubMed          Journal:  J Clin Exp Hepatol        ISSN: 0973-6883


  17 in total

Review 1.  Liver transplantation and the management of progressive familial intrahepatic cholestasis in children.

Authors:  Ashley Mehl; Humberto Bohorquez; Maria-Stella Serrano; Gretchen Galliano; Trevor W Reichman
Journal:  World J Transplant       Date:  2016-06-24

2.  Sequencing of FIC1, BSEP and MDR3 in a large cohort of patients with cholestasis revealed a high number of different genetic variants.

Authors:  Carola Dröge; Michele Bonus; Ulrich Baumann; Caroline Klindt; Elke Lainka; Simone Kathemann; Florian Brinkert; Enke Grabhorn; Eva-Doreen Pfister; Daniel Wenning; Alexander Fichtner; Daniel N Gotthardt; Karl Heinz Weiss; Patrick McKiernan; Ratna Dua Puri; I C Verma; Stefanie Kluge; Holger Gohlke; Lutz Schmitt; Ralf Kubitz; Dieter Häussinger; Verena Keitel
Journal:  J Hepatol       Date:  2017-07-19       Impact factor: 25.083

3.  Progressive Familial Intrahepatic Cholestasis (PFIC) in Indian Children: Clinical Spectrum and Outcome.

Authors:  Sajan Agarwal; Bikrant Bihari Lal; Dinesh Rawat; Archana Rastogi; Kishore G S Bharathy; Seema Alam
Journal:  J Clin Exp Hepatol       Date:  2016-05-24

Review 4.  Progressive familial intrahepatic cholestasis.

Authors:  Anshu Srivastava
Journal:  J Clin Exp Hepatol       Date:  2013-11-23

5.  Mutations in TJP2 cause progressive cholestatic liver disease.

Authors:  Melissa Sambrotta; Sandra Strautnieks; Efterpi Papouli; Peter Rushton; Barnaby E Clark; David A Parry; Clare V Logan; Lucy J Newbury; Binita M Kamath; Simon Ling; Tassos Grammatikopoulos; Bart E Wagner; John C Magee; Ronald J Sokol; Giorgina Mieli-Vergani; Joshua D Smith; Colin A Johnson; Patricia McClean; Michael A Simpson; A S Knisely; Laura N Bull; Richard J Thompson
Journal:  Nat Genet       Date:  2014-03-09       Impact factor: 38.330

6.  Therapeutic interventions in progressive familial intrahepatic cholestasis: experience from a tertiary care centre in north India.

Authors:  Satvinder Kaur; Deepa Sharma; Nishant Wadhwa; Subash Gupta; Sujit Kumar Chowdhary; Anupam Sibal
Journal:  Indian J Pediatr       Date:  2011-07-19       Impact factor: 1.967

7.  Cryptogenic cholestasis in young and adults: ATP8B1, ABCB11, ABCB4, and TJP2 gene variants analysis by high-throughput sequencing.

Authors:  Giovanni Vitale; Stefano Gitto; Francesco Raimondi; Alessandro Mattiaccio; Vilma Mantovani; Ranka Vukotic; Antonietta D'Errico; Marco Seri; Robert B Russell; Pietro Andreone
Journal:  J Gastroenterol       Date:  2017-12-13       Impact factor: 7.527

8.  Progressive Familial Intrahepatic Cholestasis Presenting With an Intracranial Bleed and Mimicking Abusive Head Trauma.

Authors:  Suzanne Haney; James Harper; Edward Truemper
Journal:  WMJ       Date:  2019-04

9.  Progressive familial intrahepatic cholestasis: a single-center experience of living-donor liver transplantation during two decades in Japan.

Authors:  Tomohide Hori; Hiroto Egawa; Yasutsugu Takada; Mikiko Ueda; Fumitaka Oike; Yasuhiro Ogura; Seisuke Sakamoto; Mureo Kasahara; Kohei Ogawa; Aya Miyagawa-Hayashino; Yukihide Yonekawa; Tohru Yorifuji; Ken-Ichiro Watanabe; Hiraku Doi; Justin H Nguyen; Feng Chen; Ann-Marie T Baine; Lindsay B Gardner; Shinji Uemoto
Journal:  Clin Transplant       Date:  2010-12-16       Impact factor: 2.863

10.  Effects of partial internal biliary diversion on long-term outcomes in patients with progressive familial intrahepatic cholestasis: experience in 44 patients.

Authors:  Hamid Reza Foroutan; Ali Bahador; Sultan Mohsin Ghanim; Seyed Mohsen Dehghani; Mohammad Hossein Anbardar; Mohammad Reza Fattahi; Mehdi Forooghi; Omidreza Azh; Ali Tadayon; Alireza Sherafat; Amir Arsalan Yaghoobi; Mohammad Ali Ashraf
Journal:  Pediatr Surg Int       Date:  2020-03-23       Impact factor: 1.827

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