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

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.

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.