PFIC1 associated post-transplant graft steatosis and inflammation
Research type
Research Study
Full title
PFIC1 associated post-transplant graft steatosis and inflammation
IRAS ID
360441
Contact name
Girish Gupte
Contact email
Sponsor organisation
BIRMINGHAM WOMEN'S AND CHILDREN'S NHS FOUNDATION TRUST
Duration of Study in the UK
0 years, 1 months, 30 days
Research summary
Progressive Familial Intrahepatic cholestasis type I (PFIC1) is a rare congenital hepatopathy. Presentation can be intermittently or chronically, patients suffer from
infantile cholestasis with pruritus, which progresses to cirrhosis and liver insufficiency. As FIC1 is expressed in various other tissues than liver, PFIC1 patients might also present with hearing loss, pancreatitis, hypoparathyroidism and diarrhoea. So far, treatment has been mostly symptomatic (e.g., nutritional, vitamin-supplementation and anti-pruritogenic agents) and often less effective. Surgical biliary diversion (SBD) procedures proved to have some effectiveness in alleviating pruritus and reduce progression of liver fibrosis and disease. Recently, compounds inhibiting the ileal apical sodium bile salt transporter (ASBT)/ ileal bile acid transporter (IBAT) have been developed, successfully tested
and will be soon commonly available (NCT03566238, NCT03659916). In theory, the effect
should be similar to SBD. Some PFIC1 patients, however, do not respond to available treatment and progress to endstage liver disease, which ultimately requires liver transplantation (LTx). Graft steatosis, progressive inflammation and fibrosis after liver transplantation for PFIC1 is increasingly recognized. Modification of the intestinal ble acids (BA) pool by administration of BA resins, SBD or ileal bile acid transporter inhibition (IBATi) seems to offer a remedy to this phenomenon. The underlying pathomechanism, however, remains elusive. Therefore, this project aims to further elucidate the association between the bile acid pool, intestinal microbiota and the regulation of the enterohepatic circulation and signalling in PFIC1
patients before and after liver transplantation and respective SBD or IBATi.REC name
North East - Newcastle & North Tyneside 2 Research Ethics Committee
REC reference
25/NE/0169
Date of REC Opinion
22 Sep 2025
REC opinion
Further Information Favourable Opinion