TORNA ALL’ELENCO

The natural course of fic1 deficiency: Results from the napped-consortium in Hepatology

2018
AOU Città della Salute di Torino

Tipo pubblicazione

Conference Abstract

Autori/Collaboratori (38)Vedi tutti...

Van Wessel D

Thompson RJ

Grammatikopoulos T


et alii...

Abstract

Background: Severe deficiency of FIC1 (FIC1-def) is due to mutations in the ATP8B1gene, and is responsible for progressive familial intrahepatic cholestasis type 1. The ATP8B1encodes the FIC1-protein, which functions as an aminophospholipid translocase. Because of secondary impaired biliary bile salt secretion, patients typically present with pruritus and low gamma-GT cholestasis in early childhood. FIC1 is also expressed in other tissues, such as pancreas and intestine, and extrahepatic manifestations may occur in FIC1-def patients. Ursodeoxycholic acid or surgical biliary diversion (SBD) techniques might be beneficial for some patients, yet many patients require liver transplantation (LTx) at some stage. We aim to better understand the natural course of FIC1-def and the efficacy of interventions. Therefore, we have set up an extensive international consortium, “NAPPED” (NAtural course and Prognosis of PFIC and Effect of biliary Diversion). Methods: We present retrospective follow up data on individual patients from 22 centers in Europe, North-America, Asia and Australia. All patients were either compound heterozygous or homozygous for disease associated mutations in the ATP8B1gene. We used time-dependent Cox regression for native liver survival (NLS), adjusted for gender and birth year, in patients that had undergone SBD (SBD+ve) or not (SBD-ve). Continuous variables are expressed as median [range]. Results: We included 46 FIC1-def patients (predominately males, 76%; P<0.001). Age at first visit was 0.5 [0-16.8] years. Use of ursodeoxycholic acid prior to first visit was 39%. Age at last follow up was 5.4 [0.25-27.8] years. Overall SBD rates at five/ ten years of age were 37/43%, for males (36/45%) and females (50/50%, respectively; p=0.15). SBD rates in compound heterozygous and homozygous patients were 34/34% and 37/45%, respectively (p=0.29). Overall five/ten-year NLS was 74/46%. Five/ten-year NLS in males and females was 71/49% and 88/58%, respectiv

DOI : 10.1002/hep.30257

Keywords

endogenous compound; ursodeoxycholic acid; adult; adulthood; Asia; Australia; child; cholestasis; clinical article; conference abstract; controlled study; Europe; female; follow up; gender; gene mutation; genetic association; genotype; heterozygosity; homozygosity; human; infant; intestine; liver transplantation; male; mortality; multicenter study; North America; pancreas; phenotype; prognosis; protein expression; retrospective study; school child; surgery; young adult;