TORNA ALL’ELENCO

The natural course of BSEP deficiency: Results from the global 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: BSEP deficiency (BSEP-def), due to mutations in the ABCB11gene, is responsible for progressive familial intrahepatic cholestasis type 2. The ABCB11gene encodes the canalicular Bile Salt Export Pump (BSEP). BSEP-def patients typically present with pruritus and cholestasis in early life, that usually progresses to the need for liver transplantation (LTx). Patients may benefit from ursodeoxycholic acid (UDCA) or from surgical biliary diversion (SBD) techniques. We aim to better understand the natural course of BSEP-def and the efficacy of interventions. Methods: We present retrospective follow up data on patients with compound heterozygous or homozygous ABCB11mutations from 22 centers in Europe, North-America, Asia and Australia (the NAPPED-consortium,NAtural course and Prognosis of PFIC and Effect of biliary Diversion). In total 203 patients (53% males) wereincluded and categorized according to genotype: mild (at least one D482G or E297G mutation; n=68), moderate (at least one missense mutation, but not D482G or E297G; n=100) or severe (mutations leading to truncated or otherwise non-functional protein; n=35). Cox regression analysis was applied for the endpoints SBD and native liver survival (NLS) studying the association with gender, age at diagnosis, birth year, genotype category and SBD as a time-dependent factor for NLS. Continuous variables are expressed as median [range]. Results: Overall median age at first visit was 9 months [0-195] and at last follow up 5.5 years [0.1-31.4]. Use of UDCA at first visit was 47%. Overall SBD rates at five/ten years of age were 27/34%, mild category patients were more likely to have undergone SBD (HR mild vs severe = 5.4, 95%CI 1.7-17.6; p<0.01). Overall five/ten-year NLS was 63/46%. Age at diagnosis and genotype were associated with NLS, in contrast to sex and UDCA. NLS was significantly higher in SBD+ve than in SBDve patients (HR=0.44; 95%CI 0.23-0.88, p=0.007; Figure) after adjustment for age and genotype c

DOI : 10.1002/hep.30256

Keywords

bile salt export pump; endogenous compound; ursodeoxycholic acid; adult; adulthood; Asia; Australia; cancer patient; cancer prognosis; cancer surgery; cancer survival; child; conference abstract; controlled study; diagnosis; drug therapy; Europe; female; follow up; gender; genetic association; genetic susceptibility; genotype; heterozygosity; homozygosity; human; incidence; liver cell carcinoma; major clinical study; male; missense mutation; multicenter study; North America; preschool child; retrospective study; school child; surgery; young adult;