A common variant in the hepatobiliary phospholipid transporter
                    modulates liver injury in PBC but not in PSC

Beata Kruk; Malgorzata Milkiewicz; Joanna Raszeja-Wyszomirska; Piotr Milkiewicz; Marcin Krawczyk

doi:10.1055/s-0042-1759911

Zeitschrift für Gastroenterologie, Table of Contents

Z Gastroenterol 2023; 61(01): e7
DOI: 10.1055/s-0042-1759911

Abstracts | GASL

Poster Visit Session l Basic Hepatology (Fibrogenesis, NPC, Transport) 27/01/2023, 12.30 pm – 13.15 pm

A common variant in the hepatobiliary phospholipid transporter modulates liver injury in PBC but not in PSC

Beata Kruk

¹Medical University of Warsaw, Warsaw, Poland

,

Malgorzata Milkiewicz

²Pomeranian Medical University in Szczecin, Szczecin, Poland

,

Joanna Raszeja-Wyszomirska

¹Medical University of Warsaw, Warsaw, Poland

,

Piotr Milkiewicz

¹Medical University of Warsaw, Warsaw, Poland

,

Marcin Krawczyk

³Saarland University Medical Center, Saarland University, Homburg

› Author Affiliations

Abstract

Full Text

Background Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) represent two chronic cholestatic liver diseases. The ABCB4 gene encodes the hepatobiliary phospholipid transporter and its genetic defects cause cholestatic phenotypes (Stättermayer et al., J Hepatol. 2020). Here we investigate the ABCB4 c.711A-T genetic variant in patients with PBC and PSC.

Methods Two cohorts of patients were analysed. The Szczecin cohort comprised 196 patients with PBC (174 females, 42% with cirrhosis) and 135 patients with PSC (39 females, 39% with cirrhosis). The Warsaw cohort consisted of 260 patients with PBC (241 females, 44% with cirrhosis) and 276 patients with PSC (97 females, 33% with cirrhosis). The control cohort was composed of 468 individuals. ABCB4 c.711A-T was genotyped using TaqMan assay.

Results In both PBC cohorts, carriers of the risk ABCB4 c.711A-T variant presented more frequently with cirrhosis (Szczecin: OR=1.841, P=0.025; Warsaw: OR=1.528, P=0.039). The association between ABCB4 c.711A-T and cirrhosis risk in PBC remained significant (P=0.03) in multivariate regression models. The ABCB4 risk allele was also associated with increased serum AST, GGT and ALP. During 8±4 years follow-up, a total of 22 patients in the Szczecin PBC cohort developed cirrhosis and this risk was higher among carriers of the risk ABCB4 variant (OR=5.65, P=0.04). In contrast to PBC, the ABCB4 polymorphism had no effects on liver phenotypes the PSC. Conclusions The frequent ABCB4 c.711A-T polymorphism modulates liver injury in PBC. Its inclusion in the diagnostic work-up of PBC patients might help to quantify their risk of progressive