Protective potential of the gallbladder in primary sclerosing cholangitis

• Published in: JHEP reports Vol. 5; no. 4; p. 100649
• Main Authors: Cazzagon, Nora, Gonzalez-Sanchez, Ester, El-Mourabit, Haquima, Wendum, Dominique, Rainteau, Dominique, Humbert, Lydie, Corpechot, Christophe, Chazouillères, Olivier, Arrivé, Lionel, Housset, Chantal, Lemoinne, Sara
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2023; Elsevier
• Subjects: Abcb4 knockout mice; Bile acids; Cholecystectomy; Gallbladder volume; Life Sciences; Magnetic resonance imaging; Cholecystectomy; PSC; ABC; Bile acids; IBD; UDCA; Abcb4 knockout mice; CK19; C4; HPLC-MS/MS; Magnetic resonance imaging; FGF19; ULN; Gallbladder volume; CFTR; BA; MRC; ABC, ATP-binding cassette transporter; HPLC-MS/MS, high-performance liquid chromatography coupled to tandem mass spectrometry; CK19, cytokeratin 19; FGF19, fibroblast growth factor 19; CFTR, cystic fibrosis transmembrane conductance regulator; BA, bile acid; C4, 7α-hydroxy-4-cholesten-3-one; ULN, upper limit of normal; PSC, primary sclerosing cholangitis; IBD, inflammatory bowel disease; MRC, magnetic resonance cholangiography; UDCA, ursodeoxycholic acid; Abcb4 knockout mice Bile acids Cholecystectomy Gallbladder volume Magnetic resonance imaging
• ISSN: 2589-5559; 2589-5559
• DOI: 10.1016/j.jhepr.2022.100649

Gallbladder enlargement is common in patients with primary sclerosing cholangitis (PSC). The gallbladder may confer hepatoprotection against bile acid overload, through the sequestration and cholecystohepatic shunt of bile acids. The aim of this study was to assess the potential impact of the gallbladder on disease features and bile acid homeostasis in PSC. Patients with PSC from a single tertiary center who underwent liver MRI with three-dimensional cholangiography and concomitant analyses of serum bile acids were included. Gallbladder volume was measured by MRI and a cut-off of 50 ml was used to define gallbladder enlargement. Bile acid profiles and PSC severity, as assessed by blood tests and MRI features, were compared among patients according to gallbladder size (enlarged vs. normal-sized) or presence (removed vs. conserved). The impact of cholecystectomy was also assessed in the Abcb4 knockout mouse model of PSC. Sixty-one patients with PSC, all treated with ursodeoxycholic acid (UDCA), were included. The gallbladder was enlarged in 30 patients, whereas 11 patients had been previously cholecystectomized. Patients with enlarged gallbladders had significantly lower alkaline phosphatase, a lower tauro-vs. glycoconjugate ratio and a higher UDCA vs. total bile acid ratio compared to those with normal-sized gallbladders. In addition, gallbladder volume negatively correlated with the hydrophobicity index of bile acids. Cholecystectomized patients displayed significantly higher aspartate aminotransferase and more severe bile duct strictures and dilatations compared to those with conserved gallbladder. In the Abcb4 knockout mice, cholecystectomy caused an increase in hepatic bile acid content and in circulating secondary bile acids, and an aggravation in cholangitis, inflammation and liver fibrosis. Altogether, our findings indicate that the gallbladder fulfills protective functions in PSC. In patients with primary sclerosing cholangitis (PSC), gallbladder status impacts on bile acid homeostasis and disease features. We found evidence of lessened bile acid toxicity in patients with PSC and enlarged gallbladders and of increased disease severity in those who were previously cholecystectomized. In the Abcb4 knockout mouse model of PSC, cholecystectomy causes an aggravation of cholangitis and liver fibrosis. Overall, our results suggest that the gallbladder plays a protective role in PSC. [Display omitted] •Gallbladder enlargement is associated with alleviated cholestasis in patients with PSC.•Gallbladder volume is negatively correlated with bile acid hydrophobicity in PSC.•Cholecystectomized patients with PSC display more severe cholangiographic features.•Cholecystectomy aggravates cholangitis and liver fibrosis in Abcb4 knockout mice.