Protective potential of the gallbladder in primary sclerosing cholangitis

Background & Aims: 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 gallbladder on disease features and bile acid homeostasis in PSC. Methods: PSC patients from a single tertiary center who underwent liver magnetic resonance imaging (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 the 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. Results: Sixty-one PSC patients, all treated with ursodeoxycholic acid (UDCA), were included. The gallbladder was found enlarged in 30 patients, whereas 11 patients had been previously cholecystectomized. Patients with enlarged gallbladders compared to those with normal-sized gallbladders, had significantly lower alkaline phosphatase, lower tauro- vs. glycoconjugates ratio and higher UDCA vs. total bile acids ratio. In addition, the gallbladder volume was negatively correlated with the hydrophobicity index of bile acids. Cholecystectomized patients compared to others displayed significantly higher aspartate aminotransferase and more severe bile duct strictures and dilatations. 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. Conclusion: Altogether, our findings indicate that the gallbladder fulfills protective functions in PSC.