Abstract

Background: Whether ileal absorption of bile acid is up or downregulated in chronic cholestasis is still debated, and most evidence has come from animal studies.

Aims: To compare ileal bile acid absorption in patients with primary biliary cirrhosis (PBC) and in healthy control subjects, and to assess the effect of ursodeoxycholic acid (UDCA).

Patients: We studied 14 PBC patients before and during (n=11) UDCA administration, 14 healthy control subjects, and 14 Crohn’s disease patients (as disease controls).

Methods: We used cholescintigraphy to measure retention in the enterohepatic circulation over five successive days of the bile acid analogue ⁷⁵Se-homocholic acid-taurine (⁷⁵SeHCAT) as an index of ileal bile acid absorption. Results were expressed as ⁷⁵SeHCAT fractional turnover rate (FTR) and t½12.

Results:⁷⁵SeHCAT FTR was 0.19 (0.11)/day, 0.34 (0.11)/day (p<0.001), and 0.83 (0.32)/day in PBC patients, healthy controls (p<0.0001), and Crohn’s patients (p<0.001), respectively, which increased to 0.36 (0.16)/day in PBC patients during UDCA treatment (p<0.005). ⁷⁵SeHCAT t½12 was 4.8 (2.1) days in PBC patients, 2.2 (0.5) days (p<0.001) in healthy controls, and 1.0 (0.5) days (p<0.001) in Crohn’s disease patients. ⁷⁵SeHCAT t½12 decreased to 2.2 (0.93) days (p< 0.001) in PBC patients during UDCA treatment.

Conclusions: Our results support the concept that ileal bile acid absorption is upregulated in PBC patients, and that this effect may contribute towards damaging the cholestatic liver. This upregulation of bile acid absorption is abolished by UDCA.