Intestinal absorption of the bile acid analogue 75Se-homocholic acid-taurine is increased in primary biliary cirrhosis, and reverts to normal during ursodeoxycholic acid administration

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 (75)Se-homocholic acid-taurine ((75)SeHCAT) as an index of ileal bile acid absorption. Results were expressed as (75)SeHCAT fractional turnover rate (FTR) and t(1/2)12.

Results: (75)SeHCAT 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). (75)SeHCAT t(1/2)12 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. (75)SeHCAT t(1/2)12 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.

Figure 1

Daily fractional turnover rate (K) (A) and t½12 (B) of ⁷⁵Se-homocholic acid-taurine (⁷⁵SeHCAT) in healthy controls, Crohn’s disease patients, and in patients with primary biliary cirrhosis (PBC). Bars represent the mean value for each group.

Figure 2

Effect of ursodeoxycholic acid (UDCA) treatment on daily fractional turnover rate (K) (A) and on t½12 (B) of ⁷⁵Se-homocholic acid-taurine (⁷⁵SeHCAT) in patients with primary biliary cirrhosis. The shaded area represents the range of values for healthy controls.