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. 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 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 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.

Intestinal bile acid physiology and pathophysiology

“…Intestinal MRP2 but not MRP3 is decreased by cholestasis in rats [50] and in humans [48,51] , although the significance of these findings is uncertain. In contrast, increased absorption has been reported in primary biliary cirrhosis, thus contributing to cholestasis in this condition [52] . Hypertriglicerydemia also reduces ASBT expression and inhibits BA absorption [53] , an effect which in turn might exacerbate hypertriglyceridemia [54] .…”

Apical Sodium-Dependent Transporter Inhibitors in Primary Biliary Cholangitis and Primary Sclerosing Cholangitis

“…An adaptive regulation leading to the downregulation of intestinal ASBT has been shown in both animal and human studies [16,17] . In contrast, increased absorption of BAs has been reported in PBC, thus contributing to cholestasis in this condition [18] . Nevertheless, ASBT inhibition is an attractive therapeutic option in cholestatic conditions based on the hypothesis that interrupting the EHC of BAs may also reduce the circulating BA pool and hepatic levels of potentially cytotoxic BAs.…”

Bile acids: Trying to understand their chemistry and biology with the hope of helping patients #

“…63 Such inappropriate conservation of bile acids could be prevented, at least in principle, by sequestrant administration or by inhibiting ileal transport. A potent nonabsorbable inhibitor Fig.…”