Direct assessment of the mechanism for a raised serum bile acid level in chronic liver disease

Background : Impaired hepatic uptake is the major cause of raised serum bile acid levels in liver disease, but confirmation in humans by direct measurement is lacking. The synthetic γ-labelled bile acid 75 Se-homocholic acid taurine ( 75 SeHCAT) provides a tool for the direct measurement of hepatic bile acid handling. Objective : To determine the interrelationships among hepatic handling of 75 SeHCAT, the kinetics of its disappearance from plasma and serum bile acid levels in patients with chronic liver disease. Design : We studied 12 patients with primary biliary cirrhosis and 14 with cirrhosis arising from other causes. Fasting serum bile acid levels were measured enzymatically. After intravenous administration of 7 5 SeHCAT, we determined plasma disappearance rates (initial K 1 , late K 2 ) from serial blood samples and hepatic uptake and excretory rates directly from dynamic abdominal γ-camera scanning. Both scanning and sampling were carried out over a period of 90 min. Results : Serum bile acid concentrations correlated with K 1 and with hepatic uptake (R s = -0.53, P< 0.01 ; R s = -0.47, P< 0.02, respectively) but neither with K 2 nor with the excretory rate. K 1 and uptake were reduced (P< 0.05) in patients with high serum bile acid levels and in those with varices. Serum bile acid levels were higher in patients with varices (P<0.05), which might suggest that portosystemic shunting occurred. However, this is unlikely because the varices were not independent of liver function. Conclusion : Hepatic bile acid uptake and excretion are independent processes. Hepatic uptake is related to initial, whereas hepatic excretion is related to late, plasma disappearance. Impaired hepatic uptake is a major determinant of the rise in serum bile acid levels in chronic liver disease.