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 gamma-labelled bile acid 75Se-homocholic acid taurine (75SeHCAT) provides a tool for the direct measurement of hepatic bile acid handling.


OBJECTIVE
To determine the interrelationships among hepatic handling of 75SeHCAT, the kinetics of its disappearance from plasma and serum bile acid levels in patients with chronic liver disease.


METHODS
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 75SeHCAT, we determined plasma disappearance rates (initial K1, late K2) from serial blood samples and hepatic uptake and excretory rates directly from dynamic abdominal gamma-camera scanning. Both scanning and sampling were carried out over a period of 90 min.


RESULTS
Serum bile acid concentrations correlated with K1 and with hepatic uptake (Rs = -0.53, P < 0.01; Rs = -0.47, P < 0.02, respectively) but neither with K2 nor with the excretory rate. K1 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.


CONCLUSIONS
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.
de Caestecker
J S
JS
Department of Medicine, St George's Hospital Medical School, London, UK.
Jazrawi
R P
RP
Nisbett
J A
JA
Joseph
A E
AE
Maxwell
J D
JD
Northfield
T C
TC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001647:Bile Acids and Salts / Q000097:blood*; D005260:Female; D006801:Humans; D008099:Liver / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000503:physiopathology*; D008105:Liver Cirrhosis, Biliary / Q000175:diagnosis / Q000503:physiopathology*; D008111:Liver Function Tests; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D008875:Middle Aged; D012644:Selenium Radioisotopes; D013656:Taurocholic Acid / Q000031:analogs & derivatives
D001647:Bile Acids and Salts; D012644:Selenium Radioisotopes; D013656:Taurocholic Acid; C033638:23-seleno-25-homotaurocholic acid