de Caestecker J S, Jazrawi R P, Nisbett J A, Joseph A E, Maxwell J D, Northfield T C
Department of Medicine, St George's Hospital Medical School, London, UK.
Eur J Gastroenterol Hepatol. 1995 Oct;7(10):955-61. doi: 10.1097/00042737-199510000-00009.
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.
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.
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.
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.
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.
肝脏摄取功能受损是肝病患者血清胆汁酸水平升高的主要原因，但缺乏在人体中通过直接测量来证实这一点的研究。合成的γ标记胆汁酸75硒-同型胆酸牛磺酸（75SeHCAT）为直接测量肝脏对胆汁酸的处理提供了一种工具。
确定慢性肝病患者肝脏对75SeHCAT的处理、其从血浆中消失的动力学以及血清胆汁酸水平之间的相互关系。
我们研究了12例原发性胆汁性肝硬化患者和14例由其他原因引起的肝硬化患者。采用酶法测定空腹血清胆汁酸水平。静脉注射75SeHCAT后，我们通过连续采集血样测定血浆消失率（初始K1、后期K2），并通过动态腹部γ相机扫描直接测定肝脏摄取率和排泄率。扫描和采样均在90分钟内完成。
血清胆汁酸浓度与K1以及肝脏摄取相关（Rs分别为-0.53，P<0.01；Rs为-0.47，P<0.02），但与K2和排泄率均无关。血清胆汁酸水平高的患者以及有静脉曲张的患者，其K1和摄取率降低（P<0.05）。有静脉曲张的患者血清胆汁酸水平更高（P<0.05），这可能提示存在门体分流。然而，这可能性不大，因为静脉曲张并非独立于肝功能之外。
肝脏胆汁酸摄取和排泄是独立的过程。肝脏摄取与初始血浆消失相关，而肝脏排泄与后期血浆消失相关。肝脏摄取功能受损是慢性肝病患者血清胆汁酸水平升高的主要决定因素。
