| Co-Investigator(Kenkyū-buntansha) |
KAMEOKA Nobuhisa Kyushu University, Faculty of Medicine, Res.Fellow, 医学部, 医員
SHIMIZU Shuji Kyushu University, Faculty of medicine, Assist.Prof., 医学部, 助手 (70274454)
CHIJIIWA Kazuo Kyushu University, Faculty of Medicine, Lecturer, 医学部, 講師 (90179945)
牧野 一郎 九州大学, 医学部, 医員
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
To examine bile acid synthesis in chronic liver diseases, serum total 7 alpha-hydroxycholesterol (7AHC) level was measured by gas-liquid chromatography-mass spectrometry in patients with cirrhosis (n=23), patients with chronic hepatitis (n=21), and control subjects (n=18). The serum 7AHC levels were significantly lower in patients with cirrhosis than the controls (78(]SY.+-。[)59 pmol/ml vs.237(]SY.+-。[)97 pmol/ml, mean(]SY.+-。[)SD). However, in patients with chronic hepatitis, the level was fully retained (262(]SY.+-。[)102 pmol/ml). Serum 7AHC levels of 17 patients with cirrhosis classified as Child B and C ranged from 33 to 69 pmol/ml, and all were less than the normal range (between 104 and 466 pmol/ml), however, those levels of some patients classified as Child A were within the normal range. Serum 7AHC levels significantly correlated with serum albumin, cholinesterase, total bile acids, direct bilirubin, alkaline phosphatase, indocyanine green (ICG) retention rate, hepaplastin test
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, and lecithin-cholesterol acyltransferase activities. We concluded that bile acid synthesis is well preserved in patients with chronic hepatitis and that it is decreased in most patients with cirrhosis. Serun 7AHC may be a new parameter of liver function testing to assess hepatic bile acid synthesis in patients with chronic liver diseases.
The next study was designed to examine the maximal bile acid synthesis in patients with chronic liver diseases. Cholestyramine (CS ; 12g/day) was administered for 3 days to patients with compensated lifer cirrhosis (n=7), patients with chronic hepatitis (n=10), and control subjects (n=9), and serum total 7AHC level was measured by gas-liquid chromatography-mass spectrometry. A preliminary study showed that CS increased the serum value to the maximum by the third day. Before CS treatment, there were no significant differences in serum 7AHC levels among the groups. Three days of CS treatment increased the serrum level 5.71(]SY.+-。[)2.91-fold in the controls, 3.25(]SY.+-。[)0.85-fold in patients with chronic hepatitis, and 1.70(]SY.+-。[)0.78-fold in cirrhotic patients. Cirrhotic patients had significantly lower serum 7AHC levels after the treatment compared with oter groups. Serum 7AHC levels stimulated by CS significantly correlated with serum albumin levels and indocyanine green retention rate. It is concluded that 3 days of CS loading increased the bile acid synthesis of its maximal level. The CS test showed that patients with chronic hepatitis had enough hepatic reserve for bile acid synthesis ; however, patients with compensated liver cirrhosis had significantly decreased capacity. Less
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