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  • 1
    ISSN: 1573-2568
    Keywords: hepatolithiasis ; cholesterol ; bile acid ; gallstone ; bile ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A detailed comparison was made of the bile acid composition in gallstones (brown pigment stones) and paired bile and liver from both affected and unaffected lobes by gallstones, which were taken at operation from 16 patients with hepatolithiasis, with the aim of elucidating whether stone formation is derived from possible local disturbances limited to intrahepatic bile ducts. Brown pigment stones in the intrahepatic bile ducts, most of which were accompanied by bile with high cholesterol saturation, had significantly more cholesterol, and less calcium bilirubinate and bile acid than those found in the extrahepatic bile ducts. Intrahepatic gallstones had significantly lower amounts of secondary and unconjugated bile acids, the bile acids modified by bacterial intervention, than extrahepatic stones. Bile specimens from both affected and unaffected lobes showed significantly increased molar percentages of cholesterol and decreased percentages of bile acids than bile from controls. In contrast, liver specimens from both lobes showed significantly higher concentrations of total bile acids. Secondary bile acids were present in a much lower proportion in bile and liver from both lobes than in bile and liver from controls. On the other hand, unconjugated bile acids were present in a much higher proportion in bile and liver from patients and only in negligible amounts in bile from controls. Furthermore, the plasma levels of mevalonate and those of 7α-hydroxy-4-cholestene-3-one were found to be significantly higher and lower in patients than in controls, respectively, indicating that in hepatolithiasis cholesterol synthesis might increase and bile acid synthesis might decrease in the liver. These findings suggested that alterations of bile acid composition in gallstones, bile, and liver of patients with hepatolithiasis may be attributed to not only secondary changes resulting from local disturbances limited to intrahepatic bile ducts but also possible primary alterations of hepatocyte metabolism, such as bile acid conjugation and primary defects in cholesterol and bile acid synthesis.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1435-5922
    Keywords: gallstone disease ; bile acids ; cholesterol ; cholesterol 7α-hydroxylase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Patients with cholesterol gallstone disease have a reduced pool of bile acids. Overly sensitive feedback inhibition of bile acid synthesis has been postulated to explain this size reduction. To test this hypothesis, hepatic bile acid concentration and the activity of cholesterol 7α-hydroxylase, the rate-limiting enzyme for bile acid biosynthesis, were determined in ten patients with cholesterol gallstones and ten patients without gallstones. The bile acids present in liver tissue are the sum of those returning to liver and those newly synthesized in liver. If an overly sensitive feedback inhibition truly existed in our gallstone patients, a decreased concentration of hepatic bile acids would have been expected. However, patients with cholesterol gallstones had significantly higher total (143.3 ±25.5 vs 64.5±10.8 nmol/g liver,P〈0.01), chenodeoxycholic (64.1±9.9 vs 29.8±5.4,P〈0.01), deoxycholic (22.8±10.9 vs 2.0±0.7,P〈0.05), and ursodeoxycholic acid (6.2±1.4 vs 1.5±0.6,P〈0.01) concentrations than patients without gallstones. The activity of cholesterol 7α-hydroxylase did not differ significantly between the two groups. Impaired hepatic transport or secretion of bile acids is strongly suspected in cholesterol gallstone patients. The findings of the present study showed no evidence of overly sensitive feedback inhibition of bile acid synthesis in cholesterol gallstone patients. Bile acid pool size may be affected by the inappropriate increase of hepatic bile acids rather than by overly sensitive feedback inhibition.
    Type of Medium: Electronic Resource
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