Hepatic levels of bile acids in end-stage chronic cholestatic liver disease
Hepatic levels of bile acids in end-stage chronic cholestatic liver disease
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DOI：
10.1016/0009-8981(96)06305-x
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发表时间：
1996-07-30
影响因子：
5
通讯作者：
Koebe, HG
中科院分区：
文献类型：
--
作者：
Fischer, S;Beuers, U;Koebe, HG
在慢性胆汁淤积性肝病中，疏水性和潜在的细胞毒性胆汁酸被认为在肝脏中积聚。为了验证这一假设，我们调查了接受肝移植的(A)终末期慢性淤胆性肝病患者和(B)酒精性/慢性肝炎起源的终末期肝硬变患者的肝脏和血清中胆汁酸的水平和模式。对(C)正常肝组织进行胆汁酸分析。慢性胆汁淤积组胆汁酸水平为215+/-39.1nmol/g肝(湿重)，B组和C组胆汁酸水平分别为120+/-32.7和56.1+/-24.2nmol/g肝(P<；0.01和P<；0.005)。胆酸是慢性胆汁淤积症的主要胆汁酸(51%)，与C组相比升高了8倍(P<；0.005)。鹅去氧胆酸占总胆汁酸的41%，增加了4倍(P<；0.005)。慢性胆汁淤积组脱氧胆酸仅占胆汁酸的1.5%，C组为27%(P<；0.01)，B组无脱氧胆酸。慢性胆汁淤积组胆石酸水平较C组升高，其硫酸盐化功能受损(P<；0.05)。慢性胆汁淤积症患者的血清胆汁酸模式与移植肝脏的胆汁酸模式一致。我们的结论是，疏水性鹅去氧胆酸的肝脏蓄积和石胆酸的硫酸盐化受损可能通过这些胆汁酸的洗涤作用而导致慢性淤胆性肝病的组织退化。
In chronic cholestatic liver disease hydrophobic and potentially cytotoxic bile acids are assumed to accumulate in the liver. To test this hypothesis we investigated bile acid levels and pattern in livers and serum of patients with, (A) end-stage chronic cholestatic liver disease, and with (B) end-stage cirrhosis of alcoholic/chronic hepatitic origin who underwent liver transplantation. Bile acids were also analyzed in (C) normal liver tissue. Levels of bile acids were 215 +/- 39.1 nmol/g liver (wet weight) in chronic cholestasis and 120 +/- 32.7 and 56.1 +/- 24.2 nmol/g liver in group B and group C (P < 0.01 and P < 0.005), respectively. Cholic acid was the prevailing bile acid in chronic cholestasis (51%) and was elevated eight-fold as compared to group C (P < 0.005). Chenodeoxycholic acid contributed 41% to total bile acids and was elevated four-fold (P < 0.005). Deoxycholic acid contributed only 1.5% to bile acids in chronic cholestasis as compared to 27% in group C (P < 0.01) and was absent in group B. Levels of lithocholic acid tended to be increased in chronic cholestasis as compared to group C and its sulfation was impaired (P < 0.05). The pattern of serum bile acids in chronic cholestasis agreed well with the bile acid pattern in the explanted livers. We conclude that hepatic accumulation of hydrophobic chenodeoxycholic acid and impaired sulfation of lithocholic acid might contribute to tissue degeneration in chronic cholestatic liver disease due to the detergent effects of these bile acids.