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1.
Ursodeoxycholic acid limits liver histologic alterations and portal hypertension induced by bile duct ligation in the rat. 总被引:6,自引:0,他引:6
J L Poo G Feldmann S Erlinger A Braillon C Gaudin M Dumont D Lebrec 《Gastroenterology》1992,102(5):1752-1759
Chronic administration of ursodeoxycholic acid (UDCA) has recently been suggested as a potential treatment for cholestatic liver disease. The purpose of this study was to examine the effects of chronic oral administration of UDCA on the histological, biochemical, and hemodynamic abnormalities induced by bile duct ligation in the rat. Fifty-one rats with ligation-section of the common bile duct were randomly and blindly assigned to receive UDCA (25 mg/kg each day) or placebo by gavage for 4 weeks. At the end of the treatment period, morphometric analysis showed that in rats treated with UDCA, hepatocyte and sinusoidal volume fractions were significantly higher than in rats receiving placebo [41.9 +/- 3.2% vs. 28.1 +/- 1.8%, (mean +/- SE) and 7.4 +/- 0.1% vs. 4.3 +/- 0.3%, respectively], whereas bile duct volume fraction (reflecting bile ductular proliferation) and connective tissue fraction were significantly lower in rats treated with UDCA than in rats receiving placebo (14.2 +/- 1.5% vs. 20.0 +/- 1.0% and 35.4 +/- 2.4% vs. 47.6 +/- 1.7%, respectively). Serum aminotransferase and alkaline phosphatase activities, and total serum bile acids and individual bile acid concentrations were not significantly different between the two groups. Portal pressure (12.7 +/- 0.5 mm Hg vs. 17.1 +/- 0.5 mm Hg), portal tributary blood flow (5.7 +/- 0.4 vs. 9.3 +/- 0.4 mL.min-1.100 g-1 body weight), and cardiac index (41.1 +/- 1.8 vs. 50.6 +/- 1.4 mL.min-1.100 g-1 body weight) were significantly lower in UDCA-treated rats than in placebo-treated animals. In portal vein stenosed rats, chronic administration of UDCA had no hemodynamic effects, a finding that suggests UDCA has no direct vasoactive effect on splanchnic circulation. It is concluded that in rats with bile duct ligation UDCA limits the severity of liver disease and consequently of portal hypertension and hyperkinetic circulation. 相似文献
2.
J Furui 《Nihon Shokakibyo Gakkai zasshi》1990,87(3):799-810
Serial changes of total bile acid concentrations (TBA) in the peripheral and portal blood after partial hepatectomy were examined on rats with both normal and impaired liver which was induced by CCl4. Changes of TBA in the peripheral blood, clearance index and intrahepatic shunt index were marked in proportion to the volume of resection and in the damaged liver. No significant changes of TBA in the portal blood were seen. TBA in the peripheral blood were significantly correlated with TBA in the portal blood, clearance index and intrahepatic shunt index. Clearance index was also significantly correlated with the rate of regeneration. Therefore, it is concluded that decrease of hepatic extraction of bile acid and increase of intrahepatic shunts between portal vein and hepatic vein elevated TBA in the peripheral blood. It seems useful for evaluation of postoperative hepatic regeneration to measure TBA in the peripheral and portal blood and to calculate clearance index after partial hepatectomy. 相似文献
3.
KIMIHIDE NAKAMURA MASASHI YONEDA ATSUSHI KIMURA KEISUKE TAMORI SHIRO YOKOHAMA YOICHI SATO TAKAFUMI KATO TAKENAO HASEGAWA HIDEAKI SAITO MASARU AOSHIMA MASANORI FUJITA ISAO MAKINO 《Journal of gastroenterology and hepatology》1996,11(4):385-390
The present study was undertaken in order to investigate the influence of ursodeoxycholic acid (UDCA) on the composition of sulfate-conjugated bile acids in the serum and urine of patients with chronic active hepatitis and compensated liver cirrhosis. After a 12 week UDCA treatment (600 mg/day), total serum bile acid concentration increased two-fold in patients with compensated liver cirrhosis and increased slightly in patients with chronic active hepatitis. The percentage of sulfated bile acids significantly increased in patients with both compensated liver cirrhosis and chronic active hepatitis. UDCA made up 63% of the total serum bile acids in compensated liver cirrhosis and 61% in chronic active hepatitis after UDCA treatment. Of the serum bile acids after UDCA treatment, 35.2 and 53.9% of UDCA was sulfate conjugated in compensated liver cirrhosis and chronic active hepatitis, respectively. Urinary excretion of total bile acid and UDCA after UDCA treatment in compensated liver cirrhosis were higher than in chronic active hepatitis. UDCA made up 68% of the total urinary bile acids in compensated liver cirrhosis and 64% in chronic active hepatitis after UDCA treatment. Of the urinary bile acids after UDCA treatment, 51.8 and 54.8% of UDCA was sulfate conjugated in compensated liver cirrhosis and chronic active hepatitis, respectively. UDCA treatment for compensated liver cirrhosis was less effective than for chronic active hepatitis. We found that sulfate conjugation is one of the major metabolic pathways for UDCA after UDCA treatment in chronic liver diseases. 相似文献
4.
Role of portal and splenic vein shunts and impaired hepatic extraction in the elevated serum bile acids in liver cirrhosis 总被引:3,自引:0,他引:3
To study the mechanism for the elevation of serum bile acids in liver cirrhosis, bile acid concentrations were measured in the portal, superior mesenteric, and splenic veins, using percutaneous transhepatic catheterization, and compared with those of peripheral veins in 41 patients with mild to moderately advanced cirrhosis. The demonstrated gradient of bile acid concentration was superior mesenteric vein greater than portal vein greater than peripheral vein nearly equal to splenic vein, suggesting that the superior mesenteric vein is the main route of transport for the intestinally absorbed bile acids. Bile acid concentrations in peripheral vein were correlated with the measured portal and splenic vein shunt indexes. The ursodeoxycholic acid oral tolerance test carried out in 10 patients during portal vein catheterization demonstrated that hepatic extraction of this bile acid was correlated with indocyanine green clearance and that it was inversely correlated with portal vein shunt index. These findings are consistent with the view that distorted hepatic blood flow has a significant role in elevating serum bile acid, at least in patients with moderately advanced liver cirrhosis. 相似文献
5.
The effect on bile acid clearance of portacaval end-to-side shunt, with and without arterialization of the hepatic portal venous bed, was studied in dogs. Portacaval shunt reduced liver blood flow by 75%, and peripheral serum bile acid concentration rose from 3 to 239 muM. Arterialization maintained total liver blood flow within physiological range and serum bile acid concentration was only 19 muM. Since hepatic bile acid extraction was similar in both groups, bile acid clearance was determined largely by total liver blood flow. The results of this study indicate that hepatic clearance of substances originating from portal blood is impaired in portacaval shunt and can be restored by increasing the arterial blood supply to the liver. 相似文献
6.
《International Hepatology Communications》1997,6(2):85-91
The effects of ursodeoxycholic acid (UDCA) on the liver function test values were investigated in patients with chronic hepatitis (CH) and liver cirrhosis (LC) in whom treatment with glycyrrhizin (SNMC) for more than 6 months had failed to improve serum transaminase levels. Twenty-six patients treated with Stronger neo minophagen C (SNMC), 60 ml, i.v., three times/week) for more than 6 months were given UDCA (Urso, 600 mg/day) in addition (SNMC + UDCA group) and 22 patients were given UDCA (Urso, 600 mg/day) alone (UDCA group). The mean AST, ALT, γ-GTP and total bile acid (TBA) values during the 3 months before UDCA treatment and the 3 months after the start of UDCA treatment were compared in each case. The results showed that AST, ALT and γ-GTP were improved by 28, 34 and 46%, respectively in the 24 patients with CH, type C in the SNMC + UDCA group, and 27, 30 and 39%, respectively in the 14 patients with CH, type C in the UDCA group. UDCA was also effective in improving AST and ALT in the patients in the SNMC + UDCA group who were resistant to interferon therapy. The percentages of improvement in AST, ALT and γ-GTP in the 10 LC patients were lower than in the CH patients in both SNMC + UDCA and UDCA group. In conclusion, UDCA is useful in decreasing the serum transaminase levels of patients with CH, even when they are being treated with SNMC. 相似文献
7.
To determine whether hepatic artery blood flow is essential in maintaining the function and structure of bile ductules/ducts, the acute effects of hepatic artery ligation on bile secretion and hepatic ultrastructure were examined in anesthetized, bile duct-cannulated guinea pigs. Sixty minutes after hepatic artery ligation, spontaneous bile flow (5.08 +/- 0.4 microliter per min per gm liver) was virtually the same as that before hepatic artery ligation (5.31 +/- 0.3 microliter per min per gm), as were the choleretic effects of 10 CU per kg per 30 min secretin (7.14 +/- 0.9 vs. 7.21 +/- 0.9 microliter per min per gm), 300 micrograms per kg per 30 min glucagon (6.72 +/- 0.9 vs. 6.59 +/- 0.8 microliter per min per gm) and 60 mumoles per kg per 30 min glycochenodeoxycholate (6.43 +/- 0.6 vs. 6.45 +/- 0.6 microliter per min per gm). The failure of hepatic artery ligation to affect bile secretory function could not be attributed to the existence of collateral arterial blood flow to the liver. First of all, hepatic artery ligation resulted in diminishing significantly hepatic venous, but not portal, oxygen content. More importantly, in isolated guinea pig livers, perfused through the portal vein alone, secretin, glucagon and glycochenodeoxycholate produced changes in bile flow and composition similar to those seen in vivo. Electron microscopy showed no major ultrastructural changes of hepatic parenchyma and biliary epithelium 2 hr after hepatic artery ligation, or 2 hr after perfusing the liver through the portal vein alone save for some portal edema in the latter instance.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
8.
9.
Role of active oxygen species and lipid peroxidation in liver injury induced by ischemia-reperfusion 总被引:1,自引:0,他引:1
T Yoshikawa H Oyamada H Ichikawa Y Naito S Ueda K Tainaka T Takemura T Tanigawa S Sugino M Kondo 《Nihon Shokakibyo Gakkai zasshi》1990,87(2):199-205
The role of superoxide and lipid peroxidation in liver injury induced by ischemia-reperfusion was investigated in rats. Ischemic condition of the liver was created by applying small clamps to the right branch of portal vein and the right hepatic artery for 15 min. Clamping of hepatic artery and portal vein could decrease the hepatic blood flow to about 30% of that measured before the clamping. Levels of serum GPT and thiobarbituric acid (TBA) reactive substances in the liver tissue were significantly increased 30 min after the reperfusion following 15 min of ischemia. The increase in serum GPT and TBA reactants in the liver tissue was significantly inhibited by the treatment with superoxide dismutase combined with catalase. The treatment with allopurinol significantly inhibited the elevation of serum GPT levels and showed a tendency to inhibit the increase in TBA reactants in liver tissue. These results suggest that active oxygen species and lipid peroxidation may play an important role in the pathogenesis of ischemia-reperfusion injury in the liver, and hypoxanthine-xanthine oxidase system may be one of the main sources of active oxygen species. 相似文献
10.
TOSHIAKI NAKASHIMA YOSHIHIRO NAKAGAWA ATSUSHI SANO YOSHIKUNI SAKAMOTO TOSHIHIDE SHIMA TOSHIKAZU NAKAJIMA YOSHIFUMI SETO TADAO OKUNO KEI KASHIMA 《Journal of gastroenterology and hepatology》1990,5(2):121-125
Abstract In rats with an interrupted enterohepatic circulation of bile acids, levels of serum taurine-conjugated bile acids were increased significantly 3 h after intravenous administration of taurine. Similarly, serum taurine- or glycine-conjugated ursodeoxycholic acid (UDCA) was increased significantly 2 h after UDCA administration. These findings suggested that the administered taurine or UDCA was taken up into hepatocytes and utilized to form conjugated bile acids, which were thereafter regurgitated into the systemic circulation from the liver. The proportion of regurgitated taurine-conjugated bile acids relative to total serum bile acids measured by taurine loading (30%) almost coincided with that of regurgitated taurine- or glycine-conjugated UDCA relative to total serum bile acids measured by UDCA loading (31.6%). Thus, the present study showed conclusively that at least 30% of serum bile acids are derived from newly conjugated bile acids that are regurgitated from the liver in rats with bile fistula. 相似文献
11.
The concentration of total bile acids in the serum was measured in thirty-three patients before and after esophageal transection for esophageal varices, in an attempt to determine the influence of this surgery on the naturally developed portasystemic shunt and also the liver function relating to the bile acid metabolism. The levels of fasting total bile acids in the serum were decreased on the first postoperative day, but gradually increased up to the preoperative levels by the twenty-first postoperative day. The maximum value of total bile acids, as determined in ursodeoxycholic acid tolerance tests, was decreased after the esophageal transection (p less than 0.01). The average of the maximum total bile acids in UDCA tolerance tests was 79.5 microM in the preoperative stage, and 61.0 microM in the postoperative stage. This finding suggested that esophageal transection abolished the portasystemic collaterals and contributed to an increase in efficient hepatic blood flow, which led to the improvement of liver function. 相似文献
12.
目的评价消黄方治疗慢性乙型肝炎(湿热瘀阻型)轻度黄疸的临床疗效。方法慢性乙型肝炎(湿热瘀阻型)轻度黄疸患者68例,随机数字表简单随机分组,消黄方组38例,熊去氧胆酸(UDCA)组30例。两组基础治疗方案为拉米夫定100 mg,每天1次,口服(或替比夫定600 mg,每天1次,口服);复方甘草酸苷60 ml,每天1次,静滴;还原型谷胱甘肽1.2 g,每天1次,静滴。UDCA组加UDCA 250 mg,每天3次,口服;消黄方组加消黄方100 ml,每天2次,口服。疗程4周。治疗前后观察两组中医证候、肝功能、肝纤维化指标及APRI指数变化。结果 (1)与UDCA组相比,消黄方治疗慢性乙型肝炎(湿热瘀阻型)轻度黄疸的有效率略高(89.5%vs76.7%),但差异无统计学意义(P>0.05)。(2)与治疗前相比,消黄方在改善性乙型肝炎轻度黄疸患者肝功能及血脂水平(ALT、AST、GGT、LDH、TBil、DBil、pre-A、TBA、TC、apo-A、HDL等)方面差异有统计学意义(P<0.01或P<0.05)。与UDCA组相比,消黄方可有效降低TBil、DBil、TBA、TC水平,提高apo-A含量(P<0.05)。(3)与治疗前相比,两组患者透明质酸(HA)均降低,差异具有统计学意义(P<0.05),消黄方对C-IV也显示出较好的改善作用(P<0.05)。(4)与治疗前相比,消黄方组可显著降低患者APRI指数(P<0.01),且与UDCA组比较差异有统计学意义(P<0.05)。结论消黄方可缓解慢性乙型肝炎(湿热瘀阻型)轻度黄疸患者临床症状,改善肝功能、肝纤维化指标,对肝内胆汁淤积性黄疸有较好的临床疗效。 相似文献
13.
Bile acid glycine and taurine conjugates in serum of patients with primary biliary cirrhosis: effect of ursodeoxycholic treatment. 总被引:4,自引:1,他引:3
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We have applied a specific and accurate high pressure liquid chromatographic technique to determine fasting serum glycine and taurine conjugates of individual bile acids in patients with primary biliary cirrhosis before and during ursodeoxycholic acid therapy. The study was carried out in nine patients in whom the diagnosis of primary biliary cirrhosis was established according to accepted criteria. After one year of UDCA therapy liver function tests significantly improved. Total serum bile acid concentration did not change significantly (29.2 (31.5) v 28.3 (26.4) microM). Total UDCA (1.7 (2.2) v 13.3 (14.5) microM) and glyco UDCA (0.8 (1.6) v 10.9 (11.4 microM) but not tauro UDCA levels increased significantly (p less than 0.01); UDCA (7.7 (12.6) v 40.2 (12.7)%) became the major species of the circulating bile acids. Primary bile acids (23 (28.3) v 11.2 (10.5) and their glycoconjugates fell significantly (p less than 0.01). There were no significant changes in the concentrations of conjugates of the secondary bile acids (4.5 (3.8) v 3.9 (3.0]. Our study shows that oral administration of UDCA to patients with primary biliary cirrhosis induced marked changes in the circulating pool of endogenous bile acids together with improvement in liver function test values. The data also suggest that the beneficial effect of longterm administration of UDCA in these patients might be mediated through changes in the circulating primary bile acids and UDCA rather than through changes in the circulating secondary bile acids, deoxycholate and lithocholate. 相似文献
14.
Ermenegildo E. Frezza Giorgio E. Gerunda Mario Plebani Alessandra Galligioni Alda Giacomini Daniele Neri Alvise Maffei Faccioli Dr. Claudio Tiribelli 《Digestive diseases and sciences》1993,38(7):1291-1296
The origin, mechanism, and significance of the bile duct proliferation (BDP) associated with cholestasis remain unexplained. This study examined the effect of oral administration of ursodeoxycholic acid (UDCA) on both BDP and cholestasis in the rat. After bile duct ligation, male Sprague-Dawley rats were treated for 30 days with either UDCA (5 mg/day) (group A) or saline solution (group B). Animals were sacrificed at day 30. The serum activity of aminotransferase (ALT, AST), alkaline phosphatase, and -glutamyltransferase (GGT) was significantly lower (P<0.01) in the UDCA-treated rats. Total serum bilirubin and total serum bile acids were lower (P<0.001) in group A. Moreover, the control of BA in bile was reduced also (P<0.02). Conversely, serum cholesterol levels were not different between the two groups. Histological examination showed that the number of ductular cells in the portal areas was significantly (P<0.001) reduced in UDCA-treated as compared to saline-treated rats. The replication activity, assessed as the number of bromodeoxyuridine-positive cells, was also significantly lower in treated animals (33±11 vs 64±22 per 1000 cells;P<0.001). Lobular bile ductules were three times larger in group B, and extrahepatic duct measurements confirmed this increase in size of the larger biliary ducts (P<0.001). These findings demonstrate that UDCA reduces BDP in response to BD ligation. Although the mechanism(s) of this effect is still hypothetical, UDCA may reduce the level of irritating bile salts such as chenodeoxycholic acid and lithocolate and increase periductular bile acid recirculation. These data support the beneficial effect of UDCA treatment in chronic cholestatic disease. 相似文献
15.
Differences in the efficacy of ursodeoxycholic acid and bile acid metabolism between viral liver diseases and primary biliary cirrhosis 总被引:4,自引:0,他引:4
Nakashima T Yoh T Sumida Y Kakisaka Y Mitsuyoshi H 《Journal of gastroenterology and hepatology》2001,16(5):541-547
AIM AND METHODS: The effects of ursodeoxycholic acid (UDCA, 600 mg/day) on liver function test values, and serum and urinary bile acids levels in hepatitis C virus-related chronic hepatitis (CH, n = 39) and liver cirrhosis (LC, n = 25), and in primary biliary cirrhosis (PBC, n = 25) were compared. RESULTS: The percentages of improvement in alanine transaminase (ALT) and gamma-glutamyl transpeptidase (gamma-GTP) in CH were almost the same in LC. The rates of improvement in ALT in PBC were negatively correlated with histological stages in the liver. Total serum bile acid levels in LC rose to the same extent as in CH, but the increases in PBC were significantly smaller at stages 3-4 than stages 1-2. The urinary levels of hydroxylated metabolites of UDCA only slightly increased in LC, but they increased significantly at PBC stages 3-4. CONCLUSIONS: The efficacy of UDCA was preserved in LC, but diminished at PBC stages 3-4. The poor enrichment of UDCA in the bile acid pool and extensive biotransformation of UDCA may cause the limited efficacy of UDCA in the cirrhotic stage of PBC. 相似文献
16.
Effect of bile acids on ischemia-reperfusion liver injury 总被引:1,自引:0,他引:1
O. Chazouillres F. Ballet C. Legendre M. T. Bonnefis C. Rey Y. Chrtien R. Poupon 《Journal of hepatology》1991,13(3):318-322
We investigated whether stimulation of bile flow by taurocholic acid (TCA), ursodeoxycholic acid (UDCA) or its taurine conjugate (TUDCA) could protect the liver from ischemia-reperfusion injury. The isolated perfused rat liver model was used. In livers perfused without bile acids (n = 8), 60 min of ischemia induced a significant reduction in bile flow and in portal flow, together with a marked increase in LDH, AST and uric acid release in the perfusate. These alterations were maximal at the beginning of reperfusion. In livers perfused with TCA (n = 6), UDCA (n = 7) or TUDCA (n = 6), bile flow was significantly increased as compared to controls during the pre-ischemic phase, as well as during the reperfusion phase. However, no significant improvement was observed in any of the biochemical, hemodynamic or histologic parameters studied. The results show that stimulation of bile flow either by TCA, UDCA or TUDCA does not reduce ischemia-reperfusion liver injury. Furthermore, the results do not provide evidence for a cytoprotective effect of UDCA or TUDCA in this model of liver injury. 相似文献
17.
M Ando 《Nihon Shokakibyo Gakkai zasshi》1992,89(10):2586-2593
Using the ANIT induced model of cholestasis in rats, the therapeutic effects of UDCA to the intrahepatic cholestasis were evaluated by changes of serum chemistry and liver histology. ANIT was administered once at a dosage of 40 mg/kg b.w. per os and UDCA was given ad libitum for 7 days by a drinking water containing UDCA at 0.5 and 5.0% solution. In the period of bile duct epithelial degeneration and necrosis, effects of UDCA for jaundice was not detected, but hepato-cellular disturbances were appeared histologically. Moreover, the elevation of serum levels of chenodeoxy-cholic acid, deoxycholic acid and lithocholic acid was accompanied. On the other hand, in the recovery stage of the bile duct epithelium, serum bilirubin was decreased significantly in the UDCA group which seemed to be related with the potent choleretic effect of UDCA. These results may indicate that UDCA is effective for the intrahepatic cholestasis in the case with no bile duct epithelial damage but in the presence of it hepato-cellular injury is introduced by the accumulated toxic bile acids in the blood. 相似文献
18.
O. Riggio M. Merli C. Cangiano R. Capocaccia A. Cascino A. Lala F. Leonetti M. Mauceri M. Pepe F. Rossi Fanelli M. Savioli G. Tamburrano L. Capocaccia 《Metabolism: clinical and experimental》1982,31(6):627-634
Glucose intolerance and hyperinsulinemia frequently occur in patients with chronic liver failure. To investigate the importance of glucose counterregulating factors, an oral glucose tolerance test was performed on 18 patients with compensated liver cirrhosis, matched for liver function tests and degree of portal hypertension, and 10 healthy controls. Blood glucose, immunoreactive insulin, C-peptide, immunoreactive glucagon, glucagon like immunoreactivity, growth hormone, cortisol and free fatty acids were determined in both groups at 30 min intervals for 240 min. Despite the similarity in the severity of liver damage five cirrhotic patients showed normal glucose tolerance, eight impaired glucose tolerance and five overt diabetes. Immunoreactive insulin was significantly higher in cirrhotic patients than in controls both before and during the oral glucose tolerance test. As basal C-peptide values were significantly higher and C-peptide/immunoreactive insulin ratio was significantly lower in cirrhotic patients than in the control subjects, both hyperproduction and hypodegradation seem to be responsible for the high insulin levels. Immunoreactive glucagon and cortisol showed no statistical differences between cirrhotic patients and control subjects whereas high basal growth hormone and free fatty acids values were observed in the cirrhotic group. Basal values and maximum increase or decrease of all the factors examined were tested by a correlation analysis with the blood glucose at 120 min and evaluated by a stepwise linear regression analysis. Only basal blood glucose, basal free fatty acids and immunoreactive insulin increment correlated significantly with blood glucose at 120 min. By the stepwise procedure these factors were found to account for 86% of the variance of the glucose level at 120 min. In chronic liver disease we failed to establish a pathogenetic role of hormones involved in the glucose counterregulating system. Free fatty acids may play an important role in glucose intolerance in chronic liver failure. 相似文献
19.
BACKGROUND/AIMS: Ursodeoxycholic acid (UDCA) decreases biliary secretion of cholesterol and is therefore used for the dissolution of cholesterol gallstones. It remains unclear whether these changes in biliary cholesterol excretion are associated with changes in cholesterol synthesis and bile acid synthesis. We therefore studied the activities of rate-limiting enzymes of cholesterol synthesis and bile acid synthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase and cholesterol 7alpha-hydroxylase, respectively, in normal subjects during UDCA feeding. METHODS: UDCA was given to 8 healthy volunteers (5 men, 3 women; age 24-44 years) in a single dose of 10-15 mg/kg body weight for 40 days. Before and during (days 3, 5, 10, 20, 30 and 40) UDCA treatment, urinary excretion of mevalonic acid and serum concentrations of 7alpha-hydroxy-4-cholesten-3-one (7alpha-HCO) were determined as markers of cholesterol and bile acid synthesis, respectively. The Wilcoxon signed rank test and Spearman's rank correlation coefficient were used for statistical analysis. RESULTS: Cholesterol synthesis and serum lipid concentrations remained unchanged during UDCA treatment for 40 days. However, synthesis of bile acids increased during long-term treatment with UDCA as reflected by an increase in 7alpha-HCO serum concentrations from 39.7 +/- 21.3 ng/ml (median 32.8 ng/ml) before treatment to 64.0 +/- 30.4 ng/ml (median 77.5 ng/ml) at days 30-40 of UDCA treatment (p < 0.05). CONCLUSIONS: UDCA treatment does not affect cholesterol synthesis in the liver, but does increase bile acid synthesis after prolonged treatment. This may represent a compensatory change following decreased absorption of endogenous bile acids as observed with UDCA therapy. 相似文献
20.
Relationship between biliary and serum bile acids and response to ursodeoxycholic acid in patients with primary biliary cirrhosis 总被引:3,自引:0,他引:3
K.D. Lindor M.D. M.A. Lacerda M.D. R.A. Jorgensen R.N. C.K. DeSotel R.N. A.K. Batta Ph.D. G. Salen M.D. E.R. Dickson M.D. S.S. Rossi Ph.D. A.F. Hofmann M.D. 《The American journal of gastroenterology》1998,93(9):1498-1504
Objective: Ursodeoxycholic acid (UDCA) improves liver biochemistries and enriches the bile with UDCA in patients with primary biliary cirrhosis. The aim of this study was to determine whether the degree of enrichment of bile correlated with that of serum and whether either of these measures correlated with improvement in measures of liver disease.
Methods: In a randomized study, biliary and serum bile acid analyses were performed at entry and after 2 yr of UDCA or placebo.
Results: The percentage of ursodeoxycholic acid in bile increased by 42% in the UDCA group ( n = 61 ) compared with 8% in the placebo group ( n = 57 ) ( p < 0.0001 ). Measurement of serum bile acids in 32 patients (18 ursodeoxycholic acid, 14 placebo) indicated that at 2 yr, ursodeoxycholic acid comprised 65% of serum bile acids in the treated group and 7% in the placebo group. Agreement between bile and serum was fair ( r = 0.75 , p ≤ 0.00002 ) because in some patients, plasma but not biliary bile acids were enriched with UDCA. Changes in biliary ursodeoxycholic acid correlated significantly but weakly with the changes in serum alkaline phosphatase, AST, bilirubin, and in Mayo risk score. Correlations between changes in serum bile acid composition and biochemical measures of disease activity were even weaker.
Conclusion: The measurement of biliary bile acids is superior to that of serum bile acids for assessing the compliance and changes in the circulating bile acids in patients receiving ursodeoxycholic acid for the treatment of primary biliary cirrhosis. Furthermore, measures to further increase the proportion of ursodeoxycholic acid in circulating bile acids should be explored. 相似文献
Methods: In a randomized study, biliary and serum bile acid analyses were performed at entry and after 2 yr of UDCA or placebo.
Results: The percentage of ursodeoxycholic acid in bile increased by 42% in the UDCA group ( n = 61 ) compared with 8% in the placebo group ( n = 57 ) ( p < 0.0001 ). Measurement of serum bile acids in 32 patients (18 ursodeoxycholic acid, 14 placebo) indicated that at 2 yr, ursodeoxycholic acid comprised 65% of serum bile acids in the treated group and 7% in the placebo group. Agreement between bile and serum was fair ( r = 0.75 , p ≤ 0.00002 ) because in some patients, plasma but not biliary bile acids were enriched with UDCA. Changes in biliary ursodeoxycholic acid correlated significantly but weakly with the changes in serum alkaline phosphatase, AST, bilirubin, and in Mayo risk score. Correlations between changes in serum bile acid composition and biochemical measures of disease activity were even weaker.
Conclusion: The measurement of biliary bile acids is superior to that of serum bile acids for assessing the compliance and changes in the circulating bile acids in patients receiving ursodeoxycholic acid for the treatment of primary biliary cirrhosis. Furthermore, measures to further increase the proportion of ursodeoxycholic acid in circulating bile acids should be explored. 相似文献