Total serum bile acids in renal transplanted patients receiving cyclosporine A.

BACKGROUND: A direct relationship between serum bile acids (SBA) and hepatic and hepatobiliary dysfunction has been demonstrated. However, there is little evidence that SBA are related to renal insufficiency. In a previous study, we showed that hemodialysis patients with advanced chronic renal failure (ACRF) have an increase of SBA in predialysis and a decrease in postdialysis. Consequently, it was assumed that the restoration of renal function in transplanted patients might decrease SBA levels. AIM OF THIS STUDY: Transplanted patients receiving cyclosporine A (CyA) were studied by monitoring CyA and SBA levels to determine if a probable relationship exists between renal function, CyA treatment and SBA levels. SUBJECTS. MATERIALS AND METHODS: SBA levels were determined in 15 recently transplanted patients receiving CyA for 18 months and longer. In addition, 22 renal patients transplanted not less than 6 years ago were also included in the study and were characterized as the stable group. Five patients from this group received mycophenolate or azathioprine instead of CyA as immunosuppressant. In addition to SBA and CyA, creatinine, cholesterol, y-GT, viral markers and triglycerides were also determined in all patients. RESULTS: A significant and constant increase in SBA levels was observed in the recently transplanted group. However, after 18 months, SBA levels gradually decreased to those of patients considered stable under CyA treatment. In both recently transplanted and stable patients who received CyA, SBA values remained higher than normal, but stable patients under mycophenolate or azathioprine treatment showed no such increase. CONCLUSIONS: In recently transplanted patients, in patients studied for 18 months post transplant and in stable patients receiving CyA, the increase of SBA levels might be related to CyA treatment. This effect might be attributed to its cholestatic effect and also to a modification in uptake, metabolism, synthesis and excretion of SBA in the hepatocyte. These conclusions are supported by the results obtained in stable transplanted patients without CyA treatment showing normal SBA levels.

Serum bile acids and pruritus in hemodialysis patients.

BACKGROUND: Chronic renal failure (CRF) patients usually suffer from pruritus. The pathophysiology of pruritus is still incompletely understood. SUBJECTS, MATERIALS AND METHODS: In this paper we determined serum total bile acids (STBA) in hemodialysis patients with advanced CRF (ACRF) in order to obtain STBA concentration in predialysis, to assess their probable relation among patients with pruritus and in postdialysis using a polysulfone membrane for dialysis. STBA were determined in 49 ACRF patients with chronic hemodialysis and values were compared to 20 control subjects. Hemodialysis patients were divided in two groups: with and without pruritus. In all these patients, month of renal replacement therapy, diabetic patients, dose of dialysis (Kt/V), viral markers, serum creatinine, serum glucose, aspartate and alanine aminotransferase, alkaline phosphatase, hematocrits and albumin were determined. The intensity of itching among pruritic patients was measured by a score system: mild (M), moderate (MO) and severe (S). RESULTS: No significant differences were found in patients with and without pruritus in months of renal replacement therapy, duration of dialysis or dose of dialysis (Kt/V). STBA were determined in all ACRF patients in predialysis and they showed significant differences compared to controls (p < 0.05), however, no differences were observed in the results obtained when control subjects were compared to ACRF patients without pruritus. Also in predialysis, pruritic patients showed significant differences in STBA compared to patients without pruritus (p < 0.001). STBA concentration showed a significant decrease in postdialysis using a polysulfone membrane in ACRF patients with and without pruritus. Finally, correlation with STBA and itch score of pruritus was significant (p < 0.02). CONCLUSION: Hemodialysis patients with ACRF and pruritus showed an increase of STBA in predialysis and a decrease in postdialysis.

Fecal bile acid excretion profile in gallstone patients.

Epidemiological studies have shown a positive association between cholesterol gallstones and colonic cancer. These two diseases may be somehow related with bile acids metabolic alterations. The aim of this study was to evaluate the profiles of fecal bile acid in gallstone patients, in order to estimate the quality and amount of fecal bile acids. A fecal bile acid profile of ten gallstone patients and ten controls was compared using high performance liquid chromatography. Total fecal bile acid excretion was significantly increased in gallstone patients compared with controls (692.7 mg/day (302.5-846.2) vs 165.7 mg/day (138.7-221.3), p < 0.01) as was the excretion of secondary free bile acids 562.9 mg/day (253.3-704.9) vs 99.9 mg/day (88.9-154.2), p < 0.01). Lithocholic and glycodeoxycholic acid percentages have also been found to show differences with controls of 55.4 (47.4-73.9) vs 24.6 (22.1-38.4) (p < 0.01) and 29.4 (3.3-41.7) vs 2.8 (1.0-3.8) (p < 0.03), respectively but deoxycholic acid has not shown differences between the two groups. Moreover, the percentage of ursodeoxycholic acid diminished significantly in gallstone patients (1.5 (1.0-2.8) vs 8.6 (6.0-10.39) (p < 0.001), and the decrease of chenodeoxycholic acid was also significant (20.0 (11.4-23.6) vs 8.9 (3.1-10.9) (p < 0.03) along with a rise in the ratios lithocholic/deoxycholic acids (1.8 (1.4-6.4) vs 0.9 (0.6-1.6) (p < 0.05) and glycine/taurine of deoxycholic acid (7.3 (4.1-46.6) vs 0.2 (0.1-0.5) (p < 0.01). In conclusion, we have observed a significant increase of total and secondary fecal bile acid excretion as well as a rise of LCA and GDCA percentages and a rise in the ratios of LCA/DCA and glycinet/taurine of DCA.

Fecal bile acid excretion profile in gallstone patients.

Epidemiological studies have shown a positive association between cholesterol gallstones and colonic cancer. These two diseases may be somehow related with bile acids metabolic alterations. The aim of this study was to evaluate the profiles of fecal bile acid in gallstone patients, in order to estimate the quality and amount of fecal bile acids. A fecal bile acid profile of ten gallstone patients and ten controls was compared using high performance liquid chromatography. Total fecal bile acid excretion was significantly increased in gallstone patients compared with controls (692.7 mg/day (302.5-846.2) vs 165.7 mg/day (138.7-221.3), p < 0.01) as was the excretion of secondary free bile acids 562.9 mg/day (253.3-704.9) vs 99.9 mg/day (88.9-154.2), p < 0.01). Lithocholic and glycodeoxycholic acid percentages have also been found to show differences with controls of 55.4 (47.4-73.9) vs 24.6 (22.1-38.4) (p < 0.01) and 29.4 (3.3-41.7) vs 2.8 (1.0-3.8) (p < 0.03), respectively but deoxycholic acid has not shown differences between the two groups. Moreover, the percentage of ursodeoxycholic acid diminished significantly in gallstone patients (1.5 (1.0-2.8) vs 8.6 (6.0-10.39) (p < 0.001), and the decrease of chenodeoxycholic acid was also significant (20.0 (11.4-23.6) vs 8.9 (3.1-10.9) (p < 0.03) along with a rise in the ratios lithocholic/deoxycholic acids (1.8 (1.4-6.4) vs 0.9 (0.6-1.6) (p < 0.05) and glycine/taurine of deoxycholic acid (7.3 (4.1-46.6) vs 0.2 (0.1-0.5) (p < 0.01). In conclusion, we have observed a significant increase of total and secondary fecal bile acid excretion as well as a rise of LCA and GDCA percentages and a rise in the ratios of LCA/DCA and glycinet/taurine of DCA.

[Acquired sideroblastic anemia and cholestasis in a hyperthyroid patient treated with methimazole and atenolol]. / Anemia sideroblástica adquirida y colestasis en un paciente hipertiroideo tratado con metimazol y atenolol.

The authors describe a 62 year-old white male who was diagnosed as autoimmune hyperthyroidism and treated with methimazole and atenolol. Ten days later he showed itching, jaundice and choluria. All drugs were discontinued. The patient was given radioactive iodine. Two months later direct serum bilirubin levels reached 35 mg%. Endoscopic retrograde cholangiogram evidenced normal extrahepatic biliary ducts. The percutaneous liver biopsy showed marked cholestasis specially in the centrolobular zone with a slight infiltrate of mononuclear cells in the portal areas. Together with the liver disease the patient presented an anemic syndrome. Bone marrow aspiration showed rich cellularity, Perls staining showed 70% sideroblasts, with 10% ringed sideroblasts and increased extracorpuscular iron. The patient's evolution was satisfactory. Twenty months after the beginning of the disease clinical and biochemical tests were normal. A new bone marrow aspiration rendered normal. Hepatic cholestasis suffered by our patient was probably due to an adverse reaction of methimazole. Physiopathology of reversible sideroblastic anemia is discussed.

Anemia sideroblástica adquirida y colestasis en un paciente hipertiroideo tratado con metimazol y atenolol. / [Acquired sideroblastic anemia and cholestasis in a hyperthyroid patient treated with methimazole and atenolol]

The authors describe a 62 year-old white male who was diagnosed as autoimmune hyperthyroidism and treated with methimazole and atenolol. Ten days later he showed itching, jaundice and choluria. All drugs were discontinued. The patient was given radioactive iodine. Two months later direct serum bilirubin levels reached 35 mg

. Endoscopic retrograde cholangiogram evidenced normal extrahepatic biliary ducts. The percutaneous liver biopsy showed marked cholestasis specially in the centrolobular zone with a slight infiltrate of mononuclear cells in the portal areas. Together with the liver disease the patient presented an anemic syndrome. Bone marrow aspiration showed rich cellularity, Perls staining showed 70

sideroblasts, with 10

ringed sideroblasts and increased extracorpuscular iron. The patients evolution was satisfactory. Twenty months after the beginning of the disease clinical and biochemical tests were normal. A new bone marrow aspiration rendered normal. Hepatic cholestasis suffered by our patient was probably due to an adverse reaction of methimazole. Physiopathology of reversible sideroblastic anemia is discussed.

Morphologic changes in livers of hamsters treated with high doses of ursodeoxycholic acid: correlation with bile acids in bile.

The effects of high doses of ursodeoxycholic acid on bile acid composition and the liver morphology was examined in 60 male Syrian golden hamsters. The animals were allocated to five groups: I, control; II and IV received 0.5 g and 1 g of ursodeoxycholic acid per 100 g of standard diet respectively over 30 days and III and V received 0.5 g and 1 g of ursodeoxycholic acid per 100 g of standard diet respectively over 60 days. Bile acids were determined by high performance liquid chromatography. In all treated groups there was a significant increase in chenodeoxycholic and lithocholic acid in the bile. The mean glyco/tauro ratio was significantly higher than in the control group, reaching values > 1 for individual bile acids, except for lithocholic acid values which remained < 1. Under light microscopy, the livers of the hamsters showed damage which was dose/time related, namely portal inflammatory infiltrate, bile duct proliferation, cholestasis, fat infiltration and necrosis. Electron microscopy revealed pronounced changes starting with microvilli edema and extending to canalicular membrane destruction and necrosis. The changes observed in the relation glyco/tauro lithocholic acids, may be due to defence mechanisms to avoid hepatotoxicity. The hepatotoxicity resulting from ursodeoxycholic acid administration is presumed to be due primarily to lithocholic acid or some lithocholic acid metabolite.

Effect of ursodeoxycholic acid administration on bile acid composition in hamster bile.

The modification in the composition of bile acids in hamster by the administration of high dose of ursodeoxycholic acid (UDCA) was investigated. Male Golden Syrian hamsters were divided into five groups: a control group, two groups that received 0.5 g of UDCA per 100 g of standard diet during 30 and 60 days and another two groups that received 1 g of UDCA per 100 g of standard diet during 30 and 60 days. After ether anaesthesia the gallbladder was removed and bile was immediately aspirated. Bile acids were determined by high performance liquid chromatography (HPLC). Taurolithocholic (TLCA) and glycolithocholic acids (GLCA) increased significantly in all treated groups. The glyco/tauro ratio of 0.69 in controls became more than 1 in treated animals except in the case of lithocholic acid (LCA) conjugates which remained less than 1. UDCA derivatives increased proportionally to the administered dose and the cholic/cheno ratio diminished significantly. A moderate increase of 3- and 7-keto derivatives of chenodeoxycholic acid (CDCA) was observed in all treated groups but the above mentioned increment was especially evident in 3-keto derivatives. A high percentage of UDCA administered in the hamster was likely transformed to CDCA and the glyco conjugates of the bile acids were the predominant species except for the LCA derivatives.