Screening of newborn infants for cholestatic hepatobiliary disease with tandem mass spectrometry.
(9/1230)
OBJECTIVE: To assess the feasibility of screening for cholestatic hepatobiliary disease and extrahepatic biliary atresia by using tandem mass spectrometry to measure conjugated bile acids in dried blood spots obtained from newborn infants at 7-10 days of age for the Guthrie test. SETTING: Three tertiary referral clinics and regional neonatal screening laboratories. DESIGN: Unused blood spots from the Guthrie test were retrieved for infants presenting with cholestatic hepatobiliary disease and from the two cards stored on either side of each card from an index child. Concentrations of conjugated bile acids measured by tandem mass spectrometry in the two groups were compared. MAIN OUTCOME MEASURES: Concentrations of glycodihydroxycholanoates, glycotrihydroxycholanoates, taurodihydroxycholanoates, and taurotrihydroxycholanoates. Receiver operator curves were plotted to determine which parameter (or combination of parameters) would best predict the cases of cholestatic hepatobiliary disease and extrahepatic biliary atresia. The sensitivity and specificity at a selection of cut off values for each bile acid species and for total bile acid concentrations for the detection of the two conditions were calculated. RESULTS: 218 children with cholestatic hepatobiliary disease were eligible for inclusion in the study. Two children without a final diagnosis and five who presented at <14 days of age were excluded. Usable blood spots were obtained from 177 index children and 708 comparison children. Mean concentrations of all four bile acid species were significantly raised in children with cholestatic hepatobiliary disease and extrahepatic biliary atresia compared with the unaffected children (P<0.0001). Of 177 children with cholestatic hepatobiliary disease, 104 (59%) had a total bile acid concentration >33 micromol/l (97.5th centile value for comparison group). Of the 61 with extrahepatic biliary atresia, 47 (77%) had total bile acid concentrations >33 micromol/l. Taurotrihydroxycholanoate and total bile acid concentrations were the best predictors of both conditions. For all cholestatic hepatobiliary disease, a cut off level of total bile acid concentration of 30 micromol/l gave a sensitivity of 62% and a specificity of 96%, while the corresponding values for extrahepatic biliary atresia were 79% and 96%. CONCLUSION: Most children who present with extrahepatic biliary atresia and other forms of cholestatic hepatobiliary disease have significantly raised concentrations of conjugated bile acids as measured by tandem mass spectrometry at the time when samples are taken for the Guthrie test. Unfortunately the separation between the concentrations in these infants and those in the general population is not sufficient to make mass screening for cholestatic hepatobiliary disease a feasible option with this method alone. (+info)
Effect of ursodeoxycholic acid administration in patients with acute viral hepatitis: a pilot study.
(10/1230)
BACKGROUND: Ursodeoxycholic acid (UDCA) is able to improve biochemical markers of cholestasis, with a parallel decrease in transaminases, in various cholestatic liver diseases. AIM: To evaluate the effects of UDCA administration on acute viral hepatitis-related cholestasis and the course of acute viral hepatitis. METHODS: Seventy-nine consecutive patients with acute viral hepatitis (HBV: 43, HCV: 11, HAV: 15, HEV: 3, Non A-E: 7) were randomized to receive either UDCA for 3 weeks or no treatment. Liver biochemistry and serum bile acid determinations were run at weekly intervals. RESULTS: No significant differences were observed in mean percentage decreases in transaminases between treated and untreated patients. By contrast, cholestatic indexes decreased significantly more quickly in patients treated with UDCA than in controls, and this effect was more evident in patients with increasing alanine transaminase levels at admission. After a peak at the end of the first week of therapy, serum levels of conjugated ursodeoxycholic acid (CUDCA) showed a gradual decrease. Conjugated cholic acid (CCA) and chenodeoxycholic acid (CCDCA) showed a progressive decrease with the resolution of viral hepatitis, but no influence of UDCA administration was observed. CONCLUSIONS: Our study demonstrates that UDCA significantly improves cholestatic indices in patients with acute viral hepatitis, but this effect does not seem to affect the course of the illness. (+info)
Recurrent cholestasis following ovarian hyperstimulation syndrome: case report.
(11/1230)
This is a case report illustrating a patient who developed recurrent cholestasis during a twin pregnancy following in-vitro fertilization (IVF) treatment. On the first occasion cholestasis developed unusually in the first trimester, and on the second occasion, it presented in the way that obstetric cholestasis (OC) is commonly seen in the third trimester. (+info)
Retrospective review of cystic fibrosis presenting as infantile liver disease.
(12/1230)
The mode of presentation, clinical course, and outcome of 12 infants with cystic fibrosis and liver disease referred over an 18 year period were investigated retrospectively. Median age at presentation was 6.5 weeks (range, 5-12). Two thirds were boys. Conjugated hyperbilirubinaemia was the presenting symptom in 11 patients, and hypoalbuminaemia in one. Jaundice was cleared over a median period of 7.36 months. Eight patients had bile duct proliferation on liver biopsy and one required cholangiography to exclude biliary atresia. Classic histological features of cystic fibrosis were only present in two children biopsied at 8 and 18 months. Three patients had meconium ileus, including one infant with concomitant alpha(1) antitrypsin deficiency, who required early liver transplantation. All other patients had no signs of significant chronic liver disease during a median follow up of 42 months (range, 10-205). Children with cystic fibrosis and infantile liver disease have a good short and medium term prognosis. (+info)
Preoperative internal biliary drainage is superior to external biliary drainage in liver regeneration and function after hepatectomy in obstructive jaundiced rats.
(13/1230)
OBJECTIVE: To examine the differences in regeneration rates and functions of the liver at the time of and after hepatectomy in obstructive jaundiced rats with preoperative external and internal biliary drainage. SUMMARY BACKGROUND DATA: The significance of biliary drainage before surgery is controversial in patients with obstructive jaundice. METHODS: After biliary obstruction for 7 days, rats were randomly divided into three groups: obstructive jaundice and hepatectomy (OJ-Hx), external biliary drainage and hepatectomy (ED-Hx), and internal biliary drainage and hepatectomy (ID-Hx). The OJ-Hx group underwent hepatectomy without biliary drainage; the other two groups underwent hepatectomy after biliary drainage for 7 days. At the time of hepatectomy, all rats were provided with internal biliary drainage. On days 0, 1, 2, 3, and 7 after hepatectomy, the DNA synthesis rate and the concentrations of adenine nucleotides and malondialdehyde in the liver were determined as markers of the hepatic regeneration rate, energy status, and lipoperoxide concentration, respectively. Portal endotoxin concentrations were measured and serum hyaluronic acid concentrations were determined as an indicator of hepatic endothelial function. RESULTS: The relative liver weight was significantly higher in the ID-Hx group than in the OJ-Hx group on days 1, 3, and 7 after hepatectomy and than in the ED-Hx group on days 1 and 2. The rate of hepatic DNA synthesis was significantly higher in the ID-Hx group than in the OJ-Hx and ED-Hx groups on day 1. The rate was similar in the ED-Hx and ID-Hx groups on day 2 but was significantly higher than in the OJ-Hx group. The hepatic malondialdehyde concentration was significantly higher on day 1 in the ED-Hx group than in the other two groups. It was lowest in the ID-Hx group throughout the study. Both biliary drainage procedures lowered the portal endotoxin concentration and serum hyaluronic acid concentration at the time of hepatectomy. The serum hyaluronic acid concentration was lowest in the ID Hx group. Hepatic adenine triphosphate concentrations and energy charge levels were similar among the three groups. CONCLUSION: Although both external and internal biliary drainage before hepatectomy improved serum liver function tests, portal endotoxin concentration, and serum hyaluronic acid concentration at the time of surgery, preoperative internal biliary drainage was superior to external drainage, as evidenced by the better liver regeneration and function after hepatectomy. (+info)
A tungsten supplemented diet attenuates bacterial translocation in chronic portal hypertensive and cholestatic rats: role of xanthine dehydrogenase and xanthine oxidase.
(14/1230)
BACKGROUND: Bacterial translocation (BT) plays a major role in the pathophysiological process of spontaneous infections in portal hypertension (PH) and cholestatic jaundice. The major mechanisms promoting BT in experimental animal models are the disruption of the intestinal ecological equilibrium and disruption of the intestinal mucosal barrier. The enzymes xanthine dehydrogenase (XD) and xanthine oxidase (XO) are often implicated as a significant source of oxidants which have a major impact on the impairment of intestinal barrier function. AIM: To investigate the incidence of BT in rats with PH and obstructive jaundice, and to evaluate the impact of XD and XO. METHODS: Animals were subjected to sham laparotomy (SL), PH by calibrated stenosis of the portal vein, and common bile duct ligation (CBDL). They were fed either a standard pellet diet or a tungsten supplemented molybdenum-free diet. Four weeks after the operative procedure, intestinal colonisation and BT to portal vein, vena cava, mesenteric lymph nodes, liver, and spleen were determined. Intestinal XD and XO activity were measured enzymatically and histochemically. RESULTS: Significant (p<0.01) intestinal bacterial overgrowth was present in all PH and CBDL groups compared with the SL group. In normally fed animals after SL, BT occurred in 12%. In PH and after CBDL, the rate of BT increased significantly (p<0.05) to 28% and 54% respectively. In the jejunum of normally fed animals subjected to PH or CBDL, a significant increase in XO was observed (p<0.01). Animals fed a tungsten supplemented diet showed a significant attenuation of BT to 14% in PH and 22% after CBDL (p<0. 05). Tungsten treatment completely suppressed jejunal XD and XO activities. CONCLUSIONS: Significant intestinal bacterial overgrowth, BT, and XD to XO conversion occurred in PH and after CBDL. XD and XO inactivation by a tungsten supplemented molybdenum-free diet significantly reduced the incidence of BT without affecting intestinal bacterial overgrowth. These data strongly support the hypothesis that increased XD to XO conversion may contribute to intestinal barrier failure in PH and after CBDL. (+info)
Cholesterol inhibits spontaneous action potentials and calcium currents in guinea pig gallbladder smooth muscle.
(15/1230)
Elevated cholesterol decreases agonist-induced contractility and enhances stone formation in the gallbladder. The current study was conducted to determine if and how the electrical properties and ionic conductances of gallbladder smooth muscle are altered by elevated cholesterol. Cholesterol was delivered as a complex with cyclodextrin, and effects were evaluated with intracellular recordings from intact gallbladder and whole cell patch-clamp recordings from isolated cells. Cholesterol significantly attenuated the spontaneous action potentials of intact tissue. Furthermore, calcium-dependent action potentials and calcium currents were reduced in the intact tissue and in isolated cells, respectively. However, neither membrane potential hyperpolarizations induced by the ATP-sensitive potassium channel opener, pinacidil, nor voltage-activated outward potassium currents were affected by cholesterol. Hyperpolarizations elicited by calcitonin gene-related peptide were reduced by cholesterol enrichment, indicating potential changes in receptor ligand binding and/or second messenger interactions. These data indicate that excess cholesterol can contribute to gallbladder stasis by affecting calcium channel activity, whereas potassium channels remained unaffected. In addition, cholesterol enrichment may also modulate receptor ligand behavior and/or second messenger interactions. (+info)
Role of glutathione, lipid peroxidation and antioxidants on acute bile-duct obstruction in the rat.
(16/1230)
The aim of this work was to evaluate the role of lipid peroxidation and glutathione on liver damage induced by 7-day biliary obstruction in the rat. Male Wistar rats were bile-duct-ligated and divided in groups of 10 animals. Groups received vitamin E (400 IU/rat, p.o., daily) or trolox (50 mg/kg, p.o., daily) or both. Lipid peroxidation increased significantly in the livers of bile-duct-ligated rats. Vitamin E and trolox prevented lipid peroxidation. GSH was oxidized in the BDL group and the GSH/GSSG ratio decreased as a consequence. However, total glutathione content increased in liver and blood indicating a possible induction in de novo synthesis of GSH. Antioxidants preserved the normal GSH/GSSG ratio. Despite the observation that antioxidants verted lipid peroxidation and oxidation of GSH, liver injury (as assessed by serum enzyme activities, bilirubin concentration, liver glycogen content and histology) was not affected by the treatments. These results suggest that drugs that inhibit lipid peroxidation and oxidation of glutathione have no effect on conventional biochemical markers of liver injury and on liver histology of bile-duct-ligated rats for 7 days. It seems more likely that the detergent action of bile salts is responsible for solubilization of plasma membranes and cell death, which in turn may lead to oxidative stress, GSH oxidation and lipid peroxidation. (+info)