Perforation of the esophagus after dilation treatment for dysphagia in a patient with eosinophilic esophagitis.
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Adolescent↗
Biomedical subjects
A Stiehl
Publications and source records attributed to A Stiehl.
Effect of colitis and ileoanal pouch on biliary enrichment of ursodeoxycholic acid in primary sclerosing cholangitis.
In primary sclerosing cholangitis (PSC), biliary enrichment of ursodeoxycholic acid (UDCA) may represent the decisive factor for its presumable beneficial effect. Up to now it is not clear how colitis and colectomy with ileo-anal pouch affect the biliary enrichment of UDCA and the biliary bile acid composition. We determined the biliary bile acid composition in 63 patients with PSC including 7 patients with ileo-anal pouch, 31 patients with colitis, and 25 patients without colitis. No differences existed between patients with and those without colitis. In patients with colectomy and pouch at a UDCA dose of 17.7 +/- 1.6 mg/kg (n = 7), biliary UDCA represented 46.4 +/- 6.7% (mean +/- SD) of total bile acids. An increase in the dose in six pouch patients from 12.5 +/- 0.9 to 22.3 +/- 1.6 mg/kg led to a slight increase in biliary enrichment of UDCA, from 39.8 +/- 8.1 to 49.4 +/- 10.7%. In five of seven patients with ileo-anal pouch, biliary UDCA enrichment was within the normal range, and in two of seven it was permanently or intermittently abnormally low. During UDCA treatment, in pouch patients the biliary content of deoxycholic acid and lithocholic acid was reduced, whereas all other bile acids were unchanged. In a minority of patients with ileo-anal pouch, biliary enrichment of UDCA may be markedly reduced, whereas patients with colitis have a biliary UDCA enrichment not different from that of patient without colitis.
Adult↗
Biliary complications after liver transplantation.
Biliary complications remain a substantial cause of morbidity following liver transplantation. They have been reported to occur in a rate of 10-15% of full-size transplantations and may be higher in living donor, split or reduced size liver transplantations. The most common biliary complications following liver transplantations are leaks and strictures. In both, the incidence varies with respect to type of graft and donor as well as the type of biliary anastomosis. The management of the biliary complications requires a multidisciplinary approach and has changed over the past decade, favoring endoscopic and radiological techniques. Surgical revision including retransplantation is reserved for patients in whom endoscopic and interventional modalities are unsuccessful.
Biliary Tract Diseases↗
Impact of dominant stenoses on the serum level of the tumor marker CA19-9 in patients with primary sclerosing cholangitis.
BACKGROUND/AIMS: Patients with primary sclerosing cholangitis (PSC) have an increased risk of developing hepatobiliary tumors. The tumor marker CA19-9 was claimed to indicate the occurrence of bile duct carcinoma. This study aimed to assess whether increased serum levels of CA19-9 in PSC patients with dominant stenoses indicate bile duct carcinoma. METHODS: The study cohort comprised 106 patients treated over a median time of 5.0 years (range 0.5 - 13 years). All patients were treated with ursodeoxycholic acid (UDCA) and whenever they developed dominant stenoses by endoscopic dilatation of these stenoses. In endoscopically treated patients, CA19-9 levels were measured before and 3, 6, 12 and 24 months after endoscopic dilatation. RESULTS: Of the 106 patients, 22 carcinoma-free patients and 3 patients with bile duct carcinoma had elevated CA 19 - 9 levels. In 14 out of 25 patients with elevated CA19-9 levels, dominant stenoses were diagnosed and treated by endoscopic dilatation. In 71.4 % of the endoscopically treated patients, CA19-9 levels decreased following the endoscopic intervention. CONCLUSIONS: In PSC patients, increased serum levels of CA19-9 are rarely due to the development of bile duct carcinoma. In patients with dominant stenoses, the relief of biliary obstruction by endoscopic dilatation may lead to a decrease of the serum levels of CA19-9.
Bile Duct Neoplasms↗
Gender-specific expression of liver organic anion transporters in rat.
BACKGROUND: Sex differences in drug pharmacokinetics have been well recognized and gender has been considered a risk factor for adverse events to medications. The aim of this study was to investigate the effect of gender on the expression of hepatocellular transport proteins involved in uptake and secretion of organic anions in rat. MATERIALS AND METHODS: Expression of the rat liver organic anion transporting polypeptides (Oatps) and multidrug resistance proteins (Mrps) was analysed by reverse transcription polymerase chain reaction (RT-PCR), immunoblot analysis and immunofluorescence microscopy in male and female rats. Regulation of these transport proteins in response to the steroid dehydroepiandrosterone (DHEA) was investigated. RESULTS: In untreated rats, protein expression significantly differed between genders being higher (Mrp2, Mrp3), comparable [Oatp1a1 (Oatp1); Oatp1b2 (Oatp4)] or lower [Oatp1a4 (Oatp2)] in female than in male rat. DHEA treatment over 3 days (100 mg d(-1)) led to a further increase in Mrp3 expression only in female rats. Mrp2 expression was not influenced by DHEA treatment. Oatp1a1 and Oatp1b2 were significantly down-regulated after DHEA treatment in both male and female rats. In contrast, Oatp1a4 was down-regulated in male rats only. CONCLUSIONS: In rat, liver transport proteins of the Oatp and Mrp family are expressed and regulated in a gender-specific manner according to sexual differences in the hepatic metabolism of steroids and drugs. These findings may partly explain the well-known sex differences in hepatic handling of organic anions.
ATP Binding Cassette Transporter, Subfamily B↗
[Primary sclerosing cholangitis].
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease, characterized by fibrosing inflammation and obliteration of intra and/or extrahepatic bile ducts. The disease belongs to the most common cholestatic diseases in adults and at present is diagnosed with increasing frequency. It is very often associated with ulcerative colitis. Patients with PSC have an increased incidence of bile duct carcinomas and those with ulcerative colitis also have an increased incidence of colonic carcinomas. Immunosuppressive treatment is little effective. Ursodeoxycholic acid (UDCA) has been shown to improve liver histology in PSC. The aim is to treat patients as early as possible to prevent progression to the advanced stages of the disease. During treatment with UDCA stenoses of major ducts may develop and early endoscopic dilatation is highly effective. In patients with endstage disease, UDCA is not effective and liver transplantation is indicated.
Bile Duct Neoplasms↗
Progressive sclerosing cholangitis after septic shock: a new variant of vanishing bile duct disorders.
BACKGROUND: We present nine patients with progressive sclerosing cholangitis after septic shock. PATIENTS: All nine patients had previously required long term treatment in an intensive care unit for septic shock: two patients with polytrauma, five with burn injury, and two with extensive surgery. They were admitted to our hospital because of cholangitis. Endoscopic retrograde cholangiography revealed severe intrahepatic stenoses in all patients and liver biopsies showed typical signs of sclerosing cholangitis. No patient had pre-existing liver disease. RESULTS: Mean follow up time was 35 months. In patients with major bile duct stenoses (3/9), 12 endoscopic dilations were performed in total. In one patient, concrements were extracted and intermittent stenting was necessary. To date, 4/9 patients have rapidly developed liver cirrhosis. During follow up, 5/9 patients died: two after fulminant cholangitis, one after liver failure, one due to liver transplantation associated problems, and one after cerebral ischaemia. One patient has been registered for transplantation and the remaining three patients show no acute signs of liver failure. CONCLUSIONS: Patients with sclerosing cholangitis, following septic shock, represent a new variant of vanishing bile duct disorders. In such patients liver disease rapidly progresses to cirrhosis. Endoscopic treatment may only transiently improve the course of the disease. Orthotopic liver transplantation is indicated in end stage disease.
Adolescent↗
Intestinal absorption and biliary secretion of ursodeoxycholic acid and its taurine conjugate.
BACKGROUND: Ursodeoxycholic acid (UDCA) and its taurine conjugate (TUDCA) exert a protective effect in cholestatic liver diseases. A greater hepatoprotective effect of TUDCA has been suggested. Absorption appears to be a limiting factor and up to now has not been studied in man. METHODS: We studied absorption and biliary bile acid secretion and composition after administration of UDCA and TUDCA in patients who had complete extrahepatic biliary obstruction caused by pancreatic carcinoma but had no intestinal or liver disease. After 5 days of intact enterohepatic circulation eight patients with a percutaneous biliary-duodenal drainage received, during two study periods, 1000 mg (1916.9 micromol; mean 29.6 micromol kg(-1)) TUDCA and 750 mg (1910.4 micromol; mean 29.5 micromol kg(-1)) UDCA in random order. Each patient served as his own control. RESULTS: After UDCA and TUDCA administration the biliary UDCA content increased to 55.2% and 54.6% of total bile acids, respectively (not significant). Biliary secretion of cholic and chenodeoxycholic acids remained unchanged whereas that of lithocholic acid increased slightly. A total of 64.6% of the orally administered TUDCA and 55.1% of the UDCA was absorbed (not significant). After TUDCA administration, biliary UDCA was preferentially (95.4%) taurine-conjugated whereas after UDCA administration biliary UDCA was mainly (79.8%) glycine-conjugated. CONCLUSIONS: After oral administration of TUDCA and UDCA, no significant differences in their absorption and in biliary bile acid secretion exist. Whether biliary enrichment with taurine conjugates of UDCA instead of glycine conjugates offers advantages in the treatment of cholestatic liver disease is unclear at present.
Aged↗
Endoscopic variceal ligation plus propranolol vs. transjugular intrahepatic portosystemic stent shunt: a long-term randomized trial.
BACKGROUND AND STUDY AIMS: After a first variceal bleeding episode in patients with cirrhosis of the liver, treatment with transjugular intrahepatic portosystemic stent shunt (TIPS) and endoscopic variceal ligation (EVL) plus propranolol were compared, with regard to prevention of variceal rebleeding, complications, and mortality. PATIENTS AND METHODS: 85 patients were randomly allocated to receive TIPS (n = 43) or EVL (n = 42). The groups were comparable regarding age, sex, etiology of liver cirrhosis, and liver function. RESULTS: The mean observation times were 4.1 years in the TIPS group and 3.6 years in the EVL group. Although the probability of rebleeding was higher in the EVL group (29.9%) than in the TIPS group (19.4%), the difference was not statistically significant. Three of five patients of the EVL group successfully underwent TIPS placement after treatment failure. The probability of TIPS dysfunction requiring shunt revision was 89 %. Hepatic encephalopathy was observed more often in the TIPS group (40.5%) than in the EVL group (20.5%; P < 0.05). The probability of survival was similar in both groups (TIPS group 75.9%, EVL group 82.2%; n.s.). CONCLUSIONS: In view of its good efficacy and the lower cost of treatment, endoscopic ligation plus propranolol may be recommended as initial procedure for prevention of recurrent variceal hemorrhage, whereas TIPS seems to be the preferable procedure in patients with recurrent bleeding after adequate endoscopic and pharmacological treatment.
Adrenergic beta-Antagonists↗
[Diagnosis and therapy of primary biliary cirrhosis and primary sclerosing cholangitis].
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Anti-Inflammatory Agents↗
[Therapy of primary sclerosing cholangitis].
In primary sclerosing cholangitis the aim of treatment is a reduction of the inflammatory destruction of the bile ducts leading to cholestasis and irreversible liver damage. Treatment with ursodeoxycholic acid may decrease the periductular inflammation. Bacterial infection of the bile ducts is frequent and should be treated by antibiotics. Medical treatment of the disease may be successful under the assumption that dominant stenoses are treated endoscopically.
Anti-Bacterial Agents↗
Downregulation of ileal bile acid absorption in bile-duct-ligated rats.
BACKGROUND/AIMS: Accumulation of toxic bile acids in cholestasis contributes to liver injury and depends on their synthesis, secretion and intestinal absorption. In the present study, we investigated the effect of cholestasis on the active ileal absorption of bile acids in vivo and the adaptation of transporters involved in ileal bile acid absorption. METHODS: Male Wistar rats underwent ligation of the common bile duct or biliary diversion. Sham-operated rats served as controls. Active ileal bile acid absorption of taurocholate was measured by an intestinal perfusion technique. Transporter mRNA levels of the Na+/bile acid cotransporting protein (IBAT), ileal lipid binding protein (ILBP) and organic anion transporter subtype 3 (Oatp3) and protein expression of IBAT and ILBP were determined in the distal ileum. RESULTS: After bile duct ligation the intestinal absorption rates of taurocholate were lower (p<0.05) and after biliary diversion absorption rates were higher compared to sham-operated animals (p<0.05). The absorption rates were inversely correlated to serum bile acid concentrations. Levels of IBAT-, ILBP- and Oatp3- mRNA were not different between the groups. However, in cholestatic rats, the expression of the 99-kDa dimer of IBAT was decreased compared to controls (p<0.05), whereas the 46-kDa monomeric protein of IBAT and the expression of ILBP was unchanged. After biliary diversion a similar pattern of protein expression was observed, despite an increased absorption rate. CONCLUSIONS: Cholestasis leads to a decreased active ileal absorption of taurocholate. The changes in protein expression may not account for the different absorption rates. The intestinal absorption of bile acids seems to be regulated by their systemic concentration.
Animals↗
Effect of tauroursodeoxycholic acid on bile acid-induced apoptosis in primary human hepatocytes.
BACKGROUND/AIMS: The accumulation of endogenous bile acids contributes to hepatocellular damage during cholestatic liver disease. To evaluate the potential role of apoptotic cell death due to increased concentrations of bile acids, primary human hepatocytes were treated with hydrophobic and hydrophilic bile acids. Because the Fas receptor-ligand system may mediate apoptosis in human liver cells, the effect of toxic bile acids on hepatocellular Fas receptor expression was evaluated. MATERIALS AND METHODS: Primary human hepatocytes were incubated with 50 and 100 microM glycochenodeoxycholic acid (GCDCA) and co-incubated with equimolar concentrations of tauroursodeoxycholic acid (TUDCA). To evaluate cytolytic and apoptotic effects, morphological alterations, hepatocellular enzyme release, nuclear DNA fragmentation and hepatocellular Fas receptor expression were evaluated. RESULTS: Apoptotic cell death was significantly increased after exposure to 50 microM GCDCA. Bile acid-induced apoptosis was not accompanied by hepatocellular Fas receptor overexpression. Tauroursodeoxycholic acid reduced apoptosis, as indicated by a significant reduction of oligonucleosomal DNA cleavage. Fas receptor expression was not significantly affected by tauroursodeoxycholic acid. At higher concentrations, direct cytolytic cell destruction was observed. CONCLUSION: Primary human hepatocytes represent a suitable model to study bile acid-induced apoptotic cell death. In these hepatocytes, already low bile acid concentrations might induce apoptotic cell death, which is not triggered by hepatocellular Fas receptor overexpression. Apoptotic DNA fragmentation was significantly reduced by co-incubation with tauroursodeoxycholic acid. The reduction of bile acid-induced apoptosis by ursodeoxycholic acid and its conjugates may contribute to the beneficial effects of these hydrophilic bile acids used for medical treatment of several cholestatic liver diseases.
Apoptosis↗
Primary sclerosing cholangitis.
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by fibrosing inflammation and obliteration of intra- and/or extrahepatic bile ducts. The disease is one of the most common cholestatic diseases in adults and is diagnosed with increasing frequency. It is very often associated with ulcerative colitis. Patients with PSC have an increased incidence of bile duct carcinomas, and those with ulcerative colitis also have an increased incidence of colonic carcinomas. In end-stage disease, liver transplantation is the treatment of choice. Immunosuppressive treatment has little effect. Ursodeoxycholic acid (UDCA), which has been shown to improve liver histology and survival in patients with primary biliary cirrhosis, has a beneficial effect in PSC, provided that patients who develop major duct stenoses are treated endoscopically. The aim is to treat patients as early as possible to prevent progression to the advanced stages of the disease. During treatment with UDCA, stenoses of major ducts may develop, and early endoscopic dilation is highly effective. Because UDCA treatment improves but does not cure cholestatic liver diseases, permanent treatment seems to be necessary. Such prolonged treatment with UDCA may be recommended because, until now, no side effects have been reported. In patients with end-stage disease, UDCA is not effective and liver transplantation is indicated.
Bile Duct Neoplasms↗
Mechanism of hepatoprotective action of bile salts in liver disease.
Ursodeoxycholic acid (UDCA) improves liver enzymes and in many instances liver histology in cholestatic liver diseases such as primary biliary cirrhosis and primary sclerosing cholangitis. Besides classic cholestatic diseases, UDCA also improves liver biochemistry in alcoholic liver disease and in chronic viral hepatitis C. The main target of UDCA treatment, however, is cholestasis, and consequently the mechanisms responsible for the beneficial effects in these diseases are of interest, and are discussed in detail in this article.
Animals↗
Influence of cholestasis on absorption of ursodeoxycholic acid.
Ursodeoxycholic acid (UDCA) has beneficial effects in cholestatic liver diseases. Absorption of UDCA is slow and incomplete. In the present study the effect of cholestasis on absorption was evaluated in 10 patients with pancreatic carcinoma and extrahepatic biliary drainage. At days 3 and 10 after insertion of the biliary drain, all patients received 750 mg UDCA in three divided doses. On both occasions intestinal absorption of UDCA was determined to evaluate the influence of cholestasis. Serum bilirubin was used as indicator of cholestasis. Biliary output of UDCA served as measure of absorption and was determined by gas-liquid chromatography. At days 4 and 11 bile consisted of less than 2% of UDCA, indicating that UDCA excretion was complete within 24 hr and no accumulation of UDCA had occurred. After insertion of the drain, serum bilirubin decreased from 12.2 +/- 2.4 mg/dl at day 3 to 5.4 +/- 0.9 mg/dl at day 10. Biliary secretion of bile acids increased from 2.0 +/- 0.3 to 3.1 +/- 0.4 mmol/day, whereas percentage of ursodeoxycholic acid in bile did not significantly increase (41.1% vs 42.1%). Absorption of UDCA increased from 39.8 +/- 5.0% to 61.1 +/- 6.2% of the administered dose, indicating an improvement of the absorption rate after decrease of cholestasis by 53.65% (P < 0.05). In conclusion, in severe cholestasis absorption of orally administered UDCA is markedly reduced. This may have implications in the treatment of patients with cholestatic disease.
Administration, Oral↗
Value of brush border cytology for dominant strictures in primary sclerosing cholangitis.
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Bile Duct Neoplasms↗
Biliary endothelin levels in liver transplant recipients do not correlate with total bile acid concentration.
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Bile↗