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M Trauner

Publications and source records attributed to M Trauner.

At least 19 recordsLinked to original sources
PubMed2006

[Addison's disease as a rare cause of chronically elevated liver enzymes].

Common causes of chronically elevated serum liver enzymes include fatty liver disease, chronic viral hepatitis, autoimmune hepatitis, or hereditary metabolic disorders. Adrenocortical insufficiency can also cause elevated liver enzymes. Since 1990 only 11 cases have been reported. We here report a 52-year-old man with elevated liver enzymes (1.5 x upper limit of normal) over the past 10 years. Furthermore, hyponatremia and hyperkalemia were noted. He complained of fatigue and low blood pressure over the past few years. At physical examination a dark complexion was noted. After ruling out chronic viral hepatitis, autoimmune disease, metabolic or hereditary disorders, rare causes of elevated liver enzymes were considered. The endocrinological work-up revealed Addison's disease as cause of serum electrolyte disturbance and elevated liver enzymes. The patient was successfully treated with hydrocortisol and fludrocortisol. After one week, liver enzymes, serum electrolytes and arterial blood pressure had normalized. In conclusion, for patients with constantly elevated liver enzymes also rare, extrahepatic diseases have to be considered. Addison's disease is a rare but fully reversible cause for elevated liver enzymes.

Addison Disease↗
PubMed2004

Bile secretory function in the obese Zucker rat: evidence of cholestasis and altered canalicular transport function.

BACKGROUND: Obese Zucker rats (ZR) have been used as an experimental model for non-alcoholic fatty liver disease and are particularly susceptible to various types of liver injury. Bile secretory function has not been assessed in ZR. AIM: To study bile secretion and expression of the main hepatobiliary transporters in ZR. METHODS: Bile flow and biliary secretion of lipids and glutathione were determined in eight and 14 week old obese ZR and their lean controls. Protein mass and mRNA of the Na(+)/taurocholate cotransporting polypeptide (Ntcp), the bile salt export pump (Bsep), and the multidrug resistant associated protein 2 (Mrp2) were assessed by western and northern blot, respectively. The effects of administration of a tumour necrosis factor alpha inactivator (etanercept) and an insulin sensitiser (rosiglitazone) were assessed in obese ZR while leptin was given to non-obese rats to study its effect on Mrp2 expression. RESULTS: ZR exhibited increased body weight and hyperlipidaemia. Only 14 week old obese ZR has fatty liver. Decreased bile flow and biliary lipid and glutathione secretion as well as reduced hepatic transport of both taurocholate and bromosulphthalein were found in obese ZR. Hepatic Mrp2 protein mass was markedly reduced (-70%) in obese rats while Ntcp and Bsep protein levels were similar to lean rats. Downregulation of Mrp2 seems to involve both transcriptional and post-transcriptional mechanisms probably related to insulin and leptin resistance. CONCLUSIONS: Obese ZR exhibit an impaired bile secretory function with significant functional and molecular alterations consistent with mild cholestasis. A defective hepatobiliary transport capacity may be a contributory factor in rendering the obese ZR more susceptible to liver injury.

Animals↗
PubMed2003

Jaundice.

Explore the source record for details and available documents.

Bilirubin↗
PubMed2001

[Diffuse hemangiomatosis of the liver and spleen in an adult].

Diffuse hemangiomatoses are extremely rare in adults. The etiology and natural history of the disease are not well understood. A case of diffuse hemangiomatosis of the liver and spleen associated with progressive liver failure, thrombocytopenia, and disturbance of blood coagulation (comparable to Kasabach-Merritt syndrome) is presented in a 62-year-old male. We describe the histopathological and immunohistochemical findings and illustrate the morphological aspects of differential diagnosis, distinguishing the disease from other vascular proliferations.

Biopsy↗
PubMed2001

Effects of ursodeoxycholic and cholic acid feeding on hepatocellular transporter expression in mouse liver.

BACKGROUND AND AIMS: Cholestasis is associated with retention of potentially toxic bile acids and alterations in hepatocellular transporter expression. Conversely, nontoxic ursodeoxycholic acid (UDCA) stimulates bile secretion and counteracts cholestasis. This study aimed to determine the effects of UDCA and cholic acid (CA) on the expression of hepatocellular transporters for bile acids (Ntcp, Bsep), organic anions (Oatp1, Mrp2), organic cations (Mdr1a/b), and phospholipids (Mdr2) in mouse liver. METHODS: Bile flow/composition was analyzed in UDCA- or CA-fed mice. Transporter expression was studied by reverse-transcription polymerase chain reaction, Western blotting, and immunofluorescence microscopy. RESULTS: UDCA had no effect on basolateral Ntcp and down-regulated Oatp1, whereas canalicular Bsep and Mrp2 were up-regulated. CA down-regulated basolateral Ntcp and Oatp1, whereas canalicular Bsep, Mrp2, and Mdr1a/b were up-regulated. Neither UDCA nor CA affected Mdr2 expression. Both UDCA and CA stimulated biliary bile acid and glutathione excretion, although only CA increased phospholipid and cholesterol excretion. CONCLUSIONS: Down-regulation of basolateral and up-regulation of canalicular transporters in response to CA may represent a defense mechanism, in an attempt to prevent hepatocellular accumulation of potentially toxic bile acids. The therapeutic effects of UDCA may be caused in part by stimulation of canalicular transporter expression in the absence of hepatocellular toxicity.

Administration, Oral↗
PubMed2001

Hepatobiliary transporter expression in percutaneous liver biopsies of patients with cholestatic liver diseases.

Reduced hepatobiliary transporter expression could explain impaired hepatic uptake and excretion of bile salts and other biliary constituents resulting in cholestasis and jaundice. Because little is known about alterations of hepatobiliary transport systems in human cholestatic liver diseases, it was the aim of this study to investigate such potential changes. Hepatic mRNA levels in hepatobiliary transport systems for bile salts (NTCP, BSEP), organic anions (OATP2, MRP2, MRP3), organic cations (MDR1), phospholipids (MDR3), and aminophospholipids (FIC1) were determined in 37 human liver biopsies and control livers by competitive reverse-transcription polymerase chain reaction (RT-PCR). Transporter tissue distribution was investigated by immunofluorescence microscopy. In patients with inflammation-induced icteric cholestasis (mainly cholestatic alcoholic hepatitis), mRNA levels of NTCP, OATP2, and BSEP were reduced by 41% (P <.001), 49% (P <.005), and 34% (P <.05) compared with controls, respectively. In addition, NTCP and BSEP immunostaining was reduced. MRP2 mRNA levels remained unchanged, but canalicular immunolabeling for MRP2 was also decreased. mRNA expression of MRP3, MDR1, MDR3, and FIC1 remained unchanged. In contrast to the alterations of transporter expression in inflammation-induced icteric cholestasis, transporter expression did not change in anicteric cholestasis caused by primary biliary cirrhosis (PBC) stages I and II. In conclusion, reduced expression of hepatobiliary transport systems for bile salts and other organic anions may contribute to inflammation-induced cholestasis in humans. Reduction of transporter gene expression can occur at the mRNA level as observed for NTCP, OATP2, and BSEP. However, reduced MRP2 immunostaining in the presence of conserved MRP2 mRNA levels suggests an additional role for posttranscriptional/posttranslational mechanisms.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2001

Cholestatic syndromes.

New insights into the regulation of hepatobiliary transport proteins have provided the basis for a better understanding of the pathogenesis of cholestatic liver diseases. Mutations of transporter genes can cause hereditary cholestatic syndromes, the study of which has shed much light on the basic mechanisms of bile secretion and cholestasis. Important new studies have been published about the pathogenesis, clinical features, and treatment of primary biliary cirrhosis, primary sclerosing cholangitis, cholestasis of pregnancy, total parenteral nutrition-induced cholestasis, and drug-induced cholestasis.

Journal Article↗
PubMed2001

Genetic disorders and molecular mechanisms in cholestatic liver disease--a clinical approach.

Cholestasis may result from genetic or acquired defects in bile secretion. Cloning of hepatobiliary transporter genes has advanced our understanding of the molecular basis of bile formation and cholestasis. Hereditary mutations of transporter genes, exposure to cholestatic injury (eg, drugs, hormones, cytokines), or the combination of both can result in reduced expression and function of hepatobiliary transport systems. These molecular changes impair hepatic uptake and excretion of bile salts and other organic anions (eg, bilirubin). Other molecular changes contibuting to cholestasis include alterations of membrane fluidity, cytoskeleton, vesicle movement, and cell contacts. Transporter mutations can be diagnosed at the molecular genetic level. Gene therapy and hepatocyte transplantation could be used in the future to correct hereditary transport defects. Drugs used to treat cholestatic liver diseases (eg, ursodeoxycholic acid) stimulate and partially restore defective transporter expression and function. New information on the molecular mechanisms of cholestasis should lead to the development of novel drugs for cholestatic liver diseases.

Alagille Syndrome↗
PubMed2000

Expression of the bile salt export pump is maintained after chronic cholestasis in the rat.

BACKGROUND & AIMS: This study assessed the expression of the recently identified adenosine triphosphate-dependent bile salt export pump and the functional ability to excrete bile salts in cholestatic models in the rat. METHODS: The effects of common bile duct ligation, endotoxin, and ethinylestradiol on bile salt export pump messenger RNA levels, protein expression, and tissue localization were determined. Changes in the expression of 3 other hepatocyte membrane transporters (Na(+) taurocholate cotransporter, multispecific organic anion transporter, and P-glycoprotein) were also determined for comparison. Functional assessment of bile salt excretion was determined after bile duct ligation. RESULTS: Expression of the bile salt export pump was diminished but relatively preserved compared with other membrane transporters. Tissue localization of the bile salt export pump persisted at the canalicular domain in all 3 models. In contrast, expressions of the Na(+) taurocholate cotransporter and multispecific organic anion transporter were more profoundly diminished. P-glycoprotein levels increased severalfold with common bile duct ligation but were unchanged with either endotoxin or ethinylestradiol. The capacity to excrete bile salts was relatively maintained 3 and even 14 days after bile duct ligation. CONCLUSIONS: Alterations in expression of the bile salt export pump may account for the functional alterations of bile salt secretion observed in cholestasis. However, relative preservation of expression is associated with persistent bile salt excretion and may lessen the extent of liver injury produced by bile salt retention.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Cholestatic syndromes.

Continued advances in the field of liver cell biology and molecular biology have provided further insights into the normal physiology of bile secretion and the pathogenesis and therapy for cholestatic syndromes. Important new data have also been published about pathogenesis, clinical features, and treatment of primary biliary cirrhosis, primary sclerosing cholangitis, drug-induced cholestasis, and cholestatic syndromes caused by viral infections.

Journal Article↗
PubMed2000

Intra-hepatic haematoma complicating transjugular intra-hepatic portosystemic shunt for Budd-Chiari syndrome associated with anti-phospholipid antibodies, aplastic anaemia and chronic hepatitis C.

Portal venous decompression with transjugular intra-hepatic portosystemic shunt (TIPS) is a new approach in the treatment of Budd-Chiari syndrome. We report on a 31-year-old female with Budd-Chiari syndrome due to anti-phospholipid antibodies with compression of the inferior vena cava treated with TIPS and stenting of the inferior vena cava. TIPS was complicated by massive intra-hepatic haematoma which was managed conservatively. Treatment options and pathogenic mechanisms of Budd-Chiari syndrome under the rare coincidence of aplastic anaemia and anti-phospholipid syndrome are discussed. TIPS may be considered for venous decompression in Budd-Chiari syndrome, but physicians should be aware of potential TIPS' complications in these patients.

Adult↗
PubMed2000

Hepatocellular bile salt transport: lessons from cholestasis.

Hepatic uptake and excretion of bile salts and several nonbile salt organic anions (eg, bilirubin) are mediated by a distinct set of polarized transport systems at the basolateral and apical plasma membrane domains of hepatocytes and bile duct epithelial cells (cholangiocytes). With the increasing availability of molecular probes for these transporters, evidence now exists that decreased or even absent expression of hepatobiliary transport proteins in hepatocytes or cholangiocytes may explain impaired transport function that results in hyperbilirubinemia and cholestasis. This review summarizes the molecular defects in hepatocellular membrane transporters that are associated with hereditary and acquired forms of cholestatic liver disease.

Bile↗