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Sample records for cholestasis

  1. Cholestasis and Pruritus: Progressive Familial Intrahepatic Cholestasis?

    Directory of Open Access Journals (Sweden)

    Gökhan Tümgör

    2016-08-01

    Full Text Available Progressive familial intrahepatic cholestasis (PFIC has a significant place among the childhood cholestasis. It is the second most frequent liver transplant indication met in some liver transplant institutions. It constitutes approximately 10-15% of all cases of cholestasis and liver transplant. PFIC is an autosomal recessively inherited disorder and causes hepatocellular-originated cholestasis. In the period from infancy to adulthood it may cause death due to liver failure. PFIC has three types and the most frequently observed clinical symptoms of all three types are; pruritus, hepatitis, growth retardation, hepatomegaly, and splenomegaly. The prognosis of these three types of PFIC is different. The complications of PFIC are; portal hypertension, liver failure, cirrhosis, hepatocellular carcinoma, and extrahepatic symptoms. Although medical and surgical treatments are applied in order to improve the patients’ life quality, most of the cases require liver transplantation in the early stage.

  2. Progressive familial intrahepatic cholestasis

    OpenAIRE

    Baussan Christiane; Gonzales Emmanuel; Davit-Spraul Anne; Jacquemin Emmanuel

    2009-01-01

    Abstract Progressive familial intrahepatic cholestasis (PFIC) refers to heterogeneous group of autosomal recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin. The exact prevalence remains unknown, but the estimated incidence varies between 1/50,000 and 1/100,000 births. Three types of PFIC have been identified and related to mutations in hepatocellular transport system genes involved in bile formation. PFIC1 and PFIC2 usually appea...

  3. Drug-induced cholestasis.

    Science.gov (United States)

    Zimmerman, H J; Lewis, J H

    1987-01-01

    Intrahepatic cholestasis, defined as arrested bile flow, mimics extrahepatic obstruction in its biochemical, clinical and morphological features. It may be due to hepatocyte lesions of which there are three types, termed canalicular, hepatocanalicular and hepatocellular, respectively; or it may be due to ductal lesions at the level of the cholangiole or portal or septal ducts. Defective bile flow due to hepatic lesions reflects abnormal modification of the ductular bile. Defective formation of canalicular bile may involve bile acid-dependent or independent flow. It appears to result most importantly from defective secretion of bile acid-dependent flow secondary to defective uptake from sinusoidal blood, defective transcellular transport and defective secretion; or from regurgitation of secreted bile via leaky tight junctions. An independent defect in bile acid-independent flow is less clear. Defective flow of bile along the canaliculus may reflect increased viscosity and impaired canalicular contractility secondary to injury of the pericanalicular microfibrillar network. Impaired flow beyond the canaliculus may result from ductal injury. Sites of lesions that contribute to cholestasis include the sinusoidal and canalicular plasma membrane, the pericanalicular network and the tight junction and, less certainly, microtubules and microfilaments and Golgi apparatus. A number of drugs that lead to cholestasis have been found to lead to injury at one or more of these sites. Other agents (alpha-naphthylisothiocyanate, methylenedianiline, contaminated rapeseed oil, paraquat) lead to ductal injury resulting in cholestasis. Reports of inspissated casts in ductules (benoxaprofen jaundice) and injury to the major excretory tree (5-fluorouridine after hepatic artery infusion) have led to other forms of ductal cholestasis. Most instances of drug-induced cholestasis present as acute, transient illness, although important chronic forms also occur. The clinical features include the

  4. Progressive familial intrahepatic cholestasis

    Institute of Scientific and Technical Information of China (English)

    Tomohide Hori; Justin H. Nguyen; Shinji Uemoto

    2010-01-01

    BACKGROUND: Three types of progressive familial intrahepatic cholestasis (PFIC) have been identiifed, but their etiologies include unknown mechanisms. DATA SOURCES: A PubMed search on "progressive familial intrahepatic cholestasis" and "PFIC" was performed on the topic, and the relevant articles were reviewed. RESULTS: The etiologies of the three PFIC types still include unknown mechanisms. Especially in PFIC type 1, enterohepatic circulation of bile acid should be considered. Ursodeoxycholic acid, partial external biliary diversion and liver transplantation have been used for the treatment of PFIC patients according to disease course. CONCLUSIONS: Since the etiologies and disease mechanisms of PFIC are still unclear, detailed studies are urgently required. Strategies for more advanced therapies are also needed. These developments in the future are indispensable, especially for PFIC type 1 patients.

  5. Intrahepatic cholestasis of pregnancy

    Directory of Open Access Journals (Sweden)

    Beuers Ulrich

    2007-05-01

    Full Text Available Abstract Intrahepatic cholestasis of pregnancy (ICP is a cholestatic disorder characterized by (i pruritus with onset in the second or third trimester of pregnancy, (ii elevated serum aminotransferases and bile acid levels, and (iii spontaneous relief of signs and symptoms within two to three weeks after delivery. ICP is observed in 0.4–1% of pregnancies in most areas of Central and Western Europe and North America, while in Chile and Bolivia as well as Scandinavia and the Baltic states roughly 5–15% and 1–2%, respectively, of pregnancies are associated with ICP. Genetic and hormonal factors, but also environmental factors may contribute to the pathogenesis of ICP. Intrahepatic cholestasis of pregnancy increases the risk of preterm delivery (19–60%, meconium staining of amniotic fluid (27%, fetal bradycardia (14%, fetal distress (22–41%, and fetal loss (0.4–4.1%, particularly when associated with fasting serum bile acid levels > 40 μmol/L. The hydrophilic bile acid ursodeoxycholic acid (10–20 mg/kg/d is today regarded as the first line treatment for intrahepatic cholestasis of pregnancy. Delivery has been recommended in the 38th week when lung maturity has been established.

  6. Intrahepatic cholestasis of pregnancy

    Institute of Scientific and Technical Information of China (English)

    Victoria Geenes; Catherine Williamson

    2009-01-01

    Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder characterized by maternal pruritus in the third trimester, raised serum bile acids and increased rates of adverse fetal outcomes. The etiology of ICP is complex and not fully understood, but it is likely to result from the cholestatic effects of reproductive hormones and their metabolites in genetically susceptible women. Equally unclear are the mechanisms by which the fetal complications occur. This article reviews the epidemiology, clinical features, diagnosis, etiology and management of ICP.

  7. Progressive familial intrahepatic cholestasis

    Directory of Open Access Journals (Sweden)

    Baussan Christiane

    2009-01-01

    Full Text Available Abstract Progressive familial intrahepatic cholestasis (PFIC refers to heterogeneous group of autosomal recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin. The exact prevalence remains unknown, but the estimated incidence varies between 1/50,000 and 1/100,000 births. Three types of PFIC have been identified and related to mutations in hepatocellular transport system genes involved in bile formation. PFIC1 and PFIC2 usually appear in the first months of life, whereas onset of PFIC3 may also occur later in infancy, in childhood or even during young adulthood. Main clinical manifestations include cholestasis, pruritus and jaundice. PFIC patients usually develop fibrosis and end-stage liver disease before adulthood. Serum gamma-glutamyltransferase (GGT activity is normal in PFIC1 and PFIC2 patients, but is elevated in PFIC3 patients. Both PFIC1 and PFIC2 are caused by impaired bile salt secretion due respectively to defects in ATP8B1 encoding the FIC1 protein, and in ABCB11 encoding the bile salt export pump protein (BSEP. Defects in ABCB4, encoding the multi-drug resistant 3 protein (MDR3, impair biliary phospholipid secretion resulting in PFIC3. Diagnosis is based on clinical manifestations, liver ultrasonography, cholangiography and liver histology, as well as on specific tests for excluding other causes of childhood cholestasis. MDR3 and BSEP liver immunostaining, and analysis of biliary lipid composition should help to select PFIC candidates in whom genotyping could be proposed to confirm the diagnosis. Antenatal diagnosis can be proposed for affected families in which a mutation has been identified. Ursodeoxycholic acid (UDCA therapy should be initiated in all patients to prevent liver damage. In some PFIC1 or PFIC2 patients, biliary diversion can also relieve pruritus and slow disease progression. However, most PFIC patients are ultimately candidates for liver transplantation

  8. Genetics Home Reference: progressive familial intrahepatic cholestasis

    Science.gov (United States)

    ... a protein called the bile salt export pump (BSEP). This protein is found in the liver, and ... ABCB11-related intrahepatic cholestasis ATP8B1-related intrahepatic cholestasis BSEP deficiency Byler disease Byler syndrome FIC1 deficiency low ...

  9. Genetic determinants of drug-induced cholestasis and intrahepatic cholestasis of pregnancy

    OpenAIRE

    Pauli-Magnus, Christiane; Meier, Peter J; Stieger, Bruno

    2010-01-01

    Intrahepatic cholestasis of pregnancy and drug-induced cholestasis are two clinically important forms of acquired cholestatic liver disease. The understanding of the underlying mechanisms of acquired cholestasis has recently made considerable progress by the identification of canalicular ATP-binding cassette (ABC) transporters as likely targets for these forms of cholestasis. Cholestasis of pregnancy is linked to estrogen and progesterone metabolites. These metabolites have been shown to impa...

  10. Intrahepatic cholestasis without jaundice

    Institute of Scientific and Technical Information of China (English)

    Thomas Namdar; Andreas Raffel; Stefan Andreas Topp; Jan Schulte am Esch; Günther Fürst; Wolfram Trudo Knoefel; Claus Ferdinand Eisenberger

    2009-01-01

    BACKGROUND: Cholangiocarcinoma (CC), the most common biliary tract malignancy, is frequently seen in advanced unresectable stages and is typically localized extrahepatically. Early diagnosis is unusual because of nonspeciifc symptoms. Painless jaundice is usually the ifrst sign of tumor. METHOD: We present a patient with a CC (Klatskin tumor) with a complete biliary drainage by an aberrant bile duct without jaundice. RESULTS: A 67-year-old woman presented with persisting elevation of liver parameters. Diagnostic tests showed a Klatskin tumor typeⅡ. A curative right hepatic trisegmentectomy was performed after liver volume augmentation by preoperative vein embolization. CONCLUSIONS: A direct drainage of the right posterior bile duct into the common bile duct as an aberrant hepatic duct is a rare variation and is present in less than 5% of the population. In case of persistently perturbed liver function tests, an aberrant bile duct can cover up severe intrahepatic cholestasis and even obscure the diagnosis of a Klatskin tumor. Up to now it has not been described in the literature.

  11. Genetic Determinants of Drug-induced Cholestasis and Intrahepatic Cholestasis of Pregnancy

    NARCIS (Netherlands)

    C. Pauli-Magnus; P.J. Meier; B. Stieger

    2010-01-01

    Intrahepatic cholestasis of pregnancy and drug-induced cholestasis are two clinically important forms of acquired cholestatic liver disease. The understanding of the underlying mechanisms of acquired cholestasis has recently made considerable progress by the identification of canalicular ATP-binding

  12. Genetic evidence of heterogeneity in intrahepatic cholestasis of pregnancy

    OpenAIRE

    Savander, M; Ropponen, A; Avela, K.; Weerasekera, N; Cormand, B; Hirvioja, M-L; Riikonen, S.; Ylikorkala, O; Lehesjoki, A-E; C. Williamson; Aittomäki, K.

    2003-01-01

    Background and aims: The aim of this study was to investigate the genetic aetiology of intrahepatic cholestasis of pregnancy (ICP) and the impact of known cholestasis genes (BSEP, FIC1, and MDR3) on the development of this disease.

  13. Renal elimination of organic anions in cholestasis

    Institute of Scientific and Technical Information of China (English)

    Adriana Mónica Tortes

    2008-01-01

    The disposition of most drugs is highly dependent on specialized transporters.OAT1 and OAT3 are two organic anion transporters expressed in the basolateral membrane of renal proximal tubule cells,identified as contributors to xenobiotic and endogenous organic anion secretion.It is well known that cholestasis may cause renal damage.Impairment of kidney function produces modifications in the renal elimination of drugs.Recent studies have demonstrated that the renal abundance of OAT1 and OAT3 plays an important role in the renal elimination of organic anions in the presence of extrahepatic cholestasis.Time elapsed after obstructive cholestasis has an important impact on the regulation of both types of organic anion transporters.The renal expression of OAT1 and OAT3 should be taken into account in order to improve pharmacotherapeutic efficacy and to prevent drug toxicity during the onset of this hepatic disease.

  14. Cholestasis and pneumonitis induced by gold therapy.

    Science.gov (United States)

    Farre, J M; Perez, T; Hautefeuille, P; Tonnel, F; Colombel, J F; Duquesnoy, B; Delcambre, B

    1989-12-01

    The authors describe the association of gold salt-induced cholestasis and lymphocytic alveolitis proved by liver biopsy and broncho-alveolar lavage. To our knowledge this is the third case report on the combination of liver disease and pulmonary infiltration induced by gold compounds. PMID:2612124

  15. A Gentleman with Anemia and Cholestasis

    Directory of Open Access Journals (Sweden)

    Siu-Tong Law

    2010-01-01

    Full Text Available Primary sclerosing cholangitis is a rare cause of cholestasis caused by progressive inflammation and fibrosis of both intrahepatic and extrahepatic bile ducts leading to multifocal ductal strictures. Herein, we report a case of primary sclerosing cholangitis and inflammatory bowel disease. The concomitant diagnosis of these two diseases is not typical. The management includes the treatment of inflammatory bowel disease and potential complications of primary sclerosing cholangitis, including dominant strictures of bile duct, portal hypertension, gallbladder diseases, cholangiocarcinoma, and colonoscopic surveillance.

  16. Impaired nonspecific cellular immunity in experimental cholestasis.

    Science.gov (United States)

    Roughneen, P T; Drath, D B; Kulkarni, A D; Rowlands, B J

    1987-11-01

    The abilities of polymorphonuclear leukocytes (PMN) and pulmonary alveolar macrophages (PAM), to demonstrate chemotaxis, phagocytosis, and superoxide release after bile duct ligation in the rat were investigated to determine the effect of cholestasis on nonspecific cellular immune mechanisms. Chemotactic response to C5a and FMLP, phagocytosis of 14C labeled Staphylococcus aureus, and zymosan-induced superoxide release were evaluated 21 days after bile duct ligation (BDL), sham operation, or in normal controls. Serum total bilirubin level was elevated after BDL (p less than 0.01). Chemotactic ability was similar to each group. PMN phagocytic uptake of 14C labeled Staphylococcus aureus was depressed in BDL (p less than 0.05). BDL rats exhibited impaired PAM phagocytic indices and improved PMN superoxide release (p less than 0.03). PAM superoxide release was similar in each study group. Alterations in phagocytic function with cholestasis are important deficits in nonspecific cellular immunity that may contribute to the high incidence of infective complications associated with obstructive jaundice. PMID:2823730

  17. Late-Onset Drug-Induced Cholestasis in a Living-Related Liver Transplant Donor With Progressive Familial Intrahepatic Cholestasis.

    Science.gov (United States)

    Harmancı, Özgür; Ensaroğlu, Fatih; Özçay, Figen; Öcal, Serkan; Korkmaz, Murat; Özdemir, B Handan; Selçuk, Haldun; Moray, Gökhan; Haberal, Mehmet

    2015-11-01

    We present a rare case of progressive familial intrahepatic cholestasis within a family. A 34-yearold female became a living-related liver transplant donor for her son, who had the disease. Nine years after the transplant, the mother developed severe intrahepatic cholestasis, for which she was evaluated after using an oral contraceptive drug. She presented with jaundice, pruritus, and increased bilirubin levels, together with elevated gamma glutamyl transferase and alkaline phosphatase levels. A liver biopsy revealed findings consistent with intrahepatic cholestasis. However, despite follow-up management and cessation of the insulting drug, her total bilirubin count continuously increased to 20 mg/dL and was accompanied by intractable pruritus. A total of 9 plasmapheresis sessions were performed, and she was started on a regimen of ursodeoxycholic acid (13 mg/kg/d) and cholestyramine (4 g, 3 times daily). The clinical and laboratory picture dramatically improved following cessation of the oral contraceptive, plasmapheresis sessions, and drug treatment. The patient's cholestasis normalized within 3 months, and she recovered uneventfully. A genetic analysis of the whole family revealed that both parents were heterozygous for the mutation c.124G>A in ABCB11, and the son was homozygous for this mutation. These findings supported varying degrees of bile salt export pump deficiency in the family members. Defective bile salt excretory system function can result in a wide spectrum of clinical presentations, ranging from progressive familial intrahepatic cholestasis requiring liver transplant to late-onset drug-induced cholestasis. Our findings suggest that, in a heterozygous carrier of a progressive familial intrahepatic cholestasis mutation, drug-induced cholestasis is responsive to treatment, after which the clinical picture can normalize within 3 months.

  18. Late-Onset Drug-Induced Cholestasis in a Living-Related Liver Transplant Donor With Progressive Familial Intrahepatic Cholestasis.

    Science.gov (United States)

    Harmancı, Özgür; Ensaroğlu, Fatih; Özçay, Figen; Öcal, Serkan; Korkmaz, Murat; Özdemir, B Handan; Selçuk, Haldun; Moray, Gökhan; Haberal, Mehmet

    2015-11-01

    We present a rare case of progressive familial intrahepatic cholestasis within a family. A 34-yearold female became a living-related liver transplant donor for her son, who had the disease. Nine years after the transplant, the mother developed severe intrahepatic cholestasis, for which she was evaluated after using an oral contraceptive drug. She presented with jaundice, pruritus, and increased bilirubin levels, together with elevated gamma glutamyl transferase and alkaline phosphatase levels. A liver biopsy revealed findings consistent with intrahepatic cholestasis. However, despite follow-up management and cessation of the insulting drug, her total bilirubin count continuously increased to 20 mg/dL and was accompanied by intractable pruritus. A total of 9 plasmapheresis sessions were performed, and she was started on a regimen of ursodeoxycholic acid (13 mg/kg/d) and cholestyramine (4 g, 3 times daily). The clinical and laboratory picture dramatically improved following cessation of the oral contraceptive, plasmapheresis sessions, and drug treatment. The patient's cholestasis normalized within 3 months, and she recovered uneventfully. A genetic analysis of the whole family revealed that both parents were heterozygous for the mutation c.124G>A in ABCB11, and the son was homozygous for this mutation. These findings supported varying degrees of bile salt export pump deficiency in the family members. Defective bile salt excretory system function can result in a wide spectrum of clinical presentations, ranging from progressive familial intrahepatic cholestasis requiring liver transplant to late-onset drug-induced cholestasis. Our findings suggest that, in a heterozygous carrier of a progressive familial intrahepatic cholestasis mutation, drug-induced cholestasis is responsive to treatment, after which the clinical picture can normalize within 3 months. PMID:26640927

  19. Hepatocanalicular bile salt export pump deficiency in patients with progressive familial intrahepatic cholestasis

    NARCIS (Netherlands)

    Jansen, PLM; Strautnieks, SS; Jacquemin, E; Hadchouel, M; Sokal, EM; Hooiveld, GJEJ; Koning, JH; De Jager-Krikken, A; Kuipers, F; Stellaard, F; Bijleveld, CMA; Gouw, A; Van Goor, H; Thompson, RJ; Muller, M

    1999-01-01

    Background & Aims: Progressive familiar intrahepatic cholestasis (PFIC), an inherited liver disease of childhood, is characterized by cholestasis and either normal or increased serum gamma-glutamyltransferase activity. Patients with normal gamma-glutamyltransferase activity have mutations of the FIC

  20. Impaired localisation and transport function of canalicular Bsep in taurolithocholate induced cholestasis in the rat

    OpenAIRE

    Crocenzi, F A; Mottino, A D; Sánchez Pozzi, E J; Pellegrino, J M; Rodríguez Garay, E A; Milkiewicz, P.; Vore, M; Coleman, R.; Roma, M G

    2003-01-01

    Background: Taurolithocholate induced cholestasis is a well established model of drug induced cholestasis with potential clinical relevance. This compound impairs bile salt secretion by an as yet unclear mechanism.

  1. Genetic variations of bile salt transporters as predisposing factors for drug-induced cholestasis, intrahepatic cholestasis of pregnancy and therapeutic response of viral hepatitis

    OpenAIRE

    Stieger, B; Geier, A.

    2011-01-01

    INTRODUCTION: Drug-induced cholestasis, intrahepatic cholestasis of pregnancy and viral hepatitis are acquired forms of liver disease. Cholestasis is a pathophysiologic state with impaired bile formation and subsequent accumulation of bile salts in hepatocytes. The bile salt export pump (BSEP) (ABCB11) is the key export system for bile salts from hepatocytes. AREAS COVERED: This article provides an introduction into the physiology of bile formation followed by a summary of the current knowled...

  2. Optimal diagnostic strategy for infantile cholestasis in pediatric surgery

    International Nuclear Information System (INIS)

    The initial goal in treatment for infantile cholestasis is to exclude surgical cholestasis, especially biliary atresia (BA). In this study, we retrospectively reviewed the diagnostic course of infantile cholestasis. Between 2000 and 2009, a total of 44 infants with cholestasis were referred to our department. The median age at admission was 54 days (range: 0-143 days). The medical charts of these infants were reviewed. The initial diagnostic approach was ultrasonography followed by the qualitative detection of bilirubin in stool. The 35 infants with acholic stool and/or a small or absent gallbladder on ultrasonography were subsequently examined by hepatobiliary scintigraphy (HBS). Twenty-nine infants with negative scintigraphy findings underwent intraoperative cholangiography (lOC), and BA was finally confirmed in 24 of 44. A choledochal cyst was noted in 2, Alagille syndrome in 2, cytomegalovirus infection in 2, panhypopituitarism in 2, multiple hemangiomas of the liver in 1, and cholecystolithiasis in 1. The remaining 10 infants were diagnosed as having neonatal hepatitis. The sensitivity and specificity of HBS for BA were 100% and 54.5%, respectively. HBS is a useful modality for detection of BA with a sensitivity of 100%. The indication for IOC should depend on these scan results. (author)

  3. Primary amyloidosis presenting intrahepatic cholestasis and fulminant hepatic failure

    OpenAIRE

    Ozturk Ates; Kemal Kosemehmetoglu; Gunes Guner; Yusuf Bayraktar

    2015-01-01

    A 69-year-old man noticed abdominal pain located on right upper quadrant. Physical examination showed hepatosplenomegaly and icteric discoloration of sclera. On evaluation, patient was diagnosed to have hepatic amyloidosis related monoclonal gammopathy of undetermined significance (MGUS) and sinusoidal obstruction syndrome with intrahepatic cholestasis. In this case report we emphasize fulminant hepatic failure due to primer amyloidosis in diagnosed with MGUS patient.

  4. Urinary reducing substances in neonatal intrahepatic cholestasis caused by citrin deficiency

    OpenAIRE

    Ajmal Kader; Christina Ong; Veena Logarajah; Kong Boo Phua; Ee Shien Tan

    2014-01-01

    Neonatal cholestasis due to citrin deficiency is an autosomal recessive metabolic disorder caused by mutations in SLC25A13 gene. Mutations in this gene have a relatively high prevalence in East-Asian races compared to European or Afro-Caribbean races. Mutations in both sets of chromosomes often lead to self-limiting early onset cholestasis and growth retardation referred as neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). It is associated with a wide range of metabolic d...

  5. Intractable itch relieved by 4-phenylbutyrate therapy in patients with progressive familial intrahepatic cholestasis type 1

    OpenAIRE

    Hasegawa, Yasuhiro; Hayashi, Hisamitsu; Naoi, Sotaro; Kondou, Hiroki; Bessho, Kazuhiko; Igarashi, Koji; Hanada, Kentaro; Nakao, Kie; Kimura, Takeshi; Konishi, Akiko; Nagasaka, Hironori; Miyoshi, Yoko; Ozono, Keiichi; Kusuhara, Hiroyuki

    2014-01-01

    Background Progressive familial intrahepatic cholestasis type 1 (PFIC1), an inherited liver disease caused by mutations in ATP8B1, progresses to severe cholestasis with a sustained intractable itch. Currently, no effective therapy has been established for PFIC1. Decreased function of the bile salt export pump (BSEP) in hepatocytes is suggested to be responsible for the severe cholestasis observed in PFIC1. We found a previously unidentified pharmacological effect of 4-phenylbutyrate (4PB) tha...

  6. Intrahepatic cholestasis of pregnancy: When should you look further?

    Institute of Scientific and Technical Information of China (English)

    Winita Hardikar; Shivani Kansal; Ronald P J Oude Elferink; Peter Angus

    2009-01-01

    Pruritis with abnormal liver function tests is the classical presentation of intrahepatic cholestasis of pregnancy (ICP), a condition associated with significant fetal complications. Although the etiology of ICP is unclear in many cases, certain features of the clinical presentation should alert the practitioner to the possibility of an underlying metabolic defect,which may not only affect subsequent pregnancies,but may be an indicator of more serious subsequent liver disease. We report a kindred of Anglo-Celtic descent, among whom many members present with ICP, gallstones or cholestasis related to use of oral contraception. Genetic studies revealed a novel mutation in the ABCB4 gene, which codes for a phospholipid transport protein. The clinical significance of this mutation and the importance of identifying such patients are discussed.

  7. Primary amyloidosis presenting intrahepatic cholestasis and fulminant hepatic failure

    Directory of Open Access Journals (Sweden)

    Ozturk Ates

    2015-06-01

    Full Text Available A 69-year-old man noticed abdominal pain located on right upper quadrant. Physical examination showed hepatosplenomegaly and icteric discoloration of sclera. On evaluation, patient was diagnosed to have hepatic amyloidosis related monoclonal gammopathy of undetermined significance (MGUS and sinusoidal obstruction syndrome with intrahepatic cholestasis. In this case report we emphasize fulminant hepatic failure due to primer amyloidosis in diagnosed with MGUS patient.

  8. Benefit of farnesoid X receptor inhibition in obstructive cholestasis

    OpenAIRE

    Stedman, Catherine; Liddle, Christopher; Coulter, Sally; Sonoda, Junichiro; Alvarez, Jacqueline G.; Evans, Ronald M; Downes, Michael

    2006-01-01

    The nuclear hormone receptors farnesoid X receptor (FXR) and pregnane X receptor have been implicated in regulating bile acid, lipid, carbohydrate, and xenobiotic metabolism. Bile duct ligation was used to increase endogenous bile acids and evaluate the roles of these receptors in modulating cholestatic liver injury. FXR knockout (KO) mice were found to be protected from obstructive cholestasis. Concurrent deletion of FXR also could ameliorate an increase in liver injury that is seen usually ...

  9. Total biliary diversion as a treatment option for patients with progressive familial intrahepatic cholestasis and Alagille syndrome

    NARCIS (Netherlands)

    van der Woerd, Wendy L; Kokke, Freddy T; van der Zee, David C; Houwen, RHJ

    2015-01-01

    BACKGROUND: Progressive familial intrahepatic cholestasis (PFIC) with low gamma-glutamyl transpeptidase (GGT) and Alagille syndrome are associated with persistent cholestasis and severe pruritus. Various types of biliary diversion have been used to reduce this pruritus and prevent liver dysfunction.

  10. Ursodeoxycholic acid in neonatal sepsis-associated cholestasis

    Directory of Open Access Journals (Sweden)

    Rita Mey Rina

    2014-07-01

    Full Text Available Background Sepsis-associated cholestasis (SAC is an intrahe-intrahepatic cholestasis caused by inflammatory cytokines. Patients with this condition have poor prognoses. Antibiotics are the mainstay of therapy, however, other adjuvant therapies, such as ursodeoxycholic acid (UDCA, have not been well established. Objective To assess the effect of UDCA for treatment of neonatal sepsis-associated cholestasis. Methods We performed a randomized, double-blind, controlled trial in 37 neonates who were diagnosed with sepsis-associated cholestasis in the Neonatal Care Unit of Cipto Mangunkusumo Hospital. Subjects were divided into two groups, with 19 neonates randomly allocated to the intervention group (received UDCA at 30 mg/kg/day divided into 3 doses for 7 days and 18 neonates to the control group (received placebo. After 7 days of treatment, we evaluated the subjects’ liver function parameters and performed a survival analysis. Results Liver function parameter improvements at day 7 were not significantly different between the UDCA group and the control group, including for mean decrease of total bilirubin (TB levels [2.2 (SD 2.9 mg/dL vs 1.7 (SD 4.6 mg/dL; P=0.080, mean decrease of direct bilirubin (DB levels [1.1 (SD 2.3 mg/dL vs 0.6 (SD 3.6 mg/dL; P=0.080, median indirect bilirubin (IB levels [0.4 (range 0.1- 5.6 mg/dL vs 0.9 (range 0.1-4.1 mg/dL; P=0.358, mean decrease of alanine aminotransferase (ALT levels [0.5 (-80.0 - 21.0 U/L vs -2.0 (ranged -167.0 - 85.0 U/L; P= 0.730, median aspartate aminotransferase (AST levels [43.0 (range 14.0-297.0 U/L vs 150.0 (range 24.0-840.0 U/L; P=0.081, and median gamma-glutamyl transpeptidase (GGT levels [125.0 (48.0-481.0 U/L vs 235.0 (56.0-456.0 U/L; P=0.108]. Five neonates in control group died compared to two in the UDCA group (P=0.232. In addition, UDCA did not significantly lengthen the survival time (hazard ratio/HR 3.62; 95%CI 0.69 to 18.77. Conclusion Ursodeoxycholic acid tends to improve total

  11. Hepatocyte-based in vitro model for assessment of drug-induced cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, Sagnik, E-mail: Sagnik.Chatterjee@pharm.kuleuven.be [Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O and N2, Herestraat 49 — bus 921, 3000 Leuven (Belgium); Richert, Lysiane, E-mail: l.richert@kaly-cell.com [KaLy-Cell, 20A rue du Général Leclerc, 67115 Plobsheim (France); Augustijns, Patrick, E-mail: Patrick.Augustijns@pharm.kuleuven.be [Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O and N2, Herestraat 49 — bus 921, 3000 Leuven (Belgium); Annaert, Pieter, E-mail: Pieter.Annaert@pharm.kuleuven.be [Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O and N2, Herestraat 49 — bus 921, 3000 Leuven (Belgium)

    2014-01-01

    Early detection of drug-induced cholestasis remains a challenge during drug development. We have developed and validated a biorelevant sandwich-cultured hepatocytes- (SCH) based model that can identify compounds causing cholestasis by altering bile acid disposition. Human and rat SCH were exposed (24–48 h) to known cholestatic and/or hepatotoxic compounds, in the presence or in the absence of a concentrated mixture of bile acids (BAs). Urea assay was used to assess (compromised) hepatocyte functionality at the end of the incubations. The cholestatic potential of the compounds was expressed by calculating a drug-induced cholestasis index (DICI), reflecting the relative residual urea formation by hepatocytes co-incubated with BAs and test compound as compared to hepatocytes treated with test compound alone. Compounds with clinical reports of cholestasis, including cyclosporin A, troglitazone, chlorpromazine, bosentan, ticlopidine, ritonavir, and midecamycin showed enhanced toxicity in the presence of BAs (DICI ≤ 0.8) for at least one of the tested concentrations. In contrast, the in vitro toxicity of compounds causing hepatotoxicity by other mechanisms (including diclofenac, valproic acid, amiodarone and acetaminophen), remained unchanged in the presence of BAs. A safety margin (SM) for drug-induced cholestasis was calculated as the ratio of lowest in vitro concentration for which was DICI ≤ 0.8, to the reported mean peak therapeutic plasma concentration. SM values obtained in human SCH correlated well with reported % incidence of clinical drug-induced cholestasis, while no correlation was observed in rat SCH. This in vitro model enables early identification of drug candidates causing cholestasis by disturbed BA handling. - Highlights: • Novel in vitro assay to detect drug-induced cholestasis • Rat and human sandwich-cultured hepatocytes (SCH) as in vitro models • Cholestatic compounds sensitize SCH to toxic effects of accumulating bile acids • Drug

  12. Relative Frequency of Peptic Ulcer and Erosion in Patients with Different Types of Cholestasis

    Directory of Open Access Journals (Sweden)

    F Joukar

    2008-04-01

    Full Text Available Introduction: Cholestasis is impairment of normal bile excretion into the duodenum and classified as mechanical and non mechanical cholestasis. Mechanical Cholestasis presents with increase in bile duct diameter or obstruction in bile duct in an ERCP. Cholestasis leads to different complications. One of these complications is mucosal peptic erosion leading to gastrointestinal bleeding, perforation and even obstruction due to stricture. We therefore carried out this study to assess the relative frequency of peptic ulcer and erosion in patients with different type of cholestasis. Methods: In a case control study, 170 patients with mechanical cholestasis on the basis of physical examination, liver function tests, radiologic and serologic assay were candidates for ERCP as final therapeutic and diagnostic test. Collected data was registered in questionnaire and evaluated by the Fisher Test. Later, sonography (common bile duct diameter in the two groups: mechanical (85 patients and non mechanical (85 patients and endoscopy was done for exact survey and location of mucosal erosions. Results: Frequency of mucosal peptic erosions in mechanical cholestatic groups was42.6% ( 36 patients and significantly more than frequency of mucosal peptic erosion in non mechanical cholestatic groups (15 patients, 17.6% (P=0.02. 51 patients (30% of the total patients with cholestasis had mucosal erosion. From these patients, 25 patients had peptic ulcer [frequency of duodenal ulcer was 17 patients (68% and gastric ulcer was 8 patients (32% ](P=0.01. There was significant difference in prevalence of duodenal ulcer in patients with mechanical (12 cases, 70.6% and non mechanical (5 cases, 29.4% cholestasis(P=0.01. There was a significant difference between prevalence of duodenal ulcer (12 cases, 70.6% and gastric ulcer(5 cases, 29.4% in patients with mechanical cholestasis (P=0.01 but this was not so in patients with non mechanical cholestasis. Conclusion: According to

  13. Effects of ursodeoxycholic acid on intrahepatic cholestasis in rats

    Institute of Scientific and Technical Information of China (English)

    李兰娟; 徐小微; 吕芳芳; 赵年丰

    2003-01-01

    Objective To investigate the effects of treatment with ursodeoxycholic acid (UDCA) on intrahepatic cholestasis in rats, and to explore its mechanism.Method Rats suffering from intrahepatic cholestasis were treated with UDCA. Their serum alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin (TBIL), direct bilirubin (DBIL), γ-glutamyl transpeptidase (γ-GT), total cholesterol (TCH), bile flow, total bile acid excretion, total Na+ and TCH of bile were measured before and after treatment. In addition, the changes of liver tissue under microscrope were observed and recorded.Results Compared with the control group, serum ALT, ALP, TBIL, DBIL, γ-GT and TCH of rats in the treatment group decreased, while bile flow, total bile acid excretion, total Na+ and TCH decreased significantly. Degeneration of hepatocytes, infiltration of inflamed cells and proliferation of small bile ducts in the treatment group were improved under microscope.Conclusion UDCA may have therapeutic effects on cholestatic hepatitis. The mechanism may involve in its hydrophilicity, choleretic effect and immune modulation.

  14. A novel ABCB11 mutation in an Iranian girl with progressive familial intrahepatic cholestasis

    Directory of Open Access Journals (Sweden)

    Sassan Saber

    2013-01-01

    Full Text Available Progressive familial intrahepatic cholestasis is an autosomal recessive liver disorder caused by (biallelic mutations in the ATP8B1 of ABCB11 gene. A nine-year-old girl with cholestasis was referred for genetic counseling. She had a family history of cholestasis in two previous expired siblings. Genetic analysis of the ABCB11 gene led to the identification of a novel homozygous mutation in exon 25. The mutation 3593- A > G lead to a missense mutation at the amino acid level (His1198Arg. This mutation caused PFIC2 due to abnormal function in the bile salt export pump protein (BSEP.

  15. Clinical Significance of Detection of Serum TBA and ALP in Diagnosis of Intrahepatic Cholestasis of Pregnancy

    International Nuclear Information System (INIS)

    To investigate the clinical value of serum total bile acid (TBA) and alkaline phosphatase (ALP) in diagnosis of intahrpatic cholestasis of pregnancy (ICP), the serum levels of TBA, ALP and cholyglycine (CG) in 47 cases with intahrpatic cholestasis of pregnancy and 60 normal pregnant women were tested by biochemistry analysis and radioimmunoassay. The results showed that the serum levels of TBA and ALP in patients with intahrpatic cholestasis of pregnancy were significantly higher than that of normal pregnancy women. There was a positively correlation between TBA and ALP with CG. The combined determination of serum TBA and ALP could be useful in the diagnosis of intahrpatic cholestasis of pregnancy. Automatic biochemistry analysis of TBA and ALP is more simple and rapid than CG detected by radioimmunoassay,and it is suitable for clinical laboratory application. (authors)

  16. Novel A TPSB1 mutation in an adult male with progressive familial intrahepatic cholestasis

    Institute of Scientific and Technical Information of China (English)

    Bao-Cheng Deng; Sa Lv; Wei Cui; Rui Zhao; Xu Lu; Jian Wu; Pei Liu

    2012-01-01

    Progressive familial intrahepatic cholestasis type 1 is a rare disease that is characterized by low serum γ-glutamyltransferase levels due to mutation in ATP8B1.We present a 23-year-old male who experienced persistent marked pruritus for eighteen years and recurrent jaundice for thirteen years,in addition to cholestasis that eventually became fatal.Genetic sequencing studies of the entire coding (exon) sequences of ATP8B1 and ABCB11 uncovered a novel heterozygous missense 3035G>T mutation (S1012I) and a synonymous 696T>C mutation in ATP8B1.The patient's progression was associated with not only impaired familial intrahepatic cholestasis 1 (FIC1) function but also impaired bile salt export pump expression due to the impaired FIC1 function.Our findings show that patients with intermittent cholestasis can develop progressive liver disease even after several decades and require regular follow up.

  17. Operative delivery rates following induction of labour for obstetric cholestasis

    Science.gov (United States)

    Webster, Jessica R; Chappell, Lucy; Cheng, Floria; Breeze, Andrew C G; Lucas, Nuala; Plaat, Felicity; Williamson, Catherine

    2011-01-01

    The aim of this study was to determine whether women induced for obstetric cholestasis (OC) have increased rates of operative delivery compared with women without OC who are induced. This retrospective case-control study included 64 women with OC (singleton pregnancies), who had labour induced compared with two control groups (matched for parity and gestational week at delivery). The majority of women were induced at 37 weeks. We found no significant increase in the rate of operative or assisted delivery in OC cases compared with either control group. Women with OC who are induced between 36 and 40 weeks gestation do not have increased rates of assisted or operative delivery compared with induced controls.

  18. Intrahepatic cholestasis of pregnancy-current achievements and unsolved problems

    Institute of Scientific and Technical Information of China (English)

    Jurate Kondrackiene; Limes Kupcinskas

    2008-01-01

    Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-related liver disorder. Maternal effects of ICP are mild; however, there is a clear association between ICP and higher frequency of fetal distress, preterm delivery, and sudden intrauterine fetal death. The cause of ICP remains elusive, but there is evidence that mutations in genes encoding hepatobiliary transport proteins can predispose for the development of ICP. Recent data suggest that ursodeoxycholic acid is currently the most effective pharmacologic treatment, whereas obstetric management is still debated. Clinical trials are required to identify the most suitable monitoring modalities that can specifically predict poor perinatal outcome. This article aims to review current achievements and unsolved problems of ICP.

  19. An exclusively based parenteral fish-oil emulsion reverses cholestasis.

    Science.gov (United States)

    Triana Junco, Miryam; García Vázquez, Natalia; Zozaya, Carlos; Ybarra Zabala, Marta; Abrams, Steven; García de Lorenzo, Abelardo; Sáenz de Pipaón Marcos, Miguel

    2014-10-25

    Prolonged parenteral nutrition (PN) leads to liver damage. Recent interest has focused on the lipid component of PN. A lipid emulsion based on w-3 fatty acids decrease conjugated bilirubin. A mixed lipid emulsion derived from soybean, coconut, olive, and fish oils reverses jaundice. Here we report the reversal of cholestasis and the improvement of enteral feeding tolerance in 1 infant with intestinal failure-associated liver disease. Treatment involved the substitution of a mixed lipid emulsion with one containing primarily omega-3 fatty acids during 37 days. Growth and biochemical tests of liver function improved significantly. This suggests that fat emulsions made from fish oils may be more effective means of treating this condition compared with an intravenous lipid emulsion containing soybean oil, medium -chain triglycerides, olive oil, and fish oil.

  20. Role of ABCC2 common variants in intrahepatic cholestasis of pregnancy

    Institute of Scientific and Technical Information of China (English)

    Silvia Sookoian; Gustavo Castano; Carlos J Pirola

    2008-01-01

    The pathogenesis of intrahepatic cholestasis of pregnancy (ICP), a disorder that adversely affects maternal wellbeing and fetal outcome, is unclear. However, multiple factors probably interact along with a genetic predisposition. We would like to add some comments on a paper recently published concerning the role of ABCB11 and ABCC2 polymorphisms in both ICP and contraceptive-induced cholestasis, especially in the light of our recently published findings about a positive association between ICP and ABCC2 common variants.

  1. Morphologic Findings in Progressive Familial Intrahepatic Cholestasis 2 (PFIC2): Correlation With Genetic and Immunohistochemical Studies

    OpenAIRE

    Evason, Kimberley; Bove, Kevin E.; Finegold, Milton J; Knisely, A. S.; Rhee, Sue; Rosenthal, Philip; Miethke, Alexander G.; Karpen, Saul J; Ferrell, Linda D; Kim, Grace E.

    2011-01-01

    Progressive familial intrahepatic cholestasis, type 2 (PFIC2), characterized by cholestasis in infancy that may progress to cirrhosis, is caused by mutation in ABCB11, which encodes bile salt export pump (BSEP). We correlated histopathologic, immunohistochemical, and ultrastructural features in PFIC2 with specific mutations and clinical course. Twelve patients with clinical PFIC2 and ABCB11 mutations were identified, and 22 liver biopsy and explant specimens were assessed. All had hepatocellu...

  2. Cholestasis progression effects on long-term memory in bile duct ligation rats

    Directory of Open Access Journals (Sweden)

    Nasrin Hosseini

    2014-01-01

    Full Text Available Background : There is evidence that cognitive functions are affected by some liver diseases such as cholestasis. Bile duct ligation induces cholestasis as a result of impaired liver function and cognition. This research investigates the effect of cholestasis progression on memory function in bile duct ligation rats. Materials and Methods: Male Wistar rats were randomly divided into five groups, which include: control group for BDL-7, control group for BDL-21, sham group (underwent laparotomy without bile duct ligation, BDL-7 group (7 days after bile duct ligation, and BDL-21 group (21 days after bile duct ligation. Step-through passive avoidance test was employed to examine memory function. In all groups, short-term (7 days after foot shock and long-term memories (21 days after foot shock were assessed. Results: Our results showed that liver function significantly decreased with cholestasis progression (P < 0.01. Also our findings indicated BDL-21 significantly impaired acquisition time (P < 0.05. Memory retrieval impaired 7 (P < 0.05 and 21 days (P < 0.001 after foot shock in BDL-7 and BDL-21 groups, respectively. Conclusion: Based on these findings, liver function altered in cholestasis and memory (short-term and long-term memory impaired with cholestasis progression in bile duct ligation rats. Further studies are needed to better insight the nature of progression of brain damage in cholestatic disease.

  3. Urinary reducing substances in neonatal intrahepatic cholestasis caused by citrin deficiency

    Directory of Open Access Journals (Sweden)

    Ajmal Kader

    2014-06-01

    Full Text Available Neonatal cholestasis due to citrin deficiency is an autosomal recessive metabolic disorder caused by mutations in SLC25A13 gene. Mutations in this gene have a relatively high prevalence in East-Asian races compared to European or Afro-Caribbean races. Mutations in both sets of chromosomes often lead to self-limiting early onset cholestasis and growth retardation referred as neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD. It is associated with a wide range of metabolic derangements including galactosemia and aminoacidemia, which can be detected on the newborn blood spot screening. Galactose, being a reducing sugar, can also be detected using Clinitest® (Clinitest® Reagent Tablets, Bayer Corporation, Diagnostics Division, Elkhart, IN, USA, a common screening test used in the work up of metabolic and hepatic diseases. In the western population classical galactosemia is often suspected when non glucose reducing substances are detected in the urine of infants with cholestasis. However in East-Asian races the prevalence of classical galactosemia is very low whilst galactosemia due to altered uridine diphosphate-galactose epimerase activity in NICCD is more common. We present a case of NICCD in an East-Asian infant with cholestasis and persistently positive urine reducing substance. Conclusion: NICCD deficiency should be considered as a differential diagnosis in any infant with cholestasis and persistently positive urinary reducing substances.

  4. Lipoprotein Abnormalities in Cholestasis I. Electro-phoretic and Ultracentrifugal Analyses

    Directory of Open Access Journals (Sweden)

    Watanabe,Makoto

    1979-08-01

    Full Text Available The alterations of lipid composition in sera of patients with liver diseases, particularly intrahepatic cholestasis and biliary obstruction, were studied by ultracentrifugation and polyacrylamide-gel disc-electrophoresis of lipoproteins and apoproteins. The elevation of serum cholesterol in intrahepatic cholestasis was greater than in biliary obstruction. The appearance of lipoprotein X in obstructive disease accounted for most of the increased cholesterol. The level of non-lipoprotein X cholesterol in intrahepatic cholestasis was significantly elevated, this being in part ascribed to the appearance of a new class of cholestatic lipoprotein, Slow-migrating HDL. The electrophoretic pattern of lipoprotein in cholestasis was generally characterized by a decrease in alpha band intensity and, in some types of cholestasis, by the appearance of Slow-migrating HDL. In addition, other abnormal lipoproteins exhibiting the characteristics of triglyceride-rich LDL (LP-Y, LP-X-like HDL and LDL-like HDL were found in some cases of intrahepatic cholestasis and biliary obstruction.

  5. Cholestasis sepsis at neonatology ward and neonatal Intensive Care Unit Cipto Mangunkusumo Hospital 2007 : incidence, mortality rate and associated risk factors

    Directory of Open Access Journals (Sweden)

    Kadim S. Bachtiar

    2008-06-01

    Full Text Available Cholestatic jaundice represents serious pathological condition. Septic-cholestasis is a kind of hepato-cellular cholestasis that occured during or after sepsis caused by biliary flow obstruction. This is a cohort study from February to June 2007 on neonatal sepsis patients at Neonatology ward Department of Child Health Faculty of Medicine University of Indonesia-Cipto Mangunkusumo General National Hospital. Aim of this study is to find out the incidence of intrahepatic cholestasis in neonatal sepsis, associated risk factors, and mortality rate in neonatal cholestasis-sepsis. From 138 neonatal sepsis patients, the incidence of intrahepatic cholestasis is 65.9%. None of the risk factors tested in this study showed statistically significant result. Mortality rate of neonatal cholestasis-sepsis is 52.8%. (Med J Indones 2008; 17: 107-13Keywords: cholestasis intrahepatic, neonatal sepsis, cholestasis sepsis, conjugated hyperbilirubinemia

  6. Ultrasonography and computed tomography in diffuse liver disease with cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Partanen, K.; Pikkarainen, P.; Pasanen, P.; Alhava, E.; Soimakallio, S. (Kuopio Univ. Central Hospital (Finland). Dept. of Clinical Radiology Kuopio Univ. Central Hospital (Finland). Dept. of Gastroenterology Kuopio Univ. Central Hospital (Finland). Dept. of Surgery)

    1990-09-01

    Ultrasonography (US) and computed tomography (CT) were performed on respectively 67 and 42 (altogether 72) patients, for the assessment of intrahepatic cholestasis. The diagnostic ability to differentiate between malignant (17 patients) and benign (55 patients) liver disease was analyzed. Coarse echogenicity of the liver led to inconclusive results in differentiating between cirrhosis (2 out of 29 patients) and malignant infiltration (4 out of 15 patients) by US. Other benign liver diseases in 23 patients, including acute hepatitis, chronic active hepatitis, fatty liver, and liver congestion, were correctly interpreted as benign. CT correctly disclosed malignant liver disease in all cases. A false positive diagnosis of malignancy was encountered in 4 (out of 17) patients with decompensated hepatic cirrhosis because of non-homogeneous expansive areas on CT in 3 cases. The true cause was in 2 patients non-uniform fatty infiltration, and in one patient with acute hepatitis A, small hypodense lesions. Among cholestatic patients, decompensated cirrhosis and malignant liver infiltration could not always be differentiated on US or CT. (orig.).

  7. Intra-hepatic cholestasis of pregnancy: A comprehensive review

    Directory of Open Access Journals (Sweden)

    Sangita Ghosh

    2013-01-01

    Full Text Available Intra-hepatic cholestasis of pregnancy is a cholestatic disorder characterized by i pruritus, with onset in the third trimester of pregnancy, without any primary skin lesions, ii elevated fasting serum bile acids > 10 μmol / L (and elevated serum transaminases, iii spontaneous relief of signs and symptoms within two to three weeks after delivery, and iv absence of other disease that cause pruritus and jaundice. It is believed to be a multi-factorial disease with interplay between genetic, environmental and hormonal factors. Incidence is between 0.02% to 2.4% of all pregnancies; with wide geographical variations. Maternal prognosis is usually good but can result in adverse fetal outcomes like meconium staining of amniotic fluid, fetal bradycardia and even fetal loss. Response to anti-histaminic is poor. Of all the medical therapies that have been described for the treatment for IHCP, ursodeoxycholic acid has the best response in relieving pruritus in mother, and probably has a role in preventing even the perinatal complications. Timely diagnosis and treatment is urged in order to prevent fetal complications and an early delivery between 37 to 38 weeks should be contemplated in severe cases, especially once fetal lung maturity is attained.

  8. Curcumin protects ANIT-induced cholestasis through signaling pathway of FXR-regulated bile acid and inflammation.

    Science.gov (United States)

    Yang, Fan; Tang, Xiaowen; Ding, Lili; Zhou, Yue; Yang, Qiaoling; Gong, Junting; Wang, Guangyun; Wang, Zhengtao; Yang, Li

    2016-01-01

    Cholestasis is a clinically significant symptom and widely associated with liver diseases, however, there are very few effective therapies for cholestasis. Danning tablet (DNT, a Chinese patent medicine preparation) has been clinically used to treat human liver and gallbladder diseases for more than 20 years in China. However, which ingredients of DNT contributed to this beneficial effect and their mechanistic underpinnings have been largely unknown. In the present study, we discovered that DNT not only demonstrated greater benefits for cholecystitis patients after cholecystectomy surgery in clinic but also showed protective effect against alpha-naphthylisothiocyanate (ANIT)-induced cholestasis model in rodent. Curcumin, one major compound derived from DNT, exerted the protective effect against cholestasis through farnesoid X receptor (FXR), which has been focused as potential therapeutic targets for treating cholestasis. The underlying mechanism of curcumin against cholestasis was restoring bile acid homeostasis and antagonizing inflammatory responses in a FXR-dependent manner and in turn contributed to overall cholestasis attenuation. Collectively, curcumin can be served as a potential treatment option for liver injury with cholestasis. PMID:27624003

  9. Prolonged cholestasis following successful removal of common bile duct stones: Beware patients on estrogen therapy

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    There are various well described forms of chronic cholestatic jaundice in adults, such as autoimmune cholangitis, drug-induced cholangitis and intrahepatic cholestasis of pregnancy. We present two cases of prolonged cholestasis following removal of gallstones at endoscopic retrograde cholangiopancreatography (ERCP) and subsequent clear cholangiography. Both patients were taking oral estrogens at the time of presentation, which were subsequently withdrawn. The first case responded rapidly to corticosteroid treatment,and the second case had a much slower resolution with ursodeoxycholic acid. Both cases highlighted the significance of estrogen-induced cholestasis in female patients with protracted jaundice following ERCP and removal of intra-ductal stones. After oral estrogens are discontinued, a short course of steroids needs to be considered.

  10. Cholestasis and Hepatic Failure in a Neonate: A Case Report of Severe Pyruvate Kinase Deficiency.

    Science.gov (United States)

    Olivier, François; Wieckowska, Anna; Piedboeuf, Bruno; Alvarez, Fernando

    2015-11-01

    Unexpected severe cholestasis is part of the presentation in some neonates with hemolytic anemia but is usually self-resolving. Here we report the case of a neonate with pyruvate kinase deficiency (PKD) who presented severe hemolytic anemia at birth, characterized by a rapidly progressive and severe cholestasis with normal γ-glutamyl transpeptidase level associated with hepatic failure. After an extensive investigation to rule out contributing conditions explaining the severity of this patient's clinical presentation, PKD has remained the sole identified etiology. The patient abruptly died of sepsis at 3 months of age before a planned splenectomy and ongoing evaluation for liver transplantation. To the best of our knowledge, only a few similar cases of severe neonatal presentation of PKD complicated with severe hepatic failure and cholestasis have been reported.

  11. Impaired Itching Perception in Murine Models of Cholestasis Is Supported by Dysregulation of GPBAR1 Signaling.

    Directory of Open Access Journals (Sweden)

    Sabrina Cipriani

    Full Text Available In cholestatic syndromes, body accumulation of bile acids is thought to cause itching. However, the mechanisms supporting this effect remain elusive. Recently, GPBAR1 (TGR5 a G-protein coupled receptor has been shown to mediate itching caused by intradermal administration of DCA and LCA. 6α-ethyl-3α, 7α-dihydroxy-24-nor-5β-cholan-23-ol (BAR502 is a non-bile acid dual ligand for FXR and GPBAR1.Cholestasis was induced in wild type and GPBAR1-/- mice by administration of α-naphthyl-isothiocyanate (ANIT or 17α-ethynylestradiol.In naïve mice skin application of DCA, TLCA, 6-ECDCA, oleanolic and betulinic acid induces a GPBAR1 dependent pruritogenic response that could be desensitized by re-challenging the mice with the same GPBAR1 agonist. In wild type and GPBAR1-/- mice cholestasis induced by ANIT fails to induce spontaneous itching and abrogates scratching behavior caused by intradermal administration of DCA. In this model, co-treatment with BAR502 increases survival, attenuates serum alkaline phosphatase levels and robustly modulates the liver expression of canonical FXR target genes including OSTα, BSEP, SHP and MDR1, without inducing pruritus. Betulinic acid, a selective GPBAR1 ligand, failed to rescue wild type and GPBAR1-/- mice from ANIT cholestasis but did not induced itching. In the 17α-ethynylestradiol model BAR502 attenuates cholestasis and reshapes bile acid pool without inducing itching.The itching response to intradermal injection of GPBAR1 agonists desensitizes rapidly and is deactivated in models of cholestasis, explain the lack of correlation between bile acids levels and itching severity in cholestatic syndromes. In models of non-obstructive cholestasis, BAR502 attenuates liver injury without causing itching.

  12. Anabolic Androgen-induced Intrahepatic Cholestasis Presented With Normal AND#947;-Glutamyl-Transpeptidase

    Directory of Open Access Journals (Sweden)

    Savvoula Savvidou

    2014-04-01

    A case report of a young male with remarkable jaundice due to acute anabolic androgen-induced cholestasis is presented. Interestingly, and #947;-glutamyl transpeptidase remained normal throughout the patient's diagnostic workup. Histopathology was indicative of pure, and ldquo;bland and rdquo; intrahepatic cholestasis with minimal inflammation but significant fibrosis. The patient was successfully treated with ursodeoxycholic acid and glucocorticosteroids. The significance of normal and #947;-glutamyl transpeptidase along with the histopathological findings and the possible pathophysiological mechanisms are finally discussed. [J Interdiscipl Histopathol 2014; 2(2.000: 98-103

  13. [Value of injection hepato-lymphography during percutaneous transhepatic cholangiography in patients with cholestasis].

    Science.gov (United States)

    Sharipov, V Sh

    2000-01-01

    Injection hepatography (IH) was made in 278 patients with cholestasis to study the drainage function of the liver. In 208 cases. IH was performed as a test during percutaneous transhepatic cholangiography (PTHC). The hepatic lymph pathways were imaged in 167 (60%) patients. Images of the biliary tract were obtained in 245 (88.1%) patients with cholestasis, it being not dilated in 34 (12.2%) patients. The fact that hepatolymphography may be performed during PTHC as an independent test permits verification of hepatic lymph circulatory disorders that are an index of the rate of inflammation in the organ. PMID:12717913

  14. Value of injection hepato lymphography during percutaneous transhepatic cholangiography in patients with cholestasis

    International Nuclear Information System (INIS)

    Injection hepatography (IH) was made in 278 patients with cholestasis to study the drainage function of the liver. In 208 cases, IH was performed as a test during percutaneous transhepatic cholangiography (PTHC). Hepatic lymph pathways were imaged in 167 (60%) patients. Images of the biliary tract were obtained in 245 (88.1%) patients with cholestasis, it being not dilated in 34 (12.2%) patients. The fact that hepatolymphography may be performed during PTHC as an independent test permits verification of hepatic lymph circulatory disorders that are an index of the rate of inflammation in the organ

  15. Unusual case of drug-induced cholestasis due to glucosamine and chondroitin sulfate

    Institute of Scientific and Technical Information of China (English)

    Stephen; Ip; Rachel; Jeong; David; F; Schaeffer; Eric; M; Yoshida

    2015-01-01

    Glucosamine(GS) and chondroitin sulfate(CS) are common over-the-counter(OTC) supplements used in the treatment of osteoarthritis. These medications are seemingly safe, but there are increasing reports of hepatotoxicity with these supplements. We reported a unique case of drug-induced cholestasis caused by GS and CS in a combination tablet. The etiology of the jaundice was overlooked despite extensive investigations over a three-month period. Unlike drug-induced hepatocellular injury, drug-induced cholestatic jaundice with GS and CS has only been reported twice before. This case emphasizes the importance of a complete medication history, especially OTC supplements, in the assessment of cholestasis.

  16. Male sex predisposes the newborn surgical patient to parenteral nutrition-associated cholestasis and to sepsis

    NARCIS (Netherlands)

    Albers, MJIJ; de Gast-Bakker, DAH; van Dam, NAM; Madern, GC; Tibboel, D

    2002-01-01

    Hypothesis: Sepsis is an epiphenomenon of parenteral nutrition-associated cholestasis (PNAC) and not a causative factor, and the incidence of sepsis is not affected by the presence or absence of PNAC. Design: Observational cohort study. Setting: Pediatric surgery department in a tertiary referral ch

  17. Hepatobiliary scintigraphy in chronic intrahepatic cholestasis. Diagnosis of primary sclerosing cholangitis

    Energy Technology Data Exchange (ETDEWEB)

    Aburano, Tamio; Takayama, Teruhiko; Shuke, Noriyuki

    1987-05-01

    Primary sclerosing cholangitis (PSC) is a rare disease of unknown origin, leading to chronic intermittent cholestasis. Due to its low incidence, insidious clinical onset and varied clinical picture, the diagnosis is often delayed by years. PSC is sometimes diagnosed falsely as another disease of chronic intermittent cholestasis, primary biliary cirrhosis (PBC). In the present study, the hepatobiliary imaging with Tc-99m diethyl IDA was done in a total of 14 patients with chronic intermittent cholestasis including 3 patients with PSC and 11 patients with PBC, in order to decide its clinical usefulness as a noninvasive method for the differentiation between PSC and PBC. All three patients with PSC showed a typical pattern of radionuclide stasis within the area of intrahepatic and/or extrahepatic ductal system, representing the stenosis on endoscopic retrograde cholangiogram. On the other hand, none of 11 patients with PBC showed any radionuclide stasis within the area of intrahepatic and/or extrahepatic ductal system. This result suggests that the radionuclide hepatobiliary imaging may be a noninvasive method for investigating patients with chronic intermittent cholestasis, leading to earlier differentiation between PSC and PBC.

  18. [Relative increase and metacritic aggravation in the diagnosis of anicteric cholestasis].

    Science.gov (United States)

    Albot, G; Geraudias, P; Kind, M

    1975-02-14

    The authors report 3 cases and report the diagnostic usefulness of two signs of minor cholestasis described by one of them in 1966. A relative increase, in the absence of obvious virus hepatitis or cirrhosis, of the serum bilirubin, cholesterol, lipids and alkaline phosphatase, together with B.S.P. excretion. suggest minor cholestasis. The sign of "metacritical aggravation" when there is some suspicion of minor cholestasis, the supervision of the course of the disease, or a retrospective inquiry, permit, in the presence of minor symptoms, such as, pain, fever, jaundice, or pruritus, one to make the diagnosis of minor cholestasis. The latter is due either to the presence of small gall stones in the common bile duct, or to inflammation of the ampulla of Vater, or sphincter of Oddi, a Vaterian ampulloma, pancreatitis, or following damage to the common bile duct. In practice, liver biopsy confirms the diagnosis, and intravenous cholangiography, by the perfusion method, is usually able to demonstrate obstruction of the common bile duct. PMID:169583

  19. Urinary excretion of bile acid glucosides and glucuronides in extrahepatic cholestasis.

    Science.gov (United States)

    Wietholtz, H; Marschall, H U; Reuschenbach, R; Matern, H; Matern, S

    1991-04-01

    Recently the formation of bile acid glucosides has been described as a novel conjugation mechanism in vitro and in vivo. In 10 patients with extrahepatic cholestasis caused by carcinoma of the head of the pancreas we investigated excretion rates and profiles of urinary bile acid glucosides. Urinary bile acid glucosides and, for comparison, bile acid glucuronides were extracted and characterized according to established methods. In controls total urinary bile acid glucoside excretion was 0.22 +/- 0.03 mumol/24 hr (mean +/- S.E.M.)-in the range of bile acid glucuronide excretion (0.41 +/- 0.06 mumol/24 hr; mean +/- S.E.M.). A gas chromatography-mass spectrometry-characterized trihydroxy bile acid glucoside of still-unknown hydroxyl positions accounted for 65% of total urinary bile acid glucosides. In extrahepatic cholestasis total urinary bile acid glucoside excretion was 0.52 +/- 0.13 mumol/24 hr (mean +/- SEM), yet significantly lower than bile acid glucuronide excretion (1.53 +/- 0.13 mumol/24 hr; mean +/- SEM; p less than 0.001). In cholestasis the primary bile acid derivatives cholic and chenodeoxycholic acid glucosides amounted to 90%, whereas the trihydroxy bile acid glucoside had decreased to 5% of total bile acid glucoside excretion, indicating its alteration during enterohepatic circulation. The data establish the composition and quantity of urinary bile acid glucosides in healthy controls and cholestasis and constitute a quantitative comparison with another glycosidic conjugation reaction, bile acid glucuronidation.

  20. Hydrolysed Formula Is a Risk Factor for Vitamin K Deficiency in Infants With Unrecognised Cholestasis

    NARCIS (Netherlands)

    van Hasselt, P. M.; de Vries, W.; de Vries, E.; Kok, K.; Cranenburg, E. C. M.; de Koning, T. J.; Schurgers, L. J.; Verkade, H. J.; Houwen, R. H. J.; Havinga, Rick

    2010-01-01

    Objectives: Vitamin K deficiency (VKD) may cause life-threatening haemorrhages, especially in breast-fed infants with unrecognised cholestasis. Interestingly, hypoallergenic formulas appear overrepresented in reported cases of VKD bleeding (VKDB) in formula-fed infants. We therefore assessed whether

  1. Enteral obeticholic acid prevents hepatic cholestasis in total parenteral nutrition-fed neonatal pigs

    Science.gov (United States)

    Total parenteral nutrition (TPN) is a vital support for neonatal infants with congenital or acquired gastrointestinal (GI) disorders and requiring small bowel resection. An adverse outcome associated with prolonged TPN use is parenteral nutrition associated cholestasis (PNAC). We previously showed t...

  2. Genetics and Molecular Modeling of New Mutations of Familial Intrahepatic Cholestasis in a Single Italian Center.

    Directory of Open Access Journals (Sweden)

    Isabella Giovannoni

    Full Text Available Familial intrahepatic cholestases (FICs are a heterogeneous group of autosomal recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin. Three distinct forms are described: FIC1 and FIC2, associated with low/normal GGT level in serum, which are caused by impaired bile salt secretion due to defects in ATP8B1 encoding the FIC1 protein and defects in ABCB11 encoding bile salt export pump protein, respectively; FIC3, linked to high GGT level, involves impaired biliary phospholipid secretion due to defects in ABCB4, encoding multidrug resistance 3 protein. Different mutations in these genes may cause either a progressive familial intrahepatic cholestasis (PFIC or a benign recurrent intrahepatic cholestasis (BRIC. For the purposes of the present study we genotyped 27 children with intrahepatic cholestasis, diagnosed on either a clinical or histological basis. Two BRIC, 23 PFIC and 2 BRIC/PFIC were identified. Thirty-four different mutations were found of which 11 were novel. One was a 2Mb deletion (5'UTR- exon 18 in ATP8B1. In another case microsatellite analysis of chromosome 2, including ABCB11, showed uniparental disomy. Two cases were compound heterozygous for BRIC/PFIC2 mutations. Our results highlight the importance of the pathogenic role of novel mutations in the three genes and unusual modes of their transmission.

  3. Mrp2 is essential for estradiol-17 beta(beta-D-glucuronide)-induced cholestasis in rats

    NARCIS (Netherlands)

    Huang, LY; Smit, JW; Meijer, DKF; Vore, M

    2000-01-01

    The present study evaluates the roles of the multidrug resistance-1 P-glycoprotein, Mdr1a/1b, the bile salt export pump (Bsep), and the multidrug resistance-associated protein-2 (Mrp2) in mediating cholestasis induced by estradiol-17 beta(beta-D-glucuronide) (E(2)17G). Administration of [H-3]E(2)17G

  4. Genetics and Molecular Modeling of New Mutations of Familial Intrahepatic Cholestasis in a Single Italian Center

    Science.gov (United States)

    Giovannoni, Isabella; Callea, Francesco; Bellacchio, Emanuele; Torre, Giuliano; De Ville De Goyet, Jean; Francalanci, Paola

    2015-01-01

    Familial intrahepatic cholestases (FICs) are a heterogeneous group of autosomal recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin. Three distinct forms are described: FIC1 and FIC2, associated with low/normal GGT level in serum, which are caused by impaired bile salt secretion due to defects in ATP8B1 encoding the FIC1 protein and defects in ABCB11 encoding bile salt export pump protein, respectively; FIC3, linked to high GGT level, involves impaired biliary phospholipid secretion due to defects in ABCB4, encoding multidrug resistance 3 protein. Different mutations in these genes may cause either a progressive familial intrahepatic cholestasis (PFIC) or a benign recurrent intrahepatic cholestasis (BRIC). For the purposes of the present study we genotyped 27 children with intrahepatic cholestasis, diagnosed on either a clinical or histological basis. Two BRIC, 23 PFIC and 2 BRIC/PFIC were identified. Thirty-four different mutations were found of which 11 were novel. One was a 2Mb deletion (5’UTR- exon 18) in ATP8B1. In another case microsatellite analysis of chromosome 2, including ABCB11, showed uniparental disomy. Two cases were compound heterozygous for BRIC/PFIC2 mutations. Our results highlight the importance of the pathogenic role of novel mutations in the three genes and unusual modes of their transmission. PMID:26678486

  5. Toxicity of taurolithocholate as a model for cholestasis in the rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Spitzer, V.M.; Loo, C.Y.

    1985-05-01

    A model was investigated to facilitate the detection of mild diffuse liver disease. The introduction of sodium taurolithocholate(TLC) into the bloodstream of rats has been shown to produce cholestasis. This study was undertaken to assess the available control over the cholestatic effect with regulated TLC. The rat model then utilized to evaluate the ability of Tc-99m Hepatolite (IDA) to predict the extent of cholestasis in mildly diseased liver. 27 Charles River rats (300-350 grams) were studied. Pentabarbital was used for anesthesia and body temperature was maintained between 37.5 and 38.5/sup 0/C. A standard tracheostomy and jugular vein and carotid artery cannulation was performed for the administration of the TLC and IDA and for blood sampling. The common bile duct was cannulated for bile collection. Bile was collected for 10 minutes post surgery and then the TLC, or just vehicle for controls, was administered. 5 minute bile collections continued for 60 minutes and blood samples were collected 9 times during the same hour period. The cumulative percent dose of IDA in the bile was found to be controllable while the blood clearance was not appreciably different for the doses investigated. Doses of 5.0, 3.75, 2.75 and 0 micromoles of TLC per 100 grams of rat weight were found to yield a 85%, 68% 45% and 15% cholestatic effect. The 45% cholestasis is reproducible and most clinically interesting the authors' studies. The 15% cholestasis for the control rats demonstrates a baseline cholestasis from the surgical intervention.

  6. Alteration in male reproductive system in experimental cholestasis: roles for opioids and nitric oxide overproduction.

    Science.gov (United States)

    Kiani, Samira; Valizadeh, Behzad; Hormazdi, Bahram; Samadi, Hoda; Najafi, Tahereh; Samini, Morteza; Dehpour, Ahmad R

    2009-08-01

    Cirrhosis is associated with impairment of the male reproductive system, hypogonadism and feminization. It is important to rule out whether the impairment in the reproductive system exists earlier in the course of cholestatic liver disease to target effective therapies at the best time point. In this study we investigated the role of endogenous opioid and nitric oxide system in alterations of the reproductive system in male rats. We performed sham or bile duct ligation surgery on male Sprague-Dawley rats and treated the animals for seven days with saline, naltrexone, an opioid receptor blocker (20 mg/kg) and N (G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor (10 mg/kg). We then evaluated the plasma level of testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH), sperm count and motility as well as biomarkers of cholestasis and nitric oxide productions. The results showed that following cholestasis, total testosterone level decrease and LH level increase in plasma of cholestatic rats and treatment with L-NAME and naltrexone could improve the plasma level of testosterone. Naltrexone could decrease the elevated level of LH in cholestatic animals. In addition, the weight of seminal vesicles and prostate significantly decreased in cholestasis as compared to the control group and treatment with L-NAME and naltrexone could improve the weights of the two organs in cholestasis. Our results demonstrate for the first time that the male reproductive system is impaired early in cholestasis and that endogenous opioid and nitric oxide system contribute to these impairments in the early course of the disease. PMID:19445924

  7. Intrahepatic Cholestasis of Pregnancy Levels of Sulfated Progesterone Metabolites Inhibit Farnesoid X Receptor Resulting in a Cholestatic Phenotype

    OpenAIRE

    Abu-Hayyeh, Shadi; Papacleovoulou, Georgia; Lövgren-Sandblom, Anita; Tahir, Mehreen; Oduwole, Olayiwola; Jamaludin, Nurul Akmal; Ravat, Sabiha; Nikolova, Vanya; Chambers, Jenny; Selden, Clare; Rees, Myrddin; Marschall, Hanns-Ulrich; Parker, Malcolm G.; Williamson, Catherine

    2013-01-01

    Intrahepatic cholestasis of pregnancy (ICP) is the most prevalent pregnancy-specific liver disease and is associated with an increased risk of adverse fetal outcomes, including preterm labor and intrauterine death. The endocrine signals that cause cholestasis are not known but 3α-sulfated progesterone metabolites have been shown to be elevated in ICP, leading us to study the impact of sulfated progesterone metabolites on farnesoid X receptor (FXR)-mediated bile acid homeostasis pathways. Here...

  8. Sustained Repression and Translocation of NTCP and Expression of MRP4 for Cholestasis after Rat 90% Partial Hepatectomy

    OpenAIRE

    Miura, Takuya; Kimura, Norihisa; Yamada, Toshiyuki; Shimizu, Takeshi; Nanashima, Naoki; YAMANA, DAISUKE; HAKAMADA, KENICHI; Tsuchida, Shigeki

    2013-01-01

    Background/Aims: To clarify the mechanism of persistent cholestasis after massive hepatectomy, the relationship between such cholestasis and the expression and localization of organic anion transporters for bile acids was examined in a rat model.Methods: Male Sprague-Dawley rats were subjected to 90% hepatectomy, and tissues were harvested on 0, 1, 3, and 7 days for microarray analysis, the quantitative real-time polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry to...

  9. Liver transplant rejection and cholestasis: Comparison of technetium 99m-diisopropyl iminodiacetic acid hepatobiliary imaging with liver biopsy

    International Nuclear Information System (INIS)

    To determine whether the scintigraphic evaluation of technetium-99m diisopropyl iminodiacetic acid (DISIDA) uptake and excretion can distinguish among liver transplant patients with biopsy evidence for rejection, cholestasis or neither condition, we reviewed scintigrams and biopsies in 36 patients. There were 76 scintigrams with corresponding biopsies. Uptake and excretion were graded from image data on scales reflecting normal through severely abnormal values. Biopsies were evaluated for findings of cholestasis and rejection. The majority of scintigrams demonstrated normal uptake (60/75, 80%) and delayed excretion (65/76, 85%), which was most marked immediately after transplantation. One-way analysis of variance showed that the mean excretion values significantly differed between patients with normal biopsies and those with cholestasis and/or rejection (P=0.0003). However, mean uptake scores demonstrated no statistically significant difference between these two groups of patients (P=0.1). These findings suggest that 99m-Tc-DISIDA scintigraphy can differentiate between transplants with and without rejection/cholestasis but not between rejection and cholestasis. If 99m-Tc-DISIDA excretion is normal, rejection and cholestasis and unlikely. (orig.)

  10. Successful Outcome of Chronic Intrahepatic Cholestasis in an Adult Patient with Sickle Cell/β+ Thalassemia

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    Efthymia Vlachaki

    2014-01-01

    Full Text Available Sickle cell/β+ thalassemia (Hb S/β+thal is considered as a variant form of sickle cell disease. Acute episodes of vasoocclusive pain crisis are characteristic for sickle cell disorders and may be complicated by an acute or chronic life-threatening organ dysfunction. Chronic intrahepatic cholestasis is a rare and severe complication in sickle cell disease, characterized by marked hyperbilirubinemia and acute hepatic failure with an often fatal course. Despite the fact that patients with Hb S/β+thal usually have a mild type of disease, herein we describe an interesting case of chronic intrahepatic cholestasis with successful outcome in an adult patient with Hb S/β+thal.

  11. Severe Cholestasis and Bile Acid Nephropathy From Anabolic Steroids Successfully Treated With Plasmapheresis.

    Science.gov (United States)

    Flores, Avegail; Nustas, Rosemary; Nguyen, Hoang-Lan; Rahimi, Robert S

    2016-01-01

    Severe cholestasis with anabolic androgenic steroids is well-known to cause acute liver injury. Treatment is usually supportive after withdrawal of the offending agent. Acute kidney injury (AKI) frequently occurs in acute liver injury and may complicate management and prognosis. We highlight the use of plasmapheresis resulting in rapid improvement in cholestatic jaundice with resolution of AKI. Plasmapheresis should be considered in special cases in which there is progressive clinical decline despite supportive care. PMID:26958570

  12. Experimental cholestasis promotes the deposition of glomerular IgA immune complexes.

    OpenAIRE

    Emancipator, S. N.; Gallo, G. R.; Razaboni, R.; Lamm, M. E.

    1983-01-01

    Previous experimental and clinical studies support a role for the hepatobiliary system in the clearance of oligomeric IgA from serum, and alterations of this system have been associated with the deposition of IgA in the renal mesangium. The present studies in mice address the question of whether the mesangial deposition of IgA following cholestasis includes immune complexes. While bile duct ligation resulted in mesangial IgA deposition within several days in approximately 75% of animals, whet...

  13. Intrahepatic Cholestasis of Pregnancy and Serum Bile Acids in HIV-Infected Pregnant Women

    OpenAIRE

    Weinberg, Adriana; Allshouse, Amanda; Kinzie, Kay; Cho, Alice; Davies, Jill K.; Mc Farland, Elizabeth J

    2015-01-01

    Objectives Intra-hepatic cholestasis of pregnancy (ICP) is uncommon, but has severe effects on pregnancy outcomes. ICP is characterized by elevated serum bile acids and liver enzymes and preferentially affects women with liver disorders. We compared bile acids and pregnancy outcomes of HIV-infected pregnant women, who commonly have elevated live enzymes, with uninfected controls. Methods Twenty-four HIV-infected, including 2 co-infected with hepatitis C virus (HCV), and 25 uninfected women we...

  14. Partial Internal Biliary Diversion: A Solution for Intractable Pruritus in Progressive Familial Intrahepatic Cholestasis Type 1

    Science.gov (United States)

    Ganesh, Ramaswamy; Suresh, Natarajan; Sathiyasekeran, Malathi; Ramachandran, Priya

    2011-01-01

    Biliary diversion offers a potential option for intractable pruritus in children with chronic cholestatic disorders. Progressive familial intrahepatic cholestasis (PFIC) is an inherited disorder of impaired bile acid transport and excretion, which presents with jaundice and pruritus in the first few months of life and progresses to cirrhosis by infancy or adolescence. We report a child with PFIC type 1 who underwent internal biliary diversion for intractable pruritus and was relieved of his symptoms. PMID:21546727

  15. Effects of Three Different Fibrates on Intrahepatic Cholestasis Experimentally Induced in Rats

    OpenAIRE

    Alaa El-Sisi; Sahar Hegazy; Eman El-Khateeb

    2013-01-01

    Background. Activation of PPAR α modulates cholesterol metabolism and suppresses bile acid synthesis. This study aims to evaluate the effect of PPAR α agonists, fenofibrate, bezafibrate, and gemfibrozil, on acute cholestasis induced by ethinylestradiol (EE) plus chlorpromazine (CPZ) in rats. Method. 100 male albino rats (150–200 gm) were divided randomly into 10 equal groups. Control group received 1% methylcellulose vehicle; disease group received CPZ plus EE for 5 consecutive days; four gro...

  16. Novel ABCB11 mutations in a Thai infant with progressive familial intrahepatic cholestasis

    OpenAIRE

    Treepongkaruna, Suporn; Gaensan, Amornphun; Pienvichit, Paneeya; Luksan, Ondrej; Knisely, AS; Sornmayura, Pattana; Jirsa, Milan

    2009-01-01

    Progressive familial intrahepatic cholestasis (PFIC) type 2 is caused by mutations in ABCB11, which encodes bile salt export pump (BSEP). We report a Thai female infant who presented with progressive cholestatic jaundice since 1 mo of age, with normal serum γ-glutamyltransferase. Immunohistochemical staining of the liver did not demonstrate BSEP along the canaliculi, while multidrug resistance protein 3 was expressed adequately. Novel mutations in ABCB11, a four-nucleotide deletion in exon 3,...

  17. Autoimmune BSEP disease: disease recurrence after liver transplantation for progressive familial intrahepatic cholestasis.

    Science.gov (United States)

    Kubitz, Ralf; Dröge, Carola; Kluge, Stefanie; Stross, Claudia; Walter, Nathalie; Keitel, Verena; Häussinger, Dieter; Stindt, Jan

    2015-06-01

    Severe cholestasis may result in end-stage liver disease with the need of liver transplantation (LTX). In children, about 10 % of LTX are necessary because of cholestatic liver diseases. Apart from bile duct atresia, three types of progressive familial intrahepatic cholestasis (PFIC) are common causes of severe cholestasis in children. The three subtypes of PFIC are defined by the involved genes: PFIC-1, PFIC-2, and PFIC-3 are due to mutations of P-type ATPase ATP8B1 (familial intrahepatic cholestasis 1, FIC1), the ATP binding cassette transporter ABCB11 (bile salt export pump, BSEP), or ABCB4 (multidrug resistance protein 3, MDR3), respectively. All transporters are localized in the canalicular membrane of hepatocytes and together mediate bile salt and phospholipid transport. In some patients with PFIC-2 disease, recurrence has been observed after LTX, which mimics a PFIC phenotype. It could be shown by several groups that inhibitory anti-BSEP antibodies emerge, which most likely cause disease recurrence. The prevalence of severe BSEP mutations (e.g., splice site and premature stop codon mutations) is very high in this group of patients. These mutations often result in the complete absence of BSEP, which likely accounts for an insufficient auto-tolerance against BSEP. Although many aspects of this "new" disease are not fully elucidated, the possibility of anti-BSEP antibody formation has implications for the pre- and posttransplant management of PFIC-2 patients. This review will summarize the current knowledge including diagnosis, pathomechanisms, and management of "autoimmune BSEP disease." PMID:25342496

  18. Fasciola hepatica infestation as a very rare cause of extrahepatic cholestasis

    Institute of Scientific and Technical Information of China (English)

    Ahmet Dobrucali; Rafet Yigitbasi; Yusuf Erzin; Oguzhan Sunamak; Erdal Polat; Hakan Yakar

    2004-01-01

    Fasciola hepatica, an endemic parasite in Turkey, is still a very rare cause of cholestasis worldwide. Through ingestion of contaminated water plants like watercress, humans can become the definitive host of this parasite. Cholestatic symptoms may be sudden but in some cases they may be preceeded by a long period of fever, eosinophilia and vague gastrointestinal symptoms. We report a woman with cholangitis symptoms of sudden onset which was proved to be due to Fasciola hepatica infestation by an endoscopic retrograde cholangiography.

  19. Influence of distal ileum exclusion on hepatic and renal functions in presence of extrahepatic cholestasis

    Directory of Open Access Journals (Sweden)

    Evandro Luis de Oliveira Costa

    2014-04-01

    Full Text Available OBJECTIVE: To verify whether the ileal exclusion interferes with liver and kidney functional changes secondary to extrahepatic cholestasis. METHODS: We studied 24 rats, divided into three groups with eight individuals each: Group 1 (control, Group 2 (ligation of the hepatic duct combined with internal biliary drainage, and Group 3 (bile duct ligation combined with internal biliary drainage and exclusion of the terminal ileum. Animals in Group 1 (control underwent sham laparotomy. The animals of groups 2 and 3 underwent ligation and section of the hepatic duct and were kept in cholestasis for four weeks. Next, they underwent an internal biliary bypass. In Group 3, besides the biliary-enteric bypass, we associated the exclusion of the last ten centimeters of the terminal ileum and carried out an ileocolic anastomosis. After four weeks of monitoring, blood was collected from all animals of the three groups for liver and kidney biochemical evaluation (albumin, ALT, AST, direct and indirect bilirubin, alkaline phosphatase, cGT, creatinine and urea. RESULTS: there were increased values of ALT, AST, direct bilirubin, cGT, creatinine and urea in rats from Group 3 (p < 0.05. CONCLUSION: ileal exclusion worsened liver and kidney functions in the murine model of extrahepatic cholestasis, being disadvantageous as therapeutic procedure for cholestatic disorders.

  20. Cholestasis in a murine experimental model: lesions include hepatocyte ischemic necrosis

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    Prado Ivete Bedin

    2003-01-01

    Full Text Available OBJECTIVE: To establish a murine experimental model of bile duct obstruction that would enable controlled observations of the acute and subacute phases of cholestasis. METHODOLOGY: Adult male isogenic BALB/c mice underwent a bile duct ligation (22 animals or a sham operation (10 animals. Fifteen days after surgery, or immediately after the animal's death, macroscopic findings were noted and histological study of the liver, biliary tree, and pancreas was performed (hematoxylin-eosin and Masson trichromic staining. RESULTS: Beginning 24 hours after surgery, all animals from the bile duct ligation group presented progressive generalized malaise. All animals presented jaundice in the parietal and visceral peritoneum, turgid and enlarged liver, and accentuated dilatation of gallbladder and common bile duct. Microscopic findings included marked dilatation and proliferation of bile ducts with accentuated collagen deposits, frequent areas of ischemic necrosis, hepatic microabscesses, and purulent cholangitis. Animals from the sham operation group presented no alterations. CONCLUSION: We established a murine experimental model of induced cholestasis, which made it possible to study acute and subacute tissue lesions. Our data suggests that in cholestasis, hepatic functional ischemia plays an important role in inducing hepatic lesions, and it also suggests that the infectious process is an important factor in morbidity and mortality.

  1. Expression and function of renal and hepatic organic anion transporters in extrahepatic cholestasis

    Institute of Scientific and Technical Information of China (English)

    Anabel Brandoni; María Herminia Hazelhoff; Romina Paula Bulacio; Adriana Mónica Torres

    2012-01-01

    Obstructive jaundice occurs in patients suffering from cholelithiasis and from neoplasms affecting the pancreas and the common bile duct.The absorption,distribution and elimination of drugs are impaired during this pathology.Prolonged cholestasis may alter both liver and kidney function.Lactam antibiotics,diuretics,non-steroidal anti-inflammatory drugs,several antiviral drugs as well as endogenous compounds are classified as organic anions.The hepatic and renal organic anion transport pathways play a key role in the pharmacokinetics of these compounds.It has been demonstrated that acute extrahepatic cholestasis is associated with increased renal elimination of organic anions.The present work describes the molecular mechanisms involved in the regulation of the expression and function of the renal and hepatic organic anion transporters in extrahepatic cholestasis,such as multidrug resistanceassociated protein 2,organic anion transporting polypeptide 1,organic anion transporter 3,bilitranslocase,bromosulfophthalein/bilirubin binding protein,organic anion transporter 1 and sodium dependent bile salt transporter.The modulation in the expression of renal organic anion transporters constitutes a compensatory mechanism to overcome the hepatic dysfunction in the elimination of organic anions.

  2. Ursodeoxycholic acid for treatment of cholestasis in patients with hepatic amyloidosis

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    Faust Dominik

    2009-01-01

    Full Text Available Background. Amyloidosis represents a group of different diseases characterized by extracellular accumulation of pathologic fibrillar proteins in various tissues and organs. Severe amyloid deposition in the liver parenchyma has extrahepatic involvement predominantly in the kidney or heart. We evaluated the effect of ursodeoxycholic acid, in four patients with severe hepatic amyloidosis of different etiologies, who presented with increased alkaline phosphatase and γ-glutamyl transferase. Case report. The study included four patients who presented with amyloidosis-associated intrahepatic cholestasis. Three of them had renal amyloidosis which developed 1-3 years before cholestasis occurred, the remaining one having intrahepatic cholestasis as the primary sign of the disease. Amyloidosis was identified from liver biopsies in all patients by its specific binding to Congo red and green birefringence in polarized light. The biochemical nature and the class of amyloid deposits were identified immunohistochemically. In addition to their regular treatment, the patients received 750 mg ursodeoxycholic acid per day. After 2-4 weeks all patients had a significant decrease of serum alkaline phosphatase and γ-glutamyl transferase, and their general status significantly improved. Conclusion. Treatment with ursodeoxycholic acid may be beneficial in patients with hepatic amyloidosis, and do extend indications for the use of ursodeoxycholic acid in amyloidotic cholestatic liver disease.

  3. Dioscin protects against ANIT-induced cholestasis via regulating Oatps, Mrp2 and Bsep expression in rats.

    Science.gov (United States)

    Zhang, Aijie; Jia, Yongming; Xu, Qinghan; Wang, Changyuan; Liu, Qi; Meng, Qiang; Peng, Jinyong; Sun, Huijun; Sun, Pengyuan; Huo, Xiaokui; Liu, Kexin

    2016-08-15

    Alpha-naphthylisothiocyanate (ANIT) is a toxicant that is widely used in rodents to model human intrahepatic cholestasis. The aim of the study is to investigate whether effects of dioscin on ANIT-induced cholestasis are related to changes in expression of hepatic transporters in rats. Effects of dioscin on cholestasis were examined by histology and biochemical marker levels. The functional changes of hepatic transporters were determined by in vitro, in situ and in vivo. qRT-PCR and western blot were used to assess the expression of hepatic transporters in cholestatic rats. Dioscin administration could ameliorate cholestasis, as evidenced by reduced biochemical markers as well as improved liver pathology. The uptakes of organic anion transporting polypeptide (Oatp) substrates were altered in liver uptake index in vivo, perfused rat liver in situ and isolated rat hepatocytes in vitro in cholestasis rats. qRT-PCR and western blot analysis indicated co-treatment of ANIT with dioscin prevented the adaptive down-regulation of Oatp1a1, 1b2, and prompted the up-regulation of Oatp1a4, multidrug resistance-associated protein (Mrp) 2 and bile salt export pump (Bsep). In addition, concerted effects on Mrp2 and Bsep occurred through up-regulation of small heterodimer partner by activating farnesoid X receptor. Dioscin might prevent impairment of hepatic function by restoring hepatic transporter expression. PMID:27317372

  4. Metabolomics coupled with multivariate data and pathway analysis on potential biomarkers in cholestasis and intervention effect of Paeonia lactiflora Pall.

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    Xiao eMa

    2016-02-01

    Full Text Available Background: The dried root of Paeonia lactiflora Pall. (PLP is a classical Chinese herbal medicine that has been used to treat hepatic disease for thousands of years. Our previous work suggested that PLP can be used to treat hepatitis with severe cholestasis. This study explored the mechanism by which PLP affects ANIT-induced cholestasis in rats using a metabolomics approach.Methods: The effects of PLP on serum indices (TBIL, DBIL, AST, ALT, ALP and TBA and the histopathology of the liver were analyzed. Moreover, UHPLC-Q-TOF was performed to identify the possible effect of PLP on metabolites. The pathway analysis was conducted to illustrate the pathways and network by which PLP treats cholestasis. Result: High-dose PLP remarkably down-regulated the serum indices and alleviated histological damage to the liver. Metabolomics analyses showed that the therapeutic effect of high-dose PLP is mainly associated with the regulation of several metabolites, such as glycocholic acid, taurocholic acid, glycochenodeoxycholic acid, L(D-arginine and L-tryptophan. A pathway analysis showed that the metabolites were related to bile acid secretion and amino acid metabolism. In addition, the significant changes in bile acid transporters also indicated that bile acid metabolism might be involved in the therapeutic effect of PLP on cholestasis. Moreover, a principal component analysis indicated that the metabolites in the high-dose PLP group were closer to those of the control, whereas those of the moderate dose or low-dose PLP group were closer to those of the ANIT group. This finding indicated that metabolites may be responsible for the differences between the effects of low-dose and moderate-dose PLP. Conclusions: The therapeutic effect of high-dose PLP on cholestasis is possibly related to regulation of bile acid secretion and amino acid metabolism. Moreover, these findings may help better understand the mechanisms of disease and provide a potential therapy for

  5. Plasma microRNA profiles in rat models of hepatocellular injury, cholestasis, and steatosis.

    Directory of Open Access Journals (Sweden)

    Yu Yamaura

    Full Text Available MicroRNAs (miRNAs are small RNA molecules that function to modulate the expression of target genes, playing important roles in a wide range of physiological and pathological processes. The miRNAs in body fluids have received considerable attention as potential biomarkers of various diseases. In this study, we compared the changes of the plasma miRNA expressions by acute liver injury (hepatocellular injury or cholestasis and chronic liver injury (steatosis, steatohepatitis and fibrosis using rat models made by the administration of chemicals or special diets. Using miRNA array analysis, we found that the levels of a large number of miRNAs (121-317 miRNAs were increased over 2-fold and the levels of a small number of miRNAs (6-35 miRNAs were decreased below 0.5-fold in all models except in a model of cholestasis caused by bile duct ligation. Interestingly, the expression profiles were different between the models, and the hierarchical clustering analysis discriminated between the acute and chronic liver injuries. In addition, miRNAs whose expressions were typically changed in each type of liver injury could be specified. It is notable that, in acute liver injury models, the plasma level of miR-122, the most abundant miRNA in the liver, was more quickly and dramatically increased than the plasma aminotransferase level, reflecting the extent of hepatocellular injury. This study demonstrated that the plasma miRNA profiles could reflect the types of liver injury (e.g. acute/chronic liver injury or hepatocellular injury/cholestasis/steatosis/steatohepatitis/fibrosis and identified the miRNAs that could be specific and sensitive biomarkers of liver injury.

  6. Impaired Itching Perception in Murine Models of Cholestasis Is Supported by Dysregulation of GPBAR1 Signaling

    OpenAIRE

    Sabrina Cipriani; Barbara Renga; Claudio D'Amore; Michele Simonetti; Antonio Angelo De Tursi; Adriana Carino; Maria Chiara Monti; Valentina Sepe; Angela Zampella; Stefano Fiorucci

    2015-01-01

    Background & Aims In cholestatic syndromes, body accumulation of bile acids is thought to cause itching. However, the mechanisms supporting this effect remain elusive. Recently, GPBAR1 (TGR5) a G-protein coupled receptor has been shown to mediate itching caused by intradermal administration of DCA and LCA. 6α-ethyl-3α, 7α-dihydroxy-24-nor-5β-cholan-23-ol (BAR502) is a non-bile acid dual ligand for FXR and GPBAR1. Methods Cholestasis was induced in wild type and GPBAR1-/- mice by administratio...

  7. Pilot study for a trial of ursodeoxycholic acid and/or early delivery for obstetric cholestasis

    Directory of Open Access Journals (Sweden)

    Briley Annette

    2009-05-01

    Full Text Available Abstract Background Obstetric cholestasis (OC is a serious problem in pregnancy. It affects about 4500 women per year in the UK. Affected women develop itching and occasionally jaundice. More importantly, the condition is associated with premature delivery, fetal distress and is believed to be an important cause of stillbirth. However, even now, there is no clear evidence as to whether the most popular treatment, a drug called ursodeoxycholic acid is beneficial to the baby, or even if it is safe in pregnancy. Nor do we know whether planned early delivery of the baby at 37–38 weeks, another popular treatment, does more good than harm. A randomised trial to evaluate both ursodeoxycholic acid and timed delivery is needed but will be complicated and expensive. We plan a preliminary study, Pilot study for a trial of ursodeoxycholic acid and/or early delivery for obstetric cholestasis (Acronym PITCH- Pregnancy Intervention Trial in Cholestasis trial, to evaluate the feasibility of a larger trial. The trial is funded by the NHS Research for Patient Benefit (RfPB Programme. Methods PITCH is a multi-centre, double blinded, randomised, controlled, factorial design trial. The trial is being run in six UK centres and women with obstetric cholestasis will be recruited for eighteen months. In this pilot trial we aim to collect data to finalise the design for the main trial. This will include measuring trial recruitment rate, including recruitment to each factorial comparison separately. We will also measure the spectrum of disease among recruits and non-recruits and compliance with the four possible treatment allocations. We will use these data to design the main trial. Discussion The ultimate aim of the main trial is to enable clinicians to manage this condition more effectively. If it transpires that ursodeoxycholic acid and early delivery are both safe and effective then steps will be taken to ensure that all women with OC who could benefit from them

  8. Successful pregnancy after ileal exclusion in progressive familial intrahepatic cholestasis type 2.

    Science.gov (United States)

    Czubkowski, Piotr; Jankowska, Irena; Pawlowska, Joanna

    2015-01-01

    Progressive familial intrahepatic cholestasis type 2 (PFIC 2) results from mutations in ABCB11 gene coding bile salt export pump (BSEP). Medical treatment is usually unsuccessful and surgery intervention is necessary. Partial external biliary diversion (PEBD) is regarded as the first choice of surgical treatment. Ileal exclusion (IE) is an alternative operation if external stoma is not tolerated; however, a favorable outcome is uncertain. In chronic liver diseases pregnancy brings additional risk of deterioration of liver function and generally is not recommended. We present the first case report of successful pregnancy in a genetically confirmed PFIC 2 patient after surgical conversion from PEBD to IE. PMID:26019043

  9. The role of bile salt export pump mutations in progressive familial intrahepatic cholestasis type II

    OpenAIRE

    Wang, Lin; Soroka, Carol J.; Boyer, James L.

    2002-01-01

    PFIC II is a subtype of progressive familial intrahepatic cholestasis (PFIC) that is associated with mutations in the ABCB11 gene encoding the bile salt export pump (BSEP). However it is not known how these mutations cause this disease. To evaluate these mechanisms, we introduced seven PFIC II–associated missense mutations into rat Bsep and assessed their effects on Bsep membrane localization and transport function in MDCK and Sf9 cells, respectively. Five mutations, G238V, E297G, G982R, R115...

  10. Most common SLC25A13 mutation in 400 Chinese infants with intrahepatic cholestasis

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To establish the real time fluorescence polymerase chain reaction(RT-PCR) with dual labeled probes for fast detection of SLC25A13 gene mutation 851del4.METHODS:Four hundred infants(< 1 year of age) with unexplained intrahepatic cholestasis from 18 provinces or municipalities in China were enrolled in this study for detecting their SLC25A13 gene mutation 851del4.Suitable primers and fluorescence-labeled probes for detecting SLC25A13 gene mutation 841del4 were designed.Normal and mutant sequences were det...

  11. [Stevens-Johnson syndrome plus intrahepatic cholestasis caused by clindamycin or chlorpheniramine].

    Science.gov (United States)

    Sahagún Flores, J E; Soto Ortiz, J A; Tovar Méndez, C E; Cárdenas Ochoa, E C; Hernández Flores, G

    2009-05-15

    A 48-year-old woman was hospitalized with the diagnosis of hepatitis. She presented with symptoms of jaundice, headache, elevated bilirubin, and elevated hepatic enzymes. She related a recent episode of a bronchial infection that was treated during the previous eight days with paracetamol (500mg, 2 doses only), chlorpheniramine, betamethasone and clindamycin. After an initial clinical and laboratorial improvement, she began to complain of pruritus of the palms and soles. Thereafter, vesicles evolving to blisters developed and a deterioration of her general health ensued. Serologies for hepatitis A, B, and C viruses were negative. Intrahepatic cholestasis and Stevens Johnson Syndrome (SJS) were the final diagnosis. The association of the Stevens Johnson Syndrome and intrahepatic cholestasis simultaneously, related to adverse drug reactions, is very rare. The drugs reportedly involved are mainly antibiotics, such as ampicillin, vancomycin, amoxicillin/clavulinic acid and erythromycin. Other drugs involved are non-steroidal anti-inflamatory drugs, such as mefenamic acid, ibuprofen, and sulindac. The reactions can be minor or severe and can even cause death, an outcome that has been reported in patients of all races and ethnic groups, but appears to be more rare in patients of Latin origin. We present a discussion of this case and review the main characteristics of the Stevens Johnson Syndrome.

  12. Seasonal cryptogenic organising pneumonia with biochemical cholestasis: a new clinical entity.

    Science.gov (United States)

    Spiteri, M A; Klenerman, P; Sheppard, M N; Padley, S; Clark, T J; Newman-Taylor, A

    1992-08-01

    The term cryptogenic organising pneumonia has been used for the combination of dyspnoea, cough, pleuritic pain, widespread shadows on chest radiographs, and histological evidence of intra-alveolar organisation with buds of granulation tissue within the alveoli. We report 12 patients with seasonal recurrence of this disorder for between 3 and 11 years. In all 12 patients, symptoms recurred between late February and early May every year, tending to increase in severity each year, and resolved between June and January. Chest radiography and computed tomography showed bilateral consolidation. Lung biopsy samples showed intra-alveolar buds of granulation tissue. There were many neutrophils within the lumina of medium-sized airways and terminal bronchioles showed evidence of obstruction by granulation tissue. Functionally, the predominant defect was restrictive and only 2 patients (life-long non-smokers) had airflow limitation. All 12 patients had very high activities of liver enzymes, suggesting intrahepatic cholestasis, but no other evidence of liver disease. Cultures of blood, sputum, lung tissue, and bronchoalveolar lavage fluid, viral screening, and complement fixation tests were consistently negative. In all patients all abnormalities responded rapidly to oral steroid therapy. These findings suggest a seasonal syndrome of organising pneumonia and biochemical abnormalities indicative of intrahepatic cholestasis. No aetiological factor has been identified, but the nature and periodicity of the illness point to an inhaled agent present in the environment for a limited period every year.

  13. Liver Cholesterol Overload Aggravates Obstructive Cholestasis by Inducing Oxidative Stress and Premature Death in Mice

    Science.gov (United States)

    Nuño-Lámbarri, Natalia; Domínguez-Pérez, Mayra; Baulies-Domenech, Anna; Monte, Maria J.; Marin, Jose J. G.; Rosales-Cruz, Patricia; Souza, Verónica; Miranda, Roxana U.; Bucio, Leticia; Montalvo-Jave, Eduardo E.; Concepción Gutiérrez-Ruiz, María; García-Ruiz, Carmen

    2016-01-01

    Nonalcoholic steatohepatitis is one of the leading causes of liver disease. Dietary factors determine the clinical presentation of steatohepatitis and can influence the progression of related diseases. Cholesterol has emerged as a critical player in the disease and hence consumption of cholesterol-enriched diets can lead to a progressive form of the disease. The aim was to investigate the impact of liver cholesterol overload on the progression of the obstructive cholestasis in mice subjected to bile duct ligation surgery. Mice were fed with a high cholesterol diet for two days and then were subjected to surgery procedure; histological, biochemical, and molecular analyses were conducted to address the effect of cholesterol in liver damage. Mice under the diet were more susceptible to damage. Results show that cholesterol fed mice exhibited increased apoptosis and oxidative stress as well as reduction in cell proliferation. Mortality following surgery was higher in HC fed mice. Liver cholesterol impairs the repair of liver during obstructive cholestasis and aggravates the disease with early fatal consequences; these effects were strongly associated with oxidative stress. PMID:27635189

  14. Liver Cholesterol Overload Aggravates Obstructive Cholestasis by Inducing Oxidative Stress and Premature Death in Mice.

    Science.gov (United States)

    Nuño-Lámbarri, Natalia; Domínguez-Pérez, Mayra; Baulies-Domenech, Anna; Monte, Maria J; Marin, Jose J G; Rosales-Cruz, Patricia; Souza, Verónica; Miranda, Roxana U; Bucio, Leticia; Montalvo-Jave, Eduardo E; Concepción Gutiérrez-Ruiz, María; García-Ruiz, Carmen; Fernández-Checa, José C; Gomez-Quiroz, Luis Enrique

    2016-01-01

    Nonalcoholic steatohepatitis is one of the leading causes of liver disease. Dietary factors determine the clinical presentation of steatohepatitis and can influence the progression of related diseases. Cholesterol has emerged as a critical player in the disease and hence consumption of cholesterol-enriched diets can lead to a progressive form of the disease. The aim was to investigate the impact of liver cholesterol overload on the progression of the obstructive cholestasis in mice subjected to bile duct ligation surgery. Mice were fed with a high cholesterol diet for two days and then were subjected to surgery procedure; histological, biochemical, and molecular analyses were conducted to address the effect of cholesterol in liver damage. Mice under the diet were more susceptible to damage. Results show that cholesterol fed mice exhibited increased apoptosis and oxidative stress as well as reduction in cell proliferation. Mortality following surgery was higher in HC fed mice. Liver cholesterol impairs the repair of liver during obstructive cholestasis and aggravates the disease with early fatal consequences; these effects were strongly associated with oxidative stress. PMID:27635189

  15. Clinical heterogeneity of neonatal intrahepatic cholestasis caused by citrin deficiency: case reports from 16 patients.

    Science.gov (United States)

    Tazawa, Yusaku; Kobayashi, Keiko; Abukawa, Daiki; Nagata, Ikuo; Maisawa, Shunichi; Sumazaki, Ryo; Iizuka, Toshiyuki; Hosoda, Yoshito; Okamoto, Manabu; Murakami, Jun; Kaji, Shunsaku; Tabata, Ayako; Lu, Yao Bang; Sakamoto, Osamu; Matsui, Akira; Kanzaki, Susumu; Takada, Goro; Saheki, Takeyori; Iinuma, Kazuie; Ohura, Toshihiro

    2004-11-01

    A deficiency of citrin, which is encoded by the SLC25A13 gene, causes both adult-onset type II citrullinemia (CTLN2) and neonatal intrahepatic cholestasis (NICCD). We analyzed 16 patients with NICCD to clarify the clinical features of the disease. Severe intrahepatic cholestasis with fatty liver was the most common symptom, but the accompanying clinical features were variable, namely; suspected cases of neonatal hepatitis or biliary atresia, positive results from newborn screening, tyrosinemia, failure to thrive, hemolytic anemia, bleeding tendencies and ketotic hypoglycemia. Laboratory data showed elevated serum bile acid levels, hypoproteinemia, low levels of vitamin K-dependent coagulation factors, and hypergalactosemia. Hypercitrullinemia was detected in 11 out of 15 patients examined. Most of the patients were given a lactose-free and/or medium chain triglycerides-enriched formula and lipid-soluble vitamins. The prognosis of the 16 patients is going fairy well at present, but we should observe these patients carefully to see if they manifest any symptom of CTLN2 in the future.

  16. Cholestasis induced antinociception and decreased gene expression of MOR1 in rat brain.

    Science.gov (United States)

    Ahmadi, S; Karami, Z; Mohammadian, A; Khosrobakhsh, F; Rostamzadeh, J

    2015-01-22

    We examined antinociception and gene expression of mu-opioid receptor 1 (MOR1) in some brain areas of cholestatic rats, 21 days after common bile duct ligation (BDL). Cholestasis was induced in male Wistar rats during laparotomy and common BDL. Pain behavior was assessed on days 7, 14 or 21 of BDL using a hotplate test in control, sham and cholestatic groups. On day 21 of BDL, other groups of rats were sacrificed, whole brains were extracted, and the hypothalamus, prefrontal cortex (PFC), hippocampus and striatum in control, sham and cholestatic rats were dissected. We used a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) method for evaluating MOR1 gene expression. The results revealed that cholestatic rats showed significant antinociception on days 14 and 21 of ligation with the most significant effect on day 21, which was prevented by naloxone (1 mg/kg). On the other hand, the expression of MOR1 gene compared to the sham group was decreased by 42% in the hypothalamus, 41% in the PFC, and 67% in the hippocampus after 21 days of BDL, while no significant change in its expression in the striatum was observed. It can be concluded that a change in endogenous opioid levels and its subsequent influence on the gene expression of MOR in some areas of the rat brain may underlie the altered nociception and other possible pathological changes such as pruritus after induction of cholestasis. PMID:25290008

  17. The peculiarities of morphological damages of the liver during obstructive cholestasis in clinic and experiment.

    Directory of Open Access Journals (Sweden)

    Gaydar Yu.A.

    2007-01-01

    Full Text Available The purpose of work was to study of the liver depending on blood level of bilirubine during obstructive cholestasis. 35 patients of 4 groups were examined: I - with the level of blood bilirubine lower 50 mM/l; II - 50-100 mM/l; III - 100-200 mM/l; IV - over 200 mM/l. The biopsies of liver were received during operation. The thin sections were stained by hematoxilin-eosin and Malori-Slinchenco. The immunohistochemical study of PCNA, p-53 and estrogen receptors markers was carried. The ligation of the common bile duct in 21 adult Vistar rats was carried and biopsies of liver were examined by the same methods on 7th and 16-18th day. The increases of inflammatory processes in the liver according to the increase of bilirubine level in the patient’s blood, and also the growth of PCNA expression were observed. The intracanalicular cholestasis was typical in III and IV groups of patients. The expression PCNA proved the activation of the reparative regeneration processes. We also observed the expression of estrogen receptors in hepatic parenchyme and intrahepatic billiar ducts. The ligation of the common bile duct in rats has resulted in acute hepatic necrobiosis by 7th day. The nodular cirrhosis has formed by the16-18th days.

  18. Nervous and Neuroendocrine regulation of the pathophysiology of cholestasis and of biliary carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Marco Marzioni; Giammarco Fava; Antonio Benedetti

    2006-01-01

    Cholangiocytes, the epithelial cells lining the biliary ducts, are the target cells in several liver diseases.Cholangiopathies and cholangiocarcinoma generate interest in many scientists since the genesis. The developing mechanisms, and the therapeutic tools of these diseases are still undefined. Several studies demonstrate that many hormones, neuropeptides and neurotransmitters regulate malignant and non-malignant cholangiocyte pathophysiology in the course of chronic biliary diseases. The aim of this review is to present the findings of several studies published in the recent years that contributed to clarifying the role of nervous and neuroendocrine regulation of the pathophysiologic events associated with cholestasis and cholangiocarcinoma development. This manuscript is organized into two parts. The first part offers an overview of the innervation of the liver and the origin of neuroendocrine hormones,neurotransmitters and neuropeptides affecting cholangiocyte function and metabolism. The first section also reviews the effects played by several neuroendocrine hormones and nervous system on cholangiocyte growth,survival and functional activity in the course of cholestasis. In the second section, we summarize the results of some studies describing the role of nervous system and neuroendocrine hormones in the regulation of malignant cholangiocyte growth.

  19. CCBE1 mutation in two siblings, one manifesting lymphedema-cholestasis syndrome, and the other, fetal hydrops.

    Directory of Open Access Journals (Sweden)

    Sohela Shah

    Full Text Available BACKGROUND: Lymphedema-cholestasis syndrome (LCS; Aagenaes syndrome is a rare autosomal recessive disorder, characterized by 1 neonatal intrahepatic cholestasis, often lessening and becoming intermittent with age, and 2 severe chronic lymphedema, mainly lower limb. LCS was originally described in a Norwegian kindred in which a locus, LCS1, was mapped to a 6.6cM region on chromosome 15. Mutations in CCBE1 on chromosome 18 have been reported in some cases of lymphatic dysplasia, but not in LCS. METHODS: Consanguineous parents of Mexican ancestry had a child with LCS who did not exhibit extended homozygosity in the LCS1 region. A subsequent pregnancy was electively terminated due to fetal hydrops. We performed whole-genome single nucleotide polymorphism genotyping to identify regions of homozygosity in these siblings, and sequenced promising candidate genes. RESULTS: Both siblings harbored a homozygous mutation in CCBE1, c.398 T>C, predicted to result in the missense change p.L133P. Regions containing known 'cholestasis genes' did not demonstrate homozygosity in the LCS patient. CONCLUSIONS: Mutations in CCBE1 may yield a phenotype not only of lymphatic dysplasia, but also of LCS or fetal hydrops; however, the possibility that the sibling with LCS also carries a homozygous mutation in an unidentified gene influencing cholestasis cannot be excluded.

  20. Dermatological Diseases Associated with Pregnancy: Pemphigoid Gestationis, Polymorphic Eruption of Pregnancy, Intrahepatic Cholestasis of Pregnancy, and Atopic Eruption of Pregnancy

    OpenAIRE

    Christine Sävervall; Freja Lærke Sand; Simon Francis Thomsen

    2015-01-01

    Dermatoses unique to pregnancy are important to recognize for the clinician as they carry considerable morbidity for pregnant mothers and in some instances constitute a risk to the fetus. These diseases include pemphigoid gestationis, polymorphic eruption of pregnancy, intrahepatic cholestasis of pregnancy, and atopic eruption of pregnancy. This review discusses the pathogenesis, clinical importance, and management of the dermatoses of pregnancy.

  1. A progressive familial intrahepatic cholestasis type 2 mutation causes an unstable, temperature-sensitive bile salt export pump

    NARCIS (Netherlands)

    Plass, JRM; Mol, O; Heegsma, J; Geuken, M; Elling, G; Muller, M; Faber, KN; Jansen, PLM

    2004-01-01

    Background Aims: Progressive familial intrahepatic cholestasis type 2 (PFIC-2) patients have a defect in the hepatocanalicular bile salt secretion. The disease is caused by mutations in the bile salt export pump (BSEP). Ten different missense mutations have been described. In this study, we analysed

  2. Clinical significance of serum glycochlicacid detection in diagnosis of intrahepatic cholestasis of pregnancy

    International Nuclear Information System (INIS)

    Intrahepatic cholestasis of pregnancy (ICP) occurred in the middle and later phase of pregnancy. ICP had considerable effect on the perinatal babies. To further study the effect of serum glycochlicacid in diagnosis of ICP, serum glycochlicacid was measured by radio-immunoassay in normal pregnancy women and ICP pregnant women. The determination of alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were taken as contrast. Serum glycochlicacid is significantly higher (P < 0.01) in ICP pregnant women than in normal pregnant women. The positive rate of serum glycochlicacid was 100%, the positive rate of ALT was 80%, the positive rate of ALP was 40%. Serum glycochlicacid is the most sensitive serologic index in diagnosis of ICP

  3. [Intrahepatic cholestasis associated with parenteral nutrition: an experimental study in rats].

    Science.gov (United States)

    Salas Martínez, J; Morán Penco, J M; Mahedero Ruiz, G; García Gamito, F; Limón Mora, M; Maciá Botejara, E; Vinagre Velasco, L M

    1989-01-01

    Intrahepatic cholestasis is a condition often observed in patients receiving parenteral nutrition, especially in new born babies who are underweight (taurina. This makes it impossible to achieve a correct conjugation of toxic biliary acids. The access of nutrients to the liver may have an effect on this. An experimental study on rats was performed, administering an oral diet at the expense of lipids (20% Intralipid, 60% of caloric needs) and glucose (40% of caloric needs) in one group, another group received amino acid supplements to this diet (16N) at a proteic rate of 2 gr/kg of weight and day orally, with an identical diet to the above, except that the proteic intake was intraperitoneal. Two control groups were established. We found a microvacuolization in hepatic fat with the help of an electronic microscope in the groups lacking proteins and those with oral or intraperitoneal supplements of amino acids, as well as an increase in plasmatic AST.

  4. Adrenal haemorrhage with cholestasis and adrenal crisis in a newborn of a diabetic mother.

    Science.gov (United States)

    Koklu, Esad; Kurtoglu, Selim; Akcakus, Mustafa; Koklu, Selmin

    2007-03-01

    The large hyperaemic foetal adrenal gland is vulnerable to vascular damage. This may occur in the neonatal period as a consequence of difficult labour, or its aetiology may not be apparent. The spectrum of presentation is considerable, ranging from asymptomatic to severe life-threatening intra-abdominal haemorrhage. The presentation of adrenal insufficiency may be delayed but the regenerative capacity of the adrenal is great, and most adrenal haemorrhage is not associated with significantly impaired function. Some reports showed that cholestatic hepatopathy with congenital hypopituitarism reversed by hydrocortisone treatment is considered in the context of the endocrine syndrome, probably as a consequence of the adrenal failure. We describe a case of bilateral adrenal haemorrhage with hepatitis syndrome and persistent hypoglycaemia in a newborn male with striking features of neonatal cholestasis and adrenal crisis.

  5. Novel ABCB11 mutations in a Thai infant with progressive familial intrahepatic cholestasis

    Institute of Scientific and Technical Information of China (English)

    Suporn Treepongkaruna; Amornphun Gaensan; Paneeya Pienvichit; Ondrej Luksan; AS Knisely; Pattana Sornmayura; Milan Jirsa

    2009-01-01

    Progressive familial intrahepatic cholestasis (PFIC) type 2 is caused by mutations in ABCB11 , which encodes bile salt export pump (BSEP). We report a Thai female infant who presented with progressive cholestatic jaundice since 1 mo of age, with normal serum γ-glutamyltransferase. Immunohistochemical staining of the liver did not demonstrate BSEP along the canaliculi, while multidrug resistance protein 3 was expressed adequately. Novel mutations in ABCB11 , a four-nucleotide deletion in exon 3, c.90_93delGAAA, and a single-nucleotide insertion in exon 5, c.249_250insT, were identified, with confirmation in her parents. These mutations were predicted to lead to synthesis of truncated forms of BSEP. Immunostaining and mutation analysis thus established the diagnosis of PFIC type 2.

  6. Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Woolbright, Benjamin L.; Dorko, Kenneth [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Antoine, Daniel J.; Clarke, Joanna I. [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Gholami, Parviz [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Li, Feng [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Kumer, Sean C.; Schmitt, Timothy M.; Forster, Jameson [Department of Surgery, University of Kansas Medical Center, Kansas City, KS (United States); Fan, Fang [Department of Pathology, University of Kansas Medical Center, Kansas City, KS (United States); Jenkins, Rosalind E.; Park, B. Kevin [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Hagenbuch, Bruno [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Olyaee, Mojtaba [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)

    2015-03-15

    Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with, or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box 1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models. - Highlights: • Cholestatic liver injury is due to cytoplasmic bile acid accumulation in hepatocytes. • Primary human hepatocytes are resistant to BA-induced injury

  7. IGF-1R contributes to stress-induced hepatocellular damage in experimental cholestasis.

    Science.gov (United States)

    Cadoret, Axelle; Rey, Colette; Wendum, Dominique; Elriz, Khaldoun; Tronche, François; Holzenberger, Martin; Housset, Chantal

    2009-08-01

    The insulin-like growth factor type 1 receptor (IGF-1R) controls aging and cellular stress, both of which play major roles in liver disease. Stimulation of insulin-like growth factor signaling can generate cell death in vitro. Here, we tested whether IGF-1R contributes to stress insult in the liver. Cholestatic liver injury was induced by bile duct ligation in control and liver-specific IGF-1R knockout (LIGFREKO) mice. LIGFREKO mice displayed less bile duct ligation-induced hepatocyte damage than controls, while no differences in bile acid serum levels or better adaptation to cholestasis by efflux transporters were found. We therefore tested whether stress pathways contributed to this phenomenon; oxidative stress, ascertained by both malondialdehyde content and heme oxygenase-1 expression, was similar in knockout and control animals. However, together with a lower level of eukaryotic initiation factor-2 alpha phosphorylation, the endoplasmic reticulum stress protein CHOP and its downstream pro-apoptotic target Bax were induced to lesser extents in LIGFREKO mice than in controls. Expression levels of cytokeratin 19, transforming growth factor-beta1, alpha-smooth muscle actin, and collagen alpha1(I) in LIGFREKO mice were all lower than in controls, indicating reduced ductular and fibrogenic responses and increased cholestasis tolerance in these mutants. This stress resistance phenotype was also evidenced by longer post-bile duct ligation survival in mutants than controls. These results indicate that IGF-1R contributes to cholestatic liver injury, and suggests the involvement of both CHOP and Bax in this process. PMID:19628767

  8. Role of Multidrug Resistance Protein 3 in Antifungal-Induced Cholestasis.

    Science.gov (United States)

    Mahdi, Zainab M; Synal-Hermanns, Uta; Yoker, Aylin; Locher, Kaspar P; Stieger, Bruno

    2016-07-01

    Drug-induced liver injury is an important clinical entity resulting in a considerable number of hospitalizations. While drug-induced cholestasis due to the inhibition of the bile salt export pump (BSEP) is well investigated, only limited information on the interaction of drugs with multidrug resistance protein 3 (MDR3) exists and its role in the pathogenesis of drug-induced cholestasis is poorly understood. Therefore, we aimed to study the interaction of drugs with MDR3 and the effect of drugs on canalicular lipid secretion in a newly established polarized cell line system that serves as a model of canalicular lipid secretion. LLC-PK1 cells were stably transfected with human Na(+)-taurocholate cotransporting polypeptide, BSEP, MDR3, and ABCG5/G8 and grown in the Transwell system. Apical phospholipid secretion and taurocholate transport were assayed to investigate the effect of selected drugs on MDR3-mediated phospholipid secretion as well as inhibition of BSEP. The established cell line displayed vectorial bile salt transport and specific phosphatidylcholine secretion into the apical compartment. The antifungal azoles, posaconazole, itraconazole, and ketoconazole, significantly inhibited MDR3-mediated phosphatidylcholine secretion. In contrast, amoxicillin clavulanate and troglitazone did not interfere with MDR3 activity. Drugs interfering with MDR3 activity did not display a parallel inhibition of BSEP. Our in vitro model for MDR3-mediated phospholipid secretion facilitates parallel screening for MDR3 and BSEP inhibitors. Our data demonstrate that the cholestatic potential of certain drugs may be aggravated by simultaneous inhibition of BSEP and MDR3. PMID:27112167

  9. Glimepiride-induced cholestasis in a man with diabetes mellitus: a case report

    Directory of Open Access Journals (Sweden)

    Omar Hesham

    2009-09-01

    Full Text Available Abstract Introduction There has been a progressive increase in the incidence of type II diabetes mellitus cases over the past decade. The availability of a wide variety of oral hypoglycemics has given rise to a number of adverse effects. In this case report, we describe the case of a patient recently diagnosed with type II diabetes. He was receiving treatment with glimepiride and experienced rapid onset of cholestatic liver injury as a side effect, which reversed upon cessation of therapy. Case presentation We present the case of a 58-year-old Egyptian man with a recent diagnosis of type II diabetes mellitus. He presented with a clinical picture of progressive jaundice three days before admission. Laboratory investigations revealed elevated bilirubin, alkaline phosphatase and gamma glutamyl transferase levels. Ultrasonography revealed intrahepatic biliary duct dilatation and two small lymph nodes in the porta hepatis; there was, however, no extrahepatic biliary duct dilatation or stones in the gall bladder. Abdominal computed tomography excluded pancreatic or hepatic focal lesions, but the tumor marker CA19-9 was elevated. The progressive improvement in the patient's symptomatology and laboratory investigations after admission argued against malignancy. A thorough and detailed history revealed that the patient had started on a new medication, glimepiride, five months earlier for the treatment of diabetes mellitus and an improvement was noted after discontinuation of this oral hypoglycemic and the introduction of insulin therapy to control his blood sugar. Conclusion Drugs are an important, often unrecognized, cause of acute cholestasis. Among the rare causes responsible for this complication is the sulfonylurea glimepiride. A thorough drug history is therefore helpful in any case of unexplained cholestasis.

  10. Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis

    International Nuclear Information System (INIS)

    Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with, or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box 1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models. - Highlights: • Cholestatic liver injury is due to cytoplasmic bile acid accumulation in hepatocytes. • Primary human hepatocytes are resistant to BA-induced injury

  11. The Effect of Fish Oil-Based Lipid Emulsion and Soybean Oil-Based Lipid Emulsion on Cholestasis Associated with Long-Term Parenteral Nutrition in Premature Infants

    Science.gov (United States)

    Wang, Leilei; Zhang, Jing; Gao, Jiejin; Qian, Yan; Ling, Ya

    2016-01-01

    Purpose. To retrospectively study the effect of fish oil-based lipid emulsion and soybean oil-based lipid emulsion on cholestasis associated with long-term parenteral nutrition in premature infants. Methods. Soybean oil-based lipid emulsion and fish oil-based lipid emulsion had been applied in our neonatology department clinically between 2010 and 2014. There were 61 qualified premature infants included in this study and divided into two groups. Soybean oil group was made up of 32 premature infants, while fish oil group was made up of 29 premature infants. Analysis was made on the gender, feeding intolerance, infection history, birth weight, gestational age, duration of parenteral nutrition, total dosage of amino acid, age at which feeding began, usage of lipid emulsions, and incidence of cholestasis between the two groups. Results. There were no statistical differences in terms of gender, feeding intolerance, infection history, birth weight, gestational age, duration of parenteral nutrition, total dosage of amino acid, and age at which feeding began. Besides, total incidence of cholestasis was 21.3%, and the days of life of occurrence of cholestasis were 53 ± 5.0 days. Incidence of cholestasis had no statistical difference in the two groups. Conclusion. This study did not find the different role of fish oil-based lipid emulsions and soybean oil-based lipid emulsions in cholestasis associated with long-term parenteral nutrition in premature infants. PMID:27110237

  12. The Effect of Fish Oil-Based Lipid Emulsion and Soybean Oil-Based Lipid Emulsion on Cholestasis Associated with Long-Term Parenteral Nutrition in Premature Infants

    Directory of Open Access Journals (Sweden)

    Leilei Wang

    2016-01-01

    Full Text Available Purpose. To retrospectively study the effect of fish oil-based lipid emulsion and soybean oil-based lipid emulsion on cholestasis associated with long-term parenteral nutrition in premature infants. Methods. Soybean oil-based lipid emulsion and fish oil-based lipid emulsion had been applied in our neonatology department clinically between 2010 and 2014. There were 61 qualified premature infants included in this study and divided into two groups. Soybean oil group was made up of 32 premature infants, while fish oil group was made up of 29 premature infants. Analysis was made on the gender, feeding intolerance, infection history, birth weight, gestational age, duration of parenteral nutrition, total dosage of amino acid, age at which feeding began, usage of lipid emulsions, and incidence of cholestasis between the two groups. Results. There were no statistical differences in terms of gender, feeding intolerance, infection history, birth weight, gestational age, duration of parenteral nutrition, total dosage of amino acid, and age at which feeding began. Besides, total incidence of cholestasis was 21.3%, and the days of life of occurrence of cholestasis were 53±5.0 days. Incidence of cholestasis had no statistical difference in the two groups. Conclusion. This study did not find the different role of fish oil-based lipid emulsions and soybean oil-based lipid emulsions in cholestasis associated with long-term parenteral nutrition in premature infants.

  13. The Effect of Fish Oil-Based Lipid Emulsion and Soybean Oil-Based Lipid Emulsion on Cholestasis Associated with Long-Term Parenteral Nutrition in Premature Infants.

    Science.gov (United States)

    Wang, Leilei; Zhang, Jing; Gao, Jiejin; Qian, Yan; Ling, Ya

    2016-01-01

    Purpose. To retrospectively study the effect of fish oil-based lipid emulsion and soybean oil-based lipid emulsion on cholestasis associated with long-term parenteral nutrition in premature infants. Methods. Soybean oil-based lipid emulsion and fish oil-based lipid emulsion had been applied in our neonatology department clinically between 2010 and 2014. There were 61 qualified premature infants included in this study and divided into two groups. Soybean oil group was made up of 32 premature infants, while fish oil group was made up of 29 premature infants. Analysis was made on the gender, feeding intolerance, infection history, birth weight, gestational age, duration of parenteral nutrition, total dosage of amino acid, age at which feeding began, usage of lipid emulsions, and incidence of cholestasis between the two groups. Results. There were no statistical differences in terms of gender, feeding intolerance, infection history, birth weight, gestational age, duration of parenteral nutrition, total dosage of amino acid, and age at which feeding began. Besides, total incidence of cholestasis was 21.3%, and the days of life of occurrence of cholestasis were 53 ± 5.0 days. Incidence of cholestasis had no statistical difference in the two groups. Conclusion. This study did not find the different role of fish oil-based lipid emulsions and soybean oil-based lipid emulsions in cholestasis associated with long-term parenteral nutrition in premature infants.

  14. The angiotensin-converting enzyme gene insertion–deletion polymorphism in a white British patient cohort with obstetric cholestasis

    Science.gov (United States)

    Müllenbach, Roman; Tetlow, Natasha; Bennett, Amanda; Pipkin, Fiona Broughton; Morgan, Linda; Williamson, Catherine

    2009-01-01

    The DD genotype of the angiotensin-converting enzyme (ACE) gene is over-represented in Finnish patients with obstetric cholestasis (OC). The purpose of this study was to establish whether this genotype is associated with cholestasis in UK cases. In a retrospective case-control study, we determined the ACE insertion/deletion frequencies in 166 British cases and 100 control women by polymerase chain reaction analysis. No significant difference in allele frequencies was found between these groups, but allele frequencies differed significantly between Finnish and UK OC cases (P = 0.0005). The prevalence of the DD genotype is lower in UK cases than in controls (χ2 [1 d.f.] = 4.32, P = 0.05) and the odds ratio for OC associated with the DD genotypeis 0.54, 95% confidence interval 0.30–0.97. In contrast to Finnish OC cases, the DD genotype of the ACE is not increased in UK cases.

  15. Discovery that theonellasterol a marine sponge sterol is a highly selective FXR antagonist that protects against liver injury in cholestasis.

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    Barbara Renga

    Full Text Available BACKGROUND: The farnesoid-x-receptor (FXR is a bile acid sensor expressed in the liver and gastrointestinal tract. Despite FXR ligands are under investigation for treatment of cholestasis, a biochemical condition occurring in a number of liver diseases for which available therapies are poorly effective, mice harboring a disrupted FXR are protected against liver injury caused by bile acid overload in rodent models of cholestasis. Theonellasterol is a 4-methylene-24-ethylsteroid isolated from the marine sponge Theonella swinhoei. Here, we have characterized the activity of this theonellasterol on FXR-regulated genes and biological functions. PRINCIPAL FINDINGS: Interrogation of HepG2 cells, a human hepatocyte cell line, by microarray analysis and transactivation assay shows that theonellasterol is a selective FXR antagonist, devoid of any agonistic or antagonistic activity on a number of human nuclear receptors including the vitamin D receptor, PPARs, PXR, LXRs, progesterone, estrogen, glucorticoid and thyroid receptors, among others. Exposure of HepG2 cells to theonellasterol antagonizes the effect of natural and synthetic FXR agonists on FXR-regulated genes, including SHP, OSTα, BSEP and MRP4. A proof-of-concept study carried out to investigate whether FXR antagonism rescues mice from liver injury caused by the ligation of the common bile duct, a model of obstructive cholestasis, demonstrated that theonellasterol attenuates injury caused by bile duct ligation as measured by assessing serum alanine aminostrasferase levels and extent of liver necrosis at histopathology. Analysis of genes involved in bile acid uptake and excretion by hepatocytes revealed that theonellasterol increases the liver expression of MRP4, a basolateral transporter that is negatively regulated by FXR. Administering bile duct ligated mice with an FXR agonist failed to rescue from liver injury and downregulated the expression of MRP4. CONCLUSIONS: FXR antagonism in vivo

  16. Transcriptional Dynamics of Bile Salt Export Pump during Pregnancy: Mechanisms and Implications in Intrahepatic Cholestasis of Pregnancy

    OpenAIRE

    Song, Xiulong; Vasilenko, Alexander; Chen, Yuan; Valanejad, Leila; Verma, Ruchi; Yan, Bingfang; Deng, Ruitang

    2014-01-01

    Bile salt export pump (BSEP) is responsible for biliary secretion of bile acids, a rate limiting step in the enterohepatic circulation of bile acids and transactivated by nuclear receptor farnesoid x receptor (FXR). Intrahepatic cholestasis of pregnancy (ICP) is the most prevalent disorder among diseases unique to pregnancy and primarily occurs in the third trimester of pregnancy with a hallmark of elevated serum bile acids. Currently, the transcriptional regulation of BSEP during pregnancy a...

  17. Antioxidant Effect of Sepia Ink Extract on Extrahepatic Cholestasis Induced by Bile Duct Ligation in Rats

    Institute of Scientific and Technical Information of China (English)

    Hanan Saleh; Amel M Soliman; Ayman S Mohamed; Mohamed-Assem S Marie

    2015-01-01

    Objective The aim of our study was to assess the complications of hepatic fibrosis associated with bile duct ligation and the potential curative role of sepia ink extract in hepatic damage induced by bile duct ligation. Methods Rattus norvegicus rats were divided into 3 groups: Sham-operated group, model rats that underwent common bile duct ligation (BDL), and BDL rats treated orally with sepia ink extract (200 mg/kg body weight) for 7, 14, and 28 d after BDL. Results There was a significant reduction in hepatic enzymes, ALP, GGT, bilirubin levels, and oxidative stress in the BDL group after treatment with sepia ink extract. Collagen deposition reduced after sepia ink extract treatment as compared to BDL groups, suggesting that the liver was repaired. Histopathological examination of liver treated with sepia ink extract showed moderate degeneration in the hepatic architecture and mild degeneration in hepatocytes as compared to BDL groups. Conclusion Sepia ink extract provides a curative effect and an antioxidant capacity on BDL rats and could ameliorate the complications of liver cholestasis.

  18. Cholestasis and protein-losing enteropathy secondary to hyperthyroidism in a 6-year-old girl.

    Science.gov (United States)

    Gargouri, Lamia; Charfi, Manel; Maalej, Bayen; Majdoub, Imen; Safi, Faiza; Fourati, Hela; Hentati, Yosr; Daoud, Emna; Mnif, Zeineb; Abid, Mohamed; Mahfoudh, Abdelmajid

    2014-09-01

    Hepatic dysfunctions are not infrequent in patients with hyperthyroidism. These disorders may be related to the effects of the excess thyroid hormone secretion, to the uses of antithyroid drugs, or to the presence of concomitant hepatic diseases. Our aim is to describe the clinical and biochemical features of liver dysfunction related to thyrotoxicosis. We report here a case of a 6-year-old girl who was admitted for jaundice and pruritus as a result of the development of hyperthyroidism due to Graves' disease. On physical examination at admission, she was found to have jaundice and hepatomegaly. Laboratory data show cholestasis and protein-losing enteropathy. Investigations exclude other causes of hepatic disorder. One month after the initiation of antithyroid drug, the patient became euthyroid with improvement in jaundice and pruritus and normalization of hepatic tests and alpha antitrypsine clearance. In conclusion, the diagnosis of hyperthyroidism may be delayed in patients in whom the primary manifestations were pruritus and jaundice. The physician should suspect thyrotoxicosis prior to hepatitis or skin manifestations. PMID:24825088

  19. Leukocytapheresis Therapy Improved Cholestasis in a Patient Suffering from Primary Sclerosing Cholangitis with Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Minoru Itou

    2009-04-01

    Full Text Available Primary sclerosing cholangitis (PSC is an autoimmune disease of the hepatobiliary system for which effective therapy has not been established. Leukocytapheresis (LCAP therapy is known to effective in patients with ulcerative colitis (UC. In addition, effects of LCAP therapy were reported on some autoimmune diseases such as Crohn’s disease, rheumatoid arthritis and rapidly progressive glomerulonephritis. Here we report the case of a 29-year-old man with PSC associated with UC who was treated with LCAP therapy. He had a 16-year history of UC and a 12-year history of PSC. Although he was under treatment with prednisolone and ursodeoxycholic acid, exacerbation of UC and PSC-associated cholestasis were seen. Since he showed side effects of prednisolone, he was treated with LCAP. Not only improvement of UC, but also decreased serum alkaline phosphatase, γ-guanosine triphosphate and total bile acids, suggesting improvement of PSC-associated cholestaisis, were seen after treatment with LCAP. Our experience with this case suggests that LCAP therapy could be a new effective therapeutic strategy for patients with PSC associated with UC.

  20. Predictors of premature delivery in patients with intrahepatic cholestasis of pregnancy

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To evaluate the predictive value of clinical symptoms and biochemical parameters for prematurity in intrahepatic cholestasis of pregnancy (ICP).METHODS: Sixty symptomatic patients with ICP were included in this retrospective analysis. Preterm delivery was defined as delivery before 37 wk gestation.Predictors of preterm delivery were disclosed by binary multivariate logistic regression analysis.RESULTS: Mean time of delivery was 38.1 ± 1.7 wk.No stillbirths occurred. Premature delivery was observed in eight (13.3%) patients. Total fasting serum bile acids were higher (47.8 ± 15.2 vs 41.0 ± 10.0 μmol/L, P <0.05), and pruritus tended to start earlier (29.0 ± 3.9 vs 31.6 ± 3.3 wk, P = 0.057) in patients with premature delivery when compared to those with term delivery.Binary multivariate logistic regression analysis revealed that early onset of pruritus (OR 1.70, 95% CI 1.23-2.95,P = 0.038) and serum bile acid (OR 2.13, 95% CI 1.13-3.25, P = 0.013) were independent predictors of preterm delivery.CONCLUSION: Early onset of pruritus and high levels of serum bile acids predict preterm delivery in ICP, and define a subgroup of patients at risk for poor neonatal outcome.

  1. Effects of Three Different Fibrates on Intrahepatic Cholestasis Experimentally Induced in Rats

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    Alaa El-Sisi

    2013-01-01

    Full Text Available Background. Activation of PPARα modulates cholesterol metabolism and suppresses bile acid synthesis. This study aims to evaluate the effect of PPARα agonists, fenofibrate, bezafibrate, and gemfibrozil, on acute cholestasis induced by ethinylestradiol (EE plus chlorpromazine (CPZ in rats. Method. 100 male albino rats (150–200 gm were divided randomly into 10 equal groups. Control group received 1% methylcellulose vehicle; disease group received CPZ plus EE for 5 consecutive days; four groups received either ursodeoxycholic acid, fenofibrate, bezafibrate, or gemfibrozil for 7 days; 2 days before EE + CPZ, three other groups received one of the three fibrates after GW6471, a selective PPARα antagonist in addition to EE + CPZ. The final group received GW6471 alone. Results. The three fibrates showed marked reduction ( in serum levels of ALP, GGT, ALT, AST, total bile acids, bilirubin, TNFα, and IL-1β and in hepatic malondialdehyde level as well as a significant increase in bile flow rate ( in addition to improvements in histopathological parameters compared to diseased group. In groups which received GW6471, these effects were completely abolished with fenofibrate and partially blocked with bezafibrate and gemfibrozil. Conclusion. Short-term administration of fibrates to EE/CPZ-induced intrahepatic cholestatic rats exerted beneficial effects on hepatocellular damage and apoptosis. Fenofibrate anticholestatic effect was solely PPARα dependent while other mechanisms played part in bezafibrate and gemfibrozil actions.

  2. Thiazolidinedione treatment inhibits bile duct proliferation and fibrosis in a rat model of chronic cholestasis

    Institute of Scientific and Technical Information of China (English)

    Fabio Marra; Carlo Spirli; Mario Strazzabosco; Massimo Pinzani; Maurizio Parola; Raffaella DeFranco; Gaia Robino; Erica Novo; Eva Efsen; Sabrina Pastacaldi; Elena Zamara; Alessandro Vercelli; Benedetta Lottini

    2005-01-01

    AIM: To investigate the effects of troglitazone (TGZ), an anti-diabetic drug which activates peroxisome proliferatoractivated receptor-γ (PPAR-γ), for liver tissue repair, and the development of ductular reaction, following common bile duct ligation (BDL) in rats.METHODS: Rats were supplemented with TGZ (0.2% w/w in the pelleted food) for 1 wk before BDL or sham operation.Animals were killed at 1, 2, or 4 wk after surgery.RESULTS: The development of liver fibrosis was reduced in rats receiving TGZ, as indicated by significant decreases of procollagen type Ⅰ gene expression and liver hydroxyproline levels. Accumulation of α-smooth-muscle actin (SMA)-expressing cells surrounding newly formed bile ducts following BDL, as well as total hepatic levels of SMA were partially inhibited by TGZ treatment, indicating the presence of a reduced number and/or activation of hepatic stellate cells (HSC) and myofibroblasts. Development of the ductular reaction was inhibited by TGZ, as indicated by histochemical evaluation and hepatic activity of γ-glutamyltransferase (GGT).CONCLUSION: Treatment with thiazolidinedione reduces ductular proliferation and fibrosis in a model of chronic cholestasis, and suggests that limiting cholangiocyte proliferation may contribute to the lower development of scarring in this system.

  3. Cell-Mediated Immunity Imbalance in Patients with Intrahepatic Cholestasis of Pregnancy

    Institute of Scientific and Technical Information of China (English)

    Bin Ling; Fengqiu Yao; Ying Zhou; Zhengzheng Chen; Guodong Shen; Yuanyuan Zhu

    2007-01-01

    Decidual lymphocytes may mediate fetal trophoblast recognition and regulate maternal immune reaction and play an essential role in the maintenance of normal pregnancy. The aim of this study was to compare the percentage of T cells, natural killer (NK) cells and natural killer T (NKT) cells within decidual parietalis of normal pregnant controls (NP) and patients with intraheptic cholestasis of pregnancy (ICP), and to investigate the production of interleukin-4 (IL-4), interferon-γ (IFN-γ) in the culture supernatant of decidual parietalis mononuclear cells (DPMCs). Compared with controls, the decidua parietalis from ICP were characterized with significant increased percentages of CD3-CD56+ cells, CD3+CD56+ cells, CD56+CD16+ cells, CD56+CD16- cells, CD56+NKG2D+ cells, and the significant decreased percentages of CD3+ cells, CD3+CD4+ cells. There were no differences found for the percentage of CD3+CD8+ cells, CD56+NKG2A+ cells between control and study group. In addition, the enhanced concentration of IFN-γ was presented in culture supernatant of DPMCs from ICP. It was suggested that the increased NK cells, NKT cells and the decreased T cells in the decidual parietalis and over-secretion of IFN-γ could be correlated with the pathophysiology of ICP patients.

  4. Effect of Bile Acid on Fetal Lung in Rat Model of Intrahepatic Cholestasis of Pregnancy

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    Ling Yu

    2014-01-01

    Full Text Available Objective. To determine the correlation between maternal bile acid (BA level and fetal pulmonary surfactant in rats and study the effects of BA on fetal lung in rat model of intrahepatic cholestasis of pregnancy. Methods. Forty pregnant rats were treated with (A 5.5 mg/kg BA, (B 1.4 mg/kg BA, and (C 1 ml physiological saline. Levels of total bile acid (TBA, ALT, AST, TBIL, DBIL, and SP-A were determined and the lungs of fetal rats were analyzed for pathological changes. Results. Groups A and B intervened with BA showed significant higher level of TBA in both maternal and fetal serum, more mortality rate of fetal rats, more concentration of SP-A in fetal serum, and wider alveolus mesenchyme of fetal rats than the control Group C. Higher level of BA associated with increased fetal risk and lower numerical density of mitochondria in type II alveolar epithelial cells. The levels of TBA in maternal serum were found to have significant positive correlation with those in fetal serum and SP-A level but negatively with the area of alveolus and the numerical density of lamellar body. Conclusions. The TBA level in maternal serum showed significant association with lung pathological changes in fetal rats.

  5. Role of ciprofloxacin in patients with cholestasis after endoscopic retrograde cholangiopancreatography

    Institute of Scientific and Technical Information of China (English)

    Thawee Ratanachu-ek; Pitchaya Prajanphanit; Kawin Leelawat; Suchart Chantawibul; Sukij Panpimanmas; Somboon Subwongcharoen; Jerasak Wannaprasert

    2007-01-01

    AIM: To determine the role of ciprofloxacin in reducing cholangitis in cholestatic patients with adequate biliary drainage after endoscopic retrograde cholangiopancreatography (ERCP).METHODS: A randomized, controlled trial was performed in 48 cholestatic patients at Rajavithi Hospital (Tertiary Referral Center for ERCP: 600 cases per year). All the 48 patients received 200 mg ciprofloxacin intravenous injection for 30 min before starting any procedures, and then were randomly divided in two groups. Twenty-two patients in study group continually received ciprofloxacin until 48 h after ERCP. Causes of biliary obstruction, bacteriology of bile and blood (in cholangitis) and clinical cholangitis were recorded.RESULTS: Forty-eight patients were enrolled and divided into continuous ciprofloxacin treatment group (n = 22) and discontinuous ciprofloxacin treatment group (n = 26). During ERCP, stones were found in 22 patients,malignant diseases in 24 patients and other pathologic lesions in 5 patients. One (4.5%) of the 22 patients who received ciprofloxacin and 2 (6.3%) of the 26 patients who discontinued ciprofloxacin after ERCP developed cholangitis (relative risk = 0.71; 95% CI = 0.14-3.65;P = 0.88). Bacterobilia was found in 27 (56.3%) out of 48 patients. E. coli and Streptococcus viridans were the most common organisms.CONCLUSION: Continual use of ciprofloxacin in patients with cholestasis after adequate biliary drainage procedures plays no role in reducing cholangitis.

  6. In Search of an Accurate Evaluation of Intrahepatic Cholestasis of Pregnancy

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    Manuela Martinefski

    2012-01-01

    Full Text Available Until now, biochemical parameter for diagnosis of intrahepatic cholestasis of pregnancy (ICP mostly used is the rise of total serum bile acids (TSBA above the upper normal limit of 11 μM. However, differential diagnosis is very difficult since overlapped values calculated on bile acids determinations, are observed in different conditions of pregnancy including the benign condition of pruritus gravidarum. The aim of this work was to determine the better markers in ICP for a precise diagnosis together with parameters associated with severity of symptoms and treatment evaluation. Serum bile acid profiles were evaluated using capillary electrophoresis in 38 healthy pregnant women and 32 ICP patients and it was calculated the sensitivity, specificity, accuracy, predictive values and the relationships of certain individual bile acids in pregnant women in order to replace TSBA determinations. The evaluation of the results shows that LCA and UDCA/LCA ratio provided information for a more complete and accurate diagnosis and evaluation of ICP than calculation of solely TSBA levels in pregnant women.

  7. Incidence and Risk Factors of Parenteral Nutrition-Associated Cholestasis in Omani Neonates; Single centre experience

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    Sharef W. Sharef

    2015-05-01

    Full Text Available Objectives: Parenteral nutrition-associated cholestasis (PNAC is one of the most challenging complications of prolonged parenteral nutrition (PN in neonates. There is a lack of research investigating its incidence in newborn infants in Oman and the Arab region. Therefore, this study aimed to assess the incidence of PNAC and its risk factors in Omani neonates. Methods: This retrospective study took place between January and April 2014. All neonates who received PN for ≥14 days during a four-year period (June 2009 to May 2013 at the neonatal intensive care unit (NICU in Sultan Qaboos University Hospital, Muscat, Oman, were enrolled. Results: A total of 1,857 neonates were admitted to the NICU over the study period and 135 neonates (7.3% received PN for ≥14 days. Determining the incidence of PNAC was only possible in 97 neonates; of these, 38 (39% had PNAC. The main risk factors associated with PNAC were duration of PN, duration of enteral starvation, gastrointestinal surgeries, blood transfusions and sepsis. Neonates with PNAC had a slightly higher incidence of necrotising enterocolitis in comparison to those without PNAC. Conclusion: This study found a PNAC incidence of 39% in Omani neonates. There were several significant risk factors for PNAC in Omani neonates; however, after logistic regression analysis, only total PN duration remained statistically significant. Preventive strategies should be implemented in NICUs so as to avoid future chronic liver disease in this population.

  8. Cytomegalovirus frequency in neonatal intrahepatic cholestasis determined by serology, histology, immunohistochemistry and PCR

    Institute of Scientific and Technical Information of China (English)

    Maria Angela Bellomo-Brandao; Paula D Andrade; Sandra CB Costa; Cecilia AF Escanhoela; Jose Vassallo; Gilda Porta; Adriana MA De Tommaso; Gabriel Hessel

    2009-01-01

    AIM: To determine cytomegalovirus (CMV) frequency in neonatal intrahepatic cholestasis by serology,histological revision (searching for cytomegalic cells), immunohistochemistry, and polymerase chain reaction (PCR), and to verify the relationships among these methods. METHODS: The study comprised 101 non-consecutive infants submitted for hepatic biopsy between March 1982 and December 2005. Serological results were obtained from the patient's files and the other methods were performed on paraffin-embedded liver samples from hepatic biopsies. The following statistical measures were calculated: frequency, sensibility, specific positive predictive value, negative predictive value, and accuracy.RESULTS: The frequencies of positive results were as follows: serology, 7/64 (11%); histological revision, 0/84; immunohistochemistry, 1/44 (2%),and PCR, 6/77 (8%). Only one patient had positive immunohistochemical findings and a positive PCR. The following statistical measures were calculated between PCR and serology: sensitivity, 33.3%; specificity,88.89%; positive predictive value, 28.57%; negative predictive value, 90.91%; and accuracy, 82.35%.CONCLUSION: The frequency of positive CMV varied among the tests. Serology presented the highest positive frequency. When compared to PCR, the sensitivity and positive predictive value of serology were low.

  9. Two Case Reports of Successful Treatment of Cholestasis With Steroids in Patients With PFIC-2.

    Science.gov (United States)

    Engelmann, Guido; Wenning, Daniel; Herebian, Diran; Sander, Oliver; Dröge, Carola; Kluge, Stefanie; Kubitz, Ralf

    2015-05-01

    Mutations in the gene encoding the canalicular bile salt export pump (BSEP) can result in progressive familial intrahepatic cholestasis type 2 (PFIC-2). Treatment options are limited, and PFIC-2 often necessitates liver transplantation. We report on a young woman and a boy who clinically presented with PFIC-2 phenotypes and dramatically improved with steroid treatment. Gene sequencing of ABCB11 encoding for BSEP revealed 2 relevant mutations in both patients. The young woman was compound heterozygous for p.T919del and p.R1235X. At the age of 5 years, partial biliary diversion was performed and rescued liver function but left serum bile salt levels elevated. At age 23 she developed systemic lupus erythematosus. Unexpectedly, steroid therapy normalized serum bile salt levels, with a strong correlation with the steroid dose. She is currently in clinical remission. The boy was compound heterozygous for the ABCB11 mutations c.150+3A>C and p.R832C and presented with intractable pruritus. When he developed colitis, he was treated with steroids. The pruritus completely disappeared and relapsed when steroids were withdrawn. To date, with low-dose budesonide, the boy has been symptom-free for >3 years. In conclusion, the clinical courses suggest that patients with BSEP deficiency and residual BSEP activity may benefit from steroid-based therapy, which represents a new treatment option. PMID:25847799

  10. Growth evaluation in infants with neonatal cholestasis Antropometria em crianças com colestase neonatal

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    Camila Carbone Prado

    2006-12-01

    Full Text Available BACKGROUD: Chronic liver diseases in childhood often cause undernutrition and growth failure. To our knowledge, growth parameters in infants with neonatal cholestasis are not available AIM: To evaluate the nutritional status and growth pattern in infants with intrahepatic cholestasis and extrahepatic cholestasis. PATIENTS AND METHODS: One hundred forty-four patients with neonatal cholestasis were followed up at the Pediatric Gastroenterology Service of the Teaching Hospital, State University of Campinas, Campinas, SP, Brazil, in a 23-year period, from 1980 to 2003. The records of these patients were reviewed and patients were classified into two groups, according to their anatomical diagnosis: patients with intrahepatic cholestasis - group 1, and patients with extrahepatic cholestasis - group 2. Records of weight and height measurements were collected at 4 age stages of growth, in the first year of life: 1 from the time of the first medical visit to the age of 4 months (T1; 2 from the 5th to the 7th month (T2; 3 from the 8th to the 10th month (T3; and 4 from the 11th to the 13th month (T4. The weight-by-age and height-by-age Z-scores were calculated for each patient at each stage. In order for the patient to be included in the study it was necessary to have the weight and/or height measurements at the 4 stages. Analyses of variance and Tukey's tests were used for statistical analysis. Repeated measurement analyses of variance of the weight-by-age Z-score were performed in a 60-patient sample, including 29 patients from group 1 and 31 patients from group 2. The height-by-age data of 33 patients were recorded, 15 from group 1 and 18 from group 2 RESULTS: The mean weight-by-age Z-scores of group 1 patients at the 4 age stages were: T1=-1.54; T2=-1.40; T3=-0.94; T4=-0.78. There was a significant difference between T2 X T3 and T1 X T4. The weight-by-age Z-scores for group 2 patients were :T1=-1.04; T2=-1.67; T3=-1.93 and T4=-1.77, with a significant

  11. Inflammatory cell function in young rodents with experimental cholestasis: investigations of functional deficits, their etiology, and their reversibility.

    Science.gov (United States)

    Roughneen, P T; Drath, D B; Kulkarni, A D; Kumar, S C; Andrassy, R J; Rowlands, B J

    1989-07-01

    Children with cholestasis are susceptible to infective complications. This may be attributable to impaired host defense. We postulated that cholestasis affects systemic polymorphonuclear leukocyte (PMN) function by impeding chemotaxis, phagocytosis, and superoxide release, which are all critical in eliciting an adequate immune response. Sprague Dawley rats (225 g) were assigned to three groups: bile duct ligated (BDL), sham (SH), and normal control (NC). On day 21 after operation, PMN and sera were isolated. Chemotactic response to C5a and FMLP (formyl-methionyl-leucyl-phenylalanine), superoxide release, and phagocytic uptake of 14C-labeled Staphylococcus aureus were performed on pooled PMN samples. Results were expressed as mean +/- SD. Serum bilirubin at day 21 was 6.3 +/- 2.9 v 0.1 +/- 0.1 and 0.1 +/- 0 mg/dL (P less than .01) in BDL, SH, and NC groups, respectively. Kinetic studies of PMN phagocytosis demonstrated impaired 14C S aureus uptake by BDL neutrophils at 60 (P less than .05), 90 (P less than .05), and 120 minutes (P less than .05) compared with SH and NC groups. No differences in PMN chemotactic response to C5a and FMLP was observed in BDL, SH and NC groups (43 +/- 14 v 40 +/- 12 and 33 +/- 1, and 43 +/- 20 v 43 +/- 14 and 28 +/- 1 cell per field, respectively). Zymosan stimulated superoxide release did not differ between groups (14.3 +/- 3.6 (BDL) v 15.1 +/- 8.7 (SH) and 12 +/- 2.0 (NC) nmol/30 min/mg cell protein, respectively. Thus, cholestasis impairs neutrophil phagocytosis in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2547052

  12. Effects of curcumin on cyclosporine-induced cholestasis and hypercholesterolemia and on cyclosporine metabolism in the rat.

    Science.gov (United States)

    Deters, Michael; Klabunde, Til; Meyer, Hartmut; Resch, Klaus; Kaever, Volkhard

    2003-04-01

    Former studies have shown that curcumin, which can be extracted from different Curcuma species, is able to stimulate bile flow and to reduce hypercholesterolemia. We investigated in a subchronic bile fistula model the ability of curcumin to reduce cyclosporine-induced cholestasis and hypercholesterolemia. Male Wistar rats were daily treated with curcumin (100 mg/kg p. o.), cyclosporine (10 mg/kg i. p.), and a combination of curcumin with cyclosporine. After two weeks a bile fistula was installed into the rats to measure bile flow and biliary excretion of bile salts, cholesterol, bilirubin, cyclosporine and its main metabolites. Blood was taken to determine the concentration of these parameters in serum or blood. Cyclosporine reduced bile flow (-14 %) and biliary excretion of bile salts (-10 %) and cholesterol (-61 %). On the other hand, cyclosporine increased serum concentrations of cholesterol and triglycerides by 32 % and 82 %, respectively. Sole administration of curcumin led to a slight decrease of bile flow (-7 %) and biliary bile salt excretion (-12 %), but showed no effect on biliary excretion of cholesterol and serum lipid concentration. When curcumin was given simultaneously with cyclosporine, the cyclosporine-induced cholestasis was enhanced but the cyclosporine-induced hyperlipidemia was not affected. Neither the biliary excretion nor the blood concentration of cyclosporine was influenced by curcumin. The blood concentration of the main cyclosporine metabolites, however, was lowered by half while their biliary excretion was strongly increased by curcumin. From these results we conclude that curcumin is not able to prevent cyclosporine-induced cholestasis and hyperlipidemia after prolonged administration in bile fistula rats.

  13. Fetal outcomes in pregnancies complicated by intrahepatic cholestasis of pregnancy in a Northern California cohort.

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    Michelle Rook

    Full Text Available BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP has important fetal implications. There is increased risk for poor fetal outcomes, including preterm delivery, meconium staining of amniotic fluid, respiratory distress, fetal distress and demise. METHODS: One hundred and one women diagnosed with ICP between January 2005 and March 2009 at San Francisco General Hospital were included in this study. Single predictor logistic regression models were used to assess the associations of maternal clinical and biochemical predictors with fetal complications. Clinical predictors analyzed included age, race/ethnicity, gravidity, parity, history of liver or biliary disease, history of ICP in previous pregnancies, and induction. Biochemical predictors analyzed included serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, direct bilirubin, albumin, total protein, and total bile acids (TBA. RESULTS: The prevalence of ICP was 1.9%. Most were Latina (90%. Labor was induced in the majority (87% and most were delivered by normal spontaneous vaginal delivery (84%. Fetal complications occurred in 33% of the deliveries, with respiratory distress accounting for the majority of complications. There were no statistically significant clinical or biochemical predictors associated with an increased risk of fetal complications. Elevated TBA had little association with fetal complications until reaching greater than 100 µmoL/L, with 3 out of 5 having reported complications. ICP in previous pregnancies was associated with decreased risk of fetal complications (OR 0.21, p = 0.046. There were no cases of late term fetal demise. CONCLUSIONS: Maternal clinical and laboratory features, including elevated TBA, did not appear to be substantial predictors of fetal complications in ICP.

  14. Primum non nocere: how active management became modus operandi for intrahepatic cholestasis of pregnancy.

    Science.gov (United States)

    Henderson, Cassandra E; Shah, Reena R; Gottimukkala, Sri; Ferreira, Khaldun K; Hamaoui, Abraham; Mercado, Ray

    2014-09-01

    The Royal College of Obstetrics and Gynecology does not endorse routine active management of intrahepatic cholestasis of pregnancy (ICP)-affected pregnancies. In contrast, the American College of Obstetricians and Gynecologists supports active management protocols for ICP. To investigate this controversy, we evaluated the evidence supporting ICP as a medical indication for early term delivery and the evolution of active management protocols for ICP. Sixteen articles published between 1986 and 2011 were identified. We created 2 groups based on whether obstetric care included active management. Group 1 comprised 6 uncontrolled reports without active management that were published between 1967 and 1983 that described high perinatal mortality rates that primarily were related to prematurity sequel. This group became the fundamental 'core' evidence for ICP-associated stillbirths and by extrapolation justification for active management. Group 2 was comprised of 10 reports in which the authors credited empirically adopted active management with the observed low stillbirth rates in ICP-affected pregnancies. Although the group 1 articles routinely are cited as evidence of ICP-associated stillbirth risk, the 1.2% stillbirth rate (4/331) in this group is similar to the background stillbirth rates of 1.1% (11/1000) and 0.6% (6/1000) in 1967 and 2011, respectively (P = .062 and P = .0614, respectively). Likewise, the stillbirth rates for articles in group 2 were similar to their respective national stillbirth rate. Nevertheless, group 2 articles have become the evidence-based support for active management. We found no evidence to support the practice of active management for ICP. PMID:24704063

  15. Suppression of the HPA Axis During Cholestasis Can Be Attributed to Hypothalamic Bile Acid Signaling.

    Science.gov (United States)

    McMillin, Matthew; Frampton, Gabriel; Quinn, Matthew; Divan, Ali; Grant, Stephanie; Patel, Nisha; Newell-Rogers, Karen; DeMorrow, Sharon

    2015-12-01

    Suppression of the hypothalamic-pituitary-adrenal (HPA) axis has been shown to occur during cholestatic liver injury. Furthermore, we have demonstrated that in a model of cholestasis, serum bile acids gain entry into the brain via a leaky blood brain barrier and that hypothalamic bile acid content is increased. Therefore, the aim of the current study was to determine the effects of bile acid signaling on the HPA axis. The data presented show that HPA axis suppression during cholestatic liver injury, specifically circulating corticosterone levels and hypothalamic corticotropin releasing hormone (CRH) expression, can be attenuated by administration of the bile acid sequestrant cholestyramine. Secondly, treatment of hypothalamic neurons with various bile acids suppressed CRH expression and secretion in vitro. However, in vivo HPA axis suppression was only evident after the central injection of the bile acids taurocholic acid or glycochenodeoxycholic acid but not the other bile acids studied. Furthermore, we demonstrate that taurocholic acid and glycochenodeoxycholic acid are exerting their effects on hypothalamic CRH expression after their uptake through the apical sodium-dependent bile acid transporter and subsequent activation of the glucocorticoid receptor. Taken together with previous studies, our data support the hypothesis that during cholestatic liver injury, bile acids gain entry into the brain, are transported into neurons through the apical sodium-dependent bile acid transporter and can activate the glucocorticoid receptor to suppress the HPA axis. These data also lend themselves to the broader hypothesis that bile acids may act as central modulators of hypothalamic peptides that may be altered during liver disease.

  16. RIP3 Inhibits Inflammatory Hepatocarcinogenesis but Promotes Cholestasis by Controlling Caspase-8- and JNK-Dependent Compensatory Cell Proliferation

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    Mihael Vucur

    2013-08-01

    Full Text Available For years, the term “apoptosis” was used synonymously with programmed cell death. However, it was recently discovered that receptor interacting protein 3 (RIP3-dependent “necroptosis” represents an alternative programmed cell death pathway activated in many inflamed tissues. Here, we show in a genetic model of chronic hepatic inflammation that activation of RIP3 limits immune responses and compensatory proliferation of liver parenchymal cells (LPC by inhibiting Caspase-8-dependent activation of Jun-(N-terminal kinase in LPC and nonparenchymal liver cells. In this way, RIP3 inhibits intrahepatic tumor growth and impedes the Caspase-8-dependent establishment of specific chromosomal aberrations that mediate resistance to tumor-necrosis-factor-induced apoptosis and underlie hepatocarcinogenesis. Moreover, RIP3 promotes the development of jaundice and cholestasis, because its activation suppresses compensatory proliferation of cholangiocytes and hepatic stem cells. These findings demonstrate a function of RIP3 in regulating carcinogenesis and cholestasis. Controlling RIP3 or Caspase-8 might represent a chemopreventive or therapeutic strategy against hepatocellular carcinoma and biliary disease.

  17. Oleanolic acid attenuates obstructive cholestasis in bile duct-ligated mice, possibly via activation of NRF2-MRPs and FXR antagonism.

    Science.gov (United States)

    Chen, Pan; Li, Jingjie; Fan, Xiaomei; Zeng, Hang; Deng, Rongrong; Li, Dongshun; Huang, Min; Bi, Huichang

    2015-10-15

    Obstructive cholestasis is characterized by impairment of hepatic canalicular bile efflux and there are no clinically effective drugs to cure except surgeries. Previously we revealed that oleanolic acid (OA) protected against lithocholic acid (LCA)-induced intrahepatic cholestasis in mice. Cholestasis caused by LCA is characterized by segmental bile duct obstruction, whether OA possesses the beneficial effect on completed obstructive cholestasis induced by bile duct ligation (BDL) remains unknown. In this study, we demonstrated that BDL-induced mice liver pathological change, and increase in serum levels of ALT, AST and ALP were all significantly reduced by OA (20 mg/kg, i.p.). Meanwhile, OA also lowered total bilirubin and total bile acids levels in serum, as well as total bile acids level in liver, in contrast, urinary total bile acids output was remarkably up-regulated by OA. Gene expression analysis showed that OA caused significant increased mRNA expression of MRP3 and MRP4 located at hepatic basolateral membrane, and restoration of MRP2 and BSEP located at hepatic cannalicular membrane. Furthermore, significant NRF2 protein accumulation in nucleus was also observed in OA treated mice. In mice primary cultured hepatocytes, the effects of OA on MRP2, MRP3 and MRP4 expression were directly proved to be mediated via NRF2 activation, and BSEP downregulation induced by OA was in part due to FXR antagonism. Luciferase assay performed in Hep G2 cells also illustrated that OA was a partial FXR antagonist. Taken together, we conclude that OA attenuates obstructive cholestasis in BDL mice, possibly via activation of NRF2-MRPs and FXR antagonism. PMID:26297978

  18. Dynamic biliary cholecystography with mebrofenin-Tc-99m in a patient with benign recurrent intrahepatic cholestasis

    International Nuclear Information System (INIS)

    A Caucasian boy with a 16-year history of benign recurrent intrahepatic cholestasis (BRIC) presented dissociation between normal hepatic extraction fraction of mebrofenin-Tc-99m (HEF over 90%) and that of intensive delayed liver 'washout' T 1/2 210 m (normal 20-25 m). This is the second case in Macedonia (population 2.3 million) showing the same pattern of bile dynamic with mebrofenin-Tc-99m: normal HEF, prolonged 'washout'. In Rotor's disease and Dubin-Johnson's syndrome HEF is depressed and 'washout' delayed, whereas in Gilbert's syndrome we found both parameters normal. In our patient the episodes of pruritus were intensive and prolonged, hyperbilirubinaemia 50-100 micromol/L. Gallbladder was hypovolemic, ejection fraction reduced (59%, normal with the employed method over 70%). Growth, body weight and bone age were subnormal. Technetium-sulfur-colloid scans showed enlarged liver, splenomegaly and reduced portal contribution to hepatic blood flow (65%, normal over 70%). (Author)

  19. Activation of the renin-angiotensin system stimulates biliary hyperplasia during cholestasis induced by extrahepatic bile duct ligation.

    Science.gov (United States)

    Afroze, Syeda H; Munshi, Md Kamruzzaman; Martínez, Allyson K; Uddin, Mohammad; Gergely, Maté; Szynkarski, Claudia; Guerrier, Micheleine; Nizamutdinov, Damir; Dostal, David; Glaser, Shannon

    2015-04-15

    Cholangiocyte proliferation is regulated in a coordinated fashion by many neuroendocrine factors through autocrine and paracrine mechanisms. The renin-angiotensin system (RAS) is known to play a role in the activation of hepatic stellate cells and blocking the RAS attenuates hepatic fibrosis. We investigated the role of the RAS during extrahepatic cholestasis induced by bile duct ligation (BDL). In this study, we used normal and BDL rats that were treated with control, angiotensin II (ANG II), or losartan for 2 wk. In vitro studies were performed in a primary rat cholangiocyte cell line (NRIC). The expression of renin, angiotensin-converting enzyme, angiotensinogen, and angiotensin receptor type 1 was evaluated by immunohistochemistry (IHC), real-time PCR, and FACs and found to be increased in BDL compared with normal rat. The levels of ANG II were evaluated by ELISA and found to be increased in serum and conditioned media of cholangiocytes from BDL compared with normal rats. Treatment with ANG II increased biliary mass and proliferation in both normal and BDL rats. Losartan attenuated BDL-induced biliary proliferation. In vitro, ANG II stimulated NRIC proliferation via increased intracellular cAMP levels and activation of the PKA/ERK/CREB intracellular signaling pathway. ANG II stimulated a significant increase in Sirius red staining and IHC for fibronectin that was blocked by angiotensin receptor blockade. In vitro, ANG II stimulated the gene expression of collagen 1A1, fibronectin 1, and IL-6. These results indicate that cholangiocytes express a local RAS and that ANG II plays an important role in regulating biliary proliferation and fibrosis during extraheptic cholestasis.

  20. Oxidative stress markers, secondary bile acids and sulfated bile acids classify the clinical liver injury type: Promising diagnostic biomarkers for cholestasis.

    Science.gov (United States)

    Masubuchi, Noriko; Sugihara, Masahiro; Sugita, Tomonori; Amano, Katsushi; Nakano, Masanori; Matsuura, Tomokazu

    2016-08-01

    Clinicians sometimes encounter difficulty in choosing a therapeutic strategy due to the uncertainty regarding the type of liver injury. In particular, cholestasis is difficult to diagnose by conventional markers at an early stage of disease. The aim of this study was to identify promising biomarkers for distinguishing the symptom-based types of liver injury (e.g. hepatocellular injury, cholestasis), which was derived from a rigorously statistical perspective. The associations between diagnostic biomarkers (e.g. bile acid components, oxidative stress markers and liver fibrosis markers) and the liver injury types were assessed by a multiple logistic regression analysis using 304 blood samples from patients with liver disease. As a result, reductions in the lithocholic acid (LCA) and deoxycholic acid (DCA) levels, and elevation of the serum sulfated bile acid (SSBA), liver fibrosis marker IV collagen (type IV collagen), hyaluronic acid (HA) and reactive oxygen species (ROS) levels were all significantly associated with cholestasis. On the other hand, elevations in the LCA and type IV collagen levels, and a reduction in the ursodeoxy cholic acid (UDCA) level, were significantly associated with hepatocellular injury. The receiver operating characteristic (ROC) analyses showed that the largest area under the ROC curve (AUC) was found for ROS, followed by DCA, HA, LCA, SSBA and type IV collagen in the cholestatic-type cases. These results indicated that ROS, the secondary bile acid levels such as DCA and LCA, and SSBA are promising biomarkers for cholestasis and for classifying the type of liver injuries. This comprehensive approach will allow for an accurate diagnosis, which will facilitate the selection of an appropriate therapy at the onset of disease. PMID:26325587

  1. Cholecysto-appendicostomy as partial internal biliary drainage in Progressive Familial Intrahepatic Cholestasis Type 1: A case report and review of literature

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    Yee Ian Yik

    2016-01-01

    Full Text Available Intractable pruritus secondary to bile salts retention in Progressive Familial Intrahepatic Cholestasis (PFIC can be relieved surgically by diverting bile drainage from ileum to reduce bile salts reabsorption into entero-hepatic circulation. We are reporting on the successful biliary diversion in a child with PFIC, with the use of the appendix as a conduit to drain bile from gallbladder to the colon (cholecysto-appendicostomy.

  2. Relapsing features of bile salt export pump deficiency after liver transplantation in two patients with progressive familial intrahepatic cholestasis type 2

    OpenAIRE

    Maggiore, G; E Gonzales; Sciveres, M; Redon, M-J; Grosse, B; Stieger, B; Davit-Spraul, A; Fabre, M.; Jacquemin, E.

    2010-01-01

    BACKGROUND & AIMS: PFIC2 is caused by mutations in ABCB11 encoding BSEP. In most cases affected children need liver transplantation that is thought to be curative. We report on two patients who developed recurrent normal GGT cholestasis mimicking primary BSEP disease, after liver transplantation. METHODS: PFIC2 diagnosis was made in infancy in both patients on absence of canalicular BSEP immunodetection and on ABCB11 mutation identification. Liver transplantation was performed at age 9 (patie...

  3. Bsep蛋白表达及调控与胆汁淤积的关系%Correlation between Bsep Protein Expression and Regulation and Cholestasis

    Institute of Scientific and Technical Information of China (English)

    王火平

    2012-01-01

    Bsep protein, also known bile salt export pump, belongs to superfamily of ATP binding cas-sette( ABC )transporters. The research on hepatocellular minute structure confirmed that it's mainly expressed in hepatocytic canalicular membrane, is an important transporter of the process of bile excretion. At present many studies indicate that there is close association between Bsep protein expression changes and functional deficiency and cholestasis. Studies of Bsep protein and other bile salt transporters comprehensively and deeply is helpful to reveal molecular mechanism of cholestasis,providing theoretical basis and new ideas for the prevention , diagnosis and treatment of cholestasis.%Bsep蛋白即胆盐输出泵,属于ATP结合盒转运体超家族.对肝细胞细微结构的研究证实其主要表达于肝细胞胆管膜侧,为胆汁生成过程中重要的转运载体.目前大量研究表明,其表达量变化及功能缺失与胆汁淤积发生之间存在密切关系.对Bsep蛋白及其他胆酸转运体的研究有助于全面深入地揭示胆汁淤积发生的部分分子机制,为胆汁淤积的预防、诊治提供理论依据和新的思路.

  4. Plasma biomarkers of liver injury and inflammation demonstrate a lack of apoptosis during obstructive cholestasis in mice

    Energy Technology Data Exchange (ETDEWEB)

    Woolbright, Benjamin L. [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Antoine, Daniel J.; Jenkins, Rosalind E. [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Bajt, Mary Lynn [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Park, B. Kevin [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)

    2013-12-15

    Cholestasis is a pathological common component of numerous liver diseases that results in hepatotoxicity, inflammation, and cirrhosis when untreated. While the predominant hypothesis in cholestatic liver injury remains hepatocyte apoptosis due to direct toxicity of hydrophobic bile acid exposure, recent work suggests that the injury occurs through inflammatory necrosis. In order to resolve this controversy, we used novel plasma biomarkers to assess the mechanisms of cell death during early cholestatic liver injury. C57Bl/6 mice underwent bile duct ligation (BDL) for 6–72 h, or sham operation. Another group of mice were given D-galactosamine and endotoxin as a positive control for apoptosis and inflammatory necrosis. Plasma levels of full length cytokeratin-18 (FL-K18), microRNA-122 (miR-122) and high mobility group box-1 protein (HMGB1) increased progressively after BDL with peak levels observed after 48 h. These results indicate extensive cell necrosis after BDL, which is supported by the time course of plasma alanine aminotransferase activities and histology. In contrast, plasma caspase-3 activity, cleaved caspase-3 protein and caspase-cleaved cytokeratin-18 fragments (cK18) were not elevated at any time during BDL suggesting the absence of apoptosis. In contrast, all plasma biomarkers of necrosis and apoptosis were elevated 6 h after Gal/End treatment. In addition, acetylated HMGB1, a marker for macrophage and monocyte activation, was increased as early as 12 h but mainly at 48–72 h. However, progressive neutrophil accumulation in the area of necrosis started at 6 h after BDL. In conclusion, these data indicate that early cholestatic liver injury in mice is an inflammatory event, and occurs through necrosis with little evidence for apoptosis. - Highlights: • The mechanism of cell death during cholestasis remains a controversial topic. • Plasma biomarkers offer new insight into cell death after bile duct ligation. • Cytokeratin-18, microRNA-122 and HMGB

  5. Neonatal intrahepatic cholestasis caused by citrin deficiency: prevalence and SLC25A13 mutations among thai infants

    Directory of Open Access Journals (Sweden)

    Treepongkaruna Suporn

    2012-10-01

    Full Text Available Abstract Background The most common causes of cholestatic jaundice are biliary atresia and idiopathic neonatal hepatitis (INH. Specific disorders underlying INH, such as various infectious and metabolic causes, including neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD especially, in East Asian populations are increasingly being identified. Since most NICCD infants recovered from liver disease by 1 year of age, they often are misdiagnosed with INH, leading to difficulty in determining the true prevalence of NICCD. Mutation(s of human SLC25A13 gene encoding a mitochondrial aspartate/glutamate carrier isoform 2 (AGC2, can lead to AGC2 deficiency, resulting in NICCD and an adult-onset fatal disease namely citrullinemia type II (CTLN2. To study the prevalence of NICCD and SLC25A13 mutations in Thai infants, and to compare manifestations of NICCD and non-NICCD, infants with idiopathic cholestatic jaundice or INH were enrolled. Clinical and biochemical data were reviewed. Urine organic acid and plasma amino acids profiles were analyzed. PCR-sequencing of all 18 exons of SLC25A13 and gap PCR for the mutations IVS16ins3kb and Ex16+74_IVS17-32del516 were performed. mRNA were analyzed in selected cases with possible splicing error. Results Five out of 39 (12.8% unrelated infants enrolled in the study were found to have NICCD, of which three had homozygous 851del4 (GTATdel and two compound heterozygous 851del4/IVS16ins3kb and 851del4/1638ins23, respectively. Two missense mutations (p.M1? and p.R605Q of unknown functional significance were identified. At the initial presentation, NICCD patients had higher levels of alkaline phosphatase (ALP and alpha-fetoprotein (AFP and lower level of alanine aminotransferase (ALT than those in non-NICCD patients (pp Conclusion NICCD should be considered in infants with idiopathic cholestasis. The preliminary estimated prevalence of NICCD was calculated to be 1/48,228 with carrier rate of 1/110 among

  6. Effects of Melittin Treatment in Cholangitis and Biliary Fibrosis in a Model of Xenobiotic-Induced Cholestasis in Mice

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    Kyung-Hyun Kim

    2015-08-01

    Full Text Available Cholangiopathy is a chronic immune-mediated disease of the liver, which is characterized by cholangitis, ductular reaction and biliary-type hepatic fibrosis. There is no proven medical therapy that changes the course of the disease. In previous studies, melittin was known for attenuation of hepatic injury, inflammation and hepatic fibrosis. This study investigated whether melittin provides inhibition on cholangitis and biliary fibrosis in vivo. Feeding 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC to mice is a well-established animal model to study cholangitis and biliary fibrosis. To investigate the effects of melittin on cholangiopathy, mice were fed with a 0.1% DDC-containing diet with or without melittin treatment for four weeks. Liver morphology, serum markers of liver injury, cholestasis markers for inflammation of liver, the degree of ductular reaction and the degree of liver fibrosis were compared between with or without melittin treatment DDC-fed mice. DDC feeding led to increased serum markers of hepatic injury, ductular reaction, induction of pro-inflammatory cytokines and biliary fibrosis. Interestingly, melittin treatment attenuated hepatic function markers, ductular reaction, the reactive phenotype of cholangiocytes and cholangitis and biliary fibrosis. Our data suggest that melittin treatment can be protective against chronic cholestatic disease in DDC-fed mice. Further studies on the anti-inflammatory capacity of melittin are warranted for targeted therapy in cholangiopathy.

  7. Effects of Melittin Treatment in Cholangitis and Biliary Fibrosis in a Model of Xenobiotic-Induced Cholestasis in Mice.

    Science.gov (United States)

    Kim, Kyung-Hyun; Sung, Hyun-Jung; Lee, Woo-Ram; An, Hyun-Jin; Kim, Jung-Yeon; Pak, Sok Cheon; Han, Sang-Mi; Park, Kwan-Kyu

    2015-09-01

    Cholangiopathy is a chronic immune-mediated disease of the liver, which is characterized by cholangitis, ductular reaction and biliary-type hepatic fibrosis. There is no proven medical therapy that changes the course of the disease. In previous studies, melittin was known for attenuation of hepatic injury, inflammation and hepatic fibrosis. This study investigated whether melittin provides inhibition on cholangitis and biliary fibrosis in vivo. Feeding 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) to mice is a well-established animal model to study cholangitis and biliary fibrosis. To investigate the effects of melittin on cholangiopathy, mice were fed with a 0.1% DDC-containing diet with or without melittin treatment for four weeks. Liver morphology, serum markers of liver injury, cholestasis markers for inflammation of liver, the degree of ductular reaction and the degree of liver fibrosis were compared between with or without melittin treatment DDC-fed mice. DDC feeding led to increased serum markers of hepatic injury, ductular reaction, induction of pro-inflammatory cytokines and biliary fibrosis. Interestingly, melittin treatment attenuated hepatic function markers, ductular reaction, the reactive phenotype of cholangiocytes and cholangitis and biliary fibrosis. Our data suggest that melittin treatment can be protective against chronic cholestatic disease in DDC-fed mice. Further studies on the anti-inflammatory capacity of melittin are warranted for targeted therapy in cholangiopathy. PMID:26308055

  8. The state of membrane of the hepatocytes and the blood erytrocytes in pations with chronic hepatitis with signs of cholestasis.

    Directory of Open Access Journals (Sweden)

    Zakharash A.D.

    2007-01-01

    Full Text Available The purpose of work was to give morphological and morphometric characteristic of the hepatocytes and the blood erytrocytes against a background to determine the state of lipid peroxidation and antioxidant system of protection in case chronic cryptogenic hepatitis. Morphological and morphometric liver parameters were measured at the icteris in 5 patients (control – 5 patients. It was found that in patients with chronic hepatitis square of hepatocytes, square of their nuclei have been decreased, their relationship change for the better of cytoplasm. The hepatocytes and their nuclei have been deformed. The modifications of morphological and morphometric characteristic of the hepatocytes and the blood erytrocytes have been determined, drastic increase of the level CD95+ lymphocytes is evidence of the system reaction of apoptosis of the cells were studied in case chronic hepatitis with signs of cholestasis. In same patients with chronic hepatitis of non-virus etiology there were determined changes of area, perimeter and deformity of erythrocytes both on the basis of free radical reactions disorder and antioxidate protection system disorders; it induces us to quest their pathogenetically substantiated treatment.

  9. High incidence of rickets in extremely low birth weight infants with severe parenteral nutrition-associated cholestasis and bronchopulmonary dysplasia.

    Science.gov (United States)

    Lee, Soon Min; Namgung, Ran; Park, Min Soo; Eun, Ho Sun; Park, Kook In; Lee, Chul

    2012-12-01

    Risk factors for rickets of prematurity have not been re-examined since introduction of high mineral formula, particularly in ELBW infants. We analyzed the incidence and the risk factors of rickets in extremely low birth weight (ELBW) infants. As a retrospective case-control study from 2004 to 2008, risk factors were analyzed in 24 patients with rickets versus 31 patients without. The frequency of rickets in ELBW infants was 24/55 (44%). Infants with rickets were diagnosed at 48.2 ± 16.1 days of age, and improved by 85.3 ± 25.3 days. By radiologic evaluation, 29% were grade 1 rickets, 58% grade 2 and 13% grade 3. In univariate analysis, infants with rickets had significantly higher incidence of patent ductus arteriosus, parenteral nutrition associated cholestasis (PNAC), severe PNAC and moderate/severe bronchopulmonary dysplasia (BPD). In multiple regression analysis, after adjustment for gestation and birth weight, rickets significantly correlated with severe PNAC and with moderate/severe BPD. Serum peak alkaline phosphatase levels were significantly elevated in rickets (P rickets of prematurity remains high and the incidence of severe PNAC and moderate/severe BPD was significantly increased 18 and 3 times, respectively.

  10. Cholestasis and hypercholesterolemia in SCD1-deficient mice fed a low-fat, high-carbohydrate diet.

    Science.gov (United States)

    Flowers, Matthew T; Groen, Albert K; Oler, Angie Tebon; Keller, Mark P; Choi, Younjeong; Schueler, Kathryn L; Richards, Oliver C; Lan, Hong; Miyazaki, Makoto; Kuipers, Folkert; Kendziorski, Christina M; Ntambi, James M; Attie, Alan D

    2006-12-01

    Stearoyl-coenzyme A desaturase 1-deficient (SCD1(-/-)) mice have impaired MUFA synthesis. When maintained on a very low-fat (VLF) diet, SCD1(-/-) mice developed severe hypercholesterolemia, characterized by an increase in apolipoprotein B (apoB)-containing lipoproteins and the appearance of lipoprotein X. The rate of LDL clearance was decreased in VLF SCD1(-/-) mice relative to VLF SCD1(+/+) mice, indicating that reduced apoB-containing lipoprotein clearance contributed to the hypercholesterolemia. Additionally, HDL-cholesterol was dramatically reduced in these mice. The presence of increased plasma bile acids, bilirubin, and aminotransferases in the VLF SCD1(-/-) mice is indicative of cholestasis. Supplementation of the VLF diet with MUFA- and PUFA-rich canola oil, but not saturated fat-rich hydrogenated coconut oil, prevented these plasma phenotypes. However, dietary oleate was not as effective as canola oil in reducing LDL-cholesterol, signifying a role for dietary PUFA deficiency in the development of this phenotype. These results indicate that the lack of SCD1 results in an increased requirement for dietary unsaturated fat to compensate for impaired MUFA synthesis and to prevent hypercholesterolemia and hepatic dysfunction. Therefore, endogenous MUFA synthesis is essential during dietary unsaturated fat insufficiency and influences the dietary requirement of PUFA.

  11. Proteomic analysis of polypeptides captured from blood during extracorporeal albumin dialysis in patients with cholestasis and resistant pruritus.

    Science.gov (United States)

    Gay, Marina; Pares, Albert; Carrascal, Montserrat; Bosch-i-Crespo, Pau; Gorga, Marina; Mas, Antoni; Abian, Joaquin

    2011-01-01

    Albumin dialysis using the molecular adsorbent recirculating system (MARS) is a new therapeutic approach for liver diseases. To gain insight into the mechanisms involved in albumin dialysis, we analyzed the peptides and proteins absorbed into the MARS strong anion exchange (SAX) cartridges as a result of the treatment of patients with cholestasis and resistant pruritus. Proteins extracted from the SAX MARS cartridges after patient treatment were digested with two enzymes. The resulting peptides were analyzed by multidimensional liquid chromatography coupled to tandem mass spectrometry. We identified over 1,500 peptide sequences corresponding to 144 proteins. In addition to the proteins that are present in control albumin-derived samples, this collection includes 60 proteins that were specific to samples obtained after patient treatment. Five of these proteins (neutrophil defensin 1 [HNP-1], secreted Ly-6/uPAR-related protein 1 [SLURP1], serum amyloid A, fibrinogen alpha chain and pancreatic prohormone) were confirmed to be removed by the dialysis procedure using targeted selected-reaction monitoring MS/MS. Furthermore, capture of HNP-1 and SLURP1 was also validated by Western blot. Interestingly, further analyses of SLURP1 in serum indicated that this protein was 3-fold higher in cholestatic patients than in controls. Proteins captured by MARS share certain structural and biological characteristics, and some of them have important biological functions. Therefore, their removal could be related either to therapeutic or possible adverse effects associated with albumin dialysis.

  12. Pediatric parenteral nutrition-associated liver disease and cholestasis: Novel advances in pathomechanisms-based prevention and treatment.

    Science.gov (United States)

    Orso, Giuseppe; Mandato, Claudia; Veropalumbo, Claudio; Cecchi, Nicola; Garzi, Alfredo; Vajro, Pietro

    2016-03-01

    Parenteral nutrition constitutes a life-saving therapeutic tool in patients unable to ingest/absorb oral or enteral delivered nutrients. Liver function tests abnormalities are a common therapy-related complication, thus configuring the so-called Parenteral Nutrition Associated Liver Disease (PNALD) or cholestasis (PNAC). Although the damage is frequently mild, and resolves after discontinuation of parenteral nutrition, in some cases it progresses into cirrhotic changes, especially in neonates and infants. We present a literature review focusing on the pathogenetic mechanisms-driven prevention and therapies for the cases where parenteral nutrition cannot be discontinued. Ursodeoxycholic acid has been proposed in patients with cholestatic hepatopathy, but its efficacy needs to be better established. Little evidence is available on efficacy of anti-oxidants, antibiotics, probiotics and anti TNFα. Lipid emulsions based on fish oil with a high content of long-chain polyunsaturated fatty acids ω-3 appear effective both in decreasing intrahepatic inflammation and in improving biliary flow. Most recent promising variations such as soybean/MCT/olive/fish oil emulsion [third generation lipid emulsion (SMOFlipid)] are under investigation. In conclusion, we remark the emergence of a number of novel pathomechanisms underlying the severe liver impairment damage (PNALD and PNAC) in patients treated with parenteral nutrition. Only few traditional and innovative therapeutic strategies have hitherto been shown promising. PMID:26698410

  13. Differential diagnosis of infantile cholestasis%婴儿胆汁淤积症的鉴别诊断思路

    Institute of Scientific and Technical Information of China (English)

    朱启镕; 王建设

    2011-01-01

    胆汁淤积是婴儿肝脏疾病最常见的临床表现.病因在很大程度上决定其预后,有些病因需要医生做出快速的诊断及采取恰当的治疗.胆道闭锁、败血症、尿路感染、甲状腺功能低下、Citrin缺陷病、酪氨酸血症及先天性胆汁酸合成缺陷都要及早诊断,因为对这些疾病及时适当的治疗可显著的改善预后.%Cholestasis is the most common manifestation of liver diseases in infancy. The clinical outcome is mostly dependent on the etiology, some of them require prompt identification and then proper management. Biliary atresia, sepsis, urinary tract infection,hypothyroidism, citrin deficiency, tyrosemia and congenital bile acid synthetic defects need highest priority, because proper management could improve the outcome significantly.

  14. Proteomic analysis of polypeptides captured from blood during extracorporeal albumin dialysis in patients with cholestasis and resistant pruritus.

    Directory of Open Access Journals (Sweden)

    Marina Gay

    Full Text Available Albumin dialysis using the molecular adsorbent recirculating system (MARS is a new therapeutic approach for liver diseases. To gain insight into the mechanisms involved in albumin dialysis, we analyzed the peptides and proteins absorbed into the MARS strong anion exchange (SAX cartridges as a result of the treatment of patients with cholestasis and resistant pruritus. Proteins extracted from the SAX MARS cartridges after patient treatment were digested with two enzymes. The resulting peptides were analyzed by multidimensional liquid chromatography coupled to tandem mass spectrometry. We identified over 1,500 peptide sequences corresponding to 144 proteins. In addition to the proteins that are present in control albumin-derived samples, this collection includes 60 proteins that were specific to samples obtained after patient treatment. Five of these proteins (neutrophil defensin 1 [HNP-1], secreted Ly-6/uPAR-related protein 1 [SLURP1], serum amyloid A, fibrinogen alpha chain and pancreatic prohormone were confirmed to be removed by the dialysis procedure using targeted selected-reaction monitoring MS/MS. Furthermore, capture of HNP-1 and SLURP1 was also validated by Western blot. Interestingly, further analyses of SLURP1 in serum indicated that this protein was 3-fold higher in cholestatic patients than in controls. Proteins captured by MARS share certain structural and biological characteristics, and some of them have important biological functions. Therefore, their removal could be related either to therapeutic or possible adverse effects associated with albumin dialysis.

  15. Alisol B 23-acetate protects against ANIT-induced hepatotoxity and cholestasis, due to FXR-mediated regulation of transporters and enzymes involved in bile acid homeostasis.

    Science.gov (United States)

    Meng, Qiang; Chen, Xin-Li; Wang, Chang-Yuan; Liu, Qi; Sun, Hui-Jun; Sun, Peng-Yuan; Huo, Xiao-Kui; Liu, Zhi-Hao; Yao, Ji-Hong; Liu, Ke-Xin

    2015-03-15

    Intrahepatic cholestasis is a clinical syndrome with systemic and intrahepatic accumulation of excessive toxic bile acids that ultimately cause hepatobiliary injury. Appropriate regulation of bile acids in hepatocytes is critically important for protection against liver injury. In the present study, we characterized the protective effect of alisol B 23-acetate (AB23A), a natural triterpenoid, on alpha-naphthylisothiocyanate (ANIT)-induced liver injury and intrahepatic cholestasis in mice and further elucidated the mechanisms in vivo and in vitro. AB23A treatment dose-dependently protected against liver injury induced by ANIT through reducing hepatic uptake and increasing efflux of bile acid via down-regulation of hepatic uptake transporters (Ntcp) and up-regulation of efflux transporter (Bsep, Mrp2 and Mdr2) expression. Furthermore, AB23A reduced bile acid synthesis through repressing Cyp7a1 and Cyp8b1, increased bile acid conjugation through inducing Bal, Baat and bile acid metabolism through an induction in gene expression of Sult2a1. We further demonstrate the involvement of farnesoid X receptor (FXR) in the hepatoprotective effect of AB23A. The changes in transporters and enzymes, as well as ameliorative liver histology in AB23A-treated mice were abrogated by FXR antagonist guggulsterone in vivo. In vitro evidences also directly demonstrated the effect of AB23A on FXR activation in a dose-dependent manner using luciferase reporter assay in HepG2 cells. In conclusion, AB23A produces protective effect against ANIT-induced hepatotoxity and cholestasis, due to FXR-mediated regulation of transporters and enzymes. PMID:25655198

  16. Ca2+-DEPENDENT PROTEIN KINASE C ISOFORMS ARE CRITICAL TO ESTRADIOL 17β-D-GLUCURONIDE-INDUCED CHOLESTASIS IN THE RAT

    OpenAIRE

    Crocenzi, Fernando A.; Enrique J Sánchez Pozzi; Ruiz, María Laura; Zucchetti, Andrés E.; Roma, Marcelo G.; Mottino, Aldo D.; Vore, Mary

    2008-01-01

    The endogenous estradiol metabolite estradiol 17β-D-glucuronide (E217G) induces an acute cholestasis in rat liver coincident with retrieval of the canalicular transporters Bsep (Abcc11) and Mrp2 (Abcc2) and their associated loss of function. We assessed the participation of Ca2+-dependent PKC isoforms (cPKC) in the cholestatic manifestations of E217G in the perfused rat liver (PRL) and in isolated rat hepatocyte couplets (IRHC). In the PRL, E217G (2 μmol/liver; intraportal, single injection) ...

  17. Promoter DNA methylation of farnesoid X receptor and pregnane X receptor modulates the intrahepatic cholestasis of pregnancy phenotype.

    Directory of Open Access Journals (Sweden)

    Romina Cabrerizo

    Full Text Available The intrahepatic cholestasis of pregnancy (ICP is a multifactorial liver disorder which pathogenesis involves the interplay among abnormal bile acid (BA levels, sex hormones, environmental factors, and genetic susceptibility. The dynamic nature of ICP that usually resolves soon after delivery suggests the possibility that its pathobiology is under epigenetic modulation. We explored the status of white blood peripheral cells-DNA methylation of CpG-enriched sites at the promoter of targeted genes (FXR/NR1H4, PXR/NR1I2, NR1I3, ESR1, and ABCC2 in a sample of 88 ICP patients and 173 healthy pregnant women in the third trimester of their pregnancies. CpG dinucleotides at the gene promoter of nuclear receptors subfamily 1 members and ABCC2 transporter were highly methylated during healthy pregnancy. We observed significant differences at the distal (-1890 and proximal promoter (-358 CpG sites of the FXR/NR1H4 and at the distal PXR/NR1I2 (-1224 promoter, which were consistently less methylated in ICP cases when compared with controls. In addition, we observed that methylation at FXR/NR1H4-1890 and PXR/NR1I2-1224 promoter sites was highly and positively correlated with BA profiling, particularly, conjugated BAs. Conversely, methylation level at the proximal FXR/NR1H4-358 CpG site was significantly and negatively correlated with the primary cholic and secondary deoxycholic acid. In vitro exploration showed that epiallopregnanolone sulfate, a reported FXR inhibitor, regulates the transcriptional activity of FXR/NR1H4 but seems to be not involved in the methylation changes. In conclusion, the identification of epigenetic marks in target genes provides a basis for the understanding of adverse liver-related pregnancy outcomes, including ICP.

  18. Swertianlarin, an Herbal Agent Derived from Swertia mussotii Franch, Attenuates Liver Injury, Inflammation, and Cholestasis in Common Bile Duct-Ligated Rats

    Directory of Open Access Journals (Sweden)

    Liangjun Zhang

    2015-01-01

    Full Text Available Swertianlarin is an herbal agent abundantly distributed in Swertia mussotii Franch, a Chinese traditional herb used for treatment of jaundice. To study the therapeutic effect of swertianlarin on cholestasis, liver injury, serum proinflammatory cytokines, and bile salt concentrations were measured by comparing rats treated with swertianlarin 100 mg/kg/d or saline for 3, 7, or 14 days after bile duct ligation (BDL. Serum alanine aminotransferase (ATL and aspartate aminotransferase (AST levels were significantly decreased in BDL rats treated with swertianlarin for 14 days (P<0.05. The reduced liver injury in BDL rats by swertianlarin treatment for 14 days was further confirmed by liver histopathology. Levels of serum tumor necrosis factor alpha (TNFα were decreased by swertianlarin in BDL rats for 3 and 7 days (P<0.05. Moreover, reductions in serum interleukins IL-1β and IL-6 levels were also observed in BDL rats treated with swertianlarin (P<0.05. In addition, most of serum toxic bile salt concentrations (e.g., chenodeoxycholic acid (CDCA and deoxycholic acid (DCA in cholestatic rats were decreased by swertianlarin (P<0.05. In conclusion, the data suggest that swertianlarin derived from Swertia mussotii Franch attenuates liver injury, inflammation, and cholestasis in bile duct-ligated rats.

  19. Paeonia lactiflora Pall. protects against ANIT-induced cholestasis by activating Nrf2 via PI3K/Akt signaling pathway

    Directory of Open Access Journals (Sweden)

    Ma X

    2015-09-01

    Full Text Available Xiao Ma,1,2 Yan-ling Zhao,2 Yun Zhu,3 Zhe Chen,1,2 Jia-bo Wang,4 Rui-yu Li,1,4 Chang Chen,1,2 Shi-zhang Wei,1,2 Jian-yu Li,3 Bing Liu,5 Rui-lin Wang,3 Yong-gang Li,3 Li-fu Wang,3 Xiao-he Xiao4 1Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Pharmacy, 302 Military Hospital of People’s Liberation Army, Beijing, People’s Republic of China; 3Department of Integrative Medical Center, 302 Military Hospital of People’s Liberation Army, Beijing, People’s Republic of China; 4China Military Institute of Chinese Medicine, 302 Military Hospital of People’s Liberation Army, Beijing, People’s Republic of China; 5School of Chinese Medicine, The University of Hong Kong, Hong Kong Background: Paeonia lactiflora Pall. (PLP, a traditional Chinese herbal medicine, has been used for hepatic disease treatment over thousands of years. In our previous study, PLP was shown to demonstrate therapeutic effect on hepatitis with severe cholestasis. The aim of this study was to evaluate the antioxidative effect of PLP on alpha-naphthylisothiocyanate (ANIT-induced cholestasis by activating NF-E2-related factor 2 (Nrf2 via phosphatidylinositol 3-kinase (PI3K/Akt signaling pathway. Materials and methods: Liquid chromatography-mass spectrometry (LC-MS was performed to identify the main compounds present in PLP. The mechanism of action of PLP and its therapeutic effect on cholestasis, induced by ANIT, were further investigated. Serum indices such as total bilirubin (TBIL, direct bilirubin (DBIL, aspartate aminotransferase (AST, alanine aminotransferase (ALT, alkaline phosphatase (ALP, γ-glutamyl transpeptidase (γ-GT, and total bile acid (TBA were measured, and histopathology of liver was also performed to determine the efficacy of treatment with PLP. Moreover, in order to illustrate the underlying signaling pathway, liver glutathione (GSH content and mRNA or protein levels of glutamate

  20. Alisol B 23-acetate protects against ANIT-induced hepatotoxity and cholestasis, due to FXR-mediated regulation of transporters and enzymes involved in bile acid homeostasis

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Qiang; Chen, Xin-li; Wang, Chang-yuan; Liu, Qi; Sun, Hui-jun; Sun, Peng-yuan; Huo, Xiao-kui; Liu, Zhi-hao; Yao, Ji-hong; Liu, Ke-xin, E-mail: kexinliu@dlmedu.edu.cn

    2015-03-15

    Intrahepatic cholestasis is a clinical syndrome with systemic and intrahepatic accumulation of excessive toxic bile acids that ultimately cause hepatobiliary injury. Appropriate regulation of bile acids in hepatocytes is critically important for protection against liver injury. In the present study, we characterized the protective effect of alisol B 23-acetate (AB23A), a natural triterpenoid, on alpha-naphthylisothiocyanate (ANIT)-induced liver injury and intrahepatic cholestasis in mice and further elucidated the mechanisms in vivo and in vitro. AB23A treatment dose-dependently protected against liver injury induced by ANIT through reducing hepatic uptake and increasing efflux of bile acid via down-regulation of hepatic uptake transporters (Ntcp) and up-regulation of efflux transporter (Bsep, Mrp2 and Mdr2) expression. Furthermore, AB23A reduced bile acid synthesis through repressing Cyp7a1 and Cyp8b1, increased bile acid conjugation through inducing Bal, Baat and bile acid metabolism through an induction in gene expression of Sult2a1. We further demonstrate the involvement of farnesoid X receptor (FXR) in the hepatoprotective effect of AB23A. The changes in transporters and enzymes, as well as ameliorative liver histology in AB23A-treated mice were abrogated by FXR antagonist guggulsterone in vivo. In vitro evidences also directly demonstrated the effect of AB23A on FXR activation in a dose-dependent manner using luciferase reporter assay in HepG2 cells. In conclusion, AB23A produces protective effect against ANIT-induced hepatotoxity and cholestasis, due to FXR-mediated regulation of transporters and enzymes. - Highlights: • AB23A has at least three roles in protection against ANIT-induced liver injury. • AB23A decreases Ntcp, and increases Bsep, Mrp2 and Mdr2 expression. • AB23A represses Cyp7a1 and Cyp8b1 through inducing Shp and Fgf15 expression. • AB23A increases bile acid metabolism through inducing Sult2a1 expression. • FXR activation is involved

  1. Diagnóstico diferencial de colestase neonatal: parâmetros clínicos e laboratoriais Differential diagnosis of neonatal cholestasis: clinical and laboratory parameters

    Directory of Open Access Journals (Sweden)

    Maria Angela Bellomo-Brandao

    2010-02-01

    Full Text Available OBJETIVO: Avaliar se os parâmetros clínicos e laboratoriais poderiam auxiliar no diagnóstico diferencial da colestase neonatal (CN intra- e extra-hepática. MÉTODOS: Estudo retrospectivo de pacientes com CN hospitalizados na Clínica de Hepatologia Pediátrica do Hospital de Clínicas da Universidade Estadual de Campinas (UNICAMP, Campinas (SP, entre dezembro de 1980 e março de 2005. A abordagem para o diagnóstico da CN foi padronizada. De acordo com o diagnóstico, os pacientes foram classificados em dois grupos: I (colestase neo natal intra-hepática e II (colestase neonatal extrahepática. Para verificar se havia associação com a variável categórica, os testes de qui-quadrado e Mann-Whitney foram utilizados com correções para idade para a análise de covariância (ANCOVA. A determinação da precisão das variáveis clínicas e laboratoriais para a diferenciação dos grupos foi realizada através da análise da curva ROC. RESULTADOS: Cento e sessenta e oito pacientes foram avaliados (grupo I = 54,8% e grupo II = 45,2%. Nos pacientes com menos de 60 dias de vida, houve predominância de causas intra-hepáticas, enquanto que naqueles com mais de 60 dias, houve predominância de etiologia extrahepática (p OBJECTIVE: To evaluate if clinical and laboratory parameters could assist in the differential diagnosis of intra and extra-hepatic neonatal cholestasis (NC. METHODS: Retrospective study of NC patients admitted at the Pediatric Hepatology Outpatient Clinic of the teaching hospital of Universidade Estadual de Campinas (UNICAMP, Campinas, Brazil, between December 1980 and March 2005. The approach to the diagnosis of NC was standardized. According to diagnosis, patients were classified into two groups: I (intra-hepatic neonatal cholestasis and II (extra-hepatic neonatal cholestasis. In order to verify if there was association with the categorical variable, the chi-square and Mann-Whitney tests were used, with corrections for age for

  2. Heterozygous Inactivation of the Nuclear Receptor PXR/NR1I2 in a Patient With Anabolic Steroid-Induced Intrahepatic Cholestasis

    Science.gov (United States)

    Liebe, Roman; Krawczyk, Marcin; Raszeja-Wyszomirska, Joanna; Kruk, Beata; Preis, Rebecca; Trottier, Jocelyn; Barbier, Olivier; Milkiewicz, Piotr; Lammert, Frank

    2016-01-01

    Introduction The incidence of liver damage due to steroid consumption is increasing due to the omnipresence of the idealized body image and the widespread availability of drugs via the Internet. The genetic factors underlying individual susceptibility are not presently known. Case Presentation A male patient developed cholestatic liver injury two weeks after a two-month course of anabolic steroids. Next-generation sequencing (NGS) of 24 cholestasis-related genes revealed a heterozygous two-basepair deletion in exon 1 of the pregnane X receptor gene (PXR). Serum bile salt levels showed marked imbalances, strongly resembling the changes observed in patients with biliary obstruction. Conclusions This case of PXR haploinsufficiency reveals transcriptional regulatory functions activated in the liver under xenobiotic stress by steroids, which appear to require two functional copies of the nuclear receptor gene. Deranged bile salt levels outline the central role of PXR in bile acid synthesis, modification, and export. PMID:27799961

  3. The effect of acetaminophen on the expression of BCRP in trophoblast cells impairs the placental barrier to bile acids during maternal cholestasis

    International Nuclear Information System (INIS)

    Acetaminophen is used as first-choice drug for pain relief during pregnancy. Here we have investigated the effect of acetaminophen at subtoxic doses on the expression of ABC export pumps in trophoblast cells and its functional repercussion on the placental barrier during maternal cholestasis. The incubation of human choriocarcinoma cells (JAr, JEG-3 and BeWo) with acetaminophen for 48 h resulted in no significant changes in the expression and/or activity of MDR1 and MRPs. In contrast, in JEG-3 cells, BCRP mRNA, protein, and transport activity were reduced. In rat placenta, collected at term, acetaminophen administration for the last three days of pregnancy resulted in enhanced mRNA, but not protein, levels of Mrp1 and Bcrp. In fact, a decrease in Bcrp protein was found. Using in situ perfused rat placenta, a reduction in the Bcrp-dependent fetal-to-maternal bile acid transport after treating the dams with acetaminophen was found. Complete biliary obstruction in pregnant rats induced a significant bile acid accumulation in fetal serum and tissues, which was further enhanced when the mothers were treated with acetaminophen. This drug induced increased ROS production in JEG-3 cells and decreased the total glutathione content in rat placenta. Moreover, the NRF2 pathway was activated in JEG-3 cells as shown by an increase in nuclear NRF2 levels and an up-regulation of NRF2 target genes, NQO1 and HMOX-1, which was not observed in rat placenta. In conclusion, acetaminophen induces in placenta oxidative stress and a down-regulation of BCRP/Bcrp, which may impair the placental barrier to bile acids during maternal cholestasis. - Highlights: • Acetaminophen induces changes in placental BCRP expression in vitro. • This drug reduces the ability of placental cells to export BCRP substrates. • Acetaminophen induces changes in Bcrp expression in rat placenta. • Placental barrier to bile acids is impaired in rats treated with this drug

  4. The effect of acetaminophen on the expression of BCRP in trophoblast cells impairs the placental barrier to bile acids during maternal cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Blazquez, Alba G., E-mail: albamgb@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); CIBERehd, Instituto de Salud Carlos III, Madrid (Spain); Briz, Oscar, E-mail: obriz@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); CIBERehd, Instituto de Salud Carlos III, Madrid (Spain); Gonzalez-Sanchez, Ester, E-mail: u60343@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); Perez, Maria J., E-mail: mjperez@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); University Hospital of Salamanca, IECSCYL-IBSAL, Salamanca (Spain); CIBERehd, Instituto de Salud Carlos III, Madrid (Spain); Ghanem, Carolina I., E-mail: cghanem@ffyb.uba.ar [Instituto de Investigaciones Farmacologicas, Facultad de Farmacia y Bioquimica, CONICET, Universidad de Buenos Aires, Buenos Aires (Argentina); Marin, Jose J.G., E-mail: jjgmarin@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); CIBERehd, Instituto de Salud Carlos III, Madrid (Spain)

    2014-05-15

    Acetaminophen is used as first-choice drug for pain relief during pregnancy. Here we have investigated the effect of acetaminophen at subtoxic doses on the expression of ABC export pumps in trophoblast cells and its functional repercussion on the placental barrier during maternal cholestasis. The incubation of human choriocarcinoma cells (JAr, JEG-3 and BeWo) with acetaminophen for 48 h resulted in no significant changes in the expression and/or activity of MDR1 and MRPs. In contrast, in JEG-3 cells, BCRP mRNA, protein, and transport activity were reduced. In rat placenta, collected at term, acetaminophen administration for the last three days of pregnancy resulted in enhanced mRNA, but not protein, levels of Mrp1 and Bcrp. In fact, a decrease in Bcrp protein was found. Using in situ perfused rat placenta, a reduction in the Bcrp-dependent fetal-to-maternal bile acid transport after treating the dams with acetaminophen was found. Complete biliary obstruction in pregnant rats induced a significant bile acid accumulation in fetal serum and tissues, which was further enhanced when the mothers were treated with acetaminophen. This drug induced increased ROS production in JEG-3 cells and decreased the total glutathione content in rat placenta. Moreover, the NRF2 pathway was activated in JEG-3 cells as shown by an increase in nuclear NRF2 levels and an up-regulation of NRF2 target genes, NQO1 and HMOX-1, which was not observed in rat placenta. In conclusion, acetaminophen induces in placenta oxidative stress and a down-regulation of BCRP/Bcrp, which may impair the placental barrier to bile acids during maternal cholestasis. - Highlights: • Acetaminophen induces changes in placental BCRP expression in vitro. • This drug reduces the ability of placental cells to export BCRP substrates. • Acetaminophen induces changes in Bcrp expression in rat placenta. • Placental barrier to bile acids is impaired in rats treated with this drug.

  5. Tumor necrosis factor-α promotes cholestasis-induced liver fibrosis in the mouse through tissue inhibitor of metalloproteinase-1 production in hepatic stellate cells.

    Directory of Open Access Journals (Sweden)

    Yosuke Osawa

    Full Text Available Tumor necrosis factor (TNF-α, which is a mediator of hepatotoxicity, has been implicated in liver fibrosis. However, the roles of TNF-α on hepatic stellate cell (HSC activation and liver fibrosis are complicated and remain controversial. To explore this issue, the role of TNF-α in cholestasis-induced liver fibrosis was examined by comparing between TNF-α(-/- mice and TNF-α(+/+ mice after bile duct ligation (BDL. Serum TNF-α levels in mice were increased by common BDL combined with cystic duct ligation (CBDL+CDL. TNF-α deficiency reduced liver fibrosis without affecting liver injury, inflammatory cell infiltration, and liver regeneration after CBDL+CDL. Increased expression levels of collagen α1(I mRNA, transforming growth factor (TGF-β mRNA, and α-smooth muscle actin (αSMA protein by CBDL+CDL in the livers of TNF-α(-/- mice were comparable to those in TNF-α(+/+ mice. Exogenous administration of TNF-α decreased collagen α1(I mRNA expression in isolated rat HSCs. These results suggest that the reduced fibrosis in TNF-α(-/- mice is regulated in post-transcriptional level. Tissue inhibitor of metalloproteinase (TIMP-1 plays a crucial role in the pathogenesis of liver fibrosis. TIMP-1 expression in HSCs in the liver was increased by CBDL+CDL, and the induction was lower in TNF-α(-/- mice than in TNF-α(+/+ mice. Fibrosis in the lobe of TIMP-1(-/- mice with partial BDL was also reduced. These findings indicate that TNF-α produced by cholestasis can promote liver fibrosis via TIMP-1 production from HSCs. Thus, targeting TNF-α and TIMP-1 may become a new therapeutic strategy for treating liver fibrosis in cholestatic liver injury.

  6. Ultrasonography of Neonatal Cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Cheon, Jung Eun [Seoul National University Hospital, Seoul (Korea, Republic of)

    2012-06-15

    Ultrasonography (US) is as an important tool for differentiation of obstructive and non-obstructive causes of jaundice in infants and children. Beyond two weeks of age, extrahepatic biliary atresia and neonatal hepatitis are the two most common causes of persistent neonatal jaundice: differentiation of extrahepatic biliary atresia, which requires early surgical intervention, is very important. Meticulous analysis should focus on size and configuration of the gallbladder and anatomical changes of the portahepatis. In order to narrow the differential diagnosis, combined approaches using hepatic scintigraphy, MR cholangiography, and, at times, percutaneous liver biopsy are necessary. US is useful for demonstrating choledochal cyst, bile plug syndrome, and spontaneous perforation of the extrahepatic bile duct

  7. Histone H3K4 trimethylation by MLL3 as part of ASCOM complex is critical for NR activation of bile acid transporter genes and is downregulated in cholestasis

    OpenAIRE

    Ananthanarayanan, M.; Li, Yanfeng; Surapureddi, S.; Balasubramaniyan, N; Ahn, Jaeyong; Goldstein, J. A.; Suchy, Frederick J.

    2010-01-01

    The nuclear receptor Farnesoid x receptor (FXR) is a critical regulator of multiple genes involved in bile acid homeostasis. The coactivators attracted to promoters of FXR target genes and epigenetic modifications that occur after ligand binding to FXR have not been completely defined, and it is unknown whether these processes are disrupted during cholestasis. Using a microarray, we identified decreased expression of mixed lineage leukemia 3 (MLL3), a histone H3 lysine 4 (H3K4) lysine methyl ...

  8. 妊娠期肝内胆汁淤积症与胎儿损伤%Intrahepatic cholestasis of pregnancy and fetal injury

    Institute of Scientific and Technical Information of China (English)

    张丽娟; 张凤华; 汤丽丽; 杨伟红; 张雪

    2013-01-01

    Intrahepatic cholestasis of pregnancy (ICP) is an unique complication in pregnancy,which usually manifests in the second or third trimester,and mainly harms the fetus.Its pathogenesis is not yet clear,and placental pathological changes are insufficient to explain the clinical phenomenon.Recent studies had shown that the important cause ofperinatal deaths may be the damage to the placental structure and function caused by the high bile acid level.In addition,the change of placental structure and function,unbilical cord factors,and endocrine changes can also cause the fetal development and intrauterine hypoxia.In recent years related researches focus on the toxic effect of bile acid on fetus heart,lungs,brain,liver,and other important organs,the placental vascular pathology,hemodynamic changes,umbilical cord blood vessel factors and the endocrine changes.%妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,Icp)是妊娠中晚期特有的并发症,主要危害胎儿,其发病机制尚不清楚,胎盘的病变不足以解释临床现象.近年研究发现,ICP患者母体高胆酸水平对胎儿脏器组织结构和功能的损害是围产儿死亡的重要原因.另外,ICP胎盘结构及功能改变,脐带因素及内分泌变化等也可导致胎儿发育受损及宫内缺氧.近年来有关胆汁酸对胎儿心、肺、脑、肝等重要脏器的毒性作用、ICP胎盘病理及血流动力学改变、胎盘血管及脐带血管因素和内分泌变化的研究有了长足的进展.

  9. Feasibility of urinary microRNA profiling detection in intrahepatic cholestasis of pregnancy and its potential as a non-invasive biomarker

    Science.gov (United States)

    Ma, Li; Zhang, Xiao-Qing; Zhou, Da-Xue; Cui, Yue; Deng, Lin-Lin; Yang, Ting; Shao, Yong; Ding, Min

    2016-01-01

    Intrahepatic cholestasis of pregnancy (ICP), a pregnancy-related liver disease, leads to complications for both mother and fetus. Circulating microRNAs (miRNAs) have emerged as candidate biomarkers for many diseases. So far, the circulating miRNAs profiling of ICP has not been investigated. To assess the urinary miRNAs as non-invasive biomarkers for ICP, a differential miRNA profiling was initially analyzed by individual quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assay in urinary samples from a screening set including 10 ICP and 10 healthy pregnancies. The selected candidate miRNAs were then validated by a validation set with 40 ICP and 50 healthy pregnancies using individual qRT-PCR assay. Compared with the expression in urine of healthy pregnant women, the expression levels of hsa-miR-151-3p and hsa-miR-300 were significantly down-regulated, whereas hsa-miR-671-3p and hsa-miR-369-5p were significantly up-regulated in urine from ICP patients (p microRNA profiling detection in ICP is feasible and maternal urinary miRNAs have the potential to be non-invasive biomarkers for the diagnosis of ICP. PMID:27534581

  10. Low dose of oleanolic acid protects against lithocholic acid-induced cholestasis in mice: potential involvement of nuclear factor-E2-related factor 2-mediated upregulation of multidrug resistance-associated proteins.

    Science.gov (United States)

    Chen, Pan; Zeng, Hang; Wang, Yongtao; Fan, Xiaomei; Xu, Chenshu; Deng, Rongrong; Zhou, Xunian; Bi, Huichang; Huang, Min

    2014-05-01

    Oleanolic acid (OA) is a natural triterpenoid and has been demonstrated to protect against varieties of hepatotoxicants. Recently, however, OA at high doses was reported to produce apparent cholestasis in mice. In this study, we characterized the protective effect of OA at low doses against lithocholic acid (LCA)-induced cholestasis in mice and explored further mechanisms. OA cotreatment (5, 10, and 20 mg/kg, i.p.) significantly improved mouse survival rate, attenuated liver necrosis, and decreased serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase; more importantly, serum total bile acids and bilirubin, as well as hepatic total bile acids were also remarkably reduced. Gene and protein expression analysis showed that hepatic expression of multidrug resistance-associated protein 2 (Mrp2), Mrp3, and Mrp4 was significantly increased by OA cotreatment, whereas other bile acid metabolism- and transport-related genes, including Na+/taurocholate cotransporter, organic anion transporter 1b2, bile salt export pump, multidrug resistance protein 3, Cyp3a11, Cyp2b10, Sulfotransferase 2a1 (Sult2a1), and UDP-glucuronosyltransferase 1a1 (Ugt1a1), were only slightly changed. OA also caused increased nuclear factor-E2-related factor (Nrf2) mRNA expression and nuclear protein accumulation, whereas nuclear receptors farnesoid X receptor (FXR), pregnane X receptor (PXR), and constitutive androstane receptor were not significantly influenced by OA. Luciferase (Luc) assays performed in HepG2 cells illustrated that OA was a strong Nrf2 agonist with moderate PXR and weak FXR agonism. Finally, in mouse primary cultured hepatocytes, OA dose- and time-dependently induced expression of Mrp2, Mrp3, and Mrp4; however, this upregulation was abrogated when Nrf2 was silenced. In conclusion, OA produces a protective effect against LCA-induced hepatotoxicity and cholestasis, possibly due to Nrf2-mediated upregulation of Mrp2, Mrp3, and Mrp4. PMID:24510383

  11. Screening for the inherited metabolic diseases in infants with cholestasis and changing pattern of diagnosis%遗传代谢病的筛查与婴儿胆汁淤积病因诊断的变化

    Institute of Scientific and Technical Information of China (English)

    李晓瑜; 马华梅; 陈红珊; 李燕虹; 沈振宇; 杜敏联

    2010-01-01

    Objective To investigate the changing pattern of diagnosis of infantile cholestasis after screening the inherited metabolic diseases in infants with cholestasis. Methods Infants under 12 months with cholestasis were identified retrospectively from hospital records from Jan. 1996 to Dec. 2007. The data were retrieved from the medical records and analyzed by focusing particularly on the changing etiology of cholestasis and inherited metabolic diseases in these infants after performing routine screening and diagnostic procedures. Results Among 421 infants identified as having cholestasis during 12-years study period, the common causes of infantile cholestasis were cytomegalovirus (CMV) infection (36. 11% ), bile duct hypoplasia or congenital biliary atresia (31.59%), metabolic disease (8.08%), miscellaneous (10.69%), and unknown ( 13.54% ). The proportion of infants with metabolic diseases after screening increased 16 folds compared with before screening( 15.76% vs 0. 92% ,P<0. 01 ), whereas the proportion of infants with unknown cause decreased from 17.43% to 9.36% (P<0.05). There was no significant change in the proportions of CMV infection, congenital biliary atresia, and miscellaneous causes. The major metabolic diseases of 34 infants included citrin deficiency (41. 18% ) and tyrosinemia (23.53%), followed by galactosemia and progressive familial intrahepatic cholestasis (8. 82% )etc. Conclusions Inherited metabolic disease has become an important cause of infantile cholestasis, which is mainly due to citrin deficiency. Therefore, it is necessary to set a routing screening of citrin deficiency in infants with cholestasis.%目的 了解开展遗传代谢病筛查后婴儿胆汁淤积的病因谱变化及与之相关的遗传代谢病种类.方法 回顾性总结1996年1月至2007年12月本院收治的婴儿胆汁淤积病例的临床资料,分析进行遗传代谢病筛查前后婴儿胆汁淤积病因的年代变迁及与胆汁淤积相关的遗

  12. High doses of ursodeoxycholic acid up-regulate the expression of placental breast cancer resistance protein in patients affected by intrahepatic cholestasis of pregnancy.

    Directory of Open Access Journals (Sweden)

    Francesco Azzaroli

    Full Text Available BACKGROUND: Ursodeoxycholic acid (UDCA administration in intrahepatic cholestasis of pregnancy (ICP induces bile acids (BA efflux from the foetal compartment, but the molecular basis of this transplacental transport is only partially defined. AIM: To determine if placental breast cancer resistance protein (BCRP, able to transport BA, is regulated by UDCA in ICP. METHODS: 32 pregnant women with ICP (14 untreated, 34.9±5.17 years; 18 treated with UDCA--25 mg/Kg/day, 32.7±4.62 years, and 12 healthy controls (33.4±3.32 years agreed to participate in the study. Placentas were obtained at delivery and processed for membrane extraction. BCRP protein expression was evaluated by immunoblotting techniques and chemiluminescence quantified with a luminograph measuring emitted photons; mRNA expression with real time PCR. Statistical differences between groups were evaluated by ANOVA with Dunn's Multiple Comparison test. RESULTS: BCRP was expressed only on the apical membrane of the syncytiotrophoblast. A significant difference was observed among the three groups both for mRNA (ANOVA, p = 0.0074 and protein (ANOVA, p<0.0001 expression. BCRP expression was similar in controls and in the untreated ICP group. UDCA induced a significant increase in placental BCRP mRNA and protein expression compared to controls (350.7±106.3 vs 100±18.68% of controls, p<0.05 and 397.8±56.02 vs 100±11.44% of controls, p<0.001, respectively and untreated ICP (90.29±17.59% of controls, p<0.05 and 155.0±13.87%, p<0.01. CONCLUSION: Our results confirm that BCRP is expressed only on the apical membrane of the syncytiotrophoblast and show that ICP treatment with high dose UDCA significantly upregulates placental BCRP expression favouring BA efflux from the foetal compartment.

  13. Clinical study on 67 cases of intrahepatic cholestasis during pregnancy%妊娠期肝内胆汁淤积症67例临床分析

    Institute of Scientific and Technical Information of China (English)

    赵菁; 陈瑶

    2012-01-01

    目的 探讨妊娠期肝内胆汁淤积症(ICP)的危害、监护与诊治方法.方法 以67例ICP患者为研究对象,并选择同期分娩的70例非ICP患者作为对照组,进行回顾性分析.结果 研究组胎儿窘迫率、羊水污染率、早产率、剖宫产率及产后出血率均显著高于对照组,差异有显著性(P<0.05).结论 ICP对胎儿危害严重,及时诊断、积极治疗、密切胎儿监护并适时终止妊娠能有效改善妊娠结局.%Objective To explore the hazard of intrahepatic cholestasis during pregnancy ( ICP ) and the method for its monitoring, diagnosis and treatment. Methods The clinical data of 67 cases of ICP were retrospectively analyzed, and 70 normal pregnant women were selected as control group. Results In comparison with control group, there were significant differences in rates of contaminated amniotic fluid, fetal distress, preterm labor, cesarean section and postpartum hemorrhage( P <0.05 ). Conclusion ICP will cause serious hazard to embryo, hence prompt diagnosis , proper treatment, carefully monitoring and timely termination of pregnancy are effective ways to improve the outcome of pregnancy.

  14. SLC25A13 gene mutation screening in infants with intrahepatic cholestasis%特发性婴儿肝内胆汁淤积症患儿 SLC25 A13基因突变分析

    Institute of Scientific and Technical Information of China (English)

    陈允; 伍秋频; 王琳琳; 陈秀奇; 唐清; 单庆文; 黄丽; 连淑君; 云翔; 高国鹏

    2014-01-01

    Objective To evaluate the SLC25A13 gene mutation in the pathogenesis of infants with intrahepatic cholestasis.Methods The genomic DNA was obtained from peripheral blood of 95 infants with intrahepatic cholestasis , who hospitalized in the department of pediatrics of the first affiliated hospital of Guangxi medical university from Oct .2011 to Mar.2012, as case group.Case group diagnosis was proven by blood amino acid mass chromatography analysis , and suspected citrin deficiency children were further proved with direct gene sequencing analysis .Fifty normal liver function infants without intrahepatic cholestasis were selected as control group .All exons of SLC25A13 gene were genotyped by pol-ymerase chain reaction single strand conformation polymorphism (PCR-SSCP) and DNA sequenced.The correlation be-tween the SLC25A13 gene and intrahepatic cholestasis in infants was analyzed .Results SLC25A13 gene mutation was found 4 patients;among whom 3 patients were found with abnormal blood amino acid mass chromatography , including 2 patients with homozygous mutation 851del4/851del4 and 1 patient with heterozygous mutation 851del4.Conclusion Ho-mozygous mutation 851del4/851del4 and heterozygous mutation 851del4 in SLC25A13 gene are revealed in infants with in-trahepatic cholestasis from Guangxi .A new mutation type P502L in patients without abnormal blood amino acid mass chro-matography analysis was reported .%目的:探讨特发性婴儿肝内胆汁淤积症患儿SLC25A13基因的突变情况。方法收集特发性婴儿肝内胆汁淤积症患儿95例作为病例组,另取50例无肝内胆汁淤积、肝功能正常的婴儿作为对照组。所有研究对象全为广西籍。病例组患儿送检血氨基酸质谱分析筛查,对筛查怀疑为Citrin缺乏症的7例全部行DNA测序分析。同时提取病例组其他患儿和对照组婴儿外周血DNA,采用聚合酶链反应-单链构象多态性和DNA测序技术检测SLC25A13基因上18

  15. EFFECTS OF INTRAHEPATIC CHOLESTASIS OF PREGNANCY COMBINED GESTATIONAL DIABETES MELLITUS ON MATERNAL AND FETAL OUTCOMES%ICP合并GDM对母儿结局的影响

    Institute of Scientific and Technical Information of China (English)

    周冬梅; 杨如

    2014-01-01

    目的:探讨妊娠期肝内胆汁淤积症(ICP)合并妊娠期糖尿病(GDM)对母儿结局的影响。方法:分析15例ICP合并GDM孕妇和50例单纯ICP孕妇的临床资料。结果:ICP合并GDM组新生儿窒息率、羊水污染率、小于胎龄儿发生率均显著高于ICP组(P<0.05)。ICP合并GDM组新生儿出生体重较单纯ICP患者轻,分娩孕周较单纯ICP患者小(P<0.05)。结论:ICP合并GDM对围产儿的影响较大,应加强产前和产时母儿监护,合理评估病情,必要时促进胎肺成熟,适时终止妊娠,以改善围生儿不良结局。%Objective:To investigate the effects of intrahepatic cholestasis of pregnancy (ICP) combined gestational diabetes mellitus (GDM) on maternal and fetal outcomes.Methods:The clinical data of 15 cases ICP combined GDM and 50 cases ICP pregnant women were analyzed.Results:The neonatal asphyxia rate, incidence of amniotic lfuid contamination and incidence of small for gestationel age infants of ICP combined GDM pregnant women were all obviously higher than that of ICP pregnant women (P<0.05). The newborn birth weight of ICP combined GDM group was signiifcantly lower,andtheterminationtimeofpregnancyofICPcombinedGDMgroupwassigniifcantlyearlierthanthatofICPgroup(P<0.05). Conclusions:ICP combined GDM has great inlfuence on perinatal infant. We should strengthen antenatal and intrapartum maternal and perinatal care, evaluate the disease reasonably, timely termination of pregnancy, so to improve the adverse outcome of perinatal infant.

  16. Níveis plasmáticos de vitamina D em crianças e adolescentes com colestase Blood levels of vitamin D in children and adolescents with chronic cholestasis

    Directory of Open Access Journals (Sweden)

    Marília D. Bastos

    2003-06-01

    Full Text Available OBJETIVO: verificar os níveis plasmáticos de vitamina D de pacientes colestáticos crônicos e relacionar com estado nutricional, tempo de colestase e uso de suplemento vitamínico. MÉTODOS: estudo transversal controlado, cujo fator em estudo é colestase crônica e o desfecho, o nível plasmático de vitamina D. Pacientes entre quatro meses a 18 anos, atendidos na unidade de gastroenterologia pediátrica do HCPA; como controles, crianças eutróficas da mesma faixa etária. Foi coletado sangue para as dosagens por radioimunoensaio, e realizadas avaliação antropométrica, pesquisa de tempo de colestase e uso de suplemento vitamínico. RESULTADOS: foram avaliadas 22 crianças e adolescentes com colestase crônica e 17 controles. O valor médio de vitamina D entre os pacientes foi de 13,7 ± 8,39 ng/ml, enquanto que nos controles foi de 25,58 ± 16,73 ng/ml (p = 0,007. A prevalência de hipovitaminose D, entre os pacientes, foi de 36%. A mediana do tempo de colestase foi de um ano. A avaliação antropométrica (NCHS demonstrou 36% de desnutrição pelo peso, e 41% para estatura. Na avaliação antropométrica pelo escore z, obtivemos prevalência de desnutrição para os critérios altura/idade e peso/idade de 33,3% e 23,8%, respectivamente. Avaliado peso em relação altura, não observamos valores abaixo de dois desvios padrão. Não foi observada relação entre o estado nutricional, o uso de suplemento oral e os níveis plasmáticos de vitamina D CONCLUSÕES: os níveis plasmáticos de vitamina D em colestáticos foram menores do que os dos controles, sem relação com estado nutricional, tempo de colestase e/ou uso suplementação vitamínica.OBJECTIVE: to verify blood levels of vitamin D in patients with chronic cholestasis, and relate them to nutritional status, length of time since the onset of cholestasis and use of vitamin supplement. METHODS: controlled cross-sectional study with chronic cholestasis as study factor and blood

  17. Clinical Analysis of 32 Patients with Intrahepatic Cholestasis of Pregnancy%32例妊娠期肝内胆汁淤积症临床分析

    Institute of Scientific and Technical Information of China (English)

    白月婷

    2012-01-01

    Objective To investigate the harm of intrahepatic cholestasis of pregnancy( ICP) and the time and manner of delivery in patients with ICP. Methods The clinical data of 32 patients with ICP from 2007 to 2011 in Haidian maternal and child health hospital were analyzed retrospectively. Results There were 13 patients had complications,3 cases were with hypertension in pregnancy,2 with severe pre-eclampsia, 1 with gestational diabetes mellitus,2 with pregnancy impaired glucose tolerance, 1 with thrombocytopenia, 1 with fetal growth restriction, 1 with still birth ,4 with amniotic fluid pollution and 1 with postpartum hemorrhage. 13 patients with the mild ICP had no amniotic fluid pollution,fetal distress or still birth. A premature delivery was seen in 2 patients with mild ICP. 6 patients with the severe ICP had premature cesarean section delivery because of serious condition or complications. Conclusion For the patients with mild ICP a full term trial of vaginal labour can be performed under the close monitoring and a relaxed cesarean section indications. The patients with severe ICP should immediately be cared in hospital with closely monitoring and positive treatment. The cesarean section should be timely carried out to terminate the gestation on the 36th weeks.%目的 探讨妊娠期肝内胆汁淤积症(ICP)的危害、分娩时机及方式.方法 回顾性分析海淀区妇幼保健院2007 ~ 2011年收治的32例ICP患者的临床资料.结果 13例患者出现并发症,其中妊娠期高血压3例,重度子痫前期2例,妊娠期糖尿病1例,妊娠期糖耐量受损2例,血小板减少1例,胎儿生长受限1例,胎死宫内1例,羊水污染4例,产后出血1例.轻度ICP患者13例,无羊水污染、胎儿窘迫、胎死宫内发生,早产2例;重度ICP患者19例,早产6例,均因病情严重、合并症/并发症剖宫产分娩.结论 轻度ICP可观察至妊足月,在密切监护下行阴道试产,并放宽剖宫产指征.一旦诊断重度ICP,需立即

  18. ICP围产儿不良结局的高危因素分析%High risk factors for adverse outcomes of perinatal infants of intrahepatic cholestasis pregnancy

    Institute of Scientific and Technical Information of China (English)

    刘翠; 王勇; 楼方

    2015-01-01

    Objective To discuss the high risk factors for adverse outcomes of perinatal infants in intrahepatic cholestasis of pregnancy ( ICP) . Methods The ICP cases were collected from Affiliated Hospital of Chengdu University. The relationship between obstetric factors and adverse outcomes of perinatal infants was retrospectively analyzed with the data of 522 cases of ICP. Results Univariate analysis showed that the time of onset earlier than 34 gestational week, high TBA, high ALT, high TBIL, high DBIL, and complicated hypertension were statistically significant (χ2 value was 35. 079, 15. 140, 12. 155, 6. 142, 9. 988 and 12. 604, respectively, all P <0. 05). Logistic regression analysis indicated that time of onset earlier than 34 gestational week, high TBA and complicated hypertension were high risk factors for adverse outcomes of ICP perinatal infants (OR value was 2. 922, 1. 770 and 1. 861, respectively, all P<0. 05). Conclusion TBA≥40μmol/L, time of onset earlier than 34 gestational week and complicated high hypertension are risk factors for adverse outcomes of ICP perinatal infants.%目的:探讨妊娠期肝内胆汁淤积症( ICP)围产儿不良结局的高危因素。方法收集在成都大学附属医院住院分娩的ICP病例。回顾性分析522例ICP病例的产科因素与围产儿不良结局之间的关系。结果单因素分析发现发病时间≤孕34周、高总胆汁酸( TBA)、高谷丙转氨酶( ALT)、高总胆红素( TBIL)、高直接胆红素( DBIL)、合并高血压对围产儿不良结局均有统计学差异(χ2值分别为35.079、15.140、12.155、6.142、9.988、12.604,均P<0.05);经Logistic回归分析发现ICP的发病时间≤孕34周、高TBA、合并高血压系ICP围产儿不良结局的高危因素,其OR值分别为2.922、1.770、1.861,均P<0.05。结论 TBA≥40μmol/L、发病时间≤孕34周、合并高血压系ICP围产儿不良结局的高危因素。

  19. 皮肤瘙痒对ICP围产儿结局的影响%Influence of skin pruritus on perinatal outcomes of intrahepatic cholestasis of pregnancy

    Institute of Scientific and Technical Information of China (English)

    刘翠; 王勇; 楼方

    2013-01-01

    Objective To study the influence of skin pruritus on the perinatal outcomes of intrahepatic cholestasis of pregnancy ( ICP ). Methods A retrospective analysis was conducted on 455 cases of ICP, who were divided into group with skin pruritus and group without skin pruritus. The group with skin pruritus was further divided into group with long-term pruritus and group with short-term pruritus. The incidence of adverse perinatal outcomes was compared among different groups. Results The differences between group with skin pruritus and group without skin pruritus were not statistically significant in the incidence of fetus distress, birth asphyxia, premature rupture of membranes, pollution of amniotic fluid, premature, small for gestational age and respiratory system disease (χ2 value was 2.010, 0.791, 2.687, 2.004, 0.770, 1.082 and 0.705, respectively, all P >0.05 ). The differences in incidence of adverse perinatal outcomes were not significantly between group with long-term pruritus and group with short-term pruritus (χ2 value was 0. 651, 2. 622, 1. 518, 0. 218, 0.034, 1. 353 and 1. 105, respectively, all P > 0.05 ). Conclusion The perinatal outcomes of ICP are not impacted by skin pruritus or the duration of pruritus. Skin pruritus neither can be used as the index to determine the severity of ICP, nor can it be used to predict perinatal outcomes.%目的 探讨皮肤瘙痒对妊娠期肝内胆汁淤积症(ICP)围产儿结局的影响.方法 采用回顾性分析的方法,将455例ICP患者分为皮肤瘙痒组、无皮肤瘙痒组,再将皮肤瘙痒组分为长时间瘙痒组、短时间瘙痒组,比较各组围产儿不良结局发生率的差异.结果 皮肤瘙痒组与无皮肤瘙痒组在胎儿窘迫、出生窒息、胎膜早破、羊水污染、早产儿、小于胎龄儿、呼吸系统疾病发生率的差异均无统计学意义(χ2值分别为2.010、0.791、2.687、2.004、0.770、1.082、0.705,均P>0.05);长时间瘙痒组与短时间瘙痒组围产儿

  20. 妊娠期肝内胆汁淤积症的临床分析%Clinical analysis of intrahepatic cholestasis of pregnancy

    Institute of Scientific and Technical Information of China (English)

    李蕾; 赵新颜; 欧晓娟; 贾继东

    2013-01-01

    Objective To generate a comprehensive clinical profile of intrahepatic cholestasis of pregnancy (ICP) by systematically reviewing ICP cases managed in our hospital.Methods The recorded clinical data,including diagnosis,complications,management,and maternal and infant outcomes,of nine ICP cases were collected retrospectively and reviewed systematically.Results Seven of the nine total ICP patients presented with pruritus.All nine of the ICP patients showed bile acid level beyond the normal range.ICP complications included gestational hypertension (n =3),diabetes mellitus (DM,n =1) and impaired glucose tolerance (IGT,n =1),and pre-eclampsia (n =1).The infant of one patient with severe ICP showed meconium-stained liquor.All nine of the ICP patients underwent surgical delivery,of which three were delivered preterm (between the 35th and 36th week of gestation).All mothers' total bile acids declined to normal levels after delivery,and all infants survived without complication.Conclusion ICP does not increase the puerpera mortality rate and does not represent a poor prognosis for infants.Bile acid levels in the ICP patients,however,may be related to the extent of premature delivery time.While the standard drug treatment of ursodeoxycholic acid is suitable for most ICP cases,those with insufficient gestational age may benefit from adjuvant corticosteroid therapy to promote fetal lung maturation prior to preterm delivery.Severe ICP cases should be managed by inducing artificial labor or performing Caesarean section.%目的 探讨妊娠期肝内胆汁淤积症(ICP)的病因、临床特点、治疗方法及母婴预后.方法 回顾性分析9例ICP患者临床特点、诊断、治疗及母婴预后情况. 结果 9例患者中,7例患者出现皮肤瘙痒;9例患者胆汁酸升高,1例胆红素升高;3例并发妊娠期高血压,2例分别并发糖尿病、糖耐量异常,1例有先兆子痫;1例羊水胎粪污染;9例患者均行手术分娩,3例早产(35 ~ 36周),

  1. 妊娠期肝内胆汁淤积症分娩时机及方式探讨%A study on the timing and manner of delivery in patients with intrahepatic cholestasis of pregnancy

    Institute of Scientific and Technical Information of China (English)

    徐洲; 王晓银; 肖兵

    2014-01-01

    目的:探讨妊娠期肝内胆汁淤积症(intrahePatic chOlestasis Of Pregnancy,ICP)分娩时机及方式对母儿结局的影响。方法对228例 ICP 病例进行回顾性研究,分析 ICP 患者终止妊娠的时机及方式与母儿结局的关系。结果重度 ICP 组早产儿、低体重儿、羊水粪染、新生儿窒息率显著高于轻度 ICP 组(P 0.05)。结论轻度 ICP 患者孕37~40周阴道分娩为宜;重度 ICP 患者胎肺成熟后以选择性剖宫产终止妊娠为宜。%Objective TO investigate the relatiOnshiP between the timing and manner Of delivery and PrOgnOsis in Patients with intrahePatic chOlestasis Of Pregnancy( ICP). Methods 228 Patients with ICP were analyzed retrOsPectively,the relatiOnshiP between the timing and manner Of delivery and the maternal and neOnatal OutcOmes were evaluated. Results The rates Of Preterm children,lOw birth weight children,mecOnium - stained amniOtic fluid, neOnatal asPhyxia Of the severe ICP Patients were significantly higher than the mild ICP Patients(P 0. 05). Conclusion Vaginal delivery at 37 ~ 40 weeks is aPPrOPriate fOr the mild ICP Patients. Elective cesarean sectiOn after fetal lung maturity is aPPrOPriate fOr severe ICP Patients.

  2. Acute cholestasis related to desloratidine

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    Ramón Pérez; Luis Rodrigo; Rosa Pérez; Ruth de Francisco

    2005-01-01

    @@ TO THE EDITOR Desloratidine (Clarinex, Neoclarytin, Aerius, Azomyr, Opulis,Allex), the principal active metabolite of loratadine is itself a new oral antihistamine drug Its main indications are for the treatment of seasonal allergic rhinitis (SAR) and chronic idiopathic urticaria (CIU). The pharmacologic profile of desloratidine offers particular benefits, in terms of histamine H1-receptor binding potency and H1 selectivity. It has a half-life of 21-27 h, permitting a once-daily dose. No specific precautions are required with respect to its administration in renal or hepatic failure. No clinically relevant racial or gender variations in the disposition of desloratidine have been noted. We present here a clinical case of acute reversible idiosyncratic liver toxicity, related to its administration.

  3. Cholestasis induced by total parenteral nutrition: effects of the addition of Taurine (Tauramin®) on hepatic function parameters; possible synergistic action of structured lipids (SMOFlipid®) Colestasis inducida por nutrición parenteral total: efecto de la adición de Taurina (Tauramin®) sobre los parámetros de función hepática; posible acción sinérgica de lípidos estructurados (SMOFlipid®)

    OpenAIRE

    J. González-Contreras; J. L. Villalobos Gámez; A. I. Gómez-Sánchez; J. M. García-Almeida; A. Enguix Armanda; F. Rius Díaz; M. I. Lucena González

    2012-01-01

    Objective: Assess the hepatoprotective effect of Taurine (Tau) in cases of hepatic cholestasis induced by Total Parenteral Nutrition (TPN). Methods: We describe a retrospective series of 54 patients who received TPN, in which cholestasis was detected at an (Intermediate) point that separates the duration of TPN into 2 Phases. From this moment -Phase 2- on, and according to clinical criteria, some patients (Group A, n = 27) received amino acids with Tau (22.41 ± 3.57 mg/kg/day)(Tauramin®), whi...

  4. Hepatoprotective effect of water soluble extract of Coleus barbatus on cholestasis on young rats Efeito hepatoprotetor do extrato aquoso de Coleus barbatus na colestase em ratos jovens

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    Ana Paula Ronquesel Battochio

    2008-06-01

    Full Text Available PURPOSE: To test the effects of water extract of Coleus barbatus (WEB on liver damage in biliary obstruction in young rats. METHODS: Forty 21 day-old male Wistar rats were divided into four groups of ten 21 day old (P21 submitted to sham or actual operation (S or L combined with WEB or Water (B or A. At P48 pentobarbital sleeping time (ST was measured. At P49 they were submitted to euthanasia to determine of serum activities of aspartate aminotransferase (AST and alanine aminotransferase (ALT, liver wet weight (PFF and, on hepatic histological slides, the frequency of mitoses (FM, the number of necrotic areas (NN, intensity of fibrosis (IF and intensity of ductal proliferation (IPD. Two Way ANOVA, the S.N.K. test and the Wilcoxon test for paired multiple comparisons were employed to study the effects of cholestasis and those of EAB and their interactions. The Pearson's coefficient of linear correlation of between paired histological variables separately for the groups LA and LD was determined. The test results were considered statistically significant when the p of alpha error OBJETIVO: Testar os efeitos do extrato aquoso de Coleus barbatus (EAB na cirrose biliar secundária por obstrução das vias biliares extra-hepáticas em ratos jovens. MÉTODOS: Quarenta ratos Wistar machos com 21 dias de vida (P21, foram distribuídos em quatro grupos de 10 animais, submetidos a operação simulada ou dupla ligadura e ressecção do ducto biliar (S ou L combinados EAB e a Água (B ou A. No P48, foi medido o tempo de sono com o pentobarbital (TS. No P49, foram submetidos a eutanásia para a determinação das atividades séricas do aspartato aminotransferase (AST e da alanina aminotransferases (ALT; após a eutanásia foram avaliados o peso fresco do fígado (PFF e, em cortes histológicos do fígado, a freqüência de mitoses (FM, o número de áreas de necrose (NN, a intensidade da fibrose (IF e da proliferação ductal (IPD. Os efeitos da colestase, os

  5. 肝移植术后早期严重肝内胆汁淤积的相关因素分析%Risk factors of severe intrahepatic cholestasis during early period after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    张胜; 周杰; 谭永法; 谭凯; 陈立言

    2012-01-01

    (32/165),两组比较,差异有统计学意义(x2=11.54,P<0.05).结论 纠正受者术前不良的临床因素;术后积极控制感染和抗排斥反应可降低原位肝移植患者术后早期严重肝内胆汁淤积的发生率,并有可能改善早期预后.%Objective To investigate the risk factors of severe intrahepatic cholestasis during early period after liver transplantation.Methods The clinical data of 225 patients who received orthotopic liver transplantation at the Nanfang Hospital of Southern Medical University from August 2004 to February 2011 were retrospectively analyzed.All patients were divided into positive group (60 patients with intrahepatic cholestasis) and negative group (165 patients without intrahepatic cholestasis).Preoperative,intraoperative and postoperative factors of the 2 groups were compared via t test,chi-square test,Wilcoxon test or Logistic regression analysis.Results The proportion of patients with hepatic cirrhosis,hepatic encephalopathy integral,ascites integral,international normalized ratio,and the levels of prothrombin time (PT),total bilirubin (TBil),aspartate aminotransferase of the positive group before operation were significantly higher than those in the negative group (x2 =6.09,Z =2.22,2.60,2.46,2.84,4.81,3.42,P < 0.05),while the levels of albumin,Na +,K +,hemoglobin,platelet (PLT) of the positive group in the operation were significantly higher than those in the negative group (t =2.10,4.97,Z =2.49,t =3.51,Z =3.66,P < 0.05).The ratio of compatible blood type of the donors and recipients,ratio of fatty liver graft,cold ischemia time,relative warm ischemia time,intraoperative blood loss,intraoperative transfusion of red blood cells,PLT,and cryoprecipitate of the positive group after the operation were significantly higher than those in the negative group (x2 =4.29,13.11,Z =2.45,2.61,3.75,3.20,2.89,3.95,P <0.05).The incidences of acute rejection,hepatic artery embolism,pulmonary infection

  6. A Retrospective, Multi-Center, Post-Marketing Observational Study to Evaluate the Effectiveness of Ademetionine 1,4-Butanedisulfonate Injection (Transmetil?) Treatment in Chinese Patients with Intrahepatic Cholestasis Caused by Viral Hepatitis

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    Obejective Ademetionine 1,4-butanedisulfonate [S-adenosyl-L-methionine (SAMe)/Transmetil?, Abbott] has been available in China for more than 15 years, and it has been shown to reduce serum bilirubin and transaminase levels in patients with viral hepatitis (VH). However, no large-scale studies have focused on the impact of SAMe treatment regimen on reducing the serum total bilirubin (TBil) in VH patients with intrahepatic cholestasis (IHC). The main objective of this study was to evaluate the effectiveness of intravenous SAMe (Transmetil?) treatment in reducing the serum TBil by 50%. Methods This retrospective, multi-center, cross-sectional medical record review involved patients aged≥18 years. Records of 1 280 hospitalized VH patients at 16 sites diagnosed with IHC who had received intravenous SAMe 1 000 mg or 2 000 mg q.d. for at least 7 days from January 1, 2006 to June 30, 2009, were screened and 905 records were randomly selected. Results The safety set (SS) included 834 patients and the full analysis set included 826 patients. TBil levels after 14 days injection treatment were available for 763 patients. TBil decreased≥ 50%versus baseline after 14 days treatment in 288 (37.7%) patients (95%CI 34.3%, 41.2%). Twenty-nine non-serious adverse events (non-SAEs) were reported in 19 (2.3%) patients, and 29 SAEs were reported in 10 patients (1.2%). All adverse events (AEs) were considered unrelated to the drug. Conclusions This retrospective study shows that intravenous SAMe administration in VH patients with IHC is associated with signiifcant reduction of TBil levels in more than 30%of patients 14 days after treatment initiation.

  7. Identification of a Large SLC25A13 Deletion via Sophisticated Molecular Analyses Using Peripheral Blood Lymphocytes in an Infant with Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency (NICCD: A Clinical and Molecular Study

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    Qi-Qi Zheng

    2016-01-01

    Full Text Available Background. Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD is a Mendelian disorder arising from biallelic SLC25A13 mutations, and SLC25A13 genetic analysis was indispensable for its definite diagnosis. However, conventional SLC25A13 analysis could not detect all mutations, especially obscure large insertions/deletions. This paper aimed to explore the obscure SLC25A13 mutation in an NICCD infant. Methods. Genomic DNA was extracted to screen for 4 high-frequency SLC25A13 mutations, and then all 18 exons and their flanking sequences were analyzed by Sanger sequencing. Subsequently, cDNA cloning, SNP analyses, and semiquantitative PCR were performed to identify the obscure mutation. Results. A maternally inherited mutation IVS16ins3kb was screened out, and then cDNA cloning unveiled paternally inherited alternative splicing variants (ASVs featuring exon 5 skipping. Ultimately, a large deletion c.329-1687_c.468+3865del5692bp, which has never been described in any other references, was identified via intensive study on the genomic DNA around exon 5 of SLC25A13 gene. Conclusions. An NICCD patient was definitely diagnosed as a compound heterozygote of IVS16ins3kb and c.329-1687_c.468+3865del5692bp. The large deletion enriched the SLC25A13 mutation spectrum, and its identification supported the concept that cDNA cloning analysis, along with other molecular tools such as semiquantitative PCR, could provide valuable clues, facilitating the identification of obscure SLC25A13 deletions.

  8. 胆盐输出泵基因V444A与特发性婴儿肝炎肝内胆汁淤积的关系%Association between BSEP V444A polymorphism and risk of idiopathic neonatal hepatitis/cholestasis

    Institute of Scientific and Technical Information of China (English)

    邓亚楠; 王琳琳; 唐清; 陈秀奇; 陈萍; 单庆文; 连淑君; 云翔

    2011-01-01

    目的:探讨胆盐输出泵BSEP基因V444A(BSEP V444A)与特发性婴儿肝炎肝内胆汁淤积的相关性.方法:以81例特发性婴儿肝炎肝内胆汁淤积患儿(病例组)和48例无肝内胆汁淤积婴儿(对照组)为研究对象,应用聚合酶链-限制性片段长度多态性(PCR-RFLP)技术对V444A片段行扩增及酶切分析.结果:BSEPV444A有3种基因型:AA纯合子、GA杂合子、GG纯合子,AA,AG和GG 3种基因型在病例组和对照组频率分别为4.9%,50.6%,44.40%和14.6%,62.5%,22.9%,两组差异显著(P=0.019).等位基因频率的相时风险分析发现,其中GG基因型在两组人群中的分布差异有显著性(P<0.05,OR=2.691,95%CI:1.205-6.008);G等位基因携带者患特发性婴儿肝炎肝内胆汁淤积的风险是A等位基因的1.951倍(OR=1.951,95%CI:1.56-3.291).结论:在广西地区小儿当中发现BSEP V444A单链核苷酸的多态性位点,BSEP V444A G等位基因可能是特发性婴儿肝炎肝内胆汁淤积的一个危险因素,G等位基因携带者可能增加特发性婴儿肝炎肝内胆汁淤积的相对危险度.%AIM: To explore the association between the V444A polymorphism in the bile salt export pump (BSEP) gene and the risk of idiopathic neonatal hepatitis/cholestasis.METHODS: Eighty-one infants with idiopathic hepatitis/cholestasis (case group) and 48 healthy infants without intrahepatic cholestasis (control group) were included in this study.The V444A polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).RESULTS: There are three V444A genotypes:AA homozygote, GA heterozygote, and GG homozygote.The frequencies of AA and AG and GG genotypes were 0.6%, 4.9% and 44.4% in the case group and 14.6%, 62.5% and 22.9% in the control group, respectively, with a significant difference between the two groups (P = 0.019).The distribution of GG genotype was significantly different between the two groups (P <0.05, OR = 2.691, 95%CI: 1

  9. ERK1/2 and p38 MAPKs are complementarily involved in estradiol 17ß-D-glucuronide-induced cholestasis: crosstalk with cPKC and PI3K.

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    Andrea C Boaglio

    Full Text Available OBJECTIVE: The endogenous, cholestatic metabolite estradiol 17ß-D-glucuronide (E(217G induces endocytic internalization of the canalicular transporters relevant to bile formation, Bsep and Mrp2. We evaluated here whether MAPKs are involved in this effect. DESIGN: ERK1/2, JNK1/2, and p38 MAPK activation was assessed by the increase in their phosphorylation status. Hepatocanalicular function was evaluated in isolated rat hepatocyte couplets (IRHCs by quantifying the apical secretion of fluorescent Bsep and Mrp2 substrates, and in isolated, perfused rat livers (IPRLs, using taurocholate and 2,4-dinitrophenyl-S-glutathione, respectively. Protein kinase participation in E(217G-induced secretory failure was assessed by co-administering selective inhibitors. Internalization of Bsep/Mrp2 was assessed by confocal microscopy and image analysis. RESULTS: E(217G activated all kinds of MAPKs. The PI3K inhibitor wortmannin prevented ERK1/2 activation, whereas the cPKC inhibitor Gö6976 prevented p38 activation, suggesting that ERK1/2 and p38 are downstream of PI3K and cPKC, respectively. The p38 inhibitor SB203580 and the ERK1/2 inhibitor PD98059, but not the JNK1/2 inhibitor SP600125, partially prevented E(217G-induced changes in transporter activity and localization in IRHCs. p38 and ERK1/2 co-inhibition resulted in additive protection, suggesting complementary involvement of these MAPKs. In IPRLs, E(217G induced endocytosis of canalicular transporters and a rapid and sustained decrease in bile flow and biliary excretion of Bsep/Mrp2 substrates. p38 inhibition prevented this initial decay, and the internalization of Bsep/Mrp2. Contrarily, ERK1/2 inhibition accelerated the recovery of biliary secretion and the canalicular reinsertion of Bsep/Mrp2. CONCLUSIONS: cPKC/p38 MAPK and PI3K/ERK1/2 signalling pathways participate complementarily in E(217G-induced cholestasis, through internalization and sustained intracellular retention of canalicular transporters

  10. Clinical and laboratory evaluation of 101 patients with intrahepatic neonatal cholestasis Avaliação clínica e laboratorial de 101 pacientes com colestase neonatal intra-hepática

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    Maria Angela Bellomo-Brandão

    2008-06-01

    Full Text Available BACKGROUND: Intrahepatic neonatal cholestasis can be the initial manifestation of a very heterogeneous group of illnesses of different etiologies. AIM: To evaluate and compare clinical and laboratory data among intrahepatic neonatal cholestasis groups of infectious, genetic-endocrine-metabolic and idiopathic etiologies. METHODS: The study evaluated retrospectively clinical and laboratory data of 101 infants, from March 1982 to December 2005, 84 from the State University of Campinas Teaching Hospital, Campinas, SP, Brazil, and 17 from the Child’s Institute of the University of São Paulo, SP, Brazil. The inclusion criteria consisted of: jaundice beginning at up to 3 months of age and hepatic biopsy during the 1st year of life. It had been evaluated: clinical findings (gender, age, birth weight, weight during the first medical visit, stature at birth, jaundice, acholia/hipocholia, choluria, hepatomegaly and splenomegaly and laboratorial (ALT, AST, FA, GGT, INR. RESULTS: According to diagnosis, patients were classified into three groups: group 1 (infectious n = 24, group 2 (genetic-endocrine-metabolic n = 21 and group 3 (idiopathic n = 56. There were no significant differences in relation to the variables: age, gender, stature at birth, jaundice, acholia/hipocholia, choluria, hepatomegaly, splenomegaly, AST, ALT, ALP, GGT, DB and albumin. Significant differences were observed in relation to the following variables: birth weight and weight during the first medical visit. Birth weight of group 1 was lower in relation group 2 and 3. Weight during the first medical visit followed the same pattern. There was a statistically significant difference in relation to the INR, as the patients of the group 2 presented higher values in relation to groups 2 and 3, despite the median was still pointing out normal values. CONCLUSIONS: There were no significant differences in relation to age, gender, stature at birth, jaundice, acholia/hipocholia, choluria

  11. 妊娠期肝内胆汁淤积症的临床特点和发病危险因素分析%The risk factors analysis and control for intrahepatic cholestasis of pregnancy

    Institute of Scientific and Technical Information of China (English)

    兰易; 黄健容

    2014-01-01

    Objective To investigate the clinical characteristics and risk factors for intrahepatic cholestasis of pregnancy(ICP), and put forward relevant control measures.Methods May 2009 to February 2013 in our hospital maternity clinic built card ICP 60 cases of pregnant women as the observation group,choosed the same period in our hospital 60 cases of childbirth without ICP as the control group,two groups have carried out surveys of maternal and neonatal outcomes,and laboratory tests.While observing the pa-tients were given drug therapy.Results All mothers were smooth delivery of the newborn,no maternal and neonatal mortality.Pro-duction of the observation group was significantly shorter than the control group gestational age,neonatal apgar 1 minute(s)and birth weight was significantly lower,cesarean section rate was significantly higher(P 0.05).Observation group BUN,LDH,PT,APTT,FIB levels higher,the differ-ence was statistically significant(P 0.05).blood pressure control and kidney damage and prenatal affecting intrahepatic cholestasis of pregnancy independent risk factor for the inci-dence(P<0.05).After treatment,the observation group 42 cases were cured,14 cases markedly effective,4 cases ecfectiveness and no case failure.markedly effective rate was 93.3%,the effective rate was 100.0%.Conclusion ICP for maternal and newborn have a certain influence,many accompanied by renal dysfunction,blood pressure control and kidney damage and check-ups during preg-nancy that affect the incidence of ICP independent risk factors,drug therapy can achieve better results.%目的:探讨妊娠期肝内胆汁淤积症(ICP)的临床特点和发病危险因素,提出相关控制措施。方法选择2009年5月至2013年2月在该院产科门诊建卡的 ICP产妇60例作为观察组,同期选择在该院住院分娩的非 ICP产妇60例作为对照组,两组都同时进行实验室检查和产妇及新生儿的预后调查。观察组给予药物综合治疗。结果所有产妇

  12. A case-control study on 121 cases of intrahepatic cholestasis of pregnancy%121例妊娠期肝内胆汁淤积症的病例对照分析

    Institute of Scientific and Technical Information of China (English)

    张东升

    2013-01-01

    Objective To analyze the impact of intrahepatic cholestasis of pregnancy (ICP) on adverse perinatal outcomes. Methods 121 cases of intrahepatic cholestasis of pregnancy women who delivered from January to September 2008 in Anhui Province maternal and child health care hospital were selected as case group,121 normal cases were matched as control group. Socio-demographic data,clinical diagnosis information and delivery information were recordsed. Differences of main adverse perinatal outcomes were compared by statistic analysis between the two groups. Results There were no significant differences in socio-demographic information between ICP group and control group(P>0.05). Also there were no significant difference of parity,fetal gender,postpartum hemorrhage,severe asphyxia between the two groups(P>0.05). The rate of remature rupture of membranes in ICP group(10.7%) was lower than that in control group(17.5%);the rate of caesarean delivery was 81.8% in ICP group,higher than that in control group (63.6%);amniotic fluid pollution rate of ICP group(31.4%) was higher than that in control group (15.7%) ;birth weight in ICP group(3 032.3±392.0)g were lower than that in control group(3 222.3±469.6)g; These differences were all of statistical significance (P 0.05 ). Conclusion After controlling the confounding factors,ICP may have adverse effect on perinatal outcomes including high rates of caesarean delivery,premature and amniotic fluid pollution. Higher level the cholic acid may reflect the severity of the desease.%  目的探讨妊娠期肝内胆汁淤积症对围产儿结局的影响。方法以2008年1~9月在我院住院分娩的121妊娠期肝内胆汁淤积产妇为研究对象,按照1︰1配对设定对照组,记录两组人口统计学特征、临床诊断,追踪分娩情况,分析两组间围产儿不良结局差异。结果 ICP组与对照组产妇的户籍、年龄、自评家庭经济状况、文化程度等人口统计学因素分布差

  13. Citrin缺陷所致婴儿肝内胆汁淤积症43例分析%Intrahepatic cholestasis caused by citrin deficiency:a clinical analysis of 43 infants

    Institute of Scientific and Technical Information of China (English)

    姜涛; 姚蔚; 欧阳文献; 谭艳芳; 李双杰

    2014-01-01

    Objective To analyze the clinical characteristics and prognosis of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD)in infants.Methods The clinical data of 43 infants with NICCD in our hospital from July 201 1 to April 2014 were collected.The diagnosis was confirmed by tandem mass spectrometry (MS-MS)analysis of blood,gas chromatography-mass spectrometry (GC-MS)a-nalysis of urine,and genetic testing,and an analysis was performed with reference to clinical manifestations and laboratory results.Results Most patients with NICCD developed jaundice early,with a round,fat face,hepatomegaly,and growth retardation.Laboratory examina-tions showed increased bilirubin,total bile acids,blood lactic acid,alpha-fetoprotein,and procalcitonin in all patients,increased alanine aminotransferase,gamma-glutamyl transpeptidase,and blood ammonia,decreased albumin and blood glucose,and dyslipidemia and coag-ulation disorders in most patients,and abnormal liver fibrosis markers (20/24)and low ceruloplasmin (17/20)in some patients.Abdomi-nal ultrasound showed hepatomegaly in 32 patients.MS-MS analysis of blood samples revealed distinctive elevation of methionine,citrul-line,tyrosine,threonine,and a variety of acyl carnitine in most patients.GC-MS analysis of urine samples revealed elevated galactose and galactitol in 20 patients,elevated 4-hydroxyphenyllactic acid and 4-hydroxyphenylpyruvic acid in 10 patients,and no abnormalities in 6 patients.Genetic testing revealed 851del4,1638ins23,and IVS6+5G>A mutations,especially 851del4 mutation.After being treated by giving lactose-free diet,strengthening medium-chain fatty acid diet,protecting the liver,and relieving cholestasis,most patients had nor-malized indices 2 months later,2 cases had liver cirrhosis,and 7 cases died.Conclusion The clinical manifestations of NICCD vary in children.MS-MS analysis of blood,GC-MS analysis of urine,and genetic testing should be performed early in children with clinically suspected NICCD

  14. 重症监护病房感染相关性淤积性黄疸患者的临床分析%The clinical analysis of severe sepsis induced cholestasis jaundice patients in intensive care unit

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    徐前程; 查磊; 刘小彬; 陈尚华

    2016-01-01

    Objective To investigate the epidemiological characteristics and prognosis assessment mortality risk factors of severe sepsis induced cholestasis jaundice (SSICJ) patients admitted into intensive care unit (ICU), and to strengthen acknowledge of SSICJ and guild clinical treatment. Methods The clinical data of 60 SSICJ patients were retrospectively analyzed with statistical description. All the patients admitted to the ICU of the Wuhu second people′s hospital affiliated to Wannan medical college from January 2011 to December 2013 were assigned to two groups (survival group and non-survival group) according to the survival outcome. Logistic regression analysis was employed to identify independent risk factors of the death of SSICJ during ICU stay. Results The respiratory system was the most common site of infection [42%(25/60)], followed by abdominal infection and blood stream infection 22%(13/60),12%(7/60) respectively. Fifty-two patients were positive in bacterial isolation and 73 strains were identified , Gram-negative bacteria was the most common pathogens [48%(35/73)], followed by Gram-positive bacteria [30%(22/73)] and fungi [22%(16/73)]. Nosocomial infections accounted for [48%(29/60)] of the enrolled patients. Overall ICU mortality of SSICJ patients was[35%(21/60)], with nosocomial infections and chronic disease infections, septic shock, the ICU mortality were increased to [41%(12/29)], [64%(9/14)], [77%(17/22)] respectively. The patient with continue increaseing cholestasis jaundice in non-survival group was more than survival group[0%(0/31) vs 86%(18/21), P<0.01], the AST was similar in the two groups[(82±21) U/L vs(89±27) U/L, P=0.30]. Logistic regression analysis showed that APACHEⅡscores[odds(OR)=2.34, 95%CI 1.20-5.81, P=0.032], coexist with septic shock(OR=4.43, 95%CI 1.76-7.38, P=0.049), pre-ICU therapy time(OR=1.56,95%CI 1.05-3.78, P=0.015) were the independent risk factors of ICU mortality. Conclusion SSICJ was a common cause of ICU admission

  15. Risk factors of parenteral nutrition associated cholestasis in preterm infant%早产儿胃肠外营养相关性胆汁淤积影响因素研究

    Institute of Scientific and Technical Information of China (English)

    杨慧; 王卫; 刘晓红

    2013-01-01

    目的 探讨早产儿胃肠外营养相关性胆汁淤积的影响因素.方法 对2008年10月至2011年5月在我院新生儿重症监护病房进行胃肠外营养持续14天以上的早产儿资料进行回顾性分析,按照是否发生胆汁淤积分为病例组和对照组,比较两组胃肠外营养时间、禁食时间、体重增长及三大营养素提供热卡等的差别.结果 研究期间共有102例早产儿应用胃肠外营养14天以上,病例组21例,对照组81例,胃肠外营养相关性胆汁淤积发生率20.6%.病例组禁食时间(天)长于对照组[(9.9±4.9)比(5.7±3.3)],氨基酸及脂肪乳提供热卡比率(%)高于对照组[(7.8±3.5)比(4.2±2.0),(17.8±8.2)比(10.5±5.4)],每天总热卡[kcal/(kg·d)]低于对照组[(109.1±35.3)比(128.8±27.6)],发生喂养困难的比例高于对照组(60.0%比33.3%),差异均有统计学意义(P<0.05).多因素分析结果显示,禁食时间长、氨基酸和脂肪乳提供热卡比率高是发生胆汁淤积的危险因素(OR值分别为4.758、6.128、3.756),经口喂养提供热卡比率高是保护性因素(OR值0.012),P均<0.05.结论 胃肠外营养相关性胆汁淤积的发生与氨基酸及脂肪乳提供热卡比率高、禁食时间长有关,经口喂养提供热卡高为保护因素.%Objective To determine risk factors of parenteral nutrition associated cholestasis ( PNAC ) in preterm infants. Methods This retrospective analysis was conductcd on hospitalization data of 102 preterm infants receiving parenteral nutrition ( PN ) for more than 14 days in N1CU. The patients were assigned into the PNAC ( 21 cases ) and the control non-PNAC ( 81 cases ) groups. The duration of time for which patients were restricted from oral feeding ( NPO ) and received parental nutrition; the patients'caloric intake from glucose, protein and intralipid; and the patients' weiglit gain were compared and subjected to statistical analyses. Results The incidence of PNAC occurrence was 20. 6% . Comparing to

  16. 中药治疗妊娠期肝内胆汁淤积症的临床疗效研究%Efficacy of traditional Chinese medicine in the treatment of intrahepatic cholestasis of pregnancy

    Institute of Scientific and Technical Information of China (English)

    李金艳; 曾敏

    2015-01-01

    Objective To discuss the efficancy of traditional Chinese medicine in treatment of intrahepatic cholestasis of pregnancy .Methods A total of 60 patients who were admitted to our hospital for severe intrahepatic cholestasis of pregnancy(ICP) from January 2009 to December 2012 were randomly divided into two group using random number table .Patients in study group (n=30) took traditional Chinese medicine three times a day plusUDCA twice a day orally .Patients in control Group (n=30)were on‐ly given UDCA twice a day orally .Conventional treatment and care for ICP were given to both groups .Biochemical index (TBA , ALT ,and AST)level ,pregnancy outcome and Caspase‐3 of the two groups were recorded and compared and compared .Results The expressing of Caspase‐3 in placental cytotrophoblast ,syncytiotrophoblast .Decidual cells and interstitial cells of study group were (10 .58 ± 2 .62)% ,(15 .8 ± 4 .02)% ,(10 .17 ± 3 .58)% ,(14 .23 ± 4 .39)% ,respectively ,which were significantly lower than those in control group(P<0 .05) ,which were (20 .46 ± 8 .68)% ,(33 .89 ± 7 .05)% ,(20 .56 ± 4 .23)% ,(28 .29 ± 5 .58)% .TBA ,ALT、AST in two groups were declined ,and ctedy group was better than in control group(P<0 .05) .The index of liver function were all lower in study group than that of control group(P<0 .05) .Incidence rate of neonatal asphyxia was lower in study group than that of con‐trol group (P<0 .05) .Conclusion Traditonal Chinese medicine can reduce the expression of Caspase‐3 in study group .It is safe and eflfective in the treatment of ICP .%目的:探讨中药治疗妊娠期肝内胆汁淤积症(IC P )的临床疗效。方法将60例IC P患者分为两组:观察组30例以中药茵陈利胆汤联合熊去氧胆酸治疗,对照组30例仅口服熊去氧胆酸药物,疗程均为20 d。对比两组血清总胆汁酸(TBA)、天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)水平、胎盘组织中Caspase‐3表达

  17. Changes of blood lipid in intrahepatic cholestasis of pregnancy and its clinical significance%妊娠期肝内胆汁淤积症血脂变化及其临床意义

    Institute of Scientific and Technical Information of China (English)

    文春蓉; 刘敏利

    2015-01-01

    Objective To explore the changes of blood lipid in intrahepatic cholestasis of pregnancy (ICP) patients and its clinical significance. Methods Collected empty stomach serum of 49 ICP patients in third trimester of pregnancy (ICP group) and 50 healthy pregnant women (control group) who gave birth in this hospital from 2010 to 2011. Measured and compared their blood lipid parameter. Divided ICP group′s patients into normal blood lipid group and abnormal blood lipid group ,and observed their liver function change. Results (1) ICP group′s total cholesterol,triacylglycerol and low density lipoprotein were all higher than control group′s while the high density lipoprotein was lower,differences showing statistical significance(P<0.05). (2)Abnor-mal blood lipid group′s alanine aminotransferase,aspartic transaminase amino acids,total bilirubin and direct bilirubin were all higher than normal blood lipid group′s,while the albumin was lower,and the amniotic fluid pollution and newborn complication′s incidence rate were higher,differences showing statistical significance(P<0.05). Conclusion The abnormal blood lipid of ICP patients is different from physiologic change of blood lipid during gestation period. It reflects the severe state of the illness and should be ICP patients′important monitoring index.%目的:探讨妊娠期肝内胆汁淤积症(ICP)患者血脂变化及其临床意义。方法收集2010~2011年在该院分娩的49例妊娠晚期ICP患者(ICP组)和50例健康孕妇(对照组)的空腹血清,测定血脂指标并进行比较。将ICP组患者分为血脂正常组(15例)和血脂异常组(34例),观察两组患者肝功能变化。结果(1)ICP组患者总胆固醇、三酰甘油、低密度脂蛋白均高于对照组,高密度脂蛋白低于对照组,差异均有统计学意义(P<0.05);(2)血脂异常组患者丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、总胆红素及结合胆红素均

  18. The value of serum bile acid in diagnosis of intrahepatic cholestasis of pregnancy%血清胆汁酸在妊娠期肝内胆汁淤积症中的诊断价值

    Institute of Scientific and Technical Information of China (English)

    王晓丽; 李博; 赵彦梅; 王昕

    2012-01-01

    目的 探讨血清胆汁酸在妊娠期肝内胆汁淤积症(ICP)诊断中的应用价值.方法 对待产的92例ICP患者的临床资料进行回顾性分析,按血清胆汁酸水平将患者分为两组,血清胆汁酸>40μmol/L为观察组(46例),血清胆汁酸≤40μmol/L为对照组(46例),观察比较两组患者皮肤瘙痒出现时间,黄疸程度,血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST),羊水污染程度.结果 观察组皮肤瘙痒出现时间早于对照组[(29.1±3.4)周比(33.9±3.2)周,P<0.05];重度黄疸、ALT>100 U/L、AST>100 U/L及羊水Ⅲ度污染例数均多于对照组[27例比15例、28例比20例、28例比18例、23例比15例,P<0.01或<0.05].结论 血清胆汁酸可作为评估ICP的敏感指标,对孕妇病情的判断、预后分析具有重要的意义,具有反映其发生妊娠不良结局的可能性.%Objective To evaluate the application value of serum bile acid in diagnosing intrahepatic cholestasis of pregnancy (ICP).Methods The clinical data of 92 prepartal patients with ICP was analyzed retrospectively.The patients were divided into observation group ( > 40 μ mol/L ) and control group ( ≤40 μ mol/L) with 46 cases each according to serum bile acid level.The nccurrence time of skin pruritus,jaundice degree,serum alanine aminotransferase (ALT),aspartate aminotransferase (AST) and degree of polluted amniotic fluid of two groups were observed and compared.Results The occurrence of skin pruritus in observation group was earlier than that in control group [(29.1 ± 3.4) weeks vs.(33.9 ± 3.2) weeks,P<0.05 ] ;the cases with severe jaundice,ALT > 100 U/L,AST > 100 U/L and amniotic fluid contamination Ⅲ degree in observation group were more than control group [27 cases vs.15 cases,28 cases vs.20 cases,28 cases vs.18 cases,23 cases vs.15 cases,P< 0.01 or < 0.05].Conclusions Serum bile acid,as a sensitive indicator to assess TCP,has important value in determining the

  19. Biliary scintigraphy in neonatal cytomegalovirus cholestasis

    International Nuclear Information System (INIS)

    Diagnostic value of hepatobiliary scintigraphy using mebrofenin-Te-99m was assessed in three newborns with cytomegalovirus (CMV) hepatitis and one baby with hepatitis B jaundice. All cases were affected by persistent jaundice with predominately conjugated bilirubin, alcoholic stools, anemia. One of this newborns (case number 1) was suspected of having biliary atresia due to the absence of intestinal excretion of the tracer. After three weeks intestinal passage was seen in scintiscan late after 24 h. Hepatobiliary scintigraphy represents a non-invasive diagnostic procedure which enables the detection of permeability of the biliary tract. (Author)

  20. Cholestasis in newborn and infancy period

    OpenAIRE

    Çokuğraş, Fügen Çullu; Beşer, Ömer Faruk

    2012-01-01

    Dear Editor Isotretinoin is a synthetic vitamin A derivative which is used for treatment of nodulocystic and severe acne It is a teratogenic factor which can lead to intrauterine death and congenital anomalies in humans and the clinical picture it causes is named isotretinoin embryopathy 1 A three months old infant who was born from a mother who used isotretinoin during her first month of pregnancy without realising that she was pregnant is presented in this article to emphasize that this dru...

  1. Genetics Home Reference: intrahepatic cholestasis of pregnancy

    Science.gov (United States)

    ... a protein called the bile salt export pump (BSEP). This protein is found in the liver, and ... pregnancy reduce the amount or function of the BSEP protein, although enough function remains for sufficient bile ...

  2. Obstructive Jaundice: A Case of Idiopathic Cholestasis

    OpenAIRE

    Worobetz, Lawrence; Haight, Ken; Brown, Murray

    1984-01-01

    A 44-year-old man presented to his family physician with intrahepatic cholestatic jaundice, which he had had for seven days. He was admitted to the Family Medicine Service of University Hospital, Saskatoon, and the jaundice was extensively investigated. Initially, it was thought to be induced by antibiotics, but this was not confirmed on controlled drug rechallenge. The precise cause was not found. This article outlines a rational and systematic method for investigating obstructive jaundice. ...

  3. 胆盐输出泵基因多态性与特发性婴儿肝炎肝内胆汁瘀积的关系%Relationship between Bile Salt Export Pump Gene Polymorphisms and lntrahepatic Cholestasis in Idiopathic In-fantile Hepatitis

    Institute of Scientific and Technical Information of China (English)

    邓亚楠; 王琳琳; 陈秀奇; 唐清; 高国鹏; 单庆文; 云翔

    2011-01-01

    目的 探讨特发性婴儿肝炎肝内胆汁瘀积患儿胆盐输出泵(BSEP)基因的突变情况.方法 收集2008年10月- 2010年2月就诊于广西医科大学第一附属医院儿科的婴儿胆汁瘀积性肝炎患儿81例(病例组),48例无肝内胆汁瘀积、肝功能正常的婴儿为对照组.提取病例组和对照组儿童外周血DNA,采用聚合酶链反应-单链构象多态性(PCR-SSCP)和DNA测序技术检测BSEP基因上2、3、4、5、6、9、10、16、17、23、24外显子基因多态性,分析BSEP基因多态性与特发性婴儿肝炎肝内胆汁瘀积之间的关系.结果在外显子24上检测到BSEP A1028A同义突变,编码的氨基酸未改变,均为丙氨酸;其他10个外显子均未发现异常突变.A1028A基因型在病例组,CC型53例(占65.4%),TC型28例(占34.6%),C等位基因频率为82.7%;对照组中CC型32例(占66.7%),TC型16例(占33.3%),C等位基因频率为83.3%.二组基因型差异经Fisher's精确概率法检验,差异无统计学意义(P>0.05);等位基因频率经Fisher's精确概率法检验,差异亦无统计学意义(P>0.05).结论 尚不能认为BSEP A1028A是特发性婴儿肝炎肝内胆汁瘀积的一个危险因素.BSEP A1028A与特发性婴儿肝炎肝内胆汁瘀积发生的易感性无关.%Objective To evaluate the bile salt export pump(BSEP) gene polymorphisms in the pathogenesis of intrahepatic cholestasis in idiopathic infantile hepatitis. Methods The genomic DNA was obtained from peripheral blood of 81 patients with idiopathic infantile cholestasis as case group, who hospitalized in the Department of Pediatrics of the First Affiliated Hospital of Guangxi Medical University from Oct. 2008 to Feb.2010,and 48 normal liver function infants without intrahepatic cholestasis as control group. The BSEP gene 2,3,4,5,6,9,10, 16,17,23,24 exons polymorphism were genotyped by polymerase chain reaction - single strand conformation polymorphism(PCR - SSCP) and sequenced. The statistical

  4. 肝内胆汁淤积症患者围生儿预后不良因素分析%Analysis of perinatal poor prognosis factor in patients with intrahepatic cholestasis of perinatal

    Institute of Scientific and Technical Information of China (English)

    刘娟; 陈雄; 汪宇平; 金玉珍; 吴颖

    2012-01-01

    目的:探讨影响肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)患者围生儿预后的相关因素.为临床采取恰当的分娩方式和选择适时的手术时机提供可靠依据.方法:随机抽取我院2009年1月-2012年4月发生胎儿窘迫50例与未发生胎儿窘迫的ICP患者50例瘙痒出现孕周、天冬氨酸转氨酶、总胆红素、血清总胆汁酸、脐血流、胎心监护、分娩方式、及新生儿吸入性肺炎、新生儿窒息(Apgar评分)、围生儿死亡率、早产率、小于胎龄儿发生率等进行对比分析,探讨影响ICP患者围生儿预后的因素.结果:发生胎儿窘迫的ICP患者脐血流(S/D值)异常升高及产前胎心监护NST评分、血清总胆汁酸水平、早产率明显高于未发生胎儿窘迫的ICP患者(P<0.05),但瘙痒出现的孕周及AL T、血清总胆红素值,两组间差异无统计学意义(P>0.05).前组新生儿吸入性肺炎、新生儿窒息、围生儿死亡率均较对照组高,其差异均有统计学意义(P<0.05);两组小于胎龄儿发生率无明显差异,无统计学意义(P>0.05).结论:脐血流S/D值及血清总胆汁酸、NST评分与ICP患者胎儿窘迫有关,致使新生儿早产率、吸入性肺炎、新生儿窒息、围生儿死亡率均升高,而瘙痒出现的孕周、AL T水平、血清总胆红素水平与之无关.妊娠期ICP严重影响围生儿的预后,应做到早期诊断、早期治疗,适时终止妊娠,降低ICP对围生儿的危害.%Objective:To study the factors influencing the perinatal prognosis in patients with intrahepatic cho-testasis of pregnancy (ICP) and to provide a reliable basis for taking appropriate mode of delivery and choosing timely moment of surgery. Methods: 50 ICP cases with fetal distress and 50 ICP cases without fetal distress were randomly selected in our hospital from January 2009 to April 2012. The comparative analysis about itching gestational age, aspartate aminotransferase, total

  5. Effect of intrahepatic cholestasis on morphology of fetal lungs in pregnant rat%妊娠期肝内胆汁淤积症对胎鼠肺脏形态的影响

    Institute of Scientific and Technical Information of China (English)

    石岩; 漆洪波

    2010-01-01

    Objective To investigate the influence of intrahepatic cholestasis of pregnancy (ICP) on the pulmonary morphologic changes of fetal rats.Methods Twenty pregnant SD rats at 15 days of gestations were randomly divided into ICP and control group.Rats in the ICP group were subcutaneously injected with 17-α-ethinylestradiol and progesterone for 5 consecutive days to establish the rat ICP model, and those of the control group received subcutaneous injection of sirasimeyu also for 5 days.The levels of serum alanine aminotransferases (ALT), aspartate transamlnase (AST), and total bile salt (TBA) were measured before and after the treatment, respectively.Maternal rats were sacrificed on 21 days of gestations and hysterotomies were performed immediately.Histopathologic changes of mammal rats' livers and fetal lungs were observed under light and electron microscopes.Results (1) The maternal serum levels of ALT, AST, and TBA showed no significant difference between the ICP and control group [ALT: (55 ± 15) vs (49 ±12) U/L; AST:(146±16)vs (145±20) U/L; TBA: (13±4) vs (14 ±4) μmol/L, P>0.05, respectively]before the ICP models were established, but higher levels were shown in the ICP group after [ALT: (94±12) vs (59±17) U/L; AST: (245±26) vs (163±27) U/L; TBA: (44±16) vs (17± 3) μmol/L, P 0.05).模型建立后(于妊娠第21天断颈处死孕鼠),实验组孕鼠血中ALT、AST及TBA水平分别为(94±12)U/L、(245±26)U/L及(44±16)μmol/L;对照组分别为(59±17)U/L、(163±27)U/L及(17±3)μmol/L,两组比较,差异有统计学意义(P<0.05).(2)孕鼠肝脏病理学检查:大体所见,实验组孕鼠肝脏边缘钝厚,色泽灰暗;对照组孕鼠肝脏边缘锐利,色泽红润.光镜下所见,实验组孕鼠中有部分肝细胞肿胀变性,胞质疏松化,肝血窦受压变窄,部分胆管扩张,偶见肝细胞坏死;对照组孕鼠则肝细胞形态及肝小叶结构均正常.(3)胎鼠肺脏组织学检查:实验组胎鼠肺脏色泽灰暗,对照组胎鼠

  6. Therapeutical Effect of Kidney-Tonifying and Dampness-Expelling Chinese Herbal Medicine on Intrahepatic Cholestasis of Pregnancy Mediated Through Up-Regulating Expressions of MRP2 and BSEP in Rat Hepatocytes%补肾祛湿方增加大鼠肝细胞MRP2、BSEP表达对抗雌激素致胆汁淤积作用

    Institute of Scientific and Technical Information of China (English)

    侯莉莉; 刘佳; 赵翠英

    2013-01-01

    目的:观察补肾祛湿方含药血清对雌激素致大鼠胆汁淤积肝细胞胆汁酸转运蛋白MRP2与BSEP表达的作用,探讨补肾祛湿方治疗妊娠肝内胆汁淤积症可能的分子机制.方法:用1 μmol/L的17β雌二醇干预大鼠原代肝细胞24 h诱导形成胆汁淤积模型后,加入补肾祛湿方含药血清处理24 h,放射免疫法测定培养液中总胆汁酸含量,提取细胞总RNA及蛋白,实时荧光定量PCR法和蛋白免疫印迹法检测MRP2、BSEP mRNA与蛋白表达水平.电子显微镜观察培养肝细胞超微结构变化.结果:补肾祛湿方含药血清可减轻肝细胞损伤,显著增加细胞培养上清总胆汁酸含量,P<0.01,并且可明显增加肝细胞MRP2、BSEP mRNA与蛋白表达水平,P<0.01.结论:补肾祛湿方治疗妊娠肝内胆汁淤积症的分子机制可能是通过改善肝细胞超微结构的损伤,增加肝细胞胆汁酸转运蛋白MRP2、BSEP mRNA与蛋白表达水平实现的.%Objective:To investigate the effect of kidney-tonifying and dampness-expelling Chinese herbal medicine on the expressions of MRP2 and BSEP in cholestasis induced by estrogen in rat hepatocytes.Methods:The model of cholestasis was induced by 17β-estradiol in cultured rat heaptocytes for 24 hours,and then the serum containing kidney-tonifying and dampness-expelling Chinese herbal medicine serum was treated for 24 hours.The level of total bile acid was detected,and the expressions of MRP2 and BSEP were analyzed by real-time RT PCR and western blotting analysis.The changes in ultrastructure of hepatocytes were observed by electron microscope.Results:The observation under electron microscope showed that compared with the blank serum group,the most hepatocytes in kidney-tonifying and dampness-expelling Chinese herbal medicine group were with normal structure.Further more,compared with the serum blank group,the serum levels of TBA was remarkably increased in group containing kidney-tonifying and dampness

  7. Estado nutricional e absorção intestinal de ferro em crianças com doença hepática crônica com e sem colestase Nutritional status and intestinal iron absorption in children with chronic hepatic disease with and without cholestasis

    Directory of Open Access Journals (Sweden)

    Regina Helena Guedes da Motta Mattar

    2005-08-01

    Full Text Available OBJETIVO: Avaliar a ingestão alimentar, a ocorrência de desnutrição energético-protéica e de anemia e a absorção intestinal de ferro em crianças com doença hepática crônica. CASUÍSTICA E MÉTODOS: Foram estudados 25 pacientes com doença hepática crônica, sendo 15 com colestase e 11 sem colestase. A idade variou entre 6,5 meses e 12,1 anos. A absorção intestinal de ferro foi avaliada pela elevação do ferro sérico uma hora após a ingestão de 1 mg/kg de ferro elementar e pela resposta à ferroterapia oral. A absorção intestinal de ferro foi comparada com um grupo de crianças com anemia ferropriva. RESULTADOS: A ingestão média de energia e proteínas nos pacientes com doença hepática com colestase foi maior do que nos pacientes sem colestase. O déficit nutricional foi mais grave nos pacientes com colestase, predominando os déficits de estatura-idade e peso-idade. A anemia foi freqüente tanto nas crianças com doença hepática com colestase (11/14; 78,6% como nas sem colestase (7/11; 63,6%. Na doença hepática com colestase, observou-se menor (p OBJECTIVES: to evaluate food intake, occurrence of energy-protein malnutrition and anemia, and intestinal iron absorption in children with chronic liver disease. METHODS: The study included 25 children with chronic liver disease, 15 with cholestasis and 11 without cholestasis. The age varied between 6.5 months and 12.1 years. Intestinal iron absorption was evaluated by the increment of serum iron one hour after the ingestion of 1 mg/kg of elemental iron and by the response to oral iron therapy. Iron intestinal absorption was compared to a group with iron deficiency anemia (without liver disease. RESULTS: The mean intake of energy and protein in the cholestatic group was higher than in patients without cholestasis. The nutritional deficit was more severe in cholestatic patients, especially with regard to height-for-age and weight-for-age indices. Anemia was found in both

  8. 胎盘胆盐输出泵蛋白的表达及其与妊娠期肝内胆汁淤积症的关系%Study on the Placental Expression of BSEP in Intrahepatic Cholestasis of Pregnancy

    Institute of Scientific and Technical Information of China (English)

    顾丽萍; 刘晓慧; 宋晔; 侯顺玉; 戴建荣

    2016-01-01

    Objective:To explore the expression of bile salt export pump(BSEP) in placenta tissue and its relationship with intrahepatic cholestasis of pregnancy (ICP). Methods:The expression of BSEP in the placenta was detected by immunohisto-chemistry and western blotting respectively in 30 women with ICP (ICP group) and 30 normal gravidas (control group) from February 2012 to August 2013 in Department of Obstetrics of Suzhou Municipal Hospital. Results:BSEP was located at the cytoplasm in the placental trophoblastic cells. The expression of BSEP in ICP group was significantly lower than control group [(0.197 7±0.111 8) vs. (0.616 0±0.384 9),P<0.001]. Conclusions:Decreased expression of BSEP in placenta may be asso-ciated with ICP.%目的:探讨胎盘组织中胆盐输出泵(bile salt export pump,BSEP)的表达水平及其与妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)的关系.方法:选取2012年2月—2013年8月在苏州市立医院本部产科住院分娩的ICP孕妇30例作为研究组(ICP组),同期分娩的健康妊娠晚期孕妇30例作为对照组,采用免疫组化(SP)法和蛋白质印迹(western blotting)法测定2组孕妇胎盘组织中BSEP蛋白的表达.结果:BSEP蛋白表达于胎盘滋养细胞的细胞质中.ICP患者胎盘组织BSEP的表达低于正常胎盘组织,差异有统计学意义[(0.197 7±0.111 8)vs.(0.616 0±0.384 9), P<0.001].结论:BSEP蛋白在胎盘组织中表达的降低可能与ICP有关.

  9. Effect of ursodeoxycholic acid combined with modified Artemisiae Scopariae decoction in intrahepatic cholestasis of pregnancy%茵陈加味汤联合熊去氧胆酸治疗妊娠肝内胆汁淤积症62例

    Institute of Scientific and Technical Information of China (English)

    陈友英; 陈宣伊; 梁国强

    2014-01-01

    Objective: to observe the efficacy of ursodeoxycholic acid combined with modified Artemisiae Scopariae decoction in the treatment for intrahepatic cholestasis of pregnancy .Methods:108 cases with ICP had been chosen and randomly divided into two groups:the A group( the ursodeoxycholic acid combined with modified Artemisiae Scopariae decoction group ,62 case ) and the B group ( the ursodeoxycholic acid group ,46 case ) , the clinical effect were compared before and after traetment .Results:The reduction of itch score , AST,ALT of the A group were significantly decreased than that in the B group ( P <0.05 ) .The TBA, CG of the A group were decreased than in the B group .Comparing the two groups , the incident of Cesarean section , Postpartum hemorrhage and the incident of meconium-stained amniotic fluid were significant (P<0.05).Conclusion:It is effective to treat ICP with combination of ursodeoxycholic acid and modified Artemisiae Scopariae decoction injection .%目的:观察茵陈加味汤联合熊去氧胆酸治疗妊娠肝内胆汁淤积症( intrahepatic cholestasis of pregnancy,ICP)的疗效。方法:采用前瞻性研究方法,将2010年至2012年本院收治的妊娠肝内胆汁淤积症孕妇108例随机分为A、B两组,A组采用茵陈加味汤联合熊去氧胆酸治疗(62例),B组采用熊去氧胆酸治疗(46例)。比较两组治疗效果及妊娠结局。结果:治疗结束时,A组治疗后皮肤瘙痒评分及TBA、AST、ALT、CG值均降低,且较B组低。两组瘙痒评分和AST、ALT值比较差异有统计学意义( P<0.05),剖宫产率、产后出血率、羊水粪染率比较差异也有统计学意义(P<0.05)。结论:茵陈加味汤联合熊去氧胆酸治疗ICP能够提高ICP的疗效,值得临床推广。

  10. Imaging characteristics of hepatobiliary scintigraphy in neonatal intrahepatic cholestasis caused by citrin deficiency%Citrin缺陷所致婴儿肝内胆汁淤积症的肝胆显像特征

    Institute of Scientific and Technical Information of China (English)

    张梅虹; 赵瑞芳; 陈瑞; 王建设

    2014-01-01

    目的 探讨citrin缺陷导致的婴儿肝内胆汁淤积症(NICCD)患儿99Tcm-二乙基乙酰苯胺亚氨二醋酸(EHIDA)肝胆显像的特征.方法 回顾性分析28例(男16例,女12例,1~8月龄)经基因确诊、同时行99Tcm-EHIDA肝胆动态显像检查的NICCD患儿资料.肝胆动态显像时心、肝、肾按正常时序和强度显影定义为摄取功能正常,肝影模糊和(或)心肾影持续时间延长者为摄取功能差;60 min内肠道显影为排泄通畅,60 min后为排泄延迟,24 h肠道仍不显影为排泄受阻.分析肝胆显像特征与血清总胆红素(TB)、直接胆红素(DB)、ALT、总胆汁酸(TBA)等指标间的关系.数据分析采用Kruskal-Wallis秩和检验.结果 28例中,20例表现为摄取功能正常,其中10例排泄通畅,10例排泄延迟;8例表现为摄取功能差,其中4例排泄延迟,4例排泄受阻.与摄取功能正常组相比,摄取功能差组TB和DB明显增高[183.6(128.7~ 280.9) mmol/L和105.5(80.0~ 141.7) mmol/L,135.6(95.7~212.6) mmol/L和73.1(53.9~ 97.9) mmol/L;Z=-2.25和-2.73,均P<0.05].与排泄通畅者相比,排泄延迟者TB、DB和TBA明显升高[分别为137.5(122.0~170.9) mmol/L和81.7(65.7~93.5) mmol/L,96.5(81.1~ 108.0) mmol/L和54.1(45.3~72.6) mmol/L,245.6(183.9~299.2) mmol/L和136.0(73.5 ~163.2) mmol/L;Z=-3.92、-3.74和-2.57,均P<0.05];排泄受阻者TB[262.0(152.1 ~ 542.8) mmol/L]和DB[192.7(118.1~407.2) mmol/L]更高(均Z=-2.82,均P<0.05).与排泄延迟组相比,排泄受阻者ALT明显增高[71.5(48.5~144.8) U/L和20.0(16.5~27.7) U/L;Z=-2.66,P<0.05).结论 99Tcm-EHIDA肝胆显像可反映NICCD患儿肝脏摄取和排泄功能受损的状况,摄取功能受损严重时,可出现排泄受阻的征象.%Objective To investigate the scintigraphic features of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and to explore the clinical significance of 99Tcm-EHIDA hepatobiliary scintigraphy.Methods Hepatobiliary scintigraphy with

  11. Protective effect of Zhizi Bopi decoction on α-naphthylisothiocyanate induced intrahepatic cholestasis in rats%栀子柏皮汤对α-萘异硫氰酸酯诱导的肝内胆汁淤积大鼠的保护作用

    Institute of Scientific and Technical Information of China (English)

    曹璐; 李俊; 黄成; 韩静文

    2013-01-01

    Objective To investigate the protective effects of Zhizi Bopi decoction on rats against a-naphthyliso-thiocyanaten ( ANIT )induced liver injury with cholestasis and analyzed the possible mechanism. Methods ANIT was used to mimick the drug-induced liver injuery. 48 h after the ANIT treatment, serum of total bilirubin ( TBIL ), alkaline phosphatase ( ALP ), alanine aminotransferase ( ALT ), aspartate aminotransferase ( AST ), 7-glutamyltranspeptidase ( GGT ), liver specimens of superoxide dismutase ( SOD ), malondialdehyde ( MDA ), gluta-thione ( GSH ), and glutathione peroxidase ( GSH-Px ) were measured. To further explore the molecular mechanisms , we measured the expression of the bile metabolism-related transporters: bile salt export pump ( BSEP ), sodi-um-taurocholate cotrans-porting polypeptide ( NTCP ) and the enzyme related to oxidative stress: cytochrome P4502E1 ( CYP2E1 ) in both mRNA and protein level. Results Zhizi Bopi decoction improved live history with reduced the serum levels of TBIL, ALP, ALT, AST, GGT. Furthermore, hepatic MDA activities and contents in liver tissue were significantly reduced, while SOD, GSH, GSH-Px activities, which had been suppressed by ANIT were significantly elevated in the groups pretreated with Zhizi Bopi decoction in a dose-dependent manmer. Additionally, Zhizi Bopi decoction was found to increase the expression of liver NTCP, and decrease the BSEP in ANIT-induced liver injury with cholestasis. CYP2E1 was decreased in accordance with the protein expression. Conclusion Zhizi Bopi decoction exerts protective effects against ANIT-induced liver injury. The mechanisms could be related to transshipment of bile metabolism-related transporters and anti-oxidative damage.%目的 探讨栀子柏皮汤对α-萘异硫氰酸酯(ANIT)诱导的肝内胆汁淤积大鼠的保护作用及可能机制.方法 实验组大鼠灌胃给予栀子柏皮汤7 d,第7天给药后4 h给ANIT造模.48 h后,测血清总胆红素(TBIL)含量、碱性磷酸

  12. Expression of IL-18 and caspase-1 in placental syncytiotrophoblast of intrahepatic cholestasis of pregnancy%妊娠期肝内胆汁淤积症胎盘合体滋养细胞中白细胞介素18和半胱氨酸天冬氨酸蛋白酶-1表达及其意义

    Institute of Scientific and Technical Information of China (English)

    黄婷; 罗红霞; 邵勇

    2013-01-01

    Objective To evaluate the expression and location of the Interleukin-18 (IL-18) ,cysteinyl aspartate-specific proteases-1 (caspase-1) and the activity of caspase-1 in human placenta syncytiotrophoblast and explore the relationship between IL-18 and caspase-1 in intrahepatic cholestasis of pregnancy (ICP). Methods Between Mar. 2011 and Nov. 2011 in the First Affiliated Hospital of Chongqing Medical University. Forty women with ICP were chosen as the study objects. They were classified into mild group (n = 20) , severe group (n = 20). Twenty healthy pregnant women who delivered in the same period were chosen as the control group ( n = 20) . Results The serum level of IL-18, ALT, AST in the severe ICP group were significantly higher than the mild ICP group and control group (P < 0. 05). The IL-18 and caspase-1 protein levels in placenta syncytiotrophoblast of the severe ICP group were significantly higher than the mild ICP group and control group (P <0. 05). Conclusion The immune injury mediated by IL-18 and caspase-1 signaling pathways may participate in the pathogenesis of ICP hepatic damage process.%目的 通过检测妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)孕妇胎盘合体滋养细胞中白细胞介素18(IL-18)和半胱氨酸天冬氨酸蛋白酶-1(caspase-1)的定位和表达及caspase-1的生物学活性,探讨其与ICP发病的关系.方法 2011年3月至11月在重庆医科大学附属第一医院选择ICP孕妇40例为研究对象,包括ICP轻度组(20例),ICP重度组(20例),以同期行择期剖宫产术的20例正常孕妇为对照组.采用免疫组化检测IL-18和caspase-1的表达.结果 ICP重度组孕妇血清中IL-18及丙氨酸转氨酶、天冬氨酸转氨酶水平显著高于轻度组和正常对照组,差异有统计学意义(P<0.05).ICP重度组胎盘合体滋养细胞中IL-18和caspase1表达水平显著高于轻度组和正常对照组,差异有统计学意义(P<0.05).结论 IL-18和caspase-1信号

  13. Clinical study on naltrexone combined with ademetionine in treatment of alcoholic liver disease complicated with cholestasis%纳曲酮联合腺苷蛋氨酸治疗酒精性肝病合并胆汁淤积的临床研究

    Institute of Scientific and Technical Information of China (English)

    马刚

    2015-01-01

    目的:探讨纳曲酮联合腺苷蛋氨酸治疗酒精性肝病合并胆汁淤积的临床疗效。方法选取2014年3月—2015年5月第四军医大学唐都医院收治的酒精性肝病合并胆汁淤积患者96例,随机分为对照组和治疗组,每组各48例。对照组在基础治疗上静脉滴注注射用丁二磺酸腺苷蛋氨酸1.0 g加入到5%葡萄糖溶液500 mL,1次/d,6周后改为口服丁二磺酸腺苷蛋氨酸肠溶片,0.5 g/次,2次/d。治疗组在对照组基础上口服盐酸纳曲酮片,25 mg/次,1次/d。两组均连续治疗10周。观察两组患者的临床疗效,同时比较两组治疗前后丙氨酸氨基转移酶(ALT)、γ-谷氨酰转肽酶(GGT)、血清胆红素(SB)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)、总胆汁酸(TBA)、白蛋白(Alb)、透明质酸酶(HA)、层黏连蛋白(LN)、III型前胶原(PC-III)、IV型胶原蛋白(IV-C)的变化。结果治疗后,对照组和治疗组的总有效率分别为77.1%、91.7%,两组比较差异具有统计学意义(P<0.05)。治疗后,两组患者Alb均显著升高、TBA、ALT、AST、TBIL、SB、GGT、HA、PC-III、IV-C、LN均显著降低,同组治疗前后差异具有统计学意义(P<0.05);且治疗组这些观察指标的改善程度优于对照组,两组比较差异具有统计学意义(P<0.05)。结论纳曲酮联合腺苷蛋氨酸治疗酒精性肝病合并胆汁淤积具有较好的临床疗效,可改善患者肝功能和肝纤维化指标,具体一定的临床推广应用价值。%Objective To observe the clinical efficacy of naltrexone combined with ademetionine in treatment of alcoholic liver disease complicated with cholestasis.Methods Patients (96 cases) with alcoholic liver disease complicated with cholestasis in Tangdu Hospital of the Fourth Military Medical University from March 2014 to May 2015 were randomly divided into control and treatment groups

  14. 进行性家族性肝内胆汁淤积非移植外科治疗荟萃分析%Treatment of progressive familial intrahepatic cholestasis with non-transplant surgery: a review of literature and meta-analysis

    Institute of Scientific and Technical Information of China (English)

    刘壵; 李龙; 侯文英; 王海斌

    2013-01-01

    Objective To review the outcome of the different choices of non-transplant surgical treatment for progress familial intrahepatic cholestasis (PFIC) by performing meta-analysis.Methods A systematic literature search of PubMed,Embase,Scopus and Chinese Biomedical Literature Database (CBM) was performed.All the articles regarding the outcome of non-transplant surgery in PFIC patients were recruited in this study.Results A total of 20 case series or case reports were included in this study.Of the 144 patients who underwent a non-transplant surgery,108 (75%) patients had favorable outcomes.Unfavorable outcomes were often associated with more advanced stage of liver fibrosis or cirrhosis.Conclusions Non-transplant surgical interventions in PFIC patients can effectively delay progression of liver cirrhosis.%目的 总结分析进行性家族性肝内胆汁淤积(PFIC)的非移植外科治疗的不同手术方式及其治疗现状.方法 检索PubMed、EMBASE、Scopus和中国生物医学文献数据库(CBM)非移植外科治疗PFIC的所有相关文献,提取临床资料,总结分析.结果 20项个案或病例系列报道纳入本研究,共144例患儿接受非移植外科治疗,其中108例(75%)预后良好.疾病进展,脏纤维化或硬化,往往提示预后不良.结论 从某种意义上讲,虽然本荟萃分析所纳入研究存在一定的不全面性和不一致性,但是非移植外科治疗确实能明显缓解PFIC患儿症状,遏制疾病进展.

  15. Identification and diagnosis of three novel mutations in SLC25A13 gene of neonatal intrahepatic cholestasis caused by citrin deficiency%Citrin缺陷导致的新生儿肝内胆汁淤积症SLC25A13基因三个新突变的识别及诊断

    Institute of Scientific and Technical Information of China (English)

    宋元宗; 盛建胜; 牛飼美晴; 胡務亮; 张春花; 小林圭子

    2008-01-01

    Objective Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD, OMIM 605814 ) is a novel autosomal recessive disease results from mutations in the gene SLC25A13 that encodes for citrin, a liver-type aspartate/glutamate cartier located in the mitochondrial inner membrane. Most of the Chinese NICCD patients diagnosed by genetic analysis had the sameSLC25A13 mutations as Japanese, however, in some cases, the known mutations were not detected. This research aimed to identify novel SLC25A13 mutations in Chinese NICCD patients and to explore the experimental conditions for their genetic diagnosis.Methods Genomic DNA was extracted from blood samples of 3 NICCD patients from Taiwan (P757), Guangdong (P1194) and Hebei (P1443) Province of China, respectively; and all the 18 exons and their flanking sequences of SLC25A13 gene were sequenced. Furthermore, the identified novel mutations were diagnosed by amplification with PCR, digestion with corresponding restriction endonuclease, and agarose gel electrophoresis.Results Three novel mutations identified in SLC25A13 gene of the 3 NICCD patients were an abnormal splicing IVS7-2A>G (P757), a missense A541D (c. 1622C > A, P1194) and a nonsense R319X (c. 955C > T, P1443). The PCR-RFLP procedures for their genetic diagnosis were also established, with specific fragments on electrophoresis after digestion of the PCR products with three different restriction endonucleases Msp Ⅰ, Hpy188Ⅰ and Taq Ⅰ, respectively.Conclusions The three novel mutations in SLC25A13 gene of Chinese NICCD patients were first identified, suggesting that SLC25A13 mutation distributed in Chinese population is somewhat different from that in Japanese. Moreover, the PCR-RFLP diagnostic procedures established in this research provide valuable tools not only for the genetic diagnosis of NICCD but also for further molecular epidemiologic investigations in Chinese population.Acknowledgement We are grateful to all research subjects and their family

  16. Effect of ursodeoxycholic acid on the expression of the hepatocellular BSEP and FXR in pregnant rats with ethinylestradiol induced intrahepatic cholestasis%熊脱氧胆酸对抗乙炔雌二醇诱发孕大鼠肝内胆汁淤积的作用机制

    Institute of Scientific and Technical Information of China (English)

    刘红; 刘建; 李金艳

    2005-01-01

    目的:研究熊脱氧胆酸(ursodeoxycholic acid,UDCA)对雌激素诱发孕鼠肝内胆汁淤积肝脏胆盐输出泵(bile salt export pump,BSEP)及肝脏法尼醇受体(farnesoid X receptor,FXR)表达的影响,探讨UDCA治疗妊娠期肝内胆汁淤积症(intrahepatis cholestasis of pregnancy,ICP)的作用机制.方法: 随机将孕15d的大鼠40只分成4组,1,2-丙二醇(propylene Glycol,PG)组,17-α-乙炔雌二醇(ethinylestradiol,EE)组,UDCA组和UDCA+EE组.用药前,用药后5d测血浆中谷丙转氨酶(ALT),谷草转氨酶(AST),碱性磷酸酶(ALP),总胆酸(TBA).同时观察肝脏形态学变化及胎鼠生长发育情况;应用免疫组化法分析肝脏BSEP及FXR的表达.结果:用药后EE组的孕鼠ALT、AST、ALP、TBA比用药前显著升高(P<0.05),PG组无明显变化(P>0.05),UDCA组,UDCA+EE组ALT,AST,ALP无明显变化(P>0.05),但TBA明显升高(P<0.05).EE组孕鼠肝脏出现肝内胆汁淤积表现,其余3组肝脏形态结构正常.EE组胎仔身长,尾长,体重,死胎数,活胎数,孕天数与其余3组比较有显著差异(P<0.05).EE组BSEP表达降低,FXR表达升高,与PG组,UDCA组,UDCA+EE组差异均有显著性(P<0.05).结论:UDCA对雌激素诱发孕鼠肝内胆汁淤积肝脏具有保护作用,能改善胎仔预后,可能是通过恢复肝脏BSEP的表达促进胆汁分泌,而不是通过影响FXR表达调节胆汁酸的合成.

  17. Apoptosis and Caspase-3 Expression in Placenta of Patients with Intrahepatic Cholestasis of Pregnancy%妊娠期肝内胆汁淤积症胎盘组织中细胞凋亡及caspase-3的表达

    Institute of Scientific and Technical Information of China (English)

    江燕; 虞国芬; 张艳; 费冬; 徐婧

    2013-01-01

    目的 探讨妊娠期肝内胆汁淤积症(ICP)胎盘组织中细胞凋亡及caspase-3的表达情况.方法 以临产前行剖宫产术终止妊娠的ICP患者为ICP组(20例),同期因骨盆、胎位、社会因素等原因临产前行剖宫产术终止妊娠的健康孕妇为对照组(20例).采用末端脱氧核苷酸转移酶介导、地高辛标记的dUTP缺口末端标记法(TUNEL)检测胎盘组织中合体滋养细胞、细胞滋养细胞、蜕膜细胞及绒毛间质细胞的凋亡情况,采用免疫组织化学法检测胎盘组织caspase-3蛋白表达水平.结果 ICP组胎盘组织中各细胞的凋亡率指数、caspase-3蛋白阳性表达率均高于对照组(P<0.05).结论 ICP胎盘组织存在细胞凋亡以及凋亡相关蛋白表达增多的改变,ICP胎盘功能减退与细胞凋亡密切相关,细胞凋亡在ICP疾病的发生、发展中起重要作用.%Objective To explore the apoptosis and caspase-3 expression in the placental tissue of patients with intrahepatic cholestasis of pregnancy (ICP). Methods Twenty ICP patients who underwent cesarean section to terminate the pregnancy before labor were selected as the ICP group, and 20 normal pregnant women who underwent cesarean section due to pelvis, fetal position or social factors as the control group. The apoptosis of syncytiotrophoblast, cytotrophoblast, decidual and interstitial cells was detected by TUNEL assay. The expression of caspase-3 protein was measured by immunohistochemistry. Results Compared with control group,the apoptosis rate and caspase-3 expression in placental tissue significantly increased in ICP group ( P<0.05). Conclusion The apoptosis and apoptosis-related protein expression increase in placenta of ICP patients. The ICP-induced placental insufficiency is closely related to the apoptosis, which plays an important role in the occurrence and development of ICP.

  18. Effect of Herba artemisiae scopariae decoction on serum and placental tissue levels of endothelin in rats with intrahepatic cholestasis of pregnancy%茵陈对妊娠期肝内胆汁淤积症模型大鼠血清及胎盘组织内皮素的影响

    Institute of Scientific and Technical Information of China (English)

    顾江红; 周玲贞; 徐道芬; 贡方红; 朱珍; 杜兰芳; 宁维翾

    2012-01-01

    To investigate the effects of Herba artemisiae scopariae on endothelin (ET) levels in rats withintrahepatic cholestasis of pregnancy (ICP).MethodsSixty 15-day pregnant SD rats were randomly divided into three groups:control group, ICP group and treatment group. ICP was induced by subcutaneous injection with estradiol benzoate (5mgokg-1od-1) and subsequent intragastric administration of 5mlod-1 normal saline for 5 d; in treatment group ICP rats received intragastric administration of 50% Herba artemisiae scopariae water decoction; and in the control group, rats received subcutaneous injection of 5ml normal saline plus intragastric perfusion with 5mlod-1 normal saline for 5 d. The serum and placental tissue levels of ET were determinate by ELISA-ABC method.ResultsThe ET levels in serum and placental tissue weresignificantly higher in ICP group than those in control group (P<0.01). The body weight and fetal survival rate in ICP group were decreased significantly as compared with those in control group (P<0.01). The average weight was higher and fetal mortality rate was lower in treatment group than those in ICP group (both P<0.05); while the serum and placental tissue ET levels in treatment group were decreased compared with ICP group(P<0.05).The increased endothelin levels in plasma and placentaltissue in ICP rats may be associated with fetal complications and Herba artemisiae scopariae can significantly reduce ET levels and improve the outcome of pregnancy in rats.%目的 研究茵陈水煎剂对妊娠期肝内胆汁淤积症(ICP)模型大鼠血清及胎盘组织内皮素(ET)的影响.方法 以苯甲酸雌二醇针剂复制SD 大鼠ICP 模型;以50%茵陈水煎剂灌胃;采用ABC-ELISA法测定大鼠血清及胎盘组织ET 值.结果 茵陈治疗可增加胎鼠平均体重,降低胎鼠死亡率,降低孕鼠血清及胎盘组织ET水平.结论 茵陈能显著降低ICP 大鼠血清及胎盘组织ET水平,明显改善妊娠结局.

  19. 妊娠期肝内胆汁淤积症IL-10、TNF-α表达变化及其与肝功能变化的关系%The expression levels of IL-10 and TNF-α in patients with intrahepatic cholestasis of pregnancy and the relationship with liver function

    Institute of Scientific and Technical Information of China (English)

    曹丽琼; 曲广第; 王冬梅

    2012-01-01

    This study aims to investigate the expression and significance of IL-10 and TNF-α in the placenta with intrahepatic cholestasis of pregnancy (ICP). Total of 37 ICP gravidas delivered by cesarean section were selected as the ICP group, and another 35 healthy pregnant women were chosen as control. Placentas of the all gravidas were collected for TNF-α and IL-10 proteins detection by Envision immunohistochemical method. The results showed that TNF-α and IL-10 were mainly expressed in intra cytoplasma of trophoeyte of placentas of both groups. In the ICP group, the expression of IL-10 was obviously lower than that of control, meanwhile the expression of TNF-a was obviously higher than that control (P< 0.05). Furthermore, TNF-a and serum transaminase were positively correlated (r = 0.270, 0.246, P < 0.05), but serum transaminase and II,-10 levels demonstrated negative correlation (r= -0.250, -0.128, P< 0.05). We can conclude that the increase of type 1 cytokine (TNF-α) is associated with a decrease of type 2 cylokine (IL-10) in TCP, and the imbalance of cytokine network may participate in the pathogenesis of ICP through affecting the liver function.%目的 探讨白细胞介素10(interleukin- 10,IL-10)、肿瘤坏死因子(tumor necrosis factor-alpha,TNF-α)在妊娠期肝内胆汁淤积症(ICP)孕妇胎盘组织中的表达及其与门冬氨酸转移酶(aspartate aminotransferase AST)、丙氨酸转移酶(alanine aminotransferase,ALT)的关系.方法 选择2010年10月至2011年5月在新疆医科大学第一附属医院产科剖宫产分娩的ICP孕妇37例为ICP组,选择同期健康孕妇35例为对照组.采用Envision免疫组化法测定IL-10、TNF-α在孕妇胎盘组织中的定位与表达水平,术前静脉血测定肝功指标:AST,ALT,采用SPSS17.0统计软件进行统计分析,计量资料比较采用t检验;等级经秩转换后采用秩和检验并进行相关性分析.结果 IL-10、TNF-α在两组孕妇胎盘组

  20. Effect of Yinhuang Mixture on Expression of MRP2 and BSEP in Rats with Intrahepatic Cholestasis of Pregnancy Induced by Estrogen and Progesterone%茵黄合剂对雌孕激素共诱导妊娠肝内胆汁淤积症大鼠胆汁酸转运蛋白MRP2与BSEP表达的影响

    Institute of Scientific and Technical Information of China (English)

    刘佳; 侯莉莉; 赵翠英

    2013-01-01

    目的:观察茵黄合剂对雌孕激素共诱导妊娠肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)大鼠胆汁酸转运蛋白多药耐药相关蛋白2(multidrug resistance-associated protein 2,MRP2)与胆盐输出泵(bile salt export pump,BSEP)表达的影响,探讨茵黄合剂治疗妊娠肝内胆汁淤积症可能的分子机制.方法:运用雌孕激素联合的方法建立孕鼠妊娠肝内胆汁淤积症模型,随机分为正常组、模型组、茵黄合剂低剂量组(9 g·kg-1·d-1,ig)和茵黄合剂高剂量组(18 g·kg-1 ·d-1,ig),分别给予生理盐水、低剂量与高剂量的茵黄合剂5d,取血,检测血清总胆汁酸(total bile acid,TBA)、总胆红素(total bilirubin,TBil)、丙氨酸转氨酶(alanine transarninase,ALT)、天冬氨酸转氨酶(aspartate aminotransferase,AST)活性,留取肝脏组织,置于液氮中保存,分别运用实时定量PCR法及蛋白免疫印迹法检测胆汁酸转运蛋白MRP2 BSEP mRNA与蛋白表达情况.结果:与正常组比较,模型组大鼠血清TBA,TBil水平增加,MRP2,BSEP mRNA与蛋白表达水平降低(P<0.01),模型组ALT,AST含量与正常组比较虽有增加,但差异无统计学意义.与模型组比较,茵黄合剂低、高剂量均能降低妊娠肝内胆汁淤积症模型大鼠血清TBA,TBil水平(P<0.01),并且可明显增加肝脏组织MRP2,BSEPmRNA与蛋白表达水平,P<0.01.结论:茵黄合剂治疗妊娠肝内胆汁淤积症的分子机制可能是通过增加肝脏组织胆汁酸转运蛋白MRP2,BSEP,mRNA与蛋白表达水平实现的.

  1. Expression and Significance Study of Organic Anion Transporting Polypeptides8 Gene in Placenta Syntrophoblastic Cell of Intrahepatic Cholestasis of Pregnancy%妊娠期肝内胆汁淤积症孕妇胎盘合体滋养细胞OATP8基因表达及意义的研究

    Institute of Scientific and Technical Information of China (English)

    李秋红; 邵勇

    2012-01-01

    Objective:To explore the expression and significance of organic anion transporting polypep-tides 8 gene(OATPS) in placenta syncytiotrophoblast of intrahepatic cholestasis of pregnancy(ICP). Methods: Patients were divided into three groups: mild ICP group(8 cases), severe ICP group(8 cases) and control group(8 cases),The location of OATP8 protein in placenta was checkedby Immunohistochemical SABC method. OATP8 mRNA and protein levels were determined by reverse transcription polymerase chain reaction (RT-PCR) and western blot. Results :①OATP8 protein was located on the cell membrane of placenta syncytiotrophoblast. ②The mRNA expression of OATP8 in severe ICP group was higher than that in control and mild ICP group(P<0.05). The mRNA expression of OATP8 in mild ICP group was higher than that in control group, were OATP8 in severe ICP group(P<0.05). ③OATP8 protein expression in the severe ICP group was significantly higher than that in mild group (P < 0.05), and the protein in mild group was higher than that in control group ( P<0.05). Conclusions:OATP8 protein expression in placenta syncytiotrophoblast increases appreciably in ICP pregnant women, which may contribute to the scavenging process of bilirubin or bileacid.%目的:探讨有机阴离子转运多肽8(OATP8)在妊娠期肝内胆汁淤积症(ICP)孕妇胎盘组织中的表达及其意义.方法:研究对象分为ICP轻度组(8例)、ICP重度组(8例)和正常对照组(8例).采用免疫组化链霉亲和素-生物素-过氧化物酶复合物( SABC)法检测胎盘组织中OATP8蛋白定位表达;采用逆转录(RT) -PCR技术检测OATP8 mRNA表达;蛋白印迹法检测OATP8蛋白表达水平.结果:①OAW8蛋白定位在胎盘合体滋养细胞膜上.②3组孕妇胎盘组织中OATP8 mRNA的表达:ICP重度组明显高于对照组和ICP轻度组,差异均有统计学意义(P<0.05),ICP轻度组高于对照组,差异有统计学意义(P<0.05);③3组孕妇胎盘组织中OATP8蛋白的表达:ICP

  2. Effects of PTPRO on Th1/Th2 bias in pregnant women with intraheptic cholestasis%PTPRO 对妊娠期肝内胆汁淤积症患者Th1/Th2 细胞偏倚的影响

    Institute of Scientific and Technical Information of China (English)

    王增芳; 王萍萍; 王增艳; 孙芳; 赵金华; 修霞

    2015-01-01

    目的 探讨受体O型蛋白酪氨酸磷酸酶(PTPRO)对妊娠期肝内胆汁淤积症(ICP)患者Th1/T h2细胞偏倚的影响.方法 分离获取正常妊娠(A组 ,30例)、轻型ICP (B组 ,28例)和重型ICP(C组 ,30例)孕妇胎盘来源的单核-巨噬细胞 ,采用RT-PCR和Western blot法分别检测 PTPRO mRNA和蛋白的表达 ,Western blot法检测NF-κB/p65的磷酸化水平.分离获取孕妇外周血T淋巴细胞 ,与胎盘来源的单核-巨噬细胞共培养 ,ELISA法检测细胞培养上清液中IFN-γ、IL-12、IL-4和IL-10水平.结果 与A组相比 ,B、C组单核-巨噬细胞 PTPRO表达和 NF-κB/p65磷酸化水平升高 ,与其共培养的外周血T淋巴细胞高分泌IFN-γ和IL-12(P<0 .05);与B组相比 ,C组PTPRO表达和NF-κB/p65磷酸化水平升高 ,IFN-γ和IL-12分泌增多(P<0 .05).结论 ICP患者胎盘单核-巨噬细胞高表达PTPRO ,促使T淋巴细胞向Th1细胞偏倚.%Objective To explore the effects of protein tyrosine phosphatase receptor-type O (PTPRO) on Th1/Th2 bias in pregnant women with intraheptic cholestasis(ICP) .Methods Monocyte-macrophages were separated from placental tissues of pregnant women with normal term (group A , 30 cases) ,mild ICP (group B ,28 cases) and severe ICP (group C ,30 cases) .The expressions of PTPRO protein and mRNA and the level of phosphorylated NF-κB/p65 were detected by RT-PCR and Western blot ,respectively .The T lymphocytes of eripheral blood and monocyte-macrophages separated from placental tissues were co-cultured and the expressions of IFN-γ,IL-12 ,IL-4 and IL-10 in supernatant were determined by ELISA .Results The expression of PTPRO and the phosphorylation level of NF-κB/p65 in monocyte-macrophages were higher and the secretions of IFN-γand IL-12 from T lymphocytes were more in groups of B and C than those in group A (P<0 .05) ,which were more in group C than those in group B(P<0 .05) .Conclusion PTPRO is highly expressed in placental monocyte-macrophages of pregnant women with

  3. Comparison of different diagnostic methods in infants with Cholestasis

    Institute of Scientific and Technical Information of China (English)

    Seyed Mohsen Dehghani; Mahmood Haghighat; Mohammad Hadi Imanieh; Bita Geramizadeh

    2006-01-01

    AIM: To evaluate different methods in differentiating idiopathic neonatal hepatitis from biliary atresia.METHODS: Sixty-five infants with cholestatic jaundice and final diagnosis of idiopathic neonatal hepatitis and biliary atresia were studied prospectively from September 2003 to March 2006. A thorough history and physical examination were undertaken and the liver enzymes were examined. All cases underwent abdominal ultrasonography, hepatobiliary scintigraphy,and percutaneous liver biopsy. The accuracy, sensitivity,specificity and predictive values of these various methods were compared.RESULTS: There were 34 girls and 31 boys, among them 46 subjects had idiopathic neonatal hepatitis (age,61 ± 17 d) and 19 had biliary atresia (age, 64 ± 18 d).The mean age at onset of jaundice was significantly lower in cases of biliary atresia when compared to idiopathic neonatal hepatitis cases (9 ± 13 d vs 20 ± 21 d;P = 0.032). The diagnostic accuracy of different methods was as follows: liver biopsy, 96.9%; clinical evaluation,70.8%; ultrasonography, 69.2%; hepatobiliary scintigraphy, 58.5%; and liver enzymes, 50.8%.CONCLUSION: Our results indicate that clinical evaluation by an experienced pediatric hepatologist and a biopsy of the liver are considered as the most reliable methods to differentiate idiopathic neonatal hepatitis and biliary atresia.

  4. Langerhans Cell Histiocytosis in 2 Cases of Cholestasis

    OpenAIRE

    Erkan, Tülay; Kutlu, Tufan; Çokuğraş, Fügen; Ceyhan, İpek; Yıldız, İnci; Özbay, Gülşen; T.Tümay, Güngör

    1995-01-01

    Two cases of Langerhans cell histiocytosis who had multiorgan involvement with obstructive jaundice anemia and hepatosplenomegaly painful ulceration purulent exudation squamous and maculopapular rash in the skin were presented The diagnosis of Langerhans cell histiocytosis was made by skin biopsies that showed the presence of S 100 staining cells We suggest that the diagnosis of Langerhans cell histiocytosis should be considered in patients presenting with clinical and biochemical evidence of...

  5. Is ursodeoxycholic acid effective for intrahepatic cholestasis of pregnancy?

    Directory of Open Access Journals (Sweden)

    Sebastián Sepúlveda Marín

    2016-04-01

    Full Text Available La colestasia intrahepática del embarazo es una condición propia de la gestación y se asocia a mayor morbilidad y mortalidad perinatal. Dentro de las alternativas terapéuticas se ha propuesto el uso del ácido ursodeoxicólico, sin embargo su beneficio sigue siendo controvertido. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos tres revisiones sistemáticas que en conjunto incluyen ocho estudios aleatorizados. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que el uso de ácido ursodeoxicólico en la colestasia intrahepática del embarazo podría reducir el riesgo de prematurez y de necesidad de hospitalización del recién nacido en unidad de cuidado intensivo. También podría disminuir el prurito materno.

  6. Pancreatic adenocarcinoma in type 2 progressive familial intrahepatic cholestasis

    Directory of Open Access Journals (Sweden)

    Green Richard M

    2010-03-01

    Full Text Available Abstract Background BSEP disease results from mutations in ABCB11, which encodes the bile salt export pump (BSEP. BSEP disease is associated with an increased risk of hepatobiliary cancer. Case Presentation A 36 year old woman with BSEP disease developed pancreatic adenocarcinoma at age 36. She had been treated with a biliary diversion at age 18. A 1.7 × 1.3 cm mass was detected in the pancreas on abdominal CT scan. A 2 cm mass lesion was found at the neck and proximal body of the pancreas. Pathology demonstrated a grade 2-3 adenocarcinoma with invasion into the peripancreatic fat. Conclusions Clinicians should be aware of the possibility of pancreatic adenocarcinoma in patients with BSEP disease.

  7. Cathepsin B inactivation attenuates hepatic injury and fibrosis during cholestasis

    OpenAIRE

    Canbay, Ali; Guicciardi, Maria Eugenia; Higuchi, Hajime; Feldstein, Ariel; Bronk, Steven F.; Rydzewski, Robert; Tanai, Makiko; Gores, Gregory J.

    2004-01-01

    Although a lysosomal, cathepsin B–dependent (Ctsb-dependent) pathway of apoptosis has been described, the contribution of this pathway to tissue damage remains unclear. Our aim was to ascertain if Ctsb inactivation attenuates liver injury, inflammation, and fibrogenesis after bile duct ligation (BDL). In 3-day BDL mice, hepatocyte apoptosis, mitochondrial cytochrome c release, and serum alanine aminotransferase (ALT) values were reduced in Ctsb–/– versus Ctsb+/+ animals. Likewise, R-3032 (a C...

  8. Pancreatic adenocarcinoma in type 2 progressive familial intrahepatic cholestasis

    OpenAIRE

    Green Richard M; Rao M Sambasiva; Patil Deepa; Bass Lee M; Whitington Peter F

    2010-01-01

    Abstract Background BSEP disease results from mutations in ABCB11, which encodes the bile salt export pump (BSEP). BSEP disease is associated with an increased risk of hepatobiliary cancer. Case Presentation A 36 year old woman with BSEP disease developed pancreatic adenocarcinoma at age 36. She had been treated with a biliary diversion at age 18. A 1.7 × 1.3 cm mass was detected in the pancreas on abdominal CT scan. A 2 cm mass lesion was found at the neck and proximal body of the pancreas. ...

  9. [Hepatic amyloidosis as cause of severe intrahepatic cholestasis].

    Science.gov (United States)

    Gavilán, J C; Bermúdez, F J; Márquez, A; Sánchez-Carrillo, J J; González-Santos, P

    2003-01-01

    The liver is frequently involved by amyloidosis, but hyperbilirubinemia and liver failure are uncommon features. A mild elevation of the serum alkaline phosphatase value and, less frequently, hepatomegaly are the most common findings. Usually the patients have no symptoms related with the liver involvement; the clinical manifestation and the long term prognosis depends on the renal and cardiac disease. We report an unusual clinical presentation of primary amyloidosis in a previously asymptomatic 65 years old woman who was admitted to the hospital because of ictericia and ascitis mimicking a drug induced acute hepatic failure.

  10. Effect of a selective JNK inhibitor on pregnant rats with ethinylestradiol induced intrahepatic cholestasis%c-Jun氨基末端激酶选择性抑制剂对雌激素诱导致妊娠期大鼠肝内胆汁淤积症的影响

    Institute of Scientific and Technical Information of China (English)

    陈秋玲; 吴新华; 李苏萍

    2012-01-01

    Objective To evaluate the influence of SP600125,a selective c-Jun N-terminal kinase (JNK) inhibitor,on the levels of serum total bile salt (TBA) and Bsep,Ntcp expression in the hepatic tissue of rats with ethinylestradiol induced intrahepatic cholestasis.Methods Rats pregnant for 15days were administered the subcutaneous injection of 17- b -estradiol propylene ( EE ) to modulate the ICP animal models,and be SP600125 to intervene.Testing the level of serum TBA and the expression of c-Jun,Bsep,Ntcp in the hepalatic tissue.Results The average gray values of c-Jun in the group of ICP models were significantly lower than the normal control group ( 101.05 ± 5.20 vs 118.99 ± 5.95,P < 0.05 ).After the intervention of SP600125,comparing with the group of ICP models,the expression of Bsep,Ntcp in the group of SP600125 intervention were significantly higher,and this change in the high dose of SP600125 intervention group was more obvious ( low dose intervention group Bsep:0.452 ±0.031 vs 0.291 ±0.043,Ntcp:0.462 ± 0.015 vs 0.285 ± 0.021,P < 0.05 ; high dose intervention group Bsep:0.568 ± 0.038 vs 0.291 ±0.043,Ntcp:0.605±0.020 vs 0.285 ±0.021,P <0.05),while the level of TBA in the serum was significantly lower.Conclusions Treatment with SP600125 can down-regulate the level of c-Jun/AP-1,and it may participate in the lower expression of Bsep、Ntcp in the ICP rats which were induced by 17-bestradiol.%目的 探讨c-Jun氨基末端激酶(JNK)选择性抑制剂SP600125对雌激素诱导的妊娠期肝内胆汁淤积症大鼠肝组织内Bsep、Ntcp蛋白的表达情况及血清总胆汁酸浓度的影响.方法 将孕15d SD大鼠皮下注射17-β-乙炔雌二醇建立ICP动物模型,并予以SP600125进行干预,检测各组孕鼠血清胆汁酸(TBA)、各组孕鼠肝脏组织c-Jun、胆盐输出泵(Bsep)及胆酸共转运蛋白(Ntcp)的表达水平.结果 在ICP模型组中c-Jun的灰度值较正常对照组显著降低(101.05 ±5.20 vs 118.99±5.95,P<0.05),

  11. Effects of farnesoid X receptor ligand on the metabolism of bile acids in rats with estrogen-induced intrahepatic cholestasis of pregnancy%法尼醇X受体激动剂对雌激素诱导的肝内胆汁淤积症孕鼠胆汁酸代谢的影响及其分子机制

    Institute of Scientific and Technical Information of China (English)

    邹姝丽; 刘建; 兰易; 程浩; 甘晓玲

    2008-01-01

    目的 研究法尼醇X受体(FXR)激动剂鹅去氧胆酸(CDCA)对雌激素诱导的肝内胆汁淤积孕鼠胆汁酸代谢的影响及其分子机制.方法 用苯甲酸雌二醇诱导孕鼠发生肝内胆汁淤积,建立妊娠期肝内胆汁淤积症(ICP)模型,将FXR激动剂CDCA作用于ICP模型组,比色法检测孕鼠血总胆汁酸,RT-PCR和免疫组织化学法检测孕鼠肝组织FXR及其靶基因胆盐转运泵(BSEP)的mRNA及蛋白质表达.结果 与模型组相比,CDCA治疗组孕鼠血清胆汁酸水平明显降低[(17.2±4.1)μmol/L比(29.3±6.4)μmol/L,P<0.017],肝组织FXR mRNA(0.76±0.09比0.53±0.06,P<0.05)及蛋白质表达(2.35±0.06比1.83±0.05,P<0.017)明显升高,BSEP mRNA(0.99±0.21比0.76±0.07,P<0.017)及蛋白质表达(1.88±0.03比1.46±0.06,P<0.017)也明显升高.结论 FXR在调节胆汁酸代谢过程中起重要作用,其激动剂CDCA通过上调BSEP的表达促进胆汁酸转运降低血胆汁酸水平,可能为ICP的治疗提供新的思路和药物靶点.%Objective To investigate the effects and mechanism of farnesoid X receptor(FXR)and its ligands on the metabolism of bile acids in rats with estrogen-induced intrahepatic cholestasis of pregnancy (ICP).Methods An ICP rat model was established with estradiol benzoate(EB)injections.Then FXR ligand chenodeoxycholic acid(CDCA)was administrated(100 mg/kg daily)to ICP rats for 5 days.The serum TBA and expression of FXR and bile salt export pump(BSEP)in the rat livers were examined by immunohistochemistry and reverse transcription PCR.Results The levels of TBA in the CDCA group rats were significantly lower than the untreated rats[(17.2±4.1)μmol/L vs(29.3±6.4)/μmol/L,P<0.017],and the expressions of mRNA and protein of FXR were significantly higher[(0.76±0.09 vs 0.53±0.06,P<0.05 and 2.35±0.06 vs 1.83±0.05,P<0.017,respectively)],and the expressions of BSEP were also higher[(0.99±0.21 vs 0.76±0.07,P<0.017 and 1.88±0.03 vs 1.46±0.06,P<0.017,respectively

  12. Expression and clinical significance of constitutive androstane receptor in placental syntrophoblast of intrahepatic cholestasis of pregnancy%妊娠期肝内胆汁淤积症孕妇胎盘合体滋养细胞中组成型雄烷受体的表达及其临床意义

    Institute of Scientific and Technical Information of China (English)

    孙雪梅; 邵勇; 王晓璐; 吴味辛

    2011-01-01

    Objective To explore the expression and clinical significance of constitutive androstane receptor(CAR)in placenta syntrophoblast from patients with intrahepatic cholestasis of pregnancy(ICP).Methods Placenta were collected from women with ICP who delivered from April 2009 to March 2010 in First Affiliated Hospital of Chongqing Medical University.According to the severity of ICP,patients were classified into mild ICP group(n=10)and severe ICP group(n=10).Ten healthy pregnant women who delivered in the same period were chosen as control group.The location of CAR protein in placenta was studied by immunohistochemical streptavidin-biotin complex(SABC)method.CAR mRNA level was determined by reverse transcription(RT)-PCR technique and CAR protein expression level was determined by western blot.Results(1)CAR was located in the placenta syncytiotrophoblastic cells in control group and mild ICP group,showed light tan when stained,and was mainly in the cytoplasm.In severe ICP group,CAR was also located in placenta syncytiotrophoblastic cells but mainly in the nucleolus,showed dark tan when stained.(2)The mRNA expressions of CAR in control group,mild ICP group,severe ICP group were 0.06 ±0.03,0.07 ±0.03 and 0.56±0.03.respectively.CAR in severe ICP group was significantly higher than those in control group and mild ICP group(P<0.05).The difference of mRNA between control group and mild ICP group wag not statistically significant(P>0.05).(3)The CAR protein levels in control group,mild ICP group,severe ICP group were 0.74±0.03,0.79±01 03 and 1.02±0.04,respectively.CAR protein expression in the severe ICP group was significantly higher than the other two groups(P<0.05).And there was no statistical significance between mild group and control group(P>0.05).Conclusion In ICP women.especially severe ICP patients,the CAR expression in placenta syncytiotrophoblastic cells increased appreciably,which may be involved in the maintenance of placenta barrier function and

  13. Cholestasis induced by total parenteral nutrition: effects of the addition of Taurine (Tauramin® on hepatic function parameters; possible synergistic action of structured lipids (SMOFlipid® Colestasis inducida por nutrición parenteral total: efecto de la adición de Taurina (Tauramin® sobre los parámetros de función hepática; posible acción sinérgica de lípidos estructurados (SMOFlipid®

    Directory of Open Access Journals (Sweden)

    J. González-Contreras

    2012-12-01

    Full Text Available Objective: Assess the hepatoprotective effect of Taurine (Tau in cases of hepatic cholestasis induced by Total Parenteral Nutrition (TPN. Methods: We describe a retrospective series of 54 patients who received TPN, in which cholestasis was detected at an (Intermediate point that separates the duration of TPN into 2 Phases. From this moment -Phase 2- on, and according to clinical criteria, some patients (Group A, n = 27 received amino acids with Tau (22.41 ± 3.57 mg/kg/day(Tauramin®, while the rest (Group B, n = 27 received the standard solution without Tau. The mean TPN durations were 39.2 ± 17.1 and 36.4 ± 18.1 days respectively, with the Intermediate points on days 19.56 ± 10.51 and 17.89 ± 11.14. They all received diets that were homogeneous in terms of kcal and macronutrients. In Phase 2, 21 patients from Group A received structured lipids (SMOFlipid®; while 20 from Group B received soy MCT/LCT [ Medium Chain Triglycerides/Long Chain Triglycerides ] (physical or structured mixture. In a retrospective study, differences could not be avoided. The analytical parameters from three periods (Initial, Intermediate, and Final were obtained from Nutridata® and Servolab®. We compared interperiod values using the Wilcoxon test SPSS® (p Objetivo: Evaluar el papel hepatoprotector de Taurina (Tau en situación de colestasis hepática inducida por Nutrición Parenteral Total (NPT. Métodos: Se describe una serie retrospectiva de 54 pacientes, que recibieron NPT, detectándose colestasis en un momento (Intermedio que separa en 2 Fases la duración de la NPT. A partir de este momento - Fase 2- y según criterios clínicos, unos -grupo A, n = 27- recibieron aminoácidos con Tau -22,41 ± 3,57 mg/kg/día (Tauramin®, mientras otros -grupo B, n = 27- recibieron solución estándar sin Tau. La duración media de NPT fue de 39,2 ± 17,1 y 36,4 ± 18,1 días respectivamente; con el punto Intermedio en día 19,56 ± 10,51 y 17,89 ± 11,14. Todos

  14. 妊娠肝内胆汁淤积症孕妇胎儿总胆酸水平对胎儿胰腺内分泌功能及胎儿生长发育的影响%Relationship of fetal total bile acid and the change of fetal pancreas endocrine secretion and its impact on fetal growth and development in intrahepatic cholestasis of pregnancy

    Institute of Scientific and Technical Information of China (English)

    程贤鹦; 张丽娟; 林莉; 刘佳; 丁依玲

    2009-01-01

    Objective To investigate the relationship of fetal total bile acid (TBA) concentration with the change of fetal pancreas endocrine secretion and its impact on fetal growth and development in intrahepatic cholestasis of pregnancy(ICP). Methods The concentrations of TBA, insulin, glucagon and glucose in the cord blood were measured in 30 fetuses with maternal ICP (case group) and 30 fetuses of normogravidas(control group) after elective cesarean section during the same period in the Department of Obstetrics of Xiangya Second Hospital of Central South University from March 2007 to February 2008. The cord blood TBA concentration was investigated by enzyme method and the concentrations of insulin and glucagon were investigated by radioimmunoassay. The glucose was measured by oxidase-superoxide method. The neonatal weight, length and the ponderal index (PI) were measured after parturition. Results (1) The cord blood insulin concentration (9.0±3.3) mU/L and the ratio of insulin over glucagon 0. 048±0. 028 in the case group was significantly lower than that of controls(10.1±3.7) mU/L,0.050±0. 020 (P 0.05]. (2)The neonatal weight and length in case group were significantly lower than that of control [(3163±478) g vs (3498±393)g, (46.5±2.3) cm vs (49.3±1.9)cm, P0.05).(2)ICP组新生儿出生体重及身长分别为(3163±478)g及(46.5±2.3)cm,对照组分别为(3498±393)g及(49.3±1.9)cm,两组分别比较,差异均有统计学意义(P<0.01);ICP组新生儿PI(3.13±0.23)明显高于对照组(2.92±0.29),差异有统计学意义(P<0.01).(3)ICP组新生儿总胆酸水平分别与胰岛素、胰高糖素水平及胰岛素/胰高糖素比值呈直线关系,且随着总胆酸水平的升高,胰岛素水平及胰岛素/胰高糖素比值均降低,胰高糖素水平升高(P<0.01);ICP组新生儿脐动脉血中胰岛素水平及胰岛素/胰高糖素比值分别与出生体重、身长呈正相关,与PI呈负相关(P均<0.01);而胰高糖素水平与出生体重、身长

  15. p21 Ablation in Liver Enhances DNA Damage, Cholestasis, and Carcinogenesis

    NARCIS (Netherlands)

    Ehedego, H.; Boekschoten, M.V.; Hu, W.; Doler, C.; Haybaeck, J.; Gassler, N.; Muller, M.R.; Liedtke, C.; Trautwein, C.

    2015-01-01

    Genetic mouse studies suggest that the NF-¿B pathway regulator NEMO (also known as IKK¿) controls chronic inflammation and carcinogenesis in the liver. However, the molecular mechanisms explaining the function of NEMO are not well defined. Here, we report that overexpression of the cell-cycle regula

  16. Prevalence of vitamin D deficiency and rickets in children with cholestasis in Iran.

    Science.gov (United States)

    Mohammadi, Bahram; Najafi, Mehri; Farahmand, Fateme; Motamed, Farzaneh; Ghajarzadeh, Mahsa; Mohammadi, Jamshid; Eshagh Roze, Mohammad

    2012-01-01

    This study was aimed to determine prevalence of vitamin D deficiency and rickets in children with cholestatic liver diseases. Forty eight children with established cholestatic liver disease who referred to gastrointestinal clinic of Children Medical Center (Tehran, Iran) between April 2010 and March 2011 were enrolled in a cross-sectional study. Laboratory analysis including calcium, phosphate, albumin, total and direct bilirubin, aminotransferases, alkalinephosphatase (ALP), prothrombin time (PT), parathyroid hormone (PTH), total protein determined by routine laboratory techniques. Mean age of participants was 299.1 ± 676.8 days (range 2-3600 days) whereas twenty one were female (43.8%) and 27 (56.3%) were male. Twenty two (45.8%) had evidences of rickets in X-ray evaluation. Three children with rickets and two with normal X-ray had vitamin D deficiency while ten in rickets group and 16 in normal group had vitamin D insufficiency. The main underlying diseases were anatomical biliary atresia in cases with rickets and idiopathic in other group. Rickets and vitamin D deficiency should be considered in chronic cholestatic children.

  17. Oxidized low-density-lipoprotein accumulation is associated with liver fibrosis in experimental cholestasis

    Directory of Open Access Journals (Sweden)

    Güldeniz Karadeniz

    2008-01-01

    Full Text Available OBJECTIVE: The aim of the present study was to examine the probable relationship between the accumulation of oxLDL and hepatic fibrogenesis in cholestatic rats. INTRODUCTION: There is growing evidence to support the current theories on how oxidative stress that results in lipid peroxidation is involved in the pathogenesis of cholestatic liver injury and fibrogenesis. One of the major and early lipid peroxidation products, OxLDL, is thought to play complex roles in various immuno-inflammatory mechanisms. METHODS: A prolonged (21-day experimental bile duct ligation was performed on Wistar-albino rats. Biochemical analysis of blood, histopathologic evaluation of liver, measurement of the concentration of malondialdehyde (MDA and superoxide-dismutase (SOD in liver tissue homogenates, and immunofluorescent staining for oxLDL in liver tissue was conducted in bile-duct ligated (n = 8 and sham-operated rats (n = 8. RESULTS: Significantly higher levels of MDA and lower concentrations of SOD were detected in jaundiced rats than in the sham-operated rats. Positive oxLDL staining was also observed in liver tissue sections of jaundiced rats. Histopathological examination demonstrated that neither fibrosis nor other indications of hepatocellular injury were found in the sham-operated group, while features of severe hepatocellular injury, particularly fibrosis, were found in jaundiced rats. CONCLUSION: Our results support the finding that either oxLDLs are produced as an intermediate agent during exacerbated oxidative stress or they otherwise contribute to the various pathomechanisms underlying the process of liver fibrosis. Whatever the mechanism, it is clear that an association exists between elevated oxLDL levels and hepatocellular injury, particularly with fibrosis. Further studies are needed to evaluate the potential effects of oxLDLs on the progression of secondary biliary cirrhosis.

  18. Prevalence of Vitamin D Deficiency and Rickets in Children with Cholestasis in Iran

    Directory of Open Access Journals (Sweden)

    Mohammad Eshagh Roze

    2012-07-01

    Full Text Available This study was aimed to determine prevalence of Vitamin D deficiency and rickets in children with cholestatic liver diseases. Forty eight children with established cholestatic liver disease who referred to gastrointestinal clinic of Children Medical Center (Tehran, Iran between April 2010 and March 2011 were enrolled in a cross-sectional study. Laboratory analysis including calcium, phosphate, albumin, total and direct bilirubin, aminotransferases, alkalinephosphatase (ALP, prothrombin time (PT, parathyroid hormone (PTH, total protein determined by routine laboratory techniques. Mean age of participants was 299.1 ± 676.8 days (range 2-3600 days whereas twenty one were female (43.8% and 27 (56.3% were male. Twenty two (45.8% had evidences of rickets in X-ray evaluation. Three children with rickets and two with normal X-ray had Vitamin D deficiency while ten in rickets group and 16 in normal group had Vitamin D insufficiency. The main underlying diseases were anatomical biliary atresia in cases with rickets and idiopathic in other group. Rickets and Vitamin D deficiency should be considered in chronic cholestatic children.

  19. Diagnosis of cholestasis%胆汁淤积的诊断

    Institute of Scientific and Technical Information of China (English)

    陶小红

    2008-01-01

    胆汁淤积这一名称首先由Popper和Schaffner在1970年提出,并定义为形态学上胆汁在肝小叶肝细胞、毛细胆管、库普弗细胞内贮积。当今对胆汁淤积的定义是肝细胞内胆汁生成障碍、胆管分泌或胆汁流动受损所引起的结果。根据其发生部位的差异分为肝内胆汁淤积和肝外胆汁淤积,肝外胆汁淤积最常见的原因是机械性阻塞;肝内胆汁淤积的原因则较为复杂,包括感染性、药物性、自身免疫性、妊娠性等,但有时两者可有交叉,如原发性硬化性胆管炎(PSC)可同时有肝外和肝内部分的病变。本文重点阐述肝内胆汁淤积的诊断。

  20. Exfoliation, cholestasis, and apparent biliary sepsis in a woman with adult-onset diabetes.

    OpenAIRE

    Heiman, D. F.; Levine, R A; Bia, F. J.

    1985-01-01

    In consultation the authors were requested to evaluate a middle-aged diabetic woman for an apparent episode of biliary sepsis. The patient had been admitted to the dermatology service with a four-day history of rash and pruritus. This was initially thought to represent an allergic reaction to dicloxacillin in someone with a previous history of penicillin hypersensitivity. Persistent right upper quadrant pain, fevers, elevations of serum alkaline phosphatase, and a radionuclide scan which did ...

  1. Down-regulation of OATP1B proteins correlates with hyperbilirubinemia in advanced cholestasis

    NARCIS (Netherlands)

    Sticova, E.; Lodererova, A.; Steeg, E. van de; Frankova, S.; Kollar, M.; Lanska, V.; Kotalova, R.; Dedic, T.; Schinkel, A.H.; Jirsa, M.

    2015-01-01

    Aim: Organic anion-transporting polypeptides OATP1B1 and OATP1B3 are sinusoidal membrane transporters mediating liver uptake of a wide range of substrates including conjugated and unconjugated bilirubin, xenobiotics and drugs. Absence of OATP1Bs in the liver causes Rotor syndrome. Our aim was to cor

  2. Role of the bile salt export pump, BSEP, in acquired forms of cholestasis

    OpenAIRE

    Stieger, B

    2010-01-01

    Generation of bile is a key function of the liver. Its impairment leads to accumulation of cytotoxic bile salts in hepatocytes and, consequently, to liver disease. The bile salt export pump, BSEP, is critically involved in the secretion of bile salts into bile. Its function can be disturbed or abolished by inherited mutations. This will lead to progressive intrahepatic cholestais and severe liver disease. In addition to mutations, BSEP can be inhibited by acquired factors, such as xenobiotics...

  3. Role of the bile salt export pump, BSEP, in acquired forms of cholestasis

    NARCIS (Netherlands)

    B. Stieger

    2010-01-01

    Generation of bile is a key function of the liver. Its impairment leads to accumulation of cytotoxic bile salts in hepatocytes and, consequently, to liver disease. The bile salt export pump, BSEP, is critically involved in the secretion of bile salts into bile. Its function can be disturbed or aboli

  4. Role of membrane transport in hepatotoxicity and pathogenesis of drug-induced cholestasis

    OpenAIRE

    Stieger, Bruno; Kullak-Ublick, Gerd A.

    2013-01-01

    Drug-induced liver injury is an important clinical entity, which can be grouped into cholestatic liver injury, hepatocellular liver injury, and mixed liver injury. Cholestatic liver injury is characterized by a reduction in bile flow and the retention within hepatocytes of cholephilic compounds such as bile salts that cause hepatotoxicity. Bile salts are taken up by hepatocytes in a largely sodium-dependent manner and to a lesser extent in a sodium-independent manner. The former process is...

  5. Effects of Melittin Treatment in Cholangitis and Biliary Fibrosis in a Model of Xenobiotic-Induced Cholestasis in Mice

    OpenAIRE

    Kyung-Hyun Kim; Hyun-Jung Sung; Woo-Ram Lee; Hyun-Jin An; Jung-Yeon Kim; Sok Cheon Pak; Sang-Mi Han; Kwan-Kyu Park

    2015-01-01

    Cholangiopathy is a chronic immune-mediated disease of the liver, which is characterized by cholangitis, ductular reaction and biliary-type hepatic fibrosis. There is no proven medical therapy that changes the course of the disease. In previous studies, melittin was known for attenuation of hepatic injury, inflammation and hepatic fibrosis. This study investigated whether melittin provides inhibition on cholangitis and biliary fibrosis in vivo. Feeding 3,5-diethoxycarbonyl-1,4-dihydrocollidin...

  6. Curcumin and hemopressin treatment attenuates cholestasis-induced liver fibrosis in rats: role of CB1 receptors.

    Science.gov (United States)

    El Swefy, Sahar; Hasan, Rehab A; Ibrahim, Amal; Mahmoud, Mona F

    2016-01-01

    Curcumin exerts hepatoprotective effects via poorly defined mechanisms. Recently, some studies suggested that this effect was mediated by antagonizing CB1 receptors in hepatic stellate cells. The current study aimed to investigate whether CB1 antagonist, hemopressin, could potentiate the hepatoprotective effect of curcumin, in comparison with silymarin in bile duct-ligated (BDL) rats. Curcumin and hemopressin each alone and in combination ameliorated biochemical and structural fibrotic injury, and downregulated cyclooxygenase-2 (COX-2) and both mRNA and protein levels of nuclear factor kappa B (NF-κB) in fibrotic liver. In contrast to the previous studies, curcumin alone did not affect the gene expression of cannabinoid receptors. However, the combination of hemopressin and curcumin reduced the expression of CB1 in fibrotic liver. Surprisingly, silymarin upregulated CB2 receptors and downregulated CB1 at mRNA level more than all the administered drugs. Both curcumin and hemopressin each alone decreased lipid peroxidation product, malondialdehyde (MDA), while the combination increased the reduced glutathione content. All the administered drugs increased the hepatic antiapoptotic marker, Bcl2. Our study suggests that hemopressin potentiates the hepatoprotective effect of curcumin on fibrotic liver. We identified a new mechanism of the hepatoprotective effect of silymarin via modulation of cannabinoid receptors in fibrotic liver.

  7. Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis

    OpenAIRE

    Liu, Yaping; Binz, Jane; Numerick, Mary Jo; Dennis, Steve; Luo, Guizhen; Desai, Bhasha; MacKenzie, Kathleen I.; Mansfield, Traci A.; Kliewer, Steven A.; Goodwin, Bryan; Jones, Stacey A.

    2003-01-01

    Farnesoid X receptor (FXR) is a bile acid–activated transcription factor that is a member of the nuclear hormone receptor superfamily. Fxr-null mice exhibit a phenotype similar to Byler disease, an inherited cholestatic liver disorder. In the liver, activation of FXR induces transcription of transporter genes involved in promoting bile acid clearance and represses genes involved in bile acid biosynthesis. We investigated whether the synthetic FXR agonist GW4064 could protect against cholestat...

  8. Effect of ATRA on Contents of liver Retinoids, Oxidative Stress and Hepatic Injury in Rat Model of Extrahepatic Cholestasis

    Institute of Scientific and Technical Information of China (English)

    JIANG Haiyan; DAN Zili; WANG Hui; LIN Jusheng

    2007-01-01

    The effects of all-trans-retinoic acid (ATRA) administration on the concentration of retinoids (RA and vitamin A) in liver, oxidative stress and the hepatic injury in a rat model of com-mon bile duct ligation (CBDL)-induced liver injury were investigated. Female rats were subjected to a sham (n=5) or CBDL (n=48). Two weeks after operation, rats undergoing CBDL were randomized to receive treatment with either ATRA at three different doses (0.1, 1.5, 7.5 mg/kg) dissolved in bean oil or only bean oil every day over a 4-week experimental period. Rats were killed and blood samples were collected from the heart for determination of the serum transaminase. The contents of retinoids in rat liver were detected by using HPLC. Malondialdehyde (MDA), glutathione (GSH) and superox-ide dismutase (SOD) levels in liver were determined by a spectrophotometric method according to the instruction of the kits. Liver pathologic changes were observed under the light microscopy and electron microscopy. The results showed that compared with sham-operated group, the levels of reti-noids in the liver tissue were significantly decreased in the CBDL group (P<0.01). ATRA (0.1 mg/kg) administration in CBDL rats partially restored the contents of retinoids (P<0.05). Liver RA and vita-min A contents in CBDL group were significantly increased after ATRA (1.5 and 7.5 mg/kg) sup-plementation as compared with sham-operated group (P<0.05). However, in ATRA-treated CBDL group, hepatic GSH level and SOD activity, depressed by CBDL, and hepatic MDA level, increased by CBDL were returned to those in sham-operated group (P<0.05). The histologic observation of liver tissues indicated that ATRA treatment notably alleviated hepatocellular swelling, steatosis, the swelling of mitochondria and proliferation of smooth endoplasmic reticulum (SER). Treatment with ATRA could reduce levels of serum transaminase as compared with sham-operated group, more greatly in 1.5 and 7.5 mg/kg ATRA-treated groups than in 0.1 mg/kg ATRA-treated group. It was concluded that ATRA treatment can recover MDA and GSH levels and SOD activity in CBDL rat liver through restoring RA and vitamin A contents, and eventually ameliorate liver injury.

  9. Serum autotaxin is increased in pruritus of cholestasis, but not of other origin, and responds to therapeutic interventions

    NARCIS (Netherlands)

    Kremer, Andreas E.; van Dijk, Remco; Leckie, Pamela; Schaap, Frank G.; Kuiper, Edith M. M.; Mettang, Thomas; Reiners, Katrin S.; Raap, Ulrike; van Buuren, Henk R.; van Erpecum, Karel J.; Davies, Nathan A.; Rust, Christian; Engert, Andreas; Jalan, Rajiv; Elferink, Ronald P. J. Oude; Beuers, Ulrich

    2012-01-01

    Pruritus is a seriously disabling symptom accompanying many cholestatic liver disorders. Recent experimental evidence implicated the lysophospholipase, autotaxin (ATX), and its product, lysophosphatidic acid (LPA), as potential mediators of cholestatic pruritus. In this study, we highlight that incr

  10. ANCA Associated Vasculitis and Renal Failure Related to Propylthiouracil and Hyperthyroidism Induced Cholestasis in the Same Case

    Directory of Open Access Journals (Sweden)

    Mehmet Tuncay

    2014-01-01

    Full Text Available Introduction. Liver involvement due to hyperthyroidism and also ANCA positive vasculitis related renal failure cases were reported separately several times before. However, to our knowledge, these two complications together in the same case had never been observed before. Case Presentation. The case of an ANCA positive 71-year-old Caucasian male with renal failure and lung involvement, subclinical hyperthyroidism, and intrahepatic cholestatic jaundice was presented in this paper. After exclusion of all of the other possibilities, cholestatic hepatitis was explained by subclinical hyperthyroidism; renal failure and lung involvement were interpreted as ANCA related vasculitis which might be a side effect of propylthiouracil use. Conclusion. The coexistence of these rare conditions in the same patient deserves emphasis and it is worth reporting. This case demonstrates that following the clinical course of the patient is essential after prescribing any medications to see whether any complication occurs or not. If the complications of this case were noticed earlier, it would be possible to treat and to prevent the permanent damages.

  11. Cholestasis and hypercholesterolemia in SCD1-deficient mice fed a low-fat, high-carbohydrate diet

    NARCIS (Netherlands)

    M.T. Flowers; A.K. Groen; A.T. Oler; M.P. Keller; Y. Choi; K.L. Schueler; O.C. Richards; H. Lan; M. Miyazaki; F. Kuipers; C.M. Kendziorski; J.M. Ntambi; A.D. Attie

    2006-01-01

    Stearoyl-coenzyme A desaturase 1-deficient (SCD1(-/-)) mice have impaired MUFA synthesis. When maintained on a very low-fat (VLF) diet, SCD1(-/-) mice developed severe hypercholesterolemia, characterized by an increase in apolipoprotein B (apoB)-containing lipoproteins and the appearance of lipoprot

  12. Degradation of the Bile Salt Export Pump at Endoplasmic Reticulum in Progressive Familial Intrahepatic Cholestasis Type II (PFIC II)

    OpenAIRE

    Wang, Lin; Dong, Huiping; Soroka, Carol J.; WEI, NING; Boyer, James L.; Hochstrasser, Mark

    2008-01-01

    The bile salt export pump (Bsep) represents the major bile salt transport system at the canalicular membrane of hepatocytes. When examined in model cell lines, genetic mutations in the BSEP gene impair its targeting and transport function, contributing to the pathogenesis of PFIC II. PFIC II mutations are known to lead to a deficiency of BSEP in human hepatocytes, suggesting that PFIC II mutants are unstable and degraded in the cell. To investigate this further, we have characterized the impa...

  13. A homozygous nonsense mutation (c.214C->A) in the biliverdin reductase alpha gene (BLVRA) results in accumulation of biliverdin during episodes of cholestasis

    DEFF Research Database (Denmark)

    Nytofte, Nikolaj S; Serrano, Maria A; Monte, Maria J;

    2011-01-01

    Green jaundice is a rare finding usually associated with end-stage liver disease. OBJECTIVE The authors investigated two unrelated Inuit women from different geographical areas in Greenland who had episodes of green jaundice associated with biliary obstruction....

  14. The effects of ursodeoxycholic acid treatment for intrahepatic cholestasis of pregnancy on maternal and fetal outcomes: a meta-analysis including non-randomized studies.

    Science.gov (United States)

    Grand'Maison, Sophie; Durand, Madeleine; Mahone, Michèle

    2014-07-01

    Objectif : Les avantages de l’utilisation d’acide ursodésoxycholique (AUDC) pour la prise en charge de la cholestase intrahépatique de la grossesse (CIG) demeurent incertains. Une analyse Cochrane de 2010 ayant porté sur des essais comparatifs randomisés n’a pas été en mesure de se prononcer pour ou contre l’utilisation d’AUDC pour la prise en charge de la CIG. Nous avons mené une méta-analyse de la littérature, en englobant tant les études non randomisées (ENR) que les ECR. Nous avions pour objectif de déterminer si les patientes ayant participé aux ENR étaient comparables à celles qui avaient participé aux ECR; nous avions également pour objectif de déterminer si l’inclusion des ENR pouvait renforcer les données probantes disponibles et orienter la pratique clinique quant à l’utilisation d’AUDC chez les femmes qui présentent une CIG. Sources de données : Nous avons mené des recherches dans Medline (Ovid), Embase (Ovid), EMB Reviews, Cinahl (Ebsco) et Web of Knowledge (Thomson Reuters) en vue d’en tirer les articles publiés entre 1966 et juin 2012. Sélection des études : Nous avons inclus tous les ECR admissibles ayant comparé l’AUDC à un placebo ou à d’autres traitements et toutes les ENR ayant comparé l’AUDC à tout autre traitement chez des femmes présentant une CIG. Synthèse des données : Nous avons inclus 11 ECR (n = 625 grossesses) et six ENR (n = 211 grossesses). Bien que les femmes ayant participé aux ECR et aux ENR aient été comparables, la qualité des études était plus faible dans le cas des ENR. De façon générale, les femmes traitées à l’AUDC ont connu une atténuation du prurit dans 73 % des ECR et dans 100 % des ENR disposant de données disponibles. Les épreuves de fonction hépatique ont présenté une amélioration dans 82 % des ECR et dans 100 % des ENR disposant de données disponibles. Bien que l’utilisation d’AUDC n’ait pas affecté le taux de césarienne, elle a été associée à une prématurité moindre, à une utilisation moindre des unités néonatales de soins intensifs (données disponibles pour seulement trois des 17 études) et à des tendances à l’augmentation du poids de naissance et à l’atténuation de la teinte méconiale du liquide amniotique. Aucune mortinaissance n’a été constatée dans le cadre de 356 grossesses ayant fait l’objet d’un traitement à l’AUDC et trois mortinaissances ont été constatées dans le cadre de 399 grossesses ayant fait l’objet d’un traitement au moyen d’un agent de comparaison. Conclusion : Le traitement à l’AUDC devrait être recommandé aux femmes qui présentent une CIG en vue d’atténuer les issues indésirables maternelles et fœtales.

  15. ATP8B1 deficiency; Pathophysiology and treatment of a cholestatic syndrome with extrahepatic symptoms

    OpenAIRE

    Stapelbroek, J.M.

    2009-01-01

    ATP8B1 deficiency is a severe and clinically highly variable hereditary disorder that is primarily characterized by intrahepatic cholestasis. It generally presents as a permanent disorder, progressive familial intrahepatic cholestasis type 1 (PFIC1), or with intermittent cholestasis (benign recurrent intrahepatic cholestasis type 1 (BRIC1)). Currently there is no effective medical therapy, and most patients need invasive surgery such as partial biliary drainage (PBD) or liver transplantation....

  16. The Bile Salt Export Pump: Clinical and Experimental Aspects of Genetic and Acquired Cholestatic Liver Disease

    OpenAIRE

    Lam, Ping; Soroka, Carol J.; Boyer, James L.

    2010-01-01

    The primary transporter responsible for bile salt secretion is the bile salt export pump (BSEP, ABCB11), a member of the ATP-binding cassette (ABC) superfamily, which is located at the bile canalicular apical domain of hepatocytes. In humans, BSEP deficiency results in several different genetic forms of cholestasis, which include progressive familial intrahepatic cholestasis type 2 (PFIC2), benign recurrent intrahepatic cholestasis type 2 (BRIC2), as well as other acquired forms of cholestasi...

  17. 双歧三联活菌片对淤胆幼鼠移行性肌电复合波影响及其干预胆汁淤积的机制%Effect of Probiotics on Migrating Myoelectric Complexes of α-Naphthylisothiocyanate Induced Cholestasis on Weaned Rats and Mechanism of Probiotics on Cholestasis

    Institute of Scientific and Technical Information of China (English)

    胡玉莲; 黄志华; 王晓东; 刘萍

    2007-01-01

    目的 观察益生菌制剂对急性肝内胆汁淤积幼鼠胃肠消化间期移行性肌电复合波(MMC)影响,探讨其干预胆汁淤积的可能机制.方法 SD幼鼠96只随机分为健康对照组16只,中毒组、干预组各40只.各组随机选出8只在胃窦、十二指肠、空肠埋置3对银丝电极,余大鼠行假手术.术后7~10 d中毒及干预组1次灌服异硫氰酸萘酯(ANIT)(200 mg/kg)诱导急性肝内胆汁淤积;干预组于ANIT灌胃前2 d,灌服双歧三联活菌片4.2×108活菌/(kg·d).观察各组灌服ANIT后48、96、144、192 h胆汁流量、血总胆红素(TB)、ALT及MMC变化.结果 1.灌服ANIT后,干预组胆汁流量减少程度及血清中TB和ALT上升较中毒组轻,且恢复快.2.灌服ANIT后中毒及干预组MMC节律完全消失,代之以Ⅱ期样节律紊乱波;随后2组MMC逐渐恢复,但干预组MMC恢复时间(132.0±42.55)h明显短于中毒组(174.0±24.84)h(P<0.05);MMC节律恢复后,192 h时中毒组MMC持续时间较干预及健康对照组明显延长,其中主要是Ⅱ期持续时间延长.结论 幼鼠急性肝内胆汁淤积时MMC周期延长,甚至节律性运动消失.双歧三联活菌片能促进肠道MMC节律性运动恢复,减轻肝脏损害,有助于改善胆汁淤积.

  18. ATP8B1 deficiency; Pathophysiology and treatment of a cholestatic syndrome with extrahepatic symptoms

    NARCIS (Netherlands)

    Stapelbroek, J.M.

    2009-01-01

    ATP8B1 deficiency is a severe and clinically highly variable hereditary disorder that is primarily characterized by intrahepatic cholestasis. It generally presents as a permanent disorder, progressive familial intrahepatic cholestasis type 1 (PFIC1), or with intermittent cholestasis (benign recurren

  19. Severe intrahepatic cholestasis and hemochromatosis secondary to hereditary spherocytosis%遗传性球形红细胞增多症合并重度肝内胆汁淤积和继发性血色病

    Institute of Scientific and Technical Information of China (English)

    赵彩彦; 王玮; 刘英辉; 王亚东; 周俊英

    2010-01-01

    @@ 一、病例资料 病例1:男性患者,23岁.主因眼黄16年,加重伴皮肤黄染1月余于2008年6月27日10:00入院.患者缘于16年前无明显诱因出现眼黄,无恶心、呕吐、腹胀、腹泻、于当地医院查肝功能异常,应用保肝药物1个月后停药.

  20. Study on the relationship between the expression of placental FXR,BSEP and intrahepatic cholestasis of pregnacy%胎盘中FXR、BSEP的表达及其与ICP关系的研究

    Institute of Scientific and Technical Information of China (English)

    孟莉; 徐建英

    2011-01-01

    目的 探讨ICP胎盘中FXR、BSEP的表达,以及母、脐血清中CG(甘胆酸)水平的变化,进而从胎盘角度探讨ICP发病机制.方法 以35例ICP患者为ICP组,对照组为40例正常妊娠者.测定两组母、脐血清CG水平、母血清肝功能指标、两组胎盘组织中FXR、BSEP的表达.结果 ICP组胎盘组织中FXR的表达与母血清、脐血清CG水平呈正相关性.BSEP的表达量与母血清、脐血清CG水平呈负相关性.结论 ICP组母、脐血清CG水平明显高于对照组.ICP时,患者胎盘上FXR表达虽明显增强,但BSEP的表达并未因此而上调,反而表达减低,引起胎盘排泌胎儿胆汁酸下降,胎儿体内胆汁酸瘀积,可能是ICP发病机制之一.

  1. 基于FXR探讨茵栀黄注射液利胆退黄的机制研究%Mechanism of Yinzhihuang Injection for Intrahepatic Cholestasis Based on FXR

    Institute of Scientific and Technical Information of China (English)

    吴海滨; 佘世锋; 兰绍阳

    2016-01-01

    目的:通过研究茵栀黄注射液对肝内胆汁淤积湿热证大鼠FXR、BSEP、NTCP蛋白和基因表达的影响,探讨茵栀黄注射液的作用靶点及机制.方法:51只雄性SD大鼠随机分为正常对照组(7只)、模型组(7只)、茵栀黄注射液组(7只)、GW4064组(7只)、Guggulsterone组(7只)、茵栀黄+GW4064组(8只)、茵栀黄+Guggulsterone组(8只)共7组.造模干预后观察各组大鼠肝组织FXR、BSEP、NTCP蛋白和基因的表达.结果:茵栀黄注射液可以上调FXR蛋白和基因的表达,P<0.05.FXR和BSEP在蛋白和基因表达量上存在显著相关,P<0.05.结论:茵栀黄注射液通过干预FXR上调BSEP利胆退黄治疗肝内胆汁淤积.

  2. Regulatory Effect of UDCA on Mrp2 and Bsep of Cholestasis in Infantile Rats%熊去氧胆酸对胆汁淤积幼年大鼠Mrp2和Bsep的调控作用

    Institute of Scientific and Technical Information of China (English)

    欧巧群; 张伟; 周永梅; 于生友; 罗梅娟

    2015-01-01

    目的:研究熊去氧胆酸(UDCA)对胆汁淤积幼年大鼠的治疗作用以及胆汁酸转运体多药耐药相关蛋白2(MRP2,大鼠基因表达为Mrp2)和胆盐输出泵(BSEP,大鼠基因表达为Bsep)表达的影响,探讨该药物作用的分子机制.方法:将SD幼年大鼠随机分为正常对照组(Normal组)、胆汁淤积模型组(ANIT组)和熊去氧胆酸治疗组(UDCA组).α-萘异硫氰酸酯(ANIT)灌胃法(80 mg/kg,每周1次,共2次)诱导肝内胆汁淤积大鼠模型,分别给予安慰剂对照以及熊去氧胆酸口服(100 mg/kg,qd)治疗10 d.实验第10天处死大鼠,留取血标本进行丙氨酸氨基转移酶(ALT)、直接胆红素(DBIL)、总胆汁酸(TBA)检查,肝脏标本分别行组织病理学检查、免疫组化以及荧光定量RT-PCR检查胆汁酸转运体Mrp2和Bsep的分布以及RNA表达情况.结果:UDCA组与ANIT组比较,ALT、DBIL和TBA水平明显下降(分别为153 U/L vs 203 U/L、7 mmol/L vs 16 mmol/L、28 mmol/L vs 51 mmol/L,P<0.05),病理损害减轻,Mrp2和Bsep表达增强.结论:熊去氧胆酸能改善胆汁淤积幼年大鼠肝脏功能,减少肝细胞损害以及炎症渗出,上调胆汁酸转运体Mrp2和Bsep的表达.

  3. To investigate the mechanism of cholestasis after rat hepatic ischemia-reperfusion%鼠肝缺血再灌注后胆汁淤积发生的分子机制

    Institute of Scientific and Technical Information of China (English)

    舒明; 彭承宏; 陈皓; 沈柏用; 邱伟华; 李宏为

    2006-01-01

    目的 探讨鼠肝缺血再灌注后胆汁淤积发生的分子机制.方法 应用70%的鼠肝缺血35 min再灌注模型,检测胆汁、血浆中胆红素、胆酸的含量;荧光定量聚合酶链反应(PCR)、免疫组织化学方法分析毛细胆管膜上胆盐输出泵(Bsep)、多耐药相关蛋白2(Mrp2)的表达;激光共聚焦方法分析Mrp2定位的改变.结果 再灌注后6 h、1、3 d,Bsep的表达明显下调(mRNA表达水平分别为0.189±0.044、0.240±0.078、0.224±0.068),与胆汁、血浆中胆酸的异常改变一致.Mrp2表达的明显下调仅发生于再灌注后的6 h(mRNA表达水平为0.038±0.032),与再灌注后1 h~5 d胆红素的异常变化不相符.再灌注后6 h~5 d,Mrp2在毛细胆管膜上定位减少、向胞浆内分布.结论 Bsep表达的减少以及Mrp2定位的异常是鼠肝缺血再灌注后胆汁淤积发生的主要分子机制.

  4. Recent advances about the role of ABCB11 in intrahepatic cholestasis of pregnancy%ABCB11基因在妊娠期肝内胆汁淤积症中研究进展

    Institute of Scientific and Technical Information of China (English)

    杜永江; 吕时铭; 姚琦玮

    2008-01-01

    ABCB11基因,也称BSEP基因,其编码的蛋白称为ABCB11蛋白,是ABC转运蛋白超家族B族成员之一.ABCB11基因的表达主要受法尼醇X受体(F3(R)调控.近年研究发现,一些药物或体内的代谢产物等对ABCB11基因的调控及由基因变异等因素引起的相关蛋白功能障碍,可能在妊娠期肝内胆汁淤积症(ICP)发病中发挥重要作用,并且ABCB11基因有可能成为靶基因而作为ICP基因治疗的一种手段.

  5. ERK1/2 and p38 MAPKs Are Complementarily Involved in Estradiol 17ß-d-Glucuronide-Induced Cholestasis: Crosstalk with cPKC and PI3K

    OpenAIRE

    Andrea C Boaglio; Zucchetti, Andrés E.; Toledo, Flavia D.; Barosso, Ismael R.; Enrique J Sánchez Pozzi; Crocenzi, Fernando A.; Roma, Marcelo G.

    2012-01-01

    OBJECTIVE: The endogenous, cholestatic metabolite estradiol 17ß-D-glucuronide (E(2)17G) induces endocytic internalization of the canalicular transporters relevant to bile formation, Bsep and Mrp2. We evaluated here whether MAPKs are involved in this effect. DESIGN: ERK1/2, JNK1/2, and p38 MAPK activation was assessed by the increase in their phosphorylation status. Hepatocanalicular function was evaluated in isolated rat hepatocyte couplets (IRHCs) by quantifying the apical secretion of fluor...

  6. Hormesis in Cholestatic Liver Disease; Preconditioning with Low Bile Acid Concentrations Protects against Bile Acid-Induced Toxicity

    OpenAIRE

    Verhaag, Esther M.; Manon Buist-Homan; Martijn Koehorst; Groen, Albert K; Han Moshage; Klaas Nico Faber

    2016-01-01

    Introduction Cholestasis is characterized by accumulation of bile acids and inflammation, causing hepatocellular damage. Still, liver damage markers are highest in acute cholestasis and drop when this condition becomes chronic, indicating that hepatocytes adapt towards the hostile environment. This may be explained by a hormetic response in hepatocytes that limits cell death during cholestasis. Aim To investigate the mechanisms that underlie the hormetic response that protect hepatocytes agai...

  7. Activity of the Bile Salt Export Pump (ABCB11) Is Critically Dependent on Canalicular Membrane Cholesterol Content

    NARCIS (Netherlands)

    C.C. Paulusma; D.R. de Waart; C. Kunne; K.S. Mok; R.P.J. Oude Elferink

    2009-01-01

    Mutations in ATP8B1 cause severe inherited liver disease. The disease is characterized by impaired biliary bile salt excretion (cholestasis), but the mechanism whereby impaired ATP8B1 function results in cholestasis is poorly understood. ATP8B1 is a type 4 P-type ATPase and is a flippase for phospha

  8. Strain background modifies phenotypes in the ATP8B1-deficient mouse

    NARCIS (Netherlands)

    S. Shah; U.R. Sanford; J.C. Vargas; H. Xu; A. Groen; C.C. Paulusma; J.P. Grenert; L. Pawlikowska; S. Sen; R.P.J. Oude Elferink; L.N. Bull

    2010-01-01

    BACKGROUND: Mutations in ATP8B1 (FIC1) underlie cases of cholestatic disease, ranging from chronic and progressive (progressive familial intrahepatic cholestasis) to intermittent (benign recurrent intrahepatic cholestasis). The ATP8B1-deficient mouse serves as an animal model of human ATP8B1 deficie

  9. Prognostic significance of cholestatic alcoholic hepatitis. VA Cooperative Study Group #119.

    Science.gov (United States)

    Nissenbaum, M; Chedid, A; Mendenhall, C; Gartside, P

    1990-07-01

    Tissue cholestasis is a histologic feature in some patients with alcoholic liver disease, but its significance is unknown. We studied prospectively the clinical, laboratory, and histologic findings of 306 chronic male alcoholics in whom liver tissue was available. Tissue cholestasis permitted identification of two groups: group I, absent or mild cholestasis (239 patients), and group II, moderate to severe cholestasis (67 patients). Statistical evaluation was performed by Student's t test and regression analyses. In patients with tissue cholestasis, 97% had elevated serum cholylglycine levels, while only 61% had significant jaundice (serum bilirubin greater than 5 mg/dl). In patients without tissue cholestasis, 66% had elevated serum cholylglycine and 13.5% jaundice. Highly significant statistical correlations (P less than 0.0001) were found between cholestasis and malnutrition, prothrombin time, AST, alkaline phosphatase, bilirubin, Maddrey's discriminant function, serum cholylglycine level, albumin, and histologic severity score. In group I, 54% survived 60 months versus 22% in group II (P less than 0.0001). Highly significant statistical correlations (P less than 0.0001) were noted between serum cholylglycine levels and the parameters enumerated earlier, but not with survival. We conclude that tissue cholestasis is a highly significant prognostic indicator of outcome in alcoholic hepatitis and is more consistently associated with bile salt retention than jaundice.

  10. REVERSIBILITY OF CHOLESTATIC CHANGES FOLLOWING EXPERIMENTAL COMMON BILE-DUCT OBSTRUCTION - FACT OR FANTASY

    NARCIS (Netherlands)

    ARONSON, DC; CHAMULEAU, RAFM; FREDERIKS, WM; GOOSZEN, HG; HEIJMANS, HSA; JAMES, J

    1993-01-01

    In 36 male Wistar rats extrahepatic cholestasis was induced by ligation and transsection of the common bile duct. After 1, 2 and 3 weeks of cholestasis the bile flow was restored by means of a Roux-en-Y choledochojejunostomy. Plasma levels of bilirubin, alkaline phosphatase, GOT and clotting factor

  11. Aquaporins: Their role in cholestatic liver disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    This review focuses on currant knowledge on hepato-cyte aquaporins (AQPs) and their significance in bile formation and cholestasis. Canalicular bile secretion results from a combined interaction of several solute transporters and AQP water channels that facilitate wa-ter flow in response to the osmotic gradients created. During choleresis, hepatocytes rapidly increase their canalicular membrane water permeability by modulat-ing the abundance of AQP8. The question was raised as to whether the opposite process, i.e. a decreased canalicular AQP8 expression would contribute to the development of cholestasis. Studies in several experi-mental models of cholestasis, such as extrahepatic obstructive cholestasis, estrogen-induced cholestasis, and sepsis-induced cholestasis demonstrated that the protein expression of hepatocyte AQP8 was impaired. In addition, biophysical studies in canalicular plasma membranes revealed decreased water permeability as-sociated with AQP8 protein downregulation. The com-bined alteration in hepatocyte solute transporters and AQP8 would hamper the efficient coupling of osmotic gradients and canalicular water flow. Thus cholestasis may result from a mutual occurrence of impaired sol-ute transport and decreased water permeability.

  12. Albumin liver dialysis as pregnancy-saving procedure in cholestatic liver disease and intractable pruritus

    Institute of Scientific and Technical Information of China (English)

    Maud Lemoine; Aurélie Revaux; Claire Francoz; Guillaume Ducarme; Sabine Brechignac; Emmanuel Jacquemin; Michèle Uzan; Nathalie Ganne-Carrié

    2008-01-01

    Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare cholestatic liver disease. Such liver disease can get worse by female hormone disorder. Albumin dialysis or Molecular Adsorbent Recirculating System (MARS) has been reported to reverse severe cholestasis-linked pruritus. Here, we report the first use of HARS during a spontaneous pregnancy and its successful outcome in a patient with PFIC3 and intractable pruritus. Albumin dialysis could be considered as a pregnancy-saving procedure in pregnant women with severe cholestasis and refractory pruritus.C 2008 The WJG Press. All rights reserved.

  13. Disease: H00624 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available is (PFIC); Benign recurrent intrahepatic cholestasis (BRIC); Intrahepatic cholestasis of pregnancy (ICP); North American Indian child...sis defect type 1. North American Indian childhood cirrhosis (NAIC) is a distinct, rapidly evolving form of ...familial cholestasis found in aboriginal children from northwestern Quebec. It has reported that a missense ...ssense mutation (R565W) in cirhin (FLJ14728) in North American Indian childhood cirrhosis. Am J Hum Genet 71...:1443-9 (2002) PMID:11045837 Drouin E, Russo P, Tuchweber B, Mitchell G, Rasquin-Weber A North American Indian cirrhosis in child

  14. Effect of melatonin on myocardial oxidative stress induced by experimental obstructive jaundice Efecto de la melatonina en el estrés oxidativo del miocardio en un modelo experimental de obstrucción biliar

    Directory of Open Access Journals (Sweden)

    A. Cruz

    2009-07-01

    Full Text Available Objective: melatonin has been demonstrated to have active antioxidant properties in different tissues during experimental cholestasis. The aim of this research was to study myocardial oxidative stress on obstructive jaundice, and to analyze the effect of melatonin on myocardial oxidative lesions. Material and methods: we achieved cholestasis by ligature and sectioning of the main bile duct. Melatonin was administered intraperitoneally (500 µg/kg/day. We measured malondialdehyde (MDA, reduced glutathione (GSH, catalase (CAT, superoxide dismutase (SOD and glutathione peroxydase (GPx antioxidant enzyme levels in the heart tissue. Results: obstructive cholestasis increased MDA and decreased GSH as well as all antioxidant enzymes. Melatonin administration significantly decreased MDA values, and increased GSH and antioxidant enzymes on the icteric animal myocardium. Conclusions: melatonin treatment prevents oxidative stress in the cardiac tissue as induced by experimental cholestasis.

  15. Quantitative liver gallbladder scintigraphy interest in the liver transplant complication and following

    International Nuclear Information System (INIS)

    Initially asked to eliminate the gallbladder complication during a cholestasis the isotope ratio may inscribe the QLBS in a grafted patient evolutive following, according to the forecast complications. 1 ref., 5 figs

  16. Jaundice

    Science.gov (United States)

    ... Autoimmune hepatitis Bile Biliary atresia Biliary stricture Bilirubin blood test Cholestasis Delta agent (Hepatitis D) Dubin-Johnson syndrome Gallstones Gilbert disease Hemolytic anemia Hepatitis A Hepatitis B Hepatitis C Malaria Newborn jaundice Pancreatic cancer Primary ...

  17. Disease: H00950 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ntrahepatic cholestasis. It also exhibits notable clinical variability showing anemia, ichthyosis, and diarrhoea. Mutations...rias IM, Wolburg H, Knisely AS, Kelly DA, Muller F, Maher ER, Gissen P Mutations

  18. Activated Charcoal

    Science.gov (United States)

    ... reduce intestinal gas (flatulence), lower cholesterol levels, prevent hangover, and treat bile flow problems (cholestasis) during pregnancy. ... pregnancy, according to some early research reports. Preventing hangover. Activated charcoal is included in some hangover remedies, ...

  19. Dermatological Diseases Associated with Pregnancy

    DEFF Research Database (Denmark)

    Sävervall, Christine; Sand, Freja Lærke; Thomsen, Simon Francis

    2015-01-01

    Dermatoses unique to pregnancy are important to recognize for the clinician as they carry considerable morbidity for pregnant mothers and in some instances constitute a risk to the fetus. These diseases include pemphigoid gestationis, polymorphic eruption of pregnancy, intrahepatic cholestasis...

  20. Vanishing bile duct syndrome in human immunodeficiency virus: Nevirapine hepatotoxicity revisited

    Institute of Scientific and Technical Information of China (English)

    Rajan; Kochar; Moises; I; Nevah; Frank; J; Lukens; Michael; B; Fallon; Victor; I; Machicao

    2010-01-01

    Vanishing bile duct syndrome (VBDS) refers to a group of disorders characterized by prolonged cholestasis as a result of destruction and disappearance ofintrahepatic bile ducts. Multiple etiologies have been indentifi ed including infections, neoplastic disorders, autoimmune conditions and drugs. The natural history of this condition is variable and may involve resolution of cholestasis or progression with irreversible damage. VBDS is extremely rare in human immunodeficiency virus (HIV)-infected patients an...

  1. Management of common bile duct stricture caused by chronic pancreatitis with metal mesh self expandable stents.

    OpenAIRE

    Deviere, J; M Cremer; Baize, M; Love, J; Sugai, B; Vandermeeren, A

    1994-01-01

    Twenty patients with chronic pancreatitis and signs of biliary obstruction were treated by endoscopic placement of self expandable metal mesh stents, and followed up prospectively. Eleven had been treated previously with plastic endoprostheses. All had persistent cholestasis, seven patients had jaundice, and three overt cholangitis. Endoscopic stent placement was successful in all cases. No early clinical complication was seen and cholestasis, jaundice or cholangitis rapidly resolved in all p...

  2. Oxidative stress influence on renal dysfunction in patients with obstructive jaundice: A case and control prospective study

    OpenAIRE

    David Martínez-Cecilia; María Reyes-Díaz; Juan Ruiz-Rabelo; Manuel Gomez-Alvarez; Carmen Muñoz Villanueva; José Álamo; Jordi Muntané; Francisco Javier Padillo

    2016-01-01

    Background: Obstructive Jaundice (OJ) is associated with a significant risk of developing acute renal failure (ARF). The involvement of oxidative stress in the development of cholestasis has been demonstrated in different experimental models. However, its role in the morbidity of human cholestasis is far to be elucidated. The aim of the study was the evaluation of oxidative stress markers in blood from patients with OJ and its relation to complications and benign/malignant evolution of choles...

  3. Hereditäre Defekte hepatobiliärer Transportproteine

    OpenAIRE

    Mwinyi, J.; Kullak-Ublick, G A

    2010-01-01

    Defects in transport proteins that are expressed at the hepatocyte canalicular membrane can cause severe impairment of hepatobiliary transport processes. Progressive familial intrahepatic cholestasis (PFIC) typically manifests in early childhood. Genetic variants in the aminophospholipid transporter FIC1 (ATP8B1 gene) cause PFIC1, characterized by elevated serum bile acids but normal or only mildly elevated gamma-GT levels. Benign recurrent intrahepatic cholestasis type 1 (BRIC1) is also caus...

  4. The Role of Bile Salt Export Pump Gene Repression in Drug-Induced Cholestatic Liver Toxicity

    OpenAIRE

    Garzel, Brandy; Yang, Hui; Zhang, Lei; Huang, Shiew-Mei; Polli, James E.; Wang, Hongbing

    2014-01-01

    The bile salt export pump (BSEP, ABCB11) is predominantly responsible for the efflux of bile salts, and disruption of BSEP function is often associated with altered hepatic homeostasis of bile acids and cholestatic liver injury. Accumulating evidence suggests that many drugs can cause cholestasis through interaction with hepatic transporters. To date, a relatively strong association between drug-induced cholestasis and attenuated BSEP activity has been proposed. However, whether repression of...

  5. Estrogen and Estrogen Receptor-α-Mediated Transrepression of Bile Salt Export Pump

    OpenAIRE

    Chen, Yuan; Vasilenko, Alex; Song, Xiulong; Valanejad, Leila; Verma, Ruchi; You, Sangmin; Yan, Bingfang; Shiffka, Stephanie; Hargreaves, Leeza; Nadolny, Christina; Deng, Ruitang

    2015-01-01

    Among diseases unique to pregnancy, intrahepatic cholestasis of pregnancy is the most prevalent disorder with elevated serum bile acid levels. We have previously shown that estrogen 17β-estradiol (E2) transrepresses bile salt export pump (BSEP) through an interaction between estrogen receptor (ER)-α and farnesoid X receptor (FXR) and transrepression of BSEP by E2/ERα is an etiological contributing factor to intrahepatic cholestasis of pregnancy. Currently the mechanistic insights into such tr...

  6. Biosynthesis and Trafficking of the Bile Salt Export Pump, BSEP: Therapeutic Implications of BSEP Mutations

    OpenAIRE

    Soroka, Carol J.; Boyer, James L.

    2013-01-01

    The bile salt export pump (BSEP, ABCB11) is the primary transporter of bile acids from the hepatocyte to the biliary system. This rate-limiting step in bile formation is essential to the formation of bile salt dependent bile flow, the enterohepatic circulation of bile acids, and the digestion of dietary fats. Mutations in BSEP are associated with cholestatic diseases such as progressive familial intrahepatic cholestasis type 2 (PFIC2), benign recurrent intrahepatic cholestasis type 2 (BRIC2),...

  7. Function and regulation of the human bile salt export pump

    OpenAIRE

    Plass, Jacqueline Regina Maria

    2005-01-01

    During the past decade, important progress has been made in our understanding of the pathophysiology of cholestasis. Inherited disorders have been explained at the molecular level and were shown to be the result of mutations in enzymes involved in bile salt biosynthesis or transmembrane transporters involved in bile formation. Acquired cholestasis, for instance due to inflammation, is linked to disregulation of these proteins. The challenge of future research is to use this knowledge to devel...

  8. Implication of hepatocytes express Bc1-2 in stillbirths of maternal intrahepatic cholestasis in pregancy%妊娠肝内胆汁淤积症死产儿肝细胞表达Bc1-2的意义

    Institute of Scientific and Technical Information of China (English)

    周群芳; 史常旭; 魏振玲

    2004-01-01

    目的通过观察妊娠肝内胆汁淤积症(ICP)死产儿肝脏及肾上腺等表达Bc1-2的情况探讨ICP死胎、死产等围生儿并发症的发生机制.方法对4例ICP死产儿或死胎的肝脏等石蜡病理切片进行Bc1-2的免疫组化染色.3例畸形引产儿为对照组.结果 4例ICP死产儿或死胎的肝脏及肾上腺细胞呈阳性表达而对照组为阴性.结论 ICP死产儿的肝细胞及肾上腺细胞受到了不良因素的作用,可能是脐血中升高的胆汁酸、胆红素所致,说明Bc1-2与ICP围生儿并发症的发生有关.

  9. Relationship of liver function, blood flow of fetal umbilical artery and non stress test in patients with intrahepatic cholestasis of pregnancy%妊娠期肝内胆汁瘀积症孕妇肝功能指标、S/D值及NST与围生儿预后的关系

    Institute of Scientific and Technical Information of China (English)

    徐博; 黄作香; 张小莎

    2008-01-01

    目的:探讨妊娠期肝内胆汁瘀积症孕妇肝功能指标、胎儿脐动脉血流测定及产前胎心监护对新生儿预后的预测价值.方法:测定肝功能指标、超声多普勒测定胎儿脐动脉血流速度比值(non-stress test,S/D)及胎心监护仪监测胎心率(NST),记录分娩方式、新生儿出生Apgar评分等.结果:随着肝功能指标的异常升高,异常S/D值和NST的发生率显著增高(P<0.05);当伴有异常肝功能指标、S/D值或NST结果时,新生儿窒息发生率和因胎儿宫内窘迫而施剖宫产率明显增加.结论:肝功能、S/D值及NST结果与围产儿缺氧密切相关,是判断新生儿预后的可靠和重要的指标.

  10. 妊娠肝内胆汁淤积症胎盘雌激素受体及血管舒缩因子的变化%The changes and sign ificance of the estrogen receptors on placenta and the levels of serum free estr iol,blood vessel endothelium factor in intrahepatic cholestasis of pregnancy.

    Institute of Scientific and Technical Information of China (English)

    王冬梅; 朱启英; 腊晓琳

    2002-01-01

    目的:探讨妊娠肝内胆汁淤积症(ICP )患者血清中一氧化氮(NO)、内皮素(ET)、游离雌三醇(E3)水平的变化和胎盘雌激素受体( ER)表达强度在ICP病理生理改变中的作用.方法:以ICP组30例为研究组 ,手术前30min取外周静脉血测定NO、ET及游离E3的含量,以年龄相近同期手术的30例正常孕妇作为对照组,产后从研究组和对照组中随机抽取20例的胎盘中央组织块用免疫组化法检测ER的表达强度.结果:ICP组的血清ET水平明显高于对照组(P<0.05),NO水平与对照组差异无显著性(P>0.05). ICP组血清游离E3水平显著高于对照组(P<0.01),胎盘ER阳性表达百分比显著高于对照组(P<0.05),血清中E3水平与胎盘组织中E R水平间呈正相关(r′s=0.598,P<0.01).结论:雌激素水平升高及胎盘中ER表达增强和ET水平的升高可能与ICP的发生、发展有关.

  11. Expression of HIF-1α mRNA and HIF-2α mRNA in Placentas of Pregnant Women with Intrahepatic Cholestasis of Pregnancy%妊娠期肝内胆汁淤积症胎盘组织缺氧诱导因子HIF-1α、HIF-2α mRNA表达水平的研究

    Institute of Scientific and Technical Information of China (English)

    胡雅毅; 王晓东; 刘淑芸

    2007-01-01

    目的 观察缺氧诱导因子-1α(HIF-1α)mRNA、缺氧诱导因子-2α(HIF-2α)mRNA在妊娠期肝内胆汁淤积症(ICP)患者胎盘组织上的表达,探讨其与ICP胎儿缺氧的关系.方法 ICP患者和正常晚孕妇女各20例, RT-PCR法检测两组胎盘组织上HIF-1α mRNA、HIF-2α mRNA的表达.结果 ICP患者胎盘组织HIF-1α mRNA、HIF-2α mRNA的表达和正常晚孕妇女差异均无统计学意义(P>0.05).结论 低氧条件下,ICP患者胎盘组织HIF蛋白合成的调节可能并不在mRNA表达水平,而在转录后水平.

  12. Expression of bile salt export pump in placenta tissue of patients with intrahepatic cholestasis of pregnancy%胆盐输出泵在妊娠期肝内胆汁淤积症患者胎盘组织中的表达

    Institute of Scientific and Technical Information of China (English)

    宋晔; 戴建荣; 侯顺玉

    2015-01-01

    目的 探讨胆盐输出泵(BSEP)在妊娠期肝内胆汁淤积症(ICP)患者胎盘组织中的表达及意义.方法 采用免疫组织化学方法测定30例ICP患者及30例正常妊娠者胎盘组织中BSEP的表达,采用Western blot检测胎盘组织中BSEP蛋白的表达.结果 正常妊娠者和ICP患者胎盘组织中BSEP阳性表达率分别为76.7% (23/30)和36.7% (11/30),ICP患者胎盘组织中BSEP阳性表达率显著低于正常妊娠者胎盘组织(P<0.05).BSEP蛋白在正常妊娠者和ICP患者胎盘组织中的表达分别为0.754±0.274和0.193±0.122,BSEP蛋白在ICP患者胎盘组织中的表达显著少于正常妊娠者胎盘组织(P <0.001).结论 BSEP在ICP患者胎盘组织中表达显著减少,可能是导致ICP的发病机制之一.

  13. The potential risky factors incurring the bad outcomes of intrahepatic cholestasis of pregnancy%影响ICP围生儿不良结局潜在风险因素及其与BSEP基因多态性的关系研究

    Institute of Scientific and Technical Information of China (English)

    林萍

    2014-01-01

    目的 探讨影响妊娠期肝内胆汁淤积症围生儿不良结局的潜在风险因素.方法 对该院2010年5月-2013年5月接受治疗的40例不良结局和46例良好结局的ICP患者进行病史记录搜集,对肝功能、血清总胆汁酸、胎儿监测结果以及BSEP基因等指标进行回顾性分析,并采用SPSS 18.0软件对搜集的数据进行独立样本t检验和X 2检验.结果 两种结局患者的TBA,S/D值,NST值差异具有统计学意义,其他指标差异无统计学意义;不良结局组BSEP基因rs2287622位点C、T等位基因频率分别为83.75%和16.25%,良好结局组该位点C、T等位基因频率分别为66.30%和33.70%,两组间比较差异有统计学意义(P<0.05).结论 血清总胆汁酸水平以及脐血流(S/D)和胎心无负荷试验(NST)的检测结果是ICP围生儿出现不良结局的高危风险因素,也是很敏感的指标,对预测ICP围生儿是否产生不良结局具有很大的指导意义,BSEP基因rs2287622位点多态性(C/T)可能和妊娠期肝内胆汁淤积有关.

  14. Expression of Bsep and Mrp2 in liver of cirrhotic rats with intrahepatic cholestasis after ischemia-reperfusion injury%肝硬化大鼠肝缺血-再灌注损伤后Bsep、Mrp2表达在胆汁淤积中的作用研究

    Institute of Scientific and Technical Information of China (English)

    舒明; 王火平; 胡笑蓉; 黄左安; 黄丹丹; 王咖; 张顺

    2015-01-01

    目的 研究肝硬化大鼠肝缺血-再灌注损伤(HIRI)后胆汁淤积的部分分子机制.方法 将健康SD大鼠随机分成A、B、C3组,每组15只,建立肝硬化、HIRI模型.A组为正常大鼠HIRI组,B组为肝硬化大鼠假手术组,C组为肝硬化大鼠HIRI组.每组大鼠肝门阻断时间为30min.分别检测各组大鼠术后第1、3、5天的胆汁DBil、TBil含量,血清AST、ALT、TBil、DBil含量;Western blot分析各组大鼠术后第1、3、5天胆盐输出泵(Bsep)、多耐药相关蛋白2(Mrp2)表达变化;免疫组织化学法分析Bsep蛋白的细胞亚定位.结果 术后第1天,C组大鼠胆汁TBil、DBil含量均低于A组(均P<0.05);术后第3天,C组大鼠胆汁TBil、DBil含量均低于A组和B组(均P<0.05);术后第5天,3组大鼠胆汁TBil、DBil含量比较差异均无统计学意义(均P>0.05).C组大鼠术后第1、3天血清AST、ALT水平均高于A组,术后第1、3、5天血清TBil、DBil含量均高于A、B组(均P<0.05).术后第1、3、5天,C组大鼠Bsep蛋白表达量均低于A组,术后第3、5天均低于B组(均P<0.05);C组Mrp2表达均低于A、B组(均P<0.05).肝细胞Bsep蛋白明显向细胞质移位.结论 与正常肝脏相比,硬化肝对缺血耐受能力差,HIRI后硬化肝的胆汁淤积情况更加严重.Bsep、Mrp2表达降低以及Bsep蛋白由细胞膜向细胞质移位的改变在硬化肝HIRI后胆汁淤积中起了重要作用.

  15. 茵陈对肝内胆汁淤积湿热证大鼠利胆退黄作用机制的研究%The Choleretic and Jaundice-relieving Mechanism of Yinchen on Rat with Intrahepatic Cholestasis and Damp-heat

    Institute of Scientific and Technical Information of China (English)

    兰绍阳; 佘世锋

    2012-01-01

    目的 通过研究茵陈对肝内胆汁淤积湿热证大鼠肝组织中胆盐输出泵(BSEP)基因表达的影响,从分子水平探讨茵陈利胆退黄的作用机制.方法 45只雄性SD大鼠随机分为3组:正常组、模型对照组和茵陈组.检测治疗后大鼠血清生化指标、肝脏组织病理的变化和肝脏BSEP的表达.结果 治疗后茵陈组大鼠体质量增加明显高于模型对照组(P<0.05).茵陈组大鼠血清TB、DB、ALT、AST、ALP、TBA浓度低于模型对照组(P<0.05);HE染色显示茵陈组大鼠肝脏的病理损害轻于模型对照组.免疫组织化学染色显示茵陈组大鼠比模型对照组有更多的BSEP阳性细胞.荧光定量RT-PCR法显示模型对照组大鼠肝组织中BSEP mRNA表达明显低于茵陈组(P<0.05).结论 茵陈能有效改善肝内胆汁淤积湿热证大鼠的肝功能、减轻病理损害,并能上调肝脏BSEP的表达.

  16. 白藜芦醇退黄保肝作用及其与胆汁酸排泄的相关性研究%Protective effects of resveratrol against α-naphthylisothiocyanate-induced cholestasis and its relationship with bile acid excretion

    Institute of Scientific and Technical Information of China (English)

    姜超; 刘家云; 翟兢; 李为苏; 王琼; 许哲

    2015-01-01

    目的:研究白藜芦醇的退黄保肝作用及其与胆汁酸代谢转运的相关性.方法:采用α-萘异硫氰酸酯(ANIT)致大鼠胆汁淤积性肝损伤模型,观察白藜芦醇退黄保肝的作用;原代大鼠三明治肝细胞模型上,观察白藜芦醇对ANIT损伤的肝细胞胆汁排泄,肝细胞内总胆固醇、总胆汁酸和总胆红素,以及对胆汁酸排泄相关代谢酶、转运体基因表达的影响.结果:白藜芦醇能显著降低ANIT所致胆汁淤积性肝损伤大鼠模型中血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)活性及总胆红素(TBIL)、直接胆红素(DBIL)和间接胆红素(IBIL)的含量.在原代大鼠三明治肝细胞模型上白藜芦醇可恢复ANIT所致原代肝细胞胆管外排指数(BEI)的降低;显著降低ANIT所致的肝细胞内总胆汁酸和总胆红素的升高,恢复ANIT所致的总胆固醇水平的降低.白藜芦醇可显著改善ANIT所致的胆汁外排转运体Bsep、Mrp2、胆汁酸摄取转运体Ntcp及胆汁酸代谢相关酶Cyp7a1、Cyp8b1 mRNA表达的降低.结论:白藜芦醇具有退黄保肝、改善胆汁淤积的作用,其机制与调节肝细胞上胆汁酸排泄相关代谢酶和转运体相关.

  17. 利福平对小鼠肝细胞胆汁酸转运体Bsep和Mrp2表达与定位的影响%Change of expression and localization of canalicular Bsep and Mrp2 in rifampicin-induced cholestasis in mice

    Institute of Scientific and Technical Information of China (English)

    曹云海; 陈熙; 张程; 石嫦娥; 徐德祥; 许建明

    2010-01-01

    目的 利福平(Rifampicin, RIF)具有肝毒性,但其机制尚不清楚.本研究在RIF诱导的肝内胆汁淤积小鼠中,探讨RIF对肝细胞胆汁酸转运体胆汁酸输出泵(bile salt export pump, Bsep)和多药抵抗相关蛋白-2(multidrug resistance-associated protein-2, Mrp2)表达和定位影响.方法 48只♀ ICR小鼠随机分为4组,RIF 1 wk组:经灌胃给予RIF(200 mg·kg-1·d -1),连续1周,于末次给药后6 h取材;RIF 6 h组:单次灌胃给予RIF(200 mg·kg-1)后6 h取材;RIF 1周对照组(CON 1 wk)与RIF 6 h对照组 (CON 6 h):经灌胃给予等容积生理盐水.所有小鼠均收集血液和肝组织,常规生化检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、总胆红素(TB)和结合胆红素(DB),并检测小鼠血清和肝组织总胆汁酸(TBA)水平.HE染色分析肝组织病理改变.RT-PCR测定肝脏肝细胞胆汁酸转运体Bsep和Mrp2 mRNA表达.免疫荧光法分析Bsep和Mrp2在肝细胞的位置.结果 给予RIF 1周后,小鼠血清TB由(1.25±0.69) μmol·L-1上升至(65.73±12.08) μmol·L-1,上升近70倍,DB由(0.77±0.40) μmol·L-1上升至(53.33±12.43) μmol·L-1,上升约80倍,ALP由(110.2±13.8) U·L-1上升至(279.5±80.4) U·L-1,上升约1.5倍,TBA由(3.15±0.89) μmol·L-1上升至(13.54±6.51) μmol·L-1,上升约5倍并伴有血清ALT和AST轻度升高;肝脏组织TBA由(0.15±0.04) μmol·g-1 liver上升至(0.30±0.19) μmol·g-1 liver,上升约2倍;肝脏组织HE染色显示肝细胞出现脂肪变性、轻度坏死和炎症.单次给予RIF 6 h后血清TB、DB、ALP、ALT、AST和TBA明显上升,但未观察到小鼠肝脏组织病理发生改变.免疫荧光分析显示,给予小鼠RIF 1 wk与单次给予RIF 6 h后肝细胞中Bsep和Mrp2的定位发生了改变.而无论单次给予RIF还是连续给药1周,肝细胞Bsep和Mrp2 mRNA表达水平均未发生变化.结论 肝细胞胆汁酸转运体Bsep和Mrp2定位改变可能是RIF诱发肝内胆汁淤积的重要机制.

  18. Study on hepatotoxicity of aqueous extracts of Polygonum multiflorum in rats after 28-day oral administration: cholestasis-related mechanism%何首乌水提物大鼠连续灌胃给药28 d肝毒性研究——胆汁淤积相关机制探讨

    Institute of Scientific and Technical Information of China (English)

    王涛; 王佳颖; 周植星; 江振洲; 李妍妍; 张良; 张陆勇

    2015-01-01

    目的:考察何首乌水提物(AEPM)对大鼠肝脏中胆汁酸合成、代谢、转运相关分子影响,探讨何首乌肝毒性相关机制.方法:SD大鼠分别灌胃AEPM60,30 g·kg-1,每天1次,连续28 d.28 d后解剖取肝脏,分别采用荧光定量PCR和Westernblot检测肝脏MRP3,MRP2,BSEP,FXR,CYP7A1等分子的mRNA和蛋白表达水平.结果:与正常组相比,AEPM高剂量组雄性大鼠肝脏中MRP3和BSEP的mRNA表达均显著升高(P<0.05),而AEPM高、低剂量组肝脏FXR的mRNA表达均显著降低(P<0.05);AEPM高、低剂量组雌性大鼠肝脏MRP3,MRP2,BSEP,CYP7A1的mRNA表达均显著升高(P<0.05).Westernblot检测结果显示,AEPM高、低剂量给药组雄性和雌性大鼠肝脏中MRP3,MRP2,BSEP,FXR,CYP7A1蛋白表达水平与mRNA变化基本一致,但均未达统计学显著差异.结论:AEPM大鼠灌胃给药28 d对肝脏胆汁酸合成、转运、排泄相关蛋白的表达具有一定的影响,在mRNA表达水平既具有胆汁淤积分子特征,同时也可见促进胆汁酸排泄的分子特征.

  19. Effect of Choleretic and Jaundice-relieving Method on the BSEP expresion in the livers of rats with intrahepatic cholestasis and damp-heat%利胆退黄法对肝内胆汁淤积湿热证大鼠BSEP表达的影响

    Institute of Scientific and Technical Information of China (English)

    兰绍阳; 佘世锋; 张达坤; 陶双友

    2012-01-01

    目的:通过研究利胆退黄法对肝内胆汁淤积湿热证大鼠肝组织中BSEP基因表达的影响,以期进一步从分子水平探讨利胆退黄法的作用靶点及机制.方法:45只雄性SD大鼠随机分为3组:正常组、模型对照组和治疗组.检测治疗后大鼠血清生化指标、肝脏组织病理的变化和肝脏BSEP的表达.结果:治疗后治疗组大鼠体重增加(31.39±3.72 g)明显高于模型对照组大鼠(22.36±3.32 g),P<0.05.治疗组大鼠血清TB、DB、ALT、AST、ALP、TBA分别为13.90±2.88 μmol/L,7.47±2.70μmol/L,75.33±9.42 U/L,216.64±31.20 U/L,226.40±32.86 U/L,19.73±2.10 μmol/L),低于模型对照组(34.72±3.65μmol/L,19.33±3.27 μmol/L,123.73±18.51 U/L,353.78±63.08 U/L,355.49±63.08 U/L,36.15±6.77 μmol/L),P <0.05;HE染色显示治疗组大鼠肝脏的病理损害轻于模型对照组.免疫组织化学染色显示治疗组大鼠比模型对照组表达更多BSEP阳性细胞.荧光定量RT- PCR法显示模型对照组大鼠肝组织中BSEP mRNA表达(2-△△CT值1.49±0.49)明显低于治疗组(2-△△CT值1.96±0.66),P<0.05.结论:利胆退黄法能有效改善肝内胆汁淤积湿热证大鼠的肝功能、减轻病理损害,并能上调肝脏BSEP的表达.

  20. 妊娠期肝内胆汁淤积症总胆汁酸、雌三醇与新生儿Apgar评分的关系%Relationship between total bile acid and estriol of patients with intrahepatic cholestasis of pregnancy and neonatal Apgar score

    Institute of Scientific and Technical Information of China (English)

    蔡林燕

    2016-01-01

    目的 研究妊娠期肝内胆汁淤积症(ICP)总胆汁酸、雌三醇与新生儿APgar评分的关系.方法 收集2013年6月-2014年12月于该院就诊的ICP患者80例,所有患者均行肝功能生化指标及激素水平检测,对其新生儿均进行出生1 min时的APgar评价,应用单因素方差分析比较正常新生儿、中度窒息新生儿及重度窒息新生儿其母亲的血清胆汁酸和雌三醇情况的差异,采用多重线性回归分析患者血清胆汁酸和雌三醇与其产儿的新生儿Apgar评分的相关性.结果 不同级别Apgar评分的新生儿相对应母亲的血清胆汁酸和雌三醇差异较大,P<0.01,差异具有统计学意义;建立回归方程发现CIP患者血清胆汁酸和雌三醇的回归系数t检验的P值均<0.05,具有统计学意义,总胆汁酸、雌三醇的标准回归系数分别-12.047、-2.473,说明其与新生儿的Apgar评分具有负相关性,且对于新生儿的Apgar评分中总胆汁酸对其影响更大.结论 ICP患者血清胆汁酸和雌三醇与其新生儿的Apgar评分呈现负相关性,ICP患者进行血清胆汁酸和雌三醇的检测对新生儿窒息有一定的预警作用.

  1. Severe sustained cholestatic hepatitis following temozolomide in a patient with glioblastoma multiforme: case study and review of data from the FDA adverse event reporting system.

    Science.gov (United States)

    Sarganas, Giselle; Orzechowski, Hans D; Klimpel, Andreas; Thomae, Michael; Kauffmann, Wolfgang; Herbst, Hermann; Bronder, Elisabeth; Garbe, Edeltraut

    2012-05-01

    Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor in adults. Its established first-line adjuvant treatment is radiotherapy in combination with temozolomide (TZM). Hematotoxicity is listed as a frequent adverse drug reaction in the US prescribing information and hepatotoxicity has been reported infrequently in the postmarketing period. We here present the case of a patient diagnosed with GBM who developed severe sustained cholestatic hepatitis following treatment with TZM. The cholestasis was not reversible after withdrawal of TZM during 6 months before the patient's death. Another 2 published case reports of sustained cholestasis following TZM treatment were identified; however, the sustained nature of cholestasis was not emphasized in these reports. Sixteen cases of cholestatic hepatitis/cholestasis associated with TZM were identified in the FDA spontaneous reporting system between 2007 and 2010. Information on the course of the cholestasis in these cases could not be retrieved. In the literature there are other published reports of hepatotoxicity associated with TZM that have reported reversibility upon withdrawal of the drug. Thus, TZM appears to cause different types of hepatotoxicity. Particular attention should be paid to sustained cholestasis as a very serious type of TZM-associated liver toxicity. PMID:22394496

  2. Disseminated Langerhans Cell Histiocytosis Presenting as Cholestatic Jaundice

    Science.gov (United States)

    Loizides, Anthony M.; Sachdeva, Soumya; Paul, Premila

    2015-01-01

    Langerhans cell histiocytosis (LCH) is a disorder associated with proliferation of Langerhans cells in various organs. LCH secondary to multisystem involvement can present in a variety of ways. Because of its infiltrative nature, LCH can involve the skin, lymph nodes, the lung or the liver. Jaundice in LCH is a manifestation of liver disease; biliary dilatation secondary to lithiasis or may be due to coexistent Niemann-Pick disease. However, a case of cholestasis has been very rarely described. Cholestasis may result from lymph nodes obstructing the porta hepatis. In this report, we describe a case of type II histiocytosis X with obstructive cholestasis and pulmonary involvement in the form of cysts without significant lymphadenopathy at the porta. PMID:25859497

  3. Disseminated langerhans cell histiocytosis presenting as cholestatic jaundice.

    Science.gov (United States)

    Kapoor, Rohit; Loizides, Anthony M; Sachdeva, Soumya; Paul, Premila

    2015-02-01

    Langerhans cell histiocytosis (LCH) is a disorder associated with proliferation of Langerhans cells in various organs. LCH secondary to multisystem involvement can present in a variety of ways. Because of its infiltrative nature, LCH can involve the skin, lymph nodes, the lung or the liver. Jaundice in LCH is a manifestation of liver disease; biliary dilatation secondary to lithiasis or may be due to coexistent Niemann-Pick disease. However, a case of cholestasis has been very rarely described. Cholestasis may result from lymph nodes obstructing the porta hepatis. In this report, we describe a case of type II histiocytosis X with obstructive cholestasis and pulmonary involvement in the form of cysts without significant lymphadenopathy at the porta. PMID:25859497

  4. Ondansetron to Treat Pruritus Due to Cholestatic Jaundice

    Science.gov (United States)

    Dillon, Sarah; Tobias, Joseph D.

    2013-01-01

    Intractable itching is a symptom of cholestatic liver disease of various causes that is bothersome and difficult to manage. Although treatment of the primary cause of cholestasis is paramount in resolving the issue, given the debilitating consequences of pruritus, symptomatic treatment is frequently necessary. Although many medications including cholestyramine, rifampin, opioid antagonists (i.e., naloxone, naltrexone), phenobarbital, and antihistamines have been used to treat cholestatic-induced pruritus, none has resulted in uniform success. We report anecdotal success with the use of ondansetron to treat pruritus associated with cholestasis following prolonged intensive care unit course of a 16-year-old. The theories accounting for pruritus with cholestasis are presented, treatment options are reviewed, and the role of ondansetron in the treatment of pruritus is discussed. PMID:24052788

  5. [Evaluation of plasma PIVKA-II as a new marker for hepatocellular carcinoma].

    Science.gov (United States)

    Tada, H; Kagawa, K; Hikita, H; Takeuchi, T; Ohta, Y; Fukui, S; Shintani, H; Deguchi, T; Okanoue, T; Takino, T

    1989-04-01

    We have measured the plasma PIVKA-II levels in 188 cases of various liver disease with HCC and malignant diseases in other organs by an EIA, using a monoclonal antibody (E-1023 kit, Eisai), and also have measured the plasma vitamin K levels in cases of HCC and cholestasis by an HPLC. Plasma PIVKA-II was detected in many cases of HCC (67%, 35 of 52 cases) and cholestasis (60%, 6 of 10 cases). In contrast, the positivities of PIVKA-II in the other diseases including benign liver diseases were very low. Combination assays of PIVKA-II and vitamin K revealed that PIVKA-II correlates with vitamin K in cholestasis but not in HCC, suggesting that PIVKA-II in HCC does not depend on a systemic deficiency of vitamin K. From these results, it was concluded that PIVKA-II is a reliable marker which can reflect the clinical course of HCC.

  6. A letter on ABCB4 from Iceland: On the highway to liver disease.

    Science.gov (United States)

    Lammert, F; Hochrath, K

    2015-12-01

    Large-scale whole-genome sequencing of the Icelandic population identified an association between several mutations of ABCB4 encoding the hepatobiliary phosphatiylcholine floppase with liver diseases and function in the general population. Whereas rare mutations of this transporter were known to cause progressive familial intrahepatic cholestasis, the genome-wide association studies in Iceland find the common ABCB4 variant c.711A>T to be a general risk factor for elevated aminotransferases and higher impact variants to be potential determinants of early-onset gallstone disease, cholestasis of pregnancy, liver cirrhosis, and hepatobiliary cancer.

  7. Fatal Bile Duct Necrosis: A Rare Complication of Transcatheter Arterial Chemoembolization in a Patient with Endocrine Hepatic Metastasis

    Directory of Open Access Journals (Sweden)

    Anne-Laure Pelletier

    2008-11-01

    Full Text Available We report the first case of fatal bile duct necrosis following transcatheter arterial chemoembolization (TACE in a 58-year-old woman. The patient underwent two TACEs to treat hepatic metastases from an ileal endocrine tumor. Persistent cholestasis occurred after the second procedure, leading to the diagnosis of bile duct necrosis confirmed by liver biopsy. The patient died of liver failure with encephalopathy six months after the second TACE. Even though this complication is very rare, physicians should consider this diagnosis in patients who develop chronic, marked cholestasis following a TACE procedure.

  8. Asymptomatic leukemic-cell infiltration of the pancreas: US findings.

    Science.gov (United States)

    Collado, Laura; Dardanelli, Esteban; Sierre, Sergio; Moguillansky, Silvia; Lipsich, José

    2011-06-01

    Pancreatic infiltration of leukemic cells is a very rare manifestation at the onset of acute lymphoblastic leukemia (ALL) in childhood. Pancreatic enlargement in this situation is unusual and pancreatic involvement is often associated with biliary obstruction, cholestasis and pancreatitis. We report a 3-month-old girl who presented with asymptomatic leukemic infiltration of the pancreas, demonstrated by US with heterogeneous pancreatic enlargement associated with multiple hypoechogenic lesions, without cholestasis. Although these manifestations are rare, ALL should be considered a cause of pancreatic enlargement.

  9. Oral contraceptives induced hepatotoxicity

    Directory of Open Access Journals (Sweden)

    B. Akshaya Srikanth

    2013-02-01

    Full Text Available Oral Contraceptives are the pharmacological agents used to prevent pregnancy. These are divided as the combined and progestogen methods and are administered orally, transdermally, systemically and via vaginal route. All these methods contain both oestrogen and progestogen. Vigorous usage of oral contraceptives and anabolic steroids as associated with cholestasis, vascular lesions and hepatic neoplasm. Benign hepatic neoplasms are clearly associated with oral contraceptives. In this article we discuss the various hepatocellular complications like cholestasis, benign neoplasm and hepatocellular carcinoma occurred by oral contraceptives. [Int J Basic Clin Pharmacol 2013; 2(1.000: 91-93

  10. Phospholipase D2 mediates signaling by ATPase class I type 8B membrane 1[S

    OpenAIRE

    Chen, Frank; Ghosh, Ayantika; Shneider, Benjamin L.

    2013-01-01

    Functional defects in ATPase class I type 8B membrane 1 (ATP8B1 or familial intrahepatic cholestasis 1, FIC1) lead to cholestasis by mechanism(s) that are not fully understood. One proposed pathophysiology involves aberrant signaling to the bile acid sensor, the farnesoid X receptor (FXR), via protein kinase C ζ (PKCζ). The following cell line-based studies investigated whether phospholipase D2 may transduce a signal from FIC1 to FXR. PLD2 gain of function led to activation of the bile salt e...

  11. Altered expression and function of canalicular transporters during early development of cholestatic liver injury in Abcb4-deficient mice

    OpenAIRE

    Cai, Shi-Ying; Mennone, Albert; Soroka, Carol J.; Boyer, James L.

    2014-01-01

    Deficiency of ABCB4 is associated with several forms of cholestasis in humans. Abcb4−/− mice also develop cholestasis, but it remains uncertain what role other canalicular transporters play in the development of this disease. We examined the expression of these transporters in Abcb4−/− mice compared with their wild-type littermate controls at ages of 10 days and 3, 6, and 12 wk. Elevated plasma bile acid levels were already detected at 10 days and at all ages thereafter in Abcb4−/− mice. The ...

  12. Hepatocyte transplantation in bile salt export pump-deficient mice: selective growth advantage of donor hepatocytes under bile acid stress

    OpenAIRE

    Chen, Huey-Ling; Chen, Hui-Ling; Yuan, Ray-Hwang; Wu, Shang-Hsin; Chen, Ya-Hui; Chien, Chin-Sung; Chou, Shi-Ping; Wang, Renxue; Ling, Victor; Chang, Mei-Hwei

    2012-01-01

    The bile salt export pump (Bsep) mediates the hepatic excretion of bile acids, and its deficiency causes progressive familial intrahepatic cholestasis. The current study aimed to induce bile acid stress in Bsep −/− mice and to test the efficacy of hepatocyte transplantation in this disease model. We fed Bsep −/− and wild-type mice cholic acid (CA) or ursodeoxycholic acid (UDCA). Both CA and UDCA caused cholestasis and apoptosis in the Bsep −/− mouse liver. Wild-type mice had minimal liver inj...

  13. Unusual causes of intrahepatic cholestatic liver disease

    Institute of Scientific and Technical Information of China (English)

    Elias E Mazokopakis; John A Papadakis; Diamantis P Kofteridis

    2007-01-01

    We report five cases with unusual causes of intrahepatic cholestasis,including consumption of Teucrium polium (family Lamiaceae) in the form of tea,Stauffer's syndrome,treatment with tamoxifen citrate for breast cancer,infection with Coxiella Burnetii (acute Q fever),and infection with Brucella melitensis (acute brucellosis).

  14.  Bile salt export pump deficiency disease: two novel, late onset, ABCB11 mutations identified by next generation sequencing.

    Science.gov (United States)

    Vitale, Giovanni; Pirillo, Martina; Mantovani, Vilma; Marasco, Elena; Aquilano, Adelia; Gamal, Nesrine; Francalanci, Paola; Conti, Fabio; Andreone, Pietro

    2016-01-01

     Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomal recessive cholestatic diseases of childhood and represents the main indication for liver transplantation at this age; PFIC2 involves ABCB11 gene, that encodes the ATPdependent canalicular bile salt export pump (BSEP). Benign intrahepatic cholestasis (BRIC) identifies a group of diseases involving the same genes and characterized by intermittent attacks of cholestasis with no progression to liver cirrhosis. Diagnosis with standard sequencing techniques is expensive and available only at a few tertiary centers. We report the application of next generation sequencing (NGS) in the diagnosis of the familial intrahepatic cholestasis with a parallel sequencing of three causative genes. We identified the molecular defects in ABCB11 gene in two different probands who developed a severe cholestatic disease of unknown origin. In the first patient a compound heterozygosity for the novel frameshift mutation p.Ser1100GlnfsX38 and the missense variant p.Glu135Lys was detected. In the second patient, triggered by contraceptive therapy, we identified homozygosity for a novel missense variant p.Ala523Gly. In conclusion, these mutations seem to have a late onset and a less aggressive clinical impact, acting as an intermediate form between BRIC and PFIC. PMID:27493120

  15. Newly Identified Mechanisms of Total Parenteral Nutrition Related Liver Injury

    OpenAIRE

    Ajay Kumar Jain; Teckman, Jeffrey H.

    2014-01-01

    Total parenteral nutrition (TPN), a lifesaving therapy, involves providing nutrition by bypassing the gut. Unfortunately it is associated with significant complications including gut atrophy and parenteral nutrition associated liver disease (PNALD). PNALD includes steatosis, cholestasis, disrupted glucose metabolism, disrupted lipid metabolism, cirrhosis, and liver failure. The etiopathogenesis remains poorly defined; however, an altered enterohepatic circulation, disrupting nuclear receptor ...

  16. Vitamin E added to intralipid and enriched in omegaven protects against PNALD in TPN-fed preterm pigs

    Science.gov (United States)

    Prolonged parenteral nutrition (PN) may lead to cholestasis and parenteral nutrition associated liver disease (PNALD). The etiology of PNALD is unknown, but plant phytosterols in soybean oil emulsions (e.g., Intralipid) have been suggested to negatively impact bile acid homeostasis (BAH) by antagoni...

  17. ESPGHAN Committee on Nutrition Position Paper. Intravenous lipid emulsions and risk of hepatotoxicity in infants and children

    DEFF Research Database (Denmark)

    Hojsak, Iva; Colomb, Virginie; Braegger, Christian;

    2016-01-01

    be performed. Available studies found that the use of multicomponent fish oil (FO) containing ILE compared to pure soya bean oil (SO) ILE reduced liver enzymes and bilirubin levels in non-cholestatic children on long-term PN and one other RCT found that FO based ILE reversed cholestasis in a proportion...

  18. Detection of Autoantibodies to Vascular Endothelial Growth Factor Receptor-3 in Bile Duct Ligated Rats and Correlations with a Panel of Traditional Markers of Liver Diseases

    Science.gov (United States)

    Duval, Florent; Cruz-Vega, Delia Elva; González-Gamboa, Ivonne; González-Garza, María Teresa; Ponz, Fernando; Sánchez, Flora; Alarcón-Galván, Gabriela; Moreno-Cuevas, Jorge E.

    2016-01-01

    There is a need for new noninvasive biomarkers (NIBMs) able to assess cholestasis and fibrosis in chronic cholestatic liver diseases (CCLDs). Tumorigenesis can arise from CCLDs. Therefore, autoantibodies to tumor-associated antigens (TAA) may be early produced in response to abnormal self-antigen expression caused by cholestatic injury. Vascular endothelial growth factor receptor-3 (VEGFR-3) has TAA potential since it is involved in cholangiocytes and lymphatic vessels proliferations during CCLDs. This study aims to detect autoantibodies directed at VEGFR-3 during bile duct ligation- (BDL-) induced cholestatic injury in rat sera and investigate whether they could be associated with traditional markers of liver damage, cholestasis, and fibrosis. An ELISA was performed to detect anti-VEGFR-3 autoantibodies in sera of rats with different degree of liver injury and results were correlated with aminotransferases, total bilirubin, and the relative fibrotic area. Mean absorbances of anti-VEGFR-3 autoantibodies were significantly increased from week one to week five after BDL. The highest correlation was observed with total bilirubin (R2 = 0.8450, P = 3.04e − 12). In conclusion, anti-VEGFR-3 autoantibodies are early produced during BDL-induced cholestatic injury, and they are closely related to cholestasis, suggesting the potential of anti-VEGFR-3 autoantibodies as NIBMs of cholestasis in CCLDs and justifying the need for further investigations in patients with CCLD. PMID:27212785

  19. Mice lacking Mrp3 (Abcc3) have normal bile salt transport, but altered hepatic transport of endogenous glucuronides

    NARCIS (Netherlands)

    N. Zelcer; K. van de Wetering; R. de Waart; G.L. Scheffer; H.U. Marschall; P.R. Wielinga; A. Kuil; C. Kunne; A. Smith; M. Valk; J. Wijnholds; R. Oude Elferink; P. Borst

    2006-01-01

    Background/Aim: Multidrug Resistance Protein 3 (MRP3) transports bile salts and glucuronide conjugates in vitro and is postulated to protect the liver in cholestasis. Whether the absence of Mrp3 affects these processes in vivo is tested. Methods: Mrp3-deficient mice were generated and the contributi

  20. Obstetric dermatoses

    DEFF Research Database (Denmark)

    Hjortø, Sofie; Skov, Lone; Lykke, Jacob Alexander

    2014-01-01

    The specific dermatoses of pregnancy are rare and consist of pemphigoid gestationis (PG), intrahepatic cholestasis of pregnancy (ICP), polymorphic eruption of pregnancy and atopic eruption of pregnancy. The dermatoses are characterized by pruritus, and they are important to recognize since PG and...

  1. Unusual causes of intrahepatic cholestatic liver disease

    OpenAIRE

    Mazokopakis, Elias E.; Papadakis, John A; Kofteridis, Diamantis P.

    2007-01-01

    We report five cases with unusual causes of intrahepatic cholestasis, including consumption of Teucrium polium (family Lamiaceae) in the form of tea, Stauffer’s syndrome, treatment with tamoxifen citrate for breast cancer, infection with Coxiella Burnetii (acute Q fever), and infection with Brucella melitensis (acute brucellosis).

  2. Prolonged Cholestatic Jaundice Associated With Flurbiprofen.

    Science.gov (United States)

    Dogan, Serkan; Celikbilek, Mehmet; Demirkan, Kutay; Yilmaz, Semih; Deniz, Kemal; Gursoy, Sebnem; Yucesoy, Mehmet

    2014-08-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely consumed drugs throughout the world for pain relief. Although the adverse effects of NSAIDs to the liver are well known, flurbiprofen-induced liver cholestasis is extremely rare. Herein, we present a patient with prolonged icterus that is associated with the use of flurbiprofen without causing ductopenia.

  3. Hepatobiliary scintigraphy in the evaluation of feline liver disease.

    Science.gov (United States)

    Newell, S M; Selcer, B A; Roberts, R E; Cornelius, L M; Mahaffey, E A

    1996-01-01

    Hepatobiliary scintigraphy (HBS) was performed in 10 cats with histologically documented hepatobiliary disease. The scintigraphic patterns were classified into one of 5 categories: normal, primary hepatocellular dysfunction, primary intrahepatic cholestasis, mixed hepatocellular and intrahepatic cholestasis, and extrahepatic obstructive patterns. Initial attempts were made to correlate specific disease entities with HBS patterns, but a consistent relationship could not be determined. A correlation between the histological severity of a given hepatic disease and the HBS pattern was made. All cats (n = 5) with a mixed hepatocellular and intrahepatic cholestasis scintigraphic pattern with normal gallbladder function had a histologically severe form of their individual hepatic disease. Three of the 4 cats with an intrahepatic cholestasis pattern and normal hepatocellular and gallbladder function had histologically mild or moderate forms of their individual hepatic diseases. One cat had an extrahepatic obstructive pattern where no radiopharmaceutical was identified in the gallbladder or small intestine by 3 hours postinjection. This study suggests that HBS can be useful in cats with hepatobiliary disease to assess the severity of hepatic dysfunction, and to determine if extrahepatic biliary obstruction is present. Correlation between HBS patterns and specific disease entities such as hepatic lipidosis or cholangitis-cholangiohepatitis syndrome could not be made in this study. PMID:8884717

  4. Bile acids modulate glucocorticoid metabolism and the hypothalamic-pituitary-adrenal axis in obstructive jaundice

    DEFF Research Database (Denmark)

    McNeilly, Alison D; Macfarlane, David P; O'Flaherty, Emmett;

    2010-01-01

    Suppression of the hypothalamic-pituitary-adrenal axis occurs in cirrhosis and cholestasis and is associated with increased concentrations of bile acids. We investigated whether this was mediated through bile acids acting to impair steroid clearance by inhibiting glucocorticoid metabolism by 5beta-reductase....

  5. Updating prognosis in primary biliary cirrhosis using a time-dependent Cox regression model. PBC1 and PBC2 trial groups

    DEFF Research Database (Denmark)

    Christensen, E; Altman, D G; Neuberger, J;

    1993-01-01

    patients followed for up to 6 years. RESULTS: In the obtained model the following time-dependent variables independently indicated a poor prognosis: high bilirubin, low albumin, ascites, gastrointestinal bleeding, and old age. When including histological variables, cirrhosis, central cholestasis, and low...

  6. Severe liver dysfunction in an infant with cystic fibrosis masquerading as metabolic liver disease

    Directory of Open Access Journals (Sweden)

    K P Srikanth

    2016-01-01

    Full Text Available We present a rare presentation of cystic fibrosis with neonatal cholestasis. Histological features of mucoviscidosis were present in liver involving the biliary tract, intestinal mucosa, pancreas, and lung. Besides, there was a rare association with autosomal dominant type of polycystic renal disease.

  7. The mechanism of increased biliary lipid secretion in mice with genetic inactivation of bile salt export pump

    NARCIS (Netherlands)

    Gooijert, K. E. R.; Havinga, R.; Wolters, Henk; Wang, R.; Ling, V.; Tazuma, S.; Verkade, H. J.

    2015-01-01

    Human bile salt export pump (BSEP) mutations underlie progressive familial intrahepatic cholestasis type 2 (PFIC2). In the PFIC2 animal model, Bsep(-/-) mice, biliary secretion of bile salts (BS) is decreased, but that of phospholipids (PL) and cholesterol (CH) is increased. Under physiological cond

  8. In silico identification and in vitro validation of potential cholestatic compounds through 3D ligand-based pharmacophore modeling of BSEP inhibitors

    NARCIS (Netherlands)

    Ritschel, T.; Hermans, S.M.; Schreurs, M.J.; Heuvel, J.J.M.W. van den; Koenderink, J.B.; Greupink, R.; Russel, F.G.

    2014-01-01

    Drug-induced cholestasis is a frequently observed side effect of drugs and is often caused by an unexpected interaction with the bile salt export pump (BSEP/ABCB11). BSEP is the key membrane transporter responsible for the transport of bile acids from hepatocytes into bile. Here, we developed a phar

  9. Endotoxin detoxification by alkaline phosphatase in cholestatic livers

    NARCIS (Netherlands)

    Poelstra, K; Bakker, WW; Hardonk, MJ; Meijer, DKF; Wisse, E; Knook, DL; Balabaud, C

    1997-01-01

    Increased expression of alkaline phosphatase (AP) in the liver is a hallmark of cholestasis but the pathophysiological role of this is not clear. We argue that deprotonation of carboxyl groups at the active site of the enzyme may be a prerequisite for optimal AP activity. Such a creation of negative

  10. An Unusual Presentation of Liver Failure in a Patient with Primary Gastrointestinal Hodgkin's Lymphoma

    Directory of Open Access Journals (Sweden)

    Gabrielle B. Rocque

    2011-01-01

    Full Text Available Introduction. Hodgkin's lymphoma (HL presenting either with primary bowel involvement or with cholestasis is unusual. The combination of primary gastrointestinal HL presenting with cholestasis and ductopenia has not been previously described. Case Report. We present a case of primary gastrointestinal HL with evidence of liver involvement, but also with prominent ductopenia on liver biopsy and associated intrahepatic cholestasis. A 50-year-old man with a history of Crohn's disease presented with a bowel obstruction, for which he underwent a small bowel resection. Histology revealed HL. His course was complicated by cholestatic liver failure. A subsequent liver biopsy revealed both focal involvement by lymphoma and ductopenia, resembling vanishing bile duct syndrome (VBDS. He was treated with chemotherapy with improvement in his cholestasis, but he eventually succumbed due to further complications of his disease and treatment toxicities. Conclusion. This case of primary gastrointestinal HL associated with ductopenia does not meet classic criteria for VBDS, but the clinical presentation and pathology are suggestive of a VBDS-like paraneoplastic process. Therapies for HL in the setting of cholestatic liver failure require special consideration, but some reports of durable remissions and recovery of liver function have been reported.

  11. Antiviral therapy effects upon hepatitis C cholestatic syndrome.

    Science.gov (United States)

    Vere, C C; Gofiţă, Eliza; Forţofoiu, C; Streba, Letiţia Adela Maria; Genunche, Amelia

    2007-01-01

    Cholestasis includes, as a syndrome, all clinical and biological manifestations caused by the deficient or simply absent biliar secretion or caused by the obstruction of the biliary ducts. The hepatic cholestasis from the chronic hepatitis C (HC VHC) is a result of the altered interlobular biliary canalicules, caused by the modified cellular transport mechanisms and it is associated with a medium to severe degree of fibrosis. The aim of this study was to evaluate the efficiency of antiviral therapy in HC VHC patients. The study included a number of 37 HC VHC patients admitted at the Medical Department no. 1 of the Emergency County Hospital of Craiova; they were treated with Pegasys, 180 microg/week and Copegus, 1000 or 1200 mg/day, taking in consideration their weight, for 48 weeks and they were monitored for 24 weeks after the treatment. The following parameters were analyzed: direct bilirubine, total cholesterol, alkaline phosphatase, gamma-glutamiltranspeptidase and leucin-aminopeptidase. Under treatment, the clinical status caused by the cholestasis (pruritus, icteric syndrome, hemoragipary syndrome) was improved in six of the given cases (16.22%). Before therapy, the hepatic cholestasis was present in 20 patients (54.05%), and after treatment in 14 patients (37.83%). During therapy, the average values for all the monitored parameters decreased: direct bilirubine (0.38 +/- 0.18 mg/dl vs. 0.34 +/- 0.24 mg/dl, p = 0.0867), total cholesterol (198.53 md/dl vs. 183.16 mg/dl, p = 0.0808), alkaline phosphatase (236.99 +/- 79.09 iu/l vs. 227.82 +/- 87.59 iu/l, p = 0.0845), gamma-glutamiltranspeptidase (47 +/- 32.89 iu/l vs. 43.91 +/- 29.66 iu/l, p = 0.1509), and leucin-aminopeptidase (32.33 +/- 13.22 iu/l vs. 28.95 +/- 14.22 iu/l, p = 0.0038). Under antiviral treatment there was noticed an improvement of the cholestasis clinical status in a small number of cases. Antiviral therapy favorably influenced the liver cholestasis associated in patients with chronic hepatitis

  12. Pathogenesis and Management of Pruritus in PBC and PSC.

    Science.gov (United States)

    Kremer, Andreas E; Namer, Barbara; Bolier, Ruth; Fischer, Michael J; Oude Elferink, Ronald P; Beuers, Ulrich

    2015-01-01

    Pruritus is a preeminent symptom in patients with chronic cholestatic liver disorders such as primary biliary cirrhosis and primary sclerosing cholangitis. More than two-thirds of these patients experience itching during the course of their disease. This symptom is also frequently observed in patients with other causes of cholestasis such as cholangiocarcinoma, inherited forms of cholestasis and intrahepatic cholestasis of pregnancy, but may accompany almost any other liver disease. The pathogenesis of pruritus of cholestasis remains largely elusive. Increased concentrations of bile salts, histamine, serotonin, progesterone metabolites and endogenous opioids have been controversially discussed as potential pruritogens. However, for these molecules, neither a correlation with itch intensity nor a causative link could be established. The G protein-coupled receptor for bile salts, TGR5, has been shown to be expressed in dorsal root ganglia and give rise to itch in rodents, albeit upon stimuli with suprapathological concentrations of bile salts. The potent neuronal activator lysophosphatidic acid (LPA) and its forming enzyme, autotaxin (ATX), could be identified in the serum of patients with cholestatic pruritus. ATX activity correlated with itch severity and effectiveness of several anti-pruritic therapeutic interventions in cholestatic patients. Thus, the ATX-LPA-axis may represent a key element in the pathogenesis of this agonizing symptom. Treatment options for pruritus of cholestasis remain limited to a few evidence-based and several experimental medical and interventional therapies. The current guideline-based recommendations include the anion exchange resins colestyramine, the pregnane X receptor-agonist and enzyme inducer rifampicin, the μ-opioid antagonist naltrexone, and the selective serotonin reuptake inhibitors sertraline. Still, a considerable part of patients is unresponsive to these drugs and requires experimental approaches including phototherapy

  13. Detection of atypical bile acids in disease states and their identification by gas chromatography-mass spectrometry-computer techniques

    Energy Technology Data Exchange (ETDEWEB)

    Szczepanik-Van Leeuwen, P. A.; Stellaard, F.

    1978-01-01

    The study of the bile acid constituents of serum, bile, urine, and stool of patients exhibiting liver disease has increased in importance with the availability of newer methods for their detection and identification. A cogent question for study has been whether specific bile acids are toxic and thus are the cause of liver disease, or whether they accumulate as a result of disease-induced alteration in metabolism. Examining a wide variety of clinical samples, we have observed that many patients with diagnosed cholestasis show the presence of atypical bile acids due to metabolic aberrations in either the side chain or in the steroid ring. Because cholestasis represents a spectrum of diseases with differing metabolic and/or anatomic defects and because our studies cover a variety of cholestatic states, we have sought to establish a correlation between the presence of these atypical bile acids and the disease state. The complexity of the bile acid mixtures to be examined requires that gas chromatographic-mass spectrometric-computer techniques be used to provide a reliable analysis. It is believed that atypical bile acids can be readily identified by GC/CI mass spectrometry with great sensitivity. It is also believed that such bile acid analysis may prove useful to the study and diagnosis of liver disease. Present data suggest that the identification of atypical bile acids in biological samples may enable differentiation between different types of intrahepatic cholestasis. Such analyses may prove useful to distinguish specific diseases, such as Byler's disease (and Byler's-like cholestasis) from other types of cholestasis and may distinguish diseases involving mitochondrial defects. Finally, the presence of atypical bile acids may indicate, by the particular compounds formed, where and what kind of damage occurs in a disease and may ultimately establish if these atypical bile acids are a cause or effect of the liver damage.

  14. Obeticholic acid for the treatment of primary biliary cirrhosis.

    Science.gov (United States)

    Trivedi, Palak J; Hirschfield, Gideon M; Gershwin, M Eric

    2016-01-01

    Primary biliary cirrhosis (PBC) is characterized by progressive nonsuppurative destruction of small bile ducts, resulting in intrahepatic cholestasis, fibrosis and ultimately end-stage liver disease. Timely intervention with ursodeoxycholic acid is associated with excellent survival, although approximately one-third of all patients fail to achieve biochemical response, signifying a critical need for additional therapeutic strategies. Obeticholic acid (OCA) is a potent ligand of the nuclear hormone receptor farnesoid X receptor (FXR). Activation of FXR inhibits bile acid synthesis and protects against toxic accumulation in models of cholestasis and facilitates hepatic regeneration in preclinical studies. Data from recent Phase II and III controlled trials suggest a therapeutic impact of OCA in PBC biochemical nonresponders, as evidenced by change in proven laboratory surrogates of long-term outcome. Dose-dependent pruritus is a common adverse effect, but may be overcome through dose-titration. Longer term studies are needed with focus on safety and long-term clinical efficacy. PMID:26549695

  15. Vitamin A-induced cholestatic hepatitis: a case report

    DEFF Research Database (Denmark)

    Becker, P.; Maurer, B.; Schirrmacher, P.;

    2007-01-01

    We report a case of intrahepatic cholestasis due to chronic vitamin A supplementation. A 70-year-old woman was admitted to the hospital for jaundice and reduced nutritional and general status with a 2-month history of increasing cholestasis. Some years previously she had suffered from breast...... and ovarian cancer with subsequent surgery and chemotherapy. Chemotherapy was terminated one month before elevated serum transaminase activities and cholestatic serum markers were noted. Following the chemotherapy, supportive care included weekly vitamin A injections (100,000 IU per injection). Liver biopsy...... showed an acute toxic liver injury with focal parenchymal necrosis, sinusoidal lesions, inflammatory infiltrate (round cells, macrophages), and activation and proliferation of stellate cells. The hepatic vitamin A concentration was found to be significantly elevated. There were no signs of intrahepatic...

  16. Acute liver failure in a patient with sickle cell/β+ thalassaemia

    International Nuclear Information System (INIS)

    We describe a rare, severe, vaso-occlusive presentation of sickle cell disease, named sickle cell intrahepatic cholestasis (SCIC). Patients with sickle cell/β+ thalassaemia frequently have mild vaso-occlusive symptoms and only one case of SCIC developing in a patient with sickle cell/β+ thalassaemia has been previously described in the world literature. The present report represents only the second described case of SCIC in a patient with sickle cell/β+ thalassaemia. An abdominal computed tomography scan and Doppler ultrasound studies demonstrated massive hepatomegaly (25 cm span). Liver biopsy was performed and demonstrated dilatation and congestion of erythrocytes, severe cholestasis and fibrosis. The case demonstrates the importance of early recognition and institution of adequate therapy. Initial and correct diagnosis does not require biopsy or surgery which carry substantial risks of bleeding and mortality

  17. The Pitfalls of Febrile Jaundice. A Case Report

    Directory of Open Access Journals (Sweden)

    Obreja Maria

    2016-04-01

    Full Text Available Jaundice in sepsis is usually caused by cholestasis, and its onset can precede other manifestations of the infection. Inflammation-induced cholestasis is a common complication in patients with an extrahepatic infection or those with inflammatory processes. We describe the case of a 47 years old female who presented with low back pain and paravertebral muscular contracture. She subsequently developed a cholestatic syndrome with clinical manifestations such as jaundice, followed by fever and sepsis with multiple organ dysfunction. Initially labeled as biliary sepsis, the diagnosis was crucially reoriented as the blood cultures were positive for Streptococcus pyogenes and the magnetic resonance imaging (MRI findings suggested spondylodiscitis as well as a paravertebral abscess.

  18. Tamoxifen-associated vasculitis in a breast cancer patient

    Directory of Open Access Journals (Sweden)

    Vargas-Viveros Pablo

    2007-01-01

    Full Text Available Abstract Background Estrogen plays a critical role in breast cancer. Thereafter, endocrine therapy is a standard of care in patients with breast carcinoma, expressing ER or PR. Case presentation Herein we report the case of a 53-year old patient, who developed cholestasis and vasculitis during the treatment with tamoxifen. This toxicity was reversable after the removal of the drug. Thereafter she continued adjuvant treatment for breast carcinoma with anastrazole. Since tamoxifen has been widely indicated for patients with breast carcinoma, we did a literature review, looking for other cases with this type of toxicity. Conclusion This case is the third with vasculitis informed in the literature, but the first one that additionally developed cholestasis and arthritis. Although it is rare, we discuss the indication of this drug in the actual era, where aromatase inhibitors offer a better security profile.

  19. Primary Biliary Cirrhosis in A Patient with Turner Syndrome

    Directory of Open Access Journals (Sweden)

    Piotr Milkiewicz

    2005-01-01

    Full Text Available An increased prevalence of X chromosome monosomy has recently been demonstrated in patients with primary biliary cirrhosis (PBC. Chronic cholestasis of unknown etiology is a common clinical feature in patients with Turner syndrome who reach the fourth and fifth decades of life. A 37-year-old patient with Turner syndrome who presented with clinical and biochemical features of chronic cholestasis is described. Subsequent investigations confirmed the diagnosis of PBC. The patient did not respond to the medical treatment and was referred for liver transplant assessment. The present case may support the importance of X chromosome genes in the development of genetic predisposition to PBC, and emphasizes the necessity for a systematic study of the prevalence of PBC in patients with Turner syndrome.

  20. [Postoperative medical icterus].

    Science.gov (United States)

    Cerf, M

    1978-06-01

    The onset of jaundice following a surgical operation sometimes raises difficult problems. It is rarely due to hemolysis, infective hepatitis or decomposated cirrhosis of the liver. One should seek as a routine hepatitis due to halotane. However the most frequent cause is "benign postoperative cholestasis". This variety of jaundice presents in the form of an icterus due to conjugated bilirubine with often a large increase in alkaline phosphatase levels. The ocurse is variable. Almost always due to severe surgical or septic trauma, accompanied by shock and/or anoxia, it raises difficult diagnostic problems. The clinical and physiopathological aspects of benign postoperative cholestasis are recalled. One should remember, above all, that this is not an autonomous clinical entity but the sign of local or general complications which should be sought carefully.

  1. [Experimental results after acute and chronic ligation of bile duct (author's transl)].

    Science.gov (United States)

    Kirchner, R; Hartung, H; Trendelenburg, C

    1980-08-01

    The bile duct was ligated in 14 bastard dogs. Bilirubine, alcaline phosphatase, GOT, GPT, GLDH, and gamma GT were measured pre- and postoperatively. On the 8th postoperative day stenosis of the choledochus was eliminated using a patch plasty for dilatation in 7 dogs, whereas the occlusion remained in the other 7 dogs. Laboratory and histological results were characteristic for cholestasis 8 days after occlusion; these changes disappeared within 4 weeks after patch plastic surgery. In the controls these parameters normalized as well within 8 weeks, in spite of the persisting occlusion. These results show, that pathological changes after short term cholestasis are fully reversible; they demonstrate as well, that there are compensatory mechanisms operating in dogs with permanent occlusion of the bile duct.

  2. Flagging Drugs That Inhibit the Bile Salt Export Pump.

    Science.gov (United States)

    Montanari, Floriane; Pinto, Marta; Khunweeraphong, Narakorn; Wlcek, Katrin; Sohail, M Imran; Noeske, Tobias; Boyer, Scott; Chiba, Peter; Stieger, Bruno; Kuchler, Karl; Ecker, Gerhard F

    2016-01-01

    The bile salt export pump (BSEP) is an ABC-transporter expressed at the canalicular membrane of hepatocytes. Its physiological role is to expel bile salts into the canaliculi from where they drain into the bile duct. Inhibition of this transporter may lead to intrahepatic cholestasis. Predictive computational models of BSEP inhibition may allow for fast identification of potentially harmful compounds in large databases. This article presents a predictive in silico model based on physicochemical descriptors that is able to flag compounds as potential BSEP inhibitors. This model was built using a training set of 670 compounds with available BSEP inhibition potencies. It successfully predicted BSEP inhibition for two independent test sets and was in a further step used for a virtual screening experiment. After in vitro testing of selected candidates, a marketed drug, bromocriptin, was identified for the first time as BSEP inhibitor. This demonstrates the usefulness of the model to identify new BSEP inhibitors and therefore potential cholestasis perpetrators. PMID:26642869

  3. Acute liver failure due to primary amyloidosis in a nephrotic syndrome: a swiftly progressive course.

    Science.gov (United States)

    Cardoso, Brigite Aguiar; Leal, Rita; Sá, Helena; Campos, Mário

    2016-01-01

    AL amyloidosis is a clonal plasma cell proliferative disorder characterised by extracellular tissue deposits of insoluble fibrils derived from κ or λ immunoglobulin light chains. The most common organs affected by AL amyloidosis are the kidney, presenting with nephrotic syndrome and/or progressive renal dysfunction, and the heart, with restrictive cardiomyopathy. Hepatic deposition of fibrils occurs in half the cases but the liver is rarely the predominantly affected organ. The most common presentation of hepatic amyloidosis is hepatomegaly with elevated alkaline phosphatase. Acute liver failure with cholestasis and jaundice is a rare complication, with a prevalence of approximately 5%, and is usually associated with a worse prognosis. We report a case of a 39-year-old man admitted to our nephrology department with an unusual presentation of primary amyloidosis with nephrotic syndrome and acute liver failure, complicated by obstructive cholestasis resulting in death 2 months after diagnosis. PMID:26965175

  4. What Causes Biliary Atresia? Unique Aspects of the Neonatal Immune System Provide Clues to Disease Pathogenesis

    OpenAIRE

    Mack, Cara L.

    2015-01-01

    Biliary atresia (BA) is the most frequent identifiable cause of neonatal cholestasis and the majority of patients will need liver transplantation for survival. Despite surgical intervention with the Kasai portoenterostomy, significant fibrosis and cirrhosis develops early in life. An increased understanding of what causes this inflammatory fibrosing cholangiopathy will lead to therapies aimed at protecting the intrahepatic biliary system from immune-mediated damage. This review focuses on stu...

  5. Technical Pitfalls and Improvements for High-speed Screening and QSAR Analysis to Predict Inhibitors of the Human Bile Salt Export Pump (ABCB11/BSEP)

    OpenAIRE

    Saito, Hikaru; Osumi, Masako; Hirano, Hiroyuki; Shin, Wangsoo; Nakamura, Ryota; Ishikawa, Toshihisa

    2009-01-01

    Drug-induced hepatotoxicity is one of the major problems encountered in drug discovery and development. Selection of a candidate compound for pre-clinical studies in the drug discovery process is a critical step that can determine the speed and expenditure of clinical development. Because inhibition of human adenosine triphosphate-binding cassette transporter ABCB11 (SPGP/bile salt export pump) has severe consequences, which include intrahepatic cholestasis and hepatotoxicity, resulting from ...

  6. Effects of Bile Acids and the Bile Acid Receptor FXR Agonist on the Respiratory Rhythm in the In Vitro Brainstem Medulla Slice of Neonatal Sprague-Dawley Rats

    OpenAIRE

    Cong Zhao; Xianbao Wang; Yuling Cong; Yi Deng; Yijun Xu; Aihua Chen; Yanru Yin

    2014-01-01

    Intrahepatic cholestasis of pregnancy is always accompanied by adverse fetal outcomes such as malfunctions of respiration. Farnesoid X receptor (FXR) plays a critical role in the homeostasis of bile acids. Thus, we are determined to explore the effects of farnesoid X receptor (FXR) and five bile acids on respiratory rhythm generation and modulation of neonatal rats. Spontaneous periodic respiratory-related rhythmical discharge activity (RRDA) was recorded from hypoglossal nerves during the pe...

  7. Bile Acid-Induced Arrhythmia Is Mediated by Muscarinic M2 Receptors in Neonatal Rat Cardiomyocytes

    OpenAIRE

    Sheikh Abdul Kadir, Siti H; Michele Miragoli; Shadi Abu-Hayyeh; Moshkov, Alexey V.; Qilian Xie; Verena Keitel; Viacheslav O. Nikolaev; Catherine Williamson; Julia Gorelik

    2010-01-01

    BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a common disease affecting up to 5% of pregnancies and which can cause fetal arrhythmia and sudden intrauterine death. We previously demonstrated that bile acid taurocholate (TC), which is raised in the bloodstream of ICP, can acutely alter the rate and rhythm of contraction and induce abnormal calcium destabilization in cultured neonatal rat cardiomyocytes (NRCM). Apart from their hepatic functions bile acids are ubiquitous signallin...

  8. Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance

    OpenAIRE

    Fang, Sungsoon; Suh, Jae Myoung; Reilly, Shannon M; Yu, Elizabeth; Osborn, Olivia; Lackey, Denise; Yoshihara, Eiji; Perino, Alessia; Jacinto, Sandra; Lukasheva, Yelizaveta; Atkins, Annette R.; Khvat, Alexander; Schnabl, Bernd; Yu, Ruth T.; Brenner, David A

    2015-01-01

    The systemic expression of the bile acid (BA) sensor farnesoid X receptor (FXR) has led to promising new therapies targeting cholesterol metabolism, triglyceride production, hepatic steatosis and biliary cholestasis. In contrast to systemic therapy, bile acid release during a meal selectively activates intestinal FXR. By mimicking this tissue-selective effect, the gut-restricted FXR agonist fexaramine (Fex) robustly induces enteric fibroblast growth factor 15 (FGF15), leading to alterations i...

  9. Bile acid-activated nuclear receptor FXR suppresses apolipoprotein A-I transcription via a negative FXR response element

    OpenAIRE

    Claudel, Thierry; Sturm, Ekkehard; Duez, Hélène; Torra, Inés Pineda; Sirvent, Audrey; Kosykh, Vladimir; Fruchart, Jean-Charles; Dallongeville, Jean; Hum, Dean W; Kuipers, Folkert; Staels, Bart

    2002-01-01

    Serum levels of HDL are inversely correlated with the risk of coronary heart disease. The anti-atherogenic effect of HDL is partially mediated by its major protein constituent apoA-I. In this study, we identify bile acids that are activators of the nuclear receptor farnesoid X receptor (FXR) as negative regulators of human apoA-I expression. Intrahepatocellular accumulation of bile acids, as seen in patients with progressive familial intrahepatic cholestasis and biliary atresia, was associate...

  10. Activation of PPAR-gamma signaling as a novel target to limit nfkb-dependet in flammation in cystic fibrosis biliar epithelium

    OpenAIRE

    Scirpo,

    2014-01-01

    Cystic fibrosis-associated liver disease (CFLD) is a chronic cholangiopathy that negatively impacts the quality of life and survival of patients with Cystic Fibrosis (CF). CF is a disease of secretory epithelia caused by genetically-determined defective function of CFTR (cystic fibrosis conductance regulator), a cAMP-activated Cl- channel that, in the liver, is uniquely expressed in the biliary epithelium. The pathogenesis of CFLD is thought to be related to the ductal cholestasis caused by t...

  11. Modulation of farnesoid X receptor results in post-translational modification of poly (ADP-ribose) polymerase 1 in the liver

    OpenAIRE

    Zhu, Yan; Li, Guodong; Dong, Yafeng; Zhou, Helen H.; Kong, Bo; Aleksunes, Lauren M.; Richardson, Jason R.; Li, Fei; Guo, Grace L.

    2012-01-01

    The farnesoid X receptor (FXR) is a bile acid-activated transcription factor belonging to the nuclear receptor superfamily. FXR deficiency in mice results in cholestasis, metabolic disorders, and tumorigenesis in liver and intestine. FXR is known to contribute to pathogenesis by regulating gene transcription; however, changes in the post-transcriptional modification of proteins associated with FXR modulation have not been determined. In the current study, proteomic analysis of the livers of w...

  12. Cholestatic hepatitis with intravenous ceftriaxone

    Directory of Open Access Journals (Sweden)

    Inderpal Kaur

    2011-01-01

    Full Text Available Drug-induced liver injury is a major health problem. Its predominant forms include acute hepatitis, cholestasis, and a mixed pattern. Ceftriaxone is a third-generation cephalosporin and is widely used in the postoperative period due to its wider spectrum, longer half-life, and better tissue penetrability. Earlier cases of high aminotransferase levels and hepatitis have also been reported with the use of ceftriaxone. Here we report a case of cholestatic hepatitis with intravenous ceftriaxone.

  13. Groove Pancreatitis with Biliary and Duodenal Stricture: An Unusual Cause of Obstructive Jaundice

    OpenAIRE

    Marta Gravito-Soares; Elisa Gravito-Soares; Ana Alves; Dário Gomes; Nuno Almeida; Guilherme Tralhão; Carlos Sofia

    2016-01-01

    Introduction: Groove pancreatitis is an uncommon cause of chronic pancreatitis that affects the groove anatomical area between the head of the pancreas, duodenum, and common bile duct. Clinical case: A 67-year-old man with frequent biliary colic and an alcohol consumption of 30–40 g/day was admitted to the hospital complaining of jaundice and pruritus. Laboratory analysis revealed cholestasis and the ultrasound scan showed intra-hepatic biliary ducts dilatation, middle third cystic dilatat...

  14. ДИСЛИПИДЕМИЯ И АССОЦИИРОВАНЫЕ МЕТАБОЛИЧЕСКИЕ ЗАБОЛЕВАНИЯ

    Directory of Open Access Journals (Sweden)

    О. Ш. Ойноткинова

    2011-01-01

    Full Text Available This article presents the pathogenesis of dyslipidemia and associated metabolic disorders with the position of lipid metabolism. The role of natural mechanism of cholesterol homeostasis changing was showed, functional disorders of the enterohepatic circulation of bile acids and intrahepatic cholestasis due to violation of the reticuloendothelial system, entailing disruption of a specific target organ, on the one hand, and the development of atherosclerosis with ischemic syndromes — on the other, were demonstrated. Diagnostic and treatment algorithm is presented.

  15. Clinical evaluation of a new serum tumour marker CA 242 in pancreatic carcinoma.

    OpenAIRE

    Pasanen, P. A.; Eskelinen, M.; Partanen, K.; Pikkarainen, P; Penttilä, I.; Alhava, E

    1992-01-01

    The aim of this study was to evaluate the new monoclonal tumour marker CA 242 in the diagnosis of pancreatic carcinoma and to compare it with the established markers CA 50 and CEA. Serum concentrations were determined in 113 patients with jaundice, in 20 patients with laboratory values suggesting cholestasis, and in 60 patients with a suspicion to have chronic pancreatitis. Twenty-four of these 193 patients had pancreatic carcinoma and two patients had carcinoma of papilla of Vater. The sensi...

  16. A prospective study of serum tumour markers carcinoembryonic antigen, carbohydrate antigens 50 and 242, tissue polypeptide antigen and tissue polypeptide specific antigen in the diagnosis of pancreatic cancer with special reference to multivariate diagnostic score.

    OpenAIRE

    Pasanen, P. A.; Eskelinen, M.; Partanen, K.; Pikkarainen, P; Penttilä, I.; Alhava, E

    1994-01-01

    The aim of this study was to assess by a stepwise multivariate discriminant analysis the value of four current serum tumour markers - carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 50 and CA 242 and tissue polypeptide antigen (TPA) - and a new serum tumour marker, tissue polypeptide specific antigen (TPS), in the diagnosis of pancreatic cancer. The serum values were measured in a prospective series of patients with jaundice, with unjaundiced cholestasis and with a suspicion of chro...

  17. Disseminated Langerhans Cell Histiocytosis Presenting as Cholestatic Jaundice

    OpenAIRE

    Kapoor, Rohit; Loizides, Anthony M; Sachdeva, Soumya; Paul, Premila

    2015-01-01

    Langerhans cell histiocytosis (LCH) is a disorder associated with proliferation of Langerhans cells in various organs. LCH secondary to multisystem involvement can present in a variety of ways. Because of its infiltrative nature, LCH can involve the skin, lymph nodes, the lung or the liver. Jaundice in LCH is a manifestation of liver disease; biliary dilatation secondary to lithiasis or may be due to coexistent Niemann-Pick disease. However, a case of cholestasis has been very rarely describe...

  18. Endoscopic Treatment of Biliary Stenosis in Patients with Alveolar Echinococcosis – Report of 7 Consecutive Patients with Serial ERC Approach

    OpenAIRE

    Marija Stojkovic; Thomas Junghanss; Mira Veeser; Tim F Weber; Peter Sauer

    2016-01-01

    Background and Aims Biliary vessel pathology due to alveolar echicococcosis (AE) results in variable combinations of stenosis, necrosis and inflammation. Modern management strategies for patients with cholestasis are desperately needed. The aim is proof of principle of serial ERC (endoscopic retrograde cholangiography) balloon dilation for AE biliary pathology. Methods Retrospective case series of seven consecutive patients with AE-associated biliary pathology and ERC treatment in an interdis...

  19. Herbal hepatoxicity from Chinese skullcap: A case report

    OpenAIRE

    Yang, Leslie; Aronsohn, Andrew; Hart, John; Jensen, Donald

    2012-01-01

    The use of herbal supplements has increased considerably over the last decade. We report a case of an elderly woman who began taking Move Free Advanced for arthritis, which in addition to glucosamine and chondroitin, contained two herbal ingredients, Chinese skullcap and Black Catechu. Our patient presented with significant cholestasis and hepatitis which significantly improved after discontinuation of the supplement. Since neither the patient nor the treating physician recognized this supple...

  20. Ondansetron to Treat Pruritus Due to Cholestatic Jaundice

    OpenAIRE

    Dillon, Sarah; Tobias, Joseph D

    2013-01-01

    Intractable itching is a symptom of cholestatic liver disease of various causes that is bothersome and difficult to manage. Although treatment of the primary cause of cholestasis is paramount in resolving the issue, given the debilitating consequences of pruritus, symptomatic treatment is frequently necessary. Although many medications including cholestyramine, rifampin, opioid antagonists (i.e., naloxone, naltrexone), phenobarbital, and antihistamines have been used to treat cholestatic-indu...

  1. Alagille Syndrome: A Review

    OpenAIRE

    Callea, Michele; Bahsi, Emrullah; Montanari, Marco; Ince, Bayram; Mancini, Giovanni E.; YAVUZ, Yasemin; Radovich, Franco; Gunay, Ayse; Piana, Gabriela; Unal, Mehmet; D’Alessandro, Giovanni; Caselli, Mauro; Clarich, Gabriella

    2013-01-01

    Alagille Syndrome (AGS) is a genetically determined multisystem disorder affecting liver, hearth, eyes, skeleton and facies, less commonly kidney and CNS. The prognosis depends on the severity of the associated anomalies. The liver pathology plays a central role in that most clinical complications are due to long standing cholestasis as a consequence of lack of bile excretion secondary to paucity/absence of interlobular bile ducts. That results in hyperbilirubinemia, hypercholesterolemia, hyp...

  2. Protective Action of Antioxidants on Hepatic Damage Induced by Griseofulvin

    OpenAIRE

    Martinez, M. del C.; Afonso, S. G.; Buzaleh, A. M.; Batlle, A.

    2014-01-01

    Erythropoietic protoporphyria (EPP) is a disease associated with ferrochelatase deficiency and characterized by the accumulation of protoporphyrin IX (PROTO IX) in erythrocytes, liver, and skin. In some cases, a severe hepatic failure and cholestasis were observed. Griseofulvin (Gris) develops an experimental EPP with hepatic manifestations in mice such as PROTO IX accumulation followed by cellular damage as wells as necrotic and inflammatory processes. The antioxidant defense system was also...

  3. Nonicteric liver damage with a gamma-glutamyl transpeptidase level of 5,609 units/l in a renal-transplant recipient receiving azathioprine.

    Directory of Open Access Journals (Sweden)

    Watanabe,Akiharu

    1984-12-01

    Full Text Available A 26-year-old male with renal allograft, who received immunosuppressive treatment with azathioprine, presented marked elevations of serum biliary tract enzymes, such as gamma-glutamyl transpeptidase (5,609 units/l and alkaline phosphatase (60.5 Bessey-Lowry units, 14 months after transplantation. Two months later the patient became icteric; he died of respiratory failure 19 months after the renal allograft. Postmortem examination revealed intrahepatic cholestasis with minimal inflammatory cell infiltration, indicating drug hepatotoxicity.

  4. Acute fatty liver of pregnancy

    OpenAIRE

    Ko, Hin Hin; Yoshida, Eric

    2006-01-01

    Acute fatty liver of pregnancy (AFLP) is a rare, potentially fatal complication that occurs in the third trimester or early postpartum period. Although the exact pathogenesis is unknown, this disease has been linked to an abnormality in fetal fatty acid metabolism. Early diagnosis of AFLP sometimes can be difficult because it shares features with other common conditions such as pre-eclampsia, viral hepatitis and cholestasis of pregnancy. However, a careful history and physical examination, in...

  5. The Association between Bile Salt Export Pump Single-Nucleotide Polymorphisms and Primary Biliary Cirrhosis Susceptibility and Ursodeoxycholic Acid Response

    OpenAIRE

    Rui-rui Chen; Yuan-jun Li; Xin-min Zhou; Lu Wang; Juan Xing; Shuang Han; Li-na Cui; Lin-hua Zheng; Kai-chun Wu; Yong-quan Shi; Zhe-yi Han; Ying Han; Dai-ming Fan

    2014-01-01

    Background. Primary biliary cirrhosis (PBC) is a chronic and progressive cholestasis liver disease. Bile salt export pump (BSEP) is the predominant bile salt efflux system of hepatocytes. BSEP gene has been attached great importance in the susceptibility of PBC and the response rate of ursodeoxycholic acid (UDCA) treatment of PBC patients. Methods. In this study, TaqMan assay was used to genotype four variants of BSEP, and the Barcelona criteria were used for evaluating the response rate of U...

  6. Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families

    OpenAIRE

    Strautnieks, S S; Byrne, J A; Pawlikowska, L.; Cebecauerova, D; Rayner, A; Dutton, L; Meier, Y; Antoniou, A; Stieger, B; Arnell, H; Ozcay, F; Al-Hussaini, H F; Bassas, A F; Verkade , H.J.; Fischler, B

    2008-01-01

    BACKGROUND & AIMS: Patients with severe bile salt export pump (BSEP) deficiency present as infants with progressive cholestatic liver disease. We characterized mutations of ABCB11 (encoding BSEP) in such patients and correlated genotypes with residual protein detection and risk of malignancy. METHODS: Patients with intrahepatic cholestasis suggestive of BSEP deficiency were investigated by single-strand conformation polymorphism analysis and sequencing of ABCB11. Genotypes sorted by likely ph...

  7. Bile Salt Export Pump is Dysregulated with Altered Farnesoid X Receptor Isoform Expression in Patients with Hepatocellular Carcinoma

    OpenAIRE

    Chen, Yuan; Song, Xiulong; Valanejad, Leila; Vasilenko, Alexander; More, Vijay; Qiu, Xi; Chen, Weikang; Lai, Yurong; Slitt, Angela; Stoner, Matthew; Yan, Bingfang; Deng, Ruitang

    2013-01-01

    As a canalicular bile acid effluxer, bile salt export pump (BSEP) plays a vital role in maintaining bile acid homeostasis. BSEP deficiency leads to severe cholestasis and hepatocellular carcinoma (HCC) in young children. Regardless of the etiology, chronic inflammation is the common pathological process for HCC development. Clinical studies showed that bile acid homeostasis is disrupted in HCC patients with elevated serum bile acid level as a proposed marker for HCC. However, the underlying m...

  8. Recent insights into the function and regulation of the bile salt export pump (ABCB11)

    OpenAIRE

    Stieger, B

    2009-01-01

    PURPOSE OF REVIEW: Generation of bile is an important function of the liver. Its impairment can be caused by inherited mutations or by acquired factors and leads to cholestasis. Bile salts are an important constituent of bile and are secreted by the bile salt export pump (BSEP) from hepatocytes. RECENT FINDINGS: Significant progress was made in the understanding of mechanisms and consequences of malfunctioning BSEP. This information was gained from extensive characterization of patients with ...

  9. ATPase Class I Type 8B Member 1 and Protein Kinase C-ζ Induce the Expression of the Canalicular Bile Salt Export Pump in Human Hepatocytes

    OpenAIRE

    Chen, Frank; Ellis, Ewa; Strom, Stephen C.; Shneider, Benjamin L.

    2010-01-01

    The exact molecular mechanism(s) of the disease that results from defects in the ATPase Class I Type 8B Member 1 gene remains controversial. Prior investigations of human ileum and in intestinal and ovarian cell lines have suggested that Familial Intrahepatic Cholestasis 1 (FIC1) activates the Farnesoid X-Receptor (FXR) via a pathway involving Protein Kinase C ζ (PKCζ). Translational investigations of human liver from individuals with FIC1 disease have been confounded by secondary affects of ...

  10. Hepatic bile acids and bile acid-related gene expression in pregnant and lactating rats

    OpenAIRE

    Zhu, Qiong N.; Xie, Hong M.; Dan Zhang; Jie Liu; Yuan F. Lu

    2013-01-01

    Background. Significant physiological changes occur during pregnancy and lactation. Intrahepatic cholestasis of pregnancy (ICP) is a liver disease closely related to disruption of bile acid homeostasis. The objective of this study was to examine the regulation of bile acid synthesis and transport in normal pregnant and lactating rats. Materials and Methods. Livers from timed pregnant SD rats were collected on gestational days (GD) 10, 14 and 19, and postnatal days (PND) 1, 7, 14 and 21. T...

  11. Acute liver function decompensation in a patient with sickle cell disease managed with exchange transfusion and endoscopic retrograde cholangiography

    OpenAIRE

    Papafragkakis, Haris; Mel A. Ona; Changela, Kinesh; Sadanandan, Swayamprabha; Jelin, Abraham; Anand, Sury; Duddempudi, Sushil

    2014-01-01

    Sickle cell intrahepatic cholestasis is a relatively uncommon complication of homozygous sickle cell anemia, which may lead to acute hepatic failure and death. Treatment is mainly supportive, but exchange transfusion is used as salvage therapy in life threatening situations. We describe a case of a 16-year-old female with homozygous sickle cell anemia who presented to the emergency room with fatigue, malaise, dark urine, lower back pain, scleral icterus and jaundice. She was found to have mar...

  12. [CLINICAL CASE OF COMBINATION OF PRIMARY SCLEROSING CHOLANGITIS WITH NONSPECIFIC ULCERATIVE COLITIS IN TWINS MONOZYGOTIC].

    Science.gov (United States)

    Gubergrits, N B; Belyayeva, N V; Klochkov, A Ye; Fomenko, P G; Lukashevich, G M

    2015-01-01

    The article presents discussion of basic hypotheses of pathogenesis of primary sclerosing cholangitis (PSC): genetically conditioned pathology, autoimmune pathology, result of inflammatory reaction in bile ducts, cholangiopathy. The authors presents a clinical case of monozygotic twins with association of PSC and nonspecific ulcerative colitis (NUC). The first twin had a severe course of PSC and mild course of NUC; he died due to bacterial complications of cholangitis. The second twin--patient B--had an opposite situation: severe course of NUC, while PSC was suspected only after determination of cholestasis biochemical markers. As soon as cholestasis was revealed, patients B was treated with Ursofalk and Budenofalk (2001). He received Salofalk as a remedy of basic therapy for NUC. Repeated liver biopsy (2005) showed no progression of PSC, but there were present minimal biochemical signs of cholestasis. So, it is necessary to investigate the first degree relatives of patients with PSC. The timely administered treatment in some cases gives the possibility of the control of the disease course.

  13. Oxidative stress influence on renal dysfunction in patients with obstructive jaundice: A case and control prospective study

    Directory of Open Access Journals (Sweden)

    David Martínez-Cecilia

    2016-08-01

    Full Text Available Background: Obstructive Jaundice (OJ is associated with a significant risk of developing acute renal failure (ARF. The involvement of oxidative stress in the development of cholestasis has been demonstrated in different experimental models. However, its role in the morbidity of human cholestasis is far to be elucidated. The aim of the study was the evaluation of oxidative stress markers in blood from patients with OJ and its relation to complications and benign/malignant evolution of cholestasis. Methods: A prospective cross-sectional study of 105 patients with OJ and 34 control subjects were included. Several markers of liver function and oxidative stress, such as lipoperoxides (LPO, as well as reduced glutathione (GSH, catalase (CAT, superoxide dismutase (SOD and glutathione peroxidase (GSH-Px activities were assessed. Results: The patients with OJ showed a marked increase in plasma levels of LPO, SOD and GSH, while GSH-Px levels were decreased. The increase in lipid peroxidation products and the depletion of SOD activity in blood were also related to renal dysfunction. The highest level of LPO was associated with malignant etiology of the disease. The logistic regression analysis showed that the age of the patient and the levels of LPO in blood were predictors of renal dysfunction in OJ patients. Conclusions: This study demonstrates a correlation between oxidative stress and renal dysfunction patients with OJ.

  14. Evaluation of two experimental models of hepatic encephalopathy in rats

    Directory of Open Access Journals (Sweden)

    García-Moreno L.M.

    2005-01-01

    Full Text Available The serious neuropsychological repercussions of hepatic encephalopathy have led to the creation of several experimental models in order to better understand the pathogenesis of the disease. In the present investigation, two possible causes of hepatic encephalopathy, cholestasis and portal hypertension, were chosen to study the behavioral impairments caused by the disease using an object recognition task. This working memory test is based on a paradigm of spontaneous delayed non-matching to sample and was performed 60 days after surgery. Male Wistar rats (225-250 g were divided into three groups: two experimental groups, microsurgical cholestasis (N = 20 and extrahepatic portal hypertension (N = 20, and a control group (N = 20. A mild alteration of the recognition memory occurred in rats with cholestasis compared to control rats and portal hypertensive rats. The latter group showed the poorest performance on the basis of the behavioral indexes tested. In particular, only the control group spent significantly more time exploring novel objects compared to familiar ones (P < 0.001. In addition, the portal hypertension group spent the shortest time exploring both the novel and familiar objects (P < 0.001. These results suggest that the existence of portosystemic collateral circulation per se may be responsible for subclinical encephalopathy.

  15. {sup 99m}Tc sestamibi imaging. Can it be a useful substitute for hepatobiliary scintigraphy in infantile jaundice?

    Energy Technology Data Exchange (ETDEWEB)

    Sadeghi, R.; Kakhki, V.R.D.; Zakavi, R. [Mashhad Univ. of Medical Sciences (Iran). Nuclear Medicine Dept.; Kianifar, H.R. [Mashhad Univ. of Medical Sciences (Iran). Paediatric Dept.; Ansari, K. [Tehran Univ. of Medical Sciences (Iran). Nuclear Medicine Dept.

    2009-07-01

    Hepatobiliary scintigraphy is an integral part in the diagnostic work-up of the neonatal cholestasis syndrome. However, less than optimal specificity is its major disadvantage. Differentiation between biliary atresia and neonatal hepatitis is nearly impossible in some cases with poor hepatocellular function. {sup 99m}Tc sestamibi (MIBI) is a cationic lipophilic agent which is a substrate of P-glycoprotein. This glycoprotein is normally expressed in biliary canalicular surfaces of hepatocytes. This property provides a hepatic excretory mechanism which is different from bilirubin excretion. In this study we evaluated the value of {sup 99m}Tc MIBI in differential diagnosis of neonatal cholestasis. 20 infants with a mean age of 2.41 months (range, 0.1-5 months) were included in the study. Ten infants turned out to have extrahepatic biliary atresia and the other ten had neonatal hepatitis. Hepatobiliary (with {sup 99m}Tc BrIDA) and {sup 99m}Tc MIBI scintigraphy were performed for all the patients. {sup 99m}Tc MIBI scintigraphy has shown bowel activity in all patients, including the patients with biliary atresia. Hepatobiliary scintigraphy revealed bowel activity only in five patients with neonatal hepatitis. Bowel visualization with {sup 99m}Tc MIBI may be seen in patients with biliary atresia and {sup 99m}Tc MIBI has limited value in differential diagnosis of neonatal cholestasis. (orig.)

  16. Effect of chemotherapy on autoimmune hepatitis in thymoma:a case report and literature review

    Institute of Scientific and Technical Information of China (English)

    Nesrine Mejri; Imen Chabchoub; Ines Gargouri; Imtinen Belaid; Faten Ezairi; Sihem Hmissa; Slim Ben Ahmed

    2013-01-01

    Autoimmune hepatitis (AIH) has rarely been described as an autoimmune paraneoplastic syndrome of thymoma. This case is the seventh case of AIH revealed by cholestasis few years after the diagnosis of thymoma and the first case treated with chemotherapy alone. We report in this paper a new approach to this rare severe condition. A 29 year-old man presented with chest pain and dyspnea with a history of thymoma surgically removed 4 years ago. CT scan showed the recurrence of an anterior mediastinal mass. Biology showed elevated liver enzymes and profound cholestasis. No sign of viral or toxic hepatitis or bile duct abnormalities were observed. Autoimmune antibodies, except for the anti-nuclear antibody, were negative. Liver biopsy showed active chronic AIH. The patient was diagnosed with recurrent thymoma with AIH and underwent 6 cycles of chemotherapy. A complete response on thymoma and cholestasis was obtained after 10 months of follow-up. Steroids and immunosuppressors are the standard treatment for AIH. The effect of chemotherapy as a specific treatment of this paraneoplastic syndrome needs to be considered.

  17. Medical treatment of cholestatic liver diseases: From pathobiology to pharmacological targets

    Institute of Scientific and Technical Information of China (English)

    Gustav Paumgartner

    2006-01-01

    Bile secretion is dependent on the coordinated functions of a number of hepatobiliary transport systems.Cholestasis may be caused by an impairment of bile secretion, an obstruction of bile flow or a combination of the two. The common consequence of all forms of cholestasis is retention of bile acids and other potentially toxic compounds in the hepatocytes leading to apoptosis or necrosis of hepatocytes and eventually to chronic cholestatic liver disease. In certain cholestatic disorders there is also leakage of bile acids into the peribiliary space causing portal inflammation and fibrosis. The following pharmacological targets for treatment of intrahepatic cholestasis can be identified: stimulation of orthograde biliary secretion and retrograde secretion of bile acids and other toxic cholephils into the systemic circulation for excretion via the kidneys to reduce their retention in the hepatocytes; stimulation of the metabolism of hydrophobic bile acids and other toxic compounds to more hydrophilic, less toxic metabolites;protection of injured cholangiocytes against toxic effects of bile; inhibition of apoptosis caused by elevated levels of cytotoxic bile acids; inhibition of fibrosis caused by leakage of bile acids into the peribiliary space. The clinical results of ursodeoxcholic acid therapy of primary biliary cirrhosis may be regarded as the first success of this strategy.

  18. Development of animal models for hepatobiliary nuclear imaging

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jin Hee; Park, Yun Hee; Ryu, Yeon Mi; Shin, Eun Kyung; Kim, Meyoung Kon [Korea University Medical College, Seoul (Korea, Republic of)

    2002-07-01

    Animal models for hepatobiliary disorders were classified into 2 different types: parenchymal hepatotoxicity and biliary-tract cholestasis. The purpose of this study was to develop animal models for hepatobiliary scintigraphy in evaluating a novel agents, such as {sup 99m}Tc-mercaptoacetyl triglycine(MAG3)-biocytin. Animal models were prepared by use of female Balb/c mice. Those were treated with 0.1, 0.5, and 2.5 ml/kg of carbon tetrachloride (CCl4) intraperitoneally for hepatotoxicity and with 30, 150, and 750 mg/kg of {alpha}-naphthylisothiocyanate (ANIT) to induce cholestasis. Dose of optimum was 0.5 ml/kg and 150 mg/kg for each model but lower (0.1 ml/kg and 30 mg/kg) and higher (2.5ml/kg and 750 mg/kg)were not be compatible for hepatobiliary models. Using these hepatobiliary models, {sup 99m}Tc-MAG3-biocytin scintigraphy was successfully carried out by using 4 parameters, e.g., peak liver/heat ratio (Rmax), peak ratio time (Tmax), half clearance time (HCT), and hepatic extraction fraction (HEF) for hepatotoxicity and cholestasis. Additionally, biochemical and histological analysis also resulted in confirming these animal models. Thus, we concluded that these animal models were highly likely to be efficient in evaluating hepatobiliary scintigraphic agent such as {sup 99m}Tc-MAG3-biocytin.

  19. Naproxen-induced liver injury

    Institute of Scientific and Technical Information of China (English)

    Sharif Ali; Jason D Pimentel; Chan Ma

    2011-01-01

    BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to induce liver injury. Patterns of the injury usually range from mild elevations of liver enzymes to sometimes severe fulminant hepatic failure. Likewise, naproxen is a propionic acid derivative NSAID that was introduced in 1980 and has been available as an over-the-counter medication since 1994, but has rarely been reported to cause liver injury. METHODS: We treated a 30-year-old woman with jaundice and intractablepruritusthatdevelopedshortlyaftertakingnaproxen. We reviewed the medical history and liver histopathology of the patient as well as all previously published case reports of naproxen-associated liver toxicity in the English language literature. RESULTS: The liver biochemical profile of the patient revealed a mixed cholestasis and hepatitis pattern. Consecutive liver biopsies demonstrated focal lobular inflammation, hepatocyte drop-out, and a progressive loss of the small interlobular bile ducts (ductopenia). The biopsy performed two years after onset of the disease showed partial recovery of a small number of bile ducts; however, 10 years passed before the biochemical profile returned to near normal. CONCLUSIONS:  Naproxen-associated liver toxicity remains a rare entity, but should be considered in any patient presenting with cholestasis shortly after its use. Liver injury is most commonly seen in a mixed pattern characterized by cholestasis and hepatitis. The resulting liver damage may take years to resolve.

  20. Nucleolar localization of cirhin, the protein mutated in North American Indian childhood cirrhosis

    International Nuclear Information System (INIS)

    Cirhin (NP116219), the product of the CIRH1A gene is mutated in North American Indian childhood cirrhosis (NAIC/CIRH1A, OMIM 604901), a severe autosomal recessive intrahepatic cholestasis. It is a 686-amino-acid WD40-repeat containing protein of unknown function that is predicted to contain multiple targeting signals, including an N-terminal mitochondrial targeting signal, a C-terminal monopartite nuclear localization signal (NLS) and a bipartite nuclear localization signal (BNLS). We performed the direct determination of subcellular localization of cirhin as a crucial first step in unraveling its biological function. Using EGFP and His-tagged cirhin fusion proteins expressed in HeLa and HepG2, cells we show that cirhin is a nucleolar protein and that the R565W mutation, for which all NAIC patients are homozygous, has no effect on subcellular localization. Cirhin has an active C-terminal monopartite nuclear localization signal (NLS) and a unique nucleolar localization signal (NrLS) between residues 315 and 432. The nucleolus is not known to be important specifically for intrahepatic cholestasis. These observations provide a new dimension in the study of hereditary cholestasis

  1. Genetic variants in adult liver diseases.

    Science.gov (United States)

    Dröge, C; Häussinger, D; Keitel, V

    2015-12-01

    In the last decades, understanding of genetic variants contributing to liver disease development has considerably improved through novel genotyping techniques. Genetic variants of single genes are known to be decisive for the development of monogenetic liver diseases of varying severity. Identification of genetic variants is an important part of the diagnostic process, e. g. the majority of patients with high iron [Fe] (HFE)-associated hemochromatosis carry the homozygous mutation p.C282Y. Detection of mutations in genes encoding hepatobiliary transport proteins like familial intrahepatic cholestasis 1 (FIC1), bile salt export pump (BSEP), or multidrug resistance protein 3 (MDR3) is the basis to differentiate various forms of intrahepatic cholestasis. Moreover, genetic variants in a variety of genes are known to act as disease modifiers and represent risk factors for disease progression and the development of cirrhosis or even hepatocellular carcinoma. Success of drug treatment or appearance of severe side effects can also be influenced by specific genetic variants. All these aspects underscore the increasing importance of genetic variants, which in the future may help to identify patients at risk for disease progression or help to guide treatment decisions. In the present overview, specific frequent genetic variants are summarized that play roles in monogenetic liver diseases, forms of intrahepatic cholestasis, gallstone development, fatty liver disease, drug-induced liver injury, and liver disease progression as well as hepatocellular carcinoma development. PMID:26666282

  2. Distinct Plasma Bile Acid Profiles of Biliary Atresia and Neonatal Hepatitis Syndrome.

    Science.gov (United States)

    Zhou, Kejun; Wang, Jun; Xie, Guoxiang; Zhou, Ying; Yan, Weihui; Pan, Weihua; Che, Yanran; Zhang, Ting; Wong, Linda; Kwee, Sandi; Xiao, Yongtao; Wen, Jie; Cai, Wei; Jia, Wei

    2015-11-01

    Biliary atresia (BA) is a severe chronic cholestasis disorder of infants that leads to death if not treated on time. Neonatal hepatitis syndrome (NHS) is another leading cause of neonatal cholestasis confounding the diagnosis of BA. Recent studies indicate that altered bile acid metabolism is closely associated with liver injury and cholestasis. In this study, we systematically measured the bile acid metabolome in plasma of BA, NHS, and healthy controls. Liver bile acids were also measured using biopsy samples from 48 BA and 16 NHS infants undergoing operative cholangiography as well as 5 normal adjacent nontumor liver tissues taken from hepatoblastoma patients as controls. Both BA and NHS samples had significantly elevated bile acid levels in plasma compared to normal controls. BA patients showed a distinct bile acid profile characterized by the higher taurochenodeoxycholic acid (TCDCA) level and lower chenodeoxycholic acid (CDCA) level than those in NHS patients. The ratio of TCDCA to CDCA in plasma was significantly higher in BA compared to healthy infants (p BSEP), and multidrug resistant protein 3 (MDR3) in BA compared to NHS. Taken together, the plasma bile acid profiles are distinct in BA, NHS, and normal infants, as characterized by the ratio of TCDCA/CDCA differentially distributed among the three groups of infants. PMID:26449593

  3. Sclerosing cholangitis following severe trauma: Description of a remarkable disease entity with emphasis on possible pathophysiologic mechanisms

    Institute of Scientific and Technical Information of China (English)

    Johannes Benninger; Rainer Grobholz; Yurdaguel Oeztuerk; Christoph H. Antoni; Eckhart G. Hahn; Manfred V. Singer; Richard Strauss

    2005-01-01

    AIM: Persistent cholestasis is a rare complication of severe trauma or infections, Little is known about the possible pathomechanisms and the clinical course,METHODS: Secondary sclerosing cholangitis was diagnosed in five patients with persistent jaundice after severe trauma (one burn injury, three accidents, one power current injury). Medical charts were retrospectively reviewed with regard to possible trigger mechanisms for cholestasis, and the clinical course was recorded.RESULTS: Diagnosis of secondary sclerosing cholangitis was based in all patients on the primary sclerosing cholangitis (PSC)-like destruction of the intrahepatic bile ducts at cholangiography after exclusion of PSC. In four patients, arterial hypotension with subsequent ischemia may have caused the bile duct damage, whereas in the case of power current injury direct thermal damage was assumed to be the trigger mechanism. The course of secondary liver fibrosis was rapidly progressive and proceeded to liver cirrhosis in all four patients with a follow-up >2 years. Therapeutic possibilities were limited.CONCLUSION: Posttraumatic sclerosing cholangitis is a rare but rapidly progressive disease, probably caused by ischemia of the intrahepatic bile ducts via the peribiliary capillary plexus due to arterial hypotension. Gastroenterologists should be aware of this disease in patients with persistent cholestasis after severe trauma.

  4. Diagnostic and therapeutic approach to cholestatic liver disease Abordaje diagnóstico y terapéutico del síndrome colestásico

    Directory of Open Access Journals (Sweden)

    T. Pérez Fernández

    2004-01-01

    Full Text Available When cholestatic liver disease is present, liver ultrasound should be performed to ascertain if cholestasis is extrahepatic or intrahepatiic. If bile ducts appear dilated and the probability of interventional treatment is high, endoscopic retrograde cholagio-pancreatography (ERCP or trans-hepatic cholangiography (THC should be the next step. If the probability of interventional therapeutics is low, cholangio-MRI should be performed. Once bile duct dilation and space occupying lesions are excluded, a work up for intrahepatic cholestasis should be started. Some especific clinical situations may be helpful in the diagnostic strategy. If cholestasis occurs in the elderly, drug-induced cholestatic disease should be suspected, whereas if it occurs in young people with risk factors, cholestatic viral hepatitis is the most likely diagnosis. During the first trimester of pregnancy cholestasis may occur in hiperemesis gravidorum, and in the third trimester of gestation cholestasis of pregnancy should be suspected. A familial history of recurrent cholestasis points to benign recurrent intrahepatic cholestasis. The occurrence of intrahepatic cholestasis in a mid-dle-aged woman is a frequent presentation of primary biliary cirrhosis, whereas primary sclerosing cholangitis should be suspected in young males with inflammatory bowel disease. The presence of vascular spider nevi, ascites, and a history of alcohol abuse should point to alcoholic hepatitis. Neonatal cholestasis syndromes include CMV, toxoplasma and rubinfections or metabolic defects such as cystic fibrosis, α1-antitripsin deficiency, bile acid synthesis defects, or biliary atresia. The treatment of cholestasis should include a management of complications such as pruritus, osteopenia and correction of fat soluble vitamin deficiencies. When hepatocellular failure or portal hypertension-related complications occur, liver transplantation should be considered.Ante la presencia de colestasis, se debe

  5. AP-1 Inhibition by SR 11302 Protects Human Hepatoma HepG2 Cells from Bile Acid-Induced Cytotoxicity by Restoring the NOS-3 Expression

    Science.gov (United States)

    González-Rubio, Sandra; Linares, Clara I.; Aguilar-Melero, Patricia; Rodríguez-Perálvarez, Manuel; Montero-Álvarez, José L.

    2016-01-01

    The harmful effects of bile acid accumulation occurring during cholestatic liver diseases have been associated with oxidative stress increase and endothelial nitric oxide synthase (NOS-3) expression decrease in liver cells. We have previously reported that glycochenodeoxycholic acid (GCDCA) down-regulates gene expression by increasing SP1 binding to the NOS-3 promoter in an oxidative stress dependent manner. In the present study, we aimed to investigate the role of transcription factor (TF) AP-1 on the NOS-3 deregulation during GCDCA-induced cholestasis. The cytotoxic response to GCDCA was characterized by 1) the increased expression and activation of TFs cJun and c-Fos; 2) a higher binding capability of these at position -666 of the NOS-3 promoter; 3) a decrease of the transcriptional activity of the promoter and the expression and activity of NOS-3; and 4) the expression increase of cyclin D1. Specific inhibition of AP-1 by the retinoid SR 11302 counteracted the cytotoxic effects induced by GCDCA while promoting NOS-3 expression recovery and cyclin D1 reduction. NOS activity inhibition by L-NAME inhibited the protective effect of SR 11302. Inducible NOS isoform was no detected in this experimental model of cholestasis. Our data provide direct evidence for the involvement of AP-1 in the NOS-3 expression regulation during cholestasis and define a critical role for NOS-3 in regulating the expression of cyclin D1 during the cell damage induced by bile acids. AP-1 appears as a potential therapeutic target in cholestatic liver diseases given its role as a transcriptional repressor of NOS-3. PMID:27490694

  6. Characterization of the role of ABCG2 as a bile acid transporter in liver and placenta.

    Science.gov (United States)

    Blazquez, Alba G; Briz, Oscar; Romero, Marta R; Rosales, Ruben; Monte, Maria J; Vaquero, Javier; Macias, Rocio I R; Cassio, Doris; Marin, Jose J G

    2012-02-01

    ABCG2 is involved in epithelial transport/barrier functions. Here, we have investigated its ability to transport bile acids in liver and placenta. Cholylglycylamido fluorescein (CGamF) was exported by WIF-B9/R cells, which do not express the bile salt export pump (BSEP). Sensitivity to typical inhibitors suggested that CGamF export was mainly mediated by ABCG2. In Chinese hamster ovary (CHO cells), coexpression of rat Oatp1a1 and human ABCG2 enhanced the uptake and efflux, respectively, of CGamF, cholic acid (CA), glycoCA (GCA), tauroCA, and taurolithocholic acid-3-sulfate. The ability of ABCG2 to export these bile acids was confirmed by microinjecting them together with inulin in Xenopus laevis oocytes expressing this pump. ABCG2-mediated bile acid transport was inhibited by estradiol 17β-d-glucuronide and fumitremorgin C. Placental barrier for bile acids accounted for 14-fold increased maternal cholanemia induced by obstructive cholestasis in pregnant rats. In rat placenta, the expression of Abcg2, which was much higher than that of Bsep, was not affected by short-term cholestasis. In pregnant rats, fumitremorgin C did not affect uptake/secretion of GCA by the liver but inhibited its fetal-maternal transfer. Compared with wild-type mice, obstructive cholestasis in pregnant Abcg2(-/-) knockout mice induced similar bile acid accumulation in maternal serum but higher accumulation in placenta, fetal serum, and liver. In conclusion, ABCG2 is able to transport bile acids. The importance of this function depends on the relative expression in the same epithelium of other bile acid exporters. Thus, ABCG2 may play a key role in bile acid transport in placenta, as BSEP does in liver. PMID:22096226

  7. Investigation of Homocystein Plasma Level in Cholestatic Rat and Its Effect on Nitric Oxide Secretion in Liver

    Directory of Open Access Journals (Sweden)

    N. Mirazi

    2005-04-01

    Full Text Available Homocystein (Hcy,one of the thio-amino acid is known as a risk factor in some cardiovascular diseases with releasing O2 radical . It has also been reported that; there is oxidative stress effects of Hcy in cholestasis. The aim of this study is to determine plasma Hcy alteration and nitric oxide (NO in liver and its effects on pathologic disfunction.In this study , 150 Spraque – Dawley male rats with 200 ± 20g body weight were used in the experiments and they were randomly divided in three control, SHAM and bile duct ligation (BDL groups (n= 10-12 . In 7th,14th,21st and 28th days cholestasis was observed in BDL group,the animal were anesthetized with ether and then blood samples were taken from heart directly and analysed for cystein , methionine by HPLC and HPLC-UV. Two hours before blood sampling , 40 and 100 mg/kg methionine were injected (I.P .All data are expressed as mean  SEM. Statistical evaluation of data performed by SPSS soft ware using analysis of variance (ANOVA followed by post hoc test. P-values less than 0.05 were considered statistically significant .The results suggest that billirubin and hepatic enzymes were significantly elevated in BDL rats compared with SHAM and controls (P<0.05. Homocystein concentration was significantly rised in 14th day in BDL group (P<0.05. The plasma cystein and methionine level were significantly elevated in BDL rats compared with SHAM and control groups ( p = 0.01 . Plasma nitrate / nitrite ratio were significantly increased in BDL rats compared with SHAM and control rats (P<0.05. With these data we suppose that some of the systemic oxidative stresses in BDL rat model of cholestasis contributes possibly through NO-dependent mechanisms disorders.

  8. Use of a low-density microarray for studying gene expression patterns induced by hepatotoxicants on primary cultures of rat hepatocytes.

    Science.gov (United States)

    de Longueville, Francoise; Atienzar, Franck A; Marcq, Laurence; Dufrane, Simon; Evrard, Stéphanie; Wouters, Lydia; Leroux, Florence; Bertholet, Vincent; Gerin, Brigitte; Whomsley, Rhys; Arnould, Thierry; Remacle, José; Canning, Mickael

    2003-10-01

    In the field of gene expression analysis, DNA microarray technology is having a major impact on many different areas including toxicology. For instance, a number of studies have shown that transcription profiling can generate the information needed to assign a compound to a mode-of-action class. In this study, we investigated whether compounds inducing similar toxicological endpoints produce similar changes in gene expression. In vitro primary rat hepatocytes were exposed to 11 different hepatotoxicants: acetaminophen, amiodarone, clofibrate, erythromycin estolate, isoniazid, alpha-naphtylylisothiocyanate, beta-naphtoflavone, 4-pentenoic acid, phenobarbital, tetracycline, and zileuton. These molecules were selected on the basis of their variety of hepatocellular effects observed such as necrosis, cholestasis, steatosis, and induction of CYP P450 enzymes. We used a low-density DNA microarray containing 59 genes chosen as relevant toxic and metabolic markers. The in vitro gene expression data generated in this study were generally in good agreement with the literature, which mainly concerns in vivo data. Furthermore, gene expression profiles observed in this study have been confirmed for several genes by real-time PCR assays. All the tested drugs generated a specific gene expression profile. Our results show that even with a relatively limited gene set, gene expression profiling allows a certain degree of classification of compounds with similar hepatocellular toxicities such as cholestasis, necrosis. The clustering analysis revealed that the compounds known to cause steatosis were linked, suggesting that they functionally regulate similar genes and possibly act through the same mechanisms of action. On the other hand, the drugs inducing necrosis and cholestasis were pooled in the same cluster. The drugs arbitrarily classified as the CYP450 inducers formed individual clusters. In conclusion, this study suggests that low-density microarrays could be useful in

  9. Cholesterol metabolism in cholestatic liver disease and liver transplantation: From molecular mechanisms to clinical implications.

    Science.gov (United States)

    Nemes, Katriina; Åberg, Fredrik; Gylling, Helena; Isoniemi, Helena

    2016-08-01

    The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein (LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X (Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers - such as cholesterol precursor sterols, plant sterols, and cholestanol - may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation. PMID:27574546

  10. EGFR participates downstream of ERα in estradiol-17β-D-glucuronide-induced impairment of Abcc2 function in isolated rat hepatocyte couplets.

    Science.gov (United States)

    Barosso, Ismael R; Zucchetti, Andrés E; Miszczuk, Gisel S; Boaglio, Andrea C; Taborda, Diego R; Roma, Marcelo G; Crocenzi, Fernando A; Sánchez Pozzi, Enrique J

    2016-04-01

    Estradiol-17β-D-glucuronide (E17G) induces acute endocytic internalization of canalicular transporters, including multidrug resistance-associated protein 2 (Abcc2) in rat, generating cholestasis. Several proteins organized in at least two different signaling pathways are involved in E17G cholestasis: one pathway involves estrogen receptor alpha (ERα), Ca(2+)-dependent protein kinase C and p38-mitogen activated protein kinase, and the other pathway involves GPR30, PKA, phosphoinositide 3-kinase/AKT and extracellular signal-related kinase 1/2. EGF receptor (EGFR) can potentially participate in both pathways since it interacts with GPR30 and ERα. Hence, the aim of this study was to analyze the potential role of this receptor and its downstream effectors, members of the Src family kinases in E17G-induced cholestasis. In vitro, EGFR inhibition by Tyrphostin (Tyr), Cl-387785 or its knockdown with siRNA strongly prevented E17G-induced impairment of Abcc2 function and localization. Activation of EGFR was necessary but not sufficient to impair the canalicular transporter function, whereas the simultaneous activation of EGFR and GPR30 could impair Abcc2 transport. The protection of Tyr was not additive to that produced by the ERα inhibitor ICI neither with that produced by Src kinase inhibitors, suggesting that EGFR shared the signaling pathway of ERα and Src. Further analysis of ERα, EGFR and Src activations induced by E17G, demonstrated that ERα activation precedes that of EGFR and EGFR activation precedes that of Src. In conclusion, activation of EGFR is a key factor in the alteration of canalicular transporter function and localization induced by E17G and it occurs before that of Src and after that of ERα.

  11. Secondary Sclerosing Cholangitis in Critically Ill Patients: Clinical Presentation, Cholangiographic Features, Natural History, and Outcome: A Series of 16 Cases.

    Science.gov (United States)

    Leonhardt, Silke; Veltzke-Schlieker, Wilfried; Adler, Andreas; Schott, Eckart; Eurich, Dennis; Faber, Wladimir; Neuhaus, Peter; Seehofer, Daniel

    2015-12-01

    Secondary sclerosing cholangitis in critically ill patients (SSC-CIP) is an important differential diagnosis in patients presenting with cholestasis and PSC-like cholangiographic changes in endoscopic retrograde cholangiography (ERC). As a relatively newly described entity, SSC-CIP is still underdiagnosed, and the diagnosis is often delayed. The present study aims to improve the early detection of SSC-CIP and the identification of its complications.A total of 2633 records of patients who underwent or were listed for orthotopic liver transplantation at the University Hospital Charité, Berlin, were analyzed retrospectively. The clinical presentation and outcome (mean follow-up 62.7 months) of the 16 identified SSC-CIP cases were reviewed.Cholestasis was the first sign of SSC-CIP. GGT was the predominant enzyme of cholestasis. Hypercholesterolemia occurred in at least 75% of the patients. SSC-CIP provoked a profound weight loss (mean 18 kg) in 94% of our patients. SSC-CIP was diagnosed by ERC in all patients. The 3 different cholangiographic features detected correspond roughly to the following stages: (I) evidence of biliary casts, (II) progressive destruction of intrahepatic bile ducts, and (III) picture of pruned tree. Biliary cast formation is a hallmark of SSC-CIP and was seen in 87% of our cases. In 75% of the patients, the clinical course was complicated by cholangiosepsis, cholangitic liver abscesses, acalculous cholecystitis, or gallbladder perforation. SSC-CIP was associated with worse prognosis; transplant-free survival was ∼40 months (mean).Because of its high rate of serious complications and unfavorable prognosis, it is imperative to diagnose SSC-CIP early and to differentiate SSC-CIP from other types of sclerosing cholangitis. Specific characteristics enable identification of SSC-CIP. Early cooperation with a transplant center and special attention to biliary complications are required after diagnosis of SSC-CIP. PMID:26656347

  12. Effects of structural injure in the bile bacterial contamination after balloon transduodenal sphincteroplasty (papillary dilation in dogs

    Directory of Open Access Journals (Sweden)

    Zavadinack Netto Martin

    2006-01-01

    Full Text Available PURPOSE: To evaluate, in dogs, the biliary sphincter subjected to dilation by hydrostatic balloon by the point of view of structural alterations of the papilla and the biochemestry and bacterial contamination of the bile. METHODS: Twenty dogs were submitted to laparotomy, duodenotomy, and enlargement of the major duodenal papilla- GA(n=10 - with balloon of 8mm inflated with pressure of 0,5atm, during 2 minutes or to the sham procedure - GB(n=10. Blood samples collected on times t(0day, t(7days and t(28days were subjected to dosages of alkaline phosphatase (ALP and gamma-glutamyltransferase (GGT for cholestasis evaluation. The collected material from the gall bladder at the same times were registered and numbered to be submitted to culture in BHI, blood agar (rich, non-selective element and Mac Conkey (selective element for Gram-negative bacillus. On the 28th day three fragments of the papilla were tranversally cut by the choledoc axis 3mm from the duodenal papilla and the cuts, stained with hematoxylin-eosin and Masson's tricome, were evaluated according to their inflammatory reaction. RESULTS: The GGT and ALP averages on the three periods in the groups A and B did not show significant differences, not being characterizes the cholestasis. The bacterian contamination was significantly higher in GA (2,19 than in GB (1,96; the contamination was lower in the initial time compared with 7 and 28 days (t0cholestasis. The morphologic lesions are more intense in the late phase, not associated with an eventual papilla esthenosis.

  13. Pyrazinamide Induced Rat Cholestatic Liver Injury through Inhibition of FXR Regulatory Effect on Bile Acid Synthesis and Transport.

    Science.gov (United States)

    Guo, Hong-Li; Hassan, Hozeifa M; Zhang, Yun; Dong, Si-Zhe; Ding, Ping-Ping; Wang, Tao; Sun, Li-Xin; Zhang, Lu-Yong; Jiang, Zhen-Zhou

    2016-08-01

    Pyrazinamide (PZA) is an indispensable first-line drug used for the treatment of tuberculosis which may cause serious hepatotoxicity; however, the mechanisms underlying these toxicities are poorly understood. Cholestasis plays an important role in drug-induced liver injury. Since there were no previous published works reported cholestasis and PZA hepatotoxicity relationship, this study aimed to identify whether PZA can induce liver injury with characterized evidences of cholestasis and to clarify expression changes of proteins related to both bile acid synthesis and transport in PZA-induced liver injury. PZA (2 g/kg) was administered for 7 consecutive days by oral gavage. Results showed there were 2-fold elevation in both ALT and AST serum levels in PZA-treated rats. In addition, a 10-fold increment in serum total bile acid was observed after PZA administration. The mRNA and protein expressions of bile acid synthesis and transport parameters were markedly altered, in which FXR, Bsep, Mrp2, Mdr2, Ostα/β, Oatp1a1, Oatp1b2, and Cyp8b1 were decreased (P < .05), while Mrp3, Ntcp, Oatp1a4, and Cyp7a1 were increased (P < .05). Moreover, treatment with the FXR agonist obeticholic acid (OCA) generated obvious reductions in serum ALT, AST, and TBA levels in PZA-treated rats. Those effects were due to transcriptional regulation of pre-mentioned target genes by OCA. Taken together, these results suggested that PZA-induced cholestatic liver injury was related to FXR inhibition, leading to the dysfunction in bile acid synthesis and transport. PMID:27255380

  14. Ursodeoxycholic acid treatment of vanishing bile duct syndromes

    Institute of Scientific and Technical Information of China (English)

    Thomas Pusl; Ulrich Beuers

    2006-01-01

    Vanishing bile duct syndromes (VBDS) are characterized by progressive loss of small intrahepatic ducts caused by a variety of different diseases leading to chronic cholestasis, cirrhosis, and premature death from liver failure. The majority of adult patients with VBDS suffer from primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Ursodeoxycholic acid (UDCA), a hydrophilic dihydroxy bile acid, is the only drug currently approved for the treatment of patients with PBC, and anticholestatic effects have been reported for several other cholestatic syndromes. Several potential mechanisms of action of UDCA have been proposed including stimulation of hepatobiliary secretion, inhibition of apoptosis and protection of cholangiocytes against toxic effects of hydrophobic bile acids.

  15. THE DIAGNOSIS OF ACUTE GALLSTONE PANCREATITIS

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    Elena Gologan

    2009-05-01

    Full Text Available Acute gallstone pancreatitis is a severe form of pancreatitis caused by an ampullary blocked gallstone. The clinical course combines elements of severe pancreatitis and obstructive jaundice with angiocolitis. Complications are very frequent in the absence of spontaneous, interventional or surgical desobstruction. The diagnosis is based upon clinical features, biochemical paramethers with cholestasis, hyperamilasemia, hyperamilasuria, hyperlipasemia, metabolic disorders. Imagistic assay is undoubtful necessary for the diagnosis; it allows identifying most of the complications, and some of these investigations are very useful in the desobstruction procedures, done at proper moment.

  16. POSTOPERATIVE COMPLICATIONS IN LIVER TRANSPLANT RECIPIENTS: MODERN СCONSIDERATIONS OF PATHOGENESIS AND MAIN AREAS OF PROPHYLAXIS AND TREATMENT

    Directory of Open Access Journals (Sweden)

    M. Sh. Khubutia

    2009-01-01

    Full Text Available The article presents analysis of scientific literature of the last 15 years about complications after orthotopic liver transplantation, depending on the severity of the initial status of recipient and expression of metabolic and functional disorders. Factors affecting the development of vascular complications (arterial and venous thrombosis, biliary complications (cholestasis, cholangitis, immune response (acute rejection, and also surgical and infectious complications and functional insufficiency of the graft are analyzed in this review. The necessity to improve monitoring in the immediate post transplant period is considered. 

  17. Obstetriske dermatoser

    DEFF Research Database (Denmark)

    Hjortø, Sofie; Skov, Lone; Lykke, Jacob Alexander

    2014-01-01

    The specific dermatoses of pregnancy are rare and consist of pemphigoid gestationis (PG), intrahepatic cholestasis of pregnancy (ICP), polymorphic eruption of pregnancy and atopic eruption of pregnancy. The dermatoses are characterized by pruritus, and they are important to recognize since PG...... and ICP increase the risk of prematurity, fetal distress and stillbirth. Diagnosis is based on medical history, morphology, blood sample and biopsy. The dermatoses are treated with respectively ursodeoxycholic acid (in case of ICP) and steroids. Breast-feeding is recommended and induction of labour...

  18. Obstetric dermatoses

    DEFF Research Database (Denmark)

    Hjortø, Sofie; Skov, Lone; Lykke, Jacob Alexander

    2014-01-01

    The specific dermatoses of pregnancy are rare and consist of pemphigoid gestationis (PG), intrahepatic cholestasis of pregnancy (ICP), polymorphic eruption of pregnancy and atopic eruption of pregnancy. The dermatoses are characterized by pruritus, and they are important to recognize since PG...... and ICP increase the risk of prematurity, fetal distress and stillbirth. Diagnosis is based on medical history, morphology, blood sample and biopsy. The dermatoses are treated with respectively ursodeoxycholic acid (in case of ICP) and steroids. Breast-feeding is recommended and induction of labour...

  19. [Correction of hepatic dysfunction as pre-treatment before systemic chemotherapy in patients with bile duct neoplasms].

    Science.gov (United States)

    Iakovlev, A Iu; Chichkanova, A S; Ulitin, D N; Mokrov, K V; Akulenko, S V

    2012-01-01

    This prospective randomized study incorporates 141 surgical department patients with hepatobiliary tumors. The 1st group patients received 800 ml/day of remaxol. The 2nd1 group patients received Ringer solution and 10% glucose at 1:1 ratio. The subgroups included: 1 subgroup-with pre-operative cholecysto- or choledochostomia and B-subgroup-without pre-operative interventions. The combined surgical and pharmaceutical correction of bile passage, bilirubinemia, cholestasis and cytolysis by remaxole leads to better hepatic dysfunction correction and allows better timing of chemotherapy in bile passage tumors. PMID:23607215

  20. Antibodies against p53 protein in serum of patients with benign or malignant pancreatic and biliary diseases.

    OpenAIRE

    Laurent-Puig, P.; Lubin, R; Semhoun-Ducloux, S; Pelletier, G.; Fourre, C; Ducreux, M.; Briantais, M J; Buffet, C; Soussi, T

    1995-01-01

    Specific markers for pancreatic or biliary cancer have been developed in the past few years. Ca 19-9 has a good sensitivity but it is also increased in benign cholestasis. Mutations in the p53 gene are commonly reported in pancreatic cancer and can be detected by a serological analysis. The aim of this work was to find out the sensitivity and specificity of this new assay in diagnosing cancer of the pancreas or of the bile ducts. The presence of antibodies against p53 was determined by an enz...

  1. Vanishing bile duct and Stevens-Johnson syndrome associated with ciprofloxacin treated with tacrolimus

    Institute of Scientific and Technical Information of China (English)

    Gokhan Okan; Serpil Yaylaci; Onder Peker; Sabahattin Kaymakoglu; Murat Saruc

    2008-01-01

    Stevens-Johnson syndrome (SJS) is a serious and potentially life-threatening disease. Vanishing bile duct syndrome (VBDS) is a rare cause of progressive cholestasis. Both syndromes are mostly related with drugs. We report a case of a patient withciprofloxacin-induced SJS and acute onset of VBDS,and reviewed the related literature. It is the first case of ciprofloxacin-induced VBDS successfully treatedwith tacrolimus. This case reminds physicians of the importance of drug reactions, their severity, techniques for diagnosis and methods of management.

  2. Exon-skipping and mRNA decay in human liver tissue: molecular consequences of pathogenic bile salt export pump mutations

    OpenAIRE

    Carola Dröge; Heiner Schaal; Guido Engelmann; Daniel Wenning; Dieter Häussinger; Ralf Kubitz

    2016-01-01

    The bile salt export pump BSEP mediates bile formation. Over 150 BSEP mutations are associated with progressive familial intrahepatic cholestasis type 2 (PFIC-2), with few characterised specifically. We examined liver tissues from two PFIC-2 patients compound heterozygous for the splice-site mutation c.150 + 3A > C and either c.2783_2787dup5 resulting in a frameshift with a premature termination codon (child 1) or p.R832C (child 2). Splicing was analysed with a minigene system and mRNA sequen...

  3. The feline bile salt export pump: a structural and functional comparison with canine and human Bsep/BSEP

    OpenAIRE

    Beusekom, C.D. van; Heuvel, J.J.M.W. van den; Koenderink, J.B.; Schrickx, J.A.; Russel, F G M

    2013-01-01

    Background The bile salt export pump (BSEP/ABCB11) is the primary transporter for the excretion of bile acids from hepatocytes into bile. In human, inhibition of BSEP by drugs has been related to drug-induced cholestasis and subsequent cytotoxic effects. The role of BSEP in canine and feline liver diseases has not been studied in detail, but the same mechanism of inhibition by drugs as in humans could play a role in veterinary medicine. The aim of this study was to investigate the functional ...

  4. Chinese Expert Consensus for the Diagnosis and Treatment of Cholestatic Liver Disease

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    Cholestatic liver disease (CLD) is a common problem in clinical practice with the main manifestation being cholestasis.Recently,there has been a steady increase in knowledge associated with the diagnosis and treatment of CLD.Therefore,the experts in China were organized by the editorial board of Chinese Journal of Experimental and Clinical Infectious Diseases (Electronic Edition),Chinese Journal of Liver Diseases (Electronic Edition) and Infection International (Electronic Edition) to collect and analyze relevant research,ultimately resulting in the development of this work (Chinese Expert consensus for the diagnosis and treatment of CLDs,also abbreviated as consensus).

  5. Ultrasound-guided percutaneous cholecysto-cholangiography for the exclusion of biliary atresia in infants

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Kyung Min; Ryeom, Hun Kyu; Choe, Byung Ho; Kim, Kap Cheol; Kim, Jong Yeol; Lee, Jong Min; Kim, Hye Jeong; Lee, Hee Jung [Kyungpook National University Hospital, Daegu (Korea, Republic of)

    2006-08-15

    The aim of this study is to determine the feasibility and effectiveness of performing an ultrasound-guided percutaneous cholecysto-cholangiogram (PCC) for excluding biliary atresia as the cause of neonatal jaundice. Between Oct. 2003 and Feb. 2005, six ultrasound-guided PCC procedures were performed to five jaundiced infants (4 females and 1 male; mean age: 60 days old) for whom possibility of biliary atresia could not be ruled out by the DISIDA scan as the cause of their neonatal jaundice. Gallbladder puncture was performed under ultrasound guidance with a 23-gauge needle. Contrast material injection during fluoroscopic examination was performed after dilatation of the gallbladder lumen with normal saline under ultrasound guidance. The criteria used for excluding biliary atresia were complete visualization of the extrahepatic biliary trees and/or contrast excretion into the duodenum. The complications and final diagnosis was assessed according to the clinical and laboratory findings. The procedures were successful in all the patients without any complication. Biliary atresia could be ruled out in all the patients. The final diagnosis was neonatal cytomegalovirus hepatitis in two patients, total parenteral nutrition-associated cholestasis in two patients, and combined cytomegalovirus hepatitis and total parenteral nutrition-associated cholestasis in one patient. Ultrasound-guided PCC is a feasible and effective method for the early definitive exclusion of biliary atresia as the cause of neonatal jaundice. By the technique of injecting normal saline before contrast injection, PCC can be done even in a totally collapsed or very small gallbladder.

  6. Endoscopic management of biliary fascioliasis: a case report

    Directory of Open Access Journals (Sweden)

    Kasnazani Kalandar A

    2010-03-01

    Full Text Available Abstract Introduction Fasciola hepatica, an endemic parasite common in Iraq and its neighboring countries, is a very rare cause of cholestasis worldwide. Humans can become definitive hosts of this parasite through their ingestion of a contaminated water plant, for example, contaminated watercress. Symptoms of cholestasis may appear suddenly and, in some cases, are preceded by long periods of fever, eosinophilia, and vague gastrointestinal symptoms. Here we report the case of a woman with a sudden onset of symptoms of cholangitis. Her infection was proved by endoscopic retrograde cholangiography to be due to Fasciola hepatica infestation. Case presentation A 38-year-old Kurdish woman from the northern region of Iraq presented with fever, right upper quadrant abdominal pain, and jaundice. An examination of the patient revealed elevated total serum bilirubin and liver enzymes. An ultrasonography also showed a dilatation of her common bile duct. During endoscopic retrograde cholangiopancreatography, a filling defect was identified in her common bile duct. After sphincterotomy and balloon extraction, one live Fasiola hepatica was extracted and physically removed. Conclusion Fasciola hepatica should be a part of the differential diagnosis of common bile duct obstruction. When endoscopic retrograde cholangiopancreatography is available, the disease can be easily diagnosed and treated.

  7. Successful orthotopic liver transplantation in an adult patient with sickle cell disease and review of the literature

    Directory of Open Access Journals (Sweden)

    Morey Blinder

    2013-05-01

    Full Text Available Sickle cell disease can lead to hepatic complications ranging from acute hepatic crises to chronic liver disease including intrahepatic cholestasis, and iron overload. Although uncommon, intrahepatic cholestasis may be severe and medical treatment of this complication is often ineffective. We report a case of a 37 year-old male patient with sickle cell anemia, who developed liver failure and underwent successful orthotopic liver transplantation. Both pre and post-operatively, he was maintained on red cell transfusions. He remains stable with improved liver function 42 months post transplant. The role for orthotopic liver transplantation is not well defined in patients with sickle cell disease, and the experience remains limited. Although considerable challenges of post-transplant graft complications remain, orthotopic liver transplantation should be considered as a treatment option for sickle cell disease patients with end-stage liver disease who have progressed despite conventional medical therapy. An extended period of red cell transfusion support may lessen the post-operative complications.

  8. Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease

    International Nuclear Information System (INIS)

    Highlights: •FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. •Activation of FXR attenuated alcohol-induced liver injury and steatosis. •Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients

  9. Metformin interferes with bile acid homeostasis through AMPK-FXR crosstalk.

    Science.gov (United States)

    Lien, Fleur; Berthier, Alexandre; Bouchaert, Emmanuel; Gheeraert, Céline; Alexandre, Jeremy; Porez, Geoffrey; Prawitt, Janne; Dehondt, Hélène; Ploton, Maheul; Colin, Sophie; Lucas, Anthony; Patrice, Alexandre; Pattou, François; Diemer, Hélène; Van Dorsselaer, Alain; Rachez, Christophe; Kamilic, Jelena; Groen, Albert K; Staels, Bart; Lefebvre, Philippe

    2014-03-01

    The nuclear bile acid receptor farnesoid X receptor (FXR) is an important transcriptional regulator of bile acid, lipid, and glucose metabolism. FXR is highly expressed in the liver and intestine and controls the synthesis and enterohepatic circulation of bile acids. However, little is known about FXR-associated proteins that contribute to metabolic regulation. Here, we performed a mass spectrometry-based search for FXR-interacting proteins in human hepatoma cells and identified AMPK as a coregulator of FXR. FXR interacted with the nutrient-sensitive kinase AMPK in the cytoplasm of target cells and was phosphorylated in its hinge domain. In cultured human and murine hepatocytes and enterocytes, pharmacological activation of AMPK inhibited FXR transcriptional activity and prevented FXR coactivator recruitment to promoters of FXR-regulated genes. Furthermore, treatment with AMPK activators, including the antidiabetic biguanide metformin, inhibited FXR agonist induction of FXR target genes in mouse liver and intestine. In a mouse model of intrahepatic cholestasis, metformin treatment induced FXR phosphorylation, perturbed bile acid homeostasis, and worsened liver injury. Together, our data indicate that AMPK directly phosphorylates and regulates FXR transcriptional activity to precipitate liver injury under conditions favoring cholestasis. PMID:24531544

  10. Marked Direct Hyperbilirubinemia due to Ceftriaxone in an Adult with Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    Daniyeh Khurram

    2015-01-01

    Full Text Available Drugs are a significant cause of liver injury. Drug-induced liver injury (DILI can cause acute hepatitis, cholestasis, or a mixed pattern. Ceftriaxone is a commonly used antibiotic and has been associated with reversible biliary sludge, pseudolithiasis, and cholestasis. A 32-year-old male with sickle cell disease was admitted to the hospital for acute sickle cell crisis. On the second day of hospitalization, he developed cough and rhonchi with chest X-ray revealing right middle lobe infiltrates. Ceftriaxone and azithromycin were initiated. Subsequently, he developed conjugated hyperbilirubinemia and mild transaminitis. His total bilirubin trended upwards from 3.3 mg/dL on admission to 17 mg/dL. It was predominantly conjugated bilirubin, with preadmission bilirubin levels of 3-4 mg/dL. His transaminases were mildly elevated as well compared to previous levels. Extensive workup for bilirubin elevation was unremarkable. Ceftriaxone was switched to levofloxacin and the hyperbilirubinemia improved. On ambulatory follow-up, his bilirubin remained below 4 mg/dL. Ceftriaxone may be associated with marked direct hyperbilirubinemia particularly in sickle cell patients with chronic liver chemistry abnormalities. In the case of elevated bilirubin with concomitant ceftriaxone use, elimination of the offending agent should be considered.

  11. Elevated copper impairs hepatic nuclear receptor function in Wilson’s disease

    Science.gov (United States)

    Wooton-Kee, Clavia Ruth; Jain, Ajay K.; Wagner, Martin; Grusak, Michael A.; Finegold, Milton J.; Lutsenko, Svetlana; Moore, David D.

    2015-01-01

    Wilson’s disease (WD) is an autosomal recessive disorder that results in accumulation of copper in the liver as a consequence of mutations in the gene encoding the copper-transporting P-type ATPase (ATP7B). WD is a chronic liver disorder, and individuals with the disease present with a variety of complications, including steatosis, cholestasis, cirrhosis, and liver failure. Similar to patients with WD, Atp7b–/– mice have markedly elevated levels of hepatic copper and liver pathology. Previous studies have demonstrated that replacement of zinc in the DNA-binding domain of the estrogen receptor (ER) with copper disrupts specific binding to DNA response elements. Here, we found decreased binding of the nuclear receptors FXR, RXR, HNF4α, and LRH-1 to promoter response elements and decreased mRNA expression of nuclear receptor target genes in Atp7b–/– mice, as well as in adult and pediatric WD patients. Excessive hepatic copper has been described in progressive familial cholestasis (PFIC), and we found that similar to individuals with WD, patients with PFIC2 or PFIC3 who have clinically elevated hepatic copper levels exhibit impaired nuclear receptor activity. Together, these data demonstrate that copper-mediated nuclear receptor dysfunction disrupts liver function in WD and potentially in other disorders associated with increased hepatic copper levels. PMID:26241054

  12. Targeting naproxen to non-parenchymal liver cells protects against endotoxin induced liver damage.

    Science.gov (United States)

    Lebbe, C; Reichen, J; Wartna, E; Sägesser, H; Poelstra, K; Meijer, D K

    1997-01-01

    Non-steroidal anti-inflammatory drugs (NSAID's) could be of value in the treatment of liver disease; however, their use in this situation is limited by renal side effects. Therefore, we explored whether naproxen covalently bound to human serum albumin NAP-HSA) was able to reduce toxicity in an acute model of liver disease induced by endotoxin in rats pretreated with Corynebacterium parvum. In the isolated perfused liver of such animals endotoxin induced cholestasis (0.62 +/- 0.05 vs. 0.24 +/- 0.09 microliter.min-1.g liver-1; p < 0.05), increased vascular resistance (11300 +/- 400 vs. 311000 +/- 2000 dyn.s.cm-5; p < 0.05) and alanine aminotransferase release (22 +/- 9 vs. 149 +/- IU/l; p < 0.05). At the highest dose tested (22 mg/kg, corresponding to 6.0 mumoles naproxen), NAP-HSA normalized ALT release (21 +/- 10 IU/l: p < 0.05) while an equimolar amount of non-targeted naproxen was only partially effective (56 +/- 19 IU/l). A conventional dose of naproxen similarly prevented transaminase release. Cholestasis and increased vascular resistance were also prevented by NAP-HSA. Drug targeting by linking drugs to proteins is a potentially useful approach to maximizing drug effect while minimizing adverse events; this could be particularly useful for compounds with potentially serious adverse effects in patients with chronic liver disease such as the nonsteroidal anti-inflammatory agents used in the present study. PMID:9169987

  13. Perturbation of bile acid homeostasis is an early pathogenesis event of drug induced liver injury in rats.

    Science.gov (United States)

    Yamazaki, Makoto; Miyake, Manami; Sato, Hiroko; Masutomi, Naoya; Tsutsui, Naohisa; Adam, Klaus-Peter; Alexander, Danny C; Lawton, Kay A; Milburn, Michael V; Ryals, John A; Wulff, Jacob E; Guo, Lining

    2013-04-01

    Drug-induced liver injury (DILI) is a significant consideration for drug development. Current preclinical DILI assessment relying on histopathology and clinical chemistry has limitations in sensitivity and discordance with human. To gain insights on DILI pathogenesis and identify potential biomarkers for improved DILI detection, we performed untargeted metabolomic analyses on rats treated with thirteen known hepatotoxins causing various types of DILI: necrosis (acetaminophen, bendazac, cyclosporine A, carbon tetrachloride, ethionine), cholestasis (methapyrilene and naphthylisothiocyanate), steatosis (tetracycline and ticlopidine), and idiosyncratic (carbamazepine, chlorzoxasone, flutamide, and nimesulide) at two doses and two time points. Statistical analysis and pathway mapping of the nearly 1900 metabolites profiled in the plasma, urine, and liver revealed diverse time and dose dependent metabolic cascades leading to DILI by the hepatotoxins. The most consistent change induced by the hepatotoxins, detectable even at the early time point/low dose, was the significant elevations of a panel of bile acids in the plasma and urine, suggesting that DILI impaired hepatic bile acid uptake from the circulation. Furthermore, bile acid amidation in the hepatocytes was altered depending on the severity of the hepatotoxin-induced oxidative stress. The alteration of the bile acids was most evident by the necrosis and cholestasis hepatotoxins, with more subtle effects by the steatosis and idiosyncratic hepatotoxins. Taking together, our data suggest that the perturbation of bile acid homeostasis is an early event of DILI. Upon further validation, selected bile acids in the circulation could be potentially used as sensitive and early DILI preclinical biomarkers. PMID:23360887

  14. Endoscopic sphincterotomy in patients with stenosis of ampulla of Vater: Three-year follow-up of exocrine pancreatic function and clinical symptoms

    Institute of Scientific and Technical Information of China (English)

    Nils Ewald; Axel Michael Marzeion; Reinhard Georg Bretzel; Hans Ulrich Kloer; Philip Daniel Hardt

    2007-01-01

    AIM: To investigate retrospectively the long-term effect of endoscopic sphincterotomy (ES) including exocrine pancreatic function in patients with stenosis of ampulla of Vater.METHODS: After diagnostic endoscopic retrograde cholangiopancreatography (ERCP) and ES because of stenosis of the ampulla of Vater (SOD Type I), follow-up examinations were performed in 60 patients (mean follow-up time 37.7 mo). Patients were asked about clinical signs and symptoms at present and before intervention using a standard questionnaire. Before and after ES exocrine pancreatic function was assessed by determination of immunoreactive fecal elastase 1. Serum enzymes indicating cholestasis as well as serum lipase and amylase were measured.RESULTS: Eighty percent of patients reported an improvement in their general condition after ES. The fecal elastase 1 concentrations (FEC) in all patients increased significantly after ES. This effect was even more marked in patients with pathologically low concentrations (< 200 ng/g) of fecal elastase prior to ES. The levels of serum lipase and amylase as well as serum alcaline phosphatase (AP) and gamma-glutamyltranspeptidase (GGT) decreased significantly after ES.CONCLUSION: The results of this study demonstrate that patients with stenosis of the ampulla of Vater can be successfully treated with endoscopic sphincterotomy. The positive effect is not only indicated by sustained improvement of clinical symptoms and cholestasis but also by improvement of exocrine pancreatic function.

  15. Concept on the pathogenesis and treatment of primary biliary cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Vasiliy Ivanovich Reshetnyak

    2006-01-01

    Primary biliary cirrhosis (PBC) is an organ-specific autoimmune disease that predominantly affects women and is characterized by chronic, progressive destruction of small intrahepatic bile ducts with portal inflammation and ultimately fibrosis, leading to liver failure in the absence of treatment. Little is known about the etiology of PBC. PBC is characterized by anti-mitochondrial antibodies and destruction of intrahepatic bile ducts. The serologic hallmark of PBC is the presence of auto-antibodies to mitochondria, especially to the E2 component of the pyruvate dehydrogenase complex (PDC). Current theories on the pathogenesis of PBC favor the hypothesis that the disease develops as a result of an inappropriate immune response following stimulation by an environmental or infectious agent. Some reports suggest that xenobiotics and viral infections may induce PBC. The pathogenetic mechanism is believed to be caused by a defect in immunologic tolerance, resulting in the activation and expansion of self-antigen specific T and B lymphocyte clones and the production of circulating autoantibodies in addition to a myriad of cytokines and other inflammatory mediators.This leads to ductulopenia and persistent cholestasis, by developing end-stage hepatic-cell failure. In this review are given our own and literary data about mechanisms of development of intrahepatic cholestasis and possible ways of its correction.

  16. Xenobiotic-sensing nuclear receptors CAR and PXR as drug targets in cholestatic liver disease.

    Science.gov (United States)

    Kakizaki, Satoru; Takizawa, Daichi; Tojima, Hiroki; Yamazaki, Yuichi; Mori, Masatomo

    2009-11-01

    Cholestasis results in the intrahepatic retention of cytotoxic bile acid and it can thus lead to liver injury and/or liver fibrosis. Cholestatic liver damage is counteracted by a variety of intrinsic hepatoprotective mechanisms including a complex network of drug metabolizing enzymes and transporters. During the last decade, much progress has been made in dissecting the mechanisms which regulate the hepatic xeno- and endobiotic metabolism by nuclear receptors. The xenobiotic receptors CAR and PXR are two important members of the NR1I nuclear receptor family. They function as sensors of toxic byproducts derived from the endogenous metabolism and of exogenous chemicals, in order to enhance their elimination. Ligands for both receptors, including phenobarbital, have already been used to treat cholestatic liver diseases before the mechanisms of these receptors were revealed. Furthermore, Yin Zhi Huang, a traditional Chinese herbal medicine, which has been used to prevent and treat neonatal jaundice, was identified to be a CAR ligand which also accelerates bilirubin clearance. Therefore, CAR and PXR have a protective effect on cholestasis by activating both detoxification enzymes and transporters. As a result, novel compounds targeting CAR and PXR with specific effects and fewer side effects will therefore be useful for the treatment of cholestatic liver diseases. This article will review the current knowledge on xenobiotic-sensing nuclear receptors CAR and PXR, while also discussing their potential role in the treatment of cholestatic liver diseases. PMID:19925451

  17. Ultrasound-guided percutaneous cholecysto-cholangiography for the exclusion of biliary atresia in infants

    International Nuclear Information System (INIS)

    The aim of this study is to determine the feasibility and effectiveness of performing an ultrasound-guided percutaneous cholecysto-cholangiogram (PCC) for excluding biliary atresia as the cause of neonatal jaundice. Between Oct. 2003 and Feb. 2005, six ultrasound-guided PCC procedures were performed to five jaundiced infants (4 females and 1 male; mean age: 60 days old) for whom possibility of biliary atresia could not be ruled out by the DISIDA scan as the cause of their neonatal jaundice. Gallbladder puncture was performed under ultrasound guidance with a 23-gauge needle. Contrast material injection during fluoroscopic examination was performed after dilatation of the gallbladder lumen with normal saline under ultrasound guidance. The criteria used for excluding biliary atresia were complete visualization of the extrahepatic biliary trees and/or contrast excretion into the duodenum. The complications and final diagnosis was assessed according to the clinical and laboratory findings. The procedures were successful in all the patients without any complication. Biliary atresia could be ruled out in all the patients. The final diagnosis was neonatal cytomegalovirus hepatitis in two patients, total parenteral nutrition-associated cholestasis in two patients, and combined cytomegalovirus hepatitis and total parenteral nutrition-associated cholestasis in one patient. Ultrasound-guided PCC is a feasible and effective method for the early definitive exclusion of biliary atresia as the cause of neonatal jaundice. By the technique of injecting normal saline before contrast injection, PCC can be done even in a totally collapsed or very small gallbladder

  18. MR cholangio-pancreatography using an open, low magnetic field of 0.2 Tesla. Early clinical results and comparison with a higher magnetic field (1.5 Tesla) and with ERCP

    International Nuclear Information System (INIS)

    Aim: To evaluate MR cholangio-pancreatography (MRCP) using an open low magnetic field apparatus in normals and in patients with mechanical cholestasis. Methods: MRCP was performed on five normals and on 30 patients, using both an 0.2 Tesla and 1.5 Tesla apparatus. With the low field system, rapid acquisition by relaxation enhancement was used, for the high field system, half Fourier acquisition single shot turbo spin-echo sequences were used. In all patients, sonography and ERCP of PTC was performed; 23 underwent surgery. Results: In all normals it was possible to show the bile duct, hepatic duct, gall bladder and intrahepatic ducts of the first order. Using the high field system, second order ducts could be shown and sometimes third order ducts. In the patients, MRCP, using either system, demonstrated all 21 obstructive sites due to tumours or stenoses. Stones were shown in 69% by the low field system and in 88% by the high field system. Conclusion: MRCP can be successfully carried out using the low field system. In the presence of mechanical cholestasis, image quality is adequate for the localisation of stenoses and occlusions, and using an open magnet, is suitable for planning further intervention. (orig.)

  19. Acute renal failure in obstructive diseases of the extrahepatic biliary ducts.

    Science.gov (United States)

    Acalovschi, I; Chirileanu, T

    1984-01-01

    A series of 46 patients with obstructive disease of the bile ducts complicated by acute renal failure (ARF) is presented. The patients exhibited obstructive jaundice with prevalence of conjugated bilirubine. In 80% of the cases biliary obstruction was associated with cholangitis. Disturbances of the liver function (from mild cholestasis to biliary cirrhosis) were also present. The renal damage was due to biliary disorders and was either present on admission (33 cases) or developed postoperatively (13 cases). Most of the patients presented nonoliguric ARF as well as poor perfusion resulting from decreased circulating blood volume (dehydration and electrolyte loss). Among the criteria used to determine the type of ARF, the urinary/plasma creatinine ratio less than 10 and urinary/plasma osmolarity ratio less than 1.1 were the most valuable. Management of ARF by dialysis alone was not satisfactory. Attention is called to the surgical treatment of the biliary disorder as being essential to prognosis. Patients not treated by radical surgery died in proportion of 87 to 100%. From the rest of 18 patients in whom the operation provided an adequate biliary drainage, in 15 the renal function was restored and 12 survived. Better prognosis in these patients was dependent not only on the ability to cure the cholestasis and infection, but on the early surgical treatment. The ultimate prognosis depends on the improvement of the liver function.

  20. Dexamethasone pretreatment attenuates lung and kidney injury in cholestatic rats induced by hepatic ischemia/reperfusion.

    Science.gov (United States)

    Zhou, Liangyi; Yao, Xiangqing; Chen, Yanling

    2012-02-01

    Hepatic ischemia followed by reperfusion (IR) results in mild to severe organ injury, in which tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) seem to be involved. Thus, we aim to assess the influence of hepatic ischemia/reperfusion injury on remote organs in addition to cholestasis and consider the possible efficacy of steroid pretreatment in reducing the injury. A common bile duct ligation model was done on 24 male Sprague-Dawley rats. After 7 days, the rats were divided randomly into control group, IR group, and dexamethasone (DEX) group. The IR group showed significant increases in serum alanine aminotransferase, aspartate aminotransferase, and creatinine levels compared with the control and DEX groups. By ELISA techniques, higher levels of TNF-α and IL-1β in lung and kidney tissues were measured in the IR group than in the control and DEX groups, these were verified by immunohistochemistry. The lung histology of the IR group rats showed neutrophil infiltration, interstitial edema, and alveolar wall thickening. Kidney histology of the IR group rats showed vacuolization of the proximal tubular epithelial cells and tubular dilatation with granular eosinophilic casts. Better morphological aspects were observed in the DEX-pretreated animals. Minimal lesions were observed in the control. The results suggest that hepatic ischemia/reperfusion injury in cholestatic rats induced lung and kidney injuries. Pretreatment with dexamethasone reduced the IR-induced injury in addition to cholestasis.

  1. Efficacy of extracorporeal albumin dialysis for acute kidney injury due to cholestatic jaundice nephrotoxicity.

    Science.gov (United States)

    Sens, Florence; Bacchetta, Justine; Rabeyrin, Maud; Juillard, Laurent

    2016-01-01

    We report a case of a 37-year-old man with Maturity Onset Diabetes of the Youth (MODY) type 5, admitted for an episode of cholestasis and a simultaneous acute kidney injury (AKI). Chronic liver disease was due to a mutation in the transcription factor 2 (TCF2) gene, thus highlighting the need for a close liver follow-up in these patients. AKI was attributed to a cholemic nephropathy based on the following rationale: (1) alternative diagnoses were actively ruled out; (2) the onset of AKI coincided with the onset of severe hyperbilirubinaemia; (3) renal pathology showed large bile tubular casts and a marked tubular necrosis and (4) creatinine serum dramatically decreased when bilirubin levels improved after the first sessions of extracorporeal albumin dialysis (ECAD), thus suggesting its role in renal recovery. Even though cholestasis can precipitate renal injury, the diagnosis of cholemic nephropathy could require a renal biopsy at times. Future studies should confirm the benefits of ECAD in cholemic nephropathy. PMID:27389722

  2. Elevated copper impairs hepatic nuclear receptor function in Wilson's disease.

    Science.gov (United States)

    Wooton-Kee, Clavia Ruth; Jain, Ajay K; Wagner, Martin; Grusak, Michael A; Finegold, Milton J; Lutsenko, Svetlana; Moore, David D

    2015-09-01

    Wilson's disease (WD) is an autosomal recessive disorder that results in accumulation of copper in the liver as a consequence of mutations in the gene encoding the copper-transporting P-type ATPase (ATP7B). WD is a chronic liver disorder, and individuals with the disease present with a variety of complications, including steatosis, cholestasis, cirrhosis, and liver failure. Similar to patients with WD, Atp7b⁻/⁻ mice have markedly elevated levels of hepatic copper and liver pathology. Previous studies have demonstrated that replacement of zinc in the DNA-binding domain of the estrogen receptor (ER) with copper disrupts specific binding to DNA response elements. Here, we found decreased binding of the nuclear receptors FXR, RXR, HNF4α, and LRH-1 to promoter response elements and decreased mRNA expression of nuclear receptor target genes in Atp7b⁻/⁻ mice, as well as in adult and pediatric WD patients. Excessive hepatic copper has been described in progressive familial cholestasis (PFIC), and we found that similar to individuals with WD, patients with PFIC2 or PFIC3 who have clinically elevated hepatic copper levels exhibit impaired nuclear receptor activity. Together, these data demonstrate that copper-mediated nuclear receptor dysfunction disrupts liver function in WD and potentially in other disorders associated with increased hepatic copper levels.

  3. Bile composition in Alagille Syndrome and PFIC patients having Partial External Biliary Diversion

    Directory of Open Access Journals (Sweden)

    Thompson Richard J

    2008-10-01

    Full Text Available Abstract Background Partial External Biliary Diversion (PEBD is a surgical intervention to treat children with Progressive Familial Intrahepatic Cholestasis (PFIC and Alagille syndrome (AGS. PEBD can reduce disease progression, and examining the alterations in biliary lipid composition may be a prognostic factor for outcome. Methods Biliary lipid composition and the clinical course of AGS and PFIC patients were examined before and after PEBD. Results Pre-PEBD bile from AGS patients had greater chenodeoxycholic/cholic acid (CDCA/CA, bile salt, cholesterol and phospholipid concentrations than PFIC patients. AGS patients, and PFIC patients with familial intrahepatic cholestasis 1 (FIC1 genotype, responded better to PEBD than PFIC patients with bile salt export protein (BSEP genotype. After successful PEBD, AGS patients have higher biliary lipid concentrations than PFIC patients and PEBD also increases biliary phospholipid concentrations in FIC1 patients. Conclusion Both AGS and FIC1 patients can benefit from PEBD, and preserved biliary phospholipid concentrations may be associated with better outcomes post-PEBD.

  4. Repeated Oral Administration of Oleanolic Acid Produces Cholestatic Liver Injury in Mice

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    Yasha Xu

    2013-03-01

    Full Text Available Oleanolic acid (OA is a triterpenoid and a fantastic molecule with many beneficial effects. However, high-doses and long-term use can produce adverse effects. This study aimed to characterize the hepatotoxic potential of OA. Mice were given OA at doses of 100–3,000 µmol/kg (45–1,350 mg/kg, po for 10 days, and the hepatotoxicity was determined by serum biochemistry, histopathology, and toxicity-related gene expression via real-time RT-PCR. Animal body weight loss was evident at OA doses of 1,000 µmol/kg and above. Serum alanine aminotransferase activities were increased in a dose-dependent manner, indicative of hepatotoxicity. Serum total bilirubin concentrations were increased, indicative of cholestasis. OA administration produced dose-dependent pathological lesions to the liver, including inflammation, hepatocellular apoptosis, necrosis, and feathery degeneration indicative of cholestasis. These lesions were evident at OA doses of 500 µmol/kg and above. Real-time RT-PCR revealed that OA produced dose-dependent increases in acute phase proteins (MT-1, Ho-1, Nrf2 and Nqo1, decreases in bile acid synthesis genes (Cyp7a1 and Cyp8b1, and decreases in liver bile acid transporters (Ntcp, Bsep, Oatp1a1, Oatp1b2, and Ostβ. Thus, the clinical use of OA and OA-type triterpenoids should balance the beneficial effects and toxicity potentials.

  5. Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Weibin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Institutes of Biomedical Science, Fudan University, Shanghai 200032 (China); Zhu, Bo; Peng, Xiaomin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Zhou, Meiling, E-mail: meilingzhou2012@gmail.com [Department of Radiology, Zhongshan Hospital of Fudan University and Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Jia, Dongwei, E-mail: jiadongwei@fudan.edu.cn [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Gu, Jianxin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Institutes of Biomedical Science, Fudan University, Shanghai 200032 (China)

    2014-01-03

    Highlights: •FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. •Activation of FXR attenuated alcohol-induced liver injury and steatosis. •Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients.

  6. Evaluation of liver enzyme levels in workers exposed to vinyl chloride vapors in a petrochemical complex: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Dolati Mandana

    2007-08-01

    Full Text Available Abstract Background Polyvinyl chloride is used in production and manufacturing of many essential tools (e.g. plastic pipes, photography films, etc.. Its production is impossible without the use of vinyl chloride monomer (VCM, which can cause liver damage in long-term. In this study we intend to assess the effects of mild to moderate long term exposure to VCM on liver and to assess the importance of liver enzyme measurements as a screening tool. Methods In this study, liver enzyme levels of 52 workers were compared to 48 control workers using the T-test. The cases all worked in a PVC production unit in a petrochemical complex and the controls were randomly selected from office personnel of the same complex. A questionnaire was also filled in about information such as age, weight, work history, etc. in both groups. Results Mean comparisons for ALP and GGT using T-test showed statistically significant differences between the two groups. For AST, ALT and bilirubin (total, direct the mean was higher in the case group but this difference was not statistically significant. Discussion This study showed that mild exposure to VCM can cause mild liver cholestasis. So, using cholestasis assessment tests such as ALP and GGT should be considered in periodic assessment of liver function in PVC producing units.

  7. Evaluation Of Gonadotropin And Testosterone Hormons In Adult Male Cholestatic Rats

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    Nasiri E

    2003-11-01

    Full Text Available Obstructive cholestasis is associated with overproduction of endogenous opioids (EOP, nitric oxide (NO, and cytokins in the blood streams. Therefore we investigated the relationship between obstructive cholestasis and function of germ cells in adult male rats."nMaterial and Methods: To study this, we used three groups of animals: No-surgery, Sham-surgery, and surgical ligation of the bile duct. After 3 weeks all animal were killed by ether, serum concentrations of FSH, LH and testosterone were determined by Radioimmunoassay, apoptosis was evaluated by DNA fragmentation detected by in situ terminal deoxynucloetidyl Transfrase-mediated dUTP nike end labeling (TUNEL."nResults: The mean of FSH level in cholestatic, control and sham groups were 13.22+ 1.038, 18.14+ 1.276, and 16.92+ 1.072 ng/ml, respectively. The mean of LH level in cholestatic, control and sham groups were 0.83 + 0.21, 2.058 ± 0.26, and 1.84 + 0.17 ng/ml, respectively. In addition, the mean of testosterone level in cholestatic, control and sham groups were 1.52 ± 0.16, 2.41 ± 0.18, and 2.31 + 0.14 ng/ml, respectively. The results of this study were indicated that serum FSH, LH and testosterone were significantly lower in cholestatic than control and sham groups (p=0.0195, P= 0.0029, and P=0.0023, respectively. However there was no significant difference in apoptotic index between all of groups (P=0.195. The apoptotic index in cholestatic, control and sham rats were 9.897± 1.374, 7.086 + 0.91, and 7.729 + 1.101, respectively. "nConclusion: These findings have been shown which as obstructive cholestasis was decreased the levels of serum gonadotropins and testosterone but it has no significant effector testicular germinal cells apoptosis."n"n"n"n 

  8. Hormesis in Cholestatic Liver Disease; Preconditioning with Low Bile Acid Concentrations Protects against Bile Acid-Induced Toxicity.

    Directory of Open Access Journals (Sweden)

    Esther M Verhaag

    Full Text Available Cholestasis is characterized by accumulation of bile acids and inflammation, causing hepatocellular damage. Still, liver damage markers are highest in acute cholestasis and drop when this condition becomes chronic, indicating that hepatocytes adapt towards the hostile environment. This may be explained by a hormetic response in hepatocytes that limits cell death during cholestasis.To investigate the mechanisms that underlie the hormetic response that protect hepatocytes against experimental cholestatic conditions.HepG2.rNtcp cells were preconditioned (24 h with sub-apoptotic concentrations (0.1-50 μM of various bile acids, the superoxide donor menadione, TNF-α or the Farsenoid X Receptor agonist GW4064, followed by a challenge with the apoptosis-inducing bile acid glycochenodeoxycholic acid (GCDCA; 200 μM for 4 h, menadione (50 μM, 6 h or cytokine mixture (CM; 6 h. Levels of apoptotic and necrotic cell death, mRNA expression of the bile salt export pump (ABCB11 and bile acid sensors, as well as intracellular GCDCA levels were analyzed.Preconditioning with the pro-apoptotic bile acids GCDCA, taurocholic acid, or the protective bile acids (tauroursodeoxycholic acid reduced GCDCA-induced caspase-3/7 activity in HepG2.rNtcp cells. Bile acid preconditioning did not induce significant levels of necrosis in GCDCA-challenged HepG2.rNtcp cells. In contrast, preconditioning with cholic acid, menadione or TNF-α potentiated GCDCA-induced apoptosis. GCDCA preconditioning specifically reduced GCDCA-induced cell death and not CM- or menadione-induced apoptosis. The hormetic effect of GCDCA preconditioning was concentration- and time-dependent. GCDCA-, CDCA- and GW4064- preconditioning enhanced ABCB11 mRNA levels, but in contrast to the bile acids, GW4064 did not significantly reduce GCDCA-induced caspase-3/7 activity. The GCDCA challenge strongly increased intracellular levels of this bile acid, which was not lowered by GCDCA

  9. [Animal experiments with 99mTc-diethyl-HIDA in acute complete bile duct occlusion (author's transl)].

    Science.gov (United States)

    Bähre, M; Biersack, H J; Breuel, H P; Degen, H; Busch, F; Grouls, V; Lindstaedt, H; Thelen, M

    1979-10-01

    In order to establish whether a complete obstructive jaundice can abolish the accumulation of diethyl-HIDA (EHIDA) in the liver parenchyma, the common bile duct was ligated in 14 mongrel dogs. Before as well as at regular intervals after ligature of the common bile duct, a sequence scintigraphy was performed with 2 mCi 99mTc-EHIDA. For evaluation, time-activity curves (Tmax, T1/2), and analogue scintigrams as well as laboratory parameters were used for assessment. Up to seven weeks after ligation of the common bile duct, there was a marked accumulation of EHIDA in the liver parenchyma. The relative liver uptake (liver/background ratio) fell from 8.9 to 2.7, whereas conversely the cholestasis indicators aP and bilirubine rose markedly. Tmax did not show any significant alterations, whereas T1/2 was prolonged from about one week after ligation. Because of the duct ligation, there was no excretion of activity into the intestines. Immediately after ligation of the common bile duct, the gallbladder was shown up as a "hot" area in which the majority of the applied activity appeared from about one hour p.i. Begining with the fifth to the seventh day after ligation, the gallbladder was seen as a "cold" area in the liver paraenchyma. Bilirubine and aP were raised by about 50 times the initial value. With longer lasting cholestasis, the scintigram no longer altered whereas bilirubine and aP rose further. Histological examination after ligation for more than five weeks showed slight alterations as a whole. Gamma-GT and in particular GPT were likewise slightly raised compared to bilirubine and aP. The conclusion was drawn from this that the good accumulation of EHIDA in the liver parenchyma which is to be observed without exception even in cholestasis lasting for several weeks could be explained by a relatively slight hepatocellular damage. Only when there is a consecutive parenchymal damage in extrahepatic jaundice, accumulation of EHIDA in the liver can be abolished.

  10. Imaging of Drug-induced Complications in the Gastrointestinal System.

    Science.gov (United States)

    McGettigan, Melissa J; Menias, Christine O; Gao, Zhenqiang J; Mellnick, Vincent M; Hara, Amy K

    2016-01-01

    Drug-induced injury commonly affects the gastrointestinal and hepatobiliary systems because of the mechanisms of absorption and metabolism. In pill esophagitis, injury is frequently related to direct contact with the esophageal mucosa, resulting in small superficial ulcers in the mid esophagus. Nonsteroidal anti-inflammatory drugs can lead to gastrointestinal tract ulcers and small bowel mucosal diaphragms (thin weblike strictures). Injury to the pancreatic and hepatobiliary systems can manifest as pancreatitis, acute or chronic hepatitis, cholestasis, or steatosis and steatohepatitis (which may progress to cirrhosis). Various drugs may also insult the hepatic vasculature, resulting in Budd-Chiari and sinusoidal obstructive syndromes. Focal lesions such as hepatic adenomas may develop after use of oral contraceptives or anabolic steroids. Ultrasonography, computed tomography, and magnetic resonance imaging can aid in diagnosis of drug-induced injuries and often are necessary to exclude other causes. PMID:26761532

  11. Clinical characteristics of caroli's disease

    Institute of Scientific and Technical Information of China (English)

    Ozlem Yonem; Yusuf Bayraktar

    2007-01-01

    Caroli's disease is a rare congenital condition characterized by non-obstructive saccular or fusiform dilatation of larger intrahepatic bile ducts. Cholangitis,liver cirrhosis, and cholangiocarcinoma are its potential complications. The diagnosis of Caroli's disease depends on demonstrating that the cystic lesions are in continuity with the biliary tree which can be showed by ultrasonography, computerized tomography, endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiography or magnetic resonance cholangiopancreatography. Treatment of Caroli's disease relies on the location of the biliary abnormalities. While localized forms confined to one lobe can be treated with surgery, liver transplantation is the only effective modality for diffuse forms. Although a rare disorder;Caroli's disease should always be considered in the differential diagnosis of chronic cholestasis of unknown cause.

  12. Adenosine kinase deficiency with neurodevelopemental delay and recurrent hepatic dysfunction: A case report

    Science.gov (United States)

    Shakiba, Marjan; Mahjoub, Fatemeh; Fazilaty, Hassan; Rezagholizadeh, Fereshteh; Shakiba, Arghavan; Ziadlou, Maryam; Gahl, William A.; Behnam, Babak

    2016-01-01

    Hypermethioninemia may be benign, present as a nonspecific sign of nongenetic conditions such as liver failure and prematurity, or a severe, progressive inborn error of metabolism. Genetic causes of hypermethioninemia include mitochondrial depletion syndromes caused by mutations in the MPV17 and DGUOK genes and deficiencies of cystathionine β-synthase, methionine adenosyltransferase types I and III, glycine N-methyltransferase, S-adenosylhomocysteine hydrolase, citrin, fumarylacetoacetate hydrolase, and adenosine kinase. Here we present a 3-year old girl with a history of poor feeding, irritability, respiratory infections, cholestasis, congenital heart disease, neurodevelopmental delay, hypotonia, sparse hair, facial dysmorphisms, liver dysfunction, severe hypermethioninemia and mild homocystinemia. Genetic analysis of the adenosine kinase (ADK) gene revealed a previously unreported variant (c.479–480 GA>TG) resulting in a stop codon (p.E160X) in ADK. A methionine-restricted diet normalized the liver function test results and improved her hypotonia. PMID:27500280

  13. Heavy flow autochtonic case of hepatitis E in elderly men

    Directory of Open Access Journals (Sweden)

    S. V. Baramzina

    2016-01-01

    Full Text Available The article presents an analysis of the first clinical cases of acute hepatitis E autochtonic on the territory of the Kirov region. HEV-infection was diagnosed in 76 year old male, not to travel outside the region and the country for a long time, eat a lot of fresh fruit. A feature of the disease in non-endemic region was: severe course of hepatitis E in the elderly, with the development of clinic of acute liver failure and encephalopathy, the presence of the expressed syndrome cytolysis, cholestasis, hepatic-cell failure.Timely treatment of a patient for medical care, the lack of severe somatic diseases, chronic liver disease and adequate pathogenetic therapy helped to keep the patient’s life. In deciphering undifferentiated acute hepatitis in the elderly should be included in the scheme of examination and determination HEV RNA, a/HEV IgM and G.

  14. Clinical findings, dental treatment, and improvement in quality of life for a child with Rothmund-Thomson syndrome.

    Science.gov (United States)

    De Oliveira, Katharina Morant Holanda; Silva, Raquel Assed Bezerra; Carvalho, Fabricio Kitazono; Silva, Lea Assed Bezerra; Nelson-Filho, Paulo; Queiroz, Alexandra Mussolino

    2016-01-01

    The purpose of this study was to report the clinical findings, dental treatment, and improvement in quality of life for a child with Rothmund-Thomson syndrome. The patient had alopecia, delayed speech, low weight and height, cholestasis, and iron deficiency anemia. Furthermore, there were carious lesions and darkened spots on all primary molars. Microdontia of a premolar was observed at the radiographic examination. The patient and family had no commitment to her oral health and dental treatment at first appointments. Oral hygiene instructions, composite restorations, endodontic treatments, teeth extractions, and stainless steel crown installations were performed. The patient was followed up for 7 years through the present due to other possible future clinical findings associated with the syndrome. An improvement in social aspects was observed after removal of toothache and improved esthetics. Such patients need continuous periodic services, which contributes to improving the quality of life in both buccal and general aspects.

  15. Prevention of vitamin K deficiency bleeding in breastfed infants: lessons from the Dutch and Danish biliary atresia registries

    DEFF Research Database (Denmark)

    Hasselt, P.M. van; Koning, T.J. de; Vries, E. de;

    2008-01-01

    OBJECTIVE: Newborns routinely receive vitamin K to prevent vitamin K deficiency bleeding. The efficacy of oral vitamin K administration may be compromised in infants with unrecognized cholestasis. We aimed to compare the risk of vitamin K deficiency bleeding under different prophylactic regimens...... in infants with biliary atresia. PATIENTS AND METHODS: From Dutch and Danish national biliary atresia registries, we retrieved infants who were either breastfed and received 1 mg of oral vitamin K at birth followed by 25 microg of daily oral vitamin K prophylaxis (Netherlands, 1991-2003), 2 mg of oral...... vitamin K at birth followed by 1 mg of weekly oral prophylaxis (Denmark, 1994 to May 2000), or 2 mg of intramuscular prophylaxis at birth (Denmark, June 2000-2005) or were fed by formula. We determined the absolute and relative risk of severe vitamin K deficiency and vitamin K deficiency bleeding...

  16. 新生儿胃肠外营养相关性胆汁淤积症临床分析

    Institute of Scientific and Technical Information of China (English)

    李向红

    2004-01-01

    @@ 胃肠外营养(parenteral nutrition,PN)的出现使许多胃肠功能衰竭的患儿得以存活.随着胃肠外营养技术的提高,其代谢和感染并发症日渐减少,而与其相关的肝胆功能的损害日益受到重视.胃肠外营养相关性胆汁淤积症(parenteral nutrition associated cholestasis,PNAC)是新生儿期长期PN的最常见并发症,部分可发展为肝功能衰竭而死亡[1].本文就我科1999~2003年10例新生儿PNAC进行临床分析.

  17. Diagnostic challenges of Wilson's disease presenting as acute pancreatitis, cholangitis, and jaundice.

    Science.gov (United States)

    Nussinson, Elchanan; Shahbari, Azmi; Shibli, Fahmi; Chervinsky, Elena; Trougouboff, Philippe; Markel, Arie

    2013-11-27

    Wilson's disease is a rare disorder of copper transport in hepatic cells, and may present as cholestatic liver disease; pancreatitis and cholangitis are rarely associated with Wilsons's disease. Moreover, cases of Wilson's disease presenting as pigmented gallstone pancreatitis have not been reported in the literature. In the present report, we describe a case of a 37-year-old man who was admitted with jaundice and abdominal pain. The patient was diagnosed with acute pancreatitis, cholangitis, and obstructive jaundice caused by pigmented gallstones that were detected during retrograde cholangiopancreatography. However, because of his long-term jaundice and the presence of pigmented gallstones, the patient underwent further evaluation for Wilson's disease, which was subsequently confirmed. This patient's unique presentation exemplifies the overlap in the clinical and laboratory parameters of Wilson's disease and cholestasis, and the difficulties associated with their differentiation. It suggests that Wilson's disease should be considered in patients with pancreatitis, cholangitis, and severe protracted jaundice caused by pigmented gallstones.

  18. Common bile duct schwannoma: A case report and review of literature

    Institute of Scientific and Technical Information of China (English)

    Luigi Fenoglio; Rodolfo Brizio; Felice Borghi; Sara Severini; Paola Cena; Elena Migliore; Christian Bracco; Fulvio Pomero; Sergio Panzone; Giovan Battista Cavallero; Alberto Silvestri

    2007-01-01

    Schwannoma is a myelin sheath tumor complicated with neurofibroma, neurofibromatosis and neurogenic sarcoma. Peripheral nerve sheath tumors represent 2%-6% of gastrointestinal tract stromal tumors (GIST),but there are deficient data about location of neurogenic tumors in the biliary system and only nine cases of schwannoma of the extrahepatic biliary tract have been reported. These tumors are clinically non-specific. They are usually symptomatic by compressing the close or adjacent structures when being retroperitoneal, and their preoperative diagnosis is extremely difficult. This paper reviews the literature data and describes a case of schwannoma of the common bile duct associated with cholestasis in a healthy young woman, diagnosed and treated in our department. This case is of interest on account of the complexity of its diagnosis and the atypical macroscopic growth pattern of the tumor.

  19. Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance.

    Science.gov (United States)

    Fang, Sungsoon; Suh, Jae Myoung; Reilly, Shannon M; Yu, Elizabeth; Osborn, Olivia; Lackey, Denise; Yoshihara, Eiji; Perino, Alessia; Jacinto, Sandra; Lukasheva, Yelizaveta; Atkins, Annette R; Khvat, Alexander; Schnabl, Bernd; Yu, Ruth T; Brenner, David A; Coulter, Sally; Liddle, Christopher; Schoonjans, Kristina; Olefsky, Jerrold M; Saltiel, Alan R; Downes, Michael; Evans, Ronald M

    2015-02-01

    The systemic expression of the bile acid (BA) sensor farnesoid X receptor (FXR) has led to promising new therapies targeting cholesterol metabolism, triglyceride production, hepatic steatosis and biliary cholestasis. In contrast to systemic therapy, bile acid release during a meal selectively activates intestinal FXR. By mimicking this tissue-selective effect, the gut-restricted FXR agonist fexaramine (Fex) robustly induces enteric fibroblast growth factor 15 (FGF15), leading to alterations in BA composition, but does so without activating FXR target genes in the liver. However, unlike systemic agonism, we find that Fex reduces diet-induced weight gain, body-wide inflammation and hepatic glucose production, while enhancing thermogenesis and browning of white adipose tissue (WAT). These pronounced metabolic improvements suggest tissue-restricted FXR activation as a new approach in the treatment of obesity and metabolic syndrome. PMID:25559344

  20. Primary Biliary Cirrhosis: Environmental Risk Factors

    Directory of Open Access Journals (Sweden)

    Deepti Dronamraju

    2010-01-01

    Full Text Available Primary biliary cirrhosis (PBC is an autoimmune disease of unclear etiology. It is a chronic, progressive condition that causes intrahepatic ductal destruction ultimately leading to symptoms of cholestasis, cirrhosis and liver failure. The disease predominantly affects middle aged Caucasian women. It has a predilection to certain regions and is found in higher incidences in North America and Northern Europe. It also has a genetic predisposition with a concordance rate of 60% among monozygotic twins. Combinations of genetic and environmental factors are proposed in the pathogenesis of this disease with a compelling body of evidence that suggests a role for both these factors. This review will elucidate data on the proposed environmental agents involved the disease's pathogenesis including xenobiotic and microbial exposure and present some of the supporting epidemiologic data.

  1. Oral Vancomycin Therapy in a Child with Primary Sclerosing Cholangitis and Severe Ulcerative Colitis

    Science.gov (United States)

    Buness, Cynthia; Miloh, Tamir

    2016-01-01

    Primary sclerosing cholangitis (PSC), a rare progressive liver disease characterized by cholestasis and bile duct fibrosis, has no accepted, effective therapy known to delay or arrest its progression. We report a 15 year old female patient diagnosed with PSC and moderate chronic active ulcerative colitis (UC) who achieved normalization of her liver enzymes and bile ducts, and resolution of her UC symptoms with colonic mucosal healing, after treatment with a single drug therapy of the antibiotic oral vancomycin. We postulate that the oral vancomycin may be acting both as an antibiotic by altering the intestinal microbiome and as an immunomodulator. Oral vancomycin may be a promising treatment for PSC that needs to be further studied in randomized trials. PMID:27738604

  2. Characterization of animal models for primary sclerosing cholangitis (PSC).

    Science.gov (United States)

    Fickert, Peter; Pollheimer, Marion J; Beuers, Ulrich; Lackner, Carolin; Hirschfield, Gideon; Housset, Chantal; Keitel, Verena; Schramm, Christoph; Marschall, Hanns-Ulrich; Karlsen, Tom H; Melum, Espen; Kaser, Arthur; Eksteen, Bertus; Strazzabosco, Mario; Manns, Michael; Trauner, Michael

    2014-06-01

    Primary sclerosing cholangitis (PSC) is a chronic cholangiopathy characterized by biliary fibrosis, development of cholestasis and end stage liver disease, high risk of malignancy, and frequent need for liver transplantation. The poor understanding of its pathogenesis is also reflected in the lack of effective medical treatment. Well-characterized animal models are utterly needed to develop novel pathogenetic concepts and study new treatment strategies. Currently there is no consensus on how to evaluate and characterize potential PSC models, which makes direct comparison of experimental results and effective exchange of study material between research groups difficult. The International Primary Sclerosing Cholangitis Study Group (IPSCSG) has therefore summarized these key issues in a position paper proposing standard requirements for the study of animal models of PSC.

  3. Pathogenesis of primary sclerosing cholangitis and advances in diagnosis and management.

    Science.gov (United States)

    Eaton, John E; Talwalkar, Jayant A; Lazaridis, Konstantinos N; Gores, Gregory J; Lindor, Keith D

    2013-09-01

    Primary sclerosing cholangitis (PSC), first described in the mid-1850s, is a complex liver disease that is heterogeneous in its presentation. PSC is characterized by chronic cholestasis associated with chronic inflammation of the biliary epithelium, resulting in multifocal bile duct strictures that can affect the entire biliary tree. Chronic inflammation leads to fibrosis involving the hepatic parenchyma and biliary tree, which can lead to cirrhosis and malignancy. The etiology of PSC is not fully understood, which in part explains the lack of effective medical therapy for this condition. However, we have begun to better understand the molecular pathogenesis of PSC. The recognition of specific clinical subtypes and their pattern of progression could improve phenotypic and genotypic classification of the disease. We review our current understanding of this enigmatic disorder and discuss important topics for future studies.

  4. Activity of gammaglutamiltransferase in addicts of Dnipropetrovsk province

    Directory of Open Access Journals (Sweden)

    E. B. Motorya

    2012-07-01

    Full Text Available Change of GGT activity is studied in patients using alcohol and narcotic substances. 2878 residents of the Dnipropetrovsk province are examined. The increase of GGT activity is marked in 528 cases (18.3 %. It may be caused by increasing synthesis as a result of activating enzymes which ensure this process. The activation may be initiated by alcohol and medicines, by the damage of cellular membranes under the action of toxic agents, under ischemia and infection-induced liver injury, and by the detachment of enzymes from cellular membranes affected by detergent bile acids under the cholestasis. Ordinary values for major part of examined patients (81.7 % may be explained by only episodic taking alcohol and narcotic drugs, which was not affect the liver parenchyma, and also by effective treatment normalized the enzyme’s activity.

  5. [Liver cirrhosis in metabolic disorders].

    Science.gov (United States)

    Tazawa, Y

    1994-01-01

    The most early cirrhosis is observed in newborns with neonatal hemachromatosis. Early cirrhosis occurs in hereditary tyrosinemia type I, peroxisomal diseases and glycogen storage disease (type IV). In Wilson's disease, a case complicated with cirrhosis was reported in a 4-year-old patient. Slowly progressive cirrhosis is seen in patients with familial progressive intrahepatic cholestasis. Focal biliary cirrhosis is found in cystic fibrosis of the pancreas. Moreover, many other metabolic disorders, except for urea cycle disorders, are occasionally or rarely complicated with cirrhosis. Early diagnosis and proper management could prevent the development of cirrhosis in patients with galactosemia, hereditary fructose intolerance, etc. The occurrence of hepatoma must be monitored in these patients. Liver transplantation is indicated in a part of the patients with cirrhosis. PMID:8114297

  6. 新生儿胆汁淤积症

    Institute of Scientific and Technical Information of China (English)

    施诚仁

    2001-01-01

    @@ 新生儿胆汁淤积症(neonatal cholestasis)是指新生儿因某种原因导致正常胆汁流减少,伴有直接胆红素增高而引起临床上以黄疸为主要表现的一种征候群.Iglesias(1999)把这种现象归为“婴儿不正常胆流”,即三“B”征(Bad Baby Bile).新生儿内科最多见的病因是肝炎和近期广泛应用的肠外静脉高营养的合并症,外科疾病则是先天性胆道闭锁.本文着重介绍新生儿胆汁淤积症的处理.

  7. Selective screening of 650 high risk Iranian patients for detection of inborn error of metabolism

    Directory of Open Access Journals (Sweden)

    Narges Pishva

    2015-02-01

    Full Text Available Objective: Although metabolic diseases individually are rare ,but overall have an incidence of 1/2000 and can cause devastating and irreversible effect if not diagnosed early and treated promptly. selective screening is an acceptable method for detection of these multi presentation diseases. Method: using panel neonatal screening for detection of metabolic diseases in 650 high risk Iranian patients in Fars province. The following clinical features were used as inclusion criteria for investigation of the patients. Lethargy, poor feeding ,persistent vomiting, cholestasis, intractable seizure ,decreased level of consciousness ,persistent hypoglycemia, unexplained acid base disturbance and unexplained neonatal death. Result: Organic acidemia with 40 cases (42% was the most frequent disorder diagnosed in our high risk populations, followed by disorder of galactose metabolism(30%, 15 patient had classic galactosemia(GALT

  8. Role of farnesoid X receptor and bile acids in alcoholic liver disease

    Directory of Open Access Journals (Sweden)

    Sharon Manley

    2015-03-01

    Full Text Available Alcoholic liver disease (ALD is one of the major causes of liver morbidity and mortality worldwide. Chronic alcohol consumption leads to development of liver pathogenesis encompassing steatosis, inflammation, fibrosis, cirrhosis, and in extreme cases, hepatocellular carcinoma. Moreover, ALD may also associate with cholestasis. Emerging evidence now suggests that farnesoid X receptor (FXR and bile acids also play important roles in ALD. In this review, we discuss the effects of alcohol consumption on FXR, bile acids and gut microbiome as well as their impacts on ALD. Moreover, we summarize the findings on FXR, FoxO3a (forkhead box-containing protein class O3a and PPARα (peroxisome proliferator-activated receptor alpha in regulation of autophagy-related gene transcription program and liver injury in response to alcohol exposure.

  9. Scrub typhus hepatitis confirmed by immunohistochemical staining

    Institute of Scientific and Technical Information of China (English)

    Jong-Hoon Chung; Sung-Chul Lim; Na-Ra Yun; Sung-Heui Shin; Choon-Mee Kim; Dong-Min Kim

    2012-01-01

    Scrub typhus is an acute febrile disease caused by Orientia tsutsugamushi (O.tsutsugamushi).We report herein the case of a woman who presented with fever and elevated serum levels of liver enzymes and who was definitively diagnosed with scrub typhus by histopathological examination of liver biopsy specimens,serological tests and nested polymerase chain reaction.Immunohistochemical staining using a monoclonal anti-O.tsutsugamushi antibody showed focally scattered positive immunoreactions in the cytoplasm of some hepatocytes.This case suggests that scrub typhus hepatitis causes mild focal inflammation due to direct liver damage without causing piecemeal necrosis or interface hepatitis.Thus,scrub typhus hepatitis differs from acute viral hepatitis secondary to liver damage due to host immune responses,which causes severe Iobular disarray with diffuse hepatocytic degeneration,necrosis and apoptosis as well as findings indicative of hepatic cholestasis,such as hepatic bile plugs or brown pigmentation of hepatocytes.

  10. Zschokkella icterica sp. nov. (Myxozoa, Myxosporea), a pathogen of wild rabbitfish Siganus luridus (Ruppell, 1829) from the Red Sea.

    Science.gov (United States)

    Diamant, A; Paperna, H

    1992-02-21

    Zschokkella icterica sp. nov. is described from the liver and gall bladder of wild rabbitfish Siganus luridus from the Red Sea. This coelozoic myxosporean produces large (300 × 400 μm) Plasmodia that inhabit the hepatic bile ducts. The species is disporoblastic and pansporoblast forming. Small plasmodia are found in the gall bladder. Spores average 9.9 urn in length, 5.8 μm in width and 3.5 um in thickness, and the polar filament has 3-4 coils. It is suggested that the hepatic bile ducts are the primary target organ, their blockage by the parasite producing cholestasis and duct breakdown. In severe infections, invasion of the liver parenchyma by the parasite occurred. In these cases, the infection was often associated with massive hepatic necrosis, ascites and jaundice.

  11. Effect of living donor liver transplantation on outcome of children with inherited liver disease and hepatocellular carcinoma.

    Science.gov (United States)

    Ozçay, Figen; Canan, Oğuz; Bilezikçi, Banu; Torgay, Adnan; Karakayali, Hamdi; Haberal, Mehmet

    2006-01-01

    We described six children with heritable liver disease and hepatocellular carcinoma treated with living-related liver transplantation. Underlying liver diseases were type-1 tyrosinemia (three patients), progressive familial intrahepatic cholestasis type II (two patients), and Wilson's disease (one patient). Two of the tumors were found incidentally during liver transplantation. Number of nodules was 12, 15, 3, 2, and 1 (in two patients). Three patients were treated with chemotherapy before the procedure. Chemotherapy was not given to any patient after liver transplantation. The mean follow-up was 17.7 +/- 6 months (range: 7-24). All patients are tumor recurrence free. Both graft and patient survival rates are 100% at a median of 18.5 months follow-up. Physicians in charge of treating children with heritable liver disease should screen them periodically for the development of hepatocellular carcinoma. Liver transplantation may offer these children better survival rates.

  12. Clinical findings, dental treatment, and improvement in quality of life for a child with Rothmund-Thomson syndrome

    Directory of Open Access Journals (Sweden)

    Katharina Morant Holanda De Oliveira

    2016-01-01

    Full Text Available The purpose of this study was to report the clinical findings, dental treatment, and improvement in quality of life for a child with Rothmund-Thomson syndrome. The patient had alopecia, delayed speech, low weight and height, cholestasis, and iron deficiency anemia. Furthermore, there were carious lesions and darkened spots on all primary molars. Microdontia of a premolar was observed at the radiographic examination. The patient and family had no commitment to her oral health and dental treatment at first appointments. Oral hygiene instructions, composite restorations, endodontic treatments, teeth extractions, and stainless steel crown installations were performed. The patient was followed up for 7 years through the present due to other possible future clinical findings associated with the syndrome. An improvement in social aspects was observed after removal of toothache and improved esthetics. Such patients need continuous periodic services, which contributes to improving the quality of life in both buccal and general aspects.

  13. Reversion of severe hepatopulmonary syndrome in a non cirrhotic patient after corticosteroid treatment for granulomatous hepatitis: A case report and review of the literature

    Institute of Scientific and Technical Information of China (English)

    Nikolaos Tzovaras; Aggelos Stefos; Sarah P Georgiadou; Nikolaos Gatselis; Georgia Papadamou; Eirini Rigopoulou; Maria Ioannou; Ioannis Skoularigis; Georgios N Dalekos

    2006-01-01

    Hepatopulmonary syndrome (HPS) is defined as a clinical triad including liver disease, abnormal pulmonary gas exchange and evidence of intrapulmonary vascular dilatations. We report a 61-year-old male presented with fatigue, long-lasting fever, loss of weight, signs of portal hypertension, hepatosplenomegaly, cholestasis and progressive dyspnoea over the last year. Clinical, laboratory and histological findings confirmed the diagnosis of granulomatous hepatitis. HPS due to hepatic granulomainduced portal hypertension was proved to be the cause of severe hypoxemia of the patient as confirmed by contrast-enhanced echocardiography. Reversion of HPS after corticosteroid therapy was confirmed by a new contrastenhanced echocardiography along with the normalization of cholestatic enzymes and improvement of the patient's conditions. This is the first case of complete reversion of HPS in a non-cirrhotic patient with hepatic granuloma,indicating that intrapulmonary shunt in liver diseases is a functional phenomenon and HPS can be developed even in miscellaneous liver involvement as in this case.

  14. Fibrosing cholestatic hepatitis following cytotoxic chemotherapy for small-cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Jaime Ceballos-Viro; José M López-Picazo; José L Pérez-Gracia; Jesús J Sola; Gregorio Aisa; Ignacio Gil-Bazo

    2009-01-01

    Fibrosing cholestatic hepatitis (FCH) is a variant of viral hepatitis reported in hepatitis B virus or hepatitis C virus infected liver, renal or bone transplantation recipients and in leukemia and lymphoma patients after conventional cytotoxic chemotherapy. FCH constitutes a well-described form of fulminant hepatitis having extensive fibrosis and severe cholestasis as its most characteristic pathological findings. Here, we report a case of a 49-year-old patient diagnosed with small-cell lung cancer who developed this condition following conventional chemotherapy-induced immunosuppression. This is the first reported case in the literature of FCH after conventional chemotherapy for a solid tumor. In addition to a detailed report of the case, a physiopathological examination of this potentially life-threatening condition and its treatment options are discussed.

  15. Reversal of intestinal failure-associated liver disease (IFALD)

    DEFF Research Database (Denmark)

    Hvas, Christian; Kodjabashia, Kamelia; Nixon, Emma;

    2016-01-01

    Patients with intestinal failure (IF) and home parenteral nutrition commonly develop abnormal liver function tests. The presentations of IF-associated liver disease (IFALD) range from mild cholestasis or steatosis to cirrhosis and decompensated liver disease. We describe the reversal of IFALD...... in an adult patient with IF secondary to severe Crohn's disease and multiple small bowel resections. The patient developed liver dysfunction and pathology consistent with IFALD. Multiple causal factors were implicated, including nutrition-related factors, catheter sepsis and the use of hepatotoxic medications....... Multidisciplinary treatment in a tertiary IF referral centre included aggressive sepsis management, discontinuation of hepatotoxic medications and a reduction of parenteral nutrition dependency through optimisation of enteral nutrition via distal enteral tube feeding. Upon this, liver function tests normalised....

  16. Neonatal haemochromatosis associated with gastroschisis.

    Science.gov (United States)

    Thornton, M P; Marven, S S; Tanner, M S; Gürtl-Lackner, B

    2008-05-01

    We describe, to our knowledge, the first case of progressive neonatal liver failure due to neonatal haemochromatosis (NH) occurring in an infant with a gastroschisis and review the literature regarding these two conditions. A 1,665 g male infant with antenatally diagnosed gastroschisis was born with a severe coagulopathy, anaemia, thrombocytopenia, hypoglycaemia and jaundice. He developed progressive liver failure, complicated by necrotising enterocolitis. Serum ferritin was elevated at 1,459 microg/L. He died on day 40 and a limited post-mortem examination confirmed significant hepatic siderosis with fibrosis and cholestasis, and siderosis of the pancreas. Although no genetic aetiology for gastroschisis has been identified, an occasional inherited tendency has been observed. There is also evidence to support an autosomal recessive inheritance in NH. PMID:18338135

  17. Combined endoscopic and ursodeoxycholic acid treatment of biliary cast syndrome in a non-transplant patient

    Institute of Scientific and Technical Information of China (English)

    Panagiotis Katsinelos; Grigoris Chatzimavroudis; Ioannis Pilpilidis; George Paroutoglou; Jannis Kountouras; Christos Zavos

    2008-01-01

    A 76-year-old diabetic man underwent cholecystectomy for gangrenous calculous cholecystitis.His postoperative course was complicated by the development of Candida albicans esophagitis necessitating antifungal therapy,and total parenteral nutrition(TPN)for 15 d.Seven weeks after cholecystectomy,he presented with cholangitis.Endoscopic retrograde ch0Iangiopancreatography(ERCP)demonstrated extrahepatic filling defects.Despite endoscopic extraction of a biliary cast,cholestasis remained unchanged.Oral administration of ursodeoxycholic acid(UDCA),750 mg/d,resulted in normalization of liver function tests.We,therefore,propose for the first time,combined endoscopic plus UDCA treatment for the management of biliary cast syndrome.(C)2008 The WJG Press.All righis reserved.

  18. Functional and histopathologic changes in the liver during sepsis.

    Science.gov (United States)

    Caruana, J A; Montes, M; Camara, D S; Ummer, A; Potmesil, S H; Gage, A A

    1982-05-01

    Although liver failure from sepsis is a frequent occurrence in serious ill, hospitalized patients, little information is available on the histologic changes of the liver. We examined the histopathology of the liver of 19 patients who died of clinical sepsis and attempted to relate certain features of the illness or treatment to the observed histopathologic changes. The most striking finding was midzonal and peripheral necrosis of a moderate to marked degree in 11 of 19 patients. Other important changes were acute inflammation and cholestasis. The severity of hepatocellular necrosis did not appear to be influenced by the premortem circulating pathogen, by the nutritional support administered or by the arterial blood pressure. It is suggested that hepatocellular necrosis is characteristic of sepsis and may be caused by loss of specific factors which normally maintain liver function and structure. PMID:6803371

  19. Portal hypertension due to portal venous thrombosis: Etiology, clinical outcomes

    Institute of Scientific and Technical Information of China (English)

    Ozgur Harmanci; Yusuf Bayraktar

    2007-01-01

    The thrombophilia in adult life has major implications in the hepatic vessels. The resulting portal vein thrombosis has various outcomes and complications. Esophageal varices, portal gastropathy, ascites, severe hypersplenism and liver failure needing liver transplantation are known well. The newly formed collateral venous circulation showing itself as pseudocholangicarcinoma sign and its possible clinical reflection as cholestasis are also known from a long time. The management strategies for these complications of portal vein thrombosis are not different from their counterpart which is cirrhotic portal hypertension, but the prognosis is unquestionably better in former cases. In this review we present and discuss the portal vein thrombosis, etiology and the resulting clinical pictures. There are controversial issues in nomenclature,management (including anticoagulation problems), follow up strategies and liver transplantation. In the light of the current knowledge, we discuss some controversial issues in literature and present our experience and our proposals about this group of patients.

  20. BONE TURNOVER AND MINERAL DENSITY OF THE LUMBAR VERTEBRAE IN WOMEN WITH PRIMARY BILIARY CIRRHOSIS BEFORE AND AFTER ORTHOTOPIC LIVER TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    I. A. Pronchenko

    2013-01-01

    Full Text Available Aim. To elucidate the role of cholestasis and menopausal status in the development of osteoporosis in women with primary biliary cirrhosis (PBC before and after orthotopic liver transplantation (OLT. Methods and re- sults. There were fulfilled 74 estimations of biochemical markers of bone metabolism, estrogen (E2, parathy- roid hormone (PTH endogenous secretion so as mineral content of lumbar vertebras in 21 women with PBC (10 women before and 17 in different terms after OLT. Bone turnover disturbances were characterized by delay of bone formation associated with hyperbilirubinaemia before OLT while increased bone turnover following OLT. Bone resorption markers correlated inversely with E2 in postmenopausal women and positively with PTH in premenopausal women. Conclusion. Bone wastes degree depended on hard and duration of disease before OLT so as menopausal status after OLT. In postmenopausal women bone wastes were associated with degree of endogenous E2 decreasing, increased bone turnover, and graft dysfunction. 

  1. MR-assisted bile duct drainage: a study of passive catheter visualization in an animal model

    International Nuclear Information System (INIS)

    Purpose: To investigate interactive MR-assisted bile duct drainage in pigs with the passive visualization technique using near real-time imaging. Methods: 8 bile duct drainages were placed in an open low-field MR system (0.2 Tesla) in 4 pigs with surgically induced cholestasis. After planning the intervention with magnetic resonance cholangiography (MRC), both the puncture and catheter placement were interactively guided using a fast T2-weighted true FISP sequence. Results: MRC enabled interventional planning in all puncture attempts. Punctures were unproblematic in all attempts, the bile ducts were punctured 6 times after the first and twice after the second attempt. Placement of the passively visible catheter was successful in all animals. The applied sequence enables interactive fluoroscopy-like positioning of the devices. Conclusion: The procedure introduced here enables reliable and fast placement of a bile duct drainage in an animal model using a low-field MR system. (orig.)

  2. Diagnostic imaging of digestive tract involvement in cystic fibrosis. Part 1: hepatobiliary disease

    International Nuclear Information System (INIS)

    Cystic fibrosis is a severe hereditary disease characterized by epithelial chloride channel dysfunction, leading to the production of abnormally thick secretions. The abnormal gene is located on the long arm of chromosome 7. Hepatobiliary involvement derives from ductal obstruction causing cholestasis, steatosis, cirrhosis and portal hypertension. Biliary sludge, cholelithiasis and gallbladder sclerosis and atrophy are common findings. As the correlation between the hepatobiliary changes and their clinical and analytical impact is very limited, imaging techniques are essential in this disease. Ultrasound is the basic imaging tool, both for initial evaluation and follow-up of the hepatic and biliary involvement, although other techniques such as radionuclide imaging, magnetic resonance and computed tomography can be highly useful. Given the long-term, chronic nature of this disease, the use of aggressive techniques or irradiation should be carefully weighed. (Author) 38 refs

  3. Regulation of post-Golgi LH3 trafficking is essential for collagen homeostasis

    Science.gov (United States)

    Banushi, Blerida; Forneris, Federico; Straatman-Iwanowska, Anna; Strange, Adam; Lyne, Anne-Marie; Rogerson, Clare; Burden, Jemima J.; Heywood, Wendy E.; Hanley, Joanna; Doykov, Ivan; Straatman, Kornelis R.; Smith, Holly; Bem, Danai; Kriston-Vizi, Janos; Ariceta, Gema; Risteli, Maija; Wang, Chunguang; Ardill, Rosalyn E.; Zaniew, Marcin; Latka-Grot, Julita; Waddington, Simon N.; Howe, S. J.; Ferraro, Francesco; Gjinovci, Asllan; Lawrence, Scott; Marsh, Mark; Girolami, Mark; Bozec, Laurent; Mills, Kevin; Gissen, Paul

    2016-01-01

    Post-translational modifications are necessary for collagen precursor molecules (procollagens) to acquire final shape and function. However, the mechanism and contribution of collagen modifications that occur outside the endoplasmic reticulum and Golgi are not understood. We discovered that VIPAR, with its partner proteins, regulate sorting of lysyl hydroxylase 3 (LH3, also known as PLOD3) into newly identified post-Golgi collagen IV carriers and that VIPAR-dependent sorting is essential for modification of lysines in multiple collagen types. Identification of structural and functional collagen abnormalities in cells and tissues from patients and murine models of the autosomal recessive multisystem disorder Arthrogryposis, Renal dysfunction and Cholestasis syndrome caused by VIPAR and VPS33B deficiencies confirmed our findings. Thus, regulation of post-Golgi LH3 trafficking is essential for collagen homeostasis and for the development and function of multiple organs and tissues. PMID:27435297

  4. Selective screening of 650 high risk Iranian patients for detection of inborn error of metabolism

    Directory of Open Access Journals (Sweden)

    Narges Pishva

    2015-02-01

    Full Text Available Objective: Although metabolic diseases individually are rare ,but overall have an incidence of 1/2000 and can cause devastating and irreversible effect if not diagnosed early and treated promptly. selective screening is an acceptable method for detection of these multi presentation diseases.Method: using panel neonatal screening for detection of metabolic diseases in 650 high risk Iranian patients in Fars province. The following clinical features were used as inclusion criteria for investigation of the patients.Lethargy, poor feeding ,persistent vomiting, cholestasis, intractable seizure ,decreased level of consciousness ,persistent hypoglycemia, unexplained acid base disturbance and unexplained neonatal death.Result: Organic acidemia with 40 cases (42% was the most frequent disorder diagnosed in our high risk populations, followed by disorder of galactose metabolism(30%, 15 patient had classic galactosemia(GALT

  5. Glucocorticosteroids for primary sclerosing cholangitis

    DEFF Research Database (Denmark)

    Giljaca, Vanja; Poropat, Goran; Stimac, Davor;

    2010-01-01

    Primary sclerosing cholangitis is a chronic cholestatic disease of intrahepatic and extrahepatic biliary ducts, characterised by chronic periductal inflammation and sclerosis of the ducts, which results in segmental stenoses of bile ducts, cholestasis, fibrosis, and ultimately, liver cirrhosis....... Patients with primary sclerosing cholangitis are at higher risk of cholangiocarcinoma as well as of colonic neoplasia, since primary sclerosing cholangitis is associated with inflammatory bowel disease in more than 80% of the patients. Several therapeutic modalities have been proposed for primary...... sclerosing cholangitis, like ursodeoxycholic acid, glucocorticosteroids, and immunomodulatory agents, but none has been successful in reversing the process of the disease. To date, liver transplantation is the only definite therapeutic solution for patients with advanced primary sclerosing cholangitis...

  6. Mycophenolate mofetil for drug-induced vanishing bile duct syndrome

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Amoxicillin/clavulanate is associated with liver injury,mostly of a cholestatic pattern. While outcomes are usually benign, progression to cirrhosis and death has been reported. The role of immunosuppressive therapy for patients with a protracted course is unclear. We report the case of an elderly patient who developed prolonged cholestasis secondary to amoxicillin/clavulanate. Vanishing bile duct syndrome was confirmed by sequential liver biopsies. The patient responded to prednisone treatment,but could not be weaned off corticosteroids, even when azathioprine was added. Complete withdrawal of both prednisone and azathioprine was possible by using mycophenolate mofetil, an inosine monophosphate dehydrogenase inhibitor. Sustained remission has been maintained for more than 3 years with low-dose mycophenolate mofetil.

  7. Hepatic failure caused by plasma cell infiltration in multiple Myeloma

    Institute of Scientific and Technical Information of China (English)

    Fadi E Rahhal; Robert R Schade; Asha Nayak; Teresa A Coleman

    2009-01-01

    Although plasma cell infiltration is not rare in autopsy of patients with multiple myeloma (MM), it is very rarely detected in living patients. This is because MM rarely causes significant liver dysfunction that requires further evaluation. A 49-year-old man presented with acute renal failure and was diagnosed with kappa light chain MM stage ?B. Thalidomide and dexamethasone were initiated. The patient developed a continuous increase in bilirubin that led to severe cholestasis. A liver biopsy revealed plasma cell infiltration. He then rapidly progressed to liver failure and died. Treatment options are limited in MM with significant liver dysfunction.Despite new drug therapies in MM, those patients with rapidly progressive liver failure appear to have a dismal outcome.

  8. Low-fat, high calorie parenteral nutrition (PN), reverses liver affection in long term PN dependent infants

    DEFF Research Database (Denmark)

    Jakobsen, Marianne Skytte; Hørby Jørgensen, Marianne; Husby, Steffen;

    2015-01-01

    INTRODUCTION: Parenteral nutrition-associated cholestasis (PNAC) is a complication of long-term parenteral nutrition (PN). Removal of lipids may reverse PNAC but compromises the energy to ensure infant growth. The purpose of this study was to test whether a low-fat, high-carbohydrate PN regimen......, which prevents and reverses PNAC in adults, could do the same in infants. This regimen could potentially avoid the problem of diminished energy input after removing nutritional lipids. METHODS: Infants developing PNAC over a 2-year period were started on a low-fat PN regimen with calories primarily from...... carbohydrates. The fat-free PN, containing 314 kJ/ml, was provided 5-6 times a week and fat, including essential fatty acids and fat-soluble vitamins, 1-2 times a week. Enteral feeding was continued according to individual tolerance. RESULTS: The study included 10 infants with short bowel syndrome (six...

  9. Sclerosing angiomatoid nodular transformation of the spleen during pregnancy: Diagnostic challenges and clinical management.

    Science.gov (United States)

    Corrado, Giacomo; Tabanelli, Valentina; Biffi, Roberto; Petralia, Giuseppe; Tinelli, Andrea; Peccatori, Fedro A

    2016-08-01

    We report the first case of sclerosing angiomatoid nodular transformation (SANT) of the spleen diagnosed during pregnancy, discussing differential diagnosis, immunohistochemical profile and treatment. A G2P1 37-year-old woman presented during the 19th week of gestation because of pruritus at lower limbs. To exclude cholestasis, an abdominal ultrasound and whole body magnetic resonance were performed and a single solid lesion with intrinsic vascularization was identified. Therefore, at 22 weeks gestation, after normal fetal assessment, the patient was referred for a splenectomy. No further treatment was suggested and the patient gave birth at 42 weeks gestation with a spontaneous delivery. Distinguishing SANT from other vascular neoplasms of the spleen during pregnancy is a difficult task. Surgical excision should be performed to exclude malignancy and to resolve symptoms, if present. PMID:27080826

  10. Fulminant Wilson's Disease Managed with Plasmapheresis as a Bridge to Liver Transplant.

    Science.gov (United States)

    Hilal, Talal; Morehead, R Scott

    2014-01-01

    New-onset jaundice can be a manifestation of multiple pathologic processes including hemolysis, parenchymal liver disease, and cholestasis; the differential diagnosis is broad and requires a systematic approach. We report a case of a patient who presented with jaundice after starting minocycline for the treatment of acne vulgaris and rapidly developed fulminant liver failure found to be due to Wilson's disease. She also manifested severe Coomb's negative hemolytic anemia and renal failure secondary to hepatorenal syndrome. As a bridge to liver transplant, she was successfully treated with plasmapheresis to decrease serum copper in addition to hemodialysis for acidosis and hyperkalemia. She was able to receive a liver and made a full recovery. The case highlights the use of plasmapheresis as an adjunctive treatment modality in cases of fulminant liver failure due to Wilson's disease.

  11. [Pharmacological aspects of oral contraceptives: part 2 (author's transl)].

    Science.gov (United States)

    Weil-levy, C; Soubrie, C; Simon, P

    1980-05-01

    This article is a long list of the known side effects of OC (oral contraception). Less serious side effects include skin alterations, genito-urinary infections, anemia, headaches, psychological problems of various kinds, cholestasis and/or jaundice, menstruation disorders, and metabolic perturbations. Very serious side effects include all cardiovascular, cerebrovascular and blood coagulation problems; carcinogenic effects are to be included among serious ones, even if not totally proven. Factors increasing the risk of severe disorders are tabagism, obesity, age, hypertension, and family antecedents of thrombotic accidents. Sex hormones are suspected to induce malformation in the fetus. OC must be carefully chosen according to the clinical and biological characteristics of the users; the lowest dosage is always recommended when effectiveness is equal. PMID:12261834

  12. Hepatobiliary Disposition of 3α,6α,7α,12α-Tetrahydroxy-Cholanoyl Taurine: A Substrate for Multiple Canalicular Transporters

    OpenAIRE

    Megaraj, Vandana; Iida, Takashi; Jungsuwadee, Paiboon; Hofmann, Alan F.; Vore, Mary

    2010-01-01

    Tetrahydroxy bile acids become major biliary bile acids in Bsep(−/−) mice and Fxr(−/−) mice fed cholic acid; we characterized disposition of these novel bile acids that also occur in patients with cholestasis. We investigated mouse Mrp2 (mMrp2) and P-glycoprotein [(P-gp) mMdr1a]-mediated transport of a tetrahydroxy bile acid, 6α-OH-taurocholic acid (6α-OH-TC), and its biliary excretion in wild-type and Mrp2(−/−) mice in the presence or absence of N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-is...

  13. 胆盐输出泵基因多态性与妊娠期肝内胆汁淤积症相关性研究

    Institute of Scientific and Technical Information of China (English)

    罗振宇; 刘淮

    2008-01-01

    妊娠肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)是发生在妊娠晚期特有的并发症,多发生于妊娠最后的3个月。文献报道ICP有家族性倾向,Reyes发现智利Arancanian印第安混血人种发病率最高,提示本病可能与种族、遗传有关。胆盐输出泵(bile salt export pump,BSEP)仅在肝细胞胆小管侧膜上特异性表达,介导单价胆盐的跨毛细胆管转运,

  14. Primary sclerosing cholangitis and pregnancy

    Directory of Open Access Journals (Sweden)

    Casper Q. Kammeijer

    2011-08-01

    Full Text Available Primary sclerosing cholangitis is a progressive disease, and coincidentally in pregnancy it is rare. It is characterized by progressive inflammation and destruction of bile ducts finally resulting in liver failure. A rare case of primary sclerosing cholangitis in pregnancy is presented. The course of the pregnancy was marked by threatened preterm delivery and exacerbation of cholestasis. She was successfully treated with ursodeoxycholic acid (UDCA. Although, primary sclerosing cholangitis has both maternal and fetal effects on pregnancy, the overall outcome is favorable. Only few cases have been reported using high dose ursodeoxycholic acid for primary sclerosing cholangitis in pregnancy, it often improves pruritus but has no protection against stillbirth. Data on the safety to the fetus or neonate and long-term outcome are scarce.

  15. Peribiliary hepatic cysts presenting as hilar cholangiocarcinoma in a patient with end-stage liver disease

    Science.gov (United States)

    Lim, Jane; Nissen, Nicholas N.; McPhaul, Christopher; Annamalai, Alagappan; Klein, Andrew S.; Sundaram, Vinay

    2016-01-01

    Peribiliary cysts are cystic dilatations of peribiliary glands in the liver. They are present in ~50% of cirrhotic patients, but are underrecognized because they are usually asymptomatic and rarely present as obstructive jaundice. A 63-year-old male with hepatitis C cirrhosis, awaiting liver transplantation, had a new finding of intrahepatic dilatation on magnetic resonance imaging. This was initially concerning for cholangiocarcinoma, but was ultimately diagnosed as peribiliary cysts. Peribiliary cysts can imitate cholangiocarcinoma on imaging. Therefore, awareness of this condition is essential because misdiagnosis may lead to inappropriate delay or denial for liver transplantation. The ideal imaging modalities to identify peribiliary cysts are magnetic resonance cholangiography and drip infusion cholangiographic computed tomography, though hepatic dysfunction may limit the usefulness of the latter. Peribiliary cysts should be considered in cirrhotic patients with cholestasis, biliary dilatations and negative biopsy of the biliary system for malignancy. PMID:27511912

  16. Relationship between serum heat—stable alkaline phosphatase level and p[regnancy

    Institute of Scientific and Technical Information of China (English)

    CaoGuo-Xian; DingMei-Juan; 等

    1998-01-01

    Serum heat-stable alkaline phosphatase(HSAP) level in 649 cases of normal pregnancy and 164 cases of high-risk pregnancy is measured by raioimmunoassay (RIA).The results indicate that the HSAP level in normal prenancy increased proportionally with gestation weeks(r=0.9843).In 33 cases of pregnancy induced hypertension and 21 cases of intrauterine fetal growth retardation,the HSAP level is significantly low.In 7 cases of neonatal asphyxia and 26 cases of ftal distress,the HSAP level in the mother's serum is also low.In 53 cases of intrahepatic cholestasis of pregnancy,the HSAP level in similar to those of normal pregnancy,This study illustrates that HSAP RIA can play an important role in the evaluation of placental function and fetal prognosis for cases of high-risk pregancy.

  17. Analysis of some biochemical and haematological parameters for Mucuna pruriens (DC) seed powder in male rats.

    Science.gov (United States)

    Chukwudi, Ndukwe Henry; Simeon, Omale; Chinyere, Aguiyi John

    2011-10-01

    The biochemical and haematological effects of the seed powder of Mucuna pruriens in male rats were evaluated to establish some biological properties of this potential biopesticide currently undergoing investigation. The result showed that Mucuna pruriens seed extract produced a significant (p<0.05) increase in white blood cell (WBC) count, as well as in bilirubin concentrations, alkaline phosphatase (ALP), protein and creatinine levels measured. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly reduced (P<0.05) in comparison with the experimental control. PCV, Hb, albumin level and WBC differential counts gave no significant difference between treated and control groups. The results revealed metabolic imbalance in the rats which suggests a mild cholestasis effect of the extract. PMID:21959815

  18. Severe iron overload and hyporegenerative anemia in a case with rhesus hemolytic disease: therapeutic approach to rare complications

    Directory of Open Access Journals (Sweden)

    Fatih Demircioğlu

    2010-09-01

    Full Text Available A 33 weeks’ gestation, a baby with rhesus hemolytic disease (RHD, who had received intrauterine transfusions twice, developed cholestatic hepatic disease and late hyporegenerative anemia. Her serum ferritin and bilirubin levels increased to 8842 ng/ml and 17.9 mg/dl, respectively. Liver biopsy showed cholestasis and severe iron overload. Treatment with recombinant erythropoietin (rHuEPO decreased the transfusion need, and intravenous deferoxamine resulted in a marked decreased in serum ferritin levels and normalization of liver function. In patients who have undergone intrauterine transfusions due to RHD, hyperferritinemia and late hyporegenerative anemia should be kept in mind. Chelation therapy in cases with symptomatic hyperferritinemia and rHuEPO treatment in cases with severe hyporegenerative anemia should be considered.

  19. Liver Hydatid Cyst and Acute Cholangitis: a Case Report.

    Science.gov (United States)

    Nemati Honar, Behzad; Hayatollah, Gholamhossein; Nikshoar, Mohammadreza; Forootan, Mojgan; Feizi, Ali Mohammad

    2016-04-01

    Amongst the cause of cystic hepatic disease, hydatid cyst is common in the Asia, South America, and Africa. The definitive therapy for hepatic hydatid disease is surgical resection. Rupture of the hydatid cyst into the biliary tree can lead to serious cholangitis. In this report, a 22-year-old man is presented with the signs and symptoms of obstructive jaundice and cholangitis. Ultrasonography reported dilated common bile duct (CBD) with sludge and stones, a hydatid cyst adjacent to the gall bladder and mild thickening of gallbladder wall without a stone. MRCP revealed dilated CBD with a cyst in segment fifth of liver. Due to signs and symptoms of obstructive jaundice in addition to lab data and imaging modalities, the ruptured hydatid cyst into a biliary tree was considered, and surgical intervention was performed to extract daughter vesicles from the CBD. Post intervention, signs and symptoms and cholestasis enzymes were subsided. PMID:27309273

  20. Influence of the Gut Microflora and of Biliary Constituents on Morphological Changes in the Small Intestine in Obstructive Jaundice

    Directory of Open Access Journals (Sweden)

    M. Saeed Quraishy

    1996-01-01

    Full Text Available Increased amounts of intestinal endotoxin are absorbed in obstructive jaundice. The precise mechanism is not known but the increased absorption may arise from alterations in the luminal contents, in the intestinal flora, in the gut wall or in interactions between all three. To examine the effects of the intestinal flora we have compared the morphological changes in the small intestine in obstructive jaundice in germ free and conventional rats while the effects of bile constituents have been examined by addition of bile constituents to the diet of bile duct ligated rats. Changes in the intestine were examined, histologically, by enzyme histochemistry, and by transmission and scanning electron microscopy. The results showed no differences in response between germ free and conventional rats. Feeding of diets containing bile salts exacerbated the lesion. Feeding of diets containing cholesterol, however, reduced the degree of intestinal changes produced by cholestasis and completely antagonised the increase in damage caused by feeding of bile salts.

  1. Diagnosis of alpha-1-antitrypsin deficiency by DNA analysis of children with liver disease

    Directory of Open Access Journals (Sweden)

    De TOMMASO Adriana Maria Alves

    2001-01-01

    Full Text Available Background - Alpha-1-antitrypsin deficiency is a genetic disorder which is transmitted in a co-dominant, autosomal form. Alpha-1-antitrypsin deficiency affects mainly the lungs and the liver leading, in the latter case, to neonatal cholestasis, chronic hepatitis or cirrhosis. A precise diagnosis of Alpha-1-antitrypsin deficiency may be obtained by biochemical or molecular analysis. Objective - The purpose of this study was to use DNA analysis to examine the presence of an alpha-1-antitrypsin deficiency in 12 children suspected of having this deficiency and who showed laboratory and clinical characteristics of the disease. Patients and Methods - Twelve patients, aged 3 months to 19 years, who had serum alpha-1-antitrypsin levels lower than normal and/or had hepatic disease of undefined etiology were studied. The mutant alleles S and Z of the alpha-1-antitrypsin gene were investigated in the 12 children. Alpha-1-antitrypsin gene organization was analyzed by amplification of genoma through the polymerase chain reaction and digestion with the restriction enzymes Xmnl (S allele and Taq 1 (Z allele. Results - Seven of the 12 patients had chronic liver disease of undefined etiology and the other five patients had low serum levels of alpha-1-antitrypsin as well as a diagnosis of neonatal cholestasis and/or chronic liver disease of undefined etiology. Five of the 12 patients were homozygous for the Z allele (ZZ and two had the S allele with another allele (*S different from Z. Conclusion - These results show that alpha-1-antitrypsin deficiency is relatively frequent in children with chronic hepatic disease of undefined etiology and/or low alpha-1-antitrypsin levels (41.6%. A correct diagnosis is important for effective clinical follow-up and for genetic counseling.

  2. Definitive exclusion of biliary atresia in infants with cholestatic jaundice: the role of percutaneous cholecysto-cholangiography.

    Science.gov (United States)

    Nwomeh, Benedict C; Caniano, Donna A; Hogan, Mark

    2007-09-01

    Definitive exclusion of biliary atresia in the infant with cholestatic jaundice usually requires operative cholangiography. This approach suffers from the disadvantage that sick infants are subjected to a time-consuming and potentially negative surgical exploration. The purpose of this study was to determine if percutaneous cholecystocholangiography (PCC) prevents unnecessary laparotomy in infants whose cholestasis is caused by diseases other than biliary atresia. This study is a 10 year retrospective review of all infants with persistent direct hyperbilirubinemia and inconclusive biliary nuclear scans who underwent further evaluation for suspected biliary atresia. A gallbladder ultrasound (US) was obtained in all patients. When the gallbladder was visualized, further imaging by PCC was done under intravenous sedation; otherwise, the standard operative cholangiogram (OCG) was performed, with liver biopsy as indicated. The primary outcome was the diagnostic accuracy of PCC, especially with respect to preventing a laparotomy. There were 35 infants with suspected biliary atresia, with a mean age of 8 weeks (range 1-14 weeks). Nine infants whose gallbladder was visualized by ultrasound underwent PCC that definitively excluded biliary atresia. Of this group, the most frequent diagnosis (five patients) was total parenteral nutrition-associated cholestasis. The other 26 infants with absent or decompressed gallbladder had laparotomy and OCG, which identified biliary atresia in 16 patients (61%). Laparotomy was avoided in all 9 patients who underwent PCC, thus reducing the negative laparotomy rate by 47%. There were no complications associated with PCC. Several alternative techniques to operative cholangiogram have been described for the definitive exclusion of biliary atresia, but many of these have distinct drawbacks. Advances in interventional radiology techniques have permitted safe percutaneous contrast evaluation of the biliary tree. Identification of a normal gall

  3. EU framework 6 project: predictive toxicology (PredTox)--overview and outcome.

    Science.gov (United States)

    Suter, Laura; Schroeder, Susanne; Meyer, Kirstin; Gautier, Jean-Charles; Amberg, Alexander; Wendt, Maria; Gmuender, Hans; Mally, Angela; Boitier, Eric; Ellinger-Ziegelbauer, Heidrun; Matheis, Katja; Pfannkuch, Friedlieb

    2011-04-15

    In this publication, we report the outcome of the integrated EU Framework 6 PROJECT: Predictive Toxicology (PredTox), including methodological aspects and overall conclusions. Specific details including data analysis and interpretation are reported in separate articles in this issue. The project, partly funded by the EU, was carried out by a consortium of 15 pharmaceutical companies, 2 SMEs, and 3 universities. The effects of 16 test compounds were characterized using conventional toxicological parameters and "omics" technologies. The three major observed toxicities, liver hypertrophy, bile duct necrosis and/or cholestasis, and kidney proximal tubular damage were analyzed in detail. The combined approach of "omics" and conventional toxicology proved a useful tool for mechanistic investigations and the identification of putative biomarkers. In our hands and in combination with histopathological assessment, target organ transcriptomics was the most prolific approach for the generation of mechanistic hypotheses. Proteomics approaches were relatively time-consuming and required careful standardization. NMR-based metabolomics detected metabolite changes accompanying histopathological findings, providing limited additional mechanistic information. Conversely, targeted metabolite profiling with LC/GC-MS was very useful for the investigation of bile duct necrosis/cholestasis. In general, both proteomics and metabolomics were supportive of other findings. Thus, the outcome of this program indicates that "omics" technologies can help toxicologists to make better informed decisions during exploratory toxicological studies. The data support that hypothesis on mode of action and discovery of putative biomarkers are tangible outcomes of integrated "omics" analysis. Qualification of biomarkers remains challenging, in particular in terms of identification, mechanistic anchoring, appropriate specificity, and sensitivity.

  4. Erythrocytes with T-state-stabilized hemoglobin as a therapeutic tool for postischemic liver dysfunction.

    Science.gov (United States)

    Suganuma, Kazuhiro; Tsukada, Kosuke; Kashiba, Misato; Tsuneshige, Antonio; Furukawa, Toshiharu; Kubota, Tetsuro; Goda, Nobuhito; Kitajima, Masaki; Yonetani, Takashi; Suematsu, Makoto

    2006-01-01

    This study aimed to examine if T-state stabilization of hemoglobin in erythrocytes could protect against postischemic organ injury. Human erythrocytes containing three different states of Hb allostery were prepared: control Hb (hRBC), CO-Hb that is stabilized under R-state with the 6-coordinated prosthetic heme (CO-hRBC), and alpha-NO-deoxyHb stabilized under T-state (alpha-NO-hRBC). To prepare alpha-NO-RBC, deoxygenated RBC was treated with FK409, a thiol-free NO donor, at its half molar concentration to that of Hb; this procedure resulted in the 5-coordinated NO binding on the alpha-subunit heme, as judged by electron spin resonance spectrometry. Rats were subject to 20 min systemic hemorrhage to maintain mean arterial pressure at 40 mm Hg, and reperfused with one of hRBCs. This protocol for ischemia, followed by 60 min reperfusion with physiological saline, caused modest metabolic acidosis and cholestasis. Administration of hRBC or COhRBC significantly attenuated cholestasis and improved acidosis. Rats treated with alpha-NO-hRBC exhibited greater recovery of metabolic acidosis and bile excretion than those treated with hRBC or CO-hRBC, displaying the best outcome of local oxygen utilization in hepatic lobules. Half-life time of alpha-NO-RBC administered in vivo was approximately 60 min. These results suggest that T-state Hb stabilization by NO serves as a stratagem to treat postischemic organ dysfunction. PMID:16987037

  5. Perturbation of bile acid homeostasis is an early pathogenesis event of drug induced liver injury in rats

    International Nuclear Information System (INIS)

    Drug-induced liver injury (DILI) is a significant consideration for drug development. Current preclinical DILI assessment relying on histopathology and clinical chemistry has limitations in sensitivity and discordance with human. To gain insights on DILI pathogenesis and identify potential biomarkers for improved DILI detection, we performed untargeted metabolomic analyses on rats treated with thirteen known hepatotoxins causing various types of DILI: necrosis (acetaminophen, bendazac, cyclosporine A, carbon tetrachloride, ethionine), cholestasis (methapyrilene and naphthylisothiocyanate), steatosis (tetracycline and ticlopidine), and idiosyncratic (carbamazepine, chlorzoxasone, flutamide, and nimesulide) at two doses and two time points. Statistical analysis and pathway mapping of the nearly 1900 metabolites profiled in the plasma, urine, and liver revealed diverse time and dose dependent metabolic cascades leading to DILI by the hepatotoxins. The most consistent change induced by the hepatotoxins, detectable even at the early time point/low dose, was the significant elevations of a panel of bile acids in the plasma and urine, suggesting that DILI impaired hepatic bile acid uptake from the circulation. Furthermore, bile acid amidation in the hepatocytes was altered depending on the severity of the hepatotoxin-induced oxidative stress. The alteration of the bile acids was most evident by the necrosis and cholestasis hepatotoxins, with more subtle effects by the steatosis and idiosyncratic hepatotoxins. Taking together, our data suggest that the perturbation of bile acid homeostasis is an early event of DILI. Upon further validation, selected bile acids in the circulation could be potentially used as sensitive and early DILI preclinical biomarkers. - Highlights: ► We used metabolomics to gain insights on drug induced liver injury (DILI) in rats. ► We profiled rats treated with thirteen hepatotoxins at two doses and two time points. ► The toxins decreased the

  6. Endoscopic Treatment of Biliary Stenosis in Patients with Alveolar Echinococcosis--Report of 7 Consecutive Patients with Serial ERC Approach.

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    Marija Stojkovic

    2016-02-01

    Full Text Available Biliary vessel pathology due to alveolar echicococcosis (AE results in variable combinations of stenosis, necrosis and inflammation. Modern management strategies for patients with cholestasis are desperately needed. The aim is proof of principle of serial ERC (endoscopic retrograde cholangiography balloon dilation for AE biliary pathology.Retrospective case series of seven consecutive patients with AE-associated biliary pathology and ERC treatment in an interdisciplinary endoscopy unit at a University Hospital which hosts a national echinococcosis treatment center. The AE patient cohort consists of 106 patients with AE of the liver of which 13 presented with cholestasis. 6/13 received bilio-digestive anastomosis and 7/13 patients were treated by ERC and are reported here. Biliary stricture balloon dilation was performed with 18-Fr balloons at the initial and with 24-Fr balloons at subsequent interventions. If indicated 10 Fr plastic stents were placed.Six patients were treated by repeated balloon dilation and stenting, one by stenting only. After an acute phase of 6 months with repeated balloon dilation, three patients showed "sustained clinical success" and four patients "assisted therapeutic success," of which one has not yet reached the six month endpoint. In one patient, sustained success could not be achieved despite repeated insertion of plastic stents and balloon dilation, but with temporary insertion of a fully covered self-expanding metal stent (FCSEMS. There was no loss to follow up. No major complications were observed.Serial endoscopic dilation is a standard tool in the treatment of benign biliary strictures. Serial endoscopic intervention with balloon dilation combined with benzimidazole treatment can re-establish and maintain biliary duct patency in AE associated pathology and probably contributes to avoid or postpone bilio-digestive anastomosis. This approach is in accordance with current ERC guidelines and is minimally disruptive

  7. Endoscopic Treatment of Biliary Stenosis in Patients with Alveolar Echinococcosis – Report of 7 Consecutive Patients with Serial ERC Approach

    Science.gov (United States)

    Stojkovic, Marija; Junghanss, Thomas; Veeser, Mira; Weber, Tim F.; Sauer, Peter

    2016-01-01

    Background and Aims Biliary vessel pathology due to alveolar echicococcosis (AE) results in variable combinations of stenosis, necrosis and inflammation. Modern management strategies for patients with cholestasis are desperately needed. The aim is proof of principle of serial ERC (endoscopic retrograde cholangiography) balloon dilation for AE biliary pathology. Methods Retrospective case series of seven consecutive patients with AE-associated biliary pathology and ERC treatment in an interdisciplinary endoscopy unit at a University Hospital which hosts a national echinococcosis treatment center. The AE patient cohort consists of 106 patients with AE of the liver of which 13 presented with cholestasis. 6/13 received bilio-digestive anastomosis and 7/13 patients were treated by ERC and are reported here. Biliary stricture balloon dilation was performed with 18-Fr balloons at the initial and with 24-Fr balloons at subsequent interventions. If indicated 10 Fr plastic stents were placed. Results Six patients were treated by repeated balloon dilation and stenting, one by stenting only. After an acute phase of 6 months with repeated balloon dilation, three patients showed “sustained clinical success” and four patients “assisted therapeutic success,” of which one has not yet reached the six month endpoint. In one patient, sustained success could not be achieved despite repeated insertion of plastic stents and balloon dilation, but with temporary insertion of a fully covered self-expanding metal stent (FCSEMS). There was no loss to follow up. No major complications were observed. Conclusions Serial endoscopic dilation is a standard tool in the treatment of benign biliary strictures. Serial endoscopic intervention with balloon dilation combined with benzimidazole treatment can re-establish and maintain biliary duct patency in AE associated pathology and probably contributes to avoid or postpone bilio-digestive anastomosis. This approach is in accordance with current

  8. Síndrome de Alagille: Presentación de un caso Alagilles syndrome: report of a case

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    Fernando Alberto Gutiérrez Mendoza

    1999-02-01

    Full Text Available Se presenta el caso de un paciente con diagnóstico de síndrome de Alagille, quien consultó por colestasis crónica iniciada en el período neonatal y cuyo diagnóstico se estableció a los cinco meses de edad. El paciente tuvo como manifestaciones mayores del síndrome, además de la colestasis, la facies característica, vértebras en mariposa y soplo cardíaco. Como manifestación menor, retardo del crecimiento. El estudio histológico demostró disminución de los conductos biliares interlobulares. El paciente evolucionó con colestasis persistente e hipertensión porta; falleció a la edad de cuatro años por insuficiencia hepática. El estudio postmortem del hígado demostró cirrosis sin cambios neoplásicos. A patient with chronic cholestasis beginning during his neonatal period is reported. Diagnosis was made at the age of five months. In adition, the patient had the characteristic facies, failure of anterior vertebral arch fusion (butterfly vertebrae, and cardiac murmur, as major clinical manifestations of the syndrome; also he had growth retardation, a minor clinical manifestation. Histologic features revealed paucity of interlobular biliar ducts. Cholestasis persisted and the patient began to have portal hypertension and died at the age of four years with hepatic failure. Postmortem studies showed a hepatic cirrhosis without neoplasic changes.

  9. Pregnancy outcomes associated with viral hepatitis.

    Science.gov (United States)

    Reddick, K L B; Jhaveri, R; Gandhi, M; James, A H; Swamy, G K

    2011-07-01

    The aim of this study was to examine the contribution of hepatitis B virus (HBV) and hepatitis C virus (HCV) to pregnancy-related complications including gestational diabetes mellitus (GDM), preterm birth (PTB), intrauterine growth restriction (IUGR), pre-eclampsia, antepartum haemorrhage and cholestasis. The Nationwide Inpatient Sample was queried for all pregnancy-related discharges, pregnancy complications and viral hepatitis from 1995 to 2005. Logistic regression was used to examine the association between HBV, HCV, HBV + HCV and pregnancy-related complications including GDM, PTB, IUGR, pre-eclampsia, antepartum haemorrhage, cholestasis and caesarean delivery. Model covariates included maternal age, race, insurance status, substance use and medical complications including liver complication, hypertension, HIV, anaemia, thrombocytopenia and sexually transmitted infections. Of 297 664 pregnant women data available for analysis, 1446 had a coded diagnosis of HBV, HCV or both. High-risk behaviours, such as smoking, alcohol and substance use were higher in women with either HBV or HCV. Women with HBV had an increased risk for PTB (aOR 1.65, CI [1.3, 2.0]) but a decreased risk for caesarean delivery (aOR 0.686, CI [0.53, 0.88]). Individuals with HCV had an increased risk for GDM (aOR 1.6, CI [1.0, 2.6]). Individuals with both HBV and HCV co-infection had an increased risk for antepartum haemorrhage (aOR 2.82, CI [1.1, 7.2]). There was no association of viral hepatitis with IUGR or pre-eclampsia. Women with hepatitis have an increased risk for complications during pregnancy. Research to determine the efficacy and cost-effectiveness of counselling patients about potential risks for adverse outcomes is warranted. PMID:21692952

  10. Etiological spectrum of recurrent jaundice in adults: A retrospective observational study from a tertiary care center

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    Gouranga Santra

    2016-01-01

    Full Text Available Introduction: Studies regarding etiological spectrum of recurrent jaundice are rare. We conducted this study to identify the causes of recurrent jaundice in a tertiary care center. Materials and Methods: Frequency of different causes of recurrent jaundice was assessed from 130 patients attended General Medicine Department over a period of 3 years. Recurrent jaundice was considered when patients had more than one episodes of jaundice with serum bilirubin ≥3 mg/dl since childhood. Recurrent jaundice was diagnosed from past medical records, records of follow-up visits, and current clinical presentation. Causes were identified from past and present medical records of history, clinical and laboratory examinations. Results: Causes of recurrent jaundice included prehepatic (30%, hepatic (59.23%, and posthepatic (10.77 % disorders. Prehepatic disorders were Gilbert′s syndrome (GS, megaloblastic anemia, autoimmune haemolytic anemia, Wilson′s disease, G6PD deficiency, etc. Hepatic disorders were exacerbations of alcoholic hepatitis, hepatitis B and C, autoimmune hepatitis, congestive cardiac failure, sarcoidosis, benign recurrent intrahepatic cholestasis, eclampsia, pregnancy induced cholestasis, falciparum malaria, drug induced liver injury (DILI, etc. Posthepatic causes were choledocholithiasis, recurrent pancreatitis, periampullary carcinoma, choledochal cyst, ascariasis, hemobilia, HIV cholangiopathy, autoimmune pancreatitis, etc. Prehepatic jaundice cases were younger. The highest level of total bilirubin was seen in alcoholic hepatitis, DILI, and hepatitis B. Alcoholic hepatitis was the most common cause of recurrent jaundice (19.23%. GS was the most common prehepatic cause. Mean age was lowest in GS and highest in DILI. Conclusion: Etiological spectrum of recurrent jaundice includes many prehepatic, hepatic or posthepatic disorders. A larger study may enlarge the spectrum.

  11. Mitochondrial genome depletion in human liver cells abolishes bile acid-induced apoptosis: role of the Akt/mTOR survival pathway and Bcl-2 family proteins.

    Science.gov (United States)

    Marin, Jose J G; Hernandez, Alicia; Revuelta, Isabel E; Gonzalez-Sanchez, Ester; Gonzalez-Buitrago, Jose M; Perez, Maria J

    2013-08-01

    Acute accumulation of bile acids in hepatocytes may cause cell death. However, during long-term exposure due to prolonged cholestasis, hepatocytes may develop a certain degree of chemoresistance to these compounds. Because mitochondrial adaptation to persistent oxidative stress may be involved in this process, here we have investigated the effects of complete mitochondrial genome depletion on the response to bile acid-induced hepatocellular injury. A subline (Rho) of human hepatoma SK-Hep-1 cells totally depleted of mitochondrial DNA (mtDNA) was obtained, and bile acid-induced concentration-dependent activation of apoptosis/necrosis and survival signaling pathways was studied. In the absence of changes in intracellular ATP content, Rho cells were highly resistant to bile acid-induced apoptosis and partially resistant to bile acid-induced necrosis. In Rho cells, both basal and bile acid-induced generation of reactive oxygen species (ROS), such as hydrogen peroxide and superoxide anion, was decreased. Bile acid-induced proapoptotic signals were also decreased, as evidenced by a reduction in the expression ratios Bax-α/Bcl-2, Bcl-xS/Bcl-2, and Bcl-xS/Bcl-xL. This was mainly due to a downregulation of Bax-α and Bcl-xS. Moreover, in these cells the Akt/mTOR pathway was constitutively activated in a ROS-independent manner and remained similarly activated in the presence of bile acid treatment. In contrast, ERK1/2 activation was constitutively reduced and was not activated by incubation with bile acids. In conclusion, these results suggest that impaired mitochondrial function associated with mtDNA alterations, which may occur in liver cells during prolonged cholestasis, may activate mechanisms of cell survival accounting for an enhanced resistance of hepatocytes to bile acid-induced apoptosis. PMID:23597504

  12. Portal Vein Embolization Before Liver Resection: A Systematic Review

    Energy Technology Data Exchange (ETDEWEB)

    Lienden, K. P. van, E-mail: k.p.vanlienden@amc.uva.nl [Academic Medical Center, Department of Radiology (Netherlands); Esschert, J. W. van den; Graaf, W. de [Academic Medical Center, Department of Surgery (Netherlands); Bipat, S.; Lameris, J. S. [Academic Medical Center, Department of Radiology (Netherlands); Gulik, T. M. van [Academic Medical Center, Department of Surgery (Netherlands); Delden, O. M. van [Academic Medical Center, Department of Radiology (Netherlands)

    2013-02-15

    This is a review of literature on the indications, technique, and outcome of portal vein embolization (PVE). A systematic literature search on outcome of PVE from 1990 to 2011 was performed in Medline, Cochrane, and Embase databases. Forty-four articles were selected, including 1,791 patients with a mean age of 61 {+-} 4.1 years. Overall technical success rate was 99.3 %. The mean hypertrophy rate of the FRL after PVE was 37.9 {+-} 0.1 %. In 70 patients (3.9 %), surgery was not performed because of failure of PVE (clinical success rate 96.1 %). In 51 patients (2.8 %), the hypertrophy response was insufficient to perform liver resection. In the other 17 cases, 12 did not technically succeed (0.7 %) and 7 caused a complication leading to unresectability (0.4 %). In 6.1 %, resection was cancelled because of local tumor progression after PVE. Major complications were seen in 2.5 %, and the mortality rate was 0.1 %. A head-to-head comparison shows a negative effect of liver cirrhosis on hypertrophy response. The use of n-butyl cyanoacrylate seems to have a greater effect on hypertrophy, but the difference with other embolization materials did not reach statistical significance. No difference in regeneration is seen in patients with cholestasis or chemotherapy. Preoperative PVE has a high technical and clinical success rate. Liver cirrhosis has a negative effect on regeneration, but cholestasis and chemotherapy do not seem to have an influence on the hypertrophy response. The use of n-butyl cyanoacrylate may result in a greater hypertrophy response compared with other embolization materials used.

  13. microRNA-222 modulates liver fibrosis in a murine model of biliary atresia

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    Shen, Wen-jun; Dong, Rui; Chen, Gong, E-mail: chengongzlp@hotmail.com; Zheng, Shan

    2014-03-28

    Highlights: • The RRV infected group showed cholestasis, retardation and extrahepatic biliary atresia. • miR-222 was highly expressed, and PPP2R2A was inhibited in the murine biliary atresia model. • miR-222 profoundly modulated the process of fibrosis in the murine biliary atresia model. • miR-222 might represent a potential target for improving biliary atresia prognosis. - Abstract: microRNA-222 (miR-222) has been shown to initiate the activation of hepatic stellate cells, which plays an important role in the pathogenesis of liver fibrosis. The aim of our study was to evaluate the role of miR-22 in a mouse model of biliary atresia (BA) induced by Rhesus Rotavirus (RRV) infection. New-born Balb/c mice were randomized into control and RRV infected groups. The extrahepatic bile ducts were evaluated. The experimental group was divided into BA group and negative group based on histology. The expression of miR-222, protein phosphatase 2 regulatory subunit B alpha (PPP2R2A), proliferating cell nuclear antigen (PCNA) and phospho-Akt were detected. We found that the experimental group showed signs of cholestasis, retardation and extrahepatic biliary atresia. No abnormalities were found in the control group. In the BA group, miR-222, PCNA and Akt were highly expressed, and PPP2R2A expression was significantly inhibited. Our findings suggest that miR-222 profoundly modulated the process of fibrosis in the murine BA model, which might represent a potential target for improving BA prognosis.

  14. Sustained Isoprostane E2 Elevation, Inflammation and Fibrosis after Acute Ischaemia-Reperfusion Injury Are Reduced by Pregnane X Receptor Activation.

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    Aimen O Amer

    Full Text Available Liver grafts donated after cardiac death are increasingly used to expand the donor pool but are prone to ischaemic-type biliary lesions. The anti-inflammatory effects of the activated pregnane X receptor have previously been shown to be beneficial in a number of inflammatory liver conditions. However, its role in reducing peri-portal inflammation and fibrosis following ischaemia-reperfusion injury has not been investigated. Hepatic injury and its response to pregnane X receptor activation was examined after partial hepatic ischaemia-reperfusion injury induced by surgically clamping the left and middle lobar blood vessels in rats. Molecular and pathological changes in the liver were examined over the following 28 days. Ischaemia-reperfusion injury resulted in transient cholestasis associated with microvillar changes in biliary epithelial cell membranes and hepatocellular injury which resolved within days after reperfusion. However, in contrast to chemically-induced acute liver injuries, this was followed by sustained elevation in isoprostane E2, peri-portal inflammation and fibrosis that remained unresolved in the ischaemic reperfused lobe for at least 28 days after clamping. Administration of pregnenolone-16α-carbonitrile--a rodent-specific pregnane X receptor activator--resulted in significant reductions in cholestasis, hepatic injury, ischaemic lobe isoprostane E2 levels, peri-portal inflammation and fibrosis. Hepatic ischaemia-reperfusion injury therefore results in inflammatory and fibrotic changes that persist well beyond the initial ischaemic insult. Drug-mediated activation of the pregnane X receptor reduced these adverse changes in rats, suggesting that the pregnane X receptor is a viable drug target to reduce ischaemic-type biliary lesions in recipients of liver transplants donated after cardiac death.

  15. Long-term outcome of endoscopic metallic stenting for benign biliary stenosis associated with chronic pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Taketo Yamaguchi; Takeshi Ishihara; Katsutoshi Seza; Akihiko Nakagawa; Kentarou Sudo; Katsuyuki Tawada; Teruo Kouzu; Hiromitsu Saisho

    2006-01-01

    AIM: Endoscopic metal stenting (EMS) offers good results in short to medium term follow-up for bile duct stenosis associated with chronic pancreatitis (CP);however, longer follow-up is needed to determine if EMS has the potential to become the treatment of first choice.METHODS: EMS was performed in eight patients with severe common bile duct stenosis due to CR After the resolution of cholestasis by endoscopic naso-biliary drainage three patients were subjected to EMS while,the other five underwent EMS following plastic tube stenting. The patients were followed up for more than5 years through periodical laboratory tests and imaging techniques.RESULTS: EMS was successfully performed in all the patients. Two patients died due to causes unrelated to the procedure: one with an acute myocardial infarction and the other with maxillary carcinoma at 2.8 and 5.5years after EMS, respectively. One patient died with cholangitis because of EMS clogging 3.6 years after EMS.None of these three patients had showed symptoms of cholestasis during the follow-up period. Two patients developed choledocholithiasis and two suffered from duodenal ulcers due to dislodgement of the stent between 4.8 and 7.3 years after stenting; however, they were successfully treated endoscopically. Thus, five of eight patients are alive at present after a mean follow-up period of 7.4 years.CONCLUSION: EMS is evidently one of the very promising treatment options for bile duct stenosis associated with CP, provided the patients are closely followed up; thus setting a system for their prompt management on emergency is desirable.

  16. Estrogen and Estrogen Receptor-α-Mediated Transrepression of Bile Salt Export Pump.

    Science.gov (United States)

    Chen, Yuan; Vasilenko, Alex; Song, Xiulong; Valanejad, Leila; Verma, Ruchi; You, Sangmin; Yan, Bingfang; Shiffka, Stephanie; Hargreaves, Leeza; Nadolny, Christina; Deng, Ruitang

    2015-04-01

    Among diseases unique to pregnancy, intrahepatic cholestasis of pregnancy is the most prevalent disorder with elevated serum bile acid levels. We have previously shown that estrogen 17β-estradiol (E2) transrepresses bile salt export pump (BSEP) through an interaction between estrogen receptor (ER)-α and farnesoid X receptor (FXR) and transrepression of BSEP by E2/ERα is an etiological contributing factor to intrahepatic cholestasis of pregnancy. Currently the mechanistic insights into such transrepression are not fully understood. In this study, the dynamics of coregulator recruitment to BSEP promoter after FXR activation and E2 treatment were established with quantitative chromatin immunoprecipitation assays. Coactivator peroxisome proliferator-activated receptor-γ coactivator-1 was predominantly recruited to the BSEP promoter upon FXR activation, and its recruitment was decreased by E2 treatment. Meanwhile, recruitment of nuclear receptor corepressor was markedly increased upon E2 treatment. Functional evaluation of ERα and ERβ chimeras revealed that domains AC of ERα are the determinants for ERα-specific transrepression on BSEP. Further studies with various truncated ERα proteins identified the domains in ERα responsible for ligand-dependent and ligand-independent transrepression. Truncated ERα-AD exhibited potent ligand-independent transrepressive activity, whereas ERα-CF was fully capable of transrepressing BSEP ligand dependently in vitro in Huh 7 cells and in vivo in mice. Both ERα-AD and ERα-CF proteins were associated with FXR in the coimmunoprecipitation assays. In conclusion, E2 repressed BSEP expression through diminishing peroxisome proliferator-activated receptor-γ coactivator-1 recruitment with a concurrent increase in nuclear receptor corepressor recruitment to the BSEP promoter. Domains AD and CF in ERα mediated ligand-independent and ligand-dependent transrepression on BSEP, respectively, through interacting with FXR. PMID:25675114

  17. A nested case-control study of maternal-neonatal transmission of hepatitis B virus in a Chinese population

    Institute of Scientific and Technical Information of China (English)

    Li-Zhang Chen; Wen-Qi Zhou; Shu-Shan Zhao; Zhi-Yu Liu; Shi-Wu Wen

    2011-01-01

    AIM: To examine the determinants of maternal-neo?natal transmission of hepatitis B virus (HBV).METHODS: A nested case-control study was conducted in Changsha, Hunan, People's Republic of China from January 1, 2005 to September 31, 2006. To avoid po?tential maternal blood contamination, we collected vein blood of newborns immediately after birth and before initial hepatitis B vaccination to determine the HBV in?fection status of the newborn. For each HBsAg-positive infant, one HBsAg-negative infant born to an HBsAg-positive mother was matched by hospital at birth (same), gender (same), and date of birth (within 1 mo). A face-to-face interview was conducted to collect clinical and epidemiological data. Conditional logistic regression analysis was used to estimate the independent effects of various determinants on maternal-neonatal transmis?sion of HBV.RESULTS: A total of 141 HBsAg-positive infants and 141 individually matched HBsAg-negative infants were included in the final analysis. Maternal first-degree family history of HBV infection, intrahepatic cholesta-sis, and premature rupture of membranes were risk factors for perinatal transmission of HBV, whereas sys?tematic treatment and HBV immunoglobulin injections for mothers with HBV infection were protective factors for maternal-neonatal transmission of HBV, after ad?justment for potential confounding factors.CONCLUSION: For HBsAg-positive mothers, system?atic treatment, HBV immunoglobulin administration, and controlling intrahepatic cholestasis and pregnancy complications may reduce the incidence of perinatal transmission of HBV.

  18. Dynamic localization of hepatocellular transporters in health and disease

    Institute of Scientific and Technical Information of China (English)

    Marcelo G Roma; Fernando A Crocenzi; Aldo D Mottino

    2008-01-01

    Vesicle-based trafficking of hepatocellular transporters involves delivery of the newly-synthesized carriers from the rough endoplasmic reticulum to either the plasma membrane domain or to an endosomal, submembrane compartment, followed by exocytic targeting to the plasma membrane. Once delivered to the plasma membrane, the transporters usually undergo recycling between the plasma membrane and the endosomal compartment, which usually serves as a reservoir of pre-existing transporters available on demand. The balance between exocytic targeting and endocytic internalization from/to this recycling compartment is therefore a chief determinant of the overall capability of the liver epithelium to secrete bile and to detoxify endo and xenobiotics. Hence, it is a highly regulated process. Impaired regulation of this balance may lead to abnormal localization of these transporters, which results in bile secretory failure due to endocytic internalization of key transporters involved in bile formation. This occurs in several experimental models of hepatocellular cholestasis, and in most human cholestatic liver diseases. This review describes the molecular bases involved in the biology of the dynamic localization of hepatocellular transporters and its regulation, with a focus on the involvement of signaling pathways in this process. Their alterations in different experimental models of cholestasis and in human cholestatic liver disease are reviewed. In addition, the causes explaining the pathological condition (e.g. disorganization of actin or actin-transporter linkers) and the mediators involved (e.g. activation of cholestatic signaling transduction pathways) are also discussed. Finally, several experimental therapeutic approaches based upon the administration of compounds known to stimulate exocytic insertion of canalicular transporters (e.g. cAMP, tauroursodeoxycholate) are described.

  19. [Clinic-epidemiological significance of drug hepatotoxicity in liver disease consultation].

    Science.gov (United States)

    Jmelnitzky, A C; Guidi, M; Bologna, A; Viola, M; Soccini, C; Barbero, R; Belloni, P; Apraiz, M

    2000-01-01

    To assess epidemiological and clinical significance of drug hepatotoxicity in the setting of liver diseases consultation, ten thousand and three hundred forty two prospectively designed clinical records from patient cared for in our Liver Unit in the period 1988-1998 were incorporated into the study; 58 out of 10,342 (prevalence = 5.6%) fulfilled at least the first three of the following causality requirements: 1.--Liver injury associated in time to drug exposition; 2.--Negative evaluation of more common other etiologies; (alcohol, viruses, immunologic, metabolic, etc) 3.--Favourable response to drug withdrawal (ALT 75%), moderate (presence of clinical complications, bilirubin > 5 mg/dl and prothrombin concentration between 50-75%), and severe (major clinical complications with bilirubin > 5 mg/dl and prothrombin concentration hypersensibility (fever, adenomegalies, rush, mononucleosis like syndrome, eosinophilia) in 29.3%. Acute injury represented 91.4% of the cases: 41.4% acute hepatitis, 15.5% "pure" cholestasis, 24.1% cholestatic hepatitis, and 10.3% indeterminate type. Four patients (4.5% of acute injury cases) were presented as severe acute liver failure, leading to liver transplant in one of them, drug association (INH-rifampicin and carbamazepine-phenobarbital) and inadverted challenge (sulphonamides and pemoline) were associated to clinical severity. Chronic injury were found in five patient (8.6%), four of them associated to chronic hepatitis and the other one to a ductopenic syndrome. Six drugs represented 53.4% of our cases; oral contraceptives (7 cases), INH alone or combined with rifampicin (6 cases), sulfonamides and clorpropamida (5 cases each), carbamazepine and amiodarone (4 cases each). Normalization of liver enzymes after drug suppression took 2 to 8 weeks in acute hepatitis type (X = 4 weeks), 4 to 20 in "pure" cholestasis (X = 12 weeks) and 8 to 24 weeks in cholestatic hepatitis or mixed type (X = 16 weeks). Two cases of chronic hepatitis

  20. Aktivitas Antifibrotik Ekstrak Buah Delima Terstandar 40% Ellagic Acid pada Tikus Putih (Rattus norvegicus sebagai Hewan Model (ANTIFIBROTIC ACTIVITY OF POMEGRANATE FRUIT EXTRACT STANDARDIZED 40% ELLAGIC ACID ON RATS (RATTUS NORVEGICUS AS ANIMAL MODEL

    Directory of Open Access Journals (Sweden)

    Wiwik Misaco Yuniarti

    2014-08-01

    Full Text Available The number of patients with chronic liver disease (fibrosis or cirrhosis of the liver is increasing fromtime to time. However, until now there is no therapy that really effective to overcome that disease. Therapyfor liver fibrosis typically use substance that have antioxidant activity, anti-inflammatory or anti fibrotic.Various efforts always done to find alternative therapies for liver fibrosis. One of them is the use ofpotential plants that suspected having such activity. Various parts of pomegranate have been shown tohave various activities that beneficial for health. This study was conducted to determine the effect ofpomegranate fruit extract standardized 40% ellagic acid on the improvement degree of liver fibrosis causedby cholestasis by measuring of serum alkaline phosphatase levels (ALP and gamma-glutamyl transferase(GGT, as a specific indicator of liver damage becaused of cholestasis. The research was conducted by using32 male rats, wistar strain, 2.5 month old, weighing between 150-200 grams. Animal models of liver fibrosis obtained by using BDL technique. Subjects were divided into a control group (P0 = without BDLand giving of pomegranate extract and treatment groups (P1 = BDL with administration of CMC, P2 =BDL with ellagic acid 90% and P3 = BDL with pomegranate fruit extract standardized 40% ellagic acid.CMC, extract (150 mg / kg BW / PO and ellagic acid (60 mg / kg BW / PO administered for 21 consecutivedays in the same volume. At the end of 21 days periods, biochemical evaluation was performed to measureserum levels of GGT and ALP. The result indicated that administration of pomegranate fruit extract ( P3significantly reduced GGT ( 10.5±9.2 mg/dl and ALP level ( 509.0±4.2 mg/dl close to normal level of GGTand ALP ( P0, GGT : 2.8 ± 1.4; ALP : 449.0±62.3 (p<0.05. The level of GGT and ALP in P3 group were lowercompared to the group ellagic acid (P2, GGT=48.5±4.8 and ALP = 691.0± 29.7 and group which only begiven CMC (P1, GGT