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Sample records for cholestasis extrahepatic

  1. 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.

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

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    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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Cholestasis and Pruritus: Progressive Familial Intrahepatic Cholestasis?

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    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.

  8. 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

  9. A Gentleman with Anemia and Cholestasis

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    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.

  10. 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.

  11. 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.

  12. 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...

  13. Ultrasonography of Neonatal Cholestasis

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    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

  14. 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.

  15. Staging of extrahepatic cholangiocarcinoma

    International Nuclear Information System (INIS)

    Preoperative staging of extrahepatic cholangiocarcinoma is important in determining the best treatment plan. Several classification systems have been suggested to determine the operability and extent of surgery. Longitudinal tumor extent is especially important in extrahepatic cholangiocarcinoma because operative methods differ depending on the tumor extent. The Bismuth-Corlette classification system provides useful information when planning for surgery. However, this classification system is not adequate for selecting surgical candidates. Anatomic variation of the bile duct and gross morphology of the tumor must be considered simultaneously. Lateral spread of the tumor can be evaluated based on the TNM staging provided by American Joint Committee on Cancer (AJCC). However, there is a potential for ambiguity in the distinction of T1 and T2 cancer from one another. In addition, T stage does not necessarily mean invasiveness. Blumgart T staging is helpful for the assessment of resectability with the consideration of nodal status and distant metastasis as suggested by the AJCC cancer staging system. Computed tomography (CT) and magnetic resonance imaging (MRI) are the primary tools used in the assessment of longitudinal and lateral spread of a tumor when determining respectability. Diagnostic laparoscopy and positron emission tomography (PET) may play additional roles in this regard. (orig.)

  16. 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.

  17. Intrahepatic cholestasis of pregnancy

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    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.

  18. 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.

  19. Progressive familial intrahepatic cholestasis

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    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

  20. Congenital extrahepatic portosystemic shunts

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    Murray, Conor P.; Yoo, Shi-Joon; Babyn, Paul S. [Department of Diagnostic Imaging, Hospital for Sick Children, 555 University Avenue, M5G 1X8, Toronto, Ontario (Canada)

    2003-09-01

    A congenital extrahepatic portosystemic shunt (CEPS) is uncommon. A type 1 CEPS exists where there is absence of intrahepatic portal venous supply and a type 2 CEPS where this supply is preserved. The diagnosis of congenital portosystemic shunt is important because it may cause hepatic encephalopathy. To describe the clinical and imaging features of three children with CEPS and to review the cases in the published literature. The diagnostic imaging and medical records for three children with CEPS were retrieved and evaluated. An extensive literature search was performed. Including our cases, there are 61 reported cases of CEPS, 39 type 1 and 22 type 2. Type 1 occurs predominantly in females, while type 2 shows no significant sexual preponderance. The age at diagnosis ranges from 31 weeks of intrauterine life to 76 years. Both types of CEPS have a number of associations, the most common being nodular lesions of the liver (n=25), cardiac anomalies (n=19), portosystemic encephalopathy (n=10), polysplenia (n=9), biliary atresia (n=7), skeletal anomalies (n=5), and renal tract anomalies (n=4). MRI is recommended as an important means of diagnosing and classifying cases of CEPS and examining the associated cardiovascular and hepatic abnormalities. Screening for CEPS in patients born with polysplenia is suggested. (orig.)

  1. 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 ...

  2. 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...

  3. 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

  4. 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.

  5. Primary hepatocellular carcinoma in extrahepatic bile duct

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    Jeong, Seok Tae; Ham, Soo Youn; Park, Cheol Min; Kim, Jung Hyuk; Cha, In Ho; Chung, Kyoo Byung; Suh, Woon Hyuck; Lee, Chang Hong [College of Medicine, Korea University, Seoul (Korea, Republic of)

    1991-03-15

    Obstructive jaundice due to hepatocellular carcinoma in an extrahepatic bile duct, without a mass lesion in the liver parenchyma, is extremely rare. We experienced two cases of primary hepatocellular carcinoma arising from an extrahepatic bile duct: one in a 53-year-old man whose {alpha} -fetoprotein value was 800 ng/ml, and another in a 39-year-old woman, in whom the mass lesion was found to be attached to an extrahepatic bile duct. These tumors had a well-marginated sausage-like shape on CT and US, and the contrast media passed freely along their margins on both PTC and ERCP. Recurrences of these tumors were observed in the extrahepatic bile duct 6 and 2 months after surgery, respectively.

  6. Extrahepatic intraductal ectopic hepatocellularcarcinoma:bileductifllingdefect

    Institute of Scientific and Technical Information of China (English)

    Moritz Schmelzle; Wolfram T. Knoefel; Claus F. Eisenberger; Hanno Matthaei; Nadja Lehwald; Andreas Raffel; Roy Y. Tustas; Natalia Pomjanski; Petra Reinecke; Marcus Schmitt; Jan Schulte am Esch

    2009-01-01

    BACKGROUND: Obstructive jaundice caused by an intraductal hepatocellular carcinoma is a rare initial symptom. We report a rare case of an extrahepatic icteric type hepatocellular carcinoma. METHODS: A 75-year-old patient was admitted to our hospital because of obstructive jaundice 3 months after resection of multilocular hepatocellular carcinoma. A postoperative bile leakage was treated by placement of a decompressing stent in the common bile duct. Endoscopic retrograde choledochoscopy showed extended blood clots iflling the bile duct system and computed tomography revealed a local swelling in the common extrahepatic bile duct. The level of alpha-fetoprotein (AFP) was only slightly elevated but that of CA19-9 was dramatically increased. Cholangiography showed an intraductal iflling defect typical of a cholangiocellular carcinoma. RESULTS: Bile duct brushing cytology showed no cholangiocellular carcinoma but hepatocellular carcinoma cells in the extrahepatic bile duct. An extrahepatic bile duct resection was performed. Histological examination conifrmed the diagnosis of extrahepatic intraductal growth of hepatocellular carcinoma. CONCLUSION: Ectopic hepatocellular carcinoma is a rare but important differentially diagnosed of extrahepatic bile duct iflling defect.

  7. 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.

  8. 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

  9. Sonographic Features of Extrahepatic Cholangio carcinoma

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    Chung, Kyoo Byung; Lee, Hwang Bok; Choi, Won Young; Jeon, Hae Jeoung; Suh, Won Hyuck [Korea University College of Medicine, Seoul (Korea, Republic of)

    1987-12-15

    The cholangio carcinoma of extrahepatic bile duct is one of the common cause of obstructive jaundice, and the sonography is now the most convenient initial examination of theses cases. The location of 25 proven cases of extrahepatic cholangio carcinoma were classified as Klatskin type(6 cases), common hepatic duct(CHD)(9 cases) and common bilduct(CBD)(10cases). And the sonographic findings were analysed. The characteristic sonographic finding of Klatskin tumor was tqpered narrowing of dilated intrahepatic ducts at portal hepatis without communication between both lobe bile ducts. The CHD, cancer showed communicating dilatation of the intrahepatic ducts, but CHD cancer showed ommunicating dilatation of the intrahepatic ducts, but there was no dilatation of gall bladder or CBD, and in case of CBD cancer, entire biliary trees were usually dilated. With the sonographic findings onle, 19 of 25 cases(76%)were diagnosed as cholangio carcinoma, and 13 of 25 cases (52%) were diagnosed correctly the involved site as well as the malignant nature. The sonographic accuracy of the extrahepatic cholangiocarcinoma was greater in Klatskin tumor than the CHD or CBD cancer. Sonogram is most valuable screening study for cholangio carcinoma, and the CT scan and direct cholangiography such as PTC or ERCP have compensatory roles in detecting hepatic metastasis, regional adenopathy and length of involved bile duct

  10. 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

  11. 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.

  12. 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

  13. Livergraftvascularvariantwith 3 extra-hepatic arteries

    Institute of Scientific and Technical Information of China (English)

    Paulo N Martins

    2010-01-01

     Vascular anatomy of the liver is varied, and the"standard"anatomy is seen in 55%-80%of cases. It is very important that extrahepatic arteries are identiifed precisely at the time of graft procurement to avoid injuries that might compromise the liver function. In the present case the liver donor had the vascular anatomy of Michels type Ⅶ, e.g. a hepatic artery originating from the celiac trunk and going to the left lobe, an accessory left hepatic artery coming from the left gastric artery, and a replaced right hepatic artery coming from the superior mesenteric artery. This pattern of vascular supply is uncommon, representing less than 5%of cases. The replaced hepatic artery was reconstructed in the back-table with polypropylene suture 7.0 by connecting it to the stump of the splenic artery, and the celiac trunk of the graft was anastomosed to the recipient common hepatic artery.

  14. Percutaneous transarterial embolization of extrahepatic arteroportal fistula

    Institute of Scientific and Technical Information of China (English)

    Gianluca Marrone; Settimo Caruso; Roberto Miraglia; Ilaria Tarantino; Riccardo Volpes; Angelo Luca

    2006-01-01

    Arteroportal fistula is a rare cause of prehepatic portalhypertension. A 44-year-old male with hepatitis virus C infection was admitted for acute variceal bleeding.Endoscopy showed the presence of large esophageal varices. The ultrasound revealed a mass near the head of pancreas, which was characterized at the colorDoppler by a turbulent flow, and arterialization of portal vein flow. CT scan of abdomen showed a large aneurysm of the gastroduodenal artery communicating into the superior mesenteric vein. The sinusoidal portal pressure measured as hepatic vein pressure gradient was normal, confirming the pre-hepatic origin of portal hypertension. The diagnosis of extrahepatic portal hypertension secondary to arteroportal fistula was established, and the percutaneous embolization was performed.Three months later, the endoscopy showed absence of esophageal varices and ascites. At the moment, the patient is in good clinical condition, without signs of portal hypertension.

  15. Extrahepatic complications to cirrhosis and portal hypertension

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens H; Bendtsen, Flemming

    2014-01-01

    In addition to complications relating to the liver, patients with cirrhosis and portal hypertension develop extrahepatic functional disturbances of multiple organ systems. This can be considered a multiple organ failure that involves the heart, lungs, kidneys, the immune systems, and other organ...... the hepatorenal syndrome. Patients with end-stage liver disease and related complications as for example the hepatopulmonary syndrome can only radically be treated by liver transplantation. As a bridge to this treatment, knowledge on the mechanisms of the pathophysiology of complications is essential...... systems. Progressive fibrosis of the liver and subsequent metabolic impairment leads to a systemic and splanchnic arteriolar vasodilatation. This affects both the haemodynamic and functional homeostasis of many organs and largely determines the course of the disease. With the progression of the disease...

  16. 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

  17. 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

  18. 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...

  19. 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.

  20. Primary cancers of extrahepatic biliary passages

    Energy Technology Data Exchange (ETDEWEB)

    Mittal, B.; Deutsch, M.; Iwatsuki, S.

    1985-04-01

    The records of 22 patients with cancers of extrahepatic biliary passages (EHBP) were analyzed to understand their natural histories and patterns of failure and to evaluate the effectiveness of various treatments. None of the preoperative investigations consistently defined the entire extent of tumor. Percutaneous transhepatic cholangiography (PTHC) was the most helpful (100%) in accurately defining the site of ductal obstruction. Computed tomography was helpful in diagnosing liver metastases in 53% and primary tumor mass in 23% of patients. The most common sites of tumor failure or persistence were: liver (67%), tumor bed (56%), peritoneum (22%), porta hepatis and lymph nodes (17%). The median survival for the entire group was 6.8 months. Surgery plays an important role in managing these tumors and in defining tumor extent for subsequent adjuvant irradiation. Patients receiving radiation doses greater than or equal to 70 TDF had a longer median survival (11 months) than patients receiving less than 70 TDF (4.4 months). All three patients, who were alive and free of disease greater than 1 year, received radiation doses greater than or equal to 70 TDF. From the data, it is difficult to comment on the effectiveness of chemotherapy. The authors have made suggestions regarding radiation volume and doses to various structures. The need for entering these patients into multi-institutional clinical trials is stressed.

  1. Primary cancers of extrahepatic biliary passages.

    Science.gov (United States)

    Mittal, B; Deutsch, M; Iwatsuki, S

    1985-04-01

    We analyzed the records of 22 patients with cancers of extrahepatic biliary passages (EHBP) to understand their natural histories and patterns of failure and to evaluate the effectiveness of various treatments. None of the preoperative investigations consistently defined the entire extent of tumor. Percutaneous transhepatic cholangiography (PTHC) was the most helpful (100%) in accurately defining the site of ductal obstruction. Computed tomography was helpful in diagnosing liver metastases in 53% and primary tumor mass in 23% of patients. The most common sites of tumor failure or persistence were: liver (67%), tumor bed (56%), peritoneum (22%), porta hepatis and lymph nodes (17%). The median survival for the entire group was 6.8 months. Surgery plays an important role in managing these tumors and in defining tumor extent for subsequent adjuvant irradiation. Patients receiving radiation doses greater than or equal to 70 TDF had a longer median survival (11 months) than patients receiving less than 70 TDF (4.4 months). All three patients, who were alive and free of disease greater than 1 year, received radiation doses greater than or equal to 70 TDF. From our data, it is difficult to comment on the effectiveness of chemotherapy. We have made suggestions regarding radiation volume and doses to various structures. The need for entering these patients into multi-institutional clinical trials is stressed. PMID:3980281

  2. Primary cancers of extrahepatic biliary passages

    International Nuclear Information System (INIS)

    The records of 22 patients with cancers of extrahepatic biliary passages (EHBP) were analyzed to understand their natural histories and patterns of failure and to evaluate the effectiveness of various treatments. None of the preoperative investigations consistently defined the entire extent of tumor. Percutaneous transhepatic cholangiography (PTHC) was the most helpful (100%) in accurately defining the site of ductal obstruction. Computed tomography was helpful in diagnosing liver metastases in 53% and primary tumor mass in 23% of patients. The most common sites of tumor failure or persistence were: liver (67%), tumor bed (56%), peritoneum (22%), porta hepatis and lymph nodes (17%). The median survival for the entire group was 6.8 months. Surgery plays an important role in managing these tumors and in defining tumor extent for subsequent adjuvant irradiation. Patients receiving radiation doses greater than or equal to 70 TDF had a longer median survival (11 months) than patients receiving less than 70 TDF (4.4 months). All three patients, who were alive and free of disease greater than 1 year, received radiation doses greater than or equal to 70 TDF. From the data, it is difficult to comment on the effectiveness of chemotherapy. The authors have made suggestions regarding radiation volume and doses to various structures. The need for entering these patients into multi-institutional clinical trials is stressed

  3. 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....

  4. 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

  5. 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.

  6. 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

  7. Comparison of Accuracy of Ultrasonography and Isotope scan in Diagnosis of Extrahepatic Biliary Atresia

    Directory of Open Access Journals (Sweden)

    M. Nemati

    2008-01-01

    Full Text Available Background/Objective: Infantile cholestasis continues to represent a diagnostic chalange. Prolonges conjugated hyperbilirubinemia can be caused by extrahepatic biliary atresia (EHBA or by nonobstructive metabolic and inflammatory causes. "nNowadays, isotopscanning including HIDA is the most popular method to rule out of EHBA and finally liver biopsy is the last step in preoperative confirmation of EHBA. Currently the role of ultrasound in these patients is a dilemma and contraversial. "nPatients and Methods: In this prospective study, 49 infants with prolonged jaundice were studied between January 2004 and April 2006 in Tabriz children's Hospital. All of these infants were evaluated with ultrasonography and isotopscan and finally all of them were biopsied under guide of sonography. "nIn their Sonogrphic evaluation, absence or pres-ence of gall bladder, its size and wall thickness and also its depletion after nutrition was controlled and beside this, triangular cord sign (TACS was checked in all of them."nResults: In diagnosis of EHBA, the PPV, NPV and accuracy of nonvisulaization of gall bladder is 75%, 81.4%, 79% respectively. The accuracy of postnutrition depletion of gall blodder in diagnosis of EHBA is 90%. "nThe PPV of TACS in diagnosis of EHBA is 100% and its NVP and accuracy are 78.5%, 80%."nOverall accuracy, PPV, NPV, specificity and sensitivity of sonographic technics (in combination with each other is 93%, 92%, 94%, 97%, 86% respectively."nOn the other hand, though the NPV and sensitivity of isotopscan is 100% but due to high false positive findings, its PPV, specificity and accuracy are low (46.6%, 51.3%, 66% respectively."nConclusion: Ultrasonographic findings are more accurate, more specific and its positive results are more reliable than isotopscanning in diagnosis of EHBA.

  8. LAPAROSCOPIC ANATOMY OF THE EXTRAHEPATIC BILIARY TRACT

    Directory of Open Access Journals (Sweden)

    E. Târcoveanu

    2005-01-01

    Full Text Available Development of mini-invasive surgery determinates a rapid improvement in laparoscopic regional anatomy. As laparoscopy is becoming common in most surgical departments, basic laparoscopic anatomy is mandatory for all residents in general surgery. Successful general surgery starts in the anatomy laboratory. Successfully minim invasive surgery starts in the operative theatre with laparoscopic exploration. The initial laparoscopic view of the right upper quadrant demonstrates primarily the subphrenic spaces, abdominal surface of the diaphragm and diaphragmatic surface of the liver. The falciform ligament is a prominent dividing point between the left subphrenic space and the right subphrenic space. The ligamentum teres hepatis is seen in the free edge of the falciform. Upward traction on the gallbladder exposes the structures of Calot’s triangle and the hepatoduodenal ligament. The liver is divided into anatomic segments based on internal anatomy that is invisible to the laparoscopist. Surface landmarks include the falciform ligament and the gallbladder fossa. The surgical procedures performed laparoscopically currently include liver biopsy, wedge resection, fenestration of hepatic cysts, laparoscopic approach of the hidatid hepatic cyst, and atypical hepatectomy. We present the laparoscopic anatomy of extrahepatic biliary tract. Once the gallbladder is elevated, inspection reveals Hartmann’s pouch and the cystic duct. The typical angular junction of the cystic duct on the common duct actually occurs in a minority of patients and the length and course of the cystic duct are highly variable. The boundaries of Calot’s triangle are often not well seen. The cystic artery is often visible under the peritoneum as it runs along the surface of the gallbladder. The variations of the structures of the hepatoduodenal ligament may occur to injuries during laparoscopic cholecystectomy. Cholangiography increases the safety of dissection of biliary tract by

  9. 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

  10. 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.

  11. Cholangiopathy in extrahepatic portal venous obstruction: radiological appearances

    Energy Technology Data Exchange (ETDEWEB)

    Nagi, B.; Kochhar, R.; Bhasin, D.; Singh, K. [Postgraduate Inst. of Medical Education and Research, Chandigarh (India). Dept. of Gastroenterology

    2000-11-01

    To evaluate cholangiographic abnormalities resulting from extrahepatic portal venous obstruction (EHPVO) by sonography and endoscopic retrograde cholangiopancreaticography (ERCP). Material and Methods: Forty-three patients with an established diagnosis of EHPVO were subjected to duplex Doppler sonography and ERCP. Of these, 8 patients had obstructive jaundice. Results: Dilated common bile duct with pericholedochal varices showing a continuous type of flow pattern was seen in 5 EHPVO patients with obstructive jaundice. ERCP revealed cholangiographic abnormalities in 40 patients (93%). Extrahepatic bile ducts were involved in 100% of cases compared to intrahepatic bile ducts (57%). Abnormalities noted were contour irregularity with indentations, displacement and angulation, strictures and filling defects in the extrahepatic ductal system. Intrahepatic bile ducts showed dilatation with areas of narrowing and filling defects. Conclusion: Cholangiographic abnormalities are very common in patients with EHPVO, even without clinical manifestations of biliary disease. Extrahepatic bile ducts are far more often involved compared to intrahepatic bile ducts. Extrinsic compression with contour irregularity is the most common cholangiographic finding. Sonographic findings are not diagnostic. Dilated common bile duct with pericholedochal varices was seen in only 5 patients.

  12. Ergotamine abuse and extra-hepatic portal hypertension.

    OpenAIRE

    Fisher, P E; Silk, D. B.; Menzies-Gow, N; Dingle, M.

    1985-01-01

    Arterial complications following ergotamine therapy have been well recognized since the beginning of this century. Venous complications, however, have only rarely been reported. A 48 year old Nigerian woman developed extra-hepatic portal hypertension coincident with a chronic overdosage of ergotamine. The literature elucidating the possible mechanisms involved is reviewed.

  13. 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...

  14. 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)

  15. 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.

  16. [Consequences of extrahepatic manifestations of hepatitis C viral infection (HCV)].

    Science.gov (United States)

    Pawełczyk, Agnieszka

    2016-01-01

    The hepatitis C virus (HCV) is a primarily hepatotropic virus. However, numerous extrahepatic symptoms are observed in patients chronically infected with HCV, e.g. cryoglobulinemia, lymphoproliferative disorders, kidney diseases, disturbances of the central and peripheral nervous system, thyroid gland, pancreas, lymph nodes and pituitary gland, that develop at various times after the infection. Complex mechanisms underlie these processes, both molecular, related to direct effects of the virus on cells or tissues and indirect mechanisms, resulting from the response of the immune system to infection (via cytokines or oxidative stress), and from the antiviral treatment used. Understanding these mechanisms may contribute to the definition of new prognostic factors, important for the early diagnosis of the infection, which in turn may improve treatment efficacy. This paper is a review of the incidence of selected extrahepatic manifestations of HCV infection and their underlying pathogenetic mechanisms and risk factors. PMID:27117111

  17. Successful surgical management of an extrahepatic biliary cystadenocarcinoma

    Directory of Open Access Journals (Sweden)

    Márcio Lobo Guimarães

    2011-10-01

    Full Text Available Extrahepatic bile duct cancer is an uncommon disease, and few cases are curable by surgery. We report a case of extrahepatic biliary cystadenocarcinoma (BCAC associated with atrophy of the left hepatic lobe. A 54-year old male was admitted with painless obstructive jaundice and a hepatic palpable mass noticed one month before presentation. Liver functions tests were consistent with cholestatic damage and serum carbohydrate antigen 19.9 (CA 19-9 was increased before treatment. Magnetic resonance imaging (MRI disclosed dilatation of the left hepatic bile duct with irregular wall thickening close to the hepatic confluence, and atrophy of left hepatic lobe. The patient was submitted to en bloc extended left hepatectomy with resection of caudate lobe, hilar lymphadenectomy, and suprapancreatic biliary tree resection. All surgical margins were grossly negative, and postoperative course was uneventful, except for a minor bile leak. The patient was discharged on the 15th postoperative day; he is alive without tumor recurrence one year after primary therapy. Although technically challenging, extended en bloc resection is feasible in adults with extrahepatic BCAC and can improve survival with acceptable and manageable morbidity.

  18. Extrahepatic portal vein aneurysm: Two case reports of surgical intervention

    Institute of Scientific and Technical Information of China (English)

    Bi Jin; Yuan Sun; Yi-Qing Li; Yu-Guo Zhao; Chuan-Shan Lai; Xian-Song Feng; Chi-Dan Wan

    2005-01-01

    We report two cases of extrahepatic portal vein aneurysm,and both of them underwent surgical intervention. The first case had a mild pain in right upper quadrant of the abdomen; the second had no obvious symptoms. Physical examination revealed nothing abnormal. Both of them were diagnosed by magnetic resonance imaging angiography (MRA). One of the aneurysms was located at the main portal vein, the other, at the confluence of the superior mesenteric vein and the splenic vein, and these two places are exactly the most common locations of the extrahepatic portal vein aneurysm reported in the literature (30.7% each site). The first case underwent aneurysmorrhaphy and the second case, aneurysm resection with splenectomy. Both of them recovered soon after the operation, and the symptom of the first case was greatly alleviated. During the follow-up of half a year, no complication and adverse effect of surgical intervention was found and the color Doppler ultrasonography revealed no recurrence of the aneurysmal dilation. We suggest that surgical intervention can alleviate the symptom of the extrahepatic portal vein aneurysm and prevent its complications effectively and safely for low risk patients.

  19. 99mTc-Macroaggregated Albumin SPECT/CT Perfusion Imaging of Omental Extrahepatic Vascularization.

    Science.gov (United States)

    Nguyen, Ba D; Yang, Ming; Roarke, Michael C

    2016-01-01

    The authors present a case of omental perfusion by an extrahepatic branch of the right hepatic artery depicted during pre-embolization planning with 99mTc-macroaggregated albumin SPECT/CT imaging. This omental scintigraphic finding corresponds to an extrahepatic branch of the right hepatic artery demonstrated by selective angiography and related CT angiography. The authors would like to add the omentum to the previously reported sites of extrahepatic vascularization encountered during the hepatic pre-embolization imaging. PMID:26650883

  20. 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

  1. Clinical features and prognosis of patients with extrahepatic metastases from hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Kiminori Uka; Kazuaki Chayama; Hiroshi Aikata; Shintaro Takaki; Hiroo Shirakawa; Soo Cheol Jeong; Keitaro Yamashina; Akira Hiramatsu; Hideaki Kodama; Shoichi Takahashi

    2007-01-01

    AIM: To assess the clinical features and prognosis of 151 patients with extrahepatic metastases from primary hepatocellular carcinoma (HCC), and describe the treatment strategy for such patients.METHODS: After the diagnosis of HCC, all 995consecutive HCC patients were followed up at regular intervals and 151 (15.2%) patients were found to have extrahepatic metastases at the initial diagnosis of primary HCC or developed such tumors during the follow-up period. We assessed their clinical features,prognosis, and treatment strategies.RESULTS: The most frequent site of extrahepatic metastases was the lungs (47%), followed by lymph nodes (45%), bones (37%), and adrenal glands (12%).The cumulative survival rates after the initial diagnosis of extrahepatic metastases at 6, 12, 24, and 36 mo were 44.1%, 21.7%, 14.2%, 7.1%, respectively. The median survival time was 4.9 mo (range, 0-37 mo). Fourteen patients (11%) died of extrahepatic HCC, others died of primary HCC or liver failure.CONCLUSION: The prognosis of HCC patients with extrahepatic metastases is poor. With regard to the cause of death, many patients would die of intrahepatic HCC and few of extrahepatic metastases. Although most of HCC patients with extrahepatic metastases should undergo treatment for the primary HCC mainly,treatment of extrahepatic metastases in selected HCC patients who have good hepatic reserve, intrahepatic tumor stage (T0-T2), and are free of portal venous invasion may improve survival.

  2. 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...

  3. 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...

  4. 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.

  5. 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.

  6. 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 ...

  7. 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.

  8. 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

  9. Plasma Lipidomics as a Tool for Diagnosis of Extrahepatic Cholangiocarcinoma in Biliary Strictures: a Pilot Study.

    Science.gov (United States)

    Prachayakul, Varayu; Thearavathanasingha, Phataraphong; Thuwajit, Chanitra; Roytrakul, Sittiruk; Jaresitthikunchai, Janthima; Thuwajit, Peti

    2016-01-01

    Biliary obstruction is a common clinical manifestation of various conditions, including extrahepatic cholangiocarcinoma. However, a screening test for diagnosis of extrahepatic cholangiocarcinoma in patients with biliary obstruction is not yet available. According to the rationale that the biliary system plays a major role in lipid metabolism, biliary obstruction may interfere with lipid profiles in the body. Therefore, plasma lipidomics may help indicate the presence or status of disease in biliary obstruction suspected extrahepatic cholangiocarcinoma. This study aimed to use plasma lipidomics for diagnosis of extrahepatic cholangiocarcinoma in patients with biliary obstruction. Plasma from healthy volunteers, patients with benign biliary obstruction extrahepatic cholangiocarcinoma, and other related cancers were used in this study. Plasma lipids were extracted and lipidomic analysis was performed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Lipid profiles from extrahepatic cholangiocarcinoma patients showed significant differences from both normal and benign biliary obstruction conditions, with no distinction between the latter two. Relative intensity of the selected lipid mass was able to successfully differentiate all extrahepatic cholangiocarcinoma samples from patient samples taken from healthy volunteers, patients with benign biliary obstruction, and patients with other related cancers. In conclusion, lipidomics is a non-invasive method with high sensitivity and specificity for identification of extrahepatic cholangiocarcinoma in patients with biliary obstruction. PMID:27644677

  10. Angiographic Findings of Extrahepatic Branches Originating from Hepatic Artery and Its Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    Xiao-dong Wang; Ren-jie Yang

    2009-01-01

    Objective: To observe the presentation and variation of extrahepatic branches originating from hepatic artery by hepatic arteriography.Methods: Hepatic arteriogram of 200 cases with unresectable hepatic primary or metastatic tumors before interventional therapy were retrospectively analyzed. Two interventional radiologists independently reviewed the type, originating artery, distribution and variation of extrahepatic artery.Results: Five types of extrahepatic artery were found, with the most common type of the right gastric artery (n=156, 78%), followed by the cystic artery (n=126, 63%), accessory left gastric artery (n=19, 9.5%), hepatic falciform artery (n=5, 2.5%), and accessory left inferior phrenic artery (n=4, 2%). In 188 cases, there were extrahepatic arteries derived from hepatic proper artery or its branches, and the most frequent originating site was the right hepatic artery (130 extrahepatic branches), followed by the proper hepatic artery (103 branches), left hepatic artery (56 branches) and middle hepatic artery (3 branches). The left hepatic artery was the arising site with the multiple types of extrahepatic branches including all above branches except the cystic artery.Conclusion: Many types of extrahepatic branches usually derive from the hepatic artery or its distal branches, and its originating sites are not constant. It is important to avoid damage of extrahepatic tissue during interventional therapy for liver tumors.

  11. Extrahepatic manifestations of chronic hepatitis C virus infection.

    Science.gov (United States)

    Cacoub, Patrice; Comarmond, Cloe; Domont, Fanny; Savey, Léa; Desbois, Anne C; Saadoun, David

    2016-02-01

    During hepatitis C virus (HCV) chronic infection, extrahepatic manifestations are frequent and polymorphous. This article reports on a large cohort of patients with HCV-related autoimmune or lymphoproliferative disorders, from mixed cryoglobulinemia vasculitis to frank lymphomas. The relationship between HCV infection and such immune-related diseases has been formally demonstrated by epidemiological, clinical, immunological and pathological data, and results of therapeutic trials. More recently, other nonliver-related HCV disorders have been reported, including cardiovascular (i.e. stroke, ischemic heart disease), renal, metabolic and central nervous system diseases. For these manifestations, most evidence comes from large epidemiological studies; there is a need for mechanistic studies and therapeutic trials for confirmation. Beyond the risk of developing liver complications, that is, cirrhosis and liver cancer, patients with HCV infection have an increased risk of morbidity and mortality related to nonliver diseases. HCV chronic infection should be analyzed as a systemic disease in which extrahepatic consequences increase the weight of its pathological burden. The need for effective viral eradication measures is underlined. PMID:26862398

  12. Microwell scaffolds for the extrahepatic transplantation of islets of Langerhans.

    Directory of Open Access Journals (Sweden)

    Mijke Buitinga

    Full Text Available Allogeneic islet transplantation into the liver has the potential to restore normoglycemia in patients with type 1 diabetes. However, the suboptimal microenvironment for islets in the liver is likely to be involved in the progressive islet dysfunction that is often observed post-transplantation. This study validates a novel microwell scaffold platform to be used for the extrahepatic transplantation of islet of Langerhans. Scaffolds were fabricated from either a thin polymer film or an electrospun mesh of poly(ethylene oxide terephthalate-poly(butylene terephthalate (PEOT/PBT block copolymer (composition: 4000PEOT30PBT70 and were imprinted with microwells, ∼400 µm in diameter and ∼350 µm in depth. The water contact angle and water uptake were 39±2° and 52.1±4.0 wt%, respectively. The glucose flux through electrospun scaffolds was three times higher than for thin film scaffolds, indicating enhanced nutrient diffusion. Human islets cultured in microwell scaffolds for seven days showed insulin release and insulin content comparable to those of free-floating control islets. Islet morphology and insulin and glucagon expression were maintained during culture in the microwell scaffolds. Our results indicate that the microwell scaffold platform prevents islet aggregation by confinement of individual islets in separate microwells, preserves the islet's native rounded morphology, and provides a protective environment without impairing islet functionality, making it a promising platform for use in extrahepatic islet transplantation.

  13. 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

  14. 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

  15. Protein induced by vitamin K absence or antagonist-II production is a strong predictive marker for extrahepatic metastases in early hepatocellular carcinoma: a prospective evaluation

    OpenAIRE

    Yoon Jung-Hwan; Lee Jeong-Hoon; Bae Hyun-Mi; Kim Yoon; Heo Dae; Lee Hyo-Suk

    2011-01-01

    Abstract Background Clinicians often experience extrahepatic metastases associated with hepatocellular carcinoma (HCC), even if no evidence of intrahepatic recurrence after treatment is observed. We investigated the pretreatment predictors of extrahepatic metastases in HCC patients. Methods Patients diagnosed with HCC without evidence of extrahepatic metastases were prospectively enrolled. We evaluated the correlation between extrahepatic metastases and pretreatment clinical variables, includ...

  16. 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.

  17. 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.

  18. Extrahepatic Manifestations and Autoantibodies in Patients with Hepatitis C Virus Infection

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    Takashi Himoto

    2012-01-01

    Full Text Available Patients with chronic hepatitis C virus (HCV infection frequently have many extrahepatic manifestations, as persistent HCV infection often triggers lymphoproliferative disorders and metabolic abnormalities. These manifestations primarily include autoimmune disorders such as cryoglobulinemia, Sjögren’s syndrome, and autoimmune thyroid disorders. It has been well established that chronic HCV infection plays important roles in the production of non-organ-specific autoantibodies, including antinuclear antibodies and smooth muscle antibodies, and organ-specific autoantibodies such as thyroid autoantibodies. However, the clinical significance of autoantibodies associated with the extrahepatic manifestations caused by HCV infection has not been fully recognized. In this paper, we mainly focus on the relationship between extrahepatic manifestations and the emergence of autoantibodies in patients with HCV infection and discuss the clinical relevance of the autoantibodies in the extrahepatic disorders.

  19. Cystic Dilation of Extrahepatic Bile Ducts in Adulthood: Diagnosis, Surgical Treatment and Long. Term Results

    Directory of Open Access Journals (Sweden)

    G. Belli

    1998-01-01

    Full Text Available To evaluate the long-term results of surgery for choledohal cyst in adulthood, a series of 13 patients over the age of 16 operated on for choledochal cyst during a period of six years and followed-up for a minimum of 3 years was analyzed. Patients with type I and IVa cysts underwent extrahepatic cyst resection and Roux-en-Y hepatico-jejunostomy. Choledochoceles (type III were managed endoscopically. No operative mortality or morbidity occurred. Type I and III cysts showed almost ideal follow-up with no sign of stricture on HIDA scan. One type IVa cyst patients developed recurrent cholangitis due to anastomotic stricture, managed percutaneously. Whenever possible, complete cyst resection and Roux-en-Y reconstruction is the treatment of choice for all extrahepatic biliary cysts. Intra- and extrahepatic dilatations are adequately treated by extrahepatic resection and careful endoscopic or radiologic surveillance. Small choledochoceles can be safely managed by endoscopic sphincterotomy.

  20. Extrahepatic portal vein obstruction and portal vein thrombosis in special situations: Need for a new classification

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    Zeeshan A Wani

    2015-01-01

    Full Text Available Extrahepatic portal vein obstruction is a vascular disorder of liver, which results in obstruction and cavernomatous transformation of portal vein with or without the involvement of intrahepatic portal vein, splenic vein, or superior mesenteric vein. Portal vein obstruction due to chronic liver disease, neoplasm, or postsurgery is a separate entity and is not the same as extrahepatic portal vein obstruction. Patients with extrahepatic portal vein obstruction are generally young and belong mostly to Asian countries. It is therefore very important to define portal vein thrombosis as acute or chronic from management point of view. Portal vein thrombosis in certain situations such as liver transplant and postsurgical/liver transplant period is an evolving area and needs extensive research. There is a need for a new classification, which includes all areas of the entity. In the current review, the most recent literature of extrahepatic portal vein obstruction is reviewed and summarized.

  1. Positron emission tomography/computer tomography in guidance of extrahepatic hepatocellular carcinoma metastasis management

    OpenAIRE

    Sun, Long; Guan, Yong-Song; Pan, Wei-Ming; Chen, Gui-Bing; Luo, Zuo-Ming; Wu, Hua

    2007-01-01

    Hepatocellular carcinoma (HCC) is one of the most common primary cancers in the world. Surgery is the gold standard for treatment of patients with HCC. Recurrence and metastasis are the major obstacles to further improve the prognosis of HCC. Most recurrences are intrahepatic. However, 30% of the recurrences are extrahepatic. The role of resection in intrahepatic recurrences is widely accepted. The role of resection in extrahepatic HCC recurrence and metastasis is not well established. 18F fl...

  2. Chronic hepatitis C virus infection: Prevalence of extrahepatic manifestations and association with cryoglobulinemia in Bulgarian patients

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To assess the prevalence of extrahepatic manifestations in Bulgarian patients with chronic hepatitis C virus (HCV) infection and identify the clinical and biological manifestations associated with cryoglobulinemia.METHODS: The medical records of 136 chronically infected HCV patients were reviewed to assess the prevalence of extrahepatic manifestations. Association between cryoglobulin-positivity and other manifestations were identified using χ2 and Fisher's exact test. Risk factors for the presence of extrahepatic manifestations were assessed by logistic regression analysis.RESULTS: Seventy six percent (104/136) of the patients had at least one extrahepatic manifestation.Clinical manifestations included fatigue (59.6%),kidney impairment (25.0%), type 2 diabetes (22.8%),paresthesia (19.9%), arthralgia (18.4%), palpable purpura (17.6%), lymphadenopathy (16.2%), pulmonary fibrosis (15.4%), thyroid dysfunction (14.7%), Raynaud's phenomenon (11.8%), B-cell lymphoma (8.8%),sicca syndrome (6.6%), and lichen planus (5.9%).The biological manifestations included cryoglobulin production (37.5%), thrombocytopenia (31.6%), and autoantibodies: anti-nuclear (18.4%), anti-smooth muscle (16.9%), anti-neutrophil cytoplasm (13.2%) and anti-cardiolipin (8.8%). All extrahepatic manifestations showed an association with cryoglobulin-positivity, with the exception of thyroid dysfunction, sicca syndrome,and lichen planus. Risks factors for the presence of extrahepatic manifestations (univariate analysis) were:age ≥ 60 years, female gender, virus transmission by blood transfusions, longstanding infection (≥ 20 years), and extensive liver fibrosis. The most significant risks factors (multivariate analysis) were longstanding infection and extensive liver fibrosis.CONCLUSION: We observed a high prevalence of extrahepatic manifestations in patients with chronic HCV infection. Most of these manifestations were associated with impaired lymphoproliferation and cryoglobulin production

  3. 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)

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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...

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

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    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.

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

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    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.

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

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    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.

  13. An inguinal hernia sac tumor of extrahepatic cholangiocarcinoma origin

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    Yamazaki Hidehiro

    2006-03-01

    Full Text Available Abstract Background Metastatic hernia sac tumor from biliary malignancy is extremely rare with only one such case previously reported. We herein report an additional case of extrahepatic cholangiocarcinoma presenting as a hernia sac tumor. Case presentation A 78-year-old man presented with an irreducible right inguinal hernia associated with a firm tumor, 2.0 cm in diameter. A computed tomography scan demonstrated a soft tissue density mass with heterogeneous enhancement within the right inguinal canal. The patient underwent a hernia repair and the hernia sac tumor was resected. Histological examination of the tumor revealed a metastatic adenocarcinoma suggesting the tumor was of pancreato-biliary origin. Further investigation using imaging studies disclosed a primary tumor in the upper bile duct. The patient died of the disease nine months after the resection. Conclusion Hernia sac tumors should be considered when an irreducible, growing mass appears within an inguinal hernia. Computed tomography may be useful for the early detection of hernia sac tumors from undiagnosed intra-abdominal malignancies.

  14. Congenital extrahepatic portosystemic shunt associated with heterotaxy and polysplenia

    Energy Technology Data Exchange (ETDEWEB)

    Newman, Beverley [Lucile Packard Children' s Hospital, Department of Radiology, Stanford University School of Medicine, Stanford, CA (United States); Feinstein, Jeffrey A. [Stanford University School of Medicine, Division of Pediatric Cardiology, Department of Pediatrics, Lucile Packard Children' s Hospital, Stanford (United States); Cohen, Ronald A.; Patel, Hitendra [Children' s Hospital and Research Center, Department of Diagnostic Radiology, Oakland, CA (United States); Feingold, Brian; Kreutzer, Jacqueline [Children' s Hospital of Pittsburgh, Department of Pediatrics, Division of Pediatric Cardiology, Pittsburgh, PA (United States); Chan, Fandics P. [Stanford University School of Medicine, Cardiovascular Imaging Section, Department of Radiology, Lucile Packard Children' s Hospital, Stanford, CA (United States)

    2010-07-15

    Heterotaxy with polysplenia is associated with many cardiovascular anomalies including the occasional occurrence of congenital extrahepatic portosystemic shunts (CEPS). Missing this anomaly can lead to inappropriate and ineffective therapy. To emphasize the importance and associated anatomy of CEPS in conjunction with heterotaxy with polysplenia. Review of three young children who presented with cyanosis and pulmonary hypertension without a cardiac etiology. They were known (1) or discovered (2) to have heterotaxy with polysplenia. There was absence of the intrahepatic inferior vena cava (IVC) with azygos or hemiazygos continuation in all three cases. In spite of normal liver function, they were discovered to have large portosystemic shunts, splenorenal in location, along with diffuse peripheral pulmonary arterial dilatation suggestive of CEPS (Abernethy malformation) with hepatopulmonary or, more accurately, portopulmonary syndrome. All CEPS were ipsilateral to the spleens. Patency of the portal veins in these cases allowed for percutaneous shunt closure with resolution of cyanosis. CEPS is associated with heterotaxy with polysplenia and can be symptomatic because of pulmonary arteriovenous (AV) shunting. Portal and hepatic vein patency are critical for determining feasibility of CEPS closure. (orig.)

  15. Morphologic Features of Extrahepatic Manifestations of Hepatitis C Virus Infection

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    Huaibin M. Ko

    2012-01-01

    Full Text Available Cirrhosis and hepatocellular carcinoma are the prototypic complications of chronic hepatitis C virus infection in the liver. However, hepatitis C virus also affects a variety of other organs that may lead to significant morbidity and mortality. Extrahepatic manifestations of hepatitis C infection include a multitude of disease processes affecting the small vessels, skin, kidneys, salivary gland, eyes, thyroid, and immunologic system. The majority of these conditions are thought to be immune mediated. The most documented of these entities is mixed cryoglobulinemia. Morphologically, immune complex depositions can be identified in small vessels and glomerular capillary walls, leading to leukoclastic vasculitis in the skin and membranoproliferative glomerulonephritis in the kidney. Other HCV-associated entities include porphyria cutanea tarda, lichen planus, necrolytic acral erythema, membranous glomerulonephritis, diabetic nephropathy, B-cell non-Hodgkin lymphomas, insulin resistance, sialadenitis, sicca syndrome, and autoimmune thyroiditis. This paper highlights the histomorphologic features of these processes, which are typically characterized by chronic inflammation, immune complex deposition, and immunoproliferative disease in the affected organ.

  16. Evaluation of blood levels of nitric oxide as a means of differentiation between neonatal hepatitis and extrahepatic biliary atresia: A pilot study

    Science.gov (United States)

    Goel, Prabudh; Bhatnagar, Veereshwar; Das, Nibhriti; Kalaivani, Mani

    2015-01-01

    Aim: The differentiation between neonatal hepatitis (NH) and extrahepatic biliary atresia (EHBA) is not always possible despite all the currently available diagnostic modalities. In this study, an attempt has been made to evaluate the role of nitric oxide (NO) levels in the peripheral blood to differentiate between the two conditions, one requiring early surgical intervention (EHBA) and the other amenable to conservative medical management (NH). Patients and Methods: Twenty patients who presented to the pediatric surgical service, over a 2 years period, with features of neonatal cholestasis were enrolled in the study. The diagnostic workup included documentation of history and clinical examination, biochemical liver function tests, ultrasonography, hepatobiliary scintigraphy (HS), and magnetic resonance cholangio-pancreaticography (MRCP). These patients did not show excretion on HS and intrahepatic ducts on MRCP. Hence, they were subjected to mini-laparotomy and operative cholangiography (OC). The EHBA patients were treated with the Kasai's portoenterostomy procedure, and the extrahepatic ducts were flushed with normal saline in NH patients. All patients were evaluated preoperatively for levels of NO in the peripheral blood by the Greiss reaction spectrophotometrically at 540 nm. Normal values were determined from a cohort of controls. The median (range) levels of NO in patients with EHBA and NH were compared, and the statistical significance of the difference was calculated by applying the Wilcox Rank Sum test. A P = 0.05 was considered as significant. Results: Of the 20 patients enrolled in the study, 17 patients were treated for EHBA (Group I) and the remaining 3 patients had patent ducts on OC and were thus diagnosed as NH (Group II). The mean age of the patients in Groups I and II was comparable: 2.79 ± 0.75 and 2.67 ± 0.58 months, respectively (P = 0.866). The median NO levels were significantly elevated in each of the two groups as compared to the controls

  17. Association between biliary complications and technique of hilar division (extrahepatic vs. intrahepatic in major liver resections

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    Gamaletsos Evangelos

    2006-08-01

    Full Text Available Abstract Background Division of major vascular and biliary structures during major hepatectomies can be carried out either extrahepatically at the porta hepatic or intrahepatically during the parenchymal transection. In this retrospective study we test the hypothesis that the intrahepatic technique is associated with less early biliary complications. Methods 150 patients who underwent major hepatectomies were retrospectively allocated into an intrahepatic group (n = 100 and an extrahepatic group (n = 50 based on the technique of hilar division. The two groups were operated by two different surgical teams, each one favoring one of the two approaches for hilar dissection. Operative data (warm ischemic time, operative time, blood loss, biliary complications, morbidity and mortality rates were analyzed. Results In extrahepatic patients, operative time was longer (245 ± 50 vs 214 ± 38 min, p Conclusion Intrahepatic hilar division is as safe as extrahepatic hilar division in terms of intraoperative blood requirements, morbidity and mortality. The extrahepatic technique is associated with more severe bile leaks and biliary injuries.

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

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    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

  19. 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.).

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. [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

  7. 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

  8. 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.

  9. Catheter tract implantation metastases associated with percutaneous biliary drainage for extrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Jun Sakata; Yoshio Shirai; Toshifumi Wakai; Tatsuya Nomura; Eiko Sakata; Katsuyoshi Hatakeyama

    2005-01-01

    AIM: To estimate the incidence of catheter tract implantation metastasis among patients undergoing percutaneous transhepatic biliary drainage (PTBD) for extrahepatic cholangiocarcinoma, and to provide data regarding the management of this unusual complication of PTBD by reviewing cases reported in the literature.METHODS: A retrospective analysis of 67 consecutive patients who underwent PTBD before the resection of extrahepatic cholangiocarcinoma was conducted. The median follow-up period after PTBD was 106 mo. The English language literature (PubMed, National Library of Medicine, Bethesda, MD, USA), from January 1966through December 2004, was reviewed.RESULTS: Catheter tract implantation metastasis developed in three patients. The cumulative incidence of implantation metastasis reached a plateau (6%)at 20 mo after PTBD. All of the three patients with implantation metastasis died of tumor progression at 3, 9, and 20 mo after the detection of this complication. Among the 10 reported patients with catheter tract implantation metastasis from extrahepatic cholangiocarcinoma (including our three patients), two survived for more than 5 years after the excision of isolated catheter tract metastases.CONCLUSION: Catheter tract implantation metastasis is not a rare complication following PTBD for extrahepatic cholangiocarcinoma. Although the prognosis for patients with this complication is generally poor, the excision of the catheter tract may enable survival in selected patients with isolated metastases along the catheter tract.

  10. Liver and extrahepatic contributions to postheparin serum lipase activity of the rat

    NARCIS (Netherlands)

    H. Jansen (Hans); W.C. Hülsmann (William)

    1974-01-01

    textabstractThe influence of the amount of heparin injected on the contributions of liver and of extrahepatic tissues to the lipase activity of postheparin serum of the rat was studied. It was found that when high doses of heparin (20 I.U./100 g bodyweight) were injected, the liver contributes for 6

  11. Diagnostic value for extrahepatic metastases of hepatocellular carcinoma in positron emission tomography/computed tomography scan

    Institute of Scientific and Technical Information of China (English)

    Ji Eun Lee; Jae Young Jang; Soung Won Jeong; Sae Hwan Lee; Sang Gyune Kim; Sang-Woo Cha; Young Seok Kim

    2012-01-01

    AIM:To evaluated the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) scan in diagnosis of hepatocellular carcinoma (HCC) and extrahepatic metastases.METHODS:A total of 138 patients with HCC who had both conventional imaging modalities and 18F-FDG PET/CT scan done between November 2006 and March 2011 were enrolled.Diagnostic value of each imaging modality for detection of extrahepatic metastases was evaluated.Clinical factors and tumor characteristics including PET imaging were analyzed as indicative factors for metastases by univariate and multivariate methods.RESULTS:The accuracy of chest CT was significantly superior compared with the accuracy of PET imaging for detecting lung metastases.The detection rate of metastatic pulmonary nodule ≥ 1 cm was 12/13(92.3%),when < 1 cm was 2/10 (20%) in PET imaging.The accuracy of PET imaging was significantly superior compared with the accuracy of bone scan for detecting bone metastases.In multivariate analysis,increased tumor size (≥ 5 cm) (P =0.042) and increased average standardized uptake value (SUV)uptake (P =0.028) were predictive factors for extrahepatic metastases.Isometabolic HCC in PET imaging was inversely correlated in multivariate analysis (P =0.035).According to the receiver operating characteristic curve,the optimal cutoff of average SUV to predict extrahepatic metastases was 3.4.CONCLUSION:18F-FDG PET/CT scan is invaluable for detection of lung metastases larger than 1 cm and bone metastases.Primary HCC having larger than 5 cm and increased average SUV uptake more than 3.4should be considered for extrahepatic metastases.

  12. Multi-slice spiral CT 3D reconstruction of extrahepatic feeding arteries in hepatocellular carcinoma:its clinical applications

    International Nuclear Information System (INIS)

    Objective: To discuss the feasibility of displaying the extrahepatic feeding arteries in hepatocellular carcinoma with the help of multi-slice spiral CT 3D reconstruction and to assess the clinical value of this technique. Methods: Triple-phase enhanced CT scanning with a 64-slice spiral CT scanner was performed in 89 patients with advanced primary hepatocellular carcinoma (HCC). Three-dimensional reconstruction techniques, including maximum intensity projection (MIP) and volume rendering (VR), with arterial phase images, were used to display the origination and course of both the intrahepatic and extrahepatic supplying arteries of HCC. The results were compared with the angiographic findings. Results: Of 59 cases with massive type HCC, extrahepatic supplying arteries were found in 33. In 21 cases of diffuse type HCC four showed extrahepatic supplying arteries,and in nine cases of nodular type HCC only one had extra-hepatic supplying arteries. The HCC could get their extrahepatic blood supply via eight pathways. A total of 44 extrahepatic supplying arteries were detected,and 19 anomalously originated hepatic arteries were found. Conclusion: The extrahepatic supplying arteries in hepatocellular carcinoma are common findings and their supplying pattern are extremely varied, which may be associated with the type and location of the tumors. Three-dimensional reconstruction technique with the help of triple-phase enhanced CT scanning on a 64-slice spiral CT scanner can provide excellent images as vivid and ideal as angiography can afford. Therefore,the times of angiography examination, the use of contrast media as well as the dose of radiation to both the patients and the physicians can be reduced as far as possible. The detailed information about extrahepatic blood supply is very useful for improving the therapeutic result of HCC. (authors)

  13. 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

  14. [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

  15. 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

  16. 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...

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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

  2. Treatment of a patient with obstructive jaundice and extrahepatic portal hypertension

    Institute of Scientific and Technical Information of China (English)

    Qing Xu; Lei Gu; Zhi-Yong Wu

    2009-01-01

    BACKGROUND:Recurrence of inlfammation in the extrahepatic bile duct can lead to bile duct stenosis, obstructive jaundice and cavernous transformation of the portal vein. The latter can develop into extrahepatic portal hypertension (PHT). It is dififcult to establish the correct method for treating these conditions. METHODS:At another hospital, a 51-year-old man developed PHT as a result of endoscopic retrograde cholangiopancreatography and endoscopic nasobiliary drainage to relieve cholelithiasis and obstructive jaundice. We dealt with the biliary tract obstruction through percutaneous transhepatic cholangial drainage (PTCD), followed by selective devascularization and a shunt operation 2 weeks after the disappearance of jaundice. Three months after cholecystojejunostomy, there were no obvious changes around the bile duct. RESULT:The patient recovered uneventfully and was discharged 14 days after operation. CONCLUSION:For this patient, surgery in stages was the best choice. The most suitable method to decrease jaundice is PTCD.

  3. Role of diffusion-weighted magnetic resonance imaging in the diagnosis of extrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To determine the clinical value of diffusion-weight- ed imaging (DWI) for the diagnosis of extrahepatic cholangiocarcinoma (EHCC) by comparing the diagnostic sensitivity of DWI and magnetic resonance cholan-giopancreatography (MRCP). METHODS: Magnetic resonance imaging examination was performed in 56 patients with suspected EHCC. T1- weighted imaging, T2-weighted imaging, MRCP and DWI sequence, DWI using single-shot spin-echo echoplanar imaging sequence with different b values (100, 300, 500, 800 and 1...

  4. Extrahepatic collaterals and liver damage in embolotherapy for ruptured hepatic artery pseudoaneurysm following hepatobiliary pancreatic surgery

    Institute of Scientific and Technical Information of China (English)

    Yoshitsugu Tajima; Tamotsu Kuroki; Ryuji Tsutsumi; Ichiro Sakamoto; Masataka Uetani; Takashi Kanematsu

    2007-01-01

    AIM: To evaluate the effects of extrahepatic collaterals to the liver on liver damage and patient outcome after embolotherapy for the ruptured hepatic artery pseudoaneurysm following hepatobiliary pancreatic surgery.METHODS: We reviewed 9 patients who underwent transcatheter arterial embolization (TAE) for the ruptured hepatic artery pseudoaneurysm following major hepatobiliary pancreatic surgery between June 1992 and April 206. We paid special attention to the extrahepatic arterial collaterals to the liver which may affect post-TAE liver damage and patient outcome.RESULTS: The underlying diseases were all malignancies, and the surgical procedures included hepatopancreatoduodenectomy in 2 patients, hepatic resection with removal of the bile duct in 5, and pancreaticoduodenectomy in 2. A total of 11 pseudoaneurysm developed: 4in the common hepatic artery, 4 in the proper hepatic artery, and 3 in the right hepatic artery. Successful hemostasis was accomplished with the initial TAE in all patients, except for 1. Extrahepatic arterial pathways to the liver, including the right inferior phrenic artery, the jejunal branches, and the aberrant left hepatic artery,were identified in 8 of the 9 patients after the completion of TAE. The development of collaterals depended on the extent of liver mobilization during the hepatic resection,the postoperative period, the presence or absence of an aberrant left hepatic artery, and the concomitant arterial stenosis adjacent to the pseudoaneurysm. The liver tolerated TAE without significant consequences when at least one of the collaterals from the inferior phrenic artery or the aberrant left hepatic artery was present. One patient, however, with no extrahepatic collaterals died of liver failure due to total liver necrosis 9 d after TAE.CONCLUSION: When TAE is performed on ruptured hepatic artery pseudoaneurysm, reduced collateral pathways to the liver created by the primary surgical procedure and a short postoperative interval may

  5. Plastic or metal stents for benign extrahepatic biliary strictures: a systematic review

    OpenAIRE

    Vleggaar Frank P; van Boeckel Petra GA; Siersema Peter D

    2009-01-01

    Abstract Background Benign biliary strictures may be a consequence of surgical procedures, chronic pancreatitis or iatrogenic injuries to the ampulla. Stents are increasingly being used for this indication, however it is not completely clear which stent type should be preferred. Methods A systematic review on stent placement for benign extrahepatic biliary strictures was performed after searching PubMed and EMBASE databases. Data were pooled and evaluated for technical success, clinical succe...

  6. Antiviral treatment prioritization in HCV-infected patients with extrahepatic manifestations - An Egyptian perspective.

    Science.gov (United States)

    El-Fishawy, Hussein; Saadi, Gamal; Hassaballa, May; Hussein, Mohamed; Doss, Wahid; Ragab, Gaafar; Barsoum, Rashad

    2016-05-01

    Egypt, the single country with highest incidence of HCV infection in the world, has embarked on a government-sponsored mass treatment program using several combinations of DAAs. Recognizing the importance of extrahepatic manifestations, independently of the hepatic, a subcommittee was assigned to develop national guidelines for respective prioritizing indications and protocols. It evaluated the benefit of treating patients with different extrahepatic manifestations, and reviewed relevant clinical trials and guidelines concerning DAA combinations available in Egypt. The latter included Sofosbuvir plus either peg-interferon, Simeprevir, Ledipasvir or daclatasvir, and the Viekera family comprising paritaprevir/ritonavir + ombitasvir with (GT-1) or without (GT-4) Dasabuvir. Any of these protocols may be used with or without Ribavirin according to indication. A blueprint was subjected to peer debate in dedicated workshops in two national meetings and subsequently to an online professional review, eventually leading to a final report that was adopted by the health authorities. Seven compelling and 10 optional indications were identified for treating patients with predominantly extrahepatic manifestations. The former include kidney disease at different stages, cryoglobulinemic vasculitis and non-Hodgkin lymphoma. Selected treatment protocols, were encoded and their use was prioritized on the basis of evidence of efficacy and safety. We concluded that any of the studied protocols may be used, preferably with ribavirin, for 12-week treatment in all patients with extrahepatic manifestations without cirrhosis and with eGFR above 30 ml/min/1.73 sqm. Ribavirin should be included in protocols for treating patients with compensated cirrhosis. Daclatasvir-based protocols are recommended for decompensated cirrhosis, while the Viekera family is recommended in patients with eGFR sqm, including those on dialysis. In kidney-transplanted patents, caution is due to avoidance of the

  7. Antiviral treatment prioritization in HCV-infected patients with extrahepatic manifestations – An Egyptian perspective

    Science.gov (United States)

    El-Fishawy, Hussein; Saadi, Gamal; Hassaballa, May; Hussein, Mohamed; Doss, Wahid; Ragab, Gaafar; Barsoum, Rashad

    2016-01-01

    Egypt, the single country with highest incidence of HCV infection in the world, has embarked on a government-sponsored mass treatment program using several combinations of DAAs. Recognizing the importance of extrahepatic manifestations, independently of the hepatic, a subcommittee was assigned to develop national guidelines for respective prioritizing indications and protocols. It evaluated the benefit of treating patients with different extrahepatic manifestations, and reviewed relevant clinical trials and guidelines concerning DAA combinations available in Egypt. The latter included Sofosbuvir plus either peg-interferon, Simeprevir, Ledipasvir or daclatasvir, and the Viekera family comprising paritaprevir/ritonavir + ombitasvir with (GT-1) or without (GT-4) Dasabuvir. Any of these protocols may be used with or without Ribavirin according to indication. A blueprint was subjected to peer debate in dedicated workshops in two national meetings and subsequently to an online professional review, eventually leading to a final report that was adopted by the health authorities. Seven compelling and 10 optional indications were identified for treating patients with predominantly extrahepatic manifestations. The former include kidney disease at different stages, cryoglobulinemic vasculitis and non-Hodgkin lymphoma. Selected treatment protocols, were encoded and their use was prioritized on the basis of evidence of efficacy and safety. We concluded that any of the studied protocols may be used, preferably with ribavirin, for 12-week treatment in all patients with extrahepatic manifestations without cirrhosis and with eGFR above 30 ml/min/1.73 sqm. Ribavirin should be included in protocols for treating patients with compensated cirrhosis. Daclatasvir-based protocols are recommended for decompensated cirrhosis, while the Viekera family is recommended in patients with eGFR sqm, including those on dialysis. In kidney-transplanted patents, caution is due to avoidance of the

  8. Extrahepatic biliary atresia with choledochal cyst: Prenatal MRI predicted and post natally confirmed: A case report

    OpenAIRE

    Madhavi Nori; J Venkateshwarlu; Vijaysekhar,; Raghavendra Prasad, G.

    2013-01-01

    Extrahepatic biliary atresia (EHBA) is an uncommon cause of neonatal jaundice. Antenatal Magnetic Resonance Imaging (MRI) diagnosis of EHBA has not been published to the best of our knowledge till date. EHBA with cystic component is likely to be mistaken for choledochal cyst. A case that was antenatally predicted and postnatally confirmed by surgery and histopathology is being reported. All imaging signs are analyzed herewith. Imaging helps in the prediction of EHBA and also helps in early po...

  9. Expression of Bcl-2 and Bax in extrahepatic biliary tract carcinoma and dysplasia

    Institute of Scientific and Technical Information of China (English)

    Sheng-Mian Li; Shu-Kun Yao; Nobuyoshi Yamamura; Toshitsugu Nakamura

    2003-01-01

    AIM: To compare the difference of expression of Bcl-2 and Bax in extrahepatic biliary tract carcinoma and dysplasia, and to analyze the role of Bcl-2 and Bax proteins in the progression from dysplasia to carcinoma and to evaluate the correlation of Bcl-2/Bax protein expression with the biological behaviors.METHODS: Expressions of Bcl-2 and Bax were examined immunohistochemically in 27 cases of extrahepatic biliary tract carcinomas (bile duct carcinoma: n=21, carcinoma of ampulla of Vater: n=6), and 10 cases of atypical dysplasia.Five cases of normal biliary epithelial tissues were used as controls. A semiquantitative scoring system was used to assess the Bcl-2 and Bax reactivity.RESULTS: The expression of Bd-2 was observed in 10 out of 27 (37.0 %) invasive carcinomas, 1 out of 10 clysplasias, none out of 5 normal epithelial tissues. Bax expression rate was 74.1% (20/27) in invasive carcinoma, 30 % (3/10) in dysplasia,and 40 % (2/5) in normal biliary epithelium. Bcl-2 and Bax activities were more intense in carcinoma than in dysplasia,with no significant difference in Bcl-2 expression (P=0.1:10),and significant difference in Bax expression (P=0.038). Level of Bax expression was higher in invasive carcinoma than in dysplasia and normal tissue (P=0.012). Bcl-2 expression was correlated to Bax expression (P=0.0059). However, Bcl-2/Bax expression had no correlation with histological subtype,grade of differentiation, or level of invasion.CONCLUSION: Increased Bcl-2/Bax expression from dysplasia to invasive tumors supports the view that this is the usual route for the development of extrahepatic biliary tract carcinoma. Bcl-2/Bax may be involved, at least in part,in the apoptotic activity in extrahepatic biliary carcinoma.

  10. Adenomas involving the extrahepatic biliary tree are rare but have an aggressive clinical course.

    Science.gov (United States)

    Loh, Kah Poh; Nautsch, Deborah; Mueller, James; Desilets, David; Mehendiratta, Vaibhav

    2016-02-01

    Biliary adenomas that are usually found in surgically removed gallbladders are rare, but can also occur in the extrahepatic biliary tree. We present a case series of extrahepatic bile duct adenomas at our institution, along with a review of the literature. All three patients with extrahepatic biliary adenomas (two in the common bile ducts, one in the hepatic duct) were female with a mean age of 74 years. On initial presentation, none of the patients had obstructive jaundice but two of the three patients had symptoms of biliary origin. Case 1 is an 85-year-old woman with an incidental biliary dilation seen on chest imaging; endoscopic ultrasound revealed a sessile adenomatous polyp in the distal bile duct. The patient refused surgery and presented with occlusive biliary stricture and jaundice 5 months after initial presentation, with cytology confirming malignant progression. Case 2 is a 78-year-old woman with a history of primary sclerosing cholangitis and who presented with cholangitis, and Gram-negative sepsis. A polypoid lesion was seen on imaging in the common hepatic duct and direct cholangioscopy with biopsies confirmed the presence of adenoma with high grade dysplasia. The patient underwent successful total bile duct resection and hepaticojejunostomy but represented 1 year later with diffuse metastatic disease to the bone, liver, and peritoneum. Case 3 is a 61-year-old woman who presented with symptoms suggestive of gallbladder pathology and was found to have a polypoid bile duct lesion on intraoperative cholangiogram. Endoscopic retrograde cholangioscopy showed an adenomatous polyp with high grade dysplasia involving the distal common bile duct. The patient underwent distal bile duct resection with choledochojejunostomy but presented with jaundice 4 years after surgery. She was found to have adenocarcinoma involving the small bowel in the Roux limb of jejunum and transverse colon. All three patients in our series presented with interval gastrointestinal

  11. 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...

  12. 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...

  13. Cystic changes in intraabdominal extrahepatic metastases from gastrointestinal stromal tumors treated with imatinib

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyo Cheol; Lee, Jeong Min; Choi, Seoung Hong; Han, Joon Koo; Choi, Byung Ihn [Seoul National University College of Medicine, Seoul (Korea, Republic of); Han, Heon; Kim, Sam Soo [Kangwon National University College of Medicine, Chuncheon (Korea, Republic of); Lee, Sang Hyun [National Cancer Center, Seoul (Korea, Republic of)

    2004-09-15

    This study was undertaken for the purpose of describing the CT features of intra-abdominal extra-hepatic metastases from gastrointestinal stromal tumors in patients who were treated with imatinib. Eleven patients with intra-abdominal extra-hepatic metastases from gastrointestinal stromal tumors, who were treated with imatinib between May 2001 and December 2003, were included in this study. The clinical findings and CT scans were retrospectively reviewed. The metastatic lesions were assessed according to the location, size (greatest diameter), attenuation, and the enhancing pattern before and after imatinib treatment. Prior to the treatment, the sizes and attenuation values of the metastatic lesions ranged from 5 to 20 cm and from 63 to 131 H, respectively. The metastatic lesions showed a heterogeneous enhancement pattern on the contrast-enhanced CT scans. After the treatment, the metastatic lesions became smaller in all 11 patients, and the corresponding attenuation value ranged from 15 to 51 H. The metastatic lesions became homogeneous and cystic in appearance on the follow-up CT scans, mimicking ascites. Intra-abdominal extra-hepatic metastases of patients with gastrointestinal stromal tumors treated with imatinib may appear as well-circumscribed cystic lesions on contrast-enhanced CT. These metastases are likely to become smaller and resemble ascites, but may persist indefinitely on the follow-up CT.

  14. Positron emission tomography/computer tomography in guidance of extrahepatic hepatocellular carcinoma metastasis management

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Hepatocellular carcinoma (HCC) is one of the most common primary cancers in the world. Surgery is the gold standard for treatment of patients with HCC. Recurrence and metastasis are the major obstacles to further improve the prognosis of HCC. Most recurrences are intrahepatic. However, 30% of the recurrences are extrahepatic. The role of resection in intrahepatic recurrences is widely accepted. The role of resection in extrahepatic HCC recurrence and metastasis is not well established. 18F fluorodeoxyglucose (18F-FDG) positron emission tomography/computer tomography (PET/CT) is useful in detecting distant metastasis from a variety of malignancies and shows superior accuracy to conventional imaging modalities in identification of intrahepatic and extrahepatic metastasis. We present one patient with one new isolated omental lymph node metastasis, who had a history of huge HCC resected six years ago. The metastatic focus was identified with 18 F-FDG PET/CT and resected. The follow-up revealed good prognosis with a long-term survival potential after resection of the omental lymphatic metastasis.

  15. Definition of ACLF and inclusion criteria for extra-hepatic organ failure.

    Science.gov (United States)

    Wang, Xiaojing; Sarin, Shiv Kumar; Ning, Qin

    2015-07-01

    A prominent characteristic of ACLF is rapid hepatic disease progression with subsequent extra-hepatic organ failure, manifesting as either hepatic coma or hepatorenal syndrome, which is associated with a high mortality rate in a short time. The APASL definition mainly emphasizes recognizing patients with hepatic failure. These patients may subsequently develop extra-hepatic multisystem organ failure leading to high mortality. It is therefore worthwhile to identify the short interim period between the development of liver failure and the onset of extra-hepatic organ failure, the potential therapeutic 'golden window.' Interventions during this period may prevent the development of complications and eventually change the course of the illness. Organ failure is suggested to be a central component of ACLF and may behave differently from chronic decompensated liver disease. Clear and practical criteria for the inclusion of organ failure are urgently needed so that patients with these life-threatening complications can be treated in a timely and appropriate manner. Recent studies suggested that the scoring systems evaluating organ failure [acute physiology, age and chronic health evaluation (APACHE) and sequential organ failure assessment (SOFA) scores] work better than those addressing the severity of liver disease [Child-Pugh and model of end-stage liver disease (MELD) scores] in ACLF. However, a key problem remains that the former scoring systems are reflective of organ failure and not predictive, thus limiting their value as an early indication for intervention.

  16. Infection of hepatitis B virus in extrahepatic endothelial tissues mediated by endothelial progenitor cells

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    Zhang Lili

    2007-04-01

    Full Text Available Abstract Background Hepatitis B virus (HBV replication has been reported to be involved in many extrahepatic viral disorders; however, the mechanism by which HBV is trans-infected into extrahepatic tissues such as HBV associated myocarditis remains largely unknown. Results In this study, we showed that human cord blood endothelial progenitor cells (EPCs, but not human umbilical vein endothelial cells (HUVECs could be effectively infected by uptake of HBV in vitro. Exposure of EPCs with HBV resulted in HBV DNA and viral particles were detected in EPCs at day 3 after HBV challenge, which were peaked around day 7 and declined in 3 weeks. Consistently, HBV envelope surface and core antigens were first detected in EPCs at day 3 after virus challenge and were retained to be detectable for 3 weeks. In contrast, HBV covalently closed circular DNA was not detected in EPCs at any time after virus challenge. Intravenous transplantation of HBV-treated EPCs into myocardial infarction and acute renal ischemia mouse model resulted in incorporation of HBV into injured heart, lung, and renal capillary endothelial tissues. Conclusion These results strongly support that EPCs serve as virus carrier mediating HBV trans-infection into the injured endothelial tissues. The findings might provide a novel mechanism for HBV-associated myocarditis and other HBV-related extrahepatic diseases as well.

  17. Extrahepatic Portal Hypertension following Liver Transplantation: a Rare but Challenging Problem

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    B. Malassagne

    1998-01-01

    Full Text Available This study reports our experience of 8 cases of extrahepatic portal hypertension after 273 orthotopic liver transplantations in 244 adult patients over a 10- year period. The main clinical feature was ascites, and the life-threatening complication was variceal bleeding. Extrahepatic portal hypertension was caused by portal vein stenosis in 6 patients, and left-sided portal hypertension in 2 patients after inadventent ligation of portal venous tributaries or portasystemic shunts. All patients with portal vein stenosis had complete relief of portal hypertension after percutaneous transhepatic venoplasty (n=4 or surgical reconstruction (n=2, after a median follow-up of 33 (range: 6–62 months. Of the 2 patients with left-sided portal hypertension, one died after splenectomy and one rebled 6 months after left colectomy. This study suggests that extrahepatic portal hypertension is a series complication after liver transplantation that could be prevented by meticulous portal anastomosis and closure of portal tributaries or portasystemic shunts to improve the portal venous flow. However, any ligation has to be performed under ultrasound guidance to avoid inadventent venous ligations.

  18. 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.)

  19. The role of radiotherapy for carcinomas of the gall bladder and extrahepatic biliary duct : retrospective analysis

    International Nuclear Information System (INIS)

    Carcinomas arising in the gall bladder(GB) or extrahepatic biliary ducts are uncommon and generally have a poor prognosis. The overall 5-year survival rates are less than 10%. Early experiences with the external radiation therapy demonstrated a good palliation with occasional long-term survival. The present report describes our experience over the past decade with irradiation of primary carcinomas of the gallbladder and extrahepatic biliary duct. From Feb. 1984 to Nov. 1995, thirty-three patients with carcinoma of the GB and extrahepatic biliary duct were treated with external beam radiotherapy with curative intent at our institution. All patients were treated with 4-MV linear accelerator and radiation dose ranged from 31.44Gy to 54.87Gy(median 44.25Gy), and three patients received additional intraluminal brachytherapy(range, 25Gy to 30Gy). Twenty-seven patients received postoperative radiation. Among 27 patients, Sixteen patients underwent radical operation with curative aim and the rest of the patients either had bypass surgery or biopsy alone. In seventeen patients, adjuvant chemotherapy was used and eleven patients were treated with 5-FU, mitomycin and leucovorin. Median follow up period was 8.5 months(range 2-97 months). The overall 2-year and 5-year survival rates in all patients were 29.9% and 13.3% respectively. In patients with GB and extrahepatic biliary duct carcinomas, the 2-year survival rates were 34.5% and 27.8% respectively. Patients who underwent radical operation showed better 2-year survival rates than those who underwent palliative operation(43.8% vs. 20.7%), albeit statistically insignificant(p>0.05). The 2-year survival rates in Stage I and II were higher than in Stage III and IV with statistical significance(p0.05). The survival of patients with relatively lower stage and/or initial good performance was significantly superior to that of others. We found an statistically insignificant trend toward better survival in patients with radical

  20. 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.

  1. 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

  2. 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...

  3. 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...

  4. 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

  5. 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...

  6. 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,...

  7. 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

  8. 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.

  9. Influential factors and formation of extrahepatic collateral artery in unresectable hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yong-Li Wang; Ming-Hua Li; Ying-Sheng Cheng; Hai-Bing Shi; Hai-Lun Fan

    2005-01-01

    AIM: To analyze the influence factors and formation of extrahepatic collateral arteries (ECAs) in unresectable hepatocellular carcinoma (HCC) with or without chemoembolization.METHODS: Detailed histories of 35 patients with 39 ECAs of HCC and images including computerized tomography scan, digital subtraction angiography were reviewed carefully to identify ECAs of HCC, ECAs arising from, and anatomic location of tumors in liver. Tumor sizes were measured, and relations of EC As with times of chemoembolization, tumor size, and the anatomic tumor location were analyzed. Complications were observed after chemoembolization through ECAs of HCC with different techniques. RESULTS: Influence factors of formation of ECAs of HCC included the times of repeated chemoembolization, thelocation of tumors in liver, the tumor size and the types of chemoembolization. ECAs in HCC appeared after 3-4 times of chemoembolization (17.9%), but a higher frequency of ECAs occurred after 5-6 times of chemoembolization (56.4%). ECAs presented easily in peripheral areas (71.8%) of liver abutting to the anterior, posterior abdominal walls, the top right of diaphragm and right kidney.ECAs also occurred easily after complete obstruction of the trunk arteries supplying HCCs or the branches of proper hepatic arteries. Extrahepatic collaterals of HCC originated from right internal thoracic (mammary) artery (RITA, 5.1%), right intercostal artery (RICA, 7.7%), left gastric artery (LGA, 12.8%), right inferior phrenic artery (RIPA, 38.5%),omental artery (OTA, 2.6%), superior mesenteric artery (SMA, 23.1%), and right adrenal and renal capsule artery (RARCA, 10.3%), respectively. The complications after chemoembolization attributed to no super selective cathet erization.CONCLUSION: The formation of ECAs in unresectable HCCis obviously correlated with multiple chemoembolization,tumor size, types of chemoembolization, anatomic locationof tumors. Extrahepatic collaterals in HCC are corresponding to the tumor

  10. Extrahepatic biliary atresia with choledochal cyst: Prenatal MRI predicted and post natally confirmed: A case report

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    Madhavi Nori

    2013-01-01

    Full Text Available Extrahepatic biliary atresia (EHBA is an uncommon cause of neonatal jaundice. Antenatal Magnetic Resonance Imaging (MRI diagnosis of EHBA has not been published to the best of our knowledge till date. EHBA with cystic component is likely to be mistaken for choledochal cyst. A case that was antenatally predicted and postnatally confirmed by surgery and histopathology is being reported. All imaging signs are analyzed herewith. Imaging helps in the prediction of EHBA and also helps in early postnatal surgical referral which in turn improves the results of Kasai′s portoenterostomy.

  11. Extrahepatic biliary atresia with choledochal cyst: Prenatal MRI predicted and post natally confirmed: A case report.

    Science.gov (United States)

    Nori, Madhavi; Venkateshwarlu, J; Vijaysekhar; Prasad, G Raghavendra

    2013-07-01

    Extrahepatic biliary atresia (EHBA) is an uncommon cause of neonatal jaundice. Antenatal Magnetic Resonance Imaging (MRI) diagnosis of EHBA has not been published to the best of our knowledge till date. EHBA with cystic component is likely to be mistaken for choledochal cyst. A case that was antenatally predicted and postnatally confirmed by surgery and histopathology is being reported. All imaging signs are analyzed herewith. Imaging helps in the prediction of EHBA and also helps in early postnatal surgical referral which in turn improves the results of Kasai's portoenterostomy. PMID:24347854

  12. Splenic Artery Aneurysm Presenting as Extrahepatic Portal Vein Obstruction: A Case Report

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    T. P. Elamurugan

    2011-01-01

    Full Text Available Splenic artery aneurysms are the most common visceral aneurysm occuring predominantly in females. They are usually asymptomatic, and the symptomatic presentation includes chronic abdominal pain of varied severity or an acute rupture with hypotension. Splenic artery aneurysm causing extrahepatic portal hypertension is very rare and is due to splenic vein thrombosis that develops secondary to compression by the aneurysm. We report one such rare presentation of splenic artery aneurysms in a pregnant female with the features of EHPVO (variceal bleed, hypersplenism treated by splenectomy along with excision of the aneurysm.

  13. 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

  14. 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.

  15. Protein induced by vitamin K absence or antagonist-II production is a strong predictive marker for extrahepatic metastases in early hepatocellular carcinoma: a prospective evaluation

    International Nuclear Information System (INIS)

    Clinicians often experience extrahepatic metastases associated with hepatocellular carcinoma (HCC), even if no evidence of intrahepatic recurrence after treatment is observed. We investigated the pretreatment predictors of extrahepatic metastases in HCC patients. Patients diagnosed with HCC without evidence of extrahepatic metastases were prospectively enrolled. We evaluated the correlation between extrahepatic metastases and pretreatment clinical variables, including serum tumor markers. A total of 354 patients were included. Seventy-six patients (21%) had extrahepatic metastases during the observation period (median, 25.3 months; range, 0.6-51.3 months). Cox regression multivariate analysis showed that serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) production levels, the intrahepatic tumor stage, platelet count, and portal vein thrombosis were independent risk factors for extrahepatic metastases. Patients with a PIVKA-II production ≥ 300 mAU/mL had a 2.7-fold (95% confidence interval; 1.5-4.8; P < 0.001) and 3.7-fold (95% confidence interval; 2.0-6.6; P < 0.001) increased risk for extrahepatic metastases after adjustment for stage, platelet count, alpha-fetoprotein ≥ 400 ng/mL, and portal vein thrombosis according to the AJCC and BCLC staging systems, respectively. PIVKA-II production levels might be a good candidate predictive marker for extrahepatic HCC metastases, especially in patients with smaller and/or fewer tumors in the liver with in stages regardless of serum alpha-fetoprotein

  16. THE ACTUALLY PRINCIPLES IN THE TREATMENT OF BILIARY OBSTRUCTION FROM EXTRAHEPATIC BILE DUCTS CANCER

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    A. Vasilescu

    2009-02-01

    Full Text Available The most common type of extrahepatic bile ducts cancer is the proximal segment which include the bifurcation of common hepatic duct (Klatskin’s tumors. The diagnosis of these kinds of tumors is always challenging. Magnetic resonance cholangiopancreatography (MRCP is the best imagistic procedure also for diagnosis and for staging. Surgical resection provides the best chance for cure in patients with biliary malignancy; unfortunately only 30% from patients with Klatskin’s tumors are diagnosed in resectable stages. The type and extension of the resection depends of the tumor stage and site. Resection of the biliary duct associated with hepatectomy and/or pancreaticoduodenectomy (performed especially for limphadenectomy has good results, from point of view of disease-free survival. In selected cases, the extrahepatic bile duct resection alone and hepatico-jejunal anastomosis is also considered as curative resection. Portal vein resection may be performed and can improve the prognosis. Palliative procedures of nonresectable bile ducts cancer consist in surgical by-pass, percutaneous biliary drainage and endoscopic endoprosthesis. Because long-term relief of jaundice is difficult without using biliary stenting, a combination of radiation therapy and stent placement is commonly used. As radiation therapy, external-beam radiotherapy is usually performed, but combined use of intraluminal brachytherapy with external beam radiation therapy is more useful for making the treatment more effective. Radiation therapy can be associated with chemotherapy (gemcitabine in unresectable bile duct cancer to extend survival and improve quality of life.

  17. Percutaneous Treatment of Malignant Jaundice Due to Extrahepatic Cholangiocarcinoma: Covered Viabil Stent Versus Uncovered Wallstents

    International Nuclear Information System (INIS)

    To compare clinical effectiveness of Viabil-covered stents versus uncovered metallic Wallstents, for palliation of malignant jaundice due to extrahepatic cholangiocarcinoma, 60 patients were enrolled in a prospective and randomized study. In half of the patients a bare Wallstent was used, and in the other half a Viabil biliary stent. Patients were followed up until death. Primary patency, survival, complication rates, and mean cost were calculated in both groups. Stent dysfunction occurred in 9 (30%) patients in the bare stent group after a mean period of 133.1 days and in 4 (13.3%) patients in the covered stent group after a mean of 179.5 days. The incidence of stent dysfunction was significantly lower in the covered stent group (P = 0.046). Tumor ingrowth occurred exclusively in the bare stent group (P = 0.007). Median survival was 180.5 days for the Wallstent and 243.5 days for the Viabil group (P = 0.039). Complications and mean cost were similar in the two groups. Viabil stent-grafts proved to be significantly superior to Wallstents for the palliation of malignant jaundice due to extrahepatic cholangiocarcinoma, with comparable cost and complication rates. Appropriate patient selection should be performed prior to stent placement.

  18. Percutaneous treatment of malignant jaundice due to extrahepatic cholangiocarcinoma: covered Viabil stent versus uncovered Wallstents.

    Science.gov (United States)

    Krokidis, Miltiadis; Fanelli, Fabrizio; Orgera, Gianluigi; Bezzi, Mario; Passariello, Roberto; Hatzidakis, Adam

    2010-02-01

    To compare clinical effectiveness of Viabil-covered stents versus uncovered metallic Wallstents, for palliation of malignant jaundice due to extrahepatic cholangiocarcinoma, 60 patients were enrolled in a prospective and randomized study. In half of the patients a bare Wallstent was used, and in the other half a Viabil biliary stent. Patients were followed up until death. Primary patency, survival, complication rates, and mean cost were calculated in both groups. Stent dysfunction occurred in 9 (30%) patients in the bare stent group after a mean period of 133.1 days and in 4 (13.3%) patients in the covered stent group after a mean of 179.5 days. The incidence of stent dysfunction was significantly lower in the covered stent group (P = 0.046). Tumor ingrowth occurred exclusively in the bare stent group (P = 0.007). Median survival was 180.5 days for the Wallstent and 243.5 days for the Viabil group (P = 0.039). Complications and mean cost were similar in the two groups. Viabil stent-grafts proved to be significantly superior to Wallstents for the palliation of malignant jaundice due to extrahepatic cholangiocarcinoma, with comparable cost and complication rates. Appropriate patient selection should be performed prior to stent placement. PMID:19495871

  19. Chronic Extrahepatic Bile Duct Dilatation: Sonographic Screening in the Patients with Opioid Addiction

    Energy Technology Data Exchange (ETDEWEB)

    Farahmand, H.; PourGholami, M.; Fathollah, Sheikh [Rafsanjan University of Medical Sciences, Rafsanjan (Iran, Islamic Republic of)

    2007-06-15

    One of the best known side effects of using opium is spasm of the sphincter of Oddi, which may increase the diameter of the extrahepatic bile ducts. Ultrasound is the first imaging modality used for evaluating the biliary system because it is commonly available and noninvasive. The principal objective of this study was to measure the common bile duct (CBD) diameter via ultrasonography in opium addicts and to evaluate the relation between the CBD diameter and the period of addiction. This research was an analytical-cross sectional study that was done on 110 opium addicts that were admitted to a drug treatment center. The diameter of the CBD in these cases was measured by ultrasonography and the results were analyzed with other factors like age, the period of addiction and the laboratory findings. According to the findings, there is a significant increase in the range of the CBD diameter in comparison with normal bile ducts. Also, the mean diameter of the CBD in the different age groups showed a significant difference (p < 0.0001) and there was a significant relation between the CBD diameter and the period of addiction (p < 0.001, r = 0.74); so, with the increased length of the addiction period, the mean CBD diameter increases. Opium addiction is one of the factors that causes extrahepatic bile duct dilatation, so in these cases, if no obstructing lesion was found on ultrasound examination and the serum bilirobine and alkaline phosphatase levels are normal, then further evaluation is not needed.

  20. Chronic Extrahepatic Bile Duct Dilatation: Sonographic Screening in the Patients with Opioid Addiction

    International Nuclear Information System (INIS)

    One of the best known side effects of using opium is spasm of the sphincter of Oddi, which may increase the diameter of the extrahepatic bile ducts. Ultrasound is the first imaging modality used for evaluating the biliary system because it is commonly available and noninvasive. The principal objective of this study was to measure the common bile duct (CBD) diameter via ultrasonography in opium addicts and to evaluate the relation between the CBD diameter and the period of addiction. This research was an analytical-cross sectional study that was done on 110 opium addicts that were admitted to a drug treatment center. The diameter of the CBD in these cases was measured by ultrasonography and the results were analyzed with other factors like age, the period of addiction and the laboratory findings. According to the findings, there is a significant increase in the range of the CBD diameter in comparison with normal bile ducts. Also, the mean diameter of the CBD in the different age groups showed a significant difference (p < 0.0001) and there was a significant relation between the CBD diameter and the period of addiction (p < 0.001, r = 0.74); so, with the increased length of the addiction period, the mean CBD diameter increases. Opium addiction is one of the factors that causes extrahepatic bile duct dilatation, so in these cases, if no obstructing lesion was found on ultrasound examination and the serum bilirobine and alkaline phosphatase levels are normal, then further evaluation is not needed

  1. Complications of extrahepatic echinococcosis:Fistulization of an adrenal hydatid cyst into the intestine

    Institute of Scientific and Technical Information of China (English)

    Juan Francisco Ruiz-Rabelo; Manuel Gomez-Alvarez; Joaquin Sanchez-Rodriguez; Sebastian Rufian Pe(n)a

    2008-01-01

    Echinococcal cysts are usually found in liver and lungs,but any other organ can potentially be involved.Extrahepatic disease due to hydatid cyst may develop in the abdominal and pelvic cavity,aside from in other less common locations,which may make both diagnosis and treatment more complex.We present a rare case of extrahepatic echinococcosis in a 70-year old patient with a 4-d history of dull abdominal pain,anemia within the transfusion range and fever.She underwent surgery for left renal hydatid cysts 30 years ago.After non operative treatment,imaging studies showed a calcified hydatid cyst in a retrogastric location communicating with a proximal jejunal loop.En-block resection of the mass together with the adrenal gland was performed including closure of the enteric fistula.Anatomic pathology confirmed the diagnosis of a calcified hydatid cyst of left adrenal origin.Surgery is the treatment of choice and most authorsrecommend removal of cyst and adrenal gland.

  2. 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

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

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    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.

  4. 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...

  5. 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

  6. 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

  7. 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...

  8. 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...

  9. Clinicopathological significance of altered Notch signaling in extrahepatic cholangiocarcinoma and gallbladder carcinoma

    Institute of Scientific and Technical Information of China (English)

    Hyun Ah Yoon; Myung Hwan Noh; Byung Geun Kim; Ji Sun Han; Jin Seok Jang; Seok Ryeol Choi; Jin Sook Jeong; Jin Ho Chun

    2011-01-01

    AIM: To investigate the role and clinicopathological significance of aberrant expression of Notch receptors and Delta-like ligand-4 (DLL4) in extrahepatic cholangiocarcinoma and gallbladder carcinoma.METHODS: One hundred and ten patients had surgically resected extrahepatic cholangiocarcinoma (CC) and gallbladder carcinoma specimens examined by immunohistochemistry of available paraffin blocks. Immunohistochemistry was performed using anti-Notch receptors 1-4 and anti-DLL4 antibodies. We scored the immunopositivity of Notch receptors and DLL4 expression by percentage of positive tumor cells with cytoplasmic expression and intensity of immunostaining. Coexistent nuclear localization was evaluated. Clinicopathological parameters and survival data were compared with the expression of Notch receptors 1-4 and DLL4.RESULTS: Notch receptor proteins showed in the cytoplasm with or without nuclear expression in cancer cells, as well as showing weak cytoplasmic expression in non-neoplastic cells. By semiquantitative evaluation, positive immunostaining of Notch receptor 1 was detected in 96 cases (87.3%), Notch receptor 2 in 97 (88.2%), Notch receptor 3 in 97 (88.2%), Notch receptor 4 in 103 (93.6), and DLL4 in 84 (76.4%). In addition, coexistent nuclear localization was noted [Notch receptor 1; 18 cases (18.8%), Notch receptor 2; 40 (41.2%), Notch receptor 3; 32 (33.0%), Notch receptor 4; 99 (96.1%), DLL4; 48 (57.1%)]. Notch receptor 1 expression was correlated with advanced tumor, node, metastasis (TNM) stage (P = 0.043), Notch receptor 3 with advanced T stage (P = 0.017), tendency to express in cases with nodal metastasis (P = 0.065) and advanced TNM stage (P = 0.052). DLL4 expression tended to be related to less histological differentiation (P = 0.095). Coexistent nuclear localization of Notch receptor 3 was related to no nodal metastasis (P = 0.027) and Notch receptor 4 with less histological differentiation (P = 0.036), while DLL4 tended to be related inversely with T

  10. The Emerging Extrahepatic Manifestations of Hepatitis C Virus Infection in Chronic Hepatitis and Mixed Cryoglobulinemia

    Directory of Open Access Journals (Sweden)

    Poupak Fallahi

    2008-08-01

    Full Text Available Hepatitis C virus (HCV is known to be responsible for both hepatic and extrahepatic diseases. Mixed cryoglobulinemia, Sjögren syndrome, and chronic polyarthritis are the most documented rheumatologic extrahepatic manifestations of HCV infection. The most frequent and clinically important extrahepatic endocrine manifestations of chronic HCV infection are thyroid disorders and type 2 diabetes mellitus. From a meta-analysis of the literature, a significant association between HCV infection and thyroid autoimmunity and/or hypothyroidism as well as a high prevalence of thyroid cancer have been reported. The pattern of thyroid disorders observed in HCV infected patients is characterized by the presence of elevated circulating anti-thyroid peroxidase antibodies with increased risk of hypothyroidism. Several clinical epidemiologic studies have reported that HCV infection is a risk factor for type 2 diabetes. The type of diabetes manifested by subjects with chronic HCV infection is not of the classical type 2 diabetes; in fact, HCV-related diabetic patients are leaner than the classical diabetic patients, and have a significantly lower LDL-cholesterol, and both systolic and diastolic blood pressure. Furthermore, patients with mixed cryoglobulinemia (mixed cryoglobulinemia and chronic HCV infection with type 2 diabetes have more frequently non-organ-specific-autoantibodies than non-diabetic patients with mixed cryoglobulinemia and those with chronic HCV infection. Based on the above-mentioned findings, it has been hypothesized that diabetes in HCV infection may have an immune-mediated pathogenesis. In patients with chronic HCV infection, we found an increased risk of carotid artery plaque and carotid intima-media thickening. These findings suggested a possible role for chronic hepatitis C in the pathogenesis of carotid artery remodelling. Recently, high prevalence rates of anti-HCV antibodies were shown in patients with hypertrophic cardiomyopathy or

  11. Protein induced by vitamin K absence or antagonist-II production is a strong predictive marker for extrahepatic metastases in early hepatocellular carcinoma: a prospective evaluation

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    Yoon Jung-Hwan

    2011-10-01

    Full Text Available Abstract Background Clinicians often experience extrahepatic metastases associated with hepatocellular carcinoma (HCC, even if no evidence of intrahepatic recurrence after treatment is observed. We investigated the pretreatment predictors of extrahepatic metastases in HCC patients. Methods Patients diagnosed with HCC without evidence of extrahepatic metastases were prospectively enrolled. We evaluated the correlation between extrahepatic metastases and pretreatment clinical variables, including serum tumor markers. Results A total of 354 patients were included. Seventy-six patients (21% had extrahepatic metastases during the observation period (median, 25.3 months; range, 0.6-51.3 months. Cox regression multivariate analysis showed that serum protein induced by vitamin K absence or antagonist-II (PIVKA-II production levels, the intrahepatic tumor stage, platelet count, and portal vein thrombosis were independent risk factors for extrahepatic metastases. Patients with a PIVKA-II production ≥ 300 mAU/mL had a 2.7-fold (95% confidence interval; 1.5-4.8; P Conclusion PIVKA-II production levels might be a good candidate predictive marker for extrahepatic HCC metastases, especially in patients with smaller and/or fewer tumors in the liver with in stages regardless of serum alpha-fetoprotein.

  12. [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.

  13. 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.

  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

    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. 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

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. Extrahepatic biliary cystadenoma with mesenchymal stroma: a true biliary cystadenoma? A case report.

    LENUS (Irish Health Repository)

    Hennessey, Derek B

    2012-02-01

    Biliary cystadenomas are benign but potentially malignant cystic neoplasms, which classically contain mesenchymal stroma similar to ovarian tissue. We report a case of an extra-hepatic biliary cystadenoma with mesenchymal stroma along with a discussion of current pathological opinion. CASE PRESENTATION: A 54-year-old female presented with abdominal pain, abnormal liver function tests and a mass on ultrasound. Computerized Tomography identified a complex multi-locular cyst in the common hepatic duct. Radical excision of the lesion and a Roux-en-Y loop bilio-enteric anastomosis was performed. Histology confirmed the presence of a benign biliary cystadenoma with ovarian type stroma. CONCLUSION: Biliary cystadenomas classically contain mesenchymal stroma similar to ovarian tissue. It now appears that cystadenomas without mesenchymal stroma appear to be more akin to similar cystic lesions of the pancreas, and may represent a dissimilar neoplasm. Therefore, malignant transformation can occur, so complete excision is recommended.

  1. Experimentally induced extrahepatic stenosis of the biliary tract - hepatobiliary dynamic scintigraphy and related procedures

    International Nuclear Information System (INIS)

    Biliary tract stenoses of varying degrees that have been artificially induced in rabbits are identified and quantified to a significant extent on the basis of hepatobiliary dynamic scintigraphy using 99mTc HIDA as well as of organisomorphic principles. Biochemical and physical parameters relevant to the function of the hepatobiliary tract are ascertained in long-term animal studies (pig model) both for physiological and experiment-induced pathological conditions. Moreover, the information provided by hepatobiliary dynamic scintigraphy is contrasted with that from parallel microsamples of bile. Comparisons between the results of contact cholangiography and hepatobiliary dynamic scintigraphy in pigs showing biliodigestive anastomoses fail to point to any links between the morphology and function of the extrahepatic biliary system. (TRV)

  2. Congenital Extrahepatic Portosystemic Shunts: Spectrum of Findings on Ultrasound, Computed Tomography, and Magnetic Resonance Imaging

    Science.gov (United States)

    Gupta, Pankaj; Sinha, Anindita; Sodhi, Kushaljit Singh; Lal, Anupam; Debi, Uma; Thapa, Babu R.; Khandelwal, Niranjan

    2015-01-01

    Congenital extrahepatic portosystemic shunt (CEPS) is a rare disorder characterised by partial or complete diversion of portomesenteric blood into systemic veins via congenital shunts. Type I is characterised by complete lack of intrahepatic portal venous blood flow due to an end to side fistula between main portal vein and the inferior vena cava. Type II on the other hand is characterised by partial preservation of portal blood supply to liver and side to side fistula between main portal vein or its branches and mesenteric, splenic, gastric, and systemic veins. The presentation of these patients is variable. Focal liver lesions, most commonly nodular regenerative hyperplasia, are an important clue to the underlying condition. This pictorial essay covers imaging characteristics in abdominopelvic region. PMID:26858845

  3. Congenital Extrahepatic Portosystemic Shunts: Spectrum of Findings on Ultrasound, Computed Tomography, and Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Pankaj Gupta

    2015-01-01

    Full Text Available Congenital extrahepatic portosystemic shunt (CEPS is a rare disorder characterised by partial or complete diversion of portomesenteric blood into systemic veins via congenital shunts. Type I is characterised by complete lack of intrahepatic portal venous blood flow due to an end to side fistula between main portal vein and the inferior vena cava. Type II on the other hand is characterised by partial preservation of portal blood supply to liver and side to side fistula between main portal vein or its branches and mesenteric, splenic, gastric, and systemic veins. The presentation of these patients is variable. Focal liver lesions, most commonly nodular regenerative hyperplasia, are an important clue to the underlying condition. This pictorial essay covers imaging characteristics in abdominopelvic region.

  4. Congenital Extrahepatic Portosystemic Shunts: Spectrum of Findings on Ultrasound, Computed Tomography, and Magnetic Resonance Imaging

    International Nuclear Information System (INIS)

    Congenital extrahepatic portosystemic shunt (CEPS) is a rare disorder characterised by partial or complete diversion of portomesenteric blood into systemic veins via congenital shunts. Type I is characterised by complete lack of intrahepatic portal venous blood flow due to an end to side fistula between main portal vein and the inferior vena cava. Type II on the other hand is characterised by partial preservation of portal blood supply to liver and side to side fistula between main portal vein or its branches and mesenteric, splenic, gastric, and systemic veins. The presentation of these patients is variable. Focal liver lesions, most commonly nodular regenerative hyperplasia, are an important clue to the underlying condition. This pictorial essay covers imaging characteristics in abdominopelvic region

  5. Primary extrahepatic hydatid cyst of the soft tissue: a case report

    Directory of Open Access Journals (Sweden)

    Guraya Salman

    2012-11-01

    Full Text Available Abstract Introduction Hydatid disease of the soft tissue is an exceedingly uncommon site to be affected by the tapeworm Echinococcus. The presentation is often vague and misleading. The diagnostic armamentarium has to be supplemented by a meticulously taken history and clinical examination. Case presentation The present case report describes a 33-year-old Saudi male with a painless swelling in the right buttock which turned out to be a primary hydatid disease of the soft tissue. The lump was successfully excised surgically and the patient had an uneventful discharge. Conclusion Surgical excision of the extrahepatic hydatid disease remains the mainstay of treatment; although medical treatment is available for the recurrent and disseminated disease.

  6. 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.

  7. 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.

  8. 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

  9. Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-induced LDL receptor degradation.

    Directory of Open Access Journals (Sweden)

    Nabil G Seidah

    Full Text Available Proprotein convertase subtilisin/kexin-9 (PCSK9 enhances the degradation of hepatic low-density lipoprotein receptor (LDLR. Deletion of PCSK9, and loss-of-function mutants in humans result in lower levels of circulating LDL-cholesterol and a strong protection against coronary heart disease. Accordingly, the quest for PCSK9 inhibitors has major clinical implications. We have previously identified annexin A2 (AnxA2 as an endogenous binding partner and functional inhibitor of PCSK9. Herein, we studied the relevance of AnxA2 in PCSK9 inhibition and lipid metabolism in vivo. Plasma analyses of AnxA2(-/- mice revealed: i a ∼1.4-fold increase in LDL-cholesterol without significant changes in VLDLs or HDLs, and ii a ∼2-fold increase in circulating PCSK9 levels. Western blotting and immunohistochemistry of AnxA2(-/- tissues revealed that the LDLR was decreased by ∼50% in extrahepatic tissues, such as adrenals and colon. We also show that AnxA2-derived synthetic peptides block the PCSK9≡LDLR interaction in vitro, and adenoviral overexpression of AnxA2 in mouse liver increases LDLR protein levels in vivo. These results suggest that AnxA2 acts as an endogenous regulator of LDLR degradation, mostly in extrahepatic tissues. Finally, we identified an AnxA2 coding polymorphism, V98L, that correlates with lower circulating levels of PCSK9 thereby extending our results on the physiological role of AnxA2 in humans.

  10. NAFLD and NASH in HCV Infection: Prevalence and Significance in Hepatic and Extrahepatic Manifestations.

    Science.gov (United States)

    Adinolfi, Luigi Elio; Rinaldi, Luca; Guerrera, Barbara; Restivo, Luciano; Marrone, Aldo; Giordano, Mauro; Zampino, Rosa

    2016-01-01

    The aim of this paper is to review and up to date the prevalence of hepatitis C virus (HCV)-associated non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) and their significance in both accelerating progression of HCV-related liver disease and development of HCV-associated extrahepatic diseases. The reported mean prevalence of HCV-related NAFLD was 55%, whereas NASH was reported in 4%-10% of cases. HCV genotype 3 directly induces fatty liver deposition, namely "viral steatosis" and it is associated with the highest prevalence and degree of severity, whereas, HCV non-3 genotype infection showed lower prevalence of steatosis, which is associated with metabolic factors and insulin resistance. The host's genetic background predisposes him or her to the development of steatosis. HCV's impairment of lipid and glucose metabolism causes fatty liver accumulation; this seems to be a viral strategy to optimize its life cycle. Irrespective of insulin resistance, HCV-associated NAFLD, in a degree-dependent manner, contributes towards accelerating the liver fibrosis progression and development of hepatocellular carcinoma by inducing liver inflammation and oxidative stress. Furthermore, NAFLD is associated with the presence of metabolic syndrome, type 2 diabetes, and atherosclerosis. In addition, HCV-related "metabolic steatosis" impairs the response rate to interferon-based treatment, whereas it seems that "viral steatosis" may harm the response rate to new oral direct antiviral agents. In conclusion, a high prevalence of NAFLD occurs in HCV infections, which is, at least in part, induced by the virus, and that NAFLD significantly impacts progression of the liver disease, therapeutic response, and some extrahepatic diseases. PMID:27231906

  11. NAFLD and NASH in HCV Infection: Prevalence and Significance in Hepatic and Extrahepatic Manifestations

    Science.gov (United States)

    Adinolfi, Luigi Elio; Rinaldi, Luca; Guerrera, Barbara; Restivo, Luciano; Marrone, Aldo; Giordano, Mauro; Zampino, Rosa

    2016-01-01

    The aim of this paper is to review and up to date the prevalence of hepatitis C virus (HCV)-associated non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) and their significance in both accelerating progression of HCV-related liver disease and development of HCV-associated extrahepatic diseases. The reported mean prevalence of HCV-related NAFLD was 55%, whereas NASH was reported in 4%–10% of cases. HCV genotype 3 directly induces fatty liver deposition, namely “viral steatosis” and it is associated with the highest prevalence and degree of severity, whereas, HCV non-3 genotype infection showed lower prevalence of steatosis, which is associated with metabolic factors and insulin resistance. The host’s genetic background predisposes him or her to the development of steatosis. HCV’s impairment of lipid and glucose metabolism causes fatty liver accumulation; this seems to be a viral strategy to optimize its life cycle. Irrespective of insulin resistance, HCV-associated NAFLD, in a degree-dependent manner, contributes towards accelerating the liver fibrosis progression and development of hepatocellular carcinoma by inducing liver inflammation and oxidative stress. Furthermore, NAFLD is associated with the presence of metabolic syndrome, type 2 diabetes, and atherosclerosis. In addition, HCV-related “metabolic steatosis” impairs the response rate to interferon-based treatment, whereas it seems that “viral steatosis” may harm the response rate to new oral direct antiviral agents. In conclusion, a high prevalence of NAFLD occurs in HCV infections, which is, at least in part, induced by the virus, and that NAFLD significantly impacts progression of the liver disease, therapeutic response, and some extrahepatic diseases. PMID:27231906

  12. NAFLD and NASH in HCV Infection: Prevalence and Significance in Hepatic and Extrahepatic Manifestations

    Directory of Open Access Journals (Sweden)

    Luigi Elio Adinolfi

    2016-05-01

    Full Text Available The aim of this paper is to review and up to date the prevalence of hepatitis C virus (HCV-associated non-alcoholic fatty liver disease (NAFLD and non-alcoholic steatohepatitis (NASH and their significance in both accelerating progression of HCV-related liver disease and development of HCV-associated extrahepatic diseases. The reported mean prevalence of HCV-related NAFLD was 55%, whereas NASH was reported in 4%–10% of cases. HCV genotype 3 directly induces fatty liver deposition, namely “viral steatosis” and it is associated with the highest prevalence and degree of severity, whereas, HCV non-3 genotype infection showed lower prevalence of steatosis, which is associated with metabolic factors and insulin resistance. The host’s genetic background predisposes him or her to the development of steatosis. HCV’s impairment of lipid and glucose metabolism causes fatty liver accumulation; this seems to be a viral strategy to optimize its life cycle. Irrespective of insulin resistance, HCV-associated NAFLD, in a degree-dependent manner, contributes towards accelerating the liver fibrosis progression and development of hepatocellular carcinoma by inducing liver inflammation and oxidative stress. Furthermore, NAFLD is associated with the presence of metabolic syndrome, type 2 diabetes, and atherosclerosis. In addition, HCV-related “metabolic steatosis” impairs the response rate to interferon-based treatment, whereas it seems that “viral steatosis” may harm the response rate to new oral direct antiviral agents. In conclusion, a high prevalence of NAFLD occurs in HCV infections, which is, at least in part, induced by the virus, and that NAFLD significantly impacts progression of the liver disease, therapeutic response, and some extrahepatic diseases.

  13. The Human Umbilical Cord: A Novel Substitute for Reconstruction of the Extrahepatic Bile Duct

    Directory of Open Access Journals (Sweden)

    Jiong Lu

    2012-01-01

    Full Text Available Reconstruction of the extrahepatic bile duct following bile duct injury or defect is one of the most common challenges for hepatobiliary surgeons. There are currently a number of surgical strategies such as biliary-enteric anastomosis, end-to-end anastomosis and autologous tissue substitute. However, sphincter of Oddi dysfunction as well as biliary stricture may occur after surgical anastomosis. Also, insufficient tissue quantity remains a problem associated with the application of tissue substitute. Therefore, considerable attention has been attracted to explore a new replacement material of the bile duct for biliary reconstruction. The human umbilical cord (HUC is abundant in resource and is convenient to collect, including two arteries and one vein, whose diameters are close to that of the common bile duct. In order to reduce immunogenicity (foreign-body reaction, cells and major histocompatibility complex (MHC antigens can be removed from the HUC and the remaining tissue (extracellular matrix, ECM can be used as a scaffold. The HUC provides a rich source of mesenchymal stem cells (MSCs. A current study has demonstrated that MSCs are able to differentiate into biliary epithelial cells in vivo and in vitro with low immunogenicity, which can be used as seed cells. The HUC might be a promising composite material of a scaffold (ECM and seed cells (biliary epithelial cells, for bile duct replacement in situ without removal of sphincter of Oddi, or biliary stricture. In addition, the patients’ own umbilical cord without any foreign-body reaction can be directly banked for possible future use in bile duct reconstruction. Therefore, we hypothesise that the HUC may be a novel substitute for reconstruction of the extrahepatic bile duct.

  14. Orbital Pseudotumor as a Rare Extrahepatic Manifestation of Hepatitis C Infection

    Directory of Open Access Journals (Sweden)

    Benjamin Misselwitz

    2016-04-01

    Full Text Available Hepatitis C is frequently accompanied by immune-related extrahepatic manifestations affecting the skin, kidneys, central and peripheral nervous system and exocrine glands. We present the case of a 40-year-old man with left-sided ptosis, exophthalmos and headache. MRI demonstrated left-sided orbital pseudotumor with lacrimal and retro-orbital contrast enhancement extending to the cavernous sinus and the vestibulocochlear nerve. Immunological tests of serum and cerebrospinal fluid identified hepatitis C virus (HCV as a potential causative agent but did not indicate any additional infectious, malignant or immunological disorder. Hepatological evaluation revealed no signs of advanced liver disease. After initial spontaneous improvement, the patient subsequently developed vestibulocochlear failure with gait disorder, tinnitus and transient left-parietal sensory loss. Lacrimal biopsy demonstrated lymphocytic infiltrate, prompting steroid treatment. After initial improvement, steroids could not be tapered below 40 mg daily for several months due to recurrent symptoms. Twelve months after the initial presentation, the patient’s chronic HCV infection was successfully treated with sofosbuvir, simeprevir and ribavirin and he remains now free of symptoms without steroids. In patients with chronic hepatitis C, lymphocytic infiltrate of the salivary and lacrimal glands is a frequent phenomenon. However, the extent of the lymphocytic infiltrate beyond the lacrimal gland to the tip of the orbit, cavernous sinus and vestibulocochlear nerve as in our patient is highly unusual. For all symptomatic extrahepatic manifestations of hepatitis C infection, treatment of HCV as the underlying immune stimulus is recommended, and it helped to control the symptoms in our patient. In addition, long-term follow-up for recurrent lymphocyte infiltrate and development of lymphoma is warranted.

  15. Radiation therapy for patients with obstructive jaundice caused by carcinoma of the extrahepatic biliary system

    Energy Technology Data Exchange (ETDEWEB)

    Kawamura, Masashi; Nakagawa, Hirofumi (National Shikoku Cancer Center Hospital, Ehime (Japan)); Kataoka, Masaaki (and others)

    1992-04-01

    From February 1980 through September 1990, 92 patients with obstructive jaundice resulting from biliary tract cancer were registered at Shikoku Cancer Center Hospital or Ehime University Hospital. Radiation therapy (RT) was used to treat 38 of these patients (30 with carcinoma of the extrahepatic bile duct, excluding ampulla of Vater, and eight patients with carcinoma of the gallbladder). Of 38 patients, 11 underwent intraoperative radiation therapy (IORT), and 27 were treated by external radiation therapy (ERT) alone. In contrast, 54 patients (39 with carcinoma of the extrahepatic bile duct and eight with carcinoma of the gallbladder) were not treated by RT. All jaundiced patients received external and/or internal biliary drainage of some kind. Among patients undergoing biliary drainage with a catheter, 21 patients who underwent RT (four with IORT) survived significantly longer than 19 patients who did not (generalized Wilcoxon test: p<0.05). There were no significant differences in survival between 7 patients with recanalization and 11 patients with no recanalization. Concerning the survival of laparotomized patients, excluding those with complete resection or perioperative death, eight patients treated with postoperative ERT survived longer than 12 patients who did not have postoperative ERT (not significant). Eleven patients underwent IORT. A patient with unresectable carcinoma of the hilar bile duct survived 2 years and 3 months after a combination treatment of ERT and IOTR. In four of eight autopsied patients, radiation effects of Grade II were observed (Oboshi and Shimosato's evaluation system for the histological effects of radiation therapy). Our experience suggests that RT is effective in patients with obstructive jaundice caused by carcinoma of the biliary system. (author).

  16. 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

  17. [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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. Use of C-Arm Cone Beam CT During Hepatic Radioembolization: Protocol Optimization for Extrahepatic Shunting and Parenchymal Enhancement

    Energy Technology Data Exchange (ETDEWEB)

    Hoven, Andor F. van den, E-mail: a.f.vandenhoven@umcutrecht.nl; Prince, Jip F.; Keizer, Bart de; Vonken, Evert-Jan P. A.; Bruijnen, Rutger C. G.; Verkooijen, Helena M.; Lam, Marnix G. E. H.; Bosch, Maurice A. A. J. van den [University Medical Center Utrecht, Department of Radiology and Nuclear Medicine (Netherlands)

    2016-01-15

    PurposeTo optimize a C-arm computed tomography (CT) protocol for radioembolization (RE), specifically for extrahepatic shunting and parenchymal enhancement.Materials and MethodsA prospective development study was performed per IDEAL recommendations. A literature-based protocol was applied in patients with unresectable and chemorefractory liver malignancies undergoing an angiography before radioembolization. Contrast and scan settings were adjusted stepwise and repeatedly reviewed in a consensus meeting. Afterwards, two independent raters analyzed all scans. A third rater evaluated the SPECT/CT scans as a reference standard for extrahepatic shunting and lack of target segment perfusion.ResultsFifty scans were obtained in 29 procedures. The first protocol, using a 6 s delay and 10 s scan, showed insufficient parenchymal enhancement. In the second protocol, the delay was determined by timing parenchymal enhancement on DSA power injection (median 8 s, range 4–10 s): enhancement improved, but breathing artifacts increased (from 0 to 27 %). Since the third protocol with a 5 s scan decremented subjective image quality, the second protocol was deemed optimal. Median CNR (range) was 1.7 (0.6–3.2), 2.2 (−1.4–4.0), and 2.1 (−0.3–3.0) for protocol 1, 2, and 3 (p = 0.80). Delineation of perfused segments was possible in 57, 73, and 44 % of scans (p = 0.13). In all C-arm CTs combined, the negative predictive value was 95 % for extrahepatic shunting and 83 % for lack of target segment perfusion.ConclusionAn optimized C-arm CT protocol was developed that can be used to detect extrahepatic shunts and non-perfusion of target segments during RE.

  6. DIFFERENCE IN BIOLOGICAL CHARACTERISTICS AND SENSITIVITY TO CHEMOTHERAPY AND RADIOTHERAPY BETWEEN INTRAHEPATIC AND EXTRAHEPATIC CHOLANGIOCARCINOMA CELLS IN VITRO

    Institute of Scientific and Technical Information of China (English)

    Xiao-ran He; Xiao-peng Wu

    2008-01-01

    Objective To investigate and compare the biological characteristics and sensitivity to chemotherapy and radiother-apy of intrahepatic and extrahepatie cholangiocarcinoma cells in vitro.Methods The intrahepatic and extrahepatie eholangiocarcinoma cell lines were established, and cells with steady passage were chosen to study the biological characteristics including morphology, growth dynamics, chromosome, and levels of cancer antigen (CA)125, CA 19-9, alpha-fetoprotein (AFP), and carcino-embryonic antigen (CEA).M.eanwhile, MTT assay was used to determine the sensitivity of both kinds of cells to 6 chemotherapeutic drugs, inclu-ding cisplatin, paclitaxel, harringtonine, 5-fluorouracil, vincristine, and aelacimomycin, and the inhibitory rate of ceils under the irradiation of 10 Gy ray was also measured.Reanlts The intrahepatic cholangiocarcinoma cells were mostly fusiform in shape, and extrahepatic eholangiocar-cinoma cells were mostly round or polygon in shape. Their doubling time was 26. 3 hours and 23.1 hours, respectively.Their average number of chromosomes was 59 (range, 38-84) and 67 (range, 49-103 ), respectively. The chromo-some karyotypes of most intrahepatlc ebolangiocarcinoma cells were hyperdiploid and hypotriploid, while hypertriploid was predominant in extrahepatic cholangioearcinoma cells. The level of CA 125 in supernatant of extrahepatic cholangio-carcinoma cells increased obviously, while levels of other determined tumor markers in both kinds of cells were all with-in normal range. The intrahepatic cholangiocarcinoma cells were low sensitive to cisplatin and paclitaxel, but not sensi-tive to the other 4 chemotherapeutic drugs. The extrahepatic cholangiocarcinoma cells were high sensitive to eisplatin,but not sensitive to the other 5 drugs. Both kinds of cells had poor sensitivity to radiotherapy.Conelusions Intrahepatic and extrahepatie cbolangiocareinoma cells show differences in shape, doubling time,chromosome karyotype, tumor marker level, and

  7. Extrahepatic Pseudoaneurysms and Ruptures of the Hepatic Artery in Liver Transplant Recipients: Endovascular Management and a New Iatrogenic Etiology

    International Nuclear Information System (INIS)

    To characterize extrahepatic pseudoaneurysm regarding incidence and etiology and determine the effectiveness of endovascular management. A retrospective audit of 1,857 liver transplants in two institutions was performed (1996–2009). Recipients’ demographics, clinical presentation, transplant type, biliary anastomosis, and presence of biliary endoprostheses were noted. Pseudoaneurysms were classified into iatrogenic (associated with biliary endoprosthesis or angioplasty) or spontaneous extrahepatic pseudoaneurysms. Spontaneous and iatrogenic pseudoaneurysms were compared for time from transplant, presenting symptoms, location in the arterial anatomy, and 3-month graft survival. Arterial patency and 6-month graft survival were calculated. Twenty pseudoaneurysms were found (1.1 %, 20/1,857): 9 (0.5 % of transplants, 9/1,857) were spontaneous and 11 (0.6 % of transplants, 11/1,857) were “iatrogenic” (due to minimally invasive procedures: 4 angioplasty and 7 biliary endoprostheses). Sixty percent (12/20) underwent endovascular management (4 coil embolization and 8 stent-grafts). Technical success was 83 % (10/12) with a mean arterial patency of 70 % (follow-up mean, 4.9; range, 0–18 months). The 1-, 3-, and 6-month graft survival was 70, 40, and 35 %, respectively. Due to minimally invasive procedures, posttransplant extrahepatic pseudoaneurysms are no longer an exclusive complication of the transplant surgery itself. Endovascular management is effective to stabilize patients but has not improved historic postsurgical graft survival.

  8. Extrahepatic Pseudoaneurysms and Ruptures of the Hepatic Artery in Liver Transplant Recipients: Endovascular Management and a New Iatrogenic Etiology

    Energy Technology Data Exchange (ETDEWEB)

    Saad, Wael E. A., E-mail: wspikes@yahoo.com; Dasgupta, Niloy; Lippert, Allison J.; Turba, Ulku C.; Davies, Mark G. [University of Virginia Health System, Division of Vascular Interventional Radiology, Department of Radiology (United States); Kumer, Sean [University of Virginia Health System, Division of Solid Organ Transplantation, Department of Surgery (United States); Gardenier, Jason C.; Sabri, Saher S.; Park, Auh-Whan [University of Virginia Health System, Division of Vascular Interventional Radiology, Department of Radiology (United States); Waldman, David L. [University of Rochester Medical Center, Department of Imaging Sciences (United States); Schmitt, Timothy [University of Virginia Health System, Division of Solid Organ Transplantation, Department of Surgery (United States); Matsumoto, Alan H.; Angle, John F. [University of Virginia Health System, Division of Vascular Interventional Radiology, Department of Radiology (United States)

    2013-02-15

    To characterize extrahepatic pseudoaneurysm regarding incidence and etiology and determine the effectiveness of endovascular management. A retrospective audit of 1,857 liver transplants in two institutions was performed (1996-2009). Recipients' demographics, clinical presentation, transplant type, biliary anastomosis, and presence of biliary endoprostheses were noted. Pseudoaneurysms were classified into iatrogenic (associated with biliary endoprosthesis or angioplasty) or spontaneous extrahepatic pseudoaneurysms. Spontaneous and iatrogenic pseudoaneurysms were compared for time from transplant, presenting symptoms, location in the arterial anatomy, and 3-month graft survival. Arterial patency and 6-month graft survival were calculated. Twenty pseudoaneurysms were found (1.1 %, 20/1,857): 9 (0.5 % of transplants, 9/1,857) were spontaneous and 11 (0.6 % of transplants, 11/1,857) were 'iatrogenic' (due to minimally invasive procedures: 4 angioplasty and 7 biliary endoprostheses). Sixty percent (12/20) underwent endovascular management (4 coil embolization and 8 stent-grafts). Technical success was 83 % (10/12) with a mean arterial patency of 70 % (follow-up mean, 4.9; range, 0-18 months). The 1-, 3-, and 6-month graft survival was 70, 40, and 35 %, respectively. Due to minimally invasive procedures, posttransplant extrahepatic pseudoaneurysms are no longer an exclusive complication of the transplant surgery itself. Endovascular management is effective to stabilize patients but has not improved historic postsurgical graft survival.

  9. 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.

  10. Hepatocellular Carcinoma associated with Extra-hepatic Primary Malignancy: its Secular change, Clinical Manifestations and Survival.

    Science.gov (United States)

    Kee, Kwong Ming; Wang, Jing-Houng; Wang, Chih-Chi; Cheng, Yu-Fan; Lu, Sheng-Nan

    2016-01-01

    Clinical manifestations between hepatocellular carcinoma (HCC) and extra-hepatic primary malignancy (EHPM) are lack of large-scale study. We enrolled 14555 HCC patients between 1986 and 2013 retrospectively. The EHPM was classified as prior, synchronous and metachronous group based on before, within and after 6 months of HCC diagnosis, respectively. The incidence rate of EHPM is 3.91% (95% confidence interval [CI]: 3.60-4.23%). Urogenital cancers, kidney and bladder, were at unexpected higher ranks. Older in age, Child-Pugh A cirrhosis, negativity of HBsAg and anti-HCV, and earlier BCLC staging are independent factors associated with EHPM. The survival rates of EHPM improve over time and also better than HCC-alone. Cox proportional-hazards regression shows independent poor prognostic factors are age >60, male, AFP levels ≥400 ng/ml, positivity of HBsAg, Child-Pugh B vs. A, Non-metachronous group, respectively, treated with local ablation, transcatheter arterial embolization, radiotherapy and supportive care vs. surgery, respectively, TNM stage IIIA vs. I, and BCLC stages A, B, C and D vs. 0, respectively. Survival of EHPM improve could be explained by early diagnosis and improve treatment of cancers. PMID:27444261

  11. Plastic or metal stents for benign extrahepatic biliary strictures: a systematic review

    Directory of Open Access Journals (Sweden)

    Vleggaar Frank P

    2009-12-01

    Full Text Available Abstract Background Benign biliary strictures may be a consequence of surgical procedures, chronic pancreatitis or iatrogenic injuries to the ampulla. Stents are increasingly being used for this indication, however it is not completely clear which stent type should be preferred. Methods A systematic review on stent placement for benign extrahepatic biliary strictures was performed after searching PubMed and EMBASE databases. Data were pooled and evaluated for technical success, clinical success and complications. Results In total, 47 studies (1116 patients on outcome of stent placement were identified. No randomized controlled trials (RCTs, one non-randomized comparative studies and 46 case series were found. Technical success was 98,9% for uncovered self-expandable metal stents (uSEMS, 94,8% for single plastic stents and 94,0% for multiple plastic stents. Overall clinical success rate was highest for placement of multiple plastic stents (94,3% followed by uSEMS (79,5% and single plastic stents (59.6%. Complications occurred more frequently with uSEMS (39.5% compared with single plastic stents (36.0% and multiple plastic stents (20,3%. Conclusion Based on clinical success and risk of complications, placement of multiple plastic stents is currently the best choice. The evolving role of cSEMS placement as a more patient friendly and cost effective treatment for benign biliary strictures needs further elucidation. There is a need for RCTs comparing different stent types for this indication.

  12. Extra-hepatic replication and infection of hepatitis E virus in neuronal-derived cells.

    Science.gov (United States)

    Drave, S A; Debing, Y; Walter, S; Todt, D; Engelmann, M; Friesland, M; Wedemeyer, H; Neyts, J; Behrendt, P; Steinmann, E

    2016-07-01

    Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and a member of the genus Orthohepevirus in the family Hepeviridae. Infection usually leads to acute hepatitis that can become fulminant, particularly among pregnant women and in patients with preexisting liver disease, or may evolve to a chronic state, especially in immunosuppressed individuals. HEV has been shown to produce a range of extra-hepatic manifestations including aplastic anaemia, acute thyroiditis, glomerulonephritis as well as neurological disorders such as Guillain-Barré syndrome, neuralgic amyotrophy and encephalitis. The pathogenesis of these neurological injuries remains largely unknown, and it is also uncertain whether or not HEV can directly infect neuronal cells. In this study, we investigated whether HEV is capable of completing the viral life cycle in human neuronal-derived cell lines such as neuroepithelioma (SK-N-MC), desmoplastic cerebellar medulloblastoma (DAOY), glioblastoma multiforme (DBTRG), glioblastoma astrocytoma (U-373 MG) and oligodendrocytic (M03.13) cells. Following transfection of these cells with HEV Gaussia luciferase reporter virus, all tested cell lines supported HEV RNA replication. Furthermore, extra- and intracellular viral capsid was detected by an HEV antigen ELISA as a marker for virus assembly and release. Permissiveness for HEV cell entry could be demonstrated for the oligodendrocytic cell line M03.13. In conclusion, these results indicate that HEV tropism is not restricted to the liver and HEV can potentially complete the full viral life cycle in neuronal-derived tissues explaining neurologic disorders during HEV infection. PMID:26891712

  13. Molecular biomarkers in extrahepatic bile duct cancer patients undergoing chemoradiotherapy for gross residual disease after surgery

    Energy Technology Data Exchange (ETDEWEB)

    Koh, Hyeon Kang; Kim, Kyu Bo; Chie, Eui Kyu; Ha, Sung W. [Seoul National University College of Medicine, Seoul (Korea, Republic of); Park, Hae Jin [Dept. of Radiation Oncology, Soonchunhyang University Hospital, Seoul (Korea, Republic of)

    2012-12-15

    To analyze the outcomes of chemoradiotherapy for extrahepatic bile duct (EHBD) cancer patients who underwent R2 resection or bypass surgery and to identify prognostic factors affecting clinical outcomes, especially in terms of molecular biomarkers. Medical records of 21 patients with EHBD cancer who underwent R2 resection or bypass surgery followed by chemoradiotherapy from May 2001 to June 2010 were retrospectively reviewed. All surgical specimens were re-evaluated by immunohistochemical staining using phosphorylated protein kinase B (pAKT), CD24, matrix metalloproteinase 9 (MMP9), survivin, and {beta}-catenin antibodies. The relationship between clinical outcomes and immunohistochemical results was investigated. At a median follow-up of 20 months, the actuarial 2-year locoregional progression-free, distant metastasis-free and overall survival were 37%, 56%, and 54%, respectively. On univariate analysis using clinicopathologic factors, there was no significant prognostic factor. In the immunohistochemical staining, cytoplasmic staining, and nuclear staining of pAKT was positive in 10 and 6 patients, respectively. There were positive CD24 in 7 patients, MMP9 in 16 patients, survivin in 8 patients, and {beta}-catenin in 3 patients. On univariate analysis, there was no significant value of immunohistochemical results for clinical outcomes. There was no significant association between clinical outcomes of patients with EHBD cancer who received chemoradiotherapy after R2 resection or bypass surgery and pAKT, CD24, MMP9, survivin, and {beta}-catenin. Future research is needed on a larger data set or with other molecular biomarkers.

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

    Directory of Open Access Journals (Sweden)

    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

  15. 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...

  16. Microbiota studies in the bile duct strongly suggest a role for Helicobacter pylori in extrahepatic cholangiocarcinoma.

    Science.gov (United States)

    Avilés-Jiménez, F; Guitron, A; Segura-López, F; Méndez-Tenorio, A; Iwai, S; Hernández-Guerrero, A; Torres, J

    2016-02-01

    Biliary tract cancer or extrahepatic cholangiocarcinoma (ECCA) represents the sixth commonest cause of cancer in the gastrointestinal tract in western countries. We aimed to characterize the microbiota and its predicted associated functions in the biliary tract of ECCA and benign biliary pathology (BBP). Samples were taken from 100 patients with ECCA and 100 patients with BBP by endoscopic cholangio-pancreatography for DNA extraction. Ten patients with ECCA and ten with BBP were selected for microbiota studies using the V4-16S rRNA gene and sequenced in Illumina platform. Microbiota analyses included sample-to-sample distance metrics, ordination/clustering and prediction of functions. Presence of Nesterenkonia sp. and Helicobacter pylori cagA and vacA genes were tested in the 100 ECCA and 100 BBP samples. Phylum Proteobacteria dominated all samples (60.4% average). Ordination multicomponent analyses showed significant microbiota separation between ECCA and BBP (p 0.010). Analyses of 4002 operational taxonomic units with presence variation in at least one category probed a separation of ECCA from BBP. Among these, Nesterenkonia decreased, whereas Methylophilaceae, Fusobacterium, Prevotella, Actinomyces, Novosphingobium and H. pylori increased in ECCA. Predicted associated functions showed increased abundance of H. pylori virulence genes in ECCA. cagA and vacA genes were confirmed by PCR in ECCA and BBP samples. This is the first microbiota report in ECCA and BBP to show significant changes in microbial composition. Bacterial species unusual for human flora were found: Methylophilaceae and Nesterenkonia are reported in hypersaline soils, and Mesorhizobium is a nitrogen-fixing bacterium. Enrichment of virulence genes confirms previous studies suggesting that H. pylori might be associated with ECCA. PMID:26493848

  17. Postoperative radiotherapy dose correlates with locoregional control in patients with extra-hepatic bile duct cancer

    Energy Technology Data Exchange (ETDEWEB)

    Im, Jung Ho; Seong, Jinsil; Lee, Jeong Shim; Kim, Yong Bae; Kim, Kyung Sik; Lee, Woo Jung [Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Lee, Ik Jae; Park, Jun Sung; Yoon, Dong Sup [Sangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2013-12-15

    To evaluate the results of postoperative radiotherapy in patients with extra-hepatic bile duct cancer (EHBDC) and identify the prognostic factors for local control and survival. Between January 2001 and December 2010, we retrospectively reviewed the cases of 70 patients with EHBDC who had undergone curative resection and received postoperative radiotherapy. The median radiation dose was 50.4 Gy (range, 41.4 to 54 Gy). The resection margin status was R0 in 30 patients (42.9%), R1 in 25 patients (35.7%), and R2 in 15 patients (21.4%). The 5-year rates of overall survival (OS), event-free survival (EFS), and locoregional control (LRC) for all patients were 42.9%, 38.3%, and 61.2%, respectively. The major pattern of failure was distant relapses (33 patients, 47.1%). A multivariate analysis showed that the postradiotherapy CA19-9 level, radiation dose (≥50 Gy), R2 resection margins, perineural invasion, and T stage were the significant prognostic factors for OS, EFS, and LRC. OS was not significantly different between the patients receiving R0 and R1 resections, but was significantly lower among those receiving R2 resection (54.6%, 56.1%, and 7.1% for R0, R1, and R2 resections, respectively). In patients with EHBDC who had undergone curative resection, a postoperative radiotherapy dose less than 50 Gy was suboptimal for OS and LRC. Higher radiation doses may be needed to obtain better LRC. Further investigation of novel therapy or palliative treatment should be considered for patients receiving R2 resection.

  18. Patterns of failure and prognostic factors in resected extrahepatic bile duct cancer: implication for adjuvant radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Koo, Tae Ryool; Eom, Keun Yong; Kim, In Ah; Cho, Jai Young; Yoon, Yoo Seok; Hwang, Dae Wook; Han, Ho Seong; Kim, Jae Sung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2014-06-15

    To find the applicability of adjuvant radiotherapy for extrahepatic bile duct cancer (EBDC), we analyzed the pattern of failure and evaluate prognostic factors of locoregional failure after curative resection without adjuvant treatment. In 97 patients with resected EBDC, the location of tumor was classified as proximal (n = 26) and distal (n = 71), using the junction of the cystic duct and common hepatic duct as the dividing point. Locoregional failure sites were categorized as follows: the hepatoduodenal ligament and tumor bed, the celiac artery and superior mesenteric artery, and other sites. The median follow-up time was 29 months for surviving patients. Three-year locoregional progression-free survival, progression-free survival, and overall survival rates were 50%, 42%, and 52%, respectively. Regarding initial failures, 79% and 81% were locoregional failures in proximal and distal EBDC patients, respectively. The most common site was the hepatoduodenal ligament and tumor bed. In the multivariate analysis, perineural invasion was associated with poor locoregional progression-free survival (p = 0.023) and progression-free survival (p = 0.012); and elevated postoperative CA19-9 (> or =37 U/mL) did with poor locoregional progression-free survival (p = 0.002), progression-free survival (p < 0.001) and overall survival (p < 0.001). Both proximal and distal EBDC showed remarkable proportion of locoregional failure. Perineural invasion and elevated postoperative CA19-9 were risk factors of locoregional failure. In these patients with high risk of locoregional failure, adjuvant radiotherapy could be considered to improve locoregional control.

  19. The palliative radiation therapy in malignant extra-hepatic biliary obstruction

    International Nuclear Information System (INIS)

    To evaluate the effectiveness of external radiation therapy and the prognostic factors, we retrospectively analyzed therapeutic results of malignant extrahepatic biliary obstruction (EHBO). We analyzed the results of the external radiation therapy in 59 patients of inoperable malignant EHBO who had been treated with more than 10 Gy of external radiation therapy from April 1984 to December 1996. There were 21 stomach cancer (35.6%), 12 pancreas cancer (20.3%). Twelve patients had slightly increased bilirubin level in liver function test without jaundice. We treated twenty four patients (40.6%) with percutaneous transhepatic biliary drainage (PTBD) and 32 patients (54%) with systemic chemotherapy (CT). We performed external radiation therapy (ERT) upto 10.8-55.8 Gy (median 37.8 Gy) with palliative aim. Overall median survival duration was 7.80±1.15 months. The response rates of jaundice were 81.8% in PTBD group and 66.7% in non-PTBD group without statistical significance. The improving rate of jaundice was not significantly different in decreased ratio of total bilirubin level. But abdominal pain was more decreased in CT group than non-CT group (p70), total radiation dose more than 35 Gy and good response of pain after therapy. There were increased in bacterial cholagitis in PTBD group and gastrointestinal complications in CT group. External radiotherapy could improve jaundice and abdominal pain in malignant EHBO patients. Overall survival duration was prolonged in patients with higher performance status and patients who had been treated with more than 35 Gy of total radiation dose. In the future, we expect not only better palliative role but also the prolongation of survival of using the ERT combined with other treatment method. But to achieve certain conclusion, we need further study consisted with many kinds of treatment methods including new technologies in RT

  20. MR-guided laser-induced thermotherapy in recurrent extrahepatic abdominal tumors

    Energy Technology Data Exchange (ETDEWEB)

    Mack, M.G.; Straub, R.; Eichler, K.; Boettger, M.; Woitaschek, D.; Vogl, T.J. [Dept. of Diagnostic and Interventional Radiology, University of Frankfurt (Germany); Roggan, A. [LMTB GmbH, Berlin (Germany)

    2001-10-01

    The aim of this study was to evaluate the feasibility of MR-guided laser-induced thermotherapy (LITT) for treatment of recurrent extrahepatic abdominal tumors. In 11 patients (6 women and 5 men; mean age 53 years, age range 29-67 years) with 14 lesions the following tumors were treated in this study: paravertebral recurrence of hypernephroma (n=1); recurrence of uterus carcinoma (n=1); recurrence of chondrosarcoma of the pubic bone (n=1); presacral recurrence of rectal carcinoma (n=1); recurrent anal cancer (n=1); metastases in the abdominal wall (n=1); and lymph node metastases from colorectal cancer (n=8). A total of 27 laser applications were performed. A fast low-angle shot 2D sequence (TR/TE/flip angle=102 ms/8 ms/70 ) was used for nearly real-time monitoring during treatment. All patients had no other treatment option. Seventeen LITT sessions were performed using a conventional laser system with a mean laser power of 5.2 W (range 4.5-5.7 W), and 10 LITT session were performed using a power laser system with a mean laser power of 28.0 W. In 10 lesions total destruction could be achieved. In the remaining recurrent tumors, significant reduction of tumor volume by 60-80% was obtained. All patients tolerated the procedure well under local anesthesia. No complications occurred during treatment. Laser-induced thermotherapy is a practicable, minimally invasive, well-tolerated technique that can produce large areas of necrosis within recurrent tumors, substantially reducing active tumor volume if not resulting in outright destruction of tumor. (orig.)

  1. 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

  2. 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.

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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.

  12. 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

  13. Usefulness and pitfalls of MAA SPECT/CT in identifying digestive extrahepatic uptake when planning liver radioembolization

    International Nuclear Information System (INIS)

    Identifying gastroduodenal uptake of 99mTc-macroaggregated albumin (MAA), which is associated with an increased risk of ulcer disease, is a crucial part of the therapeutic management of patients undergoing radioembolization for liver tumours. Given this context, the use of MAA single photon emission computed tomography (SPECT)/CT may be essential, but the procedure has still not been thoroughly evaluated. The aim of this retrospective study was to determine the effectiveness of MAA SPECT/CT in identifying digestive extrahepatic uptake, while determining potential diagnostic pitfalls. Overall, 139 MAA SPECT/CT scans were performed on 103 patients with different hepatic tumour types. Patients were followed up for at least 6 months according to standard requirements. Digestive, or digestive-like, uptake other than free pertechnetate was identified in 5.7% of cases using planar imaging and in 36.6% of cases using SPECT/CT. Uptake sites identified by SPECT/CT included the gastroduodenal region (3.6%), gall bladder (12.2%), portal vein thrombosis (6.5%), hepatic artery (6.5%), coil embolization site (2.1%) as well as falciform artery (5.0%). For 2.1% of explorations, a coregistration error between SPECT and CT imaging could have led to a false diagnosis by erroneously attributing an uptake site to the stomach or gall bladder, when the uptake actually occurred in the liver. SPECT/CT is more efficacious than planar imaging in identifying digestive extrahepatic uptake sites, with extrahepatic uptake observed in one third of scans using the former procedure. However, more than half of the uptake sites in our study were vascular in nature, without therapeutic implications. The risk of coregistration errors must also be kept in mind. (orig.)

  14. The significance of Bremsstrahlung SPECT/CT after yttrium-90 radioembolization treatment in the prediction of extrahepatic side effects

    Energy Technology Data Exchange (ETDEWEB)

    Ahmadzadehfar, Hojjat; Muckle, Marianne; Sabet, Amir; Biermann, Kim; Haslerud, Torjan; Biersack, Hans-Juergen; Ezziddin, Samer [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Wilhelm, Kai [University Hospital Bonn, Department of Radiology, Bonn (Germany); Kuhl, Christiane [University Hospital Aachen, Department of Radiology, Aachen (Germany)

    2012-02-15

    Unwanted deposition of {sup 90}Y microspheres in organs other than the liver during radioembolization of liver tumours may cause severe side effects such as duodenal ulcer. The aim of this study was to evaluate the significance of posttherapy bremsstrahlung (BS) SPECT/CT images of the liver in comparison to planar and SPECT images in the prediction of radioembolization-induced extrahepatic side effects. A total of 188 radioembolization procedures were performed in 123 patients (50 women, 73 men) over a 2-year period. Planar, whole-body and BS SPECT/CT imaging were performed 24 h after treatment as a part of therapy work-up. Any focally increased extrahepatic accumulation was evaluated as suspicious. Clinical follow-up and gastroduodenoscopy served as reference standards. The studies were reviewed to evaluate whether BS SPECT/CT imaging was of benefit. In the light of anatomic data obtained from SPECT/CT, apparent extrahepatic BS in 43% of planar and in 52% of SPECT images proved to be in the liver and hence false-positive. The results of planar scintigraphy could not be analysed further since 12 images were not assessable due to high scatter artefacts. On the basis of the gastrointestinal (GI) complications and the results of gastroduodenoscopy, true-positive, true-negative, false-positive and false-negative results of BS SPECT and SPECT/CT imaging in the prediction of GI ulcers were determined. The sensitivity, specificity, positive and negative predictive values and the accuracy of SPECT and SPECT/CT in the prediction of GI ulcers were 13%, 88%, 8%, 92% and 82%, and 87%, 100%, 100%, 99% and 99%, respectively. Despite the low quality of BS images, BS SPECT/CT can be used as a reliable method to confirm the safe distribution of {sup 90}Y microspheres and in the prediction of GI side effects. (orig.)

  15. Usefulness and pitfalls of MAA SPECT/CT in identifying digestive extrahepatic uptake when planning liver radioembolization

    Energy Technology Data Exchange (ETDEWEB)

    Lenoir, Laurence; Garin, Etienne [Comprehensive Cancer Institute Eugene Marquis, Department of Nuclear Medicine, CS 44229, Rennes (France); University of Rennes 1, Rennes (France); Liver Metabolisms and Cancer, INSERM, U-991, Rennes (France); Edeline, Julien [University of Rennes 1, Rennes (France); Comprehensive Cancer Institute Eugene Marquis, Department of Medical Oncology, CS 44229, Rennes (France); Rolland, Yann [Comprehensive Cancer Institute Eugene Marquis, Department of Medical Imaging, CS 44229, Rennes (France); Pracht, Marc [Comprehensive Cancer Institute Eugene Marquis, Department of Medical Oncology, CS 44229, Rennes (France); Raoul, Jean-Luc [Comprehensive Cancer Institute Paoli Calmette, Department of Medical Oncology, Marseille (France); Ardisson, Valerie [Comprehensive Cancer Institute Eugene Marquis, Department of Nuclear Medicine, CS 44229, Rennes (France); Bourguet, Patrick [Comprehensive Cancer Institute Eugene Marquis, Department of Nuclear Medicine, CS 44229, Rennes (France); University of Rennes 1, Rennes (France); Clement, Bruno [Liver Metabolisms and Cancer, INSERM, U-991, Rennes (France); Boucher, Eveline [Liver Metabolisms and Cancer, INSERM, U-991, Rennes (France); Comprehensive Cancer Institute Eugene Marquis, Department of Medical Oncology, CS 44229, Rennes (France)

    2012-05-15

    Identifying gastroduodenal uptake of {sup 99m}Tc-macroaggregated albumin (MAA), which is associated with an increased risk of ulcer disease, is a crucial part of the therapeutic management of patients undergoing radioembolization for liver tumours. Given this context, the use of MAA single photon emission computed tomography (SPECT)/CT may be essential, but the procedure has still not been thoroughly evaluated. The aim of this retrospective study was to determine the effectiveness of MAA SPECT/CT in identifying digestive extrahepatic uptake, while determining potential diagnostic pitfalls. Overall, 139 MAA SPECT/CT scans were performed on 103 patients with different hepatic tumour types. Patients were followed up for at least 6 months according to standard requirements. Digestive, or digestive-like, uptake other than free pertechnetate was identified in 5.7% of cases using planar imaging and in 36.6% of cases using SPECT/CT. Uptake sites identified by SPECT/CT included the gastroduodenal region (3.6%), gall bladder (12.2%), portal vein thrombosis (6.5%), hepatic artery (6.5%), coil embolization site (2.1%) as well as falciform artery (5.0%). For 2.1% of explorations, a coregistration error between SPECT and CT imaging could have led to a false diagnosis by erroneously attributing an uptake site to the stomach or gall bladder, when the uptake actually occurred in the liver. SPECT/CT is more efficacious than planar imaging in identifying digestive extrahepatic uptake sites, with extrahepatic uptake observed in one third of scans using the former procedure. However, more than half of the uptake sites in our study were vascular in nature, without therapeutic implications. The risk of coregistration errors must also be kept in mind. (orig.)

  16. Bilateral simultaneous anterior ischemic optic neuropathy, an extrahepatic manifestation of hepatitis C cured with direct acting antivirals

    Directory of Open Access Journals (Sweden)

    Prud’homme, Sylvie

    2016-04-01

    Full Text Available We report a patient with a bilateral optic anterior ischemic neuropathy as an extrahepatic complication of a chronic hepatitis C (HCV infection. The patient presented with a bilateral visual acuity loss and bilateral optic disc oedema. The optic neuropathy was associated with a sudden increase in the viral HCV load after a recent liver transplantation. The stop of the calcineurin inhibitor had no effect on the course of the optic neuropathy. Visual improvement and normalization of HCV viraemia occurred after treatment with sofosbuvir and daclatasvir, which are direct acting antivirals.

  17. Risk factors for extrahepatic biliary tract carcinoma in men: medical conditions and lifestyle: results from a European multicentre case-control study

    DEFF Research Database (Denmark)

    Ahrens, Wolfgang; Timmer, Antje; Vyberg, Mogens;

    2007-01-01

    or smoking showed no clear association, whereas some increase in risk was suggested for consumption of 40-80 g alcohol per day and more. CONCLUSIONS: Our study corroborates gallstones as a risk indicator in extrahepatic biliary tract carcinoma. Permanent overweight and obesity in adult life was identified...... as a strong risk factor for extrahepatic biliary tract carcinoma, whereas we did not find any strong lifestyle-associated risk factors. Inconsistent results across studies concerning the association of extrahepatic biliary tract carcinoma with overweight and obesity may be explained by the different......-matched by age and region. Adjusted odds ratios and 95%-confidence intervals were estimated by logistic regression. RESULTS: The analysis included 153 patients and 1421 controls. The participation proportion was 71% for patients and 61% for controls. Gallstone disease was corroborated as a risk factor...

  18. Poorly Differentiated Adenocarcinoma with Signet-ring Cell Carcinoma of the Extrahepatic Bile Duct in a 42-year-old Japanese Female: A Case Report

    Directory of Open Access Journals (Sweden)

    Nakanishi,Kuniaki

    2010-02-01

    Full Text Available Poorly differentiated adenocarcinoma without papilla or tubule formation of the extrahepatic bile duct is rare. Here we present a case (a 42-year-old Japanese woman without either pancreatobiliary maljunction or liver disease. The patient had obstructive jaundice. Imaging studies revealed a bile duct tumor obstructing the common bile duct and invading the surrounding tissues. Pathologic examination revealed a dense periductal growth of poorly differentiated adenocarcinoma containing signet-ring cells, but without papilla or tubule formation in the extrahepatic bile duct. The tumor cells directly invaded the pancreatic parenchyma and the portal vein. In the extrahepatic bile duct, poorly differentiated adenocarcinoma may be established as a distinct clinicopathologic entity if the tumors are characterized by:1 the absence of papilla or tubule formation, 2 Asian preponderance, 3 occurrence at a younger age than is usual for patients with biliary cancers, and 4 an aggressive mural invasiveness.

  19. The E-cadherin repressor slug and progression of human extrahepatic hilar cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Wang Xin-sheng

    2010-07-01

    Full Text Available Abstract Objectives This study explored the expression and function of Slug in human extrahepatic hilar cholangiocarcinoma (EHC to identify its role in tumor progression. Methods The expression of Snail and Slug mRNA in 52 human tissue samples of EHC was investigated. The mRNA of Snail and Slug were quantified using reverse transcriptase-PCR, and correlations with E-cadherin expression and clinicopathological factors were investigated. We then investigated transfection of Slug cDNA in endogenous E-cadherin-positive human EHC FRH0201 cells, selectively induced the loss of E-cadherin protein expression, and then small interfering RNA (siRNA for inhibition of Slug expression in endogenous Slug-positive human EHC QBC939 cells, selectively induced the loss of Slug protein expression. A Boyden chamber transwell assay was used for invasion. Results Slug mRNA was overexpressed in 18 cases (34.6% of EHC compared with adjacent noncancerous tissue. E-Cadherin protein expression determined in the same 52 cases by immunohistochemistry was significantly down-regulated in those cases with Slug mRNA overexpression (P = 0.0001. The tumor and nontumor ratio of Slug mRNA was correlated with nodal metastasis(p = 0.0102, distant metastasis (p = 0.0001and Survival time(p = 0.0443. However, Snail mRNA correlated with neither E-cadherin expression nor tumor invasiveness. By inhibiting Slug expression by RNA interference, we found that reduced Slug levels upregulated E-cadherin and decreased invasion in QBC939 cell. When the QBC939 cells was infected with Slug cDNA,, significant E-cadherin was downregulated and increased invasion in QBC939 cell. Conclusions The results suggested that Slug expression plays an important role in both the regulation of E-cadherin expression and in the acquisition of invasive potential in human EHC. Slug is possibly a potential target for an antitumor therapy blocking the functions of invasion and metastasis in human EHCs.

  20. Hepatitis C and B Virus Infection in Chinese Patients with Extrahepatic Bile Duct Carcinoma

    Institute of Scientific and Technical Information of China (English)

    CHENMingyi; HUANGZhiqiang; CHENLezhen; GAOYabing; PENGRuiyun; WANGDewen

    2002-01-01

    Objective:In China, the incidence of extrahepatic bile duct carcinoma (EBDC) tends to increase over the past decades. The etiology of the noted increase in EBDC is not identified. Approximately, in a half of the overall Chinese patients with EBDC, the causative factors in the development of EBDC have not been demonstrated. There is a high prevalence of hepatitis C virus (HCV) or hepatitis B virus (HBV)in China, both of which can induce malignant transformation of infected cells and strongly associated with hepatocellular carcinoma (HCC).In this study,EBDC tissues from Chinese patients were examined for the presence of HCV and HBV infection to investigate further the potential causes of EBDC. Methods:HCV NS5 protein and HBsAg were detected by labeled streptavidin biotin (LSAB) method; HCV RNA and HBV DNA were detected by in situ polymerase chain reaction (IS-PCR) in formalin fixed, paraffin embedded specimens from 51 Chinese patients with EBDC. HCV RNA and HBV DNA were detected by IS-PCR in 34 Chinese patients with specimens of benign lesions of hepatobiliary tract(control group). Results:In 51 case tissue sections of EBDC, NS5 protein was detected in 14 (27.5%), and HBsAg in 5 (9.8%), HCV RNA in 18(35.4%) and HBV DNA in 8 (15.9%), respectively, of which HCV and HBV co-infection was detected in 2 (3.9%). In 34 case tissue sections of the control group, HCV RNA was detected in 2 (5.9%), and HBV DNA in 3 (8.8%).Conclusion:In this study using standard histochemical and PCR techniques,HCV and HBV and HBV presence in EBDC tissues than would be expected on serologic grounds.The detectable rate of HCV RNA in EBDC tissues was significantly higher than in control group(x2=9.808,P=0.002).As a result ,this study indicates that there is a correlation between the presence of HCV infection and EBDC,and HCV infection has possible ctiologic significance in the development of EBDCin China.While HBV DNA was detecled in EBDC tissues with the difference in the detectable rate of HBV

  1. The Features of Extrahepatic Collateral Arteries Related to Hepatic Artery Occlusion and Benefits in the Transarterial Management of Liver Tumors

    International Nuclear Information System (INIS)

    Purpose. To investigate the extrahepatic collateral arteries related to hepatic artery occlusion (HAO) and to determine its benefits in the transarterial management of liver tumors. Methods and Findings. Eleven patients (7 hepatocellular carcinomas, 3 liver metastases, and 1 with hemangioma) with HAO confirmed with digital subtraction angiography (DSA) were admitted to our hospital. Of the 11 patients, 7 were men and 4 were women, with an average age of 41.5 ± 15.5 years (range: 29 to 70 years). DSA was performed to evaluate the collateral routes to the liver. In the 11 patients with HAO, DSA showed complete occlusion of the common hepatic artery in 9 patients and the proper hepatic artery (PHA) in 2 patients. Extrahepatic collateral arteries supplying the liver were readily evident. The collateral arteries originated from the superior mesenteric artery (SMA) in 8 patients, from the gastroduodenal artery in 2 patients, and from the left gastric artery (LGA) in 1 patient. Transcatheter treatment was successfully performed via the collateral artery in all patients except the one who had hemangioma. Conclusions. DSA is an effective method for detecting collateral circulation related to HAO and may provide information to guide transcatheter management decisions

  2. 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

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Technical Solutions to Ensure Safe Yttrium-90 Radioembolization in Patients With Initial Extrahepatic Deposition of 99mTechnetium–Albumin Macroaggregates

    International Nuclear Information System (INIS)

    Purpose: To evaluate the incidence of extrahepatic deposition of technetium-99m–labeled albumin macroaggregates (99mTc-MAA) after pretreatment angiography, before yttrium-90 radioembolizaton (90Y-RE), and to report on technical solutions that can be used to ensure safe delivery of 90Y-microspheres in patients with initial extrahepatic deposition. Materials and Methods: A retrospective analysis of 26 patients with primary and secondary liver malignancies, who were scheduled for treatment with 90Y-RE in our institution in 2009, was performed. The angiograms and single-photon emission computed tomography images of all patients were reviewed by an interventional radiologist and a nuclear medicine physician, respectively, to identify and localize extrahepatic deposition of 99mTc-MAA when present. Subsequently, the technical solutions were used to successfully perform 90Y-RE in these patients were evaluated and described. Results: Extrahepatic deposition of 99mTc-MAA was observed in 8 of 26 patients (31%). In 7 of 8 patients, a second pretreatment angiography was performed to detect the cause of extrahepatic deposition. The technical solutions to enable safe 90Y microspheres delivery included more distal placement of the microcatheter in the proper/right hepatic artery in 4 of 7 (57%) patients; (super)selective catheterization of multiple segmental branches in 2 of 7 (29%); and additional coiling of a newly detected branch in the remaining patient (14%). This was confirmed by a second MAA procedure. 90Y-RE was eventually performed in 25 of 26 (96%) patients. No procedure-related complications (99mTc-MAA after pretreatment angiography did occur in 8 of 26 (31%) patients. The technical solutions as presented allowed safe 90Y-RE delivery in 25 of 26 (96%) patients.

  9. The role of B/D ratio and A/D ratio to defferentiate malignancy from benignancy in distal extrahepatic bile duct obstruction

    Energy Technology Data Exchange (ETDEWEB)

    Rhim, Hyun Chul; Baek, JUng Hwan; Jeon, Eui Yong; Koh, Byung Hee; Cho, On Koo [Hanyang University College of Medicine, Seoul (Korea, Republic of); Kim, Young Hwan [Ulsan University College of Medicine, Ulsan (Korea, Republic of)

    1994-12-15

    To determine wheter bilirubin/extrahepatic bile duct diameter ratio(B/D ratio) or alkalinephosphatase/extrahepatic bile duct diameter ratio (A/D ratio) can be used to differentiate malignant from benigndisease in distal extrahepatic bile duct obstruction during ultrasonographic examination. We retrospectively reviewed the sonograms and laboratory data of 100 patients with obstructive jaundice (benign : n=50, malignant: : n=50). The diagnosis was confirmed either surgically (n=66) or clinically (n=34). The B/D ratio and A/D radio were calculated by means of dividing total bilirubin (mg/dl) and alkaline phosphatase (I.U.)respectively by maximum extrahepatic bile duct diameter(mm) on ultrasonogram. Significant difference in B/D ratio was found between the benignancy (0.28+0.25) and malignancy (0.98+0.84) groups (P<0.001). Significant difference in A/D ratio was also found between the benignancy (15.00+10.22) and malignancy (32.44+30.28) groups(P<0.001) Accuracies to predict malignancy according to criteria of B/D and A/D ratios were less than 75% and 65%respectively. On the other hand, the positive predictive value and specificity were relatively high. The B/D ratio and A/D ratio calculated from ultrasonograms can be used as a valuable screening index todifferentiate malignancy from benignacy in patients with distal extrahepatic bile duct obstruction, especially when the sonography is difficult because of the interposition of bowel gas or obesity

  10. A patient who has survived for a long period with repeated radiotherapy for multifocal extrahepatic metastases from hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Sunmi; Shim, Hye Kyung [Inje University Haeundae Paik Hospital, Busan (Korea, Republic of)

    2013-12-15

    Although significant advances in the treatment of intrahepatic lesions, it is reported that the prognosis for patients with hepatocellular carcinoma (HCC) who have extrahepatic metastasis remains poor. We report a patient with lung, liver, brain, bone and subcutaneous metastasis from HCC who has survived more than 7 years maintaining relatively good performance status as a result of repeated therapies. A 55-year-old male patient with HCC underwent right lobectomy of the liver and cholecystectomy in September 2006. He received wedge resection for lung metastasis twice (July 2009, January 2011) and Gamma Knife stereotactic radiosurgery for brain metastasis (April 2011). Over the last 3 years, he has developed metastasis in subcutaneous tissues, muscle, and bone with pain. He has undergone 7 courses of radiotherapy for subcutaneous tissues, muscle, and bone metastasis and been prescribed sorafenib and he is still capable of all self-care.

  11. MR Cholangiography and Dynamic Examination of Duodenal Fluid in the Differential Diagnosis between Extrahepatic Biliary Atresia and Infantile Hepatitis Syndrome

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In order to evaluate the value of magnetic resonance cholangiography (MRC) and dynamic examination of duodenal fluid in the differential diagnosis between extrahepatic biliary atresia (EHBA) and infantile hepatitis syndrome (IHS), 52 pa tients with infantile cholestatic jaundice were examined by MRC and duodenal fluid examination. Original interpretations were compared with clinical outcome. Calculated sensitivity of duodenal fluid examination in diagnosis of EHBA was 100%, and specificity was 91.1%. Sensitivity of MRC in the diagnosis of EHBA was 94.4 % and specificity 88.24 %. The sensitivity of MRC and examination of duodenal fluid combined in diagnosis of EHBA was 94.4 % and specificity 97.06 %. We are led to conclude that MRC and dynamic examination of duodenal fluid are useful in the differential diagnosis between IHS and EHBA and the combined use of the two techniques yield better resutls.

  12. Splenectomy and proximal lieno-renal shunt in a factor five deficient patient with extra-hepatic portal vein obstruction

    Directory of Open Access Journals (Sweden)

    Sahni Peush

    2006-05-01

    Full Text Available Abstract Background The clinico-surgical implication and successful management of a rare case of factor five (V deficiency with portal hypertension and hypersplenism due to idiopathic extra-hepatic portal venous obstruction is presented. Case presentation A 16-year old boy had gastro-esophageal variceal bleeding, splenomegaly and hypersplenism. During preoperative workup prolonged prothrombin time and activated partial thromboplastin time were detected, which on further evaluation turned out to be due to factor V deficiency. Proximal lieno-renal shunt and splenectomy were successfully performed with transfusion of fresh frozen plasma during and after the surgical procedure. At surgery there was no excessive bleeding. The perioperative course was uneventful and the patient is doing well on follow up. Conclusion Surgical portal decompressive procedures can be safely undertaken in clotting factor deficient patients with portal hypertension if meticulous surgical hemostasis is achieved at operation and the deficient factor is adequately replaced in the perioperative period.

  13. Assessment of metastatic liver disease in patients with primary extrahepatic tumors by contrast-enhanced sonography versus CT and MRI

    Institute of Scientific and Technical Information of China (English)

    Christoph F Dietrich; Wolfgang Blank; Matthijs Oudkerk; Dietbert Hahn; Christian Greis; Wolfgang Kratzer; Deike Strobel; Etienne Danse; Robert Fessl; Alfred Bunk; Udo Vossas; Karlheinz Hauenstein; Wilhelm Koch

    2006-01-01

    AIM: To evaluate contrast-enhanced ultrasonography (CEUS) using SonoVue(R) in the detection of liver metastases in patients with known extrahepatic primary tumors versus the combined gold standard comprising CT,MRI and clinical/histological data.METHODS: It is an international multicenter study, and there were 12 centres and 125 patients (64 males, 61 females, aged 59 ± 11 years) involved, with 102 patients per protocol. Primary tumors were colorectal in 35%,breast in 27%, pancreatic in 17% and others in 21%.CEUS using SonoVue(R) was employed with a low-mechanical-index technique and contrast-specific software using Siemens Elegra, Philips HDI 5000 and Acuson Sequoia;continuous scanning for at least five minutes.RESULTS: CEUS with SonoVue(R) increased significantly the number of focal liver lesions detected versus unenhanced sonography. In 31.4% of the patients, more lesions were found after contrast enhancement. The total numbers of lesions detected were comparable with CEUS (55), triple-phase spiral CT (61) and MRI with a liverspecific contrast agent (53). Accuracy of detection of metastatic disease (i.e. at least one metastatic lesion) was significantly higher for CEUS (91.2%) than for unenhanced sonography (81.4%) and was similar to that of triple-phase spiral CT (89.2%). In 53 patients whose CEUS examination was negative, a follow-up examination 3-6 months later confirmed the absence of metastatic lesions in 50 patients (94.4 %).CONCLUSION: CEUS is proved to be reliable in the detection of liver metastases in patients with known extrahepatic primary tumors and suspected liver lesions.

  14. 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

  15. 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)

  16. Lack of detection of negative-strand hepatitis C virus RNA in peripheral blood mononuclear cells and other extrahepatic tissues by the highly strand-specific rTth reverse transcriptase PCR.

    OpenAIRE

    Lanford, R E; Chavez, D; Chisari, F V; Sureau, C

    1995-01-01

    To further explore the controversial potential for extrahepatic replication of hepatitis C virus (HCV), the highly strand-specific rTth method of reverse transcriptase PCR was used to examine sera, liver, peripheral blood mononuclear cells, and other extrahepatic tissues from HCV-infected chimpanzees and humans. Positive-strand HCV RNA was present in the liver at approximately 10-fold-higher levels than negative-strand HCV RNA. No negative-strand RNA was detected in peripheral blood mononucle...

  17. Portal vein thrombosis: Etiology and clinical outcome of cirrhosis and malignancy-related non-cirrhotic, non-tumoral extrahepatic portal venous obstruction

    OpenAIRE

    Jain, Pankaj; Nijhawan, Sandeep

    2007-01-01

    The etiology and pathogenesis of portal vein thrombosis are unclear. Portal venous thrombosis presentation differs in cirrhotic and tumor-related versus non-cirrhotic and non-tumoral extrahepatic portal venous obstruction (EHPVO). Non-cirrhotic and non-tumoral EHPVO patients are young and present with well tolerated bleeding. Cirrhosis and tumor-related portal vein thrombosis patients are older and have a grim prognosis. Among the 118 patients with portal vein thrombosis, 15.3% had cirrhosis,...

  18. Evaluation of blood levels of nitric oxide as a means of differentiation between neonatal hepatitis and extrahepatic biliary atresia: A pilot study

    OpenAIRE

    Goel, Prabudh; Bhatnagar, Veereshwar; Das, Nibhriti; Kalaivani, Mani

    2015-01-01

    Aim: The differentiation between neonatal hepatitis (NH) and extrahepatic biliary atresia (EHBA) is not always possible despite all the currently available diagnostic modalities. In this study, an attempt has been made to evaluate the role of nitric oxide (NO) levels in the peripheral blood to differentiate between the two conditions, one requiring early surgical intervention (EHBA) and the other amenable to conservative medical management (NH). Patients and Methods: Twenty patients who prese...

  19. Clinical characteristics and the incidence of extrahepatic autoimmune disease and malignant tumor in primary biliary cirrhosis-autoimmune hepatitis overlap syndrome

    Institute of Scientific and Technical Information of China (English)

    杨蜜蜜

    2013-01-01

    Objective To analyze clinical pathologic characteristics of patients with primary biliary cirrhosis-autoimmune hepatitis overlap syndrome (PBC-AIH OS) ,the incidence of extrahepatic autoimmune disease,malignant tumor and the abdominal lymph node enlargement.Methods From January 2000 to January 2012,the clinical data of 49 patients with PBC-AIH OS were retrospectively analyzed,which included general information,clinical manifestations,biochemical parameters,immu-

  20. Interleukin-6 (IL-6) serum concentrations in dogs with hepatitis and hepatic tumours compared with those with extra-hepatic inflammation and tumours.

    Science.gov (United States)

    Neumann, Stephan; Kaup, Franz-Josef; Scheulen, Sonja

    2012-10-01

    Cytokines are part of pathogenesis in many diseases. Their measurement could be interesting for diagnostic purposes. One cytokine which participates in different inflammatory and neoplastic diseases is interleukin-6 (IL-6). The aim of this study was to investigate the IL-6 serum concentration in dogs with different liver diseases to show if there is any association between the cytokine serum level and the disease aetiology or the degree of the disease. IL-6 was measured in dogs with acute hepatitis, chronic hepatitis of different degrees and primary and secondary liver tumours. The data were compared with clinically healthy dogs and dogs with extra-hepatic diseases. For measurement, a commercial ELISA Kit (R&D Systems) was used. Compared with clinically healthy dogs and dogs with diabetes mellitus, all dogs with an intra- or extra-hepatic inflammatory or neoplastic disease have increased serum levels of IL-6. Dogs with acute hepatitis have significantly increased IL-6 serum concentrations compared with dogs with chronic hepatitis (P hepatitis exists (P > 0.05). Dogs with secondary liver tumours have significantly increased IL-6 serum concentrations in comparison to dogs with primary liver tumours (P dogs with extra-hepatic tumours. Measurement of IL-6 serum concentration may help differentiate between acute and chronic hepatitis and between primary and secondary liver tumours. Further information about the aetiology of the liver disease cannot be obtained by measuring IL-6 in the serum. PMID:23049492

  1. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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...

  4. Mixed Large Cell Neuroendocrine Carcinoma and Adenocarcinoma with Spindle Cell and Clear Cell Features in the Extrahepatic Bile Duct

    Directory of Open Access Journals (Sweden)

    John Wysocki

    2014-01-01

    Full Text Available Mixed adenoneuroendocrine carcinomas, spindle cell carcinomas, and clear cell carcinomas are all rare tumors in the biliary tract. We present the first case, to our knowledge, of an extrahepatic bile duct carcinoma composed of all three types. A 65-year-old man with prior cholecystectomy presented with painless jaundice, vomiting, and weight loss. CA19-9 and alpha-fetoprotein (AFP were elevated. Cholangioscopy revealed a friable mass extending from the middle of the common bile duct to the common hepatic duct. A bile duct excision was performed. Gross examination revealed a 3.6 cm intraluminal polypoid tumor. Microscopically, the tumor had foci of conventional adenocarcinoma (CK7-positive and CA19-9-postive surrounded by malignant-appearing spindle cells that were positive for cytokeratins and vimentin. Additionally, there were separate areas of large cell neuroendocrine carcinoma (LCNEC. Foci of clear cell carcinoma merged into both the LCNEC and the adenocarcinoma. Tumor invaded through the bile duct wall with extensive perineural and vascular invasion. Circumferential margins were positive. The patient’s poor performance status precluded adjuvant therapy and he died with recurrent and metastatic disease 5 months after surgery. This is consistent with the reported poor survival rates of biliary mixed adenoneuroendocrine carcinomas.

  5. Multidetector CT venography and contrast-enhanced MR venography of the inferior mesenteric vein in paediatric extrahepatic portal vein obstruction

    Energy Technology Data Exchange (ETDEWEB)

    Chennur, Vikash SrinivasaiahSetty; Sharma, Raju; Gamanagatti, Shivanand; Gupta, Arun Kumar [All India Institute of Medical Sciences (AIIMS), Department of Radiology, New Delhi (India); Bhatnagar, Veereshwar [AIIMS, Department of Paediatric Surgery, New Delhi (India); Vishnubhatla, Sreenivas [AIIMS, Department of Biostatistics, New Delhi (India)

    2011-03-15

    Extrahepatic portal vein obstruction (EHPVO) is a common cause of paediatric portal hypertension and the only permanent treatment is shunt surgery. The inferior mesenteric vein (IMV) is a portal venous channel that can be used for the shunt when the splenic vein/superior mesenteric vein is thrombosed or when a lienorenal shunt is not possible. To compare MDCT venography (MDCTV) and contrast-enhanced MR venography (CEMRV) for visualisation of the IMV in children with EHPVO. This was a prospective study of 26 children (4-12 years, median 10 years) who underwent MDCTV and CEMRV. The IMV visualisation was graded using 4- and 2-point scales and the difference in visualisation was assessed by calculating the exact significance probability (P). The IMV was visualised in all children on MDCTV and 25/26 children on CEMRV (96%). The images were diagnostic in 23/26 children (88%) on MDCTV and in 18/26 (69%) children on CEMRV (P = 0.063). MDCTV and CEMRV are comparable for IMV visualisation with a tendency toward MDCTV being superior. (orig.)

  6. Extrahepatic manifestations of chronic hepatitis C virus infection:297 cases from a tertiary medical center in Beijing, China

    Institute of Scientific and Technical Information of China (English)

    Cheng Zhaojing; Zhou Baotong; Shi Xiaochun; Zhang Yao; Zhang Lifan; Chen Limeng; Liu Xiaoqing

    2014-01-01

    Background Chronic hepatitis C virus (HCV) infection can affect multiple organ systems and cause a variety of extrahepatic manifestations (EMs).We sought to assess the constituent ratio of EMs in Chinese patients with chronic HCV infection and identify the clinical and biological factors associated with EM.Methods The medical records of 297 patients with chronic HCV infection were analyzed and demographic and epidemiological information was collected.The diagnosis of chronic HCV infection was based on positive anti-HCV combined with a positive HCV-RNA or at least two times of elevated aminotransferases attributable to HCV infection.Patients with HBV and/or HIV coinfection,autoimmune hepatitis,and history of alcohol abuse were excluded.Results Sixty-two percent (184/297) of the patients had at least one EM,including fatigue (29.4%),type 2 diabetes mellitus (28.2%),renal involvement (12.5%),lymphadenopathy (9.6%),fever (9.4%),thyroid dysfunction (8.1%),and arthralgia (7.4%).Neuropathy,sicca syndrome,B-cell lymphoma,Raynaud's phenomenon,and lichen planus were rare.The mean age of patients with EM was older compared with those without EM.Conclusions EMs were common in Chinese patients with chronic HCV infection,particularly fatigue,type 2 diabetes,renal impairment,lymphadenophy,fever,and thyroid dysfunction.Older age was associated with EMs.

  7. 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.

  8. 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

  9. 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

  10. Effectiveness of Repeat Angiographic Assessment in Patients Designated for Radioembolization Using Yttrium-90 Microspheres With Initial Extrahepatic Accumulation of Technitium-99m Macroaggregated Albumin: A Single Center’s Experience

    International Nuclear Information System (INIS)

    Purpose: To evaluate the efficacy of a workflow consisting of repeat assessment in patients planned for yttrium-90 (90Y) radioembolization in case of nontarget visceral technetium-99m (99mTc)-macroaggregated albumin (MAA) accumulation despite initial prophylactic coil embolization of nonhepatic arteries. Materials and Methods: In 341 patients with primary and secondary liver cancer, pretreatment hepatic angiograms, as well as single-photon emission computed tomography coregistered with magnetic resonance imaging scans, were obtained. Extrahepatic tracer deposition was identified in 33 patients (9.7%) necessitating repeat assessment. Images were reviewed to correlate the site of MAA accumulation with causative gastrointestinal vessels, and repeat angiograms served as reference standard. Results: At repeat angiography, the source of extrahepatic flow was identified and eliminated in 31 of 33 patients (93.9%). In 20 patients (60.6%), successful embolization of nontarget vessels was achieved, in 13 patients (39.4%), MAA was administered more distally. Afterward, extrahepatic MAA deposition was eliminated in 30 patients (90.9%). Conclusion: The algorithm of repeat assessment in case of extrahepatic MAA accumulation has proven highly effective to eliminate extrahepatic shunting, thus decreasing the risk of postradioembolization complications due to inadvertent visceral microsphere deposition.

  11. Chemoembolization of Extrahepatic Collateral Arteries for Treatment of Hepatocellular Carcinoma in the Caudate Lobe of the Liver

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Sungmin; Kim, Hyo-Cheol, E-mail: angiointervention@gmail.com; Chung, Jin Wook; Jung, Hyun-Seok; Hur, Saebeom; Lee, Myungsu; Jae, Hwan Jun [Seoul National University Hospital, Department of Radiology, Seoul National University College of Medicine, Institute of Radiation Medicine, Seoul National University Medical Research Center, and Clinical Research Institute (Korea, Republic of)

    2015-04-15

    PurposeThis study was designed to evaluate the efficacy and safety in performing chemoembolization of extrahepatic collateral arteries (EHC) for hepatocellular carcinoma (HCC) located in the caudate lobe.MethodsBetween January 2006 and November 2013, chemoembolization via EHC was performed in 35 patients with 35 caudate HCCs. Preprocedural and follow-up CT or MR scans, angiographic images, and medical records were reviewed retrospectively in consensus. Chi-square analysis was used to evaluate the relationship between tumor characteristics and type of EHC and that between tumor response and the characteristics of the tumor and chemoembolization.ResultsIn 31 (88.6 %) patients, EHCs supplying the caudate HCC originated from the right inferior phrenic artery (RIPA). The remaining four HCCs were supplied by the gastroduodenal artery, dorsal pancreatic artery, and right and left gastric arteries. Superselective catheterization of tumor-feeding vessels from the EHC was achieved in 27 patients (77.1 %). There were no major complications. Individual tumor response supplied by the EHC at follow-up contrast-enhanced CT were as follows: complete response (n = 18), partial response (n = 9), stable disease (n = 3), and progressive disease (n = 3). Non-RIPA EHCs were significantly more common in patients who had previously received chemoembolization via the RIPA (50 %) than those who had not (6.5 %; P = 0.01). There was no significant predictive factor associated with tumor response.ConclusionsHCC in the caudate lobe can be supplied by several EHCs. Chemoembolization via these arteries can be performed safely and effectively.

  12. Percutaneous placement of self-expandable metallic biliary stents in malignant extrahepatic strictures: indications of transpapillary and suprapapillary methods

    International Nuclear Information System (INIS)

    To compare the efficacy of suprapapillary and transpapillary methods of transhepatic biliary metallic stent placement in malignant biliary strictures and to specify the indications of each method applied. Stents were placed in 59 patients. Strictures were categorized as type A (within 3 cm of the ampulla, n = 27), type B (over 3 cm from ampulla, n = 7), type C (within 3 cm of the bending portion, n = 9), or type D (over 3 cm above the bending portion, n=16). The stenting method was suprapapillary in 34 cases and transpapillary in 25. The rates of initial and long-term patency and of early recurrence were compared. Initial patency rates for the suprapapillary and transpapillary methods were 1/7 (14.3%) and 20/20 (100%) respectively for type A (p < 0.0001), 4/5 (80.0%) and 2/2 for type B, 3/7 (42.9%) and 2/2 for type C, and 15/16 (93.8%) and 0/0 for type D. Early recurrence rates were 7/30 (23.3%) using the suprapapillary method and 4/29 (13.8%) using the transpapillary method (p = 0.51). The long-term patency rate did not differ significantly according to either type (p = 0.37) or method (p = 0 . 6 2 ). For good initial patency, the transpapillary method is recommended for strictures of the distal extrahepatic duct near the ampulla and just above the bending portion. Long-term patency is not influenced by the stenting method employed

  13. Warren shunt combined with partial splenectomy in children with extra-hepatic portal hypertension, massive splenomegaly and severe hypersplenism

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    Sretenović Aleksandar

    2014-01-01

    Full Text Available Introduction. Extra-hepatic portal vein obstruction (EHPVO is one of the most often causes of portal hypertension in children. Objective. Establishing the importance of shunt surgery in combination with partial spleen resection in selected pediatric patients with EHPVO, enormous splenomegaly and severe hypersplenism. Methods. Distal splenorenal shunt (DSRS with partial spleen resection was performed in 22 children age from 2 to 17 years with EHPVO. Indications for surgery were pain and abdominal discomfort caused by spleen enlargement, as well as symptomatic hypersplenism with leucopenia, thrombocytopenia and anemia. The partial spleen resection was performed by ligation of blood vessels to caudal two thirds of the spleen. After ischemic parenchymal demarcation transection with electrocautery LigaSure was performed with preservation of 20-30% of spleen tissue, and then Warren DSRS was created. Platelet and leucocytes counts and liver function tests were obtained before, one month and one year after surgery. Growth was assessed with SD scores (Z scores for height, weight and body mass index at the time of surgery and one year later. Results. In all patients postoperative period was without significant complications. Platelets and leucocytes counts were normalized. Patency rate of shunts was 100%. Two significant shunts stenosis were observed and successfully treated with percutaneous angioplasty. During the follow-up period (1 to 9 years all patients were asymptomatic, with improved quality of life and growth. Conclusion. Results of our study indicate that shunt surgery with a partial spleen resection is an effective and safe procedure for patients with enormous splenomegaly and severe hypersplenism caused by EHPVO.

  14. Distant Metastasis Risk Stratification for Patients Undergoing Curative Resection Followed by Adjuvant Chemoradiation for Extrahepatic Bile Duct Cancer

    International Nuclear Information System (INIS)

    Purpose: To analyze the prognostic factors predicting distant metastasis in patients undergoing adjuvant chemoradiation for extrahepatic bile duct (EHBD) cancer. Methods and Materials: Between January 1995 and August 2006, 166 patients with EHBD cancer underwent resection with curative intent, followed by adjuvant chemoradiation. There were 120 males and 46 females, and median age was 61 years (range, 34–86). Postoperative radiotherapy was delivered to tumor bed and regional lymph nodes (median dose, 40 Gy; range, 34–56 Gy). A total of 157 patients also received fluoropyrimidine chemotherapy as a radiosensitizer, and fluoropyrimidine-based maintenance chemotherapy was administered to 127 patients. Median follow-up duration was 29 months. Results: The treatment failed for 97 patients, and the major pattern of failure was distant metastasis (76 patients, 78.4%). The 5-year distant metastasis-free survival rate was 49.4%. The most common site of distant failure was the liver (n = 36). On multivariate analysis, hilar tumor, tumor size ≥2 cm, involved lymph node, and poorly differentiated tumor were associated with inferior distant metastasis-free survival (p = 0.0348, 0.0754, 0.0009, and 0.0078, respectively), whereas T stage was not (p = 0.8081). When patients were divided into four groups based on these risk factors, the 5-year distant metastasis-free survival rates for patients with 0, 1, 2, and 3 risk factors were 86.4%, 59.9%, 32.5%, and 0%, respectively (p < 0.0001). Conclusion: Despite maintenance chemotherapy, distant metastasis was the major pattern of failure in patients undergoing adjuvant chemoradiation for EHBD cancer after resection with curative intent. Intensified chemotherapy is warranted to improve the treatment outcome, especially in those with multiple risk factors.

  15. Extrahepatic sources of factor VIII potentially contribute to the coagulation cascade correcting the bleeding phenotype of mice with hemophilia A.

    Science.gov (United States)

    Zanolini, Diego; Merlin, Simone; Feola, Maria; Ranaldo, Gabriella; Amoruso, Angela; Gaidano, Gianluca; Zaffaroni, Mauro; Ferrero, Alessandro; Brunelleschi, Sandra; Valente, Guido; Gupta, Sanjeev; Prat, Maria; Follenzi, Antonia

    2015-07-01

    A large fraction of factor VIII in blood originates from liver sinusoidal endothelial cells although extrahepatic sources also contribute to plasma factor VIII levels. Identification of cell-types other than endothelial cells with the capacity to synthesize and release factor VIII will be helpful for therapeutic approaches in hemophilia A. Recent cell therapy and bone marrow transplantation studies indicated that Küpffer cells, monocytes and mesenchymal stromal cells could synthesize factor VIII in sufficient amount to ameliorate the bleeding phenotype in hemophilic mice. To further establish the role of blood cells in expressing factor VIII, we studied various types of mouse and human hematopoietic cells. We identified factor VIII in cells isolated from peripheral and cord blood, as well as bone marrow. Co-staining for cell type-specific markers verified that factor VIII was expressed in monocytes, macrophages and megakaryocytes. We additionally verified that factor VIII was expressed in liver sinusoidal endothelial cells and endothelial cells elsewhere, e.g., in the spleen, lungs and kidneys. Factor VIII was well expressed in sinusoidal endothelial cells and Küpffer cells isolated from human liver, whereas by comparison isolated human hepatocytes expressed factor VIII at very low levels. After transplantation of CD34(+) human cord blood cells into NOD/SCIDγNull-hemophilia A mice, fluorescence activated cell sorting of peripheral blood showed >40% donor cells engrafted in the majority of mice. In these animals, plasma factor VIII activity 12 weeks after cell transplantation was up to 5% and nine of 12 mice survived after a tail clip-assay. In conclusion, hematopoietic cells, in addition to endothelial cells, express and secrete factor VIII: this information should offer further opportunities for understanding mechanisms of factor VIII synthesis and replenishment.

  16. Extrahepatic sources of factor VIII potentially contribute to the coagulation cascade correcting the bleeding phenotype of mice with hemophilia A.

    Science.gov (United States)

    Zanolini, Diego; Merlin, Simone; Feola, Maria; Ranaldo, Gabriella; Amoruso, Angela; Gaidano, Gianluca; Zaffaroni, Mauro; Ferrero, Alessandro; Brunelleschi, Sandra; Valente, Guido; Gupta, Sanjeev; Prat, Maria; Follenzi, Antonia

    2015-07-01

    A large fraction of factor VIII in blood originates from liver sinusoidal endothelial cells although extrahepatic sources also contribute to plasma factor VIII levels. Identification of cell-types other than endothelial cells with the capacity to synthesize and release factor VIII will be helpful for therapeutic approaches in hemophilia A. Recent cell therapy and bone marrow transplantation studies indicated that Küpffer cells, monocytes and mesenchymal stromal cells could synthesize factor VIII in sufficient amount to ameliorate the bleeding phenotype in hemophilic mice. To further establish the role of blood cells in expressing factor VIII, we studied various types of mouse and human hematopoietic cells. We identified factor VIII in cells isolated from peripheral and cord blood, as well as bone marrow. Co-staining for cell type-specific markers verified that factor VIII was expressed in monocytes, macrophages and megakaryocytes. We additionally verified that factor VIII was expressed in liver sinusoidal endothelial cells and endothelial cells elsewhere, e.g., in the spleen, lungs and kidneys. Factor VIII was well expressed in sinusoidal endothelial cells and Küpffer cells isolated from human liver, whereas by comparison isolated human hepatocytes expressed factor VIII at very low levels. After transplantation of CD34(+) human cord blood cells into NOD/SCIDγNull-hemophilia A mice, fluorescence activated cell sorting of peripheral blood showed >40% donor cells engrafted in the majority of mice. In these animals, plasma factor VIII activity 12 weeks after cell transplantation was up to 5% and nine of 12 mice survived after a tail clip-assay. In conclusion, hematopoietic cells, in addition to endothelial cells, express and secrete factor VIII: this information should offer further opportunities for understanding mechanisms of factor VIII synthesis and replenishment. PMID:25911555

  17. Non-Hodgkin lymphoma as a cause of obstructive jaundice with simultaneous extrahepatic portal vein obstruction: A case report

    Institute of Scientific and Technical Information of China (English)

    Masao Hashimoto; Nobutaka Umekita; Kazumasa Noda

    2008-01-01

    Non-Hodgkin lymphoma is a rare cause of biliary obstruction. To the best of our knowledge, non-Hodgkin lymphoma in the peripancreatic region causing obstructive jaundice with simultaneous portal vein (PV) invasion has not yet been reported. We present a 50-year-old patient with obstructive jaundice whose extrahepatic portal vein was obstructed by the invasion of a peripancreatic non-Hodgkin lymphoma. The patient denied any other symptoms such as recurrent fever, night sweat and loss of body weight. Computed tomography (CT) revealed a 10cm mass in the retroperitoneal space behind the head of the pancreas causing obstruction of the distal bile duct and the PV. A pylorus-preserving pancreaticoduodenectomy combined with a PV resection was performed. The PV was reconstructed using an autologous right internal jugular vein graft. The resected specimen showed endoluminal invasion of both the bile duct and the PV. Histological examination showed the mass consisting of diffuse sheets of large malignant lymphoid cells. These cells were positive for CD20 and CD79a, partially positive for CD10, and negative for CD3, CD4, CD5, CD8 and CD30. The pathologic diagnosis was diffuse large B-cell type non-Hodgkin lymphoma and the patient was transferred to the Department of Hematology and Oncology for chemotherapy. He received four cycles of combined chemotherapy including cyclophosphamide, doxorubicin, vincristine and prednisone plus rituximab, and three cycles of intrathecal chemoprophylaxis including methotorexate, cytosine arbinoside and prednisone. The patient is alive with no evidence of the disease for 7 mo after operation and will receive additional courses of chemotherapy.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. Viral genotype and HLA class II alleles influence on extra-hepatic manifestations of chronic HCV infection

    Directory of Open Access Journals (Sweden)

    M. Galeazzi

    2011-09-01

    Full Text Available Objective: To test whether an association between HCV genotype, HLA class II alleles distribution and extra-hepatic manifestations (EHM can be demonstrated in a group of Italian patients with chronic HCV infection . Methods: Sixty patients affected by HCV infection with EHM were consecutively enrolled. 163 HCV patients without EHM were tested as controls for the prevalence of HCV genotypes, while we referred to literature as to the controls for HLA distribution. HCV-RNA was quantified by a RT-PCR. HLA class II alleles typing was performed using a standard microlymphocytotoxicity assay. We used chi-square or Fisher test (p<0.05 significant. Odds Ratio (OR was performed by 2X2 contingency table. Results: HCV 2c genotype was found in 63.46% of patients compared to 19.63% of controls (p<0.0001; OR=7.11. Furthermore, it correlated with carpal tunnel syndrome (p=0.03; OR=4.5 and autoimmune thyroiditis (p=0.02; OR=9.2. On the contrary, 1b genotype protected from EHM in toto (p=0.0004; OR=0.21 and particularly from carpal tunnel syndrome (p=0.0014; OR=0.07. Moreover, 3a genotype prevented HCV people from having cryoglobulinemia (p=0.05; OR=0.11. As to HLA, DR6 seemed to facilitate EHM in HCV patients (p=0.041; OR=1.61, while DQ2 (p=0.03; OR=0.5 and DQ3 (p=0.002; OR= 0.5 may play a protective role. In addition, HLA DR3 was associated with cryoglobulinemia (p=0.02; OR=9.5. Conclusions: According to our findings, 2c genotype can be considered as a major risk factor for developing HCVrelated EHM, while 1b genotype seems to prevent their onset; there are also evidences suggesting that HLA might play a role in chronic HCV infected patients.

  9. 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) ...

  10. 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.

  11. 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.

  12. 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

  13. Effect of galactosamine-induced hepatic UDP-glucuronic acid depletion on acetaminophen elimination in rats. Dispositional differences between hepatically and extrahepatically formed glucuronides of acetaminophen and other chemicals.

    Science.gov (United States)

    Gregus, Z; Madhu, C; Goon, D; Klaassen, C D

    1988-01-01

    Galactosamine (GAL) markedly depletes hepatic UDP-glucuronic acid (UDP-GA) whereas extrahepatic UDP-GA is minimally affected. This suggests that GAL predominantly inhibits hepatic glucuronidation. Therefore, the effect of GAL-induced hepatic UDP-GA depletion was examined in bile duct-cannulated rats to determine the role of hepatic glucuronidation in the disposition of acetaminophen (AA). GAL markedly altered the fate of AA-glucuronide but had little or no effect upon other AA metabolites. GAL decreased the biliary excretion of AA-glucuronide up to 92%, whereas reductions in blood levels and urinary excretion of AA-glucuronide did not exceed 50%. This suggests that AA-glucuronide excreted in bile is predominantly of hepatic origin whereas AA-glucuronide found in blood and urine is derived from both hepatic and extrahepatic tissues. Data in the present and previous studies [Gregus, Watkins, Thompson, Klaassen: J. Pharmacol. Exp. Ther. 225, 256, (1983)] indicate that GAL greatly reduced the biliary excretion of AA- and valproic acid-glucuronide whereas the biliary excretion of the glucuronides of phenolphthalein, iopanoic acid, bilirubin, and diethylstilbestrol was only partially decreased. This difference appears to be largely due to differential contributions by the liver and extrahepatic tissues in the glucuronidation of various compounds as well as the availability of glucuronides formed in extrahepatic tissues for biliary excretion. Specifically, the extrahepatically formed glucuronide conjugates of AA and valproic acid are not readily available for biliary excretion whereas the glucuronides of the other compounds are readily excreted into bile.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Simultaneous Non-Functioning Neuroendocrine Carcinoma of the Pancreas and Extra-Hepatic Cholangiocarcinoma. A Case of Early Diagnosis and Favorable Post-Surgical Outcome

    Directory of Open Access Journals (Sweden)

    Simone Maurea

    2011-05-01

    Full Text Available Context Thanks to the wide use of diagnostic imaging modalities, multiple primary malignancies are being diagnosed more frequently and different associations of malignancies have been reported in this setting. Case report In this paper, we describe the case of a patient with non-functioning well-differentiated neuroendocrine carcinoma of the head of the pancreas associated with extra-hepatic cholangiocarcinoma, in which an early diagnosis using magnetic resonance imaging allowed a good outcome. Conclusion The simultaneous association of neuroendocrine pancreatic tumors and cholangiocarcinoma has not yet been described; however, this association should be considered and, due to the high contrast of magnetic resonance imaging, this technique is recommended in such patient in order to reach an accurate diagnosis.

  15. Portal vein thrombosis: Etiology and clinical outcome of cirrhosis and malignancy-related non-cirrhotic, non-tumoral extrahepatic portal venous obstruction

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The etiology and pathogenesis of portal vein thrombosis are unclear. Portal venous thrombosis presentation differs in cirrhotic and tumor-related versus non-cirrhotic and non-tumoral extrahepatic portal venous obstruction (EHPVO). Non-cirrhotic and non-tumoral EHPVO patients are young and present with well tolerated bleeding.Cirrhosis and tumor-related portal vein thrombosis patients are older and have a grim prognosis. Among the 118 patients with portal vein thrombosis, 15.3% had cirrhosis, 42.4% had liver malignancy (primary or metastatic), 6% had pancreatitis (acute or chronic), 5% had hypercoagulable state and 31.3% had idiopathy,12% had hypercoagulable state in the EHPVO group.

  16. Atresia das vias biliares extra-hepáticas: conhecimentos atuais e perspectivas futuras Extrahepatic biliary atresia: current concepts and future directions

    Directory of Open Access Journals (Sweden)

    Elisa de Carvalho

    2007-04-01

    Full Text Available OBJETIVOS: Apresentar uma revisão atualizada sobre atresia das vias biliares extra-hepáticas, com ênfase em etiopatogenia, abordagens diagnósticas e terapêuticas e prognóstico. FONTES DOS DADOS: Foram selecionadas pelos sites de busca médica (MEDLINE e PubMed pesquisas relacionadas à atresia biliar, utilizando as seguintes palavras-chave: biliary atresia,etiopathogenesis, diagnosis, treatment, prognosis, children. SÍNTESE DOS DADOS A atresia das vias biliares extra-hepáticas é a principal indicação de transplante hepático na faixa etária pediátrica. Quanto à etiologia, o citomegalovírus, o reovírus e o rotavírus têm sido os agentes mais estudados como possíveis desencadeadores da obstrução imunomediada da árvore biliar. A resposta imune, especialmente o predomínio da resposta TH1 e do interferon gama, a susceptibilidade genética e as alterações do desenvolvimento embrionário da árvore biliar são aspectos que podem participar na etiopatogênese da obliteração das vias biliares extra-hepáticas. Ainda hoje, o único tratamento disponível é a portoenterostomia, cujos resultados são melhores quando realizada nos primeiros 2 meses de vida. Em relação ao prognóstico, as crianças não tratadas vão a óbito na totalidade, por complicações relacionadas à hipertensão portal e à cirrose hepática, e mesmo os casos tratados necessitam, em sua maioria, do transplante hepático. CONCLUSÃO: A atresia das vias biliares extra-hepáticas continua sendo a principal indicação de transplante hepático em crianças, e a mudança deste panorama depende de um melhor entendimento da etiopatogenia da obstrução biliar nos diferentes fenótipos da doença. Investigações futuras a respeito do papel do interferon gama e de outras citocinas são necessárias para avaliar se esses aspectos seriam potenciais alvos de intervenção terapêutica.OBJECTIVE: To provide an updated review on extrahepatic biliary atresia, focusing

  17. Progress of chemoradiotherapy in management of extrahepatic biliary system cancer%肝外胆道系统肿瘤放化综合治疗进展

    Institute of Scientific and Technical Information of China (English)

    李金銮

    2008-01-01

    肝外胆道系统肿瘤是一种少见且预后差的疾病,诊断时多为晚期,丧失了根治手术切除的机会,放化综合治疗成为其主要治疗手段.近年来,放化综合治疗在可切除和不可切除的肝外胆道系统肿瘤治疗上取得了一定进展.%Extrahepatic biliary system cancer(EBSC)is an uncommon disease with a poor prognosis. There is no change to making radical resection in most patients because most of the diseases are diagnosed at late stage.Chemoradiotherapy has been a major therapeutic modality of EBSC.In recent year,the progress of chemoradiotherapy has been made in management of resectable and unresectable EBSC.

  18. Hepatic and extrahepatic responses to insulin in NIDDM and nondiabetic humans. Assessment in absence of artifact introduced by tritiated nonglucose contaminants

    International Nuclear Information System (INIS)

    It is well established that patients with non-insulin-dependent diabetes mellitus (NIDDM) are resistant to insulin. However, the contribution of hepatic and extrahepatic tissues to insulin resistance remains controversial. The uncertainty may be at least in part due to errors introduced by the unknowing use in previous studies of impure isotopes to measure glucose turnover. To determine hepatic and extrahepatic responses to insulin in the absence of these errors, steady-state glucose turnover was measured simultaneously with [6-3H]- and [6-14C]glucose during sequential 5- and 4-h infusions of insulin at rates of 0.4 and 10 mU.kg-1.min-1 in diabetic and nondiabetic subjects. At low insulin concentrations, [6-3H]- and [6-14C]glucose gave similar estimates of glucose turnover. Hepatic glucose release was equal to but not below zero in the nondiabetic subjects, but persistent glucose release (P less than 0.001) and decreased glucose uptake (P less than 0.001) was observed in the diabetic patients. At high insulin concentrations, both isotopes underestimated glucose turnover during the 1st h after initiation of the high-dose insulin infusion. More time (P less than 0.05) was required to reachieve steady state in NIDDM than nondiabetic subjects. At steady state, [6-3H]- but not [6-14C]glucose systematically underestimated (P less than 0.05) glucose turnover in both groups due to the presence of a tritiated nonglucose contaminant. The percentage of radioactivity in plasma due to tritiated contaminants was linearly related to turnover

  19. 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

  20. 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

  1. 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

  2. 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.

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

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    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.

  4. 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 ...

  5. Nomogram Prediction of Survival and Recurrence in Patients With Extrahepatic Bile Duct Cancer Undergoing Curative Resection Followed by Adjuvant Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Song, Changhoon [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Kyubo, E-mail: kyubokim@snu.ac.kr [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Chie, Eui Kyu [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul (Korea, Republic of); Kim, Jin Ho [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Jang, Jin-Young; Kim, Sun Whe [Department of Surgery, Seoul National University College of Medicine, Seoul (Korea, Republic of); Han, Sae-Won; Oh, Do-Youn; Im, Seock-Ah; Kim, Tae-You; Bang, Yung-Jue [Department of Internal Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Ha, Sung W. [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul (Korea, Republic of)

    2013-11-01

    Purpose: To develop nomograms for predicting the overall survival (OS) and relapse-free survival (RFS) in patients with extrahepatic bile duct cancer undergoing adjuvant chemoradiation therapy after curative resection. Methods and Materials: From January 1995 through August 2006, a total of 166 consecutive patients underwent curative resection followed by adjuvant chemoradiation therapy. Multivariate analysis using Cox proportional hazards regression was performed, and this Cox model was used as the basis for the nomograms of OS and RFS. We calculated concordance indices of the constructed nomograms and American Joint Committee on Cancer (AJCC) staging system. Results: The OS rate at 2 years and 5 years was 60.8% and 42.5%, respectively, and the RFS rate at 2 years and 5 years was 52.5% and 38.2%, respectively. The model containing age, sex, tumor location, histologic differentiation, perineural invasion, and lymph node involvement was selected for nomograms. The bootstrap-corrected concordance index of the nomogram for OS and RFS was 0.63 and 0.62, respectively, and that of AJCC staging for OS and RFS was 0.50 and 0.52, respectively. Conclusions: We developed nomograms that predicted survival and recurrence better than AJCC staging. With caution, clinicians may use these nomograms as an adjunct to or substitute for AJCC staging for predicting an individual's prognosis and offering tailored adjuvant therapy.

  6. Nomogram Prediction of Survival and Recurrence in Patients With Extrahepatic Bile Duct Cancer Undergoing Curative Resection Followed by Adjuvant Chemoradiation Therapy

    International Nuclear Information System (INIS)

    Purpose: To develop nomograms for predicting the overall survival (OS) and relapse-free survival (RFS) in patients with extrahepatic bile duct cancer undergoing adjuvant chemoradiation therapy after curative resection. Methods and Materials: From January 1995 through August 2006, a total of 166 consecutive patients underwent curative resection followed by adjuvant chemoradiation therapy. Multivariate analysis using Cox proportional hazards regression was performed, and this Cox model was used as the basis for the nomograms of OS and RFS. We calculated concordance indices of the constructed nomograms and American Joint Committee on Cancer (AJCC) staging system. Results: The OS rate at 2 years and 5 years was 60.8% and 42.5%, respectively, and the RFS rate at 2 years and 5 years was 52.5% and 38.2%, respectively. The model containing age, sex, tumor location, histologic differentiation, perineural invasion, and lymph node involvement was selected for nomograms. The bootstrap-corrected concordance index of the nomogram for OS and RFS was 0.63 and 0.62, respectively, and that of AJCC staging for OS and RFS was 0.50 and 0.52, respectively. Conclusions: We developed nomograms that predicted survival and recurrence better than AJCC staging. With caution, clinicians may use these nomograms as an adjunct to or substitute for AJCC staging for predicting an individual's prognosis and offering tailored adjuvant therapy

  7. Very Early Presentation of Extrahepatic Portal Vein Obstruction Causing Portal Hypertension in an Infant: Uncertainties in the Management and Therapeutic Limitations.

    Science.gov (United States)

    Khodayar-Pardo, Parisá; Peña Aldea, Andrés; Ramírez González, Ana; Meseguer Carrascosa, Adela; Calabuig Bayo, Cristina

    2016-01-01

    Extrahepatic portal vein obstruction, although rare in children, is a significant cause of portal hypertension (PHT) leading to life-threatening gastrointestinal bleeding in the pediatric age group. PHT may also lead to other complications such as hyperesplenism, cholangyopathy, ascites, and even hepatopulmonary syndrome and portopulmonary hypertension that may require organ transplantation. Herein we report the case of an asymptomatic 11-month-old infant wherein a hepatomegaly and cavernous transformation of the portal vein was detected by liver ultrasound. Neither signs of thrombosis in arteriovenous system, nor affectation of biliary tract were identified in the magnetic resonance imaging study. A significant enlargement of the caudate lobe of the liver was reported. No risk factors were detected. The differential diagnosis performed was extensive. Inherited thrombophilia and storage disorders were especially considered. Liver biopsy was normal. Upper gastrointestinal esophagogastroduodenoscopy detected two small varicose cords on the distal third of the esophagus. Finding a cavernous transformation of the portal vein with evidence of collateral circulation in such an early age is a challenging condition for professionals, since PHT may lead to severe complications during childhood and can compromise growth and development. Evidence-based guidelines for the management of PHT in adults have been published. However, follow-up and treatment of pediatric patients have not yet been standardized. Moreover, management of PHT in infants faces particular difficulties such as technical restrictions that could hinder their treatment. PMID:27504083

  8. Value of 64-slice spiral CT in detection of the extrahepatic artery of primary hepatocellular carcinoma%64层螺旋 CT对原发性肝癌肝外供血动脉的诊断价值

    Institute of Scientific and Technical Information of China (English)

    王树庆; 左赞江; 宋高业; 姚斌; 杨德军; 谢柳平

    2015-01-01

    目的:探讨64层螺旋CT对原发性肝癌肝外供血动脉的诊断价值。方法回顾性分析经 DSA 证实的存在肝外供血动脉的41例肝癌患者的64层 CT 资料。分别统计 CT 和 DSA 能检出的肝癌肝外供血动脉数,将两者的结果进行 Kappa 一致性检验并分析。另总结有侧支性供血动脉的肝癌的 CT 表现特点。结果本资料75%(48/64)的肝癌肝外供血动脉能够通过 CT 正确检出。CT 与 DSA 相比,在对肝癌肝外供血动脉的检出上一致性好(k =0.62,P <0.05)。一些常规 CT 表现特点可对肝癌存在侧支性供血动脉作出提示性诊断。CT 指导后的 DSA 提高了对肝外供血动脉的检出率。结论64层 CT 对肝癌肝外供血动脉有良好的检出能力,认真分析术前 CT 特征对肝癌的肝动脉化疗栓塞术(TACE)治疗有重要的临床意义。%Objective To investigate the value of 64-slice spiral CT in detection of extrahepatic artery of primary hepatocellular carcinoma (PHC).Methods 64-slice spiral CT data of 41 patients with PHC with extrahepatic arteries were retrospectively ana-lyzed.The number of these extrahepatic arteries was measured on CT and DSA respectively.Cohen’s Kappa test was used to deter-mine the consistency between CT and DSA.The imaging features of PHC supplied by the lateral blood vessels were also summa-rized.Results Among 64 branches of the extrahepatic arteries,48 (75%)were detected by CT.64-slice spiral CT showed a good consistency on the diagnosis of PHC extrahepatic artery with DSA.Some CT characteristics of PHC were helpful for identification of the lateral blood vessels.The DSA under CT guidance improved the detection rate of extrahepatic artery.Conclusion 64-slice spiral CT has better ability in detection of PHC extrahepatic artery and improves the detection rate.Preoperative CT palys an important role in transcatheter arterial chemoembolization treatment of PHC.

  9. 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.

  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. 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

  12. ERCP在不明原因肝外阻塞性黄疸的临床应用%Clinical application of ERCP in the diagnosis of unexplained extrahepatic obstructive jaundice

    Institute of Scientific and Technical Information of China (English)

    高晓姣; 梁运啸; 农兵; 梁列新; 覃柳; 潘咏; 王彩英; 覃惠庆

    2012-01-01

    Objective To valuate the clinical application of endoscopic retrograde cholangiopancre-atography (ERCP) to the patients with unexplained extrahepatic obstructive jaundice after routine diagnostic approaches. Methods Forty-five patients consisting of 28 males and 17 females, aged 21 to 80 years old, enrolled for ERCP to determine the causes of pancreatic disease as well as extrahepatic bile duct obstruction which could not be figured out via ultrasonography, CT and/or MRCP. Results After ERCP, 42 of 45 patients were diagnosed as biliary tnicrolithiasis and were treated by endoscopic sphincterotomy (EST) technique to remove biliary microlithiasis. The patients with lower common bile tract were treated with endoscopic retrograde biliary drainage (ERBD). Together, all patients were rapidly relieved from abdominal pain and jaundice except two cases. One of them suffered from post-operative complication of mild pancreatitis but cured by conservative treatment, another one developed recurrent abdominal pain and then received cholecystectomy. Conclusion Our findings indicate that biliary microlithiasis is the main cause of unexplained extrahepatic obstructive jaundice. ERCP is a safe and reliable method for diagnosis and therapy of extrahepatic obstructive jaundice.%目的 探讨内镜逆行胰胆管造影(ERCP)在经常规检查不明原因肝外阻塞性黄疸的临床应用价值.方法 收集经B超、CT和/或MRCP检查诊断不明原因胆胰疾病或肝外胆管梗阻病人45例,男28例,女17例,年龄21~80岁,均行ERCP术.结果 45例病人行ERCP术,其中42例诊断为胆道微结石(Biliary microlithiasis,BML),42例均行乳头扩张术/EST+胆道取石术;3例为胆总管下端炎性狭窄而行胆道内支架植入术;1例ERCP取石术后并发轻症胰腺炎,经内科保守治疗后痊愈,1例因腹痛再发行胆囊切除术,其余患者经ERCP治疗后腹痛、黄疸均缓解.结论 BML是不明原因肝外阻塞性黄疸的主要原因,ERCP是不

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. Extrahepatic manifestations of chronic hepatitis C and their influence on response to treatment with Pegylated interferon alfa-2a and ribavirin

    Directory of Open Access Journals (Sweden)

    Fabri Milotka

    2013-01-01

    Full Text Available Introduction. Thirty to 50% of patients with chronic hepatitis C (CHC have one or more extrahepatic manifestations (EHMs of hepatitis C virus (HCV infection. Objective. The aim of this study was to evaluate the frequency of EHMs and to investigate the efficacy of pegylated interferon (Peg­IFN­α­2a plus ribavirin therapy in patients with HCV­related EHMs. Methods. The study included 280 patients suffering from CHC and treated with Peg­IFN­α­2a and ribavirin. The patients were divided in two groups according to presence or absence of EHMs. We evaluated virological response to antiviral therapy. Results. One or more EHMs were found among 27.9% of patients. Most frequently they had rheumatoid factor in serum (12.5%, organ­nonspecific antibodies ANA and AGMA (12.4%, thyroid hormone disorders (9.3%, vasculitis (5.7%, diabetes mellitus (4.65%, glomerulonephritis (0.71%, and porphyria cutanea tarda (0.36%. Among the patients with EHMs there was 52.6% of females vs. 30.2% of females in the group of patients without EHMs (p=0.001. HCV genotypes 1 and 4 had 85.9% patients with EHMs vs. 58.4% of patients without EHMs (p=0.000. Progressive fibrosis and cirrhosis were more frequently recorded in the EHM group of patients (32% vs. 23.2%, but without statistically significant difference (p=0.532. Serious adverse events of Peg­IFN­α­2a and ribavirin were statistically significantly recorded among the patients with EHMs (46.1% vs. 12.9%; p=0.000. Sustained virological response among the patients with and without EHMs rated 56.9% and 70.8% respectively (p=0.125. Conclusion. Patients with CHC and EHMs treated with combined Peg­IFN­α­2a and ribavirin experience handling difficulties, more often have serious adverse events, while successful outcome is achieved in about 50% of patients.

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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。

  3. 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

  4. 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),

  5. 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.

  6. Acute cholestasis related to desloratidine

    Institute of Scientific and Technical Information of China (English)

    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.

  7. 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...

  8. The Expression and Significance of DNMT3b Gene in Extrahepatic Cholangiocarcinoma Tissues%DNA甲基转移酶3b基因在肝外胆管癌组织中的表达

    Institute of Scientific and Technical Information of China (English)

    左石; 邹声泉; 孙诚谊

    2011-01-01

    Objective: To study the expression of DNA methyltransferase 3b (DNMT3b) in human extrahepatic cholangiocarcinoma tissues, analyze the relationship between its expression and clinico-pathologic features of the disease, and to explore the roles of DNMT3b during tumorigenesis and development of the disease. Methods: The expression of DNMT3b protein was detected in 24 extrahepatic cholangiocarcinoma specimens and 20 chronic cholangeitis tissue specimens by immunohistochemistry method. The results were compared between groups, and analyzed in association with clinicopatholigic features of extrahepatic cholangiocarcinoma. Results; (1) The positive cell rates of DNMT3b expression were (46. 56 ±12. 12)% and (3. 34 ±2. 73)% in extrahepatic cholangiocarcinoma specimens and in chronic cholangeitis tissues respectively. The difference between the two groups ( P = 0. 000) was significant; (2) The expression of DNMT3b protein was correlated with differentiation grade of the carcinoma. The protein levels of DNMT3b increased progressively along with the adenocarcinoma differentiation from high to moderate, and to poor. The abnormal expression of DNMT3b protein did not correlate with gender, age, tumor sizes, tumor location, metastasis of lymph node or clinical TNM stage. Conclusions: The expression of DNMT3b protein in extrahepatic cholangiocarcinoma is signifi-cantly higher than that in chronic cholangeitis tissues. DNMT3b protein level is correlated with differentiation grade of tumor, but not correlated with gender, age, tumor size, tumor location, metastasis of lymph node, or clinical TNM stage. This result suggests that over-expression of DNMT3b may relate to the pathogenesis of biliary tract carcinoma and might be an early molecular event during genesis of biliary tract carcinoma.%目的:研究DNA甲基转移酶3b( DNMT3b)在人肝外胆管癌组织中的表达情况,并分析DNMT3b的表达与胆管癌临床病理因素之间的关系,探讨其在胆管癌发生发

  9. Corona Enhancement and Mosaic Architecture for Prognosis and Selection Between of Liver Resection Versus Transcatheter Arterial Chemoembolization in Single Hepatocellular Carcinomas >5 cm Without Extrahepatic Metastases: An Imaging-Based Retrospective Study.

    Science.gov (United States)

    Li, Meng; Xin, Yongjie; Fu, Sirui; Liu, Zaiyi; Li, Yong; Hu, Baoshan; Chen, Shuting; Liang, Changhong; Lu, Ligong

    2016-01-01

    Corona enhancement and mosaic architecture are 2 radiologic features of hepatocellular carcinoma (HCC). However, neither their prognostic values nor their impacts on the selection of liver resection (LR) versus transcatheter arterial chemoembolization (TACE) as treatment modalities have been established.We retrospectively analyzed 275 patients with a single HCC lesion >5 cm without extrahepatic metastasis treated with LR or TACE. In LR patients, the overall survival (OS) and time to progression (TTP) were compared between corona enhancement negative (corona-) versus positive (corona+) and mosaic architecture negative (mosaic-) versus positive (mosaic+) patients. Furthermore, by the combination of corona and mosaic, LR patients were divided into negative for both corona and mosaic patterns (LR-/-), positive for only 1 feature (LR+/-), and positive for both (LR+/+); their OS and TTP were compared to those of the TACE group. Cox regression was performed to identify independent factors for OS.In the survival plots for LR, corona- had better OS and TTP than corona+, and mosaic- had better OS than mosaic+. There was no significant difference in TTP between the subgroups. On Cox regression analysis, corona enhancement, but not mosaic architecture, was a significant factor for OS, whereas neither were a significant factor for TTP. In TACE patients, neither corona nor mosaic patterns had significant correlations with OS or TTP. In the whole population, LR-/ and LR+/- subgroups had similar OS, which was better than the LR+/+ and TACE groups. Moreover, LR-/- and LR+/- patients had better TTP than TACE patients, but there were no differences between the LR-/- versus LR+/-, LR-/ versus LR+/+, LR+/- versus LR+/+, and LR+/+ versus TACE groups. On Cox regression analysis, the presence of corona/mosaic patterns was an independent prognostic factor for OS.Our results showed that, for patients with a single HCC >5 cm without extrahepatic metastasis, corona and mosaic patterns are

  10. 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

    Directory of Open Access Journals (Sweden)

    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

  11. Extrahepatic portosystemic shunt in a 8 month-old female maltese dogShunt portossistêmico extra-hepático em cadela maltês de 8 meses

    Directory of Open Access Journals (Sweden)

    Rafaella Cristina Reginatto

    2011-07-01

    Full Text Available The shunt portosystemic or portosystemic deviation (PSD are unique or multiples vascular communications between the systemic circulaton and the portal circulation, that permit blood flow reaches the circulatory system without first passing trhought the hepatic metabolization. May be acquired or congenital and can also be classified as intrahepatic located within the liver or extrahepatic located outside the liver parenquima. The acquired form is usually associated with intra-hepatic disorders. They usually suggest tortuous vessels that communicate with the caudal vena cava in the region of the left kidney. The congenital form is associated with genetic lineage and one of the most affected is Maltese breed. This case report describes the diagnostis and treatment of a eight year-old female Maltese dog presenting extrahepatic Portosystemic Shunt. The patient showed signs of hepatic encephalopathy, such as restlessnees, weakness, deambulation, head tremor and impaired visual. Complementary exam demonstrated: postprandial glicemia near the lower limit of reference, alkaline phosphatase (ALP and alanine aminotransferase (ALT increased and hipoalbuminemia. Ultrasonography revealed the presence of vesical calculus and bilateral kidney, liver decreases and increased echogenicity, gallbladder with anechoic content and high cellularity may suggest liver/ colangiohepatopatia and extrahepatic DPS was detected. The use of Doppler assisted in identifying the location of the bypass communication and the turbulence detecting the extrahepatic DPS. Protein-restricted diet and antibiotic therapy with amoxicillin achieved good results. The clinical treatment was decided make only the clinical and maintain the quality of life of the patient.O shunt portossistêmico ou desvio portossistêmico (DPS são comunicações vasculares únicas ou múltiplas entre a circulação sistêmica e a circulação portal, que permite que o sangue portal chegue ao sistema circulat

  12. 多层螺旋CT对肝外梗阻性黄疸的诊断价值%Diagnostic value of multi-slice spiral CT in extrahepatic obstructive jaundice

    Institute of Scientific and Technical Information of China (English)

    王小仁; 张云; 蔡顺达

    2015-01-01

    Objective To explore the diagnostic value of multi-slice spiral CT in extrahepatic obstructive jaundice.Methods MSCT findings in 12 cases ofextrahepatic obstructive jaundice confirmed by the surgery and clinic were retrospectively analyzed.Results Among 12 cases,10 cases were subjected to anhanced scanning;Among all cases,6 cases of bile duct carcinoma,3 cases of carcinoma of head of pancreas, 3 cases of bile duct stones.Conclusion CT scan can clearly without obstruction, determining the site of obstruction,further qualitative diagnosis.%目的:探讨多层螺旋CT对梗阻性黄疸的诊断价值。方法:回顾性分析由手术和临床证实的12例患者的CT资料。结果:12例患者中,10例行CT平扫加增强扫描;12例患者中胆管癌6例,胰头癌3例,胆管结石3例。结论:CT检查可明确有无梗阻的存在,确定梗阻部位,进一步行定性诊断。

  13. 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

  14. The combination of three endoscopes ( laparoscope, choledochoscope, duodenoscope) in treatment of complicated intra- and extrahepatic bile duct calculi%三镜联合治疗复杂性肝内外胆管结石的体会

    Institute of Scientific and Technical Information of China (English)

    王卫斌

    2012-01-01

    目的:分析复杂肝内外胆管结石的有效治疗方法及三镜(腹腔镜、胆道镜、十二指肠镜)联合治疗的优势.方法:回顾分析2009年8月至2011年8月为100例肝内外胆管结石患者行三镜联合手术的临床资料,并对结果进行随访.结果:79例成功施行胆总管一期缝合术,术后5~8d拔除鼻胆管,患者治愈出院.19例放置T管,12~15 d后带管出院,6~8周经胆道造影检查无特殊发现,遂拔除T管;其中3例发现胆道残留结石,术后经T管胆道镜取石成功,患者治愈出院.2例合并胆管癌,1例中转开腹,1例植入金属支架.术后随访3~6个月,2例胆管癌患者均死亡,余者均无结石复发、胆道狭窄等并发症发生.结论:三镜联合治疗复杂性肝内外胆管结石具有患者创伤小、康复快等特点,可降低并发症发生率及残石率,技术较成熟,值得临床推广应用.%Objective; To analyze the efficiency and superiority of combination of three endoscopes (laparoscope, choledocho-scope,duodenoscope) in treatment of complicated intra- and extrahepatic bile duct calculi. Methods:The clinical data of 100 patients with intra- and extrahepatic bile duct calculi who underwent combined three-microscopic surgery from Aug. 2009 to Aug. 2011 was analyzed retrospectively. Results: Primary suture of common bile duct was successfully performed in 79 patients, the nasobiliary tube was removed 5-8 days later,and these patients were cured. T-tube was placed in 19 patients who were discharged with tube 12-15 days after operation. The T-tube was removed after no special finding was noticed in the eholangiography. Residual calculi in bile duct were found in 3 patients,and the calculi were removed through T-tube sinus by choledochoscope,patients were cured and discharged. 2 cases were combined with bile duct carcinoma, 1 case was converted to laparotomy,and 1 patient was implanted metal stent. During the follow-up of 3-6 months,2 patients with carcinoma

  15. Radiofrequency Ablation of Liver Tumors in Combination with Local OK-432 Injection Prolongs Survival and Suppresses Distant Tumor Growth in the Rabbit Model with Intra- and Extrahepatic VX2 Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kageyama, Ken, E-mail: kageyamaken0112@gmail.com; Yamamoto, Akira, E-mail: loveakirayamamoto@gmail.com; Okuma, Tomohisa, E-mail: o-kuma@msic.med.osaka-cu.ac.jp; Hamamoto, Shinichi, E-mail: hamashin_tigers1975@yahoo.co.jp; Takeshita, Toru, E-mail: takeshita3595@view.ocn.ne.jp; Sakai, Yukimasa, E-mail: sakaiy@trust.ocn.ne.jp; Nishida, Norifumi, E-mail: norifumin@med.osaka-cu.ac.jp; Matsuoka, Toshiyuki, E-mail: tmatsuoka@msic.med.osaka-cu.ac.jp; Miki, Yukio, E-mail: yukio.miki@med.osaka-cu.ac.jp [Osaka City University, Department of Radiology, Graduate School of Medicine (Japan)

    2013-10-15

    Purpose: To evaluate survival and distant tumor growth after radiofrequency ablation (RFA) and local OK-432 injection at a single tumor site in a rabbit model with intra- and extrahepatic VX2 tumors and to examine the effect of this combination therapy, which we termed immuno-radiofrequency ablation (immunoRFA), on systemic antitumor immunity in a rechallenge test. Methods: Our institutional animal care committee approved all experiments. VX2 tumors were implanted to three sites: two in the liver and one in the left ear. Rabbits were randomized into four groups of seven to receive control, RFA alone, OK-432 alone, and immunoRFA treatments at a single liver tumor at 1 week after implantation. Untreated liver and ear tumor volumes were measured after the treatment. As the rechallenge test, tumors were reimplanted into the right ear of rabbits, which survived the 35 weeks and were followed up without additional treatment. Statistical significance was examined by log-rank test for survival and Student's t test for tumor volume. Results: Survival was significantly prolonged in the immunoRFA group compared to the other three groups (P < 0.05). Untreated liver and ear tumor sizes became significantly smaller after immunoRFA compared to controls (P < 0.05). In the rechallenge test, the reimplanted tumors regressed without further therapy compared to the ear tumors of the control group (P < 0.05). Conclusion: ImmunoRFA led to improved survival and suppression of distant untreated tumor growth. Decreases in size of the distant untreated tumors and reimplanted tumors suggested that systemic antitumor immunity was enhanced by immunoRFA.

  16. Chemoradiation in patients with unresectable extrahepatic and hilar cholangiocarcinoma or at high risk for disease recurrence after resection.. Analysis of treatment efficacy and failure in patients receiving postoperative or primary chemoradiation

    Energy Technology Data Exchange (ETDEWEB)

    Habermehl, D.; Lindel, K.; Rieken, S.; Haase, K.; Welzel, T.; Debus, J.; Combs, S.E. [University Hospital of Heidelberg (Germany). Dept. of Radiation Oncology; Goeppert, B.; Schirmacher, P. [Heidelberg Univ. (Germany). Inst. of Pathology; Buechler, M.W. [University Hospital of Heidelberg (Germany). Dept. of Visceral Surgery

    2012-09-15

    Background: The purpose of this work was to determine efficacy, toxicity, and patterns of recurrence after concurrent chemoradiation (CRT) in patients with extrahepatic bile duct cancer (EHBDC) and hilar cholangiocarcinoma (Klatskin tumours) in case of incomplete resection or unresectable disease. Patients and methods: From 2003-2010, 25 patients with nonmetastasized EHBDC and hilar cholangiocarcinoma were treated with radiotherapy and CRT at our institution in an postoperative setting (10 patients, 9 patients with R1 resections) or in case of unresectable disease (15 patients). Median age was 63 years (range 38-80 years) and there were 20 men and 5 women. Median applied dose was 45 Gy in both patient groups. Results: Patients at high risk (9 times R1 resection, 1 pathologically confirmed lymphangiosis) for tumour recurrence after curative surgery had a median time to disease progression of 8.7 months and an estimated mean overall survival of 23.2 months (6 of 10 patients are still under observation). Patients undergoing combined chemoradiation in case of unresectable primary tumours are still having a poor prognosis with a progression-free survival of 7.1 months and a median overall survival of 12.0 months. The main site of progression was systemic (liver, peritoneum) in both patient groups. Conclusion: Chemoradiation with gemcitabine is safe and can be applied safely in either patients with EHBDC or Klatskin tumours at high risk for tumour recurrence after resection and patients with unresectable tumours. Escalation of systemic and local treatment should be investigated in future clinical trials. (orig.)

  17. Radiofrequency Ablation of Liver Tumors in Combination with Local OK-432 Injection Prolongs Survival and Suppresses Distant Tumor Growth in the Rabbit Model with Intra- and Extrahepatic VX2 Tumors

    International Nuclear Information System (INIS)

    Purpose: To evaluate survival and distant tumor growth after radiofrequency ablation (RFA) and local OK-432 injection at a single tumor site in a rabbit model with intra- and extrahepatic VX2 tumors and to examine the effect of this combination therapy, which we termed immuno-radiofrequency ablation (immunoRFA), on systemic antitumor immunity in a rechallenge test. Methods: Our institutional animal care committee approved all experiments. VX2 tumors were implanted to three sites: two in the liver and one in the left ear. Rabbits were randomized into four groups of seven to receive control, RFA alone, OK-432 alone, and immunoRFA treatments at a single liver tumor at 1 week after implantation. Untreated liver and ear tumor volumes were measured after the treatment. As the rechallenge test, tumors were reimplanted into the right ear of rabbits, which survived the 35 weeks and were followed up without additional treatment. Statistical significance was examined by log-rank test for survival and Student’s t test for tumor volume. Results: Survival was significantly prolonged in the immunoRFA group compared to the other three groups (P < 0.05). Untreated liver and ear tumor sizes became significantly smaller after immunoRFA compared to controls (P < 0.05). In the rechallenge test, the reimplanted tumors regressed without further therapy compared to the ear tumors of the control group (P < 0.05). Conclusion: ImmunoRFA led to improved survival and suppression of distant untreated tumor growth. Decreases in size of the distant untreated tumors and reimplanted tumors suggested that systemic antitumor immunity was enhanced by immunoRFA

  18. 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.

  19. 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

    Directory of Open Access Journals (Sweden)

    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.

  20. Expression of GalNAc-T3 and its relationships with clinicopathological factors in 61 extrahepatic bile duct carcinomas analyzed using stepwise sections - special reference to its association with lymph node metastases-.

    Science.gov (United States)

    Inoue, Takahiro; Eguchi, Takashi; Oda, Yoshinao; Nishiyama, Kenichi; Fujii, Kei; Izumi, Hiroto; Kohno, Kimitoshi; Yamaguchi, Koji; Tanaka, Masao; Tsuneyoshi, Masazumi

    2007-02-01

    Extrahepatic bile duct carcinomas (EBDCs) still result in an unfavorable prognostic outcome, and little is known about their biological aggressiveness. Recently, UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyl transferase-3 (GalNAc-T3) was reported to be associated with differentiation and malignant potential of human carcinomas. Here, we investigated 61 EBDCs for their detailed clinicopathological features and GalNAc-T3 expression by immunohistochemistry, and then evaluated the relationships between the clinicopathological features and GalNAc-T3 expression patterns. Most of the EBDCs were massively invasive tumors with frequent vascular or perineural invasion and lymph node metastases. GalNAc-T3 expression was detected in all 61 EBDCs, and the expression patterns could be classified into granular and diffuse types. All four noninvasive or minimally invasive EBDCs were the granular type. Among the 58 minimally or massively invasive EBDCs, the GalNAc-T3 expression pattern at the luminal surface was the granular type in 38 cases (66%) and diffuse type in 20 cases (34%), while the expression pattern at the invasive front was the granular type in 26 cases (45%) and diffuse type in 32 cases (55%). Among the 38 cases with granular-type expression at the luminal surface, 26 cases (68%) remained the granular type and 12 cases (32%) became the diffuse type at the invasive front. All 20 cases with diffuse-type expression at the luminal surface remained the diffuse type at the invasive front. Diffuse-type GalNAc-T3 expression at the invasive front was significantly associated with lymph node metastasis (PGalNAc-T3 expression patterns and other clinicopathological factors, including tumor differentiation, depth of invasion or overall survival. In conclusion, EBDCs alter their GalNAc-T3 expression pattern during tumor growth, and the difference in the GalNAc-T3 expression pattern may be associated with lymph node metastasis. Clinically, preoperative

  1. 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

  2. General Information about Extrahepatic Bile Duct Cancer

    Science.gov (United States)

    ... Español 1-800-4-CANCER Live Chat Publications Dictionary Menu Contact Dictionary Search About Cancer Causes and Prevention Risk Factors ... Contacts Other Funding Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training ...

  3. Extra-Hepatic Storage of Copper

    DEFF Research Database (Denmark)

    Heydorn, Kaj; Damsgaard, Else; Horn, N.;

    1975-01-01

    The distribution of copper among the organs of an aborted, male foetus, expected to develop Menkes' syndrome, was entirely different from the distribution in 4 normal foetuses. Copper concentrations determined by neutron activation analysis showed a considerably reduced content in the liver......, but increased concentrations in the other organs analysed; total foetal copper was normal....

  4. Adenocarcinoma of the extrahepatic biliary tree.

    OpenAIRE

    Anderson, J B; Cooper, M J; Williamson, R. C.

    1985-01-01

    Increasing survival rates for carcinoma of the biliary tree could reflect the selection of patients for referral to a specialist centre as well as modern improvements in diagnosis and treatment. To determine the true incidence and outcome of biliary cancer, the records of 243 unselected Bristol patients were reviewed retrospectively over a 15-year period. Mean age was 64 years. Gallstones were associated in 38% of cases. Sixty-nine of 87 patients with gallbladder carcinoma were submitted to l...

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

    Directory of Open Access Journals (Sweden)

    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

  6. Association between diabetes mellitus and the risk of extrahepatic cholangiocarcinoma:a Meta-analysis%糖尿病与肝外胆管癌发病关系的Meta分析

    Institute of Scientific and Technical Information of China (English)

    刘春兴; 邹健

    2011-01-01

    目的:用Meta分析法探讨糖尿病是否增加肝外胆管癌发病风险.方法:利用中国学术期刊全文数据库、万方全文数据库及Medline,EMBASE数据库检索国内外公开发表的从建库至2010年9月的所有关于糖尿病与肝外胆管癌发病关系的中英文文献;利用随机效应模型计算纳入文献的合并RR值及其95%CI值;进行亚组分析以探究异质性来源并分析出版偏倚.结果:纳入分析的文献共7篇(病例对照研究4篇,队列研究3篇).经Meta分析,与未患糖尿病者相比,糖尿病患者肝外胆管癌发病的风险增加,相对风险值分别为OR=1.62(95%CI=1.05~2.49)(病例对照研究);RR=1.54(95%C1=1.06~2.23)(队列研究);亚组资料分析显示研究有显著异质性,但无明显发表偏倚(Egger检验,P=0.798;Begg检验,P=0.548).结论:本研究提示糖尿病可能是肝外胆管癌的致病危险因素.%Objective;To explore the association between diabetes mellitus (DM) and risks of extrahepatic cholangiocarcinoma (ECC) by meta-analysis. Methods;Databases of Chinese CNKI, Wanfang, Medline, EMBASE were searched for the articles on the relationships of DM and ECC risk from databases establishment to September 2010;Adjusted relative risks (RRs) and their corresponding 95% confidence intervals (95%CI) were calculated using a random-effect model;Potential sources of heterogeneity between studies were explored and publication bias was evaluated. Results; DM was associated with an increased risk of ECC,with pooled OR=1.62 (95%C1=1.05~2.49) for case-control studies and pooled RR=1.54 (95%C1=1.06-2.23)for cohort studies. The significant heterogeneity was mitigated in some of the subgroup analyses and publication bias was not significantly in the studies(Egger's test,P = 0.798;Begg's test,P = 0.548). Conclusion; The present study suggests that DM may be a high risk factor for ECC.

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

    Directory of Open Access Journals (Sweden)

    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

  8. 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

  9. 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

  10. 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

  11. 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

    Institute of Scientific and Technical Information of China (English)

    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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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)

  17. 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...

  18. 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 ...

  19. 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. ...

  20. 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

  1. 内镜下治疗肝内外胆管结石1478例回顾性分析——对中药联合内镜治疗肝内外胆管结石的研究%Retrospective Analysis of Endoscopy on 1478 Cases with Intra-and Extrahepatic Bile Duct stone-Research of Traditional Chinese Medicine Herb Combination with Endoscopy on Intra-and Extrahepatic Bile Duct Stone

    Institute of Scientific and Technical Information of China (English)

    高文艳; 李昊燃; 王立新; 林一帆; 王长洪; 麻树人; 陈山泉; 陆宇平; 杨卓; 巩阳; 刘杨; 季芳

    2011-01-01

    Objective: To make a retrospective analysis of 1478 cases with intrahepatolithiasis and extrahepatic bile duct stone disease treated with therapeutic endoscopy and the traditional chinese medicin(TCM)on promoting recovery of liver function, reducing the time of hospitalization and preventing stone to recur. Methods: Complete clinical data of 1478 cases were collected from March 2004 to March 2009 in department of traditional chinese medicine of Shenyang military region general hospital. To analysis the information of cases treated with therapeutic endoscopy and combinated with the TCM ,to observe the therapeutic efficacy. The cases that removing calculus succeed and had the history of operation on biliary tract were followed up for 1 year. Results: 1410 cases were removing calculus 1 times ,achievement ratio was 95.40%. 946 cases were combinated with Qingyilidantuihuang Decoction. After treatment, the time of hospitalization in the group of TCM was shorter than the group of non-TCM. The numerus of icteric index decreasing daily in the group of TCM were higher than the group of non-TCM. In 68 cases with refractory stone, 18 cases were ERBD,the other 50 cases injected TCM decoction through nasobiliary drainage and removing calculus succed in the end. The recurrence rate of the group of TCM (2.30%) was lower than the group of nonTCM's (6.36%) significantly. Conclusion: After the treatment of endoscopy,the cases that combinated with TCM can promote the liver function as soon as possible and reduce the time of hospitalization in the near future. It can prevent or delay the recur of calculus in long -time. Injecting TCM decoction through nasobiliary drainage to dissolve stone for refractory stone can increase the achievement ratio of removing stone.%目的 回顾性分析中药联合内镜治疗肝内外胆管结石临床疗效.方法 分析本院既往5年肝内外胆管结石患者.分为中药组及非中药组.比较两组患者黄疸

  2. 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

  3. 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.

  4. Comparison of the Efficacy of Endoscopic vs.Percutaneous Transhepatic Biliary Metal Stent Place-ment for the Treatment of Malignant Extrahepatic Biliary Obstruction%经内镜与经皮肝穿刺胆道金属支架置入治疗肝外胆管恶性梗阻的对比分析

    Institute of Scientific and Technical Information of China (English)

    吴明浩

    2014-01-01

    【目的】探讨应用不同方式胆道金属支架置入治疗肝外胆管恶性梗阻的效果,为临床上选择更适当的方法治疗晚期恶性梗阻性黄疸提供依据。【方法】回顾性分析本院2009年1月至2013年1月经内镜胆道金属支架置入术(EMBD)治疗肝外胆管恶性梗阻患者80例(EMBD组)及经皮肝穿刺胆管造影(PTC)胆道金属支架置入术治疗肝外胆管恶性梗阻患者80例(PTC组)的临床资料。比较两组的手术成功率、术后并发症发生率、支架通畅时间及患者生存期。【结果】两组患者术后肝功能均有明显改善,两组之间比较总胆红素(TB)、碱性磷酸酶(ALP)及谷氨酰基转移酶(GGT)下降程度无显著性差异(P>0.05),PTC组的手术成功率高于 EMBD组,但并发症的发生率明显高于 EMBD组(P<0.05)。两组病人术后支架通畅时间及生存期比较无显著性差异(P >0.05)。【结论】对于肝外胆道恶性梗阻患者可首选 EMBD,如手术失败可考虑经PTC途径行胆道支架置入。%[Objective]To explore the efficacy of different ways of metal stent placement for the treatment of advanced malignant obstructive jaundice in order to provide the basis for selecting better method for clinical treat-ment.[Methods]Clinical data of 80 patients with malignant extrahepatic biliary obstruction undergoing endoscopic biliary metal stent placement and 80 patients with malignant extrahepatic biliary obstruction undergoing percutane-ous transhepatic biliary metal stent placement in our hospital from Jan.2009 to Jan.2013 were analyzed retrospec-tively.The achievement ratio of operation,the incidence of postoperative complications,the unobstructed time of stents and the survival time of patients between two groups were compared.[Results]Liver function of two groups after operation was significantly improved.There was no significant difference in the decline of total

  5. Influence of glutamine on morphological and functional changes of liver in the presence of extrahepatic biliary obstruction in rats Influência da glutamina em alterações funcionais e morfológicas do fígado na vigência de obstrução biliar extra-hepática em ratos

    Directory of Open Access Journals (Sweden)

    Manoel Camelo de Paiva Neto

    2010-08-01

    Full Text Available PURPOSE: To study the influence of glutamine on functional and morphological changes of liver in the extrahepatic biliary obstruction through an experimental model in rats. METHODS: Seventy Wistar rats were divided into four groups: control (group C fictitious operation, (group FO, submitted to laparotomy with handling of bile ducts, but without hepatic duct ligation, (group EBO submitted to laparotomy and hepatic duct ligation, one of them submitted to supplementation with glutamine 2% (group G. The control group consisted of 6 animals. The animals from groups FO, EBO and G were divided into three groups consisting of 6 animals each, being sacrificed at 7, 14 and 21 days after operation, respectively. Blood samples were collected for biochemical analysis and a fragment of liver tissue was collected from the middle lobe for histological analysis. RESULTS: Both for biochemical analysis (BT, aspartate and alanine aminotransferase AST, ALT and alkaline phosphatase FAL and for histopathological changes (fibrosis, portal inflammation, parenchymal inflammation, hepatocytic changes and duct proliferation, no statistical difference between groups submitted to extrahepatic biliary obstruction (EBO with and without treatment with glutamine (G was observed. CONCLUSION: Glutamine supplementation did not alter the prognosis of liver enzymes and histopathological changes in animals submitted to extrahepatic biliary obstruction.OBJETIVO: Estudar a influência da glutamina em alterações funcionais e morfológicas do fígado na obstrução biliar extra-hepática por meio de um modelo experimental desenvolvido em ratos. MÉTODOS: Setenta ratos Wistar distribuídos em quatro grupos: controle (grupo C; operação fictícia (grupo OF, submetido à laparotomia com manuseio das vias biliares, mas sem ligadura do ducto hepático; (grupo OBE, submetido à laparotomia exploradora e ligadura do ducto hepático, sendo um deles submetido à suplementação com glutamina a

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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。

  12. 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

  13. Clinical Observation of Endoscopic Biliary Metallic Stent Drainage in Management of Hilar Cholangiocarcinoma and Extrahepatic Malignant Biliary Obstruction%内镜下金属支架引流术治疗肝门部胆管癌和肝外恶性胆道梗阻临床观察

    Institute of Scientific and Technical Information of China (English)

    周慧; 宛新建; 陆伦根; 罗声政; 蔡晓波; 李雷; 朱峰

    2012-01-01

    临床上恶性胆道梗阻性疾病预后较差.对于不能手术切除者,通常选择内镜下置入胆道支架以解除梗阻,然而该技术对进展期肝门部肿瘤的疗效报道不一.目的:探讨内镜下金属支架引流术对肝门部胆管癌和肝外恶性胆道梗阻的疗效和并发症发生情况.方法:纳入上海交通大学附属第一人民医院2006年6月~2009年6月收治的82例接受ERCP下置入自膨式金属胆道支架引流治疗的恶性胆道狭窄患者,根据病变部位分为肝门部胆管癌组和肝外恶性胆道梗阻组,对其ERCP参数和术后6个月随访记录进行回顾性分析,并分析随访期间急性胆管炎发生的危险因素.结果:两组支架置入成功率均为100%.与肝外恶性胆道梗阻组相比,肝门部胆管癌组术后1周总胆红素降低显效率较低,术后6个月内急性胆管炎发生率增高,初次发生时间提前,支架再狭窄率增高(P=0.000).ERCP术中括约肌切开为随访期间发生急性胆管炎的危险因素(P=0.004,OR:8.196).结论:内镜下金属支架引流术对肝门部胆管癌的疗效不及肝外恶性胆道梗阻,且更易早期发生急性胆管炎和支架再狭窄,术中括约肌切开可增加术后急性胆管炎的发生风险.%Background: The prognosis (or malignant biliary obstructive diseases is poor. For unresectable lesions, endoscopic biliary stenl drainage was usually applied to palliate obstruction. However, controversies exist regarding the therapeutic effect of this technique for advanced hilar cholangiocarcinoma. Aims: To assess (he therapeutic effect and complications of endoscopic biliary metallic stent drainage in management of hilar cholangiocarcinoma and extrahepatic malignant biliary obstruction. Methods: A total of 82 patients with malignant biliary obstructive diseases were enrolled from Jun. 2006 to Jun. 2009 at Shanghai First People' s Hospital, Shanghai Jiaotong University. All patients received endoscopic biliary

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. Complications of the extrahepatic biliary surgery in companion animals.

    Science.gov (United States)

    Mehler, Stephen J

    2011-09-01

    Surgery of the biliary tract is demanding and is associated with several potentially life-threatening complications. Veterinarians face challenges in obtaining accurate diagnosis of biliary disease, surgical decision-making, surgical hemostasis and bile peritonitis. Intensive perioperative monitoring is required to achieve early recognition of common postoperative complications. Proper treatment and ideally, avoidance of surgical complications can be achieved by gaining a clear understanding physiology, anatomy, and the indications for hepatobiliary surgery.

  3. The extrahepatic role of TFR2 in iron homeostasis

    Directory of Open Access Journals (Sweden)

    Laura eSilvestri

    2014-05-01

    Full Text Available Transferrin receptor 2 (TFR2, a protein homologous to the cell iron importer transferrin receptor 1 (TFR1, is expressed in the liver and erythroid cells and is reported to bind diferric transferrin, although at lower affinity than TFR1. TFR2 gene is mutated in type 3 hemochromatosis, a disorder characterized by iron overload and inability to upregulate hepcidin in response to iron. Liver TFR2 is considered a sensor of diferric transferrin, possibly in a complex with HFE. In erythroid cells TFR2 is a partner of erythropoietin receptor (EPOR and stabilizes the receptor on the cell surface. However, Tfr2 null mice as well as TFR2 hemochromatosis patients do not show defective erythropoiesis and tolerate repeated phlebotomy. The iron deficient Tfr2-Tmprss6 double knock out mice have higher red cells count and more severe microcytosis than the liver specific Tfr2 and Tmprss6 double knock out mice. TFR2 in the bone marrow might be a sensor of iron deficiency that protects against excessive microcytosis in a way that involves EPOR, although the mechanisms remain to be worked out.

  4. Extrahepatic Textiloma Long Misdiagnosed as Calcified Echinococcal Cyst

    Science.gov (United States)

    Cattaneo, Federico; Graffeo, Massimo; Brunetti, Enrico

    2013-01-01

    Textiloma or gossypiboma is a retained surgical swab in the body after an operation and is a complication that can remain undetected for many years and may represent a diagnostic dilemma depending on its location. It may be confused with several focal lesions and an accurate history taking, combined with clinical and instrumental data, is key to suspecting the diagnosis. We report a case of abdominal textiloma that was initially misdiagnosed as echinococcal cyst and discuss the differential diagnosis based on sonographic features and the WHO-IWGE classification. PMID:23533840

  5. Extrahepatic Textiloma Long Misdiagnosed as Calcified Echinococcal Cyst

    Directory of Open Access Journals (Sweden)

    Federico Cattaneo

    2013-01-01

    Full Text Available Textiloma or gossypiboma is a retained surgical swab in the body after an operation and is a complication that can remain undetected for many years and may represent a diagnostic dilemma depending on its location. It may be confused with several focal lesions and an accurate history taking, combined with clinical and instrumental data, is key to suspecting the diagnosis. We report a case of abdominal textiloma that was initially misdiagnosed as echinococcal cyst and discuss the differential diagnosis based on sonographic features and the WHO-IWGE classification.

  6. Extrahepatic Textiloma Long Misdiagnosed as Calcified Echinococcal Cyst

    OpenAIRE

    Federico Cattaneo; Massimo Graffeo; Enrico Brunetti

    2013-01-01

    Textiloma or gossypiboma is a retained surgical swab in the body after an operation and is a complication that can remain undetected for many years and may represent a diagnostic dilemma depending on its location. It may be confused with several focal lesions and an accurate history taking, combined with clinical and instrumental data, is key to suspecting the diagnosis. We report a case of abdominal textiloma that was initially misdiagnosed as echinococcal cyst and discuss the differential d...

  7. Extrahepatic lesions causing false-positive liver scans

    Energy Technology Data Exchange (ETDEWEB)

    Chaudhuri, T.K.

    1976-02-01

    Photoscanning of the liver is a valuable diagnostic procedure for intrahepatic lesions. Thus /sup 99m/Tc-sulfur colloid liver scan in patients with primary or secondary neoplasm of the liver, liver abscess, cyst or cirrhosis of the liver may show either focal defect or heterogeneous distribution of the colloid. We are presenting here three cases of retroperitoneal (renal or extrarenal) mass causing such changes in the liver scintiscan, although the liver itself was quite normal in each case.

  8. [Reflexions on carcinomas of the extra-hepatic bile ducts].

    Science.gov (United States)

    Arianoff, A A; Vielle, G; Dewulf, E; Arianoff, V

    1975-01-01

    The authors present 12 cases of true malignant ampulloma and 23 cases of carcinoma of the biliary tract (MBT). They analyze frequency, symptomatology, pathology, radiology, treatment and results. They stress that decreasing malignancy is in the following order: cancer of the MBT, cancer of the gallbladder, and ampulloma. The latter is the least lethal with the most long-term cures. As to cancer of the MBT no cure is to be expected, but palliative surgery (resection or tumor by-pass) will bring temporary cure; consequently this should always be tried when possible despite the high operative mortality. PMID:1114872

  9. Microwell scaffolds for the extrahepatic transplantation of islets of langerhans

    NARCIS (Netherlands)

    Buitinga, M.; Truckenmuller, R.; Engelse, M.A.; Moroni, L.; Ten Hoopen, H.W.; van Blitterswijk, C.A.; de Koning, E.J.; van Apeldoorn, A.A.; Karperien, M.

    2013-01-01

    Allogeneic islet transplantation into the liver has the potential to restore normoglycemia in patients with type 1 diabetes. However, the suboptimal microenvironment for islets in the liver is likely to be involved in the progressive islet dysfunction that is often observed post-transplantation. Thi

  10. Microwell Scaffolds for the Extrahepatic Transplantation of Islets of Langerhans

    NARCIS (Netherlands)

    Buitinga, M.; Truckenmüller, R.K.; Engelse, M.A.; Moroni, L.; Hoopen, ten H.W.M.; Blitterswijk, van C.A.; Koning, de E.J.P.; Apeldoorn, van A.A.; Karperien, H.B.J.

    2013-01-01

    Allogeneic islet transplantation into the liver has the potential to restore normoglycemia in patients with type 1 diabetes. However, the suboptimal microenvironment for islets in the liver is likely to be involved in the progressive islet dysfunction that is often observed post-transplantation. Thi

  11. Hepatic and extra-hepatic metabolism of neurotensin

    International Nuclear Information System (INIS)

    Neurotensin (NT), released into the portal circulation from N cells in the ileum, is detected in the systemic circulation primarily as N-terminal immunoreactivity (N-NT), although it is the C-terminal end which is essential for NT bioactivity. The authors have examined the potential role of the liver in NT clearance using the isolated perfused rat liver model (IPRL) in a recycling system. With N-terminal and C-terminal directed radioimmunoassays and high performance liquid chromatography (HPLC), they demonstrated rapid metabolism of intact NT to inactive N-terminal fragments. C-terminal immunoreactivity (C-NT) elimination was rapid (t1/2 of 20.4 +/- 6.0 min) and significantly faster than for N-NT elimination (t1/2 of 82.7 +/- 7 min). HPLC demonstrated that C-NT was in the form of intact NT (no free C-terminal fragments) whereas N-NT was intact NT initially and predominantly N terminal fragments at 60 min. To assess whether this NT disappearance might be due to metabolism within the perfusate itself by a peptidase released from liver, the authors further incubated NT in perfusate previously circulated through liver. A rapid and progressive breakdown of intact NT to N-terminal fragments was again shown. These data demonstrate that NT is efficiently degraded to inactive N-terminal fragments by the IPRL and that a substantial proportion of this attributable to release of a peptidase by the liver into the circulation

  12. Imaging findings of unusual intra- and extrahepatic portosystemic collaterals

    Energy Technology Data Exchange (ETDEWEB)

    Ito, K. [Department of Radiology, Yamaguchi University School of Medicine, Yamaguchi (Japan)], E-mail: itokatsu@med.kawasaki-m.ac.jp; Fujita, T.; Shimizu, A.; Sasaki, K.; Tanabe, M.; Matsunaga, N. [Department of Radiology, Yamaguchi University School of Medicine, Yamaguchi (Japan)

    2009-02-15

    We describe unusual portosystemic shunts demonstrated using computed tomography (CT) and magnetic resonance imaging (MRI), including gallbladder varices, aberrant left gastric vein to left portal vein collaterals, intrahepatic and transhepatic portosystemic venous shunt, and mesenteric varices. Familiarity with the CT and MRI features of unusual portosystemic shunts will help in making the correct diagnosis for affected patients.

  13. Extrahepatic production of acute phase serum amyloid A

    OpenAIRE

    Upragarin, N.; Landman, W.J.M.; Gaastra, W; Gruys, E.

    2005-01-01

    Amyloidosis is a group of diseases characterized by the extracellular deposition of protein that contains non-branching, straight fibrils on electron microscopy (amyloid fibrils) that have a high content of ß-pleated sheet conformation. Various biochemically distinct proteins can undergo transformation into amyloid fibrils. The precursor protein of amyloid protein A (AA) is the acute phase protein serum amyloid A (SAA). The concentration of SAA in plasma increa...

  14. Effect of histone deacetylase inhibitor on expression of HDAC1 in gallbladder carcinoma cell line and extrahepatic cholangiocarcinoma cell line in vivo and in vitro%组蛋白去乙酰化酶抑制剂对胆囊癌细胞系和肝外胆管癌细胞系HDAC1表达的影响

    Institute of Scientific and Technical Information of China (English)

    王欣; 黄凯; 徐立宁

    2008-01-01

    目的 观察组蛋白去乙酰化酶抑制剂-曲古抑菌素(TSA)在体外和体内对胆囊癌细胞和肝外胆管癌细胞HDAC1表达的影响.方法 用TSA作用于胆囊癌细胞系(Mz-ChA-1)和肝外胆管癌细胞系(QBC939、KMBC、OZ),然后用逆转录-聚合酶链反应(RT-PCR)检测HDAC1之mR-NA的表达变化,用Western blot检测其蛋白的表达变化.将这些细胞接种在裸鼠皮下建立胆囊癌和肝外胆管癌裸鼠种植瘤模型,用免疫组织化学方法 观察TSA在体内对裸鼠种植瘤组织中HDAC1蛋白表达的影响.结果 TSA可以减弱胆囊癌细胞系(Mz-ChA-1)和肝外胆管癌细胞系(QBC939、KMBC、OZ)HDAC1 mRNA和蛋白的表达;TSA作用前后的胆囊癌细胞系(Mz-ChA-1)和肝外胆管癌细胞系(KMBC)裸鼠成瘤组织中的各种蛋白的表达均无变化.结论 TSA在体外可以抑制胆囊癌和肝外胆管癌HDAC1的表达;TSA抑制HDAC1表达的作用可能受到体内环境的影响而消失.%Objective To study the effect of histone deacetylase inhibitor-trichostatin A (TSA) on the HDAC1 expression in gallbladder carcinoma and extrahepatic cholangioearcinoma cells in vivo and in vitro. Methods The cells from gallbladder carcinoma cell line ( Mz-ChA-1 ) and cholangiocarcinoma cell lines (QBC939, KMBC and OZ) were treated with TSA, and the expression of HDAC1 mRNA and protein was detected by RT-PCR assay and Western blot respectively. These cells were subcutaneously transplanted into nude mice to establish the transplanted cholangiocarcinoma and gallbladder carcinoma models. The effect of TSA on the expression of HDAC1 protein in transplanted cancer tissues in vivo was observed. Results TSA could down-regulate the expression of HDAC1 mRNA and protein in gallbladder carcinoma cells and cholangiocarcinoma cells. TSA could not down-or up-regulate the expression of HDAC1 protein in the transplanted biliary tract cancer models in nude mice. Conclusion TSA might down-regulate the expression of HDAC1 in

  15. A blinded prospective study comparing four current noninvasive approaches in the differential diagnosis of medical versus surgical jaundice

    Energy Technology Data Exchange (ETDEWEB)

    O' Connor, K.W.; Snodgrass, P.J.; Swonder, J.E.; Mahoney, S.; Burt, R.; Cockerill, E.M.; Lumeng, L.

    1983-06-01

    A prospective study was undertaken to compare the diagnostic accuracy of clinical evaluation, ultrasound, computed tomography, and technetium 99m-HIDA or -PIPIDA biliary scans in distinguishing between intrahepatic and extrahepatic jaundice. A final diagnosis was established in each of the 50 patients who completed the study, among whom 29 had intrahepatic cholestasis and 21 had extrahepatic obstruction. In the diagnosis of extrahepatic obstruction, the sensitivities of clinical evaluation, ultrasound, computed tomography, and nuclear medicine biliary scan were 95%, 55%, 63%, and 41%, respectively; the specificities were 76%, 93%, 93%, and 88%; and the overall accuracies were 84%, 78%, 81%, and 68%. These data support the conclusion that when the clinical evaluation is carefully performed, it is the single most effective noninvasive means of detecting extrahepatic biliary obstruction in a jaundiced patient. Although ultrasound, computed tomography, and radionuclide biliary scan are less sensitive, they are highly reliable if they indicate that extrahepatic obstruction is present. A flow chart of invasive and noninvasive approaches for evaluation of the jaundiced patient is presented.

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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...

  2. 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.

  3. 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.

  4. 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...

  5. 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. ...

  6. [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.

  7. Significance of forkhead/winged helix transcription factor P3 + regulatory T cells infiltration in extrahepatic cholangiocarcinoma%肝外胆管癌组织叉状头/翅膀状螺旋转录因子3阳性调节性T细胞浸润及其临床意义

    Institute of Scientific and Technical Information of China (English)

    王文斌; 刘三光; 刘兵; 李月红

    2015-01-01

    目的 观察叉状头/翅膀状螺旋转录因子3(Foxp3)阳性调节性T细胞(Treg)在肝外胆管癌(EHCC)组织中的浸润,探讨环氧合酶-2(COX-2)蛋白表达与Foxp3+ Treg细胞浸润的关系.方法 采用免疫组织化学法检测Foxp3+ Treg在94例胆管癌组织和COX-2蛋白在77例胆管癌组织中的表达,分析浸润细胞以及COX-2蛋白表达与临床和预后的关系,观察肝外胆管癌组织中COX-2蛋白表达对Foxp3+ Treg浸润的影响.结果 94例肝外胆管癌组织中均存在浸润的Foxp3+ Treg细胞,中位值为2.35个/高倍视野.Foxp3+ Treg细胞的浸润与肝外胆管癌患者的组织学分级、临床分期和淋巴结转移无明显相关(P>0.05).但Foxp3+ Treg细胞低计数组患者的生存时间明显高于高计数组(P<0.05).多因素分析表明Foxp3+Treg细胞浸润是肝外胆管癌预后的独立影响因素.77例胆管癌组织中COX-2表达阳性率为81.8%.COX-2蛋白的表达与组织学分级、临床分期和淋巴结转移无明显相关(P>0.05).COX-2蛋白表达与Foxp3+ Treg细胞浸润之间呈正相关(r=4.89,P <0.05).结论 肝外胆管癌组织中Foxp3+ Treg细胞浸润与肝外胆管癌患者的预后负相关,是影响肝外胆管癌预后的独立影响因素.COX-2蛋白表达可能促进Foxp3+ Treg细胞的浸润.%Objective To explore the infiltration of regulatory T cells (Tregs) and its significance in extrahepatic cholangiocarcinoma (EHCC) and to elucidate the putative effects of cytochrome C oxidase-2 (COX-2) expression on the infiltration of Tregs.Methods The infiltration of forkhead/winged helix transcription factor P3 (Foxp3) + Tregs and the expression of COX-2 were studied by immunohistochemistry in 94 and 77 cases of EHCC respectively.The correlation between the expression of COX-2 and Foxp3 +Tregs infiltration with clinicopathological features and prognosis was analyzed.The influence of COX-2 expression on infihration of Foxp3 + Tregs was evaluated.Results Foxp3 + Tregs

  8. DNA甲基转移酶1基因在人肝外胆管癌组织和细胞中的表达及意义%The Expression and Significance of DNA Methyltransferase 1 Gene in Extrahepatic Cholangiocarcinoma Tissues and Cells

    Institute of Scientific and Technical Information of China (English)

    左石; 邹声泉; 孙诚谊

    2011-01-01

    Objective: To study the expression of DNA methyltransferase 1 (DNMT1) in human ex-trahepatic cholangiocarcinoma (ECC) tissues and cell line QBC939, and to analyze the relationship between the expression level of DNMT1 and clinicopathologic features of ECC, and so as to explore the roles of DNMT1 in the tumorigenesis of ECC. Methods: The expression of DNMT1 protein was detected in 24 ECC specimens and in 20 chronic cholangeitis tissue specimens with immunohistochemistry method. The results of the two kinds of tissues were compared, and their relationship with the clinico-patholigic features of ECC was analyzed. RT-PCR and Western Blot were used to detect the expression of DNMT1 gene and protein in human biliary tract carcinoma cell line QBC939 respectively. Results: (1) The rates of positive DNMT1 protein expression cells were (37. 57 ± 11. 24) % and (10. 73 ± 6. 61 ) % in ECC specimens and in chronic cholangeitis specimens respectively. There were significant differences between the two groups (P=0.005 ) ; (2) The increased expression of DNMT1 protein was correlated with differentiation grade of carcinoma. The protein levels of DNMT1 were high in poorly differentiated cholangiocarcinoma, moderate in moderately differentiated cholangiocarcinoma, and low in well differentiated cholangiocarcinoma. The increased expression of DNMT1 protein was not correlated with gender, age, size of tumor, tumor location, lymph node metastasis or clinical TNM stage. (3) DNMT1 mRNA and protein were both positive in human biliary tract carcinoma cell line QBC939. Conclusions: (1) The expression level of DNMT1 protein in ECC is significantly higher than that in chronic cholangeitis tissues. The increased DNMT1 protein level is correlated with the differentiation grade of tumor and is not correlated with gender, age, tumor size, tumor location, lymph node metastasis or clinical TNM stage. This result suggests that the over-expression of DNMT1 may relate to the pathogen-esis of biliary

  9. 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),

  10. 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

  11. 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

  12. 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.

  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. 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.

  16. {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.)

  17. microRNA-222 modulates liver fibrosis in a murine model of biliary atresia

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. Analysis of divergences of the results of choleography and radioscintigraphy to evaluate the extrahepatic biliary ducts

    Energy Technology Data Exchange (ETDEWEB)

    Zubovskij, G.A.; Popova, Z.P.; Ogneva, T.V.; Sycheva, N.A.; Mikhajlova, N.A.; Medvedeva, Eh.S. (Nauchno-Issledovatel' skij Inst. Rentgenologii i Radiologii, Moscow (USSR))

    A great share of hepatic and bile cyst diseases among gastrointestinal diseases necessitates attempts to collect the most complete information on the state of the above organs while using an optimum complex of examination methods. The authors present the results of a multimodality study of 98 patients including i.v. cholecystography and computerized hepatobiliscintigraphy with sup(99m)Tc-HIDA. A detailed analysis of coincidences and divergences in diagnosis is provided. A conclusion has been made as to the great informative value of the x-ray methods for detection of organic defects of the biliary ducts and the advantages of radionuclide study in the evaluation of functional disorders in the liver and biliary tract.

  19. Wilson病的肝外表现%Extrahepatic Manifestations of Wilson's Disease

    Institute of Scientific and Technical Information of China (English)

    江正辉

    2000-01-01

    @@ 1引言 Wilson病(以下简称WD)又称肝豆状核变性,是一种伴随原发性铜代谢障碍的常染色体隐性遗传性疾病.发病率一般为1:35 000~100 000,但各地有差异.多发于青少年期(10~25岁),故有少年型或成人型之分.

  20. Survival After Accidental Extrahepatic Distribution of Y90 Microspheres to the Mesentery During a Radioembolization Procedure

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir; Ahmadzadehfar, Hojjat [University Hospital, Department of Nuclear Medicine (Germany); Schaefer, Nico [University Hospital, Department of Surgery (Germany); Wilhelm, Kai; Schueller, Heinrich [University Hospital, Department of Radiology, Division of Radiation Oncology (Germany); Ezziddin, Samer, E-mail: samer.ezziddin@ukb.uni-bonn.de [University Hospital, Department of Nuclear Medicine (Germany)

    2012-08-15

    We present the acute management and outcome of a patient after an accidental mesenteric distribution of Y90 microspheres during radioembolization (RE). This report describes and highlights: (1) the incidence of a significant reflux during a RE session while injecting into a replaced right hepatic artery from the superior mesenteric artery, (2) the appearance of diffuse mesenteric Y90 distribution in bremsstrahlung-imaging, (3) the management protocol with the radiation protection agent amifostine, (4) the development of typical adverse effects in the expected time window, and (5) survival of the patient without long-term sequelae. This report should sensitize physicians to this particular problem and may help to avoid as well as manage similar radioembolization incidences.

  1. Extrahepatic tissue concentrations of vitamin K are lower in rats fed a high vitamin E diet

    Directory of Open Access Journals (Sweden)

    Peterson James W

    2006-07-01

    Full Text Available Abstract Background An adverse hematological interaction between vitamins E and K has been reported, primarily in patients on anticoagulants. However, little is known regarding circulating levels or tissue concentrations of vitamin K in response to vitamin E supplementation. The purpose of this study was to examine the effect of different levels of dietary α-tocopherol on phylloquinone and menaquinone-4 concentrations, while maintaining a constant intake of phylloquinone, in rat tissues. Methods Male 4-wk old Fischer 344 rats (n = 33 were fed one of 3 diets for 12 wk: control (n = 13 with 30 mg all-rac-α-tocopherol acetate/kg diet; vitamin E-supplemented (n = 10 with 100 mg all-rac-α-tocopherol acetate/kg diet; and vitamin E-restricted (n = 10 with Results Phylloquinone concentrations were lower (P ≤ 0.05 in the vitamin E-supplemented compared to the vitamin E-restricted group (mean ± SD spleen: 531 ± 58 vs.735 ± 77; kidney: 20 ± 17 vs. 94 ± 31, brain: 53 ± 19 vs.136 ± 97 pmol/g protein respectively; no statistically significant differences between groups were found in plasma, liver or testis. Similar results were noted with menaquinone-4 concentrations in response to vitamin E supplementation. Conclusion There appears to be a tissue-specific interaction between vitamins E and K when vitamin E is supplemented in rat diets. Future research is required to elucidate the mechanism for this nutrient-nutrient interaction.

  2. Alterations of seminal and hormonal parameters: An extrahepatic manifestation of HCV infection?

    Institute of Scientific and Technical Information of China (English)

    Marilena Durazzo; Alberto Premoli; Cataldo Di Bisceglie; Angela Bertagna; Emanuela Fagà; Giampaolo Biroli; Chiara Manieri; Simona Bo; Gianfranco Pagano

    2006-01-01

    AIM: To evaluate the possible influences of HCV infection and relative antiviral treatment on seminal parameters and reproductive hormonal serum levels.METHODS: Ten male patients with HCV-related chronic hepatitis and 16 healthy male volunteers were studied.In all subjects seminal parameters (nemaspermic concentration, progressive motility, morphology) and hormonal levels were determined. Seminal parameters and inhibin B, follicle-stimulating hormone, luteinizing hormone, total and free testosterone, estradiol, prolactine in patients were measured after six and twelve months of antiviral combined (interferon + ribavirin) treatment.RESULTS: Patients before treatment showed a significantly lower nemaspermic motility and morphology as well as lower inhibin B and free testosterone levels than controls. Inhibin B levels in cases were improved six and 12 mo after treatment in five responders (161.9 ± 52.8 pg/mL versus 101.7 ± 47.0 pg/mL and 143.4 ± 46.1 pg/mL versus 95.4 ± 55.6 pg/mL, respectively). Hormonal pattern of patients did not significantly change after treatment, with the exception of estradiol levels with an initial reduction and an overall subsequent increment (19.7 ± 6.4 pg/mL versus 13.6 ± 5.0 pg/mL versus 17.3 ± 5.7 pg/mL). However in 1-year responders a significant increment of free testosterone (14.2 ± 2.54 pg/mL versus 17.1 ± 2.58 pg/mL) occurred. An impairment of nemaspermic morphology occurred, while other seminal parameters did not change significantly during antiviral treatment.CONCLUSION: Patients with HCV infection show worse spermatic parameters than controls, suggesting a possible negative influence of virus on spermatogenesis, with further mild impairment during antiviral treatment. However therapy could improve the spermatic function, as suggested by the increased inhibin B levels and improved hormonal pattern in responders. Further studies are needed to confirm these preliminary intriguing results.

  3. Extrahepatic portal vein obstruction with parkinsonism and symmetric hyperintense basal ganglia on T1 weighted MRI

    Directory of Open Access Journals (Sweden)

    Jayalakshmi Sita

    2006-01-01

    Full Text Available Abnormal high signal in the globus pallidus on T1 weighted magnetic resonance imaging (MRI of the brain has been well described in patients with chronic liver disease. It may be related to liver dysfunction or portal-systemic shunting. We report a case of extra hepatic portal vein obstruction with portal hypertension and esophageal varices that presented with extra pyramidal features. T1 weighted MRI brain scans showed increased symmetrical signal intensities in the basal ganglia. Normal hepatic function in this patient emphasizes the role of portal- systemic communications in the development of these hyperintensities, which may be due to deposition of paramagnetic substances like manganese in the basal ganglia.

  4. Profile of extrahepatic portal venous obstruction (ehpvo) in a tertiary care hospital in pakistan

    International Nuclear Information System (INIS)

    To study the clinical and laboratory profile of patients with EHPVO in a tertiary care hospital of Pakistan and to differentiate EHPVO from cirrhosis of liver and to see the effect on liver function tests. This is a prospective observational study conducted at Department of Gastroenterology, Pakistan Institute of Medical Sciences, Islamabad. Twenty five patients of 12-55 years of age with the features of portal hypertension were included in this study. After careful history and physical examination patients were subjected for laboratory investigations including liver function test, renal function test, blood CP, PT, APTT, HbsAg and anti HCV, other specialized procedures including endoscopy, liver biopsy and ultra sound was also done in all patients. Portal vein thrombosis was the predominant cause of EHPVO, accounting for 88% of cases. All patients were presented with upper GI bleeding, splenomegaly was observed in 88% of patients. None of the patients had clinical, biochemical or liver biopsy evidence of chronic liver disease. The diagnosis of extra hepatic portal venous obstruction and differentiation from cirrhosis can be easily made by characteristic clinical features, normal liver function tests and doppler ultrasound. Portal vein thrombosis (PVT) is the predominant cause of EHPVO in Pakistani patients, as seen at this tertiary care hospital in Pakistan. (author)

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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。

  10. 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 ...

  11. 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

  12. 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...

  13. 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

  14. 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...

  15. 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.

  16. 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.

  17. 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...

  18. 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.

  19. 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

  20. [PRIMARY SCLEROSING CHOLANGITIS

    Science.gov (United States)

    Dantas, Waldomiro

    2000-01-01

    Primary sclerosing cholangitis (PSC) is a chronic cholestatic and progressive disease, of unknown etiology, characterized by inflammation and fibrosis of intra-hepatic and extra-hepatic biliary tree. Two thirds of the patients have, simultaneously, ulcerative colitis (UC); on the other hand, PSC is the most common chronic hepatic disease in patients with inflammatory bowel disease (IBD). Patients who have both diseases simultaneously are prone to develop colorectal carcinoma and cholangiocarcinoma. The disease predominantly affects young men, may be asymptomatic or presented as fluctuating jaundice, pruritus and increased levels of the cholestasis biochemical markers, or as secondary billiary cirrhosis. The diagnostic gold standard are the cholangiographic abnormalities, consisting of multifocal stenosis and dilatations, involving both the intrahepatic and the extrahepatic biliary tree. Liver biopsy is useful only for staging the disease and to confirm the diagnosis, in the atypical forms. Ursodeoxycholic acid is a promising drug, nowadays, mainly in the first stages of the disease, in spite of doubtful efficacy. Combination therapy, using ursodeoxicolic acid, methotrexate and alternating antibiotics monthly may be sucessfull in PSC before bile strictures occur. Liver transplantation is the only life-saving therapeutic alternative, able to improve significantly the survival and the life quality of the patients. PMID:12140588

  1. Histologic features of the portal plate in extrahepatic biliary atresia and their impact on prognosis--a Danish study

    DEFF Research Database (Denmark)

    Mirza, Qazaz; Kvist, Nina; Petersen, Bodil Laub

    2009-01-01

    BACKGROUND/PURPOSE: The aims of this study are as follows: METHOD: From 1979 to 2003, 57 children have been operated by the Kasai procedure. Only 40 of these have had their portal plate removed for histologic examination. We divided the patients according to clinical outcome into a successful and...

  2. Diet-induced alterations in intestinal and extrahepatic lipid metabolism in liver fatty acid binding protein knockout mice

    OpenAIRE

    Newberry, Elizabeth P.; Kennedy, Susan M; Xie, Yan; Luo, Jianyang; Davidson, Nicholas O.

    2008-01-01

    Liver fatty acid binding protein (L-FABP) is highly expressed in both enterocytes and hepatocytes and binds multiple ligands, including saturated (SFA), unsaturated fatty acids (PUFA), and cholesterol. L-fabp−/− mice were protected against obesity and hepatic steatosis on a high saturated fat (SF), high cholesterol “Western” diet and manifested a similar phenotype when fed with a high SF, low cholesterol diet. There were no significant differences in fecal fat content or food consumption betw...

  3. Non-functioning well-differentiated neuroendocrine tumor of the extrahepatic bile duct:an unusual suspect?

    Institute of Scientific and Technical Information of China (English)

    Harsheet Sethi; Mansoor Madanur; Parthi Srinivasan; Bernard Portmann; Nigel Heaton; Mohamed Rela

    2007-01-01

    BACKGROUND: Neuroendocrine tumors (NETs) arising in the biliary tree are extremely rare, and 37 cases were identiifed in the English literature. METHODS: A well-differentiated NET was found arising from the junction of the cystic and common hepatic ducts, in a 51-year-old male presenting with pedal edema and weight loss with abnormal liver enzymes and a normal serum bilirubin level. No mass was seen on radiological imaging and biopsy of the liver was suggestive of an early cholangiopathy. A bile leak complicating the liver biopsy led to an ERCP that demonstrated a iflling defect suggestive of a mass in the common bile duct (CBD). RESULTS: He underwent a successful excision of the tumor with a Roux-en-Y hepaticojejunostomy. The diagnosis of NET was made on histological and immunohistochemical analysis of the resected specimen. He remains well and disease free 22 months after surgery. CONCLUSIONS: Recognition of biliary NET continues to be a challenge and an increased awareness of these tumors in rare sites will result in optimal management of these tumors.

  4. Characterization of Human Hepatic and Extrahepatic UDP-Glucuronosyltransferase Enzymes Involved in the Metabolism of Classic Cannabinoids

    OpenAIRE

    Mazur, Anna; Lichti, Cheryl F.; Prather, Paul L.; Zielinska, Agnieszka K.; Bratton, Stacie M.; Gallus-Zawada, Anna; Finel, Moshe; Miller, Grover P.; Radomińska-Pandya, Anna; Moran, Jeffery H.

    2009-01-01

    Tetrahydrocannabinol (Δ9-THC), the primary psychoactive ingredient in marijuana, is subject to cytochrome P450 oxidation and subsequent UDP-glucuronosyltransferase (UGT)-dependent glucuronidation. Many studies have shown that CYP2C9 and CYP3A4 are the primary enzymes responsible for these cytochrome P450-dependent oxidations, but little work has been done to characterize phase II metabolic pathways. In this study, we test the hypothesis that there are specific human UG...

  5. CRM-1 knockdown inhibits extrahepatic cholangiocarcinoma tumor growth by blocking the nuclear export of p27Kip1.

    Science.gov (United States)

    Luo, Jian; Chen, Yongjun; Li, Qiang; Wang, Bing; Zhou, Yanqiong; Lan, Hongzhen

    2016-08-01

    Cholangiocarcinoma is a deadly disease which responds poorly to surgery and conventional chemotherapy or radiotherapy. Early diagnosis is difficult due to the anatomical and biological characteristics of cholangiocarcinoma. Cyclin-dependent kinase inhibitor 1B (p27Kip1) is a cyclin‑dependent kinase inhibitor and in the present study, we found that p27Kip1 expression was suppressed in the nucleus and increased in the cytoplasm in 53 samples of cholangiocarcinoma from patients with highly malignant tumors (poorly-differentiated and tumor-node-metastsis (TNM) stage III-IV) compared with that in samples from 10 patients with chronic cholangitis. The expression of phosphorylated (p-)p27Kip1 (Ser10), one of the phosphorylated forms of p27Kip1, was increased in the patient samples with increasing malignancy and clinical stage. Coincidentally, chromosome region maintenance 1 (CRM-1; also referred to as exportin 1 or Xpo1), a critical protein responsible for protein translocation from the nucleus to the cytoplasm, was also overexpressed in the tumor samples which were poorly differentiated and of a higher clinical stage. Through specific short hairpin RNA (shRNA)-mediated knockdown of CRM-1 in the cholangiocarcinoma cell line QBC939, we identified an elevation of cytoplasmic p27Kip1 and a decrease of nuclear p27Kip1. Furthermore, the viability and colony formation ability of QBC939 cells was largely reduced with G1 arrest. Consistent with the findings of the in vitro experiments, in a xenograft mouse model, the tumors formed in the CRM-1 knockdown group were markedly smaller and weighed less than those in the control group in vivo. Taken together, these findings demonstrated that the interplay between CRM-1 and p27Kip1 may provide potentially potent biomarkers and functional targets for the development of future cholangiocarcinoma treatments. PMID:27279267

  6. CRM-1 knockdown inhibits extrahepatic cholangiocarcinoma tumor growth by blocking the nuclear export of p27Kip1.

    Science.gov (United States)

    Luo, Jian; Chen, Yongjun; Li, Qiang; Wang, Bing; Zhou, Yanqiong; Lan, Hongzhen

    2016-08-01

    Cholangiocarcinoma is a deadly disease which responds poorly to surgery and conventional chemotherapy or radiotherapy. Early diagnosis is difficult due to the anatomical and biological characteristics of cholangiocarcinoma. Cyclin-dependent kinase inhibitor 1B (p27Kip1) is a cyclin‑dependent kinase inhibitor and in the present study, we found that p27Kip1 expression was suppressed in the nucleus and increased in the cytoplasm in 53 samples of cholangiocarcinoma from patients with highly malignant tumors (poorly-differentiated and tumor-node-metastsis (TNM) stage III-IV) compared with that in samples from 10 patients with chronic cholangitis. The expression of phosphorylated (p-)p27Kip1 (Ser10), one of the phosphorylated forms of p27Kip1, was increased in the patient samples with increasing malignancy and clinical stage. Coincidentally, chromosome region maintenance 1 (CRM-1; also referred to as exportin 1 or Xpo1), a critical protein responsible for protein translocation from the nucleus to the cytoplasm, was also overexpressed in the tumor samples which were poorly differentiated and of a higher clinical stage. Through specific short hairpin RNA (shRNA)-mediated knockdown of CRM-1 in the cholangiocarcinoma cell line QBC939, we identified an elevation of cytoplasmic p27Kip1 and a decrease of nuclear p27Kip1. Furthermore, the viability and colony formation ability of QBC939 cells was largely reduced with G1 arrest. Consistent with the findings of the in vitro experiments, in a xenograft mouse model, the tumors formed in the CRM-1 knockdown group were markedly smaller and weighed less than those in the control group in vivo. Taken together, these findings demonstrated that the interplay between CRM-1 and p27Kip1 may provide potentially potent biomarkers and functional targets for the development of future cholangiocarcinoma treatments.

  7. [Radiotherapy of cancers of the pancreas and extrahepatic biliary tree. Gross tumor volume (GTV). Clinical target volume (CTV)].

    Science.gov (United States)

    Atlan, D; Mornex, F

    2001-10-01

    Anatomical data of pancreas, biliary tree, regional lymph nodes is required to define GTV and CTV. In case of postoperative irradiation, CTV is designed in collaboration with radiation oncologist and surgeon oncologist. For exclusive radiotherapy, endodigestive ultrasonography, CT scan and MRI could help radiation oncologist defining GTV. Although, accuracy of all the imaging techniques in past years remains poor. Currently, no available literature is published regarding security margins for the definition of CTV. Therefore, recommendations according to clinical experience are proposed. PMID:11715305

  8. Amylase level in extrahepatic bile duct in adult patients with choledochal cyst plus anomalous pancreatico-biliary ductal union

    Institute of Scientific and Technical Information of China (English)

    In-Ho Jeong; Jin-Hong Kim; Jae-Ho Han; Wook-Hwan Kim; Yong-Sik Jung; Hong Kim; Bong-Wan Kim; Jung-Woon Kim; Jeong Hong; Hee-Jung Wang; Myung-Wook Kim; Byung-Moo Yoo

    2005-01-01

    AIM: To investigate the relationship between pancreatic amylase in bile duct and the clinico-pathological features in adult patients with choledochal cyst and anomalous pancreatico-biliary ductal union (APBDU).METHODS: From 39 patients who underwent surgery for choledochal cyst between March 1995 and March 2003,we selected 15 adult patients who had some symptoms and were radiologically diagnosed as APBDU, and their clinico-pathological features were subsequently evaluated retrospectively. However, we could not obtain biliary amylase in all the patients because of the surgeon's slip.Therefore, we measured the amylase level in gall bladder of 10 patients and in common bile duct of 11 patients.RESULTS: Levels of amylase in common bile duct and gall bladder ranged from 11 500 to 212 000 IU/L, and the younger the patients, the higher the biliary amylase level (r= -0.982, P<0.01). Pathologically, significant correlation was found between the size of choledochal cyst and the grade of inflammation (r= 0.798,P<0.01). And, significant correlation was found between the level of amylase in gall bladder and the grade of hyperplasia. On the other hand, there was no correlation to the age of symptomatic onset or inflammatory grade (r = 0.743, P<0.05). Level of lipase was elevated from 6 000 to 159 000 IU/L in bile duct and from 14 400 to 117 000 IU/L in the gall bladder;however, there was no significant correlation with age or clinico-pathological features.CONCLUSION: The results support the notion that amylase has a particular role in the onset of symptoms, and suggest that a large amount of biliary amylase induces early onset of symptom, thereby making early diagnosis possible.

  9. 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...

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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...

  15. 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

  16. Metastasis of hepatocellular carcinoma presented as a tumor of the maxillary sinus and retrobulbar tumor

    Directory of Open Access Journals (Sweden)

    Kolarević Daniela

    2011-01-01

    Full Text Available Introduction. Hepatocellular carcinoma (HCC is the most frequent primary malignant tumor of the liver. It is usually seen in the 6th and 7th decades of life and chronic hepatitis B is the most frequent cause. Extrahepatic metastasis of HCC is an indicator of a poor prognosis and the most common sites are lungs, bones, lymph nodes, kidneys and adrenal glands. We reported a case of isolated metastasis in the right maxilla, which had been found initially, before the tumor in the liver was diagnosed. Case report. A 70-year-old man underwent dental surgery of the upper right molar. Prolonged bleeding control was difficult for up to two weeks, so the biopsy was performed. Histopathological analysis revealed a metastatic hepatocellular carcinoma. Computerized tomography (CT of the abdomen revealed a diffusely heterogeneous liver parenchyma with irregular borders and two foci of mass lesions. There were metastasis in the spleen and also two pathological retroperitoneal lymph nodes were detected, but no ascit, liver cirrhosis, cholestasis or portal vein thrombosis were seen. CT of the orbital and maxillary regions revealed a tumor mass in the right maxillary sinus, spreading to the alveolar sinus, nasal cavity and partially infratemporal space. A tumor mass was in the right orbit as well, infiltrating the surrounding bones and muscles. Clinically, there was proptosis of the right eye accompanied by amaurosis. The treatment started with chemotherapy based on 5-fluorouracil (sorafenib was not available. After three cycles, control CTs showed a stable disease in the liver, but progression in the right maxillary sinus and orbit. Enucleation of the right eye was performed and postoperative radiotherapy was planed. The patient deteriorated rapidly and died, about 6 months after the disease had been diagnosed. Conclusion. Extrahepatic metastasis of HCC represents a progressive phase of the disease with poor prognosis, so the main aim of the treatment should be

  17. The phospholipid flippase ATP8B1 mediates apical localization of the cystic fibrosis transmembrane regulator.

    Science.gov (United States)

    van der Mark, Vincent A; de Jonge, Hugo R; Chang, Jung-Chin; Ho-Mok, Kam S; Duijst, Suzanne; Vidović, Dragana; Carlon, Marianne S; Oude Elferink, Ronald P J; Paulusma, Coen C

    2016-09-01

    Progressive familial intrahepatic cholestasis type 1 (PFIC1) is caused by mutations in the gene encoding the phospholipid flippase ATP8B1. Apart from severe cholestatic liver disease, many PFIC1 patients develop extrahepatic symptoms characteristic of cystic fibrosis (CF), such as pulmonary infection, sweat gland dysfunction and failure to thrive. CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel essential for epithelial fluid transport. Previously it was shown that CFTR transcript levels were strongly reduced in livers of PFIC1 patients. Here we have investigated the hypothesis that ATP8B1 is important for proper CFTR expression and function. We analyzed CFTR expression in ATP8B1-depleted intestinal and pulmonary epithelial cell lines and assessed CFTR function by measuring short-circuit currents across transwell-grown ATP8B1-depleted intestinal T84 cells and by a genetically-encoded fluorescent chloride sensor. In addition, we studied CFTR surface expression upon induction of CFTR transcription. We show that CFTR protein levels are strongly reduced in the apical membrane of human ATP8B1-depleted intestinal and pulmonary epithelial cell lines, a phenotype that coincided with reduced CFTR activity. Apical membrane insertion upon induction of ectopically-expressed CFTR was strongly impaired in ATP8B1-depleted cells. We conclude that ATP8B1 is essential for correct apical localization of CFTR in human intestinal and pulmonary epithelial cells, and that impaired CFTR localization underlies some of the extrahepatic phenotypes observed in ATP8B1 deficiency. PMID:27301931

  18. [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.

  19. Gemcitabine, Oxaliplatin, Tarceva &/or Cisplatin in HCC & Biliary Tree Cancers

    Science.gov (United States)

    2016-03-15

    Hepatocellular Carcinoma; Cholangiocellular Carcinoma; Cholangiocarcinoma of the Extrahepatic Bile Duct; Bile Duct Cancer; Periampullary Adenocarcinoma; Gallbladder Cancer; Extrahepatic Bile Duct Cancer

  20. ETIOLOGY, PATHOGENESIS AND MORPHOLOGY OF BILIARY ATRESIA

    Directory of Open Access Journals (Sweden)

    O. E. Iryshkin

    2012-01-01

    Full Text Available Biliary atresia is an inflammatory fibrosing process, which invades both extrahepatic and intrahepatic bile ducts. There are two forms of biliary atresia: embryonic form, associated with another visceral malformations, and perinatal form, which is an isolated disease. Biliary atresia is a heterogeinc disease which may appear as a result of different etiological factors, the most important of them are genetics, viral infection, vascular factors, toxins and disregulation of immune system. The characteristic morphological features of biliaryatresia are: intracellular and ductular cholestasis, ductular proliferation, giant cell transformation, portal and perilobular oedema and/or fibrosis. As the patalogical process progresses, ductopenia appears, and fibrosis turns to cirrhosis. Embryonic form mophologically manifests with ductal plate malformation is, what is an important diagnostic criterion. Pro- gnosis of biliary atresia depends on form of disease, age of patient and type of surgical operation. Today surgical treatment includes two steps: palliative portoenterostomia, performed in neonatal period and further liver trans- plantation. However liver transplantation is more preferable as first and single-step treatment. 

  1. Morphologic features of chronic hepatitis associated with primary sclerosing cholangitis and chronic ulcerative colitis

    Energy Technology Data Exchange (ETDEWEB)

    Ludwig, J.; Barham, S.S.; LaRusso, N.F.; Elveback, L.R.; Wiesner, R.H.; McCall, J.T.

    Histologic, ultrastructural, chemical, and statistical methods were used to study liver biopsy and autopsy specimens from 43 patients who had primary sclerosing cholangitis (PSC), with or without chronic ulcerative colitis (CUC), and from 19 patients who had CUC without PSC. In all study groups, essentially the same abnormalities were found in the hepatic parenchyma outside the major bile ducts, although nondiagnostic tissue samples were observed also. Specimens from patients with extrahepatic PSC were indistinguishable from those patients with combined extra- and intrahepatic PSC. Common findings included periductal fibrosis and inflammation, portal edema and fibrosis, focal proliferation of bile ducts and ductules, focal bile duct obliteration and loss of bile ducts, copper deposition, and cholestasis. Proliferation of bile ducts in some portal tracts and obliteration or absence of bile duct in others were the most characteristic changes. In most specimens, inflammatory changes appeared mild, yet biliary cirrhosis had developed in 34% of the patients. Specimens from patients with PSC, with or without CUC, more often contained bile and strikingly increased stainable copper (Grades 2 and 3) than did specimens from patients with CUC without PSC. Hepatic copper contents, measured by atomic absorption spectrophotometry, also were higher in specimens from patients with PSC. Study of PCS specimens by transmission electron microscopy and by energy-dispersive X-ray microanalysis revealed that most copper was sequestered in lipolysosomes. The recognition of strikingly similar morphologic features in many liver specimens from patients with either PSC or CUC or both suggests that the causes of these conditions are closely related.

  2. The Interstitial Lymphatic Peritoneal Mesothelium Axis in Portal Hypertensive Ascites: When in Danger, Go Back to the Sea

    Directory of Open Access Journals (Sweden)

    M. A. Aller

    2010-01-01

    Full Text Available Portal hypertension induces a splanchnic and systemic low-grade inflammatory response that could induce the expression of three phenotypes, named ischemia-reperfusion, leukocytic, and angiogenic phenotypes.During the splanchnic expression of these phenotypes, interstitial edema, increased lymph flow, and lymphangiogenesis are produced in the gastrointestinal tract. Associated liver disease increases intestinal bacterial translocation, splanchnic lymph flow, and induces ascites and hepatorenal syndrome. Extrahepatic cholestasis in the rat allows to study the worsening of the portal hypertensive syndrome when associated with chronic liver disease. The splanchnic interstitium, the mesenteric lymphatics, and the peritoneal mesothelium seem to create an inflammatory pathway that could have a key pathophysiological relevance in the production of the portal hypertension syndrome complications. The hypothetical comparison between the ascitic and the amniotic fluids allows for translational investigation. From a phylogenetic point of view, the ancestral mechanisms for amniotic fluid production were essential for animal survival out of the aquatic environment. However, their hypothetical appearance in the cirrhotic patient is considered pathological since ultimately they lead to ascites development. But, the adult human being would take advantage of the potential beneficial effects of this “amniotic-like fluid” to manage the interstitial fluids without adverse effects when chronic liver disease aggravates.

  3. The canine hepatic progenitor cell niche: molecular characterisation in health and disease.

    Science.gov (United States)

    Kruitwagen, H S; Spee, B; Viebahn, C S; Venema, H B; Penning, L C; Grinwis, G C M; Favier, R P; van den Ingh, T S G A M; Rothuizen, J; Schotanus, B A

    2014-09-01

    Hepatic progenitor cells (HPCs) are an adult stem cell compartment in the liver that contributes to liver regeneration when replication of mature hepatocytes is insufficient. In this study, laser microdissection was used to isolate HPC niches from the livers of healthy dogs and dogs with lobular dissecting hepatitis (LDH), in which HPCs are massively activated. Gene expression of HPC, hepatocyte and biliary markers was determined by quantitative reverse transcriptase PCR. Expression and localisation of selected markers were further studied at the protein level by immunohistochemistry and immunofluorescent double staining in samples of normal liver and liver from dogs with LDH, acute and chronic hepatitis, and extrahepatic cholestasis. Activated HPC niches had higher gene expression of the hepatic progenitor markers OPN, FN14, CD29, CD44, CD133, LIF, LIFR and BMI1 compared to HPCs from normal liver. There was lower expression of albumin, but activated HPC niches were positive for the biliary markers SOX9, HNF1β and keratin 19 by immunohistochemistry and immunofluorescence. Laminin, activated stellate cells and macrophages are abundant extracellular matrix and cellular components of the canine HPC niche. This study demonstrates that the molecular and cellular characteristics of canine HPCs are similar to rodent and human HPCs, and that canine HPCs are distinctively activated in different types of liver disease. PMID:24923752

  4. Interleukin-6 (IL-6) serum concentrations in dogs with hepatitis and hepatic tumours compared with those with extra-hepatic inflammation and tumours

    OpenAIRE

    Neumann, Stephan; Kaup, Franz-Josef; Scheulen, Sonja

    2010-01-01

    Cytokines are part of pathogenesis in many diseases. Their measurement could be interesting for diagnostic purposes. One cytokine which participates in different inflammatory and neoplastic diseases is interleukin-6 (IL-6). The aim of this study was to investigate the IL-6 serum concentration in dogs with different liver diseases to show if there is any association between the cytokine serum level and the disease aetiology or the degree of the disease. IL-6 was measured in dogs with acute hep...

  5. Extrahepatic Manifestations of Hepatitis B Virus Infection: Addison’s Disease and Myelofibrosis in a Patient with Persistent Hepatitis B Surface Antigenemia

    Directory of Open Access Journals (Sweden)

    François Somlo

    1993-01-01

    Full Text Available A 60-year-old white male patient was admitted to the hospital with acute abdominal pain, seemingly a self-limited ileus. He was found to be hepatitis B surface antigen (HBsAg-positive. Previous dental treatment was suspected to be the initial source of the infection with hepatitis B virus. Five months later he was re-admitted with a diagnosis of adrenal insufficiency (Addison’s disease which responded well to steroids. Four years later he developed fever and leucocytosis. A bone marrow biopsy revealed myelofibrosis. He had several episodes of pyrexia during his lifetime. After a 12-year period the patient suffered a fatal myocardial infarction. At autopsy the adrenal glands were reduced to scarred remnants and HBsAg was found to be present in the residual adrenocortical cells by immunoflouresence methods. Bone marrow at autopsy revealed myelosclerosis as well HBsAg (via immunofluoresence. Hepatitis B virus was therefore closely correlated with the development of Addison’s disease and myelofibrosis in this case.

  6. Complications after surgical attenuation of congenital extrahepatic portosystemic shunts in dogs can be prevented by intraoperative Doppler ultrasonographic assessment of portal hemodynamics

    NARCIS (Netherlands)

    Szatmári, Viktor

    2005-01-01

    Under normal circumstances the blood from the gastrointestinal tract flows via the portal vein to the liver. The detoxified blood leaves the liver via the hepatic veins to the caudal vena cava, which latter enters the heart. Portosystemic shunting occurs when an anomalous vein allows the portal bloo

  7. Contrast-enhanced computed tomography angiography and volume-rendered imaging for evaluation of cellophane banding in a dog with extrahepatic portosystemic shunt

    Directory of Open Access Journals (Sweden)

    H. Yoon

    2011-04-01

    Full Text Available A 4-year-old, 1.8 kg, male, castrated Maltese was presented for evaluation of urolithiasis. Urinary calculi were composed of ammonium biurate. Preprandial and postprandial bile acids were 44.2 and 187.3 μmol/ , respectively (reference ranges 0–10 and 0–20 μmol/ , respectively. Single-phase contrast-enhanced computed tomography angiography (CTA with volume-rendered imaging (VRI was obtained. VRI revealed a portocaval shunt originating just cranial to a tributary of the gastroduodenal vein and draining into the caudal vena cava at the level of the epiploic foramen. CTA revealed a 3.66 mm-diameter shunt measured at the level of the termination of the shunt and a 3.79 mm-diameter portal vein measured at the level between the origin of the shunt and the porta of the liver. Surgery was performed using cellophane banding without attenuation. Follow-up single-phase CTA with VRI was obtained 10 weeks after surgery. VRI revealed no evidence of portosystemic communication on the level of a cellophane band and caudal to the cellophane band. CTA demonstrated an increased portal vein diameter (3.79–5.27 mm measured at the level between the origin of the shunt and the porta of the liver. Preprandial and postprandial bile acids were 25 and 12.5 μmol/ , respectively (aforementioned respective reference ranges, 3 months post-surgery. No problems were evident at 6 months.

  8. Extrahepatic Fasciola Hepatica: A Case Report and Literature Review%肝外肝片吸虫病1例及文献复习

    Institute of Scientific and Technical Information of China (English)

    王斌; 游潮; 贺民; 王翔; 刘翼; 廖琳

    2007-01-01

    目的: 提高对肝片吸虫病肝外异位感染临床特点的认识.方法: 结合1例肝片吸虫病肝外异位感染患者的临床资料及文献复习,对本病的临床表现、实验室及影像学检查、诊断和治疗进行分析.结果: 该患者脑、眼异位感染肝片吸虫,临床表现为反复脑出血、眼部症状,血中嗜酸性粒细胞增高,吸虫ELSIA(+).口服砒喹酮治疗,效果良好.结论: 肝片吸虫病脑、眼异位同时感染非常罕见,仔细收集患者有生食水生植物等可能已附有囊蚴的历史非常重要.

  9. 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....

  10. 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.

  11. 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...

  12. 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.

  13. TGR5: pathogenetic role and/or therapeutic target in fibrosing cholangitis?

    Science.gov (United States)

    Keitel, Verena; Reich, Maria; Häussinger, Dieter

    2015-06-01

    Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease affecting the intrahepatic and extrahepatic biliary tree leading to bile duct strictures, progressive cholestasis, and development of liver fibrosis and cirrhosis. The pathogenesis of PSC is still elusive; however, both an immune-mediated injury of the bile ducts as well as increased recruitment of intestinal-primed T lymphocytes to the biliary tracts seem to contribute to disease development and progression. TGR5 (Gpbar-1) is a G-protein-coupled receptor responsive to bile acids, which is expressed in cholangiocytes, intestinal epithelial cells, and macrophages of the liver and intestine as well as in CD14-positive monocytes of the peripheral blood. Activation of TGR5 in biliary epithelial cells promotes chloride and bicarbonate secretion, triggers cell proliferation, and prevents apoptotic cell death. In immune cells, stimulation of TGR5 inhibits cytokine expression and secretion, thus reducing systemic as well as hepatic and intestinal inflammation. The expression pattern of TGR5 in the liver and intestine as well as the potential protective functions of TGR5 suggest a role for this receptor in the pathogenesis of PSC. While mutations in the coding region of the TGR5 gene are too rare to contribute to overall disease susceptibility, the expression and localization of the receptor have not been studied in PSC livers. Pharmacological activation of TGR5 in mice promotes protective mechanisms in biliary epithelial cells and reduces hepatic and systemic inflammation; however, it also provokes pruritus. Further studies are needed to predict the potential benefits as well as side effects of TGR5 agonist treatment in PSC patients.

  14. A genetic screen in zebrafish identifies the mutants vps18, nf2 and foie gras as models of liver disease.

    Science.gov (United States)

    Sadler, Kirsten C; Amsterdam, Adam; Soroka, Carol; Boyer, James; Hopkins, Nancy

    2005-08-01

    Hepatomegaly is a sign of many liver disorders. To identify zebrafish mutants to serve as models for hepatic pathologies, we screened for hepatomegaly at day 5 of embryogenesis in 297 zebrafish lines bearing mutations in genes that are essential for embryonic development. Seven mutants were identified, and three have phenotypes resembling different liver diseases. Mutation of the class C vacuolar protein sorting gene vps18 results in hepatomegaly associated with large, vesicle-filled hepatocytes, which we attribute to the failure of endosomal-lysosomal trafficking. Additionally, these mutants develop defects in the bile canaliculi and have marked biliary paucity, suggesting that vps18 also functions to traffic vesicles to the hepatocyte apical membrane and may play a role in the development of the intrahepatic biliary tree. Similar findings have been reported for individuals with arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome, which is due to mutation of another class C vps gene. A second mutant, resulting from disruption of the tumor suppressor gene nf2, develops extrahepatic choledochal cysts in the common bile duct, suggesting that this gene regulates division of biliary cells during development and that nf2 may play a role in the hyperplastic tendencies observed in biliary cells in individuals with choledochal cysts. The third mutant is in the novel gene foie gras, which develops large, lipid-filled hepatocytes, resembling those in individuals with fatty liver disease. These mutants illustrate the utility of zebrafish as a model for studying liver development and disease, and provide valuable tools for investigating the molecular pathogenesis of congenital biliary disorders and fatty liver disease.

  15. An unhappy triad: Hemochromatosis, porphyria cutanea tarda and hepatocellular carcinoma-A case report

    Institute of Scientific and Technical Information of China (English)

    Martina T Mogl; Andreas Pascher; Sabine J Presser; Michael Schwabe; Peter Neuhaus; Natascha C Nuessler

    2007-01-01

    Liver fibrosis and cirrhosis are predisposing factors for the development of hepatocellular carcinoma (HCC). Hemosiderosis has also been described to trigger carcinogenesis. A significant iron overload, as found in hereditary hemochromatosis (HHC), is a risk factor for HCC and may also promote the symptoms of porphyria cutanea tarda (PCT). A 68-year old male patient presented to our clinic with a suspected HCC,elevated alpha-fetoprotein but normal liver function tests. He reported a 25 year-old history of vitiligo upon exposure to sunlight. The patient underwent an extended left hemihepatectomy, and the recovery was uneventful, with the exception of a persistent hyperbilirubinemia. Perfusion problems and extrahepatic cholestasis were ruled out by CT-scan with angiography and MR-cholangiopancreatography. However, MRI showed an iron overload. Histology confirmed the HCC (pT3, pN0, G3, R0) and revealed a portal fibrosis and hemosiderosis. Based on the skin lesions we suspected a PCT that was confirmed by laboratory tests showing elevated porphyrin, uroporphyrin, coproporphyrin and porphobilinogen. Concurrently, molecular diagnostics revealed homozygosity for the C282Y mutation within the hemochromatosis HFE gene. After phlebotomy and normalization of liver function tests the patient was discharged. This is the first case ever showing the unusual combination of HCC in a fibrotic liver with HHC and PCT. This diagnosis not only warrants oncological follow-up but also symptomatic therapy to normalize iron metabolism and thereby improve liver function and alleviate the symptoms of HHC and PCT. Thus progression of fibrosis may be prevented and liver regeneration supported.

  16. A multistep approach in the cytologic evaluation of liver biopsy samples of dogs with hepatic diseases.

    Science.gov (United States)

    Stockhaus, C; Van Den Ingh, T; Rothuizen, J; Teske, E

    2004-09-01

    Cytologic criteria were evaluated for their diagnostic value in liver disease in dogs. Therefore, histopathologic and cytologic examination was performed on liver biopsy samples of 73 dogs with liver diseases and 28 healthy dogs. Logistic regression analysis was used to select the measured parameters to be included in a multistep approach. With the logistic regression method, different characteristic cytologic parameters could be defined for each histopathologic diagnosis. In malignant lymphoma of the liver, the presence of large numbers of lymphoblasts with a minimum of 5% of all cells was found. Clusters of epithelial cells with several cytologic characteristics of malignancy intermixed with normal hepatocytes were indicative of metastatic carcinoma or cholangiocellular carcinoma. Liver cells in hepatocellular carcinoma were characterized by a high nucleus/cytoplasm ratio, large cell diameters, increased numbers of nucleoli per nuclei, small numbers of cytoplasmic vacuoles, and frequently, small numbers of lymphocytes. Extrahepatic cholestasis was characterized by excessive extracellular bile pigment in the form of biliary casts, an increased number of nucleoli within hepatocytes, decreased hepatic cell size, and low numbers of lymphocytes. In destructive cholangiolitis, increased numbers of neutrophils and a small mean nuclear size within hepatocytes were seen. Acute and nonspecific reactive hepatitis are diagnosed based on the presence of moderate reactive nuclear patterns, including more pronounced chromatin, prominent nucleoli, increased numbers of inflammatory cells, excluding lymphocytes, and the absence of increased numbers of bile duct cell clusters. Increased number of mast cells also was indicative of nonspecific reactive hepatitis. Important cytologic criteria for the diagnosis of liver cirrhosis, in addition to chronic hepatitis, are intracellular bile accumulation and increased numbers of bile duct cell clusters. In summary, the stepwise approach

  17. Liver transplantation in Greek children: 15 years experience

    Directory of Open Access Journals (Sweden)

    Dimitrios Takoudas

    2010-09-01

    Full Text Available Liver transplantation (LT is the only available live-saving procedure for children with irreversible liver failure. This paper reports our experience from the follow-up of 16 Greek children with end-stage liver failure who underwent a LT. Over a period of 15 years, 16 pediatric liver recipients received follow up after being subjected to OLT (orthotopic liver transplantation due to end-stage liver failure. Nine children initially presented with extrahepatic biliary atresia, 2 with acute liver failure after toxic mushroom ingestion, 2 with intrahepatic cholestasis, 2 with metabolic diseases and one with hepatoblastoma. Ten children received a liver transplant in the Organ Transplantation Unit of Aristotle University of Thessaloniki and the rest in other transplant centers. Three transplants came from a living-related donor and 13 from a deceased donor. Six children underwent immunosuppressive treatment with cyclo­sporine, mycophenolate mofetil and corticosteroids, and 7 with tacrolimus, mycophenolate mofetil and corticosteroids. Three out of 16 children died within the first month after the transplantation due to post-transplant complications. Three children presented with acute rejection and one with chronic organ rejection which was successfully managed. Five children presented with cytomegalovirus infection, 5 with Epstein-Barr virus, 2 with HSV1,2, 2 with ParvoB19 virus, 2 with varicella-zoster virus and one with C. Albicans infection. One child presented with upper gastrointestinal hemorrhage and one with small biliary paucity. A satisfying outcome was achieved in most cases, with good graft function, except for the patient with small biliary paucity who required re-transplantation. The long-term clinical course of liver transplanted children is good under the condition that they are attended in specialized centers.

  18. Cancer review: Cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Yezaz Ahmed Ghouri

    2015-01-01

    Full Text Available Cholangiocarcinoma (CCA is the most common biliary tract malignancy. CCA is classified as intrahepatic, perihilar or distal extrahepatic; the individual subtypes differ in their biologic behavior, clinical presentation, and management. Throughout the last decades, CCA incidence rates had significantly increased. In addition to known established risk factors, novel possible risk factors (i.e. obesity, hepatitis C virus have been identified that are of high importance in developed countries where CCA prevalence rates have been low. CCA tends to develop on the background of inflammation and cholestasis. In recent years, our understanding of the molecular mechanisms of cholangiocarcinogenesis has increased, thereby, providing the basis for molecularly targeted therapies. In its diagnostic evaluation, imaging techniques have improved, and the role of complementary techniques has been defined. There is a need for improved CCA biomarkers as currently used ones are suboptimal. Multiple staging systems have been developed, but none of these is optimal. The prognosis of CCA is considered dismal. However, treatment options have improved throughout the last two decades for carefully selected subgroups of CCA patients. Perihilar CCA can now be treated with orthotopic liver transplantation with neoadjuvant chemoradiation achieving 5-year survival rates of 68%. Classically considered chemotherapy-resistant, the ABC-02 trial has shown the therapeutic benefit of combination therapy with gemcitabine and cisplatin. The benefits of adjuvant treatments for resectable CCA, local ablative therapies and molecularly targeted therapies still need to be defined. In this article, we will provide the reader with an overview over CCA, and discuss the latest developments and controversies.

  19. The nutritional therapy of cholestatic liver disease in infants%婴儿胆汁淤积性肝病的营养治疗

    Institute of Scientific and Technical Information of China (English)

    黄志华; 李雪松

    2013-01-01

    There are various causes of cholestatic liver disease in infants that include extrahepatic biliary tract diseases, liver diseases, anatomical abnormality, metabolic or endocrine diseases, poisoning, infection, and so on. The causes leads to re-duction or interruption in bile lfow and thus results in nutrients malabsorption and comprehensive metabolic disorder. The aims of nutritional therapy for cholestatic liver disease are to reduce the risk of cholestasis related complications, to promote recov-ery of liver diseases, to restore bile flow, to promote growth and improve the comprehensive metabolic disorders, to improve quality of life and to prepare children for liver transplantation.%婴儿胆汁淤积性肝病的病因甚多,包括肝外胆道疾病、肝内疾病、解剖异常、代谢或内分泌疾病、中毒、感染等。由于胆流减少或中断,引起肠道营养物质吸收障碍及综合代谢紊乱。胆汁淤积性肝病的营养治疗,主要是减少胆汁淤积相关并发症;促进肝脏病变恢复,恢复胆流;促进生长发育和改善综合代谢紊乱;提高生存质量,为患儿后期肝移植奠定基础。

  20. Bile acid interactions with cholangiocytes

    Institute of Scientific and Technical Information of China (English)

    Xuefeng Xia; Heather Francis; Shannon Glaser; Gianfranco Alpini; Gene LeSage

    2006-01-01

    Cholangiocytes are exposed to high concentrations of bile acids at their apical membrane. A selective transporter for bile acids, the Apical Sodium Bile Acid Cotransporter (ASBT) (also referred to as Ibat; gene name Slc10a2)is localized on the cholangiocyte apical membrane. On the basolateral membrane, four transport systems have been identified (t-ASBT, multidrug resistance (MDR)3,an unidentified anion exchanger system and organic solute transporter (Ost) heteromeric transporter, OstαOstβ. Together, these transporters unidirectionally move bile acids from ductal bile to the circulation. Bile acids absorbed by cholangiocytes recycle via the peribiliaryplexus back to hepatocytes for re-secretion into bile.This recycling of bile acids between hepatocytes and cholangiocytes is referred to as the cholehepatic shunt pathway. Recent studies suggest that the cholehepatic shunt pathway may contribute in overall hepatobiliary transport of bile acids and to the adaptation to chronic cholestasis due to extrahepatic obstruction. ASBT is acutely regulated by an adenosine 3', 5'-monophosphate (cAMP)-dependent translocation to the apical membrane and by phosphorylation-dependent ubiquitination and proteasome degradation. ASBT is chronically regulated by changes in gene expression in response to biliary bile acid concentration and inflammatory cytokines.Another potential function of cholangiocyte ASBT is to allow cholangiocytes to sample biliary bile acids in order to activate intracellular signaling pathways. Bile acids trigger changes in intracellular calcium, protein kinase C (PKC), phosphoinositide 3-kinase (PI3K), mitogenactivated protein (MAP) kinase and extracellular signalregulated protein kinase (ERK) intracellular signals.Bile acids significantly alter cholangiocyte secretion,proliferation and survival. Different bile acids have differential effects on cholangiocyte intracellular signals,and in some instances trigger opposing effects on cholangiocyte secretion

  1. PET-CT in Determining the Radioembolization Dose Delivered to Patients With Liver Metastasis, Primary Liver Cancer, or Biliary Cancer

    Science.gov (United States)

    2016-03-01

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Stage D Adult Primary Liver Cancer (BCLC); Unspecified Adult Solid Tumor, Protocol Specific

  2. Damage Control Operation for Extrahepatic Bile Duct Injury (Report of 15 Cases )%肝外胆管外伤的损伤控制性手术治疗(附15例报道)

    Institute of Scientific and Technical Information of China (English)

    江宗兴; 戴睿武; 田伏洲; 杨锁军; 刘彦莉

    2008-01-01

    目的 探讨损伤控制性手术(DCO)治疗肝外胆管外伤的经验.方法 回顾分析我中心2002年6月至2007年9月期间采用DCO原则治疗15例严重外伤致肝外胆管损伤患者的临床资料.结果 15例肝外胆管损伤患者均按DCO原则治疗,经复苏病情稳定后再接受相应术式的再次确定性手术. 本组患者无一例死亡,再次手术后发生胆瘘2例(13.3%),结肠小肠瘘1例(6.7%),切口感染、裂开2例(13.3%),急性肝功能衰竭1例(6.7%).通过引流、对症、支持治疗后均治愈,治愈率达100%.中位随访期28个月,无一例术后出现胆管狭窄及相关并发症.结论 合并肝外胆管损伤的严重外伤患者,应积极按照DCO原则,选用合适的手术方式处理,以达到提高存活率和减少并发症的目的 .

  3. 肝外合成凝血相关蛋白在肝衰竭和肝硬化中的变化特点%Changes of extra-hepatic tissues synthetical protein in liver failure and cirrhosis

    Institute of Scientific and Technical Information of China (English)

    陈静; 丛玉隆

    2015-01-01

    Objective To study the changes of anti‐coagulation proteins synthesized from Beijing Aviation General Hospital by extra‐hepatic tissues in the developing trends of liver diseases and the relation between these proteins and bleeding‐clotting ,and to explore early sensitive indicator of liver diseases .Methods Coagulation Ⅷ(FⅧ) activity was measured by one clotting stage way ;tissue factor pathway inhibitor (TFPI) ,blood clots regulato‐ry proteins (TM ) ,von willebrand factor (vWF) and tissue factor (TF) concentration were measured by ELISA method .Results (1)TFPI:Ag detected values CHB patients 239 .3 ± 206 .4 ,liver cirrhosis patients 315 .0 ± 258 .6 , liver failure patients 319 .5 ± 298 .1 ,all higher than normal control 104 .0 ± 87 .1(F=5 .453 ,P<0 .05);(2)vWF :Ag detected values CHB patients 70 .3 ± 29 .5 ,liver cirrhosis patients 105 .5 ± 57 .9 ,liver failure patients 179 .3 ± 61 .7 ,all higher than normal control 21 .9 ± 7 .2(F=20 .104 ,P<0 .05);(3)TF detected values CHB patients 86 .0 ± 85 .7 ,liver cirrhosis patients 234 .2 ± 202 .9 ,liver failure patients 344 .7 ± 214 .6 ,all higher than normal control 12 .9 ± 8 .1(F=8 .619 ,P<0 .05);(4)FⅧ :C detected values CHB patients 157 .2 ± 53 .4 ,liver cirrhosis patients 206 .9 ± 86 .9 ,liver failure patients 335 .7 ± 117 .7 ,all higher than normal control 105 .5 ± 46 .2(F=13 .418 ,P<0 .05) .Conclusion Ex‐tra‐hepatic synthesis of coagulation proteins and disease development are negatively correlated ,that is ,these proteins rise with the aggravation of the disease ,suggesting that vessel wall damage is consistent with the severity of the dis‐ease and can be used as a comparatively sensitive indicator of monitoring vascular injury ;five detector increased in blood perhaps have relate to coagulation disorder in end‐stage liver disease patients .%目的:研究北京航空总医院肝外组织合成的凝血相关蛋白在肝病发展趋势中的变化及其与出凝血的关系,寻找肝病早期敏感指标。方法凝血因子Ⅷ(FⅧ)活性测定采用凝固法;组织因子途径抑制物(T FPI )、血栓调节蛋白(TM)、血管性血友病因子(vWF)及组织因子(TF)水平测定采用酶联免疫吸附试验。结果(1)TFPI:Ag检测值慢性乙型肝炎组239.3±206.4,肝硬化组315.0±258.6,肝衰竭组319.5±298.1,均高于健康对照组的104.0±87.1,差异有统计学意义(F=5.453,P<0.05));(2)vWF :Ag检测值慢性乙型肝炎组70.3±29.5,肝硬化组105.5±57.9,肝衰竭组179.3±61.7,均高于健康对照组的21.9±7.2,差异有统计学意义(F=20.104,P<0.05);(3)T F检测值慢性乙型肝炎组86.0±85.7,肝硬化组234.2±202.9,肝衰竭组344.7±214.6,均高于健康对照组的12.9±8.1,差异有统计学意义( F=8.619,P<0.05);(4)FⅧ:C检测值慢性乙型肝炎组157.2±53.4,肝硬化组206.9±86.9,肝衰竭组335.7±117.7,均高于健康对照组的105.5±46.2,差异有统计学意义( F=13.418, P<0.05)。结论肝外合成的凝血相关蛋白均与病情的发展呈负相关,即随着病情的加重而升高,提示血管壁的损伤与病情严重程度一致;5种蛋白可作为监测血管损伤的较为敏感指标。

  4. 带蒂肝圆韧带覆盖修补肝外胆管缺损1例%A case report of repairing a large segment defect of extrahepatic bile duct with round ligament of liver

    Institute of Scientific and Technical Information of China (English)

    甘泉; 陈超; 李伟

    2011-01-01

    1 临床资料患者女性,41岁,因"右上腹部疼痛伴呕吐8天"于2011年01月03日入院,诊断为"胆囊结石",于2010年01月05日行腹腔镜胆囊切除术,术中损伤胆总管,中转开腹行胆总管单纯缝合.术后第1天出现腹膜炎表现,腹腔引流管引出黄色胆汁.

  5. Effects of supplement with glucose on the model rats for the investigation of extrahepatic metabolism%术后补充葡萄糖对肝外代谢模型大鼠的影响

    Institute of Scientific and Technical Information of China (English)

    信艳红; 李捷伟; 刘吉祥; 李晓冬; 夏少晴; 贺平; 黄伟

    2007-01-01

    目的:研究术后补充葡萄糖对肝外代谢模型大鼠的存活时间以及血液生化指标的影响.方法:16只SD大鼠采用阻断肝动脉加门静脉-腔静脉分流的方法建立肝外代谢模型,并随机分成Ⅰ、Ⅱ两组,每组8只.模型Ⅰ组术后胃内注射25%葡萄糖3 mL,模型Ⅱ组注射等体积注射用水,观察其存活时间.另取29只SD大鼠,随机分成对照组(n=6)和模型组(n=23),于建立模型后0.5(n=3)、1(n=3)、2(n=12)和4 h(n=5),分别测定血清葡萄糖、胆红素、肌酐、尿素氮、尿酸、K+、Na+和Cl-浓度.于术后2 h取血的12只大鼠中,6只术后胃内注射25%葡萄糖3 mL,另6只胃内注射等体积注射用水.结果:模型大鼠的存活时间为(6.7土1.6)h,术后补充葡萄糖使存活时间延长到(14.5+3.2)h(P<0.01).建立模型后0.5 h,血糖平均下降52.3%,到4 h仅为正常对照的5.0%,而血清胆红素升高了17.2倍.建立模型后1 h,血清尿素氮、肌酐和K+浓度开始升高,补充葡萄糖使其明显得到改善.结论:肝外代谢模型大鼠的主要病理生理变化是低血糖、高胆红素血症和肾功能不全,术后补充葡萄糖能明显延长模型大鼠的存活时间,改善其肾脏功能.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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...

  13. 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...

  14. Cholangiocytes and blood supply

    Institute of Scientific and Technical Information of China (English)

    Eugenio Gaudio; Antonio Franchitto; Luigi Pannarale; Guido Carpino; Gianfranco Alpini; Heather Francis; Shannon Glaser; Domenico Alvaro; Paolo Onori

    2006-01-01

    The microvascular supply of the biliary tree, the peribiliary plexus (PBP), stems from the hepatic artery branches and flows into the hepatic sinusoids. A detailed three-dimensional study of the PBP has been performed by using the Scanning Electron Microscopy vascular corrosion casts (SEMvcc) technique. Considering that the PBP plays a fundamental role in supporting the secretory and absorptive functions of the biliary epithelium, their organization in either normalcy and pathology is explored. The normal liver shows the PBP arranged around extra- and intrahepatic biliary tree.In the small portal tract PBP was characterized by a single layer of capillaries which progressively continued with the extrahepatic PBP where it showed a more complex vascular network. After common duct ligation (BDL), progressive modifications of bile duct and PBP proliferation are observed. The PBP presents a threedimensional network arranged around many bile ducts and appears as bundles of vessels, composed by capillaries of homogeneous diameter with a typical round mesh structure. The PBP network is easily distinguishable from the sinusoidal network which appears normal. Consider