WorldWideScience

Sample records for cholestasis extrahepatic

  1. Percutaneous transhepatic biliary drainage in malignant extrahepatic cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Hoevels, J.

    1985-03-01

    The technique of non-surgical percutaneous transhepatic biliary drainage has been improved recently. Combined internal and external drainage of bile was enabled by manipulation of a guide wire and a drainage catheter through the stenosed or obstructed section of the extrahepatic biliary ducts. Experience have been gained concerning internal drainage of bile by percutaneous transhepatic insertion of an endoprosthesis for some years now.

  2. Percutaneous transhepatic biliary drainage in malignant extrahepatic cholestasis

    International Nuclear Information System (INIS)

    The technique of non-surgical percutaneous transhepatic biliary drainage has been improved recently. Combined internal and external drainage of bile was enabled by manipulation of a guide wire and a drainage catheter through the stenosed or obstructed section of the extrahepatic biliary ducts. Experience have been gained concerning internal drainage of bile by percutaneous transhepatic insertion of an endoprosthesis for some years now. (orig./WU)

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

    Directory of Open Access Journals (Sweden)

    Evandro Luis de Oliveira Costa

    2014-04-01

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

  4. 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.

  5. 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.

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

    OpenAIRE

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

    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...

  7. INCREASE OF GLYCOSAMINOGLYCANS AND METALLOPROTEINASES 2 AND 9 IN LIVER EXTRACELLULAR MATRIX ON EARLY STAGES OF EXTRAHEPATIC CHOLESTASIS

    Directory of Open Access Journals (Sweden)

    Pedro Luiz Rodrigues GUEDES

    2014-12-01

    Full Text Available Context Cholestasis produces hepatocellular injury, leukocyte infiltration, ductular cells proliferation and fibrosis of liver parenchyma by extracellular matrix replacement. Objective Analyze bile duct ligation effect upon glycosaminoglycans content and matrix metalloproteinase (MMPs activities. Methods Animals (6-8 weeks; n = 40 were euthanized 2, 7 or 14 days after bile duct ligation or Sham-surgery. Disease evolution was analyzed by body and liver weight, seric direct bilirubin, globulins, gamma glutamyl transpeptidase (GGT, alkaline phosphatase (Alk-P, alanine and aspartate aminotransferases (ALT and AST, tissue myeloperoxidase and MMP-9, pro MMP-2 and MMP-2 activities, histopathology and glycosaminoglycans content. Results Cholestasis caused cellular damage with elevation of globulins, GGT, Alk-P, ALT, AST. There was neutrophil infiltration observed by the increasing of myeloperoxidase activity on 7 (P = 0.0064 and 14 (P = 0.0002 groups which leads to the magnification of tissue injuries. Bile duct ligation increased pro-MMP-2 (P = 0.0667, MMP-2 (P = 0.0003 and MMP-9 (P<0.0001 activities on 14 days indicating matrix remodeling and establishment of inflammatory process. Bile duct ligation animals showed an increasing on dermatan sulfate and/or heparan sulfate content reflecting extracellular matrix production and growing mitosis due to parenchyma depletion. Conclusions Cholestasis led to many changes on rats’ liver parenchyma, as so as on its extracellular matrix, with major alterations on MMPs activities and glycosaminoglycans content.

  8. A Gentleman with Anemia and Cholestasis

    Directory of Open Access Journals (Sweden)

    Siu-Tong Law

    2010-01-01

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

  9. 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.

  10. Intrahepatic cholestasis without jaundice

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  11. 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...

  12. Ultrasonography of Neonatal Cholestasis

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-06-15

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

  13. 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.)

  14. Progressive familial intrahepatic cholestasis

    Directory of Open Access Journals (Sweden)

    Baussan Christiane

    2009-01-01

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

  15. 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.

  16. Congenital extrahepatic portosystemic shunts

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  17. 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 ...

  18. Extrahepatic bile duct atresia from the pathologist’s perspective: pathological features and differential diagnosis

    Directory of Open Access Journals (Sweden)

    Peter Van Eyken

    2014-06-01

    Full Text Available Extrahepatic biliary atresia (EHBA refers to stenosis or atresia of the extrahepatic biliary tree. It accounts for 25-30% of cases of neonatal cholestasis. If left untreated, EHBA progresses to biliary cirrhosis and is universally fatal within the first 2 years of life. Early diagnosis is crucial since surgical treatment (Kasai procedure is the only treatment option. Histopathologic examination of liver biopsy specimens is a key element in the diagnostic work-up of infants with suspected EHBA. Pathologic diagnosis aims at excluding non-surgically correctable causes of neonatal cholestasis thereby leading to surgical exploration for confirmation of the diagnosis. All published data indicate that pathologists can diagnose EHBA with high sensitivity, high specificity and reasonable interobserver agreement. The most useful histologic features in the diagnosis of EHBA are portal tract changes including ductular proliferation and bile plugs in ducts and ductules. These lesions are not pathognomonic but can be seen in extrahepatic obstruction of any cause. Total parenteral nutrition (TPN-associated cholestasis and alpha1-antitrypsin (A1AT deficiency cannot be differentiated from EHBA without access to clinical data and may lead to false-positive diagnosis. False-negative interpretation may be caused by early age at diagnosis or by small/indequate specimens. The pathologist also plays a role in the examination of the resected fibrotic segment and of explant specimens. Histopathology can yield prognostic information, being also an indispensable tool in research for the possible pathogenesis of this disease. A well-coordinated, multidisciplinary approach is required in the assessment of suspected cases of EHBA.  Proceedings of the International Course on Perinatal Pathology (part of the 10th International Workshop on Neonatology · October 22nd-25th, 2014 · Cagliari (Italy · October 25th, 2014 · The role of the clinical pathological dialogue in

  19. 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...

  20. Infection by cytomegalovirus in patients with neonatal cholestasis Infecção por cytomegalovirus em pacientes com colestase neonatal

    Directory of Open Access Journals (Sweden)

    Nara Léia Gelle de OLIVEIRA

    2002-04-01

    Full Text Available Background - Neonatal cholestasis syndrome with an intra or extrahepatic origin has been associated to viral infections. The participation of the cytomegalovirus in the etiopathogenesis of neonatal hepatitis has been already known for some time, but only recently there have been indications that this virus may be one of the possible etiological factors for extrahepatic biliary atresia. Aims - To assess the prevalence of infection by cytomegalovirus in patients with intrahepatic cholestasis and extrahepatic cholestasis. To compare the clinical characteristics of the intrahepatic cholestasis and extrahepatic cholestasis groups with the cytomegalovirus serological results. Patients and Methods - This study consisted of 76 patients with neonatal cholestasis who were admitted between January 1980 and January 1999 when they underwent a cytomegalovirus serologic study using the ELISA method. A case note was kept on each patient with the following data: age of patient at admission, serologic result for cytomegalovirus, history of maternal infection, prematurity, fetal distress, birth weight, ponderal gain, choluria and fecal acholia. The final anatomic diagnosis of cholestasis was based on the results of an abdominal ultrasonography, a liver biopsy and its evolution. The patients were then divided into two groups: group I - intrahepatic cholestasis and group II - extrahepatic cholestasis. Each of these groups were then divided into two subgroups: subgroup A - positive serology (IgM for cytomegalovirus and subgroup B - negative serology (IgM for cytomegalovirus. Results - The frequency of positive serology (IgM for cytomegalovirus was 29.4% in children with intrahepatic cholestasis and 28.5% in children with extrahepatic cholestasis. In comparison with group IIB, group IIA presented a higher rate of maternal infection history. The patients in group IIA demonstrated a delayed access to the service in comparison with group IA. The groups did not

  1. 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

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

    Directory of Open Access Journals (Sweden)

    Faust Dominik

    2009-01-01

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

  3. Liver transplant rejection and cholestasis

    International Nuclear Information System (INIS)

    This paper reports on liver transplant biopsies with Tc-99m hepatobiliary scintigraphy in patients with and without rejection (RE) and or cholestasis (CS). The authors reviewed 76 Tc-99m disofenin hepatobiliary studies and corresponding liver biopsies. Uptake was assigned a value of 0 to 3 (0 = normal). Excretion was assigned a value of 0 to 2 (0 = normal). Biopsies were graded on scales of (1) 0 to 12 for findings of CS (0 = normal) and (2) 0 to 2 for RE (0 = normal)

  4. TYPE IC CHOLEDOCHAL CYST PRESENTING AN EXTRAHEPATAL CHOLESTASIS IN A 3 YEAR OLD BOY

    Directory of Open Access Journals (Sweden)

    Muhammad Reza

    2015-10-01

    Full Text Available Choledochal cyst is a rare congenital dilatation of the bile ducts, mostly diagnosed in childhood. Whenappropriate resection is not performed, cholangiocarcinoma may occur in a high incidence within thesecond decade of life. This report aims to present a rare case in experience of diagnosis and managementtype IC choledochal cyst in children. We present case of a 3-year-old boy who came with jaundice anditchy skin, abdominal pain, brownish urine, pales colored of stool. Abdominal ultrasonography andcomputed tomography scan revealed type IC choledochal cyst. Patient underwent complete cyst removalsurgery and bilioenteric anastomosis through Roux-en-y hepaticojejunostomy. Excision biopsy confirmedthe diagnosis of type IC choledochal cyst. Post surgical follow up shown good physical and laboratorycondition  and  there was no  recurrence  of  symptoms. Early  surgical  procedure  through Roux-en-yhepatojejunostomy, has been performed. Long  term  follow up also  facilities good prognostic  to  thepatient. [MEDICINA 2015;46:56-60].Kista  koledokus  adalah merupakan  penyakit  saluran  empedu  bawaan  yang  jarang  dijumpai  danbanyak terdiagnosis pada saat usia anak-anak. Tindakan berupa reseksi kista adalah yang terpentingdilakukan,  jika  tidak  segera  dilakukan  maka  dapat  meningkatkan  resiko  terjadinyacholangiocarcinoma dalam usia dekade kedua penderita dalam kehidupan. Tujuan kasus ini dilaporkanuntuk menggambarkan pengalaman dalam mendiagnosis dan tata  laksana kista koledokal tipe ICyang jarang pada anak-anak. Laporan kasus ini pada anak laki-laki berumur 3 tahun dengan keluhankulit tampak kuning dan gatal, nyeri perut, urin berwarna kecoklatan, tinja yang pucat. Ultrasonografidan CT  scan abdomen memperlihatkan adanya kista koledokus. Tindakan bedah  eksisi kista dananastomosis bilioenterik dengan menggunakan tehnik hepatojejunostomi Roux-en-y. Diagnosa kistakoledokus  tipe  IC  terkonfirmasi  saat  tindakan  eksisi biopsi. Evaluasi  setelah dilakukan  tindakanbedah memperlihatkan hasil yang bagus, baik dari pemeriksaan fisik maupun pemeriksaan penunjangdan hilangnya keluhan yang ada sebelumnya. Walaupun prosedur tindakan hepatojejunustomi Roux-en-y secara dini telah dilakukan, penderita masih membutuhkan evaluasi dalam jangka waktu yanglama. [MEDICINA 2015;46:56-60].

  5. Primary hepatocellular carcinoma in extrahepatic bile duct

    Energy Technology Data Exchange (ETDEWEB)

    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. 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.

  7. Intrahepatic cholestasis and cutaneous bullae associated with glibenclamide therapy.

    OpenAIRE

    Wongpaitoon, V.; Mills, P R; Russell, R I; Patrick, R. S.

    1981-01-01

    Intrahepatic cholestasis and cutaneous bullae associated with glibenclamide therapy are described in a 61-year-old diabetic patient who presented wit hypoglycaemic coma. These features have not previously been reported as side effects of glibenclamide therapy, but intrahepatic cholestasis may occur with chlorpropamide, a similar sulphonylurea agent. The mechanism of this cholestasis is not clear at present.

  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

    International Nuclear Information System (INIS)

    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. Sonographic Features of Extrahepatic Cholangio carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    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

  11. 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

  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. Extrahepatic biliary obstruction; postoperative morbidity and mortality

    International Nuclear Information System (INIS)

    The objectives of this study are to evaluate the surgical management, both definitive and palliative, in selected patients with biliary obstruction and to find out the postoperative morbidity and mortality in these patients. Duration of the study is two years conducted from June 2002 to May 2004. The study was carried out at. the surgical. unit 4 of the Combined Military Hospital and surgical department of the Military Hospital. Thirty eight cases of biliary obstruction were included. A convenient sampling technique was followed. Data analyzed by using SPSS version 10.0 for windows on computer. Descriptive statistics like frequency, percentage, average etc were computed for data presentation. Any inferential test-was not found to be applicable for this descriptive type case series. We selected 38 patients with features of extrahepatic biliary obstruction. Out of these (n 38) 15 patients (39.5%) suffered from benign diseases while those having malignant diseases were 23 (60.5%). 19 (50%) patients died within two years of follow up while 19 (50%) were the survivors. Mortality was maximum for the malignant cases. In benign cases only one patient died. Maximum deaths 6 (31.6%) occurred in the period of up to one month of operation. 20 patients had one or another complication of operation and hence the morbidity came out to be 52%. According to our results the mortality and morbidity related to extrahepatic biliary obstruction in our patients was higher compared to other studies which can only be reduced by early detection and treatment. (author)

  14. New Insights on Intrahepatic Cholestasis of Pregnancy.

    Science.gov (United States)

    Floreani, Annarosa; Gervasi, Maria Teresa

    2016-02-01

    Intrahepatic cholestasis of pregnancy (ICP) is characterized by maternal pruritus, and elevated serum transaminases and bile acids. Genetic defects in at least 6 canalicular transporters have been found. Association studies stress the variability of genotypes, different penetrance, and influence of environmental factors. Serum autotaxin is a sensitive, specific, and robust diagnostic marker. Elevated maternal bile acids correlate with fetal complications. Long-term sequelae for mothers include the gallstone risk and chronic liver disease. There is an association between ICP and hepatitis C. Current treatment is ursodeoxycholic acid, owing to benefits on pruritus, liver function, safety, and decreased rates of adverse effects. PMID:26593298

  15. 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

  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. 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.

  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. 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

  20. 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....

  1. 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

  2. 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.

  3. 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

  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. 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

  6. 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.

  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. Intrahepatic cholestasis in subclinical and overt hyperthyroidism: two case reports

    Directory of Open Access Journals (Sweden)

    Soylu Aliye

    2008-04-01

    Full Text Available Abstract Introduction Non-specific abnormalities in liver function tests might accompany the clinical course of hyperthyroidism. Hyperthyroidism can cause the elevation of hepatic enzymes and bilirubin. Jaundice is rare in overt hyperthyroidism, especially in subclinical hyperthyroidism. On the other hand, the use of anti-thyroid drugs has rarely been associated with toxic hepatitis and cholestatic jaundice. Case presentation Here we present two cases of cholestasis that accompanied two distinct forms of clinical hyperthyroidism. The first patient had a clinical presentation of severe cholestasis in the absence of congestive failure related to hyperthyroidism. The second case had developed intrahepatic cholestasis in the presence of subclinical hyperthyroidism, and improved with rifampicin treatment. Conclusion Hyperthyroidism should be a consideration in non-specific liver dysfunction.

  10. 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...

  11. Retroperitoneal lymphadenopathy: an extrahepatic feature of chronic active hepatitis.

    OpenAIRE

    Hayek, T.; Markel, A.; Goldfeld, M.; Ben-Arie, Y.; Brook, G. J.

    1994-01-01

    We report a patient with chronic active hepatitis in whom one of the initial findings was retroperitoneal lymphadenopathy, detected by abdominal ultrasound examination. Extrahepatic presenting findings of chronic active hepatitis may include arthritis, urticaria, pleurisy and pericarditis, while abdominal lymphadenopathy has been only rarely described. Chronic active hepatitis should be included in the differential diagnosis of abdominal lymphadenopathy.

  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. 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.

  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. Lithocholic acid disrupts phospholipid and sphingolipid homeostasis leading to cholestasis

    OpenAIRE

    Matsubara, Tsutomu; Tanaka, Naoki; Patterson, Andrew D.; Cho, Joo-Youn; Krausz, Kristopher W.; Frank J. Gonzalez

    2011-01-01

    Lithocholic acid (LCA) is an endogenous compound associated with hepatic toxicity during cholestasis. LCA exposure in mice resulted in decreased serum lysophosphatidylcholine (LPC) and sphingomyelin levels due to elevated lysophosphatidylcholine acyltransferase (LPCAT) and sphingomyelin phosphodiesterase (SMPD) expression. Global metabolome analysis indicated significant decreases in serum palmitoyl-, stearoyl-, oleoyl- and linoleoyl-LPC levels after LCA exposure. LCA treatment also resulted ...

  16. 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.

  17. [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

  18. Adjuvant Radio-chemotherapy for extrahepatic biliary tract cancers

    OpenAIRE

    Mentha Gilles; Roth Arnaud D; Bonet Beltrán Marta; Allal Abdelkarim S

    2011-01-01

    Abstract Background Extrahepatic biliary duct cancers (EBDC) are uncommon malignancies characterized by a poor prognosis with high rate of loco-regional recurrence. The purpose of the present study is to assess the feasibility and the potential impact of adjuvant radiotherapy (RT) in a series of patients treated in one institution. Methods Twenty three patients with non-metastatic bile duct cancer treated surgically with curative intent (4 gallbladder, 7 ampullary and 12 cholangiocarcinoma) r...

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

    Directory of Open Access Journals (Sweden)

    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

  20. Role of Adjuvant Chemoradiotherapy for Resected Extrahepatic Biliary Tract Cancer

    International Nuclear Information System (INIS)

    Purpose: To evaluate the effect of adjuvant chemoradiotherapy (CRT) on locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) for patients with extrahepatic biliary tract cancer treated with curative resection. Methods and Materials: The study involved 168 patients with extrahepatic biliary tract cancer undergoing curative resection between August 2001 and April 2009. Of the 168 patients, 115 received adjuvant CRT (CRT group) and 53 did not (no-CRT group). Gender, age, tumor size, histologic differentiation, pre- and postoperative carbohydrate antigen 19-9 level, resection margin, vascular invasion, perineural invasion, T stage, N stage, overall stage, and the use of adjuvant CRT were analyzed to identify the prognostic factors associated with LRC, DFS, and OS. Results: For all patients, the 5-year LRC, DFS, and OS rate was 54.8%, 30.6%, and 33.9%, respectively. On univariate analysis, the 5-year LRC, DFS, and OS rates in the CRT group were significantly better than those in the no-CRT group (58.5% vs. 44.4%, p = .007; 32.1% vs. 26.1%, p = .041; 36.5% vs. 28.2%, p = .049, respectively). Multivariate analysis revealed that adjuvant CRT was a significant independent prognostic factor for LRC, DFS, and OS (p < .05). Conclusion: Our results have suggested that adjuvant CRT helps achieve LRC and, consequently, improves DFS and OS in patients with extrahepatic biliary tract cancer.

  1. 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.

  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. Intrahepatic cholestasis in subclinical and overt hyperthyroidism: two case reports

    OpenAIRE

    Soylu Aliye; Taskale Mustafa; Ciltas Aydin; Kalayci Mustafa; Kumbasar A Baki

    2008-01-01

    Abstract Introduction Non-specific abnormalities in liver function tests might accompany the clinical course of hyperthyroidism. Hyperthyroidism can cause the elevation of hepatic enzymes and bilirubin. Jaundice is rare in overt hyperthyroidism, especially in subclinical hyperthyroidism. On the other hand, the use of anti-thyroid drugs has rarely been associated with toxic hepatitis and cholestatic jaundice. Case presentation Here we present two cases of cholestasis that accompanied two disti...

  8. 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

  9. Alpha 1 Antitrypsin Deficiency in Infants with Neonatal Cholestasis

    Directory of Open Access Journals (Sweden)

    Maryam Monajemzadeh

    2013-10-01

    Full Text Available Objective: Alpha1-antitrypsin deficiency (A1ATD is the most important indication for liver transplantation in children. The gene frequencies vary in different ethnic groups. In the present study, we attempt to determine the frequencies of the most common defective alleles, Z and S, in Iranian children suffering from idiopathic neonatal cholestasis. Eighty-seven infants were typed for Z and S alleles.Methods: In a single center study, 87 consecutive liver biopsies from infants with cholestasis were reviewed and patients with neonatal cholestasis enrolled in the study and cases with confirmed biliary tract atresia excluded. Formalin fixed paraffin embedded blocks were used for DNA extraction. AAT genotype was determined by polymerase chain reaction (PCR assay and amplification of the two most common deficiency variants, S and Z alleles, and then sequencing of PCR products.Findings: There were 48 (55.2% males and 39 (44.8% females, with a median age of 60 days. Out of 87 of the study subject, 2 (2.2% were heterozygous for the S allele, and no ZZ, SS or MZ individual was found in the patients. No other polymorphism was found in the sequencing results.Conclusion: In comparison to other populations, AAT deficiency seems not to be an important etiologic factor for neonatal cholestatic liver disease in Iran; however, further studies are recommended to estimate the true mutant gene frequencies.

  10. 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.

  11. 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

  12. 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.

  13. A meaningful appraisal of cholestasis in serum total bilirubin, cholyglyine, alpha-fetoprotein and carbohydrate antigen19-9

    International Nuclear Information System (INIS)

    Objective: Appraise the clinical significant how the serum total bilirubin (TB), cholylglycine (CG), α-fetoprotein (AFP), carbohydrate antigen 19-9 (CA 19-9) have their concentration changes in the pathological changes of intrahepatic cholestasis through a combined detection to them. Methods: The serum samples from 96 cases of chronic virus hepatitis, 26 cases of liver cirrhosis and 50 cases of normal people were detected by biochemistry for TB, by radioimmunoassay for CG, by electro chemiluminescence for AFP and CA19-9. Results: There is no obvious deference of serum TB in the group without intrahepatic cholestasis, the group of cholestasis without clinical symptoms and the control groups. There is also a marked deference (P<0.01) in the group of cholestasis with clinical symptoms, the group of liver cirrhosis, the group without intrahepatic cholestasis, the control group and the group of cholestasis without clinical symptoms. the serum CG from the groups of intrahepatic cholestasis, the group without intrahepatic cholestasis, and the control group all show a very obvious deference (P<0.01). The serum CA19-9 from the groups of intrahepatic cholestasis and the group without intrahepatic cholestasis show an obvious deference. The serum AFP, CA19-9 from the group of liver cancer show a very obvious deference (P<0.01). Conclusions: In clinc bilirubin is a rough index to reflect cholestasis. It has its own limit in deciding patterns of deferent bile obstruction. In the early stage of intrahepatic cholestasis, that the index of CG is high obviously points out existence of intrahepatic cholestasis. CG and the liver impairment are well interrelated and they are comparatively sensitive indexes of liver function. AFP reflects the regeneration of the liver cell necrosis and it means alarm to the seriousness of intrahepatic cholestasis. CA19-9 is a marker of tumor of biliary tract. The index increase through an initial observation is interrelated to the seriousness of

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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...

  19. 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.

  20. Evaluation and management of intrahepatic and extrahepatic cholangiocarcinoma.

    Science.gov (United States)

    Esnaola, Nestor F; Meyer, Joshua E; Karachristos, Andreas; Maranki, Jennifer L; Camp, E Ramsay; Denlinger, Crystal S

    2016-05-01

    Cholangiocarcinomas are rare biliary tract tumors that are often challenging to diagnose and treat. Cholangiocarcinomas are generally categorized as intrahepatic or extrahepatic depending on their anatomic location. The majority of patients with cholangiocarcinoma do not have any of the known or suspected risk factors and present with advanced disease. The optimal evaluation and management of patients with cholangiocarcinoma requires thoughtful integration of clinical information, imaging studies, cytology and/or histology, as well as prompt multidisciplinary evaluation. The current review focuses on recent advances in the diagnosis and treatment of patients with cholangiocarcinoma and, in particular, on the role of endoscopy, surgery, transplantation, radiotherapy, systemic therapy, and liver-directed therapies in the curative or palliative treatment of these individuals. Cancer 2016;122:1349-1369. © 2016 American Cancer Society. PMID:26799932

  1. 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.

  2. 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)

  3. 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.

  4. Diagnostic value of glycocholic acid for intrahepatic cholestasis in pregnancy

    International Nuclear Information System (INIS)

    The content of glycocholic acid (CG) in pregnant women's sera is detected with CG radioimmunoassay (RIA). The content of CG in sera of normal pregnant women after 32 weeks is ascended slightly with the increasing of pregnant month. It is less than 7.0 μmol/l before 31 weeks in pregnancy and less than 9.4 μmol/l after 32 weeks. The serum CG content of patients with intrahepatic cholestasis in pregnancy (ICP) is increased by 100%. The CG value of about half patients appears earlier than pruritus and ALT rise, the earliest CG increasing appears in the 20th pregnant week. It is the most sensitive method for ICP early diagnosis. 136 cases of ICP patients are observed and the results show that the higher the CG content, the higher the rate of intrauterine fetal anoxia; therefore, the dynamic observation of CG content in ICP patients is a dependable objective for surveillance fetal prognosis

  5. 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.

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

    OpenAIRE

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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...

  9. 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.

  10. 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

  11. 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...

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

    Directory of Open Access Journals (Sweden)

    Ajmal Kader

    2014-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Watanabe,Makoto

    1979-08-01

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

  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. An inguinal hernia sac tumor of extrahepatic cholangiocarcinoma origin

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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.).

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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.

  20. Clinical and ABCB11 profiles in Korean infants with progressive familial intrahepatic cholestasis

    Science.gov (United States)

    Park, Ji Sook; Ko, Jae Sung; Seo, Jeong Kee; Moon, Jin Soo; Park, Sung Sup

    2016-01-01

    AIM: To investigate clinical profiles and mutations of ABCB11 in Koreans with progressive familial intrahepatic cholestasis 2 and review the differences between Koreans and others. METHODS: Of 47 patients with neonatal cholestasis, five infants had chronic intrahepatic cholestasis with normal γ-glutamyl transpeptidase. Direct sequencing analyses of ABCB11, including exons and introns, were performed from peripheral blood. RESULTS: Living donor-liver transplantation was performed in four patients because of rapidly progressive hepatic failure and hepatocellular carcinoma. Three missense mutations were found in two patients: compound heterozygous 677C>T (S226L)/3007G>A (G1003R) and heterozygous 2296G>A (G766R). The mutations were located near and in the transmembranous space. CONCLUSION: Alterations in the transmembrane of the bile salt export pump in the Korean infants were different from those previously reported in Chinese, Japanease, Taiwanese, and European patients. PMID:27239116

  1. 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.

  2. Imaging diagnosis--extrahepatic biliary tract obstruction secondary to a duodenal foreign body in a cat.

    Science.gov (United States)

    Della Santa, Daniele; Schweighauser, Ariane; Forterre, Franck; Lang, Johann

    2007-01-01

    A 13-month-old, neutered female domestic shorthaired cat was evaluated for vomiting, anorexia, and lethargy. The cat was icteric and hyperbilirubinemic. Radiographically a partially radiolucent proximal duodenal foreign body was suspected. Ultrasonographically, there was a foreign body at the level of the duodenal papilla and dilation of the common bile duct and cystic duct; a diagnosis of extrahepatic biliary tract obstruction secondary to a duodenal foreign body was made. Sonographic findings were confirmed at surgery and a duodenal foreign body was removed. This information defines duodenal foreign body as a cause of extrahepatic biliary obstruction in cats. PMID:17899980

  3. 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.

  4. [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

  5. 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

  6. 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

  7. Adjuvant Radio-chemotherapy for extrahepatic biliary tract cancers

    Directory of Open Access Journals (Sweden)

    Mentha Gilles

    2011-06-01

    Full Text Available Abstract Background Extrahepatic biliary duct cancers (EBDC are uncommon malignancies characterized by a poor prognosis with high rate of loco-regional recurrence. The purpose of the present study is to assess the feasibility and the potential impact of adjuvant radiotherapy (RT in a series of patients treated in one institution. Methods Twenty three patients with non-metastatic bile duct cancer treated surgically with curative intent (4 gallbladder, 7 ampullary and 12 cholangiocarcinoma received 3D conformal external beam RT to a median total dose of 50.4Gy. Concurrent chemotherapy based on 5-FU was delivered to 21 patients (91%. Surgical margins were negative in 11 patients (48%, narrow in 2 (9%, and microscopically involved in 8 (35%. Eleven patients (55% had metastatic nodal involvement. The average follow-up time for all patients was 30 months (ranging from 3-98. Results Acute gastrointestinal grade 2 toxicity (RTOG scale was recorded in 2 patients (9%. Nausea or vomiting grade 1 and 2 was observed in 8 (35% and 2 patients (9% respectively. Only one patient developed a major late radiation-induced toxicity. The main pattern of recurrence was both loco-regional and distant (liver, peritoneum and/or lung. No difference was observed in loco-regional control according to the tumor location. The 5-year actuarial loco-regional control rate was 48.3% (67% and 30% for patients operated on with negative and positive/narrow/unknown margins respectively, p = 0.04. The 5-year actuarial overall survival was of 35.9% for the entire group (61.4% in case of negative margins and 16.7% in case of positive/narrow/unknown margins, p = 0.07. Conclusions Postoperative RT with 50-60 Gy is feasible with acceptable acute and late toxicities. The potential benefit observed in our series may support the use of adjuvant RT in patients with locally advanced disease. Prospective randomized trials are warranted to confirm definitively the role of RT in this tumor

  8. Adjuvant Radio-chemotherapy for extrahepatic biliary tract cancers

    International Nuclear Information System (INIS)

    Extrahepatic biliary duct cancers (EBDC) are uncommon malignancies characterized by a poor prognosis with high rate of loco-regional recurrence. The purpose of the present study is to assess the feasibility and the potential impact of adjuvant radiotherapy (RT) in a series of patients treated in one institution. Twenty three patients with non-metastatic bile duct cancer treated surgically with curative intent (4 gallbladder, 7 ampullary and 12 cholangiocarcinoma) received 3D conformal external beam RT to a median total dose of 50.4Gy. Concurrent chemotherapy based on 5-FU was delivered to 21 patients (91%). Surgical margins were negative in 11 patients (48%), narrow in 2 (9%), and microscopically involved in 8 (35%). Eleven patients (55%) had metastatic nodal involvement. The average follow-up time for all patients was 30 months (ranging from 3-98). Acute gastrointestinal grade 2 toxicity (RTOG scale) was recorded in 2 patients (9%). Nausea or vomiting grade 1 and 2 was observed in 8 (35%) and 2 patients (9%) respectively. Only one patient developed a major late radiation-induced toxicity. The main pattern of recurrence was both loco-regional and distant (liver, peritoneum and/or lung). No difference was observed in loco-regional control according to the tumor location. The 5-year actuarial loco-regional control rate was 48.3% (67% and 30% for patients operated on with negative and positive/narrow/unknown margins respectively, p = 0.04). The 5-year actuarial overall survival was of 35.9% for the entire group (61.4% in case of negative margins and 16.7% in case of positive/narrow/unknown margins, p = 0.07). Postoperative RT with 50-60 Gy is feasible with acceptable acute and late toxicities. The potential benefit observed in our series may support the use of adjuvant RT in patients with locally advanced disease. Prospective randomized trials are warranted to confirm definitively the role of RT in this tumor location

  9. Hepaticocystic duct and a rare extra-hepatic "cruciate" arterial anastomosis: a case report

    Directory of Open Access Journals (Sweden)

    Abeysuriya Vasitha

    2008-02-01

    Full Text Available Abstract Introduction The variations in the morphological characteristics of the extra-hepatic biliary system are interesting. Case presentation During the dissection of cadavers to study the morphological characteristics of the extra-hepatic biliary system, a 46-year-old male cadaver was found to have drainage of the common hepatic duct drains directly into the gall bladder neck. The right and left hepatic ducts were not seen extra-hepatically. Further drainage of the bile away from the gallbladder and into the duodenum was provided by the cystic duct. Formation of the common bile duct by the union of the common hepatic duct and cystic duct was absent. Further more the right hepatic artery was found to be communicating with the left hepatic artery by a "bridging artery" after giving rise to the cystic artery. An accessory hepatic artery originated from the "bridging artery" forming a "cruciate" hepatic arterial anastomosis. Conclusion Combination of a Hepaticocystic duct and an aberrant variation in the extra-hepatic arterial system is extremely rare.

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

    OpenAIRE

    SAKATA, JUN; Shirai, Yoshio; Wakai, Toshifumi; Nomura, Tatsuya; Sakata, Eiko; Hatakeyama, Katsuyoshi

    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.

  11. 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

  12. 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

  13. 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

  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. 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

  16. Gadopentetate dimeglumine-enhanced MR cholangiopancreatography in infants with cholestasis

    International Nuclear Information System (INIS)

    Biliary atresia (BA) is a progressive, obliterative cholangiopathy that occurs in neonates with hepatic portoenterostomy the treatment of choice, but early surgery is important for optimum outcomes. MRI, including MR cholangiopancreatography (MRCP) may be a diagnostically useful alternative to US, but the heavily T2-weighted sequences used include not only bile duct signals, but also other heterogeneously high signal intensities from surrounding structures. To evaluate the effects of gadolinium when used to decrease background signal intensity on T2-weighted MR cholangiopancreatography (MRCP) in infants and to evaluate the qualitative improvement of the depiction of the common bile duct (CBD) for evaluating neonatal cholestasis. Our Institutional Review Board approved this prospective study. MRCP was performed with gadopentetate dimeglumine injection using a 1.5-T scanner. Pre- and postcontrast MRCP images were compared. Forty-nine infants (male:female = 21:28; age 0-12 months, mean 2.3) were included. The final diagnoses were biliary atresia (BA) in 28 cases and non-BA in 21. Quantitative analysis was conducted using region-of-interest measurements of mean signal intensities of the liver, pancreatic head and gallbladder (if defined). Qualitative analysis was performed by four radiologists who subjectively scored image confidence in the presence of CBD on a 4-point scale (0 for definitely absent, 1 for probably absent, 2 for probably present, and 3 for definitely present). The signal-to-noise ratios were significantly decreased in the liver and pancreatic head after contrast medium enhancement (mean 5.7→4.0 in liver and mean 44.9→12.7 in the pancreatic head; P < 0.0001), and this finding was constant in both the BA and the non-BA group. The mean confidence score in the presence of CBD decreased in the BA group (0.9→0.5; P < 0.0001), but did not change significantly in the non-BA group (2.0→2.1; P = 0.459) after contrast medium enhancement. Both intra- and

  17. 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.

  18. 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.

  19. 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)

  20. 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...

  1. 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...

  2. Effects of ursodeoxycholic acid treatment on nutrition and liver function in patients with cystic fibrosis and longstanding cholestasis.

    OpenAIRE

    Cotting, J; Lentze, M J; Reichen, J

    1990-01-01

    The prevalence of biliary and hepatic diseases is increasing in patients with cystic fibrosis as more of them reach adult life. There is no effective treatment or method of preventing cholestasis in cystic fibrosis, although beneficial effects have been ascribed to the tertiary bile acid, ursodeoxycholate, in other forms of chronic cholestasis. We evaluated prospectively the effects of a six month course of ursodeoxycholate (15-20 mg/kg per day) in eight, mostly adult, patients with cystic fi...

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

    Energy Technology Data Exchange (ETDEWEB)

    Engeler, C.M.; Kuni, C.C.; Engeler, C.E.; DuCret, R.P.; Boudreau, R.J. (Minnesota Univ., Minneapolis, MN (United States). Dept. of Radiology); Nakhieh, R. (Henry Ford Hospital, Detroit, MI (United States). Dept. of Lab. Medicine and Pathology)

    1992-10-01

    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 {sup 99m}-Tc-DISIDA scintigraphy can differentiate between transplants with and without rejection/cholestasis but not between rejection and cholestasis. If {sup 99m}-Tc-DISIDA excretion is normal, rejection and cholestasis and unlikely. (orig.).

  4. 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.)

  5. 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.

  6. 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...

  7. 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...

  8. Helical CT cholangiography with multiplanar reformation: utility in patients with extrahepatic biliary obstruction

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the utility of the CT cholangiography by using helical CT with multiplanar reformation in patients with extrahepatic biliary obstruction. Helical CT was performed in 36 patients of extrahepatic biliary obstruction confirmed by operation or invasive cholangiography(percutaneous transhepatic cholangiography or endoscopic retrograde cholagiopancreatography). The cause of obstructions were 18 benign diseases(11 common bile duct stones, four choledochal cysts, three pancreatitis) and 18 malignant diseases (seven common bile duct carcinomas, seven pancreatic head carcinomas, three ampullary carcinomas, one periampullary duodenal carcinoma). After helical scanning through the extrahepatic bile duct, retrospective reconstruction of the helical data was performed. And then, CT cholagiogram was obtained with multiplanar reformation. We evaluated the technical success rate and the accuracy in determinating the level and the cause of the obstruction. We compared findings of the CT cholagiogram with that of operation or invasive cholangiography. In 100% (36/36) of cases, CT cholangiography could be obtained successfully. The accuracy of the CT cholangiography in determinating the level of the obstruction was 100% (11 cases of suprapancreatic duct, 13 cases of intrapancreatic duct, 13 cases of infrapancreatic duct and ampulla), and the accuracy in determinating the cause of the obstruction was 91.7% (all cases of 18 benign diseases, and 15 cases of 18 malignant diseases). In evaluating the obstruction of extrahepatic bile ducts, the CT cholangiography by using helical CT with multiplanar reformation is an useful noninvasive method in determinating the level and the cause of biliary obstruction and therefore could replace the invasive cholangiography

  9. 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...

  10. 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 < 30 ml/min/1.73 sqm, including those on dialysis. In kidney-transplanted patents, caution is due

  11. Percutaneous treatment of extrahepatic bile duct stones assisted by balloon sphincteroplasty and occlusion balloon

    International Nuclear Information System (INIS)

    To describe the technical feasibility and usefulness of extrahepatic biliary stone removal by balloon sphincteroplasty and occlusion balloon pushing. Fifteen patients with extrahepatic bile duct stones were included in this study. Endoscopic stone removal was not successful in 13 patients, and two patients refused the procedure due to endoscopy phobia. At first, all patients underwent percutaneous transhepatic biliary drainage (PTBD). A few days later, through the PTBD route, balloon assisted dilatation for common bile duct (CBD) sphincter was performed, and then the stones were pushed into the duodenum using an 11.5 mm occlusion balloon. Success rate, reason for failure, and complications associated with the procedure were evaluated. Eight patients had one stone, five patients had two stones, and two patients had more than five stones. The procedure was successful in 13 patients (13/15). In 12 of the patients, all stones were removed in the first trial. In one patients, residual stones were discovered on follow-up cholangiography, and were subsequently removed in the second trial. Technical failure occurred in two patients. Both of these patients had severely dilated CBD and multiple stones with various sizes. Ten patients complained of pain in the right upper quadrant and epigastrium of the abdomen immediately following the procedure, but there were no significant procedure-related complications such as bleeding or pancreatitis. Percutaneous extrahepatic biliary stone removal by balloon sphincteroplasty and subsequent stone pushing with occlusion balloon is an effective, safe, and technically feasible procedure which can be used as an alternative method in patients when endoscopic extrahepatic biliary stone removal was not successful

  12. 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.

  13. CD24 expression predicts distant metastasis in extrahepatic bile duct cancer

    OpenAIRE

    Kyubo Kim; Hye Sook Min; Eui Kyu Chie; Jin-Young Jang; Sun Whe Kim; Sae-Won Han; Do-Youn Oh; Seock-Ah Im; Tae-You Kim; Yung-Jue Bang; Ja-June Jang; Sung W Ha

    2013-01-01

    AIM: To evaluate the prognostic significance of CD24 expression in patients undergoing adjuvant chemoradiotherapy for extrahepatic bile duct (EHBD) cancer. METHODS: Eighty-four patients with EHBD cancer who underwent curative resection followed by adjuvant chemoradiotherapy were enrolled in this study. Postoperative radiotherapy was delivered to the tumor bed and regional lymph nodes up to a median of 40 Gy (range: 40-56 Gy). All patients also received fluoropyrimidine chemotherapy for radios...

  14. 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

  15. Percutaneous treatment of extrahepatic bile duct stones assisted by balloon sphincteroplasty and occlusion balloon

    Energy Technology Data Exchange (ETDEWEB)

    Park, Yong Sung; Kim, Ji Hyung; Choi, Young Woo; Lee, Tae Hee; Hwang, Cheol Mog; Cho, Young Jun; Kim, Keum Won [Konyang University Hospital, Daejeon (Korea, Republic of)

    2005-12-15

    To describe the technical feasibility and usefulness of extrahepatic biliary stone removal by balloon sphincteroplasty and occlusion balloon pushing. Fifteen patients with extrahepatic bile duct stones were included in this study. Endoscopic stone removal was not successful in 13 patients, and two patients refused the procedure due to endoscopy phobia. At first, all patients underwent percutaneous transhepatic biliary drainage (PTBD). A few days later, through the PTBD route, balloon assisted dilatation for common bile duct (CBD) sphincter was performed, and then the stones were pushed into the duodenum using an 11.5 mm occlusion balloon. Success rate, reason for failure, and complications associated with the procedure were evaluated. Eight patients had one stone, five patients had two stones, and two patients had more than five stones. The procedure was successful in 13 patients (13/15). In 12 of the patients, all stones were removed in the first trial. In one patients, residual stones were discovered on follow-up cholangiography, and were subsequently removed in the second trial. Technical failure occurred in two patients. Both of these patients had severely dilated CBD and multiple stones with various sizes. Ten patients complained of pain in the right upper quadrant and epigastrium of the abdomen immediately following the procedure, but there were no significant procedure-related complications such as bleeding or pancreatitis. Percutaneous extrahepatic biliary stone removal by balloon sphincteroplasty and subsequent stone pushing with occlusion balloon is an effective, safe, and technically feasible procedure which can be used as an alternative method in patients when endoscopic extrahepatic biliary stone removal was not successful.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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.

  18. 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.

  19. 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...

  20. 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...

  1. 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...

  2. ER stress contributes to alpha-naphthyl isothiocyanate-induced liver injury with cholestasis in mice.

    Science.gov (United States)

    Yao, Xiaomin; Li, Yue; Cheng, Xiaoyan; Li, Hongwei

    2016-06-01

    Endoplasmic reticulum (ER) stress is involved in the development of several liver diseases and tumors. This study investigated the underlying mechanisms of α-naphthyl isothiocyanate (ANIT)-induced liver injury with cholestasis in mice and found ER stress contributes to the injury. All animals were randomly divided into three groups. In the ANIT-intoxicated group, mice were intragastrically given 100mg/kg ANIT (dissolved in corn oil), while the other groups received an equal volume of vehicle as control. After 24 and 48h of ANIT administration, blood samples and liver tissues of all animals were collected for serum biochemistry and hepatic histopathological examinations to evaluate liver injuries with cholestasis. Hepatocellular apoptosis was assessed by the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. The expression of hepatic ER stress-related markers was determined by real-time PCR, immunohistochemical assay and Western blot. ANIT was found to significantly induce liver injury with cholestasis compared with control mice as evidenced by the increase of serum transaminases and total bilirubin (TBil), and histopathological changes in mice. ANIT remarkably induced hepatocellular apoptosis, upregulated the expression of caspase-9 and cytochrome c, and inhibited the gene and protein expression of proliferating cell nuclear antigen (PCNA). The gene expression of ER stress-related markers, including glucose-regulated protein 78 (GRP78), protein kinase R-like ER kinase (PERK), eukaryotic initiation factor 2α (eIF2α), inositol requiring enzyme-1α (IRE-1α) and activating transcription factor 6 (ATF6) was upregulated by ANIT in mice. ANIT also upregulated the protein expression of GRP78 and activated the phosphorylation of IRE1. These results suggested that ANIT induced liver injury with cholestasis partly due to its ability to activate the ER stress pathway. PMID:27173049

  3. 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,...

  4. 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

  5. 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

  6. 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

  7. Altered integrity and decreased expression of hepatocyte tight junctions in rifampicin-induced cholestasis in mice

    International Nuclear Information System (INIS)

    Rifampicin is a well-known hepatotoxicant, but little is known about the mechanism of rifampicin-induced hepatotoxicity. The aim of this study was to characterize the expression and localization of hepatocyte tight junctions in rifampicin-induced cholestasis in mice. Cholestasis was induced by administration of rifampicin (200 mg/kg) for 7 consecutive days or treatment with a single dose of rifampicin (200 mg/kg) by gastric intubation. The expression of mRNA for hepatic zonula occludens (ZO)-1, ZO-2, ZO-3, occludin and claudin-1 was determined using RT-PCR. Localization of ZO-1 and occludin was detected using immunofluorescence. Results showed that there was an 82-fold increase in the conjugated bilirubin in serum in rifampicin-treated mice. In addition, an 8-fold increase in total bile acid in serum was observed after a seven-day administration of rifampicin. The integrity of hepatocyte ZO-1 and occludin was altered by a seven-day administration of rifampicin. Importantly, the integrity and intensity of hepatocyte tight junctions were altered as early as 30 min after a single dose of rifampicin. The expression of hepatic ZO-1 and ZO-2 mRNA was significantly decreased, beginning as early as 30 min and remaining a lower level 12 h after a single dose of rifampicin. Taken together, these results suggest that the altered integrity and internalization of hepatocyte tight junctions are associated with rifampicin-induced cholestasis.

  8. Effect of Obstructive Cholestasis on Sperm Parameters in the Adult Male Rats

    Directory of Open Access Journals (Sweden)

    E. Nasiri

    2005-10-01

    Full Text Available Introduction & Objective: Obstructive cholestasis is associated with overproduction of endogenous opioids , nitric oxide and cytokins in the blood streams. These consequences may affect sex hormones since proper fertility will be resulted from physiological balance of sex hormones, we investigated the relationship between obstructive cholestasis and gonadotropins and sperm parameters in adult male rats.Materials & Methods: To study this, we used three groups of animals: control (No-surgery, Sham (surgical control, and cholestatic (surgical ligation of the bile duct. After 3 weeks all animals were killed by ether, and serum concentrations of FSH and LH were determined by radioimmunoassay, sperm parameters were evaluated by light microscop.Results: The findings of this study showed that LH and FSH levels decreased significantly in cholestatic compared to control and sham groups (p0.05.Conclusion: These findings indicated that obstructive cholestasis lead to decrease in the levels of serum gonadotropins, but it has no significant effect on sperm parameters. We speculated that spermatogenesis, and sperm parameters were not dependent on gonadotropin hormones but other factors may involved.

  9. 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

  10. 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

  11. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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

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

    Directory of Open Access Journals (Sweden)

    Yu Yamaura

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

  15. Maternal and neonatal outcome in obstetric cholestasis: a comparison of early versus late term delivery

    International Nuclear Information System (INIS)

    To evaluate maternal and neonatal outcome in Obstetric Cholestasis (OC) in early versus late term delivery. Study Design: Retrospective cohort study. Place and Duration of Study: Aga khan hospital for women (AKHW) Karimabad, Karachi, from 1st Jan, 2011 to 31st Oct, 2012. Patient and Methods: This was a retrospective cohort study. All patients of OC with singleton pregnancy, admitted for labor induction between Jan 2011 to Oct 2012 were included in the study. At or after 37 week of gestation, patient is offered labor induction. Patients were divided in two groups as in early term delivery (Group A) and late term delivery (Group B). Early term delivery is taken from 37+o to 37+6 and late term delivery at or after 38 weeks of gestation. The demographic, laboratory and clinical data of these patients were collected from their medical record. Maternal and neonatal outcome were analyzed using SPSS version 19. Results: The study found that in obstetric cholestasis patients admitted for labor induction, the risk of caesarean delivery was higher in group A (before 38 weeks) as compared to group B (after 38 weeks). There was no difference in postpartum hemorrhage and drop in hemoglobin between two groups. Obstetric cholestasis was not associated with adverse perinatal outcome such as intrauterine death (IUD), low Apgar Scores, respiratory distress and neonatal intensive care admission in both the groups. However more cases of neonatal jaundice were observed in babies born after 38 weeks. Conclusion: OC patients who deliver after 38 weeks of gestation have a higher chance of vaginal delivery without increasing the risk of IUD. (author)

  16. 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

  17. 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...

  18. Value of fasting serum glycocholic acid radioimmunoassay in the diagnosis of intrahepatic cholestasis of pregnancy

    International Nuclear Information System (INIS)

    1606 pregnant women were detected for their fasting serum glycocholic acid with radioimmunoassay (CG RIA) during January 1990 to April 1992. 63 cases of intrahepatic cholestasis of pregnancy (ICP) were diagnosed and verified. The upper limit of normal CG was 2640 mg/L, the positive detected rate was 98% and the incidence of ICP was 3.9%. A preliminary analysis was made on its value in the diagnosis of ICP, its relationship to contamination of amniotic fluid and choice of child delivery way. It is found that CG RIA is of value in early diagnosis of ICP, in predication of fetal distress and hence, is helpful in lowering perinatal mortality

  19. 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

  20. 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...

  1. 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

  2. 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.

  3. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  5. External Radiation Therapy Combined with Hyperthermia in the Carcinoma of Extrahepatic Biliary System

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Hoon Sik [Hallym University College of Medicine, Seoul (Korea, Republic of)

    1992-06-15

    From January 1980 to September 1990, 7 patients with carcinoma of the extrahepatic biliary system received external radiation therapy combined with hyperthermia. of the 3 patients with extrahepatic bile duct cancer, two were primary cholangiocarcinoma and one was metastatic peripancreatic carcinoma. Of the 4 patients with carcinoma of the gallbladder, two were locoregionally advanced and unresectable carcinoma and the remaining two were local-regional recurrence after cholecystectomy. They were all pathologically proven adenocarcinoma. The radiation dose received ranged from 3000 cGy/2 weeks to 5040 cGy/ 7 weeks. The hyperthermia was done once or twice a week and 4 to 12 sessions in total. The tumor response was confirmed by T-tube cholangiography, percutaneous transhepatic cholangiography and CT scan. 6 out of 7(86%) showed partial regression of the tumor. The median survival time was 7 months (range 4-11 Months). 6 out of 7 patients were dead : one died of septicemia, 4 of primary disease, one of distant metastases. Only one out of 7 patients is still alive but new metastatic lesion was found. There was not any treatment related deaths. There was also no evidence of treatment related problems with liver, stomach and duodenum, although the observation period was short.

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. The adverse influence of pregnancy upon sulphation: a clue to the pathogenesis of intrahepatic cholestasis of pregnancy?

    Science.gov (United States)

    Davies, M H; Ngong, J M; Yucesoy, M; Acharya, S K; Mills, C O; Weaver, J B; Waring, R H; Elias, E

    1994-12-01

    Sulphation of oestrogens and monohydroxy bile acids is important in attenuating their cholestatic potential. Thus, impairment of sulphation could lead to retention of cholestatic compounds and precipitate intrahepatic cholestasis in susceptible individuals. We tested the hypothesis that such a mechanism may be involved in the pathogenesis of intrahepatic cholestasis of pregnancy. In vivo and in vitro assessment of sulphation capacity was performed in patients with cholestasis of pregnancy, compared with control females on and off the oestrogen-containing oral contraceptive pill and control individuals during normal pregnancy and post partum, to assess the influence of high oestrogen states upon this metabolic pathway. During in vivo studies utilising paracetamol as a metabolic probe, the proportion of paracetamol sulphate and sulphate: glucuronide ratio were decreased in those with elevated oestrogens, whether the rise in oestrogens was endogenous, in pregnancy (paracetamol sulphate p < 0.05; paracetamol sulphate:glucuronide ratio p < 0.01), or exogenous, with the contraceptive pill (paracetamol sulphate p = 0.2; paracetamol sulphate:glucuronide ratio p < 0.001). In vitro, platelet sulphotransferase activity was measured, utilising phenol as substrate. Sulphotransferase activity decreased during pregnancy compared with repeat measurements post partum (p < 0.005) and compared with non-pregnant individuals (p < 0.05). In conclusion, we have shown that elevated oestrogens are associated with significant impairment in sulphation capacity. An imbalance of sulphation with glucuronidation provoked by high circulating oestrogen levels may be contributory in the pathogenesis of cholestasis of pregnancy. PMID:7699239

  13. 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.

  14. Colorectal cancer patients before resection of hepatic metastases. Impact of 18F-FDG PET on detecting extrahepatic disease

    International Nuclear Information System (INIS)

    Aim: Evaluation of the role of FDG-PET in comparison to conventional staging methods for detecting extrahepatic tumour deposits prior to resection of liver metastases. Patients, methods: In our prospective study, 58 patients (24 women, 34 men; age 33-81 years) with liver metastases of colorectal carcinoma underwent FDG-PET. Images were acquired in 3D-mode including transmission scans and reconstructed iteratively. For conventional staging all patients underwent abdominal ultrasound, helical computed tomography (CT) of the thorax and abdomen, and colonoscopy/rectoscopy. A preliminary therapeutic decision was established without knowledge of the FDG-PET findings. Thereafter, it was revised or confirmed according to the results of FDG-PET. Results: In 3/58 patients extrahepatic tumour deposits were concordantly identified with both conventional staging methods and FDG-PET. However, in one case, both conventional methods and FDG-PET were false positive regarding pulmonary metastases. In 12/58 patients, nothing but FDG-PET detected extrahepatic tumour masses, which were later confirmed either by histology or follow-up. Conclusion: Our study suggests than in 21% of patients exclusively FDG-PET is an appropriate diagnostic tool to reveal extrahepatic metastases or local recurrence of colorectal carcinoma. Our results demonstrate that FDG-PET provides relevant additional information for accurate therapeutic planning as compared to the conventional combination of staging methods. Therefore, FDG-PET has to exert a decisive influence on the decision for resection of hepatic metastases. (orig.)

  15. 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

  16. 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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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

  18. 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.

  19. Local proliferation and extrahepatic recruitment of liver macrophages (Kupffer cells) in partial-body irradiated rats

    International Nuclear Information System (INIS)

    The relative significance of local proliferation and extrahepatic recruitment of Kupffer cells was investigated by partial-body irradiation before the induction of macrophage hyperplasia by zymosan. There was no difference in growth of the Kupffer cells population between nonirradiated rats and rats irradiated with the liver shielded, whereas irradiation of the liver with the rest of the body (bone marrow) shielded resulted in strong inhibition of growth (-61%). Splenectomy combined with bone marrow irradiation inhibited growth to a lesser extent as compared to liver irradiation (-38%). Monocyte and other leukocyte numbers were strongly reduced in peripheral blood and their accumulation in the liver was completely prevented by bone marrow irradiation. Our results demonstrate that local proliferation of resident Kupffer cells represents the predominant source for their increased number during hyperplasia

  20. 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)

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

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

    International Nuclear Information System (INIS)

    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)

  7. 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).

  8. Hypervitaminosis A inducing intra-hepatic cholestasis--a rare case report.

    Science.gov (United States)

    Ramanathan, Vivek S; Hensley, Gary; French, Samuel; Eysselein, Victor; Chung, David; Reicher, Sonya; Pham, Binh

    2010-04-01

    The use of over-the-counter supplements is commonplace in today's health conscious society. We present an unusual case of intrahepatic cholestasis caused by vitamin A intoxication. The patient consumed one Herbalife shake with two multivitamin tablets of the same brand for 12 years. When calculated this equated to more than the recommended daily allowance for vitamin A consumption. Deranged liver function tests were consistent with a cholestatic process. Liver biopsy was obtained and revealed features pathognomonic of vitamin A toxicity, without the usual fibrosis. When the supplements were ceased, his jaundice and alkaline phosphatase completely normalized. This case highlights the importance of health care providers documenting non-prescribed dietary supplements and considering them in the etiology of cholestatic liver disease. PMID:19944093

  9. The observation of serum cholyglycine levels in patients with intrahepatic cholestasis of pregnancy

    International Nuclear Information System (INIS)

    To explore the clinical significance of empty abdominal serum Cholyglycine(CG) levels on the diagnosis of patient with Intrahepatic Cholestasis of Pregnancy(ICP), the serum levels of CG, TBA, TBIL and ALT in 400 normal pregnant women and in 87 pregnant patients with ICP were analyzed retrospectively. The results showed that the serum CG levels of patients with ICP were significant higher than that of normal control (P<0.001). The positive rate of serum CG was 100%. The serum levels of TBA, TBIL and ALT in patients with ICP were slightly higher than that of normal controls. The positive rates of TBA, TBIL and ALT were 36.5%, 12.2% and 35.6% respectively. The serum CG levels may be regarded as an economical and sensitive indicator in diagnosis of patients with ICP in the earlier stage. (authors)

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. Biliary tree stem/progenitor cells in glands of extrahepatic and intraheptic bile ducts: an anatomical in situ study yielding evidence of maturational lineages

    OpenAIRE

    Carpino, Guido; Cardinale, Vincenzo; Onori, Paolo; Franchitto, Antonio; Berloco, Pasquale Bartolomeo; Rossi, Massimo; Wang, Yunfang; Semeraro, Rossella; Anceschi, Maurizio; Brunelli, Roberto; Alvaro, Domenico; Reid, Lola M.; Gaudio, Eugenio

    2011-01-01

    Stem/progenitors have been identified intrahepatically in canals of Hering and extrahepatically in glands of the biliary tree. Glands of the biliary tree (peribiliary glands: PBGs) are tubulo-alveolar glands with mucinous and serous acini, located deep within intrahepatic and extrahepatic bile ducts. We have shown that biliary tree stem/progenitors (BTSCs) are multipotent, giving rise in vitro and in vivo to hepatocytes, cholangiocytes or pancreatic islets. Cells with the phenotype of BTSCs a...

  16. Pancreatic enzymes in the epithelium of intrahepatic large bile ducts and in hepatic bile in patients with extrahepatic bile duct obstruction.

    OpenAIRE

    Terada, T.; Morita, T; Hoso, M; Nakanuma, Y

    1994-01-01

    AIM--To determine whether pancreatic enzymes are present in hepatic bile and in intrahepatic bile duct epithelium. METHODS--The activity and proteins of pancreatic enzymes (pancreatic alpha-amylase, lipase, trypsin/trypsinogen) in hepatic bile were investigated using biochemical and western blot analyses in 25 patients with extrahepatic bile duct obstruction. Immunolocalization of enzyme proteins was evaluated by immunohistochemistry in 20 necropsy livers with extrahepatic bile duct obstructi...

  17. 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.

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

    OpenAIRE

    John Wysocki; Rishi Agarwal; Laura Bratton; Jeremy Nguyen; Mandy Crause Weidenhaft; Nathan Shores; Kimbrell, Hillary Z.

    2014-01-01

    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 c...

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

    International Nuclear Information System (INIS)

    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

  20. Epidermal growth factor upregulates Skp2/Cks1 and p27kip1 in human extrahepatic cholangiocarcinoma cells

    Science.gov (United States)

    Kim, Ja-yeon; Kim, Hong Joo; Park, Jung Ho; Park, Dong Il; Cho, Yong Kyun; Sohn, Chong Il; Jeon, Woo Kyu; Kim, Byung Ik; Kim, Dong Hoon; Chae, Seoung Wan; Sohn, Jin Hee

    2014-01-01

    AIM: To evaluate the expression status of S-phase kinase-associated protein 2 (Skp2)/cyclin-dependent kinases regulatory subunit 1 (Cks1) and p27kip1, and assess the prognostic significance of Skp2/Cks1 expression with p27kip1 in patients with extrahepatic cholangiocarcinoma. METHODS: Seventy-six patients who underwent curative resection for histologically confirmed extrahepatic cholangiocarcinoma at our institution from December 1994 to March 2008 were enrolled. Immunohistochemical staining for Skp2, Cks1, p27kip1, and Ki67, along with other relevant molecular biologic experiments, were performed. RESULTS: By Cox regression analyses, advanced age (> 65 years), advanced AJCC tumor stage, poorly differentiated histology, and higher immunostaining intensity of Skp2 were identified as independent prognostic factors in patients with extrahepatic cholangiocarcinoma. Exogenous epidermal growth factor (EGF, especially 0.1-10 ng/mL) significantly increased the proliferation indices by MTT assay and the mRNA levels of Skp2/Cks1 and p27kip1 in SNU-1196, SNU-1079, and SNU-245 cells. The protein levels of Skp2/Cks1 (from nuclear lysates) and p27kip1 (from cytosolic lysate) were also significantly increased in these cells. There were significant reductions in the protein levels of Skp2/Cks1 and p27kip1 (from nuclear lysate) after the treatment of LY294002. By chromatin immunoprecipitation assay, we found that E2F1 transcription factor directly binds to the promoter site of Skp2. CONCLUSION: Higher immunostaining intensity of Skp2/Cks1 was an independent prognostic factor for patients with extrahepatic cholangiocarcinoma. EGF upregulates the mRNA and protein levels of Skp2/Cks1 and p27kip1 via the PI3K/Akt pathway and direct binding of E2F1 transcription factor with the Skp2 promoter. PMID:24574749

  1. 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

  2. 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.

  3. The Effects of Cholestasis and Cirrhosis on Gastric Acid and Pepsin Secretions in Rat: Involvement of Nitric Oxide

    OpenAIRE

    Fatemeh Nabavizadeh; Rohallah Moloudi; Ahmad Reza Dehpour; Hossein Nahrevanian; Kaveh Shahvaisi; Ehsan Salimi

    2010-01-01

    Objective(s)The liver has major role in the organism homeostasis, interactions with other systems, synthesis and metabolism of bile production, drug detoxification and hormone inactivation. Cholestasis can be defined as an impairment of the bile flow which can lead to hepatocytes necrosis and finally cirrhosis. Some studies reported a gastric acid secretion reduction in cirrhotic subjects, while others reported normal production gastric acid secretion. Our aim was to evaluate the effects of c...

  4. 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

  5. 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...

  6. 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.

  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. 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.

  9. 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.

  10. Colloid Carcinoma of the Extrahepatic Biliary Tract with Metastatic Lymphadenopathy Mimicking Cystic Neoplasm: A Case Report

    International Nuclear Information System (INIS)

    The patient is a previously healthy 52-year-old woman who presented with dyspepsia for two months. Multiple imaging modalities including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) showed diffuse bile duct dilatation with an obstructive lesion of the distal extrahepatic biliary duct (EHD) as well as two masses in the peripancreatic area. The peripancreatic masses appeared cystic with posterior acoustic enhancement on ultrasound, low density on CT imaging, and high signal intensity on T2-weighted MRI. The lesion in the distal EHD exhibited similar characteristics on CT and MRI. A Whipple procedure was performed and histological specimens showed malignant cells with large mucin pools that was consistent with a diagnosis of colloid carcinoma of the EHD with metastatic lymphadenopathies. Colloid carcinoma, also called mucinous carcinoma, is classified as a histologic variant of adenocarcinoma. Because the colloid carcinoma of the biliary tree is exceedingly rare, the imaging characteristics and the clinical features of colloid carcinoma remain relatively unknown. We report a case of colloid carcinoma of the common bile duct and its accompanied metastatic lymphadenopathies with characteristic imaging findings reflecting abundant intratumoral mucin pools

  11. Imaging and radiological interventions in extra-hepatic portal vein obstruction

    Science.gov (United States)

    Pargewar, Sudheer S; Desai, Saloni N; Rajesh, S; Singh, Vaibhav P; Arora, Ankur; Mukund, Amar

    2016-01-01

    Extrahepatic portal vein obstruction (EHPVO) is a primary vascular condition characterized by chronic long standing blockage and cavernous transformation of portal vein with or without additional involvement of intrahepatic branches, splenic or superior mesenteric vein. Patients generally present in childhood with multiple episodes of variceal bleed and EHPVO is the predominant cause of paediatric portal hypertension (PHT) in developing countries. It is a pre-hepatic type of PHT in which liver functions and morphology are preserved till late. Characteristic imaging findings include multiple parabiliary venous collaterals which form to bypass the obstructed portal vein with resultant changes in biliary tree termed portal biliopathy or portal cavernoma cholangiopathy. Ultrasound with Doppler, computed tomography, magnetic resonance cholangiography and magnetic resonance portovenography are non-invasive techniques which can provide a comprehensive analysis of degree and extent of EHPVO, collaterals and bile duct abnormalities. These can also be used to assess in surgical planning as well screening for shunt patency in post-operative patients. The multitude of changes and complications seen in EHPVO can be addressed by various radiological interventional procedures. The myriad of symptoms arising secondary to vascular, biliary, visceral and neurocognitive changes in EHPVO can be managed by various radiological interventions like transjugular intra-hepatic portosystemic shunt, percutaneous transhepatic biliary drainage, partial splenic embolization, balloon occluded retrograde obliteration of portosystemic shunt (PSS) and revision of PSS. PMID:27358683

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.)

  3. Geographic Variation of Intrahepatic Cholangiocarcinoma, Extrahepatic Cholangiocarcinoma, and Hepatocellular Carcinoma in the United States

    Science.gov (United States)

    Cuccinelli, James E.; Zou, Zhaohui; Tatalovich, Zaria; McGlynn, Katherine A.

    2015-01-01

    Background Intrahepatic (ICC) and extrahepatic cholangiocarcinomas (ECC) are tumors that arise from cholangiocytes in the bile duct, but ICCs are coded as primary liver cancers while ECCs are coded as biliary tract cancers. The etiology of these tumors is not well understood. It has been suggested that the etiology of ICC is more similar to that of another type of liver cancer, hepatocellular carcinoma (HCC), than to the etiology of ECC. If this is true, geographic incidence patterns and trends in ICC incidence should be more similar to that of HCC than ECC. Methods To examine this hypothesis, data from the North American Association of Central Cancer Registries Cancer in North America data file were analyzed. Incidence rates and joinpoint trends were calculated by demographic subgroup. County-level incidence rates were mapped. Results Overall incidence rates, racial distribution, male:female ratio, and peak ages were more similar between ICC and ECC than with HCC. During 2000–2009, average annual incidence rates of ECC increased. During 2005–2009, average annual ICC incidence rates also increased. High rates for all three cancer sites were found in the Pacific region, particularly Hawaii and Alaska. Rates of ICC and ECC were also high in the Northeast and the upper Midwest, while rates of HCC were high in the South. Conclusions Demographic patterns and geographical variation were more closely related between ICC and ECC than HCC, suggesting that the etiology of ICC and ECC may be similar. Increasing rates of both tumors suggest that further etiology studies are warranted. PMID:25837669

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

    International Nuclear Information System (INIS)

    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.

  5. Hepatic and extrahepatic uptake of HDL-derived plasma cholesterol in exercised and sedentary rats

    International Nuclear Information System (INIS)

    The present investigation was designed to study high density lipoprotein (HDL)-derived plasma cholesterol (C) turnover in hepatic and extrahepatic tissues of sedentary (S) and exercised (E) rats. 4-week-old Long Evans rats were exercised for 1 hr, 6 days weekly, for a period of 38 weeks, on a motor-driven treadmill at 0.8 mph at a 12% grade. Animals were injected with HDL that was labelled in vitro with 3H-cholesteryl ester. Serial blood samples and tissues were collected. HDL-C concentration was lower in E vs S rats (23.0 +/- 1.2 and 26.6 +/- 1.9 mg/dl, p < 0.01). While total plasma C was not different, liver C was higher in S vs E rats (8.2 +/- 0.8 and 7.2 +/- 0.5 mg/g). Adrenal C was higher in E vs S rats (29.5 +/- 2.3 and 20.7 +/- 2.3 mg/g, p < 0.01). Multicompartmental analysis of plasma and tissue tracer response led to development of an 8-component model (5 physiological; 3 nonphysiological) that depicted HDL-derived plasma C turnover. Plasma fraction of tracer declined more rapidly in E vs S rats. E rats cleared nonphysiological tracer more rapidly than S rats, but delayed release of tracer into the plasma longer. Fractional rate of tracer uptake into adrenals, liver, testes, and carcass was greater in E rats. There was a greater fractional turnover rate of tracer in adrenals and liver in S vs E rats. Hence HDL-derived plasma C turnover is altered with vigorous exercise

  6. 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.

  7. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Kay, Chul Seung; Jang, Hong Suk; Kim, Sung Hwan; Ryu, Mi Ryeong; Kim, Yeon Shil; Chung, Su Mi; Yoon, Sei Chul [College of Medicine, The Catholic Univ. of Korea, Seoul (Korea, Republic of)

    1999-06-01

    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 (p<0.05). The significant prognostic factors were high performance status (Karnofski Performance Status >70), 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

  9. 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.)

  10. 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

  11. Colestasis intrahepática del embarazo en una adolescente Intrahepatic cholestasis of a pregnant teenager

    Directory of Open Access Journals (Sweden)

    Alberto Martínez Sarmiento

    2013-06-01

    Full Text Available Introducción: la colestasis gravídica es una afección que se presenta con mayor frecuencia en el segundo o tercer trimestres, siendo el prurito y la elevación de los ácidos biliares en sangre sus características fundamentales. Se considera una enfermedad multifactorial y aunque el pronóstico materno es bueno, puede ocurrir prematuridad, sufrimiento y muerte fetales. Objetivo: presentar el caso y la revisión bibliográfica en la literatura nacional e internacional. Caso clínico: se presenta el caso de una gestante de 18 años de edad con un tiempo de gestación de 17,5 sem, que fue vista en consulta de hepatología por presentar prurito, íctero y coluria. Durante su estudio lo más significativo fue un aumento ligero de las transaminasas (ALAT/ASAT, asociado a un aumento de la bilirrubina y de la fosfatasa alcalina (FA. Resultados: a las 29,3 sem, la gestante comenzó con manifestaciones de parto pretérmino por lo que se decidió la interrupción del embarazo (cesárea. El recién nacido presentó al nacer 1 260 g y fue trasladado a sala de terapia intensiva neonatológica. La evolución clínica posparto de la madre fue satisfactoria, con desaparición de la sintomatología en las primeras 48 h y la normalización de las alteraciones analíticas en el transcurso de 4-8 sem. Conclusiones: la presentación clínica y bioquímica de la gestante así como su evolución, fueron suficientes para establecer el diagnóstico de una colestasis gravídica. La paciente es seguida por consulta de hepatología y está pendiente de valoración por el genetista debido al riesgo de esta afección en embarazos sucesivos.Introduction: cholestasis of pregnancy is a condition that occurs most often in the second or third quarters. Pruritus and elevated bile acids in blood are its fundamental characteristics. It is considered a multifactorial disease and although maternal prognosis is good, prematurity, fetal distress and death can occurred. Objective: to

  12. 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. PMID:26431088

  13. 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

  14. Diagnosis of extra-hepatic cholangiocarcinoma from PET-CT analysis including delayed image

    International Nuclear Information System (INIS)

    Several PET studies demonstrated lower sensitivity of extra-hepatic cholangiocarcinoma(EHC) compared to that of intra-hepatic cholangiocarcinoma. The reason was suggested that infiltrating carcinoma is the most common type of EHC. The aim of this study was to evaluate the effectiveness of visual analysis and delayed image of PET-CT for differentiating EHC including infiltrating type. PET-CT performed on 57 patients (22 women, 37 men: mean ageSD, 59.013.8y) with suspected malignant EHC from Sep. 2005 to Aug. 2007. Final diagnosis was histologically proven EHC in 42 cases, benign GB mass in 10 cases, and benign lesions in 5 cases (stricture: n=4) without evidence of malignancy during 6 mo. follow up. PET images was obtained 1 hour after IV administration of 555 MBq of FDG. Delayed image at 3 hours was taken in 30 cases. Positive PET-CT was applied for visual analysis and semiquantitative analysis from early and delayed images. In visual analysis, PET-CT demonstrated the sensitivity of 95.2%(40/42), and the specificity of 86.7%(13/15). Maximal SUV(mSUV) of EHC (5.03.3, n=42) was higher than that of benign lesions (2.11.9, n=15) (p=0.06). mSUV of infiltrating type of EHC (3.71.8, n=15) was significantly lower than that of non-infiltrating type (5.63.3, n=26) (p=0.04). In quantitative analysis, the sensitivity and specificity of PET-CT using cut-off value (mSUV=3.0) presented 81%(34/42) and 92.3%(14/15), respectively. When quantitative analysis using the criteria (mSUV = 3.0 or retention rate at 3 hr = 10%), both sensitivity and specificity were higher: 92.9%(39/42) and 92.3%(14/15), respectively. When RR at 3 hr =10% applied for malignancy criteria, about 10% of the cases of infiltrating EHC was detected additionally. Semiquantitative analysis using mSUV and RR obtained from delayed PET image as well as visual analysis can provide more accurate diagnosis of EHC

  15. 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.

  16. 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

  17. 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.

  18. High rates of resolution of cholestasis in parenteral nutrition-associated liver disease with fish oil-based lipid emulsion monotherapy

    Science.gov (United States)

    Our research was conducted to determine factors leading to resolution of cholestasis in patients with parenteral nutrition-associated liver disease treated with fish-oil-based lipid emulsion (FOLE). We used a prospective observational study of 57 infants <6 months of age with parenteral nutrition-as...

  19. Effect of Intrahepatic Cholestasis of Pregnancy on Cytokines, Hemorheology and Coagulation Function of Pregnant Women

    Directory of Open Access Journals (Sweden)

    Cui-ge YU

    2015-12-01

    Full Text Available Abstract Objective: To explore the effect of intrahepatic cholestasis of pregnancy (ICP on the cytokines, hemorheology and coagulation function of pregnant women. Methods: A total of 43 singleton pregnant women with ICP delivered in Shaanxi Provincial People’s Hospital from June 2014 to June 2015 were selected as observation group, and 45 singleton healthy pregnant women accompanied by indications of cesarean section were selected as control group. Automatic Viscometer was used to detect the hematological indexes, Automatic Coagulometer to detect the indexes related to coagulation function and radioimmunoassay to determine the levels of cell inflammatory factors, and the pregnancy outcomes were closely observed. Results: The levels of interleukin-12 (IL-12, interleukin-18 (IL-18, tumor necrosis factor-α (TNF-α, high and low shear rates of whole blood viscosity, hematokrit, plasma viscosity and erythrocyte sedimentation rate (ESR in observation group were all dramatically higher than those in control group, and all the differences were statistically significant (P<0.01. There was no statistical significance between two groups with regard to prothrombin When compared with control group, the levels of D-dimer (D-D and fibrinogen (FIB in observation group increased dramatically (P<0.01, but platelet (PLT decreased markedly (P<0.01. The incidence of amniotic fluid pollution and premature delivery in observation group was higher than in control group (P<0.05 or P<0.01, and that of fetal distress, neonatal asphyxia and low birth weight tended to be higher than in control group, but there was no statistical significance (P>0.05. Conclusion: Both the hemorheology and coagulation function of pregnant women with ICP manifest significantly high viscosity and hypercoagulability, and the release of cell inflammatory factors increases, which all exert adverse influence on pregnancy outcome. time (PT and activated

  20. 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

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

    International Nuclear Information System (INIS)

    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

  2. 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

  3. 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.

  4. 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.

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

    International Nuclear Information System (INIS)

    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.

  6. 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.

  7. 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.

  8. 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.

  9. Study of a new hepatobiliary radiotracer: sup(99m)Tc diethyl IDA. Its value in the diagnosis of cholestasis

    International Nuclear Information System (INIS)

    This work examines a new means of investigation: Technetium 99 (2,6 diethyl acetanilido) imino-diacetic acid, or HEPATOBIDA, hepatobiliary scintigraphy. A survey of different scintigraphic techniques is necessary. At first the kinetic study of hepatobiliary radiotracers was carried out with multiprobe systems giving quantitative information on the various organs or pools concerned. With the appearance of the scintillation camera it became possible to obtain not only quantitative data but also topographical and morphological information. Since 1976 the derivatives of iminodiacetic acid have been widely adopted, possessing features most closely resembling those of the ideal hepatobiliatropic molecules. Examinations have been performed at the Angers Radioisotopes Service with the diethyl derivative or HEPATOBIDA (Nuclear Solca Lab.) The results recorded in a group of cholestasis patients are studied, with normal data supplied by a set of 8 reference subjects free from hepatobiliary diseases

  10. 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)

  11. 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...

  12. Results of the evaluation of numerical parameters of the hepatobiliary functional scintigraphy in the differential diagnosis of neonatal cholestasis

    International Nuclear Information System (INIS)

    The present study serves to differentiate the various causes of pathological icterus in the neonatal and infant period by means of data from hepatobiliary functional scintigraphy. There is only good differentiation between extrahepatic biliary atresia and the group of intrahepatic liver-diseases. The neonatal hepatitis and intrahepatic biliary atresia, both located primarily in the liver, can be differentiated only with difficulty by the hepatobiliary functional scintigraphy, because in both diseases the hepatocytes are impaired. The other causes, such as choledochal cysts, are represented by too few patients in the study to perform a useful statistical analysis. The most appropriate parameters can be found by a statistical method, the so-called Maximum-Likelihood-Method. These are the ascent of the liver curve at the time of 420 seconds p.i. (cut-off-point 0.14), the activity in the liver at the end of the examination (cut-off-point 29), the maximum of the intestinal activity (cut-off-point 11), the quotient between liver activity and the activity of the whole range of measurement at the time of the maximum of the activity of the whole range of measurement (cut-off-point 0.65), the elimination-index (cut-off-point 970) and the clinical parameter GGT (cut-off-point 200). Besides these parameters we determine in this study some others, which describe the phases of the tracer-uptake in the liver (accumulation, retention and elimination) quantitatively. From these the best are described above. We find a sensitivity of the test of 100% for diagnosing an extrahepatic biliary atresia. The specificity of the test is 85.7%

  13. 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...

  14. 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

  15. 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.

  16. 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,...

  17. 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-

  18. 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.

  19. Hepatic and Extrahepatic Insulin Clearance Are Differentially Regulated: Results From a Novel Model-Based Analysis of Intravenous Glucose Tolerance Data.

    Science.gov (United States)

    Polidori, David C; Bergman, Richard N; Chung, Stephanie T; Sumner, Anne E

    2016-06-01

    Insulin clearance is a highly variable and important factor that affects circulating insulin concentrations. We developed a novel model-based method to estimate both hepatic and extrahepatic insulin clearance using plasma insulin and C-peptide profiles obtained from the insulin-modified frequently sampled intravenous glucose tolerance test. Data from 100 African immigrants without diabetes (mean age 38 years, body weight 81.7 kg, fasting plasma glucose concentration 83 mg/dL, and fasting insulin concentration 37 pmol/L) were used. Endogenous insulin secretion (calculated by C-peptide deconvolution) and insulin infusion rates were used as inputs to a new two-compartment model of insulin kinetics and hepatic and extrahepatic clearance parameters were estimated. Good agreement between modeled and measured plasma insulin profiles was observed (mean normalized root mean square error 6.8%), and considerable intersubject variability in parameters of insulin clearance among individuals was identified (the mean [interquartile range] for hepatic extraction was 25.8% [32.7%], and for extrahepatic insulin clearance was 20.7 mL/kg/min [11.7 mL/kg/min]). Parameters of insulin clearance were correlated with measures of insulin sensitivity and acute insulin response to glucose. The method described appears promising for future research aimed at characterizing variability in insulin clearance and the mechanisms involved in the regulation of insulin clearance. PMID:26993071

  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. 18F-FDG PET or PET/CT for detecting extrahepatic metastases or recurrent hepatocellular carcinoma: A systematic review and meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chun-Yi [Department of Nuclear Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan (China); Chen, Jin-Hua [Biostatistics Center and Graduate Institute of Biostatistics, Taichung, Taiwan (China); Liang, Ji-An [Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan (China); School of Medicine, China Medical University, Taichung, Taiwan (China); Lin, Cheng-Chieh [School of Medicine, China Medical University, Taichung, Taiwan (China); Department of Community Medicine and Health Examination Center, China Medical University Hospital, Taichung, Taiwan (China); Jeng, Long-Bin [School of Medicine, China Medical University, Taichung, Taiwan (China); Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan (China); Kao, Chia-Hung, E-mail: d10040@mail.cmuh.org.tw [School of Medicine, China Medical University, Taichung, Taiwan (China); Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan (China)

    2012-09-15

    Aim: Positron emission tomography (PET) using F18-flurodeoxy-glucose (FDG) has been widely used for reflecting cellular metabolism. However, the feasibility of FDG PET in the diagnosis of hepatocellular carcinoma (HCC) is limited. The aim of the study was to assess the ability of FDG PET (PET/CT) in the detection of extrahepatic metastases or recurrent HCC. Materials and methods: We conducted MEDLINE, EMBASE and COCHRANE searches (last update, April 2011). Eight eligible articles were identified evaluating F18-FDG PET (PET/CT) in extrahepatic metastases or recurrent HCC. Two authors independently evaluated the methodological quality of each study. We estimated pooled sensitivities, specificities, summary receiver-operating-characteristic (SROC) curves, and summary likelihood ratios. Results: Eight eligible studies were enrolled in this study. The pooled estimates of sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of FDG PET (PET/CT) in the detection of metastatic HCC were 76.6%, 98.0%, 14.68, and 0.28, respectively. The pooled estimates of sensitivity, specificity, LR+ and LR− of FDG PET (PET/CT) in the detection of recurrent HCC were 81.7%, 88.9%, 4.72, and 0.19, respectively. Conclusion: Based on the results of this systematic review, F-18 FDG PET (PET/CT) was useful in ruling in extrahepatic metastases of HCC and valuable for ruling out the recurrent HCC.

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

    International Nuclear Information System (INIS)

    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

  3. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-12-15

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

  5. 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.

  6. 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.

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

    Science.gov (United States)

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

    2015-09-01

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

  8. 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

  9. 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.

  10. 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.

  11. Emergency use of intravenous phytonadione (vitamin K1) for treatment of severe bleeding in a child with chronic cholestasis.

    Science.gov (United States)

    Glatstein, Miguel; Idan-Prusak, Dafna; Yahav, Aiala; Ovental, Amit; Rimon, Ayelet; Scolnik, Dennis

    2013-01-01

    We present a 5-year-old boy with multiple hematomas associated with chronic cholestasis. A week before admission he suffered minor trauma at day care. The next day he complained of trunk and limb pain and orthopedic consultation, including leg x-rays, revealed no abnormalities. Over the next 5 days multiple hematomas developed over his body and increased in size. In the Emergency Department he was in pain and looked sick but alert. He had fever and tachycardia, with normal blood pressure and respiratory status and physical examination showed several hematomas on the legs, which increased in size during observation in the Emergency Department over 2 hours. Blood work revealed multiple coagulation abnormalities, and International Normalized Ratio was 12. Intravenous phytonadione (vitamin K1) was immediately administered with normalization of coagulation abnormalities within 1 hour and the hematomas stopped growing in size. In addition to missing follow-up with the Pediatric Gastroenterology Department, social service agency inquiry found he had not taken his medications for several months. With severe abnormal bleeding and hepatic disease, intravenous vitamin K1 may be lifesaving, even before obtaining confirmatory blood work, fresh-frozen plasma, or blood transfusion. PMID:21642829

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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) ...

  20. The Features of Extrahepatic Collateral Arteries Related to Hepatic Artery Occlusion and Benefits in the Trans arterial Management of Liver Tumors

    International Nuclear Information System (INIS)

    To investigate the extrahepatic collateral arteries related to hepatic artery occlusion (HAO) and to determine its benefits in the trans arterial 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.

  1. Evolving Role of Endoscopic Retrograde Cholangiopancreatography in Management of Extrahepatic Hepatic Ductal Injuries due to Blunt Trauma: Diagnostic and Treatment Algorithms

    Directory of Open Access Journals (Sweden)

    Nikhil P. Jaik

    2007-11-01

    Full Text Available Extrahepatic hepatic ductal injuries (EHDIs due to blunt abdominal trauma are rare. Given the rarity of these injuries and the insidious onset of symptoms, EHDI are commonly missed during the initial trauma evaluation, making their diagnosis difficult and frequently delayed. Diagnostic modalities useful in the setting of EHDI include computed tomography (CT, abdominal ultrasonography (AUS, nuclear imaging (HIDA scan, and cholangiography. Traditional options in management of EHDI include primary ductal repair with or without a T-tube, biliary-enteric anastomosis, ductal ligation, stenting, and drainage. Simple drainage and biliary decompression is often the most appropriate treatment in unstable patients. More recently, endoscopic retrograde cholangiopancreatography (ERCP allowed for diagnosis and potential treatment of these injuries via stenting and/or papillotomy. Our review of 53 cases of EHDI reported in the English-language literature has focused on the evolving role of ERCP in diagnosis and treatment of these injuries. Diagnostic and treatment algorithms incorporating ERCP have been designed to help systematize and simplify the management of EHDI. An illustrative case is reported of blunt traumatic injury involving both the extrahepatic portion of the left hepatic duct and its confluence with the right hepatic duct. This injury was successfully diagnosed and treated using ERCP.

  2. 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.

  3. 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

  4. 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

    International Nuclear Information System (INIS)

    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

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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

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

    Directory of Open Access Journals (Sweden)

    Yosuke Osawa

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

  12. 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.

  13. 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 ...

  14. Hepatic and extra-hepatic sequelae, and prevalence of viral hepatitis C infection estimated from routine data in at-risk groups

    Directory of Open Access Journals (Sweden)

    Sorge Chiara

    2010-04-01

    Full Text Available Abstract Background Concerns about the hepatitis C virus (HCV are due to the high risk of chronic liver disease and poor treatment efficacy. Synthesizing evidence from multiple data sources is becoming widely used to estimate HCV-infection prevalence. This paper aims to estimate the prevalence of HCV infection, and the hepatic and extrahepatic sequelae in at-risk groups, using routinely collected data in the Lazio region, Italy. Methods HCV laboratory surveillance and dialysis, hospital discharge, and drug-user registers were used as information sources to identify at-risk groups and to estimate HCV prevalence and sequelae. Full name and birth date were used as linkage keys for the various health registries. Prevalence was estimated as the percentage of cases within the general population and the at-risk groups, with 95% confidence intervals (95% CI from 1997 to 2001. The risk of sequelae was estimated through a follow-up of hospital discharges up to December 31, 2004 and calculated as the prevalence ratio in HCV-positive and HCV-negative people, within each at-risk group, with 95% CI. Results There were 65,127 HCV-infected people in the study period; the prevalence was 1.24% (95%CI = 1.23%-1.25% in the whole population, higher in males and older adults. Drug users (35.1%; 95%CI = 34.6-35.7 and dialysis patients (21.1%; 95%CI = 20.2%-22.0% showed the highest values. Medical procedures with little exposure to blood resulted in higher estimates, ranging between 1.3% and 3.4%, which was not conclusively attributable to the surgical procedures. Cirrhosis, hepatocellular carcinoma and encephalopathy were the most frequent hepatic sequelae; cryoglobulinaemia and non-Hodgkin's lymphoma were the most frequent extrahepatic sequelae. Conclusions Synthesising data from multiple routine sources improved estimates of HCV prevalence and sequelae in dialysis patients and drug users, although prevalence validity should be assessed in survey and sequelae need a

  15. Assessment of intra and extrahepatic perfusion during hepatic artery infusion chemotherapy using slow-injected gadolinium-enhanced MR imaging through implanted catheter-port system

    International Nuclear Information System (INIS)

    Twenty-four studies of intra-arterially slow-injected gadolinium-enhanced MR imaging through an implanted catheter-port system (reservoir-MR) were carried out in 15 patients with liver tumor. The flow rate of gadolinium injection was 0.1 ml/sec and a total of 3 mL was injected. Six consecutive phases, each with an acquisition time of 14 seconds, were obtained every 30 seconds. In all studies, the signal intensity of the drug delivery portion became very high. Twenty-three of 24 studies showed intrahepatic perfusion in the first phase. The hepatic vein was enhanced at the first phase in 10 and the second phase in 14. The abdominal aorta was enhanced at the second phase in all 24 studies. The portal vein was enhanced at the first phase in 4, the second phase in 13, and the third phase in 7 studies. Both intra- and extrahepatic perfusion were more clearly demonstrated by reservoir-MRI than by digital subtraction angiography through an implanted catheter-port system (reservoir-DSA); however, morphological changes in the hepatic artery were better demonstrated by reservoir-DSA than by reservoir-MRI. (author)

  16. 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.

  17. An investigation into hepatic and extrahepatic factors associated with the decrease in phenytoin steady state plasma levels in the wistar rat during chronic treatment with phenytoin

    International Nuclear Information System (INIS)

    The aim of this study was to determine which hepatic and extrahepatic changes occur in the Wistar rat that influences the kinetics of phenytoin after chronic treatment with it. Blood levels of phenytoin (DPH) were determined weekly, 8 hours and 24 hours after the last dosage per day in the form of a Epanutin suspension of 27,5 mg DPH. No metabolism of DPH by the gastro-intestinal tract microflora could be found after incubation under aerobic as well as anaerobic conditions of the caecum contents and 4-14C-DPH of the control rats and rats treated for 4 weeks. No change in the absorption surface could be found of the small intestine mucosa after treatment. These results was substantiated with absorption studies with D-U-14C-xylose as well as electron microscopic investigations. The in vivo elimination of 4-14C-DPH showed that the half-lives of DPH and its metabolites were approximately 550 minutes, while the half-life of DPH as such was only 69,3. No unaltered DPH could be detected in the urine after 15 weeks treatment. Electron microscopic investigations showed a progressive increase in the agranular endoplasmatic reticulum (AER) occurred in the liver after treatment. This increase in the AER is furthermore associated with progressive decrease in the half-life of DPH over a long period

  18. 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

  19. 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

  20. 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

  1. 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

  2. 3α-6α-Dihydroxy-7α-fluoro-5β-cholanoate (UPF-680), physicochemical and physiological properties of a new fluorinated bile acid that prevents 17α-ethynyl-estradiol-induced cholestasis in rats

    International Nuclear Information System (INIS)

    3α-6α-Dihydroxy-7α-fluoro-5β-cholanoate (UPF-680), the 7α-fluorine analog of hyodeoxycholic acid (HDCA), was synthesized to improve bioavailability and stability of ursodeoxycholic acid (UDCA). Acute rat biliary fistula and chronic cholestasis induced by 17α-ethynyl-estradiol (17EE) models were used to study and compare the effects of UPF-680 (dose range 0.6-6.0 μmol/kg min) with UDCA on bile flow, biliary bicarbonate (HCO3-), lipid output, biliary bile acid composition, hepatic enzymes and organic anion pumps. In acute infusion, UPF-680 increased bile flow in a dose-related manner, by up to 40.9%. Biliary HCO3- output was similarly increased. Changes were observed in phospholipid secretion only at the highest doses. Treatment with UDCA and UPF-680 reversed chronic cholestasis induced by 17EE; in this model, UDCA had no effect on bile flow in contrast to UPF-680, which significantly increased bile flow. With acute administration of UPF-680, the biliary bile acid pool became enriched with unconjugated and conjugated UPF-680 (71.7%) at the expense of endogenous cholic acid and muricholic isomers. With chronic administration of UPF-680 or UDCA, the main biliary bile acids were tauro conjugates, but modification of biliary bile acid pool was greater with UPF-680. UPF-680 increased the mRNA for cytochrome P450 7A1 (CYP7A1) and cytochrome P450 8B (CYP8B). Both UDCA and UPF-680 increased the mRNA for Na+ taurocholate co-transporting polypeptide (NCTP). In conclusion, UPF-680 prevented 17EE-induced cholestasis and enriched the biliary bile acid pool with less detergent and cytotoxic bile acids. This novel fluorinated bile acid may have potential in the treatment of cholestatic liver disease

  3. Innervation of Extrahepatic Biliary Tract, With Special Reference to the Direct Bidirectional Neural Connections of the Gall Bladder, Sphincter of Oddi and Duodenum in Suncus murinus, in Whole-Mount Immunohistochemical Study.

    Science.gov (United States)

    Yi, S-Q; Ren, K; Kinoshita, M; Takano, N; Itoh, M; Ozaki, N

    2016-06-01

    Sphincter of Oddi dysfunction is one of the most important symptoms in post-cholecystectomy syndrome. Using either electrical or mechanical stimulation and retrogradely transported neuronal dyes, it has been demonstrated that there are direct neural pathways connecting gall bladder and the sphincter of Oddi in the Australian opossum and the golden hamster. In the present study, we employed whole-mount immunohistochemistry staining to observe and verify that there are two different plexuses of the extrahepatic biliary tract in Suncus murinus. One, named Pathway One, showed a fine, irregular but dense network plexus that ran adhesively and resided on/in the extrahepatic biliary tract wall, and the plexus extended into the intrahepatic area. On the other hand, named Pathway Two, exhibiting simple, thicker and straight neural bundles, ran parallel to the surface of the extrahepatic biliary tract and passed between the gall bladder and duodenum, but did not give off any branches to the liver. Pathway Two was considered to involve direct bidirectional neural connections between the duodenum and the biliary tract system. For the first time, morphologically, we demonstrated direct neural connections between gall bladder and duodenum in S. murinus. Malfunction of the sphincter of Oddi may be caused by injury of the direct neural pathways between gall bladder and duodenum by cholecystectomy. From the viewpoint of preserving the function of the major duodenal papilla and common bile duct, we emphasize the importance of avoiding kocherization of the common bile duct so as to preserve the direct neural connections between gall bladder and sphincter of Oddi. PMID:26179953

  4. 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

  5. Therapeutic effects of antigen affinity-purified polyclonal anti-receptor of advanced glycation end-product (RAGE) antibodies on cholestasis-induced liver injury in rats.

    Science.gov (United States)

    Xia, Peng; Deng, Qing; Gao, Jin; Yu, Xiaolan; Zhang, Yang; Li, Jingjing; Guan, Wen; Hu, Jianjun; Tan, Quanhui; Zhou, Liang; Han, Wei; Yuan, Yunsheng; Yu, Yan

    2016-05-15

    Cholestasis leads to acute hepatic injury, fibrosis/cirrhosis, inflammation, and duct proliferation. We investigated whether blocking receptor of advanced glycation end-products (RAGE) with polyclonal anti-RAGE antibodies (anti-RAGE) could regulate acute liver injury and fibrosis in a rat bile duct ligation (BDL) model. Male Wister rats received 0.5mg/kg rabbit anti-RAGE or an equal amount of rabbit IgG by subcutaneous injection twice a week after BDL. Samples of liver tissue and peripheral blood were collected at 14 days after BDL. Serum biochemistry and histology were used to analyze the degree of liver injury. Quantitative real-time PCR (qPCR) and immunohistochemical staining were used to further analyze liver injury. Anti-RAGE improved the gross appearance of the liver and the rat survival rate. Liver tissue histology and relevant serum biochemistry indicated that anti-RAGE attenuated liver necrosis, inflammation, liver fibrosis, and duct proliferation in the BDL model. qPCR and western blotting showed significant reductions in interleukin-1β expression levels in the liver by treatment with anti-RAGE. Anti-RAGE also significantly reduced the mRNA levels of α1(1) collagen (Col1α1) and cholesterol 7α-hydroxylase, and the ratio of tissue inhibitor of matrix metalloproteinase-1 to matrix metalloproteinases (MMPs) in the liver. In addition, anti-RAGE regulated the transcriptional level of Col1α1 and MMP-9 in transforming growth factor-β-induced activated LX-2 cells in vitro. Anti-RAGE was found to inhibit hepatic stellate cell proliferation in vivo and in vitro. Therefore, anti-RAGE can protect the liver from injury induced by BDL in rats. PMID:26970185

  6. INSULIN-LIKE GROWTH FACTOR-1, CYTOLYSIS AND CHOLESTASIS IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE AND ITS COMBINATION WITH TYPE 2 DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    L. V. Zhuravlyova

    2014-07-01

    Full Text Available Purpose. The study was designed to assess the relationship between the level of plasma concentration of insulin-like growth factor-1 (IGF-1 and indices of the functional state of the liver in patients with non-alcoholic fatty liver disease (NAFLD and its combination with diabetes mellitus (DM 2 types depending on the trophological status.Materials and methods. It were examined 90 patients with non-alcoholic fatty liver disease and its combination with type 2 diabetes mellitus –with normal body weight and obesity, as well as 20 healthy individuals. The study was carried out using the following methods: clinical, laboratory and instrumental (including liver biopsy.Results. It was inverse the relationship between the level of IGF-1, and the level of AST, ALT, AST/ALT, total and conjugated bilirubin, alkaline phosphatase in groups of patients with comorbid disorder. There was established the significant decrease of plasma level of IGF-1, and also impairment of liver function indices in all groups in comparison with the controls, and most pronounced changes in patients with comorbid disorders and obesity.Conclusion. The established relationships suggests that the decrease of IGF-1 may represent the presence of syndromes of cytolysis and cholestasis in patients with NAFLD, type 2 DM and obesity. In order to determination the disorder of the reparative function of the liver isrecommended to determine the level of IGF-1 in patients with combination of NAFLD and type 2 DM. Patients with the level of IGF-1 < 143,9 ± 4,92 ng/ml should refer to the risk of progression of liver function disorders.

  7. 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.

  8. 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.

  9. Utility of chemical-shift MR imaging in detecting small amounts of fat in extrahepatic abdominal tumors; Utilidad de la tecnica de desplazamiento quimico den RM para la deteccion de pequenas cantidades de grasa en tumores abdominales extrahepaticos

    Energy Technology Data Exchange (ETDEWEB)

    Martin, J.; Falco, J.; Puig, J.; Donoso, L. [Unidad de Diagnostico por Imagen de Alta Tecnologia (UDIAT). Sabadell (Spain)

    1999-07-01

    To determine the utility of the chemical shift technique in magnetic resonance imaging (MRI) to confirm small amounts of fat in extrahepatic intraabdominal tumours. 7 extrahepatic abdominal tumours that are suspected to have fat as seen in the axial computed tomography (TC) are analysed retrospectively. In order to confirm the fat content, the chemical displacement technique with gradient echo sequences (GE) in phase (P) and in opposite phase (OP) was used with MRI 1 T equipment. The tumours corresponded to renal angiomyolipoma (AML) (n=4), intraperitoneal liposarcoma (n=1), retroperitoneal liposarcoma (n=1) and intraabdominal extramedular hematopoiesis (n=1). To confirm the existence of fat in the tumours, we used a quantitative percentage variation parameter of the intensity of the signals (VIS) between the images in P and OP, according to the formula: IS{sub (}p)-IS({sub o}p)x100/IS{sub (}op), where IS is the intensity of the signal. The chemical shift technique showed fat in the seven tumours. Upon visual inspection, all the tumoral areas that were suspected to have fat showed a notable difference in the signal intensity, being hypointense in OP and hyperintense in P. In these areas the average VIS percentage was 170% while in the rest of the tumour the average VIS percentage was 3%. The chemical shift technique with RG sequences can be easily used in MRI equipment and allows us to confirm if a specific abdominal tumour has fat, even if there is only a small quantity. (Author) 13 refs.

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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...

  15. 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

  16. 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。

  17. Conjugated bile acids promote cholangiocarcinoma cell invasive growth through activation of sphingosine 1-phosphate receptor 2

    OpenAIRE

    Liu, Runping; Zhao, Renping; Zhou, Xiqiao; Liang, Xiuyin; Campbell, Deanna JW; Zhang, Xiaoxuan; ZHANG, LUYONG; Shi, Ruihua; Wang, Guangji; Pandak, William M.; Sirica, Alphonse E.; Hylemon, Phillip B.; Zhou, Huiping

    2014-01-01

    Cholangiocarcinoma (CCA) is an often fatal primary malignancy of the intra- and extrahepatic biliary tract that is commonly associated with chronic cholestasis and significantly elevated levels of primary and conjugated bile acids (CBAs), which are correlated with bile duct obstruction (BDO). BDO has also recently been shown to promote CCA progression. However, whereas there is increasing evidence linking chronic cholestasis and abnormal bile acid profiles to CCA development and progression, ...

  18. 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

  19. Role of radiation therapy in cancer of the extra-hepatic biliary system: an analysis of thirteen patients and a review of the literature of the effectiveness of surgery, chemotherapy and radiotherapy

    International Nuclear Information System (INIS)

    An analysis of the role of radiotherapy in the management of gallbladder (GB) and extra-hepatic bile duct (EHBD) cancer is based upon thirteen patients irradiated in our hospital and a review of the literature. These patients were treated as part of curative or palliative management in conjunction with surgery, after surgical failure or recurrence, and as the only palliative modality. Doses ranged from 3800 to 7225 rad. Significant palliation was obtained in 92 percent of the patients; average total bilirubin value decreased from 9.1 mg. percent before to 1.7 mg. percent after radiotherapy. The mean survival of all patients was 12.7 months after surgery (7.1 in GB, 16.1 in EHBD), and was 7.3 months after initiation of radiotherapy (6.3 in GB, 8.0 in EHBD). Two patients were alive and well with no evidence of disease 12 and 16 months after radiotherapy, and local tumor control was achieved in two. Complications included possible biliary fibrosis. Based upon a critical review of the surgical, chemotherapeutic, and radiotherapeutic literature, it is concluded that present surgical therapy fails because of extensive regional disease in which local recurrences follow various simple and radical surgical maneuvers; palliative surgery often fails. Survival rates have been poor following any therapy at present, although encouraging results are seen with carefully planned megavoltage radiotherapy. A proposal is made to evaluate the role of radiotherapy systematically: as part of curative therapy post-operatively to decrease local recurrences and to increase the length and quality of survival; to treat incisional recurrences; as part of advanced disease management to increase the effectiveness and length of palliation; and in conjunction with chemotherapy to further consolidate therapeutic gains made with radiotherapy alone

  20. 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.)

  1. 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.

  2. 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

  3. 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

  4. Colestasis postinfección por virus de Epstein-Barr sin elevación de gamma glutamil transpeptidasa Post-infection cholestasis due to Epstein-Barr virus infection without elevation of gamma glutamyl transpeptidase

    Directory of Open Access Journals (Sweden)

    E. González Salas

    2010-01-01

    Full Text Available El virus de Epstein-Barr es el agente responsable de la mayoría de los casos de mononucleosis infecciosa, síndrome linfoproliferativo que suele ser benigno y autolimitado, aunque puede acompañarse en ocasiones de complicaciones neurológicas, respiratorias o hematológicas. A la sintomatología clínica habitual, caracterizada por fiebre, malestar general, odinofagia y adenopatías generalizadas, es frecuente que se asocie una hepatopatía subclínica, caracterizada en el niño por un leve y transitorio aumento de las transaminasas. A diferencia del adulto, en el niño, la existencia de un síndrome colestásico es excepcional.
    Presentamos el caso clínico de una niña de 6 años que presenta una colestasis clínico-bioquímica en el curso de una infección aguda por el virus de Epstein-Barr, en la que destaca la normalidad de las cifras de gamma glutamil transpeptidasa durante toda la evolución de su proceso. The Epstein-Barr virus is the responsible agent for most of the cases of infectious mononucleosis, a lymphoproliferative syndrome that is generally benign and self-limited, although it may sometimes be accompanied by neurological, respiratory or hematological complications. Frequently, it is frequent to find that subclinical liver disease, characterized in the child by mild and transitory increase of transaminases is associated to the usual clinical symptoms, characterized by fever, general malaise, odinophagia and generalized abnormal lymph nodes. On the contrary to the adult, the existence of a cholestatic syndrome in the child is rare.
    We present the case of a 6-year old girl who presented a clinical-biochemical cholestasis during an acute infection due to Epstein-Barr virus in which the normality of the gamma glutamyl transpeptidase values during the entire course stands outs.

  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. 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 ...

  7. Extrahepatic complications to cirrhosis and portal hypertension

    DEFF Research Database (Denmark)

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

    2014-01-01

    , the circulation becomes hyperdynamic with cardiac, pulmonary as well as renal consequences for dysfunction and reduced survival. Infections and a changed cardiac function known as cirrhotic cardiomyopathy may be involved in further aggravation of other complications such as renal failure precipitating...... 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...

  8. 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 ...

  9. Extra-Hepatic Storage of Copper

    DEFF Research Database (Denmark)

    Heydorn, Kaj; Damsgaard, Else; Horn, N.; Mikkelsen, M.; Tygstrup, I.; Vestermark, S.; Weber, J.

    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....

  10. Stages of Extrahepatic Bile Duct Cancer

    Science.gov (United States)

    ... to a collection bag outside of the body. Percutaneous transhepatic biliary drainage : A procedure used to x-ray the liver ... which may include partial hepatectomy . Stent placement or percutaneous transhepatic biliary drainage as palliative therapy , to relieve jaundice and other ...

  11. Treatment Options for Extrahepatic Bile Duct Cancer

    Science.gov (United States)

    ... to a collection bag outside of the body. Percutaneous transhepatic biliary drainage : A procedure used to x-ray the liver ... which may include partial hepatectomy . Stent placement or percutaneous transhepatic biliary drainage as palliative therapy , to relieve jaundice and other ...

  12. Treatment Option Overview (Extrahepatic Bile Duct Cancer)

    Science.gov (United States)

    ... to a collection bag outside of the body. Percutaneous transhepatic biliary drainage : A procedure used to x-ray the liver ... which may include partial hepatectomy . Stent placement or percutaneous transhepatic biliary drainage as palliative therapy , to relieve jaundice and other ...

  13. 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

  14. 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

  15. Quantitative Evaluation of Liver Function Using 99mTc-DISIDA Cholescintigraphy

    International Nuclear Information System (INIS)

    Since hepatocyte clearance, leading edge parenchymal transit time and biliary excretion can be evaluated separately with hepatobiliary scan using 99mTc-DISIDA, hepatobiliary scan may be useful in differentiating intrahepatic cholestasis from extrahepatic cholestasis. Excretory liver function was analysed in 13 healthy subjects and 11 patients with clinically suspected hepatocellular disease and 9 patients with extrahepatic biliary obstruction confirmed by surgery, radiological and clinical evidence. Indices of total liver activity (% TLA), liver parenchymal uptake (% LPU), heart pool clearance (% HPC) and liver-heart rate (% LHR) were calculated from time activity curve over heart and liver. Compared with healthy subjects, significant reduction(p<0.05) in total liver activity (% TLA) and liver-heart rate (% LHR) was observed in all patients group. But no useful indices was demonstrated in differentiating hepatocellular disease from extrahepatic biliary obstruction.

  16. 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

  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. 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)

  19. 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 ...

  20. 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. ...

  1. 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

  2. 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

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

    Science.gov (United States)

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

    1996-01-01

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

  4. 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.

  5. 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

  6. 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

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

    Directory of Open Access Journals (Sweden)

    Regina Helena Guedes da Motta Mattar

    2005-08-01

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

  8. 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. 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.

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

    Institute of Scientific and Technical Information of China (English)

    张梅虹; 赵瑞芳; 陈瑞; 王建设

    2014-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    曹璐; 李俊; 黄成; 韩静文

    2013-01-01

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

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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...

  19. 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.

  20. 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...

  1. [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

  2. 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

  3. Adenosquamous Carcinoma of Extrahepatic Bile Duct: A Case Report

    OpenAIRE

    Lim, Sin Hyung; Yang, Hyeon Woong; Kim, Anna; Cha, Sang Woo; Jung, Sung Hee; Go, Hoon; Lee, Woong Chul

    2007-01-01

    Most malignant tumors originating from the biliary tract are adenocarcinomas, and adenosqamous carcinoma of Klatskin's tumor is a very rare finding. An 83-yr-old man was admitted to our hospital because of jaundice. The abdominal computed tomography and magnetic resonance cholangiopancreatography revealed wall thickening and luminal stenosis of both the intrahepatic duct confluent portion and the common hepatic duct. These findings were compatible with Klatskin's tumor, Bismuth type III. Cons...

  4. 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.

  5. 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

  6. 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

  7. Scintigraphic appearance and particular arteriographic aspects intrahepatic cholestasis

    International Nuclear Information System (INIS)

    Based on one case history, it is reviewed that prolonged cases of obstructive jaundice can take on deceiving appearances, and all the more so when they fall within the framework of a 'biological gap'. Extensive distension of the extra and intrahepatic bile ducts are at the basis of images with multiple, radiating hilar gaps on scintigraphy, and of 'chicken nests' and 'Swiss cheese' at hepatographic times in selective hepatic arteriography. These rather uncommon images should lead to a diagnosis of a surgical cholestatic liver

  8. 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...

  9. 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.

  10. 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...

  11. 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. ...

  12. 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.

  13. 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.

  14. 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

  15. 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),

  16. 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

  17. The Pitfalls of Febrile Jaundice. A Case Report

    Directory of Open Access Journals (Sweden)

    Obreja Maria

    2016-04-01

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

  18. 131I rose bengal: Its use in the evaluation of infantile jaundice

    International Nuclear Information System (INIS)

    One-hundred ten 131I-rose bengal studies (RBI) were performed in infants suspected of having biliary atresia. Fecal RBI excretion of less than 10% was observed in 72 of 73 cases of extrahepatic biliary atresia, but also in 10 of 37 cases of intrahepatic cholestasis of various origins. One-hundred twenty-two RBI tests were performed in children operated on for extrahepatic biliary atresia and 71 tests were performed between postsurgical weeks 3 and 8, and 51 tests were done later. Prognostically, early tests show that fecal RBI excretion of more than 15% was observed in 2 of 34 cases who were later completely jaundice-free and in only 1 of 37 cases where no bile flow restoration occurred. (orig.)

  19. 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

  20. 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.

  1. {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.)

  2. 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.

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

    International Nuclear Information System (INIS)

    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

  4. Tissue factor contributes to neutrophil CD11b expression in alpha-naphthylisothiocyanate-treated mice

    International Nuclear Information System (INIS)

    Cholestatic liver injury induced by alpha-naphthylisothiocyanate (ANIT) is provoked by injury to intrahepatic bile ducts and the progression of hepatic necrosis requires the procoagulant protein tissue factor (TF) and extrahepatic cells including neutrophils. Recent studies have shown that myeloid cell TF contributes to neutrophil activation. We tested the hypothesis that myeloid cell TF contributes to neutrophil activation in ANIT-treated mice. TF activity in liver homogenates increased significantly in TFflox/flox mice treated with ANIT, but not in TFflox/flox/LysMCre mice (TFΔMyeloid mice), which have reduced TF expression in monocytes/macrophages and neutrophils. Myeloid cell-specific TF deficiency did not alter expression of the chemokines KC or MIP-2 but reduced hepatic neutrophil accumulation in ANIT-treated mice at 48 h as indicated by tissue myeloperoxidase (MPO) activity. Myeloid cell TF deficiency significantly reduced CD11b expression by blood neutrophils in ANIT-treated mice, and this was associated with reduced plasma MPO protein levels, an index of neutrophil degranulation. However, myeloid cell-specific TF deficiency had no effect on ANIT-induced coagulation cascade activation. The increase in serum ALT and ALP activities in ANIT-treated mice was reduced by myeloid cell TF deficiency (p < 0.05), but the myeloid cell TF deficiency did not reduce hepatic necrosis at 48 h, as determined by histopathology and morphometry. The results suggest that myeloid cell TF contributes to neutrophil CD11b expression during cholestasis by a coagulation-independent pathway. However, the resultant reduction in neutrophil accumulation/activation is insufficient to substantially reduce ANIT hepatotoxicity, suggesting that myeloid cell TF is only one of many factors modulating hepatic necrosis during cholestasis. - Research Highlights: → Myeloid cell tissue factor contributes to liver procoagulant activity during acute cholestasis. → ANIT-induced coagulation cascade

  5. 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.

  6. 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.

  7. 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.

  8. Structure and Innervation of the Extrahepatic Biliary System in the Australian Possum, Trichosurus Vulpecula

    OpenAIRE

    R. T. A. Padbury; Baker, R. A.; Messenger, J. P.; Toouli, J.; Furness, J B

    1993-01-01

    The morphology, microanatomy and innervation of the biliary tree of the Australian possum, Trichosurus vulpecula, was examined. The gross morphology of the gallbladder, hepatic and cystic ducts, and the course of the common bile duct, conforms to those of other species. The sphincter of Oddi has an extraduodenal segment that extends 15mm from the duodenal wall; within this segment the pancreatic and common bile ducts are ensheathed together by sphincter muscle. Their lumens unite to form a co...

  9. Apparent gut excretion of Tc-99m-DISIDA in case of extrahepatic biliary atresia

    International Nuclear Information System (INIS)

    Patient had DISIDA scan at 39 days of age to exclude biliary atresia. Gut excretion was seen 18 h after injection and the diagnosis of neonatal hepatitis was made. Because of continued elevated liver function values, liver biopsy was performed and demonstrated findings consistent with biliary atresia. Exploratory laparotomy performed 8 days after the scan showed patient cystic duct, bule duct, and gall-bladder, but an atretic common hepatic duct. This case is an example of documented biliary atresia demonstrating gut excretion on the DISIDA scan. (orig.)

  10. 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)

  11. 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.

  12. Congenital absence of the common bile duct: A rare anomaly of extrahepatic biliary tract.

    Science.gov (United States)

    Mittal, Tarun; Pulle, Mohan V; Dey, Ashish; Malik, Vinod K

    2016-01-01

    Congenital absence of the common bile duct (CBD) is an extremely rare developmental anomaly with right and left hepatic ducts draining directly into the gallbladder (GB). Other synonyms for this clinical condition are "cholecystohepatic ducts", "transverse lie of the GB" or "interposition of the GB". The potential for iatrogenic injury is high, because of either inadvertent division or ligation of the ducts. Diagnosis is mostly made intraoperatively, and needs some form of biliary reconstruction. Herein, we are reporting a case of congenital absence of the CBD in a 36-year-old lady that was detected intraoperatively. PMID:27279403

  13. Decreased biliary excretion of piperacillin after percutaneous relief of extrahepatic obstructive jaundice.

    OpenAIRE

    Blenkharn, J I; Habib, N; Mok, D; John, L; McPherson, G. A.; Gibson, R. N.; Blumgart, L. H.; Benjamin, I. S.

    1985-01-01

    The biliary excretion of piperacillin has been assessed in 11 patients with obstructive jaundice due to hilar cholangiocarcinoma. After a 1-g intravenous dose administered 30 min before preliminary percutaneous transhepatic cholangiography, no drug was detected in the bile of seven patients; in four others, drug concentrations were far below the corresponding level in serum. After a period of external biliary drainage of up to 28 days, levels of antibiotic in bile after intravenous administra...

  14. 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.

  15. Effect of exercise on placental blood flow in pregnancies complicated by hypertension, diabetes or intrahepatic cholestasis.

    Science.gov (United States)

    Rauramo, I; Forss, M

    1988-01-01

    The effects of a standardized exercise test on intervillous placental blood flow were studied in 13 hypertensive, 10 diabetic and 8 cholestatic pregnant women in late pregnancy, and the results were compared with those of a normal control group. Analysis of variance for repeated measures revealed that in all the pathologic groups, placental blood flow was lower than in the controls. In all groups placental blood flow rose slightly 1 min after the cessation of exercise. The diabetics showed a decreased placental blood flow 30 min after the cessation of the exercise test (p less than 0.02). In diabetics, a fall was found in stroke volume, from 63 +/- 12 ml (mean +/- SD) before the exercise to 53 +/- 11 ml 30 min after the cessation of exercise (p less than 0.05), and a rise in peripheral vascular resistance, from 1540 +/- 200 (mean +/- SD) dynes/cm5 before exercise to 1750 +/- 390 dynes/cm5 30 min after the cessation of exercise (p less than 0.05). Pre-eclamptic patients had a higher peripheral vascular resistance than had normal controls. Pre-eclamptic, diabetic and cholestatic patients had lower cardiac index values than the normal subjects. The difference was significant in the pre-eclamptic and diabetic patients at 30 min after the cessation of exercise. Maternal heart rate, and systolic, diastolic and mean arterial blood pressures rose significantly from values at rest to values at the end of exercise in all groups. One of the pre-eclamptic patients showed a 74% decline in placental blood flow 1 min after the cessation of exercise coincident with fetal bradycardia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3176908

  16. Bile acids affect liver mitochondrial bioenergetics: possible relevance for cholestasis therapy

    OpenAIRE

    Rolo, Anabela P.; Oliveira, Paulo J.; Moreno, António J. M.; Palmeira, Carlos M.

    2000-01-01

    It has been pointed out that intracellular accumulation of bile acids cause hepatocyte injury in cholestatic disease process. This study was aimed to test if cytotoxicity of these compounds is mediated through mitochondria dysfunction. Bile acids effects on isolated rat liver mitochondrial were analyzed by monitoring changes in membrane potential and mitochondrial respiration, as well as alterations in H+ membrane permeability and mitochondrial permeability transition pore induction. Increasi...

  17. 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...

  18. 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

  19. 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...

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

    OpenAIRE

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

    1985-01-01

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

  1. 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.

  2. 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.

  3. 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

  4. Portal hypertensive biliopathy: A single center experience and literature review.

    Science.gov (United States)

    Suárez, Vanessa; Puerta, Andrés; Santos, Luisa Fernanda; Pérez, Juan Manuel; Varón, Adriana; Botero, Rafael Claudino

    2013-03-27

    Portal hypertensive biliopathy (PHB) is characterized by anatomical and functional abnormalities of the intrahepatic, extrahepatic and pancreatic ducts, in patients with portal hypertension associated to extrahepatic portal vein obstruction and less frequently to cirrhosis. These morphological changes, consisting in dilatation and stenosis of the biliary tree, are due to extensive venous collaterals occurring in an attempt to decompress the portal venous blockage. It is usually asymptomatic until it progresses to more advanced stages with cholestasis, jaundice, biliary sludge, gallstones, cholangitis and finally biliary cirrhosis. Imaging modalities of the biliary tree such as Doppler ultrasound, computed tomography, magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography are essential to establish the diagnosis and the need of therapeutical interventions. Once the diagnosis is established, treatment with ursodesoxycholic acid seems to be beneficial. Decompression of the biliary tree to dilate, remove stones or implant biliary prosthesis by endoscopic or surgical procedures (hepato-yeyunostomy) usually resolves the cholestatic picture and prevents septic complications. The ideal treatment is the decompression of the portal system, with transjugular intrahepatic porto-systemic shunt or a surgical porto-systemic shunt. Unfortunately, few patients will be candidates for these procedures due to the extension of the thrombotic process. The purpose of this paper is to report the first 3 cases of PHB seen in a Colombian center and to review the literature. PMID:23556047

  5. 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...

  6. Evaluation of anastomosis between intrahepatic or extrahepatic vessels by intra-arterial digital subtraction angiography using carbon dioxide

    International Nuclear Information System (INIS)

    Carbon dioxide (CO2) intra-arterial subtraction angiography (IADSA) was performed in 31 patients with various hepatobiliary disease. The injection sites of CO2 were proper hepatic artery (10/31; group A), segmental hepatic artery (18/31; group B), and peripheral inferior phrenic artery (3/31; group C), respectively. In group A, only the third order branches of the portal venous system were visualized anterogradely in 8 of 10 patients. In group B, the microcatheter was placed coaxially through a 5 French guiding catheter at the main arterial supply of the tumor in 7 patients and at the peripheral segmental branch of the hepatic artery in 11 patients. The portal venous system was visualized retrogradely in all of the patients regardless of the injection site. The injected CO2 may flow back into the portal vein through the anastmosis known as the peribiliary or periportal plexus. In group C, not only the portal vein but also the pulmonary artery or pericardial vein were visualized by this method. CO2-IADSA was useful to image the minute communications between the various vessels, which have been not hitherto visualized by iodinated contrast medium. (author)

  7. Non-enhanced MR portography in combination with time-SLIP method. Evaluation of extra-hepatic portal vein

    International Nuclear Information System (INIS)

    This paper describes the retrospective study of MR portography (MRP) mainly for imaging the esophageal and gastric varices, their serving vessels, change after their treatment, and of the optimal imaging conditions, using the time-SLIP (spatial labeling inversion pulse) method which enables selectively to image the portal system. Equipment used was Toshiba EXCELART Vantage 1.5TV.8.01. Imaging was done at the breath exhalation phase with fast advanced spin echo method which gave intensive signals of all blood flows slower than systolic arterial flow and with time-SLIP method of double inversion recovery-move out procedure (inversion time=1.5 sec). Examined were 22 images of 14 patients (47-81 years old, M/F 6/8) with portal hypertension and 5 of 5 (48-74, 2/3) without the hypertension. MRP imaging power was compared with CT for gastric veins and their varices; efficiency was examined for imaging the left gastric vein (LGV) by different regions of the applied selective inversion pulse; effect of varix treatment was followed; and influence of food intake and ascites was investigated. Blood serving path in the hypertension was more easily imaged; imaging efficiency was different in LGV depending on applied pulse region; fasting was found desirable before imaging and ascites interfered it; and process after treatment was effectively followed. Shortening of imaging time, synchronization with the breath movement and further search for optimal conditions were the future tasks. (R.T.)

  8. 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...

  9. 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

  10. [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

  11. 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.

  12. Combination of conservative and interventional therapy strategies for intra- and extrahepatic cholangiocellular carcinoma: a retrospective survival analysis.

    Science.gov (United States)

    Knüppel, M; Kubicka, S; Vogel, A; Malek, N P; Schneider, M; Papendorf, F; Greten, T; Wedemeyer, J; Schneider, A

    2012-01-01

    Background. Due to the predominantly advanced stage at the time of diagnosis treatment of cholangiocarcinoma is difficult. Apart from surgical resection, interventional treatment strategies are increasingly used in advanced stage tumours. The aim of the study was a retrospective comparison of the effect of the various forms of treatment on morbidity and mortality. Method. A total of 195 patients, received either chemotherapy or a combination of photodynamic therapy (PDT) or transarterial chemoembolization (TACE) and chemotherapy. Results. The median survival rate for all patients was 15.6 months, 50.8% were still alive 1 year after diagnosis. Patients, who had previously undergone surgery, survived 17.1 months longer than those without surgical treatment (P TACE 9.8 months longer (P = .04) compared to chemotherapy alone. Conclusions. It appears that surgical treatment and chemotherapy combined with PDT or TACE may prolong survival. PMID:21776251

  13. 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...

  14. 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.

  15. 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...

  16. Clinical, molecular and functional investigation on an infant with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD.

    Directory of Open Access Journals (Sweden)

    Zhan-Hui Zhang

    Full Text Available BACKGROUND AND OBJECTIVE: SLC25A13 analysis has provided reliable evidences for the definitive diagnosis of citrin deficiency (CD in the past decade. Meanwhile, these studies generated some issues yet to be resolved, including the pathogenicity of SLC25A13 missense mutations and the mRNA product from the mutation c.615+5G>A. This study aims to investigate the effect of a novel missense mutation on the aspartate/glutamate carrier (AGC function of citrin protein, and to explore the aberrant transcript from c.615+5G>A in the same CD infant. METHODS AND RESULTS: By means of screening for prevalent SLC25A13 mutations and exons sequencing, the patient proved a compound heterozygote of c.615+5G>A and a novel c.1064G>A (p.Arg355Gln mutation. An aberrant transcript with retention of the entire intron 6, r.[615+1_615+1789ins; 615+5 g>a] (GenBank accession number KJ128074, which was resulted from c.615+5G>A, was detected by RT-PCR and cDNA sequencing. After bioinformatic analyses of the novel missense mutation c.1064G>A, the growth abilities of three agc1Δ yeast strains were tested, which had been transformed with recombinant or empty vectors, respectively. Besides the bioinformatically pathogenic evidences, the growth ability of the agc1Δ strains transformed with mutant recombinant was the same as with empty vector, but significantly lower than that with normal control in functional analysis. CONCLUSIONS: A CD infant was definitely diagnosed in this paper by a genetic, transcriptional and functional analysis of SLC25A13 gene. This study provided direct laboratory evidences supporting the splice-site nature of the c.615+5G>A mutation, and the novel c.1064G>A variation, which proved a pathogenic mutation bioinformatically and functionally, enriched the SLC25A13 mutation spectrum.

  17. 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...

  18. 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

  19. High Incidence of Rickets in Extremely Low Birth Weight Infants with Severe Parenteral Nutrition-Associated Cholestasis and Bronchopulmonary Dysplasia

    OpenAIRE

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

    2012-01-01

    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...

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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...

  8. Clinical significance of determination of changes of serum FE3 and immuno-function parameters levels in patients with intrahepatic cholestasis of pregnancy (ICP)

    International Nuclear Information System (INIS)

    Objective: To study the changes of serum levels of free E3, β-HCG, IgG, IgM, IgA, C3, C4 and peripheral blood CD4+, CD8+ contents in patients with ICP. Methods Serum free E3, β-HCG (with RIA), IgG, IgM, IgA, C3 and C4 (with immuno-turbidity assay) levels and peripheral blood CD4+, CD8+ contents (with flow-cytometry) were determined in 40 patients with ICP and 40 normal pregnant controls. Results Serum free E3 levels in patients with ICP were significantly higher than those in controls (P0.05). The serum IgG contents in patients with ICP were significantly lower than those in controls (P3 and C4 contents in patients with ICP were not significantly different from those in controls (P>0.05). CD4+ percentages in the patients were not significantly different from those in controls while the CD8+ percentages were significantly higher (P+/CD8+ ratio. Conclusion Significant changes of contents of serum free E3 and IgG and a lower CD4+/CD8+ ratio were present in patients with ICP, the exact mechanisms were not determined yet. (authors)

  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.......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. 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.

  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. 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.

  13. 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

  14. Cancer review: Cholangiocarcinoma.

    Science.gov (United States)

    Ghouri, Yezaz Ahmed; Mian, Idrees; Blechacz, Boris

    2015-01-01

    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. PMID:25788866

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. Analysis of Pyridyloxobutyl and Pyridylhydroxybutyl DNA Adducts in Extra-hepatic Tissues of F344 Rats Treated Chronically with 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone and Enantiomers of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol

    OpenAIRE

    Zhang, Siyi; Wang, Mingyao; Villalta, Peter W.; Lindgren, Bruce R.; Upadhyaya, Pramod; Lao, Yanbin; Hecht, Stephen S.

    2009-01-01

    The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) are potent pulmonary carcinogens in rats. NNK and NNAL require metabolic activation to express their carcinogenicity. Cytochrome P450-catalyzed α-hydroxylation at the methyl position of NNK or NNAL generates reactive intermediates, which alkylate DNA to form pyridyloxobutyl (POB)-DNA adducts or pyridylhydroxybutyl (PHB)-DNA adducts. NNK ...

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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...

  7. Colestasia Intrahepática Familiar Progresiva Tipo 3: Presentación de Casos Clínicos y Actualización de Tema Type 3 Familial Intrahepatic Cholestasis: Clinical Cases and Update

    OpenAIRE

    JOSÉ ZACARÍAS S

    2009-01-01

    La Colestasia Intrahepática Familiar Progresiva (CIFP) comprende un grupo heterogéneo de alteraciones autosómicas recesiva caracterizadas por una colestasia hepatocelular secundaria a una interrupción del proceso normal de síntesis de la bilis. Objetivo: Describir la presentación de CIFP en 3 de 5 hijos de una familia estudiada. Caso clínico: Paciente de 5 años de edad (caso 1), que presenta una hepatoesplenomegalia, aumento de enzimas hepáticas y de ácidos biliares en suero. La ecotomografía...

  8. 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...

  9. New approaches to the autosomal recessive polycystic kidney disease patient with dual kidney-liver complications.

    Science.gov (United States)

    Telega, Grzegorz; Cronin, David; Avner, Ellis D

    2013-06-01

    Improved neonatal medical care and renal replacement technology have improved the long-term survival of patients with ARPKD. Ten-yr survival of those surviving the first year of life is reported to be 82% and is continuing to improve further. However, despite increases in overall survival and improved treatment of systemic hypertension and other complications of their renal disease, nearly 50% of survivors will develop ESRD within the first decade of life. In addition to renal pathology, patients with ARPKD develop ductal plate malformations with cystic dilation of intra- and extrahepatic bile ducts resulting in CHF and Caroli syndrome. Many patients with CHF will develop portal hypertension with resulting esophageal varices, splenomegaly, hypersplenism, protein losing enteropathy, and gastrointestinal bleeding. Management of portal hypertension may require EBL of esophageal varices or porto-systemic shunting. Complications of hepatic involvement can include ascending cholangitis, cholestasis with malabsorption of fat-soluble vitamins, and rarely benign or malignant liver tumors. Patients with ARPKD who eventually reach ESRD, and ultimately require kidney transplantation, present a unique set of complications related to their underlying hepato-biliary disease. In this review, we focus on new approaches to these challenging patients, including the indications for liver transplantation in ARPKD patients with severe chronic kidney disease awaiting kidney transplant. While survival in patients with ARPKD and isolated kidney transplant is comparable to that of age-matched pediatric patients who have received kidney transplants due to other primary renal diseases, 64-80% of the mortality occurring in ARPKD kidney transplant patients is attributed to cholangitis/sepsis, which is related to their hepato-biliary disease. Recent data demonstrate that surgical mortality among pediatric liver transplant recipients is decreased to <10% at one yr. The immunosuppressive regimen

  10. Steps forward, backward, and sideways: Intravenous lipid emulsions for critically ill neonates

    Science.gov (United States)

    A neonatologist doesn't need long-term memory to recall caring for babies who developed severe cholestasis leading to death or the need for a liver and/or intestinal transplant. Fortunately, there is no doubt that the situation has improved dramatically in the past 5 years. Cholestasis is resolving ...

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    We report a case of intrahepatic cholestasis due to chronic vitamin A supplementation. A 70-year-old woman was admitted to the hospital for jaundice and reduced nutritional and general status with a 2-month history of increasing cholestasis. Some years previously she had suffered from breast and ...

  12. Early Palliative Care With Standard Care or Standard Care Alone in Improving Quality of Life of Patients With Incurable Lung or Non-colorectal Gastrointestinal Cancer and Their Family Caregivers

    Science.gov (United States)

    2015-08-04

    Liver Cancer; Anxiety Disorder; Depression; Small Cell Lung Cancer; Extrahepatic Bile Duct Cancer; Malignant Mesothelioma; Pancreatic Cancer; Esophageal Cancer; Gastric Cancer; Non-small Cell Lung Cancer

  13. Disease: H00624 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  15. Distribuição das lesões esquistossomóticas extra-hepáticas em camundongos infectados pelas linhagens BH e SJ do Schistosoma mansoni The distribution of extra-hepatic schistosomotic lesions in mice infected by BH and SJ strains of Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    Luiz A. Magalhães

    1979-12-01

    Full Text Available Foi estudada a distribuição dos granulomas esquistossomóticos no baço, pulmões, rins, coração e intestinos de camundongos parasitados pelas linhagens BH e SJ de S. mansoni. Verificou-se que a distribuição de granulomas produzidos pelos esquistossomos das duas linhagens é semelhante, sendo que a linhagem BH produziu número significativamente maior de lesões no baço e nos pulmões.The distribution of schisiosomotic granulomae in the spleen, lungs, kidneys, heart, and intestines of mice infected by BH and SJ strains of S. mansoni was studied. No great difference was found in the distribution of granulomae of the two strains; however, the number of lesions caused by the BH strain was greater in the spleen and the lungs.

  16. Activated Charcoal

    Science.gov (United States)

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

  17. Disease: H00950 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available F, Borrone C Arthrogryposis, renal dysfunction and cholestasis syndrome: report of five patients... E, Lee JJ, Park YS, Yoo HW Clinical characteristics and VPS33B mutations in patients

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

    Directory of Open Access Journals (Sweden)

    A. Cruz

    2009-07-01

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

  19. Jaundice

    Science.gov (United States)

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

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

    International Nuclear Information System (INIS)

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

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

    Institute of Scientific and Technical Information of China (English)

    王冬梅; 朱启英; 腊晓琳

    2002-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    宋晔; 戴建荣; 侯顺玉

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    林萍

    2014-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    舒明; 王火平; 胡笑蓉; 黄左安; 黄丹丹; 王咖; 张顺

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    兰绍阳; 佘世锋

    2012-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    姜超; 刘家云; 翟兢; 李为苏; 王琼; 许哲

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    曹云海; 陈熙; 张程; 石嫦娥; 徐德祥; 许建明

    2010-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    王涛; 王佳颖; 周植星; 江振洲; 李妍妍; 张良; 张陆勇

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    兰绍阳; 佘世锋; 张达坤; 陶双友

    2012-01-01

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

  10. Acute Cholestatic Hepatitis A Virus Infection Presenting with Hemolytic Anemia and Renal Failure: A Case Report

    OpenAIRE

    Lapp, Robert T.; Fedja Rochling

    2013-01-01

    Hepatitis A virus is the most common acute viral hepatitis worldwide with approximately 1.5 million cases annually. Hepatitis A virus infection in general is self-limited. In rare cases, hepatitis A virus infection may cause renal failure, hemolytic anemia, and/or cholestasis. We report the first case of acute cholestatic hepatitis A virus infection complicated by hemolytic anemia, and renal failure in one patient. A 42-year-old Caucasian male presented with cholestasis, hemolytic anemia and ...

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

    OpenAIRE

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

    1994-01-01

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

  12. TGF-β-SMAD3 signaling mediates hepatic bile acid and phospholipid metabolism following lithocholic acid-induced liver injury[S

    OpenAIRE

    Matsubara, Tsutomu; Tanaka, Naoki; Sato, Misako; Kang, Dong Wook; Krausz, Kristopher W.; Flanders, Kathleen C.; Ikeda, Kazuo; Luecke, Hans; Wakefield, Lalage M.; Frank J. Gonzalez

    2012-01-01

    Transforming growth factor-β (TGFβ) is activated as a result of liver injury, such as cholestasis. However, its influence on endogenous metabolism is not known. This study demonstrated that TGFβ regulates hepatic phospholipid and bile acid homeostasis through MAD homolog 3 (SMAD3) activation as revealed by lithocholic acid-induced experimental intrahepatic cholestasis. Lithocholic acid (LCA) induced expression of TGFB1 and the receptors TGFBR1 and TGFBR2 in the liver. In addition, immunohisto...

  13. Hereditäre Defekte hepatobiliärer Transportproteine

    OpenAIRE

    Mwinyi, J.; Kullak-Ublick, G A

    2010-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

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

    OpenAIRE

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

    2015-01-01

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

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

    OpenAIRE

    Soroka, Carol J.; Boyer, James L.

    2013-01-01

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

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

    OpenAIRE

    Plass, Jacqueline Regina Maria

    2005-01-01

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

  18. Alagille syndrome.

    OpenAIRE

    Krantz, I D; Piccoli, D A; Spinner, N B

    1997-01-01

    Alagille syndrome (OMIM 118450) is an autosomal dominant disorder associated with abnormalities of the liver, heart, eye, skeleton, and a characteristic facial appearance. Also referred to as the Alagille-Watson syndrome, syndromic bile duct paucity, and arteriohepatic dysplasia, it is a significant cause of neonatal jaundice and cholestasis in older children. In the fully expressed syndrome, affected subjects have intrahepatic bile duct paucity and cholestasis, in conjunction with cardiac ma...

  19. Congenital Cholestatic Syndromes: What Happens When Children Grow Up?

    OpenAIRE

    Ling, Simon C.

    2007-01-01

    Although advances in the management of children with congenital cholestasis have enabled many to survive into adulthood with their native livers, even the most common of these conditions remains rare in adult hepatology practice. Among four congenital cholestatic syndromes (biliary atresia, Alagille syndrome, Caroli disease and congenital hepatic fibrosis, and progressive familial intrahepatic cholestasis), the published data on outcomes of the syndromes into adulthood suggest that a spectrum...

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

    OpenAIRE

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

    2016-01-01

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

  1. Urosodeoxycholic Acid Therapy in a Child with Trimethoprim-Sulfamethoxazole-induced Vanishing Bile Duct Syndrome

    OpenAIRE

    Cho, Hyun Jeong; Jwa, Hye Jeong; Kim, Kyu Seon; Gang, Dae Yong; Kim, Jae Young

    2013-01-01

    We present a case of a 7-year-old boy who had cholestasis after trimethoprim-sulfamethoxazole combination therapy. Liver biopsy was performed 36 days after the onset of jaundice because of no evidence of improving cholestasis. Liver histology revealed portal inflammation, bile plug, and biliary stasis around the central vein with the loss of the interlobular bile ducts. Immunohistochemical stains for cytokeratin 7 and 19 were negative. These findings were consistent with those of vanishing bi...

  2. Preventive effect of ursodeoxycholic acid on parenteral nutrition-associated liver disease in infants

    OpenAIRE

    Simić Dušica; Milojević Irina; Bogićević Dragana; Milenović Miodrag; Radlović Vladimir; Drašković Biljana; Uram-Benka Anna; Sinđić Sanja; Maksimović Ružica

    2014-01-01

    Introduction. Parenteral nutrition-associated cholestasis is well recognized phenomenon in the term and preterm infant receiving long-term parenteral nutrition. Objectives. The aim of this study was to evaluate the effect of ursodeoxycholic acid (UDCA) use on cholestasis in newborns on prolonged TPN. Methods. A total of 56 infants were enrolled in this retrospective study: control group consisted of lower (1500 g) birth weight infants (n=30), as well as the...

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

    Science.gov (United States)

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

    2012-05-01

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

  4. Treatment of glomerulonephritis associated with hepatitis C virus in patient with cirrhosis: only pegylated interferon and ribavirin

    Institute of Scientific and Technical Information of China (English)

    Adnan Ta(s); Erdem Ko(c)ak; Erdem Akbal; Seyfettin K(o)klü

    2011-01-01

    @@ To the editor: Hepatitis C virus (HCV) is a hepatotropic virus and a common cause of chronic hepatitis.Several extrahepatic complications have been associated with HCV including autoimmune and kidney diseases.It can cause a variety of extrahepatic immunological manifestations.1 Chronic HCV infection and cirrhosis are risk factors of a variety of extrahepatic diseases such as mixed cryoglobulinemia and membranoproliferative glomerulonephritis (MPGN).2 We presented a cirrhosis patient with mixed cryoglobulinemia (MC) associated with HCV; the diagnosis was made by renal biopsy and improved completely after interferon (IFN) and ribavirin treatment.

  5. Intrahepatic and systemic therapy with oxaliplatin combined with capecitabine in patients with hepatic metastases from breast cancer

    DEFF Research Database (Denmark)

    Nielsen, D L; Nørgaard, H; Weber Vestermark, Lene;

    2012-01-01

    The aim was to evaluate activity and toxicity of hepatic arterial infusion of oxaliplatin in combination with capecitabine in patients with metastatic breast cancer with liver metastases and limited extrahepatic disease....

  6. Copper Cu 64 Anti-CEA Monoclonal Antibody M5A PET in Diagnosing Patients With CEA Positive Cancer

    Science.gov (United States)

    2016-07-12

    Breast Cancer; Colon Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastrointestinal Cancer; Liver and Intrahepatic Biliary Tract Cancer; Lung Cancer; Metastatic Cancer; Pancreatic Cancer; Rectal Cancer; Thyroid Gland Medullary Carcinoma; Unspecified Adult Solid Tumor, Protocol Specific

  7. Imaging of hepatocellular carcinoma recurrence post liver resection: a pictorial essay

    International Nuclear Information System (INIS)

    This pictorial essay presents and discusses the imaging findings of patients with hepatocellular carcinoma recurrence post liver resection. A broad range of recurrence patterns is reviewed including intrahepatic and extrahepatic recurrences.

  8. CHRONIC LABORATORY EXPOSURE OF MUMMICHOG, FUNDULUS HETEROCLITUS, TO PAH-CONTAMINATED SEDIMENT AND DIET CAUSES LIVER NEOPLASMS

    Science.gov (United States)

    The mummichog, Fundulus heteroclitus, is a common estuarine teleost inhabiting tidal marshes of the eastern United States. We previoiusly reported on high prevalences of hepatic and extra-hepatic neoplasms in populations of this species from chemically contaminated environments ...

  9. Biological Therapy in Treating Patients With Metastatic Cancer

    Science.gov (United States)

    2013-02-21

    Breast Cancer; Colorectal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Head and Neck Cancer; Liver Cancer; Lung Cancer; Metastatic Cancer; Ovarian Cancer; Pancreatic Cancer; Testicular Germ Cell Tumor

  10. Kinetics of local and systemic isoforms of serum amyloid A in bovine mastitic milk

    DEFF Research Database (Denmark)

    Jacobsen, Stine; Niewold, T.A.; Kornalijnslijper, E.;

    2005-01-01

    The aim of the present study was to characterise the serum amyloid A (SAA) response to intramammary inoculation of Escherichia coli and to examine the distribution of hepatically and extrahepatically pruduced SAA isoforms in plasma and milk fra cows with mastitis.......The aim of the present study was to characterise the serum amyloid A (SAA) response to intramammary inoculation of Escherichia coli and to examine the distribution of hepatically and extrahepatically pruduced SAA isoforms in plasma and milk fra cows with mastitis....

  11. Surgery for recurrent biliary carcinoma: results for 27 recurrent cases

    OpenAIRE

    Noji, Takehiro; Tsuchikawa, Takahiro; Mizota, Tomoko; Okamura, Keisuke; Nakamura, Toru; Tamoto, Eiji; Shichinohe, Toshiaki; Hirano, Satoshi

    2015-01-01

    Background Various chemotherapies have been used as best practice to treat recurrent biliary malignancies. Conversely, relatively few surgeries have been described for recurrent extrahepatic biliary carcinoma (RExBC), so whether surgery for RExBC is feasible has remained unclear. This retrospective study was conducted to evaluate the feasibility of surgery for RExBC. Methods From February 2000 to January 2014, a total of 27 patients, comprising 18 patients with extrahepatic cholangiocarcinoma...

  12. Taking the next step forward - Diagnosing inherited infantile cholestatic disorders with next generation sequencing.

    Science.gov (United States)

    Herbst, S M; Schirmer, S; Posovszky, C; Jochum, F; Rödl, T; Schroeder, J A; Barth, T F; Hehr, U; Melter, M; Vermehren, J

    2015-10-01

    Identifying rare genetic forms of infantile cholestasis is challenging due to their similar clinical presentation and their diverse etiology. After exclusion of common non-genetic causes a huge list of rare differential diagnosis remains to be solved. More than 90 genes are associated with monogenic forms of infantile cholestasis, thus preventing routine genetic workup by Sanger sequencing. Here we demonstrate a next generation sequencing approach to discover the underlying cause in clinically well characterized patients in whom common causes of infantile cholestasis have been excluded. After validation of the analytical sensitivity massive parallel sequencing was performed for 93 genes in six prospectively studied patients. Six novel mutations (PKHD1: p.Thr777Met, p.Tyr2260Cys; ABCB11: p.Val1112Phe, c.611+1G > A, p.Gly628Trpfs*3 and NPC1: p.Glu391Lys) and two known pathogenic mutations were detected proving our multi gene panel for infantile cholestasis to be a sensitive and specific method overcoming the complexity of the phenotype-based, candidate gene approach. Three exemplary clinical cases of infants with cholestasis are presented and discussed in the context of their genetic and histopathological findings (autosomal recessive polycystic kidney disease, atypical PFIC and Niemann-Pick syndrome type C1). These case reports highlight the critical impact of integrating clinical, histopathological and genetic data during the process of multi gene panel testing to ultimately pinpoint rare genetic diagnoses. PMID:25771912

  13. Ondansetron to Treat Pruritus Due to Cholestatic Jaundice

    Science.gov (United States)

    Dillon, Sarah; Tobias, Joseph D.

    2013-01-01

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

  14. Disseminated langerhans cell histiocytosis presenting as cholestatic jaundice.

    Science.gov (United States)

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

    2015-02-01

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

  15. Ondansetron to treat pruritus due to cholestatic jaundice.

    Science.gov (United States)

    Dillon, Sarah; Tobias, Joseph D

    2013-07-01

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

  16. A prospective pilot study: Can the biliary tree be visualized in children younger than 3 months on Magnetic Resonance Cholangiopancreatography?

    Energy Technology Data Exchange (ETDEWEB)

    Siles, Pascale [La Timone Children' s Hospital, Department of Radiology, Marseille (France); Aschero, Audrey; Gorincour, Guillaume; Bourliere-Najean, Brigitte; Petit, Philippe [La Timone Children' s Hospital, Department of Pediatric Radiology, Marseille (France); Roquelaure, Bertrand [La Timone Children' s Hospital, Department of Pediatrics, Marseille (France); Delarue, Arnauld [La Timone Children' s Hospital, Department of Pediatric Surgery, Marseille (France)

    2014-09-15

    Magnetic resonance cholangiopancreatography (MRCP) could aid in the diagnosis of biliary atresia, a hepatic pathology with thin, irregular or interrupted biliary ducts. There is little published evidence of MRCP appearances in normal neonates and young infants. To assess the use of MR cholangiopancreatography in visualizing the biliary tree in neonates and infants younger than 3 months with no hepatobiliary disorder, and to assess this visibility in relationship to the child's age, weight, and sedation and fasting states. Between December 2008 and October 2010 our department performed MRI of the brain, orbits and face on 16 full-term neonates and infants. Each child was younger than 3 months (90 days) and without any hepatobiliary disorders. The children were scanned with a respiratory-gated 0.54 x 0.51 x 0.4-mm{sup 3} 3-D MRCP sequence. We used a reading grid to assess subjectively the visibility of the extrahepatic bile ducts along with extrahepatic bile duct confluence. The visibility of the extrahepatic bile duct confluence was assessed against age, weight, and sedation and fasting states. The extrahepatic bile duct confluence was seen in 10 children out of 16 (62.5%). In the neonate sub-group (corrected age younger than 30 days), the MRCP was technically workable and the extrahepatic bile duct confluence was seen in four cases out of eight (50%). This visualization was up to 75% in the subgroup older than 30 days. However, statistically there was no significant difference in visibility of the extrahepatic bile duct confluence in relationship to age, weight or MRCP performance conditions (feeding, fasting or sedation). The complete normal biliary system (extrahepatic bile duct confluence included) is not consistently visualized in infants younger than 3 months old on non-enhanced MRCP. Thus the use of MRCP to exclude a diagnosis of biliary atresia is compromised at optimal time of surgery. (orig.)

  17. Different morphologic aspects and clinical features in massive hepatic amyloidosis.

    Science.gov (United States)

    Melato, M; Manconi, R; Magris, D; Morassi, P; Benussi, D G; Tiribelli, C

    1984-01-01

    4 cases of massive hepatic amyloidosis are reported with special reference to their clinical profiles and histologic features. On the basis of these data, two different clinical and histologic courses of the disease can be distinguished. 2 patients showed marked hepatomegaly without cholestasis, whereas in the other 2 the clinical picture was characterized by much less pronounced hepatomegaly, but by severe and progressive intrahepatic cholestasis. The time course of the disease seems to be different in the two forms, the cholestatic form being more rapidly fatal than the other. PMID:6745505

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

    OpenAIRE

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

    2013-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

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

    OpenAIRE

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

    2012-01-01

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