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Sample records for cholestasis extrahepatic

  1. The role of imaging methods in identifying the causes of extrahepatic cholestasis.

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    Rogoveanu, Ion; Gheonea, Dan Ionut; Saftoiu, Adrian; Ciurea, Tudorel

    2006-09-01

    Transabdominal ultrasonography is the first choice examination used for the etiological diagnosis of extrahepatic cholestasis because it is a noninvasive, rapid method and presently widely accessible. In this article we discuss the accuracy of transabdominal ultrasonography, computed tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP), magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasonography (EUS) in detecting the main causes of extrahepatic colestasis. Although in bile duct pathology, and especially in the evaluation of patients with jaundice, transabdominal ultrasonography is the first choice exploration, helicoidal CT, ERCP and MRCP are often required to establish the local cause of jaundice, local and distant consequences evaluation, appreciation of surgical intervention opportunity and choice of the right therapeutic method.

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

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

    1991-04-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  4. Extrahepatic complications of chronic cholestasis: current diagnosis and treatment.

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    Prelipcean, Cristina Cijevschi; Mihai, Cătălina; Gogălniceanu, P; Mihai, B

    2012-01-01

    Pruritus, fatigue and osteoporosis are the main symptoms of the extra hepatic manifestations of chronic cholestasis that affect patients' quality of life. Pruritus affects more often female patients, varies as intensity during a day and for longer period of time, typically can be localized on the palms of hands and soles of feet or can be generalized. Pruritus can be treated with anions resines exchange--cholestiramine, the pregnanne X receptor agonist Rifampicine, Naltrexone. Liver transplantation can be considered if severe pruritus remains refractory to all medical treatments. Fatigue is the most disabling complain in chronic colestasis. No specific therapies are available for fatigue and liver transplantation doesn't improve it. Osteoporosis and the risk of fractures are more severe with the duration and severity of hepatic disease. For treatment are recommended regular physical exercise, vitamin D and Ca supplimentation and bisphosphonates (Alendronate 70 mg/week) in severe cases. Only patients with atherosclerotic risk and hyperlipemia can be treated with statines. Fat soluble vitamin supplementation can be administrated only in symptomatic and proved vitamin deficiency.

  5. Effect of L-arginine on metabolism of polyamines in rat's brain with extrahepatic cholestasis.

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    Sokolovic, Dusan; Bjelakovic, Gordana; Nikolic, Jelenka; Djindjic, Boris; Pavlovic, Dusica; Kocic, Gordana; Stojanovic, Ivana; Pavlovic, Voja

    2010-01-01

    Cholestatic encephalopathy results from accumulation of unconjugated bilirubin and hydrophobic bile acids in the brain. The aim of this study was to determine disturbances of polyamine metabolism in the brains of rats with experimental extrahepatic cholestasis and the effects of L-arginine administration. Wister rats were divided into groups: I: sham-operated, II: rats treated with L-arginine, III: animals with bile-duct ligation (BDL), and IV: cholestatic-BDL rats treated with L-arginine. Increased plasma gamma-glutamyltransferase and alkaline phosphatase activity and increased bile-acids and bilirubin levels in BDL rats were reduced by administration of L-arginine (P < 0.001). Cholestasis increased the brain's putrescine (P < 0.001) and decreased spermidine and spermine concentration (P < 0.05). The activity of polyamine oxidase was increased (P < 0.001) and diamine oxidase was decreased (P < 0.001) in the brains of BDL rats. Cholestasis increased the activity of arginase (P < 0.05) and decreased the level of citrulline (P < 0.001). Administration of L-arginine in BDL rats prevents metabolic disorders of polyamines and establishes a neuroprotective role in the brain during cholestasis.

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

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    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.

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

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

    2015-04-15

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

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

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    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.

  10. Renal elimination of organic anions in cholestasis

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    Adriana Mónica Tortes

    2008-01-01

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

  11. Intrahepatic cholestasis without jaundice

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

    2009-01-01

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

  12. Extrahepatic manifestations of HCV.

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    Grignoli, R; Goossens, N; Negro, F

    2015-03-01

    The hepatic consequences of an infection with the hepatitis C virus (HCV) are well recognised, but extrahepatic manifestations of HCV may be just as severe. Here we have reviewed various extrahepatic manifestations of HCV such as mixed cryoglobulinemia, lymphoma, metabolic features and neurologic consequences and we discuss pathogenesis and management of these clinical problems. We concluded with important aspects of therapy with novel anti-HCV agents and its effects on extrahepatic manifestations.

  13. Ultrasonography of Neonatal Cholestasis

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

    2012-06-15

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

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

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    Aburano, Tamio; Takayama, Teruhiko; Shuke, Noriyuki

    1987-05-01

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

  15. Experimental obstructive cholestasis: the wound-like inflammatory liver response

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    Aller María-Angeles

    2008-11-01

    Full Text Available Abstract Obstructive cholestasis causes hepatic cirrhosis and portal hypertension. The pathophysiological mechanisms involved in the development of liver disease are multiple and linked. We propose grouping these mechanisms according to the three phenotypes mainly expressed in the interstitial space in order to integrate them. Experimental extrahepatic cholestasis is the model most frequently used to study obstructive cholestasis. The early liver interstitial alterations described in these experimental models would produce an ischemia/reperfusion phenotype with oxidative and nitrosative stress. Then, the hyperexpression of a leukocytic phenotype, in which Kupffer cells and neutrophils participate, would induce enzymatic stress. And finally, an angiogenic phenotype, responsible for peribiliary plexus development with sinusoidal arterialization, occurs. In addition, an intense cholangiocyte proliferation, which acquires neuroendocrine abilities, stands out. This histopathological finding is also associated with fibrosis. It is proposed that the sequence of these inflammatory phenotypes, perhaps with a trophic meaning, ultimately produces a benign tumoral biliary process – although it poses severe hepatocytic insufficiency. Moreover, the persistence of this benign tumor disease would induce a higher degree of dedifferentiation and autonomy and, therefore, its malign degeneration.

  16. Intrahepatic cholestasis of pregnancy

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    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.

  17. Progressive familial intrahepatic cholestasis

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    Baussan Christiane

    2009-01-01

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

  18. Hepatitis C: extrahepatic manifestations.

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    Metts, Julius; Carmichael, Lesley; Kokor, Winfred; Scharffenberg, Robert

    2014-12-01

    Chronic hepatitis C virus (HCV) infection is associated with multiple extrahepatic manifestations (EHM) affecting various organs in the body. Approximately 40% to 75% of patients with chronic HCV infection experience at least one clinical EHM during the course of the HCV infection. Mixed cryoglobulinemia (type 2) is the most documented EHM associated with chronic HCV infection. This has been documented in up to 50% of patients. Clinically, it presents as arthralgia, weakness, and cutaneous symptoms. Morphologically, immune complex depositions are identified in small vessels and glomerular capillary walls, leading to leukocytoclastic vasculitis in the skin and membranoproliferative glomerulonephritis in the kidney. In other EHMs of chronic HCV infection not related to cryoglobulinemia, such as Sjögren syndrome, lichen planus, and autoimmune thyroiditis, autoimmune processes resulting in chronic inflammatory infiltrates are thought to be the underlying mechanism.

  19. Congenital extrahepatic portosystemic shunts

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

    2003-09-01

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

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

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    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

  1. Lipid profiling of lipoprotein X: Implications for dyslipidemia in cholestasis.

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    Heimerl, Susanne; Boettcher, Alfred; Kaul, Harald; Liebisch, Gerhard

    2016-08-01

    Lipoprotein X (Lp-X) is an abnormal lipoprotein that may typically be formed in intra- and extrahepatic cholestasis and potentially interfere with lipid analysis in the routine lab. To gain insight into lipid class and species composition, Lp-X, LDL and HDL from cholestatic and control serum samples were subjected to mass spectrometric analysis including phospholipids (PL), sphingolipids, free cholesterol (FC), cholesteryl esters (CE) and bile acids. Our analysis of Lp-X revealed a content of 46% FC, 49% PL with 34% phosphatidylcholine (PC) as main PL component. The lipid species pattern of Lp-X showed remarkable high fractions of mono-unsaturated species including PC 32:1 and PC 34:1 and phosphatidylethanolamine (PE) 32:1 and 34:1. LDL and HDL lipid composition in the same specimens strongly reflected the lipid composition of Lp-X with increased PC 32:1, PC 34:1, PE 32:1, PE 34:1 and FC accompanied by decreased CE compared to controls. Comparison of Lp-X and biliary lipid composition clearly indicates that Lp-X does not originate from a sole release of bile lipids. Moreover, these data present evidence for increased hepatic fatty acid and PL synthesis which may represent a reaction to high hepatic FC level observed during cholestasis.

  2. Extrahepatic manifestations of hepatitis C.

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    Palekar, Nicole A; Harrison, Stephen A

    2005-10-01

    Hepatitis C affects approximately 170 million people worldwide. Extrahepatic manifestations of chronic hepatitis C infection are clinically evident in nearly 40% of patients. Much research has been done over the last decade to better understand their incidence, clinical presentation, mechanism of disease, and the role of antiviral therapy in their treatment. Of the commonly reported manifestations, cryoglobulinemia, membranoproliferative glomerulonephritis, and porphyria cutanea tarda remain the best understood manifestations. More recently, the association of insulin resistance and diabetes mellitus with chronic hepatitis C has been demonstrated. This paper serves to review the growing body of literature detailing the extrahepatic manifestations of chronic hepatitis C.

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

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    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

  4. Pruritus and dermographism due to intrahepatic cholestasis of infancy.

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    Evans, J; Beer, W; Davies, R

    1978-04-01

    A case report of intrahepatic cholestasis of infancy presenting with chronic severe pruritus is described. This presentation is compared with similar cases attending this unit. Intrahepatic cholestasis of infancy and the pathogenesis of puritus associated with cholestasis are briefly discussed.

  5. [Extrahepatic manifestations in hepatitis C].

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    Risum, Malene

    2011-05-09

    Hepatitis C does not only affect the liver, but also manifests outside the liver. The skin, kidneys and nervous system are often involved due to mixed cryoglobulinaemia. Porphyria cutanea tarda, lymphoma and thyroid diseases among others can also attend a chronic infection, but the exact pathogenesis behind these manifestations is not clearly mapped. Antiviral treatment is reported to induce sustained virological response in more than half of the treated patients with a variable clinical response in the extrahepatic manifestations.

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

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    Faust Dominik

    2009-01-01

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

  7. Extrahepatic manifestations of hepatitis C virus infection.

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    Zignego, Anna Linda; Craxì, Antonio

    2008-08-01

    Hepatitis C virus may cause hepatic and extrahepatic diseases. Extrahepatic manifestations range from disorders for which a significant association with viral infection is supported by epidemiologic and pathogenetic data, to anecdotal observations without clear proof of causality. This article describes the diagnosis and treatment of these diseases.

  8. Sepsis as a cause of intrahepatic cholestasis

    Directory of Open Access Journals (Sweden)

    Rudić Jelena

    2009-01-01

    Full Text Available Introduction. The causes of intrahepatic cholestasis include cholestatic viral hepatitis, primary biliary cirrhosis, benign recurrent cholestasis, primary sclerosing cholangitis and sepsis. During sepsis, proinflammatory cytokines and nitric oxide cause cholestasis by impairing hepatocellular and ductal bile formation. Case Outline. We report a 48-year-old woman who was admitted to hospital due to malaise, jaundice, fever and pain in the neck. Physical examination revealed jaundice, tachycardia (pulse rate was 120/min, hypotension 90/60 mm Hg. Laboratory findings showed normocytic normochromic anaemia, inflammatory syndrome and abnormal liver function tests indicating cholestasis and hepatocellular necrosis. Abdominal ultrasonography detected hepatosplenomegaly. Chest computed tomography showed bronchopneumonic infiltrates. Percutaneous liver biopsy was performed using a Menghini needle of 1.4 mm. Pathohystological analysis of the liver tissue confirmed reactive, intrahepatic cholestasis. Blood cultures isolated Staphylococcus aureus. After the diagnosis was established the treatment with broad-spectrum antibiotics was carried out, resulting in the improvement of general condition of the patient, regression of inflammatory syndrome, disappearance of cholestasis and regression of pulmonary infiltrates. Abdominal ultrasonography after antibiotic treatment did not show hepatosplenomegaly. Conclusion. Concerning patients with cholestasis of uncertain origin, we should always think of sepsis as a possible cause in order to start antibiotic treatment in time.

  9. Extrahepatic manifestations of hepatitis E virus.

    Science.gov (United States)

    Kamar, Nassim; Marion, Olivier; Abravanel, Florence; Izopet, Jacques; Dalton, Harry R

    2016-04-01

    Hepatitis E virus can cause acute, fulminant and chronic hepatitis and has been associated with a range of extrahepatic manifestations. Guillain-Barré syndrome, neuralgic amyotrophy and encephalitis are the main neurological manifestations associated with acute and chronic hepatitis E virus infection. Renal injuries have been also reported, including membranoproliferative glomerulonephritis with or without cryoglobulinemia and membranous glomerulonephritis. Acute pancreatitis, haematological disorders and other autoimmune extrahepatic manifestations of hepatitis E virus, such as myocarditis and thyroiditis, have been also reported. In this comprehensive article, we review all published reports describing hepatitis E virus-associated extrahepatic manifestations.

  10. Genetics Home Reference: benign recurrent intrahepatic cholestasis

    Science.gov (United States)

    ... All Close All Description Benign recurrent intrahepatic cholestasis (BRIC) is characterized by episodes of liver dysfunction called ... a lack of appetite. A common feature of BRIC is the reduced absorption of fat in the ...

  11. [Extrahepatic manifestations of hepatitis C virus infection].

    Science.gov (United States)

    Roca, Bernardino

    2004-10-01

    Hepatitis C virus predominantly affects the liver, although it may also produce a number of extrahepatic manifestations, such as mixed cryoglobulinemia, salivary and lacrimal gland dysfunction, and several types of kidney disease. The pathogenesis of these conditions is not completely understood, but immunologic mechanisms are involved in many cases. In some patients with hepatitis C virus infection, the extrahepatic manifestations predominate and their proper diagnosis and management is very important.

  12. Extrahepatic intraductal ectopic hepatocellularcarcinoma:bileductifllingdefect

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  13. Extrahepatic manifestations of chronic viral hepatitis.

    Science.gov (United States)

    Pyrsopoulos, N T; Reddy, K R

    2001-02-01

    Hepatitis B (HBV) and C (HCV) viruses are well-recognized causes for chronic hepatitis, cirrhosis, and even for hepatocellular carcinoma. Apart from liver disease, these viral infections are known to be associated with a spectrum of extrahepatic manifestations. The prevalence of clinically significant extrahepatic manifestations is relatively low, but it can be associated with significant morbidity and even mortality. An awareness and recognition of these manifestations is of paramount importance in facilitating early diagnosis and in offering treatment. However, treatments are not necessarily effective, and patients may continue with disabling extrahepatic manifestations. Hepatitis B virus has been well recognized as causing a variety of manifestations that include skin rash, arthritis, arthralgia, glomerulonephritis, polyarteritis nodosa, and papular acrodermatitis. More recently, infection with hepatitis C virus has elicited considerable interest for its role in a spectrum of extrahepatic manifestations. Among the best-reported are cryoglobulinemia, glomerulonephritis, high titer of autoantibodies, idiopathic thrombocytopenic purpura, lichen planus, Mooren's corneal ulcer, Sjögren's syndrome, porphyria cutanea tarda, and necrotizing cutaneous vasculitis. The precise pathogenesis of these extrahepatic complications has not been determined, although the majority represent the clinical expression of autoimmune phenomena.

  14. Extrahepatic complications to cirrhosis and portal hypertension

    DEFF Research Database (Denmark)

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

    2014-01-01

    In addition to complications relating to the liver, patients with cirrhosis and portal hypertension develop extrahepatic functional disturbances of multiple organ systems. This can be considered a multiple organ failure that involves the heart, lungs, kidneys, the immune systems, and other organ...

  15. Extrahepatic bile duct neurilemmoma mimicking Klatskin tumor.

    Science.gov (United States)

    Kamani, Fereshteh; Dorudinia, Atosa; Goravanchi, Farhood; Rahimi, Farzaneh

    2007-04-01

    Neurilemmoma rarely develops in the biliary tree. Here, we report a 39-year-old Iranian woman with neurilemmoma in the extrahepatic bile duct presenting with progressively deepening jaundice. On the basis of clinical and radiological features, this tumor was initially suspected as Klatskin tumor. Histologically, the tumor was a typical neurilemmoma. Immunostaining showed that tumor cells were strongly and diffusely positive for S-100 protein, which supported the diagnosis of neurilemmoma. Neurilemmoma should be considered in the differential diagnosis of obstructive jaundice.

  16. 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

  17. The extrahepatic manifestations of hepatitis B virus.

    Science.gov (United States)

    Baig, Saeeda; Alamgir, Mohiuddin

    2008-07-01

    Hepatitis B Virus (HBV) leads to a number of hepatic complications, from acute to chronic hepatitis, cirrhosis and hepatocellular carcinoma, is a well-established fact. Upcoming clinical research, over the years, associates numerous extrahepatic manifestations during the acute and chronic episodes of hepatitis B with significant morbidity and mortality. A causal relationship between HBV and serious autoimmune disorders has also been observed among certain susceptible vaccine recipients in a defined temporal period following immunization. The cause of these extrahepatic manifestations is generally believed to be immune mediated. The most commonly described include skin rash, arthritis, arthralgia, glomerulonephritis, polyarteritis nodosa, and papular acrodermatitis etc. The serum-sickness like "arthritis-dermatitis" prodrome has also been observed in approximately one-third of patients acquiring HBV infections. Skin manifestations of HBV infection typically present as palpable purpura reported to be caused by chronic HBV, although this association remains controversial. To consider the relationship between HBV and other clinically significant disorders as well as serious autoimmune disorders among certain vaccine recipients is the topic of this review. Variable factors that influence extrahepatic manifestation are discussed, including possible synergy between hepatitis B virus and the immune system.

  18. 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

  19. Genetic cholestasis : Lessons from the molecular physiology of bile formation

    NARCIS (Netherlands)

    Jansen, PLM; Muller, M

    2000-01-01

    Progressive familial intrahepatic cholestasis (PFIC) is a group of severe genetic cholestatic liver diseases of early life. PFIC types 1 and 2 are characterized by cholestasis and a low to normal serum gamma-glutamyltransferase (GGT) activity, whereas in PFIC type 3, the serum GGT activity is elevat

  20. Chronic hepatitis C with extrahepatic manifestations.

    Science.gov (United States)

    Poantă, Laura; Albu, Adriana

    2007-01-01

    Chronic hepatitis C is often asymptomatic and is mostly discovered accidentally. The natural course of viral C infection varies considerably from one person to another. Chronic hepatitis C more than other forms of hepatitis is diagnosed because of extrahepatic manifestations associated with the presence of HCV such as thyroiditis, porphyria cutanea tarda, cryoglobulinemia and glomerulonephritis, specifically membranoproliferative glomerulonephritis, sicca syndrome, thrombocytopenia, lichen planus, diabetes mellitus and B-cell lymphoproliferative disorders. We report here a case of a young man with hepatitis C and porphyria cutanea tarda who developed psoriasis after the beginning of systemic interferon therapy.

  1. Extrahepatic Manifestations of Hepatitis C Virus.

    Science.gov (United States)

    Viganò, Mauro; Colombo, Massimo

    2015-12-01

    Chronic infection with the hepatitis C virus (HCV) is a major cause of liver disease worldwide and is also responsible for extrahepatic manifestations (EHMs) involving the skin, kidneys, salivary glands, eyes, thyroid, and immune system. Mixed cryoglobulinemia is the prototype EHM related to HCV infection. Although these HCV-related EHMs may contribute to significant rates of morbidity affecting patient's quality of life and survival, most of these complications can reverse after HCV eradication by interferon therapy. This notwithstanding, individual patients may have an irreversible injury in various organs that is not reversed by a cure of the HCV infection.

  2. [Extrahepatic manifestations of infection with hepatitis C virus].

    Science.gov (United States)

    García Ferrera, Waldo O; Nodarse Cuní, Hugo; Moredo Romo, Edelisa

    2009-01-01

    Since the identification of hepatitis C in 1989, it has been studied extensively. In addition to its hepatotropic; have extrahepatic effects that are directly related to extrahepatic replication with high affinity to lymphoid tissues. As a result of that characteristics, autoimmune manifestations or a widespread immune stimulation, hematological, endocrine, dermatological, Ophtalmic, salival and other miscellaneous problems can be presented in affected patients.

  3. Extrahepatic manifestations and insulin resistance in an HCV hyperendemic area.

    Science.gov (United States)

    Nagao, Yumiko; Kawaguchi, Takumi; Tanaka, Kazuo; Kumashiro, Ryukichi; Sata, Michio

    2005-08-01

    Hepatitis C virus (HCV) causes extrahepatic manifestations as well as liver diseases, and contributes to insulin resistance and type 2 diabetes mellitus. The purpose of the present study was to evaluate the relationship of extrahepatic manifestations and insulin resistance in an HCV hyperendemic area. We investigated the incidence of extrahepatic manifestations among 139 inhabitants living in an HCV hyperendemic area in 2002 and compared it to 1999 data for the same inhabitants. Insulin resistance was tested for some non-HCV or HCV-infected inhabitants we had identified during mass screenings in 1999 and 2002. For some of the inhabitants in 2002, we examined records on the prevalence of insulin resistance seven years earlier. The prevalence of extrahepatic manifestations among individuals with positivity for anti-HCV antibodies was higher than among those without HCV in both 1999 and 2002. The prevalence of each extrahepatic manifestation which we identified in 2002 was higher than in 1999. Moreover, in some non-HCV or HCV-infected inhabitants, insulin resistance in 2002 was significantly higher than in 1999. Among inhabitants who had HCV infection with extrahepatic manifestations, fasting insulin levels or HOMA-IR findings seven years prior was significantly higher than for inhabitants who had neither HCV infection nor extrahepatic manifestations (p = 0.03, p = 0.01, respectively). Insulin resistance induces HCV infection, which causes an increase in the incidence of extrahepatic manifestations in HCV-infected individuals.

  4. 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.

  5. Prolonged cholestasis and ductopenia associated with tenoxicam.

    Science.gov (United States)

    Trak-Smayra, Viviane; Cazals-Hatem, Dominique; Asselah, Tarik; Duchatelle, Veronique; Degott, Claude

    2003-07-01

    Cholestatic liver diseases leading to progressive destruction of intra-hepatic bile ducts and ductopenia encompass multiple etiologies. Pathophysiology and natural history of drug-induced cholangiopathies remain unclear. We report a case of prolonged ductopenia attributed to Tenoxicam (Tilcotil o--a non-steroidal anti-inflammatory drug of the oxicam family) ingested at therapeutic dose. A 36 year-old male patient was admitted for jaundice and Lyell syndrome starting 1 week after the ingestion of Tenoxicam. Liver biopsy showed cholestasis, non-suppurative cholangitis and polymorphous inflammatory infiltrate of the portal tracts (round cells, macrophages an eosinophils). Treatment with ursodesoxycholic acid and cholestyramine was instituted and the patient was asymptomatic 1 year after. Three years later mild biological cholestasis persisted and ductopenia was evidenced on liver biopsy. In this report we found that: (1) The toxicity of tenoxicam was probably mediated by an immunoallergic mechanism (Lyell syndrome and eosinophils on histology); (2) ductopenia was secondary to inflammatory cholangitis. Factors responsible for this chronic evolution are still unknown (genetic predisposition, vascular factors, etc.); and (3) the presence of ductopenia contrasted with the "clinical recovery" of the disease suggesting accessory bile drainage by cholangioles or partial reconstruction of the biliary tree.

  6. 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

  7. Bile duct ligation in mice: induction of inflammatory liver injury and fibrosis by obstructive cholestasis.

    Science.gov (United States)

    Tag, Carmen G; Sauer-Lehnen, Sibille; Weiskirchen, Sabine; Borkham-Kamphorst, Erawan; Tolba, René H; Tacke, Frank; Weiskirchen, Ralf

    2015-02-10

    In most vertebrates, the liver produces bile that is necessary to emulsify absorbed fats and enable the digestion of lipids in the small intestine as well as to excrete bilirubin and other metabolic products. In the liver, the experimental obstruction of the extrahepatic biliary system initiates a complex cascade of pathological events that leads to cholestasis and inflammation resulting in a strong fibrotic reaction originating from the periportal fields. Therefore, surgical ligation of the common bile duct has become the most commonly used model to induce obstructive cholestatic injury in rodents and to study the molecular and cellular events that underlie these pathophysiological mechanisms induced by inappropriate bile flow. In recent years, different surgical techniques have been described that either allow reconnection or reanastomosis after bile duct ligation (BDL), e.g., partial BDL, or other microsurgical methods for specific research questions. However, the most frequently used model is the complete obstruction of the common bile duct that induces a strong fibrotic response after 21 to 28 days. The mortality rate can be high due to infectious complications or technical inaccuracies. Here we provide a detailed surgical procedure for the BDL model in mice that induce a highly reproducible fibrotic response in accordance to the 3R rule for animal welfare postulated by Russel and Burch in 1959.

  8. Prolonged cholestasis after raloxifene and fenofibrate interaction: A case report

    Institute of Scientific and Technical Information of China (English)

    M Isabel Lucena; Raúl J Andrade; Luis Vicioso; F Jesús González; Ketevan Pachkoria; Beatriz García-Mu(n)oz

    2006-01-01

    Assigning causality in drug-induced liver injury is challenging particularly when more than one drug could be responsible. We report a woman on long-term therapy with raloxifen who developed acute cholestasis shortly after starting fenofibrate. The picture evolved into chronic cholestasis. We hypothesized that an interaction at the metabolic level could have triggered the presentation of hepatotoxicity after a very short time of exposure to fenofibrate in this patient. The findings of an overexpression of vascular endothelial growth factor in the liver biopsy suggest that angiogenesis might play a role in the persistance of toxic cholestasis.

  9. 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.

  10. Percutaneous transarterial embolization of extrahepatic arteroportal fistula

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  11. Magnetic resonance imaging of extrahepatic bile duct disruption

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Yon-Cheong; Wang, Li-Jen; Chen, Chi-Jen [Department of Radiology, Chang Gung Memorial Hospital, 5, Fu-Hsing Street, Gueishan, 33333 Taoyuan (Taiwan); Chen, Ray-Jade [Division of Trauma and Emergency Surgery, Chang Gung Memorial Hospital, 5, Fu-Hsing Street, Gueishan, 33333 Taoyuan (Taiwan)

    2002-10-01

    Blunt injury of the extrahepatic bile duct is rare and hence a large series of scientific study of its MRI is difficult to perform. We present the MRI and MR cholangiography of a case of blunt extrahepatic bile duct injury proven at surgery. The diagnosis could be established based on MRI findings of an abrupt tapering of the extrahepatic bile duct with a retracted end, a discordant small-caliber proximal duct, massive ascites, and a hematoma in proximity to the bile duct injury. This non-invasive MRI study is a promising imaging modality to evaluate biliary tract injury. (orig.)

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

    Institute of Scientific and Technical Information of China (English)

    JIANG Haiyan; DAN Zili; WANG Hui; LIN Jusheng

    2007-01-01

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

  13. Extrahepatic manifestations of chronic hepatitis B.

    Science.gov (United States)

    Han, Steven-Huy B

    2004-05-01

    Several extrahepatic manifestations are associated with chronic HBV infection, many with significant morbidity and mortality. The cause of these extrahepatic manifestations is generally believed to be immune mediated. PAN is a rare, but serious, systemic complication of chronic HBV affecting the small- and medium-sized vessels. PAN is seen more frequently in North American and European patients and rarely in Asian patients. PAN ultimately involves multiple organ systems, some with devastating consequences, though the hepatic manifestations are often more mild. The optimal treatment of HBV-associated PAN is thought to include a combination of antiviral and immunosuppressive therapies. HBV-associated GN occurs mainly in children, predominantly males, in HBV endemic areas of the world, but is only occasionally reported in the United States. In children, GN is usually self-limited with only rare progression to renal failure. In adults, the natural disease course of GN may be more relentless, slowly progressing to renal failure. Immunosuppressive therapy in HBV-related GN is not recommended, but antiviral therapy with alpha-interferon has shown promise. The serum-sickness like "arthritis-dermatitis" prodrome is seen in approximately one third of patients acquiring HBV. The joint and skin manifestations are varied, but the syndrome spontaneously resolves at the onset of clinical hepatitis with few significant sequelae. Occasionally, arthritis following the acute prodromal infection may persist; however, joint destruction is rare. The association between HBV and mixed essential cryoglobulinemia remains controversial; but a triad of purpura, arthralgias, and weakness, which can progress to nephritis, pulmonary disease, and generalized vasculitis, has characterized the syndrome. Finally, skin manifestations of HBV infection typically present as palpable purpura. Though papular acrodermatitis of childhood has been reported to be caused by chronic HBV, this association

  14. A Rare Presentation of Hepatitis A Infection with Extrahepatic Manifestations

    OpenAIRE

    Geetika Bhatt; Sandhu, Varrinder S.; Mitchell, Charlene K

    2014-01-01

    Hepatitis A has a variety of associated extrahepatic manifestations that clinicians should be aware of for early diagnosis and treatment. We report a unique case of hepatitis A presenting with multiple extrahepatic manifestations not previously described in a single patient. A 34-year-old male presented with sudden onset of left sided facial pain, swelling, and skin rash, with diffuse body pains and muscle weakness, and was found to be positive for hepatitis A immunoglobulin M (IgM). He was i...

  15. Genetic Cholestasis: Lessons from the Molecular Physiology of Bile Formation

    Directory of Open Access Journals (Sweden)

    Peter LM Jansen

    2000-01-01

    Full Text Available Progressive familial intrahepatic cholestasis (PFIC is a group of severe genetic cholestatic liver diseases of early life. PFIC types 1 and 2 are characterized by cholestasis and a low to normal serum gamma-glutamyltransferase (GGT activity, whereas in PFIC type 3, the serum GGT activity is elevated. PFIC types 1 and 2 occur due to mutations in loci at chromosome 18 and chromosome 2, respectively. The pathophysiology of PFIC type 1 is not well understood. PFIC types 2 and 3 are caused by transport defects in the liver affecting the hepatobiliary secretion of bile acids and phospholipids, respectively. Benign recurrent intrahepatic cholestasis (BRIC is linked to a mutation in the same familial intrahepatic cholestasis 1 locus at chromosome 18. Defects of bile acid synthesis may be difficult to differentiate from these transport defects.Intrahepatic cholestasis of pregnancy (ICP appears to be related to these cholestatic diseases. For example, heterozygosity in families with PFIC type 3 is associated with ICP, but ICP has also been reported in families with BRIC.In Dubin-Johnson syndrome there is no cholestasis; only the hepatobiliary transport of conjugated bilirubin is affected. This, therefore, is a mild disease, and patients have a normal lifespan.

  16. Extrahepatic morbidity and mortality of chronic hepatitis C.

    Science.gov (United States)

    Negro, Francesco; Forton, Daniel; Craxì, Antonio; Sulkowski, Mark S; Feld, Jordan J; Manns, Michael P

    2015-11-01

    Chronic hepatitis C virus (HCV) infection is associated with several extrahepatic manifestations. Patients with HCV may develop mixed cryoglobulinemia and its sequelae, ranging from cutaneous and visceral vasculitis to glomerulonephritis and B-cell non-Hodgkin lymphoma. HCV-infected patients have increased rates of insulin resistance, diabetes, and atherosclerosis, which may lead to increased cardiovascular morbidity and mortality. Neurological manifestations of HCV infection include fatigue and cognitive impairment. The mechanisms causing the extrahepatic effects of HCV infection are likely multifactorial and may include endocrine effects, HCV replication in extrahepatic cells, or a heightened immune reaction with systemic effects. Successful eradication of HCV with interferon alfa and ribavirin was shown to improve some of these extrahepatic effects; sustained virological response is associated with resolution of complications of cryoglobulinemia, reduced levels of insulin resistance, reduced incidence of diabetes and stroke, and improved fatigue and cognitive functioning. The availability of new interferon-free, well-tolerated anti-HCV treatment regimens is broadening the spectrum of patients available for therapy, including those in whom interferon was contraindicated, and will likely result in greater improvements in the extrahepatic manifestations of HCV. If these regimens are shown to confer significant benefit in the metabolic, cardiovascular, or neuropsychiatric conditions associated with HCV infection, extrahepatic manifestations of HCV may become a major indication for treatment even in the absence of liver disease.

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

    Science.gov (United States)

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

    2015-11-01

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

  18. 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.

  19. 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.

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

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    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.

  1. A newborn presented with cholestasis and diagnosed with congenital pituitary hormone deficiency

    OpenAIRE

    ÖZALKAYA, ELİF; Akdağ, Arzu; DENİZ PAPATYA, ESRA; TOPÇUOĞLU, Sevilay

    2016-01-01

    An infrequent reason of neonatal cholestasis is congenital pituitary hormone deficiency. Clinical manifestations of cholestasis and hypoglycaemia in the neonatal period. Gestational week 37, 3700 grams, girl baby born with cesarean sectioning. Hypoglicemia symptoms developed at postnatal first and cholestasis at postnatal third week. Multiple pituitary hormone deficiency was identified.  Cholestasis symptoms recovered with growth hormone therapy. Congenital pituitary hormone deficiency should...

  2. Extrahepatic manifestations in chronic hepatitis C virus carriers.

    Science.gov (United States)

    Rosenthal, E; Cacoub, P

    2015-04-01

    Patients with chronic hepatitis C virus (HCV) infection frequently present with extrahepatic manifestations covering a large spectrum, involving different organ systems leading to the concept of systemic HCV infection. These manifestations include autoimmune phenomena and frank autoimmune and/or rheumatic diseases and may dominate the course of chronic HCV infection. Chronic HCV infection causes liver inflammation affecting the development of hepatic diseases. HCV is also a lymphotropic virus that triggers B cells and promotes favorable conditions for B lymphocyte proliferation, including mixed cryoglobulinemia (MC) and MC vasculitis, which is the most prominent extrahepatic manifestation of chronic HCV infection. HCV may also promote a low-grade chronic systemic inflammation that may affect the development of some extrahepatic manifestations, particularly cardiovascular and cerebral vascular diseases. Recognition of extrahepatic symptoms of HCV infection could facilitate early diagnosis and treatment. The development of direct-acting antiviral agents (DDAs) has revolutionized HCV treatment. DDAs, as well as new B-cell-depleting or B-cell-modulating monoclonal antibodies, will expand the panorama of treatment options for HCV-related extrahepatic manifestations including cryoglobulinemic vasculitis. In this context, a proactive, integrated approach to HCV therapy should maximize the benefits of HCV therapy, even when liver disease is mild.

  3. Dermatologic Extrahepatic Manifestations of Hepatitis C.

    Science.gov (United States)

    Dedania, Bhavtosh; Wu, George Y

    2015-06-28

    Hepatitis C virus (HCV) affects millions of people worldwide, and an estimated 3.2 million people in the United States. HCV is a hepatotropic and lymphotropic virus that causes not only liver disease, but also a significant number of extrahepatic manifestations (EHMs). Up to 74% of patients affected by HCV will have HCV-related EHMs of some severity in their lifetime. The EHMs vary from simple cutaneous palpable purpura to complex lymphoproliferative disorders, including lymphomas and immune-complex deposit diseases causing local and/or systemic complications. Mixed cryoglobulinemia (MC) is manifested by multiple systemic organ involvement, mainly skin, kidney, peripheral nerves, and salivary glands, and less frequently causes widespread vasculitis and malignant lymphoma. MC affects up to 3% of HCV-infected patients with cryoglobulinemia of clinical significance, i.e. >6%. Severe disease requires immunosuppressive or plasma exchange therapy. HCV prevalence in the United States in patients with porphyria cutanea tarda (PCT) was reported to be 66%, much higher than that in general population. Therefore, all patients with PCT should be screened for HCV. The skin rash of PCT varies from large blisters to small vesicles and/or milia on the hands. Skin manifestations due to PCT usually respond to anti-HCV treatment together with reducing skin sun exposure, avoiding triggers, having routine phlebotomy (especially for people with chronic iron overload states), and using chloroquine. Lichen planus (LP), which typically affects both the skin and oral mucosa is a chronic inflammatory disease of squamous cell origin affecting about 1% of the worldwide population. The prevalence of HCV in patients with LP varies based on geographic location. We review here the basic pathophysiology, clinical features, and management of dermatologic manifestations of HCV.

  4. 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.

  5. Septic candidasis with intrahepatic cholestasis and immunoglobuline deficiency after renal transplantation.

    Science.gov (United States)

    Zazgornik, J; Schmidt, P; Kopsa, H; Fill, W; Deutsch, E

    1975-10-01

    Two renal allograft recipients with acquired immunoglobulin deficiency had a disseminated infection with candida albicans. Septic fever, intrahepatic cholestasis and pulmonary mycotic disease were the prominent clinical symptoms. Recurrence of septic fever during the clinical course was associated with increase of intrahepatic cholestasis. On the other hand there was an amelioration of cholestasis when effective antimycotic therapy was instituted. In our patients there was no evidence that intrahepatic cholestasis was drug-related. It was assumed that toxic metabolits of candida albicans were responsible for intrahepatic cholestasis.

  6. Association of Extrahepatic Manifestations with Autoimmune Hepatitis.

    Science.gov (United States)

    Wong, Guan Wee; Heneghan, Michael A

    2015-01-01

    For many patients with autoimmune hepatitis (AIH), the presence of extrahepatic features is well recognised both at the time of presentation and during long-term follow-up. Concomitant 'autoimmune disorders' have been described in 20-50% of patients with AIH, both in adults and children. Indeed, the presence of these associated phenomena has been incorporated into both the original and revised International AIH group scoring systems as an aid to codifying the diagnosis. In acute index presentations, non-specific joint pains sometimes flitting in nature have been reported in 10-60% of patients, and while joint swelling is uncommon, rheumatoid arthritis and mixed connective tissue disease have been reported in 2-4% of patients with AIH. For a majority of patients, these joint symptoms resolve within days of the introduction of immunosuppressive therapy. Rarer features at index presentation include a maculopapular skin rash and unexplained fever, which are features that tend to resolve quickly with treatment. Interestingly, joint pain and stiffness are also well recognised in the context of steroid withdrawal and cessation in AIH. The occasional co-presentation of AIH with coeliac disease is clinically important (1-6%), since for some patients, there is a risk of immunosuppression malabsorption, thus delaying effective treatment. Similarly, the co-existence of selective IgA deficiency (IgAD) can occur in patients with coeliac disease or in isolation. Selective IgAD as a co-existing extraheaptic feature seems to be more common in paediatric patients with AIH. For these patients, they are at an increased risk of respiratory and sinus infections. Although, typically associated with primary sclerosing cholangitis, the presence of inflammatory bowel disease (IBD; both Crohn's disease and ulcerative colitis) has been described in 2-8% of patients with AIH. Interestingly, for patients with autoimmune sclerosing cholangitis, a distinct pattern of IBD has been recently

  7. 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.

  8. Nuclear receptors : mediators and modifiers of inflammation-induced cholestasis

    NARCIS (Netherlands)

    Mulder, Jaap; Karpen, Saul J.; Tietge, Uwe J. F.; Kuipers, Folkert

    2009-01-01

    Inflammation-induced cholestasis (IIC) is a frequently occurring phenomenon. A central role in its pathogenesis is played by nuclear receptors (NRs). These ligand-activated transcription factors not only regulate basal expression of hepatobiliary transport systems, but also mediate adaptive response

  9. Neonatal cholestasis – differential diagnoses, current diagnostic procedures and treatment

    Directory of Open Access Journals (Sweden)

    Thomas eGötze

    2015-06-01

    Full Text Available Cholestatic jaundice in early infancy is a complex diagnostic problem. Misdiagnosis of cholestasis as physiologic jaundice delays the identification of severe liver diseases. In the majority of infants it may represent benign cases of breast milk jaundice, but few among them are masked and caused by neonatal cholestasis that requires a prompt diagnosis and treatment. Therefore, a prolonged neonatal jaundice longer than two weeks after birth must always be scrutinized because an early diagnosis is essential for appropriate management. To rapidly identify the cholestatic cases, the conjugated bilirubin needs to be determined in any infant presenting with prolonged jaundice at 14 days of age with or without depigmented stool. Once neonatal cholestasis is confirmed, a systematic approach is the key to reliably achieve the diagnosis in order to promptly initiate the specific, and in many cases, life saving therapy. This strategy is most important to promptly identify and treat infants with biliary atresia, the most common cause of neonatal cholestasis that requires a hepatoportoenterostomy as soon as possible.Here, we provide a detailed work-up approach including initial treatment recommendations and a clinically oriented overview of possible differential diagnoses in order to facilitate an early recognition and a timely diagnosis. This warrants a broad spectrum of diagnostic procedures and investigations including new methods that are described in this review.

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

    NARCIS (Netherlands)

    Hardikar, W.; Kansal, S.; Oude Elferink, R.P.J.; Angus, P.

    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

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

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    Camila Carbone Prado

    2006-12-01

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

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

    Science.gov (United States)

    Pawełczyk, Agnieszka

    2016-04-21

    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.

  13. A rare presentation of hepatitis a infection with extrahepatic manifestations.

    Science.gov (United States)

    Bhatt, Geetika; Sandhu, Varrinder S; Mitchell, Charlene K

    2014-01-01

    Hepatitis A has a variety of associated extrahepatic manifestations that clinicians should be aware of for early diagnosis and treatment. We report a unique case of hepatitis A presenting with multiple extrahepatic manifestations not previously described in a single patient. A 34-year-old male presented with sudden onset of left sided facial pain, swelling, and skin rash, with diffuse body pains and muscle weakness, and was found to be positive for hepatitis A immunoglobulin M (IgM). He was initially started on antibiotics for concerns of bacterial parotitis but did not show any improvement. A punch biopsy of his mandibular rash and swelling was done which showed lymphohistiocytic infiltration with a few eosinophils. A trial of prednisone resulted in improvement of his symptoms. Clinicians should be aware to look for hepatitis A infection in a patient with atypical clinical picture causing a widespread systemic inflammatory response. Treatment with prednisone may result in resolution.

  14. A Rare Presentation of Hepatitis A Infection with Extrahepatic Manifestations

    Directory of Open Access Journals (Sweden)

    Geetika Bhatt

    2014-01-01

    Full Text Available Hepatitis A has a variety of associated extrahepatic manifestations that clinicians should be aware of for early diagnosis and treatment. We report a unique case of hepatitis A presenting with multiple extrahepatic manifestations not previously described in a single patient. A 34-year-old male presented with sudden onset of left sided facial pain, swelling, and skin rash, with diffuse body pains and muscle weakness, and was found to be positive for hepatitis A immunoglobulin M (IgM. He was initially started on antibiotics for concerns of bacterial parotitis but did not show any improvement. A punch biopsy of his mandibular rash and swelling was done which showed lymphohistiocytic infiltration with a few eosinophils. A trial of prednisone resulted in improvement of his symptoms. Clinicians should be aware to look for hepatitis A infection in a patient with atypical clinical picture causing a widespread systemic inflammatory response. Treatment with prednisone may result in resolution.

  15. Extrahepatic manifestations of chronic hepatitis C virus infection

    OpenAIRE

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

    2016-01-01

    International audience; 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 therape...

  16. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  18. Extrahepatic manifestations of chronic hepatitis C virus infection.

    Science.gov (United States)

    Cacoub, Patrice; Gragnani, Laura; Comarmond, Cloe; Zignego, Anna Linda

    2014-12-15

    Hepatitis C virus (HCV) infected patients are known to be at risk of developing liver complications i.e. cirrhosis and liver cancer. However, the risks of morbidity and mortality are underestimated because they do not take into account non-liver consequences of chronic hepatitis C virus infection. Numerous extrahepatic manifestations have been reported in up to 74% of patients, from perceived to disabling conditions. The majority of data concern hepatitis C virus-related autoimmune and/or lymphoproliferative disorders, from mixed cryoglobulinaemia vasculitis to frank lymphomas. More recently, other hepatitis C virus-associated disorders have been reported including cardiovascular, renal, metabolic, and central nervous system diseases. This review aims to outline most of the extrahepatic manifestations that are currently being investigated, including some of autoimmune and/or lymphoproliferative nature, and others in which the role of immune mechanisms appears less clear. Beyond the liver, hepatitis C virus chronic infection should be analyzed as a multifaceted systemic disease leading to heavy direct and indirect costs. The accurate consideration of extrahepatic consequences of such a systemic infection significantly increases the weight of its pathological burden. The need for effective viral eradication measures is underlined.

  19. Hepatitis C virus-associated extrahepatic manifestations: a review.

    Science.gov (United States)

    Sène, Damien; Limal, Nicolas; Cacoub, Patrice

    2004-12-01

    The hepatitis C virus (HCV) infection is a worldwide disease that is characterized by a preferential chronic evolution with mild to severe liver disease, including cirrhosis and, in lesser proportion, hepatocarcinoma. Out of these complications, HCV is frequently reported to complicate extrahepatic manifestations. Among those associated to HCV infection with a high degree of certainty, mixed cryoglobulinemia and its complications (skin, neurological, renal, rheumatological involvement) are the most prevalent (50%) in HCV-infected patients. The other diseases include noncryoglobulinemic systemic vasculitis, splenic lymphoma with villous lymphocytes, fatigue, porphyria cutanea tarda, sicca syndrome, and autoantibodies production. The extrahepatic manifestations that share mild-degree certainty of association with HCV infection include B-cell non-Hodgkin lymphoma, autoimmune thrombocytopenia, pruritus, and type II diabetes mellitus. The other diseases such as autoimmune thyroiditis, lichen planus are more questionable for their eventual association with HCV and others (pulmonary fibrosis with or without polymyositis, progressive encephalomyelitis, Mooren's corneal ulcers, erythema nodosum, chronic polyradiculonevritis) are mostly case reports. Howerver, even in cases of tight association, the mechanisms through which HCV may promote or induce extrahepatic manifestations remain unclear and merit further investigations.

  20. 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.

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

    OpenAIRE

    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...

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

    OpenAIRE

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

    2015-01-01

    Prolonged parenteral nutrition (PN) leads to liver damage. Recent interest has focused on the lipid component of PN. A lipid emulsion based on w-3 fatty acids decrease conjugated bilirubin. A mixed lipid emulsion derived from soybean, coconut, olive, and fish oils reverses jaundice. Here we report the reversal of cholestasis and the improvement of enteral feeding tolerance in 1 infant with intestinal failure-associated liver disease. Treatment involved the substitution...

  3. Distribution of viral genotypes and extrahepatic manifestations in patients with chronic hepatitis C in Eastern Turkey

    OpenAIRE

    YILMAZ, Sibel İBA; Erol, Serpil; ÖZBEK, Ahmet; Parlak, Mehmet

    2015-01-01

    To investigate the distribution of viral genotypes, the extrahepatic manifestations, and the relationship between genotypes and extrahepatic manifestations in patients with chronic hepatitis C. Materials and methods: The study included 62 treatment-naive patients with chronic hepatitis C infection. Genotype determination was performed by DNA sequencing analysis. To investigate extrahepatic manifestations, the patients' data, recorded prospectively during the pretreatment period, were an...

  4. Recurrent pyogenic cholangitis: The pattern of thickening of the extrahepatic bile duct on CT

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Tae Hoon; Lim, Jae Hoon; Ko, Young Tae; Lee, Dong Ho; Jeong, Yu Mee; Lee, Eil Seong [Kang Hee University Hospital, Seoul (Korea, Republic of)

    1993-05-15

    The pattern of thickening of the extrahepatic bile duct on computed tomography was analysed in 30 cases with recurrent pyogenic cholangitis diagnosed by surgery (n=19) or by clinical basis (n=11). The mean wall thickness of the extrahepatic bile duct was 3.3 mm (range, 1-6.3 mm). Diffuse thickening of the extrahepatic bile ductal wall was demonstrated in 26 of 30 cases. Diffuse thickening of the extrahepatic bile duct in recurrent pyogenic cholangitis may be differentiated from focal thickening of duct in a common duct cancer or pancreatic cancer.

  5. 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.

  6. [The extrahepatic site of hepatitis C virus: clinical manifestations and prognostic value].

    Science.gov (United States)

    Krel', P E; Tsinzerling, O D

    2009-01-01

    The high incidence of recurrent chronic hepatitis C after a course of antiviral therapy determines the urgency of determining the extrahepatic reservoirs of hepatitis C virus (HCV). The most extrahepatic site for the virus is peripheral mononuclear cells (PMC). Assuming that there may be HCV replication in the PMC), these cells can be considered as a potential reservoir of HCV infection. The most common extrahepatic manifestation of HCV is cryoglobulinemia, the genesis of which may be active viral replication in the cells of the immune system. There is evidence that HCV is detectable just in the tissues of the involved organs. Thus, most systemic manifestations may be directly associated with extrahepatic HCV replication.

  7. Role of viral replication in extrahepatic syndromes related to hepatitis B virus infection.

    Science.gov (United States)

    Mason, A

    2006-03-01

    Approximately 20% of patients with hepatitis B virus (HBV) infection may experience extrahepatic disease. These manifestations include a viral prodrome with a serum sickness-like syndrome, polyarteritis nodosa, glomerulonephritis, as well as various neurological and dermatologic diseases amongst other manifestations. The viral pathogenesis is not well understood and has been difficult to study due to the lack of an animal model of HBV-related extrahepatic disease. Deposition of immune complexes and activation of the complement cascade has been most widely studied. However, circulating immune complexes are physiologic and occur more frequently than extrahepatic disease. Also, HBV-related extrahepatic syndromes occur in the absence of immune complex formation. Several studies support the notion that HBV replication in extrahepatic tissues may also precipitate disease but extrahepatic replication has commonly been observed without any apparent cytopathic or immune related tissue damage. It is clear that suppression of viral replication with antiviral therapy or spontaneous viral clearance positively correlates with resolution of extrahepatic disease. The use of continuous immunosuppressive therapy has largely been abandoned with the advent of robust antiviral strategies to manage disease. These data support the notion that a combination of factors including inadequate clearance immune complexes and viral replication in extrahepatic tissues play an important role in the pathogenesis. This conceptual framework is potentially significant as it emphasizes the importance of antiviral treatment in the management of extrahepatic disease.

  8. 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

  9. 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.

  10. Hepatitis B virus replication in damaged endothelial tissues of patients with extrahepatic disease.

    Science.gov (United States)

    Mason, Andrew; Theal, Jeremy; Bain, Vince; Adams, Elizabeth; Perrillo, Robert

    2005-04-01

    Hepatitis B virus (HBV) infection may be complicated by extrahepatic manifestations such as polyarteritis nodosa (PAN), glomerulonephritis, polymyositis, and dermatitis, but the etiology of these processes is not yet clear. HBV replication has been demonstrated in a variety of extrahepatic tissues and cell types, but the possible pathogenetic role of extrahepatic HBV replication has not been fully explored in patients with extrahepatic manifestations of HBV infection. In this case series, immunohistochemistry and in situ hybridization studies were performed on extrahepatic tissues from one HBsAg-positive patient with PAN and another HBsAg-positive patient with polymyositis, using HBsAg-seronegative control subjects with the same vasculitic disorders as controls. Tissue samples from the two study patients had detectable HBV RNA, replicative intermediates of HBV DNA, as well as HBsAg and HBcAg localized to vascular endothelium. In contrast, HBsAg-negative control patients had no tissue reactivity. Our results suggest that patients with HBV-related extrahepatic disease have evidence of viral replication in damaged extrahepatic endothelial tissues. While further studies would be required to support a hypothesis of causality, these findings suggest a role for both immune complex deposition and viral replication within diseased endothelial tissue in the pathogenesis of these poorly understood extrahepatic disorders.

  11. 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.

  12. EXTRAHEPATIC BILIARY DUCTAL VARIATIONS AND ITS CLINICAL SIGNIFICANCE

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    Lakshmidevi

    2016-04-01

    Full Text Available BACKGROUND Incidence of liver and Gallbladder diseases are significantly increasing in recent years. Cholecystectomy either by laparoscopic or open is the commonest surgical procedure performed by General surgeon. Liver Transplantation is emerging as one of the top most transplantation surgery as well. Variations in anatomy of Gallbladder, bile ducts and the arteries that supply them and liver are important to the surgeon, because failure to recognize them may lead to inadvertent ductal ligation, biliary leaks, haemobilia, haemorrhage and strictures after cholecystectomy and may complicate Liver transplantation surgeries. Recognition of these anomalies and normal variants may avoid diagnostic errors, aid in surgical planning and prevent inadvertent ductal injury. OBJECTIVES To study the variations in Extrahepatic Biliary Ductal system with its clinical significance. RESULTS AND CONCLUSION Extrahepatic biliary ductal system studying under various methods are established; many variations in this region and understanding of these variations is undoubtedly important for operating surgeons. Starting from open cholecystectomy or laparoscopic cholecystectomy to cadaveric liver harvesting to recent advances like “Living donor liver transplantation with duct-toduct anastomosis” (LDLT, grading of tumours like hilar cholangiocarcinoma requires definitive knowledge of the anatomy of the ductal and arterial system. Hence, we believe this study is not only confined to anatomists, but definitely be a useful guideline for general and laparoscopic surgeons, oncosurgeons and to transplant surgeons.

  13. Extrahepatic manifestations of hepatitis C infection: navigating CHASM.

    Science.gov (United States)

    Sherman, Amy C; Sherman, Kenneth E

    2015-09-01

    This article describes the importance of extrahepatic systemic manifestations of chronic hepatitis C virus (HCV) infection. While most HCV literature focuses on liver injury and fibrosis progression, a spectrum of systemic disease processes, collectively called C hepatitis-associated systemic manifestations (CHASMs), are present in a high proportion of infected persons. These include thyroid disease (Hashimoto's thyroiditis, Graves disease, and thyroid cancer), cardiovascular disease (atherosclerosis, carotid artery disease, and coronary artery disease), renal disease (MPGN and glomerulosclerosis), eye disease (Mooren's ulcers and sicca syndrome), skin disease (PCT, vasculitis, and lichen planus), lymphomas (NHL and splenic T-cell), and diabetes. Mechanistic understanding of how HCV leads to CHASM processes could lead to development of new interventions. The role of early HCV treatment and cure may result in preventive strategies for a variety of complex disease states. Key Points • Systemic extrahepatic complications of HCV comprise a spectrum of disease states in many organs and systems.• Effective treatment of HCV may reduce or eliminate some but not all of these systemic complications.• Further research into early treatment intervention as a prevention strategy for systemic disease is warranted.

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

    Directory of Open Access Journals (Sweden)

    F Joukar

    2008-04-01

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

  15. Lithocholic acid disrupts phospholipid and sphingolipid homeostasis leading to cholestasis

    Science.gov (United States)

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

    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 in decreased serum sphingomyelin levels and increased hepatic ceramide levels, and induction of LPCAT and SMPD mRNAs. Transforming growth factor-β TGF-β) induced Lpcat2/4 and Smpd3 gene expression in primary hepatocytes and the induction was diminished by pretreatment with the SMAD3 inhibitor SIS3. Furthermore, alteration of the LPC metabolites and Lpcat1/2/4 and Smpd3 expression was attenuated in LCA-treated farnesoid X receptor-null mice that are resistant to LCA-induced intrahepatic cholestasis. This study revealed that LCA induced disruption of phospholipid/sphingolipid homeostasis through TGF-β signaling and that serum LPC is a biomarker for biliary injury. PMID:21480330

  16. Neonatal cholestasis mimicking biliary atresia: Could it be urinary tract infection?

    Science.gov (United States)

    Pereira, Noella Maria Delia; Shah, Ira

    2017-01-01

    Cholestasis can occur in newborns due to infections. However, the manifestations of the underlying infections usually dominate the presentation. We present a 2-month-old infant who presented with jaundice and no fever or signs of systemic illness. Liver biopsy was suggestive of cholangitis. He was subsequently detected to have urinary tract infection with Klebsiella pneumoniae. The child was treated with appropriate antibiotics for 2 weeks following which the cholestasis resolved. Thus, neonatal cholestasis due to infections can also occur in the post-neonatal period without clinical manifestations of an underlying infection.

  17. Efficacy of surgical resection in management of isolated extrahepatic metastases of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Kun-Ming Chan; Ming-Chin Yu; Ting-Jung Wu; Chen-Fang Lee; Tse-Ching Chen; Wei-Chen Lee; Miin-Fu Chen

    2009-01-01

    AIM: To clarify the benefit of surgical excision for patients with extrahepatic metastases of hepatocellular carcinoma (HCC).METHODS: We retrospectively reviewed the medical records of 140 patients with pathologically proven extrahepatic metastases of HCC and evaluated the outcomes of those who had undergone surgical resection (SR) for extrahepatic metastatic lesions.Prognoses made on the basis of extrahepatic metastatic sites were also examined.RESULTS: The survival rates of patients who underwent SR of extrahepatic metastases were significantly better than those of patients who did not receive SR.For the SR group, 1- and 3-year survival rates were 24% and 7%, respectively, while for the non-resection group, the survival rates were 8% and 0%, respectively ( P < 0.0001).Survival rates related to metastatic sites were also significantly superior after SR of extrahepatic metastases: median survivals were 32 mo with lung metastasis, 10 mo with bone metastasis, 6.1 mo with brain metastasis.CONCLUSION: SR can provide survival benefits for patients with 1 or 2 isolated extrahepatic metastases and who concurrently exhibit good hepatic functional reserve and general performance status as well as successful treatment of intrahepatic HCC.

  18. [Surgical therapy of proximal extrahepatic bile duct tumors (Klatskin tumors)].

    Science.gov (United States)

    Timm, S; Gassel, H-J; Thiede, A

    2007-08-01

    Due to their anatomical position, the tendency of early infiltrative growth and their poor prognosis without treatment, klatskin tumors are challenging concerning diagnosis and therapy. In contrast to other tumors of the gastrointestinal tract, for which exact diagnostic and stage dependent therapeutic guidelines could be formulated, clear recommendations for klatskin tumors are missing. Thus, survival rates after local resection, e. g. resection of the bile duct bifurcation alone, show high rates of R1/2 resection and early tumor recurrence. With an additional hepatic resection formally curative resections and long-term survival can be improved. Extended liver resections including the portal vein provide the highest rates of R0 resections for hilar carcinomas of the extrahepatic bile duct. Survival rates after liver transplantation for klatskin tumors are not yet convincing. Promising first results have been reported for the combination of neoadjuvant treatment and liver transplantation and might show future perspectives for the treatment of klatskin tumors.

  19. Prolonged cholestasis and ductopenia following gold salt therapy.

    Science.gov (United States)

    Basset, Céline; Vadrot, Jacqueline; Denis, Jacques; Poupon, Joël; Zafrani, Elie Serge

    2003-04-01

    Hepatotoxicity, predominantly cholestatic, is a rare adverse effect of gold salt therapy, which usually completely resolves within a few months. We report the case of a female patient treated for rheumatoid arthritis, who had gold salt overdose, and in whom acute cholestatic hepatitis occurred three weeks after beginning of therapy. Evolution of gold concentration was followed in plasma and urine, as well as in cutaneous and liver dry tissue. Liver biopsy showed marked inflammatory changes of interlobular bile ducts that evolved towards ductopenia, which was responsible for prolonged cholestasis still present 15 months later. In addition, sialadenitis with sicca syndrome was noted six months after onset of the disease. The mechanism of hepatotoxicity was probably immunoallergic since liver lesions were associated with hypersensitivity syndrome including dermatitis and blood and tissue eosinophilia. This is the first report of gold salt hepatotoxicity with histological demonstration of cholangitis followed by ductopenia.

  20. 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.

  1. A clinical approach to intrahepatic cholestasis of pregnancy.

    Science.gov (United States)

    Diken, Zaid; Usta, Ihab M; Nassar, Anwar H

    2014-01-01

    Intrahepatic cholestasis of pregnancy (ICP) has a varying prevalence worldwide. The etiology behind this disease remains not fully understood with multiple factors influencing its development including genetic variations, dietary factors, hormonal changes, and environmental influences. Presenting mainly during the third trimester with generalized itching and resolving spontaneously postpartum, this condition is still associated with fetal morbidity and mortality. The diagnosis is based on clinical presentation in association with biochemical abnormalities. Elevation in total bile acid levels is the most frequent laboratory abnormality and seems to be the most important for gauging further management of the disease. The most appropriate gestational age for the delivery of women with ICP is yet to be determined. In this review we discuss the epidemiology, clinical features, diagnosis, etiology, and management of ICP, trying to shed light on some controversial aspects of the disease.

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

    Science.gov (United States)

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

    2014-10-25

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

  3. 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.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    Zeeshan A Wani

    2015-01-01

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

  6. Extrahepatic manifestations and autoantibodies in patients with hepatitis C virus infection.

    Science.gov (United States)

    Himoto, Takashi; Masaki, Tsutomu

    2012-01-01

    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.

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

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    G. Belli

    1998-01-01

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

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    Nasrin Hosseini

    2014-01-01

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

  10. 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.

  11. 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

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

    Science.gov (United States)

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

    2015-01-01

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

  13. 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.)

  14. 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.

  15. Results of radiation therapy in extrahepatic bile duct carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hatano, Kazuo; Cho, Keiichi; Okamoto, Moriyo (Chiba Univ. (Japan). School of Medicine) (and others)

    1992-06-01

    From January 1975 to August 1988, 40 patients with extrahepatic bile duct carcinoma were treated by external irradiation at Chiba University Hospital and the National Medical Center Hospital. Thirty-four patients (male: 20, female: 14) were evaluable. Eighteen patients were postoperative cases because the surgical margin was positive for tumor cells in the postoperative pathological examination; the other 16 were inoperable cases. Survival in postoperative and inoperable cases was not significantly different, with median survival times of 13.8 and 8.1 months, respectively. Survival in the recanalization-positive and negative-groups was significantly different (p<0.05) after irradiation, with median survival times of 13.5 and 6.0 months, respectively. Complications of therapy were recognized in 68% of all cases. They were mainly gastrointestinal symptoms such as nausea, vomiting, erosive gastritis and loss of appetite, but they were not severe. Distant metastasis was recognized in only 4 patients (10%): three had bony metastasis and one had supraclavicular and pulmonary hilar lymph node metastasis. Ninety percent of all cases died from hepatic failure or peritonitis carcinomatosa due to failure to obtain local control by external irradiation. A more effective modality of treatment is necessary to cure these patients. (author).

  16. 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.

  17. Morphologic features of extrahepatic manifestations of hepatitis C virus infection.

    Science.gov (United States)

    Ko, Huaibin M; Hernandez-Prera, Juan C; Zhu, Hongfa; Dikman, Steven H; Sidhu, Harleen K; Ward, Stephen C; Thung, Swan N

    2012-01-01

    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.

  18. [Extrahepatic manifestations of chronic hepatitis C virus infection].

    Science.gov (United States)

    Puchner, K P; Berg, T

    2009-05-01

    Current data suggest that HCV infection should be regarded as a systemic infectious disease with multiorgan involvement. More than 50 % of HCV-positive patients develop during the course of the disease at least one extrahepatic manifestation (EHM). The EHMs are often the first and only clinical signs of a chronic hepatitis C. Evidence of HCV infection should always be sought out in cases of unspecific chronic fatigue and/or rheumatic, haematological, endocrine or dermatological disorders. Key pathogenetic factors for the development of EHM are undisputably the HCV lymphotropism and cryoglobulinaemia. Nevertheless, the exact pathogenesis of many EHM still remains unclear. The therapeutic approach to EHM should concentrate on the eradication of HCV. Antiviral therapy in the form of peg-interferon and ribavirin should be regarded as the first-line therapy. Viral response leads mostly to a consecutive clinical response. However, in the case of HCV-related cytopaenias or neuropathies, antiviral therapy may trigger an aggravation of these conditions. Thus, organ-involvement, severity and course of the EHM should be always taken into account when choosing the appropriate therapeutic strategy. Immunosuppressive drugs, plasmapheresis and lately rituximab are counted among therapies that can be applied complementarly or alternatively to the antiviral therapy.

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

    Directory of Open Access Journals (Sweden)

    Kadim S. Bachtiar

    2008-06-01

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

  20. Angiography-based C-arm CT for the assessment of extrahepatic shunting before radioembolization

    Energy Technology Data Exchange (ETDEWEB)

    Heusner, Till Alexander; Hahn, S.; Forsting, M.; Antoch, G. [Inst. fuer Diagnostische und Interventionelle Radiologie und Neuroradiologie, Universitaetsklinik Essen (Germany); Hamami, M.E.; Poeppel, T.; Bockisch, A. [Klinik fuer Nuklearmedizin, Universitaetsklinik Essen (Germany); Ertle, J.; Hilgard, P. [Klinik fuer Gastroenterologie, Universitaetsklinik Essen (Germany)

    2010-07-15

    Purpose: to retrospectively assess the accuracy of angiography-based C-arm CT for the detection of extrahepatic shunting before SIRT. Materials and methods: 30 patients (mean age: 64 {+-} 12 years) with hypervascularized hepatic tumors underwent hepatic angiography, coil embolization of gastrointestinal collaterals and 99mTc-macroaggregated albumin (MAA) SPECT/CT before SIRT. Before MAA injection via a microcatheter from the intended treatment position, an angiography and angiography-based C-arm CT (XperCT trademark, Philips Healthcare) were acquired. Angiographies and XperCT trademark were performed from 48 microcatheter positions followed by MAA injections and MAA-SPECT/CT. MAA-SPECT/CT served as the reference standard for determining the accuracy of hepatic arteriography and C-arm CT for the detection of extrahepatic shunting. Results: MAA-SPECT/CT revealed extrahepatic shunting in 5 patients (17%). Hepatic arteriography yielded a true negative in 22 (73%), a false negative in 5 (17%), and an unclear result in 3 patients (10%). C-arm CT yielded a true positive in 3 (10%), true negative in 24 (80%), false positive in 1 (3%), and false negative in 2 patients (7%). The specificity and the NPV of hepatic arteriography for the detection of extrahepatic shunting were 88% and 81%, respectively. For C-arm CT the sensitivity, specificity, PPV, NPV, and accuracy for the detection of extrahepatic shunting were 60%, 96%, 75%, 92%, and 90%, respectively. Conclusion: C-arm CT offers additional information to angiography when assessing SIRT patients for extrahepatic shunting. More accurate detection of extrahepatic shunting may optimize the workflow in SIRT preparations by avoiding unnecessary repeat angiographies. (orig.)

  1. Excessive bilirubin elevation in a patient with hereditary spherocytosis and intrahepatic cholestasis.

    Science.gov (United States)

    Wree, A; Canbay, A; Müller-Beissenhirtz, H; Dechêne, A; Gerken, G; Dührsen, U; Lammert, F; Nückel, H

    2011-08-01

    Hereditary spherocytosis is a common hemolytic anemia with an estimated incidence of 1 / 2500 births. It is caused by a molecular defect in one or more of the proteins of the red blood cell cytoskeleton. Mutations in the ABCB11 gene, encoding the bile salt export pump, can entail progressive familial intrahepatic cholestasis and benign recurred intrahepatic cholestasis. A 18 year old Turkish patient with hereditary spherocytosis was admitted to hospital with pruritus and severe jaundice. Ultrasound examination presented stones in gallbladder and bile duct. After endoscopic retrograde cholangiography with extraction of small bile duct stones abdominal pain resolved and liver enzymes normalized within a few days, but bilirubin and bile acids remained highly elevated. Liver biopsy revealed a severe canalicular cholestasis. Genetic analysis showed the compound heterozygous variants ABCB11 A 444V and 3084A > G. Treatment with ursodesoxycholic acid and intermittent therapy with prednisone reduced pruritus and jaundice with concomitant improvement of blood test. Here we report the first case of a patient with combined hereditary spherocytosis and compound heterozygous ABCB11 gene variants predisposing to intrahepatic cholestasis. Therefore, patients with hemolytic disorders should be investigated for bile acid transporter diseases in case of hyperbilirubinemia and severe cholestasis.

  2. Extrahepatic manifestations of Hepatitis C Virus infection: a general overview and guidelines for a clinical approach.

    Science.gov (United States)

    Zignego, A L; Ferri, C; Pileri, S A; Caini, P; Bianchi, F B

    2007-01-01

    Hepatitis C Virus is associated with a wide series of extrahepatic manifestations. Based on available data the link between the virus and some of these extrahepatic diseases is only suggested and needs further confirmation. Hepatitis C Virus-related lymphoproliferative disorders, whose prototype is mixed cryoglobulinaemia, represent the most closely related extrahepatic manifestations of Hepatitis C Virus. Other Hepatitis C Virus-associated disorders include nephropathies, thyreopathies, sicca syndrome, idiopathic pulmonary fibrosis, porphyria cutanea tarda, lichen planus, diabetes, chronic polyarthritis, cardiopathy and atherosclerosis. A pathogenetic link between Hepatitis C Virus and some extrahepatic manifestations was confirmed by their responsiveness to antiviral therapy, which is now deemed the first therapeutic option to consider. By contrast, there are diseases where treatment with interferon was ineffective or dangerous. The aim of the present paper is to outline the most recent evidence concerning extrahepatic disorders that are possibly associated with Hepatitis C Virus infection. Special emphasis will be given to discussion of the most appropriate clinical approaches to be adopted in order to diagnose, treat (possibly prevent) and follow-up extrahepathic diseases in patients with Hepatitis C Virus infection.

  3. 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.

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

    Science.gov (United States)

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

    2015-11-01

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

  5. Thyrotoxicosis-Associated Cholestasis in a Patient with Hepatitis B Cirrhosis

    Directory of Open Access Journals (Sweden)

    Mohamed Osama Hegazi

    2008-12-01

    Full Text Available Abnormalities in liver function tests were reported in association with hyperthyroidism. Intrahepatic cholestasis is one form of this association. Reversal of hyperbilirubinemia upon correction of hyperthyroidism supports the causal relationship. Most reported cases have occurred in patients without previous liver disease. We report a case of marked cholestatic jaundice associated with hyperthyroidism caused by toxic adenoma in a patient with hepatitis B cirrhosis. Serum bilirubin returned to baseline level after correcting hyperthyroidism with radioiodine therapy. Hyperthyroidism should be considered in the differential diagnosis of cholestasis in association with chronic liver disease.

  6. 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.

  7. [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.

  8. Immaturity of the biliary excretory system predisposes neonates to intrahepatic cholestasis.

    Science.gov (United States)

    Abernathy, C O; Utili, R; Zimmerman, H J

    1979-06-01

    Intrahepatic cholestasis associated with both gram-negative bacterial infections and total parenteral nutrition (TPN) is observed more frequently in neonates than in older children or adults. Factors involved in the pathogenesis of this syndrome are uncertain. The cholestatic effects of gram-negative bacterial infections appear to result from the inhibitory effects of endotoxin on bile flow. Since the adverse effects of both endotoxin and TPN on bile flow involve primarily the bile acid-independent portion, the immaturity of the neonatal hepatic excretory system which an inadequate bile acid-dependent fraction of bile would explain the increased susceptibility of the neonate to endotoxin- and, perhaps, to TPN-induced cholestasis.

  9. [A case of sustained cholestasis caused by acute A viral hepatitis in Dubin-Johnson syndrome].

    Science.gov (United States)

    Ra, Sang Ho; Sung, Se Yong; Jung, Ho Yeon; Cha, Jae Hwang; Baik, Soon Koo; Cho, Mee Yon; Kim, Moon Young

    2012-04-01

    Dubin-Johnson syndrome is a rare clinical entity. It shows intermittent symptoms such as chronic or intermittent jaundice, abdominal pain, weakness, nausea, vomiting, anorexia and diarrhea. Symptoms are precipitated or aggravated by pregnancy, alcoholism, surgical procedures and intercurrent disease. Chronic idiopathic jaundice is typical of Dubin-Johnson syndrome and its prognosis is good. We describe a case of prolonged cholestasis for more than 10 months caused by acute A viral hepatitis in a patient with Dubin-Johnson syndrome. It is a first report of cholestasis complicated by acute A viral hepatitis in a patient with Dubin-Johnson syndrome.

  10. [Multiple extrahepatic manifestations in a patient with chronic hepatitis C treated with interferon-alfa].

    Science.gov (United States)

    Napoli, Nicola; Tortorella, Cosimo; Deramo, Maria Teresa; Antonaci, Alessandra; Parisi, Carmen Vita; Antonaci, Salvatore

    2004-11-01

    The case of a 61-years-old female patient with chronic hepatitis C who developed multiple consecutive extrahepatic manifestations is reported. One of these manifestations (lichen planus) appeared before HCV-related chronic hepatitis was diagnosed and treated with interferon-alpha, suggesting that it was likely associated with HCV itself. Other manifestations appeared during IFN-alpha treatment (polyarthritis) or after the end of treatment (ulcerative cholitis, sarcoidosis) implying a role for either HCV or IFN-alpha treatment in the pathogenesis of extrahepatic manifestations.

  11. [Efficacy of combined antiviral therapy with interferon alfa and ribavirin in chronic hepatitis C patients with extrahepatic manifestations].

    Science.gov (United States)

    Zarebska-Michaluk, Dorota; Lebensztejn, Dariusz Marek; Kryczka, Wiesław

    2007-01-01

    The aim of the study was to assess the efficacy and safety of treatment with interferon alpha and ribavirin in patients with chronic hepatitis C and extrahepatic manifestations as well as to determine prognostic factors of therapy effectiveness. 179 consecutive naive patients with chronic hepatitis C treated with interferon alpha and ribavirin were studied. 120 patients (67%) presented extrahepatic manifestations. The most frequent were cryoglobulinaemia, thrombocytopenia and thyroid gland pathology. Efficacy of antiviral treatment was lower (SVR 33.3% vs. 52.5%, p=0.013) and frequency of adverse events higher in patients with chronic hepatitis C and extrahepatic manifestations in comparison to those without extrahepatic pathology. Younger age, shorter duration of HCV infection and less advanced liver fibrosis were prognostic factors of better response to antiviral therapy in group of patients with chronic hepatitis C and extrahepatic manifestations.

  12. Oral Tocofersolan Corrects or Prevents Vitamin E Deficiency in Children With Chronic Cholestasis

    NARCIS (Netherlands)

    Thébaut, Alice; Nemeth, Antal; Le Mouhaër, Jeannie; Scheenstra, René; Baumann, Ulrich; Koot, Bart; Gottrand, Fredéric; Houwen, Roderick; Monard, Laure; de Micheaux, Sylvie Lafaye; Habes, Dalila; Jacquemin, Emmanuel

    2016-01-01

    OBJECTIVES: D-Alpha-tocopheryl polyethylene glycol 1000 succinate (Tocofersolan, Vedrop), has been developed in Europe to provide an orally bioavailable source of vitamin E in children with cholestasis. The aim was to analyze the safety/efficacy of Vedrop in a large group of children with chronic ch

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

    Science.gov (United States)

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

  14. Effect of surgically induced cholestasis on the levels of hepatic zinc and metallothionein in rat liver.

    Science.gov (United States)

    Brambila, E; Munoz-Sanchez, J L; Waalkes, M P; Albores, A

    2000-01-01

    Early effects of experimental cholestasis on the homeostasis of zinc (Zn) and metallothionein (MT) were studied in rats which had undergone bile duct ligation for 0, 3, 6, 9, 12, 16, 20, and 24 h. Transient increases in hepatic Zn levels were observed at 9 h but returned to control values at 12 h. Serum Zn levels increased at 24 h. Cholestasis was confirmed by increased serum alkaline phosphatase (AP) activity. MT increased at 3 h and reached a maximum level at 12 h and remained elevated even at 24 h after the onset of experimental cholestasis. No hepatocellular damage was detected according to the results of alanine aminotransferase (ALT) activities in serum. These results shown that the increases in Zn observed in liver are related to bile stagnation rather than to a hepatocellular damage and that increased MT occurs concurrently with increased hepatic Zn. These observations suggest that the cellular levels of Zn in cholestasis is regulated by homeostatic mechanisms, of which one could be mediated by MT.

  15. Partial External Biliary Diversion in Children With Progressive Familial Intrahepatic Cholestasis and Alagille Disease

    NARCIS (Netherlands)

    Yang, Huiqi; Porte, Robert J.; Verkade, Henkjan J.; De Langen, Zacharias J.; Hulscher, Jan B. F.

    2009-01-01

    Background: Partial external biliary diversion (PEBD) is a promising treatment for children with progressive familial intrahepatic cholestasis (PFIC) and Alagille disease. Little is known about long-term Outcomes. Patients and Methods: A retrospective chart review of all patients undergoing PEBD in

  16. Bile Acid Pool Dynamics in Progressive Familial lntrahepatic Cholestasis With Partial External Bile Diversion

    NARCIS (Netherlands)

    Jericho, Hilary S.; Kaurs, Elizabeth; Boverhof, Renze; Knisely, Alex; Shneider, Benjamin L.; Verkade, Henkjan J.; Whitington, Peter F.

    2015-01-01

    Objectives: Partial external bile diversion (PEBD) is an established therapy for low-gamma-glutamyl transferase (GGT) progressive familial intrahepatic cholestasis (PFIC). This study sought to determine whether the dynamics of the cholic acid (CA) and chenodeoxycholic acid (CDCA) pools in subjects w

  17. 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

  18. Intestinal capacity to digest and absorb carbohydrates is maintained in a rat model of cholestasis

    NARCIS (Netherlands)

    Los, E. Leonie; Wolters, Henk; Stellaard, Frans; Kuipers, Folkert; Verkade, Henkjan J.; Rings, Edmond H. H. M.

    2007-01-01

    Cholestasis is associated with systemic accumulation of bile salts and with deficiency of bile in the intestinal lumen. During the past years bile salts have been identified as signaling molecules that regulate lipid, glucose, and energy metabolism. Bile salts have also been shown to activate signal

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

    Directory of Open Access Journals (Sweden)

    Isabella Giovannoni

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

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  1. Oral Tocofersolan Corrects or Prevents Vitamin E Deficiency in Children With Chronic Cholestasis

    NARCIS (Netherlands)

    Thebaut, Alice; Nemeth, Antal; Le Mouhaer, Jeannie; Scheenstra, Rene; Baumann, Ulrich; Koot, Bart; Gottrand, Frederic; Houwen, Roderick; Monard, Laure; de Micheaux, Sylvie Lafaye; Habes, Dalila; Jacquemin, Emmanuel

    2016-01-01

    Objectives:d-Alpha-tocopheryl polyethylene glycol 1000 succinate (Tocofersolan, Vedrop), has been developed in Europe to provide an orally bioavailable source of vitamin E in children with cholestasis. The aim was to analyze the safety/efficacy of Vedrop in a large group of children with chronic cho

  2. Analysis of the histologic features in the differential diagnosis of intrahepatic neonatal cholestasis

    Institute of Scientific and Technical Information of China (English)

    Maria Angela Bellomo-Brandao; Cecilia AF Escanhoela; Luciana R Meirelles; Gilda Porta; Gabriel Hessel

    2009-01-01

    AIM: To compare the histologic features of the liver in intrahepatic neonatal cholestasis (IHNC) with infectious,genetic-endocrine-metabolic, and idiopathic etiologies.METHODS: Liver biopsies from 86 infants with IHNC were evaluated. The inclusion criteria consisted of jaundice beginning at 3 mo of age and a hepatic biopsy during the 1st year of life. The following histologic features were evaluated: cholestasis, eosinophilia, giant cells, erythropoiesis, siderosis, portal fibrosis, and the presence of a septum.RESULTS: Based on the diagnosis, patients were classified into three groups: group 1 (infectious; n = 18),group 2 (genetic-endocrine-metabolic; n = 18), and group 3 (idiopathic; n = 50). There were no significant differences with respect to the following variables:cholestasis, eosinophilia, giant cells, siderosis, portal fibrosis, and presence of a septum. A significant difference was observed with respect to erythropoiesis,which was more severe in group 1 (Fisher's exact test,P = 0.016).CONCLUSION: A significant difference was observed in IHNC of infectious etiology, in which erythropoiesis was more severe than that in genetic-endocrine-metabolic and idiopathic etiologies, whereas there were no significant differences among cholestasis, eosinophilia,giant cells, siderosis, portal fibrosis, and the presence of a septum.

  3. 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

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

    NARCIS (Netherlands)

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

    1974-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  6. 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.

  7. Assessing the risk of drug-induced cholestasis using unbound intrahepatic concentrations.

    Science.gov (United States)

    Riede, Julia; Poller, Birk; Huwyler, Jorg; Camenisch, Gian

    2017-03-02

    Inhibition of the bile salt export pump (BSEP) has been recognized as a key factor in the development of drug-induced cholestasis (DIC). The risk of DIC in human has previously been assessed using in vitro BSEP inhibition data (IC50) and unbound systemic drug exposure under assumption of the "free drug hypothesis". This concept, however, is unlikely valid as unbound intrahepatic drug concentrations are affected by active transport and metabolism. To investigate this hypothesis we experimentally determined the in vitro liver-to-blood partition coefficients (Kp,uu) for 18 drug compounds using the hepatic Extended Clearance Model (ECM). In vitro-in vivo translatability of Kp,uu values was verified for a subset of compounds in rat. Consequently, unbound intrahepatic concentrations were calculated from clinical exposure (systemic and hepatic inlet) and measured Kp,uu data. Using these values, corresponding safety margins against BSEP IC50 values were determined and compared to the clinical incidence of DIC. Depending on the ECM class of a drug, in vitro Kp,uu values deviated up to 14-fold from unity and unbound intrahepatic concentrations were affected accordingly. The use of in vitro Kp,uu-based safety margins allowed to separate clinical cholestasis frequency into three classes (no cholestasis, cholestasis in ≤ 2%, and in > 2% of subjects) for 17 out of 18 compounds. This assessment was significantly superior compared to using unbound extracellular concentrations as a surrogate for intrahepatic concentrations. Furthermore, the assessment of Kpuu according to ECM provides useful guidance for the quantitative evaluation of genetic and physiological risk factors for the development of cholestasis.

  8. 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.

  9. Prognosis of hepatocellular carcinoma patients with extrahepatic metastasis and the controllability of intrahepatic lesions.

    Science.gov (United States)

    Lee, Jung Il; Kim, Ja Kyung; Kim, Do Young; Ahn, Sang Hoon; Park, Jun Yong; Kim, Seung Up; Kim, Beom Kyung; Han, Kwang Hyub; Lee, Kwan Sik

    2014-04-01

    Although advanced hepatocellular carcinoma (HCC) with extrahepatic metastasis is recommended to be treated by a systemic chemotherapeutic agent without local treatment targeting the liver, studies reported that causes of death in these patients were mostly from progression of intrahepatic lesions. Thus, this study investigated prognosis and factors predicting survival in these patients so as to evaluate the role of local treatments against intrahepatic lesions when the patients already had extrahepatic metastasis. This retrospective study evaluated medical records of 277 patients with HCC and extrahepatic metastasis. The median survival was 5.9 months, and 257 patients died during the follow up. Factors affecting survival of HCC patients with extrahepatic metastasis were poor response to treatment of hepatic lesions (HR 2.207; 95% CI; p < 0.001), applying local treatment specifically targeting intrahepatic lesions (HR 0.591; 95% CI 0.436-0.803; p = 0.001), intrahepatic tumor size larger than 3 cm (HR 2.065; 95% CI 1.444-2.954; p < 0.001), and ECOG performance status 2 or higher (HR 1.543; 95% CI 1.057-2.253; p = 0.025). The patients with either complete or partial response to the therapy had 1- and 2-year survival rate of 48.8 and 12.1% whereas patient with either stable or progressive disease had 1-year survival rate of 11.4%. These results suggest that even in the HCC patients with extrahepatic metastasis, effective local treatment may still be beneficial for the survival especially in patients with acceptable performance status.

  10. Syndrome of Inappropriate Secretion of Antidiuretic Hormone Cholestasis and Pericardial Effusion Due to Brucellosis Infection: A Case Report

    Directory of Open Access Journals (Sweden)

    Ahmet Cumhur Dülger

    2010-01-01

    Full Text Available Syndrome of inappropriate secretion of antidiuretic hormone (SIADH is an extremely rare complication of infectious diseases. A rare case of brucellosis complicated by syndrome of inappropriate secretion of antidiuretic hormone (SIADH cholestasis and pericardial involvement is reported. A 27-year-old woman was admitted for fever, abdominal pain, and scleral icterus. Her medical history revealed no recent use of diuretic agents. In addition to cholestasis and elevated liver enzymes, euvolemic hyponatremia, hypouricemia, low plasma osmolality, and high urinary osmolality were also detected. Surrenal and thyroid tests were also within normal range. Echocardiography revealed minimal pericardial effusion with normal cardiac functions. The final diagnosis was SIADH due to Brucellosis. Hyponatremia, cholestasis, and pericardial disease were resolved with effective antibrucellar treatment with streptomycine and doxycycline. After completing treatment of brucellosis, there was not any more evidence of cholestasis and pericardial fluid.

  11. Suppression of the HPA axis during extrahepatic biliary obstruction induces cholangiocyte proliferation in the rat.

    Science.gov (United States)

    Quinn, Matthew; Ueno, Yoshiyuki; Pae, Hae Yong; Huang, Li; Frampton, Gabriel; Galindo, Cheryl; Francis, Heather; Horvat, Darijana; McMillin, Matthew; Demorrow, Sharon

    2012-01-01

    Cholestatic patients often present with clinical features suggestive of adrenal insufficiency. In the bile duct-ligated (BDL) model of cholestasis, the hypothalamic-pituitary-adrenal (HPA) axis is suppressed. The consequences of this suppression on cholangiocyte proliferation are unknown. We evaluated 1) HPA axis activity in various rat models of cholestasis and 2) effects of HPA axis modulation on cholangiocyte proliferation. Expression of regulatory molecules of the HPA axis was determined after BDL, partial BDL, and α-naphthylisothiocyanate (ANIT) intoxication. The HPA axis was suppressed by inhibition of hypothalamic corticotropin-releasing hormone (CRH) expression by central administration of CRH-specific Vivo-morpholinos or by adrenalectomy. After BDL, the HPA axis was reactivated by 1) central administration of CRH, 2) systemic ACTH treatment, or 3) treatment with cortisol or corticosterone for 7 days postsurgery. There was decreased expression of 1) hypothalamic CRH, 2) pituitary ACTH, and 3) key glucocorticoid synthesis enzymes in the adrenal glands. Serum corticosterone and cortisol remained low after BDL (but not partial BDL) compared with sham surgery and after 2 wk of ANIT feeding. Experimental suppression of the HPA axis increased cholangiocyte proliferation, shown by increased cytokeratin-19- and proliferating cell nuclear antigen-positive cholangiocytes. Conversely, restoration of HPA axis activity inhibited BDL-induced cholangiocyte proliferation. Suppression of the HPA axis is an early event following BDL and induces cholangiocyte proliferation. Knowledge of the role of the HPA axis during cholestasis may lead to development of innovative treatment paradigms for chronic liver disease.

  12. Hepatic expression of detoxification enzymes is decreased in human obstructive cholestasis due to gallstone biliary obstruction.

    Directory of Open Access Journals (Sweden)

    Jin Chai

    Full Text Available Levels of bile acid metabolic enzymes and membrane transporters have been reported to change in cholestasis. These alterations (e.g. CYP7A1 repression and MRP4 induction are thought to be adaptive responses that attenuate cholestatic liver injury. However, the molecular mechanisms of these adaptive responses in human obstructive cholestasis due to gallstone biliary obstruction remain unclear.We collected liver samples from cholestatic patients with biliary obstruction due to gallstones and from control patients without liver disease (n = 22 per group. The expression levels of bile acid synthetic and detoxification enzymes, membrane transporters, and the related nuclear receptors and transcriptional factors were measured.The levels of bile acid synthetic enzymes, CYP7B1 and CYP8B1, and the detoxification enzyme CYP2B6 were increased in cholestatic livers by 2.4-fold, 2.8-fold, and 1.9-fold, respectively (p<0.05. Conversely, the expression levels of liver detoxification enzymes, UGT2B4/7, SULT2A1, GSTA1-4, and GSTM1-4, were reduced by approximately 50% (p<0.05 in human obstructive cholestasis. The levels of membrane transporters, OSTβ and OCT1, were increased 10.4-fold and 1.8-fold, respectively, (p<0.05, whereas those of OSTα, ABCG2 and ABCG8 were all decreased by approximately 40%, (p<0.05 in human cholestatic livers. Hepatic nuclear receptors, VDR, HNF4α, RXRα and RARα, were induced (approximately 2.0-fold, (p<0.05 whereas FXR levels were markedly reduced to 44% of control, (p<0.05 in human obstructive cholestasis. There was a significantly positive correlation between the reduction in FXR mRNA and UGT2B4/7, SULT2A1, GSTA1, ABCG2/8 mRNA levels in livers of obstructive cholestatic patients (p<0.05.The levels of hepatic detoxification enzymes were significantly decreased in human obstructive cholestasis, and these decreases were positively associated with a marked reduction of FXR levels. These findings are consistent with impaired

  13. Non-Alcoholic Fatty Liver Disease and Extra-Hepatic Cancers

    Directory of Open Access Journals (Sweden)

    Claudia Sanna

    2016-05-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is a leading cause of chronic liver disease but the second cause of death among NAFLD patients are attributed to malignancies at both gastrointestinal (liver, colon, esophagus, stomach, and pancreas and extra-intestinal sites (kidney in men, and breast in women. Obesity and related metabolic abnormalities are associated with increased incidence or mortality for a number of cancers. NAFLD has an intertwined relationship with metabolic syndrome and significantly contributes to the risk of hepatocellular carcinoma (HCC, but recent evidence have fuelled concerns that NAFLD may be a new, and added, risk factor for extra-hepatic cancers, particularly in the gastrointestinal tract. In this review we critically appraise key studies on NAFLD-associated extra-hepatic cancers and speculate on how NAFLD may influence carcinogenesis at these sites.

  14. 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.

  15. Short-term variability of fetal heart rate in cholestasis of pregnancy.

    Science.gov (United States)

    Ammälä, P; Kariniemi, V

    1981-09-15

    Maternal cholestasis affects about 1% of pregnancies in Finland. Although maternal prognosis in obstetric cholestasis is always good, an increased fetal risk has been reported by several authors. In this paper the differential index (DI), describing the short-term variability of fetal heart rate, was measured in 64 pregnancies with colestasis of pregnancy by a microprocessor-based "on-line" method, which uses abdominal fetal electrocardiogram as a triggering signal. The analysis was successfull in 117 of 131 trials. In five pregnancies no successful analysis was obtained. Fetal distress developed in five fetuses of 59 but not perinatal deaths occurred. The sensitivity of the antepartum DI in predicting fetal distress in labor was 80% and the predictive value was 44%. The relative risk for intrapartum fetal distress in labor after a pathologic antepartal DI compared with normal DI was 22, which is highly significant (p less than 0.001).

  16. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

  18. Diffuse Hepatic Hemangiomatosis in the Adult without Extra-hepatic Involvement: An Extremely Rare Occurrence.

    Science.gov (United States)

    Batista, Alexandre; Matos, António Pedro; Neta, Jorge Oliveira E; Ramalho, Miguel

    2014-01-01

    We present a case of a pathologically proven multinodular diffuse hepatic hemangiomatosis (DHH) with no extra-hepatic involvement in a 68-year-old male. Cavernous hemangioma is the most common hepatic tumor. However, DHH, which is characterized by extensive replacement of liver parenchyma with hemangiomatous lesions, has been rarely reported in adults. The etiology and clinical course are not completely understood because of its rareness, although the diagnosis might be suggested by the magnetic resonance imaging findings.

  19. 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...

  20. [A variety of extrahepatic manifestations of chronic viral hepatitis B and C: basic treatment principles].

    Science.gov (United States)

    Baĭkova, T A; Lopatkina, T N

    2013-01-01

    Chronic viral hepatitides B and C are systemic diseases with a great number of extrahepatic manifestations caused by different immune abnormalities due to viral replication in and outside the liver and to the direct pathological effects of viral particles. Many of them can be the only manifestation of the infection and come to the foreground in its clinical picture, by determining the prognosis of the disease.

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

    OpenAIRE

    Takashi Himoto; Tsutomu Masaki

    2012-01-01

    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 antin...

  2. Thyrotoxicosis-Associated Cholestasis in a Patient with Hepatitis B Cirrhosis

    OpenAIRE

    2008-01-01

    Abnormalities in liver function tests were reported in association with hyperthyroidism. Intrahepatic cholestasis is one form of this association. Reversal of hyperbilirubinemia upon correction of hyperthyroidism supports the causal relationship. Most reported cases have occurred in patients without previous liver disease. We report a case of marked cholestatic jaundice associated with hyperthyroidism caused by toxic adenoma in a patient with hepatitis B cirrhosis. Serum bilirubin returned to...

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

    Science.gov (United States)

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

    2015-07-01

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

  4. 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.

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

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    Zhang Lili

    2007-04-01

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

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

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    B. Malassagne

    1998-01-01

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

  7. Extrahepatic effects of nucleoside and nucleotide analogues in chronic hepatitis B treatment.

    Science.gov (United States)

    Fung, James; Seto, Wai-Kay; Lai, Ching-Lung; Yuen, Man-Fung

    2014-03-01

    Oral nucleoside/nucleotide analogues (NAs) are the mainstay of therapy for patients with chronic hepatitis B and are generally well tolerated. Despite this, the safety profile of NAs is of paramount importance since the majority of patients will require long-term treatment. All NAs can potentially affect human DNA polymerase with decrease in mitochondrial DNA, leading to manifestations of mitochondrial toxicity. As a class effect, therefore, NAs can potentially cause extrahepatic conditions, such as myopathy, nephropathy, neuropathy, and lactic acidosis. Indeed, effects on muscles, including myopathy and creatine kinase elevations, have been described with clevudine and telbivudine use. Both adefovir and tenofovir are associated with dose-dependent nephropathy, predominantly affecting the proximal renal tubules. Neuropathy appears to be rare, and most commonly reported in patients receiving combination therapy with telbivudine and interferon. Increased risk of lactic acidosis has also been described for those with impaired liver and renal function taking entecavir. Loss of bone mineral density and hypophosphatemia have been described with the use of NAs, although the overwhelming studies have been with human immunodeficiency virus-infected patients. However, not all extrahepatic effects are detrimental. Recent evidence has suggested a potential renal beneficial effect with the use of telbivudine. The effect of NAs on pregnancy appears to be minimal for all NAs, with telbivudine and tenofovir having a more favorable category B rating. Ongoing pharmacovigilance is essential to identify new and monitor existing extrahepatic effects associated with NA use.

  8. ABC gene-ranking for prediction of drug-induced cholestasis in rats

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    Yauheniya Cherkas

    2016-01-01

    Full Text Available As legacy toxicogenomics databases have become available, improved data mining approaches are now key to extracting and visualizing subtle relationships between toxicants and gene expression. In the present study, a novel “aggregating bundles of clusters” (ABC procedure was applied to separate cholestatic from non-cholestatic drugs and model toxicants in the Johnson & Johnson (Janssen rat liver toxicogenomics database [3]. Drug-induced cholestasis is an important issue, particularly when a new compound enters the market with this liability, with standard preclinical models often mispredicting this toxicity. Three well-characterized cholestasis-responsive genes (Cyp7a1, Mrp3 and Bsep were chosen from a previous in-house Janssen gene expression signature; these three genes show differing, non-redundant responses across the 90+ paradigm compounds in our database. Using the ABC procedure, extraneous contributions were minimized in comparisons of compound gene responses. All genes were assigned weights proportional to their correlations with Cyp7a1, Mrp3 and Bsep, and a resampling technique was used to derive a stable measure of compound similarity. The compounds that were known to be associated with rat cholestasis generally had small values of this measure relative to each other but also had large values of this measure relative to non-cholestatic compounds. Visualization of the data with the ABC-derived signature showed a very tight, essentially identically behaving cluster of robust human cholestatic drugs and experimental cholestatic toxicants (ethinyl estradiol, LPS, ANIT and methylene dianiline, disulfiram, naltrexone, methapyrilene, phenacetin, alpha-methyl dopa, flutamide, the NSAIDs–—indomethacin, flurbiprofen, diclofenac, flufenamic acid, sulindac, and nimesulide, butylated hydroxytoluene, piperonyl butoxide, and bromobenzene, some slightly less active compounds (3′-acetamidofluorene, amsacrine, hydralazine, tannic acid, some

  9. Early liver biopsy, intraparenchymal cholestasis, and prognosis in patients with alcoholic steatohepatitis

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    Spahr Laurent

    2011-10-01

    Full Text Available Abstract Background Alcoholic steatohepatitis (ASH is a serious complication of alcoholic liver disease. The diagnosis of ASH requires the association of steatosis, evidence of hepatocellular injury with ballooning degeneration, and polynuclear neutrophil infiltration on liver biopsy. Whether these lesions, in addition to other histological features observed in liver tissue specimens, have prognostic significance is unclear. Methods We studied 163 patients (age 55 yrs [35-78], male/female 102/61 with recent, heavy (> 80 gr/day alcohol intake, histologically-proven ASH (97% with underlying cirrhosis, Maddrey's score 39 [13-200], no sepsis, who had a liver biopsy performed 3 days [0-10] after hospital admission for clinical decompensation. A semi-quantitative evaluation of steatosis, hepatocellular damage, neutrophilic infiltration, periportal ductular reaction, intraparenchymal cholestasis, and iron deposits was performed by two pathologists. All patients with a Maddrey's score ≥ 32 received steroids. The outcome at 3 months was determined. Statistical analysis was performed using the Wilcoxon and Fisher's exact tests, Kaplan-Meier method, and the Cox proportional hazard model. Results 43 patients died after 31 days [5-85] following biopsy. The 3-month survival rate was 74%. Mean kappa value for histological assessment by the two pathologists was excellent (0.92. Univariate analysis identified age, the Maddrey's score, the Pugh's score, the MELD score and parenchymal cholestasis, but not other histological features, as factors associated with 3-month mortality. At multivariate analysis, age (p = 0.029, OR 2.83 [1.11-7.2], intraparenchymal cholestasis (p = 0.001, OR 3.9 [1.96-7.8], and the Maddrey's score (p = 0.027, OR 3.93 [1.17-13.23] were independent predictors of outcome. Intraparenchymal cholestasis was more frequent in non survivors compared to survivors (70% versus 25%, p Conclusions In this large cohort of patients with histologically

  10. Impact of classification of hilar cholangiocarcinomas (Klatskin tumors) on the incidence of intra- and extrahepatic cholangiocarcinoma in the United States.

    Science.gov (United States)

    Welzel, Tania M; McGlynn, Katherine A; Hsing, Ann W; O'Brien, Thomas R; Pfeiffer, Ruth M

    2006-06-21

    Cholangiocarcinomas are topographically categorized as intrahepatic or extrahepatic by the International Classification of Diseases for Oncology (ICD-O). Although hilar cholangiocarcinomas (Klatskin tumors) are extrahepatic cholangiocarcinomas, the second edition of the ICD-O (ICD-O-2) assigned them a histology code 8162/3, Klatskin, which was cross-referenced to intrahepatic cholangiocarcinoma. Recent studies in the United States that included this code (8162/3, Klatskin) with intrahepatic cholangiocarcinoma reported an increasing incidence of intrahepatic cholangiocarcinoma and a decreasing incidence of extrahepatic cholangiocarcinoma. To investigate the impact of this misclassification on site-specific cholangiocarcinoma incidence rates, we calculated annual percent changes (APCs) with data from the Surveillance, Epidemiology, and End Results (SEER) program using a Poisson regression model that was age-adjusted to the year 2000 U.S. population. All statistical tests were two-sided. During 1992-2000, when SEER used ICD-O-2, 1710 intrahepatic cholangiocarcinomas, 1371 extrahepatic cholangiocarcinomas, and 269 hilar cholangiocarcinomas identified by code 8162/3, Klatskin were diagnosed. Ninety-one percent (246 of 269) of the hilar cholangiocarcinomas were incorrectly coded as intrahepatic cholangiocarcinomas, resulting in an overestimation of intrahepatic cholangiocarcinoma incidence by 13% and underestimation of extrahepatic cholangiocarcinomas incidence by 15%. However, even after the exclusion of tumors that were coded to the histology code 8162/3, Klatskin, age-adjusted annual intrahepatic cholangiocarcinoma incidence increased during this period (APC = 4%, 95% confidence interval = 2% to 6%, P<.001).

  11. Omega-3-enriched lipid emulsion for liver salvage in parenteral nutrition-induced cholestasis in the adult patient.

    Science.gov (United States)

    Jurewitsch, Brian; Gardiner, Geoffrey; Naccarato, Mark; Jeejeebhoy, Khursheed N

    2011-05-01

    The intrahepatic cholestasis attributed to parenteral nutrition (PN) in the adult patient is relatively rare and usually occurs in patients receiving long-term PN. This article reports the first case of an adult patient with cholestatic PN-associated liver disease without sepsis who received almost all her nutrition requirements through PN. Administration of an ω-3-enriched lipid emulsion added to the PN regimen reversed cholestasis and demonstrated histologic improvement on serial liver biopsy. The patient had failed to respond to other modalities of treatment for this condition and was deeply jaundiced. Liver biochemistry profiles returned to baseline, and follow-up liver biopsy showed that cholestasis had resolved and that the only residual changes were mild portal inflammation with no histochemical or ultrastructural progression. The PN regimen for the patient was restored to provide total estimated energy requirements and remains the principle source of the patient's nutrition to date.

  12. Acute renal failure in obstructive diseases of the extrahepatic biliary ducts.

    Science.gov (United States)

    Acalovschi, I; Chirileanu, T

    1984-01-01

    A series of 46 patients with obstructive disease of the bile ducts complicated by acute renal failure (ARF) is presented. The patients exhibited obstructive jaundice with prevalence of conjugated bilirubine. In 80% of the cases biliary obstruction was associated with cholangitis. Disturbances of the liver function (from mild cholestasis to biliary cirrhosis) were also present. The renal damage was due to biliary disorders and was either present on admission (33 cases) or developed postoperatively (13 cases). Most of the patients presented nonoliguric ARF as well as poor perfusion resulting from decreased circulating blood volume (dehydration and electrolyte loss). Among the criteria used to determine the type of ARF, the urinary/plasma creatinine ratio less than 10 and urinary/plasma osmolarity ratio less than 1.1 were the most valuable. Management of ARF by dialysis alone was not satisfactory. Attention is called to the surgical treatment of the biliary disorder as being essential to prognosis. Patients not treated by radical surgery died in proportion of 87 to 100%. From the rest of 18 patients in whom the operation provided an adequate biliary drainage, in 15 the renal function was restored and 12 survived. Better prognosis in these patients was dependent not only on the ability to cure the cholestasis and infection, but on the early surgical treatment. The ultimate prognosis depends on the improvement of the liver function.

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

    Directory of Open Access Journals (Sweden)

    Xiao eMa

    2016-02-01

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

  14. 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.

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

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    T. P. Elamurugan

    2011-01-01

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

  16. [Hepatitis B virus, extrahepatic immunologic manifestations and risk of viral reactivation].

    Science.gov (United States)

    Terrier, B; Cacoub, P

    2011-10-01

    Hepatitis B virus (HBV) infection is frequent with about 400 million individuals infected worldwide. Extrahepatic manifestations may be observed in up to 20% of patients infected with HBV, in both acute and chronic infections. The best-described manifestations are polyarteritis nodosa and glomerulonephritis. Besides manifestations related to HBV, patients presenting with primary autoimmune disorders and infected with HBV may exhibit reactivation of hepatitis B during immunosuppressive therapy that may be life-threatening. This article focuses on autoimmune manifestations related to HBV and its treatment, and on the risk of reactivation of HBV hepatitis in patients with primary autoimmune disorders treated with immunosuppressive agents.

  17. A case of multiple extrahepatic manifestations in a patient with untreated, chronic hepatitis C virus infection.

    Science.gov (United States)

    Meillier, Andrew; McGee, Jean; Kartan, Saritha; Baskin, Stuart

    2014-02-01

    Chronic hepatitis C virus (HCV) infection is a complex, multi-organ disorder, not just limited to the liver. Mixed cryoglobulinemia (MC) type 2 is a common extrahepatic complication, in which immunoglobulin complexes deposit in vascular endothelium. This in turn creates a diffuse inflammatory reaction, leading to a variety of disorders involving multiple systems. We report the rare case of a patient with cryoglobulinemia, cutaneous vasculitis, membroproliferative glomerulonephritis, and B cell lymphoma with a variant t(6;10) translocation in the setting of an untreated, chronic HCV infection. This case highlights the challenge associated with diagnosing and managing such a complex presentation.

  18. [Extrahepatic manifestations in patients with chronic infections due to the hepatitis C virus].

    Science.gov (United States)

    Ramos-Casals, Manuel

    2009-01-01

    Autoimmunity and viral infections are closely related, and viruses have been proposed as possible etiologic or triggering agents of systemic autoimmune diseases (SAD). The hepatitis C virus (HCV), a linear, single-stranded RNA virus, identified in 1989, is recognized as one of the viruses most often associated with autoimmune features. The association between HCV and SAD has generated growing interest in recent years. The extrahepatic manifestations often observed in patients with chronic HCV infection (both clinical and immunological) may lead to the fulfilment of the current classification criteria for some SAD.

  19. Intestinal capacity to digest and absorb carbohydrates is maintained in a rat model of cholestasis.

    Science.gov (United States)

    Los, E Leonie; Wolters, Henk; Stellaard, Frans; Kuipers, Folkert; Verkade, Henkjan J; Rings, Edmond H H M

    2007-09-01

    Cholestasis is associated with systemic accumulation of bile salts and with deficiency of bile in the intestinal lumen. During the past years bile salts have been identified as signaling molecules that regulate lipid, glucose, and energy metabolism. Bile salts have also been shown to activate signaling routes leading to proliferation, apoptosis, or differentiation. It is unclear, however, whether cholestasis affects the constitution and absorptive capacity of the intestinal epithelium in vivo. We studied small intestinal morphology, proliferation, apoptosis, expression of intestine-specific genes, and carbohydrate absorption in cholestatic (1 wk bile duct ligation), bile-deficient (1 wk bile diversion), and control (sham) rats. Absorptive capacity was assessed by determination of plasma [(2)H]- and [(13)C]glucose concentrations after intraduodenal administration of [(2)H]glucose and naturally enriched [(13)C]sucrose, respectively. Small intestinal morphology, proliferation, apoptosis, and gene expression of intestinal transcription factors (mRNA levels of Cdx-2, Gata-4, and Hnf-1alpha, and Cdx-2 protein levels) were similar in cholestatic, bile-deficient, and control rats. The (unlabeled) blood glucose response after intraduodenal administration was delayed in cholestatic animals, but the absorption over 180 min was quantitatively similar between the groups. Plasma concentrations of [(2)H]glucose and [(13)C]glucose peaked to similar extents in all groups within 7.5 and 30 min, respectively. Absorption of [(2)H]glucose and [(13)C]glucose in plasma was similar in all groups. The present data indicate that neither accumulation of bile salts in the body, nor their intestinal deficiency, two characteristic features of cholestasis, affect rat small intestinal proliferation, differentiation, apoptosis, or its capacity to digest and absorb carbohydrates.

  20. 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.

  1. Radioembolization with Y-90 Glass Microspheres: Do We Really Need SPECT-CT to Identify Extrahepatic Shunts?

    Directory of Open Access Journals (Sweden)

    Jens M Theysohn

    Full Text Available Selective Internal Radiation Therapy (SIRT with 90yttrium (Y-90 is an increasingly used therapeutic option for unresectable liver malignancies. Nontarget embolization of extrahepatic tissue secondary to vascular shunting can lead to SIRT associated complications. Our aim was to assess whether extrahepatic shunts can reliably be diagnosed based on hepatic digital subtraction angiography (DSA or whether subsequent SPECT/CT data can provide additional information.825 patients with hepatocellular carcinoma (n = 636, hepatic metastases (n = 158 or cholangiocellular carcinoma (n = 31 were retrospectively analyzed. During hepatic DSA 128 arteries causing shunt flow to gastrointestinal tissue were coilembolized (right gastric artery n = 63, gastroduodenal artery n = 29; branches to duodenum / pancreas n = 36. Technectium-99m-labeled human serum albumin (HSA was injected in all 825 patients. SPECT/CT data was used to identify additional or remaining shunts to extrahepatic tissue.An unexpected uptake of HSA in extrahepatic tissue was found by SPECT/CT in 54/825 (6.5% patients (located in stomach n = 13, duodenum n = 26, distal bowel segments n = 12, kidney n = 1, diaphragm n = 2. These patients underwent repeated DSA and newly identified shunt vessels were coilembolized in 22/54 patients, while in 12/54 patients a more distal catheter position for repeat injection of HSA was chosen. In 20/54 patients the repeated SPECT/CT data still revealed an extrahepatic HSA uptake. These patients did not receive SIRT.Most extrahepatic shunts can be identified on DSA prior to Y-90 therapy. However, SPECT-CT data helps to identify additional shunts that were initially not seen on DSA.

  2. To Resect or Not to Resect Extrahepatic Bile Duct in Gallbladder Cancer?

    Science.gov (United States)

    Gavriilidis, Paschalis; Askari, Alan; Azoulay, Daniel

    2017-01-01

    The indications for and limitations of extrahepatic bile duct resection (EHBDR) in the context of gallbladder (GB) cancer are unclear. The purpose of this review was to examine the current literature to determine the impact of EHBDR on loco-regional recurrence and survival in GB cancer. The EMBASE and Medline databases were searched up to February 2016 using the terms: extrahepatic bile duct resection and gallbladder cancer. Studies published in the last 20 years were eligible for inclusion. Given the heterogeneity of the population and the study methodologies employed, qualitative data synthesis in the form of meta-analysis was deemed implausible. Twenty-four studies fulfilled the inclusion criteria. The selected studies include 6,722 (55%) EHBDRs in a total of 12,251 GB cancer operations. The 25 studies were categorized into seven groups: 1) cancer survival all stages; 2) hepatoduodenal ligament invasion; 3) outcome in EHBDR and EHBDNR; 4) pT1b tumors; 5) pT2 tumors; 6) pT3/T4 tumors; and 7) incidental GB cancer. Radical cholecystectomy with EHBDR should be used as a standard operation for tumors involving the neck or the cystic duct of the GB (either macroscopically or microscopically). In all other cases, operative strategy should be individualized to the patient. PMID:28090223

  3. Novel Silicone-Coated 125I Seeds for the Treatment of Extrahepatic Cholangiocarcinoma.

    Science.gov (United States)

    Lin, Lizhou; Guo, Lili; Zhang, Weixing; Cai, Xiaobo; Chen, Dafan; Wan, Xinjian

    2016-01-01

    125I seeds coated with titanium are considered a safe and effective interstitial brachytherapy for tumors, while the cost of 125I seeds is a major problem for the patients implanting lots of seeds. The aim of this paper was to develop a novel silicone coating for 125I seeds with a lower cost. In order to show the radionuclide utilization ratio, the silicone was coated onto the seeds using the electro-spinning method and the radioactivity was evaluated, then the anti-tumor efficacy of silicone 125I seeds was compared with titanium 125I seeds. The seeds were divided into four groups: A (control), B (pure silicone), C (silicone 125I), D (titanium 125I) at 2 Gy or 4 Gy. Their anti-tumour activity and mechanism were assessed in vitro and in vivo using a human extrahepatic cholangiocarcinoma cell line FRH-0201 and tumor-bearing BALB/c nude mice. The silicone 125I seeds showed higher radioactivity; the rate of cell apoptosis in vitro and the histopathology in vivo demonstrated that the silicone 125I seeds shared similar anti-tumor efficacy with the titanium 125I seeds for the treatment of extrahepatic cholangiocarcinoma, while they have a much lower cost.

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

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    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.

  5. Extrahepatic biliary duct obstruction as a result of involuntary transcavitary implantation of hair in a cat

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    Michael Linton

    2015-10-01

    Full Text Available Case summary A 4-year-old male neutered domestic shorthair cat was referred for investigation of jaundice. The cat had a recent history of a skin laceration repair following trauma. Sequential serum biochemistry demonstrated increasing plasma bilirubin concentrations; abdominal ultrasonography revealed ongoing pancreatitis and apparent extrahepatic obstruction of the common bile duct. Exploratory laparotomy identified constriction of the common bile duct with foreign material (cat hair. The constricting band of hair was removed surgically; cholecystoduodenostomy was performed. Postsurgical quality of life is excellent with chronic treatment of tylosin, omeprazole and ursodeoxycholic acid. Relevance and novel information To our knowledge, this is the first reported case of extrahepatic biliary duct obstruction resulting from the intra-abdominal migration of a foreign body, in this case, hair shafts. The mechanism by which this occurred was likely a combination of physical constriction by the hair shafts and subsequent foreign body reaction surrounding this. This should be included in the differential diagnosis of a cat with jaundice.

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  7. To Resect or Not to Resect Extrahepatic Bile Duct in Gallbladder Cancer?

    Science.gov (United States)

    Gavriilidis, Paschalis; Askari, Alan; Azoulay, Daniel

    2017-02-01

    The indications for and limitations of extrahepatic bile duct resection (EHBDR) in the context of gallbladder (GB) cancer are unclear. The purpose of this review was to examine the current literature to determine the impact of EHBDR on loco-regional recurrence and survival in GB cancer. The EMBASE and Medline databases were searched up to February 2016 using the terms: extrahepatic bile duct resection and gallbladder cancer. Studies published in the last 20 years were eligible for inclusion. Given the heterogeneity of the population and the study methodologies employed, qualitative data synthesis in the form of meta-analysis was deemed implausible. Twenty-four studies fulfilled the inclusion criteria. The selected studies include 6,722 (55%) EHBDRs in a total of 12,251 GB cancer operations. The 25 studies were categorized into seven groups: 1) cancer survival all stages; 2) hepatoduodenal ligament invasion; 3) outcome in EHBDR and EHBDNR; 4) pT1b tumors; 5) pT2 tumors; 6) pT3/T4 tumors; and 7) incidental GB cancer. Radical cholecystectomy with EHBDR should be used as a standard operation for tumors involving the neck or the cystic duct of the GB (either macroscopically or microscopically). In all other cases, operative strategy should be individualized to the patient.

  8. Impaired Hepatic Adaptation to Chronic Cholestasis induced by Primary Sclerosing Cholangitis

    Science.gov (United States)

    Milkiewicz, Malgorzata; Klak, Marta; Kempinska-Podhorodecka, Agnieszka; Wiechowska-Kozlowska, Anna; Urasinska, Elzbieta; Blatkiewicz, Malgorzata; Wunsch, Ewa; Elias, Elwyn; Milkiewicz, Piotr

    2016-01-01

    Pathogenesis of primary sclerosing cholangitis (PSC) may involve impaired bile acid (BA) homeostasis. We analyzed expressions of factors mediating enterohepatic circulation of BA using ileal and colonic (ascending and sigmoid) biopsies obtained from patients with PSC with and without ulcerative colitis (UC) and explanted PSC livers. Two-fold increase of BA-activated farnesoid X receptor (FXR) protein levels were seen in ascending and sigmoid colon of PSC patients with correspondingly decreased apical sodium-dependent BA transporter (ASBT) gene expression. This was associated with increased OSTβ protein levels in each part of analyzed gut. An intestinal fibroblast growth factor (FGF19) protein expression was significantly enhanced in ascending colon. Despite increased hepatic nuclear receptors (FXR, CAR, SHP), and FGF19, neither CYP7A1 suppression nor CYP3A4 induction were observed. The lack of negative regulation of BA synthesis may be accountable for lower levels of cholesterol observed in PSC in comparison to primary biliary cholangitis (PBC). In conclusion, chronic cholestasis in PSC induces adaptive changes in expression of BA transporters and FXR in the intestine. However hepatic impairment of expected in chronic cholestasis downregulation of CYP7A1 and upregulation of CYP3A4 may promote BA-induced liver injury in PSC. PMID:28008998

  9. The role of steroid hormones in the development of intrahepatic cholestasis of pregnancy.

    Science.gov (United States)

    Pařízek, A; Dušková, M; Vítek, L; Šrámková, M; Hill, M; Adamcová, K; Šimják, P; Černý, A; Kordová, Z; Vráblíková, H; Boudová, B; Koucký, M; Malíčková, K; Stárka, L

    2015-01-01

    Intrahepatic cholestasis of pregnancy (ICP) is a disorder of liver function, commonly occurring in the third trimester but sometimes also as soon as the end of the second trimester of pregnancy. Symptoms of this disorder include pruritus, plus abnormal values of bile acids and hepatic transaminases. After birth, symptoms disappear and liver function returns to normal. Though ICP is relatively non-complicated and often symptomatically mild from the point-of-view of the mother, it presents a serious risk to the fetus, making this disease the subject of great interest. The etiology and pathogenesis of ICP is multifactorial and as yet not fully elucidated. Hormonal factors likely play a significant role, along with genetic as well as exogenous factors. Here we summarize the knowledge of changes in steroid hormones and their role in the development of intrahepatic cholestasis of pregnancy. In addition, we consider the role of exogenous factors as possible triggers of steroid hormone changes, the relationship between metabolic steroids and bile acids, as well as the combination of these factors in the development of ICP in predisposed pregnant women.

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

    Science.gov (United States)

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

    2004-11-01

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

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

    Science.gov (United States)

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

    1992-08-01

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

  12. [Clinical significance of dissociated cholestasis as a biological syndrome (author's transl)].

    Science.gov (United States)

    Cardellach, F; Sierra, J; Coca, A; Villalta, J; Martinez-Orozco, F; Ingelmo, M; Balcells-Gorina, A

    1981-10-10

    The case histories of 1200 patients admitted to our hospital over a 20 month period were reviewed to determine the degree, frequency and cause of dissociated cholestasis as a biological syndrome. Patients were divided into two groups: group I with 80 cases, included all patients whose gamma-GT levels were more than 30 mU/ml and serum-bilirubin less than 1.2 mg/ml, with alkaline phosphatase levels between 90-180 mU/ml. Group II included those with alkaline phosphatase levels higher than 180 mU/ml (57 cases). All over incidence of dissociated cholestasis was 13.82%. Main causes in group I were infectious diseases, mainly pneumonias and urinary infections and congestive cardiac failure. In group II, neoplasias such as Hodgkin's disease and epithelial metastases and obstructions of the biliary tract such as vesicular or choledocal litiasis were the main causes. Transaminase levels underwent variable increases according to the different entities, without there being any difference between the two groups. The physiopathology as well as the anatomopathological aspects which could originate the syndrome are discussed.

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

    Directory of Open Access Journals (Sweden)

    Gaydar Yu.A.

    2007-01-01

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

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

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    Natalia Nuño-Lámbarri

    2016-01-01

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

  15. 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.

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

    Science.gov (United States)

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

    2009-05-15

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

  17. 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.

  18. A novel phenotype of a hepatocyte nuclear factor homeobox A (HNF1A) gene mutation, presenting with neonatal cholestasis

    NARCIS (Netherlands)

    de Vries, Aleida G. M.; Bakker-van Waarde, Willie M.; Dassel, Anne C. M.; Losekoot, Monique; Duiker, Evelien W.; Gouw, Annette S. H.; Bodewes, Frank A. J. A.

    2015-01-01

    We report a novel phenotype of a hepatocyte nuclear factor homeobox A (HNF1A) mutation (heterozygote c.130dup, p.Leu44fs) presenting with transient neonatal cholestasis, subsequently followed by persistent elevation of transaminases, maturity-onset diabetes of the young (MODY) type 3 and hepatocellu

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

    Directory of Open Access Journals (Sweden)

    Sohela Shah

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

  20. Ultrasonography and 3D-CT Follow-Up of Extrahepatic Portal Vein Aneurysm: A Case Report

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    Norio Yukawa

    2010-01-01

    Full Text Available Extrahepatic portal vein aneurysm is a rare disorder. From 1956 to 2008, we found only 43 published English-language reports, including 67 cases, using Pub Med. We report a case of a 77-year-old woman who had complaints of lower abdominal fullness and residual urine. We performed ultrasonography (US, which demonstrated a congenital extrahepatic portal vein aneurysm. She had no obvious symptoms of the extrahepatic portal vein aneurysm. She had undergone gastrectomy without blood transfusion for gastric ulcer more than 20 years ago. Physical examination revealed no abnormal findings. US revealed a 2.2×1.8 cm, round shaped hypoechogenic lesion at the hepatic hilum. Color Doppler US showed bidirectional colors due to circular flow within this lesion. 3D-CT and CT angiography demonstrated that the saccular aneurysm at the hepatic hilum was 3.0 cm in diameter and was enhanced equal to that of portal vein.Twenty-six months after the diagnosis, the aneurysm had not grown in size. Since our patient had no serious complaints or liver disease, surgical procedures had not been employed. US and 3D-CT are noninvasive diagnostic techniques and are helpful in the diagnosis and follow-up of extrahepatic portal vein aneurysms.

  1. Two Cases of Type Va Extrahepatic Bile Duct Duplication With Distal Klatskin Tumor Surgically Treated with Whipple Procedure and Hepaticojejunostomy.

    Science.gov (United States)

    Hammad, Tariq A; Alastal, Yaseen; Khan, Muhammad Ali; Hammad, Mohammad; Alaradi, Osama; Nigam, Ankesh; Sodeman, Thomas C; Nawras, Ali

    2015-10-01

    We describe the diagnostic and therapeutic challenges of a type Va extrahepatic bile duct duplication coexistent with distally located hilar cholangiocarcinoma (Klatskin tumor). We present 2 cases that were diagnosed preoperatively and treated with a modified surgical technique of a combined pylorus-preserving Whipple procedure and hepaticojejunostomy.

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

    NARCIS (Netherlands)

    van den Hoven, Andor F.; Prince, Jip F.; de Keizer, Bart; Vonken, Evert Jan P A; Bruijnen, Rutger C G; Verkooijen, Helena M.; Lam, Marnix G E H; van den Bosch, Maurice A A J

    2016-01-01

    Purpose: To optimize a C-arm computed tomography (CT) protocol for radioembolization (RE), specifically for extrahepatic shunting and parenchymal enhancement. Materials and Methods: A prospective development study was performed per IDEAL recommendations. A literature-based protocol was applied in pa

  3. Case-term Adverse Outcomes of Chronic Hepatitis C, Extrahepatic Manifestations of a Young Man Infected in Early Childhood

    Directory of Open Access Journals (Sweden)

    S. V. Baramzina

    2015-01-01

    Full Text Available In the present article discusses the clinical case of unfavorable course of chronic hepatitis C with the outcome of cirrhosis and development of extrahepatic manifestations of a young man of 20 years as a result of infection in early childhood.

  4. Extrahepatic manifestation of chronic viral hepatitis%慢性病毒性肝炎的肝外表现

    Institute of Scientific and Technical Information of China (English)

    尤红

    2006-01-01

    @@ 在慢性乙型和丙型肝炎的临床表现中,我们可以看到病人除了常见的与肝脏相关的临床表现外,还有许多其他系统的肝外表现,被称为肝外综合征(extrahepatic syndromes).

  5. Extrahepatic synthesis of coagulation factor Ⅶ by colorectal cancer cells promotes tumor invasion and metastasis

    Institute of Scientific and Technical Information of China (English)

    TANG Jian-qiang; FAN Qing; WU Wen-han; JIA Zhi-chao; LI Hui; YANG Yin-mo; LIU Yu-cun; WAN Yuan-lian

    2010-01-01

    Background Blood coagulation factor Ⅶ (FⅦ) is physiologically synthesized in the liver and released into the blood. Binding of FⅦ to tissue factor (TF) is related to the metastatic potential of tumor cells, also a significant risk factor in the development of hepatic metastasis in patients with colorectal cancer (CRC). It has been found that some cancer cells can produce FⅦ extrahepatically. However, litte is known about FⅦ and CRC. We therefore hypothesized that CRC cells may synthese FⅦ, leading to tumor invasion and metastasis.Methods We detected the expression of FⅦ protein in 55 CRC specimens by immunohistochemical staining. The FⅦ mRNA in 45 of 55 CRC cases, 6 colon cancer cell lines and one hepatoma cell line was measured by real-time reverse transcription-PCR (RT-PCR). Transwell invasion assays were performed to evaluate the changes of cell migration and invasion of LoVo cancer cells in vitro. We further observed the likely effectors regulated by the TF/FⅦa complex Western blotting assay.Results Extrahepatic synthesis of FⅦ was detected in the cytoplasm of 32 (58.2%) CRC specimens byimmunohistochemistry, but not in normal mucosa. Liver metastasis (P=0.003) and TNM staging (P=0.005) were significantly correlated with FⅦ antigen expression. The positive ratios in stages Ⅰ, Ⅱ, Ⅲ and Ⅳ were 33.3%, 40.0%,52.4% and 87.5%, respectively. The expression of FⅦ mRNA in CRC with hepatic metastasis was significantly higher than CRC without hepatic metastasis (5.33±2.88 vs. 1.47±0.51, P=0.03). Ectopic FⅦa induced a slight increase (1.34-fold) in the number of migrating cells, which was inhibited by the specific TF antibody. The formation of TF/FⅦacomplex resulted in a marked increase in the expression of matrix metalloproteinases (MMP)-2 (3.5-fold) and MMP-9(4.7-fold) in a time-dependent and dose-dependent manner.Conclusions Extrahepatic synthesis of FⅦ by CRC cells may promote tumor invasion and metastasis. MMPs, as downstream

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

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    Poupak Fallahi

    2008-08-01

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

  7. 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

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

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    Yoon Jung-Hwan

    2011-10-01

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

  9. Minimal role of hepatic transporters in the hepatoprotection against LCA-induced intrahepatic cholestasis.

    Science.gov (United States)

    Beilke, Lisa D; Besselsen, David G; Cheng, Quiqiong; Kulkarni, Supriya; Slitt, Angela L; Cherrington, Nathan J

    2008-03-01

    The multidrug resistance-associated proteins (Mrps) are a family of adenosine triphosphate-dependent transporters that facilitate the movement of various compounds, including bile acids, out of hepatocytes. The current study was conducted to determine whether induction of these transporters alters bile acid disposition as a means of hepatoprotection during bile acid-induced cholestasis. Lithocholic acid (LCA) was used to induce intrahepatic cholestasis. C57BL/6 mice were pretreated with corn oil (CO) or known transporter inducers, phenobarbital (PB), oltipraz (OPZ), or TCPOBOP (TC) for 3 days prior to cotreatment with LCA and inducer for 4 days. Histopathology revealed that PB and TC pretreatments provide a protective effect from LCA-induced toxicity, whereas OPZ pretreatment did not. Both PB/LCA and TC/LCA cotreatment groups also had significantly lower alanine aminotransferase values than the LCA-only group. In TC/LCA cotreated mice compared with LCA only, messenger RNA (mRNA) expression of uptake transporters Ntcp and Oatp4 was significantly increased, as were sinusoidal efflux transporters Mrp3 and Mrp4. Although in PB/LCA cotreated mice, the only significant change compared with LCA-only treatment was an increase in uptake transporter Oatp4. Oatp1 was reduced in all groups compared with CO controls. No significant changes in mRNA expression were observed in Oatp2, Bsep, Mrp2, Bcrp, Mrp1, Mrp5, or Mrp6. Mrp4 protein expression was induced in the OPZ/LCA and TC/LCA cotreated groups, whereas Mrp3 protein levels remained unchanged between groups. Protein expression of Mrp1 and Mrp5 was increased in the unprotected LCA-only and OPZ/LCA mice. Thus, transporter expression did not correlate with histologic hepatoprotection, however, there was a correlation between hepatoprotection and significantly reduced total liver bile acids in the PB/LCA and TC/LCA cotreated mice compared with LCA only. In conclusion, changes in transporter expression did not correlate with

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

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    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.

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Benjamin Misselwitz

    2016-04-01

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

  13. 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.

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

    Science.gov (United States)

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

    2016-05-25

    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.

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

    Science.gov (United States)

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

    2016-01-01

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

  16. Metallothionein overexpression and its prognostic relevance in intrahepatic cholangiocarcinoma and extrahepatic hilar cholangiocarcinoma (Klatskin tumors).

    Science.gov (United States)

    Schmitz, Klaus Jürgen; Lang, Hauke; Kaiser, Gernot; Wohlschlaeger, Jeremias; Sotiropoulos, Georgios Charalambos; Baba, Hideo Andreas; Jasani, Bharat; Schmid, Kurt Werner

    2009-12-01

    Metallothionein is a group of small molecular weight cysteine-rich proteins with a broad variety of functions. Metallothionein has been shown to regulate apoptosis and proliferation. Overexpression of metallothionein frequently occurs in human tumors and is related to prognosis as well as therapy response. However, metallothionein expression and its clinical relevance in cholangiocarcinoma have not been investigated. The present study aimed to analyze metallothionein over-expression and its possible prognostic impact in intrahepatic cholangiocarcinoma and hilar extrahepatic cholangiocarcinoma (Klatskin tumors). We investigated the relationship of immunohistochemically demonstrated metallothionein expression with various clinicopathological parameters in a series of 56 intrahepatic and 56 extrahepatic cholangiocarcinoma. In noncancerous bile duct epithelia metallothionein was only occasionally weakly expressed; strong metallothionein overexpression (>50% metallothionein -positive tumor cells) was noted in 7 (12.5%) of 56 intrahepatic cholangiocarcinoma and 14 (25%) of 56 Klatskin tumors, which was associated with poor clinical outcome in univariate Kaplan-Meier testing in both intrahepatic cholangiocarcinoma (P = .002) and Klatskin tumors (P = .034). Moreover, strong metallothionein expression was identified as an independent prognostic parameter in multivariate Cox regression analysis in both intrahepatic cholangiocarcinoma (P = .005) and Klatskin tumors (P = .035). In contrast, cholangiocarcinoma with a papillary phenotype (8/112; 7.1%) exhibited a significant lack of strong metallothionein expression in all 8 of 8 cases. Strong metallothionein expression is identified as an independent poor prognostic parameter, and determination of the metallothionein expression may serve as an additional tool for the therapeutic management of patients with cholangiocarcinoma. In comparison, lack of metallothionein expression seems to be associated with cholangiocarcinoma with a

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

    Science.gov (United States)

    Misselwitz, Benjamin; Epprecht, Jana; Mertens, Joachim; Biedermann, Luc; Scharl, Michael; Haralambieva, Eugenia; Lutterotti, Andreas; Weber, Konrad P; Müllhaupt, Beat; Chaloupka, Karla

    2016-01-01

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

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    Jiong Lu

    2012-01-01

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

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

    Science.gov (United States)

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

    1989-01-01

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

  1. 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.

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

    Science.gov (United States)

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

    2007-03-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Leilei Wang

    2016-01-01

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

  5. 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.

  6. Positive lymph node metastasis has a marked impact on the long-term survival of patients with hepatocellular carcinoma with extrahepatic metastasis.

    Directory of Open Access Journals (Sweden)

    Feng Xia

    Full Text Available BACKGROUND: The prognosis of hepatocellular carcinoma (HCC patients with extrahepatic metastasis is extremely poor. However, what is the main risk factor for survival remains unclear for these patients. We aimed to find out the relative frequency, incidence and locations of extrahepatic metastases and the risk factors of long-term survival of the patients. METHODS: 132 HCC patients with extrahepatic metastasis diagnosed by 18F-FDG PET/CT and conventional workup were enrolled into this study. The incidence and locations of extrahepatic metastases were summarized, and the related risk factors of overall survival were analyzed. RESULTS: The most frequent extrahepatic metastatic sites were lymph nodes in 72 (54.5%, bone in 33 (25.0% and lung in 28 (21.2% patients. On univariate analysis, prothrombin time, Child-Pugh grade, portal/hepatic vein invasion and lymph node metastasis were independent risk factors of overall survival. On multivariate analysis, lymph node metastasis was the only independent risk factor of overall survival. The cumulative survival rates at 1- and 3-years after diagnosis of extrahepatic metastasis of HCC were 34.4% and 9.3%, respectively. The median survival time was 7 months (range 1 ∼38 months. The median survival time for patients with or without lymph node metastasis were 5 months (range 1∼38 months and 12 months (range 1∼30 months, respectively (P = 0.036. CONCLUSIONS: This study showed lymph nodes to be the most frequent site of extrahepatic metastases for primary HCC. Lymph node metastasis was the main risk factor of overall survival in patients with HCC with extrahepatic metastasis.

  7. Treatment of pruritus with Prometheus dialysis and absorption system in a patient with benign recurrent intrahepatic cholestasis.

    Science.gov (United States)

    Ołdakowska-Jedynak, Urszula; Jankowska, Irena; Hartleb, Marek; Jirsa, Milan; Pawłowska, Joanna; Czubkowski, Piotr; Krawczyk, Marek

    2014-10-01

    Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive liver disorder characterized by recurrent episodes of jaundice and itching. Episodes of cholestasis last variously from 1 week to several months, may start at any age and usually resolve spontaneously. No effective treatment has been found as yet. We report a case of genetically proven BRIC in a male patient who developed three episodes of pruritus and jaundice at the age of 14, 16 and 19 years. During the third episode, he did not respond to pharmacological medical therapy, and fractionated plasma separation and absorption (FPSA, Prometheus) was performed to manage intractable pruritus. The treatment immediately alleviated pruritus, lowered serum bilirubin concentration and induced sustained remission in the 5-year follow up. FPSA seems to be a safe and effective way of treatment for BRIC in patients with severe pruritus and prolonged jaundice.

  8. Role of extrahepatic UDP-glucuronosyltransferase 1A1: advances in understanding breast milk-induced neonatal hyperbilirubinemia

    Science.gov (United States)

    Fujiwara, Ryoichi; Maruo, Yoshihiro; Chen, Shujuan; Tukey, Robert H.

    2015-01-01

    Newborns commonly develop physiological hyperbilirubinemia (also known as jaundice). With increased bilirubin levels being observed in breast-fed infants, breast-feeding has been recognized as a contributing factor for the development of neonatal hyperbilirubinemia. Bilirubin undergoes selective metabolism by UDP-glucuronosyltransferase (UGT) 1A1 and becomes a water soluble glucuronide. Although several factors such as gestational age, dehydration and weight loss, and increased enterohepatic circulation have been associated with breast milk-induced jaundice (BMJ), deficiency in UGT1A1 expression is a known cause of BMJ. It is currently believed that unconjugated bilirubin is metabolized mainly in the liver. However, recent findings support the concept that extrahepatic tissues, such as small intestine and skin, contribute to bilirubin glucuronidation during the neonatal period. We will review the recent advances made towards understanding biological and molecular events impacting BMJ, especially regarding the role of extrahepatic UGT1A1 expression. PMID:26342858

  9. Effects of dopamine receptor agonist and antagonists on cholestasis-induced anxiolytic-like behaviors in rats.

    Science.gov (United States)

    Reza Zarrindast, Mohammad; Eslimi Esfahani, Delaram; Oryan, Shahrbano; Nasehi, Mohammad; Torabi Nami, Mohammad

    2013-02-28

    Dysfunctions in the dopamine transmission system have been suggested to contribute to the pathogenesis of hepatic encephalopathy. In an experimental animal model, cholestasis induction through bile duct ligation may present several main pathological features of hepatic encephalopathy. Dopaminergic systems are shown to play pivotal roles in regulation of anxiety-like behaviors. The main bile duct in male Wistar rats, weighing 220-240 g, was ligated using two ligatures plus duct transection in between. Anxiety-like behaviors were measured using the elevated plus maze task. Cholestasis increased the open arm time percentage (%OAT), 13 but not 10 days after bile duct ligation, indicating an anxiolytic-like effect. Sole intraperitoneal injection of apomorphine (dopamine D1/D2 receptor agonist, 0.25 mg/kg), SCH23390 (dopamine D1 receptor antagonist, 0.005, 0.01 and 0.02 mg/kg) or sulpiride (dopamine D2 receptor antagonist, 0.125, 0.25 and 0.5 mg/kg) did not alter %OAT, open arm entries percentage (%OAE) and locomotor activity in the sham-operated rats. Meanwhile, the higher dose apomorphine (0.5 mg/kg) induced anxiolytic-like behaviors in this group. The subthreshold dose injection of SCH23390 or sulpiride, partially reversed the anxiolytic-like behaviors induced by cholestasis (13 days after bile duct ligation). On the other hand, subthreshold dose of apomorphine in cholestatic rats (10 days post bile duct ligation) induced anxiolytic-like effects which could be blocked by SCH23390 or sulpiride. The effective doses of above drugs did not alter locomotor activity, number of rearings, groomings and defections. These findings suggested that the dopaminergic system may potentially be involved in the modulation of cholestasis-induced anxiolytic-like behaviors in rats.

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

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    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.

  11. 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

  12. Autoimmunity and Extrahepatic Manifestations in Treatment-Naïve Children with Chronic Hepatitis C Virus Infection

    OpenAIRE

    Giuseppe Indolfi; Elisa Bartolini; Biagio Olivito; Chiara Azzari; Massimo Resti

    2012-01-01

    Hepatitis C virus (HCV) infection has been associated with autoimmunity and extrahepatic manifestations in adults. Few data are available on these topics in children. Nonorgan specific auto-antibodies development is part of the natural course of chronic hepatitis C in children. Smooth muscle autoantibody is the most common autoantibody found, while liver-kidney microsomal type-1 antibody positivity is the most peculiar autoimmune feature of children with HCV infection. The clinical significan...

  13. Colestase neonatal prolongada: estudo prospectivo Prolonged neonatal cholestasis: a prospective study

    Directory of Open Access Journals (Sweden)

    Elizabeth Teixeira Mendes Livramento PRADO

    1999-12-01

    completo e abrangente, evoluindo para a ideal diminuição progressiva dos processos idiopáticos.Due to the urgency in choosing either clinical treatment or immediate surgical intervention, the study of the prolonged neonatal cholestasis involves two basic aims: the differential diagnosis between biliary atresia and neonatal hepatitis and the research into the associated etiological agents. So, in a prospective trial carried out in the 70´s, 77 children with prolonged neonatal cholestasis were studied in order to establish the differential diagnosis between biliary atresia and neonatal hepatitis, followed by the evaluation of 108 children towards a pathogenesis of the prolonged neonatal cholestasis. The results of the differential diagnosis showed that within 18 items examined only 8 proved to be good biliary atresia indicators. They are as follows (in decreasing order: ductular proliferation (portal tracts, fibrosis (portal tracts, cholestasis (portal tracts, stools colour -- acholia, hepatomegaly, canalicular cholestasis (lobule, infiltrate (portal tracts, giant cells (lobule. These eight items were then gathered in a sole indicator of great discriminative power, with a confidence level of 99%. The figures regarding the pathogenesis are: rubella virus 0%, herpes simplex virus 0%, listeriosis 0%, cytomegalovirus 2.2%, hepatitis B virus 2.4%, toxoplasmosis 2.8%, alpha-1-antitrypsin deficiency 13.1%, syphilis 21.1%, autoantibodies against the liver 58.4%. Such work thus revealed that those eight most important factors when differentiating biliary atresia from neonatal hepatitis remain as fundamental indicators and, when employed alongside other diagnostic methods, can help in the assembling of a multifactorial strategy less and less invasive and more precise. The pathogenic study, with its heavy dependency on time and place, has become more complete with the introduction of new diagnostic methods, evolving to the ideal progressive reduction of idiopathic processes.

  14. International diagnostic guidelines for patients with HCV-related extrahepatic manifestations. A multidisciplinary expert statement.

    Science.gov (United States)

    Ferri, Clodoveo; Ramos-Casals, Manuel; Zignego, Anna Linda; Arcaini, Luca; Roccatello, Dario; Antonelli, Alessandro; Saadoun, David; Desbois, Anne Claire; Sebastiani, Marco; Casato, Milvia; Lamprecht, Peter; Mangia, Alessandra; Tzioufas, Athanasios G; Younossi, Zobair M; Cacoub, Patrice

    2016-12-01

    Hepatitis C virus (HCV) infection is responsible for both hepatic and extra-hepatic disorders (HCV-EHDs); these latter are correlated on one hand clearly with HCV lymphotropism causing immune-system dysregulation as well as with viral oncogenic potential, and on the other hand probably with chronic inflammatory status causing cardio-metabolic complications as well as neurocognitive disturbances. The spectrum of HCV-EHDs ranges from mild or moderate manifestations, such as arthralgia, sicca syndrome, peripheral neuropathy, to severe, life-threatening complications, mainly vasculitis and neoplastic conditions. Given the clinical heterogeneity of HCV-EHDs, HCV-infected individuals are inevitably referred to different specialists according to the presenting/prevalent symptom(s); therefore, the availability of comprehensive diagnostic guidelines is necessary for a patient's whole assessment that is decisive for early diagnosis and correct therapeutic approach of various hepatic and HCV-EHDs, regardless of the specific competencies of different physicians or referral centers. In this respect, a multidisciplinary network of experts, the International Study Group of Extrahepatic Manifestations Related to Hepatitis C Virus Infection (ISG-EHCV), was organized with the intention to formulate diagnostic guidelines for the work-up of possible HCV-EHDs. There was a broad consensus among ISG-EHCV members on the proposed guidelines, which essentially are based on two main levels of patient's assessment. At the referral stage, it is proposed that all patients with HCV infection should be invariably examined by means of first-line diagnostic procedures including virological and hepatic parameter evaluation, as well as the detection of clinical findings that may suggest one or more HCV-EHDs. This preliminary assessment should reveal specific HCV-EHDs, which will be deeper analyzed by means of second-line, targeted investigations. The proposed multidisciplinary expert statement

  15. Autoimmunity and extrahepatic manifestations in treatment-naïve children with chronic hepatitis C virus infection.

    Science.gov (United States)

    Indolfi, Giuseppe; Bartolini, Elisa; Olivito, Biagio; Azzari, Chiara; Resti, Massimo

    2012-01-01

    Hepatitis C virus (HCV) infection has been associated with autoimmunity and extrahepatic manifestations in adults. Few data are available on these topics in children. Nonorgan specific auto-antibodies development is part of the natural course of chronic hepatitis C in children. Smooth muscle autoantibody is the most common autoantibody found, while liver-kidney microsomal type-1 antibody positivity is the most peculiar autoimmune feature of children with HCV infection. The clinical significance of non-organ specific autoantibodies in the course of paediatric chronic hepatitis C is still debated. Autoantibody positivity can be considered neutral for most patients, while it can be associated with negative connotations for others, especially those positive for liver-kidney microsomal type-1 autoantibody. Subclinical hypothyroidism but not autoimmune thyroiditis has been demonstrated in HCV infection in children, while only few cases of HCV-associated membranoproliferative glomerulonephritis have been described. Single reports are available in the literature reporting the anecdotal association between chronic hepatitis C and other extrahepatic manifestations such as myopathy and opsoclonus-myoclonus syndrome. Despite the low incidence of extrahepatic manifestations of chronic hepatitis C in children, overall, available data suggest a careful monitoring.

  16. Autoimmunity and Extrahepatic Manifestations in Treatment-Naïve Children with Chronic Hepatitis C Virus Infection

    Directory of Open Access Journals (Sweden)

    Giuseppe Indolfi

    2012-01-01

    Full Text Available Hepatitis C virus (HCV infection has been associated with autoimmunity and extrahepatic manifestations in adults. Few data are available on these topics in children. Nonorgan specific auto-antibodies development is part of the natural course of chronic hepatitis C in children. Smooth muscle autoantibody is the most common autoantibody found, while liver-kidney microsomal type-1 antibody positivity is the most peculiar autoimmune feature of children with HCV infection. The clinical significance of non-organ specific autoantibodies in the course of paediatric chronic hepatitis C is still debated. Autoantibody positivity can be considered neutral for most patients, while it can be associated with negative connotations for others, especially those positive for liver-kidney microsomal type-1 autoantibody. Subclinical hypothyroidism but not autoimmune thyroiditis has been demonstrated in HCV infection in children, while only few cases of HCV-associated membranoproliferative glomerulonephritis have been described. Single reports are available in the literature reporting the anecdotal association between chronic hepatitis C and other extrahepatic manifestations such as myopathy and opsoclonus-myoclonus syndrome. Despite the low incidence of extrahepatic manifestations of chronic hepatitis C in children, overall, available data suggest a careful monitoring.

  17. 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.

  18. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    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.

  20. 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

    2016-06-28

    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.

  1. Hepatic and extrahepatic clearance of circulating human lactoferrin: An experimental study in rat

    Energy Technology Data Exchange (ETDEWEB)

    Peen, E. [Haukeland Hospital, Dept. of Internal Medicine B, Bergen (Norway); Johansson, A.; Engquist, M. [Linkoeping Univ., Faculty of Health Sciences, Dept. of Medical Microbiology, Linkoeping (Sweden); Skogh, T. [Univ. Hospital of Linkoeping, Dept. of Rheumatology, Linkoeping (Sweden)

    1998-09-01

    Lactoferrin, unlabelled or {sup 125}I-labelled by 2 different methods, was given intravenously to rats. Blood, tissue and liver cell radioactivity was measured. Both of the radiolabelled preparations were eliminated by the liver, and some deposited extra hepatically. One preparation formed large aggregates - here 90% of the hepatic uptake occurred in the Kupffer cells. The other preparation, consisting mostly of protein monomers but also dimers/oligomers/micro aggregates, was taken up by hepatocytes (63% of total liver uptake), liver endothelial cells (22%) and Kupffer cells (15%). On a per cell volume basis, lactoferrin uptake was much more efficient by nonparenchymal cells compared to hepatocytes, which explains why immuno morphological staining only revealed lactoferrin in the nonparenchymal liver cells. The study demonstrates that radio-iodination of lactoferrin can affect its properties and handling, which may be important regarding contradictory reports on hepatic lactoferrin uptake. We conclude that both hepatocytes and nonparenchymal liver cells are involved in the blood clearance of lactoferrin, probably to a great extent owing to nonspecific mechanisms. Extrahepatic deposition and exposure (for instance on vessel walls/glomeruli) suggests that lactoferrin can be available to circulating anti-lactoferrin autoantibodies in autoimmune disease. (au) 56 refs.

  2. Metastatic colon cancer from extrahepatic cholangiocarcinoma presenting as painless jaundice: case report and literature review.

    Science.gov (United States)

    Vabi, Benjamin W; Carter, Jeffrey; Rong, Rong; Wang, Minhua; Corasanti, James G; Gibbs, John F

    2016-04-01

    Cholangiocarcinoma (CCA) is a rare cancer of the biliary epithelium comprising only about 3% of all gastrointestinal malignancies. It is a highly aggressive malignancy and confers a dismal prognosis with majority of patients presenting with metastatic disease. Metastatic CCA to the colon is extremely rare with only few cases reported in the literature. We present a 61-year-old patient with incidental synchronous metastatic colonic adenocarcinoma from extra-hepatic CCA. Laboratory data revealed significant indirect hyperbilirubinemia and transaminitis. Imaging study showed intrahepatic bile ducts prominence without mass lesions. Incidentally, there was diffuse colonic thickening without mass lesions or obstruction. Endoscopic retrograde cholangiopancreatography (ERCP) showed a common bile duct stricture. Brushings were consistent with CCA. Screening colonoscopy identified nodularity and biopsy and immunostaining were consistent with CCA metastasis to colon. The patient elected for palliative and comfort care. Metastatic CCA to the colon is a rare pattern of distant spread that may pose a diagnostic challenge. Some salient characteristics may assist in the differentiation of primary colon cancer and metastatic colon cancer from CCA. Little remains known about the pathogenic behavior of metastatic secondary colorectal cancer. And more so, the management approach to such metastatic cancer still remains to be defined. Screening colonoscopy in patients presenting with resectable CCA may alter management. Furthermore, whether patients with history of resected CCA may benefit from a more frequent screening colonoscopy remains to be validated.

  3. Cryoglobulinaemia in Egyptian Patients with Extrahepatic Cutaneous Manifestations of Chronic Hepatitis C Virus Infection

    Directory of Open Access Journals (Sweden)

    Doaa Salah Hegab

    2015-01-01

    Full Text Available Background. Hepatitis C is a global major health problem with extremely variable extrahepatic manifestations. Mixed cryoglobulinaemia (MC shows a striking association with hepatitis C virus (HCV infection, and it is sometimes asymptomatic. The skin is a frequently involved target organ in MC. Objective. To investigate the prevalence of cryoglobulinaemia in a sample of Egyptian patients with cutaneous manifestations of chronic HCV infection and to correlate its presence with clinical criteria and liver function tests. Methods. One hundred and eighteen patients with skin manifestations of chronic compensated hepatitis C were included. Venous blood was tested for liver function tests and serum cryoglobulins. Results. Twelve patients (10.169% were positive for serum cryoglobulins (2 with pruritus, 4 with vasculitic lesions, 3 with livedo reticularis, one with oral lichen, one with chronic urticaria, and another with Schamberg’s disease. Vasculitic lesions and livedo reticularis of the legs showed higher prevalence in cryoglobulin-positive than in cryoglobulin-negative patients. Presence of serum cryoglobulins did not relate to patients’ demographic or laboratory findings. Conclusions. Fortunately, MC is not markedly prevalent among Egyptians with cutaneous lesions of chronic hepatitis C, and cryopositivity was commonly, but not exclusively, detected with cutaneous vasculitis and livedo reticularis. Laboratory testing for cryoglobulins in every HCV patient is advisable for earlier MC detection and management.

  4. Cryoglobulinaemia in Egyptian Patients with Extrahepatic Cutaneous Manifestations of Chronic Hepatitis C Virus Infection.

    Science.gov (United States)

    Hegab, Doaa Salah; Sweilam, Mohammed Abd El Rahman

    2015-01-01

    Background. Hepatitis C is a global major health problem with extremely variable extrahepatic manifestations. Mixed cryoglobulinaemia (MC) shows a striking association with hepatitis C virus (HCV) infection, and it is sometimes asymptomatic. The skin is a frequently involved target organ in MC. Objective. To investigate the prevalence of cryoglobulinaemia in a sample of Egyptian patients with cutaneous manifestations of chronic HCV infection and to correlate its presence with clinical criteria and liver function tests. Methods. One hundred and eighteen patients with skin manifestations of chronic compensated hepatitis C were included. Venous blood was tested for liver function tests and serum cryoglobulins. Results. Twelve patients (10.169%) were positive for serum cryoglobulins (2 with pruritus, 4 with vasculitic lesions, 3 with livedo reticularis, one with oral lichen, one with chronic urticaria, and another with Schamberg's disease). Vasculitic lesions and livedo reticularis of the legs showed higher prevalence in cryoglobulin-positive than in cryoglobulin-negative patients. Presence of serum cryoglobulins did not relate to patients' demographic or laboratory findings. Conclusions. Fortunately, MC is not markedly prevalent among Egyptians with cutaneous lesions of chronic hepatitis C, and cryopositivity was commonly, but not exclusively, detected with cutaneous vasculitis and livedo reticularis. Laboratory testing for cryoglobulins in every HCV patient is advisable for earlier MC detection and management.

  5. Upregulation of PDZK1 by Calculus Bovis Sativus May Play an Important Role in Restoring Biliary Transport Function in Intrahepatic Cholestasis

    Directory of Open Access Journals (Sweden)

    Dong Xiang

    2017-01-01

    Full Text Available Intrahepatic cholestasis is a main cause of hepatic accumulation of bile acids leading to liver injury, fibrosis, and liver failure. Our previous studies proved that Calculus Bovis Sativus (CBS can restore biliary transport function through upregulating the multidrug resistance-associated protein 2 (MRP2 and breast cancer resistance protein (BCRP in 17α-ethynylestradiol- (EE- induced intrahepatic cholestasis rats. The regulation mechanism of CBS on these transporters, however, remains unclear. This study was designed to evaluate the possible relationship between the effect of CBS on transport activities and the regulation of CBS on the expression of PDZK1, a mainly scaffold protein which can regulate MRP2 and BCRP. Intrahepatic cholestasis model was induced in rats with injection of EE for five consecutive days and then the biliary excretion rates and cumulative biliary excretions were measured. The mRNA and protein expression levels of PDZK1 were detected by reverse transcription-quantitative real-time polymerase chain reaction, western blot, and immunohistochemical analysis. When treated with CBS, cumulative biliary excretions and mRNA and protein expressions of PDZK1 were significantly increased in intrahepatic cholestasis rats. This study demonstrated that CBS exerted a beneficial effect on EE-induced intrahepatic cholestasis rats by restoring biliary transport function, which may result from the upregulation of PDZK1 expression.

  6. 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.

  7. 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.

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

    Institute of Scientific and Technical Information of China (English)

    YU Cui-ge; LI Lian-xiang; LIU Xiao-qin; SHI Jian-yong

    2015-01-01

    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 signiifcant (P0.05). When compared with control group, the levels of D-dimer (D-D) and fibrinogen (FIB) in observation group increased dramatically (P0.05). Conclusion: Both the hemorheology and coagulation function of pregnant women with ICP manifest signiifcantly high viscosity and hypercoagulability, and the release of cell inlfammatory factors increases, which all exert adverse inlfuence on pregnancy outcome.

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

    Directory of Open Access Journals (Sweden)

    Minoru Itou

    2009-04-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

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

  12. Anti-Glutamic Acid Decarboxylase Antibody-Associated Ataxia as an Extrahepatic Autoimmune Manifestation of Hepatitis C Infection: A Case Report

    Directory of Open Access Journals (Sweden)

    Amer Awad

    2011-01-01

    Full Text Available Extrahepatic immunological manifestations of hepatitis C virus (HCV are well described. In addition, antiglutamic acid decarboxylase (GAD antibody-associated cerebellar ataxia is well-established entity. However, there have been no reports in the literature of anti-GAD antibody-associated ataxia as an extrahepatic manifestation of HCV infection. We report the case of a young woman with chronic hepatitis C virus and multiple extrahepatic autoimmune diseases including Sjögren syndrome and pernicious anemia who presented with subacute midline cerebellar syndrome and was found to have positive antiglutamic acid decarboxylase (GAD antibody in the serum and cerebrospinal fluid. An extensive diagnostic workup to rule out neoplastic growths was negative, suggesting the diagnosis of nonparaneoplastic antiglutamic acid decarboxylase antibody-associated cerebellar ataxia as an additional extrahepatic manifestation of hepatitis C virus infection. The patient failed to respond to high-dose steroids and intravenous immunoglobulin. Treatment with the monoclonal antibody rituximab stabilized the disease. We postulate that anti-GAD associated ataxia could be an extrahepatic manifestation of HCV infection.

  13. Anti-glutamic Acid decarboxylase antibody-associated ataxia as an extrahepatic autoimmune manifestation of hepatitis C infection: a case report.

    Science.gov (United States)

    Awad, Amer; Stüve, Olaf; Mayo, Marlyn; Alkawadri, Rafeed; Estephan, Bachir

    2011-01-01

    Extrahepatic immunological manifestations of hepatitis C virus (HCV) are well described. In addition, antiglutamic acid decarboxylase (GAD) antibody-associated cerebellar ataxia is well-established entity. However, there have been no reports in the literature of anti-GAD antibody-associated ataxia as an extrahepatic manifestation of HCV infection. We report the case of a young woman with chronic hepatitis C virus and multiple extrahepatic autoimmune diseases including Sjögren syndrome and pernicious anemia who presented with subacute midline cerebellar syndrome and was found to have positive antiglutamic acid decarboxylase (GAD) antibody in the serum and cerebrospinal fluid. An extensive diagnostic workup to rule out neoplastic growths was negative, suggesting the diagnosis of nonparaneoplastic antiglutamic acid decarboxylase antibody-associated cerebellar ataxia as an additional extrahepatic manifestation of hepatitis C virus infection. The patient failed to respond to high-dose steroids and intravenous immunoglobulin. Treatment with the monoclonal antibody rituximab stabilized the disease. We postulate that anti-GAD associated ataxia could be an extrahepatic manifestation of HCV infection.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-12-15

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

  15. 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.

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

    Science.gov (United States)

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

    2016-02-01

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

  17. 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.)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-05-15

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-02-15

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

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

    Science.gov (United States)

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

    2003-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Prud’homme, Sylvie

    2016-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Nakanishi,Kuniaki

    2010-02-01

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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    Michelle Rook

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

  6. A Study of Technical Approach Methods to Transabdominal Ultrasonography of the Extrahepatic Bile Ducts and of Following Effects from the Scan Training

    Energy Technology Data Exchange (ETDEWEB)

    Lee, In Ja [Dept. of Radiological Technology, Dongnam Health College, Suwon (Korea, Republic of); Kang, Dae Hyun [Dept. of Diagnostic Radiology, Korea University Guro Hospital, Seoul (Korea, Republic of); Kim, Bo Young [Seoul Sansung Clinic, Seoul (Korea, Republic of)

    2008-06-15

    The purposes of this study are to analyze abnormal dilatation of the extrahepatic bile ducts by using transabdominal ultrasound, to confirm the existence of bile ducts diseases and their interrelationship, and for it to give a new theoretical basis for the technical access to extrahepatic bile ducts, upon which to analyze the ripple effects of the scan training. After teaching technical access process based on the new theory about extrahepatic bile duct to the thirty students who are studying ultrasonography, we allocated three hours per one student (30 mins 6 times) to focus on the training of scanning skill. Training has been performed by one-to-one method. For evaluation, all the students have to perform the scans on (1) confluence of the right and left hepatic ducts (extrahepatic bile ducts and cystic duct), (2) the suprapancreatic bile duct, (3) the intrapancreatic bile duct, (4) intrapapilla Duct, based on the clearly divided concept. The existing training and methods have had low confidency about transabdominal ultrasonography of the extrahepatic bile duct and had limitation with which they could image only the suprapancreatic bile duct. The evaluation after finishing the train based on the new theory, however, all the students (30 students) can access to (1) confluence of the right and left hepatic ducts(extrahepatic bile ducts and cystic duct), (2) the suprapancreatic bile duct objectively. 24 students can access to (3) the intrapancreatic bile duct and only one student can even make an image for (4) the intrapapilla Duct Though the evaluation on extrahepatic bile duct has to be performed with multi-sided method considering intrahepatic cause, bile duct cause and pathophysiological cause, only if we can image the extrahepatic bile duct to ampular of Vater objectively and confidently, we can greatly reduce invasive procedure such as ERCP, which is for the purpose of simple differential diagnosis and painful to the patients. Therefore if we concentrate on

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

    Institute of Scientific and Technical Information of China (English)

    CHENMingyi; HUANGZhiqiang; CHENLezhen; GAOYabing; PENGRuiyun; WANGDewen

    2002-01-01

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

  8. 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.

  9. The effect of beta-naphthoflavone on the metabolism of amiodarone by hepatic and extra-hepatic microsomes.

    Science.gov (United States)

    Elsherbiny, Marwa E; El-Kadi, Ayman O S; Brocks, Dion R

    2010-06-02

    Amiodarone is a potent antiarrhythmic drug with several limiting side effects, some of which have been correlated with increased levels of its more toxic metabolite, desethylamiodarone. Elevated serum desethylamiodarone to amiodarone ratios are associated with a risk of amiodarone-induced pulmonary toxicity. Polycyclic aromatic hydrocarbons such as beta-naphthoflavone are known to increase desethylamiodarone levels in rat in vivo. In this article we investigated if this increase was solely due to increased formation as a result of cytochrome P450 (CYP) 1A1 and 1A2 induction in different rat hepatic and extra-hepatic tissues. Additionally, the effect of amiodarone treatment on CYP1A1 and 1A2 gene expression and activity was investigated. In rats, beta-naphthoflavone was found to increase desethylamiodarone forming activity in lung and kidney microsomes. Amiodarone increased beta-naphthoflavone mediated induction of CYP1A1 gene expression in liver, lung and kidney. However, there was no significant change in CYP1A activity. As expected, the data indicated that the increase in desethylamiodarone levels in vivo was partly due to increased formation through CYP1A1 induction, although increased formation was only evident in some extra-hepatic tissues. Amiodarone treatment did not affect basal or induced CYP1A activity.

  10. 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.

  11. [A difficult and complicated case study: neonatal intrahepatic cholestasis caused by citrin deficiency].

    Science.gov (United States)

    Song, Yuan-Zong; Hao, Hu; Ushikai, Miharu; Liu, Guo-Sheng; Xiao, Xin; Saheki, Takeyori; Kobayashi, Keiko; Wang, Zi-Neng

    2006-04-01

    Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a kind of inborn errors of metabolism, with the main clinic manifestations of jaundice, hepatomegaly, and abnormal liver function indices. As a mitochondrial solute carrier protein, citrin plays important roles in aerobic glycolysis, gluconeogenesis, urea cycle, and protein and nucleotide syntheses. Therefore citrin deficiency causes various and complicated metabolic disturbances, such as hypoglycemia, hyperlactic acidemia, hyperammonemia, hypoproteinemia, hyperlipidemia, and galactosemia. This paper reported a case of NICCD confirmed by mutation analysis of SLC25A13, the gene encoding citrin. The baby (male, 6 months old) was referred to the First Affiliated Hospital with the complaint of jaundice of the skin and sclera, which it had suffered from for nearly 6 months. Physical examination showed obvious jaundice and a palpable liver 5 cm below the right subcostal margin. Liver function tests revealed elevated enzymatic activities, like GGT, ALP, AST, and ALT, together with increased levels of TBA, bilirubin (especially conjugated bilirubin), and decreased levels of total protein/albumin and fibrinogen. Blood levels of ammonia, lactate, cholesterol, and triglyceride were also increased, and in particular, the serum AFP level reached 319,225.70 microg/L, a extremely elevated value that has rarely been found in practice before. Tandem mass analysis of a dried blood sample revealed increased levels of free fatty acids and tyrosine, methionine, citrulline, and threonine as well. UP-GC-MS analysis of the urine sample showed elevated galactose and galactitol. The baby was thus diagnosed with suspected NICCD based on the findings. It was then treated with oral arginine and multiple vitamins (including fat-soluble vitamins A, D, E, and K), and was fed with lactose-free and medium-chain fatty acids enriched formula instead of breast feeding. After half a month of treatment, the jaundice disappeared

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

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    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

  13. Changes of hemorheological indeses, coagulation function and cytokines in women with intrahepatic cholestasis of pregnancy

    Institute of Scientific and Technical Information of China (English)

    Li Zhang; Xiao-Li Li; Yuan-Xia Lan

    2015-01-01

    Objective:To explore the changes of hemorheological indexes, coagulation function and cytokines of women with intrahepatic cholestasis of pregnancy ICP.Methods: A total of 54 cases of ICP in our hospital were collected as study group, 54 cases of normal pregnancy period were collected as the control group. The changes of coagulation function, inflammatory cytokines and D- two dimer of two groups were observed and compared.Results: The blood rheology indexes such as whole blood viscosity at high shear, whole blood viscosity at low shear, plasma viscosity, hematocrit and erythrocyte sedimentation rate of study group were (4.73±0.81) mPa•s, (6.67±1.40) mPa•s, (1.93±0.38) mPa•s, (46.34±4.25)%, and the (68.92±7.93) mm/h, respectively; they were significantly higher than those of control group (P0.05). FIB, D-D of the study group respectively were (5.62±0.78) g/L, (0.45±0.11) mg/L, significantly higher than the control group. PLT was (168.44±16.35)í109/L, and was significantly reduced compared with the control group (P<0.05). The levels of IL-18, IL-12, TNF-α of the study Group were (70.22±5.33) ng/L,(47.55±4.23) ng/L and (40.45±3.45) ng/L, respectively. Compared with normal pregnancy control they was significantly increased (P<0.05). The rates of premature delivery, amniotic fluid contamination, fetal distress, neonatal asphyxia and low birth weight infants were 20.37%, 37.04%, 18.52%, 11.11% and 9.26%, significantly higher than the control group (P<0.05).Conclusion: ICP patients have significantly high viscosity changes, high coagulation and has adverse effects on pregnancy outcome, which play important roles in the clinical diagnosis.

  14. 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.

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

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    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.

  16. 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.

  17. 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.

  18. 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-

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

    OpenAIRE

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

    2016-01-01

    Extrahepatic portal vein obstruction, although rare in children, is a significant cause of portal hypertension (PHT) leading to life-threatening gastrointestinal bleeding in the pediatric age group. PHT may also lead to other complications such as hyperesplenism, cholangyopathy, ascites, and even hepatopulmonary syndrome and portopulmonary hypertension that may require organ transplantation. Herein we report the case of an asymptomatic 11-month-old infant wherein a hepatomegaly and cavernous ...

  20. 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.

  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

    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

  3. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-03-15

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  6. Measuring the Response of Extrahepatic Symptoms and Quality of Life to Antiviral Treatment in Patients with Hepatitis C

    Directory of Open Access Journals (Sweden)

    David Isaacs

    2013-01-01

    Full Text Available Background. HCV infection is associated with musculoskeletal manifestations such as chronic widespread pain, sicca syndrome, polyarthritis, and a reduced HRQOL. Little data is available on the effect of treatment on these manifestations. This study measured changes in extrahepatic symptoms and HRQOL before and after antiviral treatment in a large UK patient cohort. Methods. 118 patients completed HQLQ and rheumatological questionnaires before and after treatment with pegylated interferon-α and ribavirin, with specific regard to chronic widespread pain, sicca syndrome, and sustained virological response. Results. There was significant improvement in HQLQ domains of physical functioning, physical disability, social functioning, limitations and health distress due to hepatitis, and general health. There was significant deterioration in domains of positive well-being, health distress, and mental health. There was a significant decline prevalence of CWP (26.3% versus 15.3%, . Sicca syndrome prevalence fell insignificantly (12.7% versus 11%. SVR was associated positively with all HRQOL changes and significantly with CWP remission. Conclusions. HCV antivirals significantly improve poor HRQOL scores and CWP. Before treatment, both were common, coassociated, and unaccounted for through mixed cryoglobulinemia alone. Although a role of the hepatitis C virus in CWP cannot be deduced by these results, symptomatic improvement via antiviral treatment exists for this subset of patients.

  7. Clinic features, diagnosis and treatment of extrahepatic growing hepatocellular carcinoma%外生型肝癌的临床特点及诊治

    Institute of Scientific and Technical Information of China (English)

    赖智德; 王耀东; 严茂林; 陈忠

    2011-01-01

    Objective To evaluate the clinical features, diagnosis, treatment, definition and classification of extrahepatic growing hepatocellular carcinoma (HCC). Methods To review the reports of extrahepatic growing hepatocellular carcinoma in CNKI and CCMI from 1994 to 2010, these reports and the clinical data of patients with extrahepatic growing hepatocellular carcinoma treated in our hospital were analyzed. Results We acquired 387 patients including 35 patients in our hospital and 352 patients in 55 pieces of reports. Diagnosis of extrahepatic growing hepatocellular carcinoma mostly relied on comprehensive diagnosis based on clinical manifestations, AFP, B ultrasonography, CT, MRI, hepatic arteriography and pathological diagnosis. Conclusion Because of the special clinical and pathological features, extrahepatic growing hepatocellular carcinoma is easy to be misdiagnosed and it is difficult to be diagnosed early. Operation is the first selected therapeutic method.%目的 总结外生型肝癌的临床特点及诊治方法,探讨其定义及分型.方法 在中文生物医学期刊文献数据库和中国医院知识仓库,应用主题词和作者联合检索外生型肝癌1994-2010年的文献报告,结合我院收治的病例,进行总结分析.结果 获得有效文献55篇,共报道外生型肝癌352例,加上我院收治的35例,总共387例.外生型肝癌的诊断主要依靠临床表现、AFP、B超、CT、MRI、肝动脉造影及病理进行综合分析.结论 外生型肝癌具有独特的临床病理特点,误诊率高,不易早期诊断.手术是首选治疗方法.

  8. 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.

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

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    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.

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

    Science.gov (United States)

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

    2006-12-01

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

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

    Science.gov (United States)

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

    2012-12-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  13. Intrahepatic Cholestasis of Pregnancy with Severe Elevation of Bile Acids in the Setting of Acute Hepatitis C Infection

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    Megan L. Lawlor

    2016-01-01

    Full Text Available Intrahepatic cholestasis of pregnancy (ICP is a complication of pregnancy resulting in elevation of serum bile acid levels. ICP is often associated with underlying liver disease, including hepatitis C. Bile acids in relationship to the acute infection of hepatitis C virus have not yet been delineated in the literature. A 26-year-old gravida 4 para 2103 with dichorionic, diamniotic twin gestation and history of intravenous drug abuse developed ICP in the setting of acute hepatitis C infection. In addition to clinical symptoms of pruritus and right upper quadrant pain, she developed severe elevation in bile acids, 239 micromol/L, and transaminitis aspartate aminotransferase 1033 U/L, and alanine aminotransferase 448 U/L. She received ursodeoxycholic acid and antenatal testing was performed. Patient delivered vaginally at 33-week gestation following preterm rupture of membranes. Neonates were admitted to NICU and had uncomplicated neonatal courses. In the setting of ICP with significant transaminitis and severe elevation of bile acids, consideration of acute viral hepatitis is important, especially considering the worsening opioid epidemic and concurrent increase in intravenous drug use in the United States. Further study is needed regarding the acute form of HCV infection and its effect on ICP and associated bile acids.

  14. 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.

  15. 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

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    Dudeck, Oliver, E-mail: oliver.dudeck@med.ovgu.de; Wilhelmsen, Skadi; Ulrich, Gerhard; Loewenthal, David; Pech, Maciej; Amthauer, Holger; Ricke, Jens [University of Magdeburg, Department of Radiology and Nuclear Medicine (Germany)

    2012-10-15

    Purpose: To evaluate the efficacy of a workflow consisting of repeat assessment in patients planned for yttrium-90 ({sup 90}Y) radioembolization in case of nontarget visceral technetium-99m ({sup 99m}Tc)-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.

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

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    Sretenović Aleksandar

    2014-01-01

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

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

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    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.

  18. Beclin 1 deficiency correlated with lymph node metastasis, predicts a distinct outcome in intrahepatic and extrahepatic cholangiocarcinoma.

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    Tian-Tian Wang

    Full Text Available Autophagy can be tumor suppressive as well as promotive in regulation of tumorigenesis and disease progression. Accordingly, the prognostic significance of autophagy key regulator Beclin 1 was varied among different tumors. Here, we detected the clinicopathological and prognostic effect of Beclin 1 in the subtypes of intrahepatic cholangiocarcinoma (ICC and extrahepatic cholangiocarcinoma (ECC. Beclin 1 expression level was detected by immunohistochemistry staining in 106 ICC and 74 ECC patients. We found that Beclin 1 was lowly expressed in 126 (70% cholangiocarcinoma patients, consist of 72 ICC and 54 ECC. Moreover, the cholangiocarcinoma patients with lymph node metastasis (N1 had a lower Beclin 1 level than that of N0 subgroup (P=0.012. However, we did not detect any correlations between Beclin 1 and other clinicopathological features, including tumor subtypes, vascular invasion, HBV infection, liver cirrhosis, cholecystolithiasis and TNM stage. Survival analysis showed that, compared with the high expression subset, Beclin 1 low expression was correlated with a poorer 3-year progression-free survival (PFS, 69.1% VS 46.8%, P=041 for cholangiocarcinoma. Importantly, our stratified univariate and multivariate analysis confirmed that Beclin 1 lowly expressed ICC had an inferior PFS as well as overall survival than ECC, particularly than that of Beclin 1 highly expressed ECC patients. Thus, our study demonstrated that Beclin 1low expression, correlated with lymph node metastasis, and might be a negative prognostic biomarker for cholangiocarcinoma. Combined Beclin 1 level with the anatomical location might lead to refined prognosis for the subtypes of ICC and ECC.

  19. Experimental hepatitis A virus (HAV) infection in cynomolgus monkeys (Macaca fascicularis): evidence of active extrahepatic site of HAV replication.

    Science.gov (United States)

    Amado, Luciane A; Marchevsky, Renato S; de Paula, Vanessa S; Hooper, Cleber; Freire, Marcos da S; Gaspar, Ana Maria C; Pinto, Marcelo A

    2010-02-01

    This work studied the replication sites of hepatitis A virus (HAV) in cynomolgus monkeys (Macaca fascicularis) after intravenous inoculation. The cynomolgus monkeys were inoculated with the Brazilian hepatitis A virus strain (HAF-203). Monkeys were euthanized on days 15, 30, 45 and 60 postinoculation (pi). Liver samples, submandibular salivary gland, mesenteric lymph node and tonsils were removed for virological and pathological evaluation. Immunofluorescence analyses on liver and salivary gland sections using confocal laser scanning microscopy revealed the presence of HAV antigen (HAV Ag). The presence of HAV genome was monitored by real-time PCR. The HAV RNA was detected at 7 days postinoculation (dpi), concomitantly in serum, saliva and faeces. The highest HAV viral load was observed in faeces at 15 dpi (10(5) copies/ml), followed by serum viral load of 10(4) copies/ml at 20 dpi and saliva viral load of 10(3 )copies/ml at 7 dpi. The animals showed first histological and biochemical signs of hepatitis at 15 dpi. The HAV antigen (Ag) was present from day 7 until day 60 pi in the liver and salivary glands. The HAV replicative intermediate was also detected in the liver (4.5 x 10(4) copies/mg), salivary glands (1.9 x 10(3) copies/mg), tonsils (4.2 x 10(1) copies/mg) and lymph nodes (3.4 x 10(1) copies/mg). Our data demonstrated that the salivary gland as an extrahepatic site of early HAV replication could create a potential risk of saliva transmitted infection. In addition, the cynomolgus monkey was confirmed as a suitable model to study the pathogenesis of HAV human infection.

  20. Prevalence and pattern of growth abnormalities in children with extrahepatic portal vein obstruction: Response to shunt surgery

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    Toufeeq Ahmad Mir

    2016-01-01

    Full Text Available Objective: Growth retardation is common in children with extrahepatic portal vein obstruction (EHPVO and growth hormone (GH resistance may play a dominant role. The aim of this study was to ascertain growth parameters and growth-related hormones in children with EHPVO, comparing with controls and to study the response of shunt surgery on growth parameters. Materials and Methods: The auxological and growth-related hormone profile (GH; insulin-like growth factor binding protein-3 [IGFBP-3] and IGF-1 of thirty children with EHPVO were compared with controls. The effect of shunt surgery on growth parameters in 12 children was also studied. Results: The mean height standard deviation score (HSDS of cases (−1.797 ± 1.146 was significantly lower than that of controls (−0.036 ± 0.796; the mean weight SDS of cases (−1.258 ± 0.743 was also lower than that of controls (−0.004 ± 0.533. The mean GH level of cases (5.00 ± 6.46 ng/ml was significantly higher than that of controls (1.78 ± 2.04 ng/ml. The mean IGF-1 level of cases (100.25 ± 35.93 ng/ml was significantly lower as compared to controls (233.53 ± 115.06 ng/ml as was the mean IGFBP-3 level (2976.53 ± 1212.82 ng/ml in cases and 5183.28 ± 1531.28 ng/ml in controls. In 12 patients who underwent shunt surgery, growth parameters significantly improved. Conclusions: Marked decrease in weight and height SDSs associated with GH resistance is seen in children with EHPVO, which improves with shunt surgery.

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

    Science.gov (United States)

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

    2015-07-01

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

  2. EXPLORE ON DIAGNOSTIC AND PROGNOSTIC VALUES OF EXTRAHEPATIC CHOLANGIOCARCINOMA:UTILITY OF SERUM CA19-9 AND SERUM CEA

    Institute of Scientific and Technical Information of China (English)

    秦兴雷; 王作仁; 鲁敏; 王林; 何铨儒

    2004-01-01

    Objective To evaluate the validity of a serum carbohydrate antigen 19-9(CA19-9) determination in the diagnosis of extrahepatic cholangiocarcinoma(EHCC). Methods Serum CA19-9 concentration and serum carcinoembryonic antigen(CEA) concentration were prospectively measured by an immunoradiometric assay without knowledge of the clinical diagnosis in patients with EHCC (n=51), benign biliary diseases (n=42), and healthy individuals (n=15). Using a receiver operating characteristic (ROC) curve define a new strategy for interpreting CA19-9 and CEA in EHCC. Results The sensitivity of CA19-9 and CEA in diagnosing EHCC were 86.3% (44/51) and 25.5%(13/51), respectively. When compared with the benign biliary diseases group, the true negative rates of serum CA19-9 and serum CEA were 85.7% (36/42) and 95.2%(40/42), respectively. The false positive rates of serum CA19-9 and serum CEA were 14.3 %( 6/42) and 4.8 %( 2/42), whereas the accuracy of serum CA19-9 and serum CEA were 57.0%(53/93) and 86.0%(80/93), respectively. Serum CA19-9 concentration and serum CEA concentration were significantly elevated (P0.05), respectively. In 22 patients undergoing curative resection of EHCC, the mean serum CA19-9 concentration decreased from preoperative level of (456.6±120.4) kU·L-1 to postoperative level (62.8±17.3) kU·L-1(P<0.001). The outcomes showed that serum CA19-9 had greater diagnosis performances than serum CEA. Conclusion Serum CA19-9 is an effective tumor marker in diagnosing of cholangiocarcinoma, deciding whether the tumor has been radically resected and monitoring effect of treatment

  3. 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.

  4. Reduction in the desaturation capacity of the liver in mice subjected to high fat diet: Relation to LCPUFA depletion in liver and extrahepatic tissues.

    Science.gov (United States)

    Valenzuela, Rodrigo; Barrera, Cynthia; Espinosa, Alejandra; Llanos, Paola; Orellana, Paula; Videla, Luis A

    2015-07-01

    α-Linolenic (ALA) and linoleic (LA) acids are precursors of long chain polyunsaturated fatty acids (LCPUFAs), FAs with important biochemical and physiological functions. In this process, desaturation reactions catalyzed by Δ5- and Δ6-desaturase play a major role, enzymes that are subjected to hormonal and dietary regulation. The aim of this study was to assess the influence of a high fat diet (HFD) on activity of liver Δ5 and Δ6 desaturases, in relation to LCPUFA composition in liver and extrahepatic tissues. Male C57BL/6J mice received control diet (CD) (10% fat, 20% protein and 70% carbohydrate) or high fat diet (HFD) (60% fat, 20% protein, and 20% carbohydrate) for 12 weeks. After this time, blood and liver samples were taken for metabolic, morphologic, inflammatory, oxidative stress and desaturase activity assessment, besides FA phospholipid analysis in erythrocytes, heart, adipose tissue and brain. HFD significantly increased hepatic total fat, triacylglycerides and free FA content with macrovesicular steatosis and oxidative stress enhancement, concomitantly with higher fasting serum glucose and insulin levels, HOMA, and serum cholesterol, triacylglycerols, TNF-α, and IL-6. Diminution in liver Δ5- and Δ6-desaturase activities and LCPUFA depletion were induced by HFD, the later finding being also observed in extrahepatic tissues. In conclusion, HFD-induced reduction in the bioavailability of liver LCPUFA is associated with defective desaturation of ALA and LA, with Δ5- and Δ6-desaturase activities being correlated with insulin resistance development. Data analyzed point to the liver as a major organ responsible for extrahepatic LCPUFA homeostasis, which is markedly deranged by HFD.

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

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    M. Galeazzi

    2011-09-01

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

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

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    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.

  7. Effect of betaine supplementation on changes in hepatic metabolism of sulfur-containing amino acids and experimental cholestasis induced by alpha-naphthylisothiocyanate.

    Science.gov (United States)

    Kim, Young C; Jung, Young S; Kim, Sang K

    2005-05-01

    Alterations in the hepatic metabolism of sulfur amino acids in experimental cholestasis induced by alpha-naphthylisothiocyanate (ANIT) (100 mg/kg, po) were monitored in male mice for 1 week. We also examined the effects of betaine supplementation (1% in drinking water) for 2 weeks on the hepatotoxicity and changes in the sulfur amino acid metabolism induced by ANIT treatment. Acute ANIT challenge elevated the serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) activities, and total bilirubin contents from 5 h after the treatment, reaching a peak at t = 48-72 h. Hepatic S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) levels were decreased significantly in a manner almost inversely proportional to the changes in serum parameters measured to determine the ANIT-induced toxicity. Hepatic glutathione and cysteine levels were elevated at t = 120 h after the treatment. Betaine supplementation blocked or significantly attenuated induction of the hepatotoxicity by ANIT. The decrease in SAM and SAH levels was also inhibited by betaine intake. The results indicate that betaine supplementation may antagonize the induction of experimental cholestasis and changes in the metabolism of sulfur amino acids associated with ANIT treatment. The underlying mechanism and pharmacological significance of its action are discussed.

  8. 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

  9. 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

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

    Science.gov (United States)

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

    1988-01-01

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

  11. Extra-hepatic bile duct hamartoma in a 10-month-old with a morgagni hernia and multiple anatomical anomalies: a rare and incidental finding.

    Science.gov (United States)

    Shah, Adil A; Karass, Michael; Page, Andrew J; Shehata, Bahig M; Durham, Megan M

    2013-07-01

    Von Meyenburg complexes (VMCs), also known as bile duct hamartomas, are a part of a group of ductal plate malformations. They are typically present intrahepatically. In this case, we present to our knowledge the first report of an extra-hepatic VMC in the pediatric population. The patient presented as a 10-month-old infant with a weeklong history of progressive breathing difficulty. A chest radiograph was obtained, showing intestinal loops in the thoracic cavity consistent with a Morgagni's hernia, unrelated to his breathing difficulty. The patient then underwent an elective repair of his congenital diaphragmatic defect. During the operation, the bile duct hamartoma was found adherent to the accessory lobe of the liver, present to the left of the ligamentum teres.

  12. 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.

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

    Institute of Scientific and Technical Information of China (English)

    李金銮

    2008-01-01

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

  14. 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

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

    Science.gov (United States)

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

    2016-01-01

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

  16. Extra-hepatic metabolism of 7-ketocholesterol occurs by esterification to fatty acids via cPLA2α and SOAT1 followed by selective efflux to HDL.

    Science.gov (United States)

    Lee, Jung Wha; Huang, Jiahn-Dar; Rodriguez, Ignacio R

    2015-05-01

    Accumulation of 7-ketocholesterol (7KCh) in tissues has been previously associated with various chronic aging diseases. Orally ingested 7KCh is readily metabolized by the liver and does not pose a toxicity threat. However, 7KCh formed in situ, usually associated with lipoprotein deposits, can adversely affect surrounding tissues by causing inflammation and cytotoxicity. In this study we have investigated various mechanisms for extra-hepatic metabolism of 7KCh (e.g. hydroxylation, sulfation) and found only esterification to fatty acids. The esterification of 7KCh to fatty acids involves the combined action of cytosolic phospholipase A2 alpha (cPLA2α) and sterol O-acyltransferase (SOAT1). Inhibition of either one of these enzymes ablates 7KCh-fatty acid ester (7KFAE) formation. The 7KFAEs are not toxic and do not induce inflammatory responses. However, they can be unstable and re-release 7KCh. The higher the degree of unsaturation, the more unstable the 7KFAE (e.g. 18:0>18:1>18:2>18:3≫20:4). Biochemical inhibition and siRNA knockdown of SOAT1 and cPLA2α ablated the 7KFAE synthesis in cultured ARPE19 cells, but had little effect on the 7KCh-induced inflammatory response. Overexpression of SOAT1 reduced the 7KCh-induced inflammatory response and provided some protection from cell death. This effect is likely due to the increased conversion of 7KCh to 7KFAEs, which reduced the intracellular 7KCh levels. Addition of HDL selectively increased the efflux of 7KFAEs and enhanced the effect of SOAT1 overexpression. Our data suggests an additional function for HDL in aiding extra-hepatic tissues to eliminate 7KCh by returning 7KFAEs to the liver for bile acid formation.

  17. 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.

  18. 评价彩超对肝外胆管病变的临床诊断价值%Evaluation on clinical diagnosis value of colour ultrasound used in extrahepatic bile duct

    Institute of Scientific and Technical Information of China (English)

    何栋梁

    2015-01-01

    目的:探讨肝外胆管疾病的超声诊断价值及漏诊和误诊原因。方法:选取确诊的399例肝外胆管疾病患者病例资料,对经超声诊断的结论进行回顾性分析。结果:399例肝外胆管疾病患者超声诊断符合率为93.2%(372/399),其中肝外胆管结石诊断符合率为94.5%,肝外胆管癌诊断符合率为89.3%,胆道蛔虫诊断符合率为86.0%,胆总管囊状扩张诊断符合率为100%,漏诊、误诊27例(占6.76%)。结论:超声检查对肝外胆管疾病诊断符合率较高,具有较高的临床诊断价值,但仍需与临床表现相结合进行诊断。%Objective:To evaluate the ultrasound diagnostic value of extrahepatic bile duct diseases and misdiagnosis reasons for leakage.Methods: For the diagnosis of 399 cases of extrahepatic bile duct diseases were retrospectively analyzed, analysis of the ultrasonic diagnosis. Results: Three hundred and ninty-nine cases of extrahepatic bile duct disease, ultrasonic diagnosis diagnosis coincidence rate 93.2% (372/399). With extrahepatic bile duct stones coincidence rate 94.5%, extrahepatic bile duct carcinoma (89.3%, 86.0%, biliary ascariasis bile duct cystic expansion 100%, 27 cases of misdiagnosis.Conclusion: Ultrasound in the diagnosis of extrahepatic bile duct diseases with high value.

  19. Coinfection of hepatitis A virus genotype IA and IIIA complicated with autoimmune hemolytic anemia, prolonged cholestasis, and false-positive immunoglobulin M anti-hepatitis E virus: a case report.

    Science.gov (United States)

    Kim, Hee Sup; Jeong, Sook Hyang; Jang, Je Hyuck; Myung, Hyung Joon; Kim, Jin Wook; Bang, Soo Mee; Song, Sang Hoon; Kim, Haeryoung; Yun, Hae Sun

    2011-12-01

    A 37-year-old male presented with fever and jaundice was diagnosed as hepatitis A complicated with progressive cholestasis and severe autoimmune hemolytic anemia. He was treated with high-dose prednisolone (1.5 mg/kg), and eventually recovered. His initial serum contained genotype IA hepatitis A virus (HAV), which was subsequently replaced by genotype IIIA HAV. Moreover, at the time of development of hemolytic anemia, he became positive for immunoglobulin M (IgM) anti-hepatitis E virus (HEV). We detected HAV antigens in the liver biopsy specimen, while we detected neither HEV antigen in the liver nor HEV RNA in his serum. This is the first report of hepatitis A coinfected with two different genotypes manifesting with autoimmune hemolytic anemia, prolonged cholestasis, and false-positive IgM anti-HEV.

  20. Pathogenesis and medical therapy of primary sclerosing cholangitis. Any news?

    NARCIS (Netherlands)

    van den Berg, A; Jansen, PLM

    1999-01-01

    Primary sclerosing cholangitis is characterized by inflammation and fibrosis of the intra- and extrahepatic bile ducts. Medical therapy has focused on anticholestatic, antiinflammatory and immunosuppressive drugs. Although inflammation, fibrosis and cholestasis may all occur at the same time, inflam

  1. The research advancement of pathogenesis of intrahepatic cholestasis jaundice related to chronic hepatits B%慢性乙型肝炎肝内胆汁淤积性黄疸发病机制的研究概况

    Institute of Scientific and Technical Information of China (English)

    杨宗国; 陈晓蓉; 刘成

    2011-01-01

    慢性乙型肝炎致肝内胆汁淤积性黄疸的发病机制极其复杂,其中肝细胞凋亡、氧化应激及脂质过氧化、巨噬细胞介导的炎症反应等途径均参与肝内胆汁淤积性黄疸的发病.明确肝内胆汁淤积性黄疸的发病机制对临床靶点治疗有重要意义.%The pathogenesis of intrahepatic cholestasis jaundice caused by chronic hepatite B is extremely complicated, and the following pathways such as hepatocytes apoptosis, oxidative stress, lipid peroxidation and inflammatory response mediated by macrophage have a close link with the pathogenesis of intrahepatic cholestasis jaundice. To have a clear and complete definition on the pathogenesis of intrahepatic cholestasis jaundice is of great significance for its clinical target therapy.

  2. Corona Enhancement and Mosaic Architecture for Prognosis and Selection Between of Liver Resection Versus Transcatheter Arterial Chemoembolization in Single Hepatocellular Carcinomas >5 cm Without Extrahepatic Metastases

    Science.gov (United States)

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

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    张丽娟; 张凤华; 汤丽丽; 杨伟红; 张雪

    2013-01-01

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

  4. 基于上海市住院慢性肝病患者胆汁淤积患病率的调查研究%Cholestasis morbidity rate in first-hospitalized patients with chronic liver disease in Shanghai

    Institute of Scientific and Technical Information of China (English)

    曹旬旬; 高月求; 张文宏; 徐萍; 傅青春; 陈成伟; 李成忠; 杨长青; 马光斌

    2015-01-01

    Objective To investigate the epidemiological status of cholestasis in first-hospitalized patients with chronic liver disease in Shanghai,and to provide a scientific basis for developing prevention and treatment measures.Methods From April 2005 to September 2014,5 146 first-hospitalized patients in Shanghai with a diagnosis of chronic liver disease were enrolled in this study.Clinical data of the 4 660 patients who fit the study criteria for participation were collected for retrospective analysis.Diagnosis of cholestasis was made according to serum alkaline phosphatase (ALP) levels higher than 1.5 times the upper limit normal (ULN) and gamma-glutamyltransferase (GGT) levels higher than 3 times the ULN.The incidence rate of cholestasis was assessed for relation to age,sex,etiology,and type of liver disease,and statistically compared to the general clinical data and specific biochemical indicators with potential sexrelated differences.T-test and chi-square test were performed for the statistical analyses.Results Of the 4 660 study participants,10.26% had cholestasis;the prevalence of cholestasis increased with increasing age in male patients.The distribution of the cholestasis incidence according to the type of chronic liver disease was:75.00%,primary sclerosing cholangitis;42.86%,primary biliary cirrhosis;35.97%,hepatic tumor;30.77%,autoimmune hepatitis;28.31%,drug-induced liver disease;16.46%,alcoholic hepatitis;13.98%,cryptogenic cirrhosis;12.99%,schistosomal cirrhosis;7.53%,alcoholic cirrhosis;7.32%,mixed cirrhosis;5.94%,viral liver cirrhosis;2.70%,nonalcoholic fatty liver disease.There was no significant difference in the prevalence of cholestasis between the two sexes.In the patients with cholestasis,the levels of GGT and total bilirubin were significantly different between the two sexes.Conclusion The incidence rate of cholestasis in firsthospitalized patients with chronic liver disease was 10.26%,and the rate increased with

  5. Human extrahepatic cytochromes P450: function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts.

    Science.gov (United States)

    Ding, Xinxin; Kaminsky, Laurence S

    2003-01-01

    Cytochrome P450 (CYP) enzymes in extrahepatic tissues often play a dominant role in target tissue metabolic activation of xenobiotic compounds. They may also determine drug efficacy and influence the tissue burden of foreign chemicals or bioavailability of therapeutic agents. This review focuses on xenobiotic-metabolizing CYPs of the human respiratory and gastrointestinal tracts, including the lung, trachea, nasal respiratory and olfactory mucosa, esophagus, stomach, small intestine, and colon. Many CYPs are expressed in one or more of these organs, including CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2A13, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP2F1, CYP2J2, CYP2S1, CYP3A4, CYP3A5, and CYP4B1. Of particular interest are the preferential expression of certain CYPs in the respiratory tract and the regional differences in CYP expression profile in different parts of the gastrointestinal tract. Current research activities on the characterization of CYP expression, function, and regulation in these tissues, as well as future research needs, are discussed.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Parisá Khodayar-Pardo

    2016-07-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  9. Characteristics of the extrahepatic collateral vessels in primary hepatocellular carcinoma and the interventional treatment%原发性肝癌肝外侧支血供动脉的特点和介入治疗分析

    Institute of Scientific and Technical Information of China (English)

    吕江; 陈茂恩; 李冲

    2016-01-01

    Objective To analyze the incidence of extrahepatic collateral vessels in patients with primary hepatocel-lular carcinoma (HCC) and the influence on trans-catheter arterial chemoembolization (TACE). Method 350 cases of HCC treated with TACE were chosen, the incidence, location and timing of extrahepatic collateral vessels, and the ef-fect of TACE were evaluated. Result In 350 patients, 73 cases (20.86%) had extrahepatic collateral vessels, in which there were 85 extrahepatic collateral arteries, mainly were right inferior phrenic artery (41.18%) , gastroduodenal artery (18.82%) and gastroepiploic artery;After 1 cycle of interventional treatment, the detection rate for extrahepatic collater-al vessels was 6.86%, and then rose up to 14.00%after multiple cycles of interventional treatment, suggesting a signifi-cant correlation between the treatment and detection rate (P<0.05). 90.59%(77/85) of extrahepatic collateral vessels had successful catheterization;In 1 week after surgery, AFP decreases were observed in 87.67%(64/73) of patients. Conclu-sion Extrahepatic collateral arteries are common in primary hepatocellular carcinoma, with complicated distribution, while trans-catheter arterial chemoembolization is an effective therapy.%目的:分析原发性肝癌患者肝外侧支血供动脉的发生情况及其对介入栓塞治疗的影响。方法选取行经导管肝动脉化疗栓塞术的350例原发性肝癌患者,分析原发性肝癌患者肝外侧支血供的发生率、发生部位、介入栓塞治疗效果及肝外侧支供血动脉的发现时机等。结果350例患者中发生肝外侧支血供73例,占20.86%,其中肝外侧支动脉85条,主要以右膈下动脉、胃十二指肠及网膜动脉为主,分别占41.18%和18.82%。经1次介入治疗,肝外侧支血供动脉的发现率为6.86%,经多次介入治疗其发现率为14.00%,随着介入治疗次数的增多,肝外侧支血供动脉的发现率升高,

  10. The Role of e-NOS in Chronic Cholestasis-Induced Liver and Renal Injury in Rats: The Effect of N-Acetyl Cysteine

    Directory of Open Access Journals (Sweden)

    Yusuf Gunay

    2014-01-01

    Full Text Available Introduction. The role of chronic cholestasis (CC in liver injury and fibrosis remains unclear. The aims of this study were to define the role of endothelial nitric oxide synthase (e-NOS in CC and the protective effect of N-acetyl-L-cysteine (NAC in liver and kidney injury. Materials and Methods. Group A (sham group; Group B (CBDL; and Group C (CBDL + NAC. Group C received daily dosage of NAC (100 mg/kg intraperitoneally for up to 4 weeks. Results. The rate of bridging fibrosis was higher (100% versus 20%, P=.025, but the intensity of e-NOS in liver was lower in rats that received NAC (1.3 versus 2.7, P=.046. The necrotic area in the kidneys among rats that received NAC was lower at week 4 (48% versus 57%; P<.001. The numbers of e-NOS stained cells in kidney were similar in sham group and the two groups with CBDL. Discussion. NAC reduced the stimulus for liver fibrosis in this rat model of CC and attenuated liver and kidney injury. Our study showed that e-NOS expression increased in liver tissue of rats with CC and that this was reversed by NAC. Treatment with NAC might restore e-NOS protein expression and prevent liver injury in CC.

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

    Institute of Scientific and Technical Information of China (English)

    李晓瑜; 马华梅; 陈红珊; 李燕虹; 沈振宇; 杜敏联

    2010-01-01

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

  12. Expression of Noxa protein in extrahepatic bile duct carcinoma and its relationship with clinicopathological factors%Noxa蛋白在肝外胆管癌组织中的表达及其与临床病理的关系

    Institute of Scientific and Technical Information of China (English)

    胡海霞; 李伟; 熊正文; 李宏伟; 黄勇; 牛晓东

    2016-01-01

    Objective To study the expression of Noxa protein in extrahepatic bile duct carcinoma and normal tis-sue, and investigate its relationship with clinicopathological factors. Methods The expression of Noxa was detected in 70 cases of extrahepatic bile duct carcinoma and 70 cases of normal tissue from March 2006 to June 2009 by immunohisto-chemisty (EnVision TM). Results The positive expression rate of Noxa in extrahepatic bile duct carcinoma and normal tis-sue was 32.86%(23/70), 68.57%(48/70), respectively, with statistically significant difference (χ2=17.86, P0.05). The five-year survival rate of patients with positive expression of Noxa was significantly lower than that of pa-tients with negative expression [26.09%(6/23) vs 53.19%(25/47),χ2=4.59, P0.05);Noxa阳性表达的患者5年生存率低于Noxa阴性表达者[26.09%(6/23) vs 53.19%(25/47)],差异有统计学意义(χ2=4.59,P<0.05)。结论肝外胆管癌组织中Noxa蛋白的低表达不仅表明了癌细胞促凋亡能力的异常,而且也有利于预测淋巴结转移及临床分期的状态,同时也可作为判断患者预后的参考指标。

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  14. Progress in study on the cellular and molecular level of intrahepatic chole-stasis of pregnancy%妊娠期肝内胆汁淤积症在细胞分子水平上的认识进展

    Institute of Scientific and Technical Information of China (English)

    胡海军; 李佳平

    2015-01-01

    妊娠期肝内胆汁淤积症( intrahepatic cholestasis of pregnancy,ICP)为高危妊娠,是妊娠期特有疾病。虽然对孕妇预后良好,仍会出现早产、羊水胎粪污染、胎儿宫内窘迫、无明显先兆的胎死宫内等不良妊娠结局,故近年来越来越受到重视。然而ICP发生机制仍不清楚,可能与遗传因素,生殖激素,免疫耐受失衡以及环境因素有关,有待于进一步深入研究与探求。%Intrahepatic cholestasis of pregnancy ( ICP) is a high-risk pregnancy and it is specific. Although the prognosis is good for pregnant women,there are bad results such as premature birth,meconium stained amniotic fluid,fetal distress and no obvious sign of fetal death,etc. So in recent years more and more attentions are paid to ICP. The ICP mechanism,however,remains unclear and may be associated with genetic factors, reproductive hormones, immune tolerance instability, as well as environmental factors, which needs further research and exploration.

  15. 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.

  16. Clinical characteristics of twin pregnancy with intrahepatic cholestasis%双胎妊娠合并妊娠期肝内胆汁淤积症临床特点分析

    Institute of Scientific and Technical Information of China (English)

    吴星光

    2012-01-01

    目的 分析双胎合并妊娠期肝内胆汁淤积症的临床特点.方法 我院产科诊治的双胎妊娠患者515例,其中双胎妊娠合并妊娠期肝内胆汁淤积症17例为观察组,随机选取18例未合并肝内胆汁淤积症的双胎妊娠患者为对照组.观察并比较两组患者围生儿预后情况、孕妇生产方式及并发症发生情况.结果 双胎妊娠合并妊娠期肝内胆汁淤积症的发病率为3.30%;观察组中发生胎儿窘迫、胎儿窒息及胎儿死亡的比例分别为41.2%、52.9%和35.3%,显著高于对照组的5.6%、11.1%和0(P< 0.05);观察组患者中剖宫产比例为70.6%,显著高于对照组的33.3%(P<0.05);观察组患者发生妊高症及产后出血并发症的比例分别为58.8%和41.2%,均明显高于对照组的16.7%和5.6%(P<0.05).结论 双胎妊娠合并妊娠期肝内胆汁淤积症发病率高,胎儿预后较差,孕妇并发症多,临床工作中应该积极应对.%Objective To analyze the clinical characteristics of the twin pregnancy with intrahepatic cholestasis. Methods Five hundred and fifteen patients of twin pregnancy were chosen. Seventeen of the patients complicated with intrahepatic cholestasis were chosen as the study group, and 18 of the patients without intrahepatic cholestasis were chosen as the control group. The prognosis, maternal mode of production and occurrence of complications were compared between the two groups. Results The incidence of twin pregnancy complicated with gestational intrahepatic cholestasis were 3.30%. The occurrence of fetal distress, fetal asphyxia and fetal death in the study group were 41.2%, 52.9% and 35.3%, respectively, significantly higher than those in the control group (5.6%, 11.1% and 0%, respectively), P<0.05. The incidence of cesarean section, the pregnancy induced hypertension and postpartum hemorrhage of the study group were 70.6%, 58.8% and 41.2%, respectively, significantly higher than those in the

  17. 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.

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

    Institute of Scientific and Technical Information of China (English)

    周冬梅; 杨如

    2014-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    刘翠; 王勇; 楼方

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    白月婷

    2012-01-01

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

  1. 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.

  2. Progress in diagnosis and therapy of extrahepatic manifestations of cholestatic liver diseases%胆汁淤积性肝病肝外并发症诊治研究进展

    Institute of Scientific and Technical Information of China (English)

    陆伦根

    2016-01-01

    胆汁淤积肝外并发症主要有瘙痒、疲劳和代谢性骨病,其分子机制目前尚未完全明确,针对发病机制拟定的治疗方案可暂时缓解症状,但疗效有限,阐明发病机制有助于找到更恰当的治疗手段.瘙痒可能由胆汁淤积的某些物质在体内蓄积影响神经传导导致,现行推荐考来烯胺等药物治疗和血液净化手段可明显缓解胆汁淤积性瘙痒.疲劳可能由中枢神经系统功能异常导致,目前尚无特异性治疗方法.代谢性骨病又称为肝性骨营养不良,常表现为骨质减少和骨质疏松症,纠正可导致骨质丢失的不良因素有利于缓解代谢性骨病,推荐二膦酸盐治疗胆汁淤积性骨质疏松.患者出现难以忍受的瘙痒和骨质疏松导致频繁骨折时宜进行肝移植评估.%Extra-hepatic complications of cholestasis mainly include pruritus,fatigue and metabolic bone diseases,and their molecular mechanisms have not yet been fully identified so far.Though therapeutic regimens targeted at the pathogenesis alleviate the symptoms temporarily,the therapeutic effects are limited,and therefore expounding the pathogenesis will help find more appropriate therapeutic approaches.Pruritus may be caused by nerve conduction block resulting from accumulation of some substances in the accumulated bile,existing recommended methods like drug therapy with cholestyramine and blood purification can markedly alleviate cholestasis-induced pruritus.Fatigue may be a consequence of the central nervous system disorders,and there is currently no specific therapy.Metabolic bone diseases (MBD),also known as hepatic osteodystrophy,are often manifested by osteopenia and osteoporosis,and correcting bad factors responsible for bone loss will help relieve MBD.Bisphosphonate is recommended for treatment of cholestasis-induced osteoporosis.In the event that a patient experiences intolerable pruritus and frequent fractures resulting from osteoporosis,assessment for

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

    Institute of Scientific and Technical Information of China (English)

    左石; 邹声泉; 孙诚谊

    2011-01-01

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

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

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    Ana Paula Ronquesel Battochio

    2008-06-01

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

  5. Clinical Experience on the Treatment of 89 Cases with Intrahepatic Cholestasis During Pregnancy%治疗89例妊娠期肝内胆汁淤积症的临床体会

    Institute of Scientific and Technical Information of China (English)

    刘展

    2013-01-01

    目的:探讨治疗妊娠期肝内胆汁淤积症的临床特点、治疗方法及母婴预后。方法:选取2006年6月-2012年12月本院妇产科病区收治的89例妊娠期肝内胆汁淤积症患者,回顾性分析其诊治方法、分娩方式、产后出血量及围生儿结局。结果:89例患者阴道分娩25例,剖宫产64例,产后出血量150~670 mL;分娩孕周31~38周,早产儿57例;新生儿体重1900~4100 g,其中低体重儿58例;新生儿中轻度窒息24例,重度窒息5例。所有新生儿外观均无畸形,生后均以高危儿立即转新生儿科治疗,1例患儿因早产、窒息合并多脏器功能衰竭死亡。结论:妊娠期肝内胆汁淤积症为妊娠期严重并发症,应进行早期诊断,早期治疗,加强监护,必要时终止妊娠,从而降低围生儿的致残率、病死率,减少产妇产后出血情况的发生,保障母婴健康。%Objective:To research on the clinical characteristics of intrahepatic cholestasis of pregnancy(ICP)and its negative effects on mother and child.Method:Eighty-nine patients with intrahepatic cholestasis of pregnancy from June 2006 to December 2012 in department of obstetrics were selected.The diagnosis and treatment method,mode of delivery,postpartum hemorrhage and perinatal outcomes were retrospectively analyzed.Result:89 cases were 25 cases of vaginal delivery,cesarean section in 64 cases,the amount of 150-670 mL postpartum hemorrhage;pregnant was 31-38 weeks, 57 cases were premature infants;Neonatal weight was 1900-4100 g,including 58 cases of low birth weight infant;24 cases of newborn asphyxia,5 cases of severe asphyxia neonatorum.All neonates were no abnormal appearance,they were transferred to the Neonatal Department for treatment as high-risk infants,1 case died because of premature birth,asphyxia death combined multiple organ function failure.Conclusion:Intrahepatic cholestasis of pregnancy is a serious complication of pregnancy,should be

  6. Intrahepatic cholestasis of pregnancy characteristics and clinical prognosis of perinatal child%妊娠期肝内胆汁淤积症早期干预措施及对围生儿的影响

    Institute of Scientific and Technical Information of China (English)

    张小燕

    2012-01-01

    目的 探讨妊娠期肝内胆汁淤积症(ICP)患者的临床特点、终止妊娠方式的选择及对围生儿预后的影响.方法 选择2008年3月-2011年3月分娩的100例妊娠期肝内胆汁淤积症患者作为观察组,同期选取住院分娩的正常孕妇120例作为对照组,比较两组孕妇及新生儿情况以及观察组中分娩方式不同对新生儿的影响.结果 两组的早产、胎儿宫内窘迫、死亡及羊水污染明显高于对照组(P<0.05);观察组孕妇血清总胆汁酸值不同对新生儿的影响亦不同.结论 妊娠期肝内胆汁淤积症对母婴,特别是新生儿的危害极大,导致早产、胎儿宫内窘迫、胎死宫内、产后出血等并发症,增加了围生儿发病率和死亡率.因此应加强孕妇的健康教育,高度重视产前检查和中期妊娠胆汁酸的监测,做到早发现、早治疗,对减少母婴并发症有重要作用.%Objective To investigate the clinical features of intrahepatic cholestasis of pregnancy (ICP) in patients, mode of selection and termination of pregnancy on perinatal outcome of children. Methods March 2008-March 2011 in our hospital delivery of 100 cases patients with intrahepatic cholestasis of pregnancy as the observation group, selected hospital delivery over the same period 120 cases of normal pregnant women as the control group, the two groups of pregnant women and newborn as well as the observation group in the different mode of delivery on neonatal effects. Results The observation groups of premature delivery, fetal distress, death and amniotic significantly higher than those of the control group ( P < 0. 05) ; Observation group maternal serum total bile acid have different effects on different newborn. Conclusions Intrahepatic cholestasis of pregnancy on maternal, newborn, especially the great harm, leading to premature delivery, fetal distress, fetal death, postpartum hemorrhage and other complications, increased perinatal incidence and mortality

  7. Cholestasis in a murine experimental model: lesions include hepatocyte ischemic necrosis Colestase em modelo experimental em murinos: lesões incluem necrose isquêmica dos hepatócitos

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    Ivete Bedin Prado

    2003-01-01

    Full Text Available OBJECTIVE: To establish a murine experimental model of bile duct obstruction that would enable controlled observations of the acute and subacute phases of cholestasis. METHODOLOGY: Adult male isogenic BALB/c mice underwent a bile duct ligation (22 animals or a sham operation (10 animals. Fifteen days after surgery, or immediately after the animal's death, macroscopic findings were noted and histological study of the liver, biliary tree, and pancreas was performed (hematoxylin-eosin and Masson trichromic staining. RESULTS: Beginning 24 hours after surgery, all animals from the bile duct ligation group presented progressive generalized malaise. All animals presented jaundice in the parietal and visceral peritoneum, turgid and enlarged liver, and accentuated dilatation of gallbladder and common bile duct. Microscopic findings included marked dilatation and proliferation of bile ducts with accentuated collagen deposits, frequent areas of ischemic necrosis, hepatic microabscesses, and purulent cholangitis. Animals from the sham operation group presented no alterations. CONCLUSION: We established a murine experimental model of induced cholestasis, which made it possible to study acute and subacute tissue lesions. Our data suggests that in cholestasis, hepatic functional ischemia plays an important role in inducing hepatic lesions, and it also suggests that the infectious process is an important factor in morbidity and mortality.OBJETIVO: Realizar um modelo experimental de obstrução do ducto biliar que permita uma observação controlada das fases aguda e subaguda da colestase. MÉTODOS: Submeteram-se camundongos BALB/c, adultos, machos, a ligadura do ducto biliar (22 animais ou a cirurgia-controle (10 animais. Quinze dias após a cirurgia, ou imediatamente após a morte do animal, foram observados os achados macroscópicos e realizado o estudo histológico do fígado, árvore biliar e pâncreas (haematoxylina-eosina e tricrômico de Masson

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

    Science.gov (United States)

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

    2016-01-01

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

  9. Clinical analysis on intrahepatic cholestasis of pregnancy: A report of 96 cases%妊娠期肝内胆汁淤积症96例临床治疗体会

    Institute of Scientific and Technical Information of China (English)

    魏秀琴; 孙友红

    2011-01-01

    目的 探讨妊娠期肝内胆汁淤积症(ICP)对母儿的影响.方法 将2008年1月~2010年12月本院住院的96例ICP患者(观察组)与同期其他随机抽取的正常孕妇106名产妇(对照组)进行比较.结果 ICP早产儿(25%);胎儿宫内窘迫(31.58%);低体重儿(19.74%);围产儿死亡(3.95%);明显高于对照组(P<0.01).剖宫产率(87.5%);产后出血(21.88%):明显高于对照组(P<0.01).结论 妊娠期肝内胆汁淤积症对母婴危害极大,应提高认识,加强孕期监护,提高围生儿生存率,降低产科并发症.%Objective To investigate the influences of intrahepatic cholestasis in the course of pregnancy (ICP) on mother and baby. Methods Retrospective analysis was made on the 96 cases of ICP (observation group) and the 106 cases of normal pregnant women (control group) in our hospital, in which the morbidity of premature delivery, fetal distress, low body weight, perinatal fetus and others were measured. Results For those that suffered ICP, the morbidity of premature delivery (25%), fetal distress (31.58%), low body weight (19.74%), and perinatal fetus (3. 95%) were significantly higher than the control group (P<0.01). Furthermore, the percentage of cesarean section (87. 5%) and blood loss after delivery (21. 88%) were also significantly higher than the control group (P<0.01). Conclusion Intrahepatic cholestasis of pregnancy can induce serious damage on mother and baby, which should be paid much attention to. Clinically, we should take intensive care of these patients to increase the survival rate of perinatal outcomes and decrease the obstetrical complications.

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

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    Rafaella Cristina Reginatto

    2011-07-01

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

  11. 早产儿肠外营养相关性胆汁淤积防治进展%Progress in prevention and treatment of parenteral nutrition associated cholestasis of preterm infants

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    朱峰

    2011-01-01

    In the treatment of parenteral nutrition(PN) of preterm infants, parenteral nutrition associated cholestasis(PNAC) is the most common complication. However, the mechanisms of how this complication happens are unknown. This paper summarizes the research reports about PNAC both at home and aboard in recent years and raises various precautions on premature birth avoiding, reasonable feeding, PN projects optimizing and so on.Ursodeoxycholicacid is the first-line drug in the current treatment for PNAC.%肠外营养相关性胆汁淤积(PNAC)是早产儿肠外营养(PN)治疗过程中最常见的并发症,其病因及发病机制尚不明确.该文总结了近年来国内外有关早产儿PNAC的研究报道,提出了避免早产、合理喂养、优化PN方案等多种预防措施.熊去氧胆酸是目前治疗PNAC的一线药物.

  12. 妊娠期肝内胆汁淤积症对早期新生儿的预后评价%Effect of intrahepatic cholestasis of pregnancy to out-come of early newborns

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    陈颖; 李明美; 胡京辉; 吴明远

    2002-01-01

    本文通过对同一时期内患有妊娠期肝内胆汁淤积症(1)(Intrahepatic Chol-estasis of Pregnancy,简称ICP)母亲所娩婴儿及健康孕妇所娩婴儿各159例进行对照分析,发现ICP婴儿早产、低体重儿、羊水粪染及窒息儿患病率、难产率均明显高于对照组(P<0.05~0.0001),而ICP组婴儿高胆红素患病率略高于对照组,但无统计学意义.平均出生体重及体重回复率则明显低于对照组(T检验=0.00046,P<0.05),在疾病中呼吸系统发病最多,占ICP组患病儿的91.1%.本资料说明ICP使新生儿群体体质水平下降,但对胆红素的代谢无异常,呼吸系统患病率增高.

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

    Institute of Scientific and Technical Information of China (English)

    张胜; 周杰; 谭永法; 谭凯; 陈立言

    2012-01-01

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

  14. Influencing factors of parenteral nutrition associated cholestasis in preterm infant%早产儿胃肠外营养相关性胆汁淤积的影响因素分析

    Institute of Scientific and Technical Information of China (English)

    吴雅娟; 吕庆鹏; 李翠霞

    2016-01-01

    Objective To analyze the related factors of parenteral nutrition associated cholestasis in preterm infant and to provide theoretical basis for clinical intervention .Methods Retrospective analysis was conducted on hospitalization data of 146 preterm infants receiving parenteral nutrition (PN) in Second People’s Hospital of Nanhai District during January 2010 to April 2014.The cases were divided into control group (without cholestasis, n=110) and observation group (cholestasis, n=36), and they were compared in birth weight, PN duration, fasting time, hospitalization length, PN nutrient solution ratio, infection, antibiotics and mechanical ventilation .Results There were significant differences between two groups in birth weight , PN duration, fasting time, sugar calories ratio, amino acid calories ratio, fat lactic acid calories ratio, milk calories ratio, and total calories ratio (t value was 5.469, 12.921, 14.802, 8.156, 9.217, 10.108, 19.982 and 14.698, respectively, all P<0.05).The differences in infection incidence and mechanical ventilation rate were significant between two groups (χ2 value was 4.105 and 4.891, respectively, both P<0.05).Multiple stepwise Logistic analysis showed that long duration of PN (OR=2.147, 95%CI:1.040-3.807), long fasting time (OR=2.751,95%CI:1.970-4.408), high glucose calories ratio (OR=2.433, 95%CI:1.583-3.901), high fat lactic acid calories ratio (OR=2.907,95%CI:2.072-5.833), high amino acid calories ratio (OR=2.779,95%CI: 2.018 -4.540), mechanical ventilation (OR=1.511,95%CI:1.067 -3.908) and infection (OR=1.275, 95%CI:1.021-3.460) were risk factors of premature infants with parenteral nutrition associated cholestasis , while high birth weight was the protective factor (OR=0.672,95%CI:0.070-0.759).Conclusion Cholestasis in preterm infants threatens life and health of them.Clinicians should control infection , the use of mechanical ventilation , and opening of milk as early as possible .PN duration needs to be reduced and PN

  15. Treatment of lower gastrointestinal bleeding secondary to congenital extrahepatic portocaval shunts%先天性肝外门腔静脉分流并下消化道出血的治疗

    Institute of Scientific and Technical Information of China (English)

    黄穰浪; 王大勇; 聂晚频; 程献杰; 夏明智

    2010-01-01

    Objective To summarize the operative experience of the surgical ligation the shunt of colon and anus for children with lower gastrointestinal bleeding secondary to congenital extrahepatic portocaval shunts(CEPS).Methods Seven patients with lower gastrointestinal bleeding caused by CEPS (Abernethy type 2)were analyzed retrospectively.The diagnostic imaging and medical records for the patients were retrieved and evaluated.Surgical ligation of the veins of colon and anus was performed in all these patients.All patients were followed up from 2 to 12 years.Results The diagnosis of CEPS was confirmed by Ultrasonography (US),CT scan and colonoscopy.The colonoscopy showed blood vascular densely covered in colon and anus.And the congenital mesenterico-caval shunt was noted in all these patients by US and CT.After surgical ligation of the veins of colon and anus,the patients recovered very well,no blood bleeding was noted during follow-up term.Conclusions Lower gastrointestinal bleeding can be caused by congenital extrahepatic portocaval shunts.Surgical ligation of the veins of colon and anus is a successful treatment of lower gastrointestinal bleeding secondary to CEPS.%目的 总结先天性肝外门腔静脉分流导致便血的病例,探讨对其的诊断和治疗方法.方法 回顾分析自1990年至2010年7例先天性肝外门腔静脉异常分流并下消化道出血患儿的临床资料.,并随访其治疗效果.结果 通过B超、CT扫描和结肠镜检可以明确诊断便血是由于先天性肝外门腔静脉异常分流引起,并且判断异常血管浸润的界限和范围,术中结扎侵入结肠直肠的异常血管,随访2~10年,便血基本停止,未再出现贫血.结论 由于先天性肝外门腔静脉分流引起便血比较罕见,B超、CT和结肠镜对诊断其病因和病变范围有很好帮助,结扎肛门、直肠、结肠局部异常血管的结扎术是最简单、可行和可靠的治疗方法.

  16. 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.

  17. 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.)

  18. 妊娠期肝内胆汁淤积症118例的诊治研究及妊娠结局%Clinical research and pregnancy outcome of 118 cases of intrahepatic cholestasis of pregnancy

    Institute of Scientific and Technical Information of China (English)

    梁美燕; 罗一平; 欧阳晓红

    2014-01-01

    Objective:To observe the clinical symptoms of intrahepatic cholestasis of pregnancy(ICP).To analyze its harm of maternal and child and the effective treatments of reducing the fetal death,neonatal asphyxia,premature delivery.Methods:118 cases with intrahepatic cholestasis of pregnancy were selected from January 2008 to June 2013.The clinical data were retrospectively analyzed.The clinical characteristics,delivery mode,postpartum hemorrhage and pregnancy outcome were summarized.Results:In the 118 ICP cases,81 cases were cesarean section,and 37 cases were vaginal delivery.25 cases(21.2%) were premature delivery,19cases (16.1%) were fetal distress,and 12 cases(10.2%) were neonatal asphyxia.ICP onset time was more early.The liver damage was more serious,and the harm was more greater.Neonatal appearance had no abnormalities.1 case high risk infant was died because of multiple organ failure after new pediatric treatment.Through the comparison with another 50 cases of the treatment group,it found that the treatment had significant improvement on the maternal and child health.Conclusion:ICP can cause intrauterine fetal anoxia,premature delivery,fetal distress and neonatal asphyxia,which has a great harm to the maternal and child.The early diagnosis,early treatment,and strengthening of fetal heart rate monitoring and timely termination of pregnancy can effectively reduce the neonatal hazards and improve the maternal and child health.%目的:观察妊娠期肝内胆汁淤积症(ICP)的临床症状,分析其对母婴的危害及降低胎儿宫内死亡、新生儿窒息、早产的有效治疗方法。方法:2008年1月-2013年6月收治ICP患者118例,对其临床资料进行回顾性分析,总结其临床特点、分娩方式、产后出血量及妊娠结局。结果:118例ICP患者中,剖宫产81例,阴道分娩37例。其中早产25例(21.2%),胎儿窘迫19例(16.1%),新生儿窒息12例(10.2%)。ICP发病时间越早,其肝损伤越严重,危害

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

    Institute of Scientific and Technical Information of China (English)

    Wen Xie; Ming-sheng Chen; Cun-jin Mei; Xiao-lin Guo; Xiao-hu Zhao; Jiang-bin Wang; Zheng-qin Fan; Jian-he Gan; Qing Xie; Jun Cheng; Hong Zhao; Yu Chen; Qin Zhang; Wei Lu; Wei Liu; Ai-rong Hu; Han-wei Li; Ping Feng

    2013-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Qi-Qi Zheng

    2016-01-01

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

  2. 表现为婴儿胆汁淤积的CFTR基因缺陷致囊性纤维化病一例并文献复习%Infantile cholestasis caused by CFTR mutation: case report and literature review

    Institute of Scientific and Technical Information of China (English)

    李丽; 王能里; 龚敬宇; 王建设

    2016-01-01

    Objective To study the clinical presentation,biochemical features and genetic analysis of an infant with cholestasis related to the CFTR mutations.Method The clinical presentation,laboratory investigations and management of a case with infantile cholestasis caused by CFTR mutations were summarized and the relevant literature was reviewed.Result (1) The patient was a 5 months old boy with cholestasis which developed in neonatal period with delayed meconium exclusion.The laparoscopic exploration was performed to exclude biliary atresia because of acholic stool when he was two months old.Ursodeoxycholic acid (UDCA),cholestyramine and phenobarbital treatment was applied.The genetic analysis showed compound heterozygous mutations in CFTR.The liver function normalized when he was 11 months old.When he was 21 months old,he had normal appearance except mild splenomegaly.(2) Literatures review identified 25 infantile cholestatic cases related to cystic fibrosis (CF) diagnosed by sweat test or gene analysis.Delayed meconium passage was found in five,meconium ileus in six cases.The liver function tests characterized by the direct hyperbilirubinemia with elevated transaminase,glutamyltranspeptidase and alkaline phosphatase levels.Genetic analysis revealed eight homozygotes of delF508,four heterozygotes of delF508 and one compound heterozygotes of c.263T > G/ c.2089-2090ins in CFTR.Jaundice resolved in 20 patients,ten of them were prescribed oral ursodesoxycholic acid (15-20 mg/(kg· d)).Five patients died,none of them received oral UDCA.Two of them had persisted cholestatic until death.Among the other three dead,two died from respiratory failure and one from cardiopulmonary failure.Conclusion Cystic fibrosis should be considered in cholestatic infants with meconium ileus or delayed meconium passage.Genetic analysis could confirm the diagnosis.UDCA may be beneficial to improve the liver function.%目的 总结表现为婴儿胆汁淤积的CFTR基因缺陷致囊性纤维化

  3. 甲状腺功能亢进症伴严重药物性胆汁郁积性肝炎1例并文献复习%One case of hyperthyroidism with severe drug-induced cholestasis hepatitis and literature review

    Institute of Scientific and Technical Information of China (English)

    曹雯; 郑仁东; 陈国芳; 包薇萍; 刘超

    2014-01-01

    甲状腺功能亢进症(甲亢)本身可导致肝功能损害,而抗甲状腺药物亦可引起肝功能损伤.但出现严重药物性胆汁郁积性肝炎的病例比较少见,临床治疗较为困难.本院收治1例,在治疗甲亢的基础上,采用甲强龙静脉脉冲冲击联合口服强的松的方案,降低患者胆红素水平,使肝功能恢复正常,甲亢亦得以控制.%Hyperthyroidism can cause liver damage,while anti-thyroid drugs can also cause liver dysfunction.Severe case of drug-induced cholestasis hepatitis is rare,difficult to treat.Here we report a case with drug-induced cholestasis hepatitis.On the basis of the treatment of hyperthyroidism,intravenous methylprednisolone pulse therapy combined with oral prednisone was used to reduce bilirubin levels in patients,therefore the liver function of the patient returned back to normal,and the hyperthyroidism was controlled.

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

    Science.gov (United States)

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

    2007-02-01

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

  5. General Information about Extrahepatic Bile Duct Cancer

    Science.gov (United States)

    ... duct cancer include jaundice and pain in the abdomen. These and other signs and symptoms may be ... Dark urine . Clay colored stool . Pain in the abdomen . Fever . Itchy skin. Nausea and vomiting . Weight loss ...

  6. Treatment Options for Extrahepatic Bile Duct Cancer

    Science.gov (United States)

    ... duct cancer include jaundice and pain in the abdomen. These and other signs and symptoms may be ... Dark urine . Clay colored stool . Pain in the abdomen . Fever . Itchy skin. Nausea and vomiting . Weight loss ...

  7. Stages of Extrahepatic Bile Duct Cancer

    Science.gov (United States)

    ... duct cancer include jaundice and pain in the abdomen. These and other signs and symptoms may be ... Dark urine . Clay colored stool . Pain in the abdomen . Fever . Itchy skin. Nausea and vomiting . Weight loss ...

  8. Treatment Option Overview (Extrahepatic Bile Duct Cancer)

    Science.gov (United States)

    ... duct cancer include jaundice and pain in the abdomen. These and other signs and symptoms may be ... Dark urine . Clay colored stool . Pain in the abdomen . Fever . Itchy skin. Nausea and vomiting . Weight loss ...

  9. Extra-Hepatic Storage of Copper

    DEFF Research Database (Denmark)

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

    1975-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    杨慧; 王卫; 刘晓红

    2013-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    张东升

    2013-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    徐前程; 查磊; 刘小彬; 陈尚华

    2016-01-01

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

  13. Perbedaan Manifestasi Klinis dan Laboratorium Kolestasis Intrahepatal dengan Ekstrahepatal pada Bayi

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    Dwi Prasetyo

    2016-05-01

    Full Text Available Physiological jaundice found in infants and most symptoms are often mild. Jaundice symptoms usually disappear within 2 weeks after birth. In conjugated jaundice defects in intra-hepatic production, transmembran transport from bile, i.e. cholestasis intra hepatic (IH, or extra-hepatic (EH obstruction/cholestasis occur, resulting in bile barriers. This study was conducted to look at the differences in the clinical and laboratory manifestations of IH and EH cholestasis in infants. A cross-sectional study was performed on 72 infants with cholestasis who came to Dr. Hasan Sadikin General Hospital Bandung, during the period of January 2014–December 2015. Data analysis was performed with Pearson Chi-square test and Mann-Whitney. Subjects consisted of 43 (60% infant boys and 29 (40% infant girls, IH cholestasis were 61 (85% and EH cholestasis were 11 (15.3%. Significant differences in the clinical manifestations of acites with IH and EH cholestasis were found (p=0.047, whereas insignificant differences in venectation, hepatomegaly and splenomegaly were observed. On examination of stool color, no significant difference was found (p=0.936. The same was true for laboratory results of total bilirubin, direct bilirubin, serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase and gamma glutamyl transferase. In conclusion, we found differences in clinical manifestation of acites, while for other clinical manifestations and laboratory results no differences were found between IH and EH cholestasis.

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

    Institute of Scientific and Technical Information of China (English)

    文春蓉; 刘敏利

    2015-01-01

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

  15. Percutaneous transhepatic cholecystostomy: An effective treatment of cholestasis in early postoperative inflammatory ileus patients%经皮经肝胆囊穿刺术在术后早期炎性肠梗阻并发淤胆治疗中的应用

    Institute of Scientific and Technical Information of China (English)

    何长生; 朱维铭; 李宁

    2012-01-01

    目的 禁食、全胃肠外营养(total parenteral nutrition,TPN)时间长及应用生长抑素治疗,引起少数术后早期炎性肠梗阻(early postoperative inflammatory ileus,EPII)患者出现淤胆症状.文中探讨经皮经肝胆囊穿刺术(percutaneous transhepatic cholecystostomy,PTC)在术后EPII并发淤胆患者中的应用价值.方法 回顾性分析15例腹部手术后EPII并发淤胆患者运用PTC的治疗效果.患者均行B超或腹部CT检查,常规进行禁食、胃肠减压、灌肠、TPN、生长抑素、小剂量糖皮质激素等综合治疗,运用PTC行胆汁外引流.结果 15例患者均非手术治愈,无穿刺并发症发生,平均住院时间为(32.5±5.7)d,TPN支持时间平均为(26.6±10.5)d,穿刺后至肛门排气为1~4d,平均时间为(2.3±0.9)d.11例患者谷丙转氨酶(GPT)、谷草转氨酶(GOT)、γ-谷氨酰转肽酶(γ-GT)、碱性磷酸酶(AKP)、总胆红素、直接胆红素水平升高,穿刺后GPT、GOT、γ-GT、AKP、总胆红素、直接胆红素水平较快恢复正常,淤胆症状消失.6例患者出现低热、右上腹不适症状,穿刺后体温恢复正常,右上腹不适症状缓解.结论 PTC运用安全有效,虽不能根本改变术后EPII的病理过程,但能明显改善术后患者因禁食而长期应用TPN导致的淤胆症状,改善肝功能,恢复胆汁流,促进肠蠕动,加速康复.%Objective One of the most important issues in a patient with suspected early postoperative inflammatory ileus is the risk of cholestasis resulting from fasting, total parenteral nutrition ( TPN ) and somatostatin, which can lead to stasis of biliary function and liver dysfunction. This paper is to determine the safety and effectiveness of percutaneous transhepatic cholecystostomy ( PTC ) in the treatment of cholestasis in early postoperative inflammatory ileus patients. Methods A retrospective study was made on the treatment of PTC on 15 early postoperative inflammatory ileus patients with cholestasis. Routine

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

    Institute of Scientific and Technical Information of China (English)

    刘娟; 陈雄; 汪宇平; 金玉珍; 吴颖

    2012-01-01

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

  17. 湖北地区 Citrin 缺陷导致的新生儿肝内胆汁淤积症临床研究%Clinical research of neonatal intrahepatic cholestasis caused by Citrin deficiency in Hubei Province

    Institute of Scientific and Technical Information of China (English)

    熊小丽; 鄢素琪; 丁艳; 周俪姗; 陈鹏; 赵东赤

    2015-01-01

    目的:探讨湖北地区 Citrin 缺陷导致的新生儿肝内胆汁淤积症(NICCD)的临床表现及实验室特点。方法收集2010年9月至2013年1月在武汉市儿童医院住院20例 NICCD 患儿未经治疗时的生化指标(肝功能、血脂、乳酸、血氨、总胆汁酸、甲胎蛋白)、凝血象、血氨基酸谱、酰基肉碱谱、尿有机酸谱及 SLC25A13基因分析,并随访1年。结果 NICCD 患儿实验室检查表现为高胆红素血症、肝酶升高、胆汁酸增高,高脂血症、高甲胎蛋白、高乳酸血症、高氨血症、低蛋白血症、低血糖、凝血机制障碍;多种氨基酸升高,以瓜氨酸升高为主;酰基肉碱中以长链酰基肉碱升高为主;尿4-羟基苯乙酸、4-羟基苯乳酸、4-羟基苯丙酮酸异常增高;SLC25A13基因分析共发现6个突变位点,其中 L477R,G639S 为新发突变位点,851del4、1638ins23、IVS6+5G ﹥A 为热点突变。20例患儿黄疸均在1岁内缓解。结论 NICCD 患儿多项临床实验指标异常,高脂血症在病程早期即已出现,L477R、G639S 为新发突变位点。%Objective To explore the clinical manifestations and the characteristics of neonatal intrahepatic cholestasis caused by Citrin deficiency(NICCD)in Hubei province. Methods The biochemical indicators including liver function,blood lipid,lactic acid,blood ammonia,total bile acid,alpha feto protein,coagulogram,blood amino spec-trum,acylcrnitine spectrum,urine organic acid and SLC25A13 gene analysis of 20 cases with NICCD,who came from Wuhan Children's Hospital,during September 2010 to January 2013,were collected before treatment,then followed up for 1 year. Results Laboratory results of NICCD patients showed high blood bilirubin,elevated liver enzymes and bile acid,hyperlipidemia,high alpha feto protein,high lactic acidosis,high ammonia,hypoalbuminemia,hypoglycemia,disor-der of blood coagulation mechanism,variety of amino acids increase,mainly citrulline

  18. 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.

  19. 肝内外胆管结石多次手术原因及预后分析%Reasons and prognosis of multiple-operations for intra-and extrahepatic cholangiolithiasis

    Institute of Scientific and Technical Information of China (English)

    童里; 耿小平; 谢坤; 赵红川; 刘付宝

    2016-01-01

    Objective To discuss the reasons,surgical procedures and prognosis of multiple-operations for intra-and extrahepatic cholangiolithiasis.Methods The retrospective cohort study was adopted.The clinical data of 85 patients with intra-and extrahepatic cholangiolithiasis who underwent multiple-operations at the Second Affiliated Hospital of Anhui Medical University from January 2006 to January 2015 were collected.Individualized operations were determined according to the distribution of stones and liver functional reserve,including stones removal by incising bile duct and external biliary drainage,Roux-en-Y hepaticojejunostomy and hepatolobectomy or segmental hepatectomy.The treatment followed the principles as complete removal of stones,complete resection of lesions,correction of stenosis and adequate drainage.Bile was extracted during operation for bacilli culture.Patients received the postoperative symptomatic treatments,including anti-inflammation,hemostasis,liver protection,acid inhibition and nutritional support.The observation indicators included reoperation reasons,operation method,operation time,volume of intraoperative blood loss and transfusion,hepatic inflow occlusion,stone clearance rate,postoperative complications and treatments,bacilli culture of bile,results of pathological examination and duration of hospital stay,results of follow-up.The follow-up using outpatient examination and telephone interview was performed to detect postoperative living conditions and results of abdominal ultrasound once every 3 or 6 months in patients without stone residue and once every 1 month in patients with stone residue from postoperative week 6 to December 2015.Measurement data with normal distribution and with skewed distribution were represented as x ± s and M (range),respectively.Results (1) Reasons of reoperation:85 patients had stone residue or recurrence,including 7 combined with stenosis of bilioenteric anastomosis,5 with secondary malignant biliary tumors and 2

  20. 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

  1. Estudo anatômico das vias bilíferas extra-hepáticas no suíno. Comparação entre a dissecção convencional e por videolaparoscopia Anatomic study of the extrahepatic biliary ducts in the suine. Comparition betwenn conventional and videolaparascopic dissections

    Directory of Open Access Journals (Sweden)

    José Renan Escalante Hurtado

    1997-09-01

    Full Text Available Estudou-se no presente trabalho, através de dissecção de peças anatômicas constituidas de fígado e duodeno, a morfologia das vias bilíferas do suíno. Os animais foram separados em dois grupos iguais, sendo que o primeiro foi submetido a colecistectomia videolaparoscópica. O segundo grupo era constituído de suínos abatidos para consumo. Os animais do grupo da colecistectomia videolaparoscópica eram observados por um período curto de pós-operatório e depois abatidos para retirada de peças anatômicas, tendo sido realizado o estudo das vias bilíferas extra-hepáticas. No segundo grupo eram as peças retiradas após o abate dos animais, estas eram dissecadas, coradas com tinta guache e posteriormente submetidas a estudo radiológico com a injeção de Bário. Os dados obtidos foram analizados utilizando-se o teste de FISHER. Verificou-se que o ductus choledocus é constituído pela união do ductus cysticus e ductus hepaticus na grande maioria dos casos (84.3%. Verificou-se também que o ductus hepaticus é formado, em grande número dos casos, pela confluência do ductus principalis sinister e ductus principalis dexter. Os resultados encontrados permitem concluir que não existem diferenças significantes, no que se refere à conformação das vias bilíferas extra-hepáticas em ambos os grupos.The morphology of the biliary extrahepatic ducts of 32 Landrace pigs were studied through the dissection of anatomical specimens composed by liver and duodenum. The pigs were separated in two groups of 16 animals each. The first group was initially submited to a laparoscopic cholecystectomy, than observed during a brief postoperative period, and eventually killed for attainment of the anatomical specimens; while the second group was destined to slaughter and the anatomical specimens obtained after their death. The study of the anatomical specimens was performed by the dissection of the bilary extrahepatic ducts when they were painted with

  2. 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

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    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

  3. 妊娠期糖尿病合并妊娠肝内胆汁淤积症对围产儿的影响%The effects to the perinatal outcome in gestational diabetes mellitus complicated with intrahepatic cholestasis of pregnancy

    Institute of Scientific and Technical Information of China (English)

    李艳; 徐曦; 周淑; 刘毅; 高岚; 付利侠

    2011-01-01

    Objective To explore the effects on the perinatal outcome in gestational diabetes mellitus(GDM) complicated with intrahepatic cholestasis of pregnancy (ICP). Methods Collect the clinical datum of 1080 pregnant women of the last three year, dividing into three groups; Group GDM and ICP 180 ,Group GDM 426 and Group ICP 474,and analying the perinatal out come between group GDM and ICP and group GDM , between group GDM and ICP and group ICP. Results Hie rate of termina ting pregnancy less than 34 gestational weeks(9. 44% ) 、 the rate of neonatal asphyxia(7. 22% )、 the rate of amniotic fluid pol lution over than D (21. 11% )、the rate of small for gestational age (7. 22% ) of Group GDM and ICP was higher than group GDM and group ICP, And there is significantly difference (P <0.05) among these three groups . Conclusion The risk of adverse peri natal outcome was added in gestational diabetes mellitus complicated with intrahepatic cholestasis of pregnancy. Inorder to Impro ving the perinatal outcome , enhancing fetal monitoring and termination of pregnancy in suitable time is very important.%目的 探讨妊娠期糖尿病合并妊娠肝内胆汁淤积症对围产儿结局的影响.方法 回顾性分析我院2008年1月~2010年10月住院分娩的妊娠期糖尿病合并妊娠期肝内胆汁淤积症(GDM+ ICP组)孕妇180例临床资料,与同期住院的妊娠期糖尿病(GDM组)426例、妊娠期肝内胆汁淤积症(ICP组)474例孕妇所分娩围产儿的结局情况分别进行比较.结果 GDM+ ICP组34周前终止妊娠率、新生儿窒息率、Ⅱ度以上羊水粪染率、小于胎龄儿发生率显著高于其余两组(P<0.05).结论 妊娠期糖尿病合并妊娠肝内胆汁淤积症围产儿不良结局风险增加,应加强胎儿监护,适时终止妊娠,提高出生质量.

  4. The Influence of High Quality Nursing on Minimally Invasive in the Treatment of Postoperative Wound Pain in Intra and Extrahepatic Bile Duct Stone%优质护理对微创治疗肝内外胆管结石术后伤口疼痛的影响

    Institute of Scientific and Technical Information of China (English)

    王爱贤

    2014-01-01

    Objective:To discuss the effect of High quality nursing minimally invasive treatment of postoperative wound pain in intra and extrahepatic bile duct stone.Method:A total of 120 patients with intra and extrahepatic bile duct stone did minimally invasive treatment were selected as objects of study by the random table were selected,and 60 patients in the observation group were given high quality nursing,and 60 patients in the control group were given the control nursing,and the postoperative wound pain situation were observed in the two groups.Result:The proportion of postoperative pain with mild and below level in the observation group was higher than that in the control group(P<0.05).Conclusion:High quality nursing can maintain emotional stability ,meanwhile can be also effective in relieving postoperative pain patients.It is an effective and new way for nursing.%目的:探讨优质护理对微创治疗肝内外胆管结石术后伤口疼痛的效果。方法:按随机数字表法抽取笔者所在医院120例行微创治疗肝内外胆管结石术的患者为研究对象,观察组60例术后给予优质护理,对照组60例术后常规护理,对比两组术后疼痛情况。结果:观察组轻度及以下术后疼痛比例高于对照组(P<0.05)。结论:优质护理在保持患者情绪稳定的同时,亦有效缓解患者术后疼痛感,是一种有效的全新护理方式。

  5. The role of glutamine and C. C. K in preventing cholestasis during PN%谷氨酰胺、胆囊收缩素预防胃肠外营养期间胆汁瘀积的动物实验研究

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    王盛江; 刘立人; 慕海峰; 禹宏; 孙大强; 杨闯

    2000-01-01

    Objective Purpose: Study Glutarnine (GLN)/Cholecystokinin (CCK)'s action of preventing cholestasis during total parenteral nutrition (TPN) and detail action mechanism of GLN and CCK and relationship between each other. Methods Adopt Newzealand pure species white hares as TPN models. All hares were divided into four teams, in which 1st team was designated as TPN team, 2nd team as TPN + GLN team, 3rd team as TPN + CCK team, and 4th team as TPN + GLN + CCK team. Each team was divided into two halves in turn. One half were killed after four-week observation and the other half were killed after 8 weeks. Through blood biochemical examination, analysis of chole components, observation of macrostructure, scan of light and esectron microecopes, we observed if there were cholestasis, gallbladder constmctural alteration and its degree. Results Through blood monitoring, increases of GPT. AKP. cholehilirubin and cholesterol were observed in the first team as compared with the second to forth teams at the forth week and higher increases were found at the 8th week. In choletest,cholebilirubin and cholesterol were higher in the first and second teams than in the third and fourth ones at the 4th week and were higher instinctively in the first to third teams than in the forth team at the 8th week. Scan of light and electron microscopes demonstrated that cholepithelia became low-column shape. Dyeing was deepened. There was cytoedema and mitochondrial got swelling at the 4th week in the first and third teams. At the 8th week, there was tissue between lamina propria and muscle layer. Cyto-plasm became muddy, in which there were bigger fatty drops. There were vacuity in cytoreticulum. In the second and forth teams, we found normal cell density at the 4th week. At the 8th week, there was small alteration in the second team and normal density in the forth team. Conclusions It is true that cholestasis will take place during TPN and become serious with time prolonging. Integrality and

  6. Clinical analysis of fetal death cases in intrahepatic cholestasis of pregnancy%妊娠期肝内胆汁淤积症发生死胎的临床因素分析

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    贺晶; 陈璐; 梁琤

    2011-01-01

    Objective To investigate the clinical features,critical laboratory parameters,and fetal monitoring methods in intrahepatic cholestasis of pregnancy(ICP).Methods A retrospective analysis of 21 cases of ICP suffered with fetal death in Women's hospital.School of Medicine.Zhejiang University from January 1999 to December 2010 were discussed.Results(1)The average age of ICP patients suffered with fetal death were(30.2±4.6)years old.Among them,4 cases were older than 35 years,six cases were multipara.oneo of them suffered stillbirth 2 year before.Twenty cases were singleton pregnancies and 1 cage was twin pregnancy.(2)All 21 cases of fetal death occurred in the third trimester,12 cases occurred before 37 weeks,9 cases after 37 weeks.Nine cases were diagnosed by ultrasound in outpatient clinics,fetal heart beat disappeared in 9 patients after admission because of ICP, two disappeared after labor, one during anesthesia before emergent surgery. Perinatal mortality rate of ICP was 0. 148% (21/14 184), and fetal death occurred from 29 to 41 weeks with an average gestational age of ( 33.8 ± 4. 2 ) weeks, ( 3 ) Puritus occurred in all 21 cases while 11 of them had pruritus all over the body. Ten pregnant women felt the fetal movement decreased or disappeared before diagnosis of fetal death. The glycocholic acid levels increased in all of the 21 cases. Among them, glycocholic acid levels in 11 cases were (21.49 -64. 48) μmol/L, while in 10 cases were ≥64. 48 μmol/L Serum bile acid levels elevated in 16 cases which had been analyzed ( the other 5 cases had not been checked ), and the highest level reached 270 μmol/L Serum alanine aminotransferase and aspartate aminotransferase were increased in 14 cases. Seven cases had their total bilirubin >21 μmoL/L, and 12 cases had their direct bilirubin levels significantly elevated. Among the 21 cases of ICP, 15 cases were in severe status, while the other 6 cases were mild. (4) Nine patients had no antepartum surveillance since

  7. Diagnostic and therapeutic approach to cholestatic liver disease Abordaje diagnóstico y terapéutico del síndrome colestásico

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    T. Pérez Fernández; P. López Serrano; E. Tomás; Mª L. Gutiérrez; J. L. Lledó; G. Cacho; C. Santander; C. M. Fernández Rodríguez

    2004-01-01

    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 ex...

  8. Effects of albumin administration in serum liver enzymes of rats in the presence of extrahepatic biliary obstruction Efeitos da administração de albumina nos níveis séricos de enzimas hepáticas em ratos com obstrução biliar extra-hepática

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    Jorge Fernando Rebouças Lessa

    2011-01-01

    Full Text Available PURPOSE: To study the influence of albumin on changes of liver function in the extrahepatic biliary obstruction through an experimental model in rats. METHODS: Sixty rats were divided into four groups: Group C (Control: 6 animals. Group M (Fictitious Operation: 18 rats underwent laparotomy and handling of the bile ducts; Groups O (extrahepatic biliary obstruction and A (Treated with 2% albumin: 18 animals in each group underwent ligation of the ductus liver; The animals in groups M, O and A were divided into three subgroups of 6 animals each to be killed in the 7, 14 and 21 days postoperative (POD. Blood was drawn for determination of total bilirubin (TB, indirect bilirubin (IB, direct bilirubin (DB, alkaline phosphatase (ALP, aspartate aminotransferase (AST and alanine aminotransferase (ALT. RESULTS: On POD 7, BI levels were 4.5 mg / dl in group O and 2.1 mg / dl in group A (p = 0.025. On the 14th POD, the levels of PA were 1185.2 U / l in the group and O 458.3 U / l in group A (p = 0.004. ALT levels were 101.7 U / l in the group O and 75.7 U / l in group A (= 0.037. On POD 21, the levels of ALP were 1069.5 U / l in the group O and 468.3 U / l in group A (p = 0, 004. CONCLUSION: The administration of albumin reduced the serum levels of bilirubin in the 7th day of supplementationOBJETIVO: Estudar a influência da albumina em alterações funcionais do fígado na obstrução biliar extra-hepática por meio de um modelo experimental desenvolvido em ratos. MÉTODOS: 60 ratos distribuídos em quatro grupos: Grupo C (Controle: 6 animais. Grupo M (Operação Fictícia: 18 ratos submetidos à laparotomia e manuseio das vias biliares; Grupos O (Obstrução Biliar Extra-hepática e A (Tratados com albumina a 2%: 18 animais, em cada grupo, submetidos à ligadura do ducto hepático; Os animais dos grupos M, O e A foram distribuídos em três subgrupos de 6 animais cada, para serem mortos nos 7°, 14° e 21° dias pós- operatórios (DPO. Foi colhido sangue

  9. 带蒂壁层腹膜瓣翻转修复肝外胆管损伤的实验研究%Experimental study on flip-flop repair of the extrahepatic bile duct defect with parietal pedicled peritoneal graft

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    陈超; 郭春良

    2013-01-01

    [Objective] To observe the expression of TGF- β1 in the repaired bile duct defect with parietal pedicled peritoneal graft and explore the feasibility of using pedicled peritoneal graft to flip-flop repair the extrahepatic bile duct defect, and to find an ideal material and a good procedure for the clinical management of bile duct injury. [Methods] A total of 20 Japanese white rabbits were divided into 5 groups at random, 4 in each group. The bile duct defect was flip-flop repaired by pedicled peritoneal graft. Laparotomy was then performed in the 5 groups at the following interval: 1 week, 2 weeks, 3 weeks), 5 weeks and 12 weeks. The tissues were harvested for light microscopic examination and the expression of TGF- β1 was studied by using immunohistochemical SP staining method. [Results] TGF- β1 was expressed strongly within 3 weeks, by 5 weeks, the expression was degraded gradually. By 12 weeks TGF- β1 was expressed weakly, which had no significant difference with preoperation (P> 0.05). [Conclusions] The low expression of TGF- β 1 in the later postoperative period, indicates impossibility of biliary stricture. Flip-flop repairment of the extrahepatic bile duct defect with parietal pedicled peritoneal graft is a good procedure for the repairment of bile duct defect.%[目的]观察带蒂壁层腹膜瓣翻转修补肝外胆管损伤模型中修复段胆管组织中转化生长因子β1 (transforming growth factor-β1,TGF-β1)表达的表达情况,探讨自体带蒂壁层腹膜瓣修补肝外胆管损伤的可行性,为临床胆管损伤处理探索新的手术方式.[方法]20只雄性日本大耳白兔随机分为5组,每组4只,利用带蒂壁层腹膜瓣翻转修补肝外胆管损伤,分别于修复术后1、2、3、5和12周切取胆管缺损修复区组织行光镜检查及免疫组化方法观察TGF-β1的表达.[结果]在修复术后3周前明显高表达,5周后TGF-β1逐渐呈低表达,12周后表达明显下降,与正常胆管表

  10. Expressions of SHP and CYP7A1 in pregnant rats with intrahepatic cholestasis%小异二聚体伴侣与胆固醇7a-羟化酶在肝内胆汁淤积症孕鼠中的表达

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    兰易; 刘建; 程浩; 邹姝丽; 甘晓玲

    2008-01-01

    Objectives To investigate the expressions of small heterodimer partner (SHP) and target gene cholesterol-7-hydroxylase (CYP7A1) in livers of rats with intrahepatic cholestasis of pregnancy (ICP), and to study the mechanism of ICP. Methods Thirty SD rats (pregnant for 15 days) were equally and randomly divided into two groups: an estradiol benzoate (EB) group and a normal saline (NS) group. Two ml blood was drawn from each rat before and on the 5th day after medicine administration to measure the levels of ALT, AST, ALP, TBA, TBIL, and DBIL. After delivery, the histopathological changes of the mother rat livers were studied. The mRNA and protein expressions of SHP and CYP7A1 in the livers were determined by RT-PCR and Western blot. Results (1) In the EB group, the serum levels of ALT, AST, ALE TBA, TBil, and DBil after EB administration increased significantly (P0.05); (2) Intrahepatic cholestasis appeared in the EB group, but not in the NS group; (3) The mRNA expressions of SHP and CYP7A1 were significantly higher in the EB group than in the NS group [(SHPmRNA: NS 0.365±0.0317 vs EB 0.4865±0.0237, P0.05).雌激素组孕鼠肝脏出现肝内胆汁淤积表现,对照组肝脏形态、结构正常.雌激素组和对照组SHP mRNA分别为0.4865±0.0237和0.3657±0.0317, CYP7A1 mRNA分别为0.4311±0.0157和0.3285±0.0123,差异均有统计学意义(P<0.01).雌激素组和对照组SHP蛋白表达分别为0.5033±0.0274和0.3762±0.0284, CYP7A1蛋白表达分别为0.4802±0.0217和0.3570±0.0175,差异均有统计学意义(P<0.01).结论 雌激素诱导的胆汁淤积促进肝脏SHP及其靶基因CYP7A1表达增加,导致胆汁酸合成进一步增加,从而引发胆汁淤积,这可能是妊娠期肝内胆汁淤积症发病机制之一.

  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. S-腺苷蛋氨酸联合熊去氧胆酸治疗极低出生体质量患儿肠外营养相关性胆汁淤积症的疗效观察%Efficacy of S-adenosylmethionine and ursodeoxycholic acid on parenteral nutrition associated cholestasis in very low birth weight infants

    Institute of Scientific and Technical Information of China (English)

    何伟彬; 杨辉; 戴怡蘅

    2013-01-01

    目的 观察S-腺苷蛋氨酸联合熊去氧胆酸治疗极低出生体质量患儿肠外营养相关性胆汁淤积症的疗效.方法 研究对象为本院2008年1月-2012年10月出生的极低出生体质量患儿67例,出生后接受静脉营养(PN)并出现肠外营养相关性胆汁淤积症(PNAC),随机分为观察组36例,对照组31例.对照组在减少肠外营养基础上给予口服熊去氧胆酸10~30mg/(kg·d)治疗10d,观察组在对照组治疗基础上联合S-腺苷蛋氨酸30~50mg/(kg·d)治疗10d.治疗前后分别检测2组患儿血清谷丙转氨酶(ALT)、总胆红素(TBIL)、直接胆红素(DBIL)和总胆酸(TBA)的水平.结果 2组各观察指标ALT、TBIL、DBIL、TBA的水平均较治疗前下降,差异有统计学意义(P<0.01).观察组ALT、TBIL、DBIL、TBA的水平较对照组下降更明显(P<0.05).结论 S-腺苷蛋氨酸联合熊去氧胆酸治疗极低出生体质量患儿胆汁淤积症疗效更显著,安全性高,值得临床推广.%Objective To observe the efficacy of the S - adenosylmethionine and ursodeoxy-cholic acid on parenteral nutrition associated cholestasis in very low birth weight infants. Methods Sixty-seven very low birth weight infants received parenteral nutrition (PN) after born, and suffered from parenteral nutrition associated cholestasis (PN AC). They were randomly divided into observation group (n =36) and the control group (n = 31). In the control group, the patients received the reduced dose of parenteral nutrition, and were treated with ursodeoxycholic acid of dosage 10 - 30 mg/(kg·d) for 10 days. In the observation group, the patients received same treatment as those in the control group, and treated with S- adenosylmethionine of dosage 30~50 mg/(kg·d) for 10 days. Before and after treatment in two groups, we detected their serum levels of alanine amino-transferase (ALT), total bilirubin (TBIL), direct bilirubin (DBIL), and total bile acid (TBA). Results Levels of ALT, TBIL, DBIL and TBA in

  13. Effects of FXR and CYP7A1 on metabolism of acid bile of pregnant rats with intra-hepatic cholestasis%FXR、CYP7A1在妊娠期肝内胆汁淤积症孕鼠胆汁酸代谢中的作用

    Institute of Scientific and Technical Information of China (English)

    兰易; 刘建; 邹姝丽; 程浩; 甘晓玲

    2008-01-01

    目的 分析法尼醇受体(FXR)及其靶基因胆固醇7α-羟化酶(CYP7A1)在妊娠期肝内胆汁淤积症(intrahe-patic cholestasis of pregnancy,ICP)孕鼠肝脏的表达情况,探讨FXR与CYP7AI在ICP发病机制中的作用.方法 用随机数字表法将30只孕15 d的SD大鼠分成2组:生理盐水(NS)组和苯甲酸雌二醇(estradiol benzoate,EB)组,每组15只.用药前和用药后第5天分别测定血清中ALT、AST、ALJP、TBA水平,同时观察肝脏形态学变化,并应用RT-PCR和Westernblot分别检测肝脏FXR、CYP7A1两者mRNA和蛋白的表达.结果 EB组用药后备血清生化指标比用药前显著升高(P0.05);EB组孕鼠肝脏出现肝内胆汁淤积表现,Ns组肝脏形态结构正常;EB组FXR和CYP7A1两者的mRNA和蛋白表达均显著高于Ns组(P<0.01).结论 EB诱导的ICP孕鼠肝脏FXR及CYP7A1表达均增加,说明存在胆汁酸合成自身反馈调节障碍,导致胆汁酸合成增加,这可能是ICP发病机制之一.

  14. Comparative study of conscious sedation and intravenous anesthesia used to endoscopic retrograde cholangio pancreatiography in treatment of extrahepatic bile duct stones%清醒镇静与静脉麻醉在内窥镜逆行胰胆管造影术治疗肝外胆管结石中的比较研究

    Institute of Scientific and Technical Information of China (English)

    胡辉; 荆绪斌; 邹细岩; 吴锦雄

    2014-01-01

    目的 探讨清醒镇静与静脉麻醉在内窥镜逆行胰胆管造影术(ERCP)治疗肝外胆管结石中的安全性、有效性.方法 将100例采用ERCP治疗的肝外胆管结石患者按入组顺序进行编号,50例奇数者采用静脉麻醉(静脉麻醉组),给予静脉注射丙泊酚;50例偶数者采用清醒镇静(清醒镇静组),给予肌肉注射地西泮及哌替啶.观察两组患者术中反应(拔镜行为、自行体位改变)、生命体征变化情况、操作时间、取石成功率及并发症发生情况.结果 清醒镇静组术中拔镜行为、自行体位改变发生率明显高于静脉麻醉组[24%(12/50)比2%(1/50)、18%(9/50)比0],差异均有统计学意义(P<0.01).两组用药后5min平均动脉压、心率均较术前明显降低,差异有统计学意义(P<0.05);进镜后10 min、术后清醒时与术前比较差异无统计学意义(P>0.05);两组脉搏血氧饱和度比较差异均无统计学意义(P>0.05).两组取石成功率均为98%(49/50).静脉麻醉组操作时间明显短于清醒镇静组[(38.2±6.3) min比(49.1±9.9) min],差异有统计学意义(P<0.01).两组并发症发生率比较差异无统计学意义(P>0.05).结论 静脉麻醉和清醒镇静均可用于ERCP治疗肝外胆管结石,但静脉麻醉能明显减轻患者不适,缩短操作时间.%Objective To evaluate the safety and effectiveness of conscious sedation and intravenous anesthesia used to endoscopic retrograde cholangio pancreatiography (ERCP) in treatment of extrahepatic bile duct stones.Methods A total of 100 cases of extrahepatic bile duct stones patients in treatment of ERCP were encoded by the group order,50 cases of odd used intravenous anesthesia (intravenous anesthesia group),intravenous injection of propofol; 50 cases of even used conscious sedation (conscious sedation group),muscle injection of diazepam and pethidine.Intraoperative reaction (extubation behavior,own postural changes),changes in vital signs

  15. Preliminary experiences of Rex shunt for extrahepatic portal vein obstruction via a conduit of internal jugular vein%颈内静脉搭桥Rex手术治疗小儿肝外门静脉梗阻的初步探讨

    Institute of Scientific and Technical Information of China (English)

    温哲; 王哲; 刘涛; 张向向; 王红英; 申刚; 张靖; 梁奇峰; 刘斐

    2016-01-01

    Objective To evaluate the outcomes of treating extrahepatic portal vein obstruction (EHPVO) by Rex shunt (superior mesenteric-left port vein bypass) with internal jugular vein graft.Methods From October 2014 to June 2015,8 patients of extrahepatic portal vein obstruction underwent Rex shunting with internal jugular vein as a venous graft.The surgical outcomes were evaluated over a follow-up period of 1-9 months.A median longitudinal abdominal incision was made.After peritoneal cavity was satisfactorily opened,round hepatic ligament was resected and lifted.For inflow vein,left portal vein in Rex recess was liberated for around 3 cm.Superior mesenteric vein was identified by tracking mid-colon vein and dissected around 3 crn for outflow.Through 2 small transverse incisions on left side of neck,7~9 cm of left internal jugular vein was harvested as a venous graft.Shunt was established by two end-to-side anastomoses at both ends of jugular vein graft between left portal and superior mesenteric veins.Results There were 5 boys and 3 girls with an average age of 4 (1.3~7) years.The manifestations included gastrointestinal hemorrhage (n =6),hypersplenism (n =6) and hemorrhage & splenomegaly (n =4).Preoperative liver function and blood coagulation were all normal while endoscopy revealed esophageal gastric varices (n =7).Portal vein cavernoma was identified by ultrasound and computed tomography (CT).Portal vein system retrograde angiography showed the presence of left portal vein bifurcation (n =7) and unidentifiable (n =1) (confirmed intraoperatively as atresia).Vascular patency of left portal vein in Rex recess was confirmed (n =7) during surgical exploration followed by Rex shunting.Warren shunt was performed for left portal vein atresia.After shunting,angiography through superior mesenteric vein demonstrated patency of vein graft,better development of intrahepatic portal system and regression of extrahepatic collateral varicose vessels.Portal vein pressure (PVP) was

  16. Expression of Estrogen Receptor mRNA and Genes Related to Regulation of Bile acid Metabolism in Fetal Rat Liver of Pregnant Rats with Intrahepatic Cholestasis%雌激素受体及胆汁酸代谢相关基因在胆汁淤积孕鼠胎鼠肝脏中的表达

    Institute of Scientific and Technical Information of China (English)

    时青云; 赵晋; 林宇庚; 闫时; 周新; 林颖奇

    2011-01-01

    目的 探讨雌激素受体(estrogen receptor,ERα)与胆汁酸代谢相关基因胆固醇7α羟化酶(cholesterol 7α-hydroxylase,CYP7A1)、胆固醇27α羟化酶(cholesterol 27-hydroxylase,CYP27A1)、胆固醇12α羟化酶(cholesterol 12α-hydroxylase,CYP8B1)mRNA在妊娠期肝内胆汁淤积孕鼠胎鼠肝脏中的表达及其意义.方法 将60只清洁级SD孕鼠自孕第13天均分为2组:对照组孕鼠皮下注射精制植物油2.0 mL*kg-1*d-1;研究组孕鼠皮下注射17-α-乙炔雌二醇1.25 mg*kg-1*d-1.2组孕鼠分别于妊娠第13、17、21天断尾采母鼠血2 mL检测血清生物化学指标,于妊娠第21天处死.抽取母鼠、胎鼠血并提取母鼠、胎鼠肝脏组织.应用酶联免疫吸附试验检测2组孕鼠以及胎鼠血清中胆酸浓度;应用实时定量PCR技术检测各组胎鼠肝脏ERα、CYP7A1、CYP27A1、CYP8B1的mRNA表达量.结果 ①胆酸指标比较:在妊娠第17天时对照组、研究组母鼠胆汁酸浓度分别为(24.6±1.3)μmol/L、(58.7±3.2)μmol/L,研究组母鼠胆汁酸浓度明显高于对照组(t=2.462,P<0.05);在妊娠第21天时对照组、研究组母鼠胆汁酸浓度分别为(26.5±3.1)μmol/L、(66.4±2.7)μmol/L,研究组母鼠胆汁酸浓度与妊娠第17天时研究组以及对照组相比(F=5.43,P<0.05),差异有统计学意义.②胎鼠肝脏CYP7A1 mRNA、CYP27A1 mRNA、CYP8B1 mRNA表达:研究组中CYP7A1 mRNA(1.25±0.01)、CYP27A1 mRNA(2.05±0.03)、CYP8B1 mRNA明显高于对照组(0.35±0.02、0.75±0.03、0.85±0.02),P值均<0.05,差异有统计学意义.③胎鼠肝脏雌激素受体的表达:研究组中ERα mRNA(0.75±0.02)明显高于对照组ERα mRNA(0.45±0.01).结论 妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)孕鼠胎鼠肝细胞ER、CYP7A1、CYP27A1、CYP8B1的表达升高,胆汁酸的合成与代谢调节机制存在障碍,可能是导致ICP胎儿围生期死亡发生的原因之一.%Objective To study the expression of estrogen receptor(ER) and

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

    Institute of Scientific and Technical Information of China (English)

    刘壵; 李龙; 侯文英; 王海斌

    2013-01-01

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

  18. 妊娠期肝内胆汁淤积症的新生儿血清胱抑素c测定分析%Newborn Infants Suffering from Intrahepatic Cholestasis of Pregnancy (ICP) by Measuring the Content of Serum Cystatin C (CysC)

    Institute of Scientific and Technical Information of China (English)

    李作娅; 李伟; 夏梅梅; 任盛

    2012-01-01

    目的:通过对妊娠期肝内胆汁淤积症(ICP)的新生儿血清胱抑C(CysC)血尿素氮(BuN),血肌肝(scR)测定分析,探讨妊娠期肝内胆汁淤积症的新生儿肾功能变化.方法:对35例妊娠期肝内胆汁淤积症(ICP)的新生儿与正常对照组新生儿均于生后24小对内和第七天,分别测定血清胱抑素C(CysC)、血尿素氮(BuN)、血肌肝(scR)水平,并将两组测定数据进行对比分析.结果:妊娠期肝内胆汁淤积症(ICP)的新生儿组血清胱抑素C(CysC)与正常对照组的新生儿比较明显增高(p<0.05),而血清尿素氮( BUN)及肌肝SCR两组比较差异无统计学意义.一周后两组胱抑素C(CysC)、肌肝(BuN)、尿素氮( BUN)比较无差异(P>0.05).结论:妊娠期肝内胆汁淤积症ICP的新生儿有一过性肾损害,血清胱抑素C与血尿素氨、血肌酐比较,是早期诊断肾功能损害更灵敏的指标.%Objective: To explore changes in renal functions of newborn infants suffering from Intrahepatic Cholestasis of Pregnancy (ICP) by measuring the content of serum cystatin C (CysC), Urea nitrogen (BUN) and serum creatinine (SCr).Methods: The contents of serum cystatin C (CysC), Urea nitrogen (BUN) and serum creatinine (SCr) of 35 newborn children suffering from ICP were measured within 24 hours of birth and the seventh day of birth, respectively. As the control, the measuring were performed in the exactly the same way for regular new born children.Results: the children suffering from ICP showed obvious increase in CysC in contrast with the control (p0.05).Conclusion: transient kidney injuries exist in newborn infants suffering from ICP. Compared with BUN and SCr, CysC is a sensitive indicator for kidney injury early diagnosis.

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

    Institute of Scientific and Technical Information of China (English)

    宋元宗; 盛建胜; 牛飼美晴; 胡務亮; 张春花; 小林圭子

    2008-01-01

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

  20. 雌激素受体α对胆汁酸转运相关基因的调控及其与孕鼠肝内胆汁淤积症发生的相关性%Regulation of estrogen receptor αon bile acid transporters related gene and its correlation with intrahepatic cholestasis in pregnant rats

    Institute of Scientific and Technical Information of China (English)

    宋昭逸; 王晶晶; 时青云

    2016-01-01

    Objective To investigate the regulation of estrogen receptor α( ERα) on bile acid transporters related gene ,such as farnesoid X receptor (FXR), sodium taurocholate co-transporting polypeptide (NTCP)and bile salt export pump (BSEP),to evaluate ERα’ s correlation with intrahepatic cholestasis in pregnant rats .Methods Forty SPF class pregnant Sprague-Dawley rats were selected and divided into four groups randomly with 10 in each.Since the 15th day of pregnancy , rats in control group were injected subcutaneously with refined vegetable oil 2.0 mL/kg· d, those in the low-dose, moderate-dose and high-dose groups received 17α-ethynylestradiol (EE) 1.0 mg/kg· d, 1.25 mg/kg· d, 1.5 mg/kg· d.All rats were sacrificed on the 21st day of pregnancy and maternal hepatic tissue were collected .The serum levels of biochemical indicators , protein and mRNA expressions of ERαFXR, NTCP, BSEP were examined .Results Biochemical:the serum levels of ALT , AST, TBS, BIL were significantly lower in the control group than that in the treatment groups ( P<0.05 ) .Protein and mRNA expression of ERα, FXR, NTCP, BSEP: compared with control group, low-dose, moderate-dose, high-dose group activated ERαsignificantly; FXR, NTCP, BSEP decreased in a dose-dependent manner , which were all significantly lower than that in control group ( P<0.05 ) .Conclusions Along with the rise of estrogen,the repression of ERαrise and FXR, NTCP, BSEP decrease, these findings suggest lower metabolism and transporting function of bile acid .We propose that this may contribute to development of the EE-induced intrahepatic cholestasis of pregnancy .%目的:探讨雌激素受体α( estrogen receptor α, ERα)对参与调节胆汁酸转运相关的基因,如法尼醇X受体(farnesoid X receptor, FXR)、钠离子-牛磺胆酸共转运蛋白(sodium taurocholate co-transprorting polypeptide,NTCP)、胆盐输出泵(bile salt export pump, BSEP)的调控作用及其对孕鼠肝内

  1. 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.

  2. Nesfatin-1 alleviates extrahepatic cholestatic damage of liver in rats

    Directory of Open Access Journals (Sweden)

    Ali Solmaz

    2016-11-01

    Full Text Available Obstructive jaundice (OJ can be defined as cessation of bile flow into the small intestine due to benign or malignant changes. Nesfatin-1, recently discovered anorexigenic peptide derived from nucleobindin-2 in hypothalamic nuclei, was shown to have anti-inflammatory and antiapoptotic effects. This study is aimed to investigate the therapeutic effects of nesfatin-1 on OJ in rats. Twenty-four adult male Wistar-Hannover rats were randomly assigned to three groups: sham (n = 8, control (n = 8, and nesfatin (n = 8. After bile duct ligation, the study groups were treated with saline or nesfatin-1, for 10 days. Afterward, blood and liver tissue samples were obtained for biochemical analyses, measurement of cytokines, determination of the oxidative DNA damage, DNA fragmentation, and histopathologic analyses. Alanine aminotransferase and gamma-glutamyl transferase levels were decreased after the nesfatin treatment; however, these drops were statistically non-significant compared to control group (p = 0.345, p = 0.114. Malondialdehyde levels decreased significantly in nesfatin group compared to control group (p = 0.032. Decreases in interleukin-6 and tumor necrosis factor-α levels from the liver tissue samples were not statistically significant in nesfatin group compared to control group. The level of oxidative DNA damage was lower in nesfatin group, however this result was not statistically significant (p = 0.75. DNA fragmentation results of all groups were similar. Histopathological examination revealed that there was less neutrophil infiltration, edema, bile duct proliferation, hepatocyte necrosis, basement membrane damage, and parenchymal necrosis in nesfatin compared to control group. The nesfatin-1 treatment could alleviate cholestatic liver damage caused by OJ due to its anti-inflammatory and antioxidant effects.

  3. Cystic Echinococcosis: A Case of Extrahepatic Intra-Abdominal Involvement

    Science.gov (United States)

    Carvalho, André; Fernandes, Teresa; Gonçalves, José

    2017-01-01

    Hydatid disease, or echinococcal disease, is a parasitic infestation caused by the larval stage of the Echinococcus tapeworm and it primarily affects the liver and lung but involvement of other organs is also possible secondary to peritoneal seeding or hematogeneous dissemination. We describe a rare case of extensive abdominal disease, with lesions affecting the liver, peritoneum, and lesser omentum, requiring aggressive surgical intervention. Complementary diagnostic exams were crucial to reach the diagnosis and evaluate the extension of the disease. PMID:28194292

  4. Extrahepatic right hepatic duct diverticulum:a rare entity

    Institute of Scientific and Technical Information of China (English)

    Eduardo SM Fernandes; Raquel L Bernardo; Moacir M Fernandes; Rogério MC Araújo; Renato Sebbe; Asterio Monte; José F Coelho; Antonio AP Souza; Joaquim Ribeiro Filho

    2010-01-01

    BACKGROUND: Douglas described choledochal cysts in 1852 and Todani proposed an anatomy-based classiifcation in 1977. The classiifcation is the most extensively used, but does not include some rare variations. We present a case of hepatic duct diverticulum, one of the variations, and discuss its diagnosis and treatment. METHODS: A 57-year-old woman presented with upper abdominal pain and discomfort associated with nausea and vomiting. She was ifnally diagnosed with cholelithiasis and right hepatic duct diverticulum. RESULT: The patient underwent resection of the hepatic duct diverticulum and cholecystectomy, and was asymptomatic 26 months after surgery. CONCLUSIONS: Hepatic duct diverticulum is a rare form of choledochal cyst, not included in Todani's classiifcation. Todani's classiifcation including this and other uncommon variations of choledochal cysts must be reviewed. The best diagnostic imaging methods and treatment for choledochal cysts must be deifned.

  5. 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

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

    Science.gov (United States)

    Mehler, Stephen J

    2011-09-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-02-15

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

  8. [Extrahepatic manifestations of hepatitis C virus: the thyroid disorders].

    Science.gov (United States)

    Antonelli, Alessandro; Ferri, Clodoveo; Fallahi, Poupak; Ferrari, Silvia Martina; Ghinoi, Alessandra; Mascia, Maria Teresa; Ferrannini, Ele

    2005-01-01

    The prevalence of thyroid disorders has been studied in patients with chronic hepatitis C virus (HCV) infection by many studies. In general, thyroid dysfunction in chronic C hepatitis may include all forms of thyroid alterations, i.e. hypothyroidism and hyperthyroidism, Hashimoto's disease and isolated increases in antithyroid autoantibodies. The prevalence of various thyroid disorders and serum anti-thyroid autoantibodies is generally higher in chronic hepatitis type C than in hepatitis B or D or control series. The results of most studies in patients with hepatitis C confirm a higher prevalence of autoimmune thyroid involvement and hypothyroidism than in controls. More recently, some epidemiological studies have suggested a possible association between HCV and thyroid cancer. These last data need to be confirmed by other studies, but seem to be sufficient to suggest careful thyroid monitoring during the follow-up of patients with HCV infection.

  9. Extrahepatic immune related manifestations in chronic hepatitis C virus infection.

    Science.gov (United States)

    Tampaki, Maria; Koskinas, John

    2014-09-21

    The association of chronic hepatitis C with immune related syndromes has been frequently reported. There is a great range of clinical manifestations affecting various systems and organs such as the skin, the kidneys, the central and peripheral nervous system, the musculoskeletal system and the endocrine glands. Despite the high prevalence of immune related syndromes in patients with chronic hepatitis C, the exact pathogenesis is not always clear. They have been often associated with mixed cryoglobulinemia, a common finding in chronic hepatitis C, cross reaction with viral antigens, or the direct effect of virus on the affected tissues. The aim of this review is to analyze the reported hepatitis C virus immune mediated syndromes, their prevalence and clinical manifestations and to discuss the most supported theories regarding their pathogenesis.

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

    Institute of Scientific and Technical Information of China (English)

    王欣; 黄凯; 徐立宁

    2008-01-01

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

  11. Protective effect of capillary artemisia polysaccharide for liver oxidative damage rats with intrahepatic cholestasis of pregnancy%茵陈多糖对妊娠胆汁淤积大鼠肝脏氧化损伤的保护作用研究

    Institute of Scientific and Technical Information of China (English)

    范丽梅; 徐立堃; 张兰; 胡春玲; 林常青; 李莉群

    2013-01-01

    目的 探讨茵陈多糖对妊娠胆汁淤积大鼠肝脏氧化损伤的保护作用.方法 采用随机数字表法将32只妊娠SD大鼠分为对照组、模型组、低剂量组及高剂量组,妊娠16周除对照组外均采用苯甲酸雌二醇注射法建立妊娠胆汁淤积大鼠模型,造模成功后低剂量组[50 mg/(kg·d)]及高剂量组[100mg/(kg·d)]分别给予茵陈多糖干预,1周后检测各组大鼠肝脏生化指标[血清谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)、碱性磷酸酶(alkaline phosphatase,ALP)、直接胆红素(direct bilirubin,DBIL)及间接胆红素(indirect bilirubin,IBLI)]及氧化还原酶[超氧化物歧化酶(erythrocuprein,SOD)、丙二醛(malonaldehyde,MDA)、谷胱甘肽过氧化物酶(glutathione peroxidase,GPx)、过氧化氢酶(catalase,CAT)]活力变化.结果茵陈多糖干预1周后,低剂量组及高剂量组血清ALT、AST、ALP、DBIL及IBLI水平明显低于模型组(P < 0.05),低剂量组及高剂量组间差异有统计学意义(P < 0.05).低剂量组及高剂量组肝组织匀浆MDA水平低于模型组(P < 0.05),SOD、GPx,、CAT平高于模型组(P < 0.05),低剂量组同高剂量组间差异有统计学意义(P < 0.05).结论 茵陈多糖能够减轻妊娠胆汁淤积大鼠肝脏氧化损伤,发挥对肝功能的保护作用.%Objective To investigate the protective effects of capillary artemisia polysaccharide on liver oxidative damage rats with intrahepatic cholestasis of pregnancy (ICP). Methods 32 SD rats were divided into the control group (CG), model group (MG), high-dose group (HG) and low-dose group (LG) with random digits table. Animal model of ICP were made with injecting estradiol benzoate in rats with 16 weeks of pregnancy except CG. Rats in HG [100 mg/ (kg·d)] and LG [(50 mg/(kg·d)) were interfered with artemisia capillaries polysaccharides. Biochemical indicators in rats liver (serum ALT, AST, ALP, DBIL and IBLI) and oxidordeuctase

  12. CYP1B1基因A119S多态性与妊娠期肝内胆汁淤积症风险关系的研究%Study on the relationship between gene polymorphism of CYP1B1 A119S and risk of intrahepatic cholestasis of pregnancy

    Institute of Scientific and Technical Information of China (English)

    朱壮彦; 富晓敏; 穆雅琴; 赵富玺

    2013-01-01

    Objective: To explore the relationship between gene polymorphism of CYP1B1 A119S and the occurrence of intrahepat-io cholestasis of pregnancy (ICP) . Methods: Allele - specific polymerase chain reaction method (AS - PCR) was used to analyze gene polymorphism locus in exon 2 codon 119 (G -T) of CYP1B1 in 73 cases with endometrial cancer and 90 normal women. Three genotypes were defined, including homozygous wild type (G/G) , heterozygous variant (G/T) , and homozygous variant (T/T) . Results: The prevalence rates of CYP1 Bl A119S genotypes G/G, G/T, and T/T were 3. 8% , 39. 7% , and 16. 5% in ICP group, 64. 4% , 26. 7% , and 8. 9% in control group. The frequencies of CYP1B1 G and T alleles were 63. 7% and 36. 3% in ICP group, 77. 8% and 22. 2% in control group, respectively. There were statistically significant differences in distribution frequencies of polymorphism genotypes and alleles of CYP1B1 A119S between the two groups (P<0. 05) . Compared with G/G, the OR value of T/T was 2. 719 (1.007-7.341), the OR value of GT was 2. 190 (1. 096 -4. 375) , respectively. The risk of ICP in patients with T allele increased by 1. 995 times (1. 226 -3. 246) . Conclusion: The distributions of three gene polymorphism locus of CYP1B1 have a certain correlation with risk of ICP, mutant genotypes increase the risk of ICP.%目的:探讨CYP1BI基因A119S多态性与妊娠期肝内胆汁淤积症(ICP)发生危险性的关系.方法:用等位基因特异性PCR (AS-PCR)法,对73例妊娠期肝内胆汁淤积症患者和90例正常女性的CYP1B1 A119S多态位点进行检测分析,确定出多态性的3种基因型,即野生型G/G、杂合型G/T、突变型T/T.结果:CYP1B1基因A119S多态性G/G、G/T、T/T 3种基因型分布频率,ICP组分别为3.8%、39.7%和16.5%,对照组分别为64.4%、26.7%和8.9%;ICP组G、T等位基因频率为63.7%,36.3%,对照组为77.8%,22.2%.CYP1 B1 A119S多态性基因型及等位基因型在两组间分布频率

  13. 早期应用脂肪乳对极低出生体重儿胃肠外营养相关性胆汁淤积的影响%Effect of early fat emulsion usage on parenteral nutrition associated with cholestasis of very low birth weight infant

    Institute of Scientific and Technical Information of China (English)

    杨军; 李水霞

    2015-01-01

    objectiveTo study the effect of fat emulsion ociated in parenteral nutrition (PN) associated with cholestasis (PNAC) of very low birth weight infant (VLBWI) .MethodsTo study retrospectively the clinical data of 18 VLBWI PNAC (PNAC group,18 cases) and 36 without PNAC (non-PNAC group,36 cases) ,matched by stop taking food of time ,gestational age, birth weight and duration of PN , Meanwhile, the associated factors with PNAC were also analyzed in two groups.Results Within 2 weeks after birth fat emulsion calories, PNAC group was significantly higher than non PNAC,( 23.0±7.3)% vs(15.1±4.5)%, t= 3.815,p= 0.016, the difference was statistically significant. Two groups in the ratio of total calories, the ratio of amino acid calories,the ratio of sugar calories difference has no statistical significance (P> 0.05). PN in use process, the two groups in the fat emulsion, amino acid and sugar intake of total difference has no statistical significance (P > 0.05).ConclusionsThe occurrence of PNAC is associated with higher calorie ratio of fat emulsion intake during the first two weeks of PN support after birth in VLBWI.Further prospective randomized double blind controlled studies should be performed.%目的:探讨胃肠外营养(PN)中的脂肪乳对极低出生体重儿(VLBWI)胃肠外营养相关性胆汁淤积(PNAC)的影响。方法:回顾性分析2009年1月至2015年4月静脉营养(PN)超过14d的VLBWI中的PNAC病例和配对非PNAC病例临床资料(两组在胎龄、出生体重、PN持续时间和禁食时间相匹配),比较两组发生PNAC相关因素的差异。结果:PNAC组(18例)生后2周内脂肪乳热卡比明显高于非PNAC组(36例),为23.0±7.3%vs 15.1±4.5%,t=3.815,p=0.016,差异有统计学意义,而在总热卡比、氨基酸热卡比及糖热卡比差异无统计学意义(P>0.05)。两组在PN应用期间脂肪乳、氨基酸及糖的累计摄入量差异无统计学意义(P>0.05)。结论:极低出生体

  14. 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.

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

    Science.gov (United States)

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

    2003-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sebastián Sepúlveda Marín

    2016-04-01

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

  17. 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.

  18. Subdural hemorrhage: A unique case involving secondary vitamin K deficiency bleeding due to biliary atresia.

    Science.gov (United States)

    Miyao, Masashi; Abiru, Hitoshi; Ozeki, Munetaka; Kotani, Hirokazu; Tsuruyama, Tatsuaki; Kobayashi, Naho; Omae, Tadaki; Osamura, Toshio; Tamaki, Keiji

    2012-09-10

    Extrahepatic biliary atresia (EHBA) is a rare disease characterized by progressive and obliterative cholangiopathy in infants and is one of the major causes of secondary vitamin K deficiency bleeding (VKDB) due to cholestasis-induced fat malabsorption. Breast feeding increases the tendency of bleeding in EHBA patients because breast milk contains low amounts of vitamin K. A 2-month-old female infant unexpectedly died, with symptoms of vomiting and jaundice prior to death. She had been born by uncomplicated vaginal delivery and exhibited normal growth and development with breastfeeding. There was no history of trauma. She received vitamin K prophylaxis orally. In an emergency hospital, a CT scan showed a right intracranial hematoma and mass effect with midline shift to the left. In the postmortem examination, severe atresia was observed in the whole extrahepatic bile duct. Histologically, cholestasis, periductal fibrosis, and distorted bile ductules were noted. The gallbladder was not identified. A subdural hematoma and cerebellar tonsillar herniation were found; however, no traumatic injury in any part of the body was observed. Together, these findings suggest that the subdural hemorrhage was caused by secondary vitamin K deficiency resulting from a combination of cholestasis-induced fat malabsorption and breastfeeding. Subdural hemorrhage by secondary VKDB sometimes occurs even when vitamin K prophylaxis is continued. This case demonstrated that intrinsic factors, such as secondary VKDB (e.g., EHBA, neonatal hepatitis, chronic diarrhea), should also be considered in infant autopsy cases presenting with subdural hemorrhage.

  19. 妊娠肝内胆汁淤积症患者血清 SOCS3含量检测及其与胎盘中过氧化反应、凋亡过程关系的研究%Detection of serum SOCS3 contents in patients with intrahepatic cholestasis of pregnancy and its correlation with peroxidation response and apoptosis process in placenta

    Institute of Scientific and Technical Information of China (English)

    曾学平; 谭三阳; 赵涛

    2016-01-01

    Objective To study the serum suppressor of cytokine signaling(SOCS)content of patients with intrahepatic cholestasis of pregnancy and analyze its correlation with peroxidation response index and apoptosis index in placenta tissue. Methods 50 cases of intrahepatic cholestasis of pregnancy treated and laboring in our hospital from June 2013 to August 2014 were enrolled as observation group;50 cases of healthy parturient women laboring during the same period were enrolled as control group. Serum was collected and SOCS - 3 content was detected;placen-ta tissue was collected and mRNA contents of survivin,Xiap,Bcl - 2,CCO,SDH,SOD,GSH - Px,CAT,HO - 1 and MDA were detected. Re-sults serum SOCS3 content of observation group was lower than that of control group. mRNA contents of survivin,Xiap,Bcl - 2,CCO and SDH in placenta of observation group were lower than those of control group and were positively correlated with SOCS - 3. SOD,GSH - Px,CAT and HO - 1 contents in placenta tissue of observation group were lower than those of control group and were positively correlated with SOCS - 3. MDA content was higher than that of control group and was negatively correlated with SOCS - 3. Conclusion Serum SOCS3 content of patients with in-trahepatic cholestasis of pregnancy abnormally decreases and may cause occurrence of the disease through participating in the regulation of peroxida-tion response and apoptosis process in placenta.%目的:研究妊娠肝内胆汁淤积症患者血清中细胞因子信号传导负调控因子( SOCS)的含量并分析其与胎盘组织中过氧化反应指标、凋亡指标的相关性。方法选择2013年6月至2014年8月就诊和分娩的妊娠肝内胆汁淤积症患者50例作为观察组,将同期分娩的健康产妇50例作为对照组,采集血清并检测 SOCS -3含量,采集胎盘组织并检测 Survivin、Xiap、Bcl -2、细胞色素 c 氧化酶(CCO)、琥珀酸脱氢酶(SDH)、超氧化物歧化酶(SOD)、谷

  20. 胆汁酸代谢主要调节核受体和相关基因在胆汁淤积孕鼠肝脏中的表达%Expression of FXR mRNA, PPAR alpha mRNA and bile acid metabolism related genes in intrahepatic cholestasis of pregnant rats

    Institute of Scientific and Technical Information of China (English)

    时青云; 林宇庚; 周新; 林颖奇; 闫时

    2010-01-01

    Objective To study the expressions of FXR, PPARα and Bile acid metabolism related genes in intrahepatic cholestasis of pregnant rats. Methods 60 clean SD pregnant rats were selected and divided randomly into three groups. Since the 13th day of pregnancy rats in control group were injected then were treated with fenofibrate for another four days untill the 21th day. All rats were killed at the 21th day and livers were collected for study. The levels of serum TBA were examined by ELISA. The mRNA expressions of PPAR α, FXR, CYP7A1, CYP27A1 and CYP8B1 were examined by real-time PCR. Results (1)The levels of TBA were significantly higher in no-treated group (68.7 ± 4.2) μmol/L and treated group (69.5 ± 3.8) μmol/L compared with that of control group (26.6 ± 2.3) μmol/L at the 17th day (P < 0.05) and no difference found between treated and no-treated groups (P > 0.05). The levels of TBA were higher in notreated group (69.4 ± 3.7) μmol/L and treated group (48.5 ± 4.8) μmol/L as compared to control group (27.1 ± 3.2) μmol/L at the 21th day (P < 0.05). The lever of TBA was significantly lower in Treated group compared with No-treated group (P < 0.05). (2) The mRNA expressions of CYP7A1, FXR, CYP27A1 and CYP8B1 increased in No-treated group (1.55 ± 0.03, 1.75 ± 0.02, 2.45 ± 0.01, 2.15 ± 0.01, respectively)and were all higher as compared to control group (0.75 ± 0.02, 1.25 ± 0.03, 0.65 ± 0.03, 1.50 ± 0.02,respectively) (P < 0.05). However, the mRNA expression of PPAR α decreased in No-treated group (0.85 ±0.02) compared with control group (1.45 ± 0.02) (P < 0.05). The mRNA expressions of CYP27A1, PPAR α and CYP8B1 increased in treated group (1.25 ± 0.01, 1.65 ± 0.05, 1.65 ± 0.02, respectively) and were all higher than that of control group (P < 0.05). Conclusion Abnormal expressions of CYP7A1, FXR, CYP27A1,CYP8B1 and PPARα may play a role in pathogenesis of estrogen-induced intrahepatic cholestasis. Activator of PPAR α may be used

  1. Effect of InsR/FoxO1 on the expression of POMC in the hypothalamus of intrahepatic cholestasis of pregnancy rats offspring%InsR/FoxO1信号通路对妊娠胆汁淤积症子代大鼠下丘脑中POMC表达的影响

    Institute of Scientific and Technical Information of China (English)

    闫时; 王晶晶; 宋昭逸; 时青云

    2015-01-01

    Objective:To study the effect of InsR/FoxO1 on the expression of POMC in the hypothalamus of the intrahepatic cholestasis of pregnancy rats offspring. Methods:40 clean SD pregnant rats were selected and divided into two groups at random,20 in every group. Since the 13th day of pregnancy,Control group was injected subcutaneously with refined vegetable oil 2 . 0 ml/( kg · d ) , ICP group was injected subcutaneously with the 17-α-ethynylestradio ( EE ) 1 . 0 mg/( kg · d ) . 20 Female 0 ffspring in both ICP group and control group were selected at random and feed to six months. At the 24 weeks of age,offspring underwent a glucose tolerance test. All rats were killed at the six months. The mRNA of InsR、FoxO1 and POMC in hypothala-mus were examined by real-time PCR and western blot. The expression of POMC in hypothalam-ic arcuate of 6 months offspring was also examined by immunohistochemistry. Result:The glu-cose values of female in ICP group were higher than that of control group offspring(P<0. 05).The mRNA expressions of InsR、FoxO1 and POMC in hypothalamus in ICP group offspring were different with control offspring at six months ( P<0 . 05 ) . The positive cells of POMC in hypotha-lamic arcuate in ICP group were little than that control group. Conclusion:Bile acid levers is higher in ICP group. The bad intrauterine environment may be a major contributor to change of InsR/FoxO1 and POMC decreased. ICP offspring showed a hunger state and then gained weight.%目的:探讨胰岛素受体(InsR)/胰岛素调节转录因子(FoxO1)信号通路对妊娠肝内胆汁淤积症出生后6 个月子代大鼠下丘脑中阿片-促黑素细胞皮质素原( POMC )表达的影响. 方法:40只清洁级SD孕鼠随机分为2组,每组20只. 孕第13天时,对照组孕鼠皮下注射精制植物油2. 0ml/(kg·d),ICP组孕鼠皮下注射17-α-乙炔雌二醇1. 0 mg/( kg·d) ,直至孕21天. 从ICP组和对照组出生子代中各随机选取雌性20只喂养至6月龄.

  2. Clinical analysis of risk factors of parenteral nutrition-associated cholestasis in very low birthweight infants%极低出生体质量儿胃肠外营养相关性胆汁淤积危险因素临床分析

    Institute of Scientific and Technical Information of China (English)

    杨军; 李水霞; 陈莉娜

    2015-01-01

    Objective To investigate the risk factors of parenteral nutrition-associated cholestasis (PNAC)in very low birth weight infants (VLBWI).Methods VLBWI who were accorded with inclusion and exclusion criteria of this study:treatment for parenteral nutrition (PN)for over 14 days in West China Second University Hospital of Sichuan University from May 2008 to May 2014 were chosen as study subjects.By retrospectively analyzed method,they were divided into PNAC group and non PNAC group according to whether suflered from PNAC or not.First of all,according to the clinical experience,the influence factors of PNAC were identified and carried on the single factor analysis,then comprehensively considered with statistically significant variables and professional knowledge,multiple factors unconditional logistic regression analysis method was used to further analyze the independent and risk factors of PNAC. Results ① A total of 1 72 cases of VLBWI were chosen as study subjects finally.According to whether suffered from PNAC or not,they were divided into PNAC group (n=29)and non PNAC group (n=143), and the incidence of PNAC was 1 6.9%.There were no significant differences between two groups among gender ratio,gestational age at delivery and mode of delivery,etc.(P > 0.05 ).② According to clinical experience,the single factor analysis results about 27 clinical observation items and 1 9 nutritional factors which may lead to PNAC showed that 8 clinical observation items and 5 nutritional factors were influence factors of PNAC,such as VLBWI,less than appropriate for gestational age (SGA),long fasting time and longer duration of PN,higher amino acid and fat emulsion calories,milk lower calories,higher neonatal infections,such as infectious pneumonia,sepsis,neonatal necrotizing enterocolitis (NEC)and septic shock rate,lower breastfeeding and oral probiotics rate,and all the differences were statistically significant (t/χ2 =3.306,3.306,1.790,1.231,3.1 93,2.81 5,2.5 1 9,4.61 5,3

  3. The Pitfalls of Febrile Jaundice. A Case Report

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    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.

  4. Unusual duodenal perforation following endoscopic retrograde cholangiopancreatography

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    Martin Kobborg

    2011-02-01

    Full Text Available Perforation is a known but rare complication to Endoscopic retrograde cholangiopancreatography (ERCP with endoscopic sphincterotomy (ES. Most of the perforations are located in the periampullary area due to ES. This report presents an unusual perforation in the third part of the duodenum following ES. The patient an eigthy-sixt-year-old man underwent ERCP with ES. The patient had Magnetic Resonance Cholangio-pancreatography (MRCP and Computerized Tomography (CT verified cholelithiasis and intra- and extrahepatic cholestasis. The perforation was not found under the ERCP procedure but was clinically revealed when the patient developed pneumoscrotum after the procedure. A CT-scan with oral contrast later confirmed the duodenal perforation.

  5. 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

  6. Clinical characteristics and the incidence of extrahepatic autoimmune disease and malignant tumor in primary biliary cirrhosis-autoimmune hepatitis overlap syndrome%原发性胆汁性肝硬化-自身免疫性肝炎重叠综合征的临床病理特征及肝外自身免疫性疾病和恶性肿瘤的发生情况

    Institute of Scientific and Technical Information of China (English)

    杨蜜蜜; 周璐; 林睿; 张洁; 王邦茂

    2013-01-01

    能伴发的自身免疫性疾病和恶性肿瘤.影像学检查存在腹腔淋巴结肿大可能对PBC-AIHOS的诊断有指导意义.%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,immunological parameters,liver histopathological features,the incidence of extrahepatic autoimmune disease and malignant tumor,imaging findings and the efficacy.Results Among 49 PBC-AIH OS patients,the percentage of patients between 51 and 60 years old was 59.2% (29/49),and the mean age of onset was (57.2±8.9) years old.Female was 83.7% (41/49).The percentage of jaundice and pruritus in the main symptoms of initial visit was 42.9% (21/49).The serum level of alanine aminotransferase (ALT),aspartate transaminase (AST),alkaline phosphatase (ALP),γ-glutamyl transpeptadase (GGT) and total bilirubin (TBil) of 49 patients all increased.Among 31 patients who accepted IgA,IgG and IgM level test,the level of IgM increased in 58.1% (18/31) of patients,and the level of IgG increased in 61.3% (19/31) of patients.Ninety-eight percent of patients were antinuclear antibody (ANA) positive,6.1 % (3/49) were anti-smooth muscle antibody (SMA) positive,89.8% (44/49) of patients were anti mitochondrial antibody (AMA) and or AMA-M2 positive.All patients had interface hepatitis.Forty-nine percent (24/49) of patients had both histological features of autoimmune hepatitis (AIH) and primary biliray cirrhosis (PBC).After being treated with ursodeoxycholic acid (UDCA) and immunosuppressant,the percentage of remission,incomplete response and failure was 65.3% (32/49),26.5% (13/49) and 8.2

  7. Isolated Liver Hilar Infiltration by IgG4 Inflammation Mimicking Cholangiocarcinoma

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    Laurent Bochatay

    2016-10-01

    Full Text Available IgG4-related disease represents a heterogeneous group of disease characterized by infiltration of various tissues by IgG4 plasmocytes. In case of liver infiltration, this condition classically mimics primary sclerosing cholangitis or multifocal cholangiocarcinoma due to inflammation that preferentially affects the intra- and extrahepatic bile duct. Diagnostic criteria have recently been reviewed in order to better define the disease and help physicians make the diagnosis. Herein, we present the case of a patient who died after liver surgery for suspected cholangiocarcinoma that finally turned out to be IgG4-associated liver disease, a condition being out of current consensual criteria. The patient presented with progressive cholestasis identified by MR cholangiography as an isolated hilar mass responsible for dilatation of the left and right intrahepatic bile duct suspicious for a Klatskin tumor. The IgG4 blood level was normal as was biliary cytology. The patient underwent right portal embolization followed by right extended hepatectomy. Pathologic examination found no tumor but intense fibrosclerotic infiltration with a marked inflammatory infiltrate characterized by IgG4-positive plasmocytes. Despite immunosuppressive treatment, cholestasis was never controlled and successive biopsies of the remaining liver showed progressive cholestasis, liver infiltrate and no bile duct regeneration. The patient finally presented an upper gastrointestinal hemorrhage leading to death 4 months after hepatectomy and appropriate immunosuppressive therapy.

  8. Isolated Liver Hilar Infiltration by IgG4 Inflammation Mimicking Cholangiocarcinoma

    Science.gov (United States)

    Bochatay, Laurent; Majno, Pietro; Giostra, Emiliano; Frossard, Jean Louis

    2016-01-01

    IgG4-related disease represents a heterogeneous group of disease characterized by infiltration of various tissues by IgG4 plasmocytes. In case of liver infiltration, this condition classically mimics primary sclerosing cholangitis or multifocal cholangiocarcinoma due to inflammation that preferentially affects the intra- and extrahepatic bile duct. Diagnostic criteria have recently been reviewed in order to better define the disease and help physicians make the diagnosis. Herein, we present the case of a patient who died after liver surgery for suspected cholangiocarcinoma that finally turned out to be IgG4-associated liver disease, a condition being out of current consensual criteria. The patient presented with progressive cholestasis identified by MR cholangiography as an isolated hilar mass responsible for dilatation of the left and right intrahepatic bile duct suspicious for a Klatskin tumor. The IgG4 blood level was normal as was biliary cytology. The patient underwent right portal embolization followed by right extended hepatectomy. Pathologic examination found no tumor but intense fibrosclerotic infiltration with a marked inflammatory infiltrate characterized by IgG4-positive plasmocytes. Despite immunosuppressive treatment, cholestasis was never controlled and successive biopsies of the remaining liver showed progressive cholestasis, liver infiltrate and no bile duct regeneration. The patient finally presented an upper gastrointestinal hemorrhage leading to death 4 months after hepatectomy and appropriate immunosuppressive therapy. PMID:27843427

  9. {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.)

  10. Interaction among peroxisome proliferators-activated receptor alpha, cytochrome P450 oxysterol 7α-hydroxylase and estrogen receptor and its association with intrahepatic cholestasis in pregnant rats%过氧化物酶增殖体激活受体α、氧固醇7α羟化酶及雌激素受体间调控关系及其与孕鼠肝内胆汁淤积发生的相关性

    Institute of Scientific and Technical Information of China (English)

    时青云; 林宇庚; 周新; 林颖奇; 闫时

    2010-01-01

    Objective To investigate the relationship between interaction of peroxisome proliferators-activated receptor alpha (PPARα), cytochrome P450 oxysterol 7α-hydroxylase (CYP7B1) and estrogen receptor (ER) and intrahepatic cholestasis in pregnant rats. Methods Eighty clean SD pregnant rats were selected and divided into four groups randomly with 20 in each. Since the 13th day of pregnancy,rats in the control group was injected subcutaneously with refined vegetable oil 2.0 ml · kg-1 · d -1 , those in the low-dose, moderate-dose and high-dose groups received 17-α-ethynylestradiol (EE) 1.0 mg · kg-1 · d-1,1.25 mg · kg-1 · d-1 and 1.5 mg · kg-1 · d-1, respectively. All rats were sacrificed at the 21at day of pregnancy and maternal hepatic tissues were collected. The serum levels of alanine aminotransferase(ALT), aspartate transaminase (AST), total bile acid (TBA) and bilirubin (BIL) were determined by enzyme linked immunosorbent assay (ELISA). The mRNA expressions of PPARα, CYP7B1, Erα and Erβ in maternal rat livers were examined by real-time PCR. Results (1) Biochemical indicators: the serum levels of ALT,AST, TBA and BIL were significantly lower in the control group than in the rest 3 groups,respectively [ control group: (41.1 ± 2.8 ) U/L, (44.4 ± 3.6) U/L, (26.4 ± 5.6 ) μmol/L and( 2.8 ± 0.2)U/L;low-dose group: (48.2 ±3.4) U/L,(47.9 ±3.7) U/L,(36.4 ±4.2) μmol/L and (4.2 ±0.2) U/L;moderate-dose group: (70.4 ± 5.3 ) U/L, (68.4 ± 5.6) U/L, (64.3 ± 3.8 ) μmol/L and ( 6.2 ± 1.2)U/L; high-dose group: (72.4 ±7.6) U/L, (70.2 ±3.8) U/L, (72.4 ±7.8) μmol/L and (8.2 ±2.2)U/L, P 0.05 ). (3) mRNA expression of CYP7B1 and PPARα: the mRNA expression of CYP7B1 in pregnant rat livers increased from the low-dose group to the high-dose group, and were all higher than that of the control group ( low-dose group: 0.93 ± 0.01; moderate-dose group: 0.99 ±0.06; high-dose group: 1.22 ± 0.04; control group: 0.75 ± 0.02, P 0.05).(3)CYP7B1 mRNA及PPARα m

  11. 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.

  12. Comparative hepatic and extrahepatic enantioselective sulfoxidation of albendazole and fenbendazole in sheep and cattle.

    Science.gov (United States)

    Virkel, G; Lifschitz, A; Sallovitz, J; Pis, A; Lanusse, C

    2004-05-01

    The enantioselective sulfoxidation of the prochiral anthelmintic compounds albendazole (ABZ) and fenbendazole (FBZ) was investigated in liver, lung and small intestinal microsomes obtained from healthy sheep and cattle. The microsomal fractions were incubated with a 40 microM concentration of either ABZ or FBZ. Inhibition of the flavin-containing monooxygenase (FMO) system was carried out by preincubation with 100 microM methimazole (MTZ) either with or without heat pretreatment (2 min at 50 degrees C). ABZ and FBZ were metabolized to the (+) and (-) enantiomers of their sulfoxide metabolites, named albendazole sulfoxide (ABZSO) and oxfendazole (OFZ), respectively. ABZ sulfoxidation rates were higher (p < 0.001) than those observed for FBZ. The FMO-mediated liver sulfoxidation of ABZ was enantioselective (100%) toward the (+) ABZSO production in both species. Liver sulfoxidation of FBZ by FMO was also enantioselective toward (+) OFZ (sheep = 65%; cattle = 79%). Cytochrome P450 was found to be mainly involved in the production of (-) ABZSO in the liver. MTZ did not affect the sulfoxidation of ABZ by lung microsomes, which may indicate that FMO is not involved in the production of ABZSO in this tissue. A significant (p < 0.05) inhibition of (-) ABZSO production by liver microsomes was observed after ABZ incubation in the presence of erythromycin (cattle = 21%) and ketoconazole (sheep = 36%). Both CYP3A substrates induced a reduction in the production of (-) ABZSO (sheep = 67-78%, cattle = 50-78%) by lung microsomes. Overall, the results reported here contribute to the identification of the metabolic pathways involved in the biotransformation of benzimidazole anthelmintics extensively used for parasite control in ruminants.

  13. A physiologically based pharmacokinetic (PB-PK) model for ethylene dibromide; relevance of extrahepatic metabolism

    NARCIS (Netherlands)

    Hissink, A.M.; Wormhoudt, L.W.; Sherratt, P.J.; Hayes, J.D.; Commandeur, J.N.M.; Vermeulen, N.P.E.; Bladeren, van P.J.

    2000-01-01

    A physiologically-based pharmacokinetic (PB-PK) model was developed for ethylene dibromide (1,2-dibromoethane, EDB) for rats and humans, partly based on previously published in vitro data (Ploemen et al., 1997). In the present study, this PB-PK model has been validated for the rat. In addition, new

  14. 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.

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

    Institute of Scientific and Technical Information of China (English)

    江正辉

    2000-01-01

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

  16. Cryoglobulinemic glomerulonephritis: an extrahepatic manifestation of hepatitis C virus (HCV infection

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    Giovanni Garini

    2007-12-01

    Full Text Available A 66-year-old woman was admitted to our Department for evaluation of a nephrotic syndrome. Physical examination revealed ankle edema, palpable purpura of the legs and hypertension. There was no hepatosplenomegaly. The main laboratory findings were haemoglobin 11.4 g/dl, serum creatinine 1.4 mg/dl, proteinuria 3.5 g/day with reduced serum albumin (3.1 g/dl, rheumatoid factor (RF activity 125 IU/ml, and serum C4 levels 2.3 mg/dl. Cryocrit was 24%, with type II (IgG-IgM-κ cryoglobulins. The patient was positive for HCV antibodies and serum HCV RNA; the genotype was 1b. A percutaneous renal biopsy showed a cryoglobulinemic membranoproliferative glomerulonephritis with moderate histologic severity. The primary goal in patients with mild-to-moderate disease is viral clearance, so combination therapy with interferon-α (3 MU thrice weekly and ribavirin (800 mg/day was started. Twelve weeks later, serum HCV RNA had disappeared, a result that was confirmed at the end of antiviral therapy in week 48, and during the post-treatment follow-up. Proteinuria returned to the normal range, cryoglobulins decreased to undetectable levels and serum C4 levels normalized. RF activity decreased, but remained above normal. The message provided by this illustrative case is that antiviral therapy represents the first-line treatment for HCV-related cryoglobulinemic patients with mild-to-moderate kidney involvement, because it provides the best chance of viral clearance and subsequent disease improvement.

  17. Endoscopic treatment of difficult extrahepatic bile ductstones, EPBD or EST: An anatomic view

    Institute of Scientific and Technical Information of China (English)

    Jun Ding; Fu Li; Hong-Yi Zhu; Xi-Wen Zhang

    2015-01-01

    Large bile duct stone (〉 10 mm) or multiple stones(≥ 3) are challenging for endoscopists. Endoscopicsphincterotomy (EST) is a routine therapeutic endoscopicretrograde cholangiopancreatography (ERCP) procedureusually used. It is safe and effective, but severeperforation or massive bleeding are the main causesof mortality. Because of the permanent destroy ofOddi sphincter, the use of EST is still controversial.Endoscopic papillary balloon dilation (EPBD) givesanother way to open the sphincter. Less incidence ofbleeding, perforation and partly preserving the Oddisphincter's function are the main advantages. Buthigh incidence of post-ERCP pancreatitis becomes apredominant problem. According to the anatomicalfeature of Oddi sphincter, limited EST + EPBD seems amore reasonable procedure. Compared to the formertwo procedures, it makes the stone extraction processmuch easier with lower incidences of short-term andlong-term complications.

  18. A journey towards an extrahepatic islets delivery device with a tissue engineering toolbox in hand

    NARCIS (Netherlands)

    Marchioli, Giulia

    2017-01-01

    Type one diabetes affects 542’000 children per year worldwide and heavily worsens the quality of life of these young patients and their families. In addition to this, diabetes also accounts for substantial costs on national healthcare systems. An emerging treatment for managing unbalanced glucose me

  19. Extrahepatic portal venous obstruction: The effects of early ligation of splenic artery during splenectomy

    Directory of Open Access Journals (Sweden)

    Gazula Suhasini

    2009-01-01

    Full Text Available Aim: To objectively demonstrate the gain in blood volume and blood components following early ligation of splenic artery during splenectomy and splenorenal shunts in children with extra hepatic portal venous obstruction (EHPVO. Methods: Twenty-eight children (20 males and 8 females, mean age: 9.9 (±3.2 years with EHPVO and hypersplenism were recruited. We followed a protocol of systematically locating and ligating the splenic artery first, followed by a 30-minute waiting period to allow the massive spleen to decongest via the splenic vein and venous collaterals and then completing the splenectomy by standard procedure. No intravenous fluid was administered during this 30-minute period. Blood samples were drawn just prior to splenic artery ligation and soon after splenectomy for the estimation of hematological and biochemical parameters. Results: We noticed a highly significant increase in the hemoglobin, hematocrit, leukocyte, platelet, and RBC counts by early ligation of the splenic artery (p < 0.0004. The gain in hemoglobin and hematocrit was equivalent to a transfusion of atleast 100-150 ml of packed RBC. The increase in platelet count was equivalent to a platelet transfusion of atleast 4 units of platelet concentrates in an adult. There is a positive correlation between the splenic weight and the platelet gain (p= 0.0568 and the splenic volume on preoperative imaging and the platelet gain (p= 0.0251. Conclusion: Early ligation of the splenic artery during splenectomy results in passive splenic decongestion and thereby a significant gain in blood components. This protocol appears to be a feasible blood conservation method to avoid blood transfusions in this group of hypersplenic EHPVO patients.

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  1. Treatment of extrahepatic manifestations of chronic hepatitis C viral infection--a challenge.

    Science.gov (United States)

    Tănăsescu, C; Ionescu, R

    2010-01-01

    Often, chronic hepatitis C infection is clinically manifested as extra hepatic disease. Therapy of the extra hepatic manifestations (EHM) is always difficult and based on the optimal and individual association of antiviral treatment, immunosuppressant and plasma cleaning techniques. We observed for 4 years 246 patients admitted to "Colentina" Internal Medicine Clinic, of whom 168 were diagnosed as chronic C hepatitis. 130 of those patients have had at least one EHM. In our experience, the presence of an EHM is significantly correlated with lack of early viral response and sustained viral response, as well. Cryoglobulinemic vasculitis needs to be treated with oral or pulse corticotherapy associated to plasmapheresis. When present, peripheral neuropathy and cryocrit greater than 10% are indicators of need of more than 3 plasmapheresis sessions.

  2. Thymic cyst haemorrhages and transient cholestasis in a 4-week-old infant

    NARCIS (Netherlands)

    Koopman, LP; Plotz, FB; Meuzelaar, JJ; Knoester, H

    1998-01-01

    We report a 4-week-old boy with acute respiratory distress, due to massive haemorrhages in multiple thymic cysts. A right hemithymectomy was performed because of mechanical obstruction of the trachea by the cysts. The origin of the multilocular thymic cysts remained unclear. Most likely, these haemo

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

    Directory of Open Access Journals (Sweden)

    Mohammad Eshagh Roze

    2012-07-01

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

  4. A STUDY ON DETECTION OF SERUMFASTING TOTAL BILE ACID AND CHOLOYGLYCIN IN NEONATE FOR CHOLESTASIS

    Institute of Scientific and Technical Information of China (English)

    郭文; 吴明昌; 裴学义; 关德华; 徐洛

    1996-01-01

    Enzyme-linked colorimetric analysis and radioimmunossay were employed to detect serum fasting total bile acids(FBA) and choloyglyein (CG) respectively in eases of 32 neonatal hepatitis, 33 cases of neona-tal uneonjugated hyperbilirubinemia and 34 cases of breast milk jaundice(BMJ). FBA and CG in acute period of neonatal hepatitis were obviously elevated and decreased gradually in convalescent and recovered period. The difference was significant for each stage as compared with controls. Acute FBA correlated strongly with the course. Both neonatal unconjugated hyperbilirubinemia and BMJ differed significantlyfrom controls in FBA and CG. The results suggested that serum FBA and CGr were helpful in judging the course and state of neonatal hepatitis, and eholestasls might existed in neonatal unconjngated hyperbilirubinemia.

  5. Prolonged intrahepatic cholestasis and renal failure secondary to anabolic androgenic steroid-enriched dietary supplements.

    Science.gov (United States)

    Krishnan, Prashant V; Feng, Zhen-Zhou; Gordon, Stuart C

    2009-08-01

    The illegal enrichment of anabolic androgenic steroids in over-the-counter dietary supplements is well documented, but the health consequences have not been widely recognized. Three recent reports document cholestatic jaundice and nephropathy due to these compounds. We present 3 additional cases of anabolic androgenic steroid-enriched dietary supplement-induced hepatotoxicity and 1 case of renal failure, and we review the literature and the relevant features of this growing health concern. Recognition of this entity could obviate the need for invasive diagnostic testing and hospitalization and facilitate diagnosis and appropriate counseling.

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

  8. Diagnosis of cholestasis%胆汁淤积的诊断

    Institute of Scientific and Technical Information of China (English)

    陶小红

    2008-01-01

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

  9. [Development of vibration-induced intrahepatic cholestasis in pilots and new ways of correcting these disorders].

    Science.gov (United States)

    Preobrazhenskiĭ, V N; Vasilenko, V V; Taianovskiĭ, V Iu

    1999-01-01

    Data of analysis of the role of vibration in the development of hepatobiliary pathology in helicopter pilots are reported. Vibration was found to drastically deteriorate colloid-osmotic qualities of the bile and increase the lithogenesis risk. Exposure to vibration over 10 and more years of the flying career may instigate cholelithiasis. Dynamic USI with functional testing for early diagnostics and correction with ursodeoxycholic acid (ursosan) of disorders in the colloid-osmotic properties of the bile and can be proposed as one of the methods to prevent cholelithiasis.

  10. Glucocorticosteroids for primary sclerosing cholangitis

    DEFF Research Database (Denmark)

    Giljaca, Vanja; Poropat, Goran; Stimac, Davor

    2010-01-01

    Primary sclerosing cholangitis is a chronic cholestatic disease of intrahepatic and extrahepatic biliary ducts, characterised by chronic periductal inflammation and sclerosis of the ducts, which results in segmental stenoses of bile ducts, cholestasis, fibrosis, and ultimately, liver cirrhosis....... Patients with primary sclerosing cholangitis are at higher risk of cholangiocarcinoma as well as of colonic neoplasia, since primary sclerosing cholangitis is associated with inflammatory bowel disease in more than 80% of the patients. Several therapeutic modalities have been proposed for primary...... sclerosing cholangitis, like ursodeoxycholic acid, glucocorticosteroids, and immunomodulatory agents, but none has been successful in reversing the process of the disease. To date, liver transplantation is the only definite therapeutic solution for patients with advanced primary sclerosing cholangitis...

  11. Common bile duct schwannoma: A case report and review of literature

    Institute of Scientific and Technical Information of China (English)

    Luigi Fenoglio; Rodolfo Brizio; Felice Borghi; Sara Severini; Paola Cena; Elena Migliore; Christian Bracco; Fulvio Pomero; Sergio Panzone; Giovan Battista Cavallero; Alberto Silvestri

    2007-01-01

    Schwannoma is a myelin sheath tumor complicated with neurofibroma, neurofibromatosis and neurogenic sarcoma. Peripheral nerve sheath tumors represent 2%-6% of gastrointestinal tract stromal tumors (GIST),but there are deficient data about location of neurogenic tumors in the biliary system and only nine cases of schwannoma of the extrahepatic biliary tract have been reported. These tumors are clinically non-specific. They are usually symptomatic by compressing the close or adjacent structures when being retroperitoneal, and their preoperative diagnosis is extremely difficult. This paper reviews the literature data and describes a case of schwannoma of the common bile duct associated with cholestasis in a healthy young woman, diagnosed and treated in our department. This case is of interest on account of the complexity of its diagnosis and the atypical macroscopic growth pattern of the tumor.

  12. Melatonin prevents brain oxidative stress induced by obstructive jaundice in rats.

    Science.gov (United States)

    Cruz, Adolfo; Túnez, Isaac; Martínez, Rubén; Muñoz-Castañeda, Juan Rafael; Ramírez, Luz María; Recio, Marta; Ochoa, Luís; Arjona, Alvaro; Montilla, Pedro; Muntané, Jordi; Padillo, Francisco J

    2007-12-01

    The aim of the study was to analyze the impact of melatonin on brain oxidative stress in experimental biliary obstruction. Cholestasis was done by a double ligature and section of the extrahepatic biliary duct. Melatonin was injected intraperitoneally (500 microg/kg/day). Malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) contents were determined in the brain tissue. Biliary obstruction raised MDA and reduced GSH contents in the cortex, cerebellum, and hypothalamus areas. Moreover, the scavenger enzyme activity significantly dropped in all areas of the brain. Melatonin drastically reduced MDA concentration and enhanced GSH concentration, as well as all antioxidant enzyme activity in all brain areas obtained from the bile duct-ligated animals. In conclusion, the treatment with melatonin decreased lipid peroxidation and recovered the antioxidant status in the brain from cholestatic animals.

  13. The Sea Lamprey as an Etiological Model for Biliary Atresia

    Directory of Open Access Journals (Sweden)

    Yu-Wen Chung-Davidson

    2015-01-01

    Full Text Available Biliary atresia (BA is a progressive, inflammatory, and fibrosclerosing cholangiopathy in infants that results in obstruction of both extrahepatic and intrahepatic bile ducts. It is the most common cause for pediatric liver transplantation. In contrast, the sea lamprey undergoes developmental BA with transient cholestasis and fibrosis during metamorphosis, but emerges as a fecund adult with steatohepatitis and fibrosis in the liver. In this paper, we present new histological evidence and compare the sea lamprey to existing animal models to highlight the advantages and possible limitations of using the sea lamprey to study the etiology and compensatory mechanisms of BA and other liver diseases. Understanding the signaling factors and genetic networks underlying lamprey BA can provide insights into BA etiology and possible targets to prevent biliary degeneration and to clear fibrosis. In addition, information from lamprey BA can be used to develop adjunct treatments for patients awaiting or receiving surgical treatments. Furthermore, the cholestatic adult lamprey has unique adaptive mechanisms that can be used to explore potential treatments for cholestasis and nonalcoholic steatohepatitis (NASH.

  14. 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.

  15. Human leukocyte antigen class II transgenic mouse model unmasks the significant extrahepatic pathology in toxic shock syndrome.

    Science.gov (United States)

    Tilahun, Ashenafi Y; Marietta, Eric V; Wu, Tsung-Teh; Patel, Robin; David, Chella S; Rajagopalan, Govindarajan

    2011-06-01

    Among the exotoxins produced by Staphylococcus aureus and Streptococcus pyogenes, the superantigens (SAgs) are the most potent T-cell activators known to date. SAgs are implicated in several serious diseases including toxic shock syndrome (TSS), Kawasaki disease, and sepsis. However, the immunopathogenesis of TSS and other diseases involving SAgs are still not completely understood. The commonly used conventional laboratory mouse strains do not respond robustly to SAgs in vivo. Therefore, they must be artificially rendered susceptible to TSS by using sensitizing agents such as d-galactosamine (d-galN), which skews the disease exclusively to the liver and, hence, is not representative of the disease in humans. SAg-induced TSS was characterized using transgenic mice expressing HLA class II molecules that are extremely susceptible to TSS without d-galN. HLA-DR3 transgenic mice recapitulated TSS in humans with extensive multiple-organ inflammation affecting the lung, liver, kidneys, heart, and small intestines. Heavy infiltration with T lymphocytes (both CD4(+) and CD8+), neutrophils, and macrophages was noted. In particular, the pathologic changes in the small intestines were extensive and accompanied by significantly altered absorptive functions of the enterocytes. In contrast to massive liver failure alone in the d-galN sensitization model of TSS, findings of the present study suggest that gut dysfunction might be a key pathogenic event that leads to high morbidity and mortality in humans with TSS.

  16. 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.

  17. 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.

  18. Isolated extrahepatic bile duct rupture: a rare consequence of blunt abdominal trauma. Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Balzarotti Ruben

    2012-05-01

    Full Text Available Abstract A 16-year-old girl suffered blunt abdominal trauma. Clinically, a severe motor impairment with paraesthesia of the legs was found. Posterior osteosynthesis in T10-L1 with laminectomy in T10-T12 and posterolateral arthrodesis in T11-T12 was performed because of a dorsal traumatic vertebral fracture. On hospital day 7, because of an acute abdomen, surgical laparoscopic exploration showed sterile bloody fluid without any evident hemorrhagic injury. On hospital day 11, the patient was reoperated on by the laparoscopic approach for increasing abdominal pain and fever: a peritoneal biliary fluid was aspirated. After conversion to open surgery, cholecystectomy was performed. Intraoperative cholangiography was considered as normal. On arrival at our institution 13 days after injury, the patient was operated on for a biliary peritonitis. Intraoperatively, a trans-cystic cholangiography showed a biliary leakage of the common bile duct; a T-tube was placed into the common bile duct; a subhepatic drainage was placed too. On postoperative day 30, a T-tube cholangiography showed a normal biliary tree, without any leakage, and the T-tube was subsequently removed. The patient had a complete recovery.

  19. 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.

  20. Hepatitis C virus as a multifaceted disease: a simple and updated approach for extrahepatic manifestations of hepatitis C virus infection.

    Science.gov (United States)

    Khattab, Mahmoud Aboelneen; Eslam, Mohammed; Alavian, Seyed Moayed

    2010-01-01

    Hepatitis C virus infection is an emerging disease and a public health problem in the world. There are accumulating data regarding extra hepatic manifestation of HCV, such as rheumatologic manifestations, endocrine, hematologic, dermatologic, renal, neurologic, and systemic manifestations. The therapy of them needs more attention to some exacerbations of extra hepatic manifestation and in some situation it needs different approaches. In this review we tried to provide latest evidence for extra hepatic manifestation and management of them.

  1. Evaluation of the Potential Impact of Inhibition of Trichloroethylene Metabolism in the Liver on Extra-Hepatic Toxicity

    Science.gov (United States)

    The interaction between trichloroethylene (TCE) and chloroform (CHCI3) is less than additive, with co-exposure to TCE and CHCl3 resulting in less hepatic and renal toxicity than observed with CHCl3 alone. Vapor uptake data demonstrate that co-exposure to CHCl3 decreases the rate ...

  2. 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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mehmet Tuncay

    2014-01-01

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

  5. Rescue of defective ATP8B1 trafficking by CFTR correctors as a therapeutic strategy for familial intrahepatic cholestasis

    DEFF Research Database (Denmark)

    van der Woerd, Wendy L; Wichers, Catharina G K; Vestergaard, Anna L;

    2016-01-01

    in cystic fibrosis transmembrane conductance regulator (CFTR), associated with cystic fibrosis, impair protein folding and trafficking. The aim of this study was to investigate whether compounds that rescue CFTR F508del trafficking are capable of improving p.I661T-ATP8B1 plasma membrane expression. METHODS...... functionality. Combination therapy of SAHA and compound C4 resulted in an additional improvement of ATP8B1 cell surface abundance. CONCLUSIONS: This study shows that several CFTR correctors can improve trafficking of p.I661T-ATP8B1 to the plasma membrane in vitro. Hence, these compounds may be suitable...... in other protein folding diseases. Using these compounds, we could indeed show improved trafficking to the (apical) plasma membrane of a mutated ATP8B1 protein, carrying the p.I661T missense mutation. This is the most frequently identified mutation in this rare cholestatic disorder. Importantly, ATP8B1...

  6. 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

  7. [Animal experiments with 99mTc-diethyl-HIDA in acute complete bile duct occlusion (author's transl)].

    Science.gov (United States)

    Bähre, M; Biersack, H J; Breuel, H P; Degen, H; Busch, F; Grouls, V; Lindstaedt, H; Thelen, M

    1979-10-01

    In order to establish whether a complete obstructive jaundice can abolish the accumulation of diethyl-HIDA (EHIDA) in the liver parenchyma, the common bile duct was ligated in 14 mongrel dogs. Before as well as at regular intervals after ligature of the common bile duct, a sequence scintigraphy was performed with 2 mCi 99mTc-EHIDA. For evaluation, time-activity curves (Tmax, T1/2), and analogue scintigrams as well as laboratory parameters were used for assessment. Up to seven weeks after ligation of the common bile duct, there was a marked accumulation of EHIDA in the liver parenchyma. The relative liver uptake (liver/background ratio) fell from 8.9 to 2.7, whereas conversely the cholestasis indicators aP and bilirubine rose markedly. Tmax did not show any significant alterations, whereas T1/2 was prolonged from about one week after ligation. Because of the duct ligation, there was no excretion of activity into the intestines. Immediately after ligation of the common bile duct, the gallbladder was shown up as a "hot" area in which the majority of the applied activity appeared from about one hour p.i. Begining with the fifth to the seventh day after ligation, the gallbladder was seen as a "cold" area in the liver paraenchyma. Bilirubine and aP were raised by about 50 times the initial value. With longer lasting cholestasis, the scintigram no longer altered whereas bilirubine and aP rose further. Histological examination after ligation for more than five weeks showed slight alterations as a whole. Gamma-GT and in particular GPT were likewise slightly raised compared to bilirubine and aP. The conclusion was drawn from this that the good accumulation of EHIDA in the liver parenchyma which is to be observed without exception even in cholestasis lasting for several weeks could be explained by a relatively slight hepatocellular damage. Only when there is a consecutive parenchymal damage in extrahepatic jaundice, accumulation of EHIDA in the liver can be abolished.

  8. 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

  9. 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.

  10. A nontumorigenic variant of FGF19 treats cholestatic liver diseases.

    Science.gov (United States)

    Luo, Jian; Ko, Brian; Elliott, Michael; Zhou, Mei; Lindhout, Darrin A; Phung, Van; To, Carmen; Learned, R Marc; Tian, Hui; DePaoli, Alex M; Ling, Lei

    2014-07-30

    Hepatic accumulation of bile acids is central to the pathogenesis of cholestatic liver diseases. Endocrine hormone fibroblast growth factor 19 (FGF19) may reduce hepatic bile acid levels through modulation of bile acid synthesis and prevent subsequent liver damage. However, FGF19 has also been implicated in hepatocellular carcinogenesis, and consequently, the potential risk from prolonged exposure to supraphysiological levels of the hormone represents a major hurdle for developing an FGF19-based therapy. We describe a nontumorigenic FGF19 variant, M70, which regulates bile acid metabolism and, through inhibition of bile acid synthesis and reduction of excess hepatic bile acid accumulation, protects mice from liver injury induced by either extrahepatic or intrahepatic cholestasis. Administration of M70 in healthy human volunteers potently reduces serum levels of 7α-hydroxy-4-cholesten-3-one, a surrogate marker for the hepatic activity of cholesterol 7α-hydroxylase (CYP7A1), the enzyme responsible for catalyzing the first and rate-limiting step in the classical bile acid synthetic pathway. This study provides direct evidence for the regulation of bile acid metabolism by FGF19 pathway in humans. On the basis of these results, the development of nontumorigenic FGF19 variants capable of modulating CYP7A1 expression represents an effective approach for the prevention and treatment of cholestatic liver diseases as well as potentially for other disorders associated with bile acid dysregulation.

  11. Obstructive jaundice activates nitroxidergic neurons of the vago-vagal neural circuit that regulates the hepatobiliary system in rabbits.

    Science.gov (United States)

    Hu, Ming-E; Lin, Yung-Chang; Chang, Hung-Ming; Tyan, Yeu-Sheng; Lan, Chyn-Tair

    2012-01-01

    In this study, we investigated