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Sample records for cholestasis intrahepatic

  1. Intrahepatic cholestasis of pregnancy

    Institute of Scientific and Technical Information of China (English)

    Victoria Geenes; Catherine Williamson

    2009-01-01

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

  2. 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

  3. Intrahepatic cholestasis without jaundice

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  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. Genetics Home Reference: benign recurrent intrahepatic cholestasis

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    ... 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 ...

  6. Sepsis as a cause of intrahepatic cholestasis

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    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.

  7. New Insights on Intrahepatic Cholestasis of Pregnancy.

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    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.

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

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    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

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

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    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.

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

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    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.

  11. 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.

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

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    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.

  13. 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.

  14. A clinical approach to intrahepatic cholestasis of pregnancy.

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    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.

  15. 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.

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

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    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.

  17. 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

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

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    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.

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

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

    2015-01-01

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

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

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    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.

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

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    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.

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

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    Ajmal Kader

    2014-06-01

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

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

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    Efthymia Vlachaki

    2014-01-01

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

  4. 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.

  5. 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...

  6. 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.

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

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    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.

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

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    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.

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

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    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.

  10. 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.

  11. [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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. [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

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

    Directory of Open Access Journals (Sweden)

    Cui-ge YU

    2015-12-01

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

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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。

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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

    Institute of Scientific and Technical Information of China (English)

    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.

  14. 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

  15. 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

  16. 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

  17. 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

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

    Institute of Scientific and Technical Information of China (English)

    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.

  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)

    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. 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.

  1. 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.

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

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    Kadim S. Bachtiar

    2008-06-01

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

  3. 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

  4. Unusual causes of intrahepatic cholestatic liver disease

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    Elias E Mazokopakis; John A Papadakis; Diamantis P Kofteridis

    2007-01-01

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

  5. 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

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

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    刘娟; 陈雄; 汪宇平; 金玉珍; 吴颖

    2012-01-01

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

  7. 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

  8. 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.

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

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    Watanabe,Makoto

    1979-08-01

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

  10. 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

    Institute of Scientific and Technical Information of China (English)

    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

  11. 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

    Institute of Scientific and Technical Information of China (English)

    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.

  12. Intrahepatic ovulation

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    Artur L. Wozniak, HBSc

    2014-01-01

    Full Text Available Ectopic ovaries are a rare finding in the literature, with fewer than 50 published cases to date. This phenomenon has been found in the omentum, bladder, mesentery, and uterus; attached to the colon; inside the left labia majora; and in the kidney. Various etiologies have been proposed, including postsurgical or postinflammatory transplantation, malignant origins, and abnormal embryologic development. We report the ultrasonographic, computed tomographic (CT, and magnetic resonance (MR imaging of, what is to the best of our knowledge, the first case of an intrahepatic ectopic ovary.

  13. 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

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

    Institute of Scientific and Technical Information of China (English)

    刘壵; 李龙; 侯文英; 王海斌

    2013-01-01

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

  15. 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)

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    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.

  16. 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

  17. 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

  18. 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.

  19. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. [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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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...

  8. 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

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

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

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

  10. 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

  11. 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.

  12. Biochemical Characterization of P4-ATPase Mutations Associated with Intrahepatic Cholestatic Disease

    DEFF Research Database (Denmark)

    Gantzel, Rasmus; Vestergaard, Anna Lindeløv; Mikkelsen, Stine;

    The cholestatic disorders progressive familial intrahepatic cholestasis type 1 (PFIC1, also referred to as Byler’s disease) and benign recurrent intrahepatic cholestasis type 1 (BRIC1) are caused by mutation of the P4-ATPase ATP8B1. The substrate of ATP8B1 is very likely to be phosphatidylserine...... families have been investigated, and more than 50 distinct disease mutations have been identified, with roughly half being missense mutations. In this project we try to answer the question whether PFIC1 mutations are generally more disturbing than BRIC1 mutations with respect to expression, structural...... stability and function. We investigate the mutations in our well functioning system of ATP8A2, being expressed in mammalian HEK293T cells, affinity-purified, and reconstituted in lipid vesicles. Well-known mutations from both groups of patients have been selected for study. I91P in ATP8A2 (L127P in ATP8B1...

  13. Biochemical characterization of P4-ATPase mutations associated with Intrahepatic Cholestatic Disease

    DEFF Research Database (Denmark)

    Gantzel, Rasmus; Vestergaard, Anna Lindeløv; Mikkelsen, Stine

    Progressive familial intrahepatic cholestasis type 1 (PFIC1) and benign recurrent intrahepatic cholestasis type 1 (BRIC1) are caused by mutation of the P4-ATPase ATP8B1 that flips phospholipid from the exoplasmic leaflet to the cytoplasmic leaflet of canalicular membranes. It is hypothesized...... that PFIC1 mutations are the most disturbing with respect to expression, structural stability and/or function. Although recent data indicates that the specific phospholipid substrate of ATP8B1 is phosphatidylcholine (PC) [1] whereas ATP8A2 flips phosphatidylserine (PS) and phosphatidylethanolamine (PE......), there may be several mechanistic similarities between ATP8B1 and ATP8A2, and here we investigate known disease mutations using our well-functioning methodology for expression, affinity purification and assay of the partial reactions of ATP8A2. Mutations I91P (L127P in ATP8B1) and L308F (I344F) are located...

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

    Directory of Open Access Journals (Sweden)

    Faust Dominik

    2009-01-01

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

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

    Medline Plus

    Full Text Available ... What are the limitations of TIPS? What is a Transjugular Intrahepatic Portosystemic Shunt (TIPS)? A transjugular intrahepatic ... encourage linking to this site. × Recommend RadiologyInfo to a friend Send to (friend's e-mail address): From ( ...

  20. 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.

  1. Intrahepatic cholangiocarcinoma: current perspectives

    Directory of Open Access Journals (Sweden)

    Buettner S

    2017-02-01

    Full Text Available Stefan Buettner, Jeroen LA van Vugt, Jan NM IJzermans, Bas Groot Koerkamp Department of Surgery, Erasmus MC University Medical Center, Rotterdam, the Netherlands Abstract: Intrahepatic cholangiocarcinoma (ICC is the second most common malignancy arising from the liver. ICC makes up about 10% of all cholangiocarcinomas. It arises from the peripheral bile ducts within the liver parenchyma, proximal to the secondary biliary radicals. Histologically, the majority of ICCs are adenocarcinomas. Only a minority of patients (15% present with resectable disease, with a median survival of less than 3 years. Multidisciplinary management of ICC is complicated by large differences in disease course for individual patients both across and within tumor stages. Risk models and nomograms have been developed to more accurately predict survival of individual patients based on clinical parameters. Predictive risk factors are necessary to improve patient selection for systemic treatments. Molecular differences between tumors, such as in the epidermal growth factor receptor status, are promising, but their clinical applicability should be validated. For patients with locally advanced disease, several treatment strategies are being evaluated. Both hepatic arterial infusion chemotherapy with floxuridine and yttrium-90 embolization aim to downstage locally advanced ICC. Selected patients have resectable disease after downstaging, and other patients might benefit because of postponing widespread dissemination and biliary obstruction. Keywords: intrahepatic cholangiocarcinoma, diagnosis, treatment, developments 

  2. 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

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    Nara Léia Gelle de OLIVEIRA

    2002-04-01

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

  5. Pathology of intrahepatic cholangiocarcinoma

    Science.gov (United States)

    Vijgen, Sandrine; Terris, Benoit

    2017-01-01

    Intrahepatic cholangiocarcinoma (iCC) is a primary carcinoma of the liver with increasing significance and major pathogenic, clinical and therapeutic challenges. Classically, it arises from malignant transformation of cholangiocytes bordering small portal bile duct (BD) to second-order segmental large BDs. It has three major macroscopic growth pattern [mass-forming (MF), periductal infiltrative (PI), and intraductal growth (IG)] and histologically is a desmoplastic stroma-rich adenocarcinoma with cholangiocyte differentiation. Recent data pointed out noteworthy degree of heterogeneity in regards of their epidemiology and risk factors, pathological and molecular features, pathogenesis, clinical behaviors and treatment. Notably, several histological variants are described and can coexist within the same tumor. Several different cells of origin have also been depicted in a fraction of iCCs, amongst which malignant transformation of ductules, of hepatic stem/progenitor cells, of periductal glands or through oncogenic reprogramming of adult hepatocytes. A degree of pathological overlap with hepatocellular carcinoma (HCC) may be observed in a portion of iCC. A series of precursor lesions are today characterized and emphasize the existence of a multistep carcinogenesis process. Overall, these new data have brought up in proposal of new histological or molecular classifications, which could soon replace current anatomic-based classification and could have major impact on establishment of prognosis and on development of novel target treatment approaches. PMID:28261592

  6. Intrahepatic Transposition of Bile Ducts

    Science.gov (United States)

    Delić, Jasmin; Savković, Admedina; Isaković, Eldar; Marković, Sergije; Bajtarevic, Alma; Denjalić, Amir

    2012-01-01

    Objective. To describe the intrahepatic bile duct transposition (anatomical variation occurring in intrahepatic ducts) and to determine the frequency of this variation. Material and Methods. The researches were performed randomly on 100 livers of adults, both sexes. Main research methods were anatomical macrodissection. As a criterion for determination of variations in some parts of bile tree, we used the classification of Segmentatio hepatis according to Couinaud (1957) according to Terminologia Anatomica, Thieme Stuugart: Federative Committee on Anatomical Terminology, 1988. Results. Intrahepatic transposition of bile ducts was found in two cases (2%), out of total examined cases (100): right-left transposition (right segmental bile duct, originating from the segment VIII, joins the left liver duct-ductus hepaticus sinister) and left-right intrahepatic transposition (left segmental bile duct originating from the segment IV ends in right liver duct-ductus hepaticus dexter). Conclusion. Safety and success in liver transplantation to great extent depends on knowledge of anatomy and some common embryological anomalies in bile tree. Variations in bile tree were found in 24–43% of cases, out of which 1–22% are the variations of intrahepatic bile ducts. Therefore, good knowledge on ductal anatomy enables good planning, safe performance of therapeutic and operative procedures, and decreases the risk of intraoperative and postoperative complications. PMID:22550601

  7. Renal elimination of organic anions in cholestasis

    Institute of Scientific and Technical Information of China (English)

    Adriana Mónica Tortes

    2008-01-01

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

  8. Primary intrahepatic malignant epithelioid mesothelioma

    Directory of Open Access Journals (Sweden)

    Iraklis Perysinakis

    2014-01-01

    CONCLUSION: To our knowledge this is the eighth adult case of primary intrahepatic malignant mesothelioma reported in the literature. These tumors are rarely diagnosed preoperatively. Absence of previous asbestos exposure does not exclude malignant mesothelioma from the differential diagnosis. Proper surgical treatment may offer prolonged survival to the patient, without adjuvant therapy.

  9. Sarcomatoid Change in Intrahepatic Cholangiocarcinoma

    DEFF Research Database (Denmark)

    Albrechtsen, Nicolai Jacob Wewer; Zhang, Da; Abdulkarim, Bashar;

    2013-01-01

    Sarcomatoid transformation is a rare but well documented change that may occur in intrahepatic cholangiocarcinomas.We report a tumor of this type to illustrate the difficulties in properly diagnosing cholangiocarcinoma when only the sarcomatous component is sampled by transcutaneous needle biopsy...

  10. 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.

  11. 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.

  12. [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.

  13. Splenosis simulating an intrahepatic mass

    Institute of Scientific and Technical Information of China (English)

    晁明; 徐宏伟

    2004-01-01

    Splenosis is the autotransplantation of splenic tissue that usually follows traumatic rupture of the spleen. Splenic implants may be seeded within or beyond the peritoneal cavity.1 The most frequent locations of splenosis in the descending order are the serosal surface of the small intestine, the greater omentum, parietal peritoneum, surface of the large intestine, mesentery, undersurface of the diaphragm and the thorax.1,2 However, intrahepatic splenosis is very rare. We recently encountered a patient in whom results of ultrasonography (US) and computed tomography (CT) revealed an intrahepatic mass that consisted of ectopic splenic tissue. To our knowledge, this is the fifth report of ectopic splenic tissue in the liver in the English-language literature. We present the imaging findings of the splenic implants in the liver and discuss the diagnosis and its practical significance.

  14. SARCOMATOID CHANGE IN INTRAHEPATIC CHOLANGIOCARCINOMA

    OpenAIRE

    Wewer Albrechtsen; Da Zhang; A. Bashar Abdulkarim; Damjanov Ivan

    2013-01-01

    Sarcomatoid transformation is a rare but well documented change that may occur in intrahepatic cholangiocarcinomas. We report a tumor of this type to illustrate the difficulties in properly diagnosing cholangiocarcinoma when only the sarcomatous component is sampled by transcutaneous needle biopsy. The proper diagnosis of the tumor was suggested by finding the expression of cytokeratin 7 in the sarcomatous spindle cells. The surgically resected tumor comprised a spindle cell sarcomatous and a...

  15. Sarcomatoid change in intrahepatic cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Albrechtsen Wewer Nicolai

    2013-03-01

    Full Text Available Sarcomatoid transformation is a rare but well documented change that may occur in intrahepatic cholangiocarcinomas. We report a tumor of this type to illustrate the difficulties in properly diagnosing cholangiocarcinoma when only the sarcomatous component is sampled by transcutaneous needle biopsy. The proper diagnosis of the tumor was suggested by finding the expression of cytokeratin 7 in the sarcomatous spindle cells. The surgically resected tumor comprised a spindle cell sarcomatous and an adenocarcinomatous component accounting for approximately 30% and 70% of the total tumor mass respectively

  16. 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.

  17. Multiple intrahepatic pseudocysts in acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    David Casado; Luis Sabater; Julio Calvete; Empar Mayordomo; Luis Aparisi; Juan Sastre; Salvador Lledo

    2007-01-01

    Liver pseudocysts are a very rare complication in acute pancreatitis with only a few cases previously described. The lack of experience and literature on this condition leads to difficulties in the differential diagnosis and management. We report herein a case of acute pancreatitis who developed multiple intrahepatic pseudocysts. After complete imaging evaluation, the diagnosis was still unclear and the patient was operated on. The presence of liver lesions in patients with acute pancreatitis should raise the possibility of intrahepatic pseudocysts.

  18. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-03-15

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

  20. 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...

  1. 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...

  2. The transjugular intrahepatic portosystemic shunt (TIPS)

    Energy Technology Data Exchange (ETDEWEB)

    Owen, A.R. [Department of Radiology, Austin Health, Heidelberg, Melbourne (Australia)], E-mail: andrewowen@doctors.org.uk; Stanley, A.J. [Department of Gastroenterology, Glasgow Royal Infirmary, Glasgow (United Kingdom); Vijayananthan, A. [Department of Biomedical Imaging, University of Malaya, Kuala Lumpur (Malaysia); Moss, J.G. [Department of Radiology, Gartnavel General Hospital, Glasgow (United Kingdom)

    2009-07-15

    The creation of an intrahepatic portosystemic shunt via a transjugular approach (TIPS) is an interventional radiological procedure used to treat the complications of portal hypertension. TIPS insertion is principally indicated to prevent or arrest variceal bleeding when medical or endoscopic treatments fail, and in the management refractory ascites. This review discusses the development and execution of the technique, with focus on its clinical efficacy. Patient selection, imaging surveillance, revision techniques, and complications are also discussed.

  3. 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

  4. 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.

  5. Heterogeneity of the intrahepatic biliary epithelium

    Institute of Scientific and Technical Information of China (English)

    Shannon Glaser; Heather Francis; Sharon DeMorrow; Gene LeSage; Giammarco Fava; Marco Marzioni; Julie Venter; Gianfranco Alpini

    2006-01-01

    The objectives of this review are to outline the recent findings related to the morphological heterogeneity of the biliary epithelium and the heterogeneous pathophysiological responses of different sized bile ducts to liver gastrointestinal hormones and peptides and liver injury/toxins with changes in apoptotic, proliferative and secretory activities. The knowledge of biliary function is rapidly increasing because of the recognition that biliary epithelial cells (cholangiocytes) are the targets of human cholangiopathies, which are characterized by proliferation/damage of bile ducts within a small range of sizes. The unique anatomy, morphology, innervation and vascularization of the biliary epithelium are consistent with function of cholangiocytes within different regions of the biliary tree. The in vivo models [e.g., bile duct ligation (BDL), partial hepatectomy, feeding of bile acids,carbon tetrachloride (CCl4) or α-naphthylisothiocyanate (ANIT)] and the in vivo experimental tools [e.g., freshly isolated small and large cholangiocytes or intrahepatic bile duct units (IBDU) and primary cultures of small and large murine cholangiocytes] have allowed us to demonstrate the morphological and functional heterogeneity of the intrahepatic biliary epithelium.These models demonstrated the differential secretory activities and the heterogeneous apoptotic and proliferative responses of different sized ducts. Similar to animal models of cholangiocyte proliferation/injury restricted to specific sized ducts, in human liver diseases bile duct damage predominates specific sized bile ducts.Future studies related to the functional heterogeneity of the intrahepatic biliary epithelium may disclose new pathophysiological treatments for patients with cholangiopathies.

  6. 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.

  7. Radiopaque intrahepatic duct stones in plain radiograph: case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Mi Young; Suh, Chang Hae; Park, Chan Sup; Chung, Won Kyun [College of Medicine, Inha University, Seongnam (Korea, Republic of)

    1994-04-15

    We experienced 3 cases of intrahepatic duct stones detected on plain radiographs. The patients had history of multiple episodes of recurrent cholangitis. Radiographic characteristics of these stones included multiple, round or rectangular radiopaque densities surrounded by calcified rim; these densities showed a branching pattern along the intrahepatic ducts.

  8. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Camila Carbone Prado

    2006-12-01

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

  13. 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

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

    Science.gov (United States)

    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.

  15. 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.

  16. Intrahepatic arterioportal shunt: helical CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Quiroga, S.; Sebastia, M.C.; Moreiras, M.; Pallisa, E.; Rius, J.M.; Alvarez-Castells, A. [I. D. I. Hospital General i Universitari Vall d`Hebron, Barcelona (Spain). Servei de Radiodiagnostic

    1999-08-01

    The purpose of this study was to characterize the appearance of intrahepatic arterioportal shunts (APS) on two-phase helical CT, with emphasis on the importance of the hepatic arterial-dominant phase (HAP) to demonstrate perfusion disorders. We review eight cases of APS diagnosed by helical CT in our institution from January 1996 to March 1997 and describe the CT findings that established diagnosis. Five of them were confirmed by angiography. In seven (87.5 %) cases of APS we found early enhancement of the peripheral portal branches during the HAP of helical CT, whereas the superior mesenteric and splenic veins remained unenhanced. In five (62.5 %) cases of APS, transient, peripheral, triangular parenchymal enhancement was depicted during the HAP of helical CT; in four of these cases there was associated early enhancement of the portal branches. Helical CT can show perfusion alterations that might remain undiagnosed with conventional CT. An understanding of the hemodynamic changes that occur in APS can help in the interpretation of focal transient hepatic parenchymal enhancement and to differentiate APS from hypervascular tumors. We believe that the helical CT findings described herein are characteristic enough to suggest the diagnosis of APS. (orig.) With 3 figs., 1 tab., 16 refs.

  17. 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.

  18. 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.

  19. Intrahepatic haematoma in a patient on long-term haemodialysis.

    Science.gov (United States)

    Lai, K N; Disney, A P; Mathew, T H

    Spontaneous intrahepatic haematoma is an uncommon potentially fatal complication in uraemic patients receiving long-term haemodialysis, particularly in those taking anticoagulant and antiplatelet drugs. Prompt diagnosis, withdrawal of anticoagulant and antiplatelet therapy, cautious transfusion, and careful dialysis with regional heparinisation are essential in the management and may help to avoid surgical intervention in the presence of a tendency to bleed. Noninvasive organ imaging such as ultrasonography and computerised axial tomography are helpful in diagnosis and monitoring of progress. A case of intrahepatic haematoma in a 37-year-old man who had been receiving long-term haemodialysis since 1976 is described.

  20. Radiofrequency ablation for incidentally identified primary intrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Witold Zgodzinski; N.Joseph Espat

    2005-01-01

    Cholangiocarcinoma is the second most common primary hepato-biliary malignancy. The majority of patients with primary hepatic tumors are not suitable candidates for resection, due to advanced stage of the disease at presentation, anatomic limitations and medical comorbidities. At present, radiofrequency ablation (RFA) may offer an alternative, feasible and safe therapy for selected patients with hepatic tumors, who are not otherwise candidates for hepatic resection. Herein, we present the case of successful RFA in a patient with a solitary, primary intrahepatic cholangiocarcinoma. The patient remained free of disease 24 mo after the procedure, and is still followed up. This is the first report of RFA application inthe treatment of primary intrahepatic cholangiocarcinoma.

  1. 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.

  2. Calcified Klatskin tumor mimicking intrahepatic stone: case report.

    Science.gov (United States)

    Park, H S; Han, J K; Lee, H S; Lee, K H; Kim, S H; Kim, K W; Kim, Y J; Kim, H-C; Choi, B I

    2005-01-01

    Calcification is a relatively uncommon manifestation of malignant liver neoplasm. Calcifications in peripheral cholangiocarcinomas but not in Klatskin tumor have been reported. We present a rare case of Klatskin tumor that had dystrophic calcification mimicking a intrahepatic stone in a 65-year-old man.

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

    Science.gov (United States)

    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.

  4. Taurolithocholic acid promotes intrahepatic cholangiocarcinoma cell growth via muscarinic acetylcholine receptor and EGFR/ERK1/2 signaling pathway.

    Science.gov (United States)

    Amonyingcharoen, Sumet; Suriyo, Tawit; Thiantanawat, Apinya; Watcharasit, Piyajit; Satayavivad, Jutamaad

    2015-01-01

    Cholangiocarcinoma (CCA) is a malignant cancer of the biliary tract and its occurrence is associated with chronic cholestasis which causes an elevation of bile acids in the liver and bile duct. The present study aimed to investigate the role and mechanistic effect of bile acids on the CCA cell growth. Intrahepatic CCA cell lines, RMCCA-1 and HuCCA-1, were treated with bile acids and their metabolites to determine the growth promoting effect. Cell viability, cell cycle analysis, EdU incorporation assays were conducted. Intracellular signaling proteins were detected by western immunoblotting. Among eleven forms of bile acids and their metabolites, only taurolithocholic acid (TLCA) concentration dependently (1-40 µM) increased the cell viability of RMCCA-1, but not HuCCA-1 cells. The cell cycle analysis showed induction of cells in the S phase and the EdU incorporation assay revealed induction of DNA synthesis in the TLCA-treated RMCCA-1 cells. Moreover, TLCA increased the phosphorylation of EGFR, ERK 1/2 and also increased the expression of cyclin D1 in RMCCA-1 cells. Furthermore, TLCA-induced RMCCA-1 cell growth could be inhibited by atropine, a non-selective muscarinic acetylcholine receptor (mAChR) antagonist, AG 1478, a specific EGFR inhibitor, or U 0126, a specific MEK 1/2 inhibitor. These results suggest that TLCA induces CCA cell growth via mAChR and EGFR/EKR1/2 signaling pathway. Moreover, the functional presence of cholinergic system plays a certain role in TLCA-induced CCA cell growth.

  5. 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.

  6. Intrahepatic Duct Stones Harboring Ascariasis Ova: A Case Report.

    Science.gov (United States)

    Lee, Chen-Fang; Lee, Wei-Chen; Wu, Ren-Chin; Chen, Tse-Ching

    2016-03-01

    Ascariasis lumbricoides is one of the most common helminthic infestations in humans. Despite the fact that the prevalence of ascariasis in developed countries has been decreasing, biliary ascariasis can cause serious complications, such as acute cholangitis, pancreatitis, and liver abscess. Here we presented a rare ascariasis-related complication-hepatolithiasis.A 60-year-old female patient had symptoms of recurrent cholangitis. Abdominal computed tomography scan revealed left intrahepatic duct stones with left liver lobe atrophy. Endoscopic retrograde cholangiopancreatography was performed, but the stones could not be removed due to left main intrahepatic duct stenosis. The patient was treated with left hemi-hepatectomy. Unexpectedly, Ascaris ova were found on the histopathological examination. She received antihelminthic therapy orally and was on regular follow-up without any complications.Our study indicates that clinicians should be aware of biliary ascariasis in patients with hepatolithiasis, though not living in endemic areas.

  7. Sonography-guided percutaneous microwave ablation of intrahepatic primary cholangiocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Yu Mingan [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Liang Ping, E-mail: Liangping301@hotmail.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Yu Xiaoling; Cheng Zhigang; Han Zhiyu; Liu Fangyi; Yu Jie [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China)

    2011-11-15

    Objective: To evaluate the efficacy and safety of sonography-guided percutaneous microwave ablation of intrahepatic primary cholangiocarcinoma. Materials and methods: From May 2006 to March 2010, 15 patients (11 men, 4 women; mean age, 57.4 years) with 24 histologically proven intrahepatic primary cholangiocarcinoma lesions (mean tumor size, 3.2 {+-} 1.9 cm; range, 1.3-9.9 cm) were treated with microwave ablation. Results: Thirty-eight sessions were performed for 24 nodules in 15 patients. The follow-up period was 4-31 months (mean, 12.8 {+-} 8.0 months). The ablation success rate, the technique effectiveness rate, and the local tumor progression rate were 91.7% (22/24), 87.5% (21/24), and 25% (6/24) respectively according to the results of follow-up. The cumulative overall 6, 12, 24 month survival rates were 78.8%, 60.0%, and 60.0%, respectively. Major complication occurred including liver abscess in two patients (13.3%) and needle seeding in one patient (6.7%). Both complications were cured satisfied with antibiotic treatment combined to catheter drainage for abscess and resection for needle seeding. The minor complications and side effects were experienced by most patients which subsided with supportive treatment. Conclusion: Microwave ablation can be used as a safe and effective technique to treat intrahepatic primary cholangiocarcinoma.

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

  9. [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.

  10. [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.

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

    Science.gov (United States)

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

    2014-07-01

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

  12. 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

  13. 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

  14. 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...

  15. 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.

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

    NARCIS (Netherlands)

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

    2002-01-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    1991-04-01

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

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  1. 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. Intrahepatic Pseudoaneurysms Complicating Transjugular Liver Biopsy in Liver Transplantation Patients: Three Case Reports

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Seung Won; Ko, Gi Young; Yoon, Hyun Ki; Gwon, Dong Il; Sung, Kyu Bo [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2010-04-15

    An intrahepatic pseudoaneurysm is a rare complication following transjugular liver biopsy. Transarterial embolization is considered a safe and effective treatment for treating pseudoaneurysms. Herein we report three cases of intrahepatic pseudoaneurysms following transjugular liver biopsies. The three pseudoaneurysms were managed by the following methods: transarterial embolization, percutaneous transhepatic embolization, and close observation

  3. Mucins and NCAM (CD56 in intrahepatic cholangiocarcinogenesis

    Directory of Open Access Journals (Sweden)

    Anna Beatriz Telles Esperança

    2014-06-01

    Full Text Available Introduction: Cholangiocarcinoma is the second most common malignant neoplasm of the hepatobiliary system. During cholangiocarcinogenesis phenotypic changes occur in the ductal epithelium, including the expression of mucins (MUC. However, the evaluating studies of the expression of mucins in the different stages of cholangiocarcinogenesis are scarce. CD56 has also contributed in differentiating benign ductal proliferation and cholangiocarcinoma; however, its expression has not been evaluated in dysplastic epithelium of the bile duct yet. Objective: To assess immunohistochemical profile of (MUC 1, 2, 5, 6, and CD56 in cholangiocarcinoma, pre-neoplastic and reactive lesions in the epithelium of intrahepatic bile ducts. Material and methods: Immunohistochemical expression of MUC 1, 2, 5, 6, and CD56 were studied for 11 cases of cholangiocarcinoma and 83 intrahepatic bile ducts (67 reactive and 16 dysplastic. Variables were considered significant when p < 0.05. Results: The expression of MUC1 occurred in about 90% of the cholangiocarcinomas, contrasting with the low frequency of positive cases in reactive and dysplastic bile ducts (p < 0.001. However, there was no statistically significant difference in the expression of MUC5, MUC6 and CD56 between the reactive or dysplastic lesions and cholangiocarcinoma. The anti-MUC2 antibody was negative in all cases. Conclusions: MUC1 contributed for the differential diagnosis between cholangiocarcinoma and pre-neoplastic and reactive/regenerative lesions of intrahepatic bile ducts, and it should compose the antibodies panel aiming at improvement of these differential diagnoses. In contrast, MUC2, MUC5, MUC6 and CD56 were not promising in differentiating all the phases of cholangiocarcinogenesis.

  4. Spontaneous rupture of intrahepatic biliary ducts with biliary peritonitis.

    Science.gov (United States)

    Aydin, Unal; Yazici, Pinar; Coker, Ahmet

    2007-01-01

    Spontaneous rupture of intrahepatic biliary ducts is a rare cause of acute abdomen due to biliary peritonitis. We report a 92-year-old woman with 48-h history of upper abdominal pain, nausea and vomiting and peritoneal signs. CT scan showed free fluid in the abdomen and mild dilatation of the common bile duct. Exploratory laparotomy showed bile in the abdominal cavity with leak-age from a ruptured bile duct radicle in segment 3, as confirmed on intraoperative cholangiography. She underwent cholecystectomy, choledochotomy with removal of gallstones, repair of the perforation with primary suture and placement of a T-tube. She had an uneventful recovery.

  5. Etiological and clinicopathologic characteristics of intrahepatic cholangiocarcinoma in young patients

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To investigate the prevalence,risk factors,and clinicopathologic characteristics of intrahepatic cholangiocarcinoma(ICC)in young patients.METHODS:A retrospective analysis was performed in ICC patients referred to the Eastern Hepatobiliary Surgery Hospital in Shanghai,China.Among 317 consecutively enrolled patients,40 patients were aged ≤40 years(12.61%).We compared the risk factors and clinicopathologic characteristics of these patients(groupⅠ:n=40)with those aged>40 years(group Ⅱ:n=277).RESULTS:Group I...

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

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    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.

  7. Giant Intrahepatic Portal Vein Aneurysm: Leave it or Treat it?

    Science.gov (United States)

    Shrivastava, Amit; Rampal, Jagdeesh S; Nageshwar Reddy, D

    2017-03-01

    Portal vein aneurysm (PVA) is a rare vascular dilatation of the portal vein. It is a rare vascular anomaly representing less than 3% of all visceral aneurysms and is not well understood. Usually, PVA are incidental findings, are asymptomatic, and clinical symptoms are proportionally related to size. Patients present with nonspecific epigastric pain or gastrointestinal bleeding with underlying portal hypertension. PVA may be associated with various complications such as biliary tract compression, portal vein thrombosis/rupture, duodenal compression, gastrointestinal bleeding, and inferior vena cava obstruction. Differential diagnoses of portal vein aneurysms are solid, cystic, and hypervascular abdominal masses, and it is important that the radiologists be aware of their multi-modality appearance; hence, the aim of this article was to provide an overview of the available literature to better simplify various aspects of this rare entity and diagnostic appearance on different modality with available treatment options. In our case, a 55-year-old male patient came to the gastroenterology OPD for further management of pancreatitis with portal hypertension and biliary obstruction with plastic stents in CBD and PD for the same. In this article, we have reported a case of largest intrahepatic portal vein aneurysm and its management by endovascular technique. As per our knowledge, this is the largest intrahepatic portal vein aneurysm and first case where the endovascular technique was used for the treatment of the same.

  8. Fibroblast growth factor receptor 2 translocations in intrahepatic cholangiocarcinoma.

    Science.gov (United States)

    Graham, Rondell P; Barr Fritcher, Emily G; Pestova, Ekaterina; Schulz, John; Sitailo, Leonid A; Vasmatzis, George; Murphy, Stephen J; McWilliams, Robert R; Hart, Steven N; Halling, Kevin C; Roberts, Lewis R; Gores, Gregory J; Couch, Fergus J; Zhang, Lizhi; Borad, Mitesh J; Kipp, Benjamin R

    2014-08-01

    Patients with cholangiocarcinoma often present with locally advanced or metastatic disease. There is a need for effective therapeutic strategies for advanced stage cholangiocarcinoma. Recently, FGFR2 translocations have been identified as a potential target for tyrosine kinase inhibitor therapies. This study evaluated 152 cholangiocarcinomas and 4 intraductal papillary biliary neoplasms of the bile duct for presence of FGFR2 translocations by fluorescence in situ hybridization and characterized the clinicopathologic features of cases with FGFR2 translocations. Thirteen (10 women, 3 men; 8%) of 156 biliary tumors harbored FGFR2 translocations, including 12 intrahepatic cholangiocarcinomas (12/96; 13%) and 1 intraductal papillary neoplasm of the bile duct. Histologically, cholangiocarcinomas with FGFR2 translocations displayed prominent intraductal growth (62%) or anastomosing tubular glands with desmoplasia (38%). Immunohistochemically, the tumors with FGFR2 translocations frequently showed weak and patchy expression of CK19 (77%). Markers of the stem cell phenotype in cholangiocarcinoma, HepPar1 and CK20, were negative in all cases. The median cancer-specific survival for patients whose tumors harbored FGFR2 translocations was 123 months compared to 37 months for cases without FGFR2 translocations (P = .039). This study also assessed 100 cholangiocarcinomas for ERBB2 amplification and ROS1 translocations. Of the cases tested, 3% and 1% were positive for ERBB2 amplification and ROS1 translocation, respectively. These results confirm that FGFR2, ERRB2, and ROS1 alterations are potential therapeutic targets for intrahepatic cholangiocarcinoma.

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

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    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

  10. 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).

  11. Intrahepatic portosystemic venous shunts: diagnosis by Doppler ultrasound; Cortocircuitos venosos portosistemicos intrahepaticos: diagnostico mediante ecografia Doppler

    Energy Technology Data Exchange (ETDEWEB)

    Garofano, M. P.; Medina, A.; Lopez, G.; Garrido, C. [Hospital Universitario Virgen de las Nieves. Granada (Spain)

    2001-07-01

    Intrahepatic portosystemic venous shunts are venous vascular lesions that allow intrahepatic portal vessels to communicate with hepatic veins. They may present in patients with portal hypertension or b discovered incidentally; it is considered that the latter may be congenital or acquired. A noninvasive methods. Doppler ultrasound aids in the diagnosis of these anomalous communications by providing images of the vessels and the direction, velocity and volume of the blood flow through the shunt. We present four cases of intrahepatic portosystemic venous shunt. (Author) 8 refs.

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

  13. 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.

  14. Bile peritonitis due to intra-hepatic bile duct rupture

    Institute of Scientific and Technical Information of China (English)

    R Lochan; BV Joypaul

    2005-01-01

    Generalized biliary peritonitis is a serious intra-abdominal emergency. Most of them occur due to duodenal ulcer perforation and rapidly evolve into bacterial peritonitis due to contamination by gut organisms and food. In this situation, recognition of the pathology and its treatment is straightforward and is usually associated with a good outcome. There are a few unusual causes of biliary peritonitis, of which rupture of the biliary tree is one.We describe a rare case of biliary peritonitis due to rupture of an intra-hepatic biliary radical. Unusual causes of peritonitis do interrupt our daily routine emergency surgical experience. Rapid recognition of the presence of peritonitis, adequate resuscitation, recognition of operative findings, establishment of biliary anatomy, and performance of a meticulous surgical procedure resulted in a good outcome.

  15. Bile peritonitis due to intra-hepatic bile duct rupture.

    Science.gov (United States)

    Lochan, R; Joypaul, B V

    2005-11-14

    Generalized biliary peritonitis is a serious intra-abdominal emergency. Most of them occur due to duodenal ulcer perforation and rapidly evolve into bacterial peritonitis due to contamination by gut organisms and food. In this situation, recognition of the pathology and its treatment is straightforward and is usually associated with a good outcome. There are a few unusual causes of biliary peritonitis, of which rupture of the biliary tree is one. We describe a rare case of biliary peritonitis due to rupture of an intra-hepatic biliary radical. Unusual causes of peritonitis do interrupt our daily routine emergency surgical experience. Rapid recognition of the presence of peritonitis, adequate resuscitation, recognition of operative findings, establishment of biliary anatomy, and performance of a meticulous surgical procedure resulted in a good outcome.

  16. Clinicopathological Characteristics and Prognostic Factors of Intrahepatic Biliary Cystadenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Ming-Yue Xu; Xian-Jie Shi; Tao Wan; Yu-Rong gang; Hong-Guang Wang; Wen-Zhi Zhang; Lei He

    2015-01-01

    Background:Surgical resection is generally considered the main curative treatment for intrahepatic biliary cystadenocarcinoma (IBCA) or suspected IBCAs,but controversy exists regarding the prognosis for IBCAs.This study aimed to describe the clinicopathological characteristics of IBCA and identify prognostic factors that may influence the survival of patients treated with surgical procedures.Methods:Thirty-four patients with histologically confirmed IBCA treated between January 2000 and June 2014 were included.The clinical characteristics of patients with IBCA were compared with those of 41 patients with intrahepatic biliary cystadenoma (IBC);factors that significant difference were analyzed for prognosis analysis of IBCA using multivariate/univariate Cox proportional hazards regression models.Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test.Results:IBCAs had a strong female predominance,and the most common presenting symptoms were abdominal pain or discomfort.Compared with IBCs,IBCAs occurred in older patients,in more male patients,and were associated statistically significant abnormal increase in alanine aminotransferase (P =0.01) and total bilirubin (P =0.04).Mural nodules were more frequently seen with IBCAs and may associate with malignancy.It was difficult to differentiate between IBC and IBCA based on laboratory examination and imaging findings.Although complete resection is recommended,enucleation with negative margins also achieved good outcomes.Median overall patient survival was 76.2 months;survival at 1,3,and 5 years was 88.0%,68.7%,and 45.8%,respectively.Radical resection and noninvasive tumor type were independent prognostic factors for overall survival.Conclusions:It remains difficult to distinguish between cystadenomas and cystadenocarcinomas based on laboratory examination and image findings.Complete resection is recommended for curative treatment,and patients should be closely followed

  17. The miRNAome of Opisthorchis viverrini induced intrahepatic cholangiocarcinoma

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    Jin Peng

    2014-12-01

    Full Text Available Intrahepatic cholangiocarcinoma (ICC is an aggressive cancer, arising in the biliary ducts that extend into the liver. The highest incidence of ICC occurs in Southeast Asia, particularly in the Mekong River Basin countries of Thailand, Laos, Cambodia, and Vietnam, where it is strongly associated with chronic infection by the food-borne liver fluke Opisthorchis viverrini (OV, one of only three eukaryote pathogens considered Group one carcinogens. Intrahepatic cholangiocarcinoma is usually diagnosed at an advanced stage, with a poor prognosis and survival often less than 24 months. Hence, biomarkers that enable the early detection of ICC would be desirable and have a potentially important impact on the public health in the resource-poor regions where this cancer is most prevalent. As microRNAs (miRNAs remain well preserved after formalin fixation, there is much interest in developing them as biomarkers that can be investigated using tumor biopsy samples preserved in formalin fixed paraffin embedded (FFPE tumor blocks. Recently, we reported the first comprehensive profiling of tissue-based miRNA expression using FFPE from the three most common subtypes of OV-induced ICC tumors: moderately differentiated ICC, papillary ICC, and well-differentiated ICC. We observed that each subtype of OV-induced ICC exhibited a distinct miRNA profile, which suggested the involvement of specific sets of miRNAs in the progression of this cancer. In addition, non-tumor tissue adjacent to ICC tumor tissue on the same FFPE block shared a similar miRNA dysregulation profile with the tumor tissue than with normal (non-tumor liver tissue (individuals without ICC or OV infection. Herein, we provide a detailed description of the microarray analysis procedures used to derive these findings.

  18. Huge hepatocellular carcinoma with multiple intrahepatic metastases: An aggressive multimodal treatment

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    Satoshi Yasuda

    2015-01-01

    Conclusion: Multimodal treatment involving hepatectomy and TACE might be a good treatment strategy for patients with huge HCC with multiple intrahepatic metastases if the tumors are localized in the liver without distant or peritoneal metastasis.

  19. Simultaneous intrahepatic and subgaleal hemorrhage in antiphospholipid syndrome following anticoagulation therapy.

    Science.gov (United States)

    Park, In-Chul; Baek, Yang-Hyun; Han, Sang-Young; Lee, Sung-Wook; Chung, Won-Tae; Lee, Sung-Won; Kang, Sang-Hyeon; Cho, Duk-Song

    2013-10-14

    Warfarin is a widely used anticoagulant. Interindividual differences in drug response, a narrow therapeutic range and the risk of bleeding render warfarin difficult to use clinically. An 18-year-old woman with antiphospholipid syndrome received long-term warfarin therapy for a recurrent deep vein thrombosis. Six years later, she developed right flank pain. We diagnosed intrahepatic and subgaleal hemorrhages secondary to anticoagulation therapy. After stopping oral anticoagulation, a follow-up computed tomography showed improvement in the hemorrhage. After restarting warfarin because of a recurrent thrombosis, the intrahepatic hemorrhage recurred. We decided to start clopidogrel and hydroxychloroquine instead of warfarin. The patient has not developed further recurrent thrombotic or bleeding episodes. Intrahepatic hemorrhage is a very rare complication of warfarin, and our patient experienced intrahepatic and subgaleal hemorrhage although she did not have any risk factors for bleeding or instability of the international normalized ratio control.

  20. Distant skeletal muscle metastasis from intrahepatic cholangiocarcinoma presenting as Budd-Chiari syndrome

    Institute of Scientific and Technical Information of China (English)

    Oh Sung Kwon; Young Sook Park; Jong Eun Joo; Dae Won Jun; Sang Heum Kim; Mee Yeon Chung; Nam In Kim; Moon Hee Song; Han Hyo Lee; Seung Hwan Kim; Yoon Ju Jo

    2007-01-01

    Intrahepatic cholangiocarcinoma is a malignant neoplasm arising from the biliary epithelium, which frequently invades adjacent organs or metastasizes to other visceral organs such as the lungs, bones, adrenals, and brain. However, distant skeletal muscle metastasis of cholangiocarcinoma has never been described before to the best of our knowledge and, furthermore, Budd-Chiari syndrome secondary to intrahepatic cholangiocarcinoma is also extremely rare. Here we present the first case overall of distant muscle metastasis from intrahepatic cholangiocarcinoma presenting as Budd-Chiari syndrome. A 44-year-old man admitted to the hospital with complaints of abdominal distension, edema of both legs, back pain and anorexia of 30 o" duration. Computed tomography and ultrasonography-guided percutaneous muscle biopsy established intrahepatic cholangiocarcinoma with disseminated thrombosis from inferior vena cava to bilateral iliac and femoral veins, and multiple skeletal muscle metastases in bilateral buttock and erector spinal muscle.

  1. Cardiac and renal effects of a transjugular intrahepatic portosystemic shunt in cirrhosis

    DEFF Research Database (Denmark)

    Busk, Troels M; Bendtsen, Flemming; Møller, Søren

    2013-01-01

    Refractory ascites and recurrent variceal bleeding are among the serious complications of portal hypertension and cirrhosis for which a transjugular intrahepatic portosystemic shunt (TIPS) can be used. Cirrhotic patients have varying degrees of haemodynamic derangement, mainly characterized...

  2. 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

  3. 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

  4. Is Hepatectomy Necessary in Dealing with Left Hepatolithiasis with Intrahepatic Duct Stricture?

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    Dominique Franco

    1997-01-01

    Full Text Available Background: Hepatolithiasis with intrahepatic biliary strictures, more common in Southeast Asia than elsewhere, remains a difficult problem to manage. Hepatic resection has recently been advocated as one of the treatment modalities for hepatolithiasis; however, this procedure is not without risk. This study was designed to achieve complete clearance of the stones, eliminate bile stasis, and avoid the potential risks of hepatic resection in the patient with hepatolithiasis and intrahepatic biliary stricture.

  5. Review to better understand the macroscopic subtypes and histogenesis of intrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Yuichi; Sanada; Yujo; Kawashita; Satomi; Okada; Takashi; Azuma; Shigetoshi; Matsuo

    2014-01-01

    Intrahepatic cholangiocarcinoma is macroscopically classified into three subtypes, mass-forming-type, periductal infiltrating-type, and intraductal growth-type. Each subtype should be preoperatively differentiated to perform the valid surgical resection. Recent researches have revealed the clinical, radiologic, pathobiological characteristics of each subtype. We reviewed recently published studies covering various aspects of intrahepatic cholangiocarcinoma(ICC), focusing especially on the macroscopic subtypes and stem cell features to better understand the pathophysiology of ICC and to establish the valid therapeutic strategy.

  6. Adjuvant therapy for intrahepatic cholangiocarcinoma: the debate continues.

    Science.gov (United States)

    Zhu, Andrew X; Knox, Jennifer J

    2012-01-01

    Presentation of the Case A 37-year-old woman presented at 35 weeks of gestation with her third child with failure to adequately gain weight and was noted by her obstetrician to have delay in the growth of her baby. Ultrasound of the abdomen incidentally revealed the presence of a liver lesion. After additional evaluation, she ultimately delivered her daughter at 36 weeks uneventfully. She subsequently underwent additional evaluation. Liver magnetic resonance imaging (MRI) revealed a 5-cm solitary solid mass in segment 4A of the liver, concerning for malignancy. Serum α-fetoprotein, carcinoembryonic antigen, cancer antigen (CA)19-9, CA15-3, and CA125 were all normal. Liver biopsy was positive for adenocarcinoma. The tumor cells demonstrated a phenotype suggesting a possible breast primary, although the immunohistochemistry did not support that diagnosis and the tumor was negative for mammaglobin, gross cystic disease fluid protein (GCDFP)-15, estrogen receptor (ER), and progesterone receptor (PR) (Table 1). The tumor was also CDX2 and cardiotrophin-1 negative, but cytokeratin (CK) 19 positive. Her endoscopic retrograde cholangiopancreatography, upper endoscopy, colonoscopy, breast mammogram, and breast MRI were completely normal. A positron emission tomography-computed tomography scan showed a fluorodeoxyglucose-avid 5.8-cm × 6.0-cm hypoattenuating lesion with peripheral enhancement involving segment 4 and segment 8 at the dome. In addition, central necrosis within the lesion was noted. The left main portal vein was mildly attenuated by the mass. She eventually underwent a left hepatectomy en bloc with caudate resection, portal lymphadenectomy, cholecystectomy, and omental pedicle flap. On exploration of the abdomen, no additional disease was noted. The final pathology revealed a 9.4-cm moderately to poorly differentiated adenocarcinoma of the intrahepatic bile ducts. Venous invasion was present. Perineural invasion was absent. The margins were negative. Thirteen

  7. 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

  8. 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.

  9. 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.

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

    Science.gov (United States)

    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.

  11. Intrahepatic synthese of immunoglobulin G in chronic liver disease.

    Science.gov (United States)

    Kronborg, I J; Knopf, P M

    1980-04-01

    A method has been developed to measure the in vitro production of immunoglobulin (Ig) by liver biopsy specimens. Five to 30 mg of liver tissue was cultured for 24 h in Dulbecco's modified Eagle's medium/10% foetal calf serum (FCS) containing radiolabelled leucine (L-[4,5-3H] leucine). The culture medium was collected, centrifuged and the supernatant dialysed to remove labelled leucine. The residual radioactivity was a measure of newly synthesized 3H-labelled proteins released into the medium. The quantity of IgG was determined by immunoprecipitation with monospecific antisera to IgG heavy chains. The presence of IgG in the supernatant was confirmed by chromatography on protein-A Sepharose column. In 6 biopsies without evidence of active inflammation (4 normal and 2 fatty liver by histological criteria) less than 1% of the protein synthesized was IgG. In contrast in the presence of active inflammation in 4 cases of alcoholic hepatitis the IgG percentage ranged from 2 to 6%. Maximal levels of IgG production were detected in 3 cases of chronic active hepatitis (CAH) and ranged from 5 to 30%. The increased Ig synthesis by the liver in alcoholic hepatitis and CAH is presumed to be an index of the intrahepatic host response and may have important implications for mechanisms of liver damage in these diseases.

  12. Transjugular intrahepatic portosystemic shunt in liver transplant recipients

    Institute of Scientific and Technical Information of China (English)

    Armin Finkenstedt; Ivo W Graziadei; Karin Nachbaur; Werner Jaschke; Walter Mark; Raimund Margreiter; Wolfgang Vogel

    2009-01-01

    AIM: To evaluate the efficacy of transjugular intrahepatic portosystemic shunts (TIPSs) after liver transplantation (LT).METHODS: Between November 1996 and December 2005, 10 patients with severe recurrent hepatitis C virus infection ( n = 4), ductopenic rejection ( n = 5) or portal vein thrombosis ( n = 1) were included in this analysis. Eleven TIPSs (one patient underwent two TIPS procedures) were placed for management of therapy-refractory ascites ( n = 7), hydrothorax ( n = 2)or bleeding from colonic varices ( n = 1). The median time interval between LT and TIPS placement was 15(4-158) mo.RESULTS: TIPS placement was successful in all patients. The mean portosystemic pressure gradient was reduced from 12.5 to 8.7 mmHg. Complete and partial remission could be achieved in 43% and 29%of patients with ascites. Both patients with hydrothorax did not respond to TIPS. No recurrent bleeding was seen in the patient with colonic varices. Nine of 10patients died during the study period. Only one of two patients, who underwent retransplantation after the TIPS procedure, survived. The median survival period after TIPS placement was 3.3 (range 0.4-20) mo. The majority of patients died from sepsis with multiorgan failure.

  13. Transcaval transjugular intrahepatic portosystemic shunt: preliminary clinical results

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kwang Hun; Lee, Do Yun; Won, Jong Yoon [Yonsei University College of Medicine, Seoul (Korea, Republic of); Park, Sang Joon [Hallym University College of Medicine, Seoul (Korea, Republic of); Kim, Jae Kyu; Yoon, Woong [Chonnam National University Hospital, Gwangju (Korea, Republic of)

    2003-03-01

    To determine the feasibility of transcaval transjugular intrahepatic portosystemic shunt (TIPS) creation in patients with unusual anatomy between the hepatic veins and portal bifurcation, and inaccessible or inadequate hepatic veins. Transcaval TIPS, performed in six patients, was indicated by active variceal bleeding (n=2), recurrent variceal bleeding (n=2), intractable ascites (n=1), and as a bridge to liver transplantation (n=1). The main reasons for transcaval rather than classic TIPS were the presence of an unusually acute angle between the hepatic veins and the level of the portal bifurcation (n=3), hepatic venous occlusion (n=2), and inadequate small hepatic veins (n=1). Technical and functional success was achieved in all patients. The entry site into liver parenchyma from the inferior vena cava was within 2 cm of the atriocaval junction. Procedure-related complications included the death of one patient due to hemoperitoneum despite the absence of contrast media spillage at tractography, and another suffered reversible hepatic encephalopathy. In patients with unusual anatomy between the hepatic veins and portal bifurcation, and inaccessible or inadequate hepatic veins, transcaval TIPS creation is feasible.

  14. Intrahepatic porto-hepatic venous shunts in Rendu-Osler-Weber disease: imaging demonstration

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, Shunro; Mori, Hiromu; Yamada, Yasunari; Hayashida, Tomoko; Hori, Yuzo; Kiyosue, Hiro [Department of Radiology, Oita Medical University, Idaigaoka 1-1, Hasama-machi, 879-5593, Oita (Japan)

    2004-04-01

    This study describes the imaging features of the intrahepatic portohepatic venous (PHV) shunt, which is a potential cause of portosystemic encephalopathy in Rendu-Osler-Weber disease. Six patients with Rendu-Osler-Weber disease (two men, four women; age range 42-73 years) were retrospectively studied. There were two from one family and three from another family. Of these patients, one was diagnosed with definitive portosystemic encephalopathy because of a psychiatric disorder. We retrospectively reviewed the radiological examinations, including abdominal angiography (n=6), three-phase dynamic helical computed tomography (CT; n=3), and conventional enhanced CT (n=1). In one patient, CT during angiography and CT angioportography were also performed. Evaluation was placed on the imaging features of intrahepatic PHV shunts. On angiography, intrahepatic PHV shunts showing multiple and small shunts <5 mm in diameter in an apparent network were detected in all patents. In two patients, a large shunt with a size of either 7 or 10 mm was associated. These intrahepatic PHV shunts were predominantly distributed in the peripheral parenchyma. Intrahepatic PHV shunts would be characterized by small and multiple shunts in an apparent network on the periphery with or without a large shunt. (orig.)

  15. 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

  16. [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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    Marco Marzioni; Giammarco Fava; Antonio Benedetti

    2006-01-01

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

  19. 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

  20. Two Anomalies in One: A Rare Case of an Intrahepatic Gallbladder with a Cholecystogastric Fistula

    Directory of Open Access Journals (Sweden)

    Mohammad F. Ali

    2017-03-01

    Full Text Available The gallbladder can be situated in a variety of anomalous positions. An intrahepatic gallbladder – the second most common ectopic location of the gallbladder – is one that is completely embedded within the liver parenchyma. Described in the literature as early as 1935, intrahepatic gallbladders predominantly result from a developmental anomaly but in some instances have been reported to be secondary to chronic inflammation. The significance of an intrahepatic gallbladder lies in the fact that 60% of the cases are associated with gallstones and may present a challenge for the general surgeon during cholecystectomy and other biliary operations in addition to causing misdiagnosis on imaging. Intrahepatic gallbladders are unusual, but the incidence of an intrahepatic gallbladder with a cholecystogastric fistula is rare. Cholecystogastric fistulas commonly are a complication of long-term cholelithiasis or chronic cholecystitis with subsequent gallstone ileus. Herein, we present the case of an 80-year-old man who presented with 2 months of progressive weakness, fatigue, decreased appetite, and intermittent right-sided abdominal pain, and was found to have a markedly distended and irregular intrahepatic gallbladder measuring 12.2 × 11.5 × 13.4 cm on CT, as well as a cholecystogastric fistula on esophagogastroduodenoscopy. During esophagogastroduodenoscopy, the gallbladder was entered directly via the fistulous tract. The patient was on i.v. antibiotics with tube feeds via a nasojejunal tube initially, followed by p.o. which he tolerated. He was eventually discharged with referral for surgical evaluation. Given the potential for cholelithiasis and fistulation, physicians should have a high index of suspicion and recommend timely endoscopic and/or surgical management to avoid future complications.

  1. Bile Duct Leaks from the Intrahepatic Biliary Tree: A Review of Its Etiology, Incidence, and Management

    Directory of Open Access Journals (Sweden)

    Sorabh Kapoor

    2012-01-01

    Full Text Available Bile leaks from the intrahepatic biliary tree are an important cause of morbidity following hepatic surgery and trauma. Despite reduction in mortality for hepatic surgery in the last 2 decades, bile leaks rates have not changed significantly. In addition to posted operative bile leaks, leaks may occur following drainage of liver abscess and tumor ablation. Most bile leaks from the intrahepatic biliary tree are transient and managed conservatively by drainage alone or endoscopic biliary decompression. Selected cases may require reoperation and enteric drainage or liver resection for management.

  2. Does bilioenteric anastomosis impair results of liver resection in primary intrahepatic lithiasis?

    Institute of Scientific and Technical Information of China (English)

    Paulo; Herman; Marcos; V; Perini; Vincenzo; Pugliese; Julio; Cesar; Pereira; Marcel; Autran; C; Machado; William; A; Saad; Luiz; AC; D; Albuquerque; Ivan; Cecconello

    2010-01-01

    AIM:To evaluate the long-term results of liver resection for the treatment of primary intrahepatic lithiasis.Prognostic factors,especially the impact of bilioenteric anastomosis on recurrence of symptoms were assessed.METHODS:Forty one patients with intrahepatic stones and parenchyma fibrosis/atrophy and/or biliary stenosis were submitted to liver resection.Resection was associated with a Roux-en-Y hepaticojejunostomy in all patients with bilateral stones and in those with unilateral disease and dilation of...

  3. Paucity of intrahepatic bile ducts in infancy: experience of a tertiary center Hipoplasia de vias biliares intra-hepáticas na infância: experiência de um serviço terciário

    Directory of Open Access Journals (Sweden)

    Adriana Maria Alves De Tommaso

    2004-09-01

    Full Text Available BACKGROUND: Intrahepatic cholestasis secondary to paucity of bile duct is an alteration of the anatomic integrity of the biliary tract. Can be defined only histologically and, clinically, two categories are recognized: syndromic and non-syndromic, where the prognosis is generally more severe. AIM: To evaluate the history, clinical and biochemical characteristics, etiology and improvement of children who have paucity of intrahepatic bile duct followed at tertiary center. PATIENTS AND METHODS: Eleven children with paucity of intrahepatic bile duct, followed at the Pediatric Hepatology Service of the University Hospital, Campinas, SP, Brazil, were evaluated in the period from 1986 to 2001. RESULTS: Among the patients, three presented the syndromic and eight the non-syndromic form (two with alpha-1-antitrypsin deficiency, one with lues, one secondary to sepsis, three with probable etiology by cytomegalovirus and one without a definite etiology. Referral ranged from 31 to 1185 days. Birth weights ranged from 1920 g to 3590 g. Most of the patients presented pale stools. The median bile duct/portal tract ratio was 0.14. The majority of the children presented a favorable follow-up, regardless of the form of presentation. CONCLUSION: Paucity of intrahepatic bile ducts should be considered in children with cholestasis and its differentiation from extrahepatic causes of neonatal cholestasis is important in order to avoid surgery. Diagnosis of non-syndromic form should not be regarded as unfavorable prognosis, as the evolution is probably related to the etiology in this form of presentation.RACIONAL: A hipoplasia das vias biliares intra-hepáticas é causa de colestase secundária a uma alteração na integridade anatômica do trato biliar. A definição é dada pelo exame histopatológico e, do ponto de vista clínico, pode ser classificada em sindrômica e não-sindrômica onde o prognóstico é, geralmente, mais grave. OBJETIVO: Avaliar a hist

  4. Radiation Exposure in Transjugular Intrahepatic Portosystemic Shunt Creation

    Energy Technology Data Exchange (ETDEWEB)

    Miraglia, Roberto, E-mail: rmiraglia@ismett.edu; Maruzzelli, Luigi, E-mail: lmaruzzelli@ismett.edu; Cortis, Kelvin, E-mail: kelvincortis@ismett.edu [Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Radiology Service, Department of Diagnostic and Therapeutic Services (Italy); D’Amico, Mario, E-mail: mdamico@ismett.edu [University of Palermo, Department of Radiology (Italy); Floridia, Gaetano, E-mail: gfloridia@ismett.edu; Gallo, Giuseppe, E-mail: ggallo@ismett.edu; Tafaro, Corrado, E-mail: ctafaro@ismett.edu; Luca, Angelo, E-mail: aluca@ismett.edu [Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Radiology Service, Department of Diagnostic and Therapeutic Services (Italy)

    2016-02-15

    PurposeTransjugular intrahepatic portosystemic shunt (TIPS) creation is considered as being one of the most complex procedures in abdominal interventional radiology. Our aim was twofold: quantification of TIPS-related patient radiation exposure in our center and identification of factors leading to reduced radiation exposure.Materials and methodsThree hundred and forty seven consecutive patients underwent TIPS in our center between 2007 and 2014. Three main procedure categories were identified: Group I (n = 88)—fluoroscopic-guided portal vein targeting, procedure done in an image intensifier-based angiographic system (IIDS); Group II (n = 48)—ultrasound-guided portal vein puncture, procedure done in an IIDS; and Group III (n = 211)—ultrasound-guided portal vein puncture, procedure done in a flat panel detector-based system (FPDS). Radiation exposure (dose-area product [DAP], in Gy cm{sup 2} and fluoroscopy time [FT] in minutes) was retrospectively analyzed.ResultsDAP was significantly higher in Group I (mean ± SD 360 ± 298; median 287; 75th percentile 389 Gy cm{sup 2}) as compared to Group II (217 ± 130; 178; 276 Gy cm{sup 2}; p = 0.002) and Group III (129 ± 117; 70; 150 Gy cm{sup 2}p < 0.001). The difference in DAP between Groups II and III was also significant (p < 0.001). Group I had significantly longer FT (25.78 ± 13.52 min) as compared to Group II (20.45 ± 10.87 min; p = 0.02) and Group III (19.76 ± 13.34; p < 0.001). FT was not significantly different between Groups II and III (p = 0.73).ConclusionsReal-time ultrasound-guided targeting of the portal venous system during TIPS creation results in a significantly lower radiation exposure and reduced FT. Further reduction in radiation exposure can be achieved through the use of modern angiographic units with FPDS.

  5. 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.

  6. Spontaneous perforation of gallbladder with intrahepatic biloma formation: sonographic signs and correlation with computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Hollanda, Erick Sabbagh de; Torres, Ulysses dos Santos; Gual, Fabiana; Oliveira, Eduardo Portela de; Cardoso, Luciana Vargas; Criado, Divanei Aparecida Bottaro, E-mail: usantor@yahoo.com.br [Faculdade de Medicina de Sao Jose do Rio Preto (Famerp), SP (Brazil). Hospital de Base

    2013-09-15

    Spontaneous perforation of gallbladder is a severe and infrequent complication of acute cholecystitis that requires early and accurate diagnosis. Concomitant development of intrahepatic collections is rarely observed in such cases. The present report emphasizes the relevance of imaging studies in this setting, describing the typical sonographic and tomographic findings for the diagnosis of such condition. (author)

  7. Endoscopic transcystic stent placement for an intrahepatic abscess due to gallbladder perforation

    Institute of Scientific and Technical Information of China (English)

    Myung Soo Kang; Do Hyun Park; Ki Du Kwon; Jeong Hoon Park; Suck-Ho Lee; Hong-Soo Kim; Sang-Heum Park; Sun-Joo Kim

    2007-01-01

    Perforation of the gallbladder with cholecystohepatic communication is a rare cause of liver abscess. Because it is a rare entity, the treatment modality has not been fully established. We report for the first time a patient with an intrahepatic abscess due to gallbladder perforation successfully treated by endoscopic stent placement into the gallbladder who had a poor response to continuous percutaneous drainage.

  8. A fatal case of primary basaloid squamous cell carcinoma in the intrahepatic bile ducts

    DEFF Research Database (Denmark)

    Kirkegaard, Johan; Grunnet, Mie; Hasselby, Jane Preuss

    2014-01-01

    of diagnosis but expired 20 months after surgery with epidural, lung, and spine metastasis. In addition to the unusual clinical presentation, the diagnosis of the liver tumor was that of a primary basaloid squamous cell carcinoma of the intrahepatic bile ducts, an entity with only one previous report...

  9. Tumor Implantation into the Intrahepatic Bile Duct after Percutaneous Ethanol Injection Therapy for Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Shogo Tanaka

    2009-11-01

    Full Text Available A 74-year-old man who had undergone transcatheter arterial embolization for hepatitis C virus-related hepatocellular carcinoma (Couinaud’s segment III/IV in April 2003 and percutaneous ethanol injection for recurrence at the same site in February 2006 was found to have dilation of the intrahepatic bile duct by computed tomography in October 2008. Contrast-enhanced computed tomography and magnetic resonance cholangiopancreatography showed a thrombosis occupying the left hepatic duct to the lateral branches with peripheral bile duct dilation. Serum concentration of alpha-fetoprotein was elevated. We performed a left hepatectomy under a preoperative diagnosis of hepatocellular carcinoma with bile duct invasion. The cut surface of the resected specimen showed a tumor thrombosis occupying the region between the left hepatic duct and lateral branches, but no tumor in the liver parenchyma. Histologic examination showed that the thrombosis in the intrahepatic bile duct was hepatocellular carcinoma. Since part of the hepatocellular carcinoma in the region treated with percutaneous ethanol injection was adjacent to the tumor thrombosis in the intrahepatic bile duct in diagnostic imaging, we diagnosed implantation into the intrahepatic bile duct due to percutaneous ethanol injection. The postoperative course was uneventful and the patient is doing well without recurrence 8 months after the operation.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-03-15

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

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    Leilei Wang

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  14. Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas

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    Selaru, Florin M; Streppel, Mirte M; Lucas, Donald J; Niknafs, Noushin; Guthrie, Violeta Beleva; Maitra, Anirban; Argani, Pedram; Offerhaus, G Johan A; Roa, Juan Carlos; Roberts, Lewis R; Gores, Gregory J; Popescu, Irinel; Alexandrescu, Sorin T; Dima, Simona; Fassan, Matteo; Simbolo, Michele; Mafficini, Andrea; Capelli, Paola; Lawlor, Rita T; Ruzzenente, Andrea; Guglielmi, Alfredo; Tortora, Giampaolo; de Braud, Filippo; Scarpa, Aldo; Jarnagin, William; Klimstra, David; Karchin, Rachel; Velculescu, Victor E; Hruban, Ralph H; Vogelstein, Bert; Kinzler, Kenneth W; Papadopoulos, Nickolas; Wood, Laura D

    2014-01-01

    Through exomic sequencing of 32 intrahepatic cholangiocarcinomas, we discovered frequent inactivating mutations in multiple chromatin-remodeling genes (including BAP1, ARID1A and PBRM1), and mutation in one of these genes occurred in almost half of the carcinomas sequenced. We also identified frequent mutations at previously reported hotspots in the IDH1 and IDH2 genes encoding metabolic enzymes in intrahepatic cholangiocarcinomas. In contrast, TP53 was the most frequently altered gene in a series of nine gallbladder carcinomas. These discoveries highlight the key role of dysregulated chromatin remodeling in intrahepatic cholangiocarcinomas. PMID:24185509

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. Intrahepatic distribution of hepatitis B virus antigens in patients with and without hepatocellular carcinoma

    Science.gov (United States)

    Safaie, Parham; Poongkunran, Mugilan; Kuang, Ping-Ping; Javaid, Asad; Jacobs, Carl; Pohlmann, Rebecca; Nasser, Imad; Lau, Daryl TY

    2016-01-01

    AIM: To study the intrahepatic expression of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in chronic hepatitis B patients with and without hepatocellular carcinoma. METHODS: A total of 33 chronic hepatitis B patients (mean age of 40.3 ± 2.5 years), comprising of 14 HBeAg positive and 19 HBeAg negative patients; and 13 patients with hepatitis B virus related hepatocellular carcinoma (mean age of 49.6 ± 4.7 years), were included in our study. Immunohistochemical staining for HBcAg and HBsAg was done using standard streptavidin-biotin-immunoperoxidase technique on paraffin-embedded liver biopsies. The HBcAg and HBsAg staining distributions and patterns were described according to a modified classification system. RESULTS: Compared to the HBeAg negative patients, the HBeAg positive patients were younger, had higher mean HBV DNA and alanine transaminases levels. All the HBeAg positive patients had intrahepatic HBcAg staining; predominantly with “diffuse” distribution (79%) and “mixed cytoplasmic/nuclear” pattern (79%). In comparison, only 5% of the HBeAg-negative patients had intrahepatic HBcAg staining. However, the intrahepatic HBsAg staining has wider distribution among the HBeAg negative patients, namely; majority of the HBeAg negative cases had “patchy” HBsAg distribution compared to “rare” distribution among the HBeAg positive cases. All but one patient with HCC were HBeAg negative with either undetectable HBV DNA or very low level of viremia. Intrahepatic HBcAg and HBsAg were seen in 13 (100%) and 10 (77%) of the HCC patients respectively. Interestingly, among the 9 HCC patients on anti-viral therapy with suppressed HBV DNA, HBcAg and HBsAg were detected in tumor tissues but not the adjacent liver in 4 (44%) and 1 (11%) patient respectively. CONCLUSION: Isolated intrahepatic HBcAg and HBsAg can be present in tumors of patients with suppressed HBV DNA on antiviral therapy; that may predispose them to cancer development

  20. Calorie Restricted High Protein Diets Downregulate Lipogenesis and Lower Intrahepatic Triglyceride Concentrations in Male Rats

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    Lee M. Margolis

    2016-09-01

    Full Text Available The purpose of this investigation was to assess the influence of calorie restriction (CR alone, higher-protein/lower-carbohydrate intake alone, and combined CR higher-protein/lower-carbohydrate intake on glucose homeostasis, hepatic de novo lipogenesis (DNL, and intrahepatic triglycerides. Twelve-week old male Sprague Dawley rats consumed ad libitum (AL or CR (40% restriction, adequate (10%, or high (32% protein (PRO milk-based diets for 16 weeks. Metabolic profiles were assessed in serum, and intrahepatic triglyceride concentrations and molecular markers of de novo lipogenesis were determined in liver. Independent of calorie intake, 32% PRO tended to result in lower homeostatic model assessment of insulin resistance (HOMA-IR values compared to 10% PRO, while insulin and homeostatic model assessment of β-cell function (HOMA-β values were lower in CR than AL, regardless of protein intake. Intrahepatic triglyceride concentrations were 27.4 ± 4.5 and 11.7 ± 4.5 µmol·g−1 lower (p < 0.05 in CR and 32% PRO compared to AL and 10% PRO, respectively. Gene expression of fatty acid synthase (FASN, stearoyl-CoA destaurase-1 (SCD1 and pyruvate dehydrogenase kinase, isozyme 4 (PDK4 were 45% ± 1%, 23% ± 1%, and 57% ± 1% lower (p < 0.05, respectively, in CR than AL, regardless of protein intake. Total protein of FASN and SCD were 50% ± 1% and 26% ± 1% lower (p < 0.05 in 32% PRO compared to 10% PRO, independent of calorie intake. Results from this investigation provide evidence that the metabolic health benefits associated with CR—specifically reduction in intrahepatic triglyceride content—may be enhanced by consuming a higher-protein/lower-carbohydrate diet.

  1. The roles of Notch1 expression in the migration of intrahepatic cholangiocarcinoma

    OpenAIRE

    Zhou, Qi; Wang, Yafeng; Peng, Baogang; Liang, Lijian; Li, Jiaping

    2013-01-01

    Background Notch signaling, a critical pathway for tissue development, contributes to tumorigenesis in many tissues; however, the roles of Notch signaling in Intrahepatic Cholangiocarcinoma (ICC) remains unclear. In this study, we evaluated the expression and effects of Notch1 on cell migration in ICC. Methods Multiple cellular and molecular approaches were performed including gene transfection, siRNA transfection, RT-PCR, Western blotting, Rac activation assays and immunofluorescence. Result...

  2. Treatment of Portosystemic Shunt Myelopathy with a Stent Graft Deployed through a Transjugular Intrahepatic Route

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Deepak, E-mail: deepakjain02@yahoo.com; Arora, Ankur, E-mail: aroradrankur@yahoo.com [Institute of Liver and Biliary Sciences, Department of Radiology (India); Deka, Pranjal, E-mail: drpranjaldeka@gmail.com [Institute of Liver and Biliary Sciences, Department of Hepatopancreatobiliary Surgery (India); Mukund, Amar, E-mail: dramarmukund@gmail.com; Bhatnagar, Shorav, E-mail: drshorav@yahoo.com [Institute of Liver and Biliary Sciences, Department of Radiology (India); Jindal, Deepti, E-mail: deepijindal@rediffmail.com; Kumar, Niteen, E-mail: drniteenkumar@gmail.com; Pamecha, Viniyendra, E-mail: viniyendra@yahoo.co.uk [Institute of Liver and Biliary Sciences, Department of Hepatopancreatobiliary Surgery (India)

    2013-08-01

    A case of surgically created splenorenal shunt complicated with shunt myelopathy was successfully managed by placement of a stent graft within the splenic vein to close the portosystemic shunt and alleviate myelopathy. To our knowledge, this is the first report of a case of shunt myelopathy in a patient with noncirrhotic portal fibrosis without cirrhosis treated by a novel technique wherein a transjugular intrahepatic route was adopted to deploy the stent graft.

  3. 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.

  4. Irreversible Electroporation of a Hepatocellular Carcinoma Lesion Adjacent to a Transjugular Intrahepatic Portosystemic Shunt Stent Graft

    Energy Technology Data Exchange (ETDEWEB)

    Niessen, Christoph; Jung, Ernst Michael; Wohlgemuth, Walter A. [Department of Radiology, University Medical Center Regensburg, Regensburg D-93053 (Germany); Trabold, Benedikt [Department of Anaesthesia, University Medical Center Regensburg, Regensburg D-93053 (Germany); Haimerl, Michael; Schreyer, Andreas; Stroszczynski, Christian; Wiggermann, Philipp [Department of Radiology, University Medical Center Regensburg, Regensburg D-93053 (Germany)

    2013-07-01

    We report in a 65-year-old man hepatocellular carcinoma adjacent to a transjugular intrahepatic portosystemic shunt stent-graft which was successfully treated with irreversible electroporation (IRE). IRE is a new non-thermal tissue ablation technique which uses electrical pulses to induce cell necrosis by irreversible membrane poration. IRE proved to be more advantageous in the ablation of perivascular tumor with little injury to the surrounding structures.

  5. Asymptomatic Intrahepatic Portosystemic Venous Shunt: To Treat or Not To Treat?

    Science.gov (United States)

    Palvanov, Arkadiy; Marder, Ruth Leah; Siegel, David

    2016-09-01

    Intrahepatic portosystemic venous shunts (IPSVSs) are rare vascular malformations. They can be asymptomatic or present with various symptoms including encephalopathy. We present two cases of IPSVS, one involving a patient presenting with altered mental status and the other discovered incidentally. While there is no question that patients presenting with symptomatic IPSVS should undergo definitive treatment, there is no consensus regarding elective therapy for asymptomatic lesions.

  6. Modified rendezvous intrahepatic bile duct cannulation technique to pass a PTBD catheter in ERCP

    Institute of Scientific and Technical Information of China (English)

    Tae; Hoon; Lee; Sang-Heum; Park; Sae; Hwan; Lee; Chang-Kyun; Lee; Suck-Ho; Lee; Il-Kwun; Chung; Hong; Soo; Kim; Sun-Joo; Kim

    2010-01-01

    The rendezvous procedure combines an endoscopic technique with percutaneous transhepatic biliary drainage(PTBD).When a selective common bile duct cannulation fails,PTBD allows successful drainage and retrograde access for subsequent rendezvous techniques.Traditionally,rendezvous procedures such as the PTBDassisted over-the-wire cannulation method,or the parallel cannulation technique,may be available when a bile duct cannot be selectively cannulated.When selective intrahepatic bile duct(IHD) cannulation fai...

  7. Ultrasonic Contrast Portography for Demonstration of Intrahepatic Porto-systemic Shunts

    Directory of Open Access Journals (Sweden)

    Yi-Hong Chou

    2016-03-01

    Full Text Available Spontaneous intrahepatic porto-systemic shunts (IHPSS can be disclosed with ultrasound (US and color Doppler ultrasound (CDU. However, direct evidence of the shunt on US or CDU may not be convincing. In this report we demonstrate the presence of IHPSS by ultrasonic contrast portography with intravenous injection of microbubble-based contrast agent (MBCA. With this technique, the MBCA was depicted to enter the hepatic vein through the shunt, and then flowed into the inferior vena cava.

  8. Clinical effect of laparoscopic hepatolobectomy in patients with intrahepatic bile duct stones

    Institute of Scientific and Technical Information of China (English)

    Pei Yu; Yan-Xia Zhong

    2016-01-01

    Objective:To study the clinical effect of laparoscopic hepatolobectomy in patients with intrahepatic bile duct stones. Methods:Patients with intrahepatic bile duct stones receiving hepatolobectomy were chosen for study, patients receiving laparoscopic surgery and patients receiving open surgery were screened and enrolled in laparoscopic group and open group respectively, and then degree of stress response, degree of liver damage and Nrf2-ARE signaling pathway function of two groups were compared. Results:At T1 and T2 points in time, stress indicators and Nrf2-ARE signaling pathway function of two groups had no difference;at T3 and T4 points in time, blood sugar, cortisol and angiotensin levels of laparoscopic group were lower, and insulin level as well as Nrf2 and ARE contents were higher;at T4 point in time, 8-OhdG, PCO, CYP1A and CYP3A contents of laparoscopic group were lower. Conclusion: Laparoscopic hepatolobectomy helps to relieve stress response, protect liver cells from damage and enhance Nrf2-ARE signaling pathway function;it’s an ideal method of surgical treatment of intrahepatic bile duct stones.

  9. Postpartum Acute Liver Dysfunction: A Case of Acute Fatty Liver of Pregnancy Developing Massive Intrahepatic Calcification

    Science.gov (United States)

    Bhat, Khalid Javid; Shovkat, Rabia; Samoon, Hamad Jeelani

    2015-01-01

    The function of the liver is particularly affected by the unique physiologic milieu of the pregnancy. Pregnancy-related liver diseases encompass a spectrum of different etiologies that are related to gestation or one of its complications. Hepatic calcification, a rare entity, is usually associated with infectious, vascular, or neoplastic lesions in the liver. To the best of our knowledge, only one case of rapidly occurring pregnancy-related intrahepatic calcification has been documented in a patient with severe eclampsia or hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome. Here we present a case of immediate “postpartum” acute fatty liver of pregnancy (AFLP) in a 23-year-old hypertensive primigravida, complicated by acute renal dysfunction who developed dense intrahepatic calcification in less than a month after the initial diagnosis. A multidisciplinary approach for the management was used, to which the patient responded aptly. This case illustrates the first description of intrahepatic calcification in AFLP syndrome and highlights some of the challenges met in making the final diagnosis. PMID:27785315

  10. Trousseau's Syndrome Caused by Intrahepatic Cholangiocarcinoma: An Autopsy Case Report and Literature Review

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    Takashi Yuri

    2014-05-01

    Full Text Available An autopsy case report of Trousseau's syndrome caused by intrahepatic cholangiocarcinoma is presented, and seven previously reported cases are reviewed. A 73-year-old woman experiencing light-headedness and dementia of unknown cause for 6 months developed severe hypotonia. A hypointense lesion compatible with acute cerebral infarction was detected by magnetic resonance imaging. Abdominal computed tomography revealed an ill-defined large liver mass in the right lobe. The mass was not further investigated because of the patient's poor condition. She died of multiple organ failure, and an autopsy was conducted. Postmortem examination revealed intrahepatic cholangiocarcinoma, fibrous vegetations on the mitral valves and multiple thromboemboli in the cerebrum, spleen and rectum. Trousseau's syndrome is defined as an idiopathic thromboembolism in patients with undiagnosed or concomitantly diagnosed malignancy. This syndrome is encountered frequently in patients with mucin-producing carcinomas, while the incidence in patients with intrahepatic cholangiocarcinoma is uncommon. We found that tissue factor and mucin tumor marker (CA19-9, CA15-3 and CA-125 expression in cancer cells may be involved in the pathogenesis of thromboembolism. A patient with unexplained thromboembolism may have occult visceral malignancy; thus, mucin tumor markers may indicate the origin of a mucin-producing carcinoma, and postmortem examination may play an important role in revealing the hidden malignancy.

  11. Hybrid technique coil embolisation for intrahepatic arterioportal fistula in a cat: case report

    Directory of Open Access Journals (Sweden)

    Akiko Uemura

    2016-04-01

    Full Text Available Case summary A 13-month-old, female, mixed breed, 4.0 kg cat was referred with a 6 month history of decreased appetite, loss of vigour and intermittent vomiting. Physical examination revealed no cyanosis or wasting, and no audible heart murmur was auscultated. Blood profile revealed mild anaemia and mildly elevated postprandial serum ammonia (109 µg/dl. Abdominal ultrasonography revealed dilation of an intrahepatic portal vein branch and an intrahepatic aneurysm, with splenomegaly and ascites. Hepatic arteriovenous fistula/hepatic artery–portal vein fistula with multiple acquired portosystemic shunts was strongly suspected. Medical control was achieved using antibiotics, liver-protecting agents, a low-protein diet and blood transfusions. However, because medical treatment proved ineffective, coil embolisation was performed on day 11, using a hybrid approach via the mesenteric vein. Subsequent follow-up showed good appetite, with no signs of diarrhoea or ascites. Abdominal ultrasonography revealed that the mosaic pattern around the site of coil placement in the portal vein branch had improved and pulsatility had disappeared. Relevance and novel information Intrahepatic arterioportal fistula involves a circulatory shunt between the hepatic artery and the hepatic or portal vein within the liver, and may be congenital or acquired. Both forms have been reported in humans, but most cases in cats have been congenital. Few reports have described treatment methods or prognosis in cats. We report here that coil embolisation using a hybrid approach is a procedure offering easy, effective treatment by blocking hepatofugal blood flow.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

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

    Institute of Scientific and Technical Information of China (English)

    赵彩彦; 王玮; 刘英辉; 王亚东; 周俊英

    2010-01-01

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

  19. 妊娠期胆汁淤积症对新生儿中枢神经的影响%Affection of intrahepatic cholestasis of pregnancy (ICP) on neonatal central nervous system

    Institute of Scientific and Technical Information of China (English)

    刘静; 万俊; 蒋犁

    2004-01-01

    妊娠期肝内胆汁淤积症时在各种机制作用下母儿胆汁酸淤积,通过胆汁酸、胆红素的细胞毒作用,影响胎盘血流灌注、血液携氧能力、机体抗氧化防御系统引起胎儿窘迫、窒息致中枢神经系统缺氧损伤.神经细胞中钙稳态是保证其结构完整和功能正常的重要因素,烯醇化酶是缺氧缺血性脑损伤早期的标志酶.通过检测新生儿脐动脉血中的游离钙,烯醇化酶浓度来预测脑损伤及其严重程度,对早期干预具有十分重要的意义.

  20. 疱疹样脓疱病并发妊娠期肝内胆汁淤积症1例%A case of impetigo herpetiformis and gestational intrahepatic cholestasis

    Institute of Scientific and Technical Information of China (English)

    樊平申; 李淼; 高天文; 廖文俊; 陈必良

    2004-01-01

    报告1例疱疹样脓疱病并发妊娠期肝内胆汁淤积症.患者女,26岁.妊娠34-1周,躯干和四肢出现红斑、脓疱伴瘙痒和疼痛5个月,加重1个月,近期出现黄疸.入院时血清丙氨酸转氨酶、天冬氨酸转氨酶、血清胆红素和胆汁酸均升高,皮损组织病理改变符合疱疹样脓疱病.行剖宫产术,给予糖皮质激素、局部抗感染及对症支持等治疗后皮损痊愈.

  1. Clinical value of prenatal care with different methods on intrahepatic cholestasis of pregnancy%产前不同监测方法对ICP胎儿监测的临床意义

    Institute of Scientific and Technical Information of China (English)

    蒋惠玲; 王冬梅; 王志梅

    2008-01-01

    目的:探讨妊娠期肝内胆汁淤积症(ICP)的产前监测方法.方法:对我院同期的ICP患者与正常孕妇60例进行肝功能、S/D值(脐动脉收缩期最大血流速/舒张末期最低血流速)、Manning评分、无应激试验(NST)及羊水污染、Apgar 评分、胎儿体重进行对比分析;通过x2检验分析Manning评分各项监测指标中对ICP有意义的项目;利用多元回归分析的方法了解不同产前监测方法与ICP新生儿Apgar评分的关系.结果:ICP患者与正常孕妇在肝功能指标、S/D值、Manning评分及羊水污染率、Apgar评分间的差异有统计学意义;在Manning评分各项监测指标中对ICP的监测有意义的指标是胎动和肌张力;产前监测ICP患者的转氨酶及NST水平变化可预测ICP患者新生儿的Apgar评分,而胆红素、胆汁酸、甘胆酸、S/D值、Manning 评分的变化与ICP患者新生儿的Apgar评分的变化无相关性.结论:ICP患者Manning评分的监测指标中胎动和肌张力的变化对胎儿宫内情况有监测意义;在对ICP患者的各种产前监测方法中,转氨酶水平及NST评分的监测能够反应新生儿出生状态.

  2. 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.

  3. [Is intrahepatic cholangiojejunostomy in liver hilus-localized malignant occlusive jaundice a better alternative to endoscopic transhepatic drainage?].

    Science.gov (United States)

    Paquet, K J; Koussouris, P

    1987-10-01

    The malignant obstruction of the hepatic confluence has a poor prognosis and no chance of cure. Therefore the therapy of choice today is usually a transpapillary drainage and surgical interventions are avoided. Before the indication for a transhepatic drainage is established the malignant etiology of this disease should be verified in every case and inoperability should be cleared in case of doubt by laparotomy. In a few cases a curative resection is possible. From January 1st, 1979 to September 1st, 1986 we succeeded in a curative resection in one out of fourteen cases; in thirteen cases an intrahepatic cholangio-enterostomy, eleven times with the left intrahepatic duct and two times with the right intrahepatic duct, was performed. Though the rate of postoperative complication was 54%, in hospital mortality was only 7%. The curatively operated woman is now living for six years postoperatively and the man with a benign intrahepatic stricture after right hepatectomy because of hepatocellular cancer is now living 44 months after the first operation. The mean survival time of the palliative operated patients is 12.3 months. Thus the intrahepatic cholangio-enterostomy seems to be superior to the endoscopic transpapillary drainage in comparable cases of tumor obstruction of the hepatic confluence concerning life quality and life expectancy.

  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. Combination therapy using PSE and TIO ameliorates hepatic encephalopathy due to intrahepatic portosystemic venous shunt in idiopathic portal hypertension

    Directory of Open Access Journals (Sweden)

    Seiichiro Kojima

    2016-09-01

    Full Text Available A 64-year-old woman treated for anemia and ascites exhibited hepatic encephalopathy. Abdominal ultrasonography and computed tomography (CT showed communication between the portal vein and the middle hepatic vein, indicating an intrahepatic portosystemic venous shunt (PSS. Since hepatic encephalopathy of the patient was resistant to medical treatment, interventional radiology was performed for the treatment of shunt obliteration. Hepatic venography showed anastomosis between the hepatic vein branches, supporting the diagnosis of idiopathic portal hypertension (IPH. To minimize the increase in portal vein pressure after shunt obliteration, partial splenic artery embolization (PSE was first performed to reduce portal vein blood flow. Transileocolic venous obliteration (TIO was then performed, and intrahepatic PSS was successfully obliterated using coils with n-butyl-2-cyanoacrylate (NBCA. In the present case, hepatic encephalopathy due to intrahepatic PSS in the patient with IPH was successfully treated by combination therapy using PSE and TIO.

  6. Surgical management of intrahepatic vessels in children with stage Ⅲ/Ⅳ hepatoblastoma

    Institute of Scientific and Technical Information of China (English)

    PANG Yan-li; ZHAO Wei; YANG He-ying; LIU Qiu-liang; ZHANG Da; QIN Pan; YUE Ming

    2013-01-01

    Background Hepatoblastoma (HB) is a rare childhood tumor.We investigated the effect of intraoperative management of the intrahepatic major vessels in children with HB.Methods Between April 2005 and August 2012,surgical resection was performed on 50 children with hepatoblastoma.These children were divided into a vessel-ligation group (n=20) and a vessel-repair group (n=30).In the vessel-ligation group,the intrahepatic major vessels were ligated and removed together with the tumor and the affected liver lobe/liver parenchyma.In the vessel-repair group,the affected intrahepatic major vessels were dissected and preserved as much as possible and the normal liver lobe/liver parenchyma and blood supply from these vessels were also preserved.The outcomes were analyzed by postoperative follow-up.Results In the vessel-ligation group,two patients gave up surgery,six patients underwent palliative resection,and 12 patients underwent en b/oc resection; four patients died of liver failure and eight patients fully recovered and were discharged.In the vessel-repair group,all 30 patients underwent en b/oc resection and were discharged after satisfactory healing.After a follow-up time of 5-36 months (median:20 months),two patient in the vessel-ligation group survived and 22 patients in the vessel-repair group survived.Conclusions Patients with HB can be successfully treated by tumor resection with vascular repair.This method prevents postoperative liver failure,ensures Patient safetv during the perioperative period,and allows for early chemotherapy.

  7. Intrahepatic Left to Right Portoportal Venous Collateral Vascular Formation in Patients Undergoing Right Portal Vein Ligation

    Energy Technology Data Exchange (ETDEWEB)

    Lienden, K. P. van, E-mail: k.p.vanlienden@amc.uva.nl [Academic Medical Center, University of Amsterdam, Department of Interventional Radiology (Netherlands); Hoekstra, L. T. [Academic Medical Center, University of Amsterdam, Department of Surgery (Netherlands); Bennink, R. J. [Academic Medical Center, University of Amsterdam, Department of Nuclear Medicine (Netherlands); Gulik, T. M. van [Academic Medical Center, University of Amsterdam, Department of Surgery (Netherlands)

    2013-12-15

    Purpose: We investigated intrahepatic vascular changes in patients undergoing right portal vein ligation (PVL) or portal vein embolization (PVE) in conjunction with the ensuing hypertrophic response and function of the left liver lobe. Methods: Between December 2008 and October 2011, 7 patients underwent right PVL and 14 patients PVE. Computed tomographic (CT) volumetry to assess future remnant liver (FRL) and functional hepatobiliary scintigraphy were performed in all patients before and 3 weeks after portal vein occlusion. In 18 patients an intraoperative portography was performed to assess perfusion through the occluded portal branches. Results: In all patients after initially successful PVL, reperfused portal veins were observed on CT scan 3 weeks after portal occlusion. This was confirmed in all cases during intraoperative portography. Intrahepatic portoportal collaterals were identified in all patients in the PVL group and in one patient in the PVE group. In all other PVE patients, complete occlusion of the embolized portal branches was observed on CT scan and on intraoperative portography. The median increase of FRL volume after PVE was 41.6 % (range 10-305 %), and after PVL was only 8.1 % (range 0-102 %) (p = 0.179). There were no differences in FRL function between both groups. Conclusion: Preoperative PVE and PVL are both methods to induce hypertrophy of the FRL in anticipation of major liver resection. Compared to PVE, PVL seems less efficient in inducing hypertrophy of the nonoccluded left lobe. This could be caused by the formation of intrahepatic portoportal neocollateral vessels, through which the ligated portal branches are reperfused within 3 weeks.

  8. Role of ErbB family receptor tyrosine kinases in intrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Aberrant expression and signaling of epidermal growth factor receptor (ErbB) family receptor tyrosine kinases, most notably that of ErbB2 and ErbB1, have been implicated in the molecular pathogenesis of intrahepatic cholangiocarcinoma. Constitutive overexpression of ErbB2 and/or ErbB1 in malignant cholangiocytes has raised interest in the possibility that agents which selectively target these receptors could potentially be effective in cholangiocarcinoma therapy. However, current experience with such ErbB-directed therapies have at best produced only modest responses in patients with biliary tract cancers. This review provides a comprehensive and critical analysis of both preclinical and clinical studies aimed at assessing the role of altered ErbB2 and/or ErbB1 expression, genetic modifications, and dysregulated signaling on cholangiocarcinoma development and progression. Specific limitations in experimental approaches that have been used to assess human cholangiocarcinoma specimens for ErbB2 and/or ErbB1 overexpression and gene amplification are discussed. In addition, current rodent models of intrahepatic cholangiocarcinogenesis associated with constitutive ErbB2 overexpression are reviewed. Select interactive relationships between ErbB2 or ErbB1 with other relevant molecular signaling pathways associated with intrahepatic cholangiocarcinoma development and progression are also detailed, including those linking ErbB receptors to bile acid, cyclooxygenase-2, interleukin-6/gp130, transmembrane mucins, hepatocyte growth factor/Met, and vascular endothelial growth factor signaling. Lastly, various factors that can limit therapeutic efficacy of ErbB-targeted agents against cholangiocarcinoma are considered.

  9. Body composition changes after transjugular intrahepatic portosystemic shunt in patients with cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Jonathan; Montomoli; Peter; Holland-Fischer; Giampaolo; Bianchi; Henning; GrФnbk; Hendrik; Vilstrup; Giulio; Marchesini; Marco; Zoli

    2010-01-01

    AIM:To investigate the effect of transjugular intra-hepatic porto-systemic shunt (TIPS) on malnutrition in portal hypertensive cirrhotic patients.METHODS: Twenty-one patients with liver cirrhosis and clinical indications for TIPS insertion were investigated before and 1, 4, 12, 52 wk after TIPS. For each patient we assayed body composition parameters [dry lean mass, fat mass, total body water (TBW)], routine liver and kidney function tests, and free fatty acids (FFA). Glucose and insulin were measured for t...

  10. Pancreaticoportal Fistula and Disseminated Fat Necrosis After Revision of a Transjugular Intrahepatic Portosystemic Shunt

    Energy Technology Data Exchange (ETDEWEB)

    Klein, Seth J., E-mail: kleins@mir.wustl.edu; Saad, Nael [Washington University School of Medicine, Interventional Radiology Section, Mallinckrodt Institute of Radiology (United States); Korenblat, Kevin [Washington University School of Medicine, Division of Gastroenterology, Department of Internal Medicine (United States); Darcy, Michael D. [Washington University School of Medicine, Interventional Radiology Section, Mallinckrodt Institute of Radiology (United States)

    2013-04-15

    A 59-year old man with alcohol related cirrhosis and portal hypertension was referred for transjugular intrahepatic portosystemic shunt (TIPS) to treat his refractory ascites. Ten years later, two sequential TIPS revisions were performed for shunt stenosis and recurrent ascites. After these revisions, he returned with increased serum pancreatic enzyme levels and disseminated superficial fat necrosis; an iatrogenic pancreaticoportal vein fistula caused by disruption of the pancreatic duct was suspected. The bare area of the TIPS was subsequently lined with a covered stent-graft, and serum enzyme levels returned to baseline. In the interval follow-up period, the patient has clinically improved.

  11. Diffusion weighted MRI in intrahepatic bile duct adenoma arising from the cirrhotic liver

    Energy Technology Data Exchange (ETDEWEB)

    An, Chansik [Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Park, Sumi; Choi, Yoon Jung [National Health Insurance Corporation Ilsan Hospital, Goyang (Korea, Republic of)

    2013-10-15

    A 64-year-old male patient with liver cirrhosis underwent a CT study for hepatocellular carcinoma surveillance, which demonstrated a 1.4-cm hypervascular subcapsular tumor in the liver. On gadoxetic acid-enhanced MRI, the tumor showed brisk arterial enhancement and persistent hyperenhancement in the portal phase, but hypointensity in the hepatobiliary phase. On diffusion-weighted MRI, the tumor showed an apparent diffusion coefficient twofold greater than that of the background liver parenchyma, which suggested that the lesion was benign. The histologic diagnosis was intrahepatic bile duct adenoma with alcoholic liver cirrhosis.

  12. Liver resection for the treatment of a congenital intrahepatic portosystemic venous shunt

    Institute of Scientific and Technical Information of China (English)

    Michail Papamichail; Amir Ali; Alberto Quaglia; John Karani; Nigel Heaton

    2015-01-01

    Intrahepatic portosystemic shunts (IPSS) are rare congenital anomalies arising from disordered portal vein em-bryogenesis. It has been described in both children and adults and may be asymptomatic or be associated with a variety of neurophysiological and pulmonary complications. When rec-ognized, early intervention to occlude the shunt will reverse the associated complications. Literature review reports of surgical and radiological occlusion of the shunt, but due to its rarity, a standard therapeutic protocol has not been established. A case of a 38-year-old woman with abdominal pain and low grade encephalopathy, diagnosed with an IPSS and treated by right hepatectomy was reported.

  13. Current diagnosis and management of post-transjugular intrahepatic portosystemic shunt refractory hepatic encephalopathy.

    Science.gov (United States)

    Pereira, Keith; Carrion, Andres F; Martin, Paul; Vaheesan, Kirubahara; Salsamendi, Jason; Doshi, Mehul; Yrizarry, Jose M

    2015-12-01

    Transjugular intrahepatic portosystemic shunt has evolved into an important option for management of complications of portal hypertension. The use of polytetrafluoroethylene covered stents enhances shunt patency. Hepatic encephalopathy (HE) remains a significant problem after TIPS placement. The approach to management of patients with refractory hepatic encephalopathy typically requires collaboration between different specialties. Patient selection for TIPS requires careful evaluation of risk factors for HE. TIPS procedure-related technical factors like stent size, attention to portosystemic pressure gradient reduction and use of adjunctive variceal embolization maybe important. Conservative medical therapy in combination with endovascular therapies often results in resolution or substantial reduction of symptoms. Liver transplantation is, however, the ultimate treatment.

  14. Intrahepatic Portosystemic Venous Shunt: Successful Embolization Using the Amplatzer Vascular Plug II

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young Ju; Shin, Byung Seok; Lee, In Ho; Ohm, Joon Young; Lee, Byung Seok; Ahn, Moon Sang [Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon (Korea, Republic of); Kim, Ho Jun [Dept. of Radiology, Konyang University Hospital, Konyang University College of Medicine, Daejeon (Korea, Republic of)

    2012-11-15

    A 67-year-old woman presented with memory impairment and behavioral changes. Brain MRI indicated hepatic encephalopathy. Abdominal CT scans revealed an intrahepatic portosystemic venous shunt that consisted of two shunt tracts to the aneurysmal sac that communicated directly with the right hepatic vein. The large tract was successfully occluded by embolization using the newly available AMPLATZERTM Vascular Plug II and the small tract was occluded by using coils. The patient's symptoms disappeared after shunt closure and she remained free of recurrence at the 3-month follow-up evaluation.

  15. RE: Endovascular Treatment of Congenital Intrahepatic Portosystemic Shunts with Amplatzer Plugs

    Energy Technology Data Exchange (ETDEWEB)

    Sierre, Sergio; Alonso, Jose; Lipsich, Jose [Hospital Nacional de Pediatria ' JP Garrahan' , Combate de los Pozos, Buenos (Argentina)

    2012-01-15

    In our paper entitled 'Endovascular treatment of congenital portal vein fistulas with the Amplatzer occlusion device' published in the Journal of Vascular and Interventional Radiology in 2004, we already reported the use of the AVP in the treatment of an intrahepatic portosystemic venous shunt. This situation does not undervalue the quality of the reported case, but for didactic purposes, we believe it is important to state that the work of Dr. Lee confirms, as was previously reported, that these devices are useful and safe for these rare situations.

  16. Novel Image Guidance Techniques for Portal Vein Targeting During Transjugular Intrahepatic Portosystemic Shunt Creation.

    Science.gov (United States)

    Farsad, Khashayar; Kaufman, John A

    2016-03-01

    The most challenging part of transjugular intrahepatic portosystemic shunt creation is arguably the transvenous access from the hepatic vein to the portal vein. As experience and technology have evolved, the image guidance aspect of this critical step in the procedure has become more robust. Improved means to target the portal vein include both direct and indirect methods of portal vein opacification, cross-sectional imaging for both targeting and access, and novel use of transabdominal and intravascular ultrasound guidance. These techniques are described herein.

  17. Liver resection for the treatment of a congenital intrahepatic portosystemic venous shunt

    Institute of Scientific and Technical Information of China (English)

    Michail Papamichail; Amir Ali; Alberto Quaglia; John Karani; Nigel Heaton

    2016-01-01

    Intrahepatic portosystemic shunts (IPSS) are rare congenital anomalies arising from disordered portal vein em-bryogenesis. It has been described in both children and adults and may be asymptomatic or be associated with a variety of neurophysiological and pulmonary complications. When rec-ognized, early intervention to occlude the shunt will reverse the associated complications. Literature review reports of surgical and radiological occlusion of the shunt, but due to its rarity, a standard therapeutic protocol has not been established. A case of a 38-year-old woman with abdominal pain and low grade encephalopathy, diagnosed with an IPSS and treated by right hepatectomy was reported.

  18. Recanalization of an Occluded Intrahepatic Portosystemic Covered Stent via the Percutaneous Transhepatic Approach

    Energy Technology Data Exchange (ETDEWEB)

    Chan, Chih Yang; Liang, Po Chin [National Taiwan University Hospital, Taipei (China)

    2010-08-15

    A 41-year-old woman with liver cirrhosis had recurrent portal hypertension and bleeding from esophageal varices due to complete occlusion of a previously inserted transjugular intrahepatic portosystemic shunt stent. Because recanalization of the stent by the transjugular approach was unsuccessful, ultrasound-guided entry to the splenic vein and portal vein was used. After catheter-directed intrathrombus thrombolysis, successful opening of the stent was achieved and a stent was placed. We herein report a rare case in which thrombolysis and recanalization of a TIPS stent were performed via a percutaneous transhepatic approach

  19. Intrahepatic Vascular Anatomy in Rats and Mice--Variations and Surgical Implications.

    Directory of Open Access Journals (Sweden)

    Constanze Sänger

    Full Text Available The intra-hepatic vascular anatomy in rodents, its variations and corresponding supplying and draining territories in respect to the lobar structure of the liver have not been described. We performed a detailed anatomical imaging study in rats and mice to allow for further refinement of experimental surgical approaches.LEWIS-Rats and C57Bl/6N-Mice were subjected to ex-vivo imaging using μCT. The image data were used for semi-automated segmentation to extract the hepatic vascular tree as prerequisite for 3D visualization. The underlying vascular anatomy was reconstructed, analysed and used for determining hepatic vascular territories.The four major liver lobes have their own lobar portal supply and hepatic drainage territories. In contrast, the paracaval liver is supplied by various small branches from right and caudate portal veins and drains directly into the vena cava. Variations in hepatic vascular anatomy were observed in terms of branching pattern and distance of branches to each other. The portal vein anatomy is more variable than the hepatic vein anatomy. Surgically relevant variations were primarily observed in portal venous supply.For the first time the key variations of intrahepatic vascular anatomy in mice and rats and their surgical implications were described. We showed that lobar borders of the liver do not always match vascular territorial borders. These findings are of importance for the design of new surgical procedures and for understanding eventual complications following hepatic surgery.

  20. Intrahepatic biliary cystic neoplasms: Surgical results of 9 patients and literature review

    Institute of Scientific and Technical Information of China (English)

    Ali Emre; Kür(s)at Rahmi Serin; (I)lgin (O)zden; Yaman Tekant; Orhan Bilge; Aydin Alper; Mine Güllüo(g)lu; Koray Güven

    2011-01-01

    AIM: To investigate the eligible management of the cystic neplasms of the liver.METHODS: The charts of 9 patients who underwent surgery for intrahepatic biliary cystic liver neoplasms between 2003 and 2008 were reviewed retrospectively. Informed consent was obtained from the patients and approval was obtained from the designated review board of the institution.RESULTS: All patients were female with a median(range) age of 49 (27-60 years). The most frequent symptom was abdominal pain in 6 of the patients. Four patients had undergone previous laparotomy (with otherdiagnoses) which resulted in incomplete surgery or recurrences. Liver resection (n=6) or enucleation (n=3) was performed. The final diagnosis was intrahepatic biliary cystadenoma in 8 patients and cystadenocarcinoma in 1 patient. All symptoms resolved after surgery.There has been no recurrence during a median (range)31 (7-72) mo of follow up.CONCLUSION: In spite of the improvement in imagingmodalities and increasing recognition of biliary cystadenoma and cystadenocarcinoma, accurate preoperative diagnosis may be difficult. Complete surgical removal(liver resection or enucleation) of these lesions yields satisfying long-term results.

  1. Intrahepatic natural killer T cell populations are increased in human hepatic steatosis

    Institute of Scientific and Technical Information of China (English)

    Michael Adler; Sarah Taylor; Kamalu Okebugwu; Herman Yee; Christine Fielding; George Fielding; Michael Poles

    2011-01-01

    AIM: To determine if natural killer T cell (NKT) populations are affected in nonalcoholic fatty liver disease(NAFLD).METHODS: Patients undergoing bariatric surgery underwent liver biopsy and blood sampling during surgery.The biopsy was assessed for steatosis and immunocyte infiltration. Intrahepatic lymphocytes (IHLs) were isolated from the remainder of the liver biopsy,and peripheral blood mononuclear cells (PBMCs) were isolated from the blood. Expression of surface proteins on both IHLs and PBMCs were quantified using flow cytometry.RESULTS: Twenty-seven subjects participated in this study. Subjects with moderate or severe steatosis had a higher percentage of intrahepatic CD3+/CD56+ NKT cells (38.6%) than did patients with mild steatosis(24.1%, P = 0.05) or those without steatosis (21.5%, P= 0.03). Patients with moderate to severe steatosis alsohad a higher percentage of NKT cells in the blood (12.3%) as compared to patients with mild steatosis (2.5% P =0.02) and those without steatosis (5.1%, P = 0.05).CONCLUSION: NKT cells are significantly increased in the liver and blood of patients with moderate to severe steatosis and support the role of NKT cells in NAFLD.

  2. Intrahepatic cholangiocarcinoma in a patient with Wilson's disease: a case report.

    Science.gov (United States)

    Mukai, Yosuke; Wada, Hiroshi; Eguchi, Hidetoshi; Yamada, Daisaku; Asaoka, Tadafumi; Noda, Takehiro; Kawamoto, Koichi; Gotoh, Kunihito; Takeda, Yutaka; Tanemura, Masahiro; Umeshita, Koji; Hori, Yumiko; Morii, Eiichi; Doki, Yuichiro; Mori, Masaki

    2016-12-01

    The incidence of hepatobiliary malignancies, and especially intrahepatic cholangiocarcinoma (ICC), for patients with Wilson's disease (WD), is very low, even for cirrhotic patients. A 44-year-old male was admitted to our department for treatment of a liver tumor. He was diagnosed with WD at the age of 15. According to radiological findings, his liver tumor was a suspected hepatocellular carcinoma (HCC) or a combined hepatocellular and cholangiocellular carcinoma. A partial resection of liver segments 8 (S8) and 5 (S5) was subsequently performed due to the intraoperative suspicion of intrahepatic metastasis at the surface of S5. Postoperative histology revealed that the resected portion of S8 contained an ICC; the removed S5 portion comprised a regenerative nodule with hemosiderosis. To date, the patient has survived without tumor recurrence for more than 44 months following surgery. A survey of the literature, inclusive of case reports, would suggest that surgical resection is the primary course of action for a WD patient with ICC, if liver function can be preserved and curative resection performed.

  3. Rapid intra-hepatic dissemination of hepatocellular carcinoma with pulmonary metastases following combined loco-regional therapy

    Energy Technology Data Exchange (ETDEWEB)

    Pua, Uei [Dept. of Diagnostic Radiology, Tan Tock Seng Hospital, Singapore (Singapore)

    2013-08-15

    This manuscript describes an unusual case of rapid intra-hepatic dissemination of hepatocellular carcinoma with pulmonary metastases occurring 1 month after combined chemoembolization and radiofrequency ablation. Inferior vena cava and portal vein invasion tumor thrombus was also detected, possibly accounting for the mechanism of disease dissemination route of disease.

  4. Endoscopic variceal ligation plus propranolol vs. transjugular intrahepatic portosystemic stent shunt : A long-term randomized trial

    NARCIS (Netherlands)

    Sauer, P; Hansmann, J; Richter, GM; Stremmel, W; Stiehl, A

    2002-01-01

    Background and Study Aims: After a first variceal bleeding episode in patients with cirrhosis of the liver, treatment with transjugular intrahepatic portosystemic stent shunt (TIPS) and endoscopic variceal ligation (EVL) plus propranolol were compared, with regard to prevention of variceal rebleedin

  5. Decrease of deleted in malignant brain tumour-1 (DMBT-1) expression is a crucial late event in intrahepatic cholangiocarcinoma

    DEFF Research Database (Denmark)

    Sasaki, M; Huang, S-F; Chen, M-F;

    2003-01-01

    AIMS: To investigate the participation of DMBT-1, a candidate tumour suppressor gene, in the development of intrahepatic cholangiocarcinoma via intraductal papillary neoplasm of the liver (IPN-L) arising in hepatolithiasis. DMBT-1 plays a role in mucosal immune defence. METHODS AND RESULTS: The e...

  6. Intrahepatic and hilar mass-forming cholangiocarcinoma: Qualitative and quantitative evaluation with diffusion-weighted MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Fattach, Hassan El, E-mail: hassangreenmed@gmail.com [Department of Abdominal Imaging, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, 2 rue Ambroise Paré, 75010 Paris (France); Dohan, Anthony, E-mail: anthony.dohan@lrb.aphp.fr [Department of Abdominal Imaging, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, 2 rue Ambroise Paré, 75010 Paris (France); Université Paris-Diderot, Sorbonne Paris Cité, 10 Avenue de Verdun, 75010 Paris (France); UMR INSERM 965-Paris 7 “Angiogenèse et recherche translationnelle”, 2 rue Amboise Paré, 75010 Paris (France); Guerrache, Youcef, E-mail: docyoucef05@yahoo.fr [Department of Abdominal Imaging, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, 2 rue Ambroise Paré, 75010 Paris (France); Dautry, Raphael, E-mail: raphael.dautry@lrb.aphp.fr [Department of Abdominal Imaging, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, 2 rue Ambroise Paré, 75010 Paris (France); Université Paris-Diderot, Sorbonne Paris Cité, 10 Avenue de Verdun, 75010 Paris (France); and others

    2015-08-15

    Highlights: • DW-MR imaging helps depicts all intrahepatic or hilar mass-forming cholangiocarcinomas. • DW-MRI provides best conspicuity of intrahepatic or hilar mass-forming cholangiocarcinomas than the other MRI sequences (P < 0.001). • The use of normalized ADC using the liver as reference organ results in the most restricted distribution of ADC values of intrahepatic or hilar mass-forming cholangiocarcinomas (variation coefficient = 16.6%). - Abstract: Objective: To qualitatively and quantitatively analyze the presentation of intrahepatic and hilar mass-forming cholangiocarcinoma with diffusion-weighted magnetic resonance imaging (DW-MRI). Materials and methods: Twenty-eight patients with histopathologically proven mass-forming cholangiocarcinoma (hilar, n = 17; intrahepatic, n = 11) underwent hepatic DW-MRI at 1.5-T using free-breathing acquisition and three b-values (0,400,800 s/mm{sup 2}). Cholangiocarcinomas were evaluated qualitatively using visual analysis of DW-MR images and quantitatively with conventional ADC and normalized ADC measurements using liver and spleen as reference organs. Results: All cholangiocarcinomas (28/28; 100%) were visible on DW-MR images. DW-MRI yielded best conspicuity of cholangiocarcinomas than the other MRI sequences (P < 0.001). Seven cholangiocarcinomas (7/11; 64%) showed hypointense central area on DW-MR images. Conventional ADC value of cholangiocarcinomas (1.042 × 10{sup −3} mm{sup 2}/s ± 0.221 × 10{sup −3} mm{sup 2}/s; range: 0.616 × 10{sup −3} mm{sup 2}/s to 2.050 × 10{sup −3} mm{sup 2}/s) was significantly lower than that of apparently normal hepatic parenchyma (1.362 × 10{sup −3} mm{sup 2}/s ± 0.187 × 10{sup −3} mm{sup 2}/s) (P < 0.0001), although substantial overlap was found. No significant differences in ADC and normalized ADC values were found between intrahepatic and hilar cholangiocarcinomas. The use of normalized ADC using the liver as reference organ resulted in the most restricted

  7. Intrahepatic CD8+ lymphocyte trapping during tolerance induction using mushroom derived formulations: A possible role for liver in tolerance induction

    Institute of Scientific and Technical Information of China (English)

    Mony Shuvy; Tiberiu Hershcovici; Cristina Lull-Noguera; Harry Wichers; Ofer Danay; Dan Levanon; Lidya Zolotarov; Yaron Ilan

    2008-01-01

    AIM: To determine the immunomodulatory effect of Shiitake (a mushroom extract),we tested its effect on liver-mediated immune regulation in a model of immune-mediated colitis.METHODS: Four groups of mice were studied.Colitis was induced by intracolonic instillation of TNBS in groups A and B.Groups A and C were treated daily with Shiitake extract,while groups B and D received bovine serum albumin.Mice were evaluated for development of macroscopic and microscopic.The immune effects of Shiitakke were determined by FACS analysis of intra-hepatic and intrasplenic lymphocytes and IFN-γ ELISPOT assay.RESULTS: Administration of Shiitake resulted in marked alleviation of colitis,manifested by significant improvement in the macroscopic and microscopic scores,and by reduction in IFN-γ-producing colonies in group A,compared to group B mice (1.5 pfu/mL vs 3.7 pfu/mL,respectively).This beneficial effect was associated with a significant increase in the intrahepatic CD8+ lymphocyte trapping,demonstrated by an increased intrasplenic/intrahepatic CD4/CD8 lymphocyte ratio.These effects were accompanied by a 17% increase in the number of intrahepatic natural killer T (NKT) cells.A similar effect was observed when Shiitake was administered to animals without disease induction.CONCLUSION: Shiitake extract affected livermediated immune regulation by altering the NKT lymphocyte distribution and increasing intrahepatic CD8+ T lymphocyte trapping,thereby leading to alleviation of immune-mediated colitis.

  8. 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

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

    Science.gov (United States)

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

    2015-04-15

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

  10. Transjugular Intrahepatic Portosystemic Shunt for Maintenance of Portal Venous Patency in Liver Transplant Candidates

    Directory of Open Access Journals (Sweden)

    Ron Charles Gaba

    2013-01-01

    Full Text Available Maintenance of portal venous patency is vital to liver transplant candidates, as the presence of portal vein thrombosis (PVT adversely impacts clinical outcomes by increasing surgical complexity and decreasing postoperative survival. By enhancing portal venous blood flow, transjugular intrahepatic portosystemic shunt (TIPS creation may enable clearance of PVT and preservation of portal venous patency in cirrhotic patients. Herein, we describe four cases in which TIPS produced and sustained an open portal venous system in liver transplant candidates with partial PVT. All patients demonstrated rapid and effective flow-enabled clearance of clot and intermediate to long-term preservation of portal venous flow. On this basis, we propose that maintenance of portal venous patency in liver transplant candidates with partial PVT represents a developing indication for TIPS.

  11. Transjugular Intrahepatic Portosystemic Shunt (TIPS Migration to the Heart Diagnosed by Emergency Department Ultrasound

    Directory of Open Access Journals (Sweden)

    Carlan Wendler

    2012-12-01

    Full Text Available A 57-year-old man presented to our emergency department with altered mental status. He had a past medical history significant for cirrhosis and previous placement of a transjugular intrahepatic portosystemic shunt (TIPS. On cardiac auscultation, a new heart murmur and an unexpected degree of cardiac ectopy were noted. On the 12-lead electrocardiogram, the patient was noted to have multiple premature atrial contractions, corroborating the irregular heart rhythm on physical exam. A focused bedside emergency ultrasound of the heart was then performed. This exam revealed an apparent foreign body in the right atrium. It appeared as if the patient’s TIPS had migrated from the heart into the right atrium. This case, as well as the literature describing thisunusual complication of TIPS placement, is reviewed in this case report

  12. [Research advances in diagnosis and treatment of post-transjugular intrahepatic portosystemic shunt hepatic encephalopathy].

    Science.gov (United States)

    Yang, J F; Zhang, B Q

    2016-07-20

    Transjugular intrahepatic portosystemic shunt (TIPS) has become an important minimally invasive interventional technique for the treatment of complications of cirrhotic portal hypertension, and currently, it is often used in cirrhotic patients with esophagogastric variceal bleeding (EVB), intractable ascites, hepatic hydrothorax, and Budd-Chiari syndrome. On one hand, TIPS can effectively reduce portal vein pressure and the risk of EVB and intractable ascites; on the other hand, it may reduce the blood flow in liver perfusion, aggravate liver impairment, and cause porto-systemic encephalopathy. Related influencing factors should be evaluated comprehensively in order to prevent the development of post-TIPS hepatic encephalopathy. The diagnosis and treatment of post-TIPS hepatic encephalopathy is still a great challenge in current clinical practice. This article reviews the diagnosis and treatment of post-TIPS hepatic encephalopathy to enhance people's knowledge of this disease.

  13. Hepatic Encephalopathy due to Congenital Multiple Intrahepatic Portosystemic Venous Shunts Successfully Treated by Percutaneous Transhepatic Obliteration

    Directory of Open Access Journals (Sweden)

    Shinsuke Takenaga

    2016-11-01

    Full Text Available Hepatic encephalopathy due to intrahepatic portosystemic venous shunts (IPSVS in a non-cirrhotic condition is rare. Here we report a rare case of a patient with congenital multiple IPSVS successfully treated by percutaneous transhepatic obliteration. The patient was a 67-year-old woman who presented to our hospital with progressive episodes of consciousness disorder and vomiting. Laboratory tests revealed hyperammonemia (192.0 μg/dL, and computed tomography revealed multiple IPSVS in both lobes. There was no evidence of underlying liver disease or hepatic trauma. Transcatheter embolization for IPSVS was performed because conservative therapy was not sufficiently effective. After endovascular shunt closure, hepatic encephalopathy improved. The serum ammonia level normalized during the 5-year follow-up period. Thus, transcatheter embolization may be an effective therapy for patients with symptomatic and refractory IPSVS. Careful follow-up is necessary for portal hypertension-related complications after transcatheter embolization for IPSVS.

  14. Radioembolization of hepatic tumors. Flow redistribution after the occlusion of intrahepatic arteries

    Energy Technology Data Exchange (ETDEWEB)

    Lauenstein, T.C. [University Hospital Essen (Germany). Radiology; Heusner, T.A.; Antoch, G. [University Hospital Duesseldorf (Germany). Radiology; Hamami, M.; Bockisch, A. [University Hospital Essen (Germany). Dept. of Nuclear Medicine; Ertle, J.; Schlaak, J.F.; Gerken, G. [University Hospital Essen (Germany). Gastroenterology and Hepatology

    2011-11-15

    Radioembolization using 90yttrium is an emerging therapy option for unresectable liver malignancies. In order to reduce the number of yttrium injections, endovascular occlusion of a segmental hepatic artery has been proposed. The aim of this study was to assess whether sufficient vascular redistribution of the occluded liver segments through intrahepatic collaterals can be observed. 27 patients with hepatocellular carcinoma (n = 16) or hepatic metastases (n = 11) were studied. Hepatic angiography was performed on average 16 days prior to radioembolization. The segment II/III artery (n = 9) or the segment IV artery (n = 18) was occluded using coils. Technectium-99m-labeled macroaggregated albumin (99mTc-MAA) was injected into the right and the remaining part of the left hepatic artery in order to identify any hepatic volume not included in the perfused area. Patients underwent a SPECT/CT on average 1 h after the 99mTc-MAA injection. Two radiologists evaluated the SPECT/CT scans regarding the presence of non-perfused hepatic segments. Furthermore, hepatic perfusion was assessed by digital subtraction angiography (DSA) on the day of radioembolization. In 16 / 27 patients (59 %) a perfusion of the occluded liver segment was visible on the SPECT/CT scan. In 8 / 11 patients without flow redistribution at the time of the SPECT/CT, perfusion of the occluded segment through hepatic collaterals was observed during angiography prior to radioembolization. Hence, flow redistribution was eventually found in 24 / 27 patients (89 %). Flow redistribution after the occlusion of intrahepatic arteries prior to radioembolization can be successfully induced in the majority of patients with anatomical variants of the hepatic arteries. (orig.)

  15. Residual intrahepatic stones after percutaneous biliary extraction : longterm follow up of complications

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Seung Min; Shim, Hyung Jin; Lee, Hwa Yeon; Lim, Sang Jun; Park, Hyo Jin; Kim, Yang Soo; Choi, Young Hee [Chungang Univ. College of Medicine, Seoul (Korea, Republic of); Kwak, Byung Kuck [National Medical Center, Seoul (Korea, Republic of); Park, Ji Young [Sung Ae Hospital, Seoul (Korea, Republic of)

    1997-08-01

    To evaluate and compare the radiologic and clinical follow-up of complications between a group in whom stone removal after percutaneous biliary extraction had been complete, and a group in whom this had been incomplete. Twenty-two patients in whom stone removal had been incomplete, and 20 from whom stones had been completely removed were evaluated with particular attention to complications such as cholangitis, liver abscess, biliary sepsis, and pain. Cholangitis was diagnosed on the basis of typical clinical symptoms such as pain, high fever, jaundice and leukocytosis. Pain without other cholangitic symptoms was excluded. Liver abscess was diagnosed by percutaneous aspiration of pus, and biliary sepsis by bacterial growth on blood culture, or laboratory findings such as increased fibrinogen products, decreased fibrinogen, and increased prothrombin time with cholangitic symptoms. 'Complete removal' means no residual stones on follow-up sonogram and cholangiogram performed within three to seven days after pecutaneous biliary extraction. Mean follow-up period was 26.5 months in the incomplete removal group and 34.2 months in the complete removal group. In twelve of 22 patients (54.5%) in the incomplete removal group, complications occurred, as follows:cholangitis, ten cases (45.5%);liver absces, one (4.5%);biliary sepsis, one (4.5%);and pain, seven(31.8%). In contrast, only two of twenty patients (10%) in the complete removal group suffered complications, all of which involved the recurrence of stones in the common duct, and cholangitis. Complete removal of intrahepatic stones significantly helps to reduce the incidence of possible complications. Even in the case of an impacted stone, aggressive interventional procedures, aimed at complete removal, should be considered. If nonsurgical procedures fail, early partial hepatectomy should be considered, particulary for the stones localized in the left intrahepatic duct.

  16. Intrahepatic cytokine profile in renal-transplant patients infected by hepatitis C virus.

    Science.gov (United States)

    Kamar, Nassim; Rostaing, Lionel; Sandres-Saune, Karine; Selves, Janick; Barthe, Carole; Dubois, Martine; Alric, Laurent; Durand, Dominique; Izopet, Jacques

    2005-08-01

    In order to examine the immunopathogenesis of hepatitis C virus (HCV)-related liver injury in renal-transplant patients, intra-hepatic cytokine profiles were examined in 38 liver biopsies from 38 patients by measuring messenger RNA (mRNA) concentrations by a real-time PCR method of a Th1 cytokine (i.e., interferon (IFN)-gamma), a Th2 cytokines (i.e., interleukine (IL)-10), a proinflammatory cytokine (i.e., IL-8), and a potent fibrogenic factor (transforming growth factor [TGF]-beta). There was no significant difference in TGF-beta, IFN-gamma, IL-10, or IL-8 levels of expression according to liver-activity grade, liver-fibrosis stage, the concentration of HCV RNA at liver biopsies, or the HCV genotype. However, IFN-gamma/beta-actin mRNA concentration was higher than the IL-10/beta-actin mRNA concentration in patients with F3 Metavir score. Median IFN-gamma/beta-actin mRNA concentration tended to be higher in patients with A3 and A4 Metavir activity grades compared with those with A0 and A1 activity grades. There was a significant correlation between the duration of HCV infection and both TGF-beta/beta-actin (r(2)=0.19, P=0.04) and IL-8/beta-actin mRNA concentrations (r(2)=0.19, P=0.03). IFN-gamma/beta-actin mRNA concentration also increased according to the duration of HCV (r(2)=0.19, P=0.07). Finally, there was a significant correlation between the duration of HCV infection and liver fibrosis stage (r(2)=0.17, P=0.045). Intrahepatic Th1 cytokine profile seems to be predominant in patients with extensive fibrosis and activity scores, suggesting that it might be responsible for liver injury in renal transplant patients.

  17. Inactivation of Smad4 is a prognostic factor in intrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    YAN Xue-qiang; ZHANG Wei; ZHANG Bi-xiang; LIANG Hui-fang; ZHANG Wan-guang; CHEN Xiao-ping

    2013-01-01

    Background Smad4 is found mutated in many cancers.It acts as a tumor suppressor in the regulation of TGF-β signaling pathway.The objective of this work was to study the expression of Smad4 in intrahepatic cholangiocarcinoma (ICC) and its relationship with the biological behavior and prognosis of the disease.Methods Forty-nine paraffin-embedded ICC specimens and nine normal liver tissues were analyzed by immunohistochemical methods using Smad4 monoclonal antibodies.The expression of Smad4 was compared with the clinical pathological characteristics of the patients.Results The expression of Smad4 was 100% positive in normal liver tissues,which was higher than that in the ICC (44.9%).Negative labeling of the Smad4 protein was found in 26.1% (6/23) of well-differentiated ICCs and 61.5%(16/26) of poorly to moderately differentiated ICCs,and 34.3% (12/35) and 71.4% (10/14) showed negative Smad4 labeling (P=0.018) of ICC at pathological Tumor Node Metastasis (pTNM) stage Ⅰ-Ⅱ and pTNM stage Ⅲ-Ⅳ separately.Furthermore,72% (8/11) of lymph node metastatic ICCs and 73.3% (11/15) of intrahepatic metastatic ICCs showed negative labeling of the Smad4 protein.The loss of Smad4 expression in those metastatic ICCs was significantly more severe compared with non-metastatic ICCs (P=0.000).Conclusions The expression of Smad4 was associated with the histological grade,clinical stage,and metastasis of ICC (P <0.05).The detection of Smad4 may be helpful in determining the degree of malignancy and prognosis of ICC.

  18. Multimodal Therapy including Yttrium-90 Radioembolization as a Bridging Therapy to Liver Transplantation for a Huge and Locally Advanced Intrahepatic Cholangiocarcinoma.

    Science.gov (United States)

    Rayar, Michel; Levi Sandri, Giovanni Battista; Houssel-Debry, Pauline; Camus, Christophe; Sulpice, Laurent; Boudjema, Karim

    2016-09-01

    Treatment of intrahepatic cholangiocarcinoma remains a major challenge. For an unresectable lesion without extrahepatic spread, liver transplantation could be a potential solution but it is still associated with poor oncologic results owing to the absence of effective neoadjuvant treatment. We report the case of a young man with locally advanced intrahepatic cholangiocarcinoma presenting with multiple intrahepatic metastases and vascular structure involvement. The lesion was significantly downstaged by a multimodal therapy including intra-arterial Yttrium-90 radioembolization, systemic chemotherapy and external radiotherapy, allowing liver transplantation. Three years after the procedure, oncologic outcome is excellent with no sign of recurrence. Multimodal therapy including Yttrium-90 radioembolization could be relevant as neoadjuvant treatment before liver transplantation for unresectable intrahepatic cholangiocarcinoma.

  19. A small solitary non-parasitic hepatic cyst causing an intra-hepatic bile duct stricture: a case report

    Directory of Open Access Journals (Sweden)

    Hong Taeho

    2010-08-01

    Full Text Available Abstract Introduction We report an unusual presentation of a small hepatic cyst causing cholangitis. Case presentation A 70-year-old Asian man was hospitalized for aggravated chronic pain in the right upper portion of his abdomen. Fever developed after admission. Laboratory tests revealed elevated hepatobiliary enzymes, inflammatory markers and carbohydrate antigen 19-9 without hyperbilirubinemia. Ultrasound and computed tomography demonstrated dilatation of the left intra-hepatic bile ducts. Endoscopic retrograde cholangiopancreatography showed that the right intra-hepatic bile ducts were normally filled with contrast medium, but the left intra-hepatic bile ducts were not seen in the confluence. A left hepatectomy was performed because a hidden malignancy could not be excluded. The surgical findings showed no tumor around the bile duct but rather a 2 cm cyst in segment four of Couinaud's category of the liver around the hilum. The pathology report was a solitary non-parasitic hepatic cyst compressing the bile duct. Conclusion A very small solitary hepatic cyst might cause hepatic duct stricture if it is located near the hepatic hilum, and should be considered in the differential diagnosis of a hepatic duct stricture.

  20. Intrahepatic cholangiocarcinoma in a worker at an offset color proof-printing company: An autopsy case report.

    Science.gov (United States)

    Tomimaru, Yoshito; Kobayashi, Shogo; Wada, Hiroshi; Hama, Naoki; Kawamoto, Koichi; Eguchi, Hidetoshi; Kira, Toshihiko; Morii, Eiichi; Doki, Yuichiro; Mori, Masaki; Nagano, Hiroaki

    2015-04-01

    A 40-year-old Japanese man visited our hospital after test results indicated elevated hepatobiliary enzymes. He had worked at a printing plant for 8 years and been exposed to organic solvents, including 1,2-dichloropropane (1,2-DCP) and dichloromethane (DCM). Abdominal computed tomography (CT) showed an intrahepatic tumor with dilation of the intrahepatic bile duct. He was diagnosed with intrahepatic cholangiocarcinoma. He had no known risk factors for cholangiocarcinoma. Extended left hepatectomy with lymph node dissection was performed and the tumor was histologically diagnosed as well-differentiated adenocarcinoma. A histological examination also showed biliary intraepithelial preneoplastic lesions in non-cancerous liver areas. Two years after surgery, the patient developed jaundice, esophageal varices and ascites. A CT examination showed liver cirrhosis without recurrence of the cholangiocarcinoma. Although a liver transplantation was planned as a therapeutic option for his liver cirrhosis, his liver failure progressed rapidly and he died before transplantation could be performed. At autopsy, fibrosis was found in the whole liver, especially in the wall of the bile duct and periductal area suggesting chronic bile duct injury due to exposure to organic solvents. Taken together, the current case may suggest that exposure to organic solvents, including 1,2-DCP and DCM, is a risk factor for cholangiocarcinoma. Identifying risk factors for cholangiocarcinoma will help identify the mechanism and help prevent development of the disease.

  1. Intrahepatic infiltrating NK and CD8 T cells cause liver cell death in different phases of dengue virus infection.

    Science.gov (United States)

    Sung, Jui-Min; Lee, Chien-Kuo; Wu-Hsieh, Betty A

    2012-01-01

    Elevated liver enzyme level is an outstanding feature in patients with dengue. However, the pathogenic mechanism of liver injury has not been clearly demonstrated. In this study, employing a mouse model we aimed to investigate the immunopathogenic mechanism of dengue liver injury. Immunocompetent C57BL/6 mice were infected intravenously with dengue virus strain 16681. Infected mice had transient viremia, detectable viral capsid gene and cleaved caspase 3 in the liver. In the mean time, NK cell and T cell infiltrations peaked at days 1 and 5, respectively. Neutralizing CXCL10 or depletion of Asialo GM1(+) cells reduced cleaved caspase 3 and TUNEL(+) cells in the liver at day 1 after infection. CD8(+) T cells infiltrated into the liver at later time point and at which time intrahepatic leukocytes (IHL) exhibited cytotoxicity against DENV-infected targets. Cleaved caspase 3 and TUNEL(+) cells were diminished in mice with TCRβ deficiency and in those depleted of CD8(+) T cells, respectively, at day 5 after infection. Moreover, intrahepatic CD8(+) T cells were like their splenic counterparts recognized DENV NS4B(99-107) peptide. Together, these results show that infiltrating NK and CD8(+) T cells cause liver cell death. While NK cells were responsible for cell death at early time point of infection, CD8(+) T cells were for later. CD8(+) T cells that recognize NS4B(99-107) constitute at least one of the major intrahepatic cytotoxic CD8(+) T cell populations.

  2. Intrahepatic infiltrating NK and CD8 T cells cause liver cell death in different phases of dengue virus infection.

    Directory of Open Access Journals (Sweden)

    Jui-Min Sung

    Full Text Available Elevated liver enzyme level is an outstanding feature in patients with dengue. However, the pathogenic mechanism of liver injury has not been clearly demonstrated. In this study, employing a mouse model we aimed to investigate the immunopathogenic mechanism of dengue liver injury. Immunocompetent C57BL/6 mice were infected intravenously with dengue virus strain 16681. Infected mice had transient viremia, detectable viral capsid gene and cleaved caspase 3 in the liver. In the mean time, NK cell and T cell infiltrations peaked at days 1 and 5, respectively. Neutralizing CXCL10 or depletion of Asialo GM1(+ cells reduced cleaved caspase 3 and TUNEL(+ cells in the liver at day 1 after infection. CD8(+ T cells infiltrated into the liver at later time point and at which time intrahepatic leukocytes (IHL exhibited cytotoxicity against DENV-infected targets. Cleaved caspase 3 and TUNEL(+ cells were diminished in mice with TCRβ deficiency and in those depleted of CD8(+ T cells, respectively, at day 5 after infection. Moreover, intrahepatic CD8(+ T cells were like their splenic counterparts recognized DENV NS4B(99-107 peptide. Together, these results show that infiltrating NK and CD8(+ T cells cause liver cell death. While NK cells were responsible for cell death at early time point of infection, CD8(+ T cells were for later. CD8(+ T cells that recognize NS4B(99-107 constitute at least one of the major intrahepatic cytotoxic CD8(+ T cell populations.

  3. 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

  4. 3-dimensional resin casting and imaging of mouse portal vein or intrahepatic bile duct system.

    Science.gov (United States)

    Walter, Teagan J; Sparks, Erin E; Huppert, Stacey S

    2012-10-25

    In organs, the correct architecture of vascular and ductal structures is indispensable for proper physiological function, and the formation and maintenance of these structures is a highly regulated process. The analysis of these complex, 3-dimensional structures has greatly depended on either 2-dimensional examination in section or on dye injection studies. These techniques, however, are not able to provide a complete and quantifiable representation of the ductal or vascular structures they are intended to elucidate. Alternatively, the nature of 3-dimensional plastic resin casts generates a permanent snapshot of the system and is a novel and widely useful technique for visualizing and quantifying 3-dimensional structures and networks. A crucial advantage of the resin casting system is the ability to determine the intact and connected, or communicating, structure of a blood vessel or duct. The structure of vascular and ductal networks are crucial for organ function, and this technique has the potential to aid study of vascular and ductal networks in several ways. Resin casting may be used to analyze normal morphology and functional architecture of a luminal structure, identify developmental morphogenetic changes, and uncover morphological differences in tissue architecture between normal and disease states. Previous work has utilized resin casting to study, for example, architectural and functional defects within the mouse intrahepatic bile duct system that were not reflected in 2-dimensional analysis of the structure(1,2), alterations in brain vasculature of a Alzheimer's disease mouse model(3), portal vein abnormalities in portal hypertensive and cirrhotic mice(4), developmental steps in rat lymphatic maturation between immature and adult lungs(5), immediate microvascular changes in the rat liver, pancreas, and kidney in response in to chemical injury(6). Here we present a method of generating a 3-dimensional resin cast of a mouse vascular or ductal network

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    Zakharash A.D.

    2007-01-01

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

  7. 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.

  8. 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.

  9. 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.

  10. [A case of curative resection after downsizing chemotherapy in initially unresectable locally advanced intrahepatic cholangiocarcinoma].

    Science.gov (United States)

    Aoki, Yu; Suzuki, Takayuki; Kato, Atsushi; Shimizu, Hiroaki; Ohtsuka, Masayuki; Yoshitomi, Hideyuki; Furukawa, Katsunori; Takayashiki, Tsukasa; Kuboki, Satoshi; Takano, Shigetsugu; Okamura, Daiki; Suzuki, Daisuke; Sakai, Nozomu; Kagawa, Shingo; Miyazaki, Masaru

    2014-11-01

    This case report describes an 83-year-old man with intrahepatic cholangiocarcinoma who was referred by a local hospital. Abdominal computed tomography (CT) showed a large tumor in hepatic segments 4, 5, and 8 involving the right hepatic vein and inferior vena cava, which is normally indicative of an unresectable locally advanced tumor. After systemic chemotherapy with gemcitabine and cisplatin, the observed decrease in the level of tumor marker suggested that the cancer was responding to treatment, while radiological findings showed the main tumor shrunk without the presence of distant metastases. Thus, hepatic left trisectionectomy with bile duct resection was performed after portal vein embolization. Pathological examination revealed negative margins (R0). Eighteen months after surgery, the patient is free of disease and shows no signs of recurrence. An initially unresectable, locally advanced biliary tract cancer may be down sized by chemotherapy, which makes radical resection possible, at least in a proportion of patients. This approach provides longer survival and may have a potential for disease eradication as a new multidisciplinary approach for patients with unresectable locally advanced biliary tract cancer.

  11. Transjugular Intrahepatic Portosystemic Shunt Placement During Pregnancy: A Case Series of Five Patients

    Energy Technology Data Exchange (ETDEWEB)

    Ingraham, Christopher R., E-mail: cringra@uw.edu; Padia, Siddharth A., E-mail: spadia@uw.edu; Johnson, Guy E., E-mail: gej@uw.edu [University of Washington, Department of Interventional Radiology (United States); Easterling, Thomas R., E-mail: easter@uw.edu [University of Washington, Department of Obstetrics and Gynecology (United States); Liou, Iris W., E-mail: irisl@medicine.washington.edu [University of Washington, Department of Medicine (United States); Kanal, Kalpana M., E-mail: kkanal@uw.edu [University of Washington, Physics Section, Department of Radiology (United States); Valji, Karim, E-mail: kvalji@uw.edu [University of Washington, Department of Interventional Radiology (United States)

    2015-10-15

    Background and AimsComplications of portal hypertension, such as variceal hemorrhage and ascites, are associated with significant increases in both mortality and complications during pregnancy. Transjugular intrahepatic portosystemic shunt (TIPS) is a well-established procedure for treating portal hypertension, but the safety of TIPS during pregnancy is largely unknown. In this series, we review five patients who underwent TIPS placement while pregnant and describe their clinical outcomes.MethodsFive pregnant patients with cirrhosis and portal hypertension underwent elective TIPS for complications of portal hypertension (four for secondary prevention of variceal bleeding and one for refractory ascites). Outcomes measured were recurrent bleeding episodes or need for further paracenteses during pregnancy, estimated radiation dose to the fetus and gestational age at delivery. All patients were followed after delivery to evaluate technical and clinical success of the procedure.ResultsAll five patients survived pregnancy and went on to deliver successfully. When TIPS was performed for secondary prevention of variceal bleeding (n = 4), no patients demonstrated variceal bleeding after TIPS placement. When TIPS was performed for refractory ascites (n = 1), no further paracenteses were required. All patients delivered successfully, albeit prematurely. Average radiation dose estimated to the fetus was 16.3 mGy.ConclusionsThis series suggests that TIPS can be performed in selective pregnant patients with portal hypertension, with little added risk to the mother or fetus.

  12. Molecular hydrogen attenuates hypoxia/reoxygenation injury of intrahepatic cholangiocytes by activating Nrf2 expression.

    Science.gov (United States)

    Yu, Jianhua; Zhang, Weiguang; Zhang, Rongguo; Jiang, Guixing; Tang, Haijun; Ruan, Xinxian; Ren, Peitu; Lu, Baochun

    2015-11-01

    Hypoxia/reoxygenation (H/R) injury of cholangiocytes causes serious biliary complications during hepatobiliary surgeries. Molecular hydrogen (H2) has been shown to be effective in protecting various cells and organs against oxidative stress injury. Human liver cholangiocytes were used to determine the potential protective effects of hydrogen against cholangiocyte H/R injury and explore the underlying mechanisms. We found that H2 ameliorated H/R-induced cholangiocytes apoptosis. Our study revealed that H2 activated NF-E2-related factor 2 (Nrf2) and downstream cytoprotective protein expression. However, the protective function of H2 was abolished when Nrf2 was silenced. Apoptosis in cholangiocytes isolated from a rat model of liver ischemia/reperfusion injury indicated that H2 significantly attenuates ischemia/reperfusion cholangiocyte injury in vivo. In conclusion, our study shows that H2 protects intrahepatic cholangiocytes from hypoxia/reoxygenation-induced apoptosis in vitro or in vivo, and this phenomenon may depend on activating Nrf2 expression.

  13. Transjugular intrahepatic portosystemic shunt-placement increases arginine/asymmetric dimethylarginine ratio in cirrhotic patients

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To analyze the change of dimethylarginine plasma levels in cirrhotic patients receiving transjugular intrahepatic portosystemic shunt (TIPS). METHODS: TO determine arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and nitric oxide (NO) plasma levels, blood samples were collected from the superior cava, hepatic, and portal vein just before, directly after, and 3 mo after TIPS-placement.RESULTS: A significant increase in the arginine/ADMA ratio after TIPS placement was shown. Moreover, TIPS placement enhanced renal function and thereby decreased systemic SDMA levels. In patients with renal dysfunction before TIPS placement, both the arginine/ ADMA ratio and creatinine clearance rate increased significantly, while this was not the case in patients with normal renal function before TIPS placement. Hepatic function did not change significantly after TIPS placement and no significant decline in ADMA plasma levels was measured.CONCLUSION: The increase of the arginine/ADMA ratio after TIPS placement suggests an increase in intracellular NO bioavailability. In addition, this study suggests that TIPS placement does not alter dimethylarginine dimethylaminohydrolase (DDAH) activity and confirms the major role of the liver as an ADMA clearing organ.

  14. Transjugular intrahepatic portosystemic shunt for the management of acute variceal hemorrhage.

    Science.gov (United States)

    Loffroy, Romaric; Estivalet, Louis; Cherblanc, Violaine; Favelier, Sylvain; Pottecher, Pierre; Hamza, Samia; Minello, Anne; Hillon, Patrick; Thouant, Pierre; Lefevre, Pierre-Henri; Krausé, Denis; Cercueil, Jean-Pierre

    2013-10-07

    Acute variceal hemorrhage, a life-threatening condition that requires a multidisciplinary approach for effective therapy, is defined as visible bleeding from an esophageal or gastric varix at the time of endoscopy, the presence of large esophageal varices with recent stigmata of bleeding, or fresh blood visible in the stomach with no other source of bleeding identified. Transfusion of blood products, pharmacological treatments and early endoscopic therapy are often effective; however, if primary hemostasis cannot be obtained or if uncontrollable early rebleeding occurs, transjugular intrahepatic portosystemic shunt (TIPS) is recommended as rescue treatment. The TIPS represents a major advance in the treatment of complications of portal hypertension. Acute variceal hemorrhage that is poorly controlled with endoscopic therapy is generally well controlled with TIPS, which has a 90% to 100% success rate. However, TIPS is associated with a mortality of 30% to 50% in such a setting. Emergency TIPS should be considered early in patients with refractory variceal bleeding once medical treatment and endoscopic sclerotherapy failure, before the clinical condition worsens. Furthermore, admission to specialized centers is mandatory in such a setting and regional protocols are essential to be organized effectively. This review article discusses initial management and then focuses on the specific role of TIPS as a primary therapy to control acute variceal hemorrhage, particularly as a rescue therapy following failure of endoscopic approaches.

  15. MiR-145 functions as a tumor suppressor targeting NUAK1 in human intrahepatic cholangiocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Xinkui; Sun, Daoyi; Chai, Hao; Shan, Wengang [Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province (China); Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Nanjing, Jiangsu Province (China); Yu, Yue [Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Nanjing, Jiangsu Province (China); Pu, Liyong [Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province (China); Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Nanjing, Jiangsu Province (China); Cheng, Feng, E-mail: docchengfeng@njmu.edu.cn [Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province (China); Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Nanjing, Jiangsu Province (China)

    2015-09-18

    The dysregulation of micro (mi)RNAs is associated with cancer development. The miRNA miR-145 is downregulated in intrahepatic cholangiocarcinoma (ICC); however, its precise role in tumor progression has not yet been elucidated. Novel (nua) kinase family (NUAK)1 functions as an oncogene in various cancers and is a putative target of miR-145 regulation. In this study, we investigated the regulation of NUAK1 by miR-145 in ICC. We found that miR-145 level was significantly decreased in ICC tissue and cell lines, which corresponded with an increase in NUAK1 expression. NUAK1 was found to be a direct target of miR-145 regulation. The overexpression of miR-145 in ICC cell lines inhibited proliferation, growth, and invasion by suppressing NUAK1 expression, which was associated with a decrease in Akt signaling and matrix metalloproteinase protein expression. Similar results were observed by inhibiting NUAK1 expression. These results demonstrate that miR-145 can prevent ICC progression by targeting NUAK1 and its downstream effectors, and can therefore be useful for clinical diagnosis and targeted therapy of ICC. - Highlights: • MiR-145 suppresses ICC proliferation and invasion abilities. • We demonstrated that miR-145 directly targets NUAK1 in ICC. • MiR-145 expression in ICC was associated with Akt signaling and MMPs expression.

  16. Comparison of a new stent and Wallstent for transjugular intrahepatic portosystemic shunt in a porcine model

    Institute of Scientific and Technical Information of China (English)

    Gao Jun Teng; Michael A. Bettmann; P. Jack Hoopes; Li Yang

    2001-01-01

    AIM To evaluate a new balloon-expandablestainless steel stent (Cordis stent ) in atransjugular intrahepatic portosystemic shunt(TIPS) porcine model and compared withWallstent.METHODS TIPS was performed in 26 normaldomestic pigs weighing 20 kg-30 kg using aCordis stent or Wallstent (13 pigs in each stent).All pigs were sacrificed at the 14th day afterTIPS. The stent deployment delivery system,stent patency, and stent recoil after placementwere evaluated. Proliferative response inrepresentative histological sections from thecenter, hepatic and portal regions of the twostent designs were quantified.RESULTS The shunt was widely patent in 4pigs in the Cordis stent group (4/12, prematuredead in 1 pig), and in 5 pigs in the Wallstentgroup (5/13). All remaining stents of bothdesigns were occluded or stenotic. The meanquantified proliferation including thickness ofthe proliferation and the ratio of proliferation:total area in three assayed regions in Cordisstent and Wallstent was 2.18 mm:2.00 mm, and59.18 mm2: 51.66 mm2, respectively (P >0.05).The delivery system and mechanical propertiesof the Cordis stent fuctioned well.CONCLUSION The new Cordis stent isappropriate for TIPS procedure.

  17. Hepatitis viruses infection and risk of intrahepatic cholangiocarcinoma: evidence from a meta-analysis

    Directory of Open Access Journals (Sweden)

    Zhou Yanming

    2012-07-01

    Full Text Available Abstract Background Studies investigating the association between Hepatitis B virus (HBV and hepatitis C virus (HCV infections and intrahepatic cholangiocarcinoma (ICC have reported inconsistent findings. We conducted a meta-analysis of epidemiological studies to explore this relationship. Methods A comprehensive search was conducted to identify the eligible studies of hepatitis infections and ICC risk up to September 2011. Summary odds ratios (OR with their 95% confidence intervals (95% CI were calculated with random-effects models using Review Manager version 5.0. Results Thirteen case–control studies and 3 cohort studies were included in the final analysis. The combined risk estimate of all studies showed statistically significant increased risk of ICC incidence with HBV and HCV infection (OR = 3.17, 95% CI, 1.88-5.34, and OR = 3.42, 95% CI, 1.96-5.99, respectively. For case–control studies alone, the combined OR of infection with HBV and HCV were 2.86 (95% CI, 1.60-5.11 and 3.63 (95% CI, 1.86-7.05, respectively, and for cohort studies alone, the OR of HBV and HCV infection were 5.39 (95% CI, 2.34-12.44 and 2.60 (95% CI, 1.36-4.97, respectively. Conclusions This study suggests that both HBV and HCV infection are associated with an increased risk of ICC.

  18. Intrahepatic transplantation of hepatic oval cells for fulminant hepatic failure in rats

    Institute of Scientific and Technical Information of China (English)

    Chen-Xuan Wu; Qi Zou; Zheng-Yan Zhu; Ying-Tang Gao; Yi-Jun Wang

    2009-01-01

    AIM:To evaluate the effect of intrahepatic transplantation of hepatic oval cells (HOC) on fulminant hepatic failure (FHF) in rats. METHODS:HOC obtained from rats were labeled wi th green fluocescent protein (GFP) or 5, 6- carboxyfluorescein diacetate succinmidyl ester (CFDASE). Cell fluorescence was observed under fluorescent microscope at 6, 24, 48 and 72 h after labeling. CFDASE labeled HOC (5 × 106 cells each rat) were injected into livers of rats with FHF induced by D-galactosamine. Serum albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) levels were measured at different time points. Liver function of rats was examined on days 3, 7, 14 and 21 after HOC transplantation. RESULTS:The positive rate of GFP and CFDA-SE labeled HOC was 10% and 90%, respectively, with no significant change in cell viabilities. The survival rate was higher in HOC transplantation group than in control group, especially 48 (9/15 vs 6/15) and 72 h (9/15 vs 4/15) after HOC transplantation. The serum ALT, AST and TBil levels were decreased while the serum Alb level was increased after HOC transplantation. Fluorescence became faded and diffused in liver tissues, suggesting that proliferation and differentiation occur in transplanted HOC. CONCLUSION:CFDA-SE is superior to GFP in labeling HOC, although fluorescence intensity is decreased progressively with cell division. HOC transplantation can improve the liver function and increase the survival rate of recipients.

  19. Risk factors for intrahepatic cholangiocarcinoma: A case- control study in China

    Institute of Scientific and Technical Information of China (English)

    Yan-Ming Zhou; Zheng-Feng Yin; Jia-Mei Yang; Bin Li; Wen-Yu Shao; Feng Xu; Yu-Lan Wang; Dian-Qi Li

    2008-01-01

    AIM: To carry out a hospital-based case-control study to investigate risk factors for intrahepatic cholangiocarcinoma (ICC) in China.METHODS: A total of 312 ICC cases and 438 matched controls were included in the study. The presence of diabetes mellitus, hypertention, hepatolithiasis, primary sclerosing cholangitis, liver fluke infection (Clonorchis sinensis), was investigated through clinical records. Blood from all participants was tested for hepatitis B surface antigen (HBsAg) and anti-HCV antibodies. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using conditional logistic regression.RESULTS: Compared with controls, ICC patients had a higher prevalence of HBsAg seropositivity (48.4% vs 9.6%, P < 0.000), and hepatolithiasis (5.4% vs 1.1%, P = 0.001). By multivariate analysis, the significant risk factors for development of ICC were HBsAg seropositivity (adjusted OR, 8.876, 95% CI, 5.973-13.192), and hepatolithiasis (adjusted OR, 5.765, 95% CI, 1.972-16.851). The prevalence of anti-HCV seropositivity, diabetes mellitus, hypertention, cigarette smoking, and alcohol consumption were not significantly different between cases and controls.CONCLUSION: These findings suggest that HBV infection and hepatolithiasis are strong risk factors for development of ICC in China.

  20. MUC1 and MUC5AC mucin expression in liver fluke-associated intrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Chanchai Boonla; Banchob Sripa; Peti Thuwajit; Ubon Cha-On; Anucha Puapairoj; Masanao Miwa; Sopit Wongkham

    2005-01-01

    AIM: To investigate the expressions of MUC1 and MUC5AC in intrahepatic cholangiocarcinoma (ICC). Association of expressions of mucins MUC1 and MUC5AC with clinical findings, metastasis, and survival of the liver fluke-associated ICC patients was determined.METHODS: The expressions of MUC1 and MUC5AC mucins were examined by immunohistochemical staining in 87cases of histologically-proven ICC. The expressions of mucins in relationship between clinicopathological significance and prognosis of the patients were evaluated.RESULTS: Fifty-two patients (60%) exhibited both MUC1 and MUC5AC expressions, whereas 31% expressed either MUC1or MUC5AC, and 9% expressed neither. High MUC1immunoreactivity displayed a significant correlation with tumor progression as reflected by vascular invasion (P<0.001),whereas high expression of MUC5AC significantly correlated with neural invasion (P = 0.022) and advanced ICC stage (P = 0.008). Patients with high expression of MUC1 had a significantly shorter survival (P = 0.0002). According to multivariate analyses, MUC1 reactivity (P = 0.026),histological grading and stage of tumor represented the least probability of survival.CONCLUSION: MUC1 is overexpressed in liver flukeassociated cholangiocarcinoma and relates to vascular invasion and poor prognosis, whereas MUC5AC mucin is neoexpressed and relates to neural invasion and advanced ICC stage. High MUC1 expression in tumor may be useful for predicting the poor outcome of ICC patients.

  1. A case of advanced intrahepatic cholangiocarcinoma successfully treated with chemosensitivity test-guided systemic chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Kazumichi Abe; Takeru Wakatsuki; Fumiko Katsushima; Kyoko Monoe; Yukiko Kanno; Atsushi Takahashi; Junko Yokokawa; Hiromasa Ohira

    2009-01-01

    Intrahepatic cholangiocarcinoma (ICC) is a relatively rare and highly fatal neoplasm that arises from the biliary epithelium. Prognosis is generally poor and survival is limited to a few months. Here we present a case of advanced ICC successfully treated by chemosensitivity test-guided systemic chemotherapy combining S-1 and cisplatin (CDDP). A 65-year-old woman with a liver tumor was referred to our hospital on November 21, 2007. Abdominal ultrasonography and computed tomography (CT) showed low-density masses of 50 and 15 mm in diameter, respectively in segment Ⅷ of the liver and in the enlarged lymph node in the para-aorta. Ultrasonography-guided fine needle biopsy diagnosed the tumors as ICC. Since the patient was inoperable for lymph node metastasis, she underwent systemic chemotherapy with gemcitabine. Six months after initiation of chemotherapy, CT revealed ICC progression in the liver and pleural dissemination with pleural effusion. The patient was admitted to our hospital for anticancer drug sensitivity testing on June 9, 2008. Based on the sensitivity test results, we elected to administer systemic chemotherapy combining S-1 and CDDP. Two months into the second chemotherapy treatment, CT revealed a reduction of the tumors in the liver and lymph node and a decrease in pleural effusion.After eight cycles of the second chemotherapy, 17 mo after ICC diagnosis, she is alive and well with no sign of recurrence. We conclude that chemosensitivity testing may effectively determine the appropriate chemotherapy regimen for advanced ICC.

  2. GNAS1 T393C Polymorphism Is Associated with Clinical Course in Patients with Intrahepatic Cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Klaus J. Schmitz

    2007-02-01

    Full Text Available BACKGROUND/AIMS: The GNAS1 locus encodes the Gas protein, which stimulates the formation of cycloadenosinemonophosphate (cAMP. The cAMP pathway mediates pleiotropic effects, including the regulation of apoptosis and proliferation. We have recently shown that TT genotypes of the single-nucleotide polymorphism T393C in the gene GNAS1 predict the clinical outcome of patients with various carcinomas. METHODS: Eighty-seven patients with intrahepatic cholangiocarcinoma (ICC were retrospectively genotyped to elucidate a potential association between T393C genotypes and clinical outcome. RESULTS: ICCs of patients with homozygous TT genotypes revealed a higher proliferation rate and a lower apoptotic rate. Homozygous TT patients were at highest risk for cancer-related deaths (hazard ratio = 2.74; 95% confidence interval = 1.03-7.28 compared with C-allele carriers. Kaplan-Meier curves for disease-specific overall and local recurrence-free survival in a subgroup with Ro-resected ICC showed a significant association of T393 homozygosity with outcome, which was confirmed in multivariate Cox regression analysis. CONCLUSIONS: GNAS1 T393C is a novel independent host factor for disease progression in patients with ICC. Our finding that TT homozygosity (and not CC homozygosity was associated with unfavorable clinical outcome points to the complex and differing functional effects induced by GNAS1 T393C polymorphism in various human carcinomas.

  3. Duodenal variceal bleeding after balloon-occluded retrograde transverse obliteration: Treatment with transjugular intrahepatic portosystemic shunt

    Institute of Scientific and Technical Information of China (English)

    Min Joung Kim; Byoung Kuk Jang; Woo Jin Chung; Jae Seok Hwang; Young Hwan Kim

    2012-01-01

    We report a case of duodenal varix bleeding as a long term complication of balloon occluded retrograde transvenous obliteration (BRTO),which was successfully treated with a transjugular intrahepatic portosystemic shunt (TIPS).A 57-year-old man was admitted to the emergency room suffering from melena.He had undergone BRTO to treat gastric varix bleeding 5 mo before admission.Endoscopy and a computed tomography (cr) scan showed complete obliteration of the gastric varix,but the nodular varices in the second portion of the duodenum expanded after BRTO,and spurting blood was seen.TIPS was performed for treatment of duodenal variceal bleeding,because attempts at endoscopic varix ligation were unsuccessful.The postoperative course was uneventful and the patient was discharged without complications.A follow up CT scan obtained 21 mo after TIPS revealed a patent TIPS tract and complete obliteration of duodenal varices,but multinodular hepatocellular carcinoma had developed.He died of hepatic failure 28 mo after TIPS.

  4. Intrahepatic mass-forming cholangiocarcinoma: prognostic value of preoperative gadoxetic acid-enhanced MRI

    Energy Technology Data Exchange (ETDEWEB)

    Koh, Jieun; Chung, Yong Eun; Kim, Myeong-Jin; Choi, Jin-Young [Yonsei University, College of Medicine, Department of Radiology, Research Institute of Radiological Science, Seoul (Korea, Republic of); Nahm, Ji Hae; Park, Young Nyun [Yonsei University, College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Kim, Ha Yan [Yonsei University, College of Medicine, Biostatistics Collaboration Unit, Severance Hospital, Seoul (Korea, Republic of); Kim, Kyung-Sik [Yonsei University, College of Medicine, Department of General Surgery, Seoul (Korea, Republic of)

    2016-02-15

    To assess whether gadoxetic acid-enhanced MRI could be used as a prognostic factor for intrahepatic mass-forming cholangiocarcinomas (IMCCs). Forty-one patients with pathologically proven IMCCs who underwent preoperative gadoxetic acid-enhanced MRI were included. The signal intensity of the IMCCs on hepatobiliary phase (HBP) MRI was qualitatively analyzed by two radiologists, and categorized into intermediate or hypointense groups. Analysis of clinicopathological prognostic factors and correlations of imaging and histology were also performed. Survival time and time to recurrence (TTR) were analyzed. Of the 41 IMCCs, 23 were in the intermediate group and 18 were in the hypointense group on HBP MRI. IMCCs in the intermediate group were associated with shorter survival time (P = 0.048) and TTR (P = 0.002) than the IMCCs of the hypointense group. Only the intermediate group on HBP MRI had a significantly shorter TTR on multivariate analysis (P = 0.012). The IMCCs of the intermediate group showed a tendency for more abundant tumour fibrous stroma than those of the hypointense group (P = 0.027). The enhancement of IMCCs on HBP gadoxetic acid-enhanced MRI appears to correlate with tumour aggressiveness and outcomes due to the tumour fibrous stromal component. Thus, HBP images could be a useful prognostic factor for IMCCs after surgery. (orig.)

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  6. Intrahepatic transneedle inoculation of VX2 particles for obtaining a solitary hepatic tumor in an animal model

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jin Han; Choi, Jong Cheol; Shin, Tae Beom; Park, Byeong Ho [Dong-A University, School of Medicine, Busan (Korea, Republic of)

    2005-07-15

    The purpose of this study was to develop a large animal (rabbit) model which has a proper solitary intrahepatic tumor with lower leakage rates through less traumatic methods. Consequently, we evaluated tumor progression following the intrahepatic inoculation of VX2 cells into New Zealand white rabbits to acquire baseline data on the progression of a VX2 tumor. Twenty New Zealand white rabbits, each weighting 2.5-3 kg, were selected for this study. A 1 mm{sup 3} VX2 tumor fragment was created and then minced to enable the particles to pass through a 21 G needle mounting in a tuberculin syringe with 0.1 ml of normal saline. The minced VX2 tumor particles were injected into the subcapsular parenchyma of the left hepatic lobe. A 21 G needle was used to avoid penetrating large hepatic vessels. In order to prevent hemorrhage or leakage of the VX2 tumor cells through the injection route, a purse-string suture around the puncture site was made using black silk 4-0. The tumor particles were then injected through the center of the suture. While removing the needle, the suture was tightened to prevent hemorrhage or leakage of the VX2 tumor cells through the injection route. Finally, the injection site was covered with a Surgical patch. The inoculated intrahepatic VX2 tumors were then imaged with a 16 channel multidetector CT every week for the duration of the study. The CT images covered from the lung apex to the pelvic floor. Two radiologists evaluated the size, location, and peritoneal seeding of the tumors as well as metastasis of other organs. Three rabbits were sacrificed as random beginning in the second week, and this process continued on a weekly basis for the duration of the study. The CT images and pathologic findings for the sacrificed rabbits were correlated. The inoculated intrahepatic VX2 tumors were not visible in the first week. By the second week 66.7% were visible on CT images and by the third week all tumors were visible. Of the twenty rabbits, three (15

  7. Relationship between the intrahepatic expression of 'e' and 'c' epitopes of the nucleocapsid protein of hepatitis B virus and viraemia.

    Science.gov (United States)

    Ballaré, M; Lavarini, C; Brunetto, M R; Petruzzelli, E; Dovis, M; Molino, G; Bonino, F

    1989-01-01

    The relationship between hepatitis B viraemia and intrahepatic HBV nucleocapsid proteins (HBcAg and HBeAg) was studied in 18 patients with chronic hepatitis B. Monoclonal antibodies (MoABs) were obtained in BALB/c mice primed with recombinant HBV nucleocapsid proteins. Four MoABs reacting with recombinant proteins gave positive results in competitive assays. Two reacted as anti-HBc and two as anti-HBe. One of them showed a strong affinity for the cytoplasmic, membrane-bound antigen (P23e) of infected hepatocytes while the latter showed a higher specificity for serum HBeAg than for the intrahepatic antigen. Anti-HBc MoABs had a staining capacity for liver cell nuclei comparable with that of polyclonal antibodies. Overall the anti-HBc MoABs stained the liver cell nuclei in 86% of cases, while anti-HBe MoABs stained in 58% of cases. The hepatocyte cytoplasm was stained by anti-HBc MoABs and anti-HBe MoABs in 64% and 72% of cases respectively. Not one of 12 control liver biopsies was stained. Viraemia (HBV-DNA) was measured by dot blot hybridization and was correlated with the number of hepatocytes containing the nucleocapsid antigen. The highest levels of HBV-DNA (greater than 10(8) genomes/ml) were detected in patients with prevalent nuclear staining while the lowest ones were observed in those with prevalent cytoplasmic expression of this antigen. The application of anti-HBV-nucleocapsid MoABs in diagnostics requires careful scrutiny since some are specific for the circulating antigen while others show a higher affinity for the intrahepatic antigen. PMID:2467769

  8. Effect of transforming growth factor-β1 on human intrahepatic cholangiocarcinoma cell growth

    Institute of Scientific and Technical Information of China (English)

    Tetsuya Shimizu; Takashi Tajiri; Shigeki Yokomuro; Yoshiaki Mizuguchi; Yutaka Kawahigashi; Yasuo Arima; Nobuhiko Taniai; Yasuhiro Mamada; Hiroshi Yoshida; Koho Akimaru

    2006-01-01

    AIM: To elucidate the biological effects of transforming growth factor-β1 (TGF-β1) on intrahepatic cholangiocarcinoma (ICC).METHODS: We investigated the effects of TGF-β1 on human ICC cell lines (HuCCT1, MEC, and HuH-28) by monitoring the influence of TGF-β1 on tumor growth and interleukin-6 (IL-6) expression in ICC cells.RESULTS: All three human ICC cell lines produced TGF-β1 and demonstrated accelerated growth in the presence of TGF-β1 with no apoptotic effect. Studies on HuCCT1 revealed a TGF-β1-induced stimulation of the expression of TGF-β1, as well as a decrease in TGF-β1 mRNA expression induced by neutralizing anti-TGF-β1 antibody. These results indicate that TGF-β1 stimulates the production and function of TGF-β1 in an autocrine fashion. Further, IL-6 secretion was observed in all three cell lines and exhibited an inhibitory response to neutralizing anti-TGF-β1 antibody. Experiments using HuCCT1 revealed a TGF-β1-induced acceleration of IL-6 protein expression and mRNA levels. These findings demonstrate a functional interaction between TGF-β1 and IL-6. All three cell lines proliferated in the presence of IL-6. In contrast, TGF-β1 induced no growth effect in HuCCT1 in the presence of small interfering RNA against a specific cell surface receptor of IL-6 and signal transducer and activator of transcription-3.CONCLUSION: ICC cells produce TGF-β1 and confer a TGF-β1-induced growth effect in an autocrine fashion.TGF-β1 activates IL-6 production, and the functional interaction between TGF-β1 and IL-6 contributes to ICC cell growth by TGF-β1.

  9. Intra-arterial embolotherapy for intrahepatic cholangiocarcinoma: update and future prospects

    Science.gov (United States)

    Savic, Lynn Jeanette; Chapiro, Julius

    2017-01-01

    Intrahepatic cholangiocarcinoma (ICC) is a rare disease and carries a poor prognosis with surgery remaining the only curative treatment option. However, due to the late presentation of symptoms and close proximity of the tumors to central hepatic structures, only about 30% of patients are classified eligible to resection. As for palliative approaches, ICC constitutes a possible indication for loco-regional therapies (LRT). As such, intra-arterial therapies (IAT) are reported to be feasible, safe and effective in inducing tumor response in unresectable ICC. The paradigm of IAT is premised on the selective delivery of embolic, chemotherapeutic agents to the tumor via its feeding arteries, thus allowing dose escalation within the carcinoma and reduction of systemic toxicity. Conventional transcatheter arterial chemoembolization (cTACE) so far remains the most commonly used IAT modality. However, drug-eluting beads (DEB)-TACE was initiated with the idea of more selective targeting of the tumor owing to the combined embolizing as well as drug-eluting properties of the microspheres used in this setting. Moreover, radioembolization is performed by intra-arterial administration of very small spheres containing β-emitting yttrium-90 (Y90-RE) to the site of the tumor. Clinical evidence exists in support of survival benefits for IAT in the palliative treatment of ICC compared to surgery and systemic chemotherapy. As for combination regimens, cTACE, DEB-TACE and Y90-RE are reported to achieve conversion of patients to surgery in a sequential treatment planning and simultaneous IAT combinations may provide a therapeutic option for treatment escalation. Regarding the current status of literature, controlled randomized prospective trials to compare different IAT techniques and combination therapies as well as treatment recommendations for different IAT modalities are needed. PMID:28261591

  10. NSAID Use and Risk of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: The Liver Cancer Pooling Project.

    Science.gov (United States)

    Petrick, Jessica L; Sahasrabuddhe, Vikrant V; Chan, Andrew T; Alavanja, Michael C; Beane-Freeman, Laura E; Buring, Julie E; Chen, Jie; Chong, Dawn Q; Freedman, Neal D; Fuchs, Charles S; Gaziano, John Michael; Giovannucci, Edward; Graubard, Barry I; Hollenbeck, Albert R; Hou, Lifang; Jacobs, Eric J; King, Lindsay Y; Koshiol, Jill; Lee, I-Min; Linet, Martha S; Palmer, Julie R; Purdue, Mark P; Rosenberg, Lynn; Schairer, Catherine; Sesso, Howard D; Sigurdson, Alice J; Wactawski-Wende, Jean; Zeleniuch-Jacquotte, Anne; Campbell, Peter T; McGlynn, Katherine A

    2015-12-01

    Chronic inflammation plays a pivotal role in the pathogenesis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), the two most common types of liver cancer. A number of prior experimental studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin and ibuprofen, may potentially protect against liver cancer. However, no observational study has examined the association between aspirin duration and dose or other over-the-counter non-aspirin NSAIDs, such as ibuprofen, and liver cancer incidence. Furthermore, the association between NSAID use and risk of ICC is unclear. As part of the Liver Cancer Pooling Project, we harmonized data on 1,084,133 individuals (HCC = 679, ICC = 225) from 10 U.S.-based prospective cohort studies. Cox proportional hazards regression models were used to evaluate multivariable-adjusted HRs and 95% confidence intervals (CI). Current aspirin use, versus nonuse, was inversely associated with HCC (HR, 0.68; 95% CI, 0.57-0.81), which persisted when restricted to individuals not using non-aspirin NSAIDs and in a 5- and 10-year lag analysis. The association between aspirin use and HCC risk was stronger for users who reported daily use, longer duration use, and lower dosage. Ibuprofen use was not associated with HCC risk. Aspirin use was associated with a reduced ICC risk in men (HR, 0.64; 95% CI, 0.42-0.98) but not women (HR, 1.34; 95% CI, 0.89-2.01; P(interaction) = 0.01). The observed inverse association between aspirin use and liver cancer in our study, together with previous data, suggests the merit of future intervention studies of aspirin and other agents that affect chronic inflammatory pathways for HCC and possibly ICC.

  11. Outcomes of Locoregional Tumor Therapy for Patients with Hepatocellular Carcinoma and Transjugular Intrahepatic Portosystemic Shunts

    Energy Technology Data Exchange (ETDEWEB)

    Padia, Siddharth A., E-mail: spadia@uw.edu; Chewning, Rush H., E-mail: rchewnin@uw.edu; Kogut, Matthew J., E-mail: kogutm@uw.edu; Ingraham, Christopher R., E-mail: cringa@uw.edu; Johnson, Guy E., E-mail: gej@uw.edu [University of Washington Medical Center, Section of Interventional Radiology, Department of Radiology (United States); Bhattacharya, Renuka, E-mail: renuka@uw.edu [University of Washington Medical Center, Division of Gastroenterology and Hepatology, Department of Medicine (United States); Kwan, Sharon W., E-mail: shakwan@uw.edu; Monsky, Wayne L., E-mail: wmonsky@uw.edu; Vaidya, Sandeep, E-mail: svaidya@uw.edu [University of Washington Medical Center, Section of Interventional Radiology, Department of Radiology (United States); Hippe, Daniel S., E-mail: dhippe@uw.edu [University of Washington Medical Center, Department of Radiology (United States); Valji, Karim, E-mail: kvalji@uw.edu [University of Washington Medical Center, Section of Interventional Radiology, Department of Radiology (United States)

    2015-08-15

    PurposeLocoregional therapy for hepatocellular carcinoma (HCC) can be challenging in patients with a transjugular intrahepatic portosystemic shunt (TIPS). This study compares safety and imaging response of ablation, chemoembolization, radioembolization, and supportive care in patients with both TIPS and HCC.MethodsThis retrospective study included 48 patients who had both a TIPS and a diagnosis of HCC. Twenty-nine of 48 (60 %) underwent treatment for HCC, and 19/48 (40 %) received best supportive care (i.e., symptomatic management only). While etiology of cirrhosis and indication for TIPS were similar between the two groups, treated patients had better baseline liver function (34 vs. 67 % Child-Pugh class C). Tumor characteristics were similar between the two groups. A total of 39 ablations, 17 chemoembolizations, and 10 yttrium-90 radioembolizations were performed on 29 patients.ResultsAblation procedures resulted in low rates of hepatotoxicity and clinical toxicity. Post-embolization/ablation syndrome occurred more frequently in patients undergoing chemoembolization than ablation (47 vs. 15 %). Significant hepatic dysfunction occurred more frequently in the chemoembolization group than the ablation group. Follow-up imaging response showed objective response in 100 % of ablation procedures, 67 % of radioembolization procedures, and 50 % of chemoembolization procedures (p = 0.001). When censored for OLT, patients undergoing treatment survived longer than patients receiving supportive care (2273 v. 439 days, p = 0.001).ConclusionsAblation appears to be safe and efficacious for HCC in patients with TIPS. Catheter-based approaches are associated with potential increased toxicity in this patient population. Chemoembolization appears to be associated with increased toxicity compared to radioembolization.

  12. Postoperative bile leakage managed successfully by intrahepatic biliary ablation with ethanol

    Institute of Scientific and Technical Information of China (English)

    Tetsuya Shimizu; Takashi Tajiri; Hiroshi Yoshida; Yasuhiro Mamada; Nobuhiko Taniai; Satoshi Matsumoto; Yoshiaki Mizuguchi; Shigeki Yokomuro; Yasuo Arima; Koho Akimaru

    2006-01-01

    We report a case of postoperative refractory bile leakage managed successfully by intrahepatic biliary ablation with ethanol. A 75-year-old man diagnosed with hepatocellular carcinoma underwent extended posterior segmentectomy including the caudate lobe and a part of the anterior segment. The hepatic tumor attached to the anterior branch of the bile duct was detached carefully and resected. Fluid drained from the liver surface postoperatively contained high concentrations of total bilirubin, at a constant volume of 150 mL per day. On d 32 after surgery, a fistulogram of the drainage tube demonstrated an enhancement of the anterior bile duct.Endoscopic retrograde cholangiography demonstrated complete obstruction of the proximal anterior bile duct and no enhancement of the peripheral anterior bile duct.On d 46 after surgery, a retrograde transhepatic biliary drainage (RTBD) tube was inserted into the anterior bile duct under open surgery. However, a contrast study of RTBD taken 7 mo post-surgery revealed that the fistula remained patent despite prolonged conservative management, so we decided to perform ethanol ablation of the isolated bile duct. Four mL pure ethanol was injected into the isolated anterior bile duct for ten minutes, the procedure being repeated five times a week. Following 23 attempts, the volume of bile juice reached less than 10 mL per day. The RTBD was clamped and removed two days later. After RTBD removal, the patient had no complaints or symptoms. Follow-up magnetic resonance imaging demonstrated atrophy of the ethanol-injected anterior segment without liver abscess formation.

  13. Three-Dimensional Path Planning Software-Assisted Transjugular Intrahepatic Portosystemic Shunt: A Technical Modification

    Energy Technology Data Exchange (ETDEWEB)

    Tsauo, Jiaywei, E-mail: 80732059@qq.com; Luo, Xuefeng, E-mail: luobo-913@126.com [West China Hospital of Sichuan University, Institute of Interventional Radiology (China); Ye, Linchao, E-mail: linchao.ye@siemens.com [Siemens Ltd, Healthcare Sector (China); Li, Xiao, E-mail: simonlixiao@gmail.com [West China Hospital of Sichuan University, Institute of Interventional Radiology (China)

    2015-06-15

    PurposeThis study was designed to report our results with a modified technique of three-dimensional (3D) path planning software assisted transjugular intrahepatic portosystemic shunt (TIPS).Methods3D path planning software was recently developed to facilitate TIPS creation by using two carbon dioxide portograms acquired at least 20° apart to generate a 3D path for overlay needle guidance. However, one shortcoming is that puncturing along the overlay would be technically impossible if the angle of the liver access set and the angle of the 3D path are not the same. To solve this problem, a prototype 3D path planning software was fitted with a utility to calculate the angle of the 3D path. Using this, we modified the angle of the liver access set accordingly during the procedure in ten patients.ResultsFailure for technical reasons occurred in three patients (unsuccessful wedged hepatic venography in two cases, software technical failure in one case). The procedure was successful in the remaining seven patients, and only one needle pass was required to obtain portal vein access in each case. The course of puncture was comparable to the 3D path in all patients. No procedure-related complication occurred following the procedures.ConclusionsAdjusting the angle of the liver access set to match the angle of the 3D path determined by the software appears to be a favorable modification to the technique of 3D path planning software assisted TIPS.

  14. Radiofrequency Ablation for the Treatment of Hepatocellular Carcinoma in Patients with Transjugular Intrahepatic Portosystemic Shunts

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    Park, Jonathan K., E-mail: jonathan.park09@gmail.com [David Geffen School of Medicine at UCLA, Department of Radiology (United States); Al-Tariq, Quazi Z., E-mail: qat200@gmail.com [Stanford University School of Medicine, Department of Radiology (United States); Zaw, Taryar M., E-mail: taryar.zaw@gmail.com; Raman, Steven S., E-mail: sraman@mednet.ucla.edu; Lu, David S.K., E-mail: dlu@mednet.ucla.edu [David Geffen School of Medicine at UCLA, Department of Radiology (United States)

    2015-10-15

    PurposeTo assess radiofrequency (RF) ablation efficacy, as well as the patency of transjugular intrahepatic portosystemic shunts (TIPSs), in patients with hepatocellular carcinoma (HCC).Materials and MethodsRetrospective database review of patients with pre-existing TIPS undergoing RF ablation of HCC was conducted over a 159-month period ending in November 2013. TIPS patency pre- and post-RF ablation was assessed by ultrasound, angiography, and/or contrast-enhanced CT or MRI. Patient demographics and immediate post-RF ablation outcomes and complications were also reviewed.Results19 patients with 21 lesions undergoing 25 RF ablation sessions were included. Child-Pugh class A, B, and C scores were seen in 1, 13, and 5 patients, respectively. Eleven patients (58 %) ultimately underwent liver transplantation. Immediate technical success was seen in all ablation sessions without residual tumor enhancement (100 %). No patients (0 %) suffered liver failure within 1 month of ablation. Pre-ablation TIPS patency was demonstrated in 22/25 sessions (88 %). Of 22 cases with patent TIPS prior to ablation, post-ablation patency was demonstrated in 22/22 (100 %) at immediate post-ablation imaging and in 21/22 (95 %) at last follow-up (1 patient was incidentally noted to have occlusion 31 months later). No immediate complications were observed.ConclusionAblation efficacy was similar to the cited literature values for patients without TIPS. Furthermore, TIPS patency was preserved in the majority of cases. Patients with both portal hypertension and HCC are not uncommonly encountered, and a pre-existing TIPS does not appear to be a definite contraindication for RF ablation.

  15. Transjugular intrahepatic portosystemic shunt: results and prognostic factors in patients with post-necrotic liver cirrhosis

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    Park, Jae Hyung; Chung, Jin Wook; Han, Joon Koo; Han, Man Chung [Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Yong Joo [Kyungbook National University College of Medicine, Taegu (Korea, Republic of)

    1997-01-01

    To evaluate the effectiveness of transjugular intrahepatic portosystemic shunt(TIPS) in the management of gastroesophageal variceal bleeding and predictive factors for long-term survival in patients with post-necrotic liver cirrhosis. A total of 49 patients with post-necrotic liver cirrhosis underwent TIPS over a recent three-year period. Forty-five had a history of hepatitis B viral infection, and four, of hepatitis C viral infection. In all patients, the indication for the procedure was variceal bleeding. Child-Pugh class was A in seven patients, B in 16 and C in 26 patients at the time of the last bleeding. The effectiveness of portal decompression and bleeding control was evaluated. Long-term survival was calculated by the Kaplan-Meier method and predictive factors were analyzed using the Wilcoxon test. The procedure was technically successful in all cases. The portosystemic pressure gradient decreased significantly from 21.4 {+-} 6.4 mmHg to 12.0 {+-} 5.1 mmHg(N=45). Active variceal bleeding was controlled in 34 of the 37 emergency patients. The total length of follow-up was from one day to three and a half years(mean : 383 {+-} 357 days). Rebleeding developed in 17 patients (35%). Hepatic encephalopathy, either newly developed or aggravated, occurred in 16 (32.7%). The thirty-day mortality rate was 20.4%, and the one-year survival rate was 63.8%. The significant predictive factors for poor prognosis were Child-Pugh class C and post-TIPS hepatic encephalopathy. TIPS is effective in portal decompression in the patients with variceal bleeding due to post-necrotic liver cirrhosis. The Child-Pugh classification and hepatic encephalopathy after TIPS are considered to be significant predictive factors for long-term survival.

  16. Prevention of potential complications related to transjugular intrahepatic portosystemic shunt procedure: efficacy of polytetrafluoroethylene stent grfat

    Energy Technology Data Exchange (ETDEWEB)

    Koo, Jae Hong; Seong, Chang Kyu [School of Medicine, Kyungpook National Univ., Daegu (Korea, Republic of); Kim, Young Hwan; Choi, Jin Soo; Lee, Sang Kwon; Kim, Gab Chul [School of Medicine, Keimyung Univ., Daegu (Korea, Republic of); Kim, Yong Joo [Andong General Hospital, Andong (Korea, Republic of); Seong, Nak Kwan; Park, Young Chan [School of Medicine, Daegu Catholic Univ., Daegu (Korea, Republic of)

    2004-11-01

    The purpose of this study was to assess the efficacy of a polytetrafluoroethylene (PTFE) stent graft for preventing potential complications related to a transjugular intrahepatic portosystemic shunt (TIPS). Between January 2002 and March 2003, seven patients (males: 5, females: 2, mean age: 44) underwent TIPS stent placement using the PTFE stent graft (Nitis,Taewoong, Seoul, Korea) to prevent potential complications such as life threatening hemoperitoneum, hemobilia and early stent occlusion. Three patients were admitted for esophageal varix bleeding, three patients were admitted for gastric varix bleeding and one patient was admitted for umbilical bleeding. The extrahepatic portal vein was punctured inadvertently in four patients (main portal vein: 1 case, portal vein bifurcation: 3 cases), but contrast media extravasation into the peritoneal cavity on the tractogram was noted only in two patients. Two of four patients had chronic portal vein occlusion with intra- and extrahepatic cavernous transformation. The bile duct was inadvertently punctured and visualized on the tractogram in three patients. All the identified biliary trees or contrast media extravasations observed on the tractograms were successfully sealed off on the post-procedure portograms. The immediate post-procedure clinical recovery courses were uneventful in all patients (no hemobilia or hemoperitoneum was noted). Bleeding control was successful in all patients. The one patient who had Child-Pugh cIass C disease died of hepatic encephalopathy 3 days after TIPS placement. Five of the six living patients have not shown any complications or rebleeding during the follow up periods (9-23 months). The one patient who had biliary communication on the tractogram rebled due to TIPS stent stenosis 25 days after TIPS, and this patient was successfully treated by TIPS revision. Potential complications related to TIPS procedure can be successfully prevented with PTFE stent graft placement.

  17. Mutation inactivation of Nijmegen breakage syndrome gene (NBS1 in hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

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    Yan Wang

    Full Text Available Nijmegen breakage syndrome (NBS with NBS1 germ-line mutation is a human autosomal recessive disease characterized by genomic instability and enhanced cancer predisposition. The NBS1 gene codes for a protein, Nbs1(p95/Nibrin, involved in the processing/repair of DNA double-strand breaks. Hepatocellular carcinoma (HCC is a complex and heterogeneous tumor with several genomic alterations. Recent studies have shown that heterozygous NBS1 mice exhibited a higher incidence of HCC than did wild-type mice. The objective of the present study is to assess whether NBS1 mutations play a role in the pathogenesis of human primary liver cancer, including HBV-associated HCC and intrahepatic cholangiocarcinoma (ICC. Eight missense NBS1 mutations were identified in six of 64 (9.4% HCCs and two of 18 (11.1% ICCs, whereas only one synonymous mutation was found in 89 control cases of cirrhosis and chronic hepatitis B. Analysis of the functional consequences of the identified NBS1 mutations in Mre11-binding domain showed loss of nuclear localization of Nbs1 partner Mre11, one of the hallmarks for Nbs1 deficiency, in one HCC and two ICCs with NBS1 mutations. Moreover, seven of the eight tumors with NBS1 mutations had at least one genetic alteration in the TP53 pathway, including TP53 mutation, MDM2 amplification, p14ARF homozygous deletion and promoter methylation, implying a synergistic effect of Nbs1 disruption and p53 inactivation. Our findings provide novel insight on the molecular pathogenesis of primary liver cancer characterized by mutation inactivation of NBS1, a DNA repair associated gene.

  18. Pathological Predictors of Shunt Stenosis and Hepatic Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt

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    Fuliang He

    2016-01-01

    Full Text Available Background. Transjugular intrahepatic portosystemic shunt (TIPS is an artificial channel from the portal vein to the hepatic vein or vena cava for controlling portal vein hypertension. The major drawbacks of TIPS are shunt stenosis and hepatic encephalopathy (HE; previous studies showed that post-TIPS shunt stenosis and HE might be correlated with the pathological features of the liver tissues. Therefore, we analyzed the pathological predictors for clinical outcome, to determine the risk factors for shunt stenosis and HE after TIPS. Methods. We recruited 361 patients who suffered from portal hypertension symptoms and were treated with TIPS from January 2009 to December 2012. Results. Multivariate logistic regression analysis showed that the risk of shunt stenosis was increased with more severe inflammation in the liver tissue (OR, 2.864; 95% CI: 1.466–5.592; P=0.002, HE comorbidity (OR, 6.266; 95% CI, 3.141–12.501; P<0.001, or higher MELD score (95% CI, 1.298–1.731; P<0.001. Higher risk of HE was associated with shunt stenosis comorbidity (OR, 6.266; 95% CI, 3.141–12.501; P<0.001, higher stage of the liver fibrosis (OR, 2.431; 95% CI, 1.355–4.359; P=0.003, and higher MELD score (95% CI, 1.711–2.406; P<0.001. Conclusion. The pathological features can predict individual susceptibility to shunt stenosis and HE.

  19. Consequences of TCDD treatment on intra-hepatic lymphocytes during liver regeneration.

    Science.gov (United States)

    Horras, Christopher J; Lamb, Cheri L; King, Allie L; Hanley, Jason R; Mitchell, Kristen A

    2012-01-01

    Increasing evidence demonstrates a physiological role for the aryl hydrocarbon receptor (AhR) in regulating hepatocyte cell cycle progression. Previous studies have used a murine model of liver regeneration to show that exposure to the potent exogenous AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), suppresses hepatocyte proliferation in vivo. Based on recent reports that natural killer (NK) cells negatively regulate liver regeneration, coupled with the well-established immunomodulatory effects of TCDD, it was hypothesized that alterations in lymphocyte activation contribute to the suppression of liver regeneration in TCDD-treated mice. To test this, mice were treated with TCDD (20 μg/kg) 1 day prior to 70% partial hepatectomy (PH), in which two-thirds of the liver was surgically resected. Lymphocytes were collected from the remnant liver and analyzed by flow cytometry. Whereas exposure to TCDD did not alter the number of NK cells or CD3(+) T-cells recovered from the regenerating liver, it reduced the percentage and number of intra-hepatic NKT cells 42 h after PH. With regard to lymphocyte activation, TCDD treatment transiently increased CD69 expression on NK and NKT cells 12 h after PH, but had no effect on intracellular levels of IFNγ in NK, NKT, or CD3(+) T-cells. To determine the relevance of NK cells to the suppression of liver regeneration by TCDD, mice were treated with anti-Asialo GM-1 (ASGM-1) antibody to deplete NK cells prior to TCDD treatment and PH, and hepatocyte proliferation was measured using bromodeoxyuridine incorporation. Exposure to TCDD was found to inhibit hepatocyte proliferation in the regenerating liver of NK cell-depleted mice and control mice to the same extent. Hence, it is unlikely that enhanced numbers or increased activation of NK cells contribute to the suppression of liver regeneration in TCDD-treated mice.

  20. Hepatitis B virus infection: A favorable prognostic factor for intrahepatic cholangiocarcinoma after resection

    Institute of Scientific and Technical Information of China (English)

    Hua-Bang Zhou; Meng-Chao Wu; He-Ping Hu; Hui Wang; Yu-Qiong Li; Shuang-Xi Li; Hao Wang; Dong-Xun Zhou; Qian-Qian Tu; Qing Wang; Shan-Shan Zou

    2011-01-01

    AIM: To study the prognostic factors for intrahepatic cholangiocarcinoma (ICC) and evaluate the impact of chronic hepatitis B virus (HBV) infection on survival rate of ICC patients. METHODS: A total of 155 ICC patients who underwent macroscopic curative resections (R0 and R1) were enrolled in this retrospective study and divided into group A with HBV infection and group B without HBV infection according to their chronic HBV infection, represented by positive hepatitis B surface antigen (HBsAg) in serum or in liver tissue. Clinicopathological characteristics and survival rate of the patients were evaluated. RESULTS: All patients underwent anatomical resection. Their 1- and 3-year survival rates were 60.6% and 32.1%, respectively. Multivariate analyses revealed that HBV infection, hepatolithiasis, microscopic satellite lesion, and lymphatic metastasis were the independent prognostic factors for the survival rate of ICC patients. The median disease-free survival time of the patients was 5.0 mo. The number of tumors, microscopic satellite lesion, and vascular invasion were the independent prognostic factors for the disease-free survival rate of the patients. The prognostic factors affecting the survival rate of ICC patients with HBV infection and those without HBV infection were not completely consistent. Alkaline phosphatase > 119 U/L, microscopic satellite lesion, vascular invasion, and lymphatic metastasis were the independent factors for the patients with HBV infection, while r-glutamyltransferase > 64 U/L, microscopic satellite lesion, and poor tumor differentiation were the independent factors for the patients without HBV infection. CONCLUSION: HBV infection is a valuable clinical factor for predicting tumor invasiveness and clinical outcome of ICC patients. ICC patients with HBV infection should be distinguished from those without HBV infection because they have different clinicopathological characteristics, prognostic factors and outcomes after surgical

  1. Prognostic value of DNA alterations on chromosome 17p13.2 for intrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Ubol Chuensumran; Sopit Wongkham; Chawalit Pairojkul; Siri Chauin; Songsak Petmitr

    2007-01-01

    AIM: To characterize and evaluate DNA alterations among intrahepatic cholangiocarcinoma (ICC) patients.METHODS: DNA from tumor and corresponding normal tissues of 52 patients was amplified with 33 arbitrary primers. The DNA fragment that alters most frequently in ICC was cloned, sequenced, and identified by comparison with known nucleotide sequences in the genome database (www.ncbi.nlm.nih.gov). The DNA copy numbers of the allelic alterations in cholangiocarcinoma were determined by quantitative real-time PCR and interpreted as allelic loss or DNA amplification by comparison with the reference gene. Associations between allelic imbalance and clinicopathological parameters of ICC patients were evaluated by x2-test.The Kaplan-Meier method was used to analyze survival rates.RESULTS: From 33 primers, an altered DNA fragment (518 bp) amplified from BC17 random primer was found frequently in the tumors analyzed and mapped to chromosome 17p13.2. Sixteen of 52 (31%) cases showed DNA amplification, while 7 (13%) showed allelic loss. Interestingly, DNA amplification on chromosome 17p13.2 was associated with a good prognosis, median survival time (wk) of amp vs no amp was 44.14 vs 24.14,P = 0.002; whereas allelic loss of this DNA sequence corresponded with a poor prognosis, median survival time (wk) of loss vs no loss was 18.00 vs 28.71, P =0.019). Moreover, Kaplan-Meier curves comparing the DNA alterations with survival depicted highly significant separation that the median survival time equal to DNA amplification, allelic loss, and normal was 44.14 wk,18.00 wk, and 24.29 wk, respectively (P = 0.005).CONCLUSION: Alterations in the DNA sequence on chromosome 17p13.2 may be involved in cholangiocarcinogenesis, and could be used as a prognostic marker in the treatment of ICC patients.

  2. Yttrium-90 Radioembolization for Unresectable Standard-chemorefractory Intrahepatic Cholangiocarcinoma: Survival, Efficacy, and Safety Study

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    Rafi, Shoaib; Piduru, Sarat M. [Emory University School of Medicine, Division of Interventional Radiology and Image Guided Medicine, Department of Radiology (United States); El-Rayes, Bassel; Kauh, John S. [Emory University School of Medicine, Department of Hematology and Medical Oncology (United States); Kooby, David A.; Sarmiento, Juan M. [Emory University School of Medicine, Department of Surgical Oncology in Surgery (United States); Kim, Hyun S., E-mail: kevin.kim@emory.edu [Emory University School of Medicine, Division of Interventional Radiology and Image Guided Medicine, Department of Radiology (United States)

    2013-04-15

    To assess the overall survival, efficacy, and safety of radioembolization with yttrium-90 (Y90) for unresectable standard-chemorefractory intrahepatic cholangiocarcinoma (ICC). Patients with unresectable standard-chemorefractory ICC treated with Y90 were studied. Survival was calculated from the date of first Y90 procedure. Tumor response was assessed with the Response Evaluation Criteria in Solid Tumors criteria on follow-up computed tomography or magnetic resonance imaging scans. National Cancer Institute Common Terminology Criteria (NCI CTCAE), version 3, were used for complications. Statistical analysis was performed by the Kaplan-Meier estimator by the log rank test. Nineteen patients underwent a total of 24 resin-based Y90 treatments. Median survival from the time of diagnosis and first Y90 procedure was 752 {+-} 193 [95 % confidence interval (CI) 374-1130] and 345 {+-} 128 (95 % CI 95-595) days, respectively. Median survival with Eastern Cooperative Oncology Group (ECOG) performance status 1 (n = 15) and ECOG performance status 2 (n = 4) was 450 {+-} 190 (95 % CI 78-822) and 345 {+-} 227 (95 % CI 0-790) days, respectively (p = .214). Patients with extrahepatic metastasis (n = 11) had a median survival of 404 {+-} 309 (95 % CI 0-1010) days versus 345 {+-} 117 (95 % CI 115-575) days for patients without metastasis (n = 8) (p = .491). No mortality was reported within 30 days from first Y90 radioembolization. One patient developed grade 3 thrombocytopenia as assessed by NCI CTCAE. Fatigue and transient abdominal pain were observed in 4 (21 %) and 6 (32 %) patients, respectively. Y90 radioembolization is effective for unresectable standard-chemorefractory ICC.

  3. Application study of regular hepatectomy with choledochoscope in treatment of intrahepatic bile duct stones

    Institute of Scientific and Technical Information of China (English)

    LU De-Bin; LI Qiao-Lin

    2016-01-01

    Objective:To study the clinical effect of regular hepatectomy with choledochoscope in treatment of intrahepatic bile duct stones (IBDS);Methods:A total of 76 cases of patients with complex IBDS treated in our hospital from August 2014 to July 2015 were selected and divided into experimental group (n=38) and control group (n=38) according to random number table, and baseline information of two groups was without statistical significance. Experimental group received regular hepatectomy with choledochoscope and control group received multiple hepatolobectomy. Hepatolobectomy as well as TBIL (total bilirubin), ALB (albumin), ALT (alanine aminotransferase), AST (aspartate aminotransferase), APTT (activated partial thromboplastin time), postoperative complications, recurrence, clinical effect and other indexes of two groups 1 d before operation and 7 d after operation were observed;Results:left hemihepatectomy, left lateral lobectomy, right hemihepatectomy, right posterior lobectomy as well as left lateral and right posterior lobectomy rates of experimental group were not statistically different from those of control group. TBIL, ALB, ALT, AST and APTT of experimental group 7d after operation were not statistically different from those of control group. Excellent and good rate of treatment of experimental group (97.37%) was significantly higher than that of control group (76.32%), incidence of postoperative complications (15.79%) was significantly lower than that of control group (44.74%), stone residue rate of experimental group (5.26%) was significantly lower than that of control group (23.68%), and comparison between groups showed statistical significance;Conclusion:Regular hepatectomy with choledochoscope treatment of IBDS has higher excellent and good rate, more stable liver function indexes as well as lower rate of stone residue and incidence of postoperative complications, and it’s worth application in clinical practice.

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

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    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. 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.

  6. 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.

  7. Anatomic variation in intrahepatic bile ducts: an analysis of intraoperative cholangiograms in 300 consecutive donors for living donor liver transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jin Woo; Kim, Tae Kyoung; Kim, Kyoung Won; Kim, Ah Young; Kim, Pyo Nyun; Ha, Hyun Kwon; Lee, Moon Gyu [Ulsan University College of Medicine, Seoul (Korea, Republic of)

    2003-06-01

    To describe the anatomical variation occurring in intrahepatic bile ducts (IHDs) in terms of their branching patterns, and to determine the frequency of each variation. The study group consisted of 300 consecutive donors for liver transplantation who underwent intraoperative cholangiography. Anatomical variation in IHDs was classified according to the branching pattern of the right anterior and right posterior segmental duct (RASD and RPSD, respectively), and the presence or absence of the first-order branch of the left hepatic duct (LHD), and of an accessory hepatic duct. The anatomy of the intrahepatic bile ducts was typical in 63% of cases (n=188), showed triple confluence in 10% (n=29), anomalous drainage of the RPSD into the LHD in 11% (n=34), anomalous drainage of the RPSD into the common hepatic duct (CHD) in 6% (n=19), anomalous drainage of the RPSD into the cystic duct in 2% (n=6), drainage of the right hepatic duct (RHD) into the cystic duct (n=1), the presence of an accessory duct leading to the CHD or RHD in 5% (n=16), individual drainage of the LHD into the RHD or CHD in 1% (n=4), and unclassified or complex variation in 1% (n=3)

  8. In situ characterization of intrahepatic non-parenchymal cells in PSC reveals phenotypic patterns associated with disease severity.

    Science.gov (United States)

    Berglin, Lena; Bergquist, Annika; Johansson, Helene; Glaumann, Hans; Jorns, Carl; Lunemann, Sebastian; Wedemeyer, Heiner; Ellis, Ewa C; Björkström, Niklas K

    2014-01-01

    Liver-infiltrating T cells have been implicated in the pathogenesis of primary sclerosing cholangitis (PSC), however little information is available about changes in other cellular compartments in the liver during PSC. This study aimed to characterize non-parenchymal intrahepatic cells in PSC livers and to find associations between phenotypes and disease severity. Using immunohistochemistry, followed by automated image analysis and quantification and a principal component analysis, we have studied non-parenchymal intrahepatic cells in PSC-patient livers (n = 17) and controls (n = 17). We observed a significant increase of T cells in the PSC patients, localized to the fibrotic areas. MAIT cells, normally present at high numbers in the liver, were not increased to the same extent. PSC patients had lower expression of MHC class I than controls. However, the levels of NKp46+ NK cells were similar between patients and controls, nevertheless, NKp46 was identified as a phenotypic marker that distinguished PSC patients with mild from those with severe fibrosis. Beyond that, a group of PSC patients had lost expression of Caldesmon and this was associated with more extensive bile duct proliferation and higher numbers of T cells. Our data reveals phenotypic patterns in PSC patients associated with disease severity.

  9. In situ characterization of intrahepatic non-parenchymal cells in PSC reveals phenotypic patterns associated with disease severity.

    Directory of Open Access Journals (Sweden)

    Lena Berglin

    Full Text Available Liver-infiltrating T cells have been implicated in the pathogenesis of primary sclerosing cholangitis (PSC, however little information is available about changes in other cellular compartments in the liver during PSC. This study aimed to characterize non-parenchymal intrahepatic cells in PSC livers and to find associations between phenotypes and disease severity. Using immunohistochemistry, followed by automated image analysis and quantification and a principal component analysis, we have studied non-parenchymal intrahepatic cells in PSC-patient livers (n = 17 and controls (n = 17. We observed a significant increase of T cells in the PSC patients, localized to the fibrotic areas. MAIT cells, normally present at high numbers in the liver, were not increased to the same extent. PSC patients had lower expression of MHC class I than controls. However, the levels of NKp46+ NK cells were similar between patients and controls, nevertheless, NKp46 was identified as a phenotypic marker that distinguished PSC patients with mild from those with severe fibrosis. Beyond that, a group of PSC patients had lost expression of Caldesmon and this was associated with more extensive bile duct proliferation and higher numbers of T cells. Our data reveals phenotypic patterns in PSC patients associated with disease severity.

  10. Utility of the dual-specificity protein kinase TTK as a therapeutic target for intrahepatic spread of liver cancer.

    Science.gov (United States)

    Miao, Ruoyu; Wu, Yan; Zhang, Haohai; Zhou, Huandi; Sun, Xiaofeng; Csizmadia, Eva; He, Lian; Zhao, Yi; Jiang, Chengyu; Miksad, Rebecca A; Ghaziani, Tahereh; Robson, Simon C; Zhao, Haitao

    2016-09-13

    Therapies for primary liver cancer, the third leading cause of cancer-related death worldwide, remain limited. Following multi-omics analysis (including whole genome and transcriptome sequencing), we were able to identify the dual-specific protein kinase TTK as a putative new prognostic biomarker for liver cancer. Herein, we show that levels of TTK protein are significantly elevated in neoplastic tissues from a cohort of liver cancer patients, when compared with adjacent hepatic tissues. We also tested the utility of TTK targeted inhibition and have demonstrated therapeutic potential in an experimental model of liver cancer in vivo. Following lentiviral shRNA knockdown in several human liver cancer cell lines, we demonstrated that TTK boosts cell growth and promotes cell spreading; as well as protects against senescence and decreases autophagy. In an experimental animal model, we show that in vitro knockdown of TTK effectively blocks intrahepatic growth of human HCC xenografts. Furthermore, we note that, in vivo silencing of TTK, by systemically delivering TTK siRNAs to already tumor-bearing liver, limits intrahepatic spread of liver cancer cells. This intervention is associated with decreased tumor aggressiveness, as well as increased senescence and autophagy. Taken together, our data suggest that targeted TTK inhibition might have clinical utility as an adjunct therapy in management of liver cancer.

  11. 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

  12. Primary liver tumors. Hepatocellular versus intrahepatic cholangiocellular carcinoma; Primaere Lebertumoren. Hepatozellulaeres vs. intrahepatisches cholangiozellulaeres Karzinom

    Energy Technology Data Exchange (ETDEWEB)

    Wengert, G.J.; Bickel, H.; Breitenseher, J.; Ba-Ssalamah, A. [Medizinische Universitaet Wien, Universitaetsklinik fuer Radiologie und Nuklearmedizin, Allgemeines Krankenhaus, Wien (Austria)

    2015-01-01

    Hepatocellular carcinoma (HCC) and intrahepatic cholangiocellular carcinoma (ICC) are the most commonly occurring and important primary liver tumors. Originating from one pluripotent liver stem cell both tumor entities can occur in a cirrhotic liver and also in patients without cirrhosis. Several risk factors have been identified as causative for both carcinomas; therefore, tumor screening is advantageous, especially for high-risk patients who could be diagnosed in an early stage to allow curative treatment. Surgical resection, interventional procedures and transplantation are available as curative treatment options when diagnosed in time. Common characteristic features and morphology in cross-sectional imaging by ultrasound (US), multidetector computed tomography (CT) and magnetic resonance imaging (MRI) as well as screening aspects are presented and discussed. Recent findings show a better understanding of the carcinogenesis model of both liver tumors originating from one pluripotent liver stem cell. Further developments of modern cross-sectional imaging modalities, especially MRI in combination with diffusion-weighted imaging and intravenous administration of hepatocyte-specific contrast agents enable early detection, exact differentiation, staging and treatment evaluation of HCC and ICC In this article we discuss modern, multiparametric imaging modalities, which allow a complete and reliable diagnosis of the majority of these tumor entities. Contrast-enhanced MRI, using hepatocyte-specific contrast agents, is currently the most accurate procedure for the noninvasive diagnosis and treatment evaluation of HCC and ICC. (orig.) [German] Das hepatozellulaere Karziom (HCC) sowie das intrahepatische cholangiozellulaere Karzinom (ICC) zaehlen zu den wichtigsten primaeren Lebertumoren. Mit dem Ursprung aus einer pluripotenten Stammzelle koennen beide Tumorentitaeten bei bestehender, aber auch bei nicht bestehender Leberzirrhose auftreten. Im Folgenden werden

  13. Drug sensitivity and drug resistance profiles of human intrahepatic cholangiocarcinoma cell lines

    Institute of Scientific and Technical Information of China (English)

    Nisana Tepsiri; Liengchai Chaturat; Banchob Sripa; Wises Namwat; Sopit Wongkham; Vajarabhongsa Bhudhisawasdi; Wichittra Tassaneeyakul

    2005-01-01

    AIM: To study the effect of a number of chemotherapeutic drugs on five human intrahepatic cholangiocarcinoma (CCA) cell lines. The expressions of genes that have been proposed to influence the resistance of chemotherapeutic drugs including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), glutathione-S-transferase P1 (GSTP1), multidrug resistance protein (MDR1) and multidrug resistance-associated proteins (MRPs) were also determined.METHODS: Five human CCA cell lines (KKU-100, KKU M055, KKU-M156, KKU-M214 and KKU-OCA17) weretreated with various chemotherapeutic drugs and growth inhibition was determined by 3-(4,5-dimethylthiazol-2-yl)5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Semi-quantitative levels of gene expression were determined by a reverse transcriptase polymerase chain reaction (RT-PCR). Results of IC50 values and the ratios of gene expression were analyzed by linear regression to predict their relationship. RESULTS: Among five CCA cell lines, KKU-M055 was the most sensitive cell line towards all chemotherapeutic drugs investigated, particularly taxane derivatives with IC50 values of 0.02-3 nmol/L, whereas KKU-100 was apparently the least sensitive cell line. When compared to other chemotherapeutic agents, doxorubicin and pirarubicin showed the lowest IC50 values (<5 μmol/L) in all five CCA cell lines. Results from RT-PCR showed that TS, MRP1, MRP3 and GSTP1 were highly expressed in these five CCA cell lines while DPD and MRP2 were only moderately expressed. It should be noted that MDR1 expression was detected only in KKU-OCA17 cell lines. A strong correlation was only found between the level of MRP3 expression and the IC50 values of etoposide, doxorubicin and pirarubicin (r = 0.86-0.98, ,P<0.05). CONCLUSION: Sensitivity to chemotherapeutic agents is not associated with the histological type of CCA. Choosing of the appropriate chemotherapeutic regimen for the treatment of CCA requires knowledge of drug

  14. Integrative Molecular Analysis of Intrahepatic Cholangiocarcinoma Reveals 2 Classes That Have Different Outcomes

    Science.gov (United States)

    SIA, DANIELA; HOSHIDA, YUJIN; VILLANUEVA, AUGUSTO; ROAYAIE, SASAN; FERRER, JOANA; TABAK, BARBARA; PEIX, JUDIT; SOLE, MANEL; TOVAR, VICTORIA; ALSINET, CLARA; CORNELLA, HELENA; KLOTZLE, BRANDY; FAN, JIAN–BING; COTSOGLOU, CHRISTIAN; THUNG, SWAN N.; FUSTER, JOSEP; WAXMAN, SAMUEL; GARCIA–VALDECASAS, JUAN CARLOS; BRUIX, JORDI; SCHWARTZ, MYRON E.; BEROUKHIM, RAMEEN; MAZZAFERRO, VINCENZO; LLOVET, JOSEP M.

    2013-01-01

    BACKGROUND & AIMS Cholangiocarcinoma, the second most common liver cancer, can be classified as intra-hepatic cholangiocarcinoma (ICC) or extrahepatic cholangiocarcinoma. We performed an integrative genomic analysis of ICC samples from a large series of patients. METHODS We performed a gene expression profile, high-density single-nucleotide polymorphism array, and mutation analyses using formalin-fixed ICC samples from 149 patients. Associations with clinicopathologic traits and patient outcomes were examined for 119 cases. Class discovery was based on a non-negative matrix factorization algorithm and significant copy number variations were identified by GISTIC analysis. Gene set enrichment analysis was used to identify signaling pathways activated in specific molecular classes of tumors, and to analyze their genomic overlap with hepatocellular carcinoma (HCC). RESULTS We identified 2 main biological classes of ICC. The inflammation class (38% of ICCs) is characterized by activation of inflammatory signaling pathways, overexpression of cytokines, and STAT3 activation. The proliferation class (62%) is characterized by activation of oncogenic signaling pathways (including RAS, mitogen-activated protein kinase, and MET), DNA amplifications at 11q13.2, deletions at 14q22.1, mutations in KRAS and BRAF, and gene expression signatures previously associated with poor outcomes for patients with HCC. Copy number variation– based clustering was able to refine these molecular groups further. We identified high-level amplifications in 5 regions, including 1p13 (9%) and 11q13.2 (4%), and several focal deletions, such as 9p21.3 (18%) and 14q22.1 (12% in coding regions for the SAV1 tumor suppressor). In a complementary approach, we identified a gene expression signature that was associated with reduced survival times of patients with ICC; this signature was enriched in the proliferation class (P < .001). CONCLUSIONS We used an integrative genomic analysis to identify 2 classes

  15. Delayed-Phase Cone-Beam CT Improves Detectability of Intrahepatic Cholangiocarcinoma During Conventional Transarterial Chemoembolization

    Energy Technology Data Exchange (ETDEWEB)

    Schernthaner, Ruediger Egbert [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology (United States); Lin, MingDe [Philips Research North America, Ultrasound and Interventions (United States); Duran, Rafael; Chapiro, Julius; Wang, Zhijun; Geschwind, Jean-François, E-mail: jfg@jhmi.edu [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology (United States)

    2015-08-15

    PurposeTo evaluate the detectability of intrahepatic cholangiocarcinoma (ICC) on dual-phase cone-beam CT (DPCBCT) during conventional transarterial chemoembolization (cTACE) compared to that of digital subtraction angiography (DSA) with respect to pre-procedure contrast-enhanced magnetic resonance imaging (CE-MRI) of the liver.MethodsThis retrospective study included 17 consecutive patients (10 male, mean age 64) with ICC who underwent pre-procedure CE-MRI of the liver, and DSA and DPCBCT (early-arterial phase (EAP) and delayed-arterial phase (DAP)) just before cTACE. The visibility of each ICC lesion was graded by two radiologists on a three-rank scale (complete, partial, and none) on DPCBCT and DSA images, and then compared to pre-procedure CE-MRI.ResultsOf 61 ICC lesions, only 45.9 % were depicted by DSA, whereas EAP- and DAP-CBCT yielded a significantly higher detectability rate of 73.8 % and 93.4 %, respectively (p < 0.01). Out of the 33 lesions missed on DSA, 18 (54.5 %) and 30 (90.9 %) were revealed on EAP- and DAP-CBCT images, respectively. DSA depicted only one lesion that was missed by DPCBCT due to streak artifacts caused by a prosthetic mitral valve. DAP-CBCT identified significantly more lesions than EAP-CBCT (p < 0.01). Conversely, EAP-CBCT did not detect lesions missed by DAP-CBCT. For complete lesion visibility, DAP-CBCT yielded significantly higher detectability (78.7 %) compared to EAP (31.1 %) and DSA (21.3 %) (p < 0.01).ConclusionDPCBCT, and especially the DAP-CBCT, significantly improved the detectability of ICC lesions during cTACE compared to DSA. We recommend the routine use of DAP-CBCT in patients with ICC for per-procedure detectability and treatment planning in the setting of TACE.

  16. Flow cytometry of fine-needle-aspiration biopsies : a new method to monitor the intrahepatic immunological environment in chronic viral hepatitis

    NARCIS (Netherlands)

    Sprengers, D; van der Molen, R G; Kusters, J G; Kwekkeboom, J; van der Laan, L J W; Niesters, H G M; Kuipers, E J; De Man, R A; Schalm, S W; Janssen, H L A

    2005-01-01

    SUMMARY: Information about the character and grade of the intrahepatic immune response in viral hepatitis is important for the evaluation of disease stage and effect of therapy. Complications like haemorrhage limit the frequent performance of tissue-needle biopsies (TB), and the cells of peripheral

  17. Innate Immune Responses in Viral Hepatitis: the role of Kupffer cells and liver-derived monocytes in shaping intrahepatic immunity in mice using the LCMV infection model

    NARCIS (Netherlands)

    D. Movita (Dowty)

    2014-01-01

    markdownabstract__Abstract__ This study was performed to elucidate the immunological role of the liver in viral hepatitis. The immune functions of the liver are shaped by the intrahepatic cells present during steady state condition, as well as the recruited immune cells during liver inflammation.

  18. Mn-DPDP enhanced T1-weighted magnetic resonance cholangiography: usefulness in the diagnosis and roadmap for the treatment of intrahepatic choIedochoIithiasis

    Energy Technology Data Exchange (ETDEWEB)

    Park, Mi Suk; Kim, Ki Whang; Yu, Jeong Sik; Kim, Myeong Jin; Lee, Jong Tae; Yoo, Hyung Sik [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of); Kim, Kyoung Won; Kim, Tae Kyoung; Ha, Hyun Kwon [Asan Medical Center, Seoul (Korea, Republic of)

    2004-05-01

    To assess the preliminary findings of Mn-enhanced T1-weighted MR cholangiography for the evaluation of intrahepatic choledocholithiasis. Seven patients with recurrent pyogenic cholangitis underwent conventional heavily T2-weighted and manganese-enhanced T1-weighted MR cholangiography. For the former, the two reviewers focused on intrahepatic ductal dilatation, calculi, and stricture; and for the latter, ductal enhancement. In seven patients, 13 diseased segments were depicted and intrahepatic bile ductal dilatation was present in all 13 of these in all seven patients. Calculi were present in eight segments in six patients, and stricture in four segments in three patients. Of the 13 diseased segmental ducts, six were seen at manganese-enhanced imaging to be filled with contrast material, suggesting a functioning bile duct. Combined T2-weighted and mangafodipir trisodium-enhanced T1-weighted MR cholangiography provides both anatomic detail and functional detail of the biliary system. Combined MR cholangiography is useful for the evaluation of intrahepatic choledocholithiasis, demonstrating the stricture and function of the segmental ducts involved.

  19. Portal hypertensive enteropathy diagnosed by capsule endoscopy and demonstration of the ileal changes after transjugular intrahepatic portosystemic shunt placement: a case report

    Directory of Open Access Journals (Sweden)

    Carella Alessandra

    2011-03-01

    Full Text Available Abstract Introduction Recent data suggest that mucosal abnormalities can occur even in the duodenum, jejunum, and distal ileum of cirrhosis patients. We present a case of portal hypertensive enteropathy in a cirrhosis patient shown by capsule endoscopy and the effect of transjugular intrahepatic portosystemic shunt on the ileal pictures. Case presentation An 83-year-old Caucasian woman was admitted to our hospital for anemia and a positive fecal occult blood test. An upper gastrointestinal endoscopy revealed small varices without bleeding signs and hypertensive gastropathy. Colonoscopy was negative. To rule out any other cause of bleeding, capsule endoscopy was performed; capsule endoscopy revealed severe hyperemia of the jejunum-ileal mucosa with active bleeding. Because of the persistence of anemia and the frequent blood transfusions, not responding to β-blocker drugs or octreotide infusion, a transjugular intrahepatic portosystemic shunt was performed. Anemia improved quickly after the transjugular intrahepatic portosystemic shunt, and no further blood transfusion was necessary in the follow-up. The patient developed portal encephalopathy two months later and was readmitted to our department. We repeated the capsule endoscopy that showed a significant improvement of the gastric and ileal mucosa without any signs of bleeding. Conclusion Hypertensive enteropathy is a rare condition, but it seems more common with the introduction of capsule endoscopy in clinical practice. This case shows that the jejunum can be a source of bleeding in cirrhosis patients, and this is the first demonstration of its resolution after transjugular intrahepatic portosystemic shunt placement.

  20. Increased intrahepatic quasispecies heterogeneity correlates with off-treatment sustained response to nucleos(t)ide analogues in e antigen-positive chronic hepatitis B patients.

    Science.gov (United States)

    Chen, L; Gan, Q R; Zhang, D Q; Yao, L F; Lin, R S; Li, Q; Lin, M H; Yu, D M; Zhang, X X; Pan, C

    2016-02-01

    Finite treatment with nucleos(t)ide analogues (NAs) remains a great challenge for chronic hepatitis B in the clinic. This study aimed to investigate the relationship between intrahepatic quasispecies heterogeneity and the NAs off-treatment outcomes in a prospective cohort. Eighteen HBeAg-positive patients with chronic hepatitis B who achieved the cessation criteria underwent liver biopsy, and stopped treatment thereafter. Patients were followed up prospectively for 1 year. The reverse transcriptase (RT) gene of intrahepatic hepatitis B virus (HBV) was cloned and sequenced. Intrahepatic quasispecies heterogeneity and specific gene mutations were analysed using bioinformatic methods. Ten patients achieved sustained response, and eight patients developed viral relapse. The intrahepatic quasispecies Shannon entropy and nucleotide diversity within either RT or the surface (S) region of patients with sustained response were significantly higher (p quasispecies Shannon entropy at the nucleotide level predicted the sustained off-treatment response (area under receiver operating characteristics curve 0.925; 95% CI 0.807-1.000; p 0.003). More positive selection sites and N-glycosylation mutations within the S region were found in patients with sustained response than in the patients with viral relapse (p quasispecies heterogeneity at the end of treatment was correlated with off-treatment outcomes in HBeAg-positive patients with chronic hepatitis B. More immune escape mutations were found within the S region in patients with sustained response. The higher intrahepatic quasispecies heterogeneity indicated a more robust immune control over HBV, which in turn maintained a sustained response after withdrawal of NAs.

  1. Biological features of intrahepatic CD4+CD25+ T cells in the naturally tolerance of rat liver transplantation

    Institute of Scientific and Technical Information of China (English)

    LU Ling; ZHANG Feng; PU Liyong; YAO Aihua; YU Yue; SUN Beicheng; LI Guoqiang

    2007-01-01

    The biological features of intrahepatic CD4+CD25+ T regulatory cells in the naturally tolerance of rat liver transplantation were explored.Orthotopic liver transplantation was performed in two allogeneic rat strain combinations,one with fatal immunosuppression despite a complete major histocompatibility complex mismatch.The subjects were divided into three groups according to different donors and recipients [Tolerance group:LEW-to-DA;Rejection group:DA-to-LEW;Syngegnic group(control group):DAto-DA].The proportion of intrahepatic CD4+CD25+ T cells from three groups was determined by flow cytometry(FCM)in different time.The intrahepaitc CD4+CD25+ T cells were isolated by magnetic activated cell sorting(MACS)method and identified by FCM.The Foxp3 mRNA was detected by reverse transcriptase polymerase chain reaction(RT-PCR).And their suppression on the proliferation of CD4+CD25- T effector cells was analyzed by cell proliferation assay in vitro.Beginning immediately after transplantation,the proportion of Treg cells increased over time in both allogeneic groups but was significantly greater in the Rejection group.The proportion of Treg cells declined after day 5,and such reduction was more dramatic in the Rejection group than in the Tolerance group.Animals in the Tolerance group showed a second increase in the proportion after day 14.Intrahepatic CD4+CD25+T cells isolated from spontaneous tolerance models inhibited the proliferation of mixed lymphocyte reaction.The purity of CD4+CD25+ T cells sorted by MACS was 86%-93%.The CD4+CD25+ T cells could specifically express the Foxp3 gene compared with CD4+CD25- T cells.In vitro,the spleen cells from LEW rats can irritate the proliferation of CD4+CD25+ T cells more obviously than the syngegnic spleen cells.CD4+CD25+ Tr cells could suppress the proliferation of CD4+CD25- T cells,but the inhibition was reversed by exogenous IL-2(200 U/mL).The CD4+CD25+ T regulatory cells specifically express the Foxp3 gene,which may play an

  2. Transjugular intrahepatic portosystemic shunt vs endoscopic therapy in preventing variceal rebleeding

    Institute of Scientific and Technical Information of China (English)

    Hui Xue; Meng Zhang; Jack XQ Pang; Fei Yan; Ying-Chao Li; Liang-Shan Lv; Jia Yuan

    2012-01-01

    AIM:To compare early use of transjugular intrahepatic portosystemic shunt (TIPS) with endoscopic treatment (ET) for the prophylaxis of recurrent variceal bleeding.METHODS:In-patient data were collected from 190 patients between January 2007 and June 2010 who suffured from variceal bleeding.Patients who were older than 75 years; previously received surgical treatment or endoscopic therapy for variceal bleeding; and complicated with hepatic encephalopathy or hepatic cancer,were excluded from this research.Thirty-five cases lost to follow-up were also excluded.Retrospective analysis was done in 126 eligible cases.Among them,64 patients received TIPS (TIPS group) while 62 patients received endoscopic therapy (ET group).The relevant data were collected by patient review or telephone calls.The occurrence of rebleeding,hepatic encephalopathy or other complications,survival rate and cost of treatment were compared between the two groups.RESULTS:During the follow-up period (median,20.7and 18.7 mo in TIPS and ET groups,respectively),rebleeding from any source occurred in 11 patients in the TIPS group as compared with 31 patients in the ET group (Kaplan-Meier analysis and log-rank test,P=0.000).Rebleeding rates at any time point (6 wk,1year and 2 year) in the TIPS group were lower than in the ET group (Bonferroni correction o' =o/3).Eight patients in the TIPS group and 16 in the ET group died with the cumulative survival rates of 80.6% and 64.9%(Kaplan-Meier analysis and log-rank test x2=4.864,P =0.02),respectively.There was no significant difference between the two groups with respect to 6-wk survival rates (Bonferroni correction a' =a/3).However,significant differences were observed between the two groups in the 1-year survival rates (92% and 79%) and the 2-year survival rates (89% and 64.9%)(Bonferroni correction a' =o/3).No significant differences were observed between the two treatment groups in the occurrence of hepatic encephalopathy (12 patients in TIPS

  3. Transjugular Intrahepatic Portosystemic Shunt for Treatment of Cirrhosis-related Chylothorax and Chylous Ascites: Single-institution Retrospective Experience

    Energy Technology Data Exchange (ETDEWEB)

    Kikolski, Steven G., E-mail: skikolski@ucsd.edu; Aryafar, Hamed, E-mail: haryafar@ucsd.edu; Rose, Steven C., E-mail: scrose@ucsd.edu [University of California San Diego Health Sciences, Department of Radiology (United States); Roberts, Anne C., E-mail: acroberts@ucsd.edu [University of California San Diego Health Sciences, Department of Vascular and Interventional Radiology (United States); Kinney, Thomas B., E-mail: tbkinney@ucsd.edu [University of California San Diego Health Sciences, Department of Radiology (United States)

    2013-08-01

    PurposeTo investigate the efficacy and safety of the use of transjugular intrahepatic portosystemic shunt (TIPS) creation to treat cirrhosis-related chylous collections (chylothorax and chylous ascites).MethodsWe retrospectively reviewed data from four patients treated for refractory cirrhosis-related chylous collections with TIPS at our institution over an 8 year period.ResultsOne patient had chylothorax, and three patients had concomitant chylothorax and chylous ascites. There were no major complications, and the only procedure-related complications occurred in two patients who had mild, treatable hepatic encephalopathy. All patients had improvement as defined by decreased need for thoracentesis or paracentesis, with postprocedure follow-up ranging from 19 to 491 days.ConclusionTIPS is a safe procedure that is effective in the treatment of cirrhosis-related chylous collections.

  4. Transsplenic portal vein reconstruction–transjugular intrahepatic portosystemic shunt in a patient with portal and splenic vein thrombosis

    Directory of Open Access Journals (Sweden)

    Jason T. Salsamendi, MD

    2016-09-01

    Full Text Available Portal vein thrombosis (PVT is a potential complication of cirrhosis and can worsen outcomes after liver transplant (LT. Portal vein reconstruction–transjugular intrahepatic portosystemic shunt (PVR-TIPS can restore flow through the portal vein (PV and facilitate LT by avoiding complex vascular conduits. We present a case of transsplenic PVR-TIPS in the setting of complete PVT and splenic vein (SV thrombosis. The patient had a 3-year history of PVT complicated by abdominal pain, ascites, and paraesophageal varices. A SV tributary provided access to the main SV and was punctured percutaneously under ultrasound scan guidance. PV access, PV and SV venoplasty, and TIPS placement were successfully performed without complex techniques. The patient underwent LT with successful end-to-end anastomosis of the PVs. Our case suggests transsplenic PVR-TIPS to be a safe and effective alternative to conventional PVR-TIPS in patients with PVT and SV thrombosis.

  5. Transsplenic portal vein reconstruction-transjugular intrahepatic portosystemic shunt in a patient with portal and splenic vein thrombosis.

    Science.gov (United States)

    Salsamendi, Jason T; Gortes, Francisco J; Shnayder, Michelle; Doshi, Mehul H; Fan, Ji; Narayanan, Govindarajan

    2016-09-01

    Portal vein thrombosis (PVT) is a potential complication of cirrhosis and can worsen outcomes after liver transplant (LT). Portal vein reconstruction-transjugular intrahepatic portosystemic shunt (PVR-TIPS) can restore flow through the portal vein (PV) and facilitate LT by avoiding complex vascular conduits. We present a case of transsplenic PVR-TIPS in the setting of complete PVT and splenic vein (SV) thrombosis. The patient had a 3-year history of PVT complicated by abdominal pain, ascites, and paraesophageal varices. A SV tributary provided access to the main SV and was punctured percutaneously under ultrasound scan guidance. PV access, PV and SV venoplasty, and TIPS placement were successfully performed without complex techniques. The patient underwent LT with successful end-to-end anastomosis of the PVs. Our case suggests transsplenic PVR-TIPS to be a safe and effective alternative to conventional PVR-TIPS in patients with PVT and SV thrombosis.

  6. Severe gastrointestinal tract bleeding in a two-month-old infant due to congenital intrahepatic arterioportal fistula

    Energy Technology Data Exchange (ETDEWEB)

    Aarts, R. [Department of Radiology, University Medical Center St. Radboud, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Ijland, M.M. [Department of Pediatrics, University Medical Center St. Radboud, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Blaauw, I. de [Department of Pediatric Surgery, University Medical Center St. Radboud, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Hoogeveen, Y. [Department of Radiology, University Medical Center St. Radboud, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Boetes, C. [Department of Radiology, University Medical Center St. Radboud, P.O. Box 9101, 6500 HB Nijmegen (Netherlands)]. E-mail: C.Boetes@rad.umcn.nl; van Proosdij, M. [Department of Radiology, University Medical Center St. Radboud, P.O. Box 9101, 6500 HB Nijmegen (Netherlands)

    2006-07-15

    A 2-month-old boy was referred for assessment of severe upper gastrointestinal tract bleeding and melena. On physical examination, a continuous murmur was heard over the right upper quadrant of the abdomen. A splenomegaly and dilated veins were also noted on the abdominal wall. Liver functions were normal. There was no history of trauma or jaundice. Doppler ultrasonography, magnetic resonance arteriography and angiography suggested the presence of an intrahepatic arteriovenous fistula between the phrenic artery and the portal vein. Management consisted of successful embolization by coiling of the phrenic artery. To our knowledge this is the first documented case report of a congenital fistula between the phrenic artery and the portal vein.

  7. Recurrent thrombotic occlusion of a transjugular intrahepatic portosystemic stent-shunt due to activated protein C resistance

    Institute of Scientific and Technical Information of China (English)

    Elmar Siewert; Jan Salzmann; Edmund Purucker; Karl Schürmann; Siegfried Matern

    2005-01-01

    The transjugular intrahepatic portosystemic stent-shunt (TIPS) has successfully been used in the management of refractory variceal bleeding and ascites in patients with portal hypertension. Major drawbacks are the induction of hepatic encephalopathy and shunt dysfunction. We present a 59-year-old woman with alcoholic liver cirrhosis who received a TIPS because of recurrent bleeding from esophageal varices. Stent occlusion occurred 4 mo after placement of the TIPS. Laboratory testing revealed resistance to activated protein C (APC). Combination therapy with low-dose enoxaparin and clopidogrel could not prevent her recurrent stent occlusion. Finally, therapy with high-dose enoxaparin was sufficient to prevent further shunt complications up to now (follow-up period of 1 year). In conclusion, early occlusion of a TIPS warrants testing for thrombophilia. If risk factors are confirmed,anticoagulation should be intensified. There are currently no evidence-based recommendations regarding the best available anticoagulant therapy and surveillance protocol for patients with TIPS.

  8. Bilhemia after trans-jugular intra-hepatic porto-systemic shunt and its management with biliary decompression

    Institute of Scientific and Technical Information of China (English)

    Ashwani K Singal; Manoj K Kathuria; Advitya Malhotra; Richard W Goodgame; Roger D Soloway

    2009-01-01

    Bilhemia or bile mixing with blood is a rare clinical problem. The clinical presentation is usually transient self-resolving hyperbilirubinemia, progressive and rapidly rising conjugated hyperbilirubinemia, or recurrent cholangitis. Endoscopic retrograde cholangiopancreatography (ERCP) plays an important role in diagnosis and management. Biliary decompression with endoscopic sphincterotomy is useful in treating these patients. If not recognized and treated in time, the condition can be fatal in a significant proportion of patients. This usually occurs after blunt or penetrating hepatic trauma due to a fistulous connection between the biliary radicle and portal or hepatic venous radical. Cases have been described due to iatrogenic trauma such as liver biopsy and percutaneous biliary drainage. However, the occurrence after trans-jugular intra-hepatic porto-systemic shunt (TIPS) is very rare. We report a case of bilhemia presenting as rapidly rising bilirubin after TIPS. The patient was managed successfully with ERCP and removal of a blood clot from the common bile duct.

  9. Integrated genomic characterization reveals novel, therapeutically relevant drug targets in FGFR and EGFR pathways in sporadic intrahepatic cholangiocarcinoma.

    Directory of Open Access Journals (Sweden)

    Mitesh J Borad

    2014-02-01

    Full Text Available Advanced cholangiocarcinoma continues to harbor a difficult prognosis and therapeutic options have been limited. During the course of a clinical trial of whole genomic sequencing seeking druggable targets, we examined six patients with advanced cholangiocarcinoma. Integrated genome-wide and whole transcriptome sequence analyses were performed on tumors from six patients with advanced, sporadic intrahepatic cholangiocarcinoma (SIC to identify potential therapeutically actionable events. Among the somatic events captured in our analysis, we uncovered two novel therapeutically relevant genomic contexts that when acted upon, resulted in preliminary evidence of anti-tumor activity. Genome-wide structural analysis of sequence data revealed recurrent translocation events involving the FGFR2 locus in three of six assessed patients. These observations and supporting evidence triggered the use of FGFR inhibitors in these patients. In one example, preliminary anti-tumor activity of pazopanib (in vitro FGFR2 IC50≈350 nM was noted in a patient with an FGFR2-TACC3 fusion. After progression on pazopanib, the same patient also had stable disease on ponatinib, a pan-FGFR inhibitor (in vitro, FGFR2 IC50≈8 nM. In an independent non-FGFR2 translocation patient, exome and transcriptome analysis revealed an allele specific somatic nonsense mutation (E384X in ERRFI1, a direct negative regulator of EGFR activation. Rapid and robust disease regression was noted in this ERRFI1 inactivated tumor when treated with erlotinib, an EGFR kinase inhibitor. FGFR2 fusions and ERRFI mutations may represent novel targets in sporadic intrahepatic cholangiocarcinoma and trials should be characterized in larger cohorts of patients with these aberrations.

  10. Integrated Genomic Characterization Reveals Novel, Therapeutically Relevant Drug Targets in FGFR and EGFR Pathways in Sporadic Intrahepatic Cholangiocarcinoma

    Science.gov (United States)

    Liang, Winnie S.; Fonseca, Rafael; Bryce, Alan H.; McCullough, Ann E.; Barrett, Michael T.; Hunt, Katherine; Patel, Maitray D.; Young, Scott W.; Collins, Joseph M.; Silva, Alvin C.; Condjella, Rachel M.; Block, Matthew; McWilliams, Robert R.; Lazaridis, Konstantinos N.; Klee, Eric W.; Bible, Keith C.; Harris, Pamela; Oliver, Gavin R.; Bhavsar, Jaysheel D.; Nair, Asha A.; Middha, Sumit; Asmann, Yan; Kocher, Jean-Pierre; Schahl, Kimberly; Kipp, Benjamin R.; Barr Fritcher, Emily G.; Baker, Angela; Aldrich, Jessica; Kurdoglu, Ahmet; Izatt, Tyler; Christoforides, Alexis; Cherni, Irene; Nasser, Sara; Reiman, Rebecca; Phillips, Lori; McDonald, Jackie; Adkins, Jonathan; Mastrian, Stephen D.; Placek, Pamela; Watanabe, Aprill T.; LoBello, Janine; Han, Haiyong; Von Hoff, Daniel; Craig, David W.; Stewart, A. Keith; Carpten, John D.

    2014-01-01

    Advanced cholangiocarcinoma continues to harbor a difficult prognosis and therapeutic options have been limited. During the course of a clinical trial of whole genomic sequencing seeking druggable targets, we examined six patients with advanced cholangiocarcinoma. Integrated genome-wide and whole transcriptome sequence analyses were performed on tumors from six patients with advanced, sporadic intrahepatic cholangiocarcinoma (SIC) to identify potential therapeutically actionable events. Among the somatic events captured in our analysis, we uncovered two novel therapeutically relevant genomic contexts that when acted upon, resulted in preliminary evidence of anti-tumor activity. Genome-wide structural analysis of sequence data revealed recurrent translocation events involving the FGFR2 locus in three of six assessed patients. These observations and supporting evidence triggered the use of FGFR inhibitors in these patients. In one example, preliminary anti-tumor activity of pazopanib (in vitro FGFR2 IC50≈350 nM) was noted in a patient with an FGFR2-TACC3 fusion. After progression on pazopanib, the same patient also had stable disease on ponatinib, a pan-FGFR inhibitor (in vitro, FGFR2 IC50≈8 nM). In an independent non-FGFR2 translocation patient, exome and transcriptome analysis revealed an allele specific somatic nonsense mutation (E384X) in ERRFI1, a direct negative regulator of EGFR activation. Rapid and robust disease regression was noted in this ERRFI1 inactivated tumor when treated with erlotinib, an EGFR kinase inhibitor. FGFR2 fusions and ERRFI mutations may represent novel targets in sporadic intrahepatic cholangiocarcinoma and trials should be characterized in larger cohorts of patients with these aberrations. PMID:24550739

  11. Common and Uncommon Anatomical Variants of Intrahepatic Bile Ducts in Magnetic Resonance Cholangiopancreatography and its Clinical Implication

    Science.gov (United States)

    Sarawagi, Radha; Sundar, Shyam; Raghuvanshi, Sameer; Gupta, Sanjeev Kumar; Jayaraman, Gopal

    2016-01-01

    Summary Background Preoperative knowledge of intrahepatic bile duct (IHD) anatomy is critical for planning liver resections, liver transplantations and complex biliary reconstructive surgery. The purpose of our study was to demonstrate the imaging features of various anatomical variants of IHD using magnetic resonance cholangio-pancreatography (MRCP) and their prevalence in our population. Material/Methods This observational clinical evaluation study included 224 patients who were referred for MRCP. MRCP was performed in a 1.5-Tesla magnet (Philips) with SSH MRCP 3DHR and SSHMRCP rad protocol. A senior radiologist assessed the biliary passage for anatomical variations. Results The branching pattern of the right hepatic duct (RHD) was typical in 55.3% of subjects. The most common variant was right posterior sectoral duct (RPSD) draining into the left hepatic duct (LHD) in 27.6% of subjects. Trifurcation pattern was noted in 9.3% of subjects. In 4% of subjects, RPSD was draining into the common hepatic duct (CHD) and in 0.8% of subjects into the cystic duct. Other variants were noted in 2.6% of subjects. In 4.9% of cases there was an accessory duct. The most common type of LHD branching pattern was a common trunk of segment 2 and 3 ducts joining the segment 4 duct in 67.8% of subjects. In 23.2% of subjects, segment 2 duct united with the common trunk of segment 3 and 4 and in 3.4% of subjects segment 2, 3, and 4 ducts united together to form LHD. Other uncommon branching patterns of LHD were seen in 4.9% of subjects. Conclusions Intrahepatic bile duct anatomy is complex with many common and uncommon variations. MRCP is a reliable non-invasive imaging method for demonstration of bile duct morphology, which is useful to plan complex surgeries and to prevent iatrogenic injuries. PMID:27298653

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-05-15

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

  13. Ultrasonography of Neonatal Cholestasis

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-06-15

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

  14. 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.

  15. Correlation between serum hepatitis B virus core-related antigen and intrahepatic covalently closed circular DNA in chronic hepatitis B patients.

    Science.gov (United States)

    Suzuki, Fumitaka; Miyakoshi, Hideo; Kobayashi, Mariko; Kumada, Hiromitsu

    2009-01-01

    Nucleos(t)ide analogues are utilized for the treatment of chronic HBV infection, and HBe seroconversion and HBV DNA levels are commonly used as markers of viral status and as primary treatment endpoints. Recently, a new assay was prepared for the detection of serum HBV core-related antigen (HBcrAg), consisting of HBcAg, HBeAg, and p22cr, which is a precore protein from amino acid -28 to at least amino acid 150, by coding the precore/core region. In this study, we examined the correlation between serum HBcrAg concentration and viral status by the analysis of serum HBeAg, HBsAg, peripheral HBV DNA, and intrahepatic covalently closed circular DNA (cccDNA) in 57 chronic hepatitis B patients. Intrahepatic cccDNA was detected in all 57 patients, 42 patients were HBcrAg-positive, and serum HBcrAg concentration level was closely correlated with cccDNA. Additionally, positive HBcrAg concentration level results were observed in 6 out of 13 HBsAg seroclearance patients and 20 out of 31 HBV DNA-negative patients. Moreover, the correlation between HBcrAg and cccDNA in these 31 HBV DNA-negative patients was statistically significant (r = 0.482, P = 0.006). These data suggest that serum HBcrAg concentration is well correlated with intrahepatic cccDNA level, and that the measurement of serum HBcrAg may be clinically useful for monitoring intrahepatic HBV viral status, especially in patients under treatment with nucleos(t)ide analogues.

  16. Thick slice MR cholangiography of the intrahepatic biliary tree; Imagerie des voies biliaires intrahepatiques en cholangiographie-IRM en coupes epaisses

    Energy Technology Data Exchange (ETDEWEB)

    Leclerc, J.C.; Cannard, L.; Lefevre, F.; Debelle, L.; Beot, S.; Boccaccini, H.; Bazin, C.; Regent, D. [Centre Hospitalier Universitaire Nancy-Brabois, 54 - Vandoeuvre-les-Nancy (France)

    2001-02-01

    Purpose. To assess the value of single shot fast spin echo MR sequence (SS-FSE) in the evaluation of the normal and pathologic intrahepatic biliary tree. Material and Methods. 418 consecutive patients (457 examinations) referred for clinical and/or biological suspicion of biliary obstruction underwent MR cholangio-pancreatography (MRCP). All patients were imaged with a Signa 1.5 T GE MR unit, with High Gradient Field Strength and Torso Phased Array Coil. Biliary ducts were imaged with SS-FSE sequence, coronal and oblique coronal 20 mm thick slices on a 256 x 256 matrix. Total acquisition time was 1 second. Source images were reviewed by two radiologists blinded to clinical information. In case of disagreement, a third radiologist's opinion was requested. In all cases, MRCP results were compared with direct biliary tract evaluation, other imaging studies and clinical and biological follow-up. Results. In all cases, MRCP produced high quality images. Numerous branch of division were observed although the peripheral intrahepatic ducts were well seen in more than 90% in an area 2 cm below the capsule. The number of division was statistically higher when mechanical obstruction was present. Intrahepatic calculi or peripheral cholangio-carcinoma were well detect by MRCP. For the detection of cholangitis, MRCP sensitivity was 87.5% but the positive predictive value was only 57.7% because of a high number of false positive. The diagnosis of primary sclerosing cholangitis must be made only on strict criteria and slightly dilated peripheral bile ducts unconnected to the central ducts in several hepatic segments were a characteristic MR sign of primary sclerosing cholangitis. Conclusion. MRCP can be proposed as a first intention imaging technique for the evaluation of intrahepatic ducts. (authors)

  17. Localization of radiolabeled anti-CEA antibody in subcutaneous and intrahepatic colorectal xenografts: influence of tumor size and location within host organ on antibody uptake

    Energy Technology Data Exchange (ETDEWEB)

    Dearling, Jason L.J. [Cancer Research UK Targeting and Imaging Group, Research Department of Oncology, UCL Cancer Institute, Paul O' Gorman Building, University College London, London WC1E 6BT (United Kingdom)], E-mail: j.dearling@hotmail.com; Flynn, Aiden A.; Qureshi, Uzma [Cancer Research UK Targeting and Imaging Group, Research Department of Oncology, UCL Cancer Institute, Paul O' Gorman Building, University College London, London WC1E 6BT (United Kingdom); Whiting, Stephen [Department of Clinical Biochemistry, Royal Free and University College Medical School, UCL, Royal Free Campus, London NW3 2PF (United Kingdom); Boxer, Geoffrey M.; Green, Alan; Begent, Richard H.J.; Pedley, R. Barbara [Cancer Research UK Targeting and Imaging Group, Research Department of Oncology, UCL Cancer Institute, Paul O' Gorman Building, University College London, London WC1E 6BT (United Kingdom)

    2009-11-15

    Introduction: Radioimmunotherapy (RIT) has been shown to be more effective against solid tumor micrometastases, possibly due to an inverse relationship between tumor size and radiolabeled antibody uptake. In this study, the accretion of radiolabeled antibody in intrahepatic micrometastases in an experimental model was investigated using quantitative digital autoradiography, enabling the analysis of antibody uptake in microscopic tumors. Methods: Mice bearing subcutaneous or intrahepatic metastatic models of LS174T colorectal cancer were injected with radiolabeled anti-carcinoembryonic antigen antibody ([{sup 125}I]A5B7). Tissues were taken to investigate distribution of radionuclide and tumor uptake. In a therapy study, mice bearing intrahepatic metastatic tumors were injected with [{sup 131}I]A5B7. Results: Subcutaneous tumors and large metastatic deposits had similar uptake (e.g., {approx}15%ID/g at 24 h). Small metastatic deposits had higher uptake (e.g., {approx}80%ID/g at 24 h) and prolonged retention at later time points. Small deposit uptake was significantly reduced by accompanying large deposits in the same liver. RIT resulted in increased survival time (untreated mean survival of 21.6{+-}12.9 vs. treated mean survival of 39.1{+-}30.8 days), but there was a large range of response within groups, presumably due to variation in pattern and extent of tumor as observed in the biodistribution study. Liver function tests and body weight did not change with tumor growth or therapy response, strongly supporting the use of in vivo imaging in metastatic tumor therapy studies. Conclusions: Radioimmunodetection and therapy might be greatly influenced by the size and distribution of intrahepatic tumor deposits.

  18. A case report of an unusual type of choledochal cyst with choledocholithiasis: Saccular dilatation of the confluent portion of both intrahepatic ducts

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Young; Kim, Hee Jin; Han, Hyun Young [Dept. of Radiology, Eulji University Hospital, Daejeon (Korea, Republic of)

    2015-10-15

    A choledochal cyst is a rare congenital anomaly of the biliary system manifested as the cystic dilatation of bile ducts, usually occurring in the common bile duct. Here, we describe an unusual type of choledochal cyst in a 45-year-old male that did not fit into the most widely accepted Todani classification of these cysts. The lesion mimicked duplication anomalies of the gallbladder and was finally diagnosed as a choledochal cyst involving the confluent portion of both intrahepatic ducts.

  19. Identification of osteopontin as the most consistently over-expressed gene in intrahepatic cholangiocarcinoma:Detection by oligonucleotide microarray and real-time PCR analysis

    Institute of Scientific and Technical Information of China (English)

    Holger G Hass; Oliver Nehls; Juergen Jobst; Andrea Frilling; Ulrich Vogel; Stephan Kaiser

    2008-01-01

    AIM: To investigate the molecular pathways involved in human cholangiocarcinogenesis by gene expression profiling.METHODS: Oligonucleotide arrays (Affymetr/x U133A)were used to establish a specific gene expression profile of intrahepatic CCC in comparison to corresponding nonmalignant liver tissue.To validate the expression values of the most overexpressed genes, RT-PCR experiments were performed.RESULTS: Five hundred and fifty-two statistically differentially expressed genes/ESTs (221 probes significantly up-regulated, 331 probes down-regulated;P2;≥70%) were identified.Using these data and two-dimensional cluster analysis,a specific gene expression profile was obtained allowing fast and reproducible differentiation of CCC, which was confirmed by supervised neuronal network modelling.The most consistently overexpressed gene (median fold change 33.5, significantly overexpressed in 100%)encoded osteopontin.Furthermore, an association of various genes with the histopathological grading could be demonstrated.CONCLUSION: A highly specific gone expression profile for intrahepatic CCC was identified, allowing for its fast and reproducible discrimination against nonmalignant liver tissue and other liver masses.The most overexpressed gene in intrahepatic CCC was the gene encoding osteopontin.These data may lead to a better understanding of human cholangiocarcinogenesis.

  20. Accumulation of Intrahepatic TNF-α-Producing NKp44+ NK Cells Correlates With Liver Fibrosis and Viral Load in Chronic HCV Infection

    Science.gov (United States)

    Nel, Isabelle; Lucar, Olivier; Petitdemange, Caroline; Béziat, Vivien; Lapalus, Martine; Bédossa, Pierre; Debré, Patrice; Asselah, Tarik; Marcellin, Patrick; Vieillard, Vincent

    2016-01-01

    Abstract In the setting of chronic hepatitis C virus (HCV) infection, changes in natural killer (NK) cells have been shown to reflect activation in response to virus stimulation. The contribution of individual natural cytotoxicity receptors to HCV infection remains to be clarified. NKp44 is the sole specific natural cytotoxicity receptor expressed only on activated NK cells. In this study, peripheral blood and liver NK-cell subsets were purified from 31 patients with chronic C hepatitis or nonalcoholic steatohepatitis, and then characterized by flow cytometry. Their polyfunctional activity was determined by expression of the CD107a degranulation marker, together with intracellular cytokine production. Unlike the patients with nonalcoholic steatohepatitis, patients with chronic HCV infection had a higher frequency of NKp44+ NK cells in the liver than in their peripheral blood (P < 0.0001). Intrahepatic NKp44+ NK cells from HCV+ individuals produced higher levels of tumor necrosis factor-α than did NKp44− NK cells (P = 0.0011). Importantly, the frequency of intrahepatic NKp44+ NK cells was correlated with both HCV-RNA levels (P = 0.0234) and stage of fibrosis (P = 0.0003). Our findings suggest that the accumulation of intrahepatic tumor necrosis factor-α-producing NKp44+ resident NK cells play a role in the liver damage associated with chronic HCV infection. PMID:27175704

  1. Celecoxib ameliorates portal hypertension of the cirrhotic rats through the dual inhibitory effects on the intrahepatic fibrosis and angiogenesis.

    Directory of Open Access Journals (Sweden)

    Jin-Hang Gao

    Full Text Available BACKGROUND: Increased intra-hepatic resistance to portal blood flow is the primary factor leading to portal hypertension in cirrhosis. Up-regulated expression of cyclooxygenase-2 (COX-2 in the cirrhotic liver might be a potential target to ameliorate portal hypertension. OBJECTIVE: To verify the effect of celecoxib, a selective inhibitor of COX-2, on portal hypertension and the mechanisms behind it. METHODS: Cirrhotic liver model of rat was established by peritoneal injection of thiacetamide (TAA. 36 rats were randomly assigned to control, TAA and TAA+celecoxib groups. Portal pressures were measured by introduction of catheters into portal vein. Hepatic fibrosis was assessed by the visible hepatic fibrotic areas and mRNAs for collagen III and α-SMA. The neovasculature was determined by hepatic vascular areas, vascular casts and CD31 expression. Expressions of COX-2, vascular endothelial growth factor (VEGF, VEGF receptor-2 (VEGFR-2 and related signal molecules were quantitated. RESULTS: Compared with TAA group, the portal pressure in TAA+celecoxib group was significantly decreased by 17.8%, p<0.01. Celecoxib treatment greatly reduced the tortuous hepatic portal venules. The data of fibrotic areas, CD31expression, mRNA levels of α-SMA and collagen III in TAA+celecoxib group were much lower than those in TAA group, p<0.01. Furthermore, the up-regulation of hepatic mRNA and protein levels of VEGF, VEGFR-2 and COX-2 induced by TAA was significantly inhibited after celecoxib treatment. The expressions of prostaglandin E2 (PGE2, phosphorylated extracellular signal-regulated kinase (p-ERK, hypoxia-inducible factor-1α (HIF-1α, and c-fos were also down-regulated after celecoxib treatment. CONCLUSIONS: Long term administration of celecoxib can efficiently ameliorate portal hypertension in TAA rat model by its dual inhibitory effects on the intrahepatic fibrosis and angiogenesis. The anti-angiogenesis effect afforded by celecoxib may attribute to its

  2. Prognostic nutritional index serves as a predicative marker of survival and associates with systemic inflammatory response in metastatic intrahepatic cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Zhang C

    2016-10-01

    Full Text Available Chenyue Zhang,1,2 Haiyong Wang,1,3 Zhouyu Ning,1,2 Litao Xu,1,2 Liping Zhuang,1,2 Peng Wang,1,2 Zhiqiang Meng1,2 1Department of Integrative Oncology, Fudan University Shanghai Cancer Center, 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 3Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, People’s Republic of China Objective: The significance of the prognostic nutritional index (PNI has been widely reported and confirmed in many types of cancers. However, few studies are available indicating its prognostic power in patients with intrahepatic cholangiocarcinoma (ICC. Thus, we investigated its relationship with overall survival (OS to evaluate its role in predicting survival in patients with ICC. Patients and methods: Between October 2011 and October 2015, 173 consecutive patients with pathologically confirmed locally advanced or metastatic ICC were enrolled. First, the correlations between PNI and clinical factors were analyzed among these patients. Next, univariate and multivariate analyses were conducted to evaluate the association between PNI and OS among these patients with ICC. In addition, the relationships between PNI and three typical systemic inflammatory response (SIR markers – the neutrophil/lymphocyte ratio (NLR, the platelet/lymphocyte ratio (PLR, and the lymphocyte/monocyte ratio (LMR – were also assessed. Results: A lower PNI was linked with a shorter OS in patients with ICC, as reflected obviously in the Kaplan–Meier analyses. The patients with ICC were divided into the locally advanced group and the metastatic group. Further analyses revealed that PNI is not associated with OS in the locally advanced group. However, in the subgroup of patients with metastatic ICC, a lower PNI significantly correlated with a worsened OS. The OS for patients with a low PNI is 5 months, whereas the OS is 10.17 months for patients with a high PNI. Multivariate analyses revealed

  3. Parametric response mapping of dynamic CT for predicting intrahepatic recurrence of hepatocellular carcinoma after conventional transcatheter arterial chemoembolization

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Seung Joon; Kim, Hyung Sik [Gachon University Gil Hospital, Department of Radiology, Incheon (Korea, Republic of); Kim, Jonghoon [Sungkyunkwan University, Department of Electronic Electrical and Computer Engineering, Suwon (Korea, Republic of); Seo, Jongbum [Yonsei University, Department of Biomedical Engineering, Wonju (Korea, Republic of); Lee, Jong-min [Hanyang University, Department of Biomedical Engineering, Seoul (Korea, Republic of); Park, Hyunjin [Sungkyunwkan University, School of Electronic and Electrical Engineering, Suwon (Korea, Republic of)

    2016-01-15

    The aim of our study was to determine the diagnostic value of a novel image analysis method called parametric response mapping (PRM) for prediction of intrahepatic recurrence of hepatocellular carcinoma (HCC) treated with conventional transcatheter arterial chemoembolization (TACE). This retrospective study was approved by the IRB. We recruited 55 HCC patients who achieved complete remission (CR) after TACE and received longitudinal multiphasic liver computed tomography (CT). The patients fell into two groups: the recurrent tumour group (n = 29) and the non-recurrent tumour group (n = 26). We applied the PRM analysis to see if this technique could distinguish between the two groups. The results of the PRM analysis were incorporated into a prediction algorithm. We retrospectively removed data from the last time point and attempted to predict the response to therapy of the removed data. The PRM analysis was able to distinguish between the non-recurrent and recurrent groups successfully. The prediction algorithm detected response to therapy with an area under the curve (AUC) of 0.76, while the manual approach had AUC 0.64. Adopting PRM analysis can potentially distinguish between recurrent and non-recurrent HCCs and allow for prediction of response to therapy after TACE. (orig.)

  4. Differentiation of intrahepatic mass-forming cholangiocarcinoma from hepatocellular carcinoma on gadoxetic acid-enhanced liver MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Rihyeon; Shin, Cheong-Il; Yoon, Jeong Hee; Joo, Ijin; Kim, Seong Ho; Hwang, Inpyeong [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Lee, Jeong Min; Han, Joon Koo [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Hospital, Institute of Radiation Medicine, Seoul (Korea, Republic of); Lee, Eun Sun; Choi, Byung Ihn [Chung-Ang University Hospital, Department of Radiology, Seoul (Korea, Republic of)

    2016-06-15

    To determine the different imaging features of intrahepatic mass-forming cholangiocarcinoma (IMCC) from hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced magnetic resonance imaging (MRI). This retrospective study was institutional review board approved and the requirement for informed consent was waived. Patients who underwent gadoxetic acid-enhanced MRI with histologically confirmed IMCCs (n = 46) or HCCs (n = 58) were included. Imaging features of IMCCs and HCCs on gadoxetic acid-enhanced MRI including T2- and T1-weighted, diffusion weighted images, dynamic study and hepatobiliary phase (HBP) images were analyzed. Univariate and multivariate logistic regression analyses were performed to identify relevant differentiating features between IMCCs and HCCs. Multivariate analysis revealed heterogeneous T2 signal intensity and a hypointense rim on the HBP as suggestive findings of IMCCs and the wash-in and ''portal wash-out'' enhancement pattern as well as focal T1 high signal intensity foci as indicative of HCCs (all, p < 0.05). When we combined any three of the above four imaging features, we were able to diagnose IMCCs with 94 % (43/46) sensitivity and 86 % (50/58) specificity. Combined interpretation of enhancement characteristics including HBP images, morphologic features, and strict application of the ''portal wash-out'' pattern helped more accurate discrimination of IMCCs from HCCs. (orig.)

  5. Simultaneous resection of liver cell adenomas and an intrahepatic portosystemic venous shunt with elevation of serum PIVKA-II level.

    Science.gov (United States)

    Seyama, Yasuji; Sano, Keiji; Tang, Wei; Kokudo, Norihiro; Sakamoto, Yoshihiro; Imamura, Hiroshi; Makuuchi, Masatoshi

    2006-09-01

    A 27-year-old woman with no history of liver disease or oral contraceptive use presented with sudden abdominal pain. Laboratory data showed mild liver dysfunction with jaundice. Computed tomography and angiography revealed centrally located large liver cell adenomas (LCAs) and an intrahepatic portosystemic venous shunt (IHPSS) in the left lobe. The serum des-gamma-carboxy prothrombin (known as "protein induced by a lack of vitamin K or antagonist II," PIVKA-II) level was extremely high (6,647 mAU/ml), indicating malignant transformation of the tumors. Under the diagnosis of LCAs and IHPSS, the patient underwent simultaneous resection of the four liver tumors and portovenous shunt, and the hepatic vascular abnormality was resolved. The pathological diagnosis was LCAs without hepatocellular carcinoma. Immunohistochemical analysis with an anti-PIVKA-II monoclonal antibody showed positive staining of the adenoma cells. This case shows that LCA without malignant transformation can produce PIVKA-II, leading to high serum levels of PIVKA-II. Simultaneous resection of multiple tumors and closure of the portosystemic shunt are strongly recommended in a patient with LCA associated with IHPSS.

  6. Three-dimensional C-arm CT-guided transjugular intrahepatic portosystemic shunt placement: Feasibility, technical success and procedural time

    Energy Technology Data Exchange (ETDEWEB)

    Ketelsen, Dominik; Groezinger, Gerd; Maurer, Michael; Grosse, Ulrich; Horger, Marius; Nikolaou, Konstantin; Syha, Roland [University of Tuebingen, Department of Diagnostic and Interventional Radiology, Tuebingen (Germany); Lauer, Ulrich M. [University of Tuebingen, Internal Medicine I, Department of Gastroenterology, Hepatology and Infectious disease, Tuebingen (Germany)

    2016-12-15

    Establishment of transjugular intrahepatic portosystemic shunts (TIPS) constitutes a standard procedure in patients suffering from portal hypertension. The most difficult step in TIPS placement is blind puncture of the portal vein. This study aimed to evaluate three-dimensional mapping of portal vein branches and targeted puncture of the portal vein. Twelve consecutive patients suffering from refractory ascites by liver cirrhosis were included in this retrospective study to evaluate feasibility, technical success and procedural time of C-arm CT-targeted puncture of the portal vein. As a control, 22 patients receiving TIPS placement with fluoroscopy-guided blind puncture were included to compare procedural time. Technical success could be obtained in 100 % of the study group (targeted puncture) and in 95.5 % of the control group (blind puncture). Appropriate, three-dimensional C-arm CT-guided mapping of the portal vein branches could be achieved in all patients. The median number of punctures in the C-arm CT-guided study group was 2 ± 1.3 punctures. Procedural time was significantly lower in the study group (14.8 ± 8.2 min) compared to the control group (32.6 ± 22.7 min) (p = 0.02). C-arm CT-guided portal vein mapping is technically feasible and a promising tool for TIPS placement resulting in a significant reduction of procedural time. (orig.)

  7. Contrast-Enhanced Ultrasound in the Diagnosis of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: Controversy over the ASSLD Guideline

    Directory of Open Access Journals (Sweden)

    Le-Hang Guo

    2015-01-01

    Full Text Available Hepatocellular carcinoma (HCC and intrahepatic cholangiocarcinoma (ICC are both regarded as primary liver cancers, having different biological behaviors and prognoses. Correct differentiation between them is essential for surgical planning and prognosis assessment. In 2005, the American Association for the Study of Liver Diseases (AASLD recommended that noninvasive diagnosis of HCC is achievable by a single dynamic technique (including contrast-enhanced ultrasound (CEUS showing intense arterial uptake followed by washout of contrast in the venous-delayed phases. However, CEUS has been dropped from the diagnostic techniques in the latest AASLD guideline according to the opinion of some authors from Europe that CEUS may offer false positive HCC diagnosis in patients with ICC. Since the update of AASLD guideline has been released, increased attention has been paid to this interesting topic. Remarkable controversy over this issue is present and this removal was not well received in Europe and Asia. This commentary summarized the opinions for the role of CUES in differentiation between HCC and ICC in recent years. It is concluded that prospective studies with strict design and large case series are mandatory to solve the controversies and stratification of ICC in terms of tumor size and liver background is also essential.

  8. Endovascular Management of Refractory Hepatic Encephalopathy Complication of Transjugular Intrahepatic Portosystemic Shunt (TIPS): Comprehensive Review and Clinical Practice Algorithm.

    Science.gov (United States)

    Pereira, Keith; Carrion, Andres F; Salsamendi, Jason; Doshi, Mehul; Baker, Reginald; Kably, Issam

    2016-02-01

    Transjugular intrahepatic portosystemic shunt (TIPS) has evolved as an effective intervention for treatment of complications of portal hypertension. The use of polytetrafluoroethylene-covered stents have improved the patency of the shunts and diminished the incidence of TIPS dysfunction. However, TIPS-related refractory hepatic encephalopathy (rHE) poses a significant challenge. Approximately 3-7 % of patients with TIPS develop rHE. Refractory hepatic encephalopathy is defined as a recurrent or persistent encephalopathy despite appropriate medical treatment. Hepatic encephalopathy can be an extremely debilitating complication that profoundly affects quality of life. The approach to management of patients with rHE is complex and typically requires collaboration between different specialties. Liver transplantation is the ultimate treatment for rHE; however, the ongoing shortage of organ donation markedly limits this treatment option. Alternative therapies such as shunt occlusion or reduction can control symptoms and serve as a 'bridge' therapy to liver transplantation. Therefore, interventional radiologists play a key role in the management of these patients by offering a variety of endovascular techniques. The purpose of this review is to highlight some of these endovascular techniques and to develop a therapeutic algorithm that can be applied in clinical practice for the management of rHE.

  9. Transjugular intrahepatic portosystemic shunt in patients with active variceal bleeding due to portal hypertension and portal vein thrombosis

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Hyun Woong; Ryeom, Hun Kyu; Lee, Sang Kwon; Lee, Jong Min; Kim, Young Sun; Suh, Kyung Jin; Kim, Tae Hun; Kim, Yong Joo [Kyungpook National Univ. College of Medicine, Seoul (Korea, Republic of)

    1997-10-01

    To evaluate the feasibility and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) in patients with active variceal bleeding due to liver cirrhosis and pre-existing portal vein thrombosis. Of a total of 123 patients who underwent TIPS, 14 patients with intractable variceal bleeding due to portal hypertension and portal vein thrombosis were included in this study. Noncavernomatous portal vein occlusion was seen in eight patients, and complete portal vein occlusion with cavernomatous trans-formation in six. For all patients, the methods used for TIPS placement were the same as those used in patients with patents portal veins. In seven of eight patients with noncavernomatous occlusion, right hepatic vein-right portal vein shunting was performed; in one with knoncavernomatous occlusion, a shunt was created between the right hepatic and left portal vein. In five of six patients with cavernomatous occlusion, the right hepatic and main portal vein were connected via a collateral vein. The procedures were technically successful in all except one patient. Immediate hemostatis was achieved after all technically successful procedures, and no significant complications were encountered. Minor complications were noted in six patients (three biliary tree punctures, one transperitoneal puncture, one splenic vein perforation, one hepatic subcapsular hematoma). TIPS is a technically feasible and hemodynamically effective procedure, even in patients with active variceal bleeding due to cirrhosis and complete portal vein occlusion.

  10. Effect of transjugular intrahepatic portosystemic shunt on pulmonary gas exchange in patients with portal hypertension and hepatopulmonary syndrome

    Institute of Scientific and Technical Information of China (English)

    Graciela Martínez-Pallí; Britt B Drake; Joan-Carles García-Pagán; Joan-Albert Barberà; Miguel R Arguedas; Robert Rodriguez-Roisin; Jaume Bosch; Michael B Fallon

    2005-01-01

    AIM: To assess the impact of transjugular intrahepatic portosystemic shunt (TIPS) on pulmonary gas exchange and to evaluate the use of TIPS for the treatment of hepatopulmonary syndrome (HPS).METHODS: Seven patients, three of them with advanced HPS, in whom detailed pulmonary function tests were performed before and after TIPS placementat the University of Alabama Hospital and at the Hospital Clinic, Barcelona, were considered.RESULTS: TIPS patency was confirmed by hemodynamic evaluation. No changes in arterial blood gases were observed in the overall subset of patients. Transient arterial oxygenation improvement was observed in only one HPS patient, early after TIPS, but this was not sustained 4 mo later.CONCLUSION: TIPS neither improved nor worsened pulmonary gas exchange in patients with portal hypertension. This data does not support the use of TIPS as a specific treatment for HPS. However, it does reinforce the view that TIPS can be safely performed for the treatment of other complications of portal hypertension in patients with HPS.

  11. Endovascular Management of Refractory Hepatic Encephalopathy Complication of Transjugular Intrahepatic Portosystemic Shunt (TIPS): Comprehensive Review and Clinical Practice Algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Keith, E-mail: keithjppereira@gmail.com [Jackson Memorial Hospital/University of Miami Hospital, Department of Interventional Radiology (United States); Carrion, Andres F., E-mail: andres.carrionmonsa@jhsmiami.org [Jackson Memorial Hospital/University of Miami Hospital, Department of Hepatology (United States); Salsamendi, Jason, E-mail: JSalsamendi@med.miami.edu; Doshi, Mehul, E-mail: MDoshi@med.miami.edu; Baker, Reginald, E-mail: RBaker@med.miami.edu; Kably, Issam, E-mail: ikably@med.miami.edu [Jackson Memorial Hospital/University of Miami Hospital, Department of Interventional Radiology (United States)

    2016-02-15

    Transjugular intrahepatic portosystemic shunt (TIPS) has evolved as an effective intervention for treatment of complications of portal hypertension. The use of polytetrafluoroethylene-covered stents have improved the patency of the shunts and diminished the incidence of TIPS dysfunction. However, TIPS-related refractory hepatic encephalopathy (rHE) poses a significant challenge. Approximately 3–7 % of patients with TIPS develop rHE. Refractory hepatic encephalopathy is defined as a recurrent or persistent encephalopathy despite appropriate medical treatment. Hepatic encephalopathy can be an extremely debilitating complication that profoundly affects quality of life. The approach to management of patients with rHE is complex and typically requires collaboration between different specialties. Liver transplantation is the ultimate treatment for rHE; however, the ongoing shortage of organ donation markedly limits this treatment option. Alternative therapies such as shunt occlusion or reduction can control symptoms and serve as a ‘bridge’ therapy to liver transplantation. Therefore, interventional radiologists play a key role in the management of these patients by offering a variety of endovascular techniques. The purpose of this review is to highlight some of these endovascular techniques and to develop a therapeutic algorithm that can be applied in clinical practice for the management of rHE.

  12. Technical concepts for vascular electromagnetic navigated interventions: aortic in situ fenestration and transjugular intrahepatic porto-systemic shunts.

    Science.gov (United States)

    Penzkofer, Tobias; Isfort, Peter; Na, Hong-Sik; Wilkmann, Christoph; Osterhues, Sabine; Besting, Andreas; Hänisch, Christoph; Bisplinghoff, Stefan; Jansing, Johannes; von Werder, Sylvie; Gooding, Jorge; de la Fuente, Mathias; Mahnken, Andreas H; Disselhorst-Klug, Catherine; Schmitz-Rode, Thomas; Kuhl, Christiane K; Bruners, Philipp

    2014-04-01

    This work presents concepts for complex endovascular procedures using electromagnetic navigation technology (EMT). Navigation software interfacing a standard commercially available navigation system was developed, featuring registration, electromagnetic field distortion correction, breathing motion detection and gating, and state-of-the-art 3D imaging post processing. Protocols for endovascularly placed, in-situ fenestrated abdominal aortic stent grafts and an EMT guided transjugular intrahepatic portosystemic shunt (TIPSS) creation have been designed. A dedicated set of interventional devices was developed for each of the procedures: For aortic in-situ fenestration a combination of high-porosity stentgrafts, steerable catheters and electromagnetically navigated guidewires was used, for TIPSS a dual-navigated (sheath and stylet) TIPSS-device was designed and manufactured. The developed devices underwent phantom testing, in preparation for animal experiments to prove the feasibility of the approach. Once established, these systems could aid in performing these challenging interventional radiology procedures, exploiting the unique characteristics of electromagnetic navigation and solving multiple of the problems associated with these interventions being performed under X-ray fluoroscopy, such as lacking real-time 3D information or extensive exposure to ionizing radiation.

  13. 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

  14. 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.

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

    Institute of Scientific and Technical Information of China (English)

    王冬梅; 朱启英; 腊晓琳

    2002-01-01

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

  16. CYP1B1基因多态性与妊娠期肝内胆汁淤积症易感性的关系%Association of Gene Polymorphisms of CYP1B1 with Intrahepatic Cholestasis of Pregnancy

    Institute of Scientific and Technical Information of China (English)

    王晓莉; 谭欣; 张力; 欧容清; 颜爱华; 陈强; 邹海

    2008-01-01

    目的 研究CYP1B1基因外显子2密码子119(G-T)和外显子3密码子432(C-G)多态性与妊娠期肝内胆汁淤积症(ICP)发病的关系.方法 分别应用等位基因特异性PCR(AS-PCR)技术和人工修饰双等位基因特异性引物扩增(diASA-AMP)法,对100例ICP患者和100例正常对照孕妇CYP1B1基因外显子2密码子119(G-T)和外显子3密码子432(C-G)多态性进行分析.结果 ①CYP1B1基因密码子119多态分析表明ICP组T等位基因频率高于对照组(P0.05).结论 CYP1B1基因外显子2密码子119多态性可能与成都地区ICP易感性有关.

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

    Institute of Scientific and Technical Information of China (English)

    蔡林燕

    2016-01-01

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

  18. Dermatological Diseases Associated with Pregnancy

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  19. The role of intrahepatic CD3 +/CD4 −/CD8 − double negative T (DN T) cells in enhanced acetaminophen toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Getachew, Yonas, E-mail: yonas.getachew@utsouthwestern.edu [Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9151 (United States); Cusimano, Frank A. [Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9151 (United States); James, Laura P. [Department of Pediatrics, University of Arkansas, Little Rock, AR (United States); Thiele, Dwain L. [Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9151 (United States)

    2014-10-15

    The role of the immune system, specifically NK, NKT and CD3 cells, in acetaminophen (APAP) induced liver injury remains inconsistently defined. In the present study, wild type (C57BL/6J) mice and granzyme B deficient (GrB −/−) mice were treated with acetaminophen to assess the role of the immune system in acute liver injury. Doses of acetaminophen that induced sub lethal liver injury in wild type mice unexpectedly produced fatal hepatotoxicity in granzyme B deficient (GrB −/−) mice. Analysis revealed that GrB −/− mice had an increased population of intrahepatic CD3 (+), CD4 (−), and CD8 (−) lymphocytes expressing the CD69 activation marker and Fas ligand. Depletion of these cells in the GrB −/− and wild type mice made them less susceptible to APAP injury, while depletion of NK1.1 (+) cells or both CD4 (+) and CD8 (+) T cells failed to provide the same hepatoprotection. Transfer of the GrB −/− IHLs further exacerbated liver injury and increased mortality in wild type mice but not in LRP/LPR mice, lacking fas expression. Conclusions: Acetaminophen toxicity is enhanced by the presence of activated, FasL expressing intrahepatic CD3 (+), CD4 (−), CD8 (−), NK1.1 (−) T cells. Depletion of these cells from GrB −/− mice and wild type mice greatly reduces mortality and improves the course of liver injury recovery. - Highlights: • Intrahepatic lymphocytes (IHLs) from GrB −/− mice harbor activated DNT cells. • IHLs from GrB −/− mice exhibit enhanced Fas ligand expression. • Acetaminophen toxicity is enhanced by activated, FasL expressing DNT cells.

  20. Contribution of Cyclooxygenase End Products and Oxidative Stress to Intrahepatic Endothelial Dysfunction in Early Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Morales Arraez, Dalia; Marcelino Reyes, Raquel; Abrante, Beatriz; Diaz-Flores, Felicitas; Salido, Eduardo; Quintero, Enrique; Hernández-Guerra, Manuel

    2016-01-01

    Introduction Metabolic syndrome induces endothelial dysfunction, a surrogate marker of cardiovascular disease. In parallel, metabolic syndrome is frequently associated with non-alcoholic fatty liver disease (NAFLD), which may progress to cirrhosis. The aim of the present study was to evaluate intrahepatic endothelial dysfunction related to cyclooxygenase end products and oxidative stress as possible mechanisms involved in the pathophysiology of NAFLD. Materials and Methods Sprague-Dawley rats were fed standard diet (control-diet, CD) or high-fat-diet (HFD) for 6 weeks. Metabolic syndrome was assessed by recording arterial pressure, lipids, glycemia and rat body weight. Splanchnic hemodynamics were measured, and endothelial dysfunction was evaluated using concentration-effect curves to acetylcholine. Response was assessed with either vehicle, L-NG-Nitroarginine (L-NNA), indomethacin, tempol, or a thromboxane receptor antagonist, SQ 29548. We quantified inflammation, fibrosis, oxidative stress, nitric oxide (NO) bioavailability and thromboxane B2 levels. Results HFD rats exhibited metabolic syndrome together with the presence of NAFLD. Compared to control-diet livers, HFD livers showed increased hepatic vascular resistance unrelated to inflammation or fibrosis, but with decreased NO activity and increased oxidative stress. Endothelial dysfunction was observed in HFD livers compared with CD rats and improved after cyclooxygenase inhibition or tempol pre-incubation. However, pre-incubation with SQ 29548 did not modify acetylcholine response. Conclusions Our study provides evidence that endothelial dysfunction at an early stage of NAFLD is associated with reduced NO bioavailability together with increased cyclooxygenase end products and oxidative stress, which suggests that both pathways are involved in the pathophysiology and may be worth exploring as therapeutic targets to prevent progression of the disease. PMID:27227672

  1. Transjugular intrahepatic portosystemic shunt combined with esophagogastric variceal embolization in the treatment of a large gastrorenal shunt

    Institute of Scientific and Technical Information of China (English)

    Qin; Jiang; Ming-Quan; Wang; Guo-Bing; Zhang; Qiong; Wu; Jian-Ming; Xu; De-Run; Kong

    2016-01-01

    AIM: To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt(TIPS) combined with stomach and esophageal variceal embolization(SEVE) in cirrhotic patients with a large gastrorenal vessel shunt(GRVS).METHODS: Eighty-one cirrhotic patients with gastric variceal bleeding(GVB) associated with a GRVS were enrolled in the study and accepted TIPS combined with SEVE(TIPS + SEVE), by which portosystemic pressuregradient(PPG), biochemical, TIPS-related complications, shunt dysfunction, rebleeding, and death were evaluated. RESULTS: The PPGs before TIPS were greater than 12 mmH g in 81 patients. TIPS + SEVE treatment caused a significant decrease in PPG(from 37.97 ± 6.36 mmH g to 28.15 ± 6.52 mm Hg, t = 19.22, P < 0.001). The percentage of reduction in PPG was greater than 20%from baseline. There were no significant differences in albumin, alanine aminotransferase, aspartate aminotransferase, bilirubin, prothrombin time, or Child-Pugh score before and after operation. In all patients, rebleeding rates were 3%, 6%, 12%, 18%, and 18% at 1,3, 6, 12, and 18 mo, respectively. Five patients(6.2%)were diagnosed as having hepatic encephalopathy. The rates of shunt dysfunction were 0%, 4%, 9%, 26%,and 26%, at 1, 3, 6, 12, and 18 mo, respectively. The cumulative survival rates in 1, 3, 6, 12, and 18 mo were100%, 100%, 95%, 90%, and 90%, respectively.CONCLUSION: Our preliminary results indicated that the efficacy and safety of TIPS + SEVE were satisfactory in cirrhotic patients with GVB associated with a GRVS(GVB + GRVS).

  2. Balloon-occluded retrograde transvenous obliteration for gastric variceal bleeding: its feasibility compared with transjugular intrahepatic portosystemic shunt

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Young Ho; Yoon, Chang Jin; Park, Jae Hyung; Chung, Jin Wook; Kwon, Jong Won [Seoul Natioonal University College of Medicine, Seoul (Korea, Republic of); Choi, Guk Myung [Cheju National University College of Medicine, Jeju (Korea, Republic of)

    2003-06-01

    To assess the feasibility of balloon-occluded retrograde transvenous obliteration (BRTO) in active gastric variceal bleeding, and to compare the findings with those of transjugular intrahepatic portosystemic shunt (TIPS). Twenty-one patients with active gastric variceal bleeding due to liver cirrhosis were referred for radiological intervention. In 15 patients, contrast-enhanced CT scans demonstrated gastrorenal shunt, and the remaining six (Group 1) underwent TIPS. Seven of the 15 with gastrorenal shunt (Group 2) were also treated with TIPS, and the other eight (Group 3) underwent BRTO. All patients were followed up for 6 to 21 (mean, 14.4) months. For statistical inter-group comparison of immediate hemostasis, rebleeding and encephalopathy, Fisher's exact test was used. Changes in the Child-Pugh score before and after each procedure in each group were statistically analyzed by means of Wilcoxon's signed rank test. One patient in Group 1 died of sepsis, acute respiratory distress syndrome, and persistent bleeding three days after TIPS, while the remaining 20 survived the procedure with immediate hemostasis. Hepatic encephalopathy developed in four patients (one in Group 1, three in Group 2, and none in Group 3); one, in Group 2, died while in an hepatic coma 19 months after TIPS. Rebleeding occurred in one patient, also in Group 2. Except for transient fever in two Group-3 patients, no procedure-related complication occurred. In terms of immediate hemostasis, rebleeding and encephalopathy, there were no statistically significant differences between the groups (p > 0.05). In Group 3, the Child-Pugh score showed a significant decrease after the procedure (p = 0.02). BRTO can effectively control active gastric variceal bleeding, and because of immediate hemostasis, the absence of rebleeding, and improved liver function, is a good alternative to TIPS in patients in whom such bleeding, accompanied by gastrorenal shunt, occurs.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Contribution of Cyclooxygenase End Products and Oxidative Stress to Intrahepatic Endothelial Dysfunction in Early Non-Alcoholic Fatty Liver Disease.

    Directory of Open Access Journals (Sweden)

    Francisco Javier Gonzalez-Paredes

    Full Text Available Metabolic syndrome induces endothelial dysfunction, a surrogate marker of cardiovascular disease. In parallel, metabolic syndrome is frequently associated with non-alcoholic fatty liver disease (NAFLD, which may progress to cirrhosis. The aim of the present study was to evaluate intrahepatic endothelial dysfunction related to cyclooxygenase end products and oxidative stress as possible mechanisms involved in the pathophysiology of NAFLD.Sprague-Dawley rats were fed standard diet (control-diet, CD or high-fat-diet (HFD for 6 weeks. Metabolic syndrome was assessed by recording arterial pressure, lipids, glycemia and rat body weight. Splanchnic hemodynamics were measured, and endothelial dysfunction was evaluated using concentration-effect curves to acetylcholine. Response was assessed with either vehicle, L-NG-Nitroarginine (L-NNA, indomethacin, tempol, or a thromboxane receptor antagonist, SQ 29548. We quantified inflammation, fibrosis, oxidative stress, nitric oxide (NO bioavailability and thromboxane B2 levels.HFD rats exhibited metabolic syndrome together with the presence of NAFLD. Compared to control-diet livers, HFD livers showed increased hepatic vascular resistance unrelated to inflammation or fibrosis, but with decreased NO activity and increased oxidative stress. Endothelial dysfunction was observed in HFD livers compared with CD rats and improved after cyclooxygenase inhibition or tempol pre-incubation. However, pre-incubation with SQ 29548 did not modify acetylcholine response.Our study provides evidence that endothelial dysfunction at an early stage of NAFLD is associated with reduced NO bioavailability together with increased cyclooxygenase end products and oxidative stress, which suggests that both pathways are involved in the pathophysiology and may be worth exploring as therapeutic targets to prevent progression of the disease.

  5. Intrahepatic gene expression profiles and alpha-smooth muscle actin patterns in hepatitis C virus induced fibrosis.

    Science.gov (United States)

    Lau, Daryl T-Y; Luxon, Bruce A; Xiao, Shu-Yuan; Beard, Michael R; Lemon, Stanley M

    2005-08-01

    To gain insight into pathogenic mechanisms underlying fibrosis in hepatitis C virus (HCV)-mediated liver injury, we compared intrahepatic gene expression profiles in HCV-infected patients at different stages of fibrosis and alpha-smooth muscle actin (alpha-SMA) staining patterns. We studied 21 liver biopsy specimens: 5 had no fibrosis (Ludwig-Batts stage 0); 10 had early portal or periportal fibrosis (stages 1 and 2); and 6, advanced fibrosis (stages 3 and 4). None of the patients had hepatocellular carcinoma. Transcriptional profiles were determined by high-density oligonucleotide microarrays. ANOVA identified 157 genes for which transcript abundance was associated with fibrosis stage. These defined three distinct hierarchical clusters of patients. Patients with predominantly stage 0 fibrosis had increased abundance of mRNAs linked to glycolipid metabolism. PDGF, a potent stellate cell mitogen, was also increased. Transcripts with increased abundance in stages 1 and 2 fibrosis were associated with oxidative stress, apoptosis, inflammation, proliferation, and matrix degradation, whereas transcripts increased in stages 3 and 4 were associated with fibrogenesis and cellular proliferation. Cells staining for alpha-SMA were detectable at all stages but infrequent in advanced fibrosis without active inflammation. A high frequency of such cells was associated with mRNAs linked to glycolipid metabolism. In conclusion, the presence of alpha-SMA-positive HSCs and expression of PDGF in stage 0 fibrosis suggests that stellate cells are activated early in HCV-mediated injury, possibly in response to oxidative stress resulting from inflammation and lipid metabolism. Increased abundance of transcripts linked to cellular proliferation in advanced fibrosis is consistent with a predisposition to cancer. Supplementary material for this article can be found on the HEPATOLOGY website (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index/html).

  6. The potential of a high protein-low carbohydrate diet to preserve intrahepatic triglyceride content in healthy humans.

    Directory of Open Access Journals (Sweden)

    Eveline A Martens

    Full Text Available BACKGROUND: Protein supplementation has been shown to reduce the increases in intrahepatic triglyceride (IHTG content induced by acute hypercaloric high-fat and high-fructose diets in humans. OBJECTIVE: To assess the effect of a 12-wk iso-energetic high protein-low carbohydrate (HPLC diet compared with an iso-energetic high carbohydrate-low protein (HCLP diet on IHTG content in healthy non-obese subjects, at a constant body weight. DESIGN: Seven men and nine women [mean ± SD age: 24 ± 5 y; BMI: 22.9 ± 2.1 kg/m2] were randomly allocated to a HPLC [30/35/35% of energy (En% from protein/carbohydrate/fat] or a HCLP (5/60/35 En% diet by stratification on sex, age and BMI. Dietary guidelines were prescribed based on individual daily energy requirements. IHTG content was measured by 1H-magnetic resonance spectroscopy before and after the dietary intervention. RESULTS: IHTG content changed in different directions with the HPLC (CH2H2O: 0.23 ± 0.17 to 0.20 ± 0.10; IHTG%: 0.25 ± 0.20% to 0.22 ± 0.11% compared with the HCLP diet (CH2H2O: 0.34 ± 0.20 vs. 0.38 ± 0.21; IHTG%: 0.38 ± 0.22% vs. 0.43 ± 0.24%, which resulted in a lower IHTG content in the HPLC compared with the HCLP diet group after 12 weeks, which almost reached statistical significance (P = 0.055. CONCLUSIONS: A HPLC vs. a HCLP diet has the potential to preserve vs. enlarge IHTG content in healthy non-obese subjects at a constant body weight. TRIAL REGISTRATION: Clinicaltrials.gov NCT01551238.

  7. Transjugular intrahepatic portosystemic shunt (TIPS) versus endoscopic variceal ligation in the prevention of variceal rebleeding in patients with cirrhosis: a randomised trial

    OpenAIRE

    2001-01-01

    BACKGROUND AND AIMS—The transjugular intrahepatic portosystemic shunt (TIPS) is a new therapeutic modality for variceal bleeding. In this study we compared the two year survival and rebleeding rates in cirrhotic patients treated by either variceal band ligation or TIPS for variceal bleeding.
METHODS—Eighty cirrhotic patients (Pugh score 7-12) with variceal bleeding were randomly allocated to TIPS (n=41) or ligation (n=39), 24 hours after control of bleeding.
RESULTS—Mean follow up was 581 day...

  8. Intrahepatic B-cell follicles of chronically hepatitis C virus-infected individuals lack signs of an ectopic germinal center reaction.

    Science.gov (United States)

    Tucci, Felicia A; Broering, Ruth; Lutterbeck, Melanie; Schlaak, Joerg F; Küppers, Ralf

    2014-06-01

    Chronic infection with hepatitis C virus (HCV) often affects the B-cell compartment, leading to the occurrence of autoimmunity and B-cell lymphoproliferation, in particular mixed cryoglobulinemia and B-cell lymphomas. HCV presumably causes these lymphoproliferations by chronic antigenic stimulation and/or direct mutagenic effects on B cells. It has been speculated that the interaction of HCV with B cells and the expansion of antigen-triggered B cells happens in germinal center-like structures in the livers of HCV carriers. We studied rearranged immunoglobulin V(H) genes from seven B-cell follicles microdissected from the livers of three unselected chronic HCV patients. The follicles consisted of polyclonal naive and memory B-cell populations with only rare indication of minor clonal expansions and no evidence for active somatic hypermutation. Frequent detection of V(H) rearrangements using the VH1-69 gene segment nevertheless indicated that at least a fraction of the B cells is HCV-specific and/or autoreactive. Thus, the typical intrahepatic B-cell follicles in chronic HCV carriers do not function as ectopic germinal centers for clonal expansion and affinity maturation of B cells. Hence, autoreactive and HCV-specific B-cell clones might either develop in secondary lymphoid organs or in intrahepatic follicles only under particular, yet undefined, circumstances.

  9. Intrahepatic transplantation of CD34+ cord blood stem cells into newborn and adult NOD/SCID mice induce differential organ engraftment.

    Science.gov (United States)

    Wulf-Goldenberg, Annika; Keil, Marlen; Fichtner, Iduna; Eckert, Klaus

    2012-04-01

    In vivo studies concerning the function of human hematopoietic stem cells (HSC) are limited by relatively low levels of engraftment and the failure of the engrafted HSC preparations to differentiate into functional immune cells after systemic application. In the present paper we describe the effect of intrahepatically transplanted CD34(+) cells from cord blood into the liver of newborn or adult NOD/SCID mice on organ engraftment and differentiation. Analyzing the short and long term time dependency of human cell recruitment into mouse organs after cell transplantation in the liver of newborn and adult NOD/SCID mice by RT-PCR and FACS analysis, a significantly high engraftment was found after transplantation into liver of newborn NOD/SCID mice compared to adult mice, with the highest level of 35% human cells in bone marrow and 4.9% human cells in spleen at day 70. These human cells showed CD19 B-cell, CD34 and CD38 hematopoietic and CD33 myeloid cell differentiation, but lacked any T-cell differentiation. HSC transplantation into liver of adult NOD/SCID mice resulted in minor recruitment of human cells from mouse liver to other mouse organs. The results indicate the usefulness of the intrahepatic application route into the liver of newborn NOD/SCID mice for the investigation of hematopoietic differentiation potential of CD34(+) cord blood stem cell preparations.

  10. Sensitivity of Human Intrahepatic Cholangiocarcinoma Subtypes to Chemotherapeutics and Molecular Targeted Agents: A Study on Primary Cell Cultures

    Science.gov (United States)

    Fraveto, Alice; Cardinale, Vincenzo; Bragazzi, Maria Consiglia; Giuliante, Felice; De Rose, Agostino Maria; Grazi, Gian Luca; Napoletano, Chiara; Semeraro, Rossella; Lustri, Anna Maria; Costantini, Daniele; Nevi, Lorenzo; Di Matteo, Sabina; Renzi, Anastasia; Carpino, Guido; Gaudio, Eugenio; Alvaro, Domenico

    2015-01-01

    We investigated the sensitivity of intrahepatic cholangiocarcinoma (IHCCA) subtypes to chemotherapeutics and molecular targeted agents. Primary cultures of mucin- and mixed-IHCCA were prepared from surgical specimens (N. 18 IHCCA patients) and evaluated for cell proliferation (MTS assay) and apoptosis (Caspase 3) after incubation (72 hours) with increasing concentrations of different drugs. In vivo, subcutaneous human tumor xenografts were evaluated. Primary cultures of mucin- and mixed-IHCCA were characterized by a different pattern of expression of cancer stem cell markers, and by a different drug sensitivity. Gemcitabine and the Gemcitabine-Cisplatin combination were more active in inhibiting cell proliferation in mixed-IHCCA while Cisplatin or Abraxane were more effective against mucin-IHCCA, where Abraxane also enhances apoptosis. 5-Fluoracil showed a slight inhibitory effect on cell proliferation that was more significant in mixed- than mucin-IHCCA primary cultures and, induced apoptosis only in mucin-IHCCA. Among Hg inhibitors, LY2940680 and Vismodegib showed slight effects on proliferation of both IHCCA subtypes. The tyrosine kinase inhibitors, Imatinib Mesylate and Sorafenib showed significant inhibitory effects on proliferation of both mucin- and mixed-IHCCA. The MEK 1/2 inhibitor, Selumetinib, inhibited proliferation of only mucin-IHCCA while the aminopeptidase-N inhibitor, Bestatin was more active against mixed-IHCCA. The c-erbB2 blocking antibody was more active against mixed-IHCCA while, the Wnt inhibitor, LGK974, similarly inhibited proliferation of mucin- and mixed-IHCCA. Either mucin- or mixed-IHCCA showed high sensitivity to nanomolar concentrations of the dual PI3-kinase/mTOR inhibitor, NVP-BEZ235. In vivo, in subcutaneous xenografts, either NVP-BEZ235 or Abraxane, blocked tumor growth. In conclusion, mucin- and mixed-IHCCA are characterized by a different drug sensitivity. Cisplatin, Abraxane and the MEK 1/2 inhibitor, Selumetinib were more

  11. Technical and clinical outcome of transjugular intrahepatic portosystemic stent shunt: Bare metal stents (BMS) versus viatorr stent-grafts (VSG)

    Energy Technology Data Exchange (ETDEWEB)

    Sommer, Christof M., E-mail: cmsommer@gmx.com [Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, INF 110, 69120 Heidelberg (Germany); Gockner, Theresa L.; Stampfl, Ulrike; Bellemann, Nadine [Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, INF 110, 69120 Heidelberg (Germany); Sauer, Peter; Ganten, Tom [Department of Gastroenterology, University Hospital Heidelberg, Heidelberg (Germany); Weitz, Juergen [Department of General, Abdominal and Transplantation Surgery, University Hospital Heidelberg, Heidelberg (Germany); Kauczor, Hans U.; Radeleff, Boris A. [Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, INF 110, 69120 Heidelberg (Germany)

    2012-09-15

    Highlights: ► Twelve month mean number of TIPS revisions per patient was significantly lower in VSG. ► First TIPS revision was performed significantly later in the VSG. ► There was no significant difference of hepatic encephalopathy in both study groups. -- Abstract: Purpose: To compare retrospectively angiographical and clinical results in patients undergoing transjugular intrahepatic portosystemic stent-shunt (TIPS) using BMS or VSG. Materials and methods: From February 2001 to January 2010, 245 patients underwent TIPS. From those, 174 patients matched the inclusion criteria with elective procedures and institutional follow-up. Group (I) consisted of 116 patients (mean age, 57.0 ± 11.1 years) with BMS. Group (II) consisted of 58 patients with VSG (mean age, 53.5 ± 16.1 years). Angiographic and clinical controls were scheduled at 3, 6 and 12 months, followed by clinical controls every 6 months. Primary study goals included hemodynamic success, shunt patency as well as time to and number of revisions. Secondary study goals included clinical success. Results: Hemodynamic success was 92.2% in I and 91.4% in II (n.s.). Primary patency was significantly higher in II compared to I (53.8% after 440.4 ± 474.5 days versus 45.8% after 340.1 ± 413.8 days; p < 0.05). The first TIPS revision was performed significantly later in II compared to I (288.3 ± 334.7 days versus 180.1 ± 307.0 days; p < 0.05). In the first angiographic control, a portosystemic pressure gradient ≥15 mmHg was present in 73.9% in I and in 39.4% in II (p < 0.05). Clinical success was 73.7–86.2% after 466.3 ± 670.1 days in I and 85.7–90.5% after 617.5 ± 642.7 days in II (n.s.). Hepatic encephalopathy was 37.5% in I and 36.5% in II (n.s.). Conclusion: VSG increased primary shunt patency as well as decreased time to and number of TIPS revisions. There was a trend of higher clinical success in VSG without increased hepatic encephalopathy.

  12. Radiologic follow-up of the transjugular intrahepatic stent-shunt (TIPSS); Radiologische Nachsorge des transjugulaeren intrahepatischen Stentshunts (TIPSS)

    Energy Technology Data Exchange (ETDEWEB)

    Hansmann, H.J.; Noeldge, G.; Leutloff, U.; Radeleff, B.; Richter, G.M. [Heidelberg Univ. (Germany). Abt. Radiodiagnostik; Sauer, P. [Heidelberg Univ. (DE). Abt. Innere Medizin 4 (Schwerpunkt Gastroenterologie)

    2001-10-01

    The transjugular intrahepatic stent-shunt (TIPSS) is a well accepted minimal invasive therapy for complications of portal hypertension: recurrent variceal bleeding, refractory ascites and liver failure due to the Budd-Chiari syndrome. The high frequency of shunt stenoses and occlusions makes regular follow up examinations essential. Despite modern non invasive imaging methods direct portography still is the gold standard for shunt surveillance in TIPSS. Ultrasound is helpful to detect shunt dysfunction, but nevertheless its failure rate is considerable despite the use of contrast enhancers such as Levovist because of anatomic and physical limitations, particularly when TIPSS-tracts deep in the liver are present. Reintervention rates approach 90-100% after 24 months, with 100% in child's A patients with comparatively good liver function. However, a strict shunt surveillance program with early portography and reintervention when necessary guarantees high clinical success rates associated with very low rebleeding rates below 10%. Overall the secondary success rate is 80%. Secondary failures are mainly caused by lack of patient compliance during follow-up. In a subgroup of patients no shunt maturation is observed, requiring multiple shunt revisions. In cases of recurrent shunt occlusions an association with bile leaks is presumed. In selected cases patients with chronically recurrent shunt stenosis or occlusions may benefit from placement of TIPSS stent grafts. (orig.) [German] Der transjugulaere intrahepatische Stentshunt (TIPSS) ist eine etablierte minimal invasive Therapie der Komplikationen der portalen Hypertension (rezidivierende Varizenblutungen, therapierefraktaerer Aszites und das Leberversagen beim Budd-Chiari-Syndrom). Aufgrund einer hohen Rate von Traktstenosen und Verschluessen sind regelmaessige Kontrolluntersuchungen unabdingbar. Trotz moderner nichtinvasiver bildgebender Verfahren ist die transjugulaere Portographie mit Druckmessung der

  13. Sensitivity of Human Intrahepatic Cholangiocarcinoma Subtypes to Chemotherapeutics and Molecular Targeted Agents: A Study on Primary Cell Cultures.

    Directory of Open Access Journals (Sweden)

    Alice Fraveto

    Full Text Available We investigated the sensitivity of intrahepatic cholangiocarcinoma (IHCCA subtypes to chemotherapeutics and molecular targeted agents. Primary cultures of mucin- and mixed-IHCCA were prepared from surgical specimens (N. 18 IHCCA patients and evaluated for cell proliferation (MTS assay and apoptosis (Caspase 3 after incubation (72 hours with increasing concentrations of different drugs. In vivo, subcutaneous human tumor xenografts were evaluated. Primary cultures of mucin- and mixed-IHCCA were characterized by a different pattern of expression of cancer stem cell markers, and by a different drug sensitivity. Gemcitabine and the Gemcitabine-Cisplatin combination were more active in inhibiting cell proliferation in mixed-IHCCA while Cisplatin or Abraxane were more effective against mucin-IHCCA, where Abraxane also enhances apoptosis. 5-Fluoracil showed a slight inhibitory effect on cell proliferation that was more significant in mixed- than mucin-IHCCA primary cultures and, induced apoptosis only in mucin-IHCCA. Among Hg inhibitors, LY2940680 and Vismodegib showed slight effects on proliferation of both IHCCA subtypes. The tyrosine kinase inhibitors, Imatinib Mesylate and Sorafenib showed significant inhibitory effects on proliferation of both mucin- and mixed-IHCCA. The MEK 1/2 inhibitor, Selumetinib, inhibited proliferation of only mucin-IHCCA while the aminopeptidase-N inhibitor, Bestatin was more active against mixed-IHCCA. The c-erbB2 blocking antibody was more active against mixed-IHCCA while, the Wnt inhibitor, LGK974, similarly inhibited proliferation of mucin- and mixed-IHCCA. Either mucin- or mixed-IHCCA showed high sensitivity to nanomolar concentrations of the dual PI3-kinase/mTOR inhibitor, NVP-BEZ235. In vivo, in subcutaneous xenografts, either NVP-BEZ235 or Abraxane, blocked tumor growth. In conclusion, mucin- and mixed-IHCCA are characterized by a different drug sensitivity. Cisplatin, Abraxane and the MEK 1/2 inhibitor, Selumetinib

  14. Two-stage transjugular intrahepatic porta-systemic shunt for patients with cirrhosis and a high risk of portal-systemic encephalopathy patients as a bridge to orthotopic liver transplantation: A preliminary report

    NARCIS (Netherlands)

    T. Wroblewski; O. Rowinski; B. Ziarkiewicz-Wroblewska; B. Gornicka; J. Albrecht; E.A. Jones; M. Krawczyk

    2006-01-01

    Aim. Placement of a transjugular intrahepatic porta-systemic shunt (TIPS) is a therapeutic option for the management of bleeding esophageal varices. However, the procedure is associated with an increased risk of portal-systemic encephalopathy (PSE). In this study, a two-stage modification of the sta

  15. Transjugular intrahepatic portosystemic shunt in children; Der transjugulaere intrahepatische portosystemische Shunt bei Kindern. Erste klinische Erfahrungen und Literaturuebersicht

    Energy Technology Data Exchange (ETDEWEB)

    Huppert, P.E.; Brambs, H.J.; Schott, U.; Pereira, P.; Duda, S.H.; Claussen, C.D. [Tuebingen Univ. (Germany). Abt. fuer Radiologische Diagnostik; Astfalk, W.; Schweizer, P. [Tuebingen Univ. (Germany). Abt. Kinderchirurgie; Dopfer, R.E. [Tuebingen Univ. (Germany). Abt. Kinderheilkunde I

    1998-06-01

    Purpose: To present special methodical and clinical findings of transjugular intrahepatic portosystemic shunts (TIPSS) in children and to discuss potential indications. Patients and Methods: Between 1993 and 1996, 6 children aged 2-13 years were treated by TIPSS-insertion. In four cases, the underlying disease was extrahepatic biliary atresia (EHBA) and in two cases liver fibrosis secondary to treatment of neoplasms during early childhood. Indications for TIPSS insertion were variceal bleeding resistant to other treatment modalities in three patients, hypersplenism in one patient and both bleeding and hypersplenism in two. Portal vein punctures were performed using 16-gauge needles, because 19-gauge fine-needles showed insufficient stiffness. The mean follow-up was 24.5 months. Results: Shunt insertion succeeded in all children with a mean procedure time of 5.2 hours. Periportal fibrosis associated with EHBA, atypical course of hepatic veins and small diameters and distances of vessels were conditions making the procedure difficult. Bleeding ceased in all patients, peripheral platelet counts rose by a mean value of 58%. Procedure-related complications were minor extrahepatic bleeding in one child and temporary haemolysis in another child. Restenoses resulted in three patients and were treated successfully by means of transjugular interventions. 5 children remain free of symptoms to this day, one child underwent successful orthotopic liver transplantation 8 months after TIPSS. Conclusions: TIPSS insertion is technically more difficult in children and has to consider child growth and possible subsequent liver transplantation. Potential indications are recurrent variceal bleeding, also of intestinal origin, resistant to standard tretment and clinically significant hypersplenism. (orig.) [Deutsch] Ziel: Darstellung methodischer und klinischer Besonderheiten sowie potentieller Indikationen des transjugulaeren intrahepatischen portosystemischen Shunts (TIPSS) bei Kindern

  16. Diagnosis and treatment of mucin-producing intrahepatic biliary tumors%肝内胆管黏液性肿瘤的诊断与治疗

    Institute of Scientific and Technical Information of China (English)

    严茂林; 王耀东; 魏少明; 田毅峰; 赖智德; 邱福南; 周松强

    2013-01-01

    目的 探讨肝内胆管黏液性肿瘤(mucin-producing intrahepatic biliary tumor,MPIBT)的诊断与治疗方法.方法 回顾性分析福建省立医院肝胆外科2004-2011年收治的16例MPIBT患者的临床资料.结果 16例中男6例,女10例,年龄44~ 69岁,平均60岁.主要临床表现为黄疸合并上腹疼痛5例,急性胆管炎4例,无痛性黄疸2例;上腹疼痛不适3例;无明显症状l例;3个月内体重减轻>5 kg者5例.MPIBT的磁共振胰胆管成像(MRCP)最主要特征为肝内胆管不对称性扩张和远离肿块的肝内外胆管扩张而无肝外胆管的突然截断.原发肿瘤位于左肝胆管15例,右肝胆管l例.行半肝切除13例,其中胆肠吻合8例;3例行姑息性胆道引流术.病理学诊断:肝内胆管黏液腺癌13例,肝内胆管黏液腺瘤3例.l、2、3年生存率分别为81%、66%、56%.结论 MPIBT临床表现无特异性,MRCP有助于明确诊断与判断肿瘤累及范围,根治性切除是其首选治疗方法,姑息性胆道引流能延长患者生存时间.%Objective To investigate the diagnosis and treatment of mucin-producing intrahepatic biliary tumor (MPIBT).Methods We retrospectively analyzed the clinical,radiologic,surgical and pathologic findings of 16 MPIBT cases from January 2004 to December 2011.Results There were six men and ten women,age ranged from 44 to 69 years (mean 60 years).Clinical presentation included jaundice with abdominal dull pain in 5 patients,acute cholangitis in 4 patients,painless jaundice in 2 patients,upper abdominal dull pain in 3 patients,no obvious symptoms in 1 patient,body weight loss more than 5 kg within 3 months in 5 patients.The most characteristic appearance of MPIBT on magnetic resonance cholangiopancreatography were asymmetry of intrahepatic bile duct dilatation and the dilatation in both extraand intrahepatic bile duct distal to the hepatic mass and not sudden interruption in extrahepatic bile duct.The primary tumor located in the left

  17. 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.

  18. ANALYSE THE CLINICAL FEATURES OF 97 INTRAHEPATIC CHOLANGIOCARCINOMA PATIENTS%97例肝内胆管细胞癌临床特点分析

    Institute of Scientific and Technical Information of China (English)

    闫学强; 郑楠楠; 陈孝平

    2012-01-01

    目的 探讨肝内胆管细胞癌临床特点与生物学特点之间的联系,为临床治疗提供更多的帮助.方法 回顾性分析华中科技大学同济医学院附属同济医院,自1985年4月至2008年12月间97例肝内胆管细胞癌临床及术后病理资料.结果 1.43.98% (42/97)的患者乙肝表面抗原阳性,男性组阳性率(51.61%)明显高于女性组(28.57%),差异有显著性意义(P<0.05).2.原发肿瘤位于肝左叶的ICC患者发生转移(67.27% (37/55)明显高于位于肝右叶的ICC患者(40.48%(17/42)),差异具有显著性(P<0.05);3.病理提示肿瘤中-低分化而发生转移(66.67%(34/51))较高分化者(43.48%(20/46))高,差异具有显著性(P<0.05).4.一年内复发率27.85%(22/79),复发组术中输血率(63.64% (14/22))明显高于未复发组(31.58%(18/57))两者之间差异具有显著性(P<0.05).结论 1.慢性乙肝或血清学HBV阳性患者中,男性发展成肝内胆管细胞癌的几率更大.2.ICC发生转移特点因肿瘤的位置和分化程度不同而存在差异.3.输血是肿瘤术后复发的危险因素之一.%Objective To investigate the link between clinical features and the biological characteristics of intrahepatic cholangiocarcinoma. Method 97 cases of intrahepatic cholangiocarcinoma of clinical and pathological information were retrospectively analyzed in Wuhan Tongji hospital from April 1985 to December 2008. Results 1. 43. 98% (42/97) of patients with hepatitis B surface antigen positive in which positive rate of males (51. 61% ) was significantly higher than the female group (28. 57% ). The difference was statistically significant (P<0. 05). 2. The primary tumor in the left lobe of the ICC with liver metastasis (67. 27% (37/ 55)) significantly higher than the primary tumor in the right lobe (40. 48% (17/42)). The difference was statistically significant (P <0. 05) ; 3. It was significant (P <0. 05) that moderate-poorly differentiated tumor (66. 67% (34

  19. 表观遗传学药物对肝内胆管癌的作用%Effects of epigenetic drugs in intrahepatic cholangiocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    周文杰; 张锦前; 贺轲; 段小鹏; 黄睿; 夏正林; 何景亮; 向国安

    2016-01-01

    Objective Screening of epigenetic drugs sensitive to intrahepatic cholangiocarcinoma and exploring the mechanism.Methods Screening a 96-epigenetic library in RBE cells through cell validity assay and comparing the inhibition effect of these sensitive drugs on multiple cell lines;Giemsa staining was used to observe the cell morphological change and flow cytometry to check the cell cycle distribution;Morphological observation,flow cytometry technique and Western blotting were combined to check the cell apoptosis.Results Twenty two drugs from the 96-epigenetic library had certain inhibition on RBE cells,including twelve histone deacetylase (HDAC) targeted species;HC-toxin' s inhibition effect on four intrahepatic cholangiocarcinoma cell lines were the most obvious among the HDAC inhibitors' and were superior to that of gemcitabine;cells at G0/G1 phases in HC toxin treated group was much more than that in control group (82.93% vs.48.51%) and HC toxin brought about diverse of morphological changes,apoptosis bodies and reduced mitosis included;flow cytometry indicated intensively apoptosis inducted by HC toxin and it was not associated with Caspase-3 depended pathways for the Caspase-3 up-regulated in the trial groups tested by Western blotting was not remarkable in statistics.Conclusion HDAC inhibitors,especially HC toxin,are of great potential in the treatment of intrahepatic cholangiocarcinoma.%目的 筛选肝内胆管癌敏感的表观遗传学药物并研究其作用机制.方法 采用细胞活力实验筛选对RBE细胞敏感的药物;在多种细胞株上比较其作用;选择最敏感的药物探讨其机制:通过Giemsa染色观察肝内胆管癌细胞经药物处理后的形态学变化,用流式细胞技术检测细胞周期分布,联合流式细胞技术、Western blot检测细胞的凋亡.结果 RBE细胞分别经96种表观遗传学药物处理48 h,27 μmol/L浓度下22种药物对RBE细胞有抑制作用(细胞活力<60%),组蛋白

  20. Notch1 is overexpressed in human intrahepatic cholangiocarcinoma and is associated with its proliferation, invasiveness and sensitivity to 5-fluorouracil in vitro.

    Science.gov (United States)

    Wu, Wen-Rui; Zhang, Rui; Shi, Xiang-De; Zhu, Man-Sheng; Xu, Lei-Bo; Zeng, Hong; Liu, Chao

    2014-06-01

    The Notch signaling pathway has been reported to play crucial roles in inhibiting hepatocyte differentiation and allowing formation of intrahepatic bile ducts. However, little is known about its significance in intrahepatic cholangiocarcinoma (ICC). The aim of the present study was to investigate the effects of Notch1 expression in ICC tissues and cells. The expression of Notch1 was examined in paraffin-embedded sections of ICC (n=44) by immunohistochemistry. Notch1 was knocked down by RNA interference (RNAi) in cultured ICC cells (RBE and HCCC-9810). The proliferation, invasiveness and sensitivity to 5-fluorouracil (5-FU) were detected by Cell Counting Kit-8 (CCK-8), colony formation assays, Transwell assays and flow cytometry, respectively. The expression levels of several multidrug resistance (MDR)-related genes, MDR1-P-glycoprotein (ABCB‑1), breast cancer resistance protein (ABCG‑2) and the multidrug resistance protein isoform 1 (MRP‑1), were examined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Notch1 was overexpressed in cell membranes and cytoplasm of ICC compared with the adjacent liver tissue (35/44, 79.5%) and this was more common in cases with tumor size≥5 cm (p=0.021) and HBs-Ag positive (p=0.018). By silencing Notch1, the proliferation and invasiveness of ICC cells were inhibited and the inhibition rate of 5-FU was markedly increased. In addition, IC50 values of 5-FU in RBE cells were decreased from 148.74±0.72 to 5.37±0.28 µg/ml and the corresponding values for HCCC-9810 cells were 326.92±0.87 to 42.60±0.35 µg/ml, respectively. Furthermore, Notch1 silencing clearly increased the percentage of apoptotic cells treated by 5-FU compared with the control. Notch1 knockdown led to diminished expression levels of ABCB‑1 and MRP‑1. Therefore, Notch may play important roles in the development of ICC. Silencing Notch1 can inhibit the proliferation and invasiveness of ICC cells and increase their

  1. Recurrent Amplification at 13q34 Targets at CUL4A, IRS2, and TFDP1 As an Independent Adverse Prognosticator in Intrahepatic Cholangiocarcinoma.

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    Ting-Ting Liu

    Full Text Available Amplification of genes at 13q34 has been reported to be associated with tumor proliferation and progression in diverse types of cancers. However, its role in intrahepatic cholangiocarcinoma (iCCA has yet to be explored. We examined two iCCA cell lines and 86 cases of intrahepatic cholangiocarcinoma to analyze copy number of three target genes, including cullin 4A (CUL4A, insulin receptor substrate 2 (IRS2, and transcription factor Dp-1 (TFDP1 at 13q34 by quantitative real-time polymerase chain reaction. The cell lines and all tumor samples were used to test the relationship between copy number (CN alterations and protein expression by western blotting and immunohistochemical assays, respectively. IRS2 was introduced, and each target gene was silenced in cell lines. The mobility potential of cells was compared in the basal condition and after manipulation using cell migration and invasion assays. CN alterations correlated with protein expression levels. The SNU1079 cell line containing deletions of the target genes demonstrated decreased protein expression levels and significantly lower numbers of migratory and invasive cells, as opposed to the RBE cell line, which does not contain CN alterations. Overexpression of IRS2 by introducing IRS2 in SUN1079 cells increased the mobility potential. In contrast, silencing each target gene showed a trend or statistical significance toward inhibition of migratory and invasive capacities in RBE cells. In tumor samples, the amplification of each of these genes was associated with poor disease-free survival. Twelve cases (13.9% demonstrated copy numbers > 4 for all three genes tested (CUL4A, IRS2, and TFDP1, and showed a significant difference in disease-free survival by both univariate and multivariate survival analyses (hazard ratio, 2.69; 95% confidence interval, 1.23 to 5.88; P = 0.013. Our data demonstrate that amplification of genes at 13q34 plays an oncogenic role in iCCA featuring adverse disease

  2. 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

  3. Impressive response to dual BRAF and MEK inhibition in patients with BRAF mutant intrahepatic cholangiocarcinoma—2 case reports and a brief review

    Science.gov (United States)

    Lavingia, Viraj

    2016-01-01

    Intrahepatic cholangiocarcinoma (ICC) typically presents at an advanced stage and is associated with a poor oncological outcome. The median survival for metastatic ICC is less than 1 year with standard chemotherapy. ICC is associated with distinct oncogenic drivers including IDH (isocitrate dehydrogenase), HER-2 (human epidermal growth factor 2), and BRAF (v-Raf murine sarcoma viral oncogene homolog B), which may benefit from matching targeted therapies. Hereby we report 2 cases of BRAF V600E refractory ICC treated with dual BRAF and MEK inhibitors (dabrafenib and trametinib) with excellent clinical and radiological response to therapy and with protracted duration of disease control. Our first patient achieved CR (complete remission) at 6 months of treatment with ultimate disease progression at 9 months. The second patient achieved a PR (partial response) at 2 months from starting treatment and remains progression free at 5 months. Our results confirm the activity of dual BRAF and MEK targeting in BRAF mutated ICC, adding further support to 3 additional case-reports in the literature. Dual targeting appears superior to other case reports with BRAF inhibition alone and appear favorable to historic data with cytotoxic chemotherapy. Given the poor outlook and refractoriness of BRAF mutant ICC, future studies should focus on early integration of BRAF/MEK inhibition. PMID:28078132

  4. 妊娠期肝内胆汁淤积症致胎儿宫内窘迫的经验教训%Intrauterine Asphyxia due to Cholestasis in Pregnancy:Experience and lesson

    Institute of Scientific and Technical Information of China (English)

    马俊如

    2006-01-01

    妊娠期肝内胆汁淤积症(intrahepatic chol estasis of pregnancy,ICP)是妊娠期严重并发症之一,以妊娠中、晚期全身瘙痒、黄疸为特征,可导致早产、胎儿窘迫及胎儿死亡,因其早产率及围产儿死亡率高,近年因ICP导致围产儿死亡的医疗纠纷逐渐增多,给产科工作者带来一定的工作压力。现报告2例ICP致胎儿宫内窘迫并死亡的病例,结合文献资料,总结ICP处理过程中的经验教训。

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

    Directory of Open Access Journals (Sweden)

    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

  6. Immunohistochemical expression of mismatch repair genes: A screening tool for predicting mutator phenotype in liver fluke infection-associated intrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Upama Liengswangwong; Anant Karalak; Yukio Morishita; Masayuki Noguchi; Thiravud Khuhaprema; Petcharin Srivatanakul; Masanao Miwa

    2006-01-01

    AIM: To clarify possible contributions of DNA mismatch repair (MMR) system in carcinogenesis of liver fluke infection-associated intrahepatic cholangiocarcinoma (ICC) by using immunohistochemical assay.METHODS: A total of 29 ICC samples, which had been assessed for genomic instability by a PCR-based method, were used for study. They were examined immunohistochemically to demonstrate protein expression of two MMR genes, hMSH2 and hMLH1.Results obtained were compared with their mutator phenotype assessed previously.RESULTS: Either hMSH2or hMLH1 protein was obviously expressed in 28 of 29 (96.6%) ICC samples.Positive nuclear localization of hMSH2 or hMLH1 protein was observed in 86.2% (25/29) or 93.1% (27/29) ICC cases, respectively, while their negative nuclear reactivity was only detected in 13.8% (4/29) or 6.9% (2/29) ICC cases analyzed, respectively.CONCLUSION: Our study, probably for the first time,showed through immunohistochemical detection of hMSH2 and hMLH1 gene that DNA MMR system does not play a prominent role in liver fluke infection-associated cholangiocarcinogenesis. These results confirm previous findings on mutational status of these genes assessed through a PCR-based method. The immunohistochemical analysis has proven to be an effective and sensitive approach for screening MMR deficiency regardless of somatic inactivation or promoter hypermethylation of hMSH2 and/or hMLH1 gene. Furthermore,immunohistochemistry is more advantageous compared to mutator phenotyping assay in terms of simplicity,less time consuming and cost effectiveness for screening possible involvements of target MMR genes in tumorigenesis.

  7. Degradable Starch Microspheres Transcatheter Arterial Chemoembolization (DSM-TACE) in Intrahepatic Cholangiocellular Carcinoma (ICC): Results from a National Multi-Center Study on Safety and Efficacy

    Science.gov (United States)

    Schicho, Andreas; Pereira, Philippe L.; Pützler, Manfred; Michalik, Katharina; Albrecht, Thomas; Nolte-Ernsting, Claus; Stroszczynski, Christian; Wiggermann, Philipp

    2017-01-01

    Background The aim of this study was to evaluate the safety and efficacy of DSM (degradable starch microspheres) as an embolic agent in transarterial chemoembolization in the treatment of intrahepatic cholangiocellular carcinoma (ICC). Material/Methods This was a national, multi-center observational cohort study on the safety and efficacy of DSM-TACE using mitomycin, gemcitabine, cisplatin, doxorubicin, and carboplatin in palliative treatment of ICC. Recruitment period for the study was from January 2010 to June 2014. Primary endpoints were toxicity, safety, and response according to mRECIST criteria. Results Twenty-five DSM-TACE procedures in cases of advanced ICC were performed in seven patients. Nausea and vomiting occurred as adverse event (AE) in eight out of 25 treatments (32%), with seven of eight events (87.5%) associated with the use of gemcitabine. In 11 out of 25 treatments (44%) moderate, transient epigastric pain was registered as an adverse event (AE) within 24 hours of DSM-TACE. One case (1/25) of severe AE (4%) with thrombocytopenia led to discontinuation of the DSM-TACE-treatment. A total of 25 DSM-TACE procedures with complete clinical and imaging follow-up over a two-year-period were analyzed: objective response (OR) was achieved in three of 25 treatments (12%) Disease control (DC) was achieved in 44% (11/25) of treatments; progress was registered in 4% (1/25). Conclusions The use of DSM as an embolic agent for TACE is safe in the treatment of ICC. A standardized anti-emetic medication should be established, especially when using gemcitabine. Further prospective studies need to be conducted to find the most suitable, standardized DSM-TACE treatment regime. PMID:28192388

  8. Effects of WWOX on metastasis of intrahepatic cholangiocarcinoma%WWOX对肝内胆管细胞癌转移的影响

    Institute of Scientific and Technical Information of China (English)

    方雯; 徐三荣; 李相成; 张海

    2014-01-01

    目的:检测包含WW域的氧化还原酶(WW domain containing oxidoreductase,WWOX)在肝内胆管癌(intrahepatic cholangiocarcinoma,ICC)组织及细胞的表达情况,分析其表达水平与ICC临床特征的相关性,并探索其对ICC细胞迁移、侵袭能力的影响.方法:采用半定量/定量PCR测定ICC组织及细胞中WWOX的表达水平;转染重组质粒pcDNA3.1B-WWOX-Flag,过表达ICC细胞内的WWOX水平;采用细胞划痕及侵袭实验,观察过表达WWOX对ICC迁移、侵袭能力的影响;蛋白免疫印迹检测迁移、侵袭通路相关分子.结果:WWOX在ICC组织及细胞中表达下调,其下调与ICC的转移明显相关(P<0.05);转染pcDNA3.1B-WWOX-Flag质粒可上调ICC细胞WWOX蛋白的表达;过表达WWOX抑制ICC细胞迁移、侵袭能力(P< 0.001);过表达WWOX可激活细胞外调节蛋白激酶(extracellular regulated protein kinases,ERK)磷酸化,进而下调基质金属蛋白酶9的活性,最终抑制ICC的转移过程.结论:WWOX在ICC中表达下调,体外实验证实过表达WWOX抑制ICC的迁移、侵袭能力.

  9. Changes in cerebral blood flow after transjugular intrahepatic portosystemic shunt can help predict the development of hepatic encephalopathy: An arterial spin labeling MR study

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Gang [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China); College of Civil Aviation, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu 210016 (China); Zhang, Long Jiang [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China); Wang, Ze [Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, 3900 Chestnut St., Philadelphia, PA 19104 (United States); Qi, Rong Feng; Shi, Donghong [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China); Wang, Li [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China); College of Civil Aviation, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu 210016 (China); Fan, Xinxin [Research Institute of General Surgery, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China); Lu, Guang Ming, E-mail: kevinzhanglongjiang@yahoo.com.cn [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China)

    2012-12-15

    Background and purpose: Cerebral blood flow (CBF) changes after transjugular intrahepatic portosystemic shunt (TIPS) are still unclear. Our aim is to assess the TIPS-induced CBF changes and their potential clinical significance using the arterial spin labeling (ASL) perfusion magnetic resonance imaging. Materials and methods: Nine cirrhotic patients underwent ASL 1–8 days before and 4–7 days after TIPS. CBF was calculated at each voxel and mean CBF values were computed in the whole brain, gray matter and white matter. Changes of CBFs before and after TIPS were compared by paired t-test. Results: Voxel-wise results showed CBF diffusely increased in patients after TIPS, but no region with significant decrease in CBF was found, nor was any significant mean CBF difference detected in the whole brain, gray matter and white matter. Six patients out of nine showed a global CBF increase of 9–39%; one patient presented a global CBF decrease of 6%; another two showed a global CBF decrease of 16% and 31% respectively. Follow-up studies showed that the two patients with greatly decreased global CBF suffered from multiple episodes of overt hepatic encephalopathy (OHE) after TIPS and one died of OHE. Conclusions: CBF derived from noninvasive ASL MRI could be used as a useful biomarker to predict the development of OHE through consecutively tracking CBF changes in patients with inserted TIPS. Increased CBFs in many cortical regions could be common effects of the TIPS procedure, while decreased global CBF following TIPS might indicate the development of OHE.

  10. Efficacy of TACE in TIPS Patients: Comparison of Treatment Response to Chemoembolization for Hepatocellular Carcinoma in Patients With and Without a Transjugular Intrahepatic Portosystemic Shunt

    Energy Technology Data Exchange (ETDEWEB)

    Kuo, Yuo-Chen, E-mail: yuo-chen.kuo@ucsf.edu; Kohi, Maureen P., E-mail: maureen.kohi@ucsf.edu; Naeger, David M., E-mail: david.naeger@ucsf.edu; Tong, Ricky T., E-mail: ricky.tong@ucsf.edu; Kolli, K. Pallav, E-mail: kanti.kolli@ucsf.edu; Taylor, Andrew G., E-mail: andrew.taylor@ucsf.edu; Laberge, Jeanne M., E-mail: jeanne.laberge@ucsf.edu; Kerlan, Robert K., E-mail: robert.kerlan@ucsf.edu; Fidelman, Nicholas, E-mail: nicholas.fidelman@ucsf.edu [University of California San Francisco, Department of Radiology and Biomedical Imaging (United States)

    2013-10-15

    Purpose: To compare treatment response after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) in patients with and without a transjugular intrahepatic portosystemic shunt (TIPS). Materials and Methods: A retrospective review of patients who underwent conventional TACE for HCC between January 2005 and December 2009 identified 10 patients with patent TIPS. From the same time period, 23 patients without TIPS were selected to control for comparable Model for End-Stage Liver Disease and Child-Pugh-Turcotte scores. The two groups showed similar distribution of Barcelona Clinic Liver Cancer and United Network of Organ Sharing stages. Target HCC lesions were evaluated according to the modified response evaluation criteria in solid tumors (mRECIST) guidelines. Transplantation rate, time to tumor progression, and overall survival (OS) were documented. Results: After TACE, the rate of complete response was significantly greater in non-TIPS patients compared with TIPS patients (74 vs. 30 %, p = 0.03). Objective response rate (complete and partial response) trended greater in the non-TIPS group (83 vs. 50 %, p = 0.09). The liver transplantation rate was 80 and 74 % in the TIPS and non-TIPS groups, respectively (p = 1.0). Time to tumor progression was similar (p = 0.47) between the two groups. OS favored the non-TIPS group (p = 0.01) when censored for liver transplantation. Conclusion: TACE is less effective in achieving complete or partial response using mRECIST criteria in TIPS patients compared with those without a TIPS. Nevertheless, similar clinical outcomes may be achieved, particularly in TIPS patients who are liver-transplantation candidates.

  11. Proposal of a new staging system for intrahepatic cholangiocarcinoma: Analysis of surgical patients from a nationwide survey of the Liver Cancer Study Group of Japan

    Science.gov (United States)

    Sakamoto, Yoshihiro; Matsuyama, Yutaka; Sakamoto, Michiie; Izumi, Namiki; Kadoya, Masumi; Kaneko, Shuichi; Ku, Yonson; Kudo, Masatoshi; Takayama, Tadatoshi; Nakashima, Osamu

    2016-01-01

    BACKGROUND In the current American Joint Committee on Cancer/International Union Against Cancer staging system (seventh edition) for intrahepatic cholangiocarcinoma (ICC), tumor size was excluded, and periductal invasion was added as a new tumor classification‐defining factor. The objective of the current report was to propose a new staging system for ICC that would be better for stratifying the survival of patients based on data from the nationwide Liver Cancer Study Group of Japan database. METHODS Of 756 patients who underwent surgical resection for ICC between 2000 and 2005, multivariate analyses of the clinicopathologic factors of 419 patients who had complete data sets were performed to elucidate relevant factors for inclusion in a new tumor classification and staging system. RESULTS Overall survival data were best stratified using a cutoff value of 2 cm using a minimal P value approach to discriminate patient survival. The 5‐year survival rate of 15 patients who had ICC measuring ≤2 cm in greatest dimension without lymph node metastasis or vascular invasion was 100%, and this cohort was defined as T1. Multivariate analysis of prognostic factors for 267 patients with lymph node‐negative and metastasis‐negative (N0M0) disease indicated that the number of tumors, the presence arterial invasion, and the presence major biliary invasion were independent and significant prognostic factors. The proposed new system, which included tumor number, tumor size, arterial invasion, and major biliary invasion for tumor classification, provided good stratification of overall patient survival according to disease stage. Macroscopic periductal invasion was associated with major biliary invasion and an inferior prognosis. CONCLUSIONS The proposed new staging system, which includes a tumor cutoff size of 2 cm and major biliary invasion, may be useful for assigning patients to surgery. Cancer 2016;122:61–70. © 2015 The Authors. Cancer published by Wiley

  12. The roles of intrahepatic Valpha14(+) NK1.1(+) T cells for liver injury induced by Salmonella infection in mice.

    Science.gov (United States)

    Ishigami, M; Nishimura, H; Naiki, Y; Yoshioka, K; Kawano, T; Tanaka, Y; Taniguchi, M; Kakumu, S; Yoshikai, Y

    1999-06-01

    To investigate the roles of intrahepatic T cells in liver injury after Salmonella infection, we examined serum alanine transaminase (ALT), histopathology, and bacterial numbers in liver after infection with Salmonella choleraesuis strain 31N-1 in mice genetically lacking TCRalpha beta+, CD4(+), CD8(+), or NK1.1(+)T cells with C57BL/6 background. In control (+/+) mice, serum ALT reached a peak level by day 7 after an intraperitoneal inoculation of 2 x 10(6) CFU Salmonella choleraesuis 31N-1. In TCR-beta-/- mice, liver injury, as assessed by serum ALT level and histological examination, was significantly suppressed on day 7 after Salmonella infection but the numbers of bacteria in liver did not differ from those in normal mice, suggesting that alpha beta T cells are responsible for liver injury induced by Salmonella infection. To further determine which subsets in alpha beta T cells are important for the liver injury, we compared serum ALT level in mice genetically lacking CD4, CD8, beta2-microglobulin (beta2m, IAbeta, or Jalpha281 after Salmonella infection. In CD4(-/-) mice, serum ALT was significantly lower in comparison with control mice, but there was no difference in serum ALT levels in CD8(-/-) and IAbeta-/- mice from that in control mice. Notably, serum ALT levels and pathological lesions in liver were significantly decreased in beta2m-/- or Jalpha281(-/-) mice, which lacked in NK1.1(+) T cells bearing TCR Valpha14-Jalpha281 specific for beta2m-associated CD1d, following Salmonella infection. Taken together, it is suggested that alpha beta T cells bearing NK1.1 and CD4 may be main effector cells for liver injury after Salmonella infection.

  13. Degradable Starch Microspheres Transcatheter Arterial Chemoembolization (DSM-TACE) in Intrahepatic Cholangiocellular Carcinoma (ICC): Results from a National Multi-Center Study on Safety and Efficacy.

    Science.gov (United States)

    Schicho, Andreas; Pereira, Philippe L; Pützler, Manfred; Michalik, Katharina; Albrecht, Thomas; Nolte-Ernsting, Claus; Stroszczynski, Christian; Wiggermann, Philipp

    2017-02-13

    BACKGROUND The aim of this study was to evaluate the safety and efficacy of DSM (degradable starch microspheres) as an embolic agent in transarterial chemoembolization in the treatment of intrahepatic cholangiocellular carcinoma (ICC). MATERIAL AND METHODS This was a national, multi-center observational cohort study on the safety and efficacy of DSM-TACE using mitomycin, gemcitabine, cisplatin, doxorubicin, and carboplatin in palliative treatment of ICC. Recruitment period for the study was from January 2010 to June 2014. Primary endpoints were toxicity, safety, and response according to mRECIST criteria. RESULTS Twenty-five DSM-TACE procedures in cases of advanced ICC were performed in seven patients. Nausea and vomiting occurred as adverse event (AE) in eight out of 25 treatments (32%), with seven of eight events (87.5%) associated with the use of gemcitabine. In 11 out of 25 treatments (44%) moderate, transient epigastric pain was registered as an adverse event (AE) within 24 hours of DSM-TACE. One case (1/25) of severe AE (4%) with thrombocytopenia led to discontinuation of the DSM-TACE-treatment. A total of 25 DSM-TACE procedures with complete clinical and imaging follow-up over a two-year-period were analyzed: objective response (OR) was achieved in three of 25 treatments (12%) Disease control (DC) was achieved in 44% (11/25) of treatments; progress was registered in 4% (1/25). CONCLUSIONS The use of DSM as an embolic agent for TACE is safe in the treatment of ICC. A standardized anti-emetic medication should be established, especially when using gemcitabine. Further prospective studies need to be conducted to find the most suitable, standardized DSM-TACE treatment regime.

  14. 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

    Institute of Scientific and Technical Information of China (English)

    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.

  15. The value of contrast-enhanced ultrasonography for peripheral intrahepatic cholangiocarcinoma%肝内胆管细胞癌超声造影表现

    Institute of Scientific and Technical Information of China (English)

    毛枫; 李超伦; 黄备建; 王文平; 袁海霞; 丁红

    2013-01-01

      目的总结肝内胆管细胞癌的超声造影表现。方法回顾性分析2009年1月至2011年12月复旦大学附属中山医院收治的经手术及穿刺活检病理证实的56例肝内胆管细胞癌患者超声造影表现。结果56例肝内胆管细胞癌患者共70个病灶,所有病灶超声造影均表现为“快进快出”,门脉期及延迟期均呈低回声。肝内胆管细胞癌超声造影开始增强时间、达峰时间、表现为等回声时间、表现为低回声时间分别为(14.50±3.82)s、(22.29±4.97)s、(30.38±7.97)s、(43.54±16.80)s。70个病灶中,42个(60.0%,42/70)表现为动脉期病灶边缘不规则环状增强,28个(40.0%,28/70)表现为整体增强;动脉期增强过程中,49个病灶(70.0%,49/70)表现为“树枝状”由周边向中央延伸的特征性的增强方式。超声造影增强达峰值时,51个病灶(72.9%,51/70)表现为不均匀增强,19个(27.1%,19/70)表现为均匀增强。21个病灶(30.0%,21/70)常规二维超声检查病灶边界显示不清,超声造影病灶边界均清晰。所有病灶在门脉期及延迟期均表现为低回声。56个病灶(80.0%,56/70)超声造影表现为“快进快出”、环状增强和(或)树枝状增强。结论肝内胆管细胞癌的超声造影具有“快进快出”、环状增强和(或)树枝状增强等表现,对其诊断和鉴别诊断具有一定的价值。%Objective To investigate the diagnostic value of contrast-enhanced ultrasonography (CEUS ) for peripheral intrahepatic cholangiocarcinoma .Methods Fifty-six cholangiocarcinoma cases confirmed by pathology in Zhongshan Hospital of Fudan University had been analyzed retrospectively .Results All lesions manifested“fast in and fast out”after contrast injection and hypoechoic in portal and delayed phase.The enhancement start time,peak time,time to

  16. Pathological and Molecular Biological Fundament of CT Features of Intrahepatic Cholangiocarcinoma%肝内胆管癌CT表现的病理学和分子生物学基础

    Institute of Scientific and Technical Information of China (English)

    乔慧洁; 王滨

    2004-01-01

    肝内胆管癌(intrahepatic cholangiocarcinoma。ICC)又称胆管细胞癌或外周型胆管癌,是肝脏第二高发的原发恶性肿瘤,仅次于肝细胞癌(hepatocellular carcinoma,HCC)。ICC发生率较低,占原发性肝癌的3.25%,研究人员临床观察结果显示,近年来ICC的发病率呈上升趋势。ICC具有发生隐匿、发展迅速、

  17. 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

  18. 异柠檬酸脱氢酶基因突变在肝内胆管癌中的作用%Isocitrate dehydrogenase gene mutations in intrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    陈骏; 史炯; 毛谅; 仇毓东

    2015-01-01

    Mutations in isocitrate dehydrogenase are among the most common genetic alterations in intrahepatic cholangiocarcinoma (ICC).Mutant IDH proteins in ICC and other malignancies acquire an abnormal enzymatic activity, allowing the conversion of alpha-ketoglutarate (alphaKG) to 2-hydroxyglutarate (2HG), which inhibits the activity of multiple alphaKG-dependent dioxygenases, and results in alterations in cell differentiation and tumorigenesis.This review will focus on recent advances, which may help understand the function of IDH mutation in intrahepatic cholangiocarcinoma.%异柠檬酸脱氢酶(IDH)是肝内胆管癌(ICC)中最常见的基因变异之一.在ICC和其他恶性肿瘤中,突变翻译后的IDH酶可产生异常代谢产物羟戊二酸(2-HG),并取代正常代谢产物a酮戊二酸(a-KG),从而抑制多量a-KG依赖的双加氧酶活性,导致细胞分化改变,肿瘤形成.本文对ICC中IDH基因突变作用的研究进展进行综述.

  19. CT动态增强扫描对周围型肝内胆管细胞癌的诊断价值%The Diagnostic Value of Contrast Enhanced CT Scan in the Diagnosis of Intrahepatic Cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    易建玮

    2013-01-01

      目的 探讨螺旋CT动态增强扫描对肝内胆管细胞癌的应用价值及表现特点。方法回顾性分析经手术病理证实或/和穿刺活检的肝内胆管细胞癌28例,所有病例均行CT平扫和动态增强扫描,所有病例均做甲胎蛋白( AFP)检查。结果15例动脉期病灶边缘呈花环样或不规则状强化,门脉期、静脉期及延时期逐渐向病灶中心强化,病灶周边随时间推移逐渐降低;12例动脉期边缘轻度强化,门脉期、静脉期及延时期向心性强化;2例表现为轻度不均匀强化,随时间延长病灶中央呈网格状强化;5例合并肝内胆管轻度扩张;6例合并胆管结石或小斑片状钙化灶;23例AFP检查为阴性,5例AFP检查为阳性。结论肝内胆管细胞癌的多层螺旋CT动态增强扫描影像表现具有一定特性,对肝内胆管细胞癌确诊有一定帮助。%Objective Investigate the dynamic enhanced spiral CT scan on intrahepatic cholangiocarcinoma application value and characteristics. Methods A retrospective analysis was proved by operation and pathology or/and biopsy of the intrahepatic bile duct carcinoma in 28 cases, all cases underwent CT plain and dynamic enhanced scan, all cases were examined with alpha-fetoprotein ( AFP ) examination. Results 15 cases of arterial lesions in edge was rosette-like or irregular enhancement, portal venous phase delay period, and gradually to the center of the lesion enhancement, lesions of the peripheral with time gradually decreased;in 12 cases of arterial phase edge enhancement, portal venous phase and delay period, centripetal and strong;in 2 cases mild uneven enhancement, with extended time lesions of the central cancellate reinforcing;in 5 cases with intrahepatic bile duct mild dilatation;in 6 patients with calculus of bile duct;in 23 cases of AFP examination is negative, 5 patients tested positive for the AFP. Conclusion Intrahepatic cholangiocarcinoma dynamic enhanced multi-slice spiral CT

  20. Porcine liver: experimental model for the intra-hepatic glissonian approach Figado suíno: modelo experimental para o acesso glissoniano intra-hepático

    Directory of Open Access Journals (Sweden)

    Antonio Cavalcanti de Albuquerque Martins

    2008-04-01

    Full Text Available PURPOSE: The aim of the study is to evaluate the porcine liver as a teaching and training model for the glissonian approach. METHODS: Ten livers were removed from domestic adult white pigs weighting 35 to 45kg. Based on anatomical landmarks, the glissonian pedicles of each liver segments were dissected and biopsies were taken for histological examination, to analyze the presence of the glissonian sheath. RESULTS: During microscopic examination, a sheath of conjunctive tissue was observed wrapping each segmental pedicle in porcine liver. This could be clearly seen when histological preparation for connective tissue was obtained (Masson technique. CONCLUSION: The morphological arrangement of glissonian pedicles in porcine liver makes this model a useful tool for training the intra-hepatic glissonian approach.OBJETIVO: Avaliar a utilização do fígado suíno como um modelo experimental para o ensino e treinamento da técnica glissoniana intra-hepática nas ressecções do fígado. MÉTODOS: Foram utilizados 10 fígados inteiros de porcos adultos brancos, pesando entre 35-45 kg. Os pedículos glissonianos de vários segmentos foram dissecados e ressecados para a realização de estudos histológicos e verificação da presença da bainha conjuntiva ao longo das tríades portais. RESULTADOS: Na microscopia, uma bainha de tecido conjuntivo foi encontrada envolvendo os pedículos glissonianos no fígado suíno. A utilização de preparações específicas para o tecido conjuntivo (Masson ressaltou a presença dessa bainha em cada pedículo. CONCLUSÃO: As características morfológicas dos pedículos glissonianos suínos, fazem desse modelo experimental um método de treinamento da técnica glissoniana intra-hepática.

  1. Early and long-term clinical and radiological follow-up results of expanded-polytetrafluoroethylene-covered stent-grafts for transjugular intrahepatic portosystemic shunt procedures

    Energy Technology Data Exchange (ETDEWEB)

    Maleux, Geert; Heye, Sam; Thijs, Maria; Wilms, Guy [University Hospitals Gasthuisberg, Department of Radiology, Leuven (Belgium); Nevens, Frederik; Verslype, Chris [University Hospitals Gasthuisberg, Department of Hepatology, Leuven (Belgium); Wilmer, Alexander [University Hospitals Gasthuisberg, Department of Medical Intensive Care Unit, Leuven (Belgium)

    2004-10-01

    The purpose of this study was to assess the therapeutic efficacy and immediate and long-term safety of expanded-tetrafluoroethylene covered stent-grafts for transjugular intrahepatic portosystemic shunts in patients with portal hypertension-related complications. A cohort of 56 patients suffering from severe portal hypertension-related complications underwent implantation of an expanded-polytetrafluoroethylene-covered stent-graft. All patients suffered from severe liver cirrhosis graded Child-Pugh A (n=8; 16%), B (n=13; 21%) or C (n=35; 63%). In 44 patients, the stent-graft was placed during the initial TIPS procedure (de novo TIPS); in the other 12 patients, the stent-graft was placed to repermeabilize the previously placed bare stent (TIPS revision). Follow-up was performed with clinical assessment, duplex ultrasound and, if abnormal or inconclusive, with invasive venography and pressure measurements. Per- en immediate post-procedural complications occurred in four patients (4/56, 7%). None of them was lethal. During follow-up, stent occlusion appeared in one patient and stenosis in two; no recurrence of bleeding was noted in all patients treated for variceal bleeding (n=28), and 24 of the 28 patients (86%) suffering from refractory ascites and/or hepatic hydrothorax were free of regular paracenteses and/or drainage of pleural effusion after shunt creation. The 30-day and global mortality for the total study population (n=56) was, respectively, 7% (n=4) and 28.5% (n=16). In the patient subgroup with variceal bleeding (n=28), 30-day mortality was 3.5% (n=1) and global mortality 14.2% (n=4). In the ascites and/or hydrothorax subgroup (n=28), 8.1% (n=3) mortality at 30 days was found and global mortality was 32.4% (n=12). In 10 patients of the 56 studied patients (18%), isolated hepatic encephalopathy occurred, which was lethal in 4 (Child C) patients (7%). Three of these four patients died within the 1st month after TIPS placement. A very high primary patency rate

  2. Long-term Outcome and Analysis of Dysfunction of Transjugular Intrahepatic Portosystemic Shunt Placement in Chronic Primary Budd-Chiari Syndrome.

    Science.gov (United States)

    Hayek, Georges; Ronot, Maxime; Plessier, Aurélie; Sibert, Annie; Abdel-Rehim, Mohamed; Zappa, Magaly; Rautou, Pierre-Emmanuel; Valla, Dominique; Vilgrain, Valérie

    2016-10-31

    Purpose To evaluate the long-term safety, technical success, and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) in a series of patients with Budd-Chiari syndrome (BCS), and to determine the predictors of shunt dysfunction. Materials and Methods From 2004 to 2013, all patients with primary BCS referred for TIPS placement were included in the study. The primary and secondary technical success rates and the number and types of early (ie, before day 7) complications were noted. Factors associated with dysfunction were analyzed with uni- and multivariate analyses. Survival was analyzed with Kaplan-Meier curves. Results Fifty-four patients (34 women [63%]; mean age, 36 years ± 12 [standard deviation]) were included. Twenty-eight patients (52%) had myeloproliferative neoplasms. The mean Model for End-Stage Liver Disease score was 14.5 ± 4. The most frequent indication for TIPS was refractory ascites (50 of 54; 93%). Primary and secondary technical success rates were 93% and 98%, respectively. Early complications occurred in 17 patients (32%). After a mean follow-up of 56 months ± 41 (interquartile range, 22-92), 22 patients (42%) experienced at least one episode of TIPS dysfunction (median delay between administration of TIPS and first episode of dysfunction, 10.8 months). Cumulative 1-, 2-, 3-, 5-, and 10-year primary patency rates were 64%, 59%, 54%, 45%, and 45%, respectively. Dysfunction was associated with a myeloproliferative neoplasm (hazard ratio, 8.18; 95% confidence interval: 1.45, 46.18; P = .017), more than two initial stents (hazard ratio, 3.90; 95% confidence interval:1.16, 13.10; P = .027), and the occurrence of early complications (hazard ratio, 11.34; 95% confidence interval: 1.82, 70.69; P = .009). The 10-year survival rate was 76%. Conclusion TIPS placement in patients with chronic primary BCS was associated with a nonnegligible rate of early complications and required endovascular revision or revisions in 42% of patients

  3. 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

  4. TIPS - anastomose portossistêmica intra-hepática transjugular. Revisão TIPS - transjugular intrahepatic portosystemic shunt. A review

    Directory of Open Access Journals (Sweden)

    Gerson CARREIRO

    2001-01-01

    Full Text Available Diversas alternativas terapêuticas têm sido usadas, atualmente, na tentativa de reduzir a mortalidade de pacientes com hipertensão portal que desenvolvem varizes esofagianas. Abordagem de uma dessas alternativas que ainda é de exceção e pouco utilizada em nosso meio - o "shunt" (desvio portossistêmico intra-hepático transjugular - TIPS ("transjugular intrahepatic portasystemic shunt". O TIPS possibilita redução significativa do gradiente de pressão portohepático, uma vez que funciona como um "shunt" portocava látero-lateral, promovendo, dessa forma, descompressão eficiente do sistema portal, reduzindo significativamente o risco de sangramentos. A técnica consiste na inserção percutânea, através da veia jugular interna, de malha metálica através do parênquima hepático, sob controle angiográfico, criando verdadeira comunicação portocava. Bons resultados na utilização do TIPS têm sido atestados em diversos estudos, muito embora bem poucos deles tenham sido controlados e randomizados de modo a concluir que esse procedimento é seguro, eficaz e com boa relação custo-benefício. Dessa forma, buscou-se, nesta revisão, uma análise do estado atual da utilização do TIPS, sua técnica, principais indicações e complicações. O TIPS vem sendo utilizado nos casos de hemorragia digestiva refratária ao tratamento farmacológico e/ou endoscópico, principalmente em pacientes Child-Pugh B e C ou ainda como opção de controle do quadro, servindo como "ponte" para um futuro transplante hepático. Pode-se considerar ainda o tratamento da ascite refratária, da síndrome hepatorrenal e do hidrotórax hepático como promissoras indicações definitivas para a colocação do TIPS. As complicações dessa técnica estão relacionadas, sobretudo, a sua colocação, às conseqüências hemodinâmicas imediatas, como a encefalopatia hepática, e às complicações tardias envolvendo principalmente a oclusão do "stent" (prótese auto

  5. Application of digitized virtual anatomical techniques in transjugular intrahepatic portosystemic stent shunt and direct intrahepatic portacaval shunt%数字化虚拟解剖学技术在经颈静脉肝内门腔静脉分流术和直接性门腔分流术中的应用

    Institute of Scientific and Technical Information of China (English)

    王剑华; 周庭永; 张本斯; 吕发金; 许俊峰; 唐艳隆; 张秀君

    2011-01-01

    Objective: To validate feasibility of digitized virtual anatomical techniques applied in transjugular intrahepatic protosystemic stent shunt (TIPSS) and direct intrahepatic protacaval shunt (DIPS). Methods: Based on the smart tracking technology (Smart Prep), 64-MSCT scan of the upper abdomens of 40 individuals without liver diseases and 16 patients suffered from cirrhosis were performed. The data were analyzed using GE ADW4. 2 workstation. Results: In groups of normal and cirrhosis graded as Child-Pugh A and B, the angles between the vertical line and simulated puncture line of TIPSS were decreased, excluding those performed at 3 cm apart from the middle hepatic vein and 1 cm apart from the right hepatic vein.As to DIPS, the angles between the vertical line and simulated puncture line through the lower bisecting line were greater than those corresponding angles that performed through the upper bisecting line. Statistical difference was found in the angles between vertical line and the simulated puncture line from the point that 1 cm apart from the left branch of portal hepatic vein to the upper bisecting line in cases with liver diseases and patients suffered from cirrhosis graded as Child-Pugh A and B. Conclusion: Digitized virtual anatomic technology is an effective way to provide morphological data for TIPS and DIPS in vivo. The curvature of the puncture trocar should be adjusted in vitro according to the angles between the vertical line and simulated puncture line.%目的:利用影像数字化虚拟解剖学技术,经颈静脉肝内门腔静脉分流术(TIPSS)、直接性门腔静脉分流术(DIPS)模拟穿刺途径与水平垂线间角度进行测量,以期为临床TIPSS、DIPS术提供解剖学资料.方法:选取上腹部64-MSCT扫描正常组共40例,肝硬化组16例.用智能追踪技术启动扫描,并将所得数据在GE ADW4.2工作站进行处理.结果:正常组与肝硬化Child-Pugh A、B分级组TIPSS模拟穿刺途径与

  6. Surgical Treatment of Intrahepatic Cholelithiasis 78 cases of Curative Effect Observation%手术治疗肝内胆管结石78例疗效观察

    Institute of Scientific and Technical Information of China (English)

    朱先锐

    2013-01-01

      目的:观察手术治疗肝内胆管结石的治疗效果,总结临床经验及方法.方法:对2009年10月~2012年5月收治确诊的78例肝内胆管结石的临床资料进行回顾性分析.结果:本组78例患者术后发生近期并发症10例,占12.8%,术后残留结石14例,残留结石率17.9%,术后均获得6~17个月随访,疗效评定:优良者73例,优良率93.6%;差5例,占6.4%.结论:术前明确结石部位狭窄部位及程度等情况,结合术中B超及胆道镜检查,选择合理的术式可提高肝内胆管结石的治愈率,降低结石残余率、复发率及再手术率.%Objective:To observe the surgical treatment of intrahepatic cholelithiasis the treatment effect, to summarize clinical experience and methods. Methods:October 2009 to May 2012 78 cases were diagnosed intrahepatic cholelithiasis clinical data were retrospectively analyzed. Results:78 cases of postoperative complication occurred in 10 cases,12.8%, Postoperative residual stones in 14 cases, the residual stone rate 17.9%, after surgery the 6 ~ 17 months follow-up,Good person 73 cases, the excellent-good rate is 93.6%;Difference in 5 cases, accounting for 6.4%. Conclusion: Preoperative stone location and degree of stenosisetc,Combined with B-type ultrasonic ultrasound and intraoperative bile duct endoscopy, Reasonable choice of surgical procedures can improve the cure rate of intrahepatic cholelithiasis and lower rate of residual stones, recurrence rate and reoperation rate.

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  8. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... advised to stop taking aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) or blood thinners several days prior to ... you to stop taking aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) or blood thinners for a specified period ...

  9. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... complex and lengthy procedures requiring extended fluoroscopy use) death (rare) top of page What are the limitations ... for encephalopathy , which is an alteration of normal brain function that can lead to confusion. This is ...

  10. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... the equipment look like? How does the procedure work? How is the procedure performed? What will I experience during and after the procedure? Who interprets the results and how do I get them? What are the benefits vs. risks? What are the limitations of TIPS? ...

  11. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... pressure. top of page How does the procedure work? A TIPS reroutes blood flow in the liver ... is removed with it during a transplant operation. Studies have shown that this procedure is successful in ...

  12. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... in creating the TIPS. top of page Additional Information and Resources Society of Interventional Radiology (SIR) - Patient ... Send us your feedback Did you find the information you were looking for? Yes No Please type ...

  13. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... through the TIPS. Pressure will be applied to prevent any bleeding and the opening in the skin ... are monitored in intensive care beforehand and during recovery. You should be able to resume your normal ...

  14. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... a radiologist or other physician. To locate a medical imaging or radiation oncology provider in your community, you can search the ACR- ... with your prescribed procedure with your doctor, the medical facility staff and/or your insurance provider to get a better understanding of the possible ...

  15. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... the stent, which is less common with the current generation of GORE-TEX-lined stents Serious complications, ... of North America, Inc. (RSNA). To help ensure current and accurate information, we do not permit copying ...

  16. Molecular pathogenesis of intrahepatic cholangiocarcinoma

    DEFF Research Database (Denmark)

    Andersen, Jesper Bøje

    2014-01-01

    Cholangiocarcinoma (CCA) is an orphan cancer of the hepatobiliary tract, the incidence of which has increased in the past decade. The molecular pathogenesis of this treatment-refractory disease is poorly understood. Desmoplasia is a key causal feature of CCA; however, a majority of tumors develop...... underlying the diversity of growth patterns of this malignancy remain a clinical concern. It is crucial to advance our present understanding of the molecular pathogenesis of CCA to improve current clinical strategies and patient outcome. This will facilitate the delineation of patient subsets...

  17. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... pregnant and discuss any recent illnesses, medical conditions, allergies and medications you’re taking. You may be ... including herbal supplements, and if you have any allergies, especially to local anesthetic medications, general anesthesia or ...

  18. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... blood flow in the liver and reduces abnormally high blood pressure in the veins of the stomach, esophagus, bowel ... the liver to bypass the liver entirely, reducing high blood pressure in the portal vein and the associated risk ...

  19. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... procedure that uses imaging guidance to connect the portal vein to the hepatic vein in the liver. ... a tunnel through the liver to connect the portal vein (the vein that carries blood from the ...

  20. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... consist of a console containing a computer and electronics, a video display screen and a transducer that ... the placement of the TIPS stent, a contrast material will be injected in the hepatic vein to ...

  1. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... understanding of the possible charges you will incur. Web page review process: This Web page is reviewed regularly by a physician with expertise ... not responsible for the content contained on the web pages found at these links. About Us | Contact Us | ...

  2. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... small amount of gel is put on the skin to allow the sound waves to best travel ... collarbone with a local anesthetic . A very small skin incision is made at the site. Using ultrasound, ...

  3. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... Ultrasound scanners consist of a console containing a computer and electronics, a video display screen and a ... a video display screen that looks like a computer or television monitor. The image is created based ...

  4. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... connect the portal vein to the hepatic vein in the liver. A small metal device called a ... the liver. TIPS may successfully reduce internal bleeding in the stomach and esophagus in patients with cirrhosis. ...

  5. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... doctor all medications that you are taking, including herbal supplements, and if you have any allergies, especially ... which the sound travels. A small amount of gel is put on the skin to allow the ...

  6. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    ... doctor all medications that you are taking, including herbal supplements, and if you have any allergies, especially ... which the sound travels. A small amount of gel is put on the skin to allow the ...

  7. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... in the chest or abdomen. This condition is most commonly seen in adults, often as a result ... minimally invasive procedures such as a TIPS are most often performed by a specially trained interventional radiologist ...

  8. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... TIPS may successfully reduce internal bleeding in the stomach and esophagus in patients with cirrhosis. Tell your ... the liver into the veins of the spleen, stomach, lower esophagus, and intestines, causing enlarged vessels, bleeding ...

  9. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... of page What are some common uses of the procedure? A TIPS is used to treat the ... during the procedure. top of page What does the equipment look like? In this procedure, x-ray ...

  10. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... placed to keep the connection open and allow it to bring blood draining from the bowel back ... on the amplitude (loudness), frequency (pitch) and time it takes for the ultrasound signal to return from ...

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    Full Text Available Toggle navigation Test/Treatment Patient Type Screening/Wellness Disease/Condition Safety En Español More Info Images/Videos About Us News Physician ... any possibility that they are pregnant. Many imaging tests are not performed during pregnancy so as not ...

  12. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... hepatic vein to identify the portal venous system. Access is then gained from the hepatic vein into ... TIPS procedure to make sure that it remains open and functions properly. top of page Who interprets ...

  13. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... discuss any recent illnesses, medical conditions, allergies and medications you’re taking. You may be advised to ... night before. Your doctor will tell you which medication to take in the morning. Leave jewelry at ...

  14. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... hepatic artery, which may result in severe liver injury or bleeding that could require a transfusion or ... intervention heart arrhythmias or congestive heart failure radiation injury to the skin is a rare complication (it ...

  15. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... stent, which is less common with the current generation of GORE-TEX-lined stents Serious complications, reported ... an alteration of normal brain function that can lead to confusion. This is because toxic substances in ...

  16. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... an interventional radiology suite or occasionally in the operating room. Some interventional radiologists prefer performing this procedure ... the hepatic vein to identify the portal venous system. Access is then gained from the hepatic vein ...

  17. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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    Full Text Available ... taking. You may be advised to stop taking aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) or blood thinners ... Your physician may advise you to stop taking aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) or blood thinners ...

  18. 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.

  19. Brain regional homogeneity changes following transjugular intrahepatic portosystemic shunt in cirrhotic patients support cerebral adaptability theory—A resting-state functional MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Ni, Ling; Qi, Rongfeng [Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002 (China); Zhang, Long Jiang, E-mail: kevinzhlj@163.com [Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002 (China); Zhong, Jianhui [Department of Biomedical Engineering, Zhejiang University, Hangzhou, Zhejiang 310027 (China); Zheng, Gang [Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002 (China); Wu, Xingjiang; Fan, Xinxin [Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002 (China); Lu, Guang Ming, E-mail: cjr.luguangming@vip.163.com [Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002 (China)

    2014-03-15

    Purpose: The exact neuro-pathophysiological effect of transjugular intrahepatic portosystemic shunt (TIPS) on brain function remains unclear. The purpose of this study was to investigate the longitudinal brain activity changes in cirrhotic patients with TIPS insertion using resting-state functional MRI (fMRI) with regional homogeneity (ReHo) method. Methods: Fifteen cirrhotic patients without overt hepatic encephalopathy (OHE) planned for TIPS procedure and 15 age- and gender-matched healthy controls were included in this study. Eleven of the 15 patients underwent repeated fMRI examinations at median 7-day following TIPS, 8 patients in median 3-month, and 7 patients in median 1-year follow-up duration, respectively. Regional homogeneity was calculated by the Kendall's coefficient of concordance (KCC) and compared between patients before TIPS and healthy controls with two-sample t test as well as pre-and post-TIPS patients with paired t test. Correlations between the pre- and post-TIPS changes of ReHo and the changes of venous blood ammonia level and number connection test type A (NCT-A)/digit symbol test (DST) scores were calculated by crossing subjects. Results: Compared with healthy controls, 15 cirrhotic patients before TIPS procedure showed decreased ReHo in the bilateral frontal, parietal, temporal and occipital lobes and increased ReHo in the bilateral caudate. Compared with the pre-TIPS patients, 11 post-TIPS patients in the median 7-day follow-up examinations demonstrated decreased ReHo in the medial frontal gyrus (MFG), superior parietal gyrus (SPG), middle/superior temporal gyrus (M/STG), anterior cingulate cortex (ACC), caudate, and increased ReHo in the insula. Eight post-TIPS patients in the median 3-month follow-up examinations showed widespread decreased ReHo in the bilateral frontal and parietal lobes, ACC, caudate, and increased ReHo in the insula and precuneus/cuneus. In the median 1-year follow-up studies, seven post-TIPS patients displayed

  20. 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

  1. 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

  2. Obstetric dermatoses

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  3. 腹腔镜下胆道镜液电碎石术治疗肝内外胆管结石%The clinical analysis of cholangioscopy electrohydraulic lithotripsy with laparoscopy to treat intrahepatic bile duct calculi

    Institute of Scientific and Technical Information of China (English)

    朱晟; 喻强; 金昆; 陈明亮; 张京平

    2012-01-01

    Objective:To summarize the methods,efficacy and safety of the cholangioscopy electrohydraulic lithotripsy with laparoscopy to treat intrahepatic bile duct calculi. Methods: The clinical data of 23 cases from Jan. 2005 to Jan. 2012 with refractory extra-hepatic and intrahepatic bile duct stones underwent cholangioscopy electrohydraulic lithotripsy with laparoscopy were retrospectively analyzed. The calculi-free rate and the incidence of complications were observed. Results:The rate of lithotripsy was 100 % in 23 cases, of which 22 were one-time free of biliary calculi, the free rate was 95. 7% ;0ne cases with more calculi underwent choledochoscope lithotomy through the T tube six weeks after surgery. No complications including biliary tract perforation, bleeding, bile leakage, wound infection and others were accurred. The peritoneal drainage tube was removed 3-4 d after operation,The hospital stay time was 5-7 d. 4 weeks after surgery, routine T-tube cholangiography was done, the T-tube was pinched for 3 d and then was removed. Conclusions: Lap-aroscopic cholangioscopy combined with electrohydraulic lithotripsy could significantly improve the therapeutic effect of the extrahepatic and intrahepatic bile duct calculi,which is safe and reliable.%目的:总结腹腔镜下胆道镜液电碎石术治疗肝内外胆管结石的手术方法、效果及安全性.方法:回顾分析2005年1月至2012年1月采用腹腔镜下胆道镜液电碎石术治疗23例难取性肝内外胆管结石患者的临床资料,观察结石取净率及并发症发生率.结果:23例术中均碎石成功,其中22例一次性取净结石,结石取净率95.7%;1例因结石数量较多,术后6周经T管窦道行胆道镜取石术.无胆道穿孔、大出血、胆漏、切口感染等并发症发生.术后3~4d拔除腹腔引流管,5~7d出院.术后4周常规行T管造影,夹管3d后拔除T管.结论:腹腔镜下结合胆道镜液电碎石术可显著提高肝内外胆管结石的疗效,手术安全、可靠.

  4. PTBD治疗肝内胆管微扩张型梗阻性黄疸%The use of PTBD in patients with obstructive jaundice with nondilated intrahepatic bile ducts

    Institute of Scientific and Technical Information of China (English)

    赵之明; 于德江; 纪文斌; 段卫东; 陆宏伟; 叶晟; 李海林

    2010-01-01

    Objective To investigate the technical and clinical value of PTBD in patients with obstructive jaundice with nondilated intrahepatic bile ducts by the guiding of ultrasound combined with X-ray scan.Methods PTBD was performed in 9 patients with with nondilated intrahepatic bile ducts, guided by combining ultrasound and X-ray scan. 6 patients were punctured to right bile ducts and 3 were left bile ducts. Results Technical success was obtained in all patients. There were only two minor complications: transient hemobilia (n=1 ) and fever( n = 1 ). No hemorrhage and biliary peritonitis were found after procedures. The bilirubin was reduced by75.4 ± 29. 6ummol/L one week later. Conclusion Ultrasound-and-fluoroscopy guided PTBD in patients with nondilated bile ducts is a safe,feasible,and efficient procedure for the palliation of biliary obstruction.%目的 探讨超声实时引导结合X线透视下,经皮肝胆管穿刺置管引流术(PTBD)治疗肝内胆管微扩张型梗阻性黄疸的操作技术及其临床应用价值.方法 回顾性分析9例肝内胆管微扩张型梗阻性黄疸患者的临床资料,6例行右肝胆管PTBD,3例行左肝胆管PTBD.结果 胆管穿刺置管成功率100%,术后短暂性发热1例、一过性血性胆汁1例,未出现腹腔出血及胆汁性腹膜炎等严重并发症,术后一周胆红素平均下降(75.4±29.6)μmol/L.引流时间10 d~5个月.结论 超声引导结合X线透视下PTBD治疗肝内胆管微扩张型梗阻性黄疸是安全可行的.

  5. Treatment of post-bioptic intrahepatic arteriovenous fistulas. Results in 5 HCC patients treated with intraarterial chemo embolization and percutaneous ethanol injection; Trattamento delle fistole artero venose intraepatiche post bioptiche. Risultati in 5 pazienti con epatocarcinoma candidati a chemioembolizzazione

    Energy Technology Data Exchange (ETDEWEB)

    Maspes, Federico; Gandini, Roberto; Pocek, Marco; Montanaro, Martina; Guazzaroni, Manlio; Simonetti, Giovanni [Rome, Univ. ``Tor Vergata`` (Italy). Istituto di Radiologia

    1997-04-01

    They report their experience in the treatment of post-bioptic intrahepatic arterioportal fistulas (HAPF) in 5 patients with hepatocellular carcinoma (HCC) treated February, 1993, to May, 1995. In this retrospective study, they reviewed the imaging findings and clinical records of 3 men and 2 women (age range: 49-71 years) with HCC previously diagnosed with US, CT and biopsy. HAPF was detected by angiography (DSA) performed before chemo embolization (TACE). All HAPFs were referrable to biopsy and were treated with platinum coils positioned through coaxial catheters. TACE was performed immediately after or within a week of HAPF embolization. Therapeutic response after TACE was assessed on the basis of clinical and CT findings, while HAPF embolization success was assessed on the basis of DSA and color Doppler US findings. Complete HAPF occlusion was demonstrated in 4 patients during color Doppler follow-up and immediately after and at 13 and 24 months (in 2 patients) at DSA. Two of 5 patients died, one because of liver failure after 15 months` follow-up and the other because of complications related to liver transplantation at 11 months` follow-up. Of the extant 3 patients, one underwent liver transplantation and was followed-up for 25 months, while the other two are alive after 24 and 13 months. Their experience demonstrates that HAPF embolization HCC patients is really useful for hemodynamic redistribution before TACE and to avoid further HAPF progression.

  6. Case report: massive lower intestinal bleeding from ileal varices. Treatment with transjugular intrahepatic portosystemic shunt (TIPSS); Fallbericht: Massive untere gastrointestinale Blutung aus ilealen Varizen. Behandlung mittels transjugulaerem intrahepatischem portosystemischem Shunt (TIPSS)

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Benitez, R. [Universitaetsklinikum Heidelberg (Germany). Abteilung fuer Diagnostische und Iinterventionelle Radiologie; Universitaetsklinikum, Abteilung fuer Diagnostische und Interventionelle Radiologie, Heidelberg (Germany); Seidensticker, P.; Richter, G.M.; Stampfl, U.; Hallscheidt, P. [Universitaetsklinikum Heidelberg (Germany). Abteilung fuer Diagnostische und Iinterventionelle Radiologie

    2007-05-15

    Acute gastrointestinal bleeding in patients with liver cirrhosis is associated with a high mortality. Ileal varices and collaterals from ectopic vessels are extremely rare, encountered in less than 5% of the cirrhotic patients. The diagnosis is frequently delayed because the regular diagnostic methods such as gastroscopy or colonoscopy are unsuccessful in accurate the source of bleeding in the majority of the cases. We report an unusual case of massive and uncontrollable lower intestinal bleeding from ileal varices with right ovarian vein anastomosis in a 56 year-old female patient with liver cirrhosis and previous history of abdominal and pelvic surgery. The accurate angiographic and computed tomography diagnosis allowed fast decompression of the portal venous system using a transjugular intrahepatic portosystemic shunt. (orig.) [German] Akute gastrointestinale Blutungen sind bei Leberzirrhosepatienten mit einer hohen Mortalitaet verbunden. Ileale Varizen und Kollateralen aus anderen ektopen Gefaessen des Darms sind extrem selten und treten bei weniger als 5% aller Zirrhosepatienten auf. Die Diagnosestellung erfolgt oft verspaetet, da die ueblichen diagnostischen Untersuchungsmethoden wie Gastroskopie oder Koloskopie in den meisten Faellen die Blutungsquelle nicht ausreichend darstellen. Wir berichten ueber einen ungewoehnlichen Fall von massiver und unkontrollierbarer unterer gastroinstestinaler (GI-)Blutung aus ilealen Varizen mit Verbindung zur rechten V. ovarica einer 56-jaehrigen Frau, bei der anamnestisch eine Leberzirrhose und abdominelle Operationen sowie Operationen im Bereich des Beckens bekannt waren. Die genaue angiographische und computertomographische Diagnose erlaubte eine rasche Dekompression des Portalvenensystems mittels eines transjugulaeren portosystemischen Shunts. (orig.)

  7. 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

  8. 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

  9. Study on differences of clinicopathologic data between multicentric occurrence and intrahepatic metastusis of hepatocellular carcinoma%肝癌多中心发生与肝内转移的临床病理学差异研究

    Institute of Scientific and Technical Information of China (English)

    王健; 孙燕; 崔云龙; 郑红; 李强

    2009-01-01

    Objective To explore the incidence of muhicentric occurrence(MO)and intrahepat-ic metastasis(IM)in patients with multiple HCC related to HBV and to analyze the differentiated clin-icopathologic variables between them.Methods The clinicopathologic data of patients with multiple HCC resected in our hospital were collected.Their multiple types were confirmed by pathological anal-ysis.Then all cases were divided into group MO and group IM.The differentiated factors and progno-sis between them were statistically appraised.Results By pathology,18.0%(16/89)of all the cases and 64.0%(57/89)were confirmed tO be MO and IM.Stepwise regression analysis showed that tumor grade,size,cholinesterase,Child-Pugh grade and portal vein invasion were discriminant factors between group MO and group IM.The prognosis of MO was better than that of IM and tumor type (MO or IM)and Child-Pugh grade were the independent prognostic factors.Conclusion The multiple HCCs in our centre iS mainly caused by IM,while the incidence of MO iS only 18%.The prognosis of patients with MO HCCS iS better than that of those with IM ones.For former cases,aggressive sur- gery should be encouraged.Tumor grade,size,cholinesterase,Child-Pugh grade and portal vein inva-sion may benefit clinical doctors much in discriminating MO and IM.%目的 探讨HBV相关的多结节肝癌病人中,多中心发生与肝内转移肝癌的发病情况和两种类型肝癌的临床病理学差异因素.方法 收集天津医科大学附属肿瘤医院经手术切除的多结节肝癌病人的临床病理资料.根据多结节肝癌的病理学特征,分为多中心发生组和肝内转移组,统计学分析两种类型肝癌的差异因素和预后.结果 89例多结节肝癌病人中,16例(18.0%)为多中心发生,57例(64.0%)为肝内转移;逐步回归多因素分析显示肿瘤分级、肿瘤大小、胆碱酯酶、Child's分级和门静脉侵犯在两组间差异显著(P<0.05);多中心发生组的总体生存情况