Elevated levels of circulating osteopontin are associated with a poor survival after resection of cholangiocarcinoma.

Abstract:

BACKGROUND & AIMS:Cholangiocarcinoma (CCA) represents a primary hepatic malignancy with incidence and mortality rising globally. Surgical treatment has remained the only potentially curative treatment option, but it is still unclear which patients benefit most from extended liver surgery, highlighting the need for new pre-operative stratification strategies. Osteopontin is a secreted extracellular glyco-phosphoprotein that has been associated with inflammation, metabolic disorders and cancer. Here, we examined the potential of circulating osteopontin serum levels as a diagnostic or prognostic biomarker in patients with CCA undergoing extended liver surgery. METHODS:Osteopontin expression levels were analysed in human and murine CCA tumour samples, using semi-quantitative reverse transcriptase PCR and immunohistochemistry. Osteopontin serum concentrations were measured by enzyme-linked immunosorbent assay in 107 patients with CCA undergoing elective tumour resection as well as 55 healthy controls. Results were correlated with clinical data. RESULTS:Correlating with an upregulation in CCA tumour cells and the tumour stroma, serum levels of osteopontin were elevated in patients with cholangiocarcinoma compared to healthy controls and patients with primary sclerosing cholangitis. Importantly, pre- and postoperative elevations of osteopontin showed a striking association with poor postoperative survival. CONCLUSIONS:Serum osteopontin concentrations represent a promising prognostic biomarker in patients resectable CCA which could help to guide preoperative treatment decisions and to identify patients that will particularly benefit from extended liver surgery. Lay summary: Extended liver surgery is the only potentially curative treatment for patients with cholangiocarcinoma (CCA/biliary cancer), but it is currently unclear which patients benefit most from surgery. Detecting serum levels of osteopontin - a specific secreted glycoprotein involved in multiple human diseases - in CCA patients might help to identify those patients that particularly benefit from tumour resection.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Loosen SH,Roderburg C,Kauertz KL,Pombeiro I,Leyh C,Benz F,Vucur M,Longerich T,Koch A,Braunschweig T,Ulmer TF,Heidenhain C,Tacke F,Binnebösel M,Schmeding M,Trautwein C,Neumann UP,Luedde T

doi

10.1016/j.jhep.2017.06.020

subject

Has Abstract

pub_date

2017-10-01 00:00:00

pages

749-757

issue

4

eissn

0168-8278

issn

1600-0641

pii

S0168-8278(17)32121-9

journal_volume

67

pub_type

杂志文章
  • Prevalence and short-term mortality of acute-on-chronic liver failure: A national cohort study from the USA.

    abstract:BACKGROUND & AIMS:Acute-on-chronic liver failure (ACLF) is characterised by the presence of organ failure in patients with decompensated cirrhosis and is associated with high short-term mortality. However, there are limited data on the prevalence and short-term outcomes of ACLF in patients with cirrhosis seen in the US...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2018.12.018

    authors: Hernaez R,Kramer JR,Liu Y,Tansel A,Natarajan Y,Hussain KB,Ginès P,Solà E,Moreau R,Gerbes A,El-Serag HB,Kanwal F

    更新日期:2019-04-01 00:00:00

  • Bile duct bacterial isolates in primary sclerosing cholangitis: a study of explanted livers.

    abstract:BACKGROUND/AIMS:The pathogenesis of the inflammatory lesion in primary sclerosing cholangitis is unknown. The clinical picture is characterized by i.a. episodes of fever, the cause of which also remains speculative. Previous studies of bacterial isolates in the liver or bile ducts in primary sclerosing cholangitis have...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(98)80316-4

    authors: Olsson R,Björnsson E,Bäckman L,Friman S,Höckerstedt K,Kaijser B,Olausson M

    更新日期:1998-03-01 00:00:00

  • Demonstration of McCune-Albright mutations in the liver of children with high gammaGT progressive cholestasis.

    abstract::Two patients presented with neonatal cholestasis and acholic stools as first manifestations of McCune-Albright syndrome. Both went through an extensive evaluation including an exploratory laparotomy with peroperative cholangiography which ruled out biliary atresia. One patient presented from the fourth month of life w...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(00)80202-0

    authors: Silva ES,Lumbroso S,Medina M,Gillerot Y,Sultan C,Sokal EM

    更新日期:2000-01-01 00:00:00

  • Defective aggregation in cirrhosis is independent of in vivo platelet activation.

    abstract:BACKGROUND/AIMS:Platelet function abnormalities contribute to the hemostatic defect in patients with cirrhosis. In this study we evaluated the occurrence of in vivo platelet activation as a possible mechanism of defective platelet aggregation in patients with cirrhosis. METHODS:Nine patients with severe (Child B-C) ci...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(96)80164-4

    authors: Laffi G,Cinotti S,Filimberti E,Ciabattoni G,Caporale R,Marra F,Melani L,Grossi A,Carloni V,Gentilini P

    更新日期:1996-04-01 00:00:00

  • Putrescine decreases cytochrome P450 3A4 levels during liver regeneration in the rat.

    abstract:BACKGROUND/AIMS:The mechanism by which many cytochrome P450 (CYP) isozymes decrease during liver regeneration is unclear. Peptides and growth factors are thought to be involved. Putrescine, the first polyamine synthesised by ornithine decarboxylase, peaks early following partial hepatectomy and is known to play an esse...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(98)80295-x

    authors: Favre C,Monti JA,Scapini C,Pellegrino J,Carnovale CE,Carrillo MC

    更新日期:1998-04-01 00:00:00

  • Transarterial embolization for hepatocellular carcinoma. Antibiotic prophylaxis and clinical meaning of postembolization fever.

    abstract:BACKGROUND/AIMS:The aim of this prospective randomized controlled trial was to investigate the need for prophylactic antibiotherapy in patients with cirrhosis and hepatocellular carcinoma who underwent transarterial embolization and to establish the parameters that determine the development of fever > 38 degrees C afte...

    journal_title:Journal of hepatology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1016/0168-8278(95)80103-0

    authors: Castells A,Bruix J,Ayuso C,Brú C,Montanyà X,Boix L,Rodès J

    更新日期:1995-04-01 00:00:00

  • Enhanced free cholesterol, SREBP-2 and StAR expression in human NASH.

    abstract:BACKGROUND/AIMS:Non-alcoholic fatty liver disease (NAFLD) pathogenesis remains unknown. Due to the emerging role of free cholesterol (FC) in NAFLD, our aim was to examine the correlation between FC accumulation in patients with NAFLD and the expression of enzymes that regulate cholesterol homeostasis. METHODS:Filipin ...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2008.12.016

    authors: Caballero F,Fernández A,De Lacy AM,Fernández-Checa JC,Caballería J,García-Ruiz C

    更新日期:2009-04-01 00:00:00

  • Bone marrow-derived fibrocytes participate in pathogenesis of liver fibrosis.

    abstract:BACKGROUND/AIMS:Hepatic stellate cells (HSCs) play a key role in hepatic fibrogenesis. However, their origin is still unknown. We tested the hypothesis that bone marrow (BM) contributes to the population of HSCs. METHODS:Chimeric mice transplanted with donor BM from collagen alpha1(I)-GFP+ reporter mice were subjected...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2006.04.014

    authors: Kisseleva T,Uchinami H,Feirt N,Quintana-Bustamante O,Segovia JC,Schwabe RF,Brenner DA

    更新日期:2006-09-01 00:00:00

  • Comparison of test performance profile for blood tests of liver fibrosis in chronic hepatitis C.

    abstract:BACKGROUND/AIMS:We evaluated the test performance profile (TPP) of blood tests of liver fibrosis. METHODS:Three hundred and fifty-six patients with C chronic hepatitis were included in two centers. Metavir staging of liver specimens by two independent pathologists and the following tests were evaluated: Fibrotest (FT)...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2006.09.020

    authors: Halfon P,Bacq Y,De Muret A,Penaranda G,Bourliere M,Ouzan D,Tran A,Botta D,Renou C,Bréchot MC,Degott C,Paradis V

    更新日期:2007-03-01 00:00:00

  • Effect of ventriculo-arterial coupling on transplant outcomes in cirrhotics: Analysis of pressure-volume curve relations.

    abstract:BACKGROUND & AIMS:Ventriculo-arterial coupling (VAC) reflects the interaction between ventricular performance and effective arterial load. Current criteria for cirrhotic cardiomyopathy focus only on cardiac function without addressing the effect of hyperdynamic, low-resistance circulation. We investigated alterations i...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2016.09.009

    authors: Shin WJ,Song JG,Jun IG,Moon YJ,Kwon HM,Jung K,Kim SO,Hwang GS

    更新日期:2017-02-01 00:00:00

  • Platelet basal cytosolic calcium: the influence of plasma factors in cirrhosis.

    abstract:BACKGROUND:Platelet cytosolic calcium is necessary for normal platelet function, and may reflect intracellular signalling in vascular smooth muscle cells. METHODS:The cytosolic calcium of platelets from patients with cirrhosis and control subjects was measured in contact with plasma from either source, using FURA 2AM....

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(96)80117-6

    authors: Forrest EH,Dillon JF,Campbell TJ,Newsome PN,Hayes PC

    更新日期:1996-09-01 00:00:00

  • Mutation of TP53 gene is involved in carcinogenesis of hepatic undifferentiated (embryonal) sarcoma of the adult, in contrast with Wnt or telomerase pathways: an immunohistochemical study of three cases with genomic relation in two cases.

    abstract:BACKGROUND/AIMS:Hepatic undifferentiated (embryonal) sarcoma (HUS) is an exceptional hepatic malignant tumor in adults. Genetic studies were never reported in adult cases. METHODS:In this study concerning three cases of HUS occurring in adult, we studied the three classical ways of carcinogenesis i.e. the TP53 (p53), ...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2004.10.021

    authors: Lepreux S,Rebouissou S,Le Bail B,Saric J,Balabaud C,Bloch B,Martin-Négrier ML,Zucman-Rossi J,Bioulac-Sage P

    更新日期:2005-03-01 00:00:00

  • Interferon-γ-dependent immune responses contribute to the pathogenesis of sclerosing cholangitis in mice.

    abstract:BACKGROUND AND AIMS:Primary sclerosing cholangitis (PSC) is an idiopathic, chronic cholestatic liver disorder characterized by biliary inflammation and fibrosis. Increased numbers of intrahepatic interferon-γ- (IFNγ) producing lymphocytes have been documented in patients with PSC, yet their functional role remains to b...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2019.05.023

    authors: Ravichandran G,Neumann K,Berkhout LK,Weidemann S,Langeneckert AE,Schwinge D,Poch T,Huber S,Schiller B,Hess LU,Ziegler AE,Oldhafer KJ,Barikbin R,Schramm C,Altfeld M,Tiegs G

    更新日期:2019-10-01 00:00:00

  • Mechanisms of HBV-related hepatocarcinogenesis.

    abstract::The hepatitis B virus (HBV) is a small enveloped DNA virus, which primarily infects hepatocytes and causes acute and persistent liver disease. Epidemiological studies have provided overwhelming evidence for a causal role of chronic HBV infection in the development of hepatocellular carcinoma, but the molecular mechani...

    journal_title:Journal of hepatology

    pub_type: 杂志文章,评审

    doi:10.1016/j.jhep.2009.10.033

    authors: Neuveut C,Wei Y,Buendia MA

    更新日期:2010-04-01 00:00:00

  • Possible association between poor metabolism of mephenytoin and hepatotoxicity caused by Atrium, a fixed combination preparation containing phenobarbital, febarbamate and difebarbamate.

    abstract::Drug hepatotoxicity is partially determined by genetic factors involved in drug metabolism, which may involve the debrisoquine oxidation polymorphism mediated by cytochrome (CYP) 2D6. The purpose of this study was to assess the relationship between drug hepatotoxicity and another genetic polymorphism of drug oxidation...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(05)80620-8

    authors: Horsmans Y,Lannes D,Pessayre D,Larrey D

    更新日期:1994-12-01 00:00:00

  • Demonstration of cooperative contribution of MET- and EGFR-mediated STAT3 phosphorylation to liver regeneration by exogenous suppressor of cytokine signalings.

    abstract:BACKGROUND/AIMS:As conditional knockout mice for stat3 are impaired in liver regeneration after partial hepatectomy while those for gp130 have defects in early STAT3 phosphorylation but have normal DNA synthesis, late STAT3 phosphorylation induced independently of gp130 seems to be essential for liver regeneration. Sin...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2007.08.020

    authors: Seki E,Kondo Y,Iimuro Y,Naka T,Son G,Kishimoto T,Fujimoto J,Tsutsui H,Nakanishi K

    更新日期:2008-02-01 00:00:00

  • Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance.

    abstract::The term cirrhosis-associated immune dysfunction refers to the main syndromic abnormalities of immune function, immunodeficiency and systemic inflammation that are present in cirrhosis. The course of advanced cirrhosis, regardless of its aetiology, is complicated by cirrhosis-associated immune dysfunction and this con...

    journal_title:Journal of hepatology

    pub_type: 杂志文章,评审

    doi:10.1016/j.jhep.2014.08.010

    authors: Albillos A,Lario M,Álvarez-Mon M

    更新日期:2014-12-01 00:00:00

  • Incidence of non-alcoholic fatty liver disease in Hong Kong: a population study with paired proton-magnetic resonance spectroscopy.

    abstract:BACKGROUND & AIMS:Because abdominal ultrasonography cannot reliably quantify hepatic steatosis, accurate data on the incidence of non-alcoholic fatty liver disease (NAFLD) are lacking. We aimed to study the population incidence of NAFLD with state-of-the-art non-invasive tests. METHODS:This was a prospective cohort st...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2014.08.041

    authors: Wong VW,Wong GL,Yeung DK,Lau TK,Chan CK,Chim AM,Abrigo JM,Chan RS,Woo J,Tse YK,Chu WC,Chan HL

    更新日期:2015-01-01 00:00:00

  • Association of the IL28B genotype with insulin resistance in patients with chronic hepatitis C.

    abstract:BACKGROUND & AIMS:Insulin resistance, fibrosis and steatosis are established predictors of response to peg-interferon/ribavirin therapy in chronic hepatitis C (CHC). Several host genetic polymorphisms (IL28B, PNPLA3) modify treatment-outcome, the degree of steatosis or fibrosis. The aim of our study was to evaluate the...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2012.04.036

    authors: Stättermayer AF,Rutter K,Beinhardt S,Scherzer TM,Stadlmayr A,Hofer H,Wrba F,Steindl-Munda P,Krebs M,Datz C,Trauner M,Ferenci P

    更新日期:2012-09-01 00:00:00

  • Prediction of sustained remission of chronic hepatitis C after a 12-month course of alfa interferon.

    abstract::alpha-Interferon therapy normalizes aminotransferase levels in approximately 50% of the patients with chronic hepatitis C, but post-therapy relapses are common and predictive factors of sustained response remain largely unknown. We retrospectively assessed several parameters as predictors of sustained remission after ...

    journal_title:Journal of hepatology

    pub_type: 临床试验,杂志文章

    doi:10.1016/s0168-8278(94)80129-0

    authors: Camps J,García-Granero M,Riezu-Boj JI,Larrea E,de Alava E,Civeira MP,Castilla A,Prieto J

    更新日期:1994-07-01 00:00:00

  • Aquaretic agents: a new potential treatment of dilutional hyponatremia in cirrhosis.

    abstract::An impairment in the renal capacity to excrete water is a common finding in patients with cirrhosis and ascites. In some patients this abnormality is minor since it is only detectable by measuring urine volume or free water clearance after a water load and is not associated with changes in plasma osmolality and serum ...

    journal_title:Journal of hepatology

    pub_type: 杂志文章,评审

    doi:10.1016/s0168-8278(96)80174-7

    authors: Ginès P,Jiménez W

    更新日期:1996-04-01 00:00:00

  • Gene transfer to the rat biliary tract with the HVJ-cationic liposome method.

    abstract:BACKGROUND/AIMS:The ability to transfer foreign genes into the biliary tract would be useful for the treatment of biliary tract diseases, including cancer, cystic fibrosis and other genetic diseases. To introduce a foreign gene precisely into the rat biliary epithelial cells, we developed a new technique, inserting a p...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(99)80137-8

    authors: Uehara T,Honda K,Hatano E,Terao R,Iimuro Y,Yamamoto N,Yamamoto M,Kaneda Y,Yamaoka Y

    更新日期:1999-05-01 00:00:00

  • Gastro-oesophageal reflux and alcoholic cirrhosis. A reappraisal.

    abstract::The oesophageal pH was recorded for 3 h after a test-meal in 27 healthy control subjects (group I), 40 patients with alcoholic cirrhosis (group II), and 22 patients with a normal liver and symptoms of gastro-oesophageal reflux (control refluxers). Gastro-oesophageal reflux was observed in 10 of the cirrhotic patients....

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(87)80088-0

    authors: Arsene D,Bruley des Varannes S,Galmiche JP,Denis P,Chayvialle JA,Hellot MF,Ducrotte P,Colin R

    更新日期:1987-04-01 00:00:00

  • Problems in the management of chronic hepatitis B with interferon: experience in a randomized, multicentre study.

    abstract::In a multicentre trial, 82 patients known to be hepatitis B e antigen and hepatitis B virus DNA positive for at least 1 year, with elevated serum alanine aminotransferase levels and chronic liver lesions on biopsy, were randomized to receive either recombinant interferon alfa-2a at a dose of 4.5 million units thrice w...

    journal_title:Journal of hepatology

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:10.1016/0168-8278(90)90179-u

    authors: Realdi G,Fattovich G,Pastore G,Caredda F,Noventa F,Santantonio T,Moroni M,Criscuolo D,Maladorno D,Rugge M

    更新日期:1990-01-01 00:00:00

  • Expression of liver functions following sub-lethal and non-lethal doses of allyl alcohol and acetaminophen in the rat.

    abstract:BACKGROUND/AIMS:To relate severity of intoxication with allyl alcohol and acetaminophen to modulated hepatic gene expression of liver functions and regeneration. METHODS:Rats fasted for 12 h received acetaminophen 3.5 or 5.6 g per kg body weight, or allyl alcohol 100 or 125 microl by gastric tube, doses producing no a...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(97)80296-6

    authors: Tygstrup N,Jensen SA,Krog B,Dalhoff K

    更新日期:1997-07-01 00:00:00

  • Host- and disease-specific factors affecting steatosis in chronic hepatitis C.

    abstract:BACKGROUND/AIM:Steatosis is commonly present in chronic hepatitis C. Our aim was to evaluate host- and disease-specific factors associated with its occurrence. METHODS:Histologic findings in 60 patients were correlated with body mass index, human leukocyte antigens, and other conventional parameters. Comparisons were ...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(98)80004-4

    authors: Czaja AJ,Carpenter HA,Santrach PJ,Moore SB

    更新日期:1998-08-01 00:00:00

  • Hepatocyte proliferative activity in human liver cirrhosis.

    abstract:BACKGROUND/AIMS:The objective of this study was to validate, with an independent prospective cohort of patients, our previous data indicating that the proliferating cell nuclear antigen-labeling index (PCNA-LI) reflects the liver functional reserve in human cirrhosis and might have prognostic significance for patient s...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(99)80106-8

    authors: Delhaye M,Louis H,Degraef C,Le Moine O,Devière J,Peny MO,Adler M,Galand P

    更新日期:1999-03-01 00:00:00

  • Early post-transplant survival: Interaction of MELD score and hospitalization status.

    abstract:BACKGROUND & AIMS:Urgency-based allocation that relies on the MELD score prioritizes patients at the highest risk of waitlist mortality. However, identifying patients at greatest risk for short-term post-transplant mortality is needed in order to optimize the potential gains in overall survival obtained through improve...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2015.03.034

    authors: Bittermann T,Makar G,Goldberg DS

    更新日期:2015-09-01 00:00:00

  • The UK DCD Risk Score: A new proposal to define futility in donation-after-circulatory-death liver transplantation.

    abstract:BACKGROUND & AIMS:Primary non-function and ischaemic cholangiopathy are the most feared complications following donation-after-circulatory-death (DCD) liver transplantation. The aim of this study was to design a new score on risk assessment in liver-transplantation DCD based on donor-and-recipient parameters. METHODS:...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2017.10.034

    authors: Schlegel A,Kalisvaart M,Scalera I,Laing RW,Mergental H,Mirza DF,Perera T,Isaac J,Dutkowski P,Muiesan P

    更新日期:2018-03-01 00:00:00

  • Regional sympathetic activity, severity of liver disease and hemodynamics in patients with cirrhosis.

    abstract::One hundred and eight patients with cirrhosis (23 grade A, 46 grade B and 39 grade C, according to Pugh's classification) underwent hemodynamic studies and plasma catecholamine concentration measurements. Blood samples were withdrawn from the pulmonary artery (n = 108), the hepatic vein (n = 108), the azygos vein (n =...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/0168-8278(91)90810-x

    authors: Gaudin C,Braillon A,Poo JL,Moreau R,Hadengue A,Lebrec D

    更新日期:1991-09-01 00:00:00