Abstract:
BACKGROUND/AIMS:To examine the extent and mechanisms of apoptosis in cholestatic liver injury and to explore the role of the transcription factor nuclear factor-kappa B in protection against bile acid-induced apoptosis. METHODS:Cholestatic liver injury was induced by bile duct ligation in Wistar rats. Furthermore, primary cultures of rat hepatocytes were exposed to glycochenodeoxycholic acid (GCDCA), tauroursodeoxycholic acid (TUDCA), taurochenodeoxycholic acid (TCDCA) and to cytokines. Apoptosis was determined by TUNEL-staining, active caspase-3 staining, activation of caspase-8, -9 and -3. RESULTS:Limited hepatocyte apoptosis and an increased expression of NF-kappaB-regulated anti-apoptotic genes A1 and cIAP2 were detected in cholestatic rat livers. Bcl-2 expression was restricted to bile duct epithelium. In contrast to TCDCA and TUDCA, GCDCA induced apoptosis in a Fas-associated protein with death domain (FADD)-independent pathway in hepatocytes. Although bile acids do not activate NF-kappaB, NF-kappaB activation by cytokines (induced during cholestasis) protected against GCDCA-induced apoptosis in vitro by upregulating A1 and cIAP2. CONCLUSIONS:GCDCA induces apoptosis in a mitochondria-controlled pathway in which caspase-8 is activated in a FADD-independent manner. However, bile acid-induced apoptosis in cholestasis is limited. This could be explained by cytokine-induced activation of NF-kappaB-regulated anti-apoptotic genes like A1 and cIAP2.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Schoemaker MH,Gommans WM,Conde de la Rosa L,Homan M,Klok P,Trautwein C,van Goor H,Poelstra K,Haisma HJ,Jansen PL,Moshage Hdoi
10.1016/s0168-8278(03)00214-9subject
Has Abstractpub_date
2003-08-01 00:00:00pages
153-61issue
2eissn
0168-8278issn
1600-0641pii
S0168827803002149journal_volume
39pub_type
杂志文章abstract::An HBV strain isolated from a patient lacking conventional serological markers of HBV infection was characterized. The complete nucleotide sequence was determined following PCR amplification. Only 22 nucleotide substitutions were found relative to the reported sequence of the ayw subtype. Five of these point mutations...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80252-1
更新日期:1993-06-01 00:00:00
abstract::Calcium concentrations in pig livers were serially estimated following ischemia-reperfusion. Ischemia was produced by clamping the hepatic artery and the portal vein for 90 min (Group 1, n = 6) or for 180 min (Group 2, n = 6) during temporary side-to-side portacaval shunt performed before the induction of ischemia. Al...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80140-0
更新日期:1994-06-01 00:00:00
abstract::The effect of glucagon on the relation between urea synthesis and blood amino acid concentration was studied in seven healthy volunteers. Alanine was given as prime-continuous infusions and, after 1 hr for equilibration, the urea nitrogen synthesis rate was measured in two periods of about 2 hrs as urinary excretion c...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(90)90072-y
更新日期:1990-01-01 00:00:00
abstract:BACKGROUND/AIMS:The underlying mechanisms of steatosis, the first stage of non-alcoholic fatty liver disease (NAFLD) that is characterized by the accumulation of lipids in hepatocytes, remain unclear. Our study aimed to investigate the hypothesis that cigarette smoke is known to change circulating lipid profiles and th...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2009.03.026
更新日期:2009-09-01 00:00:00
abstract::Infections with the hepatotropic viruses non-A, non-B (NANB), hepatitis B (HBV) and delta agent (HDV) are described in two patients with haemophilia. The first patient illustrates the phenomenon of interference following a simultaneous exposure to NANB and HBV. The second patient, a carrier of hepatitis B surface anti...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(85)80775-3
更新日期:1985-01-01 00:00:00
abstract:BACKGROUND & AIMS:Hepatitis B virus (HBV) and D virus (HDV) co-infections cause the most severe form of viral hepatitis. HDV induces an innate immune response, but it is unknown how the host cell senses HDV and if this defense affects HDV replication. We aim to characterize interferon (IFN) activation by HDV, identify ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2018.02.021
更新日期:2018-07-01 00:00:00
abstract:BACKGROUND/AIMS:We reported massive liver repopulation by transplanted hepatocytes in rats given retrorsine (RS), a pyrrolizidine alkaloid which blocks proliferation of resident cells. In these studies, molecular alterations induced by RS on hepatocyte cell cycle were investigated. METHODS:Animals were treated accordi...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2005.03.029
更新日期:2005-09-01 00:00:00
abstract:BACKGROUND/AIMS:Cholesterol crystallization in a dilute, bile salt-rich model bile is a multiphase process in which early filamentous crystals gradually transform to classical cholesterol monohydrate plates. The pertinence of similar transformations in more complex model systems or native bile is, however, unclear. The...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(97)80438-2
更新日期:1997-03-01 00:00:00
abstract::The possible aggravation of liver injury by impaired cellular antioxidant function was investigated. A vitamin E-deficient diet (0.5 mg/kg alpha-tocopherol; control 100 mg/kg) significantly reduced rat liver alpha-tocopherol concentrations after 4 weeks (1.8 +/- 1.7 micrograms/g; control 34.4 +/- 2.4 micrograms/g, p <...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80665-8
更新日期:1992-11-01 00:00:00
abstract:BACKGROUND & AIMS:To determine whether amino acid mutations in the core region of hepatitis C virus (HCV) genotype 1 are associated with response to interferon (IFN) therapy and development of hepatocellular carcinoma (HCC). METHODS:We followed up 361 patients (median duration, 121 months), and IFN monotherapy was adm...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2009.10.001
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND/AIMS:Leptin has a particular profibrogenic role in the liver. We investigated whether IFN-alpha influences leptin production in patients with chronic hepatitis B (CHB) and C (CHC). Leptin was determined in serial samples from 63 CHB and 42 CHC IFN-alpha treated patients. Furthermore, we evaluated whether lep...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2006.01.025
更新日期:2006-05-01 00:00:00
abstract:BACKGROUND & AIMS:Individuals born between 1945 and 1965 account for nearly 75% of hepatitis C virus (HCV) infections in the United States. As this cohort ages, progressive HCV-related liver disease leading to cirrhosis and hepatocellular carcinoma (HCC) will place a significant burden on the healthcare system. We aim ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2015.09.006
更新日期:2016-02-01 00:00:00
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
更新日期:1996-04-01 00:00:00
abstract::Three patients with Budd-Chiari syndrome in association with the 'lupus' anticoagulant are described. This anticoagulant was looked for in our patients with an otherwise idiopathic hepatic venous thrombosis because of the presence of a pronounced thrombocytopenia, a prolonged activated partial thromboplastin time or a...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(86)80151-9
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND & AIM:Natural killer T (NKT) cells are CD1d-restricted innate-like T cells that modulate innate and adaptive immune responses. Unlike the well-characterized invariant/type I NKT cells, type II NKT cells with a diverse T cell receptor repertoire are poorly understood. This study defines the pathogenic role of...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2017.05.024
更新日期:2017-10-01 00:00:00
abstract:BACKGROUND/AIMS:Hepatitis C virus infection is known to play an important role in the pathogenesis of essential mixed cryoglobulinemia type II. Progression of hepatitis C virus infection to mixed cryoglobulinemia may be influenced by host immune response. To analyze the immunogenetic background of mixed cryoglobulinemi...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(98)80176-1
更新日期:1998-07-01 00:00:00
abstract:BACKGROUND & AIMS:Hepatocyte-like cells, differentiated from different stem cell sources, are considered to have a range of possible therapeutic applications, including drug discovery, metabolic disease modelling, and cell transplantation. However, little is known about how stem cells differentiate into mature and func...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.07.025
更新日期:2014-12-01 00:00:00
abstract:BACKGROUND & AIMS:Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease in Western countries. It is unclear how infiltrating leukocytes affect NASH-development. Our study aims to investigate the role of the homing/receptor, pair mucosal addressin cell adhesion molecule-1 (MAdCAM-1)/β7-Integri...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2017.02.001
更新日期:2017-06-01 00:00:00
abstract:BACKGROUND/AIMS:Hepatic stellate cells (HSCs) are known to play a role in hepatic regeneration. We investigated hepatocyte/HSC interaction and HSC activation at various times after 70% partial hepatectomy (PHx) in the rat. METHODS:The hepatic microcirculation was studied using intravital fluorescence microscopy (IVFM)...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2004.02.005
更新日期:2004-06-01 00:00:00
abstract:BACKGROUND & AIMS:Regulatory CD4(+) T cells (Tregs) are considered to affect outcomes of HCV infection, because they increase in number during chronic hepatitis C and can suppress T-cell functions. METHODS:Using microarray analysis, in situ immunofluorescence, ELISA, and flowcytometry, we characterised functional diff...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2013.04.011
更新日期:2013-08-01 00:00:00
abstract:BACKGROUND/AIMS:An interaction between human schistosomiasis and viral hepatitis B has often been suggested, but never established. The experimental investigation has been hampered by the lack of a suitable model. Only woodchucks are susceptible to both Schistosoma mansoni and a B-like hepatitis virus (WHV) infections....
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)00068-4
更新日期:2001-01-01 00:00:00
abstract:BACKGROUND & AIMS:To prospectively assess the diagnostic accuracy of the incorporation of additional magnetic resonance imaging (MRI) parameters in those based on contrast enhancement pattern for the diagnosis of solitary nodules between 5 and 20mm, detected during surveillance in patients with cirrhosis. METHODS:Betw...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.01.004
更新日期:2012-06-01 00:00:00
abstract:BACKGROUND/AIMS:Familial hypobetalipoproteinemia (FHBL) is a co-dominant disorder characterized by reduced plasma levels of low-density lipoproteins. It can be caused by mutations in the gene encoding apolipoprotein B-100 (apo B), leading to the formation of truncated apo Bs which have a reduced capacity to export lipi...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)80270-6
更新日期:2000-09-01 00:00:00
abstract:BACKGROUND & AIMS:In patients with primary biliary cholangitis (PBC), the efficacy of budesonide, a synthetic corticosteroid displaying high first-pass metabolism, is unresolved. In a placebo-controlled, double-blind trial, we evaluated the added-value of budesonide in those with PBC and ongoing risk of progressive dis...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.09.011
更新日期:2021-02-01 00:00:00
abstract::The integrated results of a worldwide clinical research program studying interferon-alpha 2a (IFN-alpha 2a) (Roferon-A, F. Hoffmann-La Roche Ltd, Basel, Switzerland) for the treatment of chronic hepatitis C in 1831 patients are reviewed in this paper. According to a multivariate analysis of the data available from thi...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1995-01-01 00:00:00
abstract::The ischemic biliary phenotype of hereditary hemorrhagic telangiectasia (HHT) is rare but distinct, with progressive biliary tree ischemia usually resulting in an irreversible secondary sclerosing cholangiopathy. When clinically severe, liver transplant is often indicated. We report three patients with marked HHT asso...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2013.02.006
更新日期:2013-07-01 00:00:00
abstract:BACKGROUND/AIMS:Osteopenia is a common complication in some chronic cholestatic liver diseases. Our aims were to determine the prevalence and severity of bone disease in patients with primary sclerosing cholangitis; and identify risk factors to predict the presence and progression of osteopenia. METHODS:Eighty-one pat...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0168-8278(98)80253-5
更新日期:1998-11-01 00:00:00
abstract:BACKGROUND & AIMS:Surgery in cirrhosis is associated with a high morbidity and mortality. Retrospectively reported prognostic factors include emergency procedures, liver function (MELD/Child-Pugh scores) and portal hypertension (assessed by indirect markers). This study assessed the prognostic role of hepatic venous pr...
journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.jhep.2019.07.007
更新日期:2019-11-01 00:00:00
abstract:BACKGROUND/AIMS:Hepatocellular carcinoma recurrence after curative treatment adversely influences clinical outcome. It is important to explore adjuvant therapies. This phase II/stage 1 multi-center, randomized trial investigated the safety, optimal dosage and preliminary efficacy of PI-88, a novel heparanase inhibitor,...
journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.jhep.2008.12.023
更新日期:2009-05-01 00:00:00
abstract:BACKGROUND/AIM:Liver cirrhosis is accompanied by a fall in whole-body protein turnover and alterations of the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis. However, the influence of liver cirrhosis on the GH/IGF-1 axis in the perioperative period, and the contribution of the GH/IGF-1 axis alteration in...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80224-4
更新日期:1999-08-01 00:00:00