Abstract:
BACKGROUND & AIMS:Biliary atresia represents obstructive cholangiopathy in infants progressing rapidly to cirrhosis and end-stage liver disease. Activated NK cells expressing Nkg2d have been linked to bile duct injury and obstruction by establishing contact with cholangiocytes. To define the mechanisms used by cytotoxic cells, we investigated the role of perforin and granzymes in a neonatal mouse model of rotavirus (RRV)-induced biliary atresia. METHODS:We used complementary cell lysis assays, flow cytometric analyses, quantitative PCRs and in vivo systems to determine the mechanisms of bile duct epithelial injury and the control of the tissue phenotype in experimental biliary atresia. RESULTS:RRV-infected hepatic NK and CD8 T cells increased the expression of perforin and injured cholangiocytes in short-term culture in a perforin-dependent fashion. However, the loss of perforin in vivo delayed but did not prevent the obstruction of bile ducts. Based on the increased expression of granzymes by perforin-deficient cytotoxic cells in long-term cytolytic assays, we found that the inhibition of granzymes by nafamostat mesilate (FUT-175) blocked cholangiocyte lysis. Administration of FUT-175 to perforin-deficient mice after RRV infection decreased the development of jaundice, minimized epithelial injury, and improved long-term survival. However, the inhibition of granzymes alone in wild-type mice was not sufficient to prevent the atresia phenotype in newborn mice. In infants with biliary atresia, hepatic Granzymes A and B mRNA, but not Perforin, increased at the time of portoenterostomy. CONCLUSIONS:Perforin and granzymes have complementary roles mediating epithelial injury by NK and CD8 T cells. The prevention of experimental biliary atresia can only be achieved by inhibiting both granules.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Shivakumar P,Mourya R,Bezerra JAdoi
10.1016/j.jhep.2013.09.021subject
Has Abstractpub_date
2014-02-01 00:00:00pages
370-6issue
2eissn
0168-8278issn
1600-0641pii
S0168-8278(13)00681-8journal_volume
60pub_type
杂志文章abstract:BACKGROUND/AIMS:The chemokine receptor CX3CR1 and its specific ligand fractalkine (CX3CL1) are known to modulate inflammatory and fibroproliferative diseases. Here we investigate the role of CX3CR1/fractalkine in HCV-induced liver fibrosis. METHODS:A genotype analysis of CX3CR1 variants was performed in 211 HCV-infect...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2007.09.008
更新日期:2008-02-01 00:00:00
abstract:BACKGROUND/AIMS:Multidrug resistance-associated protein 3 (MRP3) is a carrier-type transport protein belonging to the ABC transporters. It is expressed in normal tissues, and enhanced expression in many cancers has been reported. In this study, we investigated the usefulness of MRP3 as a target antigen in immunotherapy...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2008.05.012
更新日期:2008-12-01 00:00:00
abstract:BACKGROUND & AIMS:Liver fibrosis regression but also progression may occur in patients with autoimmune hepatitis (AIH) under treatment. There is a need for non-invasive surrogate markers for fibrosis development in AIH to better guide immunosuppressive treatment. The aims of the study were to assess the impact of compl...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2017.11.020
更新日期:2018-04-01 00:00:00
abstract::The First European Consensus Conference on the Treatment of Chronic Hepatitis B and C in HIV Co-infected Patients aimed to produce recommendations that could be applied across Europe. However, some important differences exist around Europe, in terms of access to treatment and tests for monitoring. This short survey of...
journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.jhep.2005.11.034
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND & AIMS:The liver is a crucial organ at the crossroads of iron and glucose metabolism. The aim of the study was to assess intra-hepatic iron in young patients with non-alcoholic fatty liver disease (NAFLD) and its association with insulin resistance and severity of liver damage. METHODS:Intrahepatic iron con...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.12.007
更新日期:2011-09-01 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::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:BACKGROUND & AIMS:Blocking intestinal bile acid (BA) absorption by inhibiting or inactivating the apical sodium-dependent BA transporter (Asbt) classically induces hepatic BA synthesis. In contrast, blocking intestinal BA absorption by inactivating the basolateral BA transporter, organic solute transporter alpha-beta (...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.03.025
更新日期:2012-08-01 00:00:00
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
更新日期:2000-01-01 00:00:00
abstract:BACKGROUND/AIMS:Lamivudine is an antiviral drug that is used to treat hepatitis B virus (HBV) infection. Long-term therapy does not completely suppress viral replication, and resistant mutants emerge. Resistance is mediated by changes in the tyrosine-methionine-apartate-aspartate (YMDD) motif in the catalytic site of t...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2004.02.009
更新日期:2004-06-01 00:00:00
abstract:BACKGROUND & AIMS:Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of stages from simple steatosis to non-alcoholic steatohepatitis (NASH). However, disease pathogenesis remains largely unknown. microRNA (miRNA or miR) expression has recently been reported to be altered in human NASH, and modulated by urs...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.08.008
更新日期:2013-01-01 00:00:00
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
更新日期:2019-04-01 00:00:00
abstract:BACKGROUND & AIMS:Biliary tree, liver, and pancreas share a common embryological origin. We previously demonstrated the presence of stem/progenitor cells of endodermal origin in the adult human extrahepatic biliary tree. This study evaluated the human foetal biliary trees as sources of stem/progenitor cells of multiple...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.07.013
更新日期:2012-11-01 00:00:00
abstract:BACKGROUND & AIMS:Anatomic resection (AR) of the tumor-bearing portal territory has been reported to be associated with a decreased recurrence of hepatocellular carcinoma (HCC). However, because of the heterogeneity of the study populations, its oncologic advantage remains controversial. The objective of the present st...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2015.10.015
更新日期:2016-03-01 00:00:00
abstract::The Hepatitis Delta Virus (HDV), a defective ribonucleic acid virus dependent on the Hepatitis B Virus (HBV) is a cause of severe liver disease that often leads to cirrhosis and death. Since the HDV finds in the HBV infection a biological niche in which to thrive indefinitely, the major victims of its infection are th...
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(86)80125-8
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND & AIMS:During chronic HCV infection, T cell dependent virus-specific antibodies are produced. However, the role of B-T cell interaction in chronic HCV is largely unknown. CD4(+)CXCR5(+) T follicular helper (TFH)-cells activate B cells and are important for clearance of various chronic viral infections. We in...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.09.024
更新日期:2015-02-01 00:00:00
abstract:BACKGROUND & AIMS:The liver is the main hematopoietic site in embryos, becoming a crucial organ in both immunity and metabolism in adults. However, how the liver adapts both the immune system and enzymatic profile to challenges in the postnatal period remains elusive. We aimed to identify the mechanisms underlying this...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2018.08.018
更新日期:2018-12-01 00:00:00
abstract::The effect of amphotericin B on hepatic microsomal cytochrome P-450 (P-450) concentration was measured in vitro, in vivo and ex vivo in the rat. In vitro, both amphotericin B (0-500 micrograms/ml) and its vehicle, sodium deoxycholate (0-410 micrograms/ml), caused similar dose-dependent decreases of P-450 concentration...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(92)90174-n
更新日期:1992-03-01 00:00:00
abstract:BACKGROUND & AIMS:To follow the local tissue delivery of doxorubicin in HCC explants from patients embolized with drug-eluting beads and to compare it with histologic modifications. METHODS:Six patients with HCC underwent chemoembolization with doxorubicin-eluting beads (caliber 100-300 μm, dose 75-150 mg) followed by...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2011.03.024
更新日期:2011-12-01 00:00:00
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
更新日期:1987-04-01 00:00:00
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
更新日期:2015-09-01 00:00:00
abstract::The clinical course of cirrhosis is mostly determined by the progressive increase of portal hypertension, hyperdynamic circulation, bacterial translocation and activation of systemic inflammation. Different disease states, encompassing compensated and decompensated cirrhosis and a late decompensated state, are related...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2017.10.020
更新日期:2018-03-01 00:00:00
abstract:BACKGROUND/AIMS:Thrombin and MC tryptase, which are agonists for proteinase-activated receptors-1 and -2, respectively, are both increased in injured liver. We have examined if rat stellate cells express these receptors and if receptor agonists influence stellate cell activation. METHODS:Expression of mRNA for protein...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(01)00285-9
更新日期:2002-03-01 00:00:00
abstract:BACKGROUND/AIMS:Heparin has been noted to inhibit inflammation independent of its known anti-coagulant activity. In the present study, we examined the ability of heparin and low molecular weight heparin to prevent immune-mediated, concanavalin A-induced liver damage. METHODS:Mice were pretreated with either heparin or...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80284-0
更新日期:1999-11-01 00:00:00
abstract::Hepatitis viruses are major threats to human health. During the last decade, highly diverse viruses related to human hepatitis viruses were found in animals other than primates. Herein, we describe both surprising conservation and striking differences of the unique biological properties and infection patterns of human...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2018.11.010
更新日期:2019-03-01 00:00:00
abstract:BACKGROUND & AIMS:Hepatocellular carcinoma (HCC) risk stratification in individuals with dysmetabolism is a major unmet need. Genetic predisposition contributes to non-alcoholic fatty liver disease (NAFLD). We aimed to exploit robust polygenic risk scores (PRS) that can be evaluated in the clinic to gain insight into t...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.11.024
更新日期:2020-11-25 00:00:00
abstract:BACKGROUND/AIMS:We previously reported that the populations of lymphocytes and the expression of activated antigens in human sinusoidal mononuclear cells were different from those in peripheral blood mononuclear cells. Attempts to culture these cells for further study failed because they died rapidly under standard cul...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(97)80016-5
更新日期:1997-01-01 00:00:00
abstract::This study set out to examine the relative effectiveness and tolerability of 12- versus 24-week courses of thrice weekly intramuscular lymphoblastoid interferon in the treatment of hepatitis B 'e' antigen (HBeAg)-positive chronic hepatitis B virus (HBV) infection, and to identify pretreatment factors predicting the ou...
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(87)80061-2
更新日期:1987-08-01 00:00:00
abstract:BACKGROUND & AIMS:SIRT1 is a class III histone deacetylase that plays diverse roles in various cancers. However, the clinical significance of SIRT1 in hepatocellular carcinoma (HCC) remains unknown. METHODS:We analysed p53 mutations and the activation of SIRT1 in 252 hepatitis B virus-positive HCC cases. None of the p...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.08.007
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND/AIMS:Lipid peroxidation has been found to be associated with Ito cell activation. Ito cells are the principal collagen-producing cells and the main storage sites of retinoids. However, the relationship between retinoids and hepatic fibrosis is complex. The aim of this study was to elucidate the role of retin...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(98)80121-9
更新日期:1998-12-01 00:00:00