Abstract:
BACKGROUND/AIMS:Vaccination strategies able to induce strong T-cell responses might contribute to eradicate hepatitis C virus (HCV) infection. We previously demonstrated that fusion of an antigen to the extra domain A from fibronectin (EDA) targets the antigen to TLR4-expressing dendritic cells (DC) and improves its immunogenicity. Here, we studied if fusion of EDA with the non-structural HCV protein NS3 might constitute an effective immunogen against HCV. METHODS:Recombinant NS3 and the fusion protein EDA-NS3 were produced and purified from E. coli, and tested in vitro for their capacity to activate maturation of DC and to favour antigen presentation. HHD transgenic mice expressing the human HLA-A2 molecule were immunized with recombinant proteins in the absence or presence of poly(I:C) and anti-CD40 agonistic antibodies and responses elicited by vaccination were tested in vitro, and in vivo, by their capacity to downregulate intrahepatic expression of HCV-NS3 RNA. RESULTS:EDA-NS3, but not NS3 alone, upregulated the expression of maturation markers, as well as Delta-like 1 and Delta-like 4 Notch ligands in DC and induced the production of IL-12. Mice immunized with EDA-NS3 had strong and long lasting NS3-specific CD4+ and CD8+ T-cell responses and, in combination with poly(I:C) and anti-CD40, downregulated intrahepatic expression of HCV-NS3 RNA. CONCLUSIONS:Recombinant EDA-NS3 may be considered for the development of vaccines against HCV infection.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Mansilla C,Gorraiz M,Martinez M,Casares N,Arribillaga L,Rudilla F,Echeverria I,Riezu-Boj JI,Sarobe P,Borrás-Cuesta F,Prieto J,Lasarte JJdoi
10.1016/j.jhep.2009.06.005subject
Has Abstractpub_date
2009-09-01 00:00:00pages
520-7issue
3eissn
0168-8278issn
1600-0641pii
S0168-8278(09)00439-5journal_volume
51pub_type
杂志文章abstract:BACKGROUND/AIMS:The impact of heterozygous HFE mutations on the course of chronic hepatitis C and iron indices was studied. METHODS:Ferritin, transferrin saturation (TS), serum iron, C282Y and H63D mutations were determined in 401 patients with chronic hepatitis C virus (HCV) infection and 295 healthy controls. Liver ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(02)00415-4
更新日期:2003-03-01 00:00:00
abstract:BACKGROUND/AIMS:ATP stimulation of purinergic P2 receptors (P2YR and P2XR) regulates several hepatic functions. Here we report the involvement of ATP-mediated signals in enhancing hepatocyte tolerance to lethal stress. METHODS:The protection given by purinergic agonists was investigated in rat hepatocytes exposed to h...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2006.02.017
更新日期:2006-08-01 00:00:00
abstract::HCV is the principal etiologic agent of post-transfusion (PTH) hepatitis. The incidence and course of HCV hepatitis in liver transplant recipients is not well established. To resolve this information deficit, all records of recipients of single liver transplant (OLTx) between March 1986 and March 1990 at the Universit...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80270-3
更新日期:1993-07-01 00:00:00
abstract:BACKGROUND/AIMS:Partial hepatectomy results in activation of genes in the residual liver tissue which serve to restore glucose homeostasis and regenerate liver mass. Expression of insulin-like growth factor binding protein-1 (IGFBP-1) is up-regulated following partial hepatectomy and IGFBP-1 can modulate both the metab...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80199-8
更新日期:1999-04-01 00:00:00
abstract:BACKGROUND & AIMS:Several studies have shown that chronic hepatitis C (CHC) infection has a negative impact on kidney function, as well as survival, in patients with chronic kidney disease (CKD) or on hemodialysis. The aim of this nationwide registry study was to describe renal disease in Swedish patients with CHC. ME...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2017.12.003
更新日期:2018-05-01 00:00:00
abstract:BACKGROUND/AIMS:A simple and reproducible hepatic immunohistochemical staining (IHS) for hepatitis C virus (HCV) is not available. We aimed to validate hepatic IHS with monoclonal antibody (Mab) IG222, directed against the HCV-envelope 2 (E2) protein. METHODS:A three-step indirect immunoperoxidase method was used for ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(02)00389-6
更新日期:2003-02-01 00:00:00
abstract:BACKGROUND/AIMS:The pathogenic relevance of the hepatitis G virus (HGV) and its sensitivity to interferon are currently under investigation. This study aimed to investigate the prevalence of HGV infection in patients with chronic hepatitis C and to elucidate if HGV co-infection modifies the clinical course and the resp...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(97)80243-7
更新日期:1997-04-01 00:00:00
abstract:BACKGROUND/AIMS:Gadolinium chloride inactivates Kupffer cells and alleviates alcohol-induced liver lesions. We investigated the mechanism of gadolinium chloride protection after oral ethanol feeding. METHODS:Rats were maintained ethanol-intoxicated for 6 weeks by feeding ethanol in a low-carbohydrate/high-fat liquid d...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)80094-x
更新日期:2000-06-01 00:00:00
abstract:BACKGROUND & AIMS:The accuracy of creatinine-based estimated GFR (eGFR) in assessing the prevalence of chronic kidney disease (CKD) and associated mortality after liver transplantation (LTx) is unknown. Using measured GFR (mGFR) by iothalamate clearance, we determined the prevalence of the entire spectrum of renal dysf...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.03.034
更新日期:2014-08-01 00:00:00
abstract:BACKGROUND:Serum carbohydrate deficient transferrin is a marker of chronic alcohol consumption; it increases above normal in healthy individuals after a daily alcohol intake of more than 60 g/d for more than 2 weeks. The influence of liver disease itself on carbohydrate deficient transferrin levels has not been suffici...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(95)80037-9
更新日期:1995-12-01 00:00:00
abstract:BACKGROUND & AIMS:Sustained viral response (SVR) after therapy with interferon-ribavirin (IF-RB) reduces liver-related (LR) complications and mortality in HIV/HCV-co-infected patients. Here, we assess the impact of end-of-treatment response with subsequent relapse (REL) on LR events (LR death, liver decompensation, hep...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2013.01.042
更新日期:2013-06-01 00:00:00
abstract::The circuitous cell signalling pathways of hepatocytes comprise several factors that operate to downgrade or even interrupt the transmission of a given signal. These down-regulating influences are essential to keep cell proliferation and cell survival in check and if impaired, can alter a delicate balance in favour of...
journal_title:Journal of hepatology
pub_type:
doi:10.1016/j.jhep.2007.09.003
更新日期:2007-12-01 00:00:00
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
更新日期:2006-09-01 00:00:00
abstract:BACKGROUND & AIMS:MicroRNAs (miRNAs) have been shown to be involved in many biological processes by affecting their target gene expression. miR-122 has been extensively studied in hepatocarcinogenesis. However, the role of miR-122 in liver fibrosis remains unknown. METHODS:The mRNA expression levels of miR-122, prolyl...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.11.011
更新日期:2013-03-01 00:00:00
abstract:BACKGROUND & AIMS:Non-alcoholic fatty liver disease (NAFLD) is characterized by increased risk of cardiovascular events and liver-fibrosis. Both could be explained by a procoagulant-imbalance that was surmised but never directly demonstrated. We investigated 113 patients with varying histological liver damage [steatosi...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.03.013
更新日期:2014-07-01 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::We investigated whether regulation of interferon-alpha gene expression could be involved in liver tumor biology and the role, if any, of hepatitis B virus in the regulation of tumor cytokine gene expression. Gene expression was investigated at the transcriptional level using 'in situ' hybridization of cytokine message...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80215-6
更新日期:1993-03-01 00:00:00
abstract:BACKGROUND & AIMS:Hepatic stellate cell (HSC) transdifferentiation into collagen-producing myofibroblasts is a key event in hepatic fibrogenesis, but the transcriptional network that controls the acquisition of the activated phenotype is still poorly understood. In this study, we explored whether the nuclear receptor c...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2016.11.003
更新日期:2017-04-01 00:00:00
abstract:BACKGROUND/AIMS:In primary biliary cirrhosis (PBC), pathogenesis is influenced by genetic factors that remain poorly elucidated up to now. We investigated the impact of sequence diversity in candidate genes involved in immunity (CTLA-4 and TNFalpha), in bile formation (10 hepatobiliary transporter genes) and in the ada...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2008.07.027
更新日期:2008-12-01 00:00:00
abstract:BACKGROUND & AIMS:Modulation of dendritic cell (DC) function has been theorized as one of the mechanisms used by hepatitis C virus (HCV) to evade the host immune response and cause persistent infection. METHODS:We used a range of cell and molecular biology techniques to study DC subsets from uninfected and HCV-infecte...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.04.007
更新日期:2014-08-01 00:00:00
abstract:BACKGROUND/AIMS:Members of the melanoma antigen encoding gene family are expressed in tumors of different histological types but not in normal tissue. For this reason, they are attractive targets for cancer immunotherapy. METHODS:In the present study, we analyzed the expression of MAGE-1 and -3 genes in the hepatocell...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(03)00484-7
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND & AIMS:Data from clinical trials suggest a potential role for on-treatment monitoring of serum HBsAg titres during interferon-alpha (pegIFN) therapy in predicting virological responses. However, baseline HBsAg titres during the natural history of chronic hepatitis B (CHB) have not been well-characterized. We...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/j.jhep.2010.01.007
更新日期:2010-04-01 00:00:00
abstract:BACKGROUND/AIMS:Currently the diagnosis and severity of hepatic steatosis can be established accurately only by liver biopsy. Previous small studies found that steatosis measured by magnetic resonance spectroscopy (MRS) and imaging (MRI) correlated with histological assessment of liver triglyceride content. However, th...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2009.04.012
更新日期:2009-08-01 00:00:00
abstract::A diagnostic test has been developed to detect hepatitis B virus (HBV) DNA in human sera. This test involves a dot-blot technique in which non-radioactive nucleic acid labelled with 2-acetylaminofluorene (AAF) is used as probe. Two series of human sera from 228 blood donors and 113 HBsAg chronic carriers were tested b...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(87)80573-1
更新日期:1987-10-01 00:00:00
abstract::TGR5 is a G protein-coupled receptor expressed in brown adipose tissue and muscle, where its activation by bile acids triggers an increase in energy expenditure and attenuates diet-induced obesity. Using a combination of pharmacological and genetic gain- and loss-of-function studies invivo, we show here that TGR5 sign...
journal_title:Journal of hepatology
pub_type: 评论,杂志文章
doi:10.1016/j.jhep.2010.02.003
更新日期:2010-06-01 00:00:00
abstract:BACKGROUND & AIMS:The role of hepatitis B virus (HBV)-specific CD4 T cells in patients with chronic HBV infection is not clear. Thus, we aimed to elucidate this in patients with chronic infection, and those with hepatitis B flares. METHODS:Through intracellular IFN-γ and TNF-α staining, HBV-specific CD4 T cells were a...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2019.08.024
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND/AIMS:Indomethacin has been shown to have adverse effects on renal function in patients with well-compensated alcoholic cirrhosis. The aim of this study was to determine whether an oral prostaglandin E1 analogue, misoprostol, could prevent this indomethacin-induced renal dysfunction. METHODS:Six patients wit...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(95)80303-3
更新日期:1995-07-01 00:00:00
abstract:BACKGROUND & AIMS:Despite the clinical and genetic significance of macrotrabecular-massive hepatocellular carcinoma (MTM-HCC), its characteristics on imaging have not been described. This study aimed to characterise MTM-HCC on gadoxetic acid-enhanced MRI and to evaluate the diagnostic accuracy and prognostic value of t...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.08.013
更新日期:2021-01-01 00:00:00
abstract:BACKGROUND:NGM282, an engineered analogue of the gut hormone FGF19, improves hepatic steatosis and fibrosis biomarkers in patients with non-alcoholic steatohepatitis (NASH). However, NGM282 increases serum cholesterol levels by inhibiting CYP7A1, which encodes the rate-limiting enzyme in the conversion of cholesterol t...
journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.jhep.2018.11.032
更新日期:2019-04-01 00:00:00
abstract:BACKGROUND/AIMS:In families of patients with clinically detected hereditary hemochromatosis (HH) early screening has been suggested to prevent morbidity and mortality. Here, we aim to identify determinants for iron overload in first-degree family members of C282Y homozygous probands with clinically detected HH. METHOD...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2008.08.014
更新日期:2009-01-01 00:00:00