Abstract:
BACKGROUND/AIMS:Gene therapy for inherited liver diseases requires permanent expression of the therapeutic gene. However, in vivo liver transduction with retroviral vectors triggers an immune elimination of transduced hepatocytes. Here we investigated whether immune response could be prevented by treatment with compounds known to induce tolerance in organ transplantation: CTLA4Ig and LF-15-0195. METHODS:CTLA4Ig was administered either via i.p. injection of the drug or by i.m. injection of recombinant adenoviruses encoding CTLA4Ig. LF-15-0195 was administered i.p. All animals were subjected to partial hepatectomy and received beta-galactosidase retroviral vectors intravenously. Appearance of anti-beta-galactosidase antibodies was monitored and the number of positive hepatocytes was assessed at day 7 and at sacrifice. RESULTS:No beta-galactosidase antibodies were detected as long as CTLA4Ig was detectable in serum. Short-term treatment with CTLA4Ig induced tolerance in a significant proportion of animals only at high dose (1 mg/kg). Administration of CTLA4Ig adenovectors resulted in prolonged secretion of CTLA4Ig and permanent absence of anti-beta-galactosidase antibodies. LF-15-0915 administration achieved tolerance in some animals. CONCLUSIONS:In conclusion, manipulation of the immune system at the time of virus delivery using clinically relevant tolerance-inducing protocols is a promising approach to achieve long term expression after retrovirus-mediated gene transfer to the liver.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Puppi J,Guillonneau C,Pichard V,Bellodi-Privato M,Cuturi MC,Anegon I,Ferry Ndoi
10.1016/j.jhep.2004.04.015subject
Has Abstractpub_date
2004-08-01 00:00:00pages
222-8issue
2eissn
0168-8278issn
1600-0641pii
S0168827804001722journal_volume
41pub_type
杂志文章abstract:BACKGROUND & AIMS:Low levels of toll-like receptor 3 (TLR3) in patients with hepatocellular carcinoma (HCC) are associated with poor prognosis, primarily owing to the loss of inflammatory signaling and subsequent lack of immune cell recruitment to the liver. Herein, we explore the role of TLR3-triggered apoptosis in HC...
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更新日期:2019-10-01 00:00:00
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pub_type: 临床试验,杂志文章,多中心研究
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更新日期:2017-03-01 00:00:00
abstract:BACKGROUND/AIMS:To evaluate the clinical, biochemical and histological implications of a concomitant HGV infection in "HCV-related" chronic liver disease. METHODS:Eighty-three HCV-RNA positive patients with chronic liver disease were tested for GBV-C/HGV coinfection by heminested PCR. RESULTS:Twenty-two (26.5%) patie...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(97)80448-5
更新日期:1997-06-01 00:00:00
abstract:BACKGROUND & AIMS:It is widely recognized that in the early stages of liver regeneration after partial hepatectomy, the hepatocytes accumulate a significant amount of lipids. The functional meaning of this transient steatosis and its effect on hepatocellular proliferation are not well defined. In addition, the basic me...
journal_title:Journal of hepatology
pub_type: 杂志文章
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更新日期:2013-10-01 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
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doi:10.1016/s0168-8278(97)80016-5
更新日期:1997-01-01 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:To evaluate the prevalence and risk factors for low bone mineral density (BMD) in persons co-infected with HIV and Hepatitis C. METHODS:HIV/HCV co-infected study participants (n=179) were recruited into a prospective cohort and underwent dual-energy X-ray absorptiometry (DXA) within 1 year of a liver...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2011.01.035
更新日期:2011-10-01 00:00:00
abstract:BACKGROUND & AIMS:This study investigates whether the aetiologic changes in liver disease and the improved management of hepatocellular carcinoma (HCC) have modified the clinical scenario of this tumour over the last 20 years in Italy. METHODS:Retrospective study based on the analysis of the ITA.LI.CA (Italian Liver C...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2011.05.026
更新日期:2012-02-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(97)80118-3
更新日期:1997-05-01 00:00:00
abstract::Interferon-alpha therapy has a beneficial effect in 30-40% of selected patients with chronic hepatitis B who respond by clearing hepatitis B e antigen (HBeAg) and hepatitis B viral (HBV) DNA from serum. This is usually associated with normalization of serum aminotransferase activities. On long-term follow-up of treate...
journal_title:Journal of hepatology
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doi:
更新日期:1995-01-01 00:00:00
abstract::The case for using emergency liver transplantation in acute liver failure was made two decades ago by a series of single centre experiences. The development of models identifying a poor prognosis assisted the selection of patients for liver transplantation but none of these delivers both high sensitivity and specifici...
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pub_type: 杂志文章,评审
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更新日期:2014-03-01 00:00:00
abstract:BACKGROUND & AIMS:Receptor mediated cell death through the activation of caspases has been identified as an important mechanism to control life and death in various tissues and is thus crucial for the maintenance of liver tissue homeostasis. Here we investigated how caspase 8 (Casp8) differentially regulates immune-med...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2013.07.026
更新日期:2013-12-01 00:00:00
abstract:BACKGROUND/AIMS:Portal hypertension is associated with systemic vasodilatation and vascular hyporeactivity, and is reversed by inhibiting nitric oxide biosynthesis. Nitric oxide and calcitonin gene-related peptide are neurotransmitters of non-adrenergic non-cholinergic nerves. The role of nitric oxide and calcitonin ge...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(98)80353-x
更新日期:1998-06-01 00:00:00
abstract::Chronic liver diseases are a serious health problem worldwide. The current gold standard to assess structural liver damage is through a liver biopsy which has several disadvantages. A non-invasive, simple and non-expensive test to diagnose liver pathology would be highly desirable. Protein glycosylation has drawn the ...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2008.12.010
更新日期:2009-03-01 00:00:00
abstract::Occasionally direct sequencing of amplified hepatitis B virus DNA leads to weak signals on autoradiograms. Using amplified C-gene sequences we investigated whether this is due to sequence heterogeneity of virus populations and use of inappropriate primers for direct sequencing. High C-gene sequence heterogeneity (poin...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80009-1
更新日期:1993-04-01 00:00:00
abstract:BACKGROUND:Retrorsine, a naturally occurring pyrrolizidine alkaloid, impairs liver regeneration after partial hepatectomy by mechanisms that are still unclear. AIM:The aim of the study was to clarify the influence of retrorsine on cell cycle progression in the regenerating liver lobes of rats after portal branch ligat...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(03)00176-4
更新日期:2003-07-01 00:00:00
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 cytotoxi...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2013.09.021
更新日期:2014-02-01 00:00:00
abstract::We measured the number and the morphometric characteristics of perisinusoidal cells in perfusion-fixed biopsy samples from 7 control patients with normal liver histology. On 1-micron section, the number of cells was 18 +/- 1.5/0.1 mm2; 25% of cells did not apparently contain lipids. There were no significant zonal dif...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(86)80047-2
更新日期:1986-01-01 00:00:00
abstract::A 36-year-old woman was admitted for hepatosplenomegaly and anemia. Bone marrow cytology showed "sea-blue histiocytes", vacuolated macrophages and plasma cells. As primary liver disease, malignancy or hematologic disorders were excluded, and plasma chitotriosidase activity was increased 27-fold over control, the prese...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80356-0
更新日期:1999-10-01 00:00:00
abstract::Hepatitis B virus (HBV) contributes to hepatocellular carcinoma (HCC) development through direct and indirect mechanisms. HBV DNA integration into the host genome occurs at early steps of clonal tumor expansion and induces both genomic instability and direct insertional mutagenesis of diverse cancer-related genes. Pro...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
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更新日期:2016-04-01 00:00:00
abstract::The global scenario of hepatitis D is changing with the widespread implementation of vaccination against hepatitis B. In high-income countries that achieved optimal control of HBV, the epidemiology of hepatitis D is dual, consisting of an ageing cohort of domestic patients with advanced liver fibrosis who represent th...
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更新日期:2021-01-20 00:00:00
abstract::Ten patients with non-alcoholic cirrhosis and ten control subjects were studied in basal conditions and after ingestion of a standard mixed test meal. Plasma somatostatin, blood glucose, plasma insulin, C-peptide and glucagon were determined before and 15, 30, 45, 60, 90, 120 and 180 min after the start of the meal. B...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(91)90906-r
更新日期:1991-01-01 00:00:00
abstract:BACKGROUND & AIMS:FibroTest™ (FT) and Transient Elastography (TE) have been validated as non-invasive markers of METAVIR fibrosis stages from F0 to F4 using biopsy, and as prognostic markers of liver related mortality in patients with chronic hepatitis C. The aim was to extend the validation of FT and TE as markers of ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2013.11.016
更新日期:2014-04-01 00:00:00
abstract::The prognostic value of portal hemodynamics, measured by pulsed echo-Doppler, was prospectively evaluated, together with clinical, biochemical and endoscopic parameters, in a series of 50 consecutive patients with compensated cirrhosis. After a mean follow-up of 6 years, 25 patients had died, all from complications of...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80521-5
更新日期:1993-01-01 00:00:00
abstract:BACKGROUND/AIMS:Nephropathy associated with alpha1-antitrypsin deficiency is assumed to be an unusual entity. We describe the case of a 23-year-old woman with severe alpha1-antitrypsin (PiZ homozygosity) deficiency who developed hepatic cirrhosis in childhood, and glomerulonephritis and nephrotic syndrome in adult life...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(97)80478-3
更新日期:1997-06-01 00:00:00
abstract::Hepatitis C virus (HCV) cDNA sequence in the nonstructural region NS3 was amplified from the serum of 66% French non-A, non-B hepatitis patients by the nested polymerase chain reaction. A 407 base-pair sequence was determined from four such cases, which revealed the presence of two different virus genotypes F1 (three ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(91)90019-8
更新日期:1991-01-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2004.12.022
更新日期:2005-05-01 00:00:00
abstract:BACKGROUND/AIMS:Haematopoietic stem cells (HSC) have previously been shown in some studies to migrate to damaged and diseased liver where a small proportion will engraft. Such cells can promote liver repair in rodent models of liver injury and lead to improved liver function in uncontrolled clinical studies. In order t...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2009.06.021
更新日期:2009-10-01 00:00:00
abstract::We previously reported that high-dose ursodeoxycholate (UDC) infusion in rats resulted in extensive glucuronidation of UDC, and speculated that the glucuronidation causes bicarbonate-rich hypercholeresis induced by UDC (Takikawa, H., Sano, N., Narita, T. and Yamanaka, M. Hepatology 1990; 11: 743-749). To test this hyp...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(92)90015-h
更新日期:1992-05-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and its burden is expected to increase further in the next years. In spite of the advances of classical therapies, such as surgery, transplantation, use of radiofrequency and transarterial embolization, the prognosis of this neoplasm ...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2013.09.009
更新日期:2014-02-01 00:00:00