Long term transgene expression by hepatocytes transduced with retroviral vectors requires induction of immune tolerance to the transgene.

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 Hepatol

journal_title

Journal of hepatology

authors

Puppi J,Guillonneau C,Pichard V,Bellodi-Privato M,Cuturi MC,Anegon I,Ferry N

doi

10.1016/j.jhep.2004.04.015

subject

Has Abstract

pub_date

2004-08-01 00:00:00

pages

222-8

issue

2

eissn

0168-8278

issn

1600-0641

pii

S0168827804001722

journal_volume

41

pub_type

杂志文章
  • Toll-like receptor 3 downregulation is an escape mechanism from apoptosis during hepatocarcinogenesis.

    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...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2019.05.031

    authors: Bonnin M,Fares N,Testoni B,Estornes Y,Weber K,Vanbervliet B,Lefrançois L,Garcia A,Kfoury A,Pez F,Coste I,Saintigny P,Viari A,Lang K,Guey B,Hervieu V,Bancel B,Bartoch B,Durantel D,Renno T,Merle P,Lebecque S

    更新日期:2019-10-01 00:00:00

  • Efficacy and tolerability of an IFN-free regimen with DCV/ASV for elderly patients infected with HCV genotype 1B.

    abstract:BACKGROUND & AIMS:Anti-hepatitis C virus (HCV) therapy by interferon (IFN)-free regimen with oral direct-acting antiviral drugs are tolerable in aged patients, with fewer adverse effects than IFN-based therapies. We investigated the efficacy and tolerability of an IFN-free anti-HCV therapy in extremely aged patients, a...

    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.2016.11.012

    authors: Toyoda H,Kumada T,Tada T,Shimada N,Takaguchi K,Senoh T,Tsuji K,Tachi Y,Hiraoka A,Ishikawa T,Shima T,Okanoue T

    更新日期:2017-03-01 00:00:00

  • Clinical implications of GBV-C/HGV infection in patients with "HCV-related" chronic hepatitis.

    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

    authors: Francesconi R,Giostra F,Ballardini G,Manzin A,Solforosi L,Lari F,Descovich C,Ghetti S,Grassi A,Bianchi G,Zauli D,Clementi M,Bianchi FB

    更新日期:1997-06-01 00:00:00

  • Impaired liver regeneration in Ldlr-/- mice is associated with an altered hepatic profile of cytokines, growth factors, and lipids.

    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

    doi:10.1016/j.jhep.2013.05.026

    authors: Pauta M,Rotllan N,Vales F,Fernandez-Hernando A,Allen RM,Ford DA,Marí M,Jiménez W,Baldán A,Morales-Ruiz M,Fernández-Hernando C

    更新日期:2013-10-01 00:00:00

  • Reducing environment protects sinusoidal lymphocytes isolated from normal human liver from apoptosis.

    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

    authors: Kinoshita K,Kanai M,Awane M,Furuke K,Shirakata Y,Gomi T,Nakamura Y,Ikai I,Yamauchi A,Inamoto T,Ohmori K,Yamaoka Y

    更新日期:1997-01-01 00:00:00

  • Hepatic regeneration in insulin-like growth factor binding protein-1 transgenic mice.

    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

    authors: Liu YY,Rajkumar K,Murphy LJ

    更新日期:1999-04-01 00:00:00

  • Controlled HIV viral replication, not liver disease severity associated with low bone mineral density in HIV/HCV co-infection.

    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

    authors: El-Maouche D,Mehta SH,Sutcliffe C,Higgins Y,Torbenson MS,Moore RD,Thomas DL,Sulkowski MS,Brown TT

    更新日期:2011-10-01 00:00:00

  • The changing scenario of hepatocellular carcinoma over the last two decades in Italy.

    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

    authors: Santi V,Buccione D,Di Micoli A,Fatti G,Frigerio M,Farinati F,Del Poggio P,Rapaccini G,Di Nolfo MA,Benvegnù L,Zoli M,Borzio F,Giannini EG,Caturelli E,Chiaramonte M,Bernardi M,Trevisani F

    更新日期:2012-02-01 00:00:00

  • Macrophages from rat livers with micronodular and macronodular cirrhosis differ with respect to mediator release and DNA-synthesis.

    abstract:BACKGROUND/AIMS:Liver macrophages play an essential role in necro-inflammatory liver damage which leads to fibrosis and cirrhosis. The aim of the present study was to compare the mediator release and the DNA synthesis of macrophages at an early and at a later stage of liver cirrhosis induced by thioacetamide. METHODS:...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/s0168-8278(97)80118-3

    authors: Vogl S,Junker U,Vogelsang H,Dargel R

    更新日期:1997-05-01 00:00:00

  • Long-term outcome of interferon-alpha therapy for chronic hepatitis B.

    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

    pub_type: 杂志文章,评审

    doi:

    authors: Di Bisceglie AM

    更新日期:1995-01-01 00:00:00

  • Timing and benefit of liver transplantation in acute liver failure.

    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...

    journal_title:Journal of hepatology

    pub_type: 杂志文章,评审

    doi:10.1016/j.jhep.2013.10.024

    authors: O'Grady J

    更新日期:2014-03-01 00:00:00

  • Caspase 8 differentially controls hepatocytes and non-parenchymal liver cells during chronic cholestatic liver injury in mice.

    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

    authors: Chaudhary K,Liedtke C,Wertenbruch S,Trautwein C,Streetz KL

    更新日期:2013-12-01 00:00:00

  • Neurally-mediated vasodilatation in normal and portal hypertensive rats: role of nitric oxide and calcitonin gene-related peptide.

    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

    authors: Moll-Kaufmann C,Sumanovski LT,Sieber CC

    更新日期:1998-06-01 00:00:00

  • Alteration of protein glycosylation in liver diseases.

    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

    authors: Blomme B,Van Steenkiste C,Callewaert N,Van Vlierberghe H

    更新日期:2009-03-01 00:00:00

  • Heterogeneity of hepatitis B virus C-gene sequences: implications for amplification and sequencing.

    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

    authors: Miska S,Günther S,Vassilev M,Meisel H,Pape G,Will H

    更新日期:1993-04-01 00:00:00

  • Retrorsine: a kinetic study of its influence on rat liver regeneration in the portal branch ligation model.

    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

    authors: Picard C,Lambotte L,Starkel P,Sempoux C,Saliez A,Van Den Berge V,de Saeger C,Horsmans Y

    更新日期:2003-07-01 00:00:00

  • Perforin and granzymes work in synergy to mediate cholangiocyte injury in experimental biliary atresia.

    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

    authors: Shivakumar P,Mourya R,Bezerra JA

    更新日期:2014-02-01 00:00:00

  • Perisinusoidal cells in patients with normal liver histology. A morphometric study.

    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

    authors: Sztark F,Dubroca J,Latry P,Quinton A,Balabaud C,Bioulac-Sage P

    更新日期:1986-01-01 00:00:00

  • Hepatosplenomegalic lipidosis: what unless Gaucher? Adult cholesteryl ester storage disease (CESD) with anemia, mesenteric lipodystrophy, increased plasma chitotriosidase activity and a homozygous lysosomal acid lipase -1 exon 8 splice junction mutation.

    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

    authors: vom Dahl S,Harzer K,Rolfs A,Albrecht B,Niederau C,Vogt C,van Weely S,Aerts J,Müller G,Häussinger D

    更新日期:1999-10-01 00:00:00

  • Mechanisms of HBV-induced hepatocellular carcinoma.

    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

    doi:10.1016/j.jhep.2016.02.021

    authors: Levrero M,Zucman-Rossi J

    更新日期:2016-04-01 00:00:00

  • The changing scenario of hepatitis D.

    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...

    journal_title:Journal of hepatology

    pub_type: 杂志文章,评审

    doi:10.1016/j.jhep.2021.01.014

    authors: Rizzetto M,Hamid S,Negro F

    更新日期:2021-01-20 00:00:00

  • Plasma somatostatin response to an oral mixed test meal in cirrhotic patients.

    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

    authors: Barreca T,Franceschini R,Cataldi A,Rolandi E

    更新日期:1991-01-01 00:00:00

  • Staging chronic hepatitis C in seven categories using fibrosis biomarker (FibroTest™) and transient elastography (FibroScan®).

    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

    authors: Poynard T,Vergniol J,Ngo Y,Foucher J,Munteanu M,Merrouche W,Colombo M,Thibault V,Schiff E,Brass CA,Albrecht JK,Rudler M,Deckmyn O,Lebray P,Thabut D,Ratziu V,de Ledinghen V,FibroFrance Study Group.,Epic3 Study Group.,

    更新日期:2014-04-01 00:00:00

  • Prognostic significance of portal hemodynamics in patients with compensated cirrhosis.

    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

    authors: Zoli M,Iervese T,Merkel C,Bianchi G,Magalotti D,Marchesini G,Gatta A,Pisi E

    更新日期:1993-01-01 00:00:00

  • Severe alpha1-antitrypsin deficiency (PiZ homozygosity) with membranoproliferative glomerulonephritis and nephrotic syndrome, reversible after orthotopic liver transplantation.

    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

    authors: Elzouki AN,Lindgren S,Nilsson S,Veress B,Eriksson S

    更新日期:1997-06-01 00:00:00

  • Evidence of two major genotypes of hepatitis C virus in France and close relatedness of the predominant one with the prototype virus.

    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

    authors: Li JS,Tong SP,Vitvitski L,Lepot D,Trépo C

    更新日期:1991-01-01 00:00:00

  • MELD score is a better prognostic model than Child-Turcotte-Pugh score or Discriminant Function score in patients with alcoholic hepatitis.

    abstract:BACKGROUND/AIMS:The aim of the present study was to compare MELD score, Child-Turcotte-Pugh (CTP) score, modified Maddrey's Discriminant Function (DF) score, and the related variables in predicting in-hospital mortality of patients with alcoholic hepatitis. METHODS:A retrospective chart review and statistical analyses...

    journal_title:Journal of hepatology

    pub_type: 杂志文章

    doi:10.1016/j.jhep.2004.12.022

    authors: Srikureja W,Kyulo NL,Runyon BA,Hu KQ

    更新日期:2005-05-01 00:00:00

  • Adhesion of human haematopoietic (CD34+) stem cells to human liver compartments is integrin and CD44 dependent and modulated by CXCR3 and CXCR4.

    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

    authors: Crosby HA,Lalor PF,Ross E,Newsome PN,Adams DH

    更新日期:2009-10-01 00:00:00

  • Effects of ursodeoxycholate, its glucuronide and disulfate and beta-muricholate on biliary bicarbonate concentration and biliary lipid excretion.

    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

    authors: Takikawa H,Sano N,Minagawa K,Yamanaka M

    更新日期:1992-05-01 00:00:00

  • Met as a therapeutic target in HCC: facts and hopes.

    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

    authors: Giordano S,Columbano A

    更新日期:2014-02-01 00:00:00