Abstract:
BACKGROUND/AIMS:The glycosphingolipid alpha-galactosylceramide has been shown to activate invariant natural killer T cells when presented in the context of CD1d and induces powerful antiviral immune responses via the production of inflammatory cytokines. The aim of this study was to investigate the safety and the antiviral activity of alpha-galactosylceramide as a novel class of treatment for chronic hepatitis C patients. METHODS:International multicenter dose-escalating randomized placebo-controlled phase I/II trial. RESULTS:Forty patients were allocated to a dose of 0.1 microg/kg (n=9), 1 microg/kg (n=9), 10 microg/kg (n=11) or to placebo (n=11). alpha-Galactosylceramide was well tolerated and no patients were withdrawn due to side effects. Although most patients showed a decrease in invariant natural killer T cells after administration, no clinically relevant suppression of viral replication was observed. Only one patient, a previous non-responder to peginterferon and ribavirin with high baseline invariant natural killer T cell levels, showed profound signs of immune activation, accompanied by a transient 1.3 log decrease in HCV-RNA and a concomitant increase in ALT after the first administration. CONCLUSIONS:alpha-Galactosylceramide used as monotherapy for interferon-refractory patients in doses of 0.1-10 microg/kg is safe and it exerts moderate immunomodulatory effects. However, in its current form it has no significant effect on HCV-RNA levels.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Veldt BJ,van der Vliet HJ,von Blomberg BM,van Vlierberghe H,Gerken G,Nishi N,Hayashi K,Scheper RJ,de Knegt RJ,van den Eertwegh AJ,Janssen HL,van Nieuwkerk CMdoi
10.1016/j.jhep.2007.04.018subject
Has Abstractpub_date
2007-09-01 00:00:00pages
356-65issue
3eissn
0168-8278issn
1600-0641pii
S0168-8278(07)00312-1journal_volume
47pub_type
杂志文章,多中心研究,随机对照试验abstract:BACKGROUND/AIMS:To analyze the kinetics of the hepatitis C virus and the patterns of resistance to interferon alpha, we assessed HCV RNA levels early during retreatment with high-dose interferon in patients who did not respond to standard treatment. METHODS:Eleven non-responders to previous therapy with 3-6 MU interfe...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章
doi:10.1016/s0168-8278(98)80343-7
更新日期:1998-06-01 00:00:00
abstract:BACKGROUND/AIMS:Previously, trichostatin A (TSA), a histone deacetylase inhibitor, has been shown to exhibit strong antifibrotic characteristics in hepatic stellate cells (HSC), which are known to play a central role in chronic liver diseases. TSA retained a more quiescent phenotype in spite of culture conditions that ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(02)00275-1
更新日期:2002-12-01 00:00:00
abstract::The results of a 3-year, placebo-controlled trial of prednisolone treatment in primary biliary cirrhosis (PBC) are presented. The active (n = 19) and placebo (n = 17) arms were initially well matched for age, menopausal status and disease severity. At 3 years hepatic symptoms were relatively improved in the prednisolo...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0168-8278(92)90065-w
更新日期:1992-07-01 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:Excessive trans-fatty acids (TFA) consumption has been thought to be a risk factor mainly for coronary artery diseases while less attention has been paid to liver disease. We aimed to clarify the impact of TFA-rich oil consumption on the hepatic pathophysiology compared to natural oil. METHODS:Mice w...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.02.029
更新日期:2010-08-01 00:00:00
abstract:BACKGROUND/AIMS:This study assesses the safety, pharmacokinetics and efficacy of transarterial chemoembolization using drug eluting beads (DEB), an embolizing device that slowly releases chemotherapy to decrease systemic toxicity. METHODS:Twenty-seven Child-Pugh A cirrhotics (76% male, 59% HCV) with untreated large/mu...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章
doi:10.1016/j.jhep.2006.10.020
更新日期:2007-03-01 00:00:00
abstract:BACKGROUND/AIMS:Patients infected with hepatitis C virus (HCV) genotype 2 or 3 usually respond better to interferon (IFN) treatment than those infected with genotype 1. In this study, we investigated whether the non-structural 5A protein (NS5A) of HCV genotypes 1 and 2 (1b-NS5A and 2a-NS5A, respectively) exerted differ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2008.06.030
更新日期:2008-12-01 00:00:00
abstract:BACKGROUND/AIMS:Progressive familial intrahepatic cholestasis type 2 (PFIC-2) patients have a defect in the hepatocanalicular bile salt secretion. The disease is caused by mutations in the bile salt export pump (BSEP). Ten different missense mutations have been described. In this study, we analysed the effect of the D4...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(03)00483-5
更新日期:2004-01-01 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:BACKGROUND/AIMS:Health-related quality of life (HRQoL) is impaired in patients with chronic hepatitis C. We investigated HRQoL and fatigue in patients with chronic hepatitis C virus (HCV) infection in relation to the degree of fibrosis and inflammation, and controlled for the influence of relevant demographic and medic...
journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.jhep.2008.07.025
更新日期:2008-12-01 00:00:00
abstract::A substantial production of prostaglandin E2 (PGE2) was induced in primary cultures of rat Kupffer cells by zymosan, calcium ionophore A23187, phorbol ester and arachidonic acid, whereas contact with latex particles, glucan or immunocomplexes led to a minor PGE2 release only. Superoxide generation, on the other hand, ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(88)80028-x
更新日期:1988-04-01 00:00:00
abstract::In 40 patients with esophageal varices, esophageal variceal pressure was assessed endoscopically using a pneumatic pressure sensor. The effects of vasopressin or nitroglycerin on variceal pressure and endoscopic findings were also assessed in two groups of seven patients. The results were as follows: (1) Variceal pres...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80309-5
更新日期:1994-09-01 00:00:00
abstract:BACKGROUND & AIMS:Virus-specific T cells capable of controlling HBV and eliminating hepatocellular carcinoma (HCC) expressing HBV antigens are deleted or dysfunctional in patients with chronic HBV or HBV-related HCC. The goal of this study was to determine if T cell receptor (TCR) gene transfer can reconstitute HBV-spe...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.10.025
更新日期:2011-07-01 00:00:00
abstract:BACKGROUND/AIMS:The aim was to study the reproducibility of magnetic resonance velocity mapping, when measuring portal vein and superior mesenteric artery blood flow, under fasting and post-prandial conditions. Magnetic resonance flow measurements for the portal vein were compared with echo-Doppler measurements in the ...
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(97)80045-1
更新日期:1997-02-01 00:00:00
abstract:BACKGROUND & AIMS:To compare the management and the virological and serological efficacy of treatments for chronic hepatitis B (CHB) in HIV positive and negative patients. METHODS:Two hundred and forty-six HIV positive and 205 HIV negative consecutive patients with past or present CHB, seen in October 2008 in particip...
journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.jhep.2010.04.041
更新日期:2010-12-01 00:00:00
abstract:BACKGROUND/AIMS:The electroencephalogram (EEG) is frequently altered in cirrhotic patients. We, therefore, performed a study to ascertain the features and the prognosis of cirrhotic patients without current overt hepatic encephalopathy (OHE) who have EEG alterations. METHODS:A series of 296 consecutive cirrhotic patie...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(01)00129-5
更新日期:2001-07-01 00:00:00
abstract:BACKGROUND/AIMS:In order to explore the role of cytokines in the pathogenesis of liver cirrhosis, we analyzed their gene expression in hepatic biopsies from patients with alcoholic liver cirrhosis, post-hepatitis C liver cirrhosis, and with idiopathic portal hypertension without cirrhosis. METHODS:We assessed the gene...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章
doi:10.1016/s0168-8278(96)80140-1
更新日期:1996-05-01 00:00:00
abstract::It has been postulated that one of the mechanisms of hypotension associated with cirrhosis is an attenuated responsiveness to catecholamines despite the increased activity of the sympathetic nervous system and the elevated plasma concentrations of the sympathetic neurotransmitter, norepinephrine. This abnormality was ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80531-8
更新日期:1993-01-01 00:00:00
abstract:BACKGROUND & AIMS:To develop an in situ molecular signature to predict postsurgical recurrence in hepatocellular carcinoma (HCC) patients. METHODS:Immunohistochemistry was performed using tissue microarrays containing both tumoral and peri-tumoral regions of the advancing tumor edge from 336 HCC patients (289 were pos...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.03.027
更新日期:2012-08-01 00:00:00
abstract:BACKGROUND & AIMS:Non-alcoholic fatty liver disease (NAFLD) affects up to 30% of the population and signifies increased risk of liver fibrosis and cirrhosis, type 2 diabetes, and cardiovascular disease. Therapies are limited. Weight loss is of benefit but is difficult to maintain. We aimed at examining the effect of 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/j.jhep.2013.02.012
更新日期:2013-07-01 00:00:00
abstract::The multidrug resistance genes encode plasma membrane glycoproteins named P-glycoproteins, that act as an ATP-dependent drug efflux pump and decrease the cytosolic concentration of chemotherapeutic agents. It has been hypothesized that in rat liver, this protein may have a physiological role as a biliary transporter o...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(94)80235-1
更新日期:1994-11-01 00:00:00
abstract:BACKGROUND & AIMS:Reactive cholangiocytes acquire a neuroendocrine-like phenotype, with synthesis and local release of neuropeptides and hormones. The mechanism that drives such phenotypical changes is still undefined. Pancreatic Duodenal Homeobox-1 (PDX-1) is a transcription factor required for pancreatic development,...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.04.022
更新日期:2010-10-01 00:00:00
abstract:BACKGROUND/AIMS:Little is known about the nucleotide excision repair (NER) pathway in the resistance of human hepatocellular carcinoma (HCC) to chemotherapeutics. We investigated expression of several NER genes in human HCC and matching non-tumor tissue (NT) and in normal liver. METHODS:Expression of CSA, CSB, XPC, hH...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2005.02.020
更新日期:2005-08-01 00:00:00
abstract:BACKGROUND/AIMS:The aim of the study was to investigate the effect of a standard albumin load on blood volume distribution, arterial compliance, and the renin-angiotensin-aldosterone system in patients with different degrees of cirrhosis. METHODS:31 patients with cirrhosis (Child classes A/B/C=8/14/9) received an intr...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(03)00160-0
更新日期:2003-07-01 00:00:00
abstract:BACKGROUND AIMS:In hepatitis C there is controversy over the linearity of the rate of progression and the significance of gender, mode of infection and viral factors. METHODS:2313 untreated patients with a reliable estimated duration of infection and liver fibrosis were included. Fibrosis progression was calculated us...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)00097-0
更新日期:2001-05-01 00:00:00
abstract::The aim of the present study was to determine the prevalence of hepatocellular carcinoma in adults with heterozygous alpha 1-antitrypsin deficiency and to assess the presence of possible co-risk factors for the development of hepatocellular carcinoma. Two hundred and forty patients with cirrhosis of different aetiolog...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80609-9
更新日期:1994-12-01 00:00:00
abstract:BACKGROUND & AIMS:The pathogenesis of autoimmune hepatitis (AIH) is not understood, but it was suggested that AIH may be related to a numerical or functional impairment of CD4+CD25+FOXP3+ regulatory T cells (Treg), which are important mediators of immune tolerance to self-antigens. However, the role of Treg in AIH is n...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.02.029
更新日期:2012-07-01 00:00:00
abstract::Activities of superoxide dismutase, catalase and glutathione peroxidase were measured in liver biopsy specimens from patients with various liver diseases, including six with chronic persistent hepatitis, nine with chronic active hepatitis, nine with non-alcoholic cirrhosis, eight with alcoholic cirrhosis and eight wit...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(90)90114-7
更新日期:1990-09-01 00:00:00
abstract:BACKGROUND & AIMS:High-density lipoprotein cholesterol (HDL-C) levels are reduced in patients with chronic liver disease and inversely correlate with disease severity. During acute conditions such as sepsis, HDL-C levels decrease rapidly and HDL particles undergo profound changes in their composition and function. We a...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.01.026
更新日期:2020-07-01 00:00:00
abstract::Two groups of patients with HBV DNA-positive chronic active hepatitis B, from 20 French hospitals, separated according to HBe status, were prospectively subjected to a comparative analysis of various epidemiological, clinical, biochemical, serologic and histologic features. There were 61 patients with anti-HBe and 215...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80352-6
更新日期:1994-05-01 00:00:00