Abstract:
BACKGROUND/AIMS:Not all alcoholics develop liver disease (ALD). Thus, excessive ethanol consumption is necessary, but not sufficient, to induce alcoholic steatohepatitis (ASH) and ALD. Since endotoxemia is present in patients with ALD, it has been proposed that gut-derived, circulating endotoxin is the necessary co-factor for ASH. But, it is not known whether endotoxemia is the consequence or the trigger for ALD. Accordingly, the aim of the current study was to determine whether endotoxemia occurs prior to development of ASH and whether gut leakiness is the primary cause of the endotoxemia in an animal model of ASH. METHODS:Time courses for development of gut hyperpermeability, nitric oxide production, oxidative injury to the gut, endotoxemia, and liver injury were assessed in rats during 10 weeks of daily alcohol gavage. RESULTS:Liver fat and serum transaminase increased after 2 weeks, but evidence of liver cell injury and inflammation (ASH) occurred after 8 weeks. Gut leakiness, intestinal oxidative injury, and endotoxemia occurred in weeks 2-4 and progressed thereafter. CONCLUSIONS:That alcohol-induced gut leakiness and endotoxemia preceded steatohepatitis indicates they are not the consequence of ALD. Our data support the hypothesis that gut leakiness resulting in endotoxemia is a key co-factor (trigger) for ASH.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Keshavarzian A,Farhadi A,Forsyth CB,Rangan J,Jakate S,Shaikh M,Banan A,Fields JZdoi
10.1016/j.jhep.2008.10.028subject
Has Abstractpub_date
2009-03-01 00:00:00pages
538-47issue
3eissn
0168-8278issn
1600-0641pii
S0168-8278(08)00797-6journal_volume
50pub_type
杂志文章abstract::The presence of HBV-DNA sequences was evaluated in DNA extracted from serum samples, peripheral blood lymphocytes and liver biopsy specimens of five HBsAg/anti-HBe-positive carriers with chronic HDV infection. DNAs were tested by polymerase chain reaction (PCR) amplification technique using two pairs of oligonucleotid...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(91)90032-7
更新日期:1991-01-01 00:00:00
abstract:BACKGROUND/AIMS:Although matrix metalloproteinases (MMPs) and their specific inhibitors (TIMPs) play an essential role in liver injury associated with tissue remodeling, the cellular origin of MMPs/TMPs within the liver remains to be clarified. METHODS:Different liver cell populations were analysed with respect to the...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80007-5
更新日期:1999-01-01 00:00:00
abstract:BACKGROUND & AIM:Hydrogen peroxide-inducible clone-5 (Hic-5), also named as transforming growth factor beta-1-induced transcript 1 protein (Tgfb1i1), was found to be induced by TGF-β. Previous studies have shown that TGF-β is a principal mediator of hepatic stellate cell (HSC) activation in liver fibrosis. However, thi...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2015.08.026
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND & AIMS:Hepatocyte-like cells (HLCs), differentiated from pluripotent stem cells by the use of soluble factors, can model human liver function and toxicity. However, at present HLC maturity and whether any deficit represents a true fetal state or aberrant differentiation is unclear and compounded by compariso...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.10.016
更新日期:2015-03-01 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 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
更新日期:2005-05-01 00:00:00
abstract:BACKGROUND/AIMS:We have developed a gene therapy strategy based on the observation that insulin-like growth factor I (IGF-I) is necessary for the acquisition and maintenance of the transformed phenotype in hepatocarcinoma. This strategy consists in transfecting the rat hepatoma cell line with an episomal vector express...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(98)80263-8
更新日期:1998-11-01 00:00:00
abstract:BACKGROUND & AIM:Chronic liver diseases are characterized by expansion of the small immature cholangiocytes - a mechanism named ductular reaction (DR) - which have the capacity to differentiate into hepatocytes. We investigated the kinetics of this differentiation, as well as analyzing several important features of the...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2019.02.003
更新日期:2019-06-01 00:00:00
abstract::Vinyl chloride monomer is a known cause of angiosarcoma of the liver. It also has other toxic effects on the liver, and it has recently been suggested that exposure to vinyl chloride also causes hepatocellular carcinoma. However, the data on which this conclusion is based is incomplete. There is inadequate ascertainme...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2009.09.012
更新日期:2009-12-01 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:BACKGROUND/AIMS:[corrected] Hepatobiliary carcinoma (HBC) has been considered to be a late complication of end-stage primary sclerosing cholangitis (PSC). The incidence of HBC is approximately 20% in PSC patients evaluated for liver transplantation. The diagnosis of HBC is difficult, at least at an early stage and the ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(01)00042-3
更新日期:2001-06-01 00:00:00
abstract:BACKGROUND & AIM:Virus-induced fulminant hepatitis is a major cause of acute liver failure. During acute viral hepatitis the impact of type I interferon (IFN-I) on myeloid cells, including liver-resident Kupffer cells (KC), is only partially understood. Herein, we dissected the impact of locally induced IFN-I responses...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2017.11.029
更新日期:2018-04-01 00:00:00
abstract:BACKGROUND & AIMS:Intrahepatic cholangiocarcinoma (ICC) is a lethal malignancy without effective treatment options. MLN0128, a second generation pan-mTOR inhibitor, shows efficacy for multiple tumor types. We evaluated the therapeutic potential of MLN0128 vs. gemcitabine/oxaliplatin in a novel ICC mouse model. METHODS...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2017.07.006
更新日期:2017-12-01 00:00:00
abstract:BACKGROUND/AIMS:In chronic hepatitis C, disease progression and clinical manifestations are heterogenous. To clarify the role and interactions of viral and host factors in inducing liver cell injury, we examined the associations of several virological and metabolic variables with serum alanine aminotransferase levels. ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2006.01.004
更新日期:2006-04-01 00:00:00
abstract:BACKGROUND & AIMS:Current antiviral therapies help keep HBV under control, but they are not curative, as they are unable to eliminate the intracellular viral replication intermediate termed covalently closed circular DNA (cccDNA). Therefore, there remains an urgent need to develop strategies to cure CHB. Functional sil...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.09.019
更新日期:2020-09-25 00:00:00
abstract::Advances in the management of the pulmonary complications of cystic fibrosis may result in an increasing prevalence of patients with chronic liver disease which may, therefore, become more important in the long-term management of cystic fibrosis patients. However, no simple and reliable test is available for the diagn...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章
doi:10.1016/0168-8278(95)80444-7
更新日期:1995-05-01 00:00:00
abstract:BACKGROUND & AIMS:Hepatic stellate cells (HSCs) have a role in liver fibrosis. Guanine nucleotide-binding α-subunit 12 (Gα12) converges signals from G-protein-coupled receptors whose ligand levels are elevated in the environment during liver fibrosis; however, information is lacking on the effect of Gα12 on HSC trans-d...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2017.10.011
更新日期:2018-03-01 00:00:00
abstract::A joint EASL/AASLD Monothematic Conference on 'Nuclear Receptors and Liver Disease' was held from February 27th to March 1st, 2009, in Vienna, Austria, to discuss the latest advances at the forefront of basic and clinical nuclear receptor research and its potential implications for liver diseases. This article reports...
journal_title:Journal of hepatology
pub_type:
doi:10.1016/j.jhep.2009.12.002
更新日期:2010-03-01 00:00:00
abstract:BACKGROUND/AIMS:Graft reperfusion in liver transplantation is usually performed by initial portal reperfusion (IPR) and delayed rearterialization. Its influence on graft microcirculation is unknown. This study aimed to assess sinusoidal perfusion in dependence to this reperfusion technique during human living-donor liv...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2004.04.017
更新日期:2004-08-01 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::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::In a rat model of chronic portal hypertension we studied ethanol-induced gastric mucosal damage and the effects of pretreatment by propranolol and sucralfate. Susceptibility to ethanol was increased in chronic portal hypertensive rats compared with sham-operated rats (55 +/- 8% vs. 25 +/- 4%). Both acute pretreatment ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(87)80568-8
更新日期:1987-10-01 00:00:00
abstract:BACKGROUND/AIMS:To study whether the host's immune response determines viral clearance in chronic hepatitis C, virological markers and antigen-specific T cell reactions were analysed in 30 chronic HCV carriers followed up during interferon-alpha therapy, 11 untreated anti-HCV positive individuals and 10 healthy control...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(98)80146-3
更新日期:1998-10-01 00:00:00
abstract:BACKGROUND & AIMS:Hepatitis B virus (HBV) and D virus (HDV) co-infections cause the most severe form of viral hepatitis. HDV induces an innate immune response, but it is unknown how the host cell senses HDV and if this defense affects HDV replication. We aim to characterize interferon (IFN) activation by HDV, identify ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2018.02.021
更新日期:2018-07-01 00:00:00
abstract::Twenty patients with paracetamol(acetaminophen)-induced acute liver damage of varying severity were studied longitudinally with assessment of clinical state, standard liver function tests and radiometric hyaluronate (HYA) assay (Pharmacia). In patients (n = 6) who developed coma, HYA rose rapidly with clinical deterio...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(91)90856-7
更新日期:1991-07-01 00:00:00
abstract:BACKGROUND:Chronic liver failure resulting from hepatitis C virus infection often necessitates orthotopic liver transplantation. Recurrence of hepatitis C virus infection after transplantation is inevitable, and the infection is usually severe. Interferon and ribavirin have both been used to treat hepatitis C virus inf...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract::The term cirrhosis-associated immune dysfunction refers to the main syndromic abnormalities of immune function, immunodeficiency and systemic inflammation that are present in cirrhosis. The course of advanced cirrhosis, regardless of its aetiology, is complicated by cirrhosis-associated immune dysfunction and this con...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2014.08.010
更新日期:2014-12-01 00:00:00
abstract::In a multicentre trial, 82 patients known to be hepatitis B e antigen and hepatitis B virus DNA positive for at least 1 year, with elevated serum alanine aminotransferase levels and chronic liver lesions on biopsy, were randomized to receive either recombinant interferon alfa-2a at a dose of 4.5 million units thrice w...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/0168-8278(90)90179-u
更新日期:1990-01-01 00:00:00
abstract::Thirty-two patients with chronic hepatitis B were randomly assigned to two groups. Sixteen patients received 10 million units of alpha-interferon per square meter of body surface (MU/m2), three times weekly for 4 months. Sixteen patients were treated simultaneously with gamma-interferon at a dose of 2 MU/m2, and 10 MU...
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(05)80212-0
更新日期:1993-03-01 00:00:00
abstract:BACKGROUND & AIMS:Although liver fibrosis is an important predictor of outcomes for biliary atresia (BA), postsurgical native liver histology has not been well reported. Here, we retrospectively evaluated postsurgical native liver histology, and developed and assessed a novel scoring system - the BA liver fibrosis (BAL...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.01.028
更新日期:2014-06-01 00:00:00