Abstract:
BACKGROUND & AIMS:The pathogenesis and progression of non-alcoholic fatty liver disease (NAFLD) is still incompletely understood. Several nuclear receptors play a role in liver lipid metabolism and can promote hepatosteatosis, but the possible role of vitamin D receptor (VDR) in NAFLD has not been investigated. METHODS:The expression of liver VDR was investigated in apolipoprotein E knockout (apoE(-/-)) mice on a high fat diet, in wild-type mice on methionine and choline deficient diet and in NAFLD patients with hepatosteatosis and non-alcoholic steatohepatitis. The relevance of VDR was assessed in apoE(-/-) mice by deletion of VDR or paricalcitol treatment and in human HepG2 cells by VDR transfection or silencing. The role of VDR in fibrosis was also determined in VDR knockout mice (VDR(-/-)) treated with thioacetamide. RESULTS:Expression of liver VDR was markedly induced in two mouse models of NAFLD, as well as in patients with hepatosteatosis, but decreased in non-alcoholic steatohepatitis. VDR deletion in high fat diet-fed apoE(-/-) mice protected against fatty liver, dyslipidemia and insulin resistance, and caused a decrease in taurine-conjugated bile acids, but did not influence fibrosis by thioacetamide. apoE(-/-)VDR(-/-) mouse livers showed decreased gene expression of CD36, DGAT2, C/EBPα and FGF21, and increased expression of PNPLA2, LIPIN1 and PGC1α. Treatment of apoE(-/-) mice on high fat diet with paricalcitol had modest opposite effects on steatosis and gene expression. Finally, this set of genes showed concordant responses when VDR was overexpressed or silenced in HepG2 cells. CONCLUSIONS:Induced hepatocyte VDR in NAFLD regulates key hepatic lipid metabolism genes and promotes high fat diet-associated liver steatosis. Therapeutic inhibition of liver VDR may reverse steatosis in early NAFLD. LAY SUMMARY:The amount of vitamin D receptor is induced early in the livers of mice and humans when they develop non-alcoholic fatty liver disease. If the gene for the vitamin D receptor is deleted, hepatic lipid metabolism changes and mice do not accumulate fat in the liver. We conclude that the vitamin D receptor can contribute to the fatty liver disease promoted by a high fat diet.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Bozic M,Guzmán C,Benet M,Sánchez-Campos S,García-Monzón C,Gari E,Gatius S,Valdivielso JM,Jover Rdoi
10.1016/j.jhep.2016.05.031subject
Has Abstractpub_date
2016-10-01 00:00:00pages
748-757issue
4eissn
0168-8278issn
1600-0641pii
S0168-8278(16)30243-4journal_volume
65pub_type
杂志文章abstract:BACKGROUND & AIMS:HCV related liver disease is one of the most important complications in persons with HIV, with accelerated fibrosis progression in coinfected persons compared to those with HCV alone. We hypothesized that HCV-HIV coinfection increases HCV related hepatocyte apoptosis and that HCV and HIV influence TRA...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.07.042
更新日期:2011-04-01 00:00:00
abstract::Data derived from population, case-control, and cohort studies conducted in several Euro-Mediterranean and African countries disclose impressive similarities in the age and modes of hepatitis B virus (HBV) transmission and in the prevalence, duration, and outcome of the four phases of the natural history of chronic in...
journal_title:Journal of hepatology
pub_type: 历史文章,杂志文章,评审
doi:10.1016/j.jhep.2010.12.030
更新日期:2011-07-01 00:00:00
abstract:BACKGROUND & AIMS:Direct-acting antiviral (DAA) therapy is used in patients with HCV-related decompensated cirrhosis with the expectation of improving hepatic function. However, little is known about the long-term hepatic benefit of successful antiviral treatment. METHODS:Patients with advanced/decompensated cirrhosis...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.03.031
更新日期:2020-09-01 00:00:00
abstract::Drug hepatotoxicity is partially determined by genetic factors involved in drug metabolism, which may involve the debrisoquine oxidation polymorphism mediated by cytochrome (CYP) 2D6. The purpose of this study was to assess the relationship between drug hepatotoxicity and another genetic polymorphism of drug oxidation...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80620-8
更新日期:1994-12-01 00:00:00
abstract::To evaluate the efficacy of recombinant interferon alpha-2b in the treatment of patients with acute post-transfusion hepatitis C, a randomized controlled trial was conducted in 33 acute post-transfusion hepatitis C patients; 16 patients received 3 million units of subcutaneously injected recombinant interferon alpha-2...
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(94)80246-7
更新日期:1994-11-01 00:00:00
abstract:BACKGROUND & AIMS:High oxidative stress plays a major role in increasing hepatic vascular resistance in cirrhosis, by facilitating liver fibrosis and by increasing hepatic vascular tone. This study is aimed at investigating whether the use of the novel isoform of recombinant human manganese superoxide dismutase (rMnSOD...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.09.010
更新日期:2013-02-01 00:00:00
abstract:BACKGROUND/AIMS:Primary sclerosing cholangitis (PSC) is associated with a high risk of cholangiocarcinoma. Our aim was to evaluate the diagnostic value of trypsinogen-1, trypsinogen-2, tumour-associated trypsin inhibitor, human chorionic gonadotropin beta and trypsin-2-alpha(1)-antitrypsin for cholangiocarcinoma and to...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2007.05.017
更新日期:2007-11-01 00:00:00
abstract:BACKGROUND/AIMS:The organic anion transporting polypeptides (OATPs) mediate the uptake of numerous amphipathic compounds into hepatocytes. Our aim was to study the expression and regulation of OATP8 (OATP1B3, SLC21A8/SLCO1B3) and OATP-C (OATP1B1, SLC21A6/SLCO1B1) in hepatocellular carcinomas (HCC). METHODS:RNA and pro...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2003.10.008
更新日期:2004-02-01 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:BACKGROUND/AIMS:In these studies, we tested the hypothesis that increased lipid intake would exacerbate the severity of nutritional steatohepatitis. METHODS:C57Bl/6J mice were fed methionine-and-choline deficient (MCD) diets containing 20% (high) or 5% (low) fat by weight for 3 weeks and compared to lipid-matched cont...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2008.03.026
更新日期:2008-09-01 00:00:00
abstract::Recently, we have shown that taurocholate transport is impaired in hepatocytes isolated from CCl4 cirrhotic rats. Na+,K+-ATPase activity depends on the lipid composition of the surrounding membrane. Therefore, we performed this study in order to detect differences in plasma membrane composition and membrane functions ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(89)90068-8
更新日期:1989-07-01 00:00:00
abstract:BACKGROUND/METHODS:The cause of fulminant hepatitis is still not fully understood. We studied 23 patients with fulminant hepatitis, using polymerase chain reaction to detect hepatitis virus genomes. Tests for HBsAg and IgM anti-HAV and IgM anti-HBc were performed in all patients. Serum samples were stored at -70 degree...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(96)80002-x
更新日期:1996-03-01 00:00:00
abstract:BACKGROUND & AIMS:Therapy of chronic hepatitis B with HBV-polymerase inhibitors, in particular tenofovir or adefovir, may affect renal function. To assess renal function more accurately in the normal range, we used the recently validated, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula to calculate ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2011.03.030
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND/AIM:The present in vivo study investigated the impact of a monoclonal antibody directed against the intercellular adhesion molecule-1 (ICAM-1) on initial microvascular reperfusion injury after liver transplantation. METHODS:Orthotopic, syngeneic liver transplantation including arterial reconstruction was pe...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)80252-4
更新日期:2000-05-01 00:00:00
abstract:BACKGROUND & AIMS:Recent studies have suggested that insulin resistance exerts a strong influence on chronic hepatitis C virus (HCV) infection. We analyzed pretreatment factors useful for predicting sustained virological response (SVR), especially interleukin (IL) 28B polymorphism and Homeostasis Model Assessment of In...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.04.027
更新日期:2012-09-01 00:00:00
abstract:BACKGROUND:Hepatopulmonary syndrome (HPS) has been defined as a clinical triad, including chronic liver disease, gas exchange defects (increased alveolar-arterial PO2 difference irrespective of the presence of arterial hypoxemia), and widespread intrapulmonary vascular dilatations. We determined the incidence and the c...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)00108-2
更新日期:2001-05-01 00:00:00
abstract:BACKGROUND & AIMS:Herpes simplex virus hepatitis is a rare, but severe disease, thus far only documented by case reports and short series. The present study was based on the SRTR registry, and included all listed patients for liver transplantation from 1985 to 2009 with a diagnosis of HSV hepatitis. METHODS:We assesse...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2011.02.029
更新日期:2011-12-01 00:00:00
abstract::Porphyria cutanea tarda (PCT) is a metabolic disorder characterized by a reduced hepatic activity of uroporphynogen decarboxylase (URO-D), an enzyme of the heme synthesis. The clinical features of PCT may be brought into light by hepatic injury induced by hepatitis C virus (HCV). A significant association between HCV ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2004.10.029
更新日期:2005-04-01 00:00:00
abstract:BACKGROUND/AIMS:Although ursodeoxycholic acid is effective for the treatment of primary biliary cirrhosis, some patients do not respond to this treatment. The objective of the present study was to investigate the effects of additional administration of colchicine in ursodeoxycholic acid-treated patients with primary bi...
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(96)80191-7
更新日期:1996-01-01 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:BACKGROUND & AIMS:Macrophages (Mϕ) represent a major component of tumor tissues and play an important role in both tumor progression and therapeutic response. Although tumor Mϕ are generally considered to be derived from circulating monocytes, emerging evidence indicates that tissue Mϕ pools can be maintained by self-r...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.10.021
更新日期:2020-10-31 00:00:00
abstract:BACKGROUND/AIMS:The applicability of adult-to-adult living donor liver transplantation has not been established yet. We report the first data in a European center of the process leading to this procedure from the first moment the patients were informed about it. METHODS:In phase 1 of the process, 121 adult patients en...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2005.02.016
更新日期:2005-07-01 00:00:00
abstract::This article summarizes the current state of antiviral therapy of hepatitis B with special attention given to areas that remain controversial or poorly defined. Strict adherence to liver association practice guidelines may result in missed opportunities to treat patients with significant underlying liver disease. In p...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2008.01.011
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND/AIMS:Interferon (IFN) with ribavirin combination therapy (CT) was proposed for the treatment of hepatitis C recurring in liver transplants. We assessed the efficacy of two protocols of CT in transplanted patients with recurrent severe hepatitis C virus (HCV) hepatitis. METHODS:Fifty-seven patients (68% geno...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章
doi:10.1016/s0168-8278(02)00109-5
更新日期:2002-08-01 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:BACKGROUND & AIMS:Aceruloplasminemia is a rare autosomal recessive neurodegenerative disease associated with brain and liver iron accumulation which typically presents with movement disorders, retinal degeneration, and diabetes mellitus. Ceruloplasmin is a multi-copper ferroxidase that is secreted into plasma and facil...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.04.039
更新日期:2010-12-01 00:00:00
abstract:BACKGROUND & AIMS:Robust data on hepatocellular carcinoma (HCC) incidence among HIV/hepatitis B virus (HBV)-coinfected individuals on antiretroviral therapy (ART) are needed to inform HCC screening strategies. We aimed to evaluate the incidence and risk factors of HCC among HIV/HBV-coinfected individuals on tenofovir d...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2019.03.032
更新日期:2019-08-01 00:00:00
abstract::Histological fibrosis stage is one of the most important prognostic factors in compensated and decompensated alcohol-related liver disease (ALD). Morphological assessment of fibrosis is useful for patient stratification, enabling individualised management, and for evaluation of treatment effects in clinical studies. I...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2018.12.003
更新日期:2019-02-01 00:00:00
abstract:BACKGROUND/AIMS:Hepatitis B virus (HBV) infection in extrahepatic tissues is controversial. To clarify whether episomal HBV can infect nonhepatic tissues, we investigated the molecular forms of HBV in the lymphatic cells of inactive HBV carriers who lacked viremia, thus avoiding contamination with HBV genomes originati...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2005.01.016
更新日期:2005-06-01 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