Abstract:
:The alterations of hepatobiliary transport that occur in cholestasis can be divided into primary defects, such as mutations of transporter genes or acquired dysfunctions of transport systems that cause defective canalicular or cholangiocellular secretion, and secondary defects, which result from biliary obstruction. The dysfunction of distinct biliary transport systems as a primary cause of cholestasis is exemplified by the genetic defects in progressive familial intrahepatic cholestasis or by the direct inhibition of transporter gene expression by cytokines. In both, the hepatocellular accumulation of toxic cholephilic compounds causes multiple alterations of hepatocellular transporter expression. In addition, lack of specific components of bile caused by a defective transporter, as in the case of mdr2/MDR3 deficiency, unmasks the toxic potential of other components. The production of bile is critically dependent upon the coordinated regulation and function of sinusoidal and canalicular transporters, for instance of Na+-taurocholate cotransporting polypeptide (NTCP) and bile salt export pump (BSEP). Whereas the downregulation of the unidirectional sinusoidal uptake system NTCP protects the hepatocyte from further intracellular accumulation of bile salts, the relative preservation of canalicular BSEP expression serves to uphold bile salt secretion, even in complete biliary obstruction. Conversely, the strong downregulation of canalicular MRP2 (MRP, multidrug resistance protein) in cholestasis forces the hepatocyte to upregulate basolateral efflux systems such as MRP3 and MRP1, indicating an inverse regulation of basolateral and apical transporters The regulation of hepatocellular transporters in cholestasis adheres to the law of parsimony, since many of the cellular mechanisms are pivotally governed by the effect of bile salts. The discovery that bile salts are the natural ligand of the farnesoid X receptor has shown us how the major bile component is able to regulate its own enterohepatic circulation by affecting transcription of the genes critically involved in transport and metabolism.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Kullak-Ublick GA,Beuers U,Paumgartner Gdoi
10.1016/s0168-8278(00)80411-0subject
Has Abstractpub_date
2000-01-01 00:00:00pages
3-18issue
1 Suppleissn
0168-8278issn
1600-0641pii
S0168827800804110journal_volume
32pub_type
杂志文章,评审abstract::Recently reports have indicated that both cimetidine and ranitidine delay cell proliferation in rats following 70% partial hepatectomy and result in an increased mortality following this procedure. The present study was designed to determine whether three H2 blocking agents (cimetidine, ranitidine, famotidine) and a n...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(89)90159-1
更新日期:1989-01-01 00:00:00
abstract:BACKGROUND/AIMS:To bridge acute liver failure (ALF) patients to orthotopic liver transplantation, several bioartificial liver (BAL) systems have been developed. The bio-component of most BAL systems consists mainly of porcine hepatocytes. Plasma or blood of ALF patients is perfused through the BAL thereby contacting po...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2004.11.041
更新日期:2005-04-01 00:00:00
abstract::Hydroxyethyl starch (HES) has gained wide clinical acceptance as a colloidal plasma substitute. We were able to study the liver biopsies of two patients with renal failure who developed ascites after repeated infusions of HES. All types of liver cells displayed massive accumulation of HES with the morphologic resembla...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(86)80030-7
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND & AIMS:Tumor shrinkage has been considered a fundamental surrogate efficacy measure for new cancer treatments. However, in patients treated with sorafenib for advanced hepatocellular carcinoma (HCC), tumor shrinkage rarely accompanies increased survival, thereby questioning the prognostic value of imaging-ba...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.02.016
更新日期:2012-07-01 00:00:00
abstract::In order to document the incidence of hepatitis delta virus (HDV) replication markers and their relationship to HBV replication, 91 HBsAg chronic carriers were studied. Of these, 51 were anti-HD-positive (19 HBeAg-positive and 32 anti-HBe-positive). Liver HDAg was found in 75% of anti-HD-positive patients. Of the 19 p...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(88)80033-3
更新日期:1988-04-01 00:00:00
abstract:BACKGROUND/AIMS:Interleukin-15 (IL-15) is expressed in many organs. It generally inhibits apoptosis and increases cellular proliferation and differentiation. However, IL-15's roles in liver are unknown. We aimed to determine if IL-15 influences hepatic integrity and regenerative activity. METHODS:Expression of IL-15 a...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2006.04.008
更新日期:2006-09-01 00:00:00
abstract:BACKGROUND/AIMS AND METHODS:The etiology of intrahepatic cholestasis of pregnancy (JCP) is unknown. We have performed comprehensive chromatographic and mass spectrometric analyses of progesterone metabolites and bile acids in serum and urine of six patients in order to characterize changes that might be of importance f...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(97)80181-x
更新日期:1997-08-01 00:00:00
abstract::This study set out to examine the relative effectiveness and tolerability of 12- versus 24-week courses of thrice weekly intramuscular lymphoblastoid interferon in the treatment of hepatitis B 'e' antigen (HBeAg)-positive chronic hepatitis B virus (HBV) infection, and to identify pretreatment factors predicting the ou...
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(87)80061-2
更新日期:1987-08-01 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::Design and endpoints of clinical trials in hepatocellular carcinoma. Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, Sherman M, Schwartz M, Lotze M, Talwalkar J, Gores GJ; for the Panel of Experts in HCC-Design Clinical Trials. The design of clinical trials in hepatocellular carcinoma (HCC) is comp...
journal_title:Journal of hepatology
pub_type: 评论,杂志文章
doi:10.1016/j.jhep.2008.07.012
更新日期:2008-10-01 00:00:00
abstract:Background & Aims:Liver enzyme abnormalities are common in patients with coronavirus disease 2019 (COVID-19). Whether or not severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to liver damage per se remains unknown. Herein, we reported the clinical characteristics and liver pathological man...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.05.002
更新日期:2020-10-01 00:00:00
abstract:BACKGROUND & AIMS:Emricasan, an oral pan-caspase inhibitor, decreased portal pressure in experimental cirrhosis and in an open-label study in patients with cirrhosis and severe portal hypertension, defined as a hepatic venous pressure gradient (HVPG) ≥12 mmHg. We aimed to confirm these results in a placebo-controlled s...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2019.12.010
更新日期:2020-05-01 00:00:00
abstract:BACKGROUND/AIMS:The impact of dietary fatty acids on the development of cancers is highly controversial. We recently demonstrated that unsaturated fatty acids trigger the downregulation of the tumor suppressor PTEN through an mTOR/NF-kappaB-dependent mechanism in hepatocytes. In this study, we investigated whether unsa...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2009.01.027
更新日期:2009-06-01 00:00:00
abstract:BACKGROUND & AIMS:We aimed at comparing overall and liver-related mortality rates, observed in HIV positive subjects followed-up in the Cohorts of Spanish Network on HIV/AIDS Research stratified by HCV co-infection status, with the expected mortality of the general population of same age and sex in Spain, for the perio...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.06.010
更新日期:2012-10-01 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::The aims of this study were to evaluate bone metabolism in primary biliary cirrhosis (PBC) and the effect of ADFR (activate, depress, free, repeat) therapy with vitamin D, calcium and calcitonin in preventing bone resorption. Sixty-nine female subjects entered the study: 38 PBC (AMA + ve) patients, 11 AMA-negative chr...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(91)90941-4
更新日期:1991-03-01 00:00:00
abstract:BACKGROUND & AIMS:Hepatocellular ballooning is a key finding in nonalcoholic steatohepatitis (NASH). It is conventionally defined by hemotoxylin and eosin (H&E) staining showing enlarged cells with rarefied cytoplasm and recently by changes in the cytoskeleton. Fat droplets are emerging as important organelles in cell ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.04.031
更新日期:2010-10-01 00:00:00
abstract:BACKGROUND & AIMS:Alcohol is the main contributing factor of alcoholic cirrhosis, but less is known about the significance of drinking pattern. METHODS:We investigated the risk of alcoholic cirrhosis among 55,917 participants (aged 50-64 years) in the Danish Cancer, Diet, and Health study (1993-2011). Baseline informa...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.12.005
更新日期:2015-05-01 00:00:00
abstract:BACKGROUND/AIMS:The tropical parasite Schistosoma mansoni causes granulomatous inflammation following lodging of eggs in portal capillaries. In vitro studies indicated that the host reaction should involve reactive oxygen intermediates; however, it is not known what occurs in vivo at the site of the disease. Moreover, ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80189-5
更新日期:1999-04-01 00:00:00
abstract:BACKGROUND/AIMS:The x gene of hepatitis B virus encodes a transactivating factor of 154 amino acids, termed HBx, which stimulates transcription of multiple viral and cellular genes. The transactivating function is probably associated with a tumorigenic potential of HBx, since x gene sequences, encoding functional HBx, ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(95)80311-4
更新日期:1995-07-01 00:00:00
abstract::A monoclonal antibody, designated K-PLC1, has been produced to a tumour-associated antigen on the cell membrane of the PLC/PRF/5 cell line. Using an indirect immunofluorescence technique this antibody produced membrane staining of three hepatocellular carcinoma (HCC) cell lines and it has positively stained 10 of 11 h...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(87)80009-0
更新日期:1987-02-01 00:00:00
abstract:BACKGROUND/AIMS:The natural history of chronic hepatitis C (HCV) is not completely understood. This study was aimed to evaluate the long-term outcome of the disease over a prolonged period of time and to identify factors associated with progression. METHODS:One hundred and sixteen patients with non-cirrhotic chronic n...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(01)00088-5
更新日期:2001-08-01 00:00:00
abstract::Abnormalities of carbohydrate metabolism, including hyperinsulinaemia and insulin resistance, are well recognised complications of cirrhosis. While diabetes mellitus can be explained in many instances on the basis of coincident pancreatic disease, in most the characteristic glucose intolerance of cirrhosis is not read...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80631-2
更新日期:1994-12-01 00:00:00
abstract:BACKGROUND/AIMS:Interferon therapy has been shown to have beneficial effects in chronic hepatitis C, but the optimal duration of treatment has not been clearly defined. The aims of this study were: (a) to perform a detailed histological comparison of the effects of a 6-month and a 12-month treatment using the Knodell s...
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)80286-8
更新日期:1996-12-01 00:00:00
abstract::Secondary biliary cirrhosis in the rat is an attractive model since unlike other models it does not rely on exogenous toxic compounds to induce cirrhosis. However, because little is known about the microcirculatory abnormalities of this model, this study investigated hemodynamics in rats with predefined functional imp...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80031-5
更新日期:1993-02-01 00:00:00
abstract:BACKGROUND & AIMS:Prevalence data for hepatitis B and C and an evaluation of a guideline based screening in the primary care setting are not yet available. We therefore implemented a hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus (HCV) screening and developed guideline based screening strategies. METHO...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2015.01.011
更新日期:2015-06-01 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:Large extracellular vesicles, specifically AnnexinV+ EpCAM+ CD147+ tumour-associated microparticles (taMPs), facilitate the detection of colorectal carcinoma (CRC), non-small cell lung carcinoma (NSCLC) as well as pancreas carcinoma (PaCa). Here we assess the diagnostic value of taMPs for detection an...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2017.02.024
更新日期:2017-08-01 00:00:00
abstract:BACKGROUND & AIMS:Weak hepatitis C virus (HCV) specific immunity in peripheral blood has been shown to be partially controlled by regulatory T cells (Treg). However, little is known about Treg present in livers of HCV-infected patients, their association with clinical parameters, and immunopathology resulting in diseas...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2009.12.013
更新日期:2010-03-01 00:00:00
abstract:BACKGROUND & AIMS:This study aimed to identify preoperative magnetic resonance (MR) imaging biomarkers for predicting microvascular invasion (MVI), to determine their diagnostic performance and to evaluate whether they are associated with early recurrence after surgery for single hepatocellular carcinoma (HCC). METHOD...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2017.04.024
更新日期:2017-09-01 00:00:00