Abstract:
:Chronic cholestatic diseases, whether occurring in infancy, childhood or adulthood, are characterized by defective bile acid transport from the liver to the intestine, which is caused by primary damage to the biliary epithelium in most cases. In this article, approaches to diagnosis and management of the main specific disorders are provided and some of the recent developments in this field are discussed. Major advances in the understanding of the cellular and molecular physiology of bile secretion have led to identification of genetic defects responsible for the different types of progressive familial intrahepatic cholestasis (PFIC). The potential role of the genes involved in PFIC in some adult cholestatic disorders remains to be determined. The majority of adult patients with chronic cholestasis have primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC). Recently, variant forms of PBC have been described. The term autoimmune cholangitis is used to describe patients having chronic non-suppurative cholangitis with negative antimitochondrial antibodies (AMA) but positive antinuclear and/or antismooth muscle antibodies. Autoimmune cholangitis and AMA-positive PBC are quite similar in terms of clinical presentation, survival and response to ursodeoxycholic acid (UDCA) therapy. In contrast, autoimmune cholangitis must be distinguished from PBC-autoimmune hepatitis (AIH) overlap syndrome in which biochemical and histological characteristics of both PBC and AIH coexist. Combination of UDCA and corticosteroids is required in most patients with overlap syndrome to obtain a complete clinical and biochemical response. Long-term UDCA treatment improves survival without liver transplantation in PBC patients. Among the putative mechanisms of the beneficial effects of UDCA, description of anti-apoptotic properties and effect on endotoxin disposal in biliary cells have provided new insights. In patients with incomplete response to UDCA, combination of UDCA with antiinflammatory or immunosuppressive drugs is under evaluation. Variant forms of PSC have also been described, including PSC-AIH overlap syndrome, especially in children or young adults, and small-duct PSC, which is characterized by normal cholangiogram in patients having chronic cholestasis, histologic features compatible with PSC and inflammatory bowel disease. Development of cholangiocarcinoma (CC) is a major feature of PSC, occurring in 10-15% of patients. Early diagnosis of CC is a difficult challenge, although positron emission tomography seems a promising tool. Unlike PBC, effective medical therapy is not yet available in PSC, reflecting the lack of knowledge about the exact pathogenesis of the disease. Currently, liver transplantation is the only effective therapy for patients with advanced disease, although recurrence of PSC in the graft may occur.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Poupon R,Chazouillères O,Poupon REdoi
10.1016/s0168-8278(00)80421-3subject
Has Abstractpub_date
2000-01-01 00:00:00pages
129-40issue
1 Suppleissn
0168-8278issn
1600-0641pii
S0168-8278(00)80421-3journal_volume
32pub_type
杂志文章,评审abstract::Hepatocellular carcinoma (HCC) is an accepted indication for liver transplantation (LT). Pre-LT adjuvant ablation treatments to prevent tumour progression and drop out from the waiting list have been increasingly adopted at most transplant centers. Trans-catheter arterial chemo-embolization (TACE) is frequently used, ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2008.02.021
更新日期:2008-07-01 00:00:00
abstract::Familial hypobetalipoproteinemia (FHBL) is an monogenic co-dominant disorder characterized by reduced plasma levels of cholesterol, low density lipoproteins (LDL) and apolipoprotein B (apoB) often associated with non-alcoholic fatty liver disease (NAFLD). It has been suggested that FHBL might predispose to gallstone d...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2005.03.012
更新日期:2005-07-01 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: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 aim of this prospective randomized controlled trial was to investigate the need for prophylactic antibiotherapy in patients with cirrhosis and hepatocellular carcinoma who underwent transarterial embolization and to establish the parameters that determine the development of fever > 38 degrees C afte...
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(95)80103-0
更新日期:1995-04-01 00:00:00
abstract::The peripheral arterial vasodilation hypothesis has been most influential in the field of cirrhosis and its complications. It has given rise to hundreds of pathophysiological studies in experimental and human cirrhosis and is the theoretical basis of life-saving treatments. It is undisputed that splanchnic arterial va...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2015.07.004
更新日期:2015-11-01 00:00:00
abstract:BACKGROUND & AIMS:Evidence on the efficacy of antiviral treatment in chronic hepatitis C (CHC) patients with hepatocellular carcinoma (HCC) after curative treatment is scarce. We aimed to evaluate the efficacy and safety of pegylated interferon-alpha plus ribavirin (pegIFN/RBV) combination therapy in these patients, co...
journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.jhep.2010.07.011
更新日期:2011-02-01 00:00:00
abstract::In an attempt to evaluate the prevalence, kinetics and impact of HCV infection in renal transplantation, we analyzed 140 kidney recipients according to the histopathological status of the liver. Thirty-three HBsAg-negative patients had chronic active hepatitis, 73 HBsAg-negative patients had a normal liver, 21 HBsAg-n...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(92)90036-o
更新日期:1992-05-01 00:00:00
abstract:BACKGROUND/AIMS:No study has compared the liver fibrosis progression rates among chronic liver diseases and the risk factors in order to better organize screening strategies. METHODS:A total of 4852 patients were retrospectively studied (chronic hepatitis C (HCV) [n=2313], human immunodeficiency virus (HIV)-HCV co-inf...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(02)00413-0
更新日期:2003-03-01 00:00:00
abstract:BACKGROUND/AIMS:Hepatic encephalopathy (HE) is a serious neuropsychiatric complication of chronic liver disease. Brain monoamines have been implicated in the pathogenesis of HE. We examined the relationship between monoamine dysfunction and the degree of portal-systemic shunting (PSS) in rats with varying degrees of PS...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2004.01.003
更新日期:2004-05-01 00:00:00
abstract:BACKGROUND & AIMS:Liver fibrosis regression but also progression may occur in patients with autoimmune hepatitis (AIH) under treatment. There is a need for non-invasive surrogate markers for fibrosis development in AIH to better guide immunosuppressive treatment. The aims of the study were to assess the impact of compl...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2017.11.020
更新日期:2018-04-01 00:00:00
abstract:AIM/METHODS:To elucidate the metabolic effect of interferon alpha, the following tests were performed on 14 patients with chronic active hepatitis C before and after interferon therapy (6 million units/day for 2 weeks): (1) oral glucose tolerance tests to measure insulin secretion; (2) euglycemic hyperinsulinemic clamp...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章
doi:10.1016/0168-8278(88)80004-7
更新日期:1998-02-01 00:00:00
abstract:BACKGROUND & AIMS:Hepatitis C virus antiviral treatment is effective for individual patients but few active injecting drug users are treated. We considered the utility of antiviral treatment for primary prevention of hepatitis C. METHODS:A hepatitis C transmission model among injecting drug users was developed, incorp...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.08.029
更新日期:2011-06-01 00:00:00
abstract:BACKGROUND & AIMS:The toll-like receptor 9 (TLR9) agonist IMO-2125 is currently evaluated in clinical trials for chronic hepatitis C therapy. The aim of this study was to investigate the in vivo mode of action of a closely related compound, referred to as immunomodulatory oligonucleotide (IMO). METHODS:We analyzed the...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.11.038
更新日期:2013-04-01 00:00:00
abstract:BACKGROUND/AIM:Smooth muscle antibodies and antinuclear antibodies characterize type 1 autoimmune hepatitis. Our aim was to correlate the appearance and disappearance of these autoantibodies with clinical and histological events. METHODS:One hundred and seven patients were evaluated successively over 128+/-9 months. A...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80096-8
更新日期:1999-03-01 00:00:00
abstract:BACKGROUND & AIMS:Chronic liver disease is characterized by fibrosis that may progress to cirrhosis. Nucleotide oligomerization domain 2 (Nod2), a member of the Nod-like receptor (NLR) family of intracellular immune receptors, plays an important role in the defense against bacterial infection through binding to the lig...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.02.012
更新日期:2014-06-01 00:00:00
abstract:BACKGROUND & AIMS:Treating HCV infection reduces overall mortality and reduces the risk of multiple extrahepatic complications. Whether the reduction in mortality is primarily due to a reduction in liver-related causes or extrahepatic complications is unknown. METHODS:We identified HCV-positive individuals treated for...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.02.022
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND/AIMS:To assess the efficacy and safety of naltrexone for the short and long term treatment of pruritus of cholestasis. METHODS:Twenty patients with pruritus and cholestasis were included. A baseline pruritus score was obtained over 1 week. Patients were then randomized to receive 50 mg/day of naltrexone or ...
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(02)00318-5
更新日期:2002-12-01 00:00:00
abstract:BACKGROUND/AIMS:The precise mechanism of formation and significance of Mallory bodies (MBs) are poorly understood. The endoplasmic reticulum (ER) is the organelle responsible for proper folding and elimination of unfolded proteins. Therefore, failure of this function increases defective proteins in the cell. METHODS:W...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2007.01.039
更新日期:2007-07-01 00:00:00
abstract:BACKGROUND/AIMS:Frequent allelic losses on the long arm of chromosome 16 in several types of human cancers have suggested that 16q harbors one or more genes that are important for suppressing tumorigenesis in the tissues in question. METHODS:To identify the locations of putative tumor suppressor genes involved in hepa...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)80163-4
更新日期:2000-07-01 00:00:00
abstract::A portal hemodynamic study was made in 7 consecutive patients with chronic portal-systemic encephalopathy by percutaneous transhepatic catheterization of the portal vein and injecting contrast medium into the superior mesenteric vein or by superior mesenteric arterial portography in comparison with patients without en...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(85)80745-5
更新日期:1985-01-01 00:00:00
abstract::HCV is the principal etiologic agent of post-transfusion (PTH) hepatitis. The incidence and course of HCV hepatitis in liver transplant recipients is not well established. To resolve this information deficit, all records of recipients of single liver transplant (OLTx) between March 1986 and March 1990 at the Universit...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80270-3
更新日期:1993-07-01 00:00:00
abstract::The effect of a single bolus of somatostatin on oesophageal variceal pressure has been studied in 7 patients with cirrhosis and 5 patients with non-cirrhotic portal hypertension using a non-invasive variceal pressure gauge. Both groups of patients demonstrated similar reductions in variceal pressure with all subjects ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(86)80085-x
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND/AIMS:Alamifovir is a purine nucleotide analogue prodrug that shows potent activity against wild type and lamivudine resistant hepatitis B virus in preclinical studies. The aim of this study was to assess the safety and potential antiviral effects of alamifovir in humans. METHODS:A randomised, placebo contro...
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.2004.07.028
更新日期:2004-11-01 00:00:00
abstract:BACKGROUND & AIMS:The liver is the main hematopoietic site in embryos, becoming a crucial organ in both immunity and metabolism in adults. However, how the liver adapts both the immune system and enzymatic profile to challenges in the postnatal period remains elusive. We aimed to identify the mechanisms underlying this...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2018.08.018
更新日期:2018-12-01 00:00:00
abstract:BACKGROUND/AIMS:Not all alcoholic patients develop severe liver disease with fibrosis progressing to cirrhosis. It is of practical importance to determine whether some markers can predict progression of liver fibrosis. METHODS:We used a baboon model that mimics human alcoholic liver disease. Cytokeratin 7 and 19 expre...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(03)00144-2
更新日期:2003-06-01 00:00:00
abstract:BACKGROUND & AIM:Following acetaminophen (APAP) overdose, acute liver injury (ALI) can occur in patients that present too late for N-acetylcysteine treatment, potentially leading to acute liver failure, systemic inflammation, and death. Macrophages influence the progression and resolution of ALI due to their innate imm...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.02.031
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND/AIMS:The roles of T cells, natural killer T cells (NKT) and macrophages in autoimmune hepatitis have been well documented. However, the roles of natural killer (NK) cells in liver injury remain obscure. Here we examined the effect of Polyinosinic: polycytidylic acid (PolyI:C)-activated NK cells on liver inju...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2004.08.021
更新日期:2004-12-01 00:00:00
abstract:BACKGROUND & AIMS:Number-needed-to-treat is used in assessing the effectiveness of a health-care intervention, and reports the number of patients who need to be treated to prevent one additional bad outcome. Although largely used in medical literature, there are no studies measuring the benefit of liver transplantation...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.01.022
更新日期:2014-06-01 00:00:00
abstract::The prolylhydroxylase inhibitor HOE 077 which has proven to be liver-selective in animals was tested in general pharmacological and toxicological studies for unwanted effects and safety. The results of these studies permit clinical development. A single-dose study in healthy volunteers was performed which showed that ...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/0168-8278(91)90009-z
更新日期:1991-01-01 00:00:00