Abstract:
BACKGROUND & AIMS:Mutations in ABCB11 can cause deficiency of the bile salt export pump (BSEP), leading to cholestasis and end-stage liver disease. Owing to the rarity of the disease, the associations between genotype and natural history, or outcomes following surgical biliary diversion (SBD), remain elusive. We aimed to determine these associations by assembling the largest genetically defined cohort of patients with severe BSEP deficiency to date. METHODS:This multicentre, retrospective cohort study included 264 patients with homozygous or compound heterozygous pathological ABCB11 mutations. Patients were categorized according to genotypic severity (BSEP1, BSEP2, BSEP3). The predicted residual BSEP transport function decreased with each category. RESULTS:Genotype severity was strongly associated with native liver survival (NLS, BSEP1 median 20.4 years; BSEP2, 7.0 years; BSEP3, 3.5 years; p <0.001). At 15 years of age, the proportion of patients with hepatocellular carcinoma was 4% in BSEP1, 7% in BSEP2 and 34% in BSEP3 (p = 0.001). SBD was associated with significantly increased NLS (hazard ratio 0.50; 95% CI 0.27-0.94: p = 0.03) in BSEP1 and BSEP2. A serum bile acid concentration below 102 μmol/L or a decrease of at least 75%, each shortly after SBD, reliably predicted NLS of ≥15 years following SBD (each p <0.001). CONCLUSIONS:The genotype of severe BSEP deficiency strongly predicts long-term NLS, the risk of developing hepatocellular carcinoma, and the chance that SBD will increase NLS. Serum bile acid parameters shortly after SBD can predict long-term NLS. LAY SUMMARY:This study presents data from the largest genetically defined cohort of patients with severe bile salt export pump deficiency to date. The genotype of patients with severe bile salt export pump deficiency is associated with clinical outcomes and the success of therapeutic interventions. Therefore, genotypic data should be used to guide personalized clinical care throughout childhood and adulthood in patients with this disease.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
van Wessel DBE,Thompson RJ,Gonzales E,Jankowska I,Sokal E,Grammatikopoulos T,Kadaristiana A,Jacquemin E,Spraul A,Lipiński P,Czubkowski P,Rock N,Shagrani M,Broering D,Algoufi T,Mazhar N,Nicastro E,Kelly DA,Nebbia G,Adoi
10.1016/j.jhep.2020.02.007subject
Has Abstractpub_date
2020-07-01 00:00:00pages
84-93issue
1eissn
0168-8278issn
1600-0641pii
S0168-8278(20)30105-7journal_volume
73pub_type
杂志文章abstract:BACKGROUND & AIMS:Liver macrophages can be involved in both pathogen clearance and/or pathogenesis. To get further insight on their role during chronic hepatitis B virus (HBV) infections, our aim was to phenotypically and functionally characterize in vivo and ex vivo the interplay between HBV, primary human liver macro...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2019.06.032
更新日期:2019-12-01 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::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:Alcoholic hepatitis is an acute life- and health-threatening disease that may be increasingly frequent. However, accurate and representative data on time trends in its incidence and prognosis are not available. This study aims to provide nationwide population-based estimates of alcoholic hepatitis inc...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.07.016
更新日期:2011-04-01 00:00:00
abstract::An impairment in the renal capacity to excrete water is a common finding in patients with cirrhosis and ascites. In some patients this abnormality is minor since it is only detectable by measuring urine volume or free water clearance after a water load and is not associated with changes in plasma osmolality and serum ...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/s0168-8278(96)80174-7
更新日期:1996-04-01 00:00:00
abstract::Non-alcoholic fatty liver disease (NAFLD) has become one of the most common forms of chronic liver disease worldwide and its prevalence is expected to continue rising. NAFLD has traditionally been considered a consequence of metabolic syndrome (MetS). However, the link between NAFLD and MetS components, especially typ...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2017.09.021
更新日期:2018-02-01 00:00:00
abstract::Worldwide, the increasingly dominant model of laboratory testing is the centralised laboratory, in which automation of analytical processes increases, enabling the analysis of large numbers of samples at a relatively low cost. However, this trend does not fulfil the requirements for care of patients with chronic hepat...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2018.05.017
更新日期:2018-10-01 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::Hepatitis A virus (HAV) infection in adults is often symptomatic and disabling. The present article summarizes our experience with phase 2 studies of an inactivated hepatitis A virus vaccine. Pre- and post-exposure prophylaxis with immune globulin (IG) is only effective for 4-6 months. We compared the safety, tolerabi...
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)80375-7
更新日期:1993-01-01 00:00:00
abstract::Three patients with Budd-Chiari syndrome in association with the 'lupus' anticoagulant are described. This anticoagulant was looked for in our patients with an otherwise idiopathic hepatic venous thrombosis because of the presence of a pronounced thrombocytopenia, a prolonged activated partial thromboplastin time or a...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(86)80151-9
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND & AIMS:Sorafenib is associated with multiple adverse events (AEs), potentially causing its permanent interruption. It is unknown how physicians' experience has impacted on the management of these AEs and consequently on clinical outcomes. We aimed to assess whether AE management changed over time and if thes...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2019.08.015
更新日期:2019-12-01 00:00:00
abstract:BACKGROUND & AIMS:The incidence of metabolic syndrome-related hepatocellular carcinoma (MS-HCC) is increasing worldwide. High resection risks are anticipated because of underlying steatohepatitis, but long-term results are unknown. To clarify the outcomes following liver resection in patients with MS-HCC and to compare...
journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.jhep.2015.01.024
更新日期:2015-07-01 00:00:00
abstract:BACKGROUND/AIMS:Protein-L-isoaspartyl methyltransferase (PIMT) is a methyltransferase that plays a crucial role in the repair of damaged proteins. In this study, we investigated whether ethanol exposure causes an accumulation of modified proteins bearing atypical isoaspartyl residues that may be related to impaired PIM...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2007.01.026
更新日期:2007-06-01 00:00:00
abstract:BACKGROUND & AIMS:Interleukin-6 (IL-6) is a crucial factor in liver regeneration following partial hepatectomy (PH); however, the role of IL-6 and IL-6 trans-signaling in particular, in hepatocyte mitosis remains controversial. IL-6 trans-signaling relies upon the release of the soluble IL-6R (sIL-6R), which binds IL-6...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.08.017
更新日期:2011-05-01 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:Little is known about genuine roles of androgens and their receptor in hepatocellular carcinoma. METHODS:In the present study, two sublines derived from a human hepatocellular carcinoma cell line KYN-1 were used: KYN-1/SM10 with androgen receptor and KYN-1/SM2 without androgen receptor. RESULTS:The bi...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(95)80282-7
更新日期:1995-03-01 00:00:00
abstract:BACKGROUND/AIMS:IgM antibodies to hepatitis C virus have been found in a variable proportion of patients with chronic hepatitis C. We have evaluated whether IgM anti-core antibodies correlate with viraemia or hepatic injury in chronic hepatitis C. METHODS:Serum from 106 patients with chronic hepatitis C with varying s...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(96)80181-4
更新日期:1996-01-01 00:00:00
abstract:BACKGROUND & AIMS:Although antiviral treatment for hepatitis C (HCV) is highly effective, side effects often occur, including weight loss, digestive symptoms, and impaired quality of life. We aimed at exploring the beneficial effects of preventive nutritional support. METHODS:In a randomized controlled trial, 53 HCV p...
journal_title:Journal of hepatology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.jhep.2012.06.029
更新日期:2012-11-01 00:00:00
abstract:BACKGROUND/AIMS:Most hepatocellular carcinomas are still discovered at an advanced stage and are left untreated as large hepatocellular carcinomas are contraindications to liver transplantation and percutaneous ethanol injection and are usually considered as poor indications for liver resection. The aim of this study w...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80319-5
更新日期:1999-12-01 00:00:00
abstract:BACKGROUND & AIMS:Roles of alcohol consumption in non-alcoholic fatty liver disease are still controversial, although several cross-sectional studies have suggested the beneficial effect of light to moderate drinking on fatty liver. We analyzed the longitudinal relationship between drinking pattern and fatty liver. ME...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.11.025
更新日期:2015-04-01 00:00:00
abstract:BACKGROUND/AIMS:Hepatitis C virus (HCV) is a major etiologic agent of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The aim of this study was to elucidate pathological effects of HCV-core protein on liver cells. METHODS:We have generated transgenic mice carrying HCV-core cDNA (Px-core) and pathologically...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)80280-9
更新日期:2000-09-01 00:00:00
abstract::It was discovered that eight patients with complications of non-cirrhotic portal hypertension had received an arsenical preparation for psoriasis as Fowler's solution some years age. Seven of them were admitted for bleeding oesophageal varices. Upon admission, splenomegaly and hypersplenism were present. Liver tests w...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(90)90276-w
更新日期:1990-07-01 00:00:00
abstract:BACKGROUND/AIMS:The relationship between HCV RNA levels and the severity of HCV-related liver disease has been addressed in a few studies, which has led to conflicting results. To clarify this point, we studied serum HCV RNA levels in patients with HCV liver disease at various stages, using a second-generation branched...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80336-5
更新日期:1999-10-01 00:00:00
abstract:BACKGROUND/AIMS:Partial hepatectomy results in activation of genes in the residual liver tissue which serve to restore glucose homeostasis and regenerate liver mass. Expression of insulin-like growth factor binding protein-1 (IGFBP-1) is up-regulated following partial hepatectomy and IGFBP-1 can modulate both the metab...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80199-8
更新日期:1999-04-01 00:00:00
abstract:BACKGROUND/AIMS:Suppressor of cytokine signaling (SOCS)-1, a negative feedback regulator of cytokine signaling pathway, also has a tumor suppressor activity, the silencing of its gene by hypermethylation is suggested to contribute to hepatocarcinogenesis. We studied the effect of the core protein of hepatitis C virus (...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2005.03.028
更新日期:2005-11-01 00:00:00
abstract::In this report we describe the case of a 7-year-old boy, suffering from autoimmune-type chronic active hepatitis (AI-CAH) associated with vitiligo, nail dystrophy, alopecia areata and a variant of liver kidney microsomal (LKM) autoantibodies. This patient's antibodies are different from LKM-1 which are directed agains...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(90)90148-k
更新日期:1990-05-01 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:Aberrant activation of the RAS pathway is ubiquitous in human hepatocarcinogenesis, but the molecular mechanisms leading to RAS induction in the absence of RAS mutations remain under-investigated. We defined the role of Ras GTPase activating proteins (GAPs) in the constitutive activity of Ras signalin...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.06.036
更新日期:2011-02-01 00:00:00
abstract::We previously reported that high-dose ursodeoxycholate (UDC) infusion in rats resulted in extensive glucuronidation of UDC, and speculated that the glucuronidation causes bicarbonate-rich hypercholeresis induced by UDC (Takikawa, H., Sano, N., Narita, T. and Yamanaka, M. Hepatology 1990; 11: 743-749). To test this hyp...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(92)90015-h
更新日期:1992-05-01 00:00:00
abstract::Hepatic fibrosis represents an important stage in the progression of chronic liver disease to cirrhosis. In the present paper we have investigated whether capsaicin-sensitive neuropeptide-containing sensory neurons may participate in the development of liver fibrosis. The expression of hepatic fibrosis induced by comm...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(90)90212-a
更新日期:1990-11-01 00:00:00