Search results for "Cholangitis"

102 NOVEL SUSCEPTIBILITY LOCI FOR PRIMARY SCLEROSING CHOLANGITIS IDENTIFIED BY GENOME-WIDE ASSOCIATION AND REPLICATION ANALYSIS

2011

Anti-neutrophil cytoplasmic antibodies in a rat model of trinitrobenzenesulphonic acid-induced liver injury

1999

Background In sera from patients with autoimmune liver diseases, e.g. primary sclerosing cholangitis (PSC) and autoimmune hepatitis, anti-neutrophil cytoplasmic antibodies (ANCAs) can be found. Until now, no animal model of ANCA induction in liver disease has been described. In this study, we describe a novel rat model of acute liver injury and subsequent ANCA production. Materials and methods The hapten reagent 2,4,6-trinitrobenzenesulphonic acid (TNBS) was injected into the portal vein of female Lewis rats. Two experimental groups were studied: group A (TNBS/ethanol) received different TNBS concentrations; control animals of group B (ethanol) were injected with 10% (v/v) ethanol/0.9% (w/v…

Autoimmune Lebererkrankungen: Diagnostik und Therapie

2004

Autoimmune Hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and overlap syndromes of these three disease entities are regarded as autoimmune liver diseases. These conditions are important differential diagnoses of elevated liver function tests as about 10 % of liver transplantations in Europe and North America are for these indications. The diagnosis is often difficult but can be facilitated by sequential measurement of relevant autoantibodies, exclusion of other liver disease, ultrasound, ERCP and liver histology. In AIH immunosuppressive therapy has been shown to prevent or stop the development of cirrhosis and improve the prognosis of the patients de…

Multicentre Survey of the Prevalence of Intrahepatic Cholestasis in 2520 Consecutive Patients with Newly Diagnosed Chronic Liver Disease

1992

In order to establish the prevalence of intrahepatic cholestasis (IHC) in chronic liver disease, we retrospectively evaluated the frequency of increased serum total bilirubin (STB), serum conjugated bilirubin (SCB) and serum alkaline phosphatase (SAP) levels in a cohort of 2520 patients with newly diagnosed chronic liver disease presenting over 2 years. 882 patients (35%) [mean age 52.2 years] had IHC involving abnormal levels of STB (mean 89.8 μmol/L), SCB (mean 52.5 μmol/L), and SAP (mean 5.7 μkat/L) together with a negative ultrasonic scan. Demographic data were not predictive of IHC. IHC was more frequent in patients with cirrhosis (43%), primary biliary cirrhosis (54%), and primary scl…

Genome-Wide Association Analysis in Primary Sclerosing Cholangitis

2010

Background & Aims We aimed to characterize the genetic susceptibility to primary sclerosing cholangitis (PSC) by means of a genome-wide association analysis of single nucleotide polymorphism (SNP) markers. Methods A total of 443,816 SNPs on the Affymetrix SNP Array 5.0 (Affymetrix, Santa Clara, CA) were genotyped in 285 Norwegian PSC patients and 298 healthy controls. Associations detected in this discovery panel were re-examined in independent case-control panels from Scandinavia (137 PSC cases and 368 controls), Belgium/The Netherlands (229 PSC cases and 735 controls), and Germany (400 cases and 1832 controls). Results The strongest associations were detected near HLA-B at chromosome 6p21…

Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis

2013

To access publisher's full text version of this article click on the hyperlink at the bottom of the page Primary sclerosing cholangitis (PSC) is a severe liver disease of unknown etiology leading to fibrotic destruction of the bile ducts and ultimately to the need for liver transplantation. We compared 3,789 PSC cases of European ancestry to 25,079 population controls across 130,422 SNPs genotyped using the Immunochip. We identified 12 genome-wide significant associations outside the human leukocyte antigen (HLA) complex, 9 of which were new, increasing the number of known PSC risk loci to 16. Despite comorbidity with inflammatory bowel disease (IBD) in 72% of the cases, 6 of the 12 loci sh…

TGF-β2 silencing to target biliary-derived liver diseases

2020

ObjectiveTGF-β2 (TGF-β, transforming growth factor beta), the less-investigated sibling of TGF-β1, is deregulated in rodent and human liver diseases. Former data from bile duct ligated and MDR2 knockout (KO) mouse models for human cholestatic liver disease suggested an involvement of TGF-β2 in biliary-derived liver diseases.DesignAs we also found upregulated TGFB2 in liver tissue of patients with primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), we now fathomed the positive prospects of targeting TGF-β2 in early stage biliary liver disease using the MDR2-KO mice. Specifically, the influence of TgfB2 silencing on the fibrotic and inflammatory niche was analysed on m…

Anti-fibrotic therapy: lost in translation?

2012

While preclinical development of potential anti-fibrotics is far advanced, with numerous pharmacological targets and promising agents, almost none has entered clinical validation. Reasons are manifold, including the usually slow progression of liver fibrosis, requiring high numbers of well-stratified patients undergoing long-term treatment when conventional liver biopsy based parameters or hard liver-related endpoints are used. Importantly, there is a notorious lack of sensitive and specific surrogate markers or imaging technologies for liver fibrosis progression or regression that would permit a rapid clinical screening for potential anti-fibrotics. Nonetheless, in view of an urgent need f…

Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis

2018

ObjectivePrimary sclerosing cholangitis (PSC) is a genetically complex, inflammatory bile duct disease of largely unknown aetiology often leading to liver transplantation or death. Little is known about the genetic contribution to the severity and progression of PSC. The aim of this study is to identify genetic variants associated with PSC disease progression and development of complications.DesignWe collected standardised PSC subphenotypes in a large cohort of 3402 patients with PSC. After quality control, we combined 130 422 single nucleotide polymorphisms of all patients—obtained using the Illumina immunochip—with their disease subphenotypes. Using logistic regression and Cox proportiona…

Diagnosis of sclerosing cholangitis in children: blinded, comparative study of magnetic resonance versus endoscopic cholangiography.

2013

Summary Background Magnetic resonance cholangiography (MRC) has been validated as comparable to endoscopic retrograde cholangiography (ERC) for the diagnosis of sclerosing cholangitis (SC) in adult patients. In children, MRC is widely used based mainly on non-comparative studies. Patients and methods ERCs and MRCs of seven children (median age 9, range: 7–20 years) with SC and 17 controls (median age 6, range: 2 months–20 years) with other chronic liver diseases were reviewed in a blinded, random and independent way. All patients underwent both examinations within a 6-months slot. All ERCs and 17 MRCs were performed under general anesthesia. One radiologist evaluated both ERCs and MRCs and …