Search results for "cholestasis"
showing 10 items of 71 documents
A Novel MicroRNA Signature for Cholestatic Drugs in Human Hepatocytes and Its Translation into Novel Circulating Biomarkers for Drug-Induced Liver In…
2019
AbstractDrug-induced liver injury (DILI) diagnosis and classification (hepatocellular, cholestatic, and mixed) relies on traditional clinical biomarkers (eg ALT and ALP), despite limitations such as extrahepatic interferences, narrow dynamic ranges, and low mechanistic value. microRNAs may be very useful for complementing traditional DILI biomarkers but most studies in this direction have considered only paracetamol poisoning. Thus the value of microRNAs (miRNAs) as biomarkers for idiosyncratic DILI has not yet been demonstrated. In this study, we first examined the effect of model cholestatic drugs on the human hepatocyte miRNome by RNAseq and RT-qPCR. Results demonstrated that chlorpromaz…
Variability in human hepatic MRP4 expression: influence of cholestasis and genotype
2007
The multidrug resistance protein 4 (MRP4) is an efflux transporter involved in the transport of endogenous substrates and xenobiotics. We measured MRP4 mRNA and protein expression in human livers and found a 38- and 45-fold variability, respectively. We sequenced 2 kb of the 5'-flanking region, all exons and intron/exon boundaries of the MRP4 gene in 95 patients and identified 74 genetic variants including 10 non-synonymous variations, seven of them being located in highly conserved regions. None of the detected polymorphisms was significantly associated with changes in the MRP4 mRNA or protein expression. Immunofluorescence microscopy indicated that none of the non-synonymous variations af…
A mitochondrial antigen-antibody system in cholestatic liver disease detected by radioimmunoassay.
2007
A radioimmunoassay (RIA) was established for the detection of antimitochondrial autoantibodies (AMAs) in patient sera. AMAs were detected by RIA in 12 of 14 patients with primary biliary cirrhosis and in 3 of 29 patients with chronic active hepatitis. AMAs were detected by indirect immunofluorescence in all sera positive by RIA. In addition, two patients with primary biliary cirrhosis and one patient with chronic active hepatitis were AMA positive when tested by indirect immunofluorescence, but negative when tested by RIA. AMAs were not detected by RIA or indirect immunofluorescence in 121 further patients with various hepatic and nonhepatic diseases, including healthy controls. The RIA det…
A prospective evaluation of magnetic resonance cholangiopancreatography in patients with suspected bile duct obstruction.
1998
Background—The value of magnetic resonance cholangiopancreatography (MRCP) is under debate.Aims—To assess the diagnostic accuracy of MRCP and endoscopic retrograde cholangiopancreatography (ERCP) and to determine whether MRCP may help to prevent unnecessary interventional procedures.Methods—Eighty six patients with suspected common bile duct obstruction who presented between January and December 1996 were enrolled. Twenty six were excluded due to anatomical reasons or because MRCP or ERCP could not be performed successfully. Results of MRCP were interpreted by two radiologists and a gastroenterologist unaware of clinical diagnosis. Final diagnosis was determined by ERCP and histopathologica…
Secondary sclerosing cholangitis after long-term treatment in an intensive care unit: clinical presentation, endoscopic findings, treatment, and foll…
2006
Background and study aims We present ten patients who developed secondary sclerosing cholangitis following long-term treatment in an intensive care unit (ICU) between 1999 and 2004. Patients and methods Ten consecutive patients who had no evidence suggestive of pre-existing hepatobiliary disease were admitted to an ICU because of trauma (n = 5), intracerebral hemorrhage (n = 3), or nonabdominal postsurgical complications (n = 2). All the patients had required treatment with long-term ventilation, catecholamines, total parenteral nutrition, and several antimicrobial agents. Results Cholestasis was first noted within 11 days after the initial insult. Endoscopic retrograde cholangiopancreatogr…
Post-infantile giant cell hepatitis in patients with primary sclerosing cholangitis and autoimmune hepatitis.
2008
In post-infancy, multinucleated giant cell hepatitis is rare. Various conditions and diseases associated with post-infantile giant cell hepatitis have been described, but the pathogenesis remains unknown. In this paper we review the case reports of four patients (3 male, 1 female; aged 22 to 32 years) with primary sclerosing cholangitis and autoimmune hepatitis. The follow-up ranges from five to seven years. All patients showed cholestasis and repeated elevation of hepatic transaminases. Patients with viral infections, metabolic disorders and toxic influences were excluded. Histopathology of liver tissue in all four patients revealed giant cell formation with up to 20 nuclei in 20-70% of al…
Hepatitis C virus (HCV) and autoimmune liver diseases
1992
Anti-HCV tests were positive in 18–45% of sera from patients with autoimmune chronic active hepatitis. High gammaglobulin levels may result in false positive results, however, some sera show true positivity. PCR testing of such sera is necessary in order to determine whether HCV is directly involved in specific forms of the disease.
Osteo-Oto-Hepato-Enteric Syndrome (O2HE) is caused by loss of function mutations in UNC45A
2017
AbstractDespite the rapid discovery of genes for rare genetic disorders, we continue to encounter individuals presenting with hitherto unknown syndromic manifestations. Here, we have studied four affected people in three families presenting with cholestasis, congenital diarrhea, impaired hearing and bone fragility, a clinical entity we have termed O2HE (Osteo-Oto-Hepato-enteric) syndrome. Whole exome sequencing of all affected individuals and their parents identified biallelic mutations in Unc-45 Myosin Chaperone A (UNC45A), as a likely driver for this disorder. Subsequent in vitro and in vivo functional studies of the candidate gene indicated a loss of function paradigm, wherein mutations …
AISF position paper on liver disease and pregnancy.
2016
Abstract The relationship between liver disease and pregnancy is of great clinical impact. Severe liver disease in pregnancy is rare; however, pregnancy-related liver disease is the most frequent cause of liver dysfunction during pregnancy and represents a severe threat to foetal and maternal survival. A rapid differential diagnosis between liver disease related or unrelated to pregnancy is required in women who present with liver dysfunction during pregnancy. This report summarizes the recommendation of an expert panel established by the Italian Association for the Study of the Liver (AISF) on the management of liver disease during pregnancy. The article provides an overview of liver disea…
Congenital hypopituitarism and multiple midline defects in a newborn with non-familial Cat Eye syndrome
2022
Abstract Background Cat eye syndrome (CES) is a rare chromosomal disease, with estimated incidence of about 1 in 100,000 live newborns. The classic triad of iris coloboma, anorectal malformations, and auricular abnormalities is present in 40% of patients, and other congenital defects may also be observed. The typical associated cytogenetic anomaly relies on an extra chromosome, derived from an inverted duplication of short arm and proximal long arm of chromosome 22, resulting in partial trisomy or tetrasomy of such regions (inv dup 22pter-22q11.2). Case presentation We report on a full-term newborn, referred to us soon after birth. Physical examination showed facial dysmorphisms, including …