Search results for "cholestasis"
showing 10 items of 71 documents
Burden of illness of progressive familial intrahepatic cholestasis in the US, UK, France, and Germany: study rationale and protocol of the PICTURE st…
2021
Background: Progressive familial intrahepatic cholestasis (PFIC) is an ultra-rare disease with a considerable burden on pediatric patients and their caregivers, impacting quality of life (QoL). The mortality rates highlight a significant need for efficacious treatments. Real-world data on associated costs and QoL are needed to gauge the potential impact of new pharmacological treatments. Methods: Clinical and socio-economic burden of PFIC on patients/caregivers, health systems, and society will be assessed. Patient/caregiver- and physician-level retrospective cross-sectional data will be collected from the US, UK, France, and Germany, for PFIC types 1, 2, 3. A representative sample of physi…
Methylene blue-aided cholangioscopy in patients with biliary strictures: feasibility and outcome analysis
2008
BACKGROUND AND STUDY AIMS: Chromoendoscopy using methylene blue is employed in the gastrointestinal tract to delineate neoplastic lesions. We tested the value of chromoendoscopy during choledochoscopy for characterization of local inflammation, neoplasias, and other alterations in patients with biliary strictures. METHODS: Patients with suspected biliary lesions were scheduled for endoscopic retrograde cholangiography with subsequent cholangioscopy. After initial inspection of the bile duct, 15 ml methylene blue (0.1 %) was administered via the working channel of the cholangioscope. Newly appearing circumscribed or unstained lesions were judged according to their macroscopic type and staini…
A Model‐Based Workflow to Benchmark the Clinical Cholestasis Risk of Drugs
2021
We present a generic workflow combining physiology-based computational modeling and in vitro data to assess the clinical cholestatic risk of different drugs systematically. Changes in expression levels of genes involved in the enterohepatic circulation of bile acids were obtained from an in vitro assay mimicking 14 days of repeated drug administration for 10 marketed drugs. These changes in gene expression over time were contextualized in a physiology-based bile acid model of glycochenodeoxycholic acid. The simulated drug-induced response in bile acid concentrations was then scaled with the applied drug doses to calculate the cholestatic potential for each compound. A ranking of the cholest…
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…
Inter-individual differences in the susceptibility of primary human hepatocytes towards drug-induced cholestasis are compound and time dependent.
2018
Abstract Cholestasis represents a major subtype of drug-induced liver injury and novel preclinical models for its prediction are needed. Here we used primary human hepatocytes (PHH) from different donors in 2D-sandwich (2D-sw) and/or 3D-spheroid cultures to study inter-individual differences in the response towards cholestatic hepatotoxins after short-term (48–72 hours) and long-term repeated exposures (14 days). The cholestatic liabilities of drugs were determined by comparing cell viability upon exposure to the highest non-cytotoxic drug concentration in the presence and absence of a non-cytotoxic concentrated bile acid mixture. In 2D-sw culture, cyclosporine A and amiodarone presented cl…
Multicentre randomized placebo-controlled trial of ursodeoxycholic acid with or without colchicine in symptomatic primary biliary cirrhosis
2000
Aim: To establish the efficacy of combination therapy with ursodeoxycholic acid (UDCA) and colchicine in patients with symptomatic primary biliary cirrhosis (PBC), defined by the presence of liver cirrhosis, pruritus or bilirubin exceeding 2 mg/mL. Methods: A total of 90 patients were randomly assigned to ursodeoxycholic acid 500 mg/daily plus placebo (UDCA group, n=44), or ursodeoxycholic acid at the same dosage plus colchicine, 1 mg/daily (UDCA/C group, n=46). The two groups were comparable for age, sex, stage of disease, severity of pruritus, bilirubin, and Mayo score. All patients underwent clinical, ultrasonographic, and biochemical examinations at entry and then every 6 months up to 3…
Case report: Trans-papillary free stenting of the cystic duct and of the common bile duct in a double biliary ducts anastomoses of a right lobe livin…
2021
Abstract Background One of the major issues related to the living donor liver transplantation recipient outcome is still the high rate of biliary complication, especially when multiple biliary ducts are present and multiple anastomoses have to be performed. Case presentation and conclusion We report a case of adult-to-adult right lobe living donor liver transplantation performed for a recipient affected by alcohol-related cirrhosis with MELD score of 17. End-stage liver disease was complicated by refractory ascites, portal hypertension, small esophageal varices and portal gastropathy, hypersplenism, and abundant right pleural effusion. Here in the attached video we described the adult-to-ad…
Quantitative Bestimmung des Gallenr�ckflusses in Blut und Leberlymphe von Ratten bei beginnender Gallenstauung
1970
1. Mit dem Ziel, die Anteile des bei einer Gallenstauung auftretenden Gallenruckflusses in Blut und Lymphe quantitativ zu erfassen, wurde ein Verfahren zur Gewinnung reiner Leberlymphe bei Ratten entwickelt. 2. Mit Hilfe dieser Methode konnte am Versuchstier mit normaler Korpertemperatur aus Messungen der Lymphstromstarke und des Eiweisgehaltes der Leberlymphe vor und wahrend einer Gallenstauung auf einen Ruckflus der fortlaufenden produzierten Galle in die Leberlymphe von ca. 7–10% geschlossen werden. 3. In Ruckflusversuchen an unterkuhlten Ratten mit Ringerlosung, die Evansblue enthielt, ergaben Analysen von Blut und Leberlymphe einen Anteil des Ruckflusses in diese Lymphe von ca. 13%.
Both cholestatic and steatotic drugs trigger extensive alterations in the mRNA level of biliary transporters in rat hepatocytes: Application to devel…
2016
Disruption of the vectorial bile acid transport in the liver is a key feature of cholestatic drugs, although many causal and mechanistic aspects are still unknown. The aim of the present study was to explore if cholestatic drugs can repress or induce the expression of hepatic transporters. To this end, sandwich-cultured rat hepatocytes were treated with cholestatic and non-cholestatic (steatotic, non-hepatotoxic, etc.) drugs and the mRNA expression of 10 uptake and efflux biliary transporters was measured. Results evidenced that all cholestatic drugs cause extensive alterations in the mRNA expression of most biliary transporters. Surprisingly, nearly all steatotic drugs also affected the ex…
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…