Search results for " Cholestasis"
showing 10 items of 13 documents
Advances in drug-induced cholestasis: Clinical perspectives, potential mechanisms and in vitro systems
2018
Despite growing research, drug-induced liver injury (DILI) remains a serious issue of increasing importance to the medical community that challenges health systems, pharmaceutical industries and drug regulatory agencies. Drug-induced cholestasis (DIC) represents a frequent manifestation of DILI in humans, which is characterised by an impaired canalicular bile flow resulting in a detrimental accumulation of bile constituents in blood and tissues. From a clinical point of view, cholestatic DILI generates a wide spectrum of presentations and can be a diagnostic challenge. The drug classes mostly associated with DIC are anti-infectious, anti-diabetic, anti-inflammatory, psychotropic and cardiov…
A Physiology-Based Model of Human Bile Acid Metabolism for Predicting Bile Acid Tissue Levels After Drug Administration in Healthy Subjects and BRIC …
2019
Drug-induced liver injury (DILI) is a matter of concern in the course of drug development and patient safety, often leading to discontinuation of drug-development programs or early withdrawal of drugs from market. Hepatocellular toxicity or impairment of bile acid (BA) metabolism, known as cholestasis, are the two clinical forms of DILI. Whole-body physiology-based modelling allows a mechanistic investigation of the physiological processes leading to cholestasis in man. Objectives of the present study were: (1) the development of a physiology-based model of the human BA metabolism, (2) population-based model validation and characterisation, and (3) the prediction and quantification of alter…
Predicting drug-induced cholestasis: preclinical models.
2018
In almost 50% of patients with drug-induced liver injury (DILI), the bile flow from the liver to the duodenum is impaired, a condition known as cholestasis. However, this toxic response only appears in a small percentage of the treated patients (idiosyncrasy). Prediction of drug-induced cholestasis (DIC) is challenging and emerges as a safety issue that requires attention by professionals in clinical practice, regulatory authorities, pharmaceutical companies, and research institutions. Area covered: The current synopsis focuses on the state-of-the-art in preclinical models for cholestatic DILI prediction. These models differ in their goal, complexity, availability, and applicability, and ca…
Phenotypic spectrum and diagnostic pitfalls of ABCB4 deficiency depending on age of onset.
2017
Genetic variants in the adenosine triphosphate-binding cassette subfamily B member 4 (ABCB4) gene, which encodes hepatocanalicular phosphatidylcholine floppase, can lead to different phenotypes, such as progressive familial intrahepatic cholestasis (PFIC) type 3, low phospholipid-associated cholelithiasis, and intrahepatic cholestasis of pregnancy. The aim of this multicenter project was to collect information on onset and progression of this entity in different age groups and to assess the relevance of this disease for the differential diagnosis of chronic liver disease. Clinical and laboratory data of 38 patients (17 males, 21 females, from 29 families) with homozygous or (compound) heter…
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.
Are the new genetic tools for diagnosis of Wilson disease helpful in clinical practice?
2020
Summary The diagnosis of Wilson disease is not always easy. For many patients, a combination of tests reflecting disturbed copper metabolism may be needed. Testing for ATP7B variants has become part of the routine diagnostic approach. The methods of genetic testing include analysis of the 21 coding exons and intronic flanking sequences, in which exons with recurrent variants would be prioritised depending on the mutation frequency in the local population. If sequencing the entire ATP7B gene cannot identify 2 variants and the suspicion for Wilson disease is high, after reviewing the clinical data, WES (whole-exome sequencing) or WGS (whole-genome sequencing) could be applied. A workflow base…
Intrahepatic cholestasis of pregnancy after ovarian hyperstimulation syndrome with wild-type ABCB4 gene: a peculiar case and literature review
2023
Background: Intrahepatic cholestasis of pregnancy (ICP) in the first trimester occurring after ovarian hyperstimulation syndrome (OHSS) is a rare condition and few cases are reported in the literature. Hyperestrogenism may explain this problem in genetically predisposed women. The objective of this article is to report one of these rare cases and offer an overview of the other published cases. Case presentation: We report a case of severe OHSS followed by ICP in the first trimester. The patient was admitted to the intensive care unit and was treated according to the guidelines for the management of OHSS. Moreover, the patient also received ursodeoxycholic acid for ICP, which brought to an i…
A cholestatic pattern predicts major liver-related outcomes in patients with non-alcoholic fatty liver disease
2022
NAFLD patients usually have an increase in AST/ALT levels, but cholestasis can also be observed. We aimed to assess in subjects with NAFLD the impact of the (cholestatic) C pattern on the likelihood of developing major liver-related outcomes (MALO).
Cholestasis in newborn infants with perinatal asphyxia
1997
Objective: The aim of this study was to characterize the liver involvement in infants who have both neonatal asphyxia and neonatal cholestasis. Methods: We describe four asphyctic newborn infants (three born at term) who developed early (age 3.8 ± 2.1 days) intrahepatic neonatal cholestasis and in whom tests for causes of neonatal liver damage were negative. Results: The clinical picture and course were benign and similar to that of sporadic 'idiopathic' neonatal hepatitis. Clinical signs and abnormal liver function tests tended to normalize within the first year of life in all. Conjugated bilirubin became normal at 6 months after the onset of cholestasis, while liver enzymes tended towards…
A 9-Year Retained T-Tube Fragment Encased within a Stone as a Rare Cause of Jaundice
2008
Biliary diseases such as cholangitis may cause jaundice and liver damage. Here, we report on an unusual cause of jaundice in an 84-year-old man 9 years after cholecystectomy. Ultrasound analysis revealed unclear extrahepatic cholestasis and subsequent ERCP showed a large biliary stone sourrounding a T-tube fragment that had remained in the common bile duct for more than 9 years after surgery. The tip of the drainage and the stone could be successfully removed using Dormia baskets. This case suggests that plastic material accidentally left in the common bile duct favours the development of large biliary casts when present over long periods of time.