Drug-induced cholestasis is one of the major mechanisms implicated in drug-induced hepatotoxicity that poses a serious problem in terms of patient morbidity and mortality, healthcare system expenses and efficacy of newly developed drugs. Impaired bile acid homeostasis due to transporter alterations, hepatocellular injury or canalicular abnormalities is the most characteristic feature of cholestasis. Given the complexity of cholestasis and the different underlying mechanisms, new models and technologies that span a variety of biological processes are needed to accurately predict drugs' cholestatic potential. This review outlines the main triggering mechanisms of drug-induced cholestasis and summarizes the currently available in vitro systems and techniques that attempt to forecast and provide mechanistic details of cholestasis caused by drugs.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s00204-025-04016-0 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Patients with AMA/anti-sp100/anti-gp210 Positivity and Cholestasis Can Manifest Conditions Beyond Primary Biliary Cholangitis.
J Clin Transl Hepatol
March 2025
Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Background And Aims: The diagnostic value of primary biliary cholangitis (PBC)-specific antibodies in patients with elevated alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels, and other identifiable causes, was unclear. Our study aimed to determine whether etiological treatments in PBC-specific antibody-positive patients could improve liver biochemical tests, thereby distinguishing them from individuals with PBC.
Methods: We enrolled patients who were positive for PBC-specific antibodies and elevated ALP and/or GGT levels but with other identifiable etiologies.
Cell-based approaches for the mechanistic understanding of drug-induced cholestatic liver injury.
Arch Toxicol
March 2025
Experimental Hepatology Unit, Health Research Institute La Fe (IISLAFE), Torre A. Instituto Investigación Sanitaria La Fe Av Fernando Abril Martorell 106, 46026, Valencia, Spain.
Drug-induced cholestasis is one of the major mechanisms implicated in drug-induced hepatotoxicity that poses a serious problem in terms of patient morbidity and mortality, healthcare system expenses and efficacy of newly developed drugs. Impaired bile acid homeostasis due to transporter alterations, hepatocellular injury or canalicular abnormalities is the most characteristic feature of cholestasis. Given the complexity of cholestasis and the different underlying mechanisms, new models and technologies that span a variety of biological processes are needed to accurately predict drugs' cholestatic potential.
View Article and Find Full Text PDFBackground & Aims: The misuse of Anabolic Androgenic Steroids (AAS), including Stanozolol, for performance enhancement has emerged as a significant cause of liver damage. This study aims to elucidate the distinctive hepatotoxicity profiles induced by Stanozolol.
Methods: Eighteen individuals were prospectively evaluated by the Latin American DILI Registry from 2013 to 2023.
In vitro-in silico analysis reveals that loss of tankyrase1/2 improves bile acid handling in genetically engineered HepG2 cultures.
Arch Toxicol
March 2025
Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.
Modelling and simulation of hepatic bile acids (BA) kinetics is instrumental to understand mechanisms underlying drug-induced cholestasis (DiCho). A recent study has shown that the loss of tankyrase1/2 (TNKS1/2) matured the hepatic phenotype in vitro in terms of cellular respiration rate and metabolism. However, whether this phenotype was accompanied with more in vivo relevant hepatic BA handling was not investigated.
View Article and Find Full Text PDFClinical features and prognosis of drug-induced liver injury in patients with non-alcoholic fatty liver.
World J Hepatol
February 2025
Department of Gastroenterology, Tianjin Second People's Hospital, Tianjin 300110, China.
Background: Acute drug-induced liver injury (DILI) events caused by chronic liver disease are relatively common. Some researchers believe that nonalcoholic fatty liver (NAFL) increases the overall risk of DILI. The clinical characteristics and prognosis of DILI in the context of NAFL disease (NAFLD) are still unclear.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!