Roadmap to DILI research in Europe. A proposal from COST action ProEuroDILINet.

Pharmacol Res

Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. University of Barcelona, Barcelona, Spain; Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), CSIC, Barcelona, Spain; Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.

Published: February 2024

In the current article the aims for a constructive way forward in Drug-Induced Liver Injury (DILI) are to highlight the most important priorities in research and clinical science, therefore supporting a more informed, focused, and better funded future for European DILI research. This Roadmap aims to identify key challenges, define a shared vision across all stakeholders for the opportunities to overcome these challenges and propose a high-quality research program to achieve progress on the prediction, prevention, diagnosis and management of this condition and impact on healthcare practice in the field of DILI. This will involve 1. Creation of a database encompassing optimised case report form for prospectively identified DILI cases with well-characterised controls with competing diagnoses, biological samples, and imaging data; 2. Establishing of preclinical models to improve the assessment and prediction of hepatotoxicity in humans to guide future drug safety testing; 3. Emphasis on implementation science and 4. Enhanced collaboration between drug-developers, clinicians and regulatory scientists. This proposed operational framework will advance DILI research and may bring together basic, applied, translational and clinical research in DILI.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phrs.2023.107046DOI Listing

Publication Analysis

Top Keywords

dili
6
roadmap dili
4
dili europe
4
europe proposal
4
proposal cost
4
cost action
4
action proeurodilinet
4
proeurodilinet current
4
current article
4
article aims
4

Similar Publications

A new human autologous hepatocyte/macrophage co-culture system that mimics drug-induced liver injury-like inflammation.

Arch Toxicol

December 2024

Department of Hepatobiliary Surgery and Visceral Transplantation, Clinic and Polyclinic for Visceral, Transplant, Thoracic and Vascular Surgery, Leipzig University Medical Center, Leipzig, Germany.

The development of in vitro hepatocyte cell culture systems is crucial for investigating drug-induced liver injury (DILI). One prerequisite for monitoring DILI related immunologic reactions is the extension of primary human hepatocyte (PHH) cultures towards the inclusion of macrophages. Therefore, we developed and characterized an autologous co-culture system of PHH and primary human hepatic macrophages (hepM) (CoC1).

View Article and Find Full Text PDF

MicroRNAs (miRNAs) have been recognised as potential biomarkers due to their specific expression patterns in different biological tissues and their changes in expression under pathological conditions. MicroRNA-122 (miR-122) is a vertebrate-specific miRNA that is predominantly expressed in the liver and plays an important role in liver metabolism and development. Dysregulation of miR-122 expression is associated with several liver-related diseases, including hepatocellular carcinoma and drug-induced liver injury (DILI).

View Article and Find Full Text PDF

Definitions, etiopathogenesis and epidemiology of ALF.

Best Pract Res Clin Gastroenterol

December 2024

Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India. Electronic address:

Acute liver failure (ALF) is a rare but preventable cause of acute hepatic dysfunction which is associated with significant mortality, unless treated appropriately. There are significant regional variations in the etiologies of ALF globally and this determines the outcomes of the disease as well as the long-term survival in patients receiving liver transplantation for management. Improvements in understanding of disease pathophysiology and critical care medicine have led to better outcomes over the last few decades.

View Article and Find Full Text PDF

Genetic and Genomic Approaches to the Study of Drug-Induced Liver Injury.

Liver Int

January 2025

Faculty of Medical Sciences, Translational & Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.

Idiosyncratic hepatotoxicity induced by prescribed drugs has been known since the early 20th century. Identifying risk factors, including genetic factors, that trigger this drug-induced liver injury (DILI) has been an important priority for many years, both to prevent drugs that cause liver injury being licensed and as a potential means of preventing at-risk patients being prescribed causative drugs. Improved methods for genomic analysis, particularly the development of genome-wide association studies, have facilitated the identification of genomic risk factors for DILI, but, to date, there are only two main examples, liver injury caused by amoxicillin-clavulanate (AC) and by flucloxacillin, where genetic risk factors causing the injury have been identified and replicated with understanding of the underlying mechanism.

View Article and Find Full Text PDF
Article Synopsis
  • Everolimus, a drug for treating certain cancers, poses a risk of hepatitis B virus (HBV) reactivation and hepatitis, particularly in patients with current or past HBV infection.
  • A study involving 377 patients on everolimus found that 28.75% of those with active HBV (HBsAg-positive) and 17.85% of those without (HBsAg-negative) developed hepatitis, with higher risks associated with specific treatments and lack of prophylaxis.
  • The research emphasizes the need for HBV screening and careful liver function monitoring for patients receiving everolimus, especially in regions where HBV is common.
View Article and Find Full Text PDF

Want 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!