Educational activities

Monthly International Seminar Series on Liver Toxicity and Steatotic Liver Disease and different EASL studio topics for DHILI will be organised at a later stage.

As a proposal within our educational activities, we will be launching from January a series of talks on Liver Toxicity and Steatotic Liver Disease, ONCE monthly, given by international experts in the field. The session outline would be a talk of around 45 min with 15 min left for discussion. Conferences will be held on the 3rd Wednesday of each month at 16.30h (CET) starting from January 17^th 2024.

These international seminar series are the result of an outstanding collaboration between the EASL DHILI Consortium (https://easldhiliconsortium.eu/) and the Halt-RONIN (UKRI-Horizon Europe) https://halt-ronin.com/

The objectives are:

• to improve collaboration between different group experts encompassing clinical investigators, researchers, basic scientists, industry partners and regulators.
• To foster scientific progress by disseminating the latest breakthroughs in research on hepatotoxicity and metabolic dysfunction-associated steatotic liver disease

Gerd A. Kullak-Ublick, M.D. has a dual appointment as Full Professor of Clinical Pharmacology and Toxicology at the University Hospital Zurich, University of Zurich/Switzerland, and as Global Head of Mechanistic Safety and Safety Signal Management at Novartis, Basel/Switzerland. Gerd also co-leads the DILI work package in the IMI TransBioLine Consortium. Gerd is board-certified in Internal Medicine, Gastroenterology/Hepatology and Clinical Pharmacology/Toxicology. His research interests are centered on drug transporters in epithelial tissues (liver, intestine, kidney, blood-bran barrier), and on mechanisms of drug-induced liver injury. Gerd is a member of the Pro-Euro DILI Consortium, the IQ DILI Consortium and the CIOMS DILI Working Group.

Drug-induced liver injury (DILI) is characterized by increased levels of biochemical markers of liver injury within days to months after the start of pharmacological treatment for any given condition. Often, patients receive more than one medication, or have underlying liver conditions which can confound the interpretation of liver laboratory testing. In clinical trials, the decision as to whether or not to interrupt treatment with a study drug is based on algorithms defined in regulatory guidances that use standard liver lab testing values – ALT, AST, bilirubin, and alkaline phosphatase. There is a need for more specific markers of liver injury that could improve the management of DILI. The IMI TransBioLine Consortium is focused on the evaluation and validation of novel liver safety biomarkers for DILI. The Consortium was issued a Letter of Determination by the FDA in 2021 that encouraged the further assessment of HMGB1 (high mobility group box 1), K18 (cytokeratin 18 full-length), cc-K18 (cytokeratin 18 – caspase-cleaved fragment), GLDH (glutamate dehydrogenase), OPN (osteopontin), MCSF1R (macrophage colony stimulating factor receptor 1), bile acids and sphingolipids. The Consortium has recruited more than 100 DILI samples in the exploratory phase which have undergone analysis for the above named biomarkers. Based on these results, a Biomarker Qualification Plan (BQP) is currently in preparation which will detail the exact Context-of-Use for each biomarker and the pre-defined endpoints that need to be met so as to fulfill regulatory requirements for qualification.