Browsing by Author "Mellinger, Jessica"

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    Clinical trial design, biomarkers and end points in metabolic and alcohol-related liver disease
    (2025) Díaz Piga, Luis Antonio; Thiele, Maja; Louvet, Alexandre; Lee, Brian P.; Ajmera, Veeral; Tavaglione, Federica; Hsu, Cynthia L.; Huang, Daniel Q.; Pose, Elisa; Bataller, Ramon; McClain, Craig; Mellinger, Jessica; Tincopa, Monica; Mitchell, Mack C.; Ratziu, Vlad; Rinella, Mary E.; Sarin, Shiv K.; Shah, Vijay H.; Szabo, Gyongyi; Wong, Vincent Wai-Sun; Bansal, Meena B.; Leggio, Lorenzo; Kamath, Patrick S.; Krag, Aleksander; Sanyal, Arun J.; Arrese, Marco; Arab Verdugo, Juan Pablo; Anstee, Quentin M.; Mathurin, Philippe; Loomba, Rohit
    Metabolic and alcohol-related liver disease (MetALD) is a newly defined entity within the spectrum of steatotic liver disease, characterized by the interplay of cardiometabolic risk factors and alcohol consumption. The evolving epidemiology and complex pathophysiology of MetALD present unique challenges and opportunities for clinical trial design. Inclusion criteria should require simultaneous evidence of metabolic dysfunction (at least two cardiometabolic features) and verified quantifiable alcohol exposure recorded over the preceding 3–6 months. Traditional histological end points are limited by invasiveness, sampling error and interpretative variability. Thus, imaging modalities, serum-based fibrosis biomarkers and quantitative measures of alcohol intake are gaining relevance as non-invasive, reproducible and patient-centric end points aiming to improve trial feasibility. Furthermore, incorporating alcohol biomarkers, stratifying patients by metabolic risk factor burden, and using adaptive designs of trials might enhance the precision and generalizability of MetALD clinical trials. Although uncertainties remain regarding optimal patient selection criteria, event rates and the dynamic interplay between metabolic dysfunction and alcohol intake, ongoing research efforts aim to refine diagnostic criteria, standardize methodologies and validate novel end points. These advances will ultimately accelerate drug development, improve trial efficiency and foster interventions to treat MetALD.
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    Metabolic dysfunction and alcohol-related liver disease (MetALD): Position statement by an expert panel on alcohol-related liver disease
    (2025) Arab Verdugo, Juan Pablo; Díaz Piga, Luis Antonio; Rehm, Jürgen; Im, Gene; Arrese, Marco; Kamath, Patrick S.; Lucey, Michael R.; Mellinger, Jessica; Thiele, Maja; Thursz, Mark; Bataller, Ramon; Burton, Robyn; Chokshi, Shilpa; Francque, Sven M.; Krag, Aleksander; Lackner, Carolin; Lee, Brian; Liangpunsakul, Suthat; MacClain, Craig; Mandrekar, Pranoti; Mitchell, Mack C.; Morgan, Marsha Y.
    In this position statement, we explore the intricate relationship between alcohol intake and metabolic dysfunction in the context of the 2023 nomenclature update for steatotic liver disease (SLD). Recent and lifetime alcohol use should be accurately assessed in all patients with SLD to facilitate classification of alcohol use in grams of alcohol per week. Alcohol biomarkers (i.e., phosphatidylethanol), use of validated questionnaires (i.e. AUDIT-C [alcohol use disorders identification test consumption]), and collateral information from friends and relatives could help facilitate differentiation between alcohol-related liver disease (ALD) per se and liver disease with both metabolic and alcohol-related components (MetALD). Heavy alcohol use can contribute to cardiometabolic risk factors such as high blood pressure, hypertriglyceridaemia, and hyperglycaemia. As a result, caution should be exercised in the application of only one metabolic dysfunction criterion to diagnose MASLD, as suggested in the 2023 nomenclature document, particularly in individuals exceeding weekly alcohol use thresholds of 140 g for women and 210 g for men. This is particularly important in those individuals with isolated high blood pressure, hypertriglyceridaemia, or hyperglycaemia, where the disease process may be driven by alcohol itself. Additionally, metabolic dysfunction and alcohol use should be reassessed over time, especially after periods of change in risk factor exposure. This approach could ensure a more accurate prognosis and effective management of SLD, addressing both metabolic and alcohol-related factors.