Evidence mapPaperPMID 41006824Full record

ReviewNature reviews. Gastroenterology & hepatology2025

Clinical trial design, biomarkers and end points in metabolic and alcohol-related liver disease.

Luis Antonio Diaz, Maja Thiele, Alexandre Louvet, Brian P Lee, Veeral Ajmera, Federica Tavaglione, Cynthia L Hsu, Daniel Q Huang, Elisa Pose, Ramon Bataller and 20 more

Abstract readReview
PubMed Publisher
In one paragraph

Review in Nature reviews. Gastroenterology & hepatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 2 pooled it
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Advancing liver health in a shifting global landscape.Nature reviews. Gastroenterology & hepatology · 2026
    Article
  4. Article
  5. Article
  6. Therapeutics for Alcohol-Associated Liver Disease.Annual review of pharmacology and toxicology · 2026
    Review
  7. Assessing alcohol consumption in an era of direct alcohol markers.JHEP reports : innovation in hepatology · 2026
    Review
  8. Review
  9. Review
  10. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

30 authors.

Luis Antonio DiazMASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, CA, USA.ORCID http://orcid.org/0000-0002-8540-4930
Maja ThieleCenter for Liver Research, Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.ORCID http://orcid.org/0000-0003-1854-1924
Alexandre LouvetService des maladies de l'appareil digestif, University Hospital of Lille, Lille, France.ORCID http://orcid.org/0000-0002-5293-007X
Brian P LeeDivision of Gastroenterology and Liver Disecases, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-2108-1287
Veeral AjmeraMASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, CA, USA.ORCID http://orcid.org/0000-0001-5626-0942
Federica TavaglioneMASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, CA, USA.ORCID http://orcid.org/0000-0002-1720-4355
Cynthia L HsuMASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, CA, USA.ORCID http://orcid.org/0000-0002-2604-1340
Daniel Q HuangDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.ORCID http://orcid.org/0000-0002-5165-5061
Elisa PoseLiver Unit, Hospital Clinic and Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Ramon BatallerLiver Unit, Hospital Clinic and Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.ORCID http://orcid.org/0000-0002-1119-7799
Craig McClainDepartment of Medicine, University of Louisville, Louisville, KY, USA.
Jessica MellingerDepartment of Internal Medicine, Division of Gastroenterology & Hepatology, Henry Ford Health-Michigan State University, Detroit, MI, USA.
Monica TincopaMASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, CA, USA.
Mack C MitchellDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0001-9018-7988
Vlad RatziuSorbonne Université, Paris, France.
Mary E RinellaPritzker School of Medicine, University of Chicago, Chicago, IL, USA.ORCID http://orcid.org/0000-0003-0620-9705
Shiv K SarinDepartment of Hepatology and Liver Transplantation, Institute of Liver & Biliary Sciences, New Delhi, India.ORCID http://orcid.org/0000-0002-0544-5610
Vijay H ShahDivision of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.ORCID http://orcid.org/0000-0001-7620-573X
Gyongyi SzaboDepartment of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Vincent Wai-Sun WongDepartment of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, China.
Meena B BansalDivision of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-7501-2191
Lorenzo LeggioClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-7284-8754
Patrick S KamathDivision of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.ORCID http://orcid.org/0000-0002-7888-1165
Aleksander KragCenter for Liver Research, Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.ORCID http://orcid.org/0000-0002-9598-4932
Arun J SanyalDivision of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.ORCID http://orcid.org/0000-0001-8682-5748
Marco ArreseDepartamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Juan Pablo ArabDepartamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.ORCID http://orcid.org/0000-0002-8561-396X
Quentin M AnsteeTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0002-9518-0088
Philippe MathurinService des maladies de l'appareil digestif, University Hospital of Lille, Lille, France.
Rohit LoombaMASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, CA, USA. roloomba@health.ucsd.edu.ORCID http://orcid.org/0000-0002-4845-9991

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

Clinical Trials as TopicLiver Diseases, AlcoholicResearch DesignAlcohol DrinkingBiomarkersEndpoint DeterminationHumansBiomarkers

Identifiers

PMID41006824

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.