Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement

Brian P Lee^#¹, Katie Witkiewitz^#², Jessica Mellinger^#³, Frank A Anania⁴, Ramon Bataller⁵, Thomas G Cotter⁶, Brenda Curtis⁷, Srinivasan Dasarathy⁸, Kelly S DeMartini⁹, Ivan Diamond¹⁰, Nancy Diazgranados¹¹, Andrea F DiMartini¹², Daniel E Falk¹³, Anne C Fernandez¹⁴, Margarita N German¹⁵, Patrick S Kamath¹⁶, Kelley M Kidwell¹⁷, Lorenzo Leggio¹⁸, Raye Litten¹⁹, Alexandre Louvet^{20

21}, Michael R Lucey¹⁵, Mary E McCaul²², Arun J Sanyal²³, Ashwani K Singal^{24

25}, Norman L Sussman^{26

27}, Norah A Terrault¹, Mark R Thursz²⁸, Elizabeth C Verna²⁹, Svetlana Radaeva³⁰, Laura E Nagy³¹, Mack C Mitchell³²

Affiliations

¹ Division of Gastroenterology and Liver Diseases, University of Southern California Keck School of Medicine and Institute for Addiction Science, University of Southern California, Los Angeles, CA, USA.
² Center on Alcohol, Substance use and Addictions, University of New Mexico, Albuquerque, NM, USA.
³ Department of Internal Medicine, Department of Psychiatry, Michigan Medicine, Ann Arbor, MI, USA.
⁴ Division of Hepatology and Nutrition, US Food and Drug Administration, Silver Spring, MD, USA.
⁵ Liver Unit, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
⁶ Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁷ Technology and Translational Research Unit, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, USA.
⁸ Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA.
⁹ Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
¹⁰ Amygdala Neurosciences, Palo Alto, CA, USA.
¹¹ Office of the Clinical Director, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
¹² Departments of Psychiatry and Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
¹³ Medications Development Branch, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
¹⁴ Department of Psychiatry, Michigan Medicine, Ann Arbor, MI, USA.
¹⁵ Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
¹⁶ Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.
¹⁷ Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
¹⁸ Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore, MD, USA.
¹⁹ Division of Treatment and Recovery, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
²⁰ Service des maladies de l'appareil digestif, University Hospital of Lille, Lille, France.
²¹ Unité INSERM INFINITE, Lille, France.
²² Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
²³ Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
²⁴ Department of Medicine, Division of Gastroenterology Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY, USA.
²⁵ Department of Medicine, Robley Rex VA Medical Center, Louisville, KY, USA.
²⁶ DURECT Corporation, Cupertino, CA, USA.
²⁷ Baylor College of Medicine, Houston, TX, USA.
²⁸ Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
²⁹ Division of Digestive and Liver Diseases, Columbia University, New York, NY, USA.
³⁰ Svetlana Radaeva, Division of Metabolism and Health Effects, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
³¹ Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. nagyL3@ccf.org.
³² Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA. mack.mitchell@utsouthwestern.edu.

^# Contributed equally.

PMID: 38849555
PMCID: PMC11829730
DOI: 10.1038/s41575-024-00936-x

Review

Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement

Brian P Lee et al. Nat Rev Gastroenterol Hepatol. 2024 Sep.

. 2024 Sep;21(9):626-645.

doi: 10.1038/s41575-024-00936-x. Epub 2024 Jun 7.

Authors

Affiliations

¹ Division of Gastroenterology and Liver Diseases, University of Southern California Keck School of Medicine and Institute for Addiction Science, University of Southern California, Los Angeles, CA, USA.
² Center on Alcohol, Substance use and Addictions, University of New Mexico, Albuquerque, NM, USA.
³ Department of Internal Medicine, Department of Psychiatry, Michigan Medicine, Ann Arbor, MI, USA.
⁴ Division of Hepatology and Nutrition, US Food and Drug Administration, Silver Spring, MD, USA.
⁵ Liver Unit, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
⁶ Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁷ Technology and Translational Research Unit, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, USA.
⁸ Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA.
⁹ Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
¹⁰ Amygdala Neurosciences, Palo Alto, CA, USA.
¹¹ Office of the Clinical Director, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
¹² Departments of Psychiatry and Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
¹³ Medications Development Branch, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
¹⁴ Department of Psychiatry, Michigan Medicine, Ann Arbor, MI, USA.
¹⁵ Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
¹⁶ Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.
¹⁷ Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
¹⁸ Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore, MD, USA.
¹⁹ Division of Treatment and Recovery, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
²⁰ Service des maladies de l'appareil digestif, University Hospital of Lille, Lille, France.
²¹ Unité INSERM INFINITE, Lille, France.
²² Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
²³ Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
²⁴ Department of Medicine, Division of Gastroenterology Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY, USA.
²⁵ Department of Medicine, Robley Rex VA Medical Center, Louisville, KY, USA.
²⁶ DURECT Corporation, Cupertino, CA, USA.
²⁷ Baylor College of Medicine, Houston, TX, USA.
²⁸ Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
²⁹ Division of Digestive and Liver Diseases, Columbia University, New York, NY, USA.
³⁰ Svetlana Radaeva, Division of Metabolism and Health Effects, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
³¹ Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. nagyL3@ccf.org.
³² Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA. mack.mitchell@utsouthwestern.edu.

^# Contributed equally.

PMID: 38849555
PMCID: PMC11829730
DOI: 10.1038/s41575-024-00936-x

Abstract

Most patients with alcohol-associated liver disease (ALD) engage in heavy drinking defined as 4 or more drinks per day (56 g) or 8 (112 g) or more drinks per week for women and 5 or more drinks per day (70 g) or 15 (210 g) or more drinks per week for men. Although abstinence from alcohol after diagnosis of ALD improves life expectancy and reduces the risk of decompensation of liver disease, few studies have evaluated whether treatment of alcohol use disorders will reduce progression of liver disease and improve liver-related outcomes. In November 2021, the National Institute of Alcohol Abuse and Alcoholism commissioned a task force that included hepatologists, addiction medicine specialists, statisticians, clinical trialists and members of regulatory agencies to develop recommendations for the design and conduct of clinical trials to evaluate the effect of alcohol use, particularly treatment to reduce or eliminate alcohol use in patients with ALD. The task force conducted extensive reviews of relevant literature on alcohol use disorders and ALD. Findings were presented at one in-person meeting and discussed over the next 16 months to develop the final recommendations. As few clinical trials directly address this topic, the 28 recommendations approved by all members of the task force represent a consensus of expert opinions.

PubMed Disclaimer

Figures

**Fig. 1 ∣. Alcohol consumption and steatotic liver disease.**
The level of alcohol consumption in gram per week is shown for male (blue) and female (pink) individuals according to the multisociety Delphi consensus statement by Rinella et al. (2023) for metabolic dysfunction-associated steatotic liver disease (MASLD), MASLD and increased alcohol intake (MetALD) and alcohol-related liver disease (ALD) in comparison to the National Institute on Alcohol Abuse and Alcoholism (NIAAA) heavy drinking levels and WHO risk levels of drinking.

See this image and copyright information in PMC

References

1. Rehm J & Shield KD Global Burden of Alcohol Use Disorders and Alcohol Liver Disease. MDPI https://www.mdpi.com/2227-9059/7/4/99 (2019). - PMC - PubMed
1. Chen CM & Yoon Y-H Surveillance Report #118 Liver Cirrhosis Mortality in the United States: National, State, and Regional Trends, 2000–2019. NIH https://www.niaaa.nih.gov/publications/surveillance-reports/surveillance... (2022).
1. National Institute on Alcohol Abuse and Alcoholism. a. What is Heavy Drinking? NIH https://www.niaaa.nih.gov/health-professionals-communities/core-resource... (2023).
1. World Health Organization. International Guide for Monitoring Alcohol Consumption and Related Harm (World Health Organization, 2000).
1. DiMartini A, Weinrieb R, Lane T, Day N & Fung J Defining the alcoholic liver transplant population: implications for future research. Liver Transpl. 7, 428–431 (2001). - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
- Nature Publishing Group
- PubMed Central
Medical
- MedlinePlus Health Information
Research Materials
- NCI CPTC Antibody Characterization Program

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement

Affiliations

Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement

Authors

Affiliations

Abstract

Figures

References

Related links

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials