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Reply to ‘Incorporating genetic variations in alcohol-associated liver disease trials for East Asian populations’

Nature Reviews Gastroenterology & Hepatology volume 22, page 358 (2025)Cite this article

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We thank Kang for their comments on our recent Consensus Statement (Lee, B. P. et al. Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement. Nat. Rev. Gastroenterol. Hepatol. 21, 626–645 (2024))1 to incorporate genetic variations into consideration (Kang, B. Incorporating genetic variations in alcohol-associated liver disease trials for East Asian populations. Nat. Rev. Gastroenterol. Hepatol. https://doi.org/10.1038/s41575-025-01060-0 (2025))2. We agree that people who are deficient in ALDH2 and drink alcohol might be at increased risk of cancer of the upper digestive tract, oesophagus and liver. The increased risk of cancer in those who are ALDH2-deficient noted by Kang was not the focus of our initiative, but we appreciate the acknowledgement of the increased risk for this population.

Our Consensus Statement and recommendations were focused on how to address alcohol use in clinical trials in patients with alcohol-associated liver disease (ALD), both to accurately measure consumption and to treat alcohol use disorders to reduce liver-related outcomes1. We noted that most people (irrespective of ethnicity) who develop advanced liver disease drink at levels considered heavy drinking by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the Centers for Disease Control and the WHO.

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References

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Authors and Affiliations

  1. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Mack C. Mitchell

  2. 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

    Brian P. Lee

  3. Department of Internal Medicine, Division of Gastroenterology & Hepatology, Henry Ford Health-Michigan State University, Detroit, MI, USA

    Jessica Mellinger

  4. Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

    Laura E. Nagy

Authors
  1. Mack C. Mitchell
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  2. Brian P. Lee
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  4. Laura E. Nagy
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Corresponding authors

Correspondence to Mack C. Mitchell or Laura E. Nagy.

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Competing interests

B.P.L. is a consultant for GlaxoSmithKline, Novo Nordisk and HepaTX. M.C.M. is a consultant for GlaxoSmithKline and HepaTX and serves on the Board of Amygdala Neurosciences. J.M. is a consultant for GlaxoSmithKline and Novo Nordisk. L.E.N. declares no competing interests.

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Mitchell, M.C., Lee, B.P., Mellinger, J. et al. Reply to ‘Incorporating genetic variations in alcohol-associated liver disease trials for East Asian populations’. Nat Rev Gastroenterol Hepatol 22, 358 (2025). https://doi.org/10.1038/s41575-025-01059-7

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