Background and Aims High alcohol intake is associated with increased mortality. We aimed to identify factors affecting mortality in people drinking extreme amounts. Approach and Results. Information was obtained from the UK Biobank on approximately 500,000 participants aged 40-70 years at baseline assessment in 2006-2010. Habitual alcohol intake, lifestyle and physiological data, laboratory test results, and hospital diagnoses and death certificate data (to June 2020) for 5136 men (2.20% of male participants) and 1504 women (0.60%) who reported taking ≥80 g/day or ≥50g/day, respectively, were used in survival analysis. Compared to all other participants, their mortality HRs were 9.40 (95% CI 7.00-12.64) for any liver disease (ICD-10 K70-K76), 2.02 (1.89-2.17) for all causes, 1.89 (1.69-2.12) for any cancer (C00-C99), and 1.87 (1.61-2.17) for any circulatory disease (I00-I99). Liver disease diagnosis or abnormal liver function tests predicted not only deaths attributed to liver disease but also those from cancers or circulatory diseases. Mortality among excessive drinkers was also associated with quantitative alcohol intake, diagnosed alcohol dependence (ICD-10 F10.2), and current smoking at assessment. Conclusions. People with chronic excessive alcohol intake experience decreased average survival but there is substantial variation in their mortality, with liver abnormality and alcohol dependence each associated with worse prognosis. Clinically, patients with these risk factors as well as high alcohol intake should be considered for early or intensive management. Research can usefully focus on the factors predisposing to dependence or liver abnormality.

TRM has conducted clinical research with AbbVie, Genfit, Gilead, and Merck but none of these are related to this manuscript.

This work was supported, in part, by the National Institutes of Health, USA (U01 AA018389). Funders had no role in study design, data analysis, conclusions, writing and revision of the paper or decisions on publication.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Information used in this analysis was obtained from the UK Biobank (application number 18870). Participants gave informed consent, and our application was approved by the UK Biobank through their procedures, consistent with the UK Biobank Ethics and Governance Framework (https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/about-us/ethics, accessed 2022-03-22).

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All data used in this study are from the UK Biobank, which can grant access to approved researchers.