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  • Review Article
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Global epidemiology of alcohol-associated cirrhosis and HCC: trends, projections and risk factors

Nature Reviews Gastroenterology & Hepatology volume 20, pages 37–49 (2023)Cite this article

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Abstract

Heavy alcohol consumption is a major cause of morbidity and mortality. Globally, alcohol per-capita consumption rose from 5.5 litres in 2005 to 6.4 litres in 2016 and is projected to increase further to 7.6 litres in 2030. In 2019, an estimated 25% of global cirrhosis deaths were associated with alcohol. The global estimated age-standardized death rate (ASDR) of alcohol-associated cirrhosis was 4.5 per 100,000 population, with the highest and lowest ASDR in Africa and the Western Pacific, respectively. The annual incidence of hepatocellular carcinoma (HCC) among patients with alcohol-associated cirrhosis ranged from 0.9% to 5.6%. Alcohol was associated with approximately one-fifth of global HCC-related deaths in 2019. Between 2012 and 2017, the global estimated ASDR for alcohol-associated cirrhosis declined, but the ASDR for alcohol-associated liver cancer increased. Measures are required to curb heavy alcohol consumption to reduce the burden of alcohol-associated cirrhosis and HCC. Degree of alcohol intake, sex, older age, obesity, type 2 diabetes mellitus, gut microbial dysbiosis and genetic variants are key factors in the development of alcohol-associated cirrhosis and HCC. In this Review, we discuss the global epidemiology, projections and risk factors for alcohol-associated cirrhosis and HCC.

Key points

  • Global alcohol consumption per capita rose from 5.5 litres in 2005 to 6.4 litres in 2016 and is projected to increase further to 7.6 litres in 2030.

  • Currently, Europe has the highest levels of alcohol consumption; however, it is projected to be surpassed by countries/regions in the Western Pacific region by 2030.

  • Alcohol was estimated to be associated with one-quarter of global cirrhosis deaths and one-fifth of liver cancer deaths in 2019.

  • Alcohol was the second-fastest-growing cause of liver-cancer deaths from 2010 to 2019.

  • Patients with alcohol-associated hepatocellular carcinoma (HCC) tend to present with advanced tumours, which relates at least in part to late diagnosis and limited access to HCC screening in comparison to other aetiologies of liver disease.

  • The risk factors for the development of cirrhosis and HCC include the amount of alcohol consumed, age, obesity, diabetes, smoking and PNPLA3 variants.

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Fig. 1: Estimated age-standardized death rates (ASDRs) for alcohol-associated cirrhosis per 100,000 population in 2019, by country/territory.
Fig. 2: Estimated age-standardized death rates (ASDRs) for alcohol-associated liver cancer per 100,000 population in 2019, by country/territory.
Fig. 3: Pathogenesis of alcohol-associated cirrhosis and alcohol-associated hepatocellular carcinoma.
Fig. 4: Risk factors for alcohol-associated cirrhosis and alcohol-associated hepatocellular carcinoma (HCC).

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Data availability

Data for Table 1, Fig. 1 and Fig. 2, estimated by the Global Burden of Disease study 201912, were obtained from the GBD Results Tool119, which is maintained by the Institute for Health Metrics and Evaluation. Raw data are available upon request.

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Acknowledgements

R.L. receives funding support from the NIAAA (U01AA029019), the NIEHS (5P42ES010337), the NCATS (5UL1TR001442), the NIDDK (U01DK130190, U01DK061734, R01DK106419, P30DK120515, R01DK121378 and R01DK124318), the NHLBI (P01HL147835) and the DOD PRCRP (W81XWH-18-2-0026). D.Q.H. receives funding support from Singapore’s Ministry of Health’s National Medical Research Council under its NMRC Research Training Fellowship (MOH-000595-01). P.M. receives funding support from the Programme Hospitalier de Recherche Clinique (French Minister for Health). H.C.-P. receives funding support from the FCT: Projectos De Investigação Científica E Desenvolvimento, Portugal.

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Authors and Affiliations

  1. NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, San Diego, CA, USA

    Daniel Q. Huang & Rohit Loomba

  2. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Daniel Q. Huang

  3. Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore

    Daniel Q. Huang

  4. Service des Maladies de l’appareil digestif, Hôpital Huriez, Lille, France

    Philippe Mathurin

  5. Unité INSERM 995, Faculté de médecine, Lille, France

    Philippe Mathurin

  6. Clínica Universitária de Gastrenterologia, Faculdade de Medicina, Departamento de Gastrenterologia, Centro Hospitalar Lisboa Norte, Lisboa, Portugal

    Helena Cortez-Pinto

  7. Division of Epidemiology, Department of Family Medicine and Public Health, University of California at San Diego, San Diego, CA, USA

    Rohit Loomba

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  1. Daniel Q. Huang
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  2. Philippe Mathurin
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All authors contributed equally to all aspects of the manuscript.

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Correspondence to Rohit Loomba.

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Competing interests

R.L. serves as a consultant or advisory board member for Anylam/Regeneron, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, CohBar, Eli Lilly, Galmed, Gilead Sciences, Glympse Bio, Inipharm, Intercept, Ionis, Janssen, Merck, Metacrine, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Pfizer, Promethera, Sagimet, 89bio and Viking Therapeutics. In addition, his institution has received grant support from Allergan, Boehringer-Ingelheim, Bristol-Myers Squibb, Cirius, Eli Lilly, Galectin Therapeutics, Galmed Pharmaceuticals, Genfit, Gilead, Intercept, Inventiva, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Pfizer, pH Pharma and Siemens. He is also co-founder of Liponexus. D.Q.H. serves as an advisory board member for Eisai. P.M. serves as a consultant or advisory member for Ipsen, Eisai, Abbvie, Sanofi, Gilead Sciences, Evive Biotech, Novo Nordisk, Bayer Healthcare, Intercept, Surrozen and Pfizer. H.C.-P. lectures and receives advisory board fees from Intercept, Genfit, Promethera Bioscience, Orphalan, Novo Nordisk and Roche Portugal.

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Nature Reviews Gastroenterology & Hepatology thanks Ramon Bataller, Shiv Sarin and the other, anonymous, reviewers for their contribution to the peer review of this work.

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Review criteria

PubMed was searched using the terms ‘alcoholic liver disease’, ‘alcohol-associated cirrhosis’, ‘alcoholic cirrhosis’, ‘alcohol-related liver disease’, ‘alcohol-associated hepatocellular carcinoma’ and ‘alcohol-associated liver cancer’ without language restrictions. Guidelines, original articles and reviews were evaluated. The literature search was performed in February 2021.

Glossary

Heavy alcohol consumption

The consumption of >40 g of pure alcohol per day over a sustained period of time.

Current alcohol drinkers

Individuals who have consumed alcoholic beverages in the previous 12-month period.

Age-standardized death rate

(ASDR). A weighted average of the age-specific death rates, where the weights are the proportions of a standard population in the corresponding age groups.

Alcohol-associated

A disease state that is attributed to heavy consumption of alcohol.

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Huang, D.Q., Mathurin, P., Cortez-Pinto, H. et al. Global epidemiology of alcohol-associated cirrhosis and HCC: trends, projections and risk factors. Nat Rev Gastroenterol Hepatol 20, 37–49 (2023). https://doi.org/10.1038/s41575-022-00688-6

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