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  • Review Article
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Global trends in hepatocellular carcinoma epidemiology: implications for screening, prevention and therapy

Nature Reviews Clinical Oncology volume 20, pages 864–884 (2023)Cite this article

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Abstract

Hepatocellular carcinoma (HCC) mortality rates are increasing globally, and particularly in the Western world. Cirrhosis remains the predominant risk factor for HCC. However, epidemiological shifts in the incidence of HCC from patients with virus-related liver disease to those with non-viral aetiologies, including alcohol-associated and metabolic dysfunction-associated steatotic liver disease, have important implications for prevention, surveillance and treatment. Hepatitis B vaccination and antiviral therapy for hepatitis B and C are effective for primary prevention of virus-related HCCs, but chemoprevention strategies for non-viral liver disease remain an unmet need. Emerging data suggest associations between aspirin, statins, metformin and coffee and reduced HCC incidence, although none has been proved to be causally related. Secondary prevention of HCC via semi-annual surveillance is associated with improvements in early detection and thus reduced mortality; however, current tools, including abdominal ultrasonography, have suboptimal sensitivity for the detection of early stage HCC, particularly in patients with obesity and/or non-viral liver disease. Promising blood-based or imaging-based surveillance strategies are emerging, although these approaches require further validation before adoption in clinical practice. In the interim, efforts should be focused on maximizing use of the existing surveillance tools given their prevalent underuse globally. Remarkable advances have been made in the treatment of HCC, including expanded eligibility for surgical therapies, improved patient selection for locoregional treatments and increased systemic treatment options, including immune-checkpoint inhibitors. In this Review, we discuss trends in the epidemiology of HCC and their implications for screening, prevention and therapy.

Key points

  • An epidemiological shift has occurred in hepatocellular carcinoma (HCC) risk factors from virus-related to non-viral liver disease, including alcohol-associated and metabolic dysfunction-associated steatotic liver disease.

  • Although effective interventions are available for primary prevention of virus-related cirrhosis and HCC, chemoprevention for non-viral liver disease remains an unmet need.

  • Secondary prevention via semi-annual ultrasonography-based surveillance of patients with cirrhosis is associated with improvements in early detection of HCC and reduced HCC-related mortality; however, the current tools have lower sensitivity for the detection of early stage HCC in patients with obesity and/or non-viral liver disease.

  • Moreover, HCC surveillance is underused in clinical practice, particularly among patients with non-viral liver disease and those followed outside of gastroenterology and/or hepatology practices, highlighting a need for multi-level interventions to increase use.

  • Tremendous therapeutic advances have been made, including expanded eligibility for surgical therapies, improved patient selection for locoregional treatments and increased systemic treatment options.

  • Immune-checkpoint inhibitors have revolutionized the HCC treatment landscape, for both patients with advanced-stage HCC and those with earlier stages of the disease.

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Fig. 1: Temporal trends in liver cancer epidemiology across different regions worldwide.
Fig. 2: Annual risk of HCC in patients with cirrhosis stratified according to the major underlying aetiology.
Fig. 3: Global incidence and mortality of liver cancer.
Fig. 4: BCLC staging system and treatment algorithm for HCC.
Fig. 5: Management of HCC with systemic therapies.

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Authors and Affiliations

  1. Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA

    Amit G. Singal

  2. Section of Gastroenterology and Hepatology and Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA

    Fasiha Kanwal

  3. Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA

    Fasiha Kanwal

  4. VA Health Services Research & Development Center for Innovations in Quality, Effectiveness, and Safety (IQuESt), Houston, TX, USA

    Fasiha Kanwal

  5. Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA

    Fasiha Kanwal

  6. Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Josep M. Llovet

  7. Translational Research in Hepatic Oncology, Liver Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain

    Josep M. Llovet

  8. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain

    Josep M. Llovet

Authors
  1. Amit G. Singal
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  2. Fasiha Kanwal
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  3. Josep M. Llovet
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The authors contributed equally to all aspects of the article.

Corresponding author

Correspondence to Amit G. Singal.

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Competing interests

A.G.S. has served as a consultant or on advisory boards for AstraZeneca, Bayer, Boston Scientific, Eisai, Exact Sciences, Exelixis, Freenome, FujiFilm Medical Sciences, Genentech, Glycotest, GRAIL, Roche and TARGET RWE. J.M.L. has received research support from from Bayer, Bristol-Myers Squibb, Eisai and Ipsen, and has received consultancy fees from AstraZeneca, Bayer, Bluejay Therapeutics, Boston Scientific, Bristol-Myers Squibb, Captor Therapeutics, Eisai, Eli Lilly, Exelixis, Genentech, Glycotest, Ipsen, Merck, Mina Alpha, Omega Therapeutics and Roche. F.K. declares no competing interests.

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Nature Reviews Clinical Oncology thanks D. Kim, P. Nahon and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Singal, A.G., Kanwal, F. & Llovet, J.M. Global trends in hepatocellular carcinoma epidemiology: implications for screening, prevention and therapy. Nat Rev Clin Oncol 20, 864–884 (2023). https://doi.org/10.1038/s41571-023-00825-3

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