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  • Review Article
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Hepatocellular carcinoma surveillance — utilization, barriers and the impact of changing aetiology

Nature Reviews Gastroenterology & Hepatology volume 20, pages 797–809 (2023)Cite this article

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Abstract

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Surveillance for HCC is critical for early detection and treatment, but fewer than one-quarter of individuals at risk of HCC undergo surveillance. Multiple failures across the screening process contribute to the underutilization of surveillance, including limited disease awareness among patients and health-care providers, knowledge gaps, and difficulty recognizing patients who are at risk. Non-alcoholic fatty liver disease and alcohol-associated liver disease are the fastest-rising causes of HCC-related death worldwide and are associated with unique barriers to surveillance. In particular, more than one-third of patients with HCC related to non-alcoholic fatty liver disease do not have cirrhosis and therefore lack a routine indication for HCC surveillance on the basis of current practice guidelines. Semi-annual abdominal ultrasound with measurement of α-fetoprotein levels is recommended for HCC surveillance, but the sensitivity of this approach for early HCC is limited, especially for patients with cirrhosis or obesity. In this Review, we discuss the current status of HCC surveillance and the remaining challenges, including the changing aetiology of liver disease. We also discuss strategies to improve the utilization and quality of surveillance for HCC.

Key points

  • Fewer than one-quarter of patients with cirrhosis receive surveillance for hepatocellular carcinoma (HCC).

  • Multiple patient-related and provider-related barriers limit the utilization of HCC surveillance; these barriers include limited disease awareness, knowledge gaps, lack of resources and failure to recognize patients at risk.

  • Non-alcoholic fatty liver disease-related HCC develops in many people without cirrhosis, but routine HCC surveillance is not recommended in the absence of cirrhosis; surveillance should be individualized on the basis of additional risk factors.

  • Unique barriers to HCC surveillance (for example, non-adherence, limited social report, stigma and psychological issues) are associated with alcohol-associated cirrhosis; a multidisciplinary approach is required to address these barriers.

  • Ultrasonography has a suboptimal sensitivity for the detection of early-stage HCC and its performance can be poorer in the presence of obesity and non-alcoholic fatty liver disease-related or alcohol-related cirrhosis.

  • Novel blood-based and imaging-based biomarkers for HCC surveillance are emerging but require validation.

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Authors and Affiliations

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

    Daniel Q. Huang

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

    Daniel Q. Huang

  3. Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA

    Amit G. Singal

  4. Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA

    Fasiha Kanwal

  5. Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA

    Fasiha Kanwal

  6. Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy

    Pietro Lampertico

  7. CRC “A. M. and A. Migliavacca” Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

    Pietro Lampertico

  8. Liver Unit, Department of Internal Medicine, Hospital Universitari Valle d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain

    Maria Buti

  9. CIBER-EHD del Instituto Carlos III, Barcelona, Spain

    Maria Buti

  10. Liver Imaging Group, Department of Radiology, UCSD School of Medicine, San Diego, CA, USA

    Claude B. Sirlin

  11. Department of Epidemiology and Population Health, Stanford University Medical Center, Stanford University, Palo Alto, CA, USA

    Mindie H. Nguyen

  12. Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford University, Palo Alto, CA, USA

    Mindie H. Nguyen

  13. NAFLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, San Diego, CA, USA

    Rohit Loomba

  14. 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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The authors contributed equally to all aspects of the article.

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Correspondence to Daniel Q. Huang.

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Competing interests

D.Q.H. has served as an advisory board member for Eisai and Gilead and has received funding from the Singapore Ministry of Health’s National Medical Research Council (MOH-000595-01). A.G.S. has served as a consultant or on advisory boards for AstraZeneca, Bayer, Eisai, Exact Sciences, Exelixis, Freenome, FujiFilm Medical Sciences, Genentech, Glycotest and GRAIL. P.L. has served on advisory boards and/or speaker bureaus for Abbvie, Arrowhead, Aligos, Alnylam, Antios, Bristol Myers Squibb, Eiger, Gilead Sciences, GlaxoSmithKline, Janssen, Merck Sharp & Dohme, Myr, Roche, Spring Bank and Vir Biotechnology. M.B. has received research support from Gilead and has served as an advisory board member for Abbvie, Gilead, GlaxoSmithKline, Janssen and Spring Bank. C.B.S. has received research grants from the American College of Radiology, Bayer, Foundation of NIH, GE Healthcare, Gilead, Pfizer, Philips and Siemens; has lab service agreements with Enanta, Gilead, ICON, Intercept, Nusirt, Shire, Synageva and Takeda; conducts institutional consulting for Bristol Myers Squibb, Exact Sciences, IBM–Watson and Pfizer; provides personal consulting for Blade, Boehringer, Epigenomics and Guerbet; receives royalties and/or honoraria from Medscape and Wolters Kluwer; owns stock options in Livivos; has an unpaid advisory board position at Quantix Bio; and serves as Chief Medical Officer for Livivos (unsalaried position with stock options) with appointment approved from his university. M.H.N. has received research support from AstraZeneca, B.K. Kee Foundation, CurveBio, Delfi, Enanta, Exact Science, Gilead, Glycotest, Helio Health, Innogen, the National Cancer Institute, Pfizer and Vir. She has served as an advisory board member or consultant to Eli Lilly, Exact Sciences, Exelixis, Gilead, GlaxoSmithKline and Intercept. R.L. received funding from the National Institute of Diabetes and Digestive and Kidney Diseases (P30DK120515) and serves as a consultant to 89bio, Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myer Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen, Madrigal, Metacrine, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, Terns Pharmaceuticals and Viking Therapeutics. In addition, his institutes have received research grants from Arrowhead Pharmaceuticals, AstraZeneca, Boehringer-Ingelheim, Bristol Myers Squibb, Eli Lilly, Galectin Therapeutics, Galmed Pharmaceuticals, Gilead, Intercept, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Novo Nordisk, Merck, Pfizer, Sonic Incytes and Terns Pharmaceuticals. F.K. declares no competing interests.

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Nature Reviews Gastroenterology & Hepatology thanks E. Giannini, R. Tateishi and A. Vogel for their contribution to the peer review of this work.

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Review criteria PubMed was searched from inception to February 2023 using the terms “hepatocellular carcinoma”, “surveillance” and “screening” without language restrictions. Original articles were evaluated. Studies were selected to provide data from diverse geographical locations on the utilization of hepatocellular carcinoma (HCC) surveillance in the presence of cirrhosis and chronic hepatitis B. We included studies that reported the utilization of HCC surveillance in a real-world setting. We excluded trials of HCC surveillance and studies of dedicated HCC surveillance programmes.

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Huang, D.Q., Singal, A.G., Kanwal, F. et al. Hepatocellular carcinoma surveillance — utilization, barriers and the impact of changing aetiology. Nat Rev Gastroenterol Hepatol 20, 797–809 (2023). https://doi.org/10.1038/s41575-023-00818-8

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