Attacking the public health crisis of hepatocellular carcinoma at its roots : Hepatology

Secondary Logo

Journal Logo

Public Policy Corner

Attacking the public health crisis of hepatocellular carcinoma at its roots

Lee, Hannah M.1; Lidofsky, Steven D.2; Taddei, Tamar H.3,4; Townshend‐Bulson, Lisa J.5

Author Information
Hepatology 77(4):p 1456-1459, April 2023. | DOI: 10.1002/hep.32741
  • Open


Hepatocellular carcinoma (HCC) is the third most common cause of cancer‐related death worldwide with significant mortality rates in the United States.1,2 Its strong association with cirrhosis and chronic hepatitis B virus (HBV) provides a compelling logic for targeted screening and prevention.3,4 Despite this, progress in identifying at‐risk individuals and early detection of HCC in these populations has lagged behind treatment advances.

Currently available tools for HCC screening are imperfect. Although HCC surveillance in high‐risk groups is endorsed by the American Association for the Study of Liver Diseases (AASLD),5 not all organizations share this view. This lack of consensus may undermine widespread adoption of surveillance programs, thus preventing HCC detection at a curable stage. HCC management involves treatments tailored to tumor burden and hepatic reserve, but disparities exist in access to the multidisciplinary teams that should oversee this complex process.

The at‐risk population for HCC is growing in response to the rise in chronic liver disease from alcohol use and NAFLD,3,4 and there is an urgency to address these issues. This will require robust research support, particularly in diagnostics and health services delivery. Stakeholders in government and professional organizations must engage to heighten HCC awareness among health practitioners and the community and to improve linkage to care.

In this public policy piece, we examine opportunities for prevention of HCC by focusing on its principal risk factors: viral hepatitis, NAFLD, and alcohol‐related liver disease (ALD). Adoption of the strategies we have highlighted below represents three key action points to reverse the course of this public health crisis:

  1. Awareness and education
  2. Screening and diagnosis
  3. Partnerships and advocacy

Viral hepatitis

Despite the launch in 2016 of the World Health Organization (WHO) global campaign to eliminate the public health burden of viral hepatitis by 2030,6 millions of Americans remain infected with HBV and hepatitis C virus (HCV). Close to half of Americans infected with viral hepatitis are unaware of their infection.7,8 Lack of awareness concerning screening and surveillance, both within the community and among health practitioners, also remains a challenge. Marginalized populations, including the homeless, the incarcerated, and people who inject drugs, are at higher risk for HBV and HCV exposure and face disparities in access to care.

We place particular focus on HBV as the incidence of HCC from HCV is decreasing because of the advent of direct acting antivirals for HCV, whereas HBV still has no curative treatments.9,10 The burden of HBV is the highest globally and is disproportionately high among the foreign‐born, in whom HBV screening rates remain lower and liver cancer mortality rates higher than in United States–born individuals.11 Vertical transmission also account for most of the burden of chronic HBV. In response, the Centers for Disease Control and Prevention (CDC) has launched the National Comprehensive Cancer Control Program (NCCP) to put liver cancer prevention concepts into action through selection of relevant strategies, choosing key partners, and measuring the extent of strategic success.12 The NCCP has developed and implemented education programs for the general public, high‐risk populations, and decision‐makers to increase knowledge and awareness of HCC and viral hepatitis.

Updated recommendations from the CDC and Advisory Committee on Immunization Practices endorsing universal HBV vaccination of adults age 59 years and younger provide another opportunity to reduce the extent of HBV infection.13 Federal efforts are needed to support education and infrastructure to implement these guidelines. Successful application should decrease HBV prevalence, thus reducing the risk of HCC. Much still needs to be done to promote greater awareness about the consequences of viral hepatitis, including HCC.


With prevalence of approximately 25%, NAFLD is positioned to become the leading cause of HCC in America. Despite this, there has been little public health response to the threat posed by NAFLD. Awareness and understanding of this disorder have been limited primarily to the gastroenterology/hepatology community.14,15 NAFLD is linked to the metabolic syndrome, itself a risk factor for HCC. Like HCC, metabolic syndrome is complex and requires multidisciplinary care. Lifestyle interventions, including weight loss through dietary modification and increased physical activity, are the only known therapies that prevent progression of hepatic fibrosis, the dominant risk factor for NAFLD‐related HCC.

Implementation of a national NAFLD public health agenda will require its recognition across disciplines as a major issue, the development of consensus guidelines for prevention, screening, and management, and an action plan to deploy them. Such a plan should empower health practitioners with a comprehensive model of care that includes pathways for screening and diagnosis as well as risk stratification tools to guide specialty referral.16 The plan should also include robust support to promote lifestyle interventions that reduce NAFLD progression and consequent HCC risk.


Currently the highest cause of liver‐related mortality worldwide, ALD has received little attention compared with other liver diseases because of the stigmata associated with alcohol use disorders, despite its significant negative health and economic impact.17,18 The recent precipitous increase in alcohol misuse in America has been paralleled by a rise in ALD‐related complications, including HCC.19 In order to offset this trend, expanded public health efforts in ALD prevention and diagnosis will be necessary.

Prevention of alcohol misuse or consumption beyond recommended maximum levels should be a critical part of a strategy to reduce the extent of ALD. There is a wealth of information in the WHO's Global Alcohol Database on alcohol use from every country, with eight categories of existing policies that span a broad spectrum of regulatory measures to curb excessive alcohol use.20 The goal is to develop a comprehensive picture of alcohol consumption and attributable disease burden and to provide global public health strategies and action plans to reduce harmful use of alcohol, such as sales restrictions and price and tax controls.21–23 Regulations can be customized locally, based on analysis of patterns of alcohol intake and socioeconomic and cultural factors. We call for consideration of tailored regional policies, instituted on a state‐by‐state basis, to prevent adverse outcomes of alcohol use, including the development of HCC.

Partnership and advocacy

Addressing the burden of HCC will require multilevel engagement from grassroots to governmental bodies and partnerships with private institutions and patient advocacy groups. Insights of those living with liver disease and their personal stories can influence and help guide the development of effective public policy interventions, incorporating patient‐centered care, to improve disease‐related outcomes.

Leading the way is the patient‐created Global Liver Institute. Their Liver Cancer Council works with committed stakeholders, including patients, caregivers, and professionals, to develop programs directed toward the needs of the liver cancer community. Their 2021 policy agenda has promoted the development of patient centric legislation, for example, the Liver Illness, Visibility, Education, and Research (LIVER) Act, introduced by US Senator Tammy Duckworth and Representative Nydia M. Velázquez. This proposed legislation would increase funding at the National Institutes of Health and CDC for liver cancer research, for expansion of HBV vaccination, and for screening and treatment for chronic liver disease and HCC.24

Like the patient‐led World Hepatitis Alliance, which pushed for the World Health Assembly Resolution for global elimination of viral hepatitis, we need groups to advocate for a public health agenda for NAFLD and ALD. We call for collaboration and engagement with noncommunicable disease (NCD) community organizations, such as the NCD Alliance, to work in concert to address these areas of unmet need.

Lessons from the COVID pandemic

The pandemic has had significant adverse economic and sociopolitical effects, diverting resources from non‐COVID‐related public health issues (e.g., viral hepatitis) and amplifying pre‐existing health disparities within the population.25 The pandemic has also catalyzed efforts to strengthen healthcare systems already in place, which can be leveraged in the future for programs in viral hepatitis, NAFLD, and ALD. The speed with which new systems in health care delivery have been built should serve as a model to provide government agencies better insight on how to prioritize resources to combat HCC and the liver diseases that drive its development.

AASLD actions

The AASLD is committed to advocacy for legislation and funding to tackle HCC and its upstream risk factors. Its efforts are spearheaded by its Public Policy Committee, which has expanded to include members of patient advocacy organizations. In partnership with government relations consultants CRD Associates, AASLD influences legislative and regulatory policies that will achieve meaningful progress, for example, the expansion of the Recalcitrant Cancer Research Act of 2012. A particularly important activity is Capitol Hill Day, open to all AASLD members, which provides face‐to‐face opportunities to convey to Congressional representatives the importance of reducing the burden of liver disease.


There are multiple opportunities to reduce the negative impact of HCC. Strengthening advocacy and support from a broad spectrum of stakeholders is critical in this endeavor. Although we have focused on prevention and management of chronic liver diseases, the precursors to HCC, we acknowledge the importance of advancing technology for HCC detection and the ongoing development of effective treatments. Additional information on AASLD's public policy activities, which are relevant to these issues, can be found online.


Lisa J. Townshend‐Bulson received grants from Gilead. Steven D. Lidofsky received grants from Gilead, Intercept, and Target.


1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.
2. Moon AM, Singal AG, Tapper EB. Contemporary epidemiology of chronic liver disease and cirrhosis. Clin Gastroenterol Hepatol. 2020;18(12):2650–66.
3. Lee YT, Wang JJ, Luu M, Noureddin M, Kosari K, Agopian VG, et al. The mortality and overall survival trends of primary liver cancer in the United States. J Natl Cancer Inst. 2021;113(11):1531–41.
4. Benson AB, D'Angelica MI, Abbott DE, Anaya DA, Anders R, Are C, et al. Hepatobiliary Cancers, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2021;19(5):541–65.
5. Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018;67(1):358–80.
6. World Health Organization. Global health sector strategy on viral hepatitis 2016–2021: towards ending viral hepatitis; 2016 [Cited 2022 Jan 15].‐HIV‐2016.06‐eng.pdf
7. U.S. Department of Health & Human Services. Viral hepatitis in the United States: data and trends. [Cited 2022 Jan 15].‐about‐viral‐hepatitis/data‐and‐trends/index.html
8. Centers for Disease Control and Prevention. Hepatitis C: by the numbers. [Cited 2022 Jan 15].‐c‐by‐the‐numbers.pdf
9. Huang AC, Mehta N, Dodge JL, Yao FY, Terrault NA. Direct‐acting antivirals do not increase the risk of hepatocellular carcinoma recurrence after local‐regional therapy or liver transplant waitlist dropout. Hepatology. 2018;68:449–61.
10. Ioannou GN, Green PK, Berry K. HCV eradication induced by direct‐acting antiviral agents reduces the risk of hepatocellular carcinoma. J Hepatol. 2017;68:25–32.
11. Endeshaw M, Hallowell BD, Razzaghi H, Senkomago V, McKenna MT, Saraiya M. Trends in liver cancer mortality in the United States: dual burden among foreign‐ and US‐born persons. Cancer. 2019;125(5):726–34.
12. Momin B, Millman AJ, Nielsen DB, Revels M, Steele CB. Promising practices for the prevention of liver cancer: a review of the literature and cancer plan activities in the National Comprehensive Cancer Control Program. Cancer Causes Control. 2018;29(12):1265–75.
13. Murthy N, Wodi AP, Bernstein H, McNally V, Cinease C, Ault K. Advisory committee on immunization practices recommended immunization schedule for adults aged 19 years or older—United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71:229–33.
14. Sanyal AJ. Putting non‐alcoholic fatty liver disease on the radar for primary care physicians: how well are we doing? BMC Med. 2018;16:148.
15. Bergqvist CJ, Skoien R, Horsfall L, Clouston AD, Jonsson JR, Powell EE. Awareness and opinions of non‐alcoholic fatty liver disease by hospital specialists. Intern Med J. 2013;43:247–53.
16. Lazarus JV, Mark HE, Anstee QM, Arab JP, Batterham RL, Castera L, et al. Advancing the global public health agenda for NAFLD: a consensus statement. Nat Rev Gastroenterol Hepatol. 2022;19:60–78.
17. Ganne‐Carrié N, Nahon P. Hepatocellular carcinoma in the setting of alcohol‐related liver disease. J Hepatol. 2019;70(2):284–93.
18. Tapper EB, Parikh ND. Mortality due to cirrhosis and liver cancer in the United States, 1999–2016: observational study. BMJ. 2018;362:k2817.
19. Grant BF, Chou SP, Saha TD, Pickering RP, Kerridge BT, Ruan WJ. Prevalence of 12‐month alcohol use, high‐risk drinking, and DSM‐IV alcohol use disorder in the United States, 2001–2002 to 2012–2013: results from the National Epidemiologic Survey on Alcohol and Related Conditions. JAMA Psychiat. 2017;74:911–23.
20. World Health Organization. Global status report on alcohol and health 2018; 2018 [Cited 2022 Jan 15].
21. Herttua K, Makela P, Martikainen P. Changes in alcohol‐related mortality and its socioeconomic differences after a large reduction in alcohol prices: a natural experiment based on register data. Am J Epidemiol. 2008;168:1110–8.
22. Parikh ND, Chung GS, Mellinger J, Blanchette JG, Naimi TS, Tapper EB. Alcohol policies and alcohol‐related liver disease mortality. Gastroenterology. 2021;161(1):350–2.
23. Ventura‐Cots M, Ballester‐Ferré MP, Ravi S, Bataller R. Public health policies and alcohol‐related liver disease. JHEP Rep. 2019;1(5):403–13.
24. Liver Illness Visibility, Education, and Research Act of 2021, H.R. 5675, 117th Cong; 2021 [Cited 2022 Jan 15].‐congress/house‐bill/5675/text
25. Cox AL, El‐Sayed MH, Kao JH, Lazarus JV, Lemoine M, Lok AS, et al. Progress towards elimination goals for viral hepatitis. Nat Rev Gastroenterol Hepatol. 2020;17(9):533–42.
Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.