Alcohol-Related Liver Disease, Followed by Metabolic Dysfunction-Associated Steatotic Liver Disease, Emerges as the Fastest-Growing Aetiologies for Primary Liver Cancer in the United States

Pojsakorn Danpanichkul; Kwanjit Duangsonk; Markos Kalligeros; Michael B Fallon; Chawinthorn Vuthithammee; Chun Wei Pan; Preenapun Saokhieo; William Derrick; Yanfang Pang; Vincent L Chen; Donghee Kim; Amit G Singal; Ju Dong Yang; Karn Wijarnpreecha

doi:10.1111/apt.18473

Alcohol-Related Liver Disease, Followed by Metabolic Dysfunction-Associated Steatotic Liver Disease, Emerges as the Fastest-Growing Aetiologies for Primary Liver Cancer in the United States

Aliment Pharmacol Ther. 2025 Jan 5. doi: 10.1111/apt.18473. Online ahead of print.

Authors

Pojsakorn Danpanichkul¹, Kwanjit Duangsonk², Markos Kalligeros³, Michael B Fallon^{4

5}, Chawinthorn Vuthithammee⁶, Chun Wei Pan⁷, Preenapun Saokhieo⁸, William Derrick⁹, Yanfang Pang^{10

11

12}, Vincent L Chen¹³, Donghee Kim¹⁴, Amit G Singal¹⁵, Ju Dong Yang¹⁶, Karn Wijarnpreecha^{4

5

17}

Affiliations

¹ Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA.
² Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
³ Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
⁴ Division of Gastroenterology and Hepatology, Department of Medicine, University of Arizona College of Medicine, Phoenix, Arizona, USA.
⁵ Department of Internal Medicine, Banner University Medical Center, Phoenix, Arizona, USA.
⁶ Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
⁷ Department of Medicine, John H. Stroger Jr Hospital of Cook County, Chicago, Illinois, USA.
⁸ Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
⁹ Texas Tech University Health Sciences Center School of Medicine, Lubbock, Texas, USA.
¹⁰ Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China.
¹¹ National Immunological Laboratory of Traditional Chinese Medicine, Baise, Guangxi, China.
¹² Center for Medical Laboratory Science, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China.
¹³ Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
¹⁴ Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA.
¹⁵ Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
¹⁶ Karsh Division of Gastroenterology and Hepatology, Comprehensive Transplant Center, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, California, Los Angeles, USA.
¹⁷ BIO5 Institute, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona, USA.

PMID: 39757456
DOI: 10.1111/apt.18473

Abstract

Objective: Primary liver cancer (PLC) is projected to be the third leading cause of cancer mortality in the United States in 2040. We examine the burden of PLC in the United States, stratified by sex, state and aetiological risk factors.

Methods: Data on PLC prevalence, incidence, death and disability-adjusted life years (DALYs) were extracted from the Global Burden of Disease Study 2021. Changes in these parameters were calculated using the Joinpoint regression model.

Results: There were 47,970 cases, 31,450 incident cases, 24,770 deaths and 576,920 DALYs from PLC in the United States. The highest prevalence (16,980), incidence (12,040), death (9840) and DALYs (213,410) from PLC were due to chronic hepatitis C virus infection. From 2000 to 2021, PLC incidences increased by 141%, and PLC deaths increased by 136%. Age-standardised incidence rates (ASIRs) and death rates (ASDRs) per 100,000 population for PLC increased, primarily driven by alcohol-related liver disease (ALD) (ASIR: annual percent change [APC]: +2.40%; ASDR: APC: +2.22%) and metabolic dysfunction-associated steatotic liver disease (MASLD) (ASIR: APC: +2.32%; ASDR: APC: +2.04%).

Conclusion: The burden of PLC in the United States has risen in the past two decades, driven mainly by ALD and followed by MASLD. These findings offer policymakers an accurate assessment of the PLC burden and emphasise the need for targeted risk factor mitigation, especially regarding alcohol related policy.

Keywords: addiction; alcohol; epidemiology; gastrointestinal cancer; metabolic dysfunction‐associated steatohepatitis; nonalcoholic fatty liver disease.

Abstract

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