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. 2025 May;82(5):851-860.
doi: 10.1016/j.jhep.2024.10.031. Epub 2024 Oct 30.

Liver cancer in 2021: Global Burden of Disease study

En Ying Tan  1 , Pojsakorn Danpanichkul  2 , Jie Ning Yong  3 , Zhenning Yu  3 , Darren Jun Hao Tan  3 , Wen Hui Lim  3 , Benjamin Koh  3 , Ryan Yan Zhe Lim  3 , Ethan Kai Jun Tham  3 , Kartik Mitra  3 , Asahiro Morishita  4 , Yao-Chun Hsu  5 , Ju Dong Yang  6 , Hirokazu Takahashi  7 , Ming-Hua Zheng  8 , Atsushi Nakajima  9 , Cheng Han Ng  10 , Karn Wijarnpreecha  11 , Mark D Muthiah  12 , Amit G Singal  13 , Daniel Q Huang  14
Affiliations

Liver cancer in 2021: Global Burden of Disease study

En Ying Tan et al. J Hepatol. 2025 May.

Abstract

Background & aims: The epidemiology of adult primary liver cancer continues to evolve, owing to the increasing prevalence of metabolic disease, rising alcohol consumption, advances in vaccination for HBV, and antiviral therapy for HCV. Disparities in care and the burden of liver cancer between populations persist. We assess trends in the burden of liver cancer and contributions by various etiologies across 204 countries and territories from 2010 to 2021.

Methods: Utilizing the methodological framework of the Global Burden of Disease Study 2021, we analyzed global and regional temporal trends in incidence and mortality, and the contributions of various etiologies of liver disease.

Results: In 2021, there were an estimated 529,202 incident cases and 483,875 deaths related to liver cancer. From 2010 to 2021, global liver cancer incident cases and deaths increased by 26% and 25%, respectively. Age-standardized incidence rates (ASIRs) and death rates (ASDRs) for liver cancer declined globally, but rose in the Americas and Southeast Asia. HBV remained the dominant cause of global incident liver cancer cases and deaths. MASLD (metabolic dysfunction-associated steatotic liver disease) was the only etiology of liver cancer with rising ASIRs and ASDRs. By contrast, ASIRs and ASDRs remained stable for alcohol-related liver cancer, and declined for HBV- and HCV-related liver cancer.

Conclusions: While age-adjusted incidence and deaths from liver cancer have started to decline, the absolute number of incident cases and deaths continues to increase. Population growth and aging contribute to the observed disconnect in the temporal trends of absolute cases and rates. Disparities remain, and the incidence and mortality associated with MASLD-related liver cancer continue to rise.

Impact and implications: Liver cancer remains a major cause of death globally, but its causes and burden in various regions are changing. This study highlights that new diagnoses and deaths related to liver cancer continue to rise. Age-adjusted death rates of liver cancer related to viral hepatitis are declining but remain high. By contrast, age-adjusted death rates of liver cancer related to MASLD (metabolic dysfunction-associated steatotic liver disease) are rising. Sustained efforts and resources are needed to eliminate viral hepatitis, reverse current trends in heavy alcohol use, and tackle the metabolic risk factors of MASLD.

Keywords: alcohol; hepatitis B; hepatitis C; hepatocellular carcinoma; hepatoma; metabolic dysfunction-associated steatohepatitis; metabolic dysfunction-associated steatotic liver disease; steatotic liver disease.

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Conflict of interest statement

Conflict of interest Daniel Q Huang has served as an advisory board member for Gilead and Roche. Yao-Chun Hsu has received research support from Gilead Sciences and Sysmex has served as an advisory board member for Gilead Sciences and has received payments for lectures from Abbvie, Bristol-Myers Squibb, Gilead Sciences, Merck Sharp & Dohme, and Novartis. Ju Dong Yang consults for AstraZeneca, Eisai, Exact Sciences, and FujiFilm Medical Sciences. Hirokazu Takahashi has received research grants from Astellas Pharma, AbbVie GK, and Sysmex. Ming-Hua Zheng has received honoraria for lectures from AstraZeneca, Hisky Medical Technologies, and Novo Nordisk and consulting fees from Boehringer Ingelheim and serves as a consultant for Eieling Technology; He also serves as an unpaid editorial board member of Hepatobiliary Surgery and Nutrition and Liver International. Amit Singal has served as a consultant or on advisory boards for Genentech, AstraZeneca, Eisai, Exelixis, Bayer, Elevar, Boston Scientific, Sirtex, Histosonics, FujiFilm Medical Sciences, Exact Sciences, Roche, Abbott, Glycotest, Freenome, and GRAIL. His research effort is supported by the National Cancer Institute R01 CA256977 and R01 CA222900. Cheng Han Ng has served as a consultant to Boxer Capital. Mark Muthiah has consulted for Roche, Astellas, Gilead, served on an advisory board for LernaBio and has received paid speaking engagements from Boston Scientific, Olympus Medical, Roche and Astellas. He is supported by the Singapore Ministry of Health through the National Medical Research Council (NMRC) Office, MOH Holdings Pte Ltd under the NMRC Clinician Scientist-Individual Research Grant (MOH-001228) and NMRC Clinician Scientist Award (MOH-001631), as well as the National Research Foundation, Singapore (NRF) under the NMRC Open Fund – Large Collaborative Grant (MOH-001325) and administered by the Singapore Ministry of Health through the NMRC Office, MOH Holdings Pte Ltd. All other authors do not have any conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details.

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