Editor's Note: A recent study titled “Trends in Hepatocellular Carcinoma Mortality Rates in the US and Projections Through 2040” by Dr. Fanpu Ji’s team from the Second Affiliated Hospital of Xi’an Jiaotong University and Dr. Mindie H. Nguyen’s team from Stanford University Medical Center was published in JAMA Network Open. This study analyzes the trends in hepatocellular carcinoma (HCC) mortality rates in the U.S. from 2006 to 2022 and uses predictive modeling to estimate age-standardized mortality rates (ASMR) through 2040.Background and Key Findings
Globally, the burden of liver cancer is significant. In 2020, it was the sixth most common cancer and the third leading cause of cancer deaths worldwide. Over the past two decades, HCC incidence and mortality have steadily risen. This study used data from the U.S. Centers for Disease Control and Prevention’s National Vital Statistics System (CDC WONDER) to calculate HCC-related ASMR. The researchers employed Joinpoint regression to evaluate trends from 2006 to 2022 and applied Prophet/ARIMA models to predict HCC-related ASMR from 2023 to 2040.
Study Scope
The study analyzed 188,280 HCC-related deaths from 2006 to 2022, with men accounting for 77.4% of deaths.
- From 2006 to 2009, the annual percentage change (APC) in overall HCC mortality was 4.1%. However, between 2009 and 2022, this rate slowed to 1.8%.
- In 2022, the HCC-related ASMR was 5.03 per 100,000 people, and it is projected to rise to 6.39 per 100,000 by 2040, with consistent trends across genders.
Etiological Trends
- Mortality rates linked to Hepatitis C Virus (HCV) and Hepatitis B Virus (HBV) infections declined.
- Mortality from Alcohol-Associated Liver Disease (ALD) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) increased significantly (Figure 1). By 2022, MASLD surpassed HBV as the third leading cause of HCC-related deaths and is projected to overtake HCV by 2032 as the second leading cause. ALD is expected to become the leading cause of HCC-related deaths by 2026.
Age and Racial Disparities
- The highest ASMR in 2022 was observed among individuals aged 65 and older, at 18.37 per 100,000, compared to 1.79 per 100,000 for individuals aged 25–64 (Figure 2).
- Among racial and ethnic groups: Non-Hispanic Alaskan and Native American populations showed the most significant ASMR increase, from 9.88 per 100,000 in 2020 to 14.71 per 100,000 in 2040. Hispanic individuals, non-Hispanic Black individuals, and non-Hispanic White individuals followed, with ASMRs of 8.86, 8.58, and 5.97 per 100,000, respectively. Asian populations are projected to have the lowest ASMR, at approximately 3.03 per 100,000 by 2040.
Public Health Implications
The study highlights the rapid increase in HCC-related ASMR linked to ALD and MASLD between 2006 and 2022. By 2026, ALD is expected to become the leading cause of HCC mortality, with MASLD projected to rank second by 2032. These findings provide valuable insights for identifying high-risk populations and guiding public health strategies in the U.S. and globally.
Expert Commentary by Dr. Emad Qayed
Accompanying the article is a commentary by Dr. Emad Qayed from Emory University, titled “The Evolving Landscape of Hepatocellular Carcinoma Mortality in the U.S.”, which underscores the study’s timeliness and its implications for future public health policies.
In the past, HCC was primarily associated with chronic viral hepatitis, especially HBV and HCV. However, with the widespread availability of antiviral therapies and vaccinations, the burden of viral hepatitis has declined, while lifestyle-related factors have become increasingly prominent. Alcohol consumption and metabolic syndrome are now key drivers of HCC.
Dr. Ji’s study reveals the rising prevalence of ALD- and MASLD-related HCC between 2006 and 2022, projecting ALD as the leading cause of HCC mortality by 2026 and MASLD as the second by 2032. This shift highlights the pressing need for strategies targeting these underlying conditions.
The study also identifies significant racial and ethnic disparities in HCC mortality, with sharp increases projected among Native American, Black, and Hispanic populations. These findings emphasize the importance of tailoring public health strategies to address the needs of diverse groups.
Although progress has been made in MASLD research and drug development—such as the FDA’s 2024 approval of resmetirom, the first MASLD treatment—the effectiveness of these therapies in reversing the upward trend of MASLD-related liver disease remains uncertain. The study’s findings highlight the critical need for continued drug development and research. From a preventive perspective, reducing alcohol consumption and promoting healthy lifestyles remain vital measures for mitigating the risks of ALD and MASLD.
