Alcohol-Associated Liver Disease, MASLD Drive Growing Liver Cancer Burden in the US

The burden of primary liver cancer in the US has increased over the past 2 decades, driven primarily by rapid growth in alcohol-associated liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD), according to findings from a recent study.1

Leveraging data from the Global Burden of Disease (GBD) 2021, the study found a 142% increase in prevalence, a 141% increase in incident cases, and a 136% increase in deaths attributable to primary liver cancer in the US between 200 and 2021. While hepatitis C virus (HCV)-associated primary liver cancer accounted for the greatest prevalence, ALD and MASLD were the fastest-growing etiologies.1

A global leading cause of cancer-related mortality, primary liver cancer is on the rise. Predominant etiological factors include hepatitis B virus (HBV), HCV, ALD, and MASLD, but advances in viral hepatitis vaccines and treatment paired with a growing prevalence of metabolic diseases and alcohol consumption have altered the epidemiological landscape of liver cancer.1,2

“Given the evolving epidemiology of primary liver cancer, continuous monitoring of its burden is crucial. However, updated epidemiological data in the United States have not yet been reported,” Karn Wijarnpreecha, MD, MPH, an associate clinical professor of internal medicine in the division of gastroenterology at the University of Arizona College of Medicine, and colleagues wrote.1 “Understanding the evolving trends of primary liver cancer can enhance public awareness of its risks and inform health policies.”

To address this gap in research and provide up-to-date epidemiological data for primary liver cancer in the US, investigators extracted information on its prevalence, incidence, death, and disability-adjusted life years (DALYs) from the GBD 2021 study. In order to estimate the proportions of liver cancer cases attributed to the etiology groups in the GBD, investigators conducted a systematic literature search using PubMed, including only population-based studies providing data on the contribution of liver cancer etiologies. Estimated proportions were then used to break down the total liver cancer estimates by their respective etiologies.1

In 2021, there were 47,970 cases (95% UI, 45,240-49,850); 31,450 incident cases (95% UI, 29,170-32,720); 24,770 deaths (95% UI, 22,900-25,830); and 576,920 DALYs (95% UI, 546,180-597,640) attributable to primary liver cancer in the United States. The estimated age-standardized prevalence rate (ASPR), age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and age-standardized DALYs (ASDALYs) were 9.31 (95% UI, 8.85-9.65); 5.58 (95% UI, 5.20-5.79); 4.24 (95% UI, 3.94-4.42); and 106.24 (95% UI, 101.12-110.00), respectively.1

Investigators called attention to a 141% increase in the number of incident primary liver cancer cases, a 136% increase in primary liver cancer deaths, and a 123% increase in DALYs between 2000 and 2021. Of note, the greatest prevalence, incidence, death, and DALYs from primary liver cancer were due to chronic HCV infection.1

From 2001 to 2021, ASIR, ASDR, and ASDALYs for primary liver cancer increased across all etiologies. Specifically, ALD-related primary liver cancer showed the greatest increase in ASIR (annual percent change [APC], 2.40%; 95% CI, 2.18%-2.62%) and ASDR (APC, 2.22%; 95% CI, 1.70%-2.74%), whereas ASDALYs increased the most with MASLD (APC, 2.08%; 95% CI, 1.87%-2.29%).1

Investigators acknowledged multiple limitations to these findings, including GBD’s reliance on the quality of primary data from national registries; missing data for things like histological subgroups of primary liver cancer and ethnicity; and the potential impact of reporting biases on estimated primary liver cancer burden and certain etiologies like alcohol.1

“These data underscore the need for public health specialists and healthcare providers to advocate for increased political will and resources to develop national and state-based policies aimed at curbing alcohol consumption and the growing prevalence of metabolic diseases,” investigators concluded.1

References

1. Danpanichkul P, Duangsonk K, Kalligeros M, et al. 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. Alimentary Pharmacology and Therapeutics. https://doi.org/10.1111/apt.18473
2. Yang JD, Hainaut P, Gores GJ, et al. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol. doi:10.1038/s41575-019-0186-y