Editorial: Steatotic Liver Diseases Emerge as Rapidly Growing Drivers of Primary Liver Cancer in the United States

With the advent of direct-acting antiviral agents for hepatitis C (HCV) in 2013 and increased uptake of vaccines for hepatitis B, the burden of viral-related chronic liver disease has significantly decreased [1, 2]. It was predicted that this would lead to a plateau or even decrease in the incidence of primary liver cancer (PLC) especially in younger cohorts and specific ethnic groups [3-5]. However, the concurrent rise in metabolic syndrome and alcohol use disorder has led to the emergence of steatotic liver disease as the most common cause of chronic liver disease [6-8]. It was previously unknown how this shift in the aetiology of liver disease affected recent trends in PLC incidence, prevalence and mortality.

Utilising the Global Burden of Disease (GBD) Study 2021, Danpanichkul et al. demonstrated that PLC cases and deaths in the United States have steadily increased from 2000 to 2021, mostly due to the increased burden of alcohol-associated liver disease (ALD) and metabolic dysfunction associated liver disease (MASLD) [9]. They found ALD to be the fastest growing aetiology of PLC, which contrasts prior data from GBD 2019, which identified MASLD as the fastest growing aetiology of PLC. The authors astutely point out the increased harmful alcohol use in the context of the COVID-19 pandemic and the rise of cardio metabolic disease in the United States, which are likely driving the rapid rise of both ALD and MASLD. Despite this, HCV is still the leading cause of PLC in the United States and contributed the highest prevalence, incidence and deaths by aetiology of liver disease in 2021, albeit with slower growth in the most recently evaluated era from 2015 to 2021.

The paper aligns with prior studies that have shown an increased frequency of PLC in males and older adults, but due to constraints of the GBD data, was unable to evaluate trends in race/ethnicity or distinguish between the specific type of PLC, i.e., hepatocellular carcinoma or cholangiocarcinoma [3, 10]. The authors work highlights the importance of continuing to bolster HCV screening and treatment programs not only to reduce the burden of HCV but also to prevent morbidity and mortality from PLC, as we have not yet seen the peak of HCV-related PLC. With PLC projected to be the third leading cause of cancer deaths by 2040, further study will be required to address many unanswered questions including the incidence of PLC in metabolic dysfunction and ALD, MetALD, and how best to refine screening to identify PLC in patients without cirrhosis, particularly the large non-cirrhotic MASLD population. Still, this important work advances our knowledge of the evolving etiologic drivers of PLC and their large impact on cancer-related death and disability-adjusted life years. Public health policies focused on curbing the drivers of SLD, like the efforts made to eradicate HCV, will be required to meaningfully decrease the ongoing rise in PLC.

Kelly Torosian: writing – original draft, conceptualization. Veeral Ajmera: conceptualization, writing – review and editing, writing – original draft.

The authors declare no conflicts of interest.

This article is linked to Danpanichkul et al papers. To view these articles, visit https://doi.org/10.1111/apt.18473 and https://doi.org/10.1111/apt.18511.