Rising burden of alcohol-associated liver disease and cancers: Insights into sex disparities and policy implications: Editorial on “Sex disparities in alcohol-associated liver disease and subtype differences in alcohol-attributable cancers in the United States” (original) (raw)

Alcohol consumption is a well-established risk factor for both liver disease and malignancy. However, the epidemiological landscape is evolving, revealing complexities that extend beyond traditional associations with liver diseases such as hepatitis, liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) [1,2]. In this issue of Clinical and Molecular Hepatology, Danpanichkul et al. provides a timely and comprehensive analysis of the trends in alcohol-associated liver disease (ALD) and alcohol-attributable cancers in the United States from 2000 to 2021 [3]. Using data from the Global Burden of Disease Study 2021, the authors demonstrate a significant and ongoing increase in ALD incidence, prevalence, and mortality, with particularly striking differences according to sex.

In 2021, there were 28,340 new cases of ALD, 227,730 prevalent cases, and 21,860 deaths attributed to ALD in the United States. Over the past two decades, ALD incidence increased by 43%, prevalence by 36%, and mortality by a staggering 79%. Although the age-standardized prevalence rate showed a modest decline, the age-standardized death rate increased, highlighting a worrisome trend toward more severe disease outcomes. Notably, a sex-specific analysis revealed that while the ALD incidence rate declined among men, it increased among women, with female mortality rising at nearly three times the rate observed in males [3]. These findings indicate a narrowing gender gap in alcohol-associated health risks and suggest that women are becoming increasingly vulnerable to the hepatotoxic and oncogenic effects of alcohol [4-6]. Concurrently, the incidence of alcohol use disorder (AUD) is rising more rapidly among women than among men [7,8]. However, women remain significantly less likely to access appropriate treatment services [7]. Recent reports also highlight a sharp increase in alcohol-related liver hospitalizations among women [9], with particularly severe disease observed among younger women and Hispanic populations [6]. Importantly, such trends are not confined to the United States. A nationwide analysis from South Korea, covering the period between 1998 and 2018, similarly revealed that women exhibited a greater increase in daily alcohol consumption compared with men [10]. Similarly, secular trends in Japan reveal a cultural shift toward increased alcohol use among younger generations, with earlier initiation of drinking and narrowing gender gaps in problematic alcohol use.11 Furthermore, in South Korea, the proportion of high-risk drinking steadily rose among women across all adult age groups from 20 to 59 years during the period 2011–2017, underscoring the emerging risk of ALD among younger female populations [12].

Beyond the liver diseases, the burden of alcohol-attributable cancers is equally concerning. In 2021, alcohol use was responsible for 23,210 cancer deaths, corresponding to an age-standardized death rate of 4.08 per 100,000 population. Primary liver cancer accounted for the largest share of alcohol-attributable cancer mortality (32%), followed by colorectal cancer (20%), esophageal cancer (17%), and breast cancer (12%). Notably, while mortality trends for breast, colorectal, and laryngeal cancers declined or remained stable, the death rates for primary liver cancer and other pharyngeal cancers increased significantly [3].

Recent mechanistic insights further elucidate the complex relationship between alcohol consumption and carcinogenesis. As summarized by Rumgay et al., alcohol and its primary metabolite, acetaldehyde, promote cancer development through multiple biological pathways, including DNA damage, disruption of methylation processes, induction of oxidative stress, chronic inflammation, and suppression of immune surveillance. Importantly, even low to moderate levels of alcohol intake have been associated with increased risks of cancers involving the upper aerodigestive tract, liver, colorectum, and breast [1]. Furthermore, alcohol appears to act synergistically with other carcinogenic exposures, particularly tobacco use, amplifying the risk of head and neck malignancies. These findings reinforce the notion that alcohol acts as a multisystemic carcinogen, with impacts extending beyond the liver to a broader spectrum of malignancies [1,2]. Given this expanding evidence base, there is a pressing need to reconsider current cancer screening practices, particularly among individuals with hazardous alcohol use or alcohol use disorder.

The study further highlights notable geographical variations across the United States. New Mexico reported the highest ALD-related age-standardized death rate (8.16 per 100,000 population), followed by West Virginia, Oklahoma, and Wyoming [3]. For alcohol-attributable cancers, the District of Columbia exhibited the highest mortality (6.54 per 100,000), with 39 states showing rising death rates over the study period [3]. These regional differences likely reflect disparities in alcohol policies, healthcare access, sociodemographic factors, and cultural norms around alcohol consumption. States with weaker alcohol control policies tended to have higher ALD and cancer mortality, reinforcing the critical need for more stringent and coordinated public health measures [13,14].

At a broader level, national alcohol control policies substantially influence the burden of alcohol-attributable diseases. Growing evidence also suggests that alcohol reduction or cessation itself can substantially lower the risk of several alcohol-related cancers. According to a recent evaluation by the International Agency for Research on Cancer (IARC), there is sufficient evidence that reducing or stopping alcohol consumption decreases the risk of oral and esophageal cancers [15]. Furthermore, mechanistic studies indicate that alcohol cessation rapidly reduces exposure to carcinogenic acetaldehyde, restores DNA integrity, and improves gut barrier function, providing biological plausibility for cancer risk reduction [15]. Recent multinational analyses demonstrate that jurisdictions with stronger policy environments—characterized by higher taxation, advertising restrictions, minimum unit pricing, and comprehensive monitoring—consistently exhibit lower prevalence of AUD and reduced mortality from ALD, HCC, and cardiovascular diseases [16]. For example, in countries with the highest Alcohol Preparedness Index scores, ALD mortality was reduced by 86%, and alcohol-attributable HCC mortality was reduced by 87% compared to countries with weak alcohol policy frameworks [16]. In contrast, areas with weaker regulatory structures experienced substantially higher alcohol-related morbidity and mortality. These findings reinforce the urgent need to strengthen national alcohol policies as an essential complement to clinical interventions, particularly in efforts to mitigate the rising burden of alcohol-related cancers and liver diseases.

Collectively, the findings of Danpanichkul et al. underscore the urgent need for multifaceted approaches to tackle alcohol-related harm. Public health efforts should aim not only to reduce alcohol consumption at the population level but also to implement targeted screening for both liver and extrahepatic cancers in high-risk groups. Gender-specific strategies are particularly needed, given the accelerating burden of ALD among women, and stronger alcohol control policies must be prioritized at both state and national levels.

Alcohol consumption poses a profound oncogenic threat that extends beyond liver disease, with sex acting as a critical modulator of risk and outcomes. Clinicians and researchers must recognize alcohol as a pervasive carcinogen and lead proactive efforts to implement personalized screening and prevention strategies that reflect emerging epidemiologic trends. Simultaneously, policymakers must intensify efforts to establish and enforce stronger alcohol control measures to mitigate the growing burden of alcohol-attributable cancers. A comprehensive approach—integrating sex-specific considerations, public health interventions, and national policy reforms—is essential to effectively address the shifting landscape of alcohol-related disease and to improve population-level health outcomes.

FOOTNOTES

Conflicts of Interest

The author has no conflicts of interest to declare.

Abbreviations

ALD

alcohol-associated liver disease

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