Correspondence to editorial on “Global epidemiology of alcohol-related liver disease, liver cancer, and alcohol use disorder, 2000-2021”

Dear Editor,

We sincerely appreciate the recent editorial highlighting our manuscript [1]. In our study, “Global Epidemiology of Alcohol-Related Liver Disease, Liver Cancer, and Alcohol Use Disorder, 2000–2021,” we examined the alcohol-related global, regional, and national epidemiological trends using the latest data from the GBD 2021 database. Our findings underscore the rising burden of alcohol-related liver disease (ALD), alcohol use disorder (AUD), and alcohol-attributable primary liver cancer in terms of incidence, prevalence, and mortality [2]. We also acknowledge the limitations pointed out by Wang et al., particularly concerning the underreporting of alcohol-related diseases, reliance on ICD-10 codes for diagnosing AUD, identifying comorbidities, and the inability to capture multiple liver diseases within the same patient, such as the overlap of metabolic dysfunction-associated and alcohol-associated liver disease (MetALD) [3,4].

Importantly, our study evaluated alcohol-attributable liver cancer based only on the primary diagnosis. However, alcohol can influence mortality in other forms of liver cancer and chronic liver disease, suggesting that our estimates are inherently conservative [5]. This is particularly concerning, given that ALD has an estimated prevalence nearly ten times lower than metabolic dysfunction-associated steatotic liver disease (MASLD). Yet, its liver-related complications—including liver disease progression—occur at a rate nearly ten times higher than MASLD alone [6]. In addition, a recent study has shown that alcohol may increase the risk of hepatocellular carcinoma in a dose-dependent fashion, being higher in patients with ALD [7]. These findings highlight ALD as the most aggressive phenotype within the steatotic liver disease spectrum and reinforce alcohol’s role as a significant disease modifier.

Beyond the increasing burden of ALD, the prevalence of metabolic comorbidities is also on the rise [8]. These risk factors act synergistically with alcohol to accelerate liver damage and promote carcinogenesis [9]. A recent position statement from 28 ALD experts [3], recommends obtaining detailed information on both recent and lifetime alcohol intake for assessing prognosis and defining management in individuals with metabolic dysfunction and steatotic liver disease. To enhance diagnostic accuracy, clinicians could also consider using alcohol biomarkers and validated questionnaires [10,11]. The presence of cardiometabolic risk factors should be evaluated within the context of alcohol consumption, as alcohol itself can contribute to other metabolic comorbidities [3]. Regular reassessment of both metabolic dysfunction and alcohol use over time is crucial, especially following changes in exposure to risk factors such as alcohol consumption or body weight. This is particularly relevant for individuals exceeding the weekly alcohol consumption thresholds. Addressing metabolic comorbidities through lifestyle modifications and pharmacological interventions remains a key strategy for reducing the overall burden of liver disease and cancer.

From a public health perspective, previous ecological studies have demonstrated that alcohol control policies are instrumental in reducing alcohol-related disease burden [12]. The World Health Organization (WHO) introduced the NCD Global Monitoring Framework, which aims for a 10% relative reduction in harmful alcohol consumption as part of its broader strategy to address behavioral risk factors [13]. In 2017, WHO identified a set of cost-effective and feasible interventions for noncommunicable disease prevention, known as the “Best Buys,” which were updated in 2023 to include 58 evidence-based interventions. Among the most effective strategies are increasing excise taxes on alcoholic beverages, enforcing comprehensive restrictions on alcohol advertising across all media platforms, and implementing strict controls on the physical availability of alcohol. WHO also developed the SAFER framework to facilitate the adoption and implementation of Best Buy policies, emphasizing the need for accessible screening, brief interventions, and treatment for alcohol-related disorders [14]. Thus, policies aimed at addressing alcohol and obesity could further contribute to reducing liver disease and primary liver cancer incidence and mortality [15].

The rising burden of ALD, compounded by the growing prevalence of metabolic comorbidities, underscores the urgent need for a dual-focus approach in both clinical and public health strategies. Comprehensive assessment of alcohol intake, alongside metabolic risk factors, is essential for optimizing patient management, while effective alcohol control policies, such as those outlined in WHO’s Best Buys and SAFER framework, play a pivotal role in curbing disease burden. By integrating targeted interventions at both individual and policy levels, we can mitigate liver disease progression and reduce the global impact of alcoholrelated and metabolic-driven carcinogenesis.

Abbreviations

ALD

alcohol-related liver disease

AUD

alcohol use disorder

GBD

global burden of disease

ICD-10

international classification of diseases

MetALD

metabolic dysfunction-associated and alcohol-associated liver disease

WHO

World Health Organization