Global Epidemiology of Alcohol-Related Liver Disease, Liver Cancer, and Alcohol Use Disorder, 2000–2021
Original article
Background
In 2021, alcohol consumption ranked as the ninth leading cause of the global disease burden.
Alcohol use has been causally linked to numerous disease and injury categories, with over 200 of the International Classification of Diseases, 10th Revision (ICD-10) three-digit categories being attributable to alcohol.
In particular, alcohol use disorder (AUD) constitutes a chronic brain disease characterized, among many other features, by compulsive heavy alcohol use and loss of control over alcohol intake, leading to significant psychological, social, and physical harm.
AUD is a highly prevalent mental health disorder, affecting around 3.7% of the global adult population in 2019.
Furthermore, alcohol-related liver disease (ALD) is a striking health consequence, with higher mortality in individuals with cirrhosis.
The economic costs due to alcohol use were estimated at 2.6% of global gross domestic product, most of them attributable to losses in productivity (61.2%).
In the United States of America (USA), the annual direct and indirect costs of ALD are projected to increase from $31 billion in 2022 to $66 billion in 2040, representing a 118% increase in this period.
Individuals with ALD have two diseases to treat (AUD and chronic liver disease), and ideal treatments should be multidisciplinary to manage and treat both comorbid conditions.
Unfortunately, timely access to AUD treatments for individuals with ALD is scarce, even in developed countries, due to several barriers at the patient, clinician, and organizational levels. For example, a retrospective study conducted in the USA, including 35,682 veterans with ALD, demonstrated that 12% received behavioral therapy after AUD diagnosis, and 1% received behavioral therapy with pharmacotherapeutic agents.
Also, difficulties in hepatocellular carcinoma (HCC) surveillance have been identified in ALD. In the USA and Europe, fewer than 30% of HCC cases are diagnosed by surveillance in patients with cirrhosis, and screening among individuals with ALD is less commonly performed than in those with hepatitis C virus-related cirrhosis.
Thus, gaps in both healthcare access and treatment likely contribute to the burden of disease due to alcohol.
While numerous studies have examined the local and regional epidemiology of ALD and AUD, there are significant gaps in understanding their global epidemiology.
The Coronavirus Disease 2019 (COVID-19) pandemic has further deepened this understanding through its significant effects on disease burden, high mortality rates, long-term health impacts, and disruptions to healthcare systems, which have undoubtedly influenced the burdens of ALD, AUD, and liver cancer.
To bridge these gaps, the researchers leveraged the Global Burden of Disease (GBD) Study 2021 data, one of the most comprehensive and up-to-date global datasets for ALD, AUD, liver cancer, and their risk factors available.
This study aimed to investigate the temporal trends of ALD, AUD, and alcohol-attributable primary liver cancer across 204 countries and territories, stratifying the data by sex, geographic location, and sociodemographic index (SDI) from 2000 to 2021.
Key findings
The global burden of alcohol use disorder, alcohol-related liver disease, and alcohol- attributable primary liver cancer
In 2021, in terms of prevalence there were:
- 111.12 million cases of AUD (+14.66% from 2000),
- 3.02 million cases of ALD (+38.68% from 2000), and
- 132,030 cases of alcohol-attributable primary liver cancer (+94.12% from 2000).
In 2021, in terms of incidence, there were:
- 55.78 million new cases of AUD (+15.24% from 2000),
- 462,690 cases of ALD (+38.29% from 2000), and
- 99,540 cases of alcohol- attributable liver cancer (+82.89% from 2000).
In 2021, in terms of mortality, there were:
- 158,470 deaths from AUD (- 3.23% from 2000),
- 354,250 deaths from ALD (+32.60% from 2000), and
- 92,230 deaths from alcohol- attributable primary liver cancer (+76.75% from 2000).
Regarding sex, changes from 2000 to 2021 from ALD and AUD were less pronounced in females than males. When analyzed during the pandemic timeframe (2019 to 2021) versus the pre-pandemic timeframe (2000 to 2019), prevalence, incidence, and mortality (except for AUD) underwent nearly equal or higher degrees of changes in the pre-pandemic compared to the pandemic timeframe.
From 2019 to 2021, AUD prevalence and incidence increased in males, whereas it decreased in females.
AUD death decreased at a higher degree in females than males.
However, ALD metrics increased more in females: prevalence by 4.90%, incidence by 4.96%, and mortality by 1.07%. In males, prevalence increased by 3.87%, incidence by 3.73%, and mortality by 0.88%.
Alcohol use disorder
The highest burden of AUD was observed in Eastern Europe. In Eastern Europe the
- age-standardized prevalence rate (ASPR) was 3,292.73,
- age-standardized incidence rate (ASIR) was 1,634.85, and
- age-standardized death rate (ASDR) was 10.66.
While a decline in ASPR was observed across most regions, ASPR increased in Australasia (APC: 0.72%), Oceania (APC: 0.13%), and Western Sub-Saharan Africa (APC: 0.08%).
Considering the age-standardized incidence rate, most regions exhibited a decrease, but ASIR increased in Australasia (APC: 0.76%), Oceania (APC: 0.12%), and Western Sub-Saharan Africa (APC: 0.10%).
The age-standardized death rate increased only in High-income North America (APC: 1.83%).
High SDI countries exhibited the highest burden of AUD with ASPR, ASIR, and ASDR of 1,847.63, 915.37, and 2.58, respectively. ASDR decreased in all SDI strata except remained stable in high SDI countries.
Alcohol-related liver disease
In 2021, the highest ASPR of ALD was observed in Eastern Europe, with an ASPR of 125.22.
In contrast, ASIR and ASDR were highest in Central Asia, with 18.56 and 11.63, respectively.
The ASPR, ASIR, and ASDR of ALD demonstrated a downward trend in most GBD regions from 2000 to 2021.
However, Central Asia (APC: 0.88%), Eastern Europe (APC: 0.68%), Central Sub-Saharan Africa (APC: 0.16%), and South Asia (APC: 0.10%) exhibited an uptrend in ASPR.
ASIR increased in Eastern Europe (APC: 0.47%) and Central Asia (APC: 0.44%).
ASDR increased in Eastern Europe (APC: 0.99%) and High-income North America (APC: 0.74%).
High SDI countries exhibited the highest ASPR of liver disease caused by alcohol with a value of 39.37, whereas low SDI countries exhibited the highest ASIR and ASDR with a value of 7.79 and 5.94, respectively. In the timeframe 2000 to 2021, ASPR, ASIR, and ASDR decreased in all SDI strata.
Alcohol-attributable primary liver cancer
In 2021, the highest burden of alcohol-attributable primary liver cancer in terms of ASRs was observed in Australasia, with an ASPR, ASIR, and ASDR of 3.77, 2.32, and 1.92, respectively.
From 2000 to 2021, Australasia (APC: 3.52%), Southern Latin America (APC: 3.46%), and High-income North America (APC: 2.72%) experienced the most notable changes in ASPR.
ASIR increased in two-thirds of regions, with the highest upward progression observed in Southern Latin America (APC: 3.26%), Australasia (APC: 2.79%), and High-income North America (APC: 2.46%).
Similarly, ASDR exhibited the most pronounced increases in Southern Latin America (APC: 3.09%), Australasia (APC: 2.47%), and High-income North America (APC: 2.30%).
ASPR of alcohol-attributable primary liver cancer increased in high (APC: 1.10%), middle (APC: 0.96%), and low-middle SDI countries (APC: 0.93%).
From the designated time frame, ASIR increased in low-middle (APC: 0.90%), middle (APC: 0.61%), and high SDI strata (APC: 0.56%).
Similarly, ASDR increased in low-middle (APC: 0.89%), middle (APC: 0.35%), and high SDI countries (APC: 0.27%).
Meaning and conclusion
Trends in alcohol use and its related health consequences have been evolving over the last few years, likely promoted by sociodemographic changes, cultural aspects, and the COVID-19 pandemic, among other factors.
The study findings are in line with trends observed from the GBD 2019 study, which highlighted the rising prevalence rates of ALD and alcohol-attributable primary liver cancer even while the prevalence rate of AUD declined.
The findings of this study suggest that factors beyond alcohol consumption contribute to the rising prevalence of ALD and primary liver cancer. Improved screening and diagnostic techniques allow for earlier and more accurate detection, while changes in disease registry systems may enhance the ability to capture current epidemiological trends, potentially leading to higher reported prevalence rates.
Furthermore, while overall AUD prevalence may be declining, higher-risk alcohol use behaviors, such as binge alcohol consumption , among specific populations could be on the rise.
Even though the global burden of AUD declined, it is still markedly high, with over 111 million people living with AUD in 2021.
The global decline masked an important regional variation in which Australasia, Oceania, and Western Sub-Saharan Africa exhibited an uptrend from age-adjusted incidence rates of AUD.
Mortality from AUD decreased or remained stable in nearly all regions except increased in High-income North America. Of note, although AUD was more frequent in countries with high SDI, countries with lower SDI exhibited higher ASDRs from ALD, which could be explained by poorer healthcare access and availability of treatments and technologies, among other social and cultural variables.
ALD and AUD co-exist, with ALD being one the most common alcohol-associated organ damage hence, policies to decrease alcohol use together with prevention and early detection of AUD are crucial for effectively reducing alcohol-related harm and ALD.
This study found that during the COVID-19 pandemic, the change in incidence and mortality from AUD, ALD, and liver cancer from alcohol exhibited a lower increase compared to pre-pandemic trends, even though several studies reported an increasing rate of ALD and alcohol consumption at the greater extent during COVID-19 pandemic. This observation may be explained by changes in access to alcohol, which was subjected to multiple factors, including the restriction of alcohol sales. For example, in South Africa, alcohol availability was limited during the COVID-19 pandemic.
However, data from a cross-sectional study including over 3,000 individuals indicated that around a fifth of alcohol consumers increased or started alcohol consumption during the pandemic. A lag time between increased alcohol consumption and liver injury from alcohol, along with other factors, might be expected. Other relevant factors, such as the interaction between alcohol use and metabolic dysfunction (e.g., obesity, type 2 diabetes mellitus, arterial, and dyslipidemia) could also contribute to this rising trend of chronic liver disease.
Interestingly, the study revealed that from 2019 to 2021, females experienced a greater increase in ALD prevalence compared to males. This trend may be attributed to the rise in alcohol consumption among females during the COVID-19 pandemic. In addition, self-underreporting of alcohol consumption is a well-recognized bias that impedes accurate tracking of epidemiological trends in AUD. This may partly explain the observed decline in AUD in the study findings, especially during the pandemic, when limited healthcare access, heightened stigma in remote surveys, and disruptions in data collection likely played a role. Moreover, whether AUD declines in female populations in areas where alcohol use among females is due to stigma remains an unproven hypothesis. Long-term data is needed to quantify the global effect of the COVID-19 pandemic on the alcohol-related disease burden, particularly liver disease, which accounts for nearly 90 percent of alcohol-related harm.
This study reported a high burden of AUD, ALD, and liver cancer attributable to alcohol, including an increased prevalence rate of liver cancer from alcohol from 2000 to 2021. Prevalence, incidence, and mortality of ALD increased from 2019 to 2021, with a steeper trend in females compared to males. Given that 49 countries exhibited an uptrend in ALD prevalence rates and 111 countries were found to have an uptrend in liver cancer prevalence rates from alcohol consumption between 2000 and 2021, it is essential to implement comprehensive strategies globally. These strategies should focus on reducing alcohol intake, preventing AUD, and effectively treating its health consequences, including ALD and HCC, in all countries and territories worldwide.
Abstract
Background/aims
Alcohol represents a leading burden of disease worldwide, including alcohol use disorder (AUD) and alcohol-related liver disease (ALD).
The researchers aim to assess the global burden of AUD, ALD, and alcohol-attributable primary liver cancer between 2000-2021.
Methods
The researchers registered the global and regional trends of AUD, ALD, and alcohol-related liver cancer using data from the Global Burden of Disease 2021 Study, the largest and most up-to-date global epidemiology database.
They estimated the annual percent change (APC) and its 95% confidence interval (CI) to assess changes in age-standardized rates over time.
Results
In 2021, there were 111.12 million cases of AUD, 3.02 million cases of ALD, and 132,030 cases of alcohol-attributable primary liver cancer.
Between 2000 and 2021, there was a 14.66% increase in AUD, a 38.68% increase in ALD, and a 94.12% increase in alcohol-attributable primary liver cancer prevalence. While the age-standardized prevalence rate for liver cancer from alcohol increased (APC: 0.59%) over these years, it decreased for ALD (APC: -0.71%) and AUD (APC: -0.90%).
There was significant variation by region, socioeconomic development level, and sex. During the last years (2019-2021), the prevalence, incidence, and death of ALD increased to a greater extent in females.
Conclusions
Given the high burden of AUD, ALD, and alcohol-attributable primary liver cancer, urgent measures are needed to prevent them at both global and national levels.