Mortality Declines but Incidence Rates Up for Cirrhosis and Other Chronic Liver Diseases

The global burden of cirrhosis and other chronic liver diseases remains high, and in the Americas, age-standardized deaths and disability-adjusted life-years (DALYs) related to metabolic dysfunction–associated steatohepatitis (MASH) have increased compared with other regions in the world. These results indicate a need for public health policies and initiatives that target the metabolic risk factors of MASH, according to new research published in Liver International.¹

MASH is one of the primary causes of cirrhosis and chronic liver disease, which were among the top 10 leading causes of death in many parts of the world in 2023. While the burden of causes like hepatitis B virus is declining due to vaccination programs and the availability of antiviral therapy, mortality due to alcohol-related liver disease (ALD) and MASH is on the rise.

“These changes in the underlying causes of liver disease have led to a corresponding shift in the landscape of cirrhosis and other chronic liver diseases,” the authors wrote. Using the Global Burden of Disease Study 2021, they have provided updated estimates on the incidence and the deaths and DALYs related to cirrhosis and chronic liver disease.

Rising rates of metabolic dysfunction–associated steatohepatitis indicate a need for public health interventions.

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Globally in 2021, there were 58.4 million incident cases, 1.4 million deaths, and 46.4 million DALYs related to cirrhosis and other chronic liver diseases. Overall, age-standardized incidence increased (annual percent change [APC] +0.35%) from 2010 to 2021 while age-standardized deaths and DALYs declined (APC: –1.74% and –1.85%, respectively).

“The decrease in death rates yet increase in incidence could reflect that despite an increase in cirrhosis and other chronic liver diseases, there have been more efficacious management strategies,” the authors noted.

They also speculated that a slight increase in the APC for the age-standardized incident rate, age-standard death rate, and age-standardized DALY from 2018 to 2021 could also be attributed to the COVID-19 pandemic, when there was a rise in obesity and alcohol consumption.

The highest number of incident cases, deaths, and DALYs was in Southeast Asia; however, the Eastern Mediterranean region had the highest age-standardized incident rate, and Africa had the highest age-standardized death rate.

The Americas had the greatest increase in deaths (+22%) and DALYs (+16%) from 2010 to 2021. The Americas were also the only region with increases of age-standardized death rate and age-standardized DALY of MASH-related cirrhosis. These rates remained stable or declined in other regions. The authors speculated that these rising rates in the Americas compared with the rest of the world “could be due to the rapidly rising obesity rates.”

Men had a higher age-standardized incident rate, age-standardized death rate, and age-standardized DALY compared with females, and their cirrhosis and chronic liver diseases were more likely to be due to alcohol and hepatitis B and C viruses compared with females.

The researchers noted that data standardization and estimate methods that were used to account for missing data could have introduced uncertainty and variability. There may have been an underreporting of alcohol consumption, which could also lead to lower estimates, and the data didn’t account for people with multiple etiologies of liver disease.

They wrote that the findings are important for health care policy makers and public health specialists and that health policies should target the metabolic risk factors of MASH to prevent cirrhosis. In addition, the approval of resmetirom (Rezdiffra)² last year provides an opportunity to alleviate the burden of MASH.

“Concerted efforts targeted at the metabolic risk factors to curb the rising incidence of MASH, increasing linkage to care for viral hepatitis and reducing heavy alcohol consumption are required to sustain the decline in the global burden of cirrhosis,” the authors concluded.

Reference

1. Tham EKJ, Tan DJH, Danpanichkul P, et al. The global burden of cirrhosis and other chronic liver diseases in 2021. Liver Int. 2025;45(3):e70001. doi:10.1111/liv.70001

2. Joszt L. FDA approves resmetirom, first treatment for NASH with liver fibrosis. AJMC^®. March 14, 2024. Accessed February 28, 2025. https://www.ajmc.com/view/fda-approves-resmetirom-first-treatment-for-nash-with-liver-fibrosis