DAY 1 - The Risk Factor Profile of Non-Alcoholic Steatohepatitis Continues to Evolve

Changes in the epidemiological landscape of non-alcoholic steatohepatitis (NASH) underscore the need for interventions that target metabolic risk factors, according to an analysis presented Monday at the American College of Gastroenterology 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania.

As the prevalence of metabolic syndrome continues to rise, affecting populations across the globe, metabolic factors play an increasingly prominent role in the pathophysiology of liver disease. Recent research has identified an association between non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome, pointing to obesity, type 2 diabetes mellitus, and dyslipidemia as metabolic risk factors that are commonly implicated in NAFLD (Streba LAM et al. World J Gastroenterol 2015;21:4103–4110). NAFLD encompasses a spectrum of diseases that includes NASH, a severe liver disease characterized by inflammation and liver damage. NASH-associated inflammation can progress to cirrhosis or hepatocellular carcinoma, which have emerged as global health priorities.

A research team led by Meghana Kakarla, MD, an internal medicine resident at Mobile Infirmary Medical Center, in Mobile, Alabama analyzed data obtained from the Global Burden of Disease (GBD) Study to understand the evolution of the different risk factors associated with NASH, including behavioral, metabolic, and environmental factors, over the past three decades. The GBD Study, conducted between 1990 and 2019, included data about 256 causes of death and 369 diseases from 204 countries and territories, which were divided into five categories based on the socio-demographic index (SDI) that reflects the regional level of development.

“Prior research has examined NASH prevalence and risk factors,” co-author Tahera Ahmadi, MD, said during a poster presentation. “Yet, there remains a gap in understanding the evolving nature of these risks, the shift from behavioral to metabolic drivers, and their projected impact on future disease burden.”

The authors used a linear regression analysis to identify and quantify trends in NASH-associated death rates and disability-adjusted life years (DALYs), which were obtained from the GBD Study. The analysis revealed an overall decrease in NASH-related death rates and DALY rates from 1990 to 2019.

“The risk factor analysis revealed a substantial shift in disease burden,” Ahmadi said. “Behavioral risks, accounting for 70% of NASH deaths and 72.45% of DALYs in 1990, decreased to 61% and 63.02%, respectively, by 2019. Conversely, metabolic risks increased from contributing 30% of deaths and 27.55% of DALYs in 1990 to 39% and 36.98%, respectively, by 2019.” Predictive modeling, which was used to project future NASH-related outcomes over the next two decades, showed that the DALY rates related to NASH would continue to decrease between 2020 and 2040, whereas the rates of NASH-associated mortality would remain stable.

“Our findings highlight a shift in the epidemiological landscape of NASH, with metabolic risks becoming increasingly prominent,” Ahmadi noted. “This underscores the need for targeted public health interventions focusing on metabolic health to mitigate the future burden of NASH.”

Continued monitoring and research are essential for identifying strategies and policies that can reduce NASH-related death rates globally, particularly in regions that may not reflect the decreasing mortality trends. A previous analysis of data from the GBD Study showed that the incidence of NASH-related liver cancer increased significantly over the study decades, as did liver cancer-related mortality and DALY rates. The study also highlighted disparities in the NASH-related liver cancer burden between different socioeconomic groups and locations (Pang J et al. Diabetol Metab Syndr 2022;14:112).

“NASH remains a public health challenge with evolving risk factors,” Ahmadi added. “Proactive measures addressing metabolic risk factors are crucial to reducing the NASH-related burden by 2040.”