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BOSTON -- A mathematical model predicts that the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) -- formerly known as nonalcoholic fatty liver disease (NAFLD) -- will substantially increase through the middle of the century.

The model predicted that the incidence of MASLD will rise by about 23% over three decades, said Phuc Le, PhD, MPH, of the Cleveland Clinic Lerner College of Medicine in a press briefing prior to presenting the study's data at the annual meeting of the American Association for the Study of Liver Diseases (AASLD).

Specifically, she reported that the model estimated that 72 million people (representing about 27.8% of the American adult population) had MASLD in 2020, with its prevalence projected to increase steadily up until 2050, affecting an estimated 34.3% of adults by that time (109 million people).

"Our model forecasts a substantial clinical burden of NAFLD over the next three decades," Le said. "In the absence of effective treatments, health systems should plan for large increases in the number of liver cancer cases and the need for liver transplant. A better understanding of the clinical burden, especially the size of the treatment population, will help prepare for the growing clinical demand."

The model simulated the U.S. population starting from the year 2000 (incorporating new births and immigrants annually based on Census data), and also tracked the natural history of MASLD progression in adults, encompassing 14 distinct health states including no steatosis, simple steatosis, metabolic dysfunction-associated steatohepatitis (MASH, formerly nonalcoholic steatohepatitis, or NASH) fibrosis, cirrhosis, decompensated cirrhosis, hepatocellular carcinoma (HCC), liver transplant, and liver-related or other causes of death.

Le and her colleagues validated their model against predicated outcomes between 2000 to 2018 and published data on the U.S. population, and found it "closely matched" trends in NAFLD prevalence, MASH proportion, incidence of HCC and liver transplant, and overall survival rates among MASLD patients.

In addition to predicting a substantial increase in MASLD prevalence, the model forecast that between 2020 and 2050:

• Among MASLD cases, MASH cases will increase from 20.0% to 21.8%.
• The prevalence of MASLD will remain relatively stable for people aged 18-29 years, but increase significantly for other age groups.
• The proportion of persons with MASLD who develop cirrhosis will increase from 1.9% to 3.1%.
• The 16.2 million people estimated to have fibrosis stage 2 or higher will increase to 25 million.
• The number of adults with MASH fibrosis stage 2 or higher will increase 6.4 million to 9.8 million.
• Liver-related mortality will increase from 0.4% of all deaths to 1%.
• MASLD should cause 19,300 new cases of HCC and 4,200 new cases of liver transplant per year by 2050, compared with 10,400 and 1,700 cases in 2020, respectively.

Norah Terrault, MD, MPH, of the Keck School of Medicine at the University of Southern California in Los Angeles, and president of the AASLD, moderated the press briefing and called the projected increase of MASLD cases "frightening."

"How are we going to solve this from the point of view of society or policy changes?" she asked Le. "I'm thinking to myself there's no way we are going to be able to transplant our way out of this."

Le emphasized the model's forecast is "not the same as reality" and were estimates of what the future could look like if there is no change in the clinical care for MASLD, and the trajectory for obesity, diabetes, and other metabolic diseases remains the same or continues to increase.

"If we improve our management of NAFLD or NAFLD-related comorbidities and develop an effective treatment for NAFLD or MASLD, obviously then the future would not be so dark ... as seen from our projections," she said, and suggested that raising awareness of MASLD/MASH, as well encouraging a collaborative approach between primary care and specialty care "could reverse the trajectory."

Terrault agreed that it is essential to bring greater awareness to the general population about what contributes to MASLD.

"Nothing would make me happier than every individual in the United States -- starting in childhood all the way to those of older age -- every time they see their physician they ask about their liver health." she said. "That they understand the liver is an important organ. Similar to the way they think about the heart being so important I want them to understand their liver is vital."

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