Global MASH costs set to double by 2040

Metabolic dysfunction–associated steatohepatitis (MASH) is set to surge by 2040, driving more cases, advanced liver disease, and medical costs that could more than double in most countries without effective intervention, according to a large modeling study spanning nine nations.

For the analysis, published in Clinical Gastroenterology and Hepatology, senior author Zobair M. Younossi, MD, MPH, professor and chairman of the Global NASH/MASH Council Center for Outcomes Research in Liver Disease and colleagues used a country-specific Markov model to project the clinical, economic, and quality-of-life burden of MASH from 2021 to 2040 in the United States, Germany, Spain, France, Italy, the United Kingdom, Japan, Brazil, and Saudi Arabia. Transition probabilities were based on published studies and meta-analyses and then adjusted to match national data on rates of decompensated cirrhosis, liver cancer, and liver transplantation.

Because population-based MASH prevalence data are limited, the researchers used a back-calculation approach to estimate baseline prevalence. They drew from published data on MASH-related cirrhosis prevalence, adjusted for country-specific obesity and type 2 diabetes rates. Incident cases were assumed to enter at early fibrosis stages, reflecting the largely asymptomatic nature of early disease. Mortality estimates were derived using U.S. NHANES-linked data for high-risk metabolic dysfunction–associated steatotic liver disease as a proxy for MASH and applied to country-specific background mortality rates from the Global Burden of Disease study.

Dr. Younossi and coauthors estimated that MASH prevalence would increase in all countries studied, accompanied by a ≥20% rise in advanced liver disease stages, including compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma and liver transplantation, driving sharp increases in costs and productivity losses.

In the United States, MASH prevalence is projected to rise from 6.71% in 2021 to 7.41% in 2040, translating to an increase from about 17.4 million to 21.8 million affected adults. During the same period, direct annual medical costs are projected to climb from $34.97 billion to $78.59 billion. Comparable trends were projected elsewhere, including Germany ($0.83 billion to $1.82 billion), Spain ($1.48 billion to $3.50 billion), France ($1.28 billion to $2.90 billion), Italy ($1.34 billion to $3.00 billion), the U.K. ($2.18 billion to $5.29 billion), Japan ($1.20 billion to $2.33 billion), Brazil ($3.41 billion to $9.81 billion) and Saudi Arabia ($1.72 billion to $3.96 billion).

The model also projected that work productivity losses would more than double in most countries by 2040. In the United States, productivity losses were estimated to rise from $111.1 billion in 2021 to $246.6 billion in 2040, reflecting both rising prevalence and progression to later disease stages associated with greater functional impairment.

“The consistency of the increasing trends in every country and every region surprised me,” Dr. Younossi told GI & Hepatology News.

Subgroup analyses highlighted geographic variation in both prevalence and growth rates. Saudi Arabia was projected to have the fastest annual percentage increase in MASH incidence (1.98% from 2021 to 2040), while Japan showed one of the steepest relative increases in prevalence, rising from 3.67% to 5.02%. Across all countries, early-stage MASH prevalence declined slightly as a proportion of total cases, while advanced disease stages increased disproportionately, reflecting aging populations and worsening metabolic risk profiles.

Liver-related mortality was projected to rise steadily. In the United States, liver-related deaths among patients with MASH were estimated to increase from 11.1 to 12.4 per 100,000 between 2021 and 2040. Larger relative increases were projected in Japan, Brazil, and Saudi Arabia, countries with rapidly rising metabolic risk factors.

The authors conducted multiple scenario and sensitivity analyses. A scenario modeling increased use of glucagon-like peptide-1 receptor agonists beginning in 2030, with assumed annual reductions of 1% to 2% in obesity and diabetes prevalence, reduced projected incidence and costs but did not fully offset overall growth in burden. Sensitivity analyses showed that projections were most influenced by assumptions around obesity and diabetes prevalence, disease progression rates, and hospitalization costs.

The analysis had limitations, including reliance on modeled estimates rather than direct longitudinal data, assumptions required to estimate undiagnosed disease, and extrapolation of U.S.-derived mortality risks to other countries.

The researchers were also not able to fully capture future changes in treatment uptake, screening practices and health care delivery, and they reported cost projections in nominal, undiscounted terms. Despite these limits, the authors highlighted the large projected impact.

“Addressing this growing challenge requires not only the development of new therapeutic options but also the implementation of both country-specific and global policy strategies to manage this major noncommunicable liver disease,” they wrote. “These strategies should support initiatives to raise public awareness, implement targeted screening for high-risk populations, improve access to health care services, and promote healthy lifestyle changes to combat the global epidemics of obesity and T2D. Without timely and coordinated action, the cost of inaction will likely result in a significant escalation of disease burden, along with profound human and economic consequences for patients and society.”

GI & Hepatology News invited senior author Zobair M. Younossi, MD, MPH, professor and chairman of the Global NASH/MASH Council Center for Outcomes Research in Liver Disease, to comment on the study.

Why does this study matter?

Dr. Younossi: MASH is increasingly recognized as one of the most common liver diseases in the world responsible for a large number of liver cancers, liver transplants and liver deaths. Despite this huge burden, awareness about this disease is suboptimal. This lack of awareness is especially true among policy makers at the national or global level where this liver disease has not been considered as an important non-communicable disease. This analysis assesses the clinical burden, humanistic burden and economic burden of MASLD in 9 countries representing different regions of the world. It shows clearly that without serious policy intervention the comprehensive burden of this disease will be increasing in every region of the world in the next two decades.

How might the findings influence clinical practice?

Dr. Younossi: We are hoping that data like this can influence policy makers to provide resources to deal with this disease by early identification of patients at risk for bad outcomes as well as address some of the environmental drivers of this disease, such as consumption of ultra processed food, high sugary beverages, and lack of physical activity. These interventions can address this disease at a higher level that can then translate into better opportunities for clinicians to offer lifestyle changes to patients with better possibility of success.

What gaps remain, and what research should be done next?

Dr. Younossi: Many other countries are affected by this disease, and we need to understand the projected burden in all settings. Also, we need to show that policy investments can potentially improve outcomes and save both lives and future healthcare costs for society.

Is there anything else you'd like to say about this work?

Dr. Younossi: In addition to policy changes, there is a need for biopharmaceutical companies to develop better biomarker tests for early identification of at-risk patients and better drug regimens that can be used for those who are at highest risk.