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Njei explains the evolving treatment landscape for MASLD and how it impacts the cost-effectiveness of noninvasive tests for screening.
As metabolic dysfunction-associated steatotic liver disease (MASLD) solidifies its position as the leading cause of chronic liver disease in the United States, a critical gap remains: most patients with clinically significant fibrosis still go undiagnosed. With the recent emergence of liver-directed therapies, the stakes of early identification have never been higher.
New research presented by Basile Njei, MD, PhD, MPH, an assistant professor at Yale School of Medicine, at Digestive Disease Week (DDW) 2026 in Chicago, IL, explores whether widespread screening using noninvasive tests (NITs) is not only clinically beneficial, but also economically justified in this new treatment era.
March 14, 2024: Madrigal Pharmaceuticals’ resmetirom (Rezdiffra), an oral, thyroid hormone receptor (THR)-β selective agonist, approved as the first MASH therapy in combination with diet and exercise
August 15, 2025: Novo Nordisk’s semaglutide (Wegovy) injection 2.4 mg, a GLP-1 receptor agonist, approved as the second MASH therapy, again in combination with diet and exercise
In the past, most of the noninvasive tests were not cost effective, because you identify a patient with fibrosis, but then you don't have a treatment for it,” Njei explained to HCPLive. “You diagnose more patients without treating them, and so the cost goes up without an improvement in the quality of life.”
He noted that MASLD carries risks that extend far beyond the liver, with affected patients facing an increased likelihood of cardiovascular events, kidney disease, and cancer. Despite this, many individuals remain undiagnosed until later stages of disease, limiting opportunities for intervention.
Traditionally, clinicians have relied on simple, accessible tools such as the FIB-4 score to assess fibrosis risk, followed by confirmatory imaging like transient elastography (TE) to evaluate liver stiffness. While effective, the broader implementation of these strategies has been limited in part by questions regarding cost-effectiveness, especially in an era when treatment options were lacking.
Now, with 2 US Food and Drug Administration approved treatment options in the forms of resmetirom (Rezdiffra) and semaglutide (Wegovy), Njei and colleagues conducted a decision-analytic Markov model informed by nationally representative NHANES data from 2017 to 2020. The study evaluated multiple screening pathways over 5- and 10-year horizons from a US payer perspective, comparing FIB-4, SAFE, ALADDIN, and LRS each followed by TE, against TE-only screening and usual care. The model also incorporated a phenotype-guided treatment strategy, assigning semaglutide to patients with obesity or diabetes and resmetirom to others with confirmed F2–F3 fibrosis.
Findings showed that across both time horizons, all lab-based NIT strategies followed by TE were cost-effective at a willingness-to-pay threshold of $50,000 per quality-adjusted life year (QALY), while TE-only screening was not. Among the approaches, SAFE + TE consistently emerged as the most cost-effective strategy, with incremental cost-effectiveness ratios (ICERs) of $8405/QALY at 5 years and $6864/QALY at 10 years, along with the highest net monetary benefit.
Of note, the study also highlighted the added value of a hybrid treatment approach. Compared to single-agent strategies, combining semaglutide and resmetirom based on patient phenotype yielded the greatest population-level benefit, underscoring the importance of personalized care in MASLD management.
While the results provide compelling, policy-relevant evidence supporting population-level screening, Njei noted that further real-world data are needed to confirm long-term outcomes, including reductions in liver decompensation, hepatocellular carcinoma, and mortality.
in management of these patients, number one. We can easily diagnose them now with simple lab tests, we have treatments that can help in reversing liver disease to a certain extent, and so that what we need moving forward is to get more data in the long term and to see how screening impacts long term outcomes. Because right now, we're still projecting, we're estimating, and in our study, for example, we are simulating scenarios of care. What will be important is for us to look long term.
Editors’ note: Njei reports no relevant disclosures.
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