Basile Njei, MD, PhD, MPH, is an assistant professor at Yale School of Medicine.

Basile Njei, MD, PhD, MPH

Optimizing MASLD Screening in the Era of Liver-Directed Therapy

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’ 

, an oral, thyroid hormone receptor (THR)-β selective agonist, approved as the first MASH therapy in combination with diet and exercise

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 

. “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, 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,” he said. “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.

Njei B, Lim JK. COST-EFFECTIVENESS OF NONINVASIVE TESTS FOR SCREENING MASLD-ASSOCIATED SIGNIFICANT LIVER FIBROSIS IN THE US POPULATION. Presented at Digestive Disease Week (DDW) 2026 in Chicago, IL, from May 2-5, 2026.

Brooks A. Resmetirom (Rezdiffra) Receives Historic FDA Approval for Noncirrhotic NASH. HCPLive. March 14, 2024. Accessed May 2, 2026. 

https://www.hcplive.com/view/resmetirom-rezdiffra-receives-historic-fda-approval-for-noncirrhotic-nash

Brooks A. FDA Approves Semaglutide (Wegovy) Injection 2.4 mg for Noncirrhotic MASH. HCPLive. August 15, 2025. Accessed May 2, 2026. 

https://www.hcplive.com/view/fda-approves-semaglutide-wegovy-injection-2-4-mg-for-noncirrhotic-mash

Videos

Njei explains the evolving treatment landscape for MASLD and how it impacts the cost-effectiveness of noninvasive tests for screening.

Optimizing MASLD Screening in the Era of Liver-Directed Therapy, With Basile Njei, MD, PhD, MPH

Using AI to Improve Risk Stratification, Disease Management in MASLD, With Basile Njei, MD, PhD, MPH

Use of a novel large language model-based tool, Fibro-GPT, may offer a promising approach to detecting advanced fibrosis and predicting hepatic decompensation in metabolic dysfunction-associated steatotic liver disease (MASLD).

American College of Gastroenterology (ACG)’s 2025 Annual Scientific Meeting

 by Basile Njei, MD, PhD, MPH, an assistant professor at Yale School of Medicine, highlight Fibro-GPT’s superior performance, interpretability, and potential cost savings in the context of MASLD care.

The most common cause of chronic liver disease, MASLD is projected to become the leading indication for liver transplant in the US. Findings from a decision analytical modeling study predict a steady increase in the prevalence of MASLD from 33.7%, or 86.3 million people, in 2020 to 41.4%, or 121.9 million people, by 2050.

“In most of our clinics, the tool we have to predict advanced fibrosis is a simple clinical score called FIB-4,” Njei explained to 

. “Unfortunately, it doesn't really do a good job in predicting liver disease, and a lot of people with advanced liver disease are either misclassified as not having advanced liver disease, or people without advanced liver disease are classified as having advanced liver disease, therefore getting tests that they do not need and liver biopsies that are not required.”

Recognizing recent advances in artificial intelligence tools like large language models and their potential to streamline MASLD care, Njei and colleagues developed Fibro-GPT using NHANES 2017–2020 data from adults with MASLD, including routinely collected variables like age, platelet count, HbA1c, eGFR, BMI, AST, and ALT. Inputs were formatted into standardized text prompts and analyzed via a secure Python interface, generating a numerical risk estimate and an explanatory summary. Fibrosis stage was determined using a 2-step method: blood-based (FIB-4) followed by vibration-controlled transient elastography (VCTE).

Fibro-GPT was trained on 162 MASLD cases and externally validated on 105 biopsy-confirmed MASLD patients using liver histopathology as the reference standard. Predictive performance for 5-year incident hepatic decompensation was assessed in an additional 337 biopsy-confirmed MASLD patients.

To further assess the tool’s economic impact, investigators modeled a US population-wide screening scenario comparing Fibro-GPT to FIB-4 as a first-line tool for detecting advanced fibrosis in MASLD.

Results showed Fibro-GPT achieved an AUROC of 0.91 in the derivation cohort, with 84% sensitivity and 86% specificity, significantly outperforming FIB-4 (AUROC, 0.62; 

 <.001). Validation on biopsy-confirmed cases showed sustained performance (AUROC, 0.90 vs FIB-4 AUROC, 0.75; 

For predicting 5-year incident hepatic decompensation, Fibro-GPT achieved AUROC 0.85, with 91% sensitivity and 67% specificity. Additional cost analysis revealed Fibro-GPT’s superior accuracy resulted in a 25% reduction in unnecessary VCTEs and an 18% reduction in liver biopsies compared to FIB-4, translating into estimated annual savings of $150-200 million in the US.

Looking ahead at how Fibro-GPT may be implemented in clinical workflows, Njei emphasized that the tool does not require any new or additional testing not already being done in the clinic. As a result, he foresees it being widely utilized by a large number of clinicians.

“We are actually trying to develop what we call Fibro-GPT 2.0, and this would include using EKG data, so EKG notes, EKG wave forms, in addition to clinical laboratory tests to predict liver disease,” Njei added.

Editors’ note: Njei has no relevant disclosures.

Njei B, Njei N. Ilagan-Ying Y, et al. Fibro-GPT: A Large Language Model for Accurate Prediction of Advanced Fibrosis and Hepatic Decompensation in MASLD. Presented at the American College of Gastroenterology (ACG)’s 2025 Annual Scientific Meeting. Phoenix, Arizona. October 27-29, 2025.

Le P, Tatar M, Dasarathy S, et al. Estimated Burden of Metabolic Dysfunction–Associated Steatotic Liver Disease in US Adults, 2020 to 2050. 

Njei explains the utility of Fibro-GPT for detecting advanced fibrosis and predicting hepatic decompensation in MASLD.

Basile Njei, MD, PhD, MPH

Articles