Jeff McIntyre is the vice president of Liver Health Programs at the Global Liver Institute.

Jeff McIntyre

Looking Ahead to the Future of MASH Management

On March 14, 2024, the US Food and Drug Administration (FDA) made history when it granted accelerated approval to Madrigal Pharmaceuticals’ resmetirom (Rezdiffra), making it the first and only treatment for noncirrhotic nonalcoholic steatohepatitis (NASH), now known as 

metabolic dysfunction-associated steatohepatitis (MASH)

One year later, resmetirom’s impact on clinical practice and patient care continues to evolve. In recognition of the anniversary of the landmark decision, the latest 

 spotlights a conversation between a trio of subject matter experts reflecting on the past year of having resmetirom as a treatment option for patients, remaining unmet needs in MASH management, and the evolving therapeutic pipeline poised to further transform care.

Estimated to affect more than 30% of the global population, MASLD is the most common chronic liver disease around the world. MASH represents an advanced stage of MASLD and has historically lacked treatment options beyond lifestyle changes with diet and exercise. In the absence of pharmacologic therapies, weight loss served as the cornerstone of disease management.

This changed in March 2024, when resmetirom became the first and only FDA-approved MASH therapeutic, earning accelerated approval for the treatment of noncirrhotic MASH with moderate to advanced fibrosis. Although lifestyle interventions continue to play a pivotal role in MASH care, as the thyroid hormone receptor-beta selective agonist is indicated in conjunction with diet and exercise, they are no longer the only tools available for disease management.

 on the 1-year anniversary of resmetirom’s FDA approval and the evolving landscape of MASH management, moderator Jeff McIntyre asks Mazen Noureddin, MD, MHSc, and Juan Pablo Arab, MD, about how developments in the MASH pipeline and noninvasive testing will shape clinical practice over the next few years.

Noureddin expresses optimism, noting that resmetirom is already benefiting patients and that future combination therapies could further improve outcomes. However, he acknowledges challenges in clinical trial recruitment, particularly the reliance on liver biopsy, and expresses hope that trials can eventually be conducted without biopsy to accelerate drug approvals and expand treatment options.

Arab shared similar optimism, emphasizing the need to refine patient selection for resmetirom and explore combination therapies. He sees potential for expanding indications beyond MASH F2-F3, including MetALD and alcohol-associated liver disease, given the mechanistic overlap. With rapid advancements in the field, he underscores the importance of personalized medicine to optimize patient outcomes.



Mazen Noureddin, MD, MHSc, is a professor of medicine and a transplant hepatologist at Houston Methodist and director of the Houston Research Institute.

Juan Pablo Arab, MD, is an associate professor of medicine in the division of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University School of Medicine.

Noureddin has relevant disclosures with Altimmune, Madrigal Pharmaceuticals, Merck, Takeda, Terns, and others. Arab and McIntyre have no relevant disclosures.

US Food and Drug Administration. FDA Approves First Treatment for Patients with Liver Scarring Due to Fatty Liver Disease. March 14, 2024. Accessed March 13, 2025. 

https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-liver-scarring-due-fatty-liver-disease

Brooks, A. Stephen Harrison, MD: Promising Phase 3 Data for Resmetirom in NASH, Fibrosis. HCPLive. February 7, 2024. Accessed March 13, 2025. 

https://www.hcplive.com/view/stephen-harrison-md-promising-phase-3-data-resmetirom-nash-fibrosis

Videos

In the final segment of this 6-part HCPLive RX Review, experts discuss resmetirom’s significance and what else gives them hope for the future of MASH care.

The Role of Noninvasive Testing in MASH

 on the 1-year anniversary of resmetirom’s FDA approval and the evolving landscape of MASH management, moderator Jeff McIntyre raises the topic of noninvasive diagnostics and biomarkers, emphasizing their potential role beyond screening and diagnosis—particularly for patient monitoring. He goes on to ask panelists Mazen Noureddin, MD, MHSc, and Juan Pablo Arab, MD, about how advances in noninvasive tools are shaping patient selection, disease monitoring, and future treatment strategies.

Arab stresses that noninvasive methods are the future. While liver biopsy remains valuable, imaging techniques like transient elastography and MRI-PDFF, along with serum tests such as ELF, offer promising alternatives. He highlights the use of simple tools like FIB-4 combined with transient elastography to efficiently stratify risk in the large population affected by steatotic liver disease.

Noureddin agrees that current noninvasive tools are effective but notes the need for further refinement. Efforts are underway to streamline diagnosis, including machine learning models and advanced biomarkers to replace the current guideline-recommended two-step approach with FIB-4 and transient elastography or ELF.

He highlights research showing that noninvasive scores predict liver-related outcomes and correlate with clinical improvements—key for regulatory approval. A major next step is eliminating biopsy in clinical trials, with ongoing work to provide regulators with the necessary evidence.



Juan Pablo Arab, MD, is an associate professor of medicine in the division of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University School of Medicine

In the fifth segment of this 6-part HCPLive RX Review, experts discuss the evolving role of noninvasive testing in MASH care.

Lifestyle Interventions for MASH Management

In the fourth segment of this 6-part HCPLive RX Review, experts discuss the continued importance of diet and exercise for managing MASH.

The Future of MASH Care: New Agents in Clinical Development

 on the 1-year anniversary of resmetirom’s FDA approval and the evolving landscape of MASH management, moderator Jeff McIntyre asks Mazen Noureddin, MD, MHSc, and Juan Pablo Arab, MD, about promising investigational therapies in the pipeline and how they might compare to resmetirom.

Noureddin begins the conversation by emphasizing combination therapy rather than competition, likening MASH treatment to type 2 diabetes management—where medications can be added, adjusted, or switched over time.

Looking at the MASH pipeline, he highlights semaglutide’s 72-week data, recent phase 2 data for efruxifermin, and the potential of dual-agents like GLP-1/GIP receptor agonists. Overall, Noureddin expresses optimism that the field is on the cusp of additional significant therapeutic advancements.

Arab echoes Noureddin’s optimism and stressed the importance of combination therapy—not just within GLP-1 receptor agonists, but also pairing them with FGF21 analogs, PPAR agonists, or other therapeutic classes.



In the third segment of this 6-part HCPLive RX Review, experts discuss investigational therapies in the MASH pipeline and the use of combination therapy.

Jeff McIntyre

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