The Evolving MASH Landscape: Identifying the Hidden Metabolic-Liver Continuum

By Anvi Ta, FNP-C, CPI
Principal Investigator, Subject Matter Expert

IMA Clinical Research

Metabolic dysfunction–associated steatohepatitis (MASH) represents one of the most significant and rapidly evolving areas of therapeutic interest in clinical development.

However, a large majority of U.S. adults are not familiar with MASH as a health concern and very few people with the disease are aware they have it. Recent surveys suggests fewer than one in five U.S. adults recognize MASH as a distinct disease term. This underscores a major public health gap in education and screening.

A substantial number of patients with metabolic dysfunction including those with obesity, type 2 diabetes, dyslipidemia, and cardiovascular disease may have progressive liver involvement that has not yet been formally recognized and documented. Therefore, the population diagnosed with MASH reflects only a portion of the underlying disease burden.

For clinical research purposes, this lack of public awareness and underdiagnosis directly impacts the ability of researchers to successfully identify and attract patients into clinical trials evaluating MASH treatments. The hidden burden of MASH represents both a clinical challenge and a strategic opportunity.

For sponsors, this gap between recognized disease and actual prevalence has meaningful operational implications.

Expanding Access Beyond Traditional Referral Pathways

Historically, many MASH studies have relied heavily on hepatology referral networks, which often capture patients at more advanced stages of fibrosis. However, as awareness of the metabolic–liver connection grows, earlier identification is increasingly occurring within primary care, endocrinology, cardiometabolic, and obesity management settings.

Community research sites within broader metabolic care ecosystems are uniquely positioned to:

• Identify patients earlier in their disease course
• Access individuals who may not yet be under hepatology care
• Capture a wider spectrum of fibrosis stages
• Characterize metabolic comorbidities with greater precision

This broader access supports more representative enrollment and allows development programs to better reflect real-world disease progression.

Implications for Feasibility and Enrollment Strategy

Under-recognition of liver disease among at-risk populations can lead to conservative feasibility estimates if projections are based solely on diagnosed MASH registries. Sites with integrated metabolic prescreening processes — including proactive identification of patients with metabolic risk, obesity, diabetes, and cardiometabolic disease — often uncover a larger eligible pool than traditional referral-only models suggest.

For sponsors, this translates into:

• Improved screening yield when metabolic risk is leveraged strategically
• More accurate characterization of baseline disease burden
• Enhanced enrollment predictability
• Reduced over-reliance on advanced-stage cohorts

As therapeutic strategies increasingly address both metabolic dysfunction and liver pathology, access to patients across the full continuum of disease becomes operationally essential — not optional.

Aligning Site Capabilities with the Evolving Landscape

The clinical development landscape for MASH is shifting toward earlier intervention, combination strategies, and broader cardiometabolic positioning. Site selection must evolve accordingly.

Sponsors benefit from selecting research partners who:

• Maintain robust databases of metabolically at-risk patients
• Proactively integrate liver assessment into metabolic care workflows
• Understand the intersection of obesity, diabetes, cardiovascular risk, and fibrosis progression
• Can operationalize screening pathways efficiently without overwhelming site resources

Earlier recognition of MASH does not reduce the biological complexity of the disease — but it does fundamentally improve how patient populations are accessed, stratified, and retained within trials.

A More Representative Approach to Development

As industry understanding continues to mature, development strategies that account for the “hidden burden” of MASH will be better positioned to:

• Reflect real-world disease prevalence
• Interpret outcomes within the appropriate metabolic context
• Support broader labeling strategies
• Accelerate recruitment in competitive enrollment environments

As MASH development accelerates, site strategy will play a defining role in enrollment performance and trial execution. Sponsors who move beyond traditional referral-based models and partner with sites that proactively integrate metabolic prescreening into their workflows will be better positioned to address a broader spectrum of patients along the disease pathway and access more patients than those typically identified through referral pathways.

Now is the time to:

• Reassess feasibility assumptions based solely on diagnosed MASH registries
• Prioritize sites with obesity, diabetes, and cardiometabolic patient pools
• Align enrollment strategies with earlier disease identification trends
• Engage research partners who understand the full metabolic–liver continuum

We believe these steps will help address the clinical challenges related to hidden disease burden and offer those who adopt these methods a strategic advantage. Sponsors who intentionally align site selection with this evolving landscape will improve recruitment efficiency, enhance population representativeness, and strengthen development outcomes in an increasingly competitive environment.

We welcome collaboration with sponsors and CRO partners seeking research sites equipped to operationalize this broader identification strategy and support successful MASH program execution.

Sponsors who intentionally align site selection with this evolving landscape will improve recruitment efficiency, enhance population representativeness, and strengthen development outcomes in an increasingly competitive environment.