More than 30% of the global population is affected by the world's most common chronic liver disease, a condition that for decades has been fundamentally misnamed. The terminology we've used didn't describe what the disease actually is, but rather what it isn't, creating diagnostic confusion, delaying treatment, and obscuring the true pathophysiology driving liver damage in hundreds of millions of patients worldwide.
In June 2023, the global liver community made a landmark decision to correct this: nonalcoholic steatohepatitis (NASH) would be renamed metabolic dysfunction-associated steatohepatitis (MASH), and nonalcoholic fatty liver disease (NAFLD) would become metabolic dysfunction-associated steatotic liver disease (MASLD). This represented a fundamental shift in how we understand and diagnose metabolic liver disease—moving from exclusionary terminology to affirmative, accurate nomenclature that reflects the disease's true nature.
For the clinical research community, this change has significant implications. It affects how we design trials, select patients, develop endpoints, and ultimately bring new therapies to the millions of people affected by this progressive liver condition. Understanding the scientific rationale behind this evolution is essential for anyone involved in metabolic liver disease research.
The term "nonalcoholic fatty liver disease" was coined decades ago when researchers had a limited understanding of the disease's underlying mechanisms. It was a diagnosis of exclusion—defined by what it wasn't rather than what it was.
This created several critical problems. The exclusionary terminology required ruling out all other potential causes before making a diagnosis, creating unnecessary diagnostic complexity and delays. Clinicians struggled with a definition that didn't describe the actual pathophysiology driving liver damage, leading to widespread diagnostic confusion. The terminology failed to capture the true metabolic drivers of the disease, despite growing evidence that metabolic dysfunction was the primary culprit, an incomplete representation of the pathophysiology that left both clinicians and researchers working with an inadequate conceptual framework.
Perhaps most troubling was the stigmatizing language embedded in the term "nonalcoholic." For many patients, the emphasis on alcohol, even in the negative, carried stigma and shame, particularly given that the disease had nothing to do with alcohol consumption. This discouraged open conversations between patients and providers and sometimes delayed diagnosis and treatment, creating barriers to care rooted in nomenclature rather than clinical reality.
As research advanced, the gap between terminology and clinical reality widened dramatically. The connection to metabolic syndrome became undeniable: a majority of diabetes patients showed liver involvement, and the disease clearly stemmed from metabolic dysfunction rather than any other cause.
This created particularly challenging situations for clinicians encountering patients with both metabolic dysfunction and moderate alcohol consumption. Under the old nomenclature, these patients fell into diagnostic limbo. Their metabolic liver disease went unrecognized because they didn't meet the strict alcohol exclusion criteria, leaving them without appropriate diagnosis or treatment pathways despite clear evidence of liver pathology.
Meanwhile, global prevalence reached epidemic proportions, affecting more than 30% of the global population. Despite this health burden, the terminology still didn't reflect what was actually causing liver damage in these individuals. The disconnect between what clinicians observed and what they could formally diagnose had become untenable, making it clear the liver disease community needed nomenclature that more accurately described the disease's true nature.
MASH is an affirmative, descriptive term that identifies the disease by its actual cause: metabolic dysfunction. Rather than listing what the disease isn't, MASH clearly states what it is—liver inflammation driven by metabolic factors.
The parent category, metabolic dysfunction-associated steatotic liver disease (MASLD), requires hepatic steatosis (fat accumulation in the liver) plus at least one of five cardiometabolic risk factors:
This definition achieves what the old nomenclature could not: it identifies patients based on the pathophysiological mechanisms actually causing their liver disease. MASH specifically refers to cases where metabolic dysfunction has progressed to cause liver inflammation and potential fibrosis—the more severe, progressive form of the disease.
The new nomenclature creates significant opportunities to improve clinical trial design and execution:
The nomenclature change has already demonstrated real-world impact across multiple fronts. FDA recognition came quickly, with resmetirom (Rezdiffra) receiving approval in March 2024 as the first drug specifically for MASH with moderate to advanced fibrosis. While the FDA approval documents still referenced "NASH," the agency has acknowledged and is transitioning to the new terminology, signaling regulatory acceptance of this evolution.
The clearer diagnostic criteria have also begun to improve insurance coverage decisions. When diagnosis is based on identification of metabolic risk factors rather than exclusion of numerous other conditions, payers can more readily assess medical necessity and approve coverage. This streamlined approach reduces administrative burden and potentially accelerates patient access to appropriate care.
Perhaps most importantly, healthcare provider clarity has improved as the terminology now accurately describes what's happening in the patient's body. This makes patient education easier and reduces the confusion that often surrounds explanations of "nonalcoholic" disease to patients. Providers can speak directly about metabolic dysfunction and its role in liver inflammation, creating more transparent and productive conversations about disease management and lifestyle interventions.
For clinical research technology platforms, the nomenclature change necessitates thoughtful adaptation:
The nomenclature change points toward several technological opportunities:
The new nomenclature creates a foundation for precision medicine approaches that were difficult to conceptualize under the old framework. Better phenotyping of metabolic dysfunction enables personalized treatment strategies. As we identify subgroups within MASH based on specific metabolic derangements such as insulin resistance versus dyslipidemia versus obesity, for example, targeted therapies tailored to these distinct pathophysiological profiles may emerge.
This precision understanding also points toward combination therapies addressing multiple metabolic dysfunction pathways simultaneously. Just as cardiovascular disease often requires multiple medications targeting different mechanisms, MASH treatment may move toward rational combinations that address the multifaceted nature of metabolic dysfunction more comprehensively than single agents can achieve.
The clearer understanding of metabolic drivers also enables prevention strategies focusing on metabolic health from early stages, potentially reducing progression from MASLD to MASH. Early intervention in patients with metabolic risk factors but minimal liver involvement may prevent advanced disease, shifting the paradigm from late-stage treatment to early-stage prevention.
Finally, unified nomenclature facilitates international research collaboration, amplifying the global health impact. When researchers worldwide use consistent terminology and diagnostic criteria, data pooling and meta-analyses become more reliable, accelerating knowledge generation and ensuring that insights from trials conducted in different regions can be meaningfully integrated to advance the field.
The change from NASH to MASH isn't merely semantic—it's a meaningful evolution in how we conceptualize, diagnose, and research metabolic liver disease. By embracing this change, the clinical research community can accelerate therapeutic development and ultimately improve outcomes for the millions of people affected by this increasingly common condition.
For more information on how Signant Health supports MASH clinical trials through eCOA solutions, patient engagement tools, and metabolic monitoring capabilities, visit our MASH solutions page.
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