Revised NAFLD Nomenclature: Global Consensus for Enhanced Clarity and Precision
Summary of Medical Lecture by Mary Rinella, MD
1. Main Clinical Topics Discussed
- The rationale and process for revising the nomenclature of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH)
- Development of a new, globally accepted, non-stigmatizing disease classification system
- The role of alcohol, metabolic dysfunction, and steatohepatitis in disease definition and natural history
- Implementation of a rigorous Delphi consensus methodology across international hepatology societies
2. Key Learning Points, Guidelines, and Recommendations
Rationale for Nomenclature Change:
- The terms "fatty" and "non-alcoholic" were identified as stigmatizing and exclusionary; 66% of respondents confirmed "fatty" was stigmatizing
- A negative/exclusionary naming convention was recognized as problematic as early as the 2002 Atlanta single-topic conference
- The new nomenclature was required to: convey underlying disease drivers, be non-stigmatizing, account for alcohol's role, accommodate other etiologies of steatosis, and adapt to future disease phenotyping
New Nomenclature Adopted:
- MASLD (Metabolic dysfunction-Associated Steatotic Liver Disease) — replaces NAFLD as the overarching term
- MASH (Metabolic dysfunction-Associated SteatoHepatitis) — replaces NASH
- MetALD — a new category for patients with metabolic dysfunction who also consume alcohol beyond accepted MASLD thresholds, but below levels defining alcohol-related liver disease (ALD)
- SLD (Steatotic Liver Disease) — proposed overarching umbrella term incorporating MASLD, MetALD, ALD, and other specific etiologies
Key Definition Changes:
- Steatohepatitis (MASH) is retained as integral to disease progression and fibrosis accumulation (~95% consensus)
- Patients exceeding defined alcohol consumption thresholds are classified separately as MetALD to preserve natural history data and biomarker integrity
- Cardiometabolic risk factors are incorporated into the definition, though mandatory dual-criterion requirements from the prior MAFLD proposal were reconsidered to avoid selecting artificially high-risk cohorts
3. Specific Clinical Data, Statistics, and Study Results Cited
- 1980: Jürgen Ludwig first coined the term NASH; the landmark paper was initially rejected by multiple journals before publication in *Mayo Clinic Proceedings*
- 2002: Atlanta single-topic conference on NAFLD first raised concerns about exclusionary terminology
- 2020: Islam, Sanyal, and George published a commentary in *Gastroenterology* proposing MAFLD (Metabolic dysfunction-Associated Fatty Liver Disease), initiating the formal nomenclature debate
- Delphi Process Statistics:
- 264 nominees participated across 56 countries
- Four survey rounds conducted over approximately three years
- Rounds 1–2 generated approximately 2,400 comments each; Round 3 generated ~800 comments
- A supermajority threshold of 67% was established a priori for consensus
- ~95% consensus that steatohepatitis must be retained in the definition
- Final acronym selection (MASLD, MASH, MetALD) determined by an independent subcommittee including hepatology, endocrinology, and pediatrics representatives
4. Practical Takeaways for Clinicians
- Adopt the new terminology: Use MASLD in place of NAFLD and MASH in place of NASH in clinical documentation, patient communication, and research
- Identify MetALD patients: Patients with metabolic risk factors who consume alcohol above MASLD-defined thresholds but below ALD criteria represent a distinct, clinically important subgroup with accelerated natural history — this population warrants specific attention and is increasingly a focus of drug development
- Preserve steatohepatitis as a clinical marker: MASH (steatohepatitis) remains the key driver of fibrosis progression and adverse outcomes; do not minimize its diagnostic and prognostic significance
- Alcohol quantification matters: Carefully assess and document alcohol use in