MASLD vs MAFLD vs NASH/MASH: Nomenclature & Criteria Guide
NAFLD to MASLD, NASH to MASH under 2023 Delphi with cardiometabolic criteria. MAFLD (2020 Eslam) stays separate. 4 frameworks and MetALD compared.
Introduction: The Naming Problem in the MASH Era
Think NASH just got renamed MASH? The 2023 Delphi consensus1 did far more than rebrand — it redefined the diagnostic criteria. The legacy NAFLD (nonalcoholic fatty liver disease) used an exclusion-based ("not alcohol, not X") definition, whereas MASLD requires at least one positive cardiometabolic criterion.
Adding to the complexity, Eslam et al. proposed MAFLD in 20202 — a separate framework with different endorsing societies, definitions, and intended use from MASLD. Drug developers must track precisely which label defines which population across the literature, trial protocols, regulatory submissions, and preclinical model selection.
This article systematically compares NAFLD / MAFLD / MASLD (MASH) / MetALD — the four frameworks — focusing on cardiometabolic criteria and alcohol thresholds. Non-invasive diagnostic biomarkers are covered in the MASLD/MASH biomarker comprehensive guide; this article stays within the classification domain.
1. Why the Nomenclature Overhaul Was Needed
1.1 Three Motivations for Renaming
The 2023 Delphi consensus1 was a multisociety process (AASLD / EASL / ALEH and others) involving 236 experts from 56 countries across four online survey rounds plus two hybrid in-person meetings. Three motivations drove the change:
- Eliminating stigma: "Fatty" and "alcoholic" carried moral connotations that reduced screening uptake and treatment adherence. The neutral medical term "steatotic" replaces them.
- Pathophysiologic precision: NAFLD was an ambiguous umbrella — "anything not alcoholic." The new term centers metabolic dysfunction (obesity, diabetes, dyslipidemia, hypertension) and distinguishes it from drug-induced or viral etiologies.
- Trial endpoint and regulatory alignment: With Resmetirom's FDA accelerated approval (March 2024, Rezdiffra) and accelerating MASH drug pipelines, regulators (FDA/EMA), sponsors, and trial sites needed uniform patient definitions. See MASH combination therapy and M&A 2026 for why industry alignment mattered.
1.2 Timeline
| Year | Event | Impact |
|---|---|---|
| 1980 | Ludwig et al. coin "nonalcoholic steatohepatitis (NASH)"5 | NASH concept established |
| 1986 | NAFLD becomes the umbrella term | Exclusion-based definition |
| 2020-03 | Eslam et al. propose MAFLD2 | Pioneering positive criteria (hepatic steatosis + metabolic dysfunction) |
| 2023-06 | Delphi consensus: NAFLD→MASLD / NASH→MASH1 | Requires ≥1 cardiometabolic criterion |
| 2023-05 | AASLD Practice Guidance (Hepatology)3 | Last major guidance under the NAFLD label (pre-Delphi) |
| 2024-03 | FDA grants accelerated approval to Resmetirom labeled "MASH" (Rezdiffra) | Regulatory documents shift to the new label |
| 2024-06 | EASL-EASD-EASO 2024 MASLD CPG (J Hepatol)4 | First European guideline consolidating MASLD and including MetALD |
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2. NAFLD / NASH (legacy 1980–2023)
2.1 NAFLD as Exclusion Diagnosis
- Hepatic steatosis ≥5% (imaging or histology) as the core requirement
- Exclusions: significant alcohol (male >30 g/day, female >20 g/day), viral hepatitis, autoimmune hepatitis, drug-induced liver injury, inherited metabolic disease (e.g., Wilson)
- NASH: NAFLD with steatohepatitis (steatosis + lobular inflammation + hepatocellular injury/ballooning); NAS ≥4 or Kleiner/Brunt-based diagnosis
2.2 Operational Limitations
- Fragile "non-" definition: The alcohol threshold (30/20 g/day) was never globally standardized and varied across studies
- Metabolic dysfunction was implicit: Although most NAFLD patients had obesity/diabetes, the definition only required "not alcoholic"
- Edge cases: Light drinkers or lean dyslipidemic patients were poorly classified
2.3 Mapping Legacy Literature
Legacy preclinical NASH models (AMLN vs GAN diet, CDAHFD, MCD, etc.) map directly onto MASH in most cases. The phenotype (steatosis + inflammation + fibrosis) is unchanged, so biological validity persists under the new label. For clinical citations, distinguish pre-June 2023 = NASH / post-June 2023 = MASH and use a bracketed note (e.g., "[MASH (formerly NASH)]") at first mention.
3. MAFLD (2020 Eslam Consensus)
3.1 Positive Criteria Design
MAFLD = Metabolic dysfunction-Associated Fatty Liver Disease2. Defined as hepatic steatosis plus at least one of:
- Obesity (BMI ≥25 kg/m² in non-Asians, ≥23 in Asians, or visceral obesity)
- Type 2 diabetes
- Evidence of metabolic dysfunction (≥2 of 7 items):
- Waist circumference ≥102 cm (M) / ≥88 cm (F)
- BP ≥130/85 mmHg or antihypertensive treatment
- TG ≥150 mg/dL or treatment
- HDL-C <40 mg/dL (M) / <50 mg/dL (F) or treatment
- Pre-diabetes (HbA1c 5.7–6.4%, IFG, or IGT)
- HOMA-IR ≥2.5
- hs-CRP >2 mg/L
3.2 Decisive Differences from NAFLD
- Alcohol co-existence permitted: MAFLD sets no alcohol threshold — MAFLD + HCV or + ALD dual diagnosis is explicitly allowed. This was Eslam's central argument.
- Dual etiology embraced: Overlap diagnoses such as "MAFLD + alcohol-related liver disease" are intentionally supported.
3.3 Adoption and Controversy
- Endorsed: Asia Pacific Association for the Study of the Liver (APASL), parts of Latin America
- Not adopted: AASLD / EASL (favored MASLD via the Delphi process)
- Controversy: Some argue MAFLD's alcohol tolerance "creates confusion" and "breaks trial enrollment"; others praise it as "reflecting real-world patients."
Impact on drug development: MAFLD as an inclusion criterion in Phase 2/3 trials is rare. Virtually all current trials use MASLD/MASH. When citing MAFLD-labeled publications, note that "MASLD and MAFLD are not fully equivalent."
4. MASLD / MASH (2023 Delphi Consensus)
4.1 MASLD Diagnostic Criteria
MASLD = Metabolic dysfunction-Associated Steatotic Liver Disease
All of the following1:
- Hepatic steatosis ≥5% (imaging / histology / serum marker combination)
- ≥1 of 5 cardiometabolic criteria (below)
- Absence of another predominant etiology (significant alcohol, drugs, monogenic disease, etc.)
4.2 Cardiometabolic Criteria (Adult Version, 5 Items)
| # | Item | Threshold |
|---|---|---|
| 1 | BMI / Waist circumference | BMI ≥25 kg/m² (≥23 for Asians) or WC M >94 cm / F >80 cm (Asian: M >90, F >80) |
| 2 | Fasting glucose / HbA1c / T2DM | FPG ≥100 mg/dL, 2-h OGTT ≥140 mg/dL, HbA1c ≥5.7%, T2DM diagnosis, or treatment |
| 3 | Blood pressure | ≥130/85 mmHg or antihypertensive therapy |
| 4 | Triglycerides | ≥150 mg/dL or lipid-lowering therapy |
| 5 | HDL-C | M ≤40 mg/dL / F ≤50 mg/dL or lipid-lowering therapy |
Pediatric criteria use different thresholds1.
4.3 MASH (Metabolic dysfunction-Associated Steatohepatitis)
- MASLD criteria met plus steatohepatitis (steatosis + lobular inflammation + ballooning)
- Histologic criteria are identical to legacy NASH. NAS, SAF, and Kleiner/Brunt scoring systems carry over unchanged
- Fibrosis staging continues to use Kleiner/Brunt (F0–F4) — see METAVIR vs Ishak fibrosis staging for scoring system comparisons
4.4 Practical Differences from Legacy NAFLD
Almost all legacy NAFLD cases (>99% by Delphi estimates) map to MASLD1. Exceptions:
- Metabolically healthy NAFLD ("lean NAFLD without metabolic risk") with all 5 cardiometabolic criteria negative → not MASLD; classified as "cryptogenic steatotic liver disease"
- Specific-etiology fatty liver (monogenic disease, drug-induced, etc.) → specific aetiology SLD as a separate category
5. MetALD: MASLD + Moderate Alcohol
5.1 Why the New Category
MASLD-eligible patients who drink moderate to significant amounts of alcohol are clinically common. The legacy "NAFLD vs ALD" binary excluded them. The Delphi consensus created a third category — MetALD1.
5.2 Alcohol Thresholds (2023 Delphi)
| Category | Male | Female |
|---|---|---|
| MASLD | <210 g/week (<30 g/day) | <140 g/week (<20 g/day) |
| MetALD | 210–420 g/week (30–60 g/day) | 140–350 g/week (20–50 g/day) |
| ALD predominant | >420 g/week (>60 g/day) | >350 g/week (>50 g/day) |
Pure ethanol basis (1 standard drink ≈ 10–14 g).
5.3 Boundary with ALD
Above the MetALD ceiling (male 420 / female 350 g/week), cases are classified as ALD predominant, though coexisting cardiometabolic criteria allow a dual-label "ALD with metabolic dysfunction." For preclinical work, see ALD vs MASLD models — the choice affects target mechanism studies (metabolic pathways vs alcohol metabolism).
5.4 Divergence from DSM-5 and WHO Drinking Criteria
Delphi thresholds are hepatology-evidence based and do not directly map to DSM-5 AUD or WHO hazardous drinking definitions. Trial protocols evaluating alcohol history must specify protocol-specific thresholds clearly.
6. Four-Framework Quick Reference
| Axis | NAFLD/NASH (1980–2023) | MAFLD (2020 Eslam) | MASLD/MASH (2023 Delphi) | MetALD (2023 Delphi) |
|---|---|---|---|---|
| Definition style | Exclusion-based | Positive criteria | Positive criteria (cardiometabolic ≥1) | MASLD + moderate alcohol |
| Hepatic steatosis threshold | ≥5% | ≥5% | ≥5% | ≥5% |
| Metabolic requirement | Implicit (none required) | Obesity/DM/metabolic dysfunction (any) | ≥1 of 5 cardiometabolic criteria | ≥1 of 5 cardiometabolic criteria |
| Alcohol tolerance | None (M ≤30/F ≤20 g/day) | Unrestricted (coexistence OK) | M <30 / F <20 g/day | M 30–60 / F 20–50 g/day |
| Exclusion required | Mandatory | Not required | Limited (monogenic, drug-induced) | Limited |
| Endorsing societies | AASLD (through 2023), EASL (through 2023) | APASL, part of Latin America | AASLD, EASL, ALEH, and others | AASLD, EASL, ALEH |
| Trial adoption | Legacy trials (majority) | Limited | Current standard (Resmetirom onward) | Emerging, adopted in new trials |
| FDA/EMA use | Legacy guidance | Not adopted | Current standard | Appearing in regulatory documents |
7. Impact on Drug Development, Clinical Trials, and Regulation
7.1 Resmetirom Approval as the Watershed
The FDA accelerated approval of Resmetirom (MAESTRO-NASH trial) on March 14, 2024 started enrollment in 2019 under the "NASH" label, but the approval documentation used "MASH"1. New Phase 3 trials have uniformly adopted MASH terminology since.
7.2 Bridging Ongoing Phase 3 Trials
- Lanifibranor (Pan-PPAR) NATiV3 trial
- Efruxifermin (FGF21 analog) HARMONY/SYMMETRY trials
- Survodutide (GLP-1/GCG dual agonist) MASH trial
Most of these switched terminology mid-trial (NASH → MASH) in reporting and publications without changing the underlying protocol definitions. Datasets transfer directly.
7.3 Preclinical Model Label Mapping
| Model | Legacy label | Current label | Notes |
|---|---|---|---|
| STAM™ mouse | NASH model | MASH model | Histology unchanged |
| AMLN / GAN diet | NASH-inducing diet | MASH-inducing diet | Induces metabolic dysfunction + steatosis + inflammation + fibrosis |
| CDAHFD | NASH model (limited) | MASH-like model | Lacks metabolic dysfunction — not a full MASLD surrogate |
| MCD diet | NASH model (traditional) | Steatohepatitis model (limited MASH surrogate) | Weight loss masks metabolic features |
7.4 Continuity of Biomarker Frameworks
Evaluation indices (ECM turnover biomarkers like PRO-C3, FIB-4, ELF, MRI-PDFF, VCTE — see MASLD/MASH biomarker comprehensive guide) transfer from the NAFLD era without cutoff revision.
8. Literature Search and Database Practical Tips
8.1 PubMed
- Scan both old and new terms: Use OR-union: "MASLD OR NAFLD OR MAFLD"
- MeSH hierarchy: MASLD is being incorporated into the MeSH tree as a sub-term of NAFLD, with usage as a search keyword expanding. Legacy papers remain reachable via the NAFLD MeSH heading (verify current indexing status in PubMed/MeSH DB as needed)
- Year filtering: Papers from June 2023 onward predominantly use MASLD/MASH; earlier ones use NAFLD/NASH
8.2 ClinicalTrials.gov
- Trial name history: Names often differ between registration and current record. Check "Study Record History"
- Condition field: "MASH," "MASLD," "NAFLD," "NASH" are currently mixed as tags. Search each label and deduplicate
8.3 Internal Reviews and Protocol Drafting
- First-mention parenthetical: Use "MASH (formerly NASH)" once; abbreviate thereafter
- Handling MAFLD-labeled papers: Cite as "MAFLD" per the source and footnote "not fully equivalent to MASLD"
- Prohibited: Do not mix labels within a single document. Pick one nomenclature per protocol
Summary
- 2023 Delphi consensus renamed NAFLD→MASLD and NASH→MASH and shifted from exclusion-based to cardiometabolic positive-criteria diagnosis
- MAFLD (2020 Eslam) is a separate framework. APASL adopted it; AASLD and EASL went with MASLD
- MetALD is a new category: MASLD plus moderate alcohol (M 210–420, F 140–350 g/week)
-
99% of legacy NAFLD cases translate directly to MASLD. Exceptions: cryptogenic SLD and specific-aetiology SLD
- Legacy NASH preclinical data and biomarker frameworks carry over to MASH unchanged. Update only the label in protocols and publications
Related Articles
- MASLD/MASH Biomarker Comprehensive Guide — Details on non-invasive tests (NITs)
- Liver Antifibrotic Landscape 2026 — Global MASH therapeutic overview
- MASH Combination Therapy and M&A 2026 — Combination strategies and acquisition plays
- Resmetirom: First Approved MASH Drug — THR-β agonist clinical development
- METAVIR vs Ishak: F1–F4 Liver Fibrosis Staging — Biopsy score selection
- AMLN vs GAN Diet: MASH Model Comparison — Preclinical model selection
- ALD vs MASLD Models — Mechanistic differences from alcoholic liver disease
References
1. Rinella ME, Lazarus JV, Ratziu V, et al. "A multisociety Delphi consensus statement on new fatty liver disease nomenclature." Hepatology. 2023;78(6):1966-1986. (PubMed PMID: 37363821)
2. Eslam M, Newsome PN, Sarin SK, et al. "A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement." Gastroenterology. 2020;158(7):1999-2014.e1. (PubMed PMID: 32044314)
3. Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. "AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease." Hepatology. 2023;77(5):1797-1835. (PubMed PMID: 36727674)
4. European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO). "EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD)." Journal of Hepatology. 2024;81(3):492-542. (PubMed PMID: 38851997)
5. Ludwig J, Viggiano TR, McGill DB, Oh BJ. "Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease." Mayo Clinic Proceedings. 1980;55(7):434-438. (PubMed PMID: 7382552)