We shall revisit the controversies the term NAFLD has faced overtime. The need for change of the name & how the name change will affect our further understanding of the disease process

1. Dr. Vivek. Goudgaon
MGE PGY2

2. Delphi: History
& framework
“NAFLD” term
evolution
NAFLD vs
MAFLD
Delphi process:
MAFLD to
MASLD

3.  Greek word (δελφύς) delphys, meaning
“womb”
 Sacred centre of ancient greeks
 3 oracles (priests/priestess) were
considered messengers of god Apollo
Temple of God Apollo

4. Chthonian Apollonian
Pythia

5.  In 1944, General Henry H. Arnold recruited
U.S. Army Air Corps
 Report on “future technological capabilities”
that might be used by the military
General Henry Arnold

6. Panellists
Facilitator Facilitator
Subject experts
Subject experts
Consensus
arrived
Subject experts

7. Term
NASH/NAFLD
by Ludwig et
al.
• 1st AASLD STC on
NAFLD: Need for
alternative name
discussed
• No consensus reached
Term MAFLD
proposed
MAFLD defined &
promoted as new
nomenclature

8. Hepatic steatosis (HS)
Histology or Imaging
No or Insignificant
alcohol intake
Exclude other
steatogenic causes
Drugs
Viral
AIH
Wilson disease
IEM
Insig alcohol: < 30g/d (M) & <20g/d(F)
AASLD PRACTICE GUIDANCE | HEPATOLOGY, VOL. 67, NO. 1, 2018

9. • Describes a disease by “what it is not” than “what it is”
• Core pathophysiology of metabolic dysfunction not depicted
Non Alcoholic
Stigmatising
Fatty
• NAFLDs with insignificant amount consumption had
independent progression of fibrosis (Korean study)
• People with risk for NAFLD with alcohol consumption more
than cutoffs set (30g/d to 60g/d)??
Alcohol consumption
thresholds

10. Conclusion:
Non heavy (especially moderate
amount) drinking was significantly &
independently associated with
worsening of non invasive markers of
fibrosis (NFS & FIB-4) compared to
non drinkers

11. NAFLD TO MAFLD: TERM & CRITERIA
REVISED (2020)
Hepatic steatosis
Histology or imaging
Obesity
(BMI>25kg/m2)
DM II
> 2 metabolic
abnormality
WC: > 94/80 cm in
M/F
BP > 130/85
mmHg
TGL > 150mg/dl
HDL-C < 40/50 in
M/F
Pre diabetes
HOMA IRS > 2.5
hs CRP > 2mg/dl
• Alcohol cutoff removed
• Criteria made for
inclusionary
• Pathophysiology addressed

12. NAFLD vs MAFLD

13. Stigmatising
Fatty
Understanding of natural history impacted
Liberal alcohol use
Mixing of etiologies
Etiology related

15. • 264 nominees from EASL,
AASLD, ALEH, APASL,
AMAGE, proportionate to
association member size
• 56 countries represented

16. Publications: 8210
NAFLD publications: >4000
Median NAFLD: 89
Citations: >1,000,000
Average h-index: >74

18. What are issues
with current
nomenclature and
can they be
addressed?
What is the
importance of
steatohepatitis in
disease definition
and endpoints?
How should the
role alcohol be
accounted for (or
not)?
How might name
change impact
disease awareness,
clinical trials and
regulatory
approval
pathways?
Can an alternate
name reduce
heterogeneity and
allow for future
advances ?

19. Round 1: April 7 – May 9, 2022
• 35 Questions/statements
• ⍨1000 comments
Round 2: June 15 – 27, 2022
• 52 Questions/statements
• 1366 comments
Round 3: Oct 17 – 27, 2022
• 42 Questions/statements
• 800 comments
✅
✅
✅
Round 4: Dec 2, 2022 – Jan 22, 2023
• 4 Questions/statements
✅
A priori threshold of consensus: Super majority (>67%)
+
Chicago Nomenclature
Consensus conference
July 8-9, 2022
(61 in person, 69 virtual)
Pan-society nomenclature meeting,
Washington DC, TLM 2022

21.  Supermajority (74%) considered current names NAFLD & NASH as
flawed terms. Favoured for name change
 Terms “Non alcoholic” & “Fatty” were considered stigmatising by 61% &
66% respectively
 A name that describes underlying pathophysiology of disease was
preferred by 89%
 Incorporating terms “metabolic disease or dysfunction” would help
patients understand their disease was agreed by 72%

22.  Overarching term (Umbrella term) which would include NAFLD, ALD
other steatogenic conditions was preferred by 78%
 Overarching terms like Fatty liver disease (FLD), steatotic liver
disease(SLD) & lipogenic liver disease (LLD) were given as options.
Instructed to rank their order as 1st , 2nd & 3rd choice
 SLD chosen by 95% (as 1st & 2nd choice combined) by respondents
 68% preferred a literal name (like SLD) over numerical subtype (type
1 & type 2)

23.  67% felt “metabolic” to be included in revised nomenclature for
NAFLD as a subtype under SLD
 Simple majority: Agreed on adding cardiometabolic risk factor
(CMRF) as a part of disease definition

24.  95% agreed to retain “steatohepatitis”. As it has prognostic
implications & should remain an important distinction
 Significant (supraminimal) alcohol dose of 30-60g/d alters the
natural history of disease (95%)
 Such group of patients with significant alcohol intake should
represent a different disease entity under the term SLD

25. Top 3 acronyms suggested for replacing NAFLD
Metabolic dysfuntion associated SLD
𝑎. 𝑀𝐴𝑆𝐿𝐷
𝑏. 𝑀𝑒𝑡𝑆𝐿𝐷
c. Metabolic steatotic liver disease: MSLD
MASLD –
30%
MetSLD –
30%
MSLD –
22%

26. 75% of external expert committee chose
 MASLD for NAFLD
 MASH for NASH
 Metabolic & alcohol related/asso liver disease
𝑀𝑒𝑡𝐴𝐿𝐷 − 28%
𝑀𝐴𝐴𝑆𝐿𝐷 − 33%
 MetALD > MAASLD: To avoid possible confusion with acronym
AASLD
 MetALD: Continuum from MASLD predominant to ALD
predominant

27. Metabolic dysfunction associated
steatotic liver disease (MASLD)
Metabolic dysfunction associated
Steatohepatitis (MASH) Metabolic dysfunction and alcohol
associated liver disease (MetALD)

28. Summarised conclusions reached at each Delphi rounds

29. Rinella M et al, Hepatology 2023, published June 23

30.  Should be inclusive rather than being exclusionary like non alcoholic
 Minimal patient heterogeneity
 Based on simple, readily available & easily measurable parameters
 Inclusion of CMRF would strengthen epidemiological & pathological
link of insulin resistance in those patients

31. Journal of Hepatology, Dec 2023. vol. 79

33. • Impact interpretation of previously published data?
• Impact on clinical trials?
• Impact on qualification of biomarkers?

34.  Add publications
Song et al. Can we use old NAFLD data under the new MASLD definition? J Hep 2023
% not
fulfilling
MASLD
% not
fulfilling
MAFLD
Community sample
(HK) NAFLD
2.3% 5.4%
Incident NAFLD 10% 24%
Biopsy proven
NAFLD
0.2% 2.2%

35. Ratziu et al. Confirmatory biomarker diagnostic studies are not needed when transitioning
from NAFLD to MASLD. J Hep 2023.
 Database from AFEF group for
study of liver fibrosis from 5
French tertiary care centers
 Data acquired for NAFLD are
valid for MASLD
 Nomenclature change will not
impact biomarker development

36. De et al. Metabolic dysfunction-associated steatotic liver disease (MASLD) definition is better than MAFLD criteria for lean
patients with non-alcoholic fatty liver disease (NAFLD). J Hep 2023
• Indian real world cohort of 1643 patients with NAFLD, 170 ‘lean’ (BMI <
23)
• 84% fulfilled MASLD definition
• 49.4% fulfilled MAFLD definition
• 16.5% lean patients not fitting into the MASLD criteria would likely be
categorized as cryptogenic SLD as per the new nomenclature