Post on 25-Jan-2021
The Comprehensive Global Burden and
Impact of NASH
Zobair M Younossi MD, MPH,
FACP, FACG, FAASLD, AGAF Chairman and Professor of Medicine
Inova Fairfax Medical Campus, Falls Church, VA
United Sates
Faculty Disclosure:
• Research Funds and/or Consultant to:
Allergan, Bristol-Myers Squibb, Echosens,
Gilead Sciences, Intercept, Merck, Novartis,
Novo Nordisk, Quest Diagnostics, Siemens,
Shionogi, Terns and Viking.
The Comprehensive Burden of NASH
Burden
CLINICAL
PRO
ECONOMIC
• Prevalence and incidence
• Liver outcomes or surrogates of mortality
• CVD and other EHM
• Life-expectancy, expected years of life lost,
• Symptoms
• HRQOL (Physical, Mental and Social health)
• Cost of illness
• Budgetary costs
• Indirect and intangible costs
• Resource utilization
• Cost-effectiveness
• Survival
• Patient experience
• Feel
• Resource utilization
• Value
Outcomes Surrogate Endpoints
• Function and WP FUNCTIONAL
• Functional status (disability)
• Absenteeism (WP)
• Presenteeism (WP)
• Days of work missed
• Ability to manage ADL
NASH
1. Younossi ZM, et al. Hepatology. 2016;64(5):1577-1586; 2. Younossi ZM. Clin Gastroenterol Hepatol. 2017;15(8):1144-1147;
3. Younossi Z. Hepatology. 2018 Aug 2.
Cirrhotic
F4 fibrosis
Early
F1 fibrosis
• Pure steatosis
• Steatosis and mild
lobular inflammation
NAFL HCC
Fibrotic
F2 fibrosis
Fibrotic
F3 fibrosis
NASH
• Steatosis in >5% of hepatocytes
• NASH requires specific pathologic criteria
• Exclusion of secondary causes and AFLD
• Risk factors are components of metabolic syndrome
Lets Get the Terminology Correct: What Is NASH and NAFLD?
1. Younossi ZM. Hepatology. 2018;68(1):349-360; 2. Chalasani N, et al. Hepatology. 2018;67(1):328-35;
3. Younossi ZM, et al. Hepatology. 2011;53(4):1874-1882; 4. Younossi ZM, et al. Hepatol Commun. 2017;1(5):421-428;
5. Anstee QM, et al. Gastroenterology. 2016;150(8):1728-1744; 6. EASL–EASD–EASO CPG NAFLD. J Hepatol. 2016;64:1388–402.
North America
24.1%
Europe
23.7%
Asia
27.4%
Middle
East
31.8%
South
America
30.5%
Africa
13.5%
In T2DM
56.8%
In T2DM
68.0%
In T2DM
30.4%
In T2DM (US)
51.8% In T2DM
67.3%
In T2DM
52.0–57.9%
Worldwide prevalence of
NAFLD is 25%
Worldwide prevalence of
NAFLD among people
with T2DM is 55.5%
Prevalence of NASH in general population is between 1.5–6.5%
Prevalence of NASH among T2DM is 37.3% (24.7-50.0%)
The Global Prevalence of NAFLD and NASH
Younossi ZM, et al. Hepatology. 2016;64:73–84; Argo CK and Caldwell SH. Clin Liver Dis. 2009;13:511–531; Younossi ZM. J Hepatol. 2019;70:531–544.
6.5%
5.9%
6.8%
5.7%
~25%
10%
Worldwide prevalence of NAFLD
among Children is about 7-10%
• Prevalence is higher in boy and increases with higher BMI
• U.S. studies have revealed a 4-fold higher risk of hepatic steatosis in Hispanic, compared to non-Hispanic
• The prevalence of NAFLD in the US increased 2.7 fold from the late 1980’s to 2010
The Global Prevalence of NAFLD and NASH
Anderson EL, et al. PLOS ONE. 10(10): e0140908. 2015; Schwimmer JB, et al. Pediatrics. 2006;118(4):1388-1393;
Vos M, et al. J Pediatr Gastroenterol Nutr. 2017 February; 64(2): 319–334.
0
5
10
15
20
25
30
35
UK Germany France Spain N Italy Russia Hungrey Romania
Prevalence of NAFLD in Europe: 20-30% Prevalence of NAFLD in Asia: 29·62%
48.3%
30.0% 33.9%
25.7% 25.0%
33.0%
20.0%
8.7%
0%5%
10%15%20%25%30%35%40%45%50%
Turkey Israel Iran SaudiArabia
UAE Kuwait Sudan Nigeria
NA
FL
D %
Prevalence of NAFLD in Latin America
Prevalence of NAFLD in the Middle East and Africa
Prevalence of NAFLD and NASH in Different Regions of the World
Younossi Z, et al. Hepatology. 69(6):2672-2682. 2019; Tsukanov V, et al. AGA. 2011. (Abstract Mo2025);
Younossi Z, et al. Hepatology. 64(5):1577-1586. 2016; López-Velázquez JA. Ann Hepatol. 2014;13(2):166-78;
Zelber-Sagi S, et al. Liver Int. 2006;26:856–863; Moghaddasifar I, et al. Int J Organ Transplant Med. 2016;7:149;
Alswat K, et al. Saudi J Gastroenterol. 2018;24:211, Ahmed M, et al. Gastroenterol Res. 2017;10(5):271-279.
The Comprehensive Global Burden and Impact of NASH
Although the Prevalence Rates for NASH
and NAFLD are Large and Growing, Which
Patient Groups and Patient Profiles Indicate
Potential Progression?
F1 F2 F3 F4
Normal NASH with fibrosis NASH with
advanced fibrosis
Cirrhotic HCC
0.592% per year
2.3% per year
Non-cirrhotic HCC
Fibrolysis Fibrogenesis
The most common cause of death
Time
Non-linear Progression
NASH
(7-30%)
Non-NASH
70-93%
Clinical Outcomes: Natural History of NAFLD and NASH
HCC, hepatocellular carcinoma.
Younossi ZM, et al. Hepatology. 2018;68:349–360; Younossi ZM, et al. Hepatology. 2018;68:361–371;
Younossi ZM. J Hepatol. 2019;70:e17–e32; Jie Li, et al. Lancet Gastroenterol Hepatol. May 2019.
N=(3,613)
0.30 0.64
4.28 7.92
23.30
0
5
10
15
20
25
0 1 2 3 4
Mort
ality
Rate
(per
1,0
0 P
YF
)
Fibrosis Stage
NASH Denotes Progressive
Disease
Components of MS
Predicts Mortality-NHANES III
Stage of Fibrosis Predicts
Mortality HCC and NAFLD- SEER
2004−2009
Growing LT Due to
NASH in the US LT Due to NASH-related HCC
Biopsy-proven NAFLD (N=289)
0%
50%
100%
150%
200%
1988-1994 1999-2004 2005-2008 2009-2012 2013-2016re
lative
to
19
88
-19
94
ALD CHB CHC NAFLD
Changes in CLD NHANES 1988-1994 and 1999-2016
Changes in CLD Mortality National Center for Health Statistics Mortality data
28,132,187 reported deaths with 700,402 LD-related deaths
Cox p
roport
ional
hazard
model
12 months of follow-up after HCC diagnosis
1.0
0.9
0.8
0.6
0.7
0.5
0 2 8 10 12
0.4
6 4
HBV
HCV
NAFLD
N=58,731
Clinical Outcomes: Natural History of NAFLD and NASH
Stepanova M, et al. Dig Dis Sci. 2013;58(10):3017-3023; Golabi P, Younossi Z, et al. Medicine. 2018;97(13):e0214; Dulai PS, et al. Hepatology. 2017;
Younossi ZM, et al. Hepatology. 2011; Younossi ZM, et al. Hepatology. 015;62(6):1723-1730; Goldberg D, et al. Gastroenterology. 2017;152(5):1090-1099;
Younossi ZM, et al. Clin Gastroenterol Hepatol. 2018; Younossi Z, et al. Clin Gastro and Hep. 20111-587; Younossi Z. ADA. 2019; Paik J, Younossi ZM. DDW. 2019.
Trends in Incidence Rates (2012-2017) Trends in Mortality Rates (2012-2017)
Liver Cancer Cirrhosis Liver Cancer Cirrhosis
Paike J and Younossi Z. 2019.
Global Outcomes: Global Burden of Disease (2012-2017)
Changes in Age-Standardized Incidence and Death Rates for Cirrhosis and
Liver Cancer According to Etiology of Liver Disease
Models Suggest a Growing Clinical Burden Driven by Advanced NASH
Cases of stage 3 fibrosis due
to NASH1
Cases of stage 4 fibrosis due to NASH1
4.5 M
3.1 M 1.3 M
2 M
20% of NAFLD
is NASH1 27% NAFLD will
be NASH1
2015 2030 Incident decompensated cirrhosis, HCC and
liver-related deaths2
120,000
100,000
80,000
60,000
40,000
20,000
0
2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Inc
ide
nt
ca
se
s/d
ea
ths
Incident-decompensated
cirrhosis
+168%
+178%
Incident liver-related deaths
+137%
Incident HCC By 2030, there are projected to be nearly
800,000 excess liver deaths
HCC, hepatocellular carcinoma; M, million; T2DM, type 2 diabetes mellitus.
Estes C, et al. Hepatology. 2018;67:123–133; Razavi H. Disease burden of non alcoholic fatty liver disease (NAFLD). Center for Disease Analysis. 2017.
http://www.elpa.eu/sites/default/files/documents/NAFLD%20Disease%20Burden%20by%20Dr.%20H.%20Razavi_NASH%20NAFLD%20Summit.pdf.
Accessed February 2019.
http://www.elpa.eu/sites/default/files/documents/NAFLD Disease Burden by Dr. H. Razavi_NASH NAFLD Summit.pdfhttp://www.elpa.eu/sites/default/files/documents/NAFLD Disease Burden by Dr. H. Razavi_NASH NAFLD Summit.pdf
21.6% 22.9%
25.4%
22.9% 21.9%
17.6% 17.9%
23.6%
26.4%
29.5%
27.6%
24.7%
22.2%
18.8%
0.0%
5.0%
10.0%
15.0%
20.0%
25.0%
30.0%
35.0%
FRANCE GERMANY ITALY SPAIN UK CHINA JAPAN
Pre
va
len
ce
3.6%
4.1%
4.4%
3.9%
4.1%
2.4%
3.0%
5.0%
6.0%
6.3%
5.9%
5.5%
3.4% 3.6%
0.0%
1.0%
2.0%
3.0%
4.0%
5.0%
6.0%
7.0%
FRANCE GERMANY ITALY SPAIN UK CHINA JAPAN
2016 2030
Pre
va
len
ce
NAFLD NASH
Estes C, et al. Hepatology. 2018;67:123–133; Razavi H. Disease burden of non alcoholic fatty liver disease (NAFLD). Center for Disease Analysis. 2017.
http://www.elpa.eu/sites/default/files/documents/NAFLD%20Disease%20Burden%20by%20Dr.%20H.%20Razavi_NASH%20NAFLD%20Summit.pdf.
Accessed February 2019.
Models to Predict Future Burden of NASH and Adverse Outcome in Europe and Asia
http://www.elpa.eu/sites/default/files/documents/NAFLD Disease Burden by Dr. H. Razavi_NASH NAFLD Summit.pdfhttp://www.elpa.eu/sites/default/files/documents/NAFLD Disease Burden by Dr. H. Razavi_NASH NAFLD Summit.pdf
Incident decompensated cirrhosis, HCC, liver-related deaths among prevalent NAFLD population1 Prevalent NASH cases by
disease stage in the UAE and
Saudi Arabia2
60
40
20
80
0
2015
2016
2017
2018
2019
2020
2021
2022
2023
2024
2025
2026
2027
2028
2029
2030
China, 2015-2030
Incid
en
t cases/d
eath
s
X 1
03
10
8
6
4
2
0
2015
2016
2017
2018
2019
2020
2021
2022
2023
2024
2025
2026
2027
2028
2029
2030
France, 2015-2030
18
14
12
10
8
6
4
2
0
16
2015
2016
2017
2018
2019
2020
2021
2022
2023
2024
2025
2026
2027
2028
2029
2030
Germany, 2015-2030 Italy, 2015-2030
16
2015
2016
2017
2018
2019
2020
2021
2022
2023
2024
2025
2026
2027
2028
2029
2030
14
12
10
8
6
4
2
0
Incid
en
t cases/d
eath
s
X 1
03
10
12
0
2015
2016
2017
2018
2019
2020
2021
2022
2023
2024
2025
2026
2027
2028
2029
2030
2
4
6
8
Japan, 2015-2030
0
2015
2016
2017
2018
2019
2020
2021
2022
2023
2024
2025
2026
2027
2028
2029
2030
2
4
6
8
10
12
Spain, 2015-2030
0
2015
2016
2017
2018
2019
2020
2021
2022
2023
2024
2025
2026
2027
2028
2029
2030
2
4
6
8
10
12
UK, 2015-2030
14
16
US, 2015-2030
Prevalent NASH cases by disease stage –
UAE, 2015-2030
35
30
25
20
15
10
– Pre
vale
nt
NA
SH
cases (
Th
ou
san
ds
)
5
F0 F1 F2 F3 Cirrhosis, HCC and
Liver Transplant
0
2015
2016
2017
2018
2019
2020
2021
2022
2023
2024
2025
2026
2027
2028
2029
2030
20
40
60
80
100
120
Incident decompensated cirrhosis Incident HCC Incident liver related deaths
2015
2016
2017
2018
2019
2020
2021
2022
2023
2024
2025
2026
2027
2028
2029
2030
0
200
400
600
800
1000
1200
F0 F1 F2 F3 Cirrhosis, HCC and
Liver Transplant
Pre
vale
nt
NA
SH
cases (
Th
ou
san
ds
)
Prevalent NASH cases by disease stage –
Saudi Arabia, 2015-2030
2015
2016
2017
2018
2019
2020
2021
2022
2023
2024
2025
2026
2027
2028
2029
2030
Models to Predict Future Burden of NASH and Adverse Outcome in Europe and Asia
1. Estes C, et al. J Hepatol. 2018;69:896–904; 2. Alswat K, et al. Saudi J Gastroenterol. 2018;24:211–219.
0
5
10
15
20
25
30
35
40
Although Most NAFLD Patients Are Obese, There Are Some Patients with Lean NAFLD
Pre
vale
nce (
%)
USA
YOUNOSSI Z
2012
TURKEY
AKYUZ U
2015
KOREA
CHO HC
2016
KOREA
SINN DH
2012
KOREA
KIM HJ
2004
INDIA
DAS K
2010
CHINA
FAN J
2005
HK
WEI JL
2015
JAPAN
NISHIOJI K
2015
JAPAN
EGUCHI Y
2012
UAE, United Arab Emirates. Wong MCS, et al. Nat Rev Gastroenterol Hepatol. 2018; 1. Lopez-Velazquez JA, et al. Ann Hepatol. 2014;13:166–178;
Zelber-Sagi S, et al. Liver Int. 2006;26:856–863; Moghaddasifar I, et al. Int J Organ Transplant Med. 2016;7:149;
Alswat K, et al. Saudi J Gastroenterol. 2018;24:211.
Long-Term Outcomes of Lean NAFLD
• Lean (BMI ≤ 25) adult participants of NHANES-III (1988 –
1994) with mortality follow-up data.
• The lean study cohort consisted of 5,375 individuals
• 10.8% of lean cohort (N = 581) had NAFLD
• Compared to lean individuals without NAFLD, lean NAFLD
subjects were significantly more likely to be
– Older: 50.92 ± 1.26 vs. 41.8 ± 0.60, p < 0.001
– Male: 58.67 ± 3.13 vs. 39.19 ± 0.86, p < 0.001
– Diabetes 20.28 ± 2.27 vs. 0.29 ± 0.11, p < 0.001
– High cholesterol 35.03 ± 2.52 vs. 13.19 ± 0.74, p < 0.001
– Hypertension 31.29 ± 2.59 vs. 13.29 ± 0.80, p < 0.001
• In the fully adjusted model, NAFLD was independently
associated with increased risk of all-cause (aHR = 1.54,
95% CI: 1.25 – 1.89) and cardiovascular (aHR = 2.38, 95%
CI: 1.50 – 3.77) mortality
Adjusted Survival Curves on Cox hazard proportion
model for all-cause mortality among Lean individuals
Golabi P, Paik J, Fukui N, Locklear C, de Avilla L, Younossi ZM. Clinical Diabetes. 2018 Sep; cd180026.
Contribution of Superimposed NAFLD on Other Liver Diseases
• Since components of Metabolic syndrome (DM, HL, HTN, Visceral
obesity) are risk factors for NAFLD, they can increase the risk for
accelerating progression either through superimposed NAFLD or
directly through DM and obesity (inflammatory states)
• Evidence available for the following
– Chronic hepatitis C
– Chronic hepatitis B
– Overlap with alcoholic liver disease
– Contribution to HCC
The Comprehensive Global Burden and Impact of NASH
What Are Economic and Patient Reported
Outcomes of NASH?
Patient Reported Outcomes
Fatigue and Health Related Quality of Life in NAFLD and NASH
• Highest rate of Fatigue in real world setting was observed in
NASH/NAFLD
• Biopsy proven NASH from STELLAR 3 and 4 (N=1667) completed 4 PRO
questionnaires [SF-36, CLDQ-NASH, EQ-5D, WPAI:SHP] pre treatment
• Fatigue and physical health related PRO scores were lower than population
norms (all p
Impact of Fatigue on Health Related Quality of Life in NASH
• Patients with biopsy-proven NASH (N=1679) enrolled in clinical trials
• Prevalence of clinically reported history of fatigue: 10.3%
• NASH patients with fatigue has significant lower PROs that subjects without fatigue
40.0
50.0
60.0
70.0
80.0
90.0
100.0
Mean
PR
O s
co
re,
0-1
00 s
cale
Fatigue No fatigueall p
The Economic Burden of NASH
• 6.65 million adults with NASH
• 688,000 advanced NASH
• $222.6 billion in lifetime direct
costs of total NASH population
• $95.4 billion in lifetime direct
costs of advanced NASH
• Indirect cost of WP loss
and other indirect costs
are enormous
Younossi ZM, et al. Hepatology. 2016;64(5):1577-1586; Younossi ZM, et al. Hepatology. 2019;69:564–572.
The Comprehensive Global Burden and Impact of NASH
What Are Some Potential Pathogenic Pathways
That Can Promote Progression of NASH?
Pathogenesis of NASH and Related Fibrosis
Bacterial
translocation
(endotoxins)
DAMPs
Kupffer cells
Inflammatory
macrophages
PAMPs
Secondary
Inflammation
and Injury
IL-1ß
TN
F
Inflammatory
monocytes
Maturation
Oxidative
Stress
Inflammatory Mechanisms
ECM
deposition
(collagen
formation) Activation/
trans-differentiation
Hepatic
stellate cells
Activated myofibroblast Activated
myofibroblasts
Scar formation/
Fibrosis
TGF-ß
PDGF Proliferation
Fibrosis
Endothelial Cell
Dysfunction Fat accumulation drives injury
Hepatocyte
Visceral Adiposity Insulin
Resistance
Dysbiosis
DAMP, danger-associated molecular patterns; ECM, extracellular matrix; IL-1β, interleukin-1beta; PAMP, pathogen-associated molecular patterns;
PDGF, platelet-derived growth factor; TGF-β, transforming growth factor beta; TNF, tumor necrosis factor; TNF-β, tumor necrosis factor-beta.
Benedict M, Zhang X. World J Hepatol. 2017;9(16):715-732; Bedossa P. Liver Int. 2017;37(suppl 1):85-89;
Younossi ZM, et al. Hepatology. 2011;53(6):1874-1882.
The Comprehensive Global Burden and Impact of NASH
Invasive and Non-Invasive Tests to Identify NASH
Patients At Risk?
Diagnostic Modalities for NAFLD, NASH and Fibrosis
• Invasive Modalities: – Histology (liver biopsy is the imperfect gold standard to diagnose NASH and stage fibrosis)
• Z Goodman
• Non-invasive Modalities: – Non-invasive modalities for NASH are not very fruitful. – Better opportunities to find non-invasive tests for fibrosis – International efforts to find NITs: LITMUS (EU-Q Anstee) and NIMBLE (US-A Sanyal)
• NAFLD fibrosis score
• FIB-4 index
• AST:ALT ratio
• AST:platelet ratio index
• Hepascore®
• FibroTest®
• FibroMeter®
• Fatty liver index
• Index of NASH
• Ultrasound
• Computer tomography
• Magnetic resonance imaging
• Magnetic resonance spectroscopy
• Transient elastography
• Acoustic radiation force impulse
• Magnetic resonance elastography
Imaging Clinical/lab tests M Middleton
• Hyaluronic acid
• Fucosylated haptoglobin (Fuc-Hpt)
• Macroglobulin-2 binding protein (Mac-2bp)
• Fuc-Hpt + Mac-2bp
• ELF score
• FIBROSpect®
• PRO C3
Biomarkers Q Anstee
Q Anstee
Papagianni M, et al. World J Hepatol. 2015;7:638–48; Golabi P, et al. Expert Rev Gastroenterol Hepatol. 2016;10:63–71.
• Research Flier: If interested to
contact Central Research Staff
TE>9 kPa
• TE29.9 or Dyslipidemia treated with meds or Hypertension treated with meds) or
2. T2DM with a history of elevation of AST or ALT (1.5-times ULN in the past 6 months) or
3. T2DM with a history of fatty liver by any radiologic modality (US, CT, MRI) or liver biopsy (any historical test will be sufficient)
4. Non-diabetics with 3 components of MS (BMI>29.9, Dyslipidemia treated with meds and Hypertension treated with meds)
• Phone consent
• Basic clinical and demographic data
• Any 2/3 of the following;
– NFS>-1.45
– FIB-4>1.45
– APRI>1.0
Link to NASH Care
• Agreed to participate by
phone N=364
• Did not meet criteria N=270
Linked to care N=94
Completed Linkage N=51
≥ 9 kPa 19.6%
≥ 8 kPa 25%
Significant
“fibrosis”
NAFLD
CAP>250dB/m 72.5%
Primary Care and Endocrinology Practices
• Strict life style modifications
• Consider biopsy for prognosis or clinical trials candidates
• Annual TE and clinical data to monitor
Linkage to NASH standard of
care to GI and Hepotology
Example of Risk Stratification: Preliminary Data
K Corey and R Basu; Younossi Z. 2019.
Chronic kidney
disease Osteoarthritis Vascular
disease
Obstructive sleep apnea
Gallstone disease
NAFLD
Polycystic ovary syndrome
Diabetes
Cerebrovascula
r disease
Cardiac
disease
Malignancy
Not to Forget NASH as a Part of a Multisystem Disorder
N Alkhouri and A Singal; L Sperling; K Cusi and R Basu; Angulo P, et al. Gastroenterology. 2015;149:389–397;
Söderberg C, et al. Hepatology. 2010;51:595–602; Ekstedt M, et al. Hepatology. 2006;44:865–873; Dam-Larsen S, et al. Scand J Gastroenterol.
2009;44:1236–1243; Rafiq N, et al. Clin Gastroenterol Hepatol. 2009;7:234–238; Hicks SB, et al. Oral abstract presented at the AASLD Liver Meeting; 31;
11 November 2018; San Francisco, USA.
NASH
Patients (D Cryer), Policy (Z Younossi, D Cryer, A
Sanyal, V Ratziu, Q Anstee, K Cusi and others) Public Health
Interventions
• Histology: Z Goodman
• Fibrosis: S Freidman
• NIT: Q Anstee, M Nouredine
• Imaging: M Middleton
• Overall: A Sanyal and S Caldwell
Role of Current
Interventions
Outcomes and
Endpoints
• Diets and Nutrition: S Zelber-Sagi
• Exercise and Function: L Gerber
• The Role of Surgery and Weight loss Medication:
S Klein
• Current Medical Regimens: K Kowdley
Current and
Future Clinical
Trials
• New Therapeutic : V Ratziu
• Challenges in Trial Design: V Ratziu and N
Alkhouri
• Clinical Trial in Pediatrics: J Lavine
• Optimal Design: N Chalasani
• Regulatory Perspective: A Sanyal
• Overall Screening and Linkage:
K Carey and R Basu
• Linkage with Diabetes: K Cusi
• Linkage with CVD: L Sperling
• Linkage with Primary Care: M Abdelmalek
Screening and
Linkage from
Different
Settings
Addressing the Epidemic of NASH: Today and Tomorrow
The Comprehensive Global Burden and Impact of NASH
• NAFLD and NASH are growing globally with epidemic of
obesity
• NASH is predominantly progressive
• Fibrosis is important predictor of long-term outcomes
• Patients with NASH, especially those with fibrosis will need
treatment and should be identified
• Although liver biopsy is the current imperfect gold standard for
NASH diagnosis, a number of non-invasive tests are being
developed
• Management of NASH requires a multidisciplinary teams
• Critical issues for treatment of NASH:
– Most meaningful surrogate endpoints
– Finding the right targets and development of regimens
(combinations)
– Finding the patients (screening and Linkage with NITs)
– Managing as teams
– Understanding the differences and similarities across
the globe
Treatment:
• Life style intervention
• Bariatric Experts (Medical,
Endoscopic, Surgical)
• New drug regimens
Primary Care- TeleMedicine
Hepatology/GI
Multidisciplinary Integrated Teams
Nutrition
Experts Exercise
Specialists
DM Experts
Diagnostic Tests:
• Clinical agorithms
• Non-invasive serum and imaging
biomarkers
• Liver biopsy
To Address the Global Burden of NASH, Creation of NASH
Global Council and Associated Registries
The Council of world
renowned
hepatologists with
interest in NASH to
collaborate in NASH
from different regions
of the world. Global
NASH Council include
over 30 countries from
all the continents
across the globe with
65 members.
Members of the
Council carry out
multiple collaborative
projects to better
understand NASH, its
clinical, economic and
PRO burden
The Global NASH Council™
The Global NASH Registry™ and The Global Liver Registry™
• Number of Subjects
Enrolled: 7,385
• Number of Total
Sites: 38 sites
• Number of Active
Sites: 25 sites (9
sites in North
America, 6 sites in
Europe, 6 sites in
Asia, 2 sites in
Australia and 2 sites
in Africa)
• A total of 7,385
enrolled among 3
disease types:
NAFLD/NASH =
3,992
• Hepatitis C = 2,546,
Hepatitis B = 847
Countries
1 Australia
2 Austria
3 Canada
4 Chile
5 China
6 Columbia
7 Cuba
8 Egypt
9 France
10 Greece
11 Hong Kong
12 India
13 Indonesia
14 Ireland
15 Italy
16 Japan
17 KSA
18 Malaysia
19 Mexico
20 Pakistan
21 Philippines
22 Portugal
23 Russia
24 S Korea
25 Singapore
26 Spain
27 Switzerland
28 Taiwan
29 Thailand
30 Turkey
31 USA
The Global NASH Registry™ The Global Liver Registry™
Acknowledgements
Beaty and Guy Beatty Center for Integrated Research
Beatty Liver and Obesity Research Program