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