disease burden of non alcoholic fatty liver disease (nafld) disease burden by... · disease burden...

Disease Burden of Non Alcoholic Fatty Liver Disease

(NAFLD)

Dr. H. Razavi

May 31, 2017

First European NASH – NAFLD Summit

2

Disclosure:

This work with funded by a multi-sponsored research grant from Intercept,

Gilead and Boehringer Ingelheim. The funders had no influence over the

design, the implementation, or the outcomes of the study.

H. Razavi has not received any personal remuneration for this or any other

project.

3

This work would not be possible without the inputs of the following

experts

• France – Drs. Vlad Ratziu & Lawrence Serfaty

• Germany – Drs. Andreas Geier, Michael Manns, Christian Trautwein &

Stefan Zeuzem

• Italy – Drs. Stefano Bellentani, Antonio Craxi, Giulio Marchesini &

Salvatore Petta

• Spain – Drs. Maria Arias-Loste, Joan Caballeria, Javier Crespo &

Manuel Romero Gomez

• United Kingdom – Drs. Quentin Anstee, Christopher Day, Jude Oben &

Philip Newsome

4

Methodology

• Convened a panel of NAFLD experts in each country

• Collect published epidemiology data for NAFLD

• Gathered country specific rates for obesity and diabetes to estimate incidence

• Used published work to estimate progression rates for non-alcoholic fatty liver

(NAFL) and nonalcoholic steatohepatitis (NASH)

• Modeled the disease progression

• Validates the forecasts against reported NASH related HCC cases

5

The disease progression model tracked the population over time,

taking into consideration the reversible nature of the disease

Compensated

Cirrhosis (F4)

– NASH

Decompensated

Cirrhosis –

NASH

Hepatocellular

Carcinoma

Liver

Transplantation

F0 –

NAFL/NASH

F3 –

NASH

Liver Related

Death

F1 –

NASH

F2 –

NASH

New (Incident)

Cases

Incidence of Adult

Obesity / Diabetes

Used to Calibrate the model

• % of population with NAFLD

• % of NASH with F3/F4

• Incident HCC due to NASH

The outputs of the model were

compared against empirical data

at multiple stages

6

NASH prevalence and obesity in the EU5 are lower than the US

BMI≥30

% of total

population ≥15+

with NAFLD

% of NAFLD with

NASH

% of total

population ≥15+

with NASH

US 28% 30% 20% 6.3%

France 16% 25% 16% 4.2%

Germany 19% 25% 18% 4.6%

Italy 16% 28% 17% 4.9%

Spain 18% 25% 17% 4.4%

UK 21% 25% 18% 4.8%

China 4% 20% 13% 2.8%

Japan 4% 20% 16% 3.4%

7

Obesity has been increasing in the European countries

NAFLD is accounting for more HCC cases in the UK

Adult obesity have been

increasing but the rate of increase

has (and is projected to) slowed.

0%

5%

10%

15%

20%

25%

30%

1980 1990 2000 2010 2020 2030

Adult Obesity Rate

UK Germany Spain France Italy

UK – The proportion of HCC

attributable to NAFLD in

Newcastle was 34.8% in 2010, a

tenfold increase as compared to

2000 (Dyson 2014)

Dyson J, Jaques B, Chattopadyhay D, Lochan R, Graham J, Das D, et al. Hepatocellular cancer: the impact of obesity, type 2 diabetes and

a multidisciplinary team. J Hepatol. 2014;60(1):110-7.

8

Most individuals will remain as NAFL but the NASH population is

expected to grow by 45% while cirrhotic cases will increase by 120%

NASH NAFL

72.3 62.7

4.5

2.5 1.6 0.9

0.0

10.0

20.0

30.0

40.0

50.0

60.0

70.0

80.0

90.0

Total F0 F1 F2 F3 F4

Mil

lio

ns

EU5, 2016

84.0 69.0

6.0

4.0

3.0 2.0

0.0

10.0

20.0

30.0

40.0

50.0

60.0

70.0

80.0

90.0

Total F0 F1 F2 F3 F4

Mil

lio

ns

EU5, 2030

9

Although the increase in total NAFLD cases is slowing down, NASH,

HCC, and liver related deaths is projected to continue to increase

0

10,000,000

20,000,000

30,000,000

40,000,000

50,000,000

60,000,000

70,000,000

80,000,000

90,000,000

1950 1960 1970 1980 1990 2000 2010 2020 2030

NAFLD & NASH Cases - EU5

NAFLD Cases NASH Cases

0

2,000,000

4,000,000

6,000,000

8,000,000

10,000,000

12,000,000

14,000,000

16,000,000

18,000,000

20,000,000

1950 1960 1970 1980 1990 2000 2010 2020 2030

NASH Cases - EU5

NASH Cases

0

1,000

2,000

3,000

4,000

5,000

6,000

7,000

8,000

9,000

1950 1960 1970 1980 1990 2000 2010 2020 2030

Annual HCC Incidence - EU5

HCC Incidence

0

5,000

10,000

15,000

20,000

25,000

30,000

35,000

40,000

45,000

50,000

1950 1960 1970 1980 1990 2000 2010 2020 2030

Annual Liver Related Deaths - EU5

NAFLD

10

Conclusions

• In the absence of interventions, advance liver diseases associated with

with NAFLD will more than double over the next 15 years while total

NAFLD cases will increase by 16%

• NAFLD is reversible – diet and exercise can reverse liver fibrosis

• Interventions are required to manage the increase in future disease

burden

• The European Union should promote awareness of NAFLD and

strategies to reduce the disease burden (including weight loss and diet)

• These same interventions will also have an impact on other non-

commutable diseases including cardiovascular diseases and diabetes

• Better reporting systems are required to track NAFLD related disease

burden to measure progress

21

US Model Transition Rates

• Model fibrosis progression as compared to Younossi 2016 and Singh 2015

2.2%

13.3% 13.3%

9.9%

0.7%

4.2% 4.2%5.1%

6%

-3%

12%

-23%

4% 4%

10%

5%

13%

10%

7%

15%14%

8%

-25.0%

-20.0%

-15.0%

-10.0%

-5.0%

0.0%

5.0%

10.0%

15.0%

20.0%

Annual Fibrosis Progression Rates

Model Max

Model Min

Younossi 2016

Singh 2015

- Singh, S., et al., Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of

paired-biopsy studies. Clin Gastroenterol Hepatol, 2015. 13(4): p. 643-54.e1-9.

- Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global Epidemiology of Non-Alcoholic Fatty Liver Disease-Meta-

Analytic Assessment of Prevalence, Incidence and Outcomes. Hepatology. 2016. Available at:

http://www.ncbi.nlm.nih.gov/pubmed/26707365

22


• Model liver related mortality as compared to Younossi 2016

0.03%

0.17%

0.05%

1.18%

0.07%0.04%

0.54%

1.32%

0.03% 0.06%0.03%

0.22%

1.07%

0.04%

0.29%

0.00%

0.20%

0.40%

0.60%

0.80%

1.00%

1.20%

1.40%

Annual Liver Related Mortality Rates

Model

Younossi 2016




23


0.44%

0.98%

0.49%

0.30%

0.57%

0.47%

0.00%

0.20%

0.40%

0.60%

0.80%

1.00%

1.20%

Annual CVD Mortality Rates

Model

Younossi 2016

• Model CVD mortality as compared to Younossi 2016




24


• Model HCC incidence as compared to Younossi 2016

0.0003%0.0093%

0.0189%0.0380%

0.3285%

0.042% 0.044% 0.036%

0.063%

0.00%

0.05%

0.10%

0.15%

0.20%

0.25%

0.30%

0.35%

Annual HCC Incidence Rates

Model

Younossi 2016




25


• Other transition rates used in model:

3.8%

61.0%

16.2%

0.0%

10.0%

20.0%

30.0%

40.0%

50.0%

60.0%

70.0%

Miscellaneous Model Transition Rates

Model

- Sanyal AJ, Banas C, Sargeant C, Luketic VA, Sterling RK, Stravitz RT, et al. Similarities and differences in outcomes of cirrhosis due to

nonalcoholic steatohepatitis and hepatitis C. Hepatology. 2006;43(4):682-9. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16502396

- Younossi ZM, Otgonsuren M, Henry L, Venkatesan C, Mishra A, Erario M, et al. Association of nonalcoholic fatty liver disease (NAFLD)

with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009. Hepatology. 2015;62(6):1723-30. Available at:


- Ries LAG, Young GL, Keel GE, Eisner MP, Lin YD, Horner M-J. SEER survival monograph: cancer survival among adults: U.S. SEER

program, 1988-2001,patient and tumor characteristics. [NIH Pub.No.07-6215]. 2007. Bethesda, MD, National Cancer Institute, SEER

Program.



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