The Global Burden of Hepatitis
Infection
Prof. Henry LY Chan
MBChB (CUHK), MD (CUHK), FRCP (Edin, Lond)
Head, Division of Gastroenterology and Hepatology
Director, Institute of Digestive Disease
Director, Center for Liver Health
Assistant Dean (Development), Faculty of Medicine
The Chinese University of Hong Kong
HCV distribution across the world
130–170 million people world wide are infected with HCV
China
30 M
Europe
18 M*
Americas
14 M*
Middle East
16 M*
N. Korea
0.2 M
S. Korea
0.8 M
Japan
3M
Africa
28 M*
Prevalence of HCV
>10%
5–10%
2–5%
1–2%
<1%
No data
India
18 M
Indonesia
9M
Australia
0.2 M
* Estimated number of chronically infected individuals (2010)
Lavanchy D. Clin Microbiol Infect 2011; 17:107–115;
CDC: http://wwwnc.cdc.gov/travel/yellowbook/2012/chapter-3-infectious-diseases-related-to-travel/hepatitis-c.htm.
Prevalence of HCV in Asia-Pacific
countries
Prevalence of HCV (%)
12
10.7
10
8
5.9
6
4
2.2 2.4
2
4.1
3.9
1.1
0.3
1.0
1.7
1.5
2.2
1.0 1.0
1.5
0
•
•
Prevalence = % anti-HCV (2010);
HCC = hepatocellular carcinoma.
Lavanchy D. Clin Microbiol Infect 2011; 17:107–115;
Lee MH, et al. Gut 2011; 60:688–694;
The burden of HCV
Risk of HCV-related cirrhosis increases
exponentially by duration of infection1
• Major burden comes from
sequelae from chronic infection
60
HCV (n=33,121)
Cirrhosis (%)
• HCV-related mortality and
morbidity mainly due to
cirrhosis and HCC
• Estimated to be the cause of
27% of cirrhosis and 25% of
HCC worldwide2
• South-East Asia ~ 75%
unaware they are infected until
they have symptoms of
cirrhosis/HCC3
40
20
0
0
10
20
30
40
Years
1. Grebely J & Dore G. Semin Liver Dis. 2011; 31:331–339;
2. Perz JF, et al. J Hepatol 2006; 45:529–538;
3. WHO Prevention and control of viral hepatitis
infection:http://who.int/csr/disease/hepatitis/GHP_Framework_En.pdf?ua=1.
The disease burden will continue to grow as the
chronically infected population ages
•
HCV
exposure
Chronic
85%
Cirrhosis
20%
HCC
4%/yr
ESLD
6%/yr
Resolved
15%
Time
(years)
Transplant/death 3–4%/yr
10
20
30
Alcohol use, obesity, co-infection with HIV or HBV
accelerate HCV progression
% = percent of original group.
Sherman K. 2006. http://www.fda.gov;
Di Bisceglie AM, et al. Hepatology 2000; 31:1014–1018.
Patterns of age-specific HCV prevalence
and HCV burden
Age-specific prevalence of HCV infection and incidence of HCV-related
advanced liver disease in four representative countries
USA
Australia
Egypt
Incidence of HCV-related advanced
liver diseases
Prevalence (%)
40
Japan
30
20
10
0
<19
20–29 30–39 40–49 50–59 60–69
Age (years)
1980
1990
2000
2010
2020
2030
Year
Hajarizadeh B, et al. Nat Rev Gastroenterol Hepatol 2013; 10:553–562.
Proportion of patients with HCV and HCC in
Asia-Pacific countries
Country/region
• Yuen
Japan
HCV-related HCC, %
MF, et al. J Gastroenterol Hepatol 2009;7924:346–
353;
Australia
30–40
New Zealand
30–40
South Korea
20
India
16
Thailand
15
Singapore
13–20
1. Venook AP, et al. The Oncologist 2010; 15:5–13.
Mainland China
12
Hong Kong
3–6
Philippines
4
Malaysia
2
Barriers to HCV treatment by global region:
physician perspective
1. Medication expense
Mean likert score*
10
2. Fear of side effects
3. Treatment duration
8
6
4
2
0
US
Canada
Latin
America
Patient
Western
Europe
Provider
* Each barrier rated on a 10-point Likert scale,
from 0 “not a barrier” to 10 “large barrier”
Cent/Eastern
Europe
Nordic
Government
Asia/
Pacific
Mid. East/
Africa
Payer
McGowan CE, et al. Hepatology 2013; 57:1325–1332.
Need to consider effectiveness for the
entire HCV population
USA
Japan
China
HCV prevalence:
~ 4.1 million
HCV prevalence:
~ 1.1 million
HCV prevalence:
~ 10 million
~ 38%
~ 68%
~ 1.6%
Diagnosed:
~ 1.6 million
Diagnosed:
~ 745,000
Diagnosed:
~ 158,000
Treated:
~ 5.5%
Treated:
~ 5%
Treated:
~ 1.6%
Ipsos HCV Monitor Q2 2013, Gilead press release 2014.
Zhuang H, Asian Pacific Perspective in Hepatitis 2011, Vietnam
>7%
2%-7%
<2%
Adopted and modified from CDC website: http://www.cdc.gov/Features/dsHepatitisAwareness/
Worldwide burden of HBV
• >350 million are chronic HBV carriers
• In the 2010 Global Burden of Disease study, HBV
infection was the 10th leading cause of death (786 000
deaths per year).
• About half the total liver cancer mortality in 2010 was
attributed to HBV infection
• From 1990 to 2010, the worldwide mortality associated
with liver cancer increased by 62%, and that associated
with cirrhosis increased by 29%.
Trepo, Chan and Lok. Lancet 2014 (in press)
HBV infection in Asia
• 74% of HBV carriers are in Asia Pacific countries
• Among 260 million HBV infected people in Asia, 160
million resides in Western Pacific region
• In Western Pacific region
– 50% of all HBV patients in the world
– 60% of HCC in the world
– 360,000 people died of HBV-related liver disease annually
WHO. Prevention & Control of Viral Hepatitis Infection: Framework for Global Action. 2012. Available:
http://www.who.int/csr/disease/hepatitis/Framework/en/index.html
HBV Infection is the Commonest
Cause of HCC in Asia
Proportion of HCC caused by HBV
100%
80%
60%
40%
20%
0%
Singapore Philippines
India
Korea
Taiwan
Hong Kong Thailand
Malaysia
APWP-HCC, Hong Kong, June 2008
Universal vaccination to newborn
• First launched 1984 in Taiwan
• Now 180 (3%) countries in the world has this program
• Prevalence of HBsAg positivity in Taiwan 2009 after 25
years of vaccination program = 0.9%
Age
<25
25
26-27
28-29
N
2857
97
199
179
%
0.9
6.2
6.0
10.6
Ni YH, et al. J Hepatol 2012;57:730-5
Prevention of HBV infection: impact of
vaccination in Taiwan
HBsAg
carriage
Chronic
hepatitis
Cirrhosis
and HCC
1980
1990
2000
2010
2020
2030
2040
HBV vaccination programme
launched in 1984
Average annual incidence of HCC in children
aged 6–14 years (per 100,000)
1981–86
1986–90
1990–94
2007
0.7
0.57
0.36
0.19
Adapted from 1. Lin HH, et al. J Med Virol 2003;69:471–474. 2. Chang MH, et al. N Engl J Med 1997;336:1855–9.
3. Chen DS. Hepatol Res 2007;37(Suppl. 2):S101–5
By end of 2011, 180 countries has universal vaccination programme
47 European countries have universal vaccination; 6 (Denmark, Finland, Iceland, Norway,
Sweden and UK) have targeted vaccination
Trepo, Chan and Lok. Lancet 2014 (in press)
Reimbursement policies differ across
Asia-Pacific countries
Low reimbursement
Partial reimbursement
High reimbursement
Lamivudine is most
commonly used
Drug use according to
reimbursement policy
Entecavir & Tenofovir
are most
commonly used
Drug resistance
Thailand, Indonesia,
Philippines, Vietnam
High cost
Hong Kong, Taiwan,
Korea, China
Japan, Singapore,
Australia, New Zealand
The increasing problem of HBV drug resistance
in Asia
794 patients receiving sequential/combination NUCs
•
Diverse drug mutations found in 306 (38.5%)
•
ETV-R ±LAM-R ±ADV-R in 45 (5.7%)
100%
100%
100
Entecavir resistant
mutations (%)
90
80
70
60
50
40%
40
29%
30
20
10
25%
24%
10%
3%
0
LAMADV LAMETV LAMADV LAMADV
LAM
ADVLdT LAMADV
LAM
(n=136)
(n=35) LAM+ADV ETV
LAM+ADV
(n=8)
LdT+ADV LAM+ADV
(n=5)
(n=38)
(n=32)
(n=2)
ETV+ADV
(n=1)
Adapted from Liu Y, et al. J Viral Hepat 2011;18:e29-39.
Summary
Large global burden of HBV and HCV infection in the world.
Key cause of hepatocellular carcinoma and mortality
HCV
• Great advances in antiviral therapy
• Challenges in accessibility and affordability of medicine
HBV
• Vaccination has significantly reduced burden in the younger
generation
• Challenges in accessibility of vaccine and antiviral therapy for
existing patients