The broad patterns of HCV morbidity and
mortality across the world. What is the
anticipated pattern in Iran?
Behzad Hajarizadeh, Jason Grebely, Gregory Dore
Viral Hepatitis Clinical Research Program
The Kirby Institute for infection and immunity in society
The University of New South Wales (UNSW), Sydney, Australia
Outline
HCV transmission routs and population at risk
Increasing burden of HCV mortality: highlighted or missed?
HCV prevalence across the world
Liver fibrosis progression in chronic HCV infection
Major determinants of current and projected burden due to HCV
Broad patterns of HCV morbidity and mortality across the world
How will new treatments affect HCV burden?
HCV age-specific prevalence in Iran
Anticipated pattern of HCV morbidity and mortality in Iran
Increasing burden of HCV mortality: highlighted or missed?
Annual age-adjusted mortality rates from HBV,
HCV and HIV infections in the United States
Ly K, et al. Annals of Internal Medicine. 2012
Fauci, A & Morens, D. NEJM 2012
HCV distribution across the world
Global pr. :
2-3%
30-170 million
people infected
Gravitz L. Nature. 2011 ; Lavanchy D. Liver International. 2009 ; GBD. J Clin Pharm. 2004 ; WHO. Weekly Epi Record. 1999
Liver fibrosis progression in chronic HCV infection
HCV-related mortality and
morbidity is mainly due to
cirrhosis and
hepatocellular carcinoma
(HCC)
Risk of HCV-related
cirrhosis increases
exponentially by duration
of infection
There are various factors
associated with a higher
risk of fibrosis progression
Grebely J & Dore G. Semin Liver Dis. 2011
Major determinants of current and projected burden due to HCV
Current and projected HCV-related
burden reflects temporal HCV
incidence and prevalence, HCV
disease progression co-factors and
HCV treatment uptake.
Given slow progression of liver
fibrosis, the temporal incidence of
HCV is the main determinant of the
future burden.
Mathematical models have been
used to define trends in incidence,
which rely on the assumption that
current age-specific prevalence
reflects the cumulative risk of
acquiring infection.
Broad patterns of HCV morbidity and mortality across the world
First pattern
o HCV is endemic; High prevalence in all age groups; High incidence
o Africa, South Asia, South-East Asia
Second pattern
o Low overall prevalence; Low incidence; High prevalence in elderly
o Japan, Southern Europe
Third pattern
o Low overall prevalence; Low incidence; High prevalence in middle age
o The United States, Australia, Northern and Western Europe
HCV incidence and age-specific prevalence in Egypt
HCV pr.: 14.7%
HCV pr. increases with age
50–59 years age group
o M: 46%
o F: 31%
HCV inc.: 7/1000 p/y,
corresponding to 500,000
new cases per year.
Guerra J, et al. J Viral Hep. 2012
Miller FD & Abu-Raddad LJ. Proc Nat Aca Sci. 2010
HCV-related mortality in Egypt
HCV is endemic
Pr. is high in all ages
Inc. is high
HCV-related mortality is
projected to be 2.5 fold
higher in 2020
compared to 1999
More than 20,000 HCVrelated deaths
occurring in 2020
Deuffic-Burban S, et al. J Hep. 2006
HCV incidence and age-specific prevalence in Japan
HCV prevalence: 1.0-1.9%
HCV incidence: 1.9 per 100,000 p/y (blood donors)
HCV pr. is strongly related to age; exponential increase in over 55 yrs
People aged 40 to 69 years account for 86% of infections.
Major HCV spread occurred in the distant past (1920s and 1940s [WW II])
Tanaka J, et al. Intervirology. 2004 ; Tanaka J, et al. Intervirology. 2008
HCV-related HCC incidence in Japan
High HCV prevalence in elderly
Peak HCV incidence occurred
several decades ago
Low current HCV prevalence,
and incidence.
Trends in age-standardized incidence of HCC in
Osaka, Japan, 1981–2003.
HCC incidence peaked in late
1980s to early 1990s and has
been decreasing afterwards.
Tanaka H, et al. Ann Intern Med. 2008
HCV incidence and age-specific prevalence in the USA
HCV prevalence:
o 1.8% in 1988-1994
o 1.6% in 1999-2002
Peak prevalence shifted from 30-39
yrs in 1988-1994 to 40-49 yrs in
1999-2002
Major HCV spread occurred in the
recent past:
o High incidence in the 1970s
and early 1980s
o Rapid decline from the mid1980s .
Armstrong GL, et al. Ann Intern Med. 2006 ; Williams IT, et al. Arch Intern Med. 2011 ; Armstrong GL, et al. Hepatology. 2000
HCV incidence and age-specific prevalence in Australia
HCV prevalence: 1.4%
Peak prevalence is 30-39 yrs,
at least 10 yrs younger than
in the US.
HCV incidence increased
throughout the 1980s and
1990s with a decline from
2000, initially related to a
heroin shortage.
The Kirby Institute. Annual Surveillance Report 2012 ; Razali K, et al. Drug and Alcohol Dependence. 2007 ; Amin J, et al. Comm Dis Int. 2004
HCV-related cirrhosis and HCC in the USA
Low prevalence and incidence
Relatively higher prevalence in
middle age
Is following Japanese profile, but
with a time lag of 20-30 years.
Number of cirrhosis is increasing
steadily to a peak level of 1.4
million in 2020
HCV-related HCC should peak in
2019 at 14,000 per year.
HCV-related mortality is
increasing with 280,000 liverrelated deaths within 2020-2029
Davis GL, et al. Gastroenterology. 2010
USA
Australia
Japan
Egypt
40
Incidence of HCV-related advanced liver diseases
Patterns of age-specific HCV prevalence and HCV burden
40
Percent
30
30
20
20
10
10
0
<19
20-29
30-39
40-49
Age (year)
50-59
60-69
0
1980
1990
2000
2010
2020
Year
Schematic presentations of various patterns of age-specific prevalence of
HCV infection and incidence of HCV-related advanced liver disease in four
representative countries
2030
How will new treatments affect HCV burden?
The sustained virological response (SVR) increased from 55% with
pegylated-interferon (PEG-IFN) and ribavirin (RBV) to 70% in the era of
PEG-IFN, RBV, and a protease inhibitor (genotype 1 only)
IFN-free agents will be available by 2018, with SVR equals to 90%.
In 2005, 3% of patients in Europe and the US received treatment, with
treatment uptake increasing by only 0.5% per year .
HCV distribution in Middle-East and EMRO countries
HCV age-specific prevalence in Iran
Merat S, et al. Int J Inf Dis. 2010
HCV prevalence: 0.5-1%
Age specific prevalence:
o Peak pr. in young or middle age
o No constant increase with age
Poorolajal J, et al. J Res Health Sci. 2011
Limited data of HCV incidence
Newly diagnosed HCV cases:
o Blood donors: 0.8-1.9/1000 p/y ;
relatively steady trend
o Surveillance: 5-8/100,000 p/y in one
province; relatively steady trend
Khedmat H, et al. Hepatitis Monthly. 2009
Amini Kafi-Abad S, et al. Transfusion. 2009
Ansari-Moghaddam A, et al. Hepatitis Monthly. 2012
Anticipated pattern of HCV morbidity and mortality in Iran
Given high coverage of HBV vaccination in infants and also
implementation of catch-up HBV vaccination programs among
adolescent, HCV seems to emerge as the leading cause of chronic viral
liver disease in the future.
Age-specific prevalence of HCV in Iran is more close to that in the US
Australia, and Western Europe than the regional countries. Then it is
anticipated that the profile of HCV-related burden in Iran is more or less
similar to the Western countries (maybe with a time lag of 10-20 yrs).
More data needed to identify the profile of HCV-related burden in Iran.
Data registry in MOHME has potentials to collect required data for
modellings but needs modifications.