Post on 24-Feb-2016
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Behzad Hajarizadeh, Jason Grebely, Gregory Dore
Viral Hepatitis Clinical Research ProgramThe Kirby Institute for infection and immunity in societyThe University of New South Wales (UNSW), Sydney, Australia
The broad patterns of HCV morbidity and mortality across the world. What is the
anticipated pattern in Iran?
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?
Ly K, et al. Annals of Internal Medicine. 2012
Annual age-adjusted mortality rates from HBV, HCV and HIV infections in the United States
Fauci, A & Morens, D. NEJM 2012
HCV distribution across the world
Gravitz L. Nature. 2011 ; Lavanchy D. Liver International. 2009 ; GBD. J Clin Pharm. 2004 ; WHO. Weekly Epi Record. 1999
Global pr. : 2-3%
30-170 million people infected
Liver fibrosis progression in chronic HCV infection
Grebely J & Dore G. Semin Liver Dis. 2011
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
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.
Major determinants of current and projected burden due to HCV
Broad patterns of HCV morbidity and mortality across the world
First patterno HCV is endemic; High prevalence in all age groups; High incidenceo Africa, South Asia, South-East Asia
Second patterno Low overall prevalence; Low incidence; High prevalence in elderlyo Japan, Southern Europe
Third patterno Low overall prevalence; Low incidence; High prevalence in middle ageo The United States, Australia, Northern and Western Europe
HCV pr.: 14.7%
HCV pr. increases with age50–59 years age groupo M: 46%o F: 31%
HCV inc.: 7/1000 p/y, corresponding to 500,000 new cases per year.
HCV incidence and age-specific prevalence in Egypt
Guerra J, et al. J Viral Hep. 2012Miller FD & Abu-Raddad LJ. Proc Nat Aca Sci. 2010
HCV is endemicPr. is high in all agesInc. is high
HCV-related mortality is projected to be 2.5 fold higher in 2020 compared to 1999
More than 20,000 HCV-related deaths occurring in 2020
HCV-related mortality in Egypt
Deuffic-Burban S, et al. J Hep. 2006
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 yrsPeople aged 40 to 69 years account for 86% of infections.Major HCV spread occurred in the distant past (1920s and 1940s [WW II])
HCV incidence and age-specific prevalence in Japan
Tanaka J, et al. Intervirology. 2004 ; Tanaka J, et al. Intervirology. 2008
HCV-related HCC incidence in Japan
Tanaka H, et al. Ann Intern Med. 2008
High HCV prevalence in elderlyPeak HCV incidence occurred several decades agoLow current HCV prevalence, and incidence.
HCC incidence peaked in late 1980s to early 1990s and has been decreasing afterwards.
Trends in age-standardized incidence of HCC in Osaka, Japan, 1981–2003.
HCV prevalence:o 1.8% in 1988-1994o 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 mid-
1980s .
HCV incidence and age-specific prevalence in the USA
Armstrong GL, et al. Ann Intern Med. 2006 ; Williams IT, et al. Arch Intern Med. 2011 ; Armstrong GL, et al. Hepatology. 2000
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.
HCV incidence and age-specific prevalence in Australia
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
Davis GL, et al. Gastroenterology. 2010
Low prevalence and incidenceRelatively 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 2020HCV-related HCC should peak in 2019 at 14,000 per year. HCV-related mortality is increasing with 280,000 liver-related deaths within 2020-2029
Schematic presentations of various patterns of age-specific prevalence of HCV infection and incidence of HCV-related advanced liver disease in four
representative countries
Patterns of age-specific HCV prevalence and HCV burden
1980 1990 2000 2010 2020 20300
10
20
30
40
Year
Inci
denc
e of
HCV
-rela
ted
adva
nced
live
r dis
ease
s<19 20-29 30-39 40-49 50-59 60-69
0
10
20
30
40
USA AustraliaJapan Egypt
Age (year)
Perc
ent
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
Poorolajal J, et al. J Res Health Sci. 2011
Ansari-Moghaddam A, et al. Hepatitis Monthly. 2012
HCV prevalence: 0.5-1%Age specific prevalence:o Peak pr. in young or middle ageo No constant increase with age
Limited data of HCV incidenceNewly diagnosed HCV cases:o Blood donors: 0.8-1.9/1000 p/y ;
relatively steady trendo Surveillance: 5-8/100,000 p/y in one
province; relatively steady trend
Khedmat H, et al. Hepatitis Monthly. 2009Amini Kafi-Abad S, et al. Transfusion. 2009
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.