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.