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.