Hepatitis and Liver Diseases October 10-12, 2016 Dubai, UAE 3rd World Congress on Hepatitis and Liver Diseases Hepatitis C Virus (HCV) infection: a global epidemiological up-date of the circulation of HCV genotypes World J. Gastroenterol. 2016 ; 22(34): 7824-7840. Dr. Arnolfo Petruzziello, PhD Unit of Virology and Molecular Biology IRCCS- Fondazione G. Pascale - Naples, Italy A. Petruzziello: HCV infection: a global epidemiology up date

Hepatitis C virus one of the major globally health burden and causes of death and morbidity; recent estimates showed an increase in its prevalence over the last decade to 2.8% (>185 million infections worldwide). A. Petruzziello: HCV infection: a global epidemiology up date

Hcv to Hcc pyramid A. Petruzziello: HCV infection: a global epidemiology up date

Total predicted deaths HCV-related 2005-2030 if 15% of HCV chronic patients will receive anti-HCV treatment with 80% of sustained viral response (SVR); if 50% of HCV chronic patients will receive anti-HCV treatment with 60% of SVR; if 50% of HCV chronic patients will receive anti-HCV treatment with 80% of SVR ; if all HCV chronic patients will receive anti-HCV treatment with 60% of SVR. S. Deuffic-Burban: Estimating the Future Health Burden of Chronic Hepatitis C and Human Immunodeficiency Virus Infections in the United States. J Viral Hepat. 2007;14(2):107-115.  A. Petruzziello: HCV infection: a global epidemiology up date

The HCV epidemiological paradigm varies regionally depending on its historical and present risk factors. A country-specific policy of prevention, diagnosis and treatment could surely reduce this disease burden A. Petruzziello: HCV infection: a global epidemiology up date

Prevalence of Chronic HCV infection Mohd Hanafiah K, Groeger J, Flaxman AD, Wiersma ST. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology 2013; 57:1333-1342 A. Petruzziello: HCV infection: a global epidemiology up date

Although antibodies to HCV (anti-HCV) are at present the most commonly available marker of HCV infection, the most important indicator of HCV diffusion seems to be its classification into its different genetic variants. A. Petruzziello: HCV infection: a global epidemiology up date

The length of the therapy and the opportunity to associate interferon and/or ribavirin with the new direct-acting antiviral (DAA) therapies still remain partially dependent on HCV genotype. A. Petruzziello: HCV infection: a global epidemiology up date

Unfortunately, however, in many countries there is a lack of robust epidemiological data with no attention to HCV genotypes distribution. A. Petruzziello: HCV infection: a global epidemiology up date

HCV genotypes HCV is classified into seven recognized genotypes on the basis of sequence of the viral genome, each differing at 30 - 35% of nucleotide sites and into 67 confirmed and 20 provisional subtypes, differing at < 15% of nucleotide sites . A. Petruzziello: HCV infection: a global epidemiology up date

HCV genotyping assays polymorphisms Kinetic amplification RFLP restriction fragment length polymorphisms Kinetic amplification Line probe assays (LiPA) A. Petruzziello: HCV infection: a global epidemiology up date

HCV genotypes distribution Epidemic subtypes (1a, 1b, 2a, and 3a) are widely distributed worldwide and account for a great proportion of the totality of HCV cases, especially in high income countries; Endemic subtypes (4, 5a, 6a) are comparatively more rare and have been restricted for long time in specific regions, as West Africa, Southern Asia, Central Africa and South Eastern Asia . A. Petruzziello: HCV infection: a global epidemiology up date

Worlwide geographic distribution of HCV genotypes Messina JP, Humphreys I, Flaxman A, Brown A, Cooke GS, Pybus OG, Barnes E. Global distribution of Hepatitis C virus Genotypes. Hepatology 2015; 61 (1):77-87. A. Petruzziello: HCV infection: a global epidemiology up date

the viraemic rate (HCV- RNA positive) genotype distribution The purpose of this study was to conduct a comprehensive review of recently published literature to estimate : anti- HCV prevalence the viraemic rate (HCV- RNA positive) genotype distribution A. Petruzziello: HCV infection: a global epidemiology up date

METHODS The average HCV prevalence, viraemic rate and genotype distribution for each continent was calculated by dividing the sum of data reported from each region to the total number of countries within the region. A. Petruzziello: HCV infection: a global epidemiology up date

Regions included in the analysis were those defined by the Global Burden of Diseases, Injuries, and Risk Factors 2010 (GBD) study, defined as … ‘‘epidemiologically homogenous as possible so that information from detailed studies in one country can plausibly be extrapolated to other countries in the region to create burden estimates that are useful to individual countries in planning for health sector activities” A. Petruzziello: HCV infection: a global epidemiology up date

GBD Regions Africa: Asia: North Africa and Middle East Australasia Central Sub- Saharan Africa Central Asia East Sub- Saharan Africa East Asia Southern Sub- Saharan Africa Pacific Asia, High- Income West Sub- Saharan Africa South Asia Southeast Asia North Africa and Middle East Australasia Americas: Europe: North America Central Europe Caribbean Eastern Europe Andean Latin America Western Europe Central Latin America Southern Latin America Tropical Latin America A. Petruzziello: HCV infection: a global epidemiology up date

Inclusion Criteria Total of 557 articles Date of publication (2000-2015); Sources: Pub Med and official databases; Language (only English); Impact factor (> 1.5); Adult populations; Sample size (> 500); Anti-HCV assay (3rd generation test); Well described PCR RT system; Genotyping (LiPa assay); General population (no blood donors or high risk groups) A. Petruzziello: HCV infection: a global epidemiology up date

Exclusion criteria Countries for which we were unable to obtain HCV genotype prevalence data were excluded from calculations of regional proportions, although their populations were included in the total population size of each region when generating regional genotype prevalence estimates. A. Petruzziello: HCV infection: a global epidemiology up date

138 studied countries over 90% global population 28.3% 26.1% 1.4% 13.8% 18.8% 11.6% A. Petruzziello: HCV infection: a global epidemiology up date

Results Studying 138 countries worldwide total global HCV prevalence is estimated at 2.5% (177 million of HCV infected adults). A. Petruzziello: HCV infection: a global epidemiology up date

Global Anti-HCV prevalence 2.9 % 2.7 1.8 1.8 1.3 A. Petruzziello: HCV infection: a global epidemiology up date

Regional Anti-HCV prevalence (%) Sub Saharan Africa Americas Asia Europe A. Petruzziello: HCV infection: a global epidemiology up date

Results The global average viraemic rate is at 67% (118.9 million of HCV RNA positive cases) A. Petruzziello: HCV infection: a global epidemiology up date

Global Anti-HCV viraemic rate. 74.8 70.5 74.0 72.4 % 68.8 64.4 A. Petruzziello: HCV infection: a global epidemiology up date

Regional Anti-HCV viraemic rate. Sub Saharan Africa Americas Asia Europe A. Petruzziello: HCV infection: a global epidemiology up date

Global HCV genotype distribution (%) 2.0 1.8 1.4 16.8 49.1 17.9 11.0 A. Petruzziello: HCV infection: a global epidemiology up date

Regional HCV genotype distribution (%) A. Petruzziello: HCV infection: a global epidemiology up date

Sub Saharan Africa Anti-HCV prevalence: 2.9% Anti-HCV infected (million): 26,9 Anti-HCV viraemic rate: 70.5% Viraemic infected (million): 19,0 Central West East Southern A. Petruzziello: HCV infection: a global epidemiology up date

Anti-HCV prevalence in Sub Saharan Africa (%) 6.0 2.4 2.4 0.9 A. Petruzziello: HCV infection: a global epidemiology up date

Anti-HCV prevalence in Sub-Saharan Africa A. Petruzziello: HCV infection: a global epidemiology up date

HCV genotype distribution in Sub Saharan Africa(%) 3.4 12.2 26.3 28.1 23.7 6.3 A. Petruzziello: HCV infection: a global epidemiology up date

HCV genotype distribution in Sub Saharan Africa % A. Petruzziello: HCV infection: a global epidemiology up date

HCV genotype distribution in Sub-Saharan Africa. A. Petruzziello: HCV infection: a global epidemiology up date

North Africa/Middle Eastern Area Anti-HCV prevalence: 2.7% Anti-HCV infected (million): 12.7 Anti-HCV viraemic rate: 68.8% Viraemic infected (million): 8.7 A. Petruzziello: HCV infection: a global epidemiology up date

Anti-HCV prevalence in North Africa/Middle Eastern Area (%) A. Petruzziello: HCV infection: a global epidemiology up date

HCV genotype distribution in North Africa/Middle Eastern Area(%) 0,3 27,3 0,8 65,3 6,3 A. Petruzziello: HCV infection: a global epidemiology up date

HCV genotype distribution in North Africa/Middle Eastern Area. A. Petruzziello: HCV infection: a global epidemiology up date

The Americas Anti-HCV prevalence: 1.3% Anti-HCV infected (million): 12.74 Anti-HCV viraemic rate: 74.0% Viraemic infected (million): 9.2 North Caribbean Andean Latin Andean Central Southern Latin Tropical Latin A. Petruzziello: HCV infection: a global epidemiology up date

Anti-HCV prevalence in The Americas (%) 1.6 1.5 1.5 1.4 1.2 1.2 A. Petruzziello: HCV infection: a global epidemiology up date

Anti-HCV prevalence in The Americas. A. Petruzziello: HCV infection: a global epidemiology up date

HCV genotype distribution in The Americas (%) 0,3 2.6 1.7 10.6 10.2 74.5 A. Petruzziello: HCV infection: a global epidemiology up date

Regional HCV genotype distribution in The Americas (%) %

HCV genotype distribution in The Americas country by country. A. Petruzziello: HCV infection: a global epidemiology up date

Asia Anti-HCV prevalence: 2.8% Anti-HCV infected (million): 111.6 Anti-HCV viraemic rate: 64.4% Viraemic infected (million): 71.9 Central East South Southeast Pacific A. Petruzziello: HCV infection: a global epidemiology up date

Anti-HCV prevalence in Asia (%) 5.8 % 2.8 2.5 1.6 1.1 A. Petruzziello: HCV infection: a global epidemiology up date

Anti-HCV prevalence in Asia. A. Petruzziello: HCV infection: a global epidemiology up date

HCV genotype distribution in Asia (%) 4.3 7.0 1.0 22.4 46.6 18.6 A. Petruzziello: HCV infection: a global epidemiology up date

HCV genotype distribution in Asia % A. Petruzziello: HCV infection: a global epidemiology up date

HCV genotype distribution country by country in Asia. A. Petruzziello: HCV infection: a global epidemiology up date

Australasia Anti-HCV prevalence: 1.8% Anti-HCV infected (million): 0.5 Anti-HCV viraemic rate: 74.8% Viraemic infected (million): 0.4 A. Petruzziello: HCV infection: a global epidemiology up date

Anti-HCV prevalence in Australasia. A. Petruzziello: HCV infection: a global epidemiology up date

HCV genotype distribution in Australasia. A. Petruzziello: HCV infection: a global epidemiology up date

Europe Anti-HCV prevalence: 1.8% Anti-HCV infected (million): 13.4 Anti-HCV viraemic rate: 72.4% Viraemic infected (million): 9.7 Central Western Eastern A. Petruzziello: HCV infection: a global epidemiology up date

Anti-HCV prevalence in Europe (%) 3.1 1.3 0.9 A. Petruzziello: HCV infection: a global epidemiology up date

Anti-HCV prevalence in Europe. A. Petruzziello: HCV infection: a global epidemiology up date

HCV genotype distribution in Europe (%) 0,7 3.7 25.5 64.4 5.5 A. Petruzziello: HCV infection: a global epidemiology up date

Regional HCV genotype distribution in Europe % A. Petruzziello: HCV infection: a global epidemiology up date

HCV genotype distribution in Europe. A. Petruzziello: HCV infection: a global epidemiology up date

Conclusions If compared to a similar study concerning the period 1990-2005, the prevalence and the number of HCV infected patients has decreased from 2.8% to 2.5% and from 185 to 177 million. The most relevant decrease is observed in the high income zones, especially Western Europe (-1.5%), Southern Africa (-1.2%) and Australasia (- 0.9%), whereas a massive increase it’s reported in the low income areas as Central Africa (+3.7%) and Central Asia (+2.0%). A. Petruzziello: HCV infection: a global epidemiology up date

However, significant regional, country and local variations exists… Conclusions Globally, genotype 1 is the most common HCV genotype (49.1%) , followed by genotype 3 (17.9%). However, significant regional, country and local variations exists… A. Petruzziello: HCV infection: a global epidemiology up date

Conclusions Although HCV genotypes 1 and 3 are the most prevalent globally (67.0% if considered together), other genotypes are particularly common in lower-income countries, as G2 in West Africa and South America and G4 and G6, respectively in Central and Northern Africa and in Southeast Asia. G2, G4, and G6 combined account for nearly one third of all HCV cases globally. A. Petruzziello: HCV infection: a global epidemiology up date

Limits of the study The lack of information available from some extended regions; lack of robust epidemiology studies at national level; High percentage of randomized studies. A. Petruzziello: HCV infection: a global epidemiology up date

Take Home Message Globally anti- HCV prevalence have decreased from 2005 to date, probably for the impact of the new DAA therapies. This finding suggests that a better knowledge of genotype distribution, especially in its subtype diversification, may be critic for the complete understanding of HCV disease and its eradication.

Samantha Marigliano and Giovanna Loquercio A special thanks to Samantha Marigliano and Giovanna Loquercio for their great support in the realization of this study A. Petruzziello: HCV infection: a global epidemiology up date

Thank you for your attention Unit of Virology and Molecular Biology “V. Tridente” IRCCS Fondazione G. Pascale - Naples (Italy)