Global distribution and prevalence of hepatitis C virus genotypes

Jane P Messina, Isla Humphreys, Abraham Flaxman, Anthony Brown, Graham S Cooke, Oliver G Pybus, Eleanor Barnes, Jane P Messina, Isla Humphreys, Abraham Flaxman, Anthony Brown, Graham S Cooke, Oliver G Pybus, Eleanor Barnes

Abstract

Hepatitis C virus (HCV) exhibits high genetic diversity, characterized by regional variations in genotype prevalence. This poses a challenge to the improved development of vaccines and pan-genotypic treatments, which require the consideration of global trends in HCV genotype prevalence. Here we provide the first comprehensive survey of these trends. To approximate national HCV genotype prevalence, studies published between 1989 and 2013 reporting HCV genotypes are reviewed and combined with overall HCV prevalence estimates from the Global Burden of Disease (GBD) project. We also generate regional and global genotype prevalence estimates, inferring data for countries lacking genotype information. We include 1,217 studies in our analysis, representing 117 countries and 90% of the global population. We calculate that HCV genotype 1 is the most prevalent worldwide, comprising 83.4 million cases (46.2% of all HCV cases), approximately one-third of which are in East Asia. Genotype 3 is the next most prevalent globally (54.3 million, 30.1%); genotypes 2, 4, and 6 are responsible for a total 22.8% of all cases; genotype 5 comprises the remaining <1%. While genotypes 1 and 3 dominate in most countries irrespective of economic status, the largest proportions of genotypes 4 and 5 are in lower-income countries.

Conclusion: Although genotype 1 is most common worldwide, nongenotype 1 HCV cases—which are less well served by advances in vaccine and drug development—still comprise over half of all HCV cases. Relative genotype proportions are needed to inform healthcare models, which must be geographically tailored to specific countries or regions in order to improve access to new treatments. Genotype surveillance data are needed from many countries to improve estimates of unmet need.

© 2014 The Authors. Hepatology published by Wiley on behalf of the American Association for the Study of Liver Diseases.

Figures

Fig. 1
Fig. 1
Relative prevalence of each HCV genotype by GBD region. Size of pie charts is proportional to the number of seroprevalent cases as estimated by Hanafiah et al.
Fig. 2
Fig. 2
(A) Countries by the majority genotype found across all associated studies. (B) Shannon Diversity Index for study countries, ranging from 0 (comprised of larger proportions of a few genotypes) to 1.2 (comprised of smaller proportions of many genotypes). (C) Number of genotyped virus samples across all studies by country.
Fig. 3
Fig. 3
Relative prevalence of each genotype across all virus samples by country. Panel A: genotypes 1–3.

References

    1. Cooke GS, Lemoine M, Thursz M, Gore C, Swan T, Kamarulzaman A, et al. Viral hepatitis and the Global Burden of Disease: a need to regroup. J Viral Hepat. 2013;20:600–601.
    1. 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.
    1. Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med. 2001;345:41–52.
    1. Causes of death in HIV-1-infected patients treated with antiretroviral therapy, 1996-2006: collaborative analysis of 13 HIV cohort studies. Clin Infect Dis. 2010;50:1387–1396. [52 Collaborators.]
    1. Razavi H, ElKhoury AC, Elbasha E, Estes C, Pasini K, Poynard T, et al. Chronic hepatitis C virus (HCV) disease burden and cost in the United States. Hepatology. 2013;57:2164–2170.
    1. Ford N, Kirby C, Singh K, Mills EJ, Cooke G, Kamarulzaman A, et al. Chronic hepatitis C treatment outcomes in low- and middle-income countries: a systematic review and meta-analysis. Bull WHO. 2012;90:540–550.
    1. Ford N, Singh K, Cooke GS, Mills EJ, von Schoen-Angerer T, Kamarulzaman A, et al. Expanding access to treatment for hepatitis C in resource-limited settings: lessons from HIV/AIDS. Clin Infect Dis. 2012;54:1465–1472.
    1. Davies A, Singh KP, Shubber Z, Ducros P, Mills EJ, Cooke G, et al. Treatment outcomes of treatment-naive Hepatitis C patients co-infected with HIV: a systematic review and meta-analysis of observational cohorts. PloS One. 2013;8:e55373.
    1. Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011;364:2405–2416.
    1. Poordad F, McCone J, Jr, Bacon BR, Bruno S, Manns MP, Sulkowski MS, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Ned. 2011;364:1195–1206.
    1. Lawitz E, Lalezari JP, Hassanein T, Kowdley KV, Poordad FF, Sheikh AM, et al. Sofosbuvir in combination with peginterferon alfa-2a and ribavirin for non-cirrhotic, treatment-naive patients with genotypes 1, 2, and 3 hepatitis C infection: a randomised, double-blind, phase 2 trial. Lancet Infect Dis. 2013;13:401–408.
    1. Lawitz E, Poordad F, Kowdley KV, Cohen DE, Podsadecki T, Siggelkow S, et al. A phase 2a trial of 12-week interferon-free therapy with two direct-acting antivirals (ABT-450/r, ABT-072) and ribavirin in IL28B C/C patients with chronic hepatitis C genotype 1. J Hepatol. 2013;59:18–23.
    1. Lawitz E, Poordad FF, Pang PS, Hyland RH, Ding X, Mo H, et al. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet. 2014;383:515–523.
    1. Everson GT, Sims KD, Rodriguez-Torres M, Hezode C, Lawitz E, Bourliere M, et al. Efficacy of an interferon- and ribavirin-free regimen of daclatasvir, asunaprevir, and BMS-791325 in treatment-naive patients with HCV genotype 1 infection. Gastroenterology. 2014;146:420–429.
    1. Timm J, Roggendorf M. Sequence diversity of hepatitis C virus: implications for immune control and therapy. World J Gastroenterol. 2007;13:4808–4817.
    1. Swadling L, Klenerman P, Barnes E. Ever closer to a prophylactic vaccine for HCV. Expert Opin Biol Ther. 2013;13:1109–1124.
    1. Barnes E, Folgori A, Capone S, Swadling L, Aston S, Kurioka A, et al. Novel adenovirus-based vaccines induce broad and sustained T cell responses to HCV in man. Sci Transl Med. 2012;4:115ra111.
    1. Simmonds P, Alberti A, Alter HJ, Bonino F, Bradley DW, Brechot C, et al. A proposed system for the nomenclature of hepatitis C viral genotypes. Hepatology. 1994;19:1321–1324.
    1. Smith DB, Bukh J, Kuiken C, Muerhoff AS, Rice CM, Stapleton JT, et al. Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment Web resource. Hepatology. 2014;59:318–327.
    1. Smith DB, Pathirana S, Davidson F, Lawlor E, Power J, Yap PL, et al. The origin of hepatitis C virus genotypes. J Gen Virol. 1997;78((Pt 2)):321–328.
    1. Pybus OG, Cochrane A, Holmes EC, Simmonds P. The hepatitis C virus epidemic among injecting drug users. Infect Genet Evol. 2005;5:131–139.
    1. Magiorkinis G, Magiorkinis E, Paraskevis D, Ho SY, Shapiro B, Pybus OG, et al. The global spread of hepatitis C virus 1a and 1b: a phylodynamic and phylogeographic analysis. PLoS Med. 2009;6:e1000198.
    1. Simmonds P. The origin and evolution of hepatitis viruses in humans. J Gen Virol. 2001;82:693–712.
    1. Pybus OG, Barnes E, Taggart R, Lemey P, Markov PV, Rasachak B, et al. Genetic history of hepatitis C virus in East Asia. J Virol. 2009;83:1071–1082.
    1. Murphy DG, Willems B, Deschenes M, Hilzenrat N, Mousseau R, Sabbah S. Use of sequence analysis of the NS5B region for routine genotyping of hepatitis C virus with reference to C/E1 and 5' untranslated region sequences. J Clin Microbiol. 2007;45:1102–1112.
    1. Markov PV, van de Laar TJ, Thomas XV, Aronson SJ, Weegink CJ, van den Berk GE, et al. Colonial history and contemporary transmission shape the genetic diversity of hepatitis C virus genotype 2 in Amsterdam. J Virol. 2012;86:7677–7687.
    1. Murray CJ, Ezzati M, Flaxman AD, Lim S, Lozano R, Michaud C, et al. GBD 2010: design, definitions, and metrics. Lancet. 2012;380:2063–2066.
    1. Shannon CE. A mathematical theory of communication. Bell Syst Tech J. 1948;27:379–423, 623-656.
    1. Organization WH. World Health Statistics Annex 1: Regional and income groupings. Geneva, Switzerland: World Health Organization; 2013.
    1. Pybus OG, Markov PV, Wu A, Tatem AJ. Investigating the endemic transmission of the hepatitis C virus. Int J Parasitol. 2007;37:839–849.
    1. Negro F, Alberti A. The global health burden of hepatitis C virus infection. Liver Int. 2011;31(Suppl 2):1–3.
    1. Sulkowski MS, Gardiner DF, Rodriguez-Torres M, Reddy KR, Hassanein T, Jacobson I, et al. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med. 2014;370:211–221.
    1. Jacobson IM, Gordon SC, Kowdley KV, Yoshida EM, Rodriguez-Torres M, Sulkowski MS, et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med. 2013;368:1867–1877.
    1. Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, Gordon SC, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;368:1878–1887.
    1. McNally J. Safety and efficacy of sofosbuvir plus GS-5816 with or without ribavirin in treatment-naive subjects with chronic HCV infection. In: , NCT01858766: United States Food and Drug Administration; 2014.
    1. Roman F, Hawotte K, Struck D, Ternes AM, Servais JY, Arendt V, et al. Hepatitis C virus genotypes distribution and transmission risk factors in Luxembourg from 1991 to 2006. World J Gastroenterol. 2008;14:1237–1243.
    1. Morice Y, Cantaloube JF, Beaucourt S, Barbotte L, De Gendt S, Goncales FL, et al. Molecular epidemiology of hepatitis C virus subtype 3a in injecting drug users. J Med Virol. 2006;78:1296–1303.
    1. Uddin G, Shoeb D, Solaiman S, Marley R, Gore C, Ramsay M, et al. Prevalence of chronic viral hepatitis in people of south Asian ethnicity living in England: the prevalence cannot necessarily be predicted from the prevalence in the country of origin. J Viral Hepat. 2010;17:327–335.
    1. OECD. International migration data: inflows of foreign population. In: OECD, editor. Paris; 2012.
    1. Frank C, Mohamed MK, Strickland GT, Lavanchy D, Arthur RR, Magder LS, et al. The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt. Lancet. 2000;355:887–891.
    1. Germer JJ, Rys PN, Thorvilson JN, Persing DH. Determination of hepatitis C virus genotype by direct sequence analysis of products generated with the Amplicor HCV test. J Clin Microbiol. 1999;37:2625–2630.
    1. Hara K, Rivera MM, Koh C, Sakiani S, Hoofnagle JH, Heller T. Important factors in reliable determination of hepatitis C virus genotype by use of the 5' untranslated region. J Clin Microbiol. 2013;51:1485–1489.
    1. Laperche S, Lunel F, Izopet J, Alain S, Deny P, Duverlie G, et al. Comparison of hepatitis C virus NS5b and 5' noncoding gene sequencing methods in a multicenter study. J Clin Microbiol. 2005;43:733–739.
    1. Kenny-Walsh E. Clinical outcomes after hepatitis C infection from contaminated anti-D immune globulin. Irish Hepatology Research Group. N Engl J Med. 1999;340:1228–1233.
    1. Esteban JI, Sauleda S, Quer J. The changing epidemiology of hepatitis C virus infection in Europe. J Hepatol. 2008;48:148–162.
    1. de Bruijne J, Schinkel J, Prins M, Koekkoek SM, Aronson SJ, van Ballegooijen MW, et al. Emergence of hepatitis C virus genotype 4: phylogenetic analysis reveals three distinct epidemiological profiles. J Clin Microbiol. 2009;47:3832–3838.
    1. Fu Y, Qin W, Cao H, Xu R, Tan Y, Lu T, et al. HCV 6a prevalence in Guangdong province had the origin from Vietnam and recent dissemination to other regions of China: phylogeographic analyses. PloS One. 2012;7:e28006.

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