Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Epidemiology and natural history of HCV infection

Abstract

Worldwide, an estimated 130–170 million people have HCV infection. HCV prevalence is highest in Egypt at >10% of the general population and China has the most people with HCV (29.8 million). Differences in past HCV incidence and current HCV prevalence, together with the generally protracted nature of HCV disease progression, has led to considerable diversity in the burden of advanced liver disease in different countries. Countries with a high incidence of HCV or peak incidence in the recent past will have further escalations in HCV-related cirrhosis and hepatocellular carcinoma (HCC) over the next two decades. Acute HCV infection is difficult to detect because of the generally asymptomatic nature of the disease and the marginalization of at-risk populations. Around 25% of patients with acute HCV infection undergo spontaneous clearance, with increased rates among those with favourable IL28B genotypes, acute symptoms and in women. The remaining 75% of patients progress to chronic HCV infection and are subsequently at risk of progression to hepatic fibrosis, cirrhosis and HCC. Chronic hepatitis C generally progresses slowly in the initial two decades, but can be accelerated during this time as a result of advancing age and co-factors such as heavy alcohol intake and HIV co-infection.

Key Points

  • Although many countries in Asia have a low-to-intermediate prevalence of HCV, around half of the global population of patients infected with HCV reside in this region

  • Many countries have 'ageing cohorts' of people with HCV owing to peak HCV incidences in the recent past (2000 in Australia, 1980s in the USA) or distant past (1920–1940s in Japan)

  • Changes in levels of HCV RNA during acute HCV infection might guide early therapeutic intervention, with levels in patients with viral clearance or persistence diverging after 3–4 months of infection

  • The disease progression of chronic HCV infection often accelerates after 20 years of infection, with lifestyle factors key drivers of hepatic fibrosis

  • Direct-acting antiviral therapies should provide a paradigm shift in treatment over the next few years

  • However, unless rates of diagnosis of HCV and access to treatment improve dramatically, direct-acting antivirals will have a limited effect on global disease burden

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The estimated prevalence of HCV infection and the distribution of HCV genotypes across the world.
Figure 2
Figure 3: Dynamics of acute HCV infection from 2 months after infection, split by infection outcome.
Figure 4: The disparity between potential HCV treatment efficacy and projected HCV treatment effectiveness.

Similar content being viewed by others

References

  1. Grebely, J. & Dore, G. J. What is killing people with hepatitis C virus infection? Semin. Liver Dis. 31, 331–339 (2011).

    Article  PubMed  Google Scholar 

  2. Dore, G. J. The changing therapeutic landscape for hepatitis C. Med. J. Aust. 196, 629–632 (2012).

    Article  PubMed  Google Scholar 

  3. Thomas, D. L. Curing hepatitis C with pills: A step toward global control. Lancet 376, 1441–1442 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Lavanchy, D. The global burden of hepatitis C. Liver Int. 29, 74–81 (2009).

    Article  PubMed  Google Scholar 

  5. The Global Burden of Hepatitis C Working Group. Global burden of disease (GBD) for hepatitis C. J. Clin. Pharmacol. 44, 20–29 (2004).

  6. Lavanchy, D. Evolving epidemiology of hepatitis C virus. Clin. Microbiol. Infect. 17, 107–115 (2011).

    Article  CAS  PubMed  Google Scholar 

  7. World Health Organization. Hepatitis C–global prevalence (update). Weekly Epidemiological Record 49, 425–427 (1999).

  8. Nerrienet, E. et al. Hepatitis C virus infection in Cameroon: A cohort-effect. J. Med. Virol. 76, 208–214 (2005).

    Article  PubMed  Google Scholar 

  9. Guerra, J., Garenne, M., Mohamed, M. K. & Fontanet, A. HCV burden of infection in Egypt: results from a nationwide survey. J. Viral Hepat. 19, 560–567 (2012).

    Article  CAS  PubMed  Google Scholar 

  10. Centers for Disease Control and Prevention. Viral hepatitis surveillance—United States, 2010 (updated 2012) [online], (2012).

  11. Rantala, M. & van de Laar, M. J. Surveillance and epidemiology of hepatitis B and C in Europe—a review. Euro Surveill. 13, 194–204 (2008).

    Article  Google Scholar 

  12. Armstrong, G. L. et al. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann. Intern. Med. 144, 705–714 (2006).

    Article  PubMed  Google Scholar 

  13. Vriend, H. J. et al. Hepatitis C virus seroprevalence in the Netherlands. Eur. J. Pub. Health 22, 819–821 (2012).

    Article  Google Scholar 

  14. Dalgard, O., Jeansson, S., Skaug, K., Raknerud, N. & Bell, H. Hepatitis C in the general adult population of Oslo: prevalence and clinical spectrum. Scand. J. Gastroenterol. 38, 864–870 (2003).

    Article  CAS  PubMed  Google Scholar 

  15. Harris, R. J. et al. Hepatitis C prevalence in England remains low and varies by ethnicity: An updated evidence synthesis. Eur. J. Pub. Health 22, 187–192 (2012).

    Article  Google Scholar 

  16. Meffre, C. et al. Prevalence of hepatitis B and hepatitis C virus infections in France in 2004: Social factors are important predictors after adjusting for known risk factors. J. Med. Virol. 82, 546–555 (2010).

    Article  PubMed  Google Scholar 

  17. The Kirby Institute. HIV, Viral Hepatitis and Sexually Transmissible Infections in Australia. Annual Surveillance Report 2012 (The Kirby Institute, the University of New South Wales, 2012).

  18. Tanaka, J. et al. Sex- and age-specific carriers of hepatitis B and C viruses in Japan estimated by the prevalence in the 3,485,648 first-time blood donors during 1995–2000. Intervirology 47, 32–40 (2004).

    Article  PubMed  Google Scholar 

  19. Alter, M. J. Epidemiology of hepatitis C virus infection. World J. Gastroenterol. 13, 2436–2441 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Alter, M. J. et al. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N. Engl. J. Med. 341, 556–562 (1999).

    Article  CAS  PubMed  Google Scholar 

  21. Chak, E., Talal, A. H., Sherman, K. E., Schiff, E. R. & Saab, S. Hepatitis C virus infection in USA: An estimate of true prevalence. Liver Int. 31, 1090–1101 (2011).

    Article  PubMed  Google Scholar 

  22. Armstrong, G. L., Alter, M. J., McQuillan, G. M. & Margolis, H. S. The past incidence of hepatitis C virus infection: Implications for the future burden of chronic liver disease in the United States. Hepatology 31, 777–782 (2000).

    Article  CAS  PubMed  Google Scholar 

  23. Williams, I. Epidemiology of hepatitis C in the United States. Am. J. Med. 107, 2–9 (1999).

    Article  Google Scholar 

  24. Williams, I. T., Bell, B. P., Kuhnert, W. & Alter, M. J. Incidence and transmission patterns of acute hepatitis C in the United States, 1982–2006. Arch. Intern. Med. 171, 242–248 (2011).

    Article  PubMed  Google Scholar 

  25. Razali, K. et al. Modelling the hepatitis C virus epidemic in Australia. Drug Alcohol Depend. 91, 228–235 (2007).

    Article  PubMed  Google Scholar 

  26. Sievert, W. et al. A systematic review of hepatitis C virus epidemiology in Asia, Australia and Egypt. Liver Int. 31, 61–80 (2011).

    Article  PubMed  Google Scholar 

  27. Yoshizawa, H. Hepatocellular carcinoma associated with hepatitis C virus infection in Japan: Projection to other countries in the foreseeable future. Oncology 62, 8–17 (2002).

    Article  PubMed  Google Scholar 

  28. Tanaka, Y. et al. Molecular evolutionary analyses implicate injection treatment for schistosomiasis in the initial hepatitis C epidemics in Japan. J. Hepatol. 42, 47–53 (2005).

    Article  CAS  PubMed  Google Scholar 

  29. Mühlberger, N. et al. HCV-related burden of disease in Europe: A systematic assessment of incidence, prevalence, morbidity, and mortality. BMC Public Health 9, 34 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Gheorghe, L., Iacob, S. & Csiki, I. E. Prevalence of hepatitis C in Romania: Different from European rates? J. Hepatol. 49, 661–662 (2008).

    Article  PubMed  Google Scholar 

  31. Lvov, D. K. et al. Prevalence of hepatitis C virus and distribution of its genotypes in Northern Eurasia. Arch. Virol. 141, 1613–1622 (1996).

    Article  CAS  PubMed  Google Scholar 

  32. Ansaldi, F. et al. Different seroprevalence and molecular epidemiology patterns of hepatitis C virus infection in Italy. J. Med. Virol. 76, 327–332 (2005).

    Article  CAS  PubMed  Google Scholar 

  33. Delarocque-Astagneau, E. et al. An incident case-control study of modes of hepatitis C virus transmission in France. Ann. Epidemiol. 17, 755–762 (2007).

    Article  PubMed  Google Scholar 

  34. Duberg, A., Janzon, R., Bäck, E., Ekdahl, K. & Blaxhult, A. The epidemiology of hepatitis C virus infection in Sweden. Euro Surveill. 13, 181–185 (2008).

    Article  Google Scholar 

  35. Prasad, L. et al. Cohort profile: The Swiss Hepatitis C Cohort Study (SCCS). Int. J. Epidemiol. 36, 731–737 (2007).

    Article  PubMed  Google Scholar 

  36. Cornberg, M. et al. A systematic review of hepatitis C virus epidemiology in Europe, Canada and Israel. Liver Int. 31, 30–60 (2011).

    Article  PubMed  Google Scholar 

  37. Defossez, G. et al. Evaluation of the French national plan to promote screening and early management of viral hepatitis C, between 1997 and 2003: A comparative cross-sectional study in Poitou-Charentes region. Eur. J. Gastroenterol. Hepatol. 20, 367–372 (2008).

    Article  PubMed  Google Scholar 

  38. Delarocque-Astagneau, E. et al. The impact of the prevention programme of hepatitis C over more than a decade: The French experience. J. Viral Hepat. 17, 435–443 (2010).

    Article  CAS  PubMed  Google Scholar 

  39. Naoumov, N. V. Hepatitis C virus infection in Eastern Europe. J. Hepatol. 31 (Suppl. 1), 84–87 (1999).

    Article  PubMed  Google Scholar 

  40. Esteban, J. I., Sauleda, S. & Quer, J. The changing epidemiology of hepatitis C virus infection in Europe. J. Hepatol. 48, 148–162 (2008).

    Article  PubMed  Google Scholar 

  41. Miller, F. D. & Abu-Raddad, L. J. Evidence of intense ongoing endemic transmission of hepatitis C virus in Egypt. Proc. Natl Acad. Sci. 107, 14757–14762 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Centers for Disease Control and Prevention. Progress toward prevention and control of hepatitis C virus infection—Egypt, 2001–2012. MMWR 61, 545–549 (2012).

  43. Frank, C. et al. The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt. Lancet 355, 887–891 (2000).

    Article  CAS  PubMed  Google Scholar 

  44. Paez Jimenez, A. et al. HCV iatrogenic and intrafamilial transmission in Greater Cairo, Egypt. Gut 59, 1554–1560 (2010).

    Article  CAS  PubMed  Google Scholar 

  45. Plancoulaine, S. et al. Dissection of familial correlations in hepatitis C virus (HCV) seroprevalence suggests intrafamilial viral transmission and genetic predisposition to infection. Gut 57, 1268–1274 (2008).

    Article  CAS  PubMed  Google Scholar 

  46. Mohamed, M. K. et al. Intrafamilial transmission of hepatitis C in Egypt. Hepatology 42, 683–687 (2005).

    Article  PubMed  Google Scholar 

  47. Ali, S. A., Donahue, R. M. J., Qureshi, H. & Vermund, S. H. Hepatitis B and hepatitis C in Pakistan: prevalence and risk factors. Int. J. Infect. Dis. 13, 9–19 (2009).

    Article  PubMed  Google Scholar 

  48. Waheed, Y., Shafi, T., Safi, S. Z. & Qadri, I. Hepatitis C virus in Pakistan: A systematic review of prevalence, genotypes and risk factors. World J. Gastroenterol. 15, 5647–5653 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Merat, S. et al. Seroprevalence of hepatitis C virus: The first population-based study from Iran. Int. J. Infect. Dis. 14, e113–e116 (2010).

    Article  PubMed  Google Scholar 

  50. Alavian, S. M. Hepatitis C infection in Iran; A review article. Iranian J. Clin. Infect. Dis. 4, 47–59 (2009).

    Google Scholar 

  51. Xia, G.-L. et al. Prevalence of hepatitis B and C virus infections in the general Chinese population. Results from a nationwide cross-sectional seroepidemiologic study of hepatitis A, B, C, D, and E virus infections in China, 1992. Int. Hepatol. Comm. 5, 62–73 (1996).

    Article  Google Scholar 

  52. Lu, J. et al. General epidemiological parameters of viral hepatitis A, B, C, and E in six regions of China: a cross-sectional study in 2007. PLoS ONE 4, e8467 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Liu, F. et al. Hepatitis C seroprevalence and associated risk factors, Anyang, China. Emerg. Infect. Dis. 15, 1819–1822 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  54. Yan, Z. et al. Changing pattern of clinical epidemiology on hepatitis C virus infection in Southwest China. Hepatitis Monthly 12, 196–204 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Paez Jimenez, A. et al. Injection drug use is a risk factor for HCV infection in urban Egypt. PLoS ONE 4, e7193 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Thaikruea, L. et al. Risk factors for hepatitis C virus infection among blood donors in northern Thailand. Transfusion 44, 1433–1440 (2004).

    Article  PubMed  Google Scholar 

  57. Ohno, T. et al. New hepatitis C virus (HCV) genotyping system that allows for identification of HCV genotypes 1a, 1b, 2a, 2b, 3a, 3b, 4, 5a, and 6a. J. Clin. Microbiol. 35, 201–207 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Simmonds, P. et al. Geographical distribution of hepatitis C virus genotypes in blood donors: An international collaborative survey. J. Clin. Microbiol. 32, 884–892 (1994).

    Google Scholar 

  59. Kaba, S. et al. Molecular epidemiology of hepatitis C in Australia. J. Gastroenterol. Hepatol. 13, 914–920 (1998).

    Article  CAS  PubMed  Google Scholar 

  60. Chlabicz, S. et al. Changing HCV genotypes distribution in Poland—Relation to source and time of infection. J. Clin. Virol. 42, 156–159 (2008).

    Article  PubMed  Google Scholar 

  61. Tallo, T. et al. Genetic characterization of hepatitis C virus strains in Estonia: Fluctuations in the predominating subtype with time. J. Med. Virol. 79, 374–382 (2007).

    Article  PubMed  Google Scholar 

  62. Katsoulidou, A. et al. Molecular epidemiology of hepatitis C virus (HCV) in Greece: Temporal trends in HCV genotype-specific incidence and molecular characterization of genotype 4 isolates. J. Viral Hepat. 13, 19–27 (2006).

    Article  CAS  PubMed  Google Scholar 

  63. Payan, C. et al. Changing of hepatitis C virus genotype patterns in France at the beginning of the third millenium: The GEMHEP GenoCII Study. J. Viral Hepat. 12, 405–413 (2005).

    Article  CAS  PubMed  Google Scholar 

  64. Delwaide, J. et al. HCV genotype 4 in Belgium: three distinct patterns among patients from European and African origin. Eur. J. Gastroenterol. Hepatol. 18, 707–712 (2006).

    Article  PubMed  Google Scholar 

  65. Fernández-Arcás, N. et al. High prevalence of hepatitis C virus subtypes 4c and 4d in Malaga (Spain): Phylogenetic and epidemiological analyses. J. Med. Virol. 78, 1429–1435 (2006).

    Article  CAS  PubMed  Google Scholar 

  66. Kamal, S. M. & Nasser, I. A. Hepatitis C genotype 4: What we know and what we don't yet know. Hepatology 47, 1371–1383 (2008).

    Article  CAS  PubMed  Google Scholar 

  67. Shobokshi, O. A., Serebour, F. E., Skakni, L., Al-Saffy, Y. H. & Ahdal, M. N. Hepatitis C genotypes and subtypes in Saudi Arabia. J. Med. Virol. 58, 44–48 (1999).

    Article  CAS  PubMed  Google Scholar 

  68. Antaki, N. et al. The unexpected discovery of a focus of hepatitis C virus genotype 5 in a Syrian province. Epidemiol. Infect. 137, 79–84 (2009).

    Article  CAS  PubMed  Google Scholar 

  69. Murphy, D. G. et al. Biological and clinicopathological features associated with hepatitis C virus type 5 infections. J. Hepatol. 24, 109–113 (1996).

    Article  CAS  PubMed  Google Scholar 

  70. Duc, A. P. et al. High prevalence of hepatitis C virus genotype 6 in Vietnam. Asian Pac. J. Allergy Immunol. 27, 153–160 (2009).

    Google Scholar 

  71. Li, C. S. Y., Chan, P. K. S. & Tang, J. W. Molecular epidemiology of hepatitis C genotype 6a from patients with chronic hepatitis C from Hong Kong. J. Med. Virol. 81, 628–633 (2009).

    Article  CAS  PubMed  Google Scholar 

  72. Lozano, R. et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380, 2095–2128 (2012).

    Article  PubMed  Google Scholar 

  73. Perz, J. F., Armstrong, G. L., Farrington, L. A., Hutin, Y. J. F. & Bell, B. P. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J. Hepatol. 45, 529–538 (2006).

    Article  PubMed  Google Scholar 

  74. Wasley, A. & Alter, M. J. Epidemiology of hepatitis C: Geographic differences and temporal trends. Semin. Liver Dis. 20, 1–16 (2000).

    Article  CAS  PubMed  Google Scholar 

  75. Anwar, W. A., Khaled, H. M., Amra, H. A., El-Nezami, H. & Loffredo, C. A. Changing pattern of hepatocellular carcinoma (HCC) and its risk factors in Egypt: Possibilities for prevention. Mutat. Res. 659, 176–184 (2008).

    Article  CAS  PubMed  Google Scholar 

  76. Deuffic-Burban, S., Mohamed, M. K., Larouze, B., Carrat, F. & Valleron, A.-J. Expected increase in hepatitis C-related mortality in Egypt due to pre-2000 infections. J. Hepatol. 44, 455–461 (2006).

    Article  PubMed  Google Scholar 

  77. Arfè, A. et al. Cancer mortality trend analysis in Italy, 1970–2007. Eur. J. Cancer Prevent. 20, 364–374 (2011).

    Article  Google Scholar 

  78. Tanaka, H. et al. Declining incidence of hepatocellular carcinoma in Osaka, Japan, from 1990 to 2003. Ann. Intern. Med. 148, 820–826 (2008).

    Article  PubMed  Google Scholar 

  79. Davis, G. L., Alter, M. J., El-Serag, H., Poynard, T. & Jennings, L. W. Aging of hepatitis C virus (HCV)-infected persons in the United States: a multiple cohort model of HCV prevalence and disease progression. Gastroenterology 138, 513–521 (2010).

    Article  PubMed  Google Scholar 

  80. Amin, J. et al. Liver cancer and hepatitis B and C in New South Wales, 1990–2002: A linkage study. Aust. NZ J. Public Health 31, 475–482 (2007).

    Article  Google Scholar 

  81. Deuffic-Burban, S., Mathurin, P. & Valleron, A. J. Modelling the past, current and future HCV burden in France: Detailed analysis and perspectives. Stat. Methods Med. Res. 18, 233–252 (2009).

    Article  PubMed  Google Scholar 

  82. Sagmeister, M., Renner, E. L., Mullhaupt, B. & Wong, J. B. Simulation of hepatitis C based on a mandatory reporting system. Eur. J. Gastroenterol. Hepatol. 14, 25–34 (2002).

    Article  PubMed  Google Scholar 

  83. Orland, J. R., Wright, T. L. & Cooper, S. Acute hepatitis C. Hepatology 33, 321–327 (2001).

    Article  CAS  PubMed  Google Scholar 

  84. Cox, A. L. et al. Prospective evaluation of community-acquired acute-phase hepatitis C virus infection. Clin. Infect. Dis. 40, 951–958 (2005).

    Article  PubMed  Google Scholar 

  85. Page-Shafer, K. et al. Testing strategy to identify cases of acute hepatitis C virus (HCV) infection and to project HCV incidence rates. J. Clin. Microbiol. 46, 499–506 (2008).

    Article  PubMed  Google Scholar 

  86. Glynn, S. A. et al. Dynamics of viremia in early hepatitis C virus infection. Transfusion 45, 994–1002 (2005).

    Article  PubMed  Google Scholar 

  87. Hajarizadeh, B., Grebely, J. & Dore, G. J. Case definitions for acute hepatitis C virus infection: A systematic review. J. Hepatol. 57, 1349–1360 (2012).

    Article  PubMed  Google Scholar 

  88. Liu, L., Fisher, B. E., Thomas, D. L., Cox, A. L. & Ray, S. C. Spontaneous clearance of primary acute hepatitis C virus infection correlated with high initial viral RNA level and rapid HVR1 evolution. Hepatology 55, 1684–1691 (2012).

    Article  CAS  PubMed  Google Scholar 

  89. Hajarizadeh, B. et al. in The 8th Australasian Viral Hepatitis Conference 150 (Australasian Society for HIV Medicine, Auckland, New Zealand, 2012).

    Google Scholar 

  90. McGovern, B. H. et al. Improving the diagnosis of acute hepatitis C virus infection with expanded viral load criteria. Clin. Infect. Dis. 49, 1051–1060 (2009).

    Article  PubMed  Google Scholar 

  91. Grebely, J. et al. Plasma interferon-γ-inducible protein-10 (IP-10) levels during acute hepatitis C virus infection. Hepatology 57, 2124–2134 (2013).

    Article  CAS  PubMed  Google Scholar 

  92. Mosley, J. W. et al. Viral and host factors in early hepatitis C virus infection. Hepatology 42, 86–92 (2005).

    Article  CAS  PubMed  Google Scholar 

  93. Micallef, J. M., Kaldor, J. M. & Dore, G. J. Spontaneous viral clearance following acute hepatitis C infection: a systematic review of longitudinal studies. J. Viral Hepat. 13, 34–41 (2006).

    Article  CAS  PubMed  Google Scholar 

  94. Page, K. et al. Acute hepatitis C virus infection in young adult injection drug users: a prospective study of incident infection, resolution, and reinfection. J. Infect. Dis. 200, 1216–1226 (2009).

    Article  PubMed  Google Scholar 

  95. Lemon, S. M. Induction and evasion of innate antiviral responses by hepatitis C virus. J. Biol. Chem. 285, 22741–22747 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Rehermann, B. Hepatitis C virus versus innate and adaptive immune responses: a tale of coevolution and coexistence. J. Clin. Invest. 119, 1745–1754 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Takaki, A. et al. Cellular immune responses persist and humoral responses decrease two decades after recovery from a single-source outbreak of hepatitis C. Nat. Med. 6, 578–582 (2000).

    Article  CAS  PubMed  Google Scholar 

  98. Tillmann, H. L. et al. A polymorphism near IL28B is associated with spontaneous clearance of acute hepatitis C virus and jaundice. Gastroenterology 139, 1586–1592 (2010).

    Article  CAS  PubMed  Google Scholar 

  99. Grebely, J. et al. Potential role for interleukin-28B genotype in treatment decision-making in recent hepatitis C virus infection. Hepatology 52, 1216–1224 (2010).

    Article  CAS  PubMed  Google Scholar 

  100. Thomas, D. L. et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 461, 798–801 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Marcello, T. et al. Interferons alpha and lambda inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics. Gastroenterology 131, 1887–1898 (2006).

    Article  PubMed  Google Scholar 

  102. Ray, S. C. et al. Acute hepatitis C virus structural gene sequences as predictors of persistent viremia: hypervariable region 1 as a decoy. J. Virol. 73, 2938–2946 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Harris, H. E. et al. Does the clinical outcome of hepatitis C infection vary with the infecting hepatitis C virus type? J. Viral Hepat. 14, 213–220 (2007).

    Article  CAS  PubMed  Google Scholar 

  104. Poynard, T., Bedossa, P. & Opolon, P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. Lancet 349, 825–832 (1997).

    Article  CAS  PubMed  Google Scholar 

  105. Wiley, T. E., Brown, J. & Chan, J. Hepatitis C infection in African Americans: Its natural history and histological progression. Am. J. Gastroenterol. 97, 700–706 (2002).

    Article  PubMed  Google Scholar 

  106. Minola, E. et al. Age at infection affects the long-term outcome of transfusion-associated chronic hepatitis C. Blood 99, 4588–4591 (2002).

    Article  CAS  PubMed  Google Scholar 

  107. Graham, C. S. et al. Influence of human immunodeficiency virus infection on the course of hepatitis C virus infection: A meta-analysis. Clin. Infect. Dis. 33, 562–569 (2001).

    Article  CAS  PubMed  Google Scholar 

  108. Gaeta, G. B. et al. Epidemiological and clinical burden of chronic hepatitis B virus/hepatitis C virus infection. A multicenter Italian study. J. Hepatol. 39, 1036–1041 (2003).

    Article  PubMed  Google Scholar 

  109. Ratziu, V., Munteanu, M., Charlotte, F., Bonyhay, L. & Poynard, T. Fibrogenic impact of high serum glucose in chronic hepatitis C. J. Hepatol. 39, 1049–1055 (2003).

    Article  CAS  PubMed  Google Scholar 

  110. Hui, J. M. et al. Insulin resistance is associated with chronic hepatitis C and virus infection fibrosis progression. Gastroenterology 125, 1695–1704 (2003).

    Article  CAS  PubMed  Google Scholar 

  111. Hourigan, L. F. et al. Fibrosis in chronic hepatitis C correlates significantly with body mass index and steatosis. Hepatology 29, 1215–1219 (1999).

    Article  CAS  PubMed  Google Scholar 

  112. Leandro, G. et al. relationship between steatosis, inflammation, and fibrosis in chronic hepatitis C: a meta-analysis of individual patient data. Gastroenterology 130, 1636–1642 (2006).

    Article  PubMed  Google Scholar 

  113. Hutchinson, S. J., Bird, S. M. & Goldberg, D. J. Influence of alcohol on the progression of hepatitis C virus infection: A meta-analysis. Clin. Gastroenterol. Hepatol. 3, 1150–1159 (2005).

    Article  PubMed  Google Scholar 

  114. Hézode, C. et al. Daily cannabis smoking as a risk factor for progression of fibrosis in chronic hepatitis C. Hepatology 42, 63–71 (2005).

    Article  CAS  PubMed  Google Scholar 

  115. Hézode, C. et al. Impact of smoking on histological liver lesions in chronic hepatitis C. Gut 52, 126–129 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  116. Pessione, F. et al. Cigarette smoking and hepatic lesions in patients with chronic hepatitis C. Hepatology 34, 121–125 (2001).

    Article  CAS  PubMed  Google Scholar 

  117. Bochud, P. Y. et al. Genotype 3 is associated with accelerated fibrosis progression in chronic hepatitis C. J. Hepatol. 51, 655–666 (2009).

    Article  CAS  PubMed  Google Scholar 

  118. Poynard, T. et al. Rates and risk factors of liver fibrosis progression in patients with chronic hepatitis C. J. Hepatol. 34, 730–739 (2001).

    Article  CAS  PubMed  Google Scholar 

  119. Seeff, L. B. Natural history of chronic hepatitis C. Hepatology 36, s35–s46 (2002).

    PubMed  Google Scholar 

  120. Thein, H. H., Yi, Q., Dore, G. J. & Krahn, M. D. Estimation of stage-specific fibrosis progression rates in chronic hepatitis C virus infection: A meta-analysis and meta-regression. Hepatology 48, 418–431 (2008).

    Article  PubMed  Google Scholar 

  121. Thein, H. H., Yi, Q., Dore, G. J. & Krahn, M. D. Natural history of hepatitis C virus infection in HIV-infected individuals and the impact of HIV in the era of highly active antiretroviral therapy: a meta-analysis. AIDS 22, 1979–1991 (2008).

    Article  PubMed  Google Scholar 

  122. Freeman, A. J. et al. Estimating progression to cirrhosis in chronic hepatitis C virus infection. Hepatology 34, 809–816 (2001).

    Article  CAS  PubMed  Google Scholar 

  123. El-Serag, H. B. & Rudolph, K. L. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132, 2557–2576 (2007).

    Article  CAS  PubMed  Google Scholar 

  124. Fattovich, G., Stroffolini, T., Zagni, I. & Donato, F. Hepatocellular carcinoma in cirrhosis: Incidence and risk factors. Gastroenterology 127, S35–S50 (2004).

    Article  PubMed  Google Scholar 

  125. Hamada, H. et al. Impact of aging on the development of hepatocellular carcinoma in patients with posttransfusion chronic hepatitis C. Cancer 95, 331–339 (2002).

    Article  PubMed  Google Scholar 

  126. Masuzaki, R. et al. Prospective risk assessment for hepatocellular carcinoma development in patients with chronic hepatitis C by transient elastography. Hepatology 49, 1954–1961 (2009).

    Article  PubMed  Google Scholar 

  127. McDonald, S. A. et al. A population-based record linkage study of mortality in hepatitis C-diagnosed persons with or without HIV coinfection in Scotland. Stat. Methods Med. Res. 18, 271–283 (2009).

    Article  PubMed  Google Scholar 

  128. Walter, S. R. et al. Trends in mortality after diagnosis of hepatitis B or C infection: 1992–2006. J. Hepatol. 54, 879–886 (2011).

    Article  PubMed  Google Scholar 

  129. Grebely, J. et al. Impact of hepatitis C virus infection on all-cause and liver-related mortality in a large community-based cohort of inner city residents. J. Viral Hepat. 18, 32–41 (2011).

    Article  CAS  PubMed  Google Scholar 

  130. Degenhardt, L. et al. Mortality among clients of a state-wide opioid pharmacotherapy program over 20 years: Risk factors and lives saved. Drug Alcohol Depend. 105, 9–15 (2009).

    Article  PubMed  Google Scholar 

  131. Lee, M. H. et al. Chronic hepatitis C virus infection increases mortality from hepatic and extrahepatic diseases: a community-based long-term prospective study. J. Infect. Dis. 206, 469–477 (2012).

    Article  CAS  PubMed  Google Scholar 

  132. Giordano, T. P. et al. Risk of non-Hodgkin lymphoma and lymphoproliferative precursor diseases in US veterans with hepatitis C virus. JAMA 297, 2010–2017 (2007).

    Article  CAS  PubMed  Google Scholar 

  133. Bonner, J., Barritt, A. S., Fried, M. & Evon, D. Time to rethink antiviral treatment for hepatitis C in patients with coexisting mental health/substance abuse issues. Dig. Dis. Sci. 57, 1469–1474 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Arora, S. et al. Outcomes of treatment for hepatitis C virus infection by primary care providers. N. Engl. J. Med. 364, 2199–2207 (2011).

    Article  CAS  PubMed  Google Scholar 

  135. Larrey, D. et al. Education by a nurse increases response of patients with chronic hepatitis C to therapy with peginterferon-α2a and ribavirin. Clin. Gastroenterol. Hepatol. 9, 781–785 (2011).

    Article  PubMed  Google Scholar 

  136. Grebely, J. et al. Directly observed therapy for the treatment of hepatitis C virus infection in current and former injection drug users. J. Gastroenterol. Hepatol. 22, 1519–1525 (2007).

    Article  CAS  PubMed  Google Scholar 

  137. Grebely, J. et al. Optimizing assessment and treatment for hepatitis C virus infection in illicit drug users: A novel model incorporating multidisciplinary care and peer support. Eur. J. Gastroenterol. Hepatol. 22, 270–277 (2010).

    Article  PubMed  Google Scholar 

  138. Norman, J. et al. The acceptability and feasibility of peer worker support role in community based HCV treatment for injecting drug users. Harm. Reduction J. 5, 8 (2008).

    Article  Google Scholar 

  139. Sylvestre, D. L. & Zweben, J. E. Integrating HCV services for drug users: A model to improve engagement and outcomes. Int. J. Drug Policy 18, 406–410 (2007).

    Article  PubMed  Google Scholar 

  140. Butt, A. A. et al. Rate and predictors of treatment prescription for hepatitis C. Gut 56, 385–389 (2007).

    Article  PubMed  Google Scholar 

  141. Lettmeier, B. et al. Market uptake of new antiviral drugs for the treatment of hepatitis C. J. Hepatol. 49, 528–536 (2008).

    Article  PubMed  Google Scholar 

  142. Volk, M. L., Tocco, R., Saini, S. & Lok, A. S. F. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology 50, 1750–1755 (2009).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The Kirby Institute is funded by the Australian Government Department of Health and Ageing and is affiliated with the Faculty of Medicine, The University of New South Wales. B. Hajarizadeh is an Australian Postgraduate Award PhD scholar. J. Grebely is supported by a National Health and Medical Research Council Career Development Fellowship. G. J. Dore is supported by a National Health and Medical Research Council Practitioner Research Fellowship. The authors would also like to thank Dr Homie Razavi (Center for Disease Analysis) for contributing epidemiological data for the figures included in this manuscript.

Author information

Authors and Affiliations

Authors

Contributions

B. Hajarizadeh researched data for the article, contributed to discussion of content, wrote the article and reviewed/edited the manuscript before submission. J. Grebely and G. J. Dore researched data for the article, contributed to discussion of content and reviewed/edited the manuscript before submission.

Corresponding author

Correspondence to Behzad Hajarizadeh.

Ethics declarations

Competing interests

J. Grebely is a consultant/advisor for Merck. G. J. Dore is a consultant/advisor and has received research grants from AbbeVie, Bristol Myers Squibb, Gilead, Janssen, Merck and Roche. B. Hajarizadeh declares no competing interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hajarizadeh, B., Grebely, J. & Dore, G. Epidemiology and natural history of HCV infection. Nat Rev Gastroenterol Hepatol 10, 553–562 (2013). https://doi.org/10.1038/nrgastro.2013.107

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrgastro.2013.107

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing