1 Nature Medicine 2013 Vol: 19(7):850-858. DOI: 10.1038/nm.3184

Global control of hepatitis C: where challenge meets opportunity

We are entering an important new chapter in the story of hepatitis C virus (HCV) infection. There are clear challenges and opportunities. On the one hand, new HCV infections are still occurring, and an estimated 185 million people are or have previously been infected worldwide. Most HCV-infected persons are unaware of their status yet are at risk for life-threatening diseases such as cirrhosis and hepatocellular carcinoma (HCC), whose incidences are predicted to rise in the coming decade. On the other hand, new HCV infections can be prevented, and those that have already occurred can be detected and treated—viral eradication is even possible. How the story ends will largely be determined by the extent to which these rapidly advancing opportunities overcome the growing challenges and by the vigor of the public health response.

Mentions
Figures
Figure 1: Outcomes associated with HCV infection.After acute infection, most persons develop viral persistence. Fatigue, joint pain, depression and a variety of skin manifestations can occur but are not usually diagnostic. In otherwise healthy persons infected at young ages, after decades some develop cirrhosis, end-state liver disease or HCC. There are wide ranges of the frequencies of these outcomes owing to differences in host factors such as race, age, HIV infection status and, for progression to end-stage disease, alcohol use. Figure 2: Global prevalence of HCV-specific antibodies.On the basis of a meta-analysis of 232 studies published in 1997–2007, point prevalences are calculated using regional population weights46. GBD, global burden of diseases. Figure 3: Dynamic course of HCV infection in the US.As the cohort born between 1945 and 1965 ages, a greater fraction will have HCV infection for sufficient time at old-enough ages to develop liver failure and HCC. Figure 4: Importance of expanding testing and treatment to impact the global prevalence of HCV infection.Because the percentage cured is a function of the distribution of many variables such as genotype, age, and race, the y axis arbitrarily shows the efficacy of treatment, which is increasing but having little impact on the overall burden of disease represented by the total area of the figure. In 2005, an estimated 130–170 million individuals had chronic HCV infection, whereas >185 million individuals had HCV-specific antibodies (ref. 46).
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    • . . . For example, Mehta et al.61 reported that the HCV infection incidence declined in consecutive injection drug–using cohorts in Baltimore from 1988 through 2008. . . .
    • . . . Although in some settings HCV incidence has declined among injection drug users, new infections still occur at incidences of 5–30% per year61, 79 . . .
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    • . . . Responses were improved in 1998 by combining interferon-α with oral ribavirin and then in 2001–2002 by linking the interferon molecule with polyethylene glycol, producing peginterferon-α62, 63, 64 . . .
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    • . . . Responses were improved in 1998 by combining interferon-α with oral ribavirin and then in 2001–2002 by linking the interferon molecule with polyethylene glycol, producing peginterferon-α62, 63, 64 . . .
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    • . . . Responses were improved in 1998 by combining interferon-α with oral ribavirin and then in 2001–2002 by linking the interferon molecule with polyethylene glycol, producing peginterferon-α62, 63, 64 . . .
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    • . . . For infection with genotype 1 HCV, an additional advance came in 2011 with the approval of the HCV protease inhibitors telaprevir and boceprevir65, 66 . . .
    • . . . The SVR rate for the most difficult-to-treat genotype 1 HCV infection was ~40% in 2010 (ref. 67) and ~66% in 2011 (refs. 65,66) and is anticipated to be >75% by 2014. (Actual SVR figures depend on multiple factors including the percentage of patients who are black or have cirrhosis.) . . .
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    • . . . For infection with genotype 1 HCV, an additional advance came in 2011 with the approval of the HCV protease inhibitors telaprevir and boceprevir65, 66 . . .
    • . . . The SVR rate for the most difficult-to-treat genotype 1 HCV infection was ~40% in 2010 (ref. 67) and ~66% in 2011 (refs. 65,66) and is anticipated to be >75% by 2014. (Actual SVR figures depend on multiple factors including the percentage of patients who are black or have cirrhosis.) . . .
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    • . . . The SVR rate for the most difficult-to-treat genotype 1 HCV infection was ~40% in 2010 (ref. 67) and ~66% in 2011 (refs. 65,66) and is anticipated to be >75% by 2014. (Actual SVR figures depend on multiple factors including the percentage of patients who are black or have cirrhosis.) . . .
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    • . . . Successful treatment of HCV infection is associated with a reduced incidence of liver disease progression, including cirrhosis, end-stage liver disease and HCC68, 69, 70, 71 . . .
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    • . . . Successful treatment of HCV infection is associated with a reduced incidence of liver disease progression, including cirrhosis, end-stage liver disease and HCC68, 69, 70, 71 . . .
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    • . . . Successful treatment of HCV infection is associated with a reduced incidence of liver disease progression, including cirrhosis, end-stage liver disease and HCC68, 69, 70, 71 . . .
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    • . . . A study of persons with advanced fibrosis or cirrhosis (Ishak fibrosis stage 4–6) who received interferon-based HCV treatment between 1990 and 2003 followed 530 patients over a median of 8.4 years72 . . .
  73. Backus, L.I. A sustained virologic response reduces risk of all-cause mortality in patients with hepatitis C Clin. Gastroenterol. Hepatol. 9, 509-516 (2011) .
    • . . . Another study of US veterans who started HCV treatment between January 2001 and June 2007 found a clear survival benefit to those who achieved SVR73 . . .
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    • . . . Moreover, a recent systematic review found clear evidence that successful therapy reduced the incidences of liver failure, HCC and mortality74. . . .
  75. Bernstein, D. Relationship of health-related quality of life to treatment adherence and sustained response in chronic hepatitis C patients Hepatology 35, 704-708 (2002) .
    • . . . Similarly, successful treatment of HCV infection can improve quality of life75, 76 . . .
    • . . . Bernstein et al.75 evaluated the change in health-related quality-of-life reports from baseline to end of follow-up for 1,441 persons from international studies of HCV treatment . . .
  76. John-Baptiste, A.A. Sustained responders have better quality of life and productivity compared with treatment failures long after antiviral therapy for hepatitis C Am. J. Gastroenterol. 104, 2439-2448 (2009) .
    • . . . Similarly, successful treatment of HCV infection can improve quality of life75, 76 . . .
    • . . . Likewise, another study reported better quality-of-life results, fewer absences from work and greater involvement in volunteer and household activities among HCV-infected persons with successful treatment responses compared to those whose treatment was unsuccessful76 . . .
  77. Liang, J. Nat. Med. 19, aaa-bbb (2013) .
    • . . . These, and other factors, have constrained HCV vaccine development (see Review in this issue of Nature Medicine by Liang77) . . .
  78. Patel, P.R. Hepatitis C virus infections from a contaminated radiopharmaceutical used in myocardial perfusion studies J. Am. Med. Assoc. 296, 2005-2011 (2006) .
    • . . . Although we know how to prevent HCV transmission from healthcare practices, the leading route of HCV transmission worldwide is unsafe medical procedures44, 46, 47, 49, 50, 78 . . .
  79. Hagan, H. Attribution of hepatitis C virus seroconversion risk in young injection drug users in 5 US cities J. Infect. Dis. 201, 378-385 (2010) .
    • . . . Although in some settings HCV incidence has declined among injection drug users, new infections still occur at incidences of 5–30% per year61, 79 . . .
  80. Hagan, H. Reduced risk of hepatitis B and hepatitis C among injection drug users in the Tacoma syringe exchange program Am. J. Public Health 85, 1531-1537 (1995) .
    • . . . Measures such as needle exchanges may have contributed to the reduced incidence in some places80 but have not been sufficient and, from a global perspective, have had a minimal impact on HCV transmission . . .
  81. van de Laar, T. Evidence of a large, international network of HCV transmission in HIV-positive men who have sex with men Gastroenterology 136, 1609-1617 (2009) .
    • . . . Multiple outbreaks of new HCV infections have been reported among male homosexual populations81, and, as with the case in injection drug users, in some instances these infections have negated the benefits of prior successful treatment82 . . .
  82. Grebely, J. Reinfection with hepatitis C virus following sustained virological response in injection drug users J. Gastroenterol. Hepatol. 25, 1281-1284 (2010) .
    • . . . Multiple outbreaks of new HCV infections have been reported among male homosexual populations81, and, as with the case in injection drug users, in some instances these infections have negated the benefits of prior successful treatment82 . . .
  83. Cottrell, E.B.; Chou, R.; Wasson, N.; Rahman, B.; Guise, J.-M. Reducing risk for mother-to-infant transmission of hepatitis C virus: a systematic review for the U.S. Preventive Services Task Force Ann. Intern. Med. 158, 109-113 (2013) .
    • . . . Methods to prevent transmission from a mother to her infant (such as cesarean section, maternal treatment and infant vaccination) that have worked for other infectious diseases have either not worked for HCV or are not yet possible83 . . .
  84. Denniston, M.M. Awareness of infection, knowledge of hepatitis C, and medical follow-up among individuals testing positive for hepatitis C: National Health and Nutrition Examination Survey 2001–2008 Hepatology 55, 1652-1661 (2012) .
    • . . . In a 2001–2008 NHANES survey of US households, 393 HCV-specific antibody–positive persons were identified, and 170 were contacted after being notified of their HCV status through the study84 . . .
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    • . . . In Europe, by 2006 it was estimated that chronic hepatitis C treatment was provided for 308,000 persons who comprised no more than 16% of the HCV-infected persons in any individual country85 . . .
  86. Volk, M.L. Public health impact of antiviral therapy for hepatitis C in the United States Hepatology 50, 1750-1755 (2009) .
    • . . . In the United States, from 2002 to 2007 an estimated 663,000 of the ~4 million HCV-infected persons were treated86 . . .
  87. Kramer, J.R. Gaps in the achievement of effectiveness of HCV treatment in national VA practice J. Hepatol. 56, 320-325 (2012) .
    • . . . In one analysis of nearly 100,000 US veterans with chronic hepatitis C, only 11.6% received and 6.4% completed treatment87. . . .
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  89. Smith, B.D. Hepatitis C virus testing of persons born during 1945 to 1965: recommendations from the Centers for Disease Control and Prevention Ann. Intern. Med. 157, 817-822 (2012) .
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