Who Should We Screen for Hepatitis C: By Risk Or Birth Cohort?

January 8, 2014

By Jung-Eun Ha

Peer Reviewed

Over the last few years major changes have occurred in the diagnosis and treatment of hepatitis C. In 2011 the U.S. Food and Drug Administration (FDA) approved a rapid finger stick antibody test for hepatitis C virus (HCV) infection [1]. The FDA also approved the protease inhibitors telapravir (Incivek; Vertex Pharmaceuticals, Cambridge, Massachusetts; Johnson & Johnson, New Brunswick, New Jersey) and boceprevir (Victrelis; Merck, Whitehouse Station, New Jersey), for the treatment of genotype 1 hepatitis C [1]. In August 2012, the Centers for Disease Control & Prevention recommended one-time screening for hepatitis C in all persons born between 1945 and 1965 [2}. In June 2013, the U.S. Preventive Services Task Force (USPSTF) also recommended screening for HCV infection in high-risk individuals and one-time screening in individuals born between 1945 and 1965 (“B” recommendation) [3]. The birth-cohort recommendation exponentially expands the size of the screening population, which was previously limited to high-risk individuals: ever IV drug users, blood transfusion or organ transplant recipients before 1992, those ever on hemodialysis, healthcare workers exposed to HCV-infected blood, children born to HCV-positive mothers, and sexual partners of HCV-positive persons.

The update affects about 82 million Americans born between 1945 and 1965 [4]. The1999-2008 National Health and Nutrition Examination Survey revealed that HCV antibody prevalence in this cohort is 3.25%, or 2.7 million people, as opposed to 0.88% prevalence in people born outside of the cohort [2]. The prevalence is about 1.6% in the general population [5]. More than two-thirds of the chronically infected belong to the 1945-1965 baby-boomer cohort. Many of them were inadvertently exposed to HCV-infected blood before the discovery of HCV in 1989 and the development of a screening test in 1992. HCV incidence was highest during the 1980s. Given the slow progression from chronic HCV infection to cirrhosis and hepatocellular carcinoma over decades [6], now is the time to screen this birth cohort before complications start to appear. Advanced fibrosis of the liver shows poor response to HCV treatment, and is also more costly to treat [7].

Relying solely on risk-based screening in this birth cohort is not sufficient, as up to 45% of people ever infected with HCV may not recall any exposure risk and thus will not likely volunteer to get screened [2]. Fifty to eighty percent of the infected don’t know their HCV status [8]. The number of people born between 1945 and 1965 needed to screen to prevent one HCV-related death is 607.

Overall, one-time HCV screening of this birth cohort is estimated to cost around $15,700 per quality-adjusted life year (QALY) [9]. By comparison, screening for colorectal cancer with colonoscopy can cost about $10,000 to $25,000 per QALY [10], and requires repeated studies. HCV screening of the 1945-1965 cohort is likely a one-time screening event, as HCV incidence has decreased drastically over the years, thanks to effective blood screening and increased awareness of HCV transmission among IV drug users. Morbidity and mortality from chronic HCV infection will be even lower, with a number of direct acting antivirals in the pipeline [11-12]. A recent proof-of-concept study of vaccine against single strain of HCV [13] suggests that mass screening may not even be necessary in the future if, and hopefully when, primary prevention is possible and feasible.

Commentary by Dr. Vin Pham of the Division of Infectious Diseases

The rationale for identifying persons earlier in the course of their disease includes having a greater likelihood of achieving successful outcome after treatment. The registrational studies for interferon-based hepatitis C therapies have consistently shown lower rates of sustained virologic response for subjects with fibrosis scores of 3 or 4, demonstrating the need to identify and treat people in the earlier stages of fibrosis. Ironically, the development of an effective vaccine against HCV may further expand the need for testing for HCV infection, since obviously vaccine would only be offered to those not already infected.

Jung-Eun Ha is a 4th year medical student at NYU School of Medicine

Peer reviewed by Vinh Pham, MD, Infectious Disease, NYU Langone Medical Center

Image courtesy of Wikimedia Commons


[1] Getchell JP, Wroblewski KE, DeMaria A, et al. Testing for HCV infection: an update of guidance for clinicians and laboratorians. MMWR Morb Mortal Wkly Rep. 2013;62(18):1-4.  http://www.medscape.com/viewarticle/804472

[2] Smith BD, Morgan RL, Beckett GA, et al. Centers for Disease Control and Prevention. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945–1965. MMWR Recomm Rep. 2012;61(RR-4):1-32.  http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6104a1.htm

[3] U.S. Preventive Services Task Force. Screening for hepatitis C virus infection in adults: U.S. Preventive Services Task Force recommendation statement. http://www.uspreventiveservicestaskforce.org/uspstf12/hepc/hepcfinalrs.htm Published June 25, 2013. Accessed August 12, 2013.

[4] Centers for Disease Control and Prevention. Population projections, United States, 2004 – 2030, by state, age and sex. http://wonder.cdc.gov/population-projections.html.  Published 2005. Updated June 26, 2009. Accessed May 18, 2013.

[5] Armstrong G, Wasley A, Simard E, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006;144(10):705–714. http://www.ncbi.nlm.nih.gov/pubmed/16702586

[6] Chen SL, Morgan TR. The natural history of hepatitis C virus (HCV) infection. Int J Med Sci. 2006;3(2):47–52.  http://www.medsci.org/v03p0047

[7] Prati GM, Aghemo A, Rumi MG, et al. Hyporesponsiveness to PegIFNalpha2B plus ribavirin in patients with hepatitis C-related advanced fibrosis. J Hepatol. 2012;56(2):341-347.

[8] Hagan H, Campbell J, Thiede H, et al. Self-reported hepatitis C virus antibody status and risk behavior in young injectors. Public Health Rep. 2006;121(6):710-719.  http://www.ncbi.nlm.nih.gov/pubmed/17278406

[9] Rein DB, Smith BD, Wittenborn JS, et al. The cost-effectiveness of birth-cohort screening for hepatitis C antibody in U.S. primary care settings. Ann Intern Med. 2012;156(4):263-270.  http://www.ncbi.nlm.nih.gov/pubmed/22056542

[10] Pignone M, Saha S, Hoerger T, Mandelblatt J. Cost-effectiveness analyses of colorectal cancer screening: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2002;137(2):96-104.  http://www.ncbi.nlm.nih.gov/pubmed/12118964

[11] Schaefer E, Chung R. Antihepatitis C virus drugs in development. Gastroenterology 2012;142(6):1340–1350.  http://www.ncbi.nlm.nih.gov/pubmed/22537441

[12] Poordad F, Dieterich D. Treating hepatitis C: current standard of care and emerging direct-acting antiviral agents. J Viral Hepat. 2012;19(7):449–464.  http://www.ncbi.nlm.nih.gov/pubmed/22676357

[13] Law JL, Chen C, Wong J, et al. A hepatitis C virus (HCV) vaccine comprising envelope glycoproteins gpE1/gpE2 derived from a single isolate elicits broad cross-genotype neutralizing antibodies in humans.  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3602185/




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