Research Article
Comparison of Hepatitis C Virus Testing Strategies: Birth Cohort Versus Elevated Alanine Aminotransferase Levels

https://doi.org/10.1016/j.amepre.2014.05.011Get rights and content

Background

Hepatitis C virus (HCV) infection is unidentified in an estimated 40%–85% of infected adults. Surveillance and modeling data have found significant increases in HCV-associated morbidity and mortality.

Purpose

To compare two HCV antibody (anti-HCV) testing strategies based on (1) elevated alanine aminotransferase levels (ALT) and (2) a birth cohort approach for people born during 1945–1965.

Methods

Data from 19,055 adults aged 20–70 years who completed the National Health and Nutrition Examination Survey in 1999–2008 were analyzed in 2013. Two independent models were evaluated, based on membership in the 1945–1965 birth cohort or elevated ALT, to compare the number of identified anti-HCV-positive (anti-HCV+) individuals; proportion of total identified cases; and the number of people that would be tested using either strategy.

Results

The prevalence of anti-HCV among adults aged 20–70 years was estimated at 2.0% (95% CI=1.8%, 2.3%), representing about 3.6 million people. The birth cohort strategy would result in testing about 85.4 million people and identifying nearly 2.8 million anti-HCV+ people with a sensitivity of 76.6%. The ALT strategy would test about 21.5 million adults and identify approximately 1.8 million anti-HCV+ people with a sensitivity of 50.0%. Implementing both strategies concurrently would identify 87.3% of anti-HCV+ adults.

Conclusions

The birth cohort strategy, which is recommended by both the CDC and the U.S. Preventive Services Task Force, would identify 1 million more anti-HCV+ people than the elevated ALT approach. Concurrent implementation would identify an even larger number of individuals ever infected.

Introduction

An estimated 4 million people have previously been infected with hepatitis C virus (HCV) in the U.S.1 All individuals infected with HCV develop antibodies (anti-HCV) and about 75%–85% have evidence of HCV-RNA, indicating chronic (current) infection.1, 2 Most people living with HCV infection are adults in their late forties to late sixties and thought to have been infected 25–45 years ago.3, 4 Without testing and treatment over their lifetimes, the CDC estimates that 60% of people with HCV infection will develop cirrhosis.5

In 2007, HCV infection surpassed HIV as an underlying or contributing cause of mortality and accounted for more than 15,000 deaths in the U.S.6 It is projected that among adults with untreated HCV infection, 37% (1,071,000) will die from complications of hepatitis C in their lifetimes.5 Recent advances in direct-acting antiviral medications for HCV infection have increased cure rates to 90% in clinical trials.7, 8 However, any benefit from these new treatments requires identification of people with current infection.

Previous studies have estimated that 40%–85% of infected individuals may be undiagnosed and are not aware of their infection, methods to reduce the progression of their liver disease, or behavioral steps to avoid transmission.9, 10, 11, 12, 13, 14 Although risk-based testing can in principle identify approximately 79%–99% of HCV-infected people,1, 15, 16 it has been limited in its effectiveness in routine clinical practice.15, 17, 18, 19, 20, 21 For example, only 58%–63% of primary care providers inquire about patients’ history of risk factors for HCV infection.19, 20, 21 When probed, patients may not fully disclose past or current exposures.22, 23, 24, 25, 26

Additionally, an estimated 20%–30% of HCV-infected individuals do not report any risk factors and would not be identified by risk-based screening strategies.13, 14, 27 It has been suggested that provider motivation and the amount of clinical staff resources (e.g., time) required for adequate and sustainable evaluation of patients for risk factors may represent further limitations to risk-based testing.13, 28, 29

Alanine aminotransferase (ALT) is an enzyme produced by the liver that is a moderately sensitive indicator of liver injury when elevated; therefore, the CDC and the American Association for the Study of Liver Disease both recommend HCV testing for persons with elevated ALT levels.30, 31 Studies suggest that providers are more likely to test patients for HCV based on elevated ALT than on assessment of exposure risk factors.17, 32

The prevalence of HCV infection among individuals with elevated ALT levels may be several-fold higher compared with those with normal ALT levels.1, 10, 11, 33 Thus, it has been suggested that HCV testing based on abnormal ALT levels alone could be used to identify 56%–69% of asymptomatic anti-HCV-positive (anti-HCV+) people.30, 34 However, three recent studies9, 15, 35 in eight unique primary care settings found that of all people with elevated ALT, 43%–86% were not tested for anti-HCV.

Testing all individuals with elevated ALT would require that these levels be measured as part of routine care and providers have ready access to results; however, current literature35, 36, 37, 38 suggests that only an estimated 46% of patients are evaluated for liver function. The ALT strategy also has other limitations, including lack of a standard definition for the upper limit of normal (ULN)39, 40; sensitivity to demographic subgroups (i.e., gender, race/ethnicity)41, 42, 43, 44, 45, 46; alcohol consumption; fatty liver45; and the requirement for multiple tests over time to establish persistence.45, 47

In 2012, the CDC recommended a one-time HCV test48 for people born during 1945–1965, a high-prevalence cohort that is estimated to account for 67%–76% of adult HCV infections.1, 16, 49 The purpose of this analysis is to compare the sensitivity, number of identified cases, and size of the population that would be tested using either the birth cohort or elevated ALT testing strategy.

Section snippets

Study Population

The National Health and Nutrition Examination Survey (NHANES) is a cross-sectional, nationally representative, multistage, stratified probability cluster survey of the U.S civilian, non-institutionalized population. Each participant is interviewed and medically examined, during which biological specimens are collected for laboratory testing. Information on informed consent procedures, the survey design, and implementation is discussed in the survey documentation.50 Data collected from 1999 to

Participant Characteristics

The estimated interview response rate for adults aged 20–70 years from 1999 to 2008 was 76.4% (n=21,313/27,897) (Figure 1). Of the 21,313 participants who were interviewed, 20,341 (95.4%) were medically examined and 19,130 provided specimens for anti-HCV testing. The final analytic sample consisted of 19,055 participants (93.7% of those examined) following exclusion of participants with indeterminate anti-HCV results (n=75).

Characteristics of the study population are reported in Table 1. The

Discussion

Our findings indicate that targeting the high-prevalence birth cohort for HCV testing has the potential to identify about 1 million more anti-HCV+ people compared to a strategy based on a single elevated ALT result. The prevalence of anti-HCV within the birth cohort is about four times that in the adult population born before 1945 or after 1965, and using the birth cohort as the basis of anti-HCV testing would identify nearly 77% of anti-HCV cases in the U.S. adult population compared to 50%

Acknowledgments

The 50% sensitivity finding for the ALT strategy was previously published in support of the CDC’s recommendation to test people born during 1945–1965 for hepatitis C infection.

(Smith BD, Morgan RL, Beckett GA, Falck-Ytter Y, Holtzman D, Ward JW. Hepatitis C virus testing of persons born during 1945–1965: recommendations from the CDC. Ann Intern Med 2012;157[11]:817–22.). Support for this paper was provided entirely by the CDC.

The findings and conclusions in this report are those of the authors

References (75)

  • S.L. Chen et al.

    The natural history of hepatitis C virus (HCV) infection

    Int J Med Sci

    (2006)
  • G.L. Armstrong et al.

    The past incidence of hepatitis C virus infection: implications for the future burden of chronic liver disease in the U.S

    Hepatology

    (2000)
  • M.J. Alter

    HCV routes of transmission: what goes around comes around

    Semin Liver Dis

    (2011)
  • K.N. Ly et al.

    The increasing burden of mortality from viral hepatitis in the U.S. between 1999 and 2007

    Ann Intern Med

    (2012)
  • N. Hayashi et al.

    Once-daily simeprevir (TMC435) with peginterferon/ribavirin for treatment-naive hepatitis C genotype 1-infected patients in Japan: the DRAGON study

    J Gastroenterol

    (2014)
  • E. Lawitz et al.

    Sofosbuvir for previously untreated chronic hepatitis C infection

    N Engl J Med

    (2013)
  • P.R. Spradling et al.

    Hepatitis B and C virus infection among 1.2 million persons with access to care: factors associated with testing and infection prevalence

    Clin Infect Dis

    (2012)
  • W.N. Southern et al.

    Hepatitis C testing practices and prevalence in a high-risk urban ambulatory care setting

    J Viral Hepat

    (2011)
  • D.W. Roblin et al.

    HCV screening practices and prevalence in an MCO, 2000–2007

    Am J Manag Care

    (2011)
  • M.M. Denniston et al.

    Awareness of infection, knowledge of hepatitis C, and medical follow-up among individuals testing positive for hepatitis C: NHANES 2001–2008

    Hepatology

    (2012)
  • H. Hagan et al.

    Self-reported hepatitis C virus antibody status and risk behavior in young injectors

    Public Health Rep

    (2006)
  • Galbraith JW, Franco R, Rodgers J, et al. Screening in emergency department identifies a large cohort of unrecognized...
  • M.L. Drainoni et al.

    Effectiveness of a risk screener in identifying hepatitis C virus in a primary care setting

    Am J Public Health

    (2012)
  • K.J. Tomaszewski et al.

    Comparison of current U.S. risk strategy to screen for hepatitis C virus with a hypothetical targeted birth cohort strategy

    Am J Public Health

    (2012)
  • T.M. Shehab et al.

    Management of hepatitis C patients by primary care physicians in the USA: results of a national survey

    J Viral Hepat

    (2001)
  • P.O. Coffin et al.

    Patient acceptance of universal screening for hepatitis C virus infection

    BMC Infect Dis

    (2011)
  • J.B. Kallman et al.

    Screening for hepatitis B, C and non-alcoholic fatty liver disease: a survey of community-based physicians

    Aliment Pharmacol Ther

    (2009)
  • E.C. Clark et al.

    Hepatitis C identification and management by family physicians

    Fam Med

    (2005)
  • E.A. Torrone et al.

    Risk behavior disclosure during HIV test counseling

    AIDS Patient Care STDS

    (2010)
  • B.R. Edlin et al.

    Overcoming barriers to prevention, care, and treatment of hepatitis C in illicit drug users

    Clin Infect Dis

    (2005)
  • D. Swan et al.

    Barriers to and facilitators of hepatitis C testing, management, and treatment among current and former injecting drug users: a qualitative exploration

    AIDS Patient Care STDS

    (2010)
  • Batki S, Sorensen J. Care of injection drug users with HIV. In: Cohen PT, Sande MA, Volberding P, eds. The AIDS...
  • S.F. O’Brien et al.

    Understanding non-disclosure of deferrable risk: a study of blood donors with a history of intravenous drug use

    Transfus Med

    (2010)
  • H.R. Rosen

    Clinical practice. Chronic hepatitis C infection

    N Engl J Med

    (2011)
  • W.N. Southern et al.

    Physician nonadherence with a hepatitis C screening program

    Qual Manag Health Care

    (2014)
  • W.R. Kim et al.

    Public Policy Committee of the American Association for the Study of Liver Disease. Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease

    Hepatology

    (2008)
  • Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease

    MMWR Recomm Rep

    (1998)
  • Cited by (16)

    • Evaluation of a strategy for identification of hepatitis C virus carriers in outpatient and emergency units: contribution to the microelimination of hepatitis C in Brazil

      2021, Brazilian Journal of Infectious Diseases
      Citation Excerpt :

      Using the birth cohort testing strategy, about 85.4 million people would be tested for anti-HCV and about 2.8 million anti-HCV-positive individuals would be identified, with a sensitivity of 76.6%. On the other hand, the ALT strategy would result in the testing of 21.5 million adults and identification of 1.8 million anti-HCV-positive people, with a sensitivity of 50.0%.19 The strategy of urgency and emergency units screening is based on international studies that showed a high prevalence of HCV in this population,20–22 ranging from 7.3% to 13.8% in some studies, suggesting emergency departments as strategical sites for the detection of HCV.20–23

    • The Association of Abnormal Liver Tests with Hepatitis C Testing in Primary Care

      2020, American Journal of Medicine
      Citation Excerpt :

      These abnormalities can serve as early signals of liver disease, and past CDC guidelines (1998) identified a positive association between elevations in alanine aminotransferase (ALT) and HCV infection.1,22–28 Despite this association, hepatitis C testing in response to liver test abnormalities has been suboptimal.26,27 We hypothesized that demographic and clinical factors, with emphasis on clinical patterns of liver test abnormality, are associated with HCV Ab testing in primary care patients with consecutively abnormal liver tests.

    • Survival effects of physical activity on mortality among persons with liver disease

      2016, Preventive Medicine Reports
      Citation Excerpt :

      Participants who answered “yes” to this question were assessed herein. Among these participants, evidence of antibodies against the Hepatitis C virus was assessed with a Hepatitis C antibody test, with methodological details described elsewhere (Smith and Yartel, 2014). Free-living PA was assessed during all waking hours using the ActiGraph 7164 accelerometer.

    • Prevention: Secondary prevention and screening

      2021, Hepatitis C: Epidemiology, Prevention and Elimination: Volume 1
    View all citing articles on Scopus
    View full text