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Hepatology. Author manuscript; available in PMC 2020 March 01.
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Published in final edited form as:

Hepatology. 2019 March ; 69(3): 1020–1031. doi:10.1002/hep.30297.

Estimating prevalence of hepatitis C virus infection in the United

States, 2013–2016
Megan G. Hofmeister1,2, Elizabeth M. Rosenthal3, Laurie K. Barker1, Eli S. Rosenberg3,
Meredith A. Barranco3, Eric W. Hall4, Brian R. Edlin5, Jonathan Mermin5, John W. Ward1,6,
A. Blythe Ryerson1
1Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia
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2Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, Georgia
3Department of Epidemiology and Biostatistics, University at Albany School of Public Health,
State University of New York, Rensselaer, New York
4Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
5National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease
Control and Prevention, Atlanta, Georgia
6Program for Viral Hepatitis Elimination, The Task Force for Global Health, Decatur, Georgia

Abstract
Hepatitis C virus (HCV) infection is the most commonly reported bloodborne infection in the
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United States, causing substantial morbidity and mortality and costing billions of dollars annually.
To update the estimated HCV prevalence among all adults aged ≥18 years in the United States, we
analyzed 2013-2016 data from the National Health and Nutrition Examination Survey (NHANES)
to estimate the prevalence of HCV in the noninstitutionalized civilian population, and used a
combination of literature reviews and population size estimation approaches to estimate the HCV
prevalence and population sizes for four additional populations: incarcerated people, unsheltered
homeless people, active-duty military personnel, and nursing home residents. We estimated that

Contact Information: Megan G. Hofmeister, MD, MS, MPH, Centers for Disease Control and Prevention, 1600 Clifton Road, MS
G-37, Atlanta, GA 30333, Phone: (404) 718-5458, Fax: (404) 718-8588, [email protected].
Megan G. Hofmeister, MD, MS, MPH; Division of Viral Hepatitis, CDC, Atlanta, GA; Epidemic Intelligence Service, CDC, Atlanta,
GA
Elizabeth M. Rosenthal, MPH; Department of Epidemiology and Biostatistics, University at Albany School of Public Health, State
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University of New York, Rensselaer, NY

Laurie K. Barker, MSPH; Division of Viral Hepatitis, CDC, Atlanta, GA
Eli S. Rosenberg, PhD; Department of Epidemiology and Biostatistics, University at Albany School of Public Health, State University
of New York, Rensselaer, NY
Meredith A. Barranco; Department of Epidemiology and Biostatistics, University at Albany School of Public Health, State University
of New York, Rensselaer, NY
Eric W. Hall; MPH, Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA
Brian R. Edlin, MD; National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC, Atlanta, GA
Jonathan Mermin, MD, MPH; National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC, Atlanta, GA
John W. Ward, MD; Division of Viral Hepatitis, CDC, Atlanta, GA; Program for Viral Hepatitis Elimination, The Task Force for
Global Health, Decatur, GA
A. Blythe Ryerson, PhD, MPH; Division of Viral Hepatitis, CDC, Atlanta, GA
Publisher's Disclaimer: Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily
represent the views of the Research Data Center, the National Center for Health Statistics, or the Centers for Disease Control and
Prevention.
 Hofmeister et al. Page 2

during 2013-2016, 1.7% (95% CI 1.4-2.0%) of all adults in the United States, approximately 4.1
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(3.4-4.9) million persons, were HCV antibody-positive (indicating past or current infection), and
1.0% (95% CI 0.8-1.1%) of all adults, approximately 2.4 (2.0-2.8) million persons, were HCV
RNA-positive (indicating current infection). This includes 3.7 million noninstitutionalized civilian
adults in the United States with HCV antibodies and 2.1 million with HCV RNA, and an estimated
0.38 million HCV antibody-positive persons and 0.25 million HCV RNA-positive persons not part
of the 2013-2016 NHANES sampling frame.

Conclusion: Over 2 million people in the United States had current HCV infection during
2013-2016. Compared to past estimates based on similar methodology, HCV antibody prevalence
may have increased while RNA prevalence may have decreased, likely reflecting the combination
of the opioid crisis, curative treatment for HCV infection, and mortality among the HCV-infected
population. Efforts on multiple fronts are needed to combat the evolving HCV epidemic, including
increasing capacity for and access to HCV testing, linkage-to-care, and cure.
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Keywords
HCV; viral hepatitis; NHANES; incarcerated; homeless

Hepatitis C virus (HCV) infection is the most commonly reported bloodborne infection in
the United States despite being underdiagnosed.(1–3) Highly efficacious, all-oral direct-
acting antiviral (DAA) therapy revolutionized hepatitis C treatment within the past decade,
dramatically improving cure rates over previous treatment modalities.(4–6) Access to these
therapies, however, is compromised by the high proportion of HCV-infected persons
unaware of their status and, for those who have been diagnosed, insurer-implemented
treatment restrictions related to concerns regarding the costs of HCV medications. Persons
with untreated chronic HCV infection, as well as those who have been cured but still have
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advanced HCV-associated disease, are at risk for hepatic fibrosis, cirrhosis, and
hepatocellular carcinoma, and HCV infection remains one of the leading causes of liver
transplantation in the United States.(7, 8) Nationwide, during 2012-2013, the annual number
of HCV-related deaths exceeded the total number of deaths reported to CDC associated with
the 60 other nationally notifiable infectious diseases combined.(9)

The prevalence of current HCV infection (indicated by HCV antibody-positivity and RNA-
positivity) in a given population at a particular time depends on several factors: the number
of people with existing chronic HCV infection (defined as detectable HCV RNA at least 6
months following acute infection), the number of people with incident HCV infection, the
number of people cured of HCV infection (through spontaneous clearance or treatment), and
the number of deaths among persons with chronic HCV infection, regardless of whether
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mortality is attributed to complications of HCV infection. An accurate estimate of hepatitis

C prevalence can inform public health interventions and resource allocation strategies aimed
at reducing the health burden and economic costs caused by hepatitis C in the United States.

The National Health and Nutrition Examination Survey (NHANES) combines interviews
and physical examinations to assess the health and nutritional status of adults and children in
the United States and to determine the prevalence of major diseases and disease risk factors.
(10) A 2014 analysis of NHANES data from 2003-2010 estimated that 3.6 million persons

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(95% confidence interval [CI] = 3.0 to 4.2 million persons) were HCV antibody-positive,
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indicating past or current HCV infection; of these, approximately 2.7 million (95% CI = 2.2
to 3.2 million persons) were HCV RNA-positive, indicating current HCV infection of 1.0%
(95% CI = 0.8% to 1.2%) among the noninstitutionalized civilian U.S. population aged ≥6
years.(11) A 2015 brief report using NHANES data from 2011-2014 estimated current HCV
infection of 0.9% (95% CI = 0.6% to 1.2%) among U.S. adults aged ≥18 years, but did not
report an estimate of HCV antibody positivity.(12)

While the NHANES national probability sample provides the best available measurement of
HCV prevalence in the general U.S. population, its sampling frame is the
noninstitutionalized, civilian population of the United States; consequently, NHANES
underestimates the true prevalence of HCV in the United States because it excludes certain
populations known to have high HCV prevalence from its sampling frame. In 2015,
researchers estimated that an additional 1.0 million persons (range: 0.4 to 1.8 million) in
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high-risk population groups unaccounted for by NHANES 2003-2010 data were HCV
antibody-positive, of whom 0.8 million (range: 0.3 to 1.5 million) were chronically infected.
(13) These estimates suggested that in the United States during 2003-2010, 4.6 million
persons had HCV antibody and 3.5 million persons were living with current HCV infection.
More recent estimates of HCV RNA prevalence are expected to be lower, as more people are
being cured because of improved HCV treatments; further, because the population in the
United States is aging, (14) and death rates increase with age, many persons in the age
cohort at highest risk for chronic infection, those born during 1945-1965, (15) are dying of
HCV-related and other causes. However, incident HCV infections linked to the opioid crisis
and other drug use have simultaneously increased the overall prevalence of persons ever
infected with HCV in the United States, (16) potentially offsetting these expected reductions
in HCV prevalence.
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To provide a new estimate of HCV prevalence among adults aged ≥18 years in the United
States, we combined estimates of prevalence in the noninstitutionalized civilian population
from NHANES 2013-2016 data with modeled estimates for four additional populations that
were not sampled by NHANES.

Methods
We used NHANES data to estimate HCV prevalence among the U.S. noninstitutionalized
civilian population, and computed additional prevalence estimates for four populations that
were not part of the NHANES sampling frame to provide a more comprehensive estimate of
national HCV prevalence among adults aged ≥18 years during 2013-2016. The sampling
frame for NHANES is the noninstitutionalized civilian population, which includes all people
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living in households, excluding institutional group quarters and those persons on active
military duty.(17) We used five-year American Community Survey (ACS) population
estimates for 2012-2016 to generate population totals for the noninstitutionalized civilian
population. We estimated HCV prevalence and population sizes for each additional
population using a combination of literature search and population-size estimation
approaches. These were combined to yield an updated estimate that reflects the total number
of HCV infections in the United States more accurately than NHANES data alone.

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Additional enhancements of earlier estimation methods (e.g., refinement of additional

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populations and expansion of search terms) are described in the accompanying Supplement.

HCV prevalence in the noninstitutionalized civilian adult population, 2013-2016

HCV antibody and RNA prevalences were calculated using data from the two most-recent
NHANES cycles (2013-2016). This complex, stratified, multistage probability survey
collected information from approximately 10,000 civilian, noninstitutionalized U.S.
residents per 2-year cycle and was designed to provide representative national health
estimates for this population.(17) Confirmed antibody data sets used in this analysis were
published in January 2018 and accessed through the Research Data Center at the National
Center for Health Statistics (NCHS). Survey participants provided blood samples for
hepatitis C antibody screening and RNA testing; further antibody confirmation was
performed among those participants who tested RNA negative. In 2013, NCHS revised its
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protocol for HCV testing of specimens from NHANES participants to align with updated
guidelines for HCV testing published in 2013 (18) and replace a laboratory test for HCV
antibody confirmation that was removed from market at the end of 2012 (Chiron® RIBA™
HCV 3.0 SIA, Chiron Corporation, Emeryville, California).(19–21) Under the protocols
used during 1999-2012, antibody screening reactive participants next received an antibody
confirmation test, and confirmed antibody positive participants then received an RNA test.
(19) During 2013-2016, NHANES participants first were tested for HCV antibody with a
screening test; those with a reactive antibody screening test then received an HCV RNA test,
and only RNA negative participants received an antibody confirmation test using a 3rd
generation line immunoassay (INNO-LIA™ HCV Score, Fujirebio, Malvern, Pennsylvania).
(20, 21) The protocol change complicates formal statistical comparison of data before and
after 2013. To estimate the national prevalence of HCV antibody and HCV RNA for
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2013-2016 among adults aged ≥18 years, data were weighted to account for sampling design
and participation in the examination component using the NCHS-provided Mobile
Examination Center (MEC) survey weights. The MEC weights for participants with valid
HCV screening and RNA test results were first multiplied by the ratio of the sum of the
MEC weights for all participants eligible for HCV testing to the sum of the MEC weights
for those with valid HCV test data within the same strata (defined by sex, age group, and
race/ethnicity), and then by the ratio of the sum of the MEC weights for all participants
eligible for antibody confirmation testing to the sum of the MEC weights for those with
valid antibody confirmation test results. This approach assumes that the prevalence of HCV
RNA is the same among those with and without data, within each strata, and that the
prevalence of confirmed antibody is the same among those with and without confirmed
antibody test results. To calculate the number of noninstitutionalized civilians in the United
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States with HCV antibody and HCV RNA during 2013-2016, prevalence estimates were
then multiplied by the estimated total noninstitutionalized civilian adult U.S. population as
of December 31, 2016 from the 2012-2016 ACS. Data collection for NHANES was
approved by the NCHS Research Ethics Review Board. Analysis of de-identified data from
the survey is exempt from the federal regulations for the protection of human research
participants. Analysis of restricted data through the NCHS Research Data Center is also
approved by the NCHS Ethics Review Board.

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HCV prevalence in four additional adult populations, 2013-2016

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Population size estimates—We used the most recent published data to estimate the size
of each of the following populations: incarcerated people, unsheltered homeless people,
active-duty military personnel, and nursing home residents (Table 1). When necessary, these
estimates were adjusted for population growth to December 31, 2016, using a ratio of 2016
to 2014 population sizes in six age group by sex strata, to allow for comparability with the
population totals represented in the 2012-2016 ACS. Each additional population nonetheless
required slightly different analytic approaches for estimating the 2016 population size and
their group-specific HCV prevalence, described in further detail in the accompanying
Supplement.

Literature review
Search process: We performed a literature review using PubMed to search for articles
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reporting HCV prevalence published in English from January 1, 2013 through December 31,
2017. We restricted the search to this time-period in order to yield prevalence estimates
reflecting the same period of the 2013-2016 NHANES cycles used for the prevalence
estimate calculations. We expanded population-specific search terms from previous
methodologies (Table 2).(13) Relevant literature search results were scarce for nursing home
and active-duty military; because evidence was insufficient to suggest that these populations
are at increased risk for HCV infection, we applied age- and sex-specific NHANES
prevalence estimates to these two populations using publicly available data (Table 1); details
on the prevalence estimation for these populations are provided in the accompanying
Supplement.(13, 27) Studies were selected for inclusion if they were conducted in the
United States and reported quantitative data on HCV prevalence among general samples of
incarcerated populations or homeless populations. Those sampling higher-risk
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subpopulations selectively were excluded (e.g., people living with HIV or people who inject
drugs).

Literature review and data extraction: A single reviewer (M.G.H.) performed a title
review on all literature search results. Two reviewers (M.G.H. and M.A.B.) independently
read abstracts and full-text articles meeting the established criteria to determine final
eligibility for inclusion in our analysis; the reviewers discussed and resolved any differences
in opinion. Once the list of articles was finalized, one reviewer (M.G.H.) extracted dates of
testing, number of persons tested for HCV antibody and HCV RNA, number testing positive
for HCV antibody and HCV RNA, and HCV prevalence from each study; this information
was then verified by an additional reviewer (M.A.B.). References from the final article set
were reviewed for any additional relevant articles.
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Data synthesis: We calculated the mean prevalence of both HCV antibody and HCV RNA
for populations for which multiple published estimates were available (those incarcerated),
using a random effects model and study sample size as weights.(28) For literature sources
that provided HCV RNA testing data, RNA prevalence was calculated as the RNA test
positivity among persons who were HCV antibody-positive and tested, multiplied by the
HCV antibody prevalence. For studies that reported prevalence of HCV antibody only,
prevalence of current HCV infection was calculated by multiplying the HCV antibody

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prevalence reported in the study by the proportion of HCV antibody-positive persons with
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HCV RNA estimated using 2013-2016 NHANES data (57.5%) (Table 3).

Combined U.S. HCV prevalence in adults

We calculated the population-specific number of adults ever infected with HCV (HCV
antibody-positive) or currently infected with HCV (HCV antibody-positive and RNA-
positive), by multiplying the population size by the respective HCV antibody prevalence and
HCV RNA prevalence estimates for each group (Table 4). Because active-duty military are
included in the ACS population estimate used in row 1 of Table 4, we subtracted the
estimated population size of this group from the ACS population size to estimate the size of
the noninstitutionalized civilian U.S. population. We then estimated the number of persons
infected with HCV from the adjusted population size and the NHANES HCV antibody
prevalence and RNA prevalence. We summed the numbers of infected persons in each
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population to obtain the overall number of persons in the United States with past and current
HCV infection, and summed the population sizes to obtain the total U.S. population size. We
calculated the final HCV prevalences by dividing the total numbers of infected persons by
the total estimated population size.

Confidence intervals
Confidence intervals (CIs) were used to account for statistical uncertainty in NHANES and
additional population prevalence estimates. For the noninstitutionalized civilian population
estimates from NHANES, reported CIs accounted for the multistage, clustered sampling
design. For the incarcerated population, the reported CIs were generated from the random
effects meta-analysis estimation. The reported CIs for unsheltered homeless persons, active-
duty military, nursing home residents, and the combined U.S. HCV prevalence were
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computed using a Monte Carlo simulation process (10,000 iterations) which resampled
parameter estimates from normal distributions defined by the point estimate and standard
errors for each population prevalence estimate.

Results
During 2013-2016, the estimated NHANES HCV antibody prevalence among persons aged
18 years or older was 1.5% (95% CI = 1.3% to 1.8%), corresponding to approximately 3.7
million persons (95% CI = 3.1 to 4.4 million persons) with past or current HCV infection in
the U.S. noninstitutionalized civilian population. The estimated NHANES HCV RNA
prevalence among persons aged 18 years or older was 0.9% (95% CI = 0.7% to 1.0%),
corresponding to approximately 2.1 million persons (95% CI = 1.8 to 2.5 million persons)
with current HCV infection in the U.S. noninstitutionalized civilian population.
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The literature search for hepatitis C prevalence data for incarcerated populations and
homeless populations yielded 2,432 unique articles, of which only eight met the inclusion
criteria (Table 2). Seven studies of incarcerated persons reported HCV prevalence, with
HCV antibody prevalence ranging from 11.9% to 20.6%. Of these, four studies reported
HCV RNA prevalence ranging from 9.1% to 15.2%; for the other three studies, HCV RNA
prevalence was calculated by multiplying the reported HCV antibody prevalence by the

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57.5% of HCV antibody-positive persons with HCV RNA from the 2013-2016 NHANES
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data (Table 3). The estimated mean HCV antibody prevalence was 16.1%, and the estimated
mean HCV RNA prevalence was 10.7%.

One study of homeless persons attending a Federally Qualified Health Center reported an
HCV antibody prevalence of 14.7%; HCV RNA prevalence was estimated at 10.8% (Table
3).

The population sizes of the four additional groups ranged from 160,600 for the unsheltered
homeless population to 2,131,000 for the incarcerated population (Table 4). We estimated
that during 2013-2016, a total of 344,100 incarcerated persons, 23,700 unsheltered homeless
persons, 13,500 active-duty military personnel, and 18,900 nursing home residents were
HCV antibody-positive, while 227,400 incarcerated persons, 17,400 unsheltered homeless
persons, 6,900 active-duty military personnel, and 6,900 nursing home residents were living
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with current HCV infection. The additional populations added approximately 5.0 million
persons to the population total, 400,100 persons to the HCV antibody-positive total, and
258,600 to the HCV RNA-positive total. We estimated that overall in the United States,
4,101,200 persons had HCV antibody and 2,386,100 persons were currently infected with
HCV during 2013-2016.

Discussion
The purpose of our study was to provide an updated estimate of HCV prevalence among
adults in the United States that would include persons in high-risk populations not part of the
NHANES sampling frame. We estimate that during 2013-2016 in the United States, 1.7% of
all adults, or approximately 4.1 million persons, were HCV antibody-positive and that 1.0%
of all adults, or approximately 2.4 million persons, were HCV RNA-positive. Our findings
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suggest that the 2013-2016 U.S. HCV prevalence estimate derived from NHANES alone
underestimates the actual number of HCV antibody-positive persons by approximately 0.38
million persons, and the number of HCV RNA-positive persons by approximately 0.25
million persons.

Our analysis of NHANES data indicates an HCV antibody prevalence of 1.5% (3.7 million
persons) during 2013-2016, higher than the previous NHANES estimate of 1.3% (3.6
million persons) during 2003-2010 that was produced using data collected before the 2013
revision of the NHANES HCV protocol.(11) While it is possible that some of this increase is
due to the change in the NHANES laboratory protocol, it also likely reflects the changing
epidemic of HCV infection in the United States.(1, 37, 38) From 2006 through 2012, state
surveillance data from Central Appalachia (Kentucky, Tennessee, Virginia, and West
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Virginia) demonstrated a 364% increase in the number of acute HCV infections among
persons ≤30 years old.(38) Furthermore, from 2011-2014, commercial laboratory data
indicated a 22% increase in national rates of HCV detection among women of childbearing
age.(39) Overall, the number of incident hepatitis C cases reported in the United States via
the National Notifiable Diseases Surveillance System increased 38.8% from 2013 through
2016, most markedly among 20-39 year olds, although increases occurred among adults of
all ages.(1)

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Our findings suggest an estimated HCV RNA prevalence in the noninstitutionalized civilian
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adult U.S. population of 0.9% (2.1 million persons, 95% CI = 1.8 to 2.5 million persons)
during 2013-2016, similar to the NHANES estimate of 0.9% for 2011-2014,(12) and lower
than the previous NHANES estimate of 1.0% (2.7 million persons, 95% CI = 2.2 to 3.2
million persons) during 2003-2010.(11) Although the 2013 change in the NHANES HCV
protocol may have played a role, the difference in these two estimates of current HCV
infection is likely due to a combination of successful HCV treatment via oral DAA therapy
and continued mortality (HCV-associated and all-cause).

While current therapies are highly efficacious, many populations have limited access to
HCV testing, care, and treatment services. A recent systematic review of the literature
indicated that only half of those infected with chronic HCV were diagnosed and aware of
their infection, with only a proportion linked to care (43%), prescribed HCV treatment
(16%), and achieving cure (9%).(40) In the Chronic Hepatitis Cohort Study, only 5.7% of
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patients with HCV infection potentially eligible for treatment initiated a DAA regimen
prescribed in 2014.(41) Kanwal et al. reported slightly higher treatment rates at the Veterans
Administration, where 10.2% of the nearly 150,000 patients with chronic HCV infection
seen during the first 16 months of the DAA era received treatment.(42) Encouragingly, oral
DAA therapy uptake has increased since the medications were first licensed. At the Veterans
Administration specifically, 62,290 veterans completed oral DAA treatment between
January 1, 2014 and September 30, 2016, and the Veterans Administration estimates that an
additional 59,200 veterans will be cured from 2017 through 2018.(43,44) These data suggest
that successful treatment, while contributing to the decline in current HCV infections, does
not entirely account for the decrease observed in NHANES-estimated current HCV
infection. Unfortunately, continued mortality contributes to the changes in HCV prevalence.
During 2016 in the United States, 18,153 hepatitis C-related deaths were reported to the
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National Vital Statistics System, representing a 6.3% decrease from 2013.(1) A recent
analysis demonstrated that HCV is substantially underreported on death certificates (even
when the main cause of death is liver-related), suggesting that the approximately 20,000
death certificates that included documentation of HCV annually during the study period
underestimate mortality in chronically HCV-infected persons.(45) Additionally, as the
population (adults born during 1945-1965, in particular) ages, deaths from competing, non-
HCV-related causes contribute to a decrease in the overall prevalence of HCV infections.

Ultimately, given the rise in the number of persons with serologic evidence of an HCV
infection in the past and the decline in the proportion of those persons currently infected
with HCV, it is likely that successful treatment played an important role in the decrease in
current HCV infection among the U.S. noninstitutionalized civilian population. We
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estimated that 4.1 million persons were ever infected with HCV and approximately 2.4
million were currently infected, suggesting that about 1.7 million had cleared the infection.
These 1.7 million adults either cleared the infection spontaneously or were cured through
antiviral treatment. Some 15%−40% of infected persons resolve HCV infection
spontaneously; women, younger persons, and those with certain immune response gene
variants are more likely than other persons to clear HCV spontaneously.(46, 47) Hundreds of
thousands have likely been cleared through treatment and cure of their infection. An HCV

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drug manufacturer estimates that at least 673,000 people in the United States initiated an
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HCV treatment regimen during 2013-2016 alone.(48)

Compared with a previous estimate of the total U.S. hepatitis C prevalence, our analysis
identified lower HCV prevalence and fewer unenumerated HCV infections in populations
not part of the NHANES sampling frame.(13) According to our estimates, 0.38 million HCV
antibody-positive and 0.25 million HCV RNA-positive persons from populations not part of
the NHANES sampling frame should be added to the HCV prevalence estimate generated
using 2013-2016 NHANES data alone. Several factors contribute to these differences. The
overall additional population size is smaller in our analysis (5.0 million persons) compared
with a previously published analysis because we concluded that people living in American
Indian/Alaska Native (AI/AN) areas (C. Ogden, personal communication, May 30, 2018),
people hospitalized for less than the 8 week duration of the NHANES sampling period, and
sheltered homeless people were included in the NHANES sampling frame and therefore did
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not include them in our analysis of additional populations.(13) This, combined with the
lower HCV prevalence reported in recent literature for incarcerated populations (16.1%
HCV antibody prevalence in recent literature vs. 23.1% HCV antibody prevalence in
previous literature) and homeless populations (14.7% vs. 32.1% HCV antibody prevalence)
accounts for the reduction in unenumerated HCV infections in additional populations in our
analysis.(13)

Our analysis had several limitations. First, the number of HCV-positive NHANES
participants during 2013-2016 is small (n=185 antibody positive, n=117 RNA positive), even
in this large nationally representative sample (n=12,105 participants aged 18 years and older,
of whom n=10,857 were tested for HCV); although NHANES uses extensively tested
protocols to encourage participation even in sensitive aspects of the study, if participants
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who did not participate in the examination component (n=446), did not undergo HCV testing
or provide a blood sample sufficient to yield conclusive HCV test results (n=789), or opted
not to participate in NHANES at all (n=6,715, or 37% of, selected participants aged 20 years
and older during 2013-2016) were disproportionately persons who had previously or
concurrently injected drugs, NHANES may underestimate HCV prevalence even in the
noninstitutionalized civilian population. However, a new study, based on a dynamic model of
HCV infection among the NHANES-eligible population from 2001 and beyond, estimated
that 1.84 million noninstitutionalized people were HCV RNA-positive in the United States
in 2015.(49) This estimate is only 15% lower than our estimate of HCV RNA prevalence in
the noninstitutionalized civilian population during 2013-2016. Second, the effect of the
NHANES change in laboratory testing methods on HCV antibody and RNA prevalence
estimates before and after 2013 could not be assessed within the NHANES population and
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thus any comparison of our current findings with previous estimates should be interpreted
with caution. The change in NHANES protocol could potentially be a cause of higher HCV
antibody prevalence in the current study; however a full crossover comparison study using
surplus NHANES sera to evaluate the effect of the 2013 change in the NHANES HCV
protocol could not be conducted due to ethical considerations of potential clinically relevant
findings from such a study, and lack of availability of RIBA test kits prevented a prospective
crossover study among NHANES participants after 2013. Third, none of the studies
identified through our literature review were designed to generate nationally representative

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estimates of HCV prevalence in the additional populations. We excluded studies that

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selectively sampled higher-risk subpopulations (e.g., people who inject drugs) in an attempt
to mitigate the potential lack of representativeness. Furthermore, a recent study published
after our literature review was closed estimated that 18% of Americans who are in prison at
any given time have antibodies to HCV, (50) slightly above our estimate, suggesting that the
studies included in our analysis for the incarcerated population provide a credible HCV
prevalence estimate for this additional population. The single study of the homeless
population, however, may not be representative of this population nationwide. Fourth, we
performed a sensitivity analysis on the homeless population estimates. Had we included the
263,500 sheltered homeless adults in 2016 in our analysis, we would have added an
additional 38,900 HCV antibody-positive persons and 28,500 HCV RNA-positive persons to
our estimates. Fifth, because the source studies were not conducted for the purpose of
synthesis into a national estimate, the application of meta-analytic and other statistical
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procedures to create confidence intervals for additional populations should be interpreted

more cautiously than confidence intervals based on NHANES alone. Sixth, because people
living in AI/AN areas could potentially be undersampled by the NHANES sampling frame,
we performed a sensitivity analysis, applying a literature-based HCV prevalence estimate
specific to people living in AI/AN areas, (51) to determine the HCV prevalence among this
population. We estimate that there were approximately 125,000 HCV RNA-positive adults
living in AI/AN areas during 2013-2016. This estimate likely represents the upper limit of
current HCV infections in AI/AN areas during this time period. Finally, when we applied the
2013-2016 NHANES HCV RNA prevalence to the additional populations, we conferred to
them the spontaneous clearance and treatment levels of the noninstitutionalized civilian
population. This assumption may not be accurate (i.e., treatment levels are likely to be lower
in the additional populations than in the noninstitutionalized civilian population), and could
have resulted in underestimation of the prevalence of current HCV infection in the three
Author Manuscript

incarcerated population studies that did not report HCV RNA prevalence; however, HCV
antibody prevalence would be unaffected. We performed a sensitivity analysis applying the
mean HCV RNA prevalence among those who tested antibody-positive from the four
incarcerated population studies that reported HCV RNA prevalence to the three incarcerated
population studies that did not report HCV RNA prevalence; the mean HCV RNA
prevalence for the incarcerated population increased from 10.7% (when the 2013-2016
NHANES HCV RNA prevalence was applied) to 11.6%, a difference of 20,700 HCV RNA-
positive persons overall (data not shown).

In summary, we estimate that during 2013-2016 in the United States, approximately 4.1
million adults had evidence of past or current HCV infection, of whom approximately 2.4
million were currently infected with HCV. Compared to past estimates based on similar
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methodology, HCV antibody prevalence may have increased while HCV RNA prevalence
may have decreased, likely reflecting the impact of the opioid crisis on HCV incidence, use
of effective treatment regimens, and continuing mortality among the HCV-infected
population. Forthcoming work will include state-level estimates of hepatitis C prevalence
using this methodology as well as delving deeper into the NHANES data to examine
differences by group and the proportion of those aware of their infection and receiving care.
Comprehensive and accurate estimates of HCV prevalence can guide health interventions

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 Hofmeister et al. Page 11

and resource allocation to link chronically infected persons to care, treatment, and ultimately
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cure. Continued efforts to reduce the burden of HCV infection will require improved
interventions to prevent new infections, expanded testing to find undiagnosed persons, and
strategies to ensure treatment so that HCV-infected persons are promptly cured.

Supplementary Material
Refer to Web version on PubMed Central for supplementary material.

Acknowledgments
Karon C. Lewis at the National Center for Health Statistics Research Data Center, CDC, for creating the NHANES
data files.

Financial Support:
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We acknowledge funding from the Centers for Disease Control and Prevention (CDC) National Center for HIV/
AIDS, Viral Hepatitis, STD, and TB Prevention Epidemic and Economic Modeling Agreement (U38 PS004646).

List of Abbreviations:
HCV hepatitis C virus

DAA direct-acting antiviral

NHANES National Health and Nutrition Examination Survey

ACS American Community Survey

NCHS National Center for Health Statistics

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MEC Mobile Examination Center

AI/AN American Indian/Alaska Native

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Table 1.

Population inclusion strategies and data sources, adults aged ≥18 years
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Population features evaluated for analytic decisions Data sources used in analysis

Population Included in Included in ACS Evidence of HCV Population-size source

NHANES population size differential prevalence
sampling estimates used HCV risk source
frame for NHANES
analyses
Noninstitutionalized civilian Yes Yes N/A NHANES ACS, 2012 – 201622
population
Incarcerated No No Yes Literature Bureau of Justice Statistics,
201623
Unsheltered homeless No No Yes Literature U.S. Department of
Housing and Urban
Development, 201624
Active-duty military No Yes No NHANES U.S. Department of
a
Defense, 201625,
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Nursing homes No No No NHANES National Survey of Long

Term Care Providers,
b
201426,
People living in AI/AN Yes Yes Yes N/A N/A
c,d
areas
d Yes Yes No N/A N/A
Hospitalized
Other high risk populations Yes Yes Yes N/A N/A
(e.g., people who inject
e
drugs, sheltered homeless)

a
Although this population is represented in the ACS population size estimate used for this NHANES analysis, these supplementary values were
utilized in the adjusted estimate calculation
b
Scaled for population growth to 2016
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c
Residents of Native American reservations and tribal lands and Alaska Native village statistical areas
d
Excluded from analysis due to inclusion in both NHANES (prevalence numerator) and ACS (population size denominator)
e
For people who inject drugs, we assessed likely bias and determined that national NHANES estimates sufficiently represented HCV prevalence in
this subpopulation

Abbreviations: NHANES, National Health and Nutrition Examination Survey; ACS, American Community Survey; HCV, hepatitis C virus; AI/AN,
American Indian/Alaska Native
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Table 2.

Search terms and results of literature search for articles with hepatitis C prevalence data among incarcerated
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populations and homeless populations (January 1, 2013 — December 31, 2017)

Unique Abstracts Full Text Articles

Population Search Terms Articles Screened Screened Included
Incarcerated (“hepatitis C” or “HCV”) and (“prison” or “jail” 1,079 56 17 7
or “correctional”)
Homeless (“hepatitis C” or “HCV”) and (“homeless” or 1,353 24 9 1
“homeless persons” or “housing unstable” or
“housing insecure”)
Total 2,432 80 26 8

Abbreviations: HCV, hepatitis C virus

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Table 3.

Hepatitis C seroprevalence studies in incarcerated populations and homeless populations

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Reference Location Study Dates Total No. No. HCV HCV No. HCV HCV RNA
Tested Antibody- Antibody RNA- Prevalence
Positive Prevalence Positive
Incarcerated

Akiyama et al.29 New York, NY 2013-2014 10,856 2234 20.6% -- a

11.8%
Barnstable b
Cocoros et al.30 County, MA
2009-2011 596 122 20.5% 23 15.2%

Dallas County, a
de la Flor et al.31 TX
2015-2016 3,042 500 16.4% -- 9.5%

Kuncio et al.32 Philadelphia, PA 2012 1,289 154 11.9% -- a

6.9%

Mahowald et al.33 Pennsylvania 2004-2012 101,727 18454 18.1% 5288 b

12.6%
Durham County, b
Schoenbachler et al.34 NC
2012-2014 669 88 13.2% 66 10.7%
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Stockman et al.35 Wisconsin 2014-2015 1,239 155 12.5% 110 b

9.1%
Mean prevalence: 16.1% 10.7%
Homeless

Coyle et al.36 Philadelphia, PA 2012-2014 1,079 159 14.7% 108 c

10.8%
Mean prevalence: 14.7% 10.8%

a
Calculated as (reported HCV Antibody Prevalence) x (NHANES 2013-2016 HCV RNA prevalence), where NHANES 2013-2016 HCV RNA
prevalence among antibody positives=0.575
b
Calculated as (Number HCV RNA-Positive/Number Tested HCV RNA) x (reported HCV Antibody Prevalence)
c
Calculated as (reported HCV Antibody Prevalence) x (Number HCV RNA-Positive/(0.924 x Number HCV Antibody-Positive)), where the
calculation is adjusted by the 92.4% of study participants reported to have received RNA testing
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Abbreviations: HCV, hepatitis C virus

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Table 4.

Estimated population sizes and hepatitis C prevalences among adults aged ≥18 years, United States 2013-2016
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HCV Antibody Prevalence HCV RNA Prevalence

Number of Ever Infected Number of Currently Infected

Estimated b b
Adult Persons Prevalence Persons Prevalence
Population
a
Population Size Estimate 95% CI Estimate 95% CI Estimate 95% CI Estimate 95% CI
c
NHANES 241,152,600 3,721,000 (3,094,000-4,434,800) 1.5% (1.3%-1.8%) 2,139,000 (1,794,200-2,529,700) 0.9% (0.7%-1.0%)

Additional
populations

Incarcerated 2,131,000 344,100 (308,800-382,500) 16.1% (14.5%-17.9%) 227,400 (201,900-255,600) 10.7% (9.5%-12.0%)
Unsheltered
homeless 160,600 23,700 (20,300-27,100) 14.7% (12.7%-16.9%) 17,400 (14,400-20,500) 10.8% (8.9%-12.8%)
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Active-duty
military 1,288,600 13,500 (8,000-18,100) 1.0% (0.6%-1.4%) 6,900 (2,700-11,200) 0.5% (0.2%-0.9%)
Nursing
homes 1,425,500 18,900 (11,700-21,000) 1.3% (0.8%-1.5%) 6,900 (4,600-9,300) 0.5% (0.3%-0.7%)

Additional
populations
d
(subtotal) 5,005,700 400,100 258,600
NHANES
(modified
estimate
excluding
additional
d
populations) 239,864,100 3,701,100 (3,077,500-4,411,100) 1.5% (1.3%-1.8%) 2,127,600 (1,784,600-2,516,200) 0.9% (0.7%-1.0%)

d
Total 244,869,800 4,101,200 (3,357,700-4,861,100) 1.7% (1.4%-2.0%) 2,386,100 (1,983,900-2,807,800) 1.0% (0.8%-1.1%)
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a
Population sizes are estimated as of December 2016 based on the American Community Survey 5-year estimates from 2012-2016.
b
Number of infected persons is calculated by multiplying the prevalence percentage estimate by the Estimated Adult Population Size; values may
not multiply due to rounding.
c
NHANES prevalence percentage estimates are based on results from 2013-2016 NHANES. Population size includes noninstitutionalized adults
eligible for NHANES from the 2012-2016 American Community Survey.
d
Values may not sum to column subtotal and total due to rounding.

Abbreviations: NHANES, National Health and Nutrition Examination Survey; HCV, hepatitis C virus
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