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Running head: SCREENING CAPSTONE PROJECT HCV
SCREENING CAPSTONE PROJECT HCV
Tracy Liichow
MPH 510 01 Spring A 2014 Applied Epidemiology
Instructor: Dr. Carol Hoban
CONCORDIA UNIVERSITY, NEBRASKA
February 28, 2014
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Abstract
Prevention of infectious diseases includes screening or testing. What is first and foremost in our
thinking is our objective which is to prevent infection. Hepatitis C is a liver disease that is the
consequence of infection with the Hepatitis C virus. The disease can cause serious health
problems for many of the people infected and the health problems include liver damage,
cirrhosis, and perhaps even death. Hepatitis C is a leading cause of liver cancer and the leading
reason for liver transplants and individuals diagnosed with Hepatitis C often do not have any
symptoms. Though they may not have any symptoms, their blood is infectious which makes
screening essential if we are to curb the rise of HCV infection in the United States.
Keywords: screening for disease, HCV, HCV testing, Hepatitis C
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SCREENING CAPSTONE PROJECT HCV
This screening project subject is the Hepatitis C Virus or HCV. The specific target
population is African Americans born between 1945 and 1965, commonly referred to as baby
boomers. According to the Centers for Disease Control (CDC) (2013):
Hepatitis C virus (HCV) infection is the most common chronic bloodborne
infection in the United States; approximately 3.2 million persons are
chronically infected. Although HCV is not efficiently transmitted sexually,
persons at risk for infection through injection drug use might seek care in STD
treatment facilities, HIV counseling and testing facilities, correctional
facilities, drug treatment facilities, and other public health settings where STD
and HIV prevention and control services are available. (p. 1)
The recommended setting for this type of project would be an HIV counseling and testing facility
located in Detroit, Michigan. However, I also recommend different types of settings with
inclusion of primary care and home testing kits.
Background
The background for this analysis includes accessing epidemiological data and studies
from the CDC as well as peer reviewed publications.
General information on HCV
There are approximately 60 notifiable diseases identified by law at the federal level in the
United States, and viral hepatitis is one of those diseases (Schneider, 2013). Viral hepatitis is a
group of viral infections that affect the liver. This paper focuses on hepatitis C and the virus that
causes it. Therefore, HCV can lead to acute and chronic liver disease in people who are infected
with it.
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HCV “is a small, enveloped RNA virus belonging to the Flaviviridae family, genus
Hepacivirus” (Penin, Dubuisson, Rey, Moradpour, & Pawlotsky, 2004, p. 5). HCV “is a
positive-stranded RNA virus” (Rosenberg, 2001, p. 451). An organism’s complete set of DNA
or RNA, including all of its genes, is called a genome (US National Library of Medicine, NIH,
US HHS, 2013). “The HCV genome is approximately 906 kb in length and the proteome
encoded is a polyprotein of a little more than 3000 amino acid residues” (Rosenberg, 2001, p.
451). We have classified HCV into six genotypes and as HCV “evolved in the population, the
variations in genome sequences have become more dramatic” (Jensen & Reau, 2013, p. 3). A
proteome is all of the proteins produced by an organism; it is an entire set of proteins (American
Medical Association, 2013). The HCV proteome polyprotein “is processed by a combination of
host and viral proteases into structural and non-structural proteins” (Rosenberg, 2001, p. 451).
HCV disperses in several forms in the serum of an infected host and it subsists within its
hosts as a collection of genetically distinct yet closely related variants (Penin et al., 2004, p. 7).
The HCV envelope proteins behave like “other viral envelope proteins involved in host cell
entry” and stimulate the joining together of the viral envelope and “a host cell membrane” (Penin
et al., 2004, p. 9). Epidemiologist Kenrad E. Nelson (2007, p. 924) indicated “HCV infections
are often persistent, indicating that the virus has evolved mechanisms to escape immune
surveillance.”
HCV is generally asymptomatic in the early stages. Most people infected with it are not
conscious of that fact and could have been infected for years without symptoms. According to
Sue Parini (2001, p. 18), a leading Registered Nurse and Infection Control Manager, “An
estimated 10,000 deaths each year in the United States are related to hepatitis C, but that number
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is expected to triple in the next few decades as the infection progresses in people who've been
asymptomatic.”
Transmission
According to the CDC (2013b) HCV transmission is transmitted primarily through
percutaneous1 or parenteral2 exposure that can result from injection-drug use, needle-stick
injuries, and inadequate infection control in health-care settings. Additionally, even though this
does not occur as frequently, HCV transmission occurs among HIV-positive persons, especially
men who have sex with men (MSM), as a result of sexual contact with an HCV-infected partner,
among persons who received non-professionally applied tattoos and among infants born to HCVinfected mothers.
Common screening test for HCV
The U.S. Preventive Services Task Force (USPSTF) (2013) recommends screening for
hepatitis C virus (HCV) infection in persons at high risk for infection and extending one-time
screening for HCV infection to adults born between 1945-1965. “Because HCV progresses
slowly, the risk for serious complications is increasing among infected Americans as time passes.
Without changes in current case identification and treatment, deaths from HCV are forecasted to
increase to 35 000 annually by 2030” (Rein et al., 2012, p. 1). More than 75% of individuals
infected with HCV are baby boomers, defined as people born from 1945 through 1965. Among
baby boomers, rates of Hepatitis C are higher in African Americans. In fact, African American
boomers are twice as likely to have Hepatitis C as are other baby boomers (Dean, 2014).
“Detection of antibodies to the hepatitis C virus is the first step to screen patients . . . The
presence of HCV antibodies is indicative of either past, current, or resolved infection and cannot
discriminate between acute and chronic HCV infection ” (Jensen & Reau, 2013, p. 29). What
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about testing and serologies? Two weeks after exposure to the virus HCV RNA is detectable by
assays; however, HCV antibodies do not become detectable until approximately 8 to 12 weeks
after exposure (Jensen & Reau, 2013). There are a number of different blood tests used to test
for Hepatitis C. Physicians have the prerogative in ordering just one or a combination of the
available tests. Usually, an individual will first receive a screening test that will show whether he
or she has developed antibodies to HCV. “Having a positive antibody test means that a person
was exposed to the virus at some time in his or her life. If the antibody test is positive, a doctor
will most likely order a second test to confirm whether the virus is still present in the person's
bloodstream” (Centers for Disease Control and Prevention, 2014, p. 1).
What is the screening test? According to Natasha Walzer, MD (2013, p. 30), “The
screening test is an enzyme immunoassay (EIA) that detects antibodies to recombinant antigens
from core and nonstructural proteins that make up the HCV virion.”
A serological test will be performed. A serological test is any of several laboratory
procedures carried out on a sample of blood serum, the clear liquid that separates from the blood
when it is allowed to clot. The purpose of such a test is to detect serum antibodies or antibodylike substances that appear specifically in association with certain diseases. An immunoassay is
a laboratory or clinical technique that uses the specific binding between an antigen and its
homologous antibody to identify and quantify a substance in a sample.
The Mayo Clinic (n.d.) describes HCV testing in the following manner:
Laboratory testing for HCV infection usually begins by screening for the
presence of HCV antibodies (anti-HCV) in serum, using an FDA-approved
anti-HCV screening test. Specimens that are repeatedly reactive by screening
tests should be confirmed by more HCV-specific tests, such as direct detection
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of HCV RNA by reverse transcriptase-PCR (RT-PCR). . . Current screening
serologic tests to detect HCV antibodies include EIA and chemiluminescence
immunoassay.
Further the Mayo Clinic (n.d.) suggests that despite “the value of serologic tests to screen for
HCV infection, several limitations of serologic testing exist:

There may be a long delay (up to 6 months) between exposure to the virus and the
development of detectable HCV antibodies.

False-reactive screening test results can occur.

A reactive screening test result does not distinguish between past (resolved) and chronic
HCV infection.

Serologic tests cannot provide information on clinical response to anti-HCV therapy.”
An example of an FDA approved anti-HCV screening test is the over-the-counter testing kit,
Hepatitis C Check, Home Access Health Corporation. “The blood sample is obtained at home
using a lancet and shipped in a weather-resistant pouch” (Walzer & Cotler, 2013, p. 31). Direct
detection of HCV RNA is used as a confirmatory test.
List information on specificity, sensitivity, and PV+ and PV- for screening test for HCV
Specificity is the probability that the test result will be negative when administered to
persons who are actually without the antibody. Sensitivity is the probability that the test result
will be positive when administered to persons who actually have the antibody. The sensitivity of
the Hepatitis C Check testing kit method “has been shown to be comparable to hospital-based
laboratory testing” (Walzer & Cotler, 2013, p. 31).
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Predictive-value positive (PVP) is the probability that a person with a positive screening
test result actually has the antibody. Predictive-value negative (PVN) is the probability that a
person with a negative screening test result actually does not have the antibody.
An example of specificity, sensitivity, and PV+ and PV- for a screening test for HCV is a
study which compared a newly developed automated and quantitative HCV core antigen test
with the HCV RNA assay. According to Kesli (2011) one of the conductors and authors of the
study:
Among the 212 specimens tested, all 52 cases in which HCV RNA was not
detected were also nonreactive for HCV Ag. For all samples with an HCV
RNA-negative result, a new sample was retested twice, 2 and 4 weeks later,
and all of them were again found to be negative. HCV Ag was found to be
negative in only 6 out of 160 HCV RNA-positive samples; these samples had
low-level viremia (5 samples with HCV RNA at levels between 75 and 249
IU/ml and 1 sample with 6,562 IU/ml). All the HCV Ag-reactive cases (n =
154) were also found to be positive with the anti-HCV test. Of all the 38 falsepositive anti-HCV results with the Architect anti-HCV assay, 28 had sample
value-to-cutoff (S/CO) ratios of less than 6 (22 had S/CO ratios between 1.3
and 2.54, 6 had S/CO ratios between 3.02 and 5.47), 7 had S/CO ratios of
between 6 and 8, and only 3 had S/CO ratios of between 12 and 16. . . The
diagnostic sensitivity, specificity, and positive and negative predictive values
of the HCV Ag assay compared to the HCV RNA test were 96.3%, 100%,
100%, and 89.7%, respectively. (p. 2)
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List populations or settings that the screening tests are commonly used for
The populations that the HCV screening test are commonly used for is determined by risk
factors. The settings that the HCV screening test are also generally determined by risk
behaviors. See table one for a list of risk behaviors. In regards to screening, risk based
screening has been unsuccessful in sufficiently identifying most individuals with HCV. This
knowledge leads public health officials to promote one time cohort screening of baby boomers.
Ethical considerations as a public health professional and specifically as an epidemiologist
There are many ethical considerations. The populations at risk for HCV infection are
often marginalized and stigmatized. The epidemiologist must be sensitive to the issues and
concerns of the at risk population. The epidemiologist must also be sensitive to the issues and
concerns that baby boomers have in addressing screening. The American culture can have a
tendency to not want to cooperate with any type of foreseen mandatory testing. The ethics that
have to be committed are the Five Principles of Morality.
Recommendations
What screening test would you recommend for your city/state and for what target
population and in what setting. Why?
I highly recommend expanding screening “to cover the birth cohort born from 1945
through 1965” which “offers a potential complement to current risk-based screening
recommendations” (Rein et al., 2012, p. 1). One time “cohort screening is estimated to identify
nearly 86% of undiagnosed cases compared with the 21% currently found through risk-based
screening” (Jensen & Reau, 2013, p. 29).
I recommend third generation EIA testing for the actual screening test.
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The location of the testing site is important. I believe testing centers should be located
where most people congregate and can receive testing.
My recommendations are in alignment with the USPSTF which recommends screening
for hepatitis C virus (HCV) infection in persons at high risk for infection and extending one-time
screening for HCV infection to adults born before 1964 and after 1945 for the city of Detroit
with a target population of Detroit residents who happen to be a majority of African Americans.
Why? As stated earlier in this paper among people born before 1964 and after 1945, rates
of Hepatitis C are higher in African Americans. African American baby boomers are twice as
likely to have Hepatitis C as are other baby boomers (Dean, 2014).
How you would you go about increasing the participation levels in the screening?
Based on my recommendations I would advocate for more testing or screening during
regular primary care visits. This would increase the participation levels. I would investigate
culturally linguistic approaches to getting the message out concerning hepatitis c infection. I
would increase funding to local health departments and community based organization
emphasizing the need to prevent HCV infection. I would perform more research on the “test to
treat model” focusing on HCV. It is good to be informed about the CDC’s initiative and the
importance placed on HCV infection and the African American community.
What role should public health play in increasing screening participation?
The role that public health should play in increasing screening participation should
include education, funding for local health departments, access to primary care facilities and
drug treatment facilities. Public health should invest in innovative projects, as well. Social
media should be explored as a means of increasing screening participation.
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As we move towards curing HCV infection epidemiology stands in the forefront. “In
clinical trials, antiviral therapy with pegylated interferon and ribavirin (PEG-IFN+R) has resulted
in a sustained viral response (SVR) (that is, cure) of HCV infection in 46% of patients infected
with genotype 1 (which infects 70% and 90% of chronically infected white and African
American persons in the United States, respectively)” (Rein et al., 2012, p. 1). According to the
American Association for the Study of Liver Diseases (AASLD) (2014, p. 1), “New direct-acting
oral agents capable of curing hepatitis C virus (HCV) infection have been approved for use in the
United States.” Therefore, as treatment improves screening or testing should be implemented
with enthusiasm.
Finally, there needs to more epidemiological, biomedical, and social and behavioral
research undertaken. In the meantime, the data derived from morbidity and mortality sources are
driving the motivation to continue and succeed. The goal is to improve the health of HCV
infected persons and prevent further infections. In conclusion, I believe as a result of “The
landscape of treatment for hepatitis C virus (HCV) infection [evolving] substantially” (American
Association for the Study of Liver Diseases, 2014, p. 1) the screening for HCV should be
strongly encouraged among the highly at risk and baby boomers with emphasis placed on
African American baby boomers.
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References
American Association for the Study of Liver Diseases. (2014, January 29). Recommendations for
Testing, Managing, and Treating Hepatitis C. Retrieved February 20, 2014, from
http://hcvguidelines.org/
American Medical Association. (2013, March 20). Proteomics. Retrieved from http://www.amaassn.org//ama/pub/physician-resources/medical-science/genetics-molecularmedicine/current-topics/proteomics.page
Centers for Disease Control and Prevention. (2013a, May 7). CDC DVH - Hepatitis C
Information For the Health Professional. Retrieved January 31, 2014, from
http://www.cdc.gov/hepatitis/hcv/
Centers for Disease Control and Prevention. (2013b, August 19). CDC DVH - Viral Hepatitis
Statistics & Surveillance - Surveillance for Viral Hepatitis – United States, 2011.
Retrieved February 1, 2014, from
http://www.cdc.gov/hepatitis/Statistics/2011Surveillance/Commentary.htm#hepC
Centers for Disease Control and Prevention. (2014, February 10). CDC DVH - Hepatitis C FAQs
for the Public. Retrieved February 27, 2014, from
http://www.cdc.gov/hepatitis/c/cfaq.htm#cFAQ54
Dean, H. (2014, February 21). Fighting Hepatitis C Among African Americans. blog.aids.gov —
HIV Policy & Programs. Research. New Media. Retrieved from
http://blog.aids.gov/2014/02/fighting-hepatitis-c-among-african-americans.html
Jensen, D., & Reau, N. (2013). Hepatitis C. New York, N.Y.: Oxford University Press.
Kesli, R., Polat, H., Terzi, Y., Kurtoglu, M. G., & Uyar, Y. (2011). Comparison of a Newly
Developed Automated and Quantitative Hepatitis C Virus (HCV) Core Antigen Test with
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the HCV RNA Assay for Clinical Usefulness in Confirming Anti-HCV Results. Journal
of Clinical Microbiology, 49(12), 4089–4093. doi:10.1128/JCM.05292-11
Mayo Clinic. (n.d.). HCV - Clinical: Hepatitis C Antibody Screen, Serum. Retrieved February
12, 2014, from http://www.mayomedicallaboratories.com/testcatalog/Clinical+and+Interpretive/80190
Nelson, K. E., & Thomas, D. L. (2007). Viral Hepatitis. In C. M. Williams (Ed.), Infectious
Disease Epidemiology: Theory and Practice (pp. 895–939). Sudbury, MA: Jones &
Bartlett Learning.
Parini, S. (2001). Hepatitis C: Speaking out about the silent epidemic. Nursing Management,
32(6), 18.
Penin, F., Dubuisson, J., Rey, F. A., Moradpour, D., & Pawlotsky, J.-M. (2004). Structural
biology of hepatitis C virus. Hepatology, 39(1), 5–19. doi:10.1002/hep.20032
Rein, D. B., Smith, B. D., Wittenborn, J. S., Lesesne, S. B., Wagner, L. D., Roblin, D. W., …
Weinbaum, C. M. (2012). The Cost-Effectiveness of Birth-Cohort Screening for Hepatitis
C Antibody in U.S. Primary Care Settings. Annals of Internal Medicine, 156(4), 263–270.
doi:10.7326/0003-4819-156-4-201202210-00378
Rosenberg, S. (2001). Recent advances in the molecular biology of hepatitis C virus. Journal of
Molecular Biology, 313(3), 451–464. doi:10.1006/jmbi.2001.5055
Schneider, M.-J. (2013). Introduction to public health. Jones & Bartlett Publishers.
U.S. Preventive Services Task Force. (2013, June 25). Screening for Hepatitis C Virus Infection
in Adults: Final Recommendation Statement. AHRQ Publication No. 12-05174-EF-2.
Retrieved February 27, 2014, from
http://www.uspreventiveservicestaskforce.org/uspstf12/hepc/hepcfinalrs.htm
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US National Library of Medicine, NIH, US HHS. (2013, September 23). What is a genome?
Retrieved October 2, 2013, from http://ghr.nlm.nih.gov/handbook/hgp/genome
Walzer, N., & Cotler, S. (2013). Diagnostic Testing. In Hepatitis C (p. 10). New York, N.Y.:
Oxford University Press.
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Footnotes
1
Percutaneous is defined adjectively as administered, removed, or absorbed by way of the
skin, as an injection, needle biopsy, or transdermal drug.
2
Parenteral is defined adjectively as taken into the body in a manner other than through
the digestive canal or not within the intestine; not intestinal.
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Tables
Table 1
Risk Factors for HCV
Illicit Drug or Intravenous Drug Use (IVDU)
Person with high-risk sexual behaviors such as unprotected sex and multiple partners
HIV-infected men who have sex with men (MSM) and engage in sexual behaviors that
increase mucosal trauma
Maternal-fetal transmission (especially among HIV-infected women)
Blood transfusion
Healthcare-related exposure to infected blood (needle stick injury, for instance).
Table 2
Features of hepatitis C virus infection
HCV RNA first detected in blood
Time until symptoms (if any)
Antibody first detected in blood
Acute illness (jaundice)
Chronic infection (mostly asx)
Cirrhosis
Mortality from Chronic Liver Disease
1-3 weeks
Average 6-7 weeks
Range 2-26 weeks
In 50-70% at onset of symptoms; in 90% by 3
months
Mild (< 20%)
75% - 85%
10% – 20%
1% - 5%
Table 3
Diagnostic Testing Used in Patients with Hepatitis C
Basic Laboratory Testing
Serologic Assays
Virologic Assays
HCV Genotyping with Subtypes
Complete metabolic panel
Complete blood count
Prothrombin time
Anti-HCV
RIBA
HCV RNA nucleic acid testing (NAT)
Quantitative
Qualitative
HCV core antigen EIA assay
1a-6
Source (all tables): Jensen, D., & Reau, N. (2013). Hepatitis C. Oxford University Press.
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Figure
Figure. Testing algorithm for hepatitis C (©2011, Natasha Walzer, MD)