T h e Ep i d e m i o l o g y o f C h ro n i c
Hepatitis C and One-Time
H e p a t i t i s C V i r u s Tes t i n g o f
Persons Bor n D uring 1 945 to 1965
in the U nited States
John W. Ward,
MD
KEYWORDS
Hepatitis C virus HCV testing Baby boomers HCV testing recommendations
KEY POINTS
Despite overall declines in hepatitis C incidence, hepatitis C virus (HCV) continues to be
transmitted; new infections are increasing in some populations, including young persons
who inject drugs.
As indicated by a national health survey, an estimated 3.2 million persons are living with
HCV in the United States.
Chronic hepatitis C is a major cause of liver disease, including hepatocellular carcinoma,
the fastest growing cancer-related cause of death.
Many if not most persons living with viral hepatitis remain undiagnosed.
To realize the health benefits anticipated from new HCV therapies, approaches to testing
must be strengthened and updated as HCV epidemiology evolves, more persons must
become aware of their HCV infection status through 1-time HCV testing, and those found
infected must be linked to care and treatment.
The Centers for Disease Control and Prevention recommendation for a 1-time HCV test for
persons born during 1945 to 1965 is a cost-effective approach to reducing HCVassociated morbidity and mortality.
Successful implementation of this policy requires public health, clinical care providers,
laboratories, and third-party payers to work together to improve HCV testing, care, and
treatment in the United States.
INTRODUCTION
Hepatitis C virus (HCV) is the most common blood-borne infection in the United States.
An estimated 4.1 million persons are infected with HCV, of whom 3.2 (2.7–3.9) million
have chronic infection.1 HCV is most often transmitted among persons who inject drugs
Division of Viral Hepatitis, Centers for Disease Control and Prevention, 1600 Clifton Road, NE,
Atlanta, GA 30333, MS G-37, USA
E-mail address: [email protected]
Clin Liver Dis 17 (2013) 1–11
http://dx.doi.org/10.1016/j.cld.2012.09.011
1089-3261/13/$ – see front matter Published by Elsevier Inc.
liver.theclinics.com
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(PWID) and through exposures to HCV-contaminated blood and blood products in health
care settings with inadequate infection control. Sexual contact and perinatal exposures
also serve as modes of transmission. Once infected with HCV, 75% to 85% of persons
remain chronically infected.2 Chronic infection with HCV can result in liver inflammation,
cirrhosis, and liver cancer; HCV infection is a leading cause of chronic liver disease, endstage liver disease, and eventual need for liver transplantation. HCV-associated mortality
is increasing in the United States, recently surpassing the number of deaths attributed to
human immunodeficiency virus (HIV)/AIDS (Fig. 1).3 Newly available therapies can clear
HCV (ie, achieve virologic cure) in most HCV-infected persons who receive treatment, and
numerous additional treatments undergoing clinical trials show promise for further benefits.4–6 However, many persons living with HCV infection are unaware of their infection
status.7–12 This review highlights the epidemiology of hepatitis C and the priorities for
prevention of HCV transmission and disease in an era of more effective antiviral therapies.
HCV TRANSMISSION
Approximately 60% to 70% of HCV-infected persons are asymptomatic during the
acute phase of infection. The average time from viral exposure to a positive antibody
to HCV (anti-HCV) seroconversion is 8 to 9 weeks, and anti-HCV can be detected in
more than 97% of persons by 6 months after exposure.13–15 The most efficient route
of HCV transmission is parenteral exposure to blood, including transfusions and injections. Among PWID, HCV infection is acquired rapidly after initiation of injecting, and
incidence rates of HCV infection are highest among young PWID.16–19 Risks for HCV
infection among PWID include years of injection drug use, injection frequency, sharing
practices, and sex work; HCV infection prevalence is strongly associated with duration
of injection drug use, reaching 65% to 90% among long-term injectors.16,18 High rates
of HCV among PWID largely explain the high rates among incarcerated populations.20
Health care-associated exposures also are major sources of HCV transmission,
including receipt of blood not screened for HCV, unsafe injections, and other health
care procedures. In the United States, reports of nosocomial HCV transmission
have increased in recent years. From 1998 to 2012, the Centers for Disease Control
and Prevention (CDC) investigated at least 33 outbreaks of HCV infection linked to
7
Rate per 100,000 Persons
2
6
5
4
3
2
1
Hepatitis B
Hepatitis C
HIV
0
1999 2000 2001 2002 2003 2004 2005 2006 2007
Year
Fig. 1. Age-adjusted rates of mortality associated with hepatitis B, hepatitis C, and HIV,
United States, 1999 to 2007. (Data from Centers for Disease Control. Sentinel counties study
of viral hepatitis and state disease surveillance.)
The Epidemiology of Chronic Hepatitis C
transmission in variety of care settings (CDC unpublished data, 2012).21 The risk of
HCV transmission after a needlestick exposure to blood from a source positive for
anti-HCV is 1.8% (range: 0%–7%).22–25 Generally, HCV is less efficiently transmitted
by mucosal exposures to blood, although noninjection-drug users who sniff cocaine
and other drugs have increased risks for HCV infection.26 HCV in plasma can survive
drying and environmental exposure to room temperature for at least 16 hours, supporting epidemiologic studies that implicate injection equipment, household exposures, and unsafe barbering practices as modes of HCV transmission.27
HCV also can be transmitted through perinatal and sexual exposures. The risk of perinatal transmission is 4% to 5% for infants born to HCV-infected, HIV-negative women,
increasing to 17% to 25% among infants born to women coinfected with HCV and
HIV.28,29 Although sexual transmission of HCV is not as common as other transmission
modes, case-control studies have reported an association between acquiring hepatitis
C and exposure to an HCV-infected sex contact or exposure to multiple sex partners.30
In addition, 15% to 20% of newly infected patients report a history of sexual exposures
in the absence of percutaneous risk factors for HCV.31 Risk of HCV transmission by
sexual exposure varies by population. HCV prevalence is low (1.5%) among longterm heterosexual partners of persons with chronic HCV infection.32–35 In contrast,
coinfection with HIV-1 seems to increase the risk of HCV sexual transmission among
men who have sex with men (MSM). In the last several years, outbreaks of HCV infection
have been reported among HIV-infected MSM without a history of injection drug use in
Europe and more recently, the United States.36–39
HEPATITIS C INCIDENCE
Hepatitis C incidence in the United States peaked at approximately 240,000 new
infections per year in the early to mid-1980s, before the discovery of HCV in 1988
(Fig. 2).40,41 In the following years, incidence of hepatitis C declined steadily until
2004, when incidence leveled at an estimated 15,000 to 20,000 new infections (0.3
cases per 100,000 population). In 2010, an estimated 17,000 new HCV infections
occurred, with injection drug use being the most commonly reported risk factor.42
However, the number of new HCV infections seems to be increasing in some areas
of the United States. For example, from 2002 to 2009, Massachusetts observed an
increase in reports of HCV among persons 15 to 24 years of age.43 These cases
Fig. 2. Estimated incidence of acute hepatitis C: United States, 1982 to 2009. (Courtesy of
Sentinel Counties Study of Viral Hepatitis and State Disease Surveillance; with permission.)
3
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were reported from all areas of the state; injection drug use was the most common risk
for HCV transmission. Other states have reported similar increases.44 Taken together,
these data suggest a new wave of HCV transmission among populations of adolescents and young adults who have recently begun to inject drugs.
HEPATITIS C PREVALENCE
Based on a national health survey, an estimated 3.2 (2.7–3.9) million persons are living
with HCV in the United States.1 However, because this survey excludes or underestimates populations at greatest risk for hepatitis C (eg, incarcerated persons), an additional 500,000 to 1,000,000 persons are likely infected with HCV.45 Chronic hepatitis C
is a major cause of liver disease; approximately 36% of all persons awaiting liver transplant and at least 50% of all persons with hepatocellular carcinoma (HCC) are HCVinfected.46,47 With a 2.5% annual increase, HCC-associated deaths are increasing
faster than other causes of cancer deaths.48
Both acute and chronic HCV infections are relatively asymptomatic. Therefore,
persons living with HCV are often unaware that they are infected until late in the course
of disease, typically resulting in a decades-long latency between acquisition of HCV
and the development of end-stage liver disease and death. After 30 years of infection,
persons living with HCV have a 15% to 35% and 1% to 3% risk for cirrhosis and HCC,
respectively.49,50 However, the risk for disease progression continues over a lifetime,
and risks of HCV-related morbidity and mortality are expected to increase as persons
with chronic hepatitis C grow older. During the next 40 to 50 years, a projected 1.76
million persons with untreated HCV infection are expected to develop cirrhosis, with
a peak prevalence of 1 million cases occurring from the mid-2020s to the mid2030s; approximately 400,000 will develop HCC.51 Of persons with hepatitis C who
do not receive needed care and treatment, approximately 1 million are expected to
die from HCV-related complications.
HCV INFECTION PREVALENCE AMONG PERSONS BORN DURING 1945 TO 1965
Of persons living with hepatitis C, an estimated 76% are adults born during 1945 to
1965 (a population known as baby boomers in the United States).52 As this population
likely has been infected for several decades, HCV-associated morbidity and mortality
are on the increase. Hepatitis C-associated mortality increased 50% during 1999 to
2007 (annual mortality change: 10.18 deaths per 100,000 population per year). In
2007, HCV caused 15,106 deaths, 73.4% of which occurred among persons aged
45 to 64 years (roughly corresponding to the baby boomer cohort); the median age
of death was 57 years, approximately 20 years less than the average life span of
persons living in the United States.3 A study of HCV-infected military veterans in
care from 1996 to 2003, many of whom were born during 1945 to 1965, reported
increased rates of cirrhosis (50%) and HCC (20-fold) during the study period.53
ECONOMIC IMPLICATIONS OF HCV INFECTION
HCV infection poses an economic burden in the United States, resulting in lost
productivity and additional health care costs for infected persons. Compared with
other employees, those with HCV infection require more sick leave per year and
short-term and long-term disability, resulting in more absences from work and lost
productivity.54 HCV infection also results in substantial direct costs for medical
care. A study of medical reimbursement claims from 2002 to 2006 revealed that hospitalization occurred in 24% of HCV-infected patients compared with 7% of controls.55
The Epidemiology of Chronic Hepatitis C
Annual health care costs for HCV-infected persons were 5-fold higher than those for
other patients, totaling $20,961 and exceeding costs for other common diseases,
including cardiovascular diseases ($18,965) and diabetes mellitus ($9677). Numerous
studies reveal the cost-effective benefits of HCV screening and care for populations at
risk for hepatitis C56,57; In 1 study, HCV therapy followed by viral clearance reduced
annual costs of patient care by half.55
NEW TREATMENTS FOR HCV
Therapy can clear HCV infection from the body, resulting in sustained virologic
response (SVR), which indicates virologic cure. Until 2011, approximately 40% of
patients who completed a 48-week course of a standard therapeutic regimen of pegylated interferon and ribavirin achieved SVR.2 In 2011, 2 new agents, boceprevir and
telaprevir, were licensed for treatment of HCV, representing the first direct-acting
agents (DAAs) with specific activity against HCV infection. Compared with pegylated
interferon/ribavirin therapy alone, the addition of telaprevir or boceprevir to this
regimen increases SVR rates from 38% to 63% and 44% to 75%, respectively.4,5
Guided by patients’ HCV RNA level during therapy, the course of treatment can be
as short as 24 to 28 weeks for patients with optimal viral response. However, serious
adverse events during therapy continue to affect 5% to 10% of patients.2 Approximately 20 HCV treatments (eg, protease and polymerase inhibitors) are undergoing
phase II or phase III clinical trials.6 These agents are expected to decrease adverse
events, shorten the duration of therapy, and improve treatment effectiveness; they
also may lead to an all-oral regimen for HCV treatment, without the need for pegylated
interferon.58 Treatment recommendations will change as new medications become
available for use in the United States.59
TESTING AND LINKAGE TO CARE
Only through HCV testing with linkage to care can HCV-infected persons receive
needed clinical management and treatment. However, at a time of increasing HCVrelated morbidity and mortality, hepatitis C is an underrecognized and undertreated
disease. In 2007, fewer than 85,000 persons were treated for HCV infection (a fraction
of the estimated 3.2 million persons infected with the virus).11 Some patients do not
meet the recommended criteria to receive therapy, and others have conditions (eg,
depression) for which therapy is contraindicated.2,59 However, as reported by the
Institute of Medicine, other barriers to improved health outcomes for persons living
with hepatitis C exist, including the lack of awareness of HCV infection as a health
threat by policy makers and the public; inadequate numbers of clinicians trained to
test, manage, and treat HCV-infected patients; and the low percentage of persons
aware of their infection.60
Since 1998, CDC has recommended HCV testing for certain high-risk populations,
including persons who have ever injected illegal drugs; recipients of transfusions and
transplants before 1992; patients with selected medical conditions (eg, dialysis and
increased alanine transaminase level); health care and public safety workers after needlesticks, sharps, or mucosal exposures to HCV-positive blood; and children born to
HCV-positive women.61 However, strategies based on risk ascertainment and certain
medical indications have been implemented with variable success. Of participants in
the National Health and Nutrition Examination Survey, only 3 (7%) of 46 HCV-infected
persons reported having been tested based on known HCV-related risk factors.12 Of
HCV-infected persons, only 45% to 85% have been tested for HCV7–9,11,12; these low
rates reflect the challenges faced by clinicians and patients when discussing sensitive
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personal behaviors, particularly when they are not relevant to the current medical care
visit.
To overcome barriers to risk-based approaches to HCV testing, CDC considered
alternative public health strategies. Because persons born during 1945 to 1965
have a 5-fold greater prevalence of HCV infection (3.25%) than other adults (Fig. 3),
accounting for more than three-fourths (76.5%) of the total anti-HCV prevalence
and 73% of HCV-related mortality in the United States, CDC is now recommending
HCV testing of persons born during these years.62 In addition to testing adults of all
ages at high risk for HCV infection, CDC recommends that adults born during 1945
to 1965 should receive 1-time testing for HCV without previous ascertainment of
HCV risk (Box 1). Further, all persons identified with HCV infection should receive
a brief alcohol screening and intervention as clinically indicated, followed by referral
to appropriate care and treatment services for HCV infection and related conditions.
With full implementation of this strategy, CDC estimates that 800,000 persons
currently unaware of their HCV infection will be identified; more than 120,000 HCVrelated deaths will be averted if these persons are linked to appropriate care and
DAA treatment.63
Critical to the effectiveness of CDC’s recommendation for 1-time HCV testing among
persons born during 1945 to 1965 is consistent implementation by the clinicians serving
persons in this birth cohort and an understanding of the need for HCV testing by the targeted population. Guided by a US Department of Health and Human Services (HHS)
action plan for viral hepatitis that outlines explicit steps to improve coordination across
HHS agencies,64 CDC has initiated several activities to foster implementation of the
new HCV testing recommendations. To improve awareness of viral hepatitis among
the public and providers, CDC recently launched the Know More Hepatitis multimedia
campaign (http://www.cdc.gov/knowmorehepatitis), which provides persons born
during 1945 to 1965 with targeted HCV testing messages and a risk-assessment
tool. The campaign also provides public health and clinical care providers online
training opportunities. To increase capacity for HCV testing and linkage to care in fiscal
year 2012, CDC provided funds to support HCV testing and linkage to care in diverse
clinical settings. Further, funds were allocated to replicate models of case-based
learning to help primary care providers deliver high-quality HCV-related care and treatment comparable with that provided by medical specialists.65
Several mechanisms are in place for the collection of surveillance and epidemiologic
data to evaluate trends in HCV testing, care, and treatment. For example, data on
7.0
Prevalence of anti-HCV
(%)
6
1988-1994
6.0
1999-2002
5.0
4.0
3.0
2.0
1.0
0.0
0
10
20
30
40
50
60
70
Age at time of survey (years)
Fig. 3. Prevalence of hepatitis C virus antibody (anti-HCV), by age at time of survey — Third
National Health and Nutrition Examination Survey (NHANES III) 1988–1994 and NHANES IV,
1999–2002. (Data from Armstrong GL, Wasley A, Simard EP, et al. The prevalence of hepatitis
C virus infection in the United States, 1999 through 2002. Ann Intern Med 2006;144(10):705–14.)
The Epidemiology of Chronic Hepatitis C
Box 1
CDC recommendation for 1-time HCV testing persons born during 1945 to 1965
In addition to testing adults at risk for HCV infection, CDC recommends that:
Adults born during 1945 to 1965 should receive 1-time testing for HCV without previous
ascertainment of HCV risk factor. (Strong recommendation, moderate quality of evidence.)
All persons with identified HCV infection should receive a brief alcohol screening and
intervention as appropriate, followed by referral to appropriate care and treatment
services for HCV infection and related conditions as indicated. (Strong recommendation,
moderate quality of evidence.)
acute and chronic HCV infection are reported to CDC through state/local hepatitis C
surveillance systems. To evaluate clinical management, CDC, in collaboration with the
CDC Foundation’s Viral Hepatitis Action Coalition, is monitoring the quality and impact
of care and treatment of more than 10,000 HCV-infected patients. In the future, questions regarding HCV testing will be incorporated into national health surveys to help
assess the impact of HCV testing recommendations, and data compiled from outpatient and inpatient health records will be analyzed to detect changes in HCV testing
patterns. CDC also evaluates point of care and other technologies to facilitate HCV
testing and surveillance.66
SUMMARY
Despite overall declines in hepatitis C incidence, HCV continues to be transmitted;
new infections are increasing in some populations, including young PWID. Chronic
HCV infections acquired in decades past are now manifesting, damaging the liver
and leading to increases in HCV-related morbidity and mortality; hepatitis C represents a major health disparity for persons born during 1945 to 1965. Many if not
most persons living with viral hepatitis remain undiagnosed. To realize the health
benefits anticipated from new HCV therapies, approaches to testing must be strengthened and updated as HCV epidemiology evolves, more persons must become aware
of their HCV infection status through 1-time HCV testing, and those found infected
must be linked to care and treatment. The CDC recommendation for a 1-time HCV
test for persons born during 1945 to 1965 is a cost-effective approach to reducing
HCV-associated morbidity and mortality.63 Successful implementation of this policy
requires public health, clinical care providers, laboratories, and third-party payers to
work together to improve HCV testing, care, and treatment in the United States.
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