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Purpose
and Goals
 This
course is designed to give nurses and other healthcare professionals an
overview of the hepatitis C virus (HCV) as a major public health problem
in the U.S. today. Topics covered include the assessment, treatment, and
prevention of hepatitis C.
Instructional
Objectives
Upon
completion of this course, the motivated learner will be able to:
- Outline the prevalence of HCV infection in the United States.
- Name the primary ways that HCV is transmitted.
- Recognize current methods for screening and diagnosis of HCV.
- List clinical indicators of both acute and chronic HCV infection.
- Name and define primary approaches to management and treatment of
HCV.
- Outline specific prevention strategies for various populations at
risk for HCV infection.
- Enumerate key components of the education process for patients with
HCV.
Introduction
 Hepatitis
C virus (HCV) infection is the most common chronic bloodborne infection
in the United States. An estimated 3.9 million (1.8%) Americans have been
infected with HCV, and 2.7 million of those are chronically infected.
Many might not be aware of their infection, however, because they are
not clinically ill. Infected persons serve as a source of transmission
to others and are at risk for chronic liver disease or other HCV-related
chronic diseases during the first two or more decades following initial
infection. Chronic liver disease is the tenth leading cause of death among
adults in the United States, and accounts for approximately 25,000 deaths
annually; and 40% of chronic liver disease is HCV-related. Because most
HCV-infected persons are between 30 and 49 years of age, the number of
deaths attributable to HCV-related chronic liver disease could increase
substantially during the next 10-20 years, as this group of infected persons
reaches ages at which complications from chronic liver disease typically
occur.
HCV
infection occurs among persons of all ages, but the highest incidence
of acute hepatitis C is found among persons aged 20-39 years, and males
predominate slightly. African Americans and whites have similar incidence
of acute disease; persons of Hispanic ethnicity have higher rates. In
the general population, the highest prevalence rates of HCV infection
are found among persons aged 30-49 years and among males. Unlike the racial/ethnic
pattern of acute disease, African Americans have a substantially higher
prevalence of chronic HCV infection than do whites.
HCV
is transmitted primarily through large or repeated direct percutaneous
exposures to blood. In the United States, the two most common exposures
associated with transmission of HCV are blood transfusion and injecting-drug
use, but their relative importance has changed over time. Blood transfusion,
which accounted for a substantial proportion of HCV infections acquired
more than 10 years ago, rarely accounts for recently acquired infections.
In contrast, injecting-drug use consistently has accounted for a substantial
proportion of HCV infections and currently accounts for 60% of HCV transmission
in the United States. Interestingly, the dramatic decline in incidence
of acute hepatitis C since 1989 correlates with a decrease in cases among
injecting-drug users. Other risk factors for transmission of HCV include
employment in patient care or clinical laboratory work, exposure to a
sex partner or household member who has had a history of hepatitis, exposure
to multiple sex partners, and low socioeconomic level. Research studies
have reported no association with military service or exposures resulting
from medical, surgical, or dental procedures, tattooing, acupuncture,
ear piercing, or foreign travel. If transmission from such exposures does
occur, the frequency might be too low to detect.
Screening
and Diagnostic Tests
Elevated
blood levels of the enzyme alanine aminotransferase (ALT) are a diagnostic
indication of liver disease but are not specific to HCV. The only tests
currently approved by the U.S. Food and Drug Administration (FDA) for
diagnosis of HCV infection are those that measure anti-HCV antibodies.
These tests detect anti-HCV in more than 97% of infected patients, but
do not distinguish between acute, chronic, or resolved infection.
The
diagnosis of HCV infection also can be made by qualitatively detecting
HCV RNA using gene amplification techniques such as RT-PCR. HCV RNA can
be detected in serum or plasma within one to two weeks after exposure
to the virus and weeks before the onset of ALT elevations or the appearance
of anti-HCV. Rarely, detection of HCV RNA might be the only evidence of
HCV infection. Assay kits for HCV RNA are available for research purposes
from various manufacturers of diagnostic reagents, and numerous laboratories
perform RT-PCR using in-house laboratory methods and reagents. Although
none of the RT-PCR tests have been approved by the FDA, RT-PCR assays
for HCV infection are used commonly in clinical practice. Because of assay
variability, rigorous quality assurance and control should be in place
in clinical laboratories performing this assay, and proficiency testing
is recommended.
At
least six different genotypes and more than 90 subtypes of HCV exist.
Approximately 70% of HCV-infected persons in the United States are infected
with genotype 1, with frequency of subtype 1a predominating over subtype
1b. Different nucleic acid detection methods are available commercially
to group isolates of HCV, based on genotypes and subtypes. Evidence is
limited regarding differences in clinical features, disease outcome, or
progression to cirrhosis or hepatocellular carcinoma (HCC) among persons
with different genotypes. However, differences do exist in responses to
antiviral therapy according to HCV genotype. Rates of response in patients
infected with genotype 1 are substantially lower than in patients with
other genotypes, and treatment regimens might differ on the basis of genotype.
Thus, genotyping might be warranted among persons with chronic hepatitis
C who are being considered for antiviral therapy.
Clinical
Presentation of HCV Infection
Persons
with acute HCV infection typically are either asymptomatic or have
a mild clinical illness; 60%-70% have no discernible symptoms; 20%-30%
might have jaundice; and 10%-20% might have nonspecific symptoms such
as anorexia, malaise, or abdominal pain. Clinical illness in patients
with acute hepatitis C who seek medical care is similar to that of other
types of viral hepatitis, and serologic testing is necessary to determine
the etiology of hepatitis in an individual patient. The course of acute
hepatitis C is variable, although elevations in serum ALT levels, often
in a fluctuating pattern, are its most characteristic feature. Normalization
of ALT levels might occur and suggests full recovery, but this is frequently
followed by ALT elevations that indicate progression to chronic disease.
Fulminant hepatic failure following acute hepatitis C is rare.
After
acute infection, 15%-25% of persons appear to resolve their infection
without sequelae. Chronic HCV infection develops in most persons,
however, with active liver disease in 60-70% of those who are chronically
infected. No clinical or epidemiologic features among patients with acute
infection have been found to be predictive of either persistent infection
or chronic liver disease.
The
course of chronic liver disease is usually insidious, progressing at a
slow rate without symptoms or physical signs in the majority of patients
during the first two or more decades after infection. Frequently, chronic
hepatitis C is not recognized until asymptomatic persons are identified
as HCV-positive during blood-donor screening, or elevated ALT levels are
detected during routine physical examinations. Most studies have reported
that cirrhosis develops in 10%-20% of persons with chronic hepatitis C
over a period of 20-30 years, and hepatocellular carcinoma (HCC) in 1-4%.
Although
factors predicting severity of liver disease have not been well defined,
recent data indicate that increased alcohol intake, being over 40 years
of age at infection, and being male are associated with more severe liver
disease. In particular, among persons with alcoholic liver disease and
HCV infection, liver disease progresses more rapidly; and among those
with cirrhosis, a higher risk for development of HCC exists. Furthermore,
even intake of moderate amounts of alcohol in patients with chronic hepatitis
C might enhance disease progression. More severe liver injury observed
in persons with alcoholic liver disease and HCV infection possibly is
attributable to alcohol-induced enhancement of viral replication or increased
susceptibility of cells to viral injury. In addition, persons who have
chronic liver disease are at increased risk for fulminant hepatitis A.
Extrahepatic
manifestations of chronic HCV infection are considered to be of immunologic
origin and include cryoglobulinemia, membranoproliferative glomerulonephritis,
and porphyria cutanea tarda. Other extrahepatic conditions have been reported,
but definitive associations of these conditions with HCV infection have
not been established. These include seronegative arthritis, Sjogren syndrome,
autoimmune thyroiditis, lichen planus, Mooren corneal ulcers, idiopathic
pulmonary fibrosis (Hamman-Rich syndrome), polyarteritis nodosa, aplastic
anemia, and B-cell lymphomas.
Clinical
Management and Treatment
HCV-positive
patients should be evaluated for presence and severity of chronic liver
disease. Initial evaluation for presence of disease should include multiple
measurements of ALT at regular intervals, because ALT activity fluctuates
in persons with chronic hepatitis C. Patients with chronic hepatitis C
should be evaluated for severity of their liver disease and for possible
treatment.
 Antiviral
therapy is recommended for patients with chronic hepatitis C who are at
greatest risk for progression to cirrhosis. These persons include anti-HCV-positive
patients with persistently elevated ALT levels, detectable HCV RNA, and
a liver biopsy that indicates either portal or bridging fibrosis or at
least moderate degrees of inflammation and necrosis.
In
patients with less severe histologic changes, indications for treatment
are less clear, and careful clinical follow-up might be an acceptable
alternative to treatment with antiviral therapy (e.g., interferon) because
progression to cirrhosis is likely to be slow, if it occurs at all. Similarly,
patients with compensated cirrhosis (without jaundice, ascites, variceal
hemorrhage, or encephalopathy) might not benefit from interferon therapy.
Careful assessment should be made, and the risks and benefits of therapy
should be thoroughly discussed with the patient.
Patients
with persistently normal ALT values should not be treated with interferon
outside of clinical trials because treatment might actually induce liver
enzyme abnormalities. Patients with advanced cirrhosis who might be at
risk for decompensation with therapy and pregnant women also should not
be treated. Interferon treatment is not FDA-approved for patients aged
less than 18 years, and more data are needed regarding treatment of persons
aged less than 18 years or greater than 60 years. Treatment of patients
who are drinking excessive amounts of alcohol or who are injecting illegal
drugs should be delayed until these behaviors have been discontinued for
at least 6 months. Other contraindications to treatment with interferon
include major depressive illness, cytopenias, hyperthyroidism, renal transplantation,
and evidence of autoimmune disease.
Therapy
for hepatitis C is a rapidly changing area of clinical practice. Combination
therapy with interferon and ribavirin, a nucleoside analogue, is now FDA-approved
for treatment of chronic hepatitis C in patients who have relapsed following
interferon treatment and is also an option for patients who have not been
treated previously. Studies of patients treated with a combination of
ribavirin and interferon have demonstrated a substantial increase in sustained
response rates, reaching 40%-50%, compared with response rates of 15%-25%
with interferon alone. However, as with interferon alone, combination
therapy in patients with genotype 1 is not as successful, and sustained
response rates among these patients are still less than 30%.
Most
patients receiving interferon experience flu-like symptoms early in treatment,
but these symptoms diminish with continued treatment. Later side effects
include fatigue, bone marrow suppression, and neuropsychiatric effects
(e.g., apathy, cognitive changes, irritability, and depression). Interferon
dosage must be reduced in 10%-40% of patients and discontinued in 5% -15%
because of severe side effects. Ribavirin can induce hemolytic anemia
and can be problematic for patients with preexisting anemia, bone marrow
suppression, or renal failure. In these patients, combination therapy
should be avoided or attempts should be made to correct the anemia. Hemolytic
anemia caused by ribavirin also can be life threatening for patients with
ischemic heart disease or cerebral vascular disease. Ribavirin is teratogenic,
and female patients should avoid becoming pregnant during therapy.
Other
treatments, including corticosteroids, ursodiol, and thymosin, have not
been effective. High iron levels in the liver might reduce the efficacy
of interferon. Use of iron-reduction therapy (phlebotomy or chelation)
in combination with interferon has been studied, but results have been
inconclusive. Because patients are becoming more interested in alternative
therapies (e.g., traditional Chinese medicine, antioxidants, naturopathy,
and homeopathy), nurses and other healthcare professionals should be prepared
to address questions regarding these topics.
Postexposure
Prophylaxis and Follow-Up
Available
data regarding the prevention of HCV infection with IG indicate that IG
is not effective for postexposure prophylaxis of hepatitis C. Research
does not support postexposure use of antiviral agents (e.g., interferon)
to prevent HCV infection, and such use is not currently recommended. Mechanisms
of the effect of interferon in treating patients with hepatitis C are
poorly understood, and an established infection might need to be present
for interferon to be an effective treatment.
The
immediate postexposure setting provides opportunity to identify persons
early in the course of their HCV infection. Studies indicate that interferon
treatment begun early in the course of HCV infection is associated with
a higher rate of resolved infection. However, no data exist indicating
that treatment begun during the acute phase of infection is more effective
than treatment begun early during the course of chronic infection. In
addition, interferon is not FDA-approved for this indication. Determination
of whether treatment of HCV infection is more beneficial in the acute
phase than in the early chronic phase will require further evaluation
with well-designed research protocols.
Prevention
and Control of HCV
Further
reducing the burden of HCV infection and HCV-related disease in the United
States requires implementation of primary prevention activities that reduce
the risks for contracting HCV infection, and secondary prevention activities
that reduce risks for liver and other chronic diseases in HCV-infected
persons. In addition, surveillance and evaluation activities are required
to determine the effectiveness of prevention programs in reducing incidence
of disease, identifying persons infected with HCV, providing appropriate
medical follow-up, and promoting healthy lifestyles and behaviors.
Primary
prevention activities can reduce or eliminate potential risk for HCV transmission
from a) blood, blood components, and plasma derivatives; b) such high-risk
activities as injecting-drug use and sex with multiple partners; and c)
percutaneous exposures to blood in healthcare and other (i.e., tattooing
and body piercing) settings. Immunization against HCV is not available;
therefore, identifying persons at risk but not infected with HCV provides
opportunity for counseling on how to reduce their risk for becoming infected.
Current
practices that exclude blood, plasma, organ, tissue, or semen donors determined
to be at increased risk for HCV by history or who have serologic markers
for HCV infection must be maintained to prevent HCV transmission from
transfusions and transplants. Viral inactivation of clotting factor concentrates
and other products derived from human plasma, including IG products, also
must be continued, and all plasma-derived products that do not undergo
viral inactivation should be HCV RNA negative by RT-PCR before release.
Healthcare
professionals in all patient care settings routinely should obtain a history
that inquires about use of illegal drugs (injecting and others) and evidence
of high-risk sexual practices, such as multiple sex partners or a history
of sexually transmitted diseases (STDs). Primary prevention of illegal
drug injecting will eliminate the greatest risk factor for HCV infection
in the United States. Although consistent data are lacking regarding the
extent to which sexual activity contributes to HCV transmission, persons
having multiple sex partners are at risk for STDs (e.g., HIV, HBV, syphilis,
gonorrhea, and chlamydia). Counseling and education to prevent initiation
of drug-injecting or high-risk sexual practices is important, especially
for adolescents. Persons who inject drugs or who are at risk for STDs
should be counseled regarding what they can do to minimize their risk
for becoming infected or of transmitting infectious agents to others,
including the need for vaccination against hepatitis B. Injecting and
non-injecting illegal drug users and sexually active men who have sex
with men also should be vaccinated against hepatitis A.
Healthcare,
emergency medical, and public safety workers should be educated regarding
risk for and prevention of bloodborne infections, including the need to
be vaccinated against hepatitis B. Standard barrier precautions and engineering
controls should be implemented to prevent exposure to blood. Protocols
should be in place for reporting and follow-up of percutaneous or permucosal
exposures to blood or body fluids that contain blood.
Currently,
no recommendations exist to restrict professional activities of healthcare
workers with HCV infection. As recommended for all healthcare workers,
those who are HCV-positive should follow strict aseptic technique and
standard precautions, including appropriate use of hand washing, protective
barriers, and care in the use and disposal of needles and other sharp
instruments.
Healthcare
professionals responsible for overseeing patients receiving home infusion
therapy should ensure that patients and their families (or caregivers)
are informed of potential risk for infection with bloodborne pathogens,
and should assess their ability to use adequate infection control practices
consistently. Patients and families should receive training with a standardized
curriculum that includes appropriate infection control procedures, and
these procedures should be evaluated regularly through home visits.
Prevalence
of anti-HCV positivity among chronic hemodialysis patients averages 10%,
with some centers reporting rates greater than 60%, and studies indicate
that HCV transmission might occur among patients in a hemodialysis center
because of incorrect implementation of infection control practices, particularly
sharing of medication vials and supplies. In chronic hemodialysis settings,
therefore, intensive efforts must be made to educate new staff and reeducate
existing staff regarding hemodialysis-specific infection control practices
that prevent transmission of HCV and other bloodborne pathogens. Hemodialysis
center precautions are more stringent than standard precautions. Standard
precautions require use of gloves only when touching blood, body fluids,
secretions, excretions, or contaminated items. In contrast, hemodialysis
center precautions require glove use whenever patients or hemodialysis
equipment is touched. Standard precautions do not restrict use of supplies,
instruments, and medications to a single patient; hemodialysis center
precautions specify that none of these items be shared among any patients.
Thus, appropriate use of hemodialysis center precautions should prevent
transmission of HCV among chronic hemodialysis patients, and isolation
of HCV-positive patients is not necessary or recommended.
Persons
who are considering tattooing or body piercing should be informed of potential
risks of acquiring infection with bloodborne and other pathogens through
these procedures. These procedures might be a source of infection if equipment
is not sterile or if the artist or piercer does not follow other proper
infection control procedures (e.g., washing hands, using latex gloves,
and cleaning and disinfecting surfaces).
Persons
who should be tested routinely for hepatitis C virus (HCV) infection based
on their risk for infection include those who:
- have ever injected illegal drugs, including those who injected once
or a few times many years ago and do not consider themselves as drug
users.
- have been diagnosed with selected medical conditions, including those
who:
- received
clotting factor concentrates produced before 1987;
- were
ever on chronic (long-term) hemodialysis; and
- have
persistently abnormal ALT levels.
- are recipients of transfusions or organ transplants, including those
who:
- were
notified that they received blood from a donor who later tested positive
for HCV infection;
- received
a transfusion of blood or blood components before July 1992; or
- received
an organ transplant before July 1992.
Persons
who should be tested routinely for HCV infection based on a recognized
exposure include healthcare, emergency medical, and public safety workers
after needle sticks, sharps, or mucosal exposures to HCV-positive blood;
and children born to HCV-positive women.
Routine
testing for HCV infection is not recommended for healthcare, emergency
medical, and public safety workers; pregnant women; household (nonsexual)
contacts of HCV-positive persons; or the general population, unless they
have specific risk factors for infection. |
National Center
of Continuing Education
