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Bloodborne Pathogens
Module 3: Viral Hepatitis and HCV Exposure
Page 24
Objectives:
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
Describe the routes of transmission for HCV exposure/infection.
Describe the effect of HCV on the liver.
State the prevalence of HCV infection in the population.
Discuss the most common risk factors associated with HCV infection.
Describe the role of donated blood or blood products in HCV
transmission.
Describe the role of hemodialysis in HCV transmission.
What is the incubation period for HCV infection.
Describe the symptoms and presentation of acute HCV infection.
Describe the complications associated with chronic HCV infection.
Define the risk of developing chronic HCV infection following acute
infection.
Describe the role of prophylactic treatment with respect to prevention of
HCV.
Define the risk of developing HCV infection following exposure.escribe
the role of immunization with respect to prevention of HCV infection.
Be familiar with the difficulties associated with HCV vaccine
development.
Be familiar with the treatment goal(s) for HCV.
Be familiar with the two most common anti-viral agents used to treat
chronic HCV infection, and common side-effects.
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Bloodborne Pathogens
Module 3: Viral Hepatitis and HCV Exposure
Page 25
Introduction
Like HBV, HCV is an infectious disease that attacks the liver. However, unlike
HBV infection, HCV often progresses to chronic infection, and almost everyone
infected with HCV becomes a carrier.
Most patients develop very mild flu-like symptoms, or no symptoms.
Acute HCV infection cannot be differentiated from HBV on the basis of clinical
presentation.
HCV Life cycle
HCV attaches to liver cells and is taken into the cytoplasm, using the cell’s
resources to replicate. New viral particles are released from these initially
infected cells to infect other liver cells.
HCV has extremely high replication rates, producing approximately
1,000,000,000,000 infectious viral particles per day. The rapid reproductive rate
creates problems with vaccine development and treatment regimens, because
changes occur in new generations as viruses reproduce. Some of these changes
will result in nonsense or noninfectious structures, but because there are so
many copies formed in a short period of time, larger numbers of them will be
functional, infectious, and different from the parent virus. Because the target
(HCV virus) changes, the vaccines and anti-viral agents become ineffective
quickly.
Host Response
The host immune system plays an essential role in limiting the replication of
HCV, but is also responsible for tissue damage resulting from HCV infection.
Much of the liver damage occurs during attempts by the immune system to clear
HCV infection.
The majority of individuals infected with HCV progress to chronic infection,
suggesting that immune response is often inadequate. And, unlike HBV infection,
prior HCV infection is not protective against re-infection.
Epidemiology
HCV is a major cause of acute hepatitis and chronic liver disease. Globally,
approximately 170,000,000 people (3% of the world’s population) are chronically
infected with HCV, and the incidence of new infection is 3 to 4 million each year.
ARO Training & Consulting
Bloodborne Pathogens
Module 3: Viral Hepatitis and HCV Exposure
Page 26
The highest prevalence of HCV infection is found among people with large and/or
repeated direct percutaneous exposures to blood:
 injecting-drug users
 persons with hemophilia who were treated with clotting factor concentrates
produced before 1987 testing was implemented – persons with hemophilia
who were treated with products before inactivation have HCV prevalence
rates as high as 90%
 recipients of transfusions from HCV-positive donors – currently, the risk of
post-transfusion HCV infection is approximately 0.001% (1/100,000) per
unit transfused
Moderate prevalence is found among people with frequent percutaneous
exposures involving introduction of small numbers of viral particles – long-term
hemodialysis patients. Prevalence of anti-HCV among chronic hemodialysis
patients is estimated at greater than 10%, and incidence increases with the
number of years on hemodialysis.
Lower prevalence is found among people with high-risk sexual practices, and
among HCWs where small, infrequent percutaneous exposures occur.
Global
Infected persons serve as a source of transmission to others and are at risk for
chronic liver disease and/or other chronic diseases associated with HCV.
Because acute symptoms are often mild, and conditions associated with chronic
infection often take up to 20 or more years to develop, many individuals who are
infected do not yet know that they are.
Reference: World Health Organization (WHO). 2000. Hepatitis C. Fact Sheet
No 164. Retrieved on August 24, 2004 from
http://www.who.int/mediacentre/factsheets/fs164/en/.
Prevalence rates of HCV vary from 0.15% in Scandinavia (15 cases per 1000
people) to 38% in northern Egypt (38 cases per 100 people); whereas, the
overall prevalence is approximately 2% in North America.
At least six different genotypes and more than 90 subtypes of HCV have been
identified, but genotype 1 accounts for approximately 70% of HCV-infection in
North America.
United States
HCV infection is the most common chronic blood-borne infection in the United
States. The CDC estimated that during the 1980s, approximately 230,000 new
infections occurred each year – by 2001, the incidence (rate of new infections)
had dropped to 25,000 (80% reduction). Approximately 3,900,000 (1.8%)
Americans have been infected with HCV - most are chronically infected
ARO Training & Consulting
Bloodborne Pathogens
Module 3: Viral Hepatitis and HCV Exposure
Page 27
(2,700,000), and many are not even aware that they are infected, because they
do not feel ill.
Race/Ethnicity distribution
Prior to screening of blood donation products, transfusion-associated disease
was the most common source of HCV infection. Currently, the most common
source of HCV infection in the U.S. is injection drug use, followed by sexual
transmission.
The highest prevalence rates of HCV infection are found among persons aged
30-49 years. 3-4% of people in this age group have antibodies to HCV (AntiHCV).
The prevalence in men is higher than women, and African Americans and whites
have similar incidence of acute disease, while persons of Hispanic ethnicity have
higher rates, although prevalence of chronic infection is higher in African
Americans than in whites.
Exposure category distribution
Injecting-drug use accounts for approximately 60% of HCV transmission in the
U.S.
Sexual activity accounts for < 20% of HCV transmission.
Other known exposures – occupational, hemodialysis, household, perinatal –
account for approximately 10% of HCV infections.
No recognized source of infection was identified in the remaining 10% of HCV
transmissions.
Prevalence rates are highest in individuals with hemophilia and injection drug
users, followed by individuals with multiple sexual partners.
Canada
Approximately 250,000 persons are currently infected with hepatitis C in Canada.
It is estimated that approximately 30% of individuals infected with HCV are
unaware of their infection, because they have not as yet developed symptoms
associated with chronic infection.
The incidence of HCV infection currently is approximately 5,000 new cases per
year, and each year approximately 1,000 Canadians die from the complications
of HCV infection.
The majority of new infections in Canada are related to contaminated injection
drug equipment and supplies. Prior to the implementation of Anti-HCV screening
tests in 1990, the greatest risk of infection was associated with transfusion of
blood or blood products. In fact, the failure to implement screening, even after
ARO Training & Consulting
Bloodborne Pathogens
Module 3: Viral Hepatitis and HCV Exposure
Page 28
screening tests became available, resulted in the exposure of thousands of
Canadians to Hepatitis C, and subsequent appointment of a Commission of
Inquiry on the Blood System in Canada (Krever Commission). The final report of
the commission was released in November 1997.
HCV prevalence is greater in certain populations. Prisoners in federal
penitentiaries are much more likely to be infected with HCV than the general
population (20-80% versus 0.8%). In 2000, it was estimated that 19.2% of all
federal prisoners and 41.2% of women prisoners were HCV antibody positive.
Much higher prevalence rates were seen in some institutions, such as the
Edmonton Institution for Women where 74.6% of prisoners tested positive for
HCV. The higher prevalence rates in the prison population is likely related to
injection drug use, although other risk factors, such as unsafe sexual behaviour,
tattooing and skin piercing may also be responsible.
References:
Ford PM, Pearson M, Sankar-Mistry P, Stevenson T, Bell D, Austin J. HIV, hepatitis C
and risk behaviour in a Canadian medium-security federal penitentiary. Queen's
University HIV Prison Study Group. Queen's J Med 2000; 93 (2):113-9.
Canadian HIV/AIDS Legal Network. 2002. Action on HIV/AIDS in Prisons: Too Little, Too
Late. Retrieved from
http://www.aidslaw.ca/Maincontent/issues/prisons/reportcard/newdevelopments.htm on
September 12, 2004.
Ford, P. 1999. HIV and hep C seroprevalence and associated risk behaviours in a
Canadian prison. Canadian HIV/AIDS Policy and Law Newsletter; 4(2/3): 52-54.
Higher HCV prevalence rates have also been reported in hemodialysis patients
due to inadequately cleaned, disinfected or sterilized equipment, and in people
with hemophilia who received blood products prior to routine HCV screening of
blood.
Reference:
Health Canada. 1999. Hepatitis C - Prevention and Control: A Public Health Consensus.
Canada Communicable Disease Report; 25S2. Retrieved at http://www.hcsc.gc.ca/pphb-dgspsp/publicat/ccdr-rmtc/99vol25/25s2/hepcec.html on September 12,
2004.
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Bloodborne Pathogens
Module 3: Viral Hepatitis and HCV Exposure
Page 29
Transmission
HCV is spread primarily by direct contact with human blood – the major causes
of HCV infection, worldwide, are use of unscreened blood transfusions, and reuse of needles and syringes that have not been adequately sterilized.
Unsafe injections are the most common cause of HCV infection in developing
countries, accounting for approximately 2,000,000 new infections each year
(42% of all new cases of HCV infection).
Since the advent of HCV screening tests for blood transfusion products, the most
common cause of HCV infection in North America is injection drug use.
Infected persons serve as a source of transmission to others and are at risk for
chronic liver disease and/or other chronic diseases associated with HCV.
Because acute symptoms are often mild, and conditions associated with chronic
infection often take up to 20 or more years to develop, many individuals who are
infected do not yet know that they are.
Risk factors for HCV include:
 blood transfusion prior to introduction of blood donor HCV Ab screening
tests
 sharing of contaminated needles, other instruments and supplies among
injection drug users
 multiple sex partners
 employment in patient care or clinical laboratory work
 exposure to an HCV-infected sex partner or household member
 contaminated equipment used for tattooing, body piercing, acupuncture,
although current data do not indicate that exposures to tattooing and body
piercing alone are at increased risk for HCV infection
 intra-nasal (snorting) cocaine use (possibly from sharing contaminated
straws).
 the risk of transmission through sexual intercourse or mother to child
during birth, is low.
At this time, it appears that the risk of transmitting hepatitis C through sexual
intercourse, mother to child during birth, and household transmission appears to
be low. Household transmission is likely due to sharing of utensils that may
contain small amounts of blood (i.e. razors, toothbrushes, etc.)
Although HCV genetic material has been found in breast milk, HCV transmission
through breast feeding has not been reported, and breast feeding is currently not
discouraged in HCV positive mothers, unless the nipples are cracked or
bleeding.
ARO Training & Consulting
Bloodborne Pathogens
Module 3: Viral Hepatitis and HCV Exposure
Page 30
Occupational exposure
Health-care workers and first responders exposed to blood in the workplace are
at risk for infection by HCV. Exposure risks include percutaneous injury, contact
of mucous membranes, or contact of non-intact skin (chapped, abraded,
dermatitis) with blood, tissues, or other body fluids (semen, vaginal secretions,
other body fluids contaminated with visible blood, CSF, synovial fluid, pleural
fluid, peritoneal fluid, pericardial fluid, and amniotic fluid, and laboratory samples
that contain HCV (e.g., suspensions of concentrated virus).
HCV is not transmitted as efficiently through occupational exposures to blood as
HBV. The risk of acquiring HCV infection after an unintentional needle-stick injury
from an HCV-positive source ranges from 3-10%, at least ten-fold less than HBV.
Although transmission from blood exposures to intact or non-intact skin seems
possible, HCV infection by this route has not been reported.
Occupational HCV Transmission
Since HBV vaccine was introduced, HCV has replaced HBV as the most
commonly identified cause of viral hepatitis among HCWs, and exposures
through needle sticks and other sharps are the most common causes of
occupational HCV transmission.
Occupational HCV transmission risk factors include local prevalence of anti-HCV
among patients and the degree of contact with blood or sharp instruments
contaminated with blood.
HCV transmission from a blood splash to the conjunctiva has been reported, and
at least one case has been associated with a bite wound. HCV has also been
transmitted in hemodialysis units, not only from patient to patient through
contaminated equipment, but also from patient to HCW.
Risk to Health-Care Workers
The average risk for infection after a needle-stick or cut exposure to HCVinfected blood averages from 1-10%.
Risk of HCV transmission following blood exposures to the eye, nose or mouth is
unknown, but thought to be small.
Medical specialists and residents, sterilization attendants, phlebotomists, lab
technicians, lab technologists, nurses, and nuclear medical technicians are at
high risk of occupational exposure to HCV.
The Canadian Needle Stick Surveillance Network reported 2621 HCW exposures
from April 1, 2000 to March 31, 2002. Source patients were identified in 85% of
exposures, and testing indicated that 7.6% of source patients were positive for
antibodies to HCV. To date, none of the exposed HCWs has seroconverted as a
result of exposure.
ARO Training & Consulting
Bloodborne Pathogens
Module 3: Viral Hepatitis and HCV Exposure
Page 31
Reference: Health Canada. 1997. Preventing The Transmission Of Bloodborne
Pathogens In Health Care And Public Service Settings. Canada Communicable Disease
Report; 23S3. Retrieved from http://www.hc-sc.gc.ca/pphb-dgspsp/publicat/ccdrrmtc/97vol23/23s3/23s3a_e.html#risk on September 12, 2004.
Risk to Emergency Responders and Public Safety Workers Acquiring HIV
in Health-Care Settings
There has been little research on HCV prevalence in emergency responders and
public safety workers. As with HCWs, emergency responders and public safety
workers exposed to blood during their work are at risk of infection; however, the
risk of acquiring HCV infection is low (~ 1.8%). In a small study conducted in the
U.S., emergency responders were found not to be at higher risk than the general
population for HCV infection. Among emergency responders identified with HCV,
infection was associated mainly with non-occupational factors; however, further
research is needed to accurately determine the risks involved.
Reference: Centers for Disease Control and Prevention (CDC). 2000. Hepatitis C Virus
Infection Among Firefighters, Emergency Medical Technicians, and Paramedics --Selected
Locations,
United
States,
1991—2000.
Retrieved
from
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm4929a3.htm
on
September
12,
2004.MMWR;49(29):660-5.
HCV Disease Progression
The route of HCV transmission may influence disease progression – HCV
infection acquired post-transfusion is more aggressive than that acquired by
injection drug use.
Differences in disease progression may be due to the concentration of infectious
viral particles injected and the resulting initial liver damage.
ARO Training & Consulting
Bloodborne Pathogens
Module 3: Viral Hepatitis and HCV Exposure
Page 32
Acute infection
HCV is responsible for approximately 20% of cases of acute hepatitis in North
America.
The incubation period ranges from 2-30 weeks (average 7 weeks), and persons
with acute HCV infection are usually either asymptomatic or have a mild clinical
illness:



60%-70% have no obvious symptoms
20%-30% may have jaundice
10%-20% may have non-specific symptoms such as anorexia, malaise,
abdominal pain, or weight loss
Symptoms, if present, usually develop in 6-7 weeks and last 2-12 weeks, with
liver damage detectable within 15-150 days (average 50 days). Clinical illness in
patients with acute HCV infection who seek medical care is similar to other types
of viral hepatitis, and serologic testing is necessary to determine the cause of
hepatitis.
Seroconversion (presence of antibody in the serum of the exposed individual)
generally takes 8-9 weeks, so that symptoms may be present before antibodies
can be detected. Anti-HCV can be detected in 80% of patients within 15 weeks of
exposure, 90% within 5 months of exposure, 97% by 6 months. In rare cases,
seroconversion may take as long as 9 months after exposure.
The course of acute hepatitis C is variable, but infection is self-limited in only 1015% of cases.
Fulminant hepatic failure following acute hepatitis C is rare.
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Bloodborne Pathogens
Module 3: Viral Hepatitis and HCV Exposure
Page 33
Chronic infection
Approximately 85% of people with acute HCV infection will progress to chronic
disease, usually 10-20 years following the acute phase of infection.
Chronic liver disease is the tenth leading cause of death among adults in the
United States. HCV is responsible for approximately 40% of chronic liver
disease, resulting in 8,000-10,000 deaths each year.
Health care and work-loss costs of HCV-related liver disease in the U.S. are
greater than $600 million a year (CDC), and end-stage liver disease resulting
from HCV infection is the most frequent indication for liver transplantation among
adults.
The majority of people with HCV infections are 30-49 years of age, so it is likely
that the number of deaths due to chronic liver disease will increase significantly
for the next 10-20 years, as complications develop or progress in these
individuals.
Chronic liver infection generally progresses slowly without symptoms, or with
only mild non-specific symptoms such as fatigue, for the first 20 years or more
following initial infection. Often, chronic HCV infection is not recognized until liver
damage is detected during routine blood testing, or anti-HCV is detected during
blood-donor screening.
When symptoms occur, nausea, anorexia, arthralgias, weakness, abdominal
discomfort, pruritus, and weight loss are most commonly reported.
People with chronic HCV infection should be discouraged from using alcohol,
because alcohol use has been associated with progressive liver disease.
Complications of chronic HCV infection
Cirrhosis
The proportion of HCV infected individuals who develop cirrhosis varies
considerably in the literature, although most sources report figures of 10%-30%.
Most often, cirrhosis due to HCV infection occurs over a period of 20-30 years,
but in rare cases, cirrhosis develops rapidly.
Individuals with HCV-related cirrhosis are at increased risk of developing liver
cancer.
Liver cancer
One to 5% of people with chronic HCV infection will develop liver cell cancer,
anywhere from 10-50 years following initial HCV infection.
ARO Training & Consulting
Bloodborne Pathogens
Module 3: Viral Hepatitis and HCV Exposure
Page 34
The majority of cases of liver cell cancer occur in people with cirrhosis. Once
cirrhosis develops, the rate of cancer may be as high as 1%-4% each year.
Coinfection with HBV and HCV also results in a higher risk of developing liver cell
cancer, and certain types of HCV are more likely to result in cancer.
Alcohol use in HCV infected patients with cirrhosis is also associated with a
greater incidence of liver cell cancer. Even moderate alcohol intake in chronic
HCV infection may intensify disease progression.
Other Complications
Complications associated with HCV infection include blood disorders,
autoimmune diseases, joint and muscle disorders, ophthalmic disease, and renal
disease.
HIV/HCV Co-infection
Coinfection with HCV and HIV results in higher hepatitis C viral loads than are
normally seen with HCV infection alone. Progression to cirrhosis is also more
rapid with HCV/HIV coinfection.
Laboratory Testing
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.
Currently available tests detect anti-HCV in greater than 97% (sensitivity of 97%)
of immunocompetent individuals with HCV infection, but do not distinguish
between acute, chronic, or resolved infection. However, in immunocompromised
individuals, sensitivity ranges from 60-90%. Because of the low sensitivity of
antibody tests in immunocompromised individuals, 10-40% of HCV infected
individuals in this group will have false negative test results.
The specificity of currently available tests is approximately 99.3%. In other words,
for each 1,000 tests performed, 7 individuals will test positive even though they
do not have HCV infection. Additional testing with a more specific test prevents
reporting of false-positive results.
HCV infection can also be diagnosed by the detection of HCV genetic material in
serum or plasma 1-2 weeks after exposure to HCV; however, these tests are
expensive to perform and HCV must be present in numbers exceeding 100-1,000
virus copies/ml for detection.
Liver biopsy, although invasive, is useful to establish the severity of disease,
guide therapy, and predict prognosis in chronically infected individuals.
ARO Training & Consulting
Bloodborne Pathogens
Module 3: Viral Hepatitis and HCV Exposure
Page 35
Treatment
Antiviral therapy is recommended for patients with chronic hepatitis C who are at
greatest risk for progression to cirrhosis - anti-HCV-positive patients with
persistently elevated liver enzyme levels, detectable HCV genetic material, and a
liver biopsy that indicates fibrosis or moderate inflammation and cell death.
Indications for antiviral treatment are not as clear in individuals with less severe
liver damage, because progression to cirrhosis is usually slow, if it occurs at all.
The risks and benefits of treatment must be assessed and discussed with each
individual.
The goals of treatment include:



elimination of the virus
prevention of cirrhosis
prevention of liver cell cancer
The current FDA-approved treatment for the initial treatment of chronic HCV is
combination therapy with interferon and ribavirin, although several new anti-viral
agents are under investigation.
Ribavirin and interferon
Combination therapy has become the therapy of choice. Sustained response
rates with combination ribavirin and interferon are approximately 40%-50%,
although in individuals infected with genotype 1, they are less than 30%.
Side effects of anti-HCV medications
The common side-effects of interferon treatment include flu-like symptoms early
in treatment, which diminish with continued treatment. Later side effects include
fatigue, bone marrow suppression, and mental disorders including apathy,
cognitive changes, irritability, and depression.
Interferon must be reduced in up to 40% of patients, and discontinued in another
5% -15% due to severe side effects.
Ribavirin can cause hemolytic anemia and should not be used in individuals with
anemia, bone marrow suppression, or renal failure. Ribavirin is also teratogenic,
therefore, female patients should avoid becoming pregnant during therapy.
HCV Vaccine
The development of a vaccine for HCV is still in progress. Due to the genetic
diversity of HCV, difficulties in finding animal models (chimpanzees are the only
available model) and cell lines that will support the growth of HCV, and
identification of HCV antigens that will produce an adequate immune response,
vaccine development is still far from completion.