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ARO Training & Consulting
Bloodborne Pathogens
Module 6: Hepatitis C Virus (HCV)
Page 68
Introduction
Like HBV, HCV is an infectious disease that attacks the liver. Most patients have
very mild flu-like symptoms, or no symptoms. Acute HCV infection cannot be
differentiated from HBV on the basis of clinical presentation. However, unlike
HBV infection, HCV often progresses to chronic infection, and almost everyone
infected with HCV becomes a carrier.
Historical Perspective
Rates of post-transfusion hepatitis in the U.S. during the 1960s exceeded 20%.
In the mid-1970s when laboratory test methods became available for HAV and
HBV, it was recognized that approximately 90% of patients with hepatitis
following exposure to blood had negative test results for HAV and HBV.
Hepatitis related to blood transfusion that was not caused by HAV or HBV, was
given the name non-A, non-B hepatitis (NANB).
Changing the practice of offering money for units of blood reduced the risk of
post-transfusion hepatitis to 10%, but it was 1987 before the virus, now known as
hepatitis C (HCV), was discovered as the primary agent responsible for most
cases of NANB hepatitis. Laboratory testing to screen donated blood for
antibodies to HCV became available in 1990. And in 1995, HCV was seen for the
first time by electron microscopy.
HCV Structure
HCV is a single-stranded RNA virus belonging to the family of viruses known as
flaviviruses (Flaviviridae family). The RNA contains the genetic codes for 10
different proteins (polyprotein). The RNA strand is encased by proteins, and
forms the core of the virus. The viral surface consists of an outer coating
(envelope) of lipids (fats) and glycoproteins. The glycoproteins extend from the
surface like spikes through the lipid and protein envelope. The proteins coded for
by the RNA are a combination of structural proteins and proteins necessary for
the virus to replicate itself.
There are several different groups or genotypes of HCV, each with slightly
different sequences.
HCV Life cycle
HCV attaches by way of two of its surface glycoproteins (E1 and E2) to receptors
on hepatocytes. HCV is then engulfed by the hepatocytes and taken into the
cytoplasm. The genetic codes found in the RNA are read or translated and
transcribed by ribosomes in the host cells to produce HCV polyproteins (protein
synthesis).
ARO Training & Consulting
Bloodborne Pathogens
Module 6: Hepatitis C Virus (HCV)
Page 69
The polyproteins are then cut into individual proteins that form the structure of
new viral particles, or specialized proteins and enzymes that direct viral
replication. The component proteins are assembled into nucleocapsids (RNA and
core proteins – core), which then attach to the surface of hepatocytes. The
hepatocyte surface membrane coats the nucleocapsid with a protective lipid
layer, and the new viral particle is released from the hepatocyte to infect other
hepatocytes.
HCV has extremely high replication rates, producing approximately
1,000,000,000,000 (10_12) infectious viral particles (virions) per day. The rapid
reproductive rate creates problems with vaccine development and treatment
regimens. Changes occur in new generations as viruses reproduce – some of
these changes will result in nonsense or noninfectious structure; however,
because there are so many copies formed in a short period of time, larger
numbers of them will be different from the parent virus, but functional and
infectious. Therefore, vaccines and anti-viral agents become ineffective quickly,
as the target on which the agent acts changes.
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.
Despite the fact that most HCV infected individuals produce antibodies against
multiple viral proteins, the majority progress to chronic HCV infection, suggesting
that immune response is often inadequate. In addition, it has been shown that
prior HCV infection is not protective against re-infection, as is the case with HBV
infection. One of the problems encountered in studying the effects of HCV is that
unlike a number of other viruses, HCV cannot currently be grown in cells in the
laboratory. Chimpanzees are the only species other than humans that develop
HCV infection leading to chronic hepatitis; therefore, study opportunities are
limited.
Although a strong CD4 helper T-cell response and certain cytokine responses
have been associated with improved ability to clear acute HCV infection, a better
understanding of host immune response against HCV and mechanisms by which
the virus can evade the immune system is necessary for development of
effective vaccine and anti-viral medications.
ARO Training & Consulting
Bloodborne Pathogens
Module 6: Hepatitis C Virus (HCV)
Page 70
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.
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 treated with clotting factor concentrates produced
before 1987 testing was implemented – persons with hemophilia 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 1.8% in the U.S. and 2% in Canada.
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.
ARO Training & Consulting
Bloodborne Pathogens
Module 6: Hepatitis C Virus (HCV)
Page 71
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
(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, of whom 3-4% have antibodies to HCV. The
prevalence in men is higher than women, and in African-American males in this
age-group was estimated to be 9-10% in 1994. 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.
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Bloodborne Pathogens
Module 6: Hepatitis C Virus (HCV)
Page 72
Canada
Approximately 250,000 persons are currently infected with hepatitis 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.
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 HCV Ab screening
tests in 1990, however, the greatest risk of infection was associated with
transfusion of blood or blood products. In fact, the failure to implement screening,
even after 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. Click here
for more information.
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
ARO Training & Consulting
Bloodborne Pathogens
Module 6: Hepatitis C Virus (HCV)
Page 73
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.
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.)
ARO Training & Consulting
Bloodborne Pathogens
Module 6: Hepatitis C Virus (HCV)
Page 74
Although HCV RNA 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.
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 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
Each year, an estimated 600,000 to 800,000 needle-stick injuries occur among
the approximately 8 million healthcare workers in Canada.
The average risk for infection after a needle-stick or cut exposure to HCVinfected blood ranges from 1-10%. Risk of HCV transmission following blood
exposures to the eye, nose or mouth is unknown, but thought to be small.
ARO Training & Consulting
Bloodborne Pathogens
Module 6: Hepatitis C Virus (HCV)
Page 75
Medical specialists and residents, sterilization attendants, phlebotomists and/or
lab technicians, 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.
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.
Acute infection
HCV is responsible for approximately 20% of cases of acute hepatitis in North
America.
ARO Training & Consulting
Bloodborne Pathogens
Module 6: Hepatitis C Virus (HCV)
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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:

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
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 last 2-12 weeks, with liver damage detectable by
increases in ALT levels (~ 10x normal) 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.
In less than or equal to 20% of these patients, symptoms may be present before
anti-HCV seroconversion. Average time period from exposure to symptom onset
is 6-7 weeks, whereas average time period from exposure to seroconversion is
8-9 weeks. 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. A return of ALT levels to normal and continued absence of HCV
RNA in the serum or plasma of previously infected individuals suggests full
recovery. However, it is more likely that ALT levels will become elevated again at
some point, indicating progression to chronic disease.
Fulminant hepatic failure following acute hepatitis C is rare. Can’t remember what
fulminant hepatic failure is? Return to Anatomy, Physiology and Pathophysiology
of the Liver. Click here or check out the glossary.
Chronic infection
Approximately 85% of people with acute HCV infection will progress to chronic
infection, usually 10-20 years following acute infection.
Chronic liver disease is the tenth leading cause of death among adults in the
United States, accounting for approximately 25,000 deaths each year (~ 1% of all
deaths). 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
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Bloodborne Pathogens
Module 6: Hepatitis C Virus (HCV)
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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 disease 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. However, ALT levels remain elevated or fluctuate in 6070% of these individuals, indicating active liver disease; while in the remaining
30%-40%, ALT levels remain normal. Often, chronic HCV infection is not
recognized until elevated ALT levels are obtained during routine blood testing, or
anti-HCV is detected during blood-donor screening. Some chronically infected
individuals may have prolonged periods of 12 months or more where ALT levels
are normal even though there is evidence of active liver disease when the liver
biopsies are examined. Therefore, ALT levels must be monitored over the long
term to assess liver damage.
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
Although it remains unclear why some people with HCV infection develop more
severe liver disease, a number of predictive factors have been identified:

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
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age >40 years at initial exposure
longer duration of acute infection
male gender
degree of fibrosis at initial liver biopsy
compromised immune status
co-infection with other liver viruses or the human immune deficiency virus
(HIV)
infection with HCV genotype 1
presence of quasispecies
iron overload
alcohol consumption
A synergistic effect has also been suggested with alcohol, coinfection with HBV,
and infection with HCV genotype 1b.
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Bloodborne Pathogens
Module 6: Hepatitis C Virus (HCV)
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Reference: Cheney, C.P, S. Chopra, C. Graham. 2000. Hepatitis C. In Infections
of the liver. Infectious Disease Clinics of North America;14(3):633-667.
Long term follow-up studies are needed to assess the lifetime consequences of
chronic hepatitis C, especially among those who became infected at young ages.
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, 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
hepatocellular carcinoma.
Hepatocellular carcinoma
Worldwide, there are approximately 250,000 to 1,200,000 new cases of
hepatocellular carcinoma each year, and the majority of cases occur in people
with cirrhosis. One to 5% of people with chronic HCV infection will develop
hepatocellular carcinoma, anywhere from 10-50 years following initial HCV
infection. However, once cirrhosis develops, the rate of hepatocellular carcinoma
may be as high as 1%-4% each year.
Coinfection with HBV and HCV also results in a higher risk of developing
hepatocellular carcinoma, and there has been some suggestion that individuals
infected with HCV 1b (subtype of genotype 1) are more likely to develop
hepatocellular carcinoma. Alcohol use in HCV infected patients with cirrhosis is
also associated with a greater incidence of hepatocellular carcinoma. Even
moderate alcohol intake in chronic HCV infection may intensify disease
progression.
Extra-hepatic manifestations
Extrahepatic manifestations of chronic HCV infection may be present in
chronically infected individuals. Sometimes, extrahepatic manifestations may be
prominent even though liver disease is mild.
Blood disorders, autoimmune diseases, joint and muscle disorders, ophthalmic
disease, and renal disease.
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Bloodborne Pathogens
Module 6: Hepatitis C Virus (HCV)
Page 79
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
Laboratory testing includes biochemicals used to asses liver function - to review
liver function tests (Module 3).
HCV-positive patients should be evaluated for the presence and severity of liver
disease. ALT should be measured at regular intervals, as levels are known to
fluctuate in individuals with chronic hepatitis C.
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%. 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.
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.
Additional testing with a more specific test prevents reporting of false-positive
results.
HCV infection can also be diagnosed by the detection of HCV RNA in serum or
plasma 1-2 weeks after exposure to HCV, using nucleic acid amplification
techniques such as reverse-transcriptase PCR (RT-PCR); whereas, it may take
weeks before ALT levels rise or anti-HCV appears. These tests are expensive to
perform and HCV must be present in numbers exceeding 100-1,000 viral
genome copies/mL for detection.
Quantitative tests for measuring the concentration (titer) of HCV RNA are
available, and are used to help predict response to antiviral therapy, but have
also proven useful to monitor treatment on an ongoing basis.
Liver biopsy, although invasive, is useful to establish the severity of disease,
guide therapy, and predict prognosis in chronically infected individuals.
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Module 6: Hepatitis C Virus (HCV)
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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 ALT levels, detectable HCV RNA, and a liver biopsy that
indicates fibrosis or moderate inflammation and necrosis.
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. Treatment in individuals with normal ALT levels may actually
encourage liver enzyme abnormalities.
The goals of treatment include:
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elimination of the virus
prevention of cirrhosis
prevention of hepatocellular carcinoma
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.
As you will recall from Module 2 and 4, interferons are naturally occurring
glycoproteins that are important in immune defense against viral infections, by
inhibiting viral protein synthesis and viral attachment, promoting production of
proteins to destroy viral particles, and increaseing the susceptibility of infected
cells to destruction by immune cells.
Treatment regimens evolved from interferon monotherapy to combination therapy
with interferon and ribavirin, due to low response rates (25-50%), especially with
genotype 1, and high relapse rates (greater than 50%). Sustained response with
interferon alone was only 10-15%.
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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%.
Interferon should not be used in individuals with major depressive illness,
cytopenias, hyperthyroidism, renal transplantation, and autoimmune disease.
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.