Hepatitis C virus
HCV …
Hepatitis C virus
Ø Genome cloned in 1989
Ø Member of the Flaviviridae family, RNA virus
Ø Leading cause of liver transplantation in the US
Ø Sustained responses in only 50% of treated patients
Ø No vaccine available ( Why??)
Ø
HCV replicates exclusively in the cytoplasm
via an RNA intermediate
Viral entry & uncoating
(+) Translation & processing
(+)
(-)
HCV RNA
Virus particle replication
assembly Replicative
intermediate
(+)
Nucleus
Hepatitis C Virus
<Genome resembled that of a flavivirus
positive stranded RNA genome
<HCV has been classified into a total of six genotypes
(type 1 to 6) on the basis of phylogenetic analysis
<High sequence divergence for 6 major genotypes…
<Genotype 1 and 4 has a poorer prognosis and
response to interferon therapy,
<In Hong Kong, genotype 1 accounts for around 67% of
cases and genotype 6 around 25%.
Hepatitis C – Epidemiology
• Occurrence: World wide distribution. WHO estimates that
some 130-170 million people (approximately 2-3% of
world population) are chronically infected with HCV.
• Reservoir: Human; virus has been transmitted
experimentally to chimpanzees.
• Period of communicability: From one or more weeks
before onset of the first symptoms; may persist in most
persons indefinitely!
Hepatitis C – Epidemiology
Incubation period: Average 6-9 wks
Range 2weeks- 6m
Chronic infection may persist for up 20 years before
the onset of cirrhosis or hepatoma..
Clinical illness (jaundice): 30-40% (20-30%)
Chronic hepatitis: 50-80%
Immunity: No protective
antibody
response identified
Chronic Hepatitis C Infection
• The spectrum of chronic hepatitis C infection is essentially
the same as chronic hepatitis B infection.
• Although initial infection may be asymptomatic (more than
90% of cases) or mild, a high percentage (50%-80%) develop a
chronic infection.
• Of chronically infected persons 50% get eventually develop
cirrhosis or cancer of the liver.
Hepatitis C Virus Infection
Typical Serologic Course
anti-HCV
Symptoms
Titre
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4
Months Years
Time after Exposure
Mode of transmission HCV is primarily
transmitted parenterally .
Sexual and mother to child have been
documented but appear far less efficient or
frequent than parenteral route
Risk Factors Associated with
Transmission of HCV
§ Transfusion or transplant from infected donor
§ Injecting drug use
§ Hemodialysis (yrs on treatment)
§ Accidental injuries with needles/sharps
§ Sexual/household exposure to anti-HCV-positive
contact
§ Multiple sex partners
§ Birth to HCV-infected mother
Laboratory Diagnosis
• HCV antibody - generally used to diagnose hepatitis C
infection. Not useful in the acute phase as it takes at
least 4 weeks after infection before antibody appears.
• HCV-RNA - various techniques are available e.g. PCR
and branched DNA. May be used to diagnose HCV
infection in the acute phase. However, its main use is in
monitoring the response to antiviral therapy.
• HCV-antigen - an EIA for HCV antigen is available. It is
used in the same capacity as HCV-RNA tests but is
much easier to carry out.
Prognostic Tests
• Genotyping – genotype 1 and 4 have a worse
prognosis overall and respond poorly to interferon
therapy
• Viral Load – patients with high viral load are
thought to have a poorer prognosis. Viral load is
also used for monitoring response to IFN therapy.
Treatment
• Interferon - may be considered for patients with
chronic active hepatitis. The response rate is around
50% but 50% of responders will relapse upon
withdrawal of treatment.
• Ribavirin - recent studies suggest that a
combination of interferon and ribavirin is more
effective than interferon alone.
• These medications have significant side effects
that require careful monitoring..!
Post-Exposure Prophylaxis - HCV
No protective antibody response identified
Prior studies of IG use to prevent post-
transfusion hepatitis may not be relevant
IG prepared from high anti-HCV titer plasma did not prevent
infection in chimpanzees …
- Control of patients and contacts: General control measure
against HBV can apply for control HCV infection!!
January 2004 Hepatitis A-E Disease States 14
Prevention of Hepatitis C
§ General measures against HBV can
apply for prevention HCV…
Prophylactic IG is not effective !!!
§ Screening of blood, organ, tissue donors
§ High-risk behavior modification
§ Blood and body fluid precautions
Counseling HCV Positive Persons:
Positive persons should:
Be considered potentially infectious
Keep cuts and skin lesions covered
Be informed of potential for sexual transmission
Be informed of potential for perinatal transmission
– no evidence against pregnancy or breastfeeding
Positive persons should not:
Donate blood, organs, tissue, or semen
Share household articles (e.g., toothbrushes, razors)
January 2004 Hepatitis A-E Disease States 16
