Transcript Slide 1
HEPATITIS C VIRUS
Maruf Aberra(MD)
Virology
RNA virus that belongs to the family
flaviviruses; sole member of the genus
hepacivirus.
Enveloped, 55-65 nm in diameter.
Circulates in various forms in the serum
(1)Lipo - Viro-Particles , represent the
infectious fraction
(2)Bound to immunoglobulin
(3)Free virions
Viral replication and Life
Cycle
Hepatocytes are major sites
of replication. Mononuclear
cell, dendritic cells also
support replication.
Viral binding
Entry
Inside hepatocytes
viral packaging and release
infect adjacent hepatocytes
or enter circulation
Genotypes and quasispecies
Genetic heterogeneity
Six distinct but related HCV genotypes and multiple subtypes
have been identified.
Genotype 1 is common (60 to 70 percent of isolates) in the United
States and Europe followed by genotypes 2 and 3
Genotype 3 is most common in India, the Far East, and Australia
Genotype 4 is most common in Africa and the Middle East
Genotype 5 is most common in South Africa
Genotype 6 is most common in Hong Kong, Vietnam and
Australia
Quasispecies-closely related yet heterogeneous sequences of
HCV within a single infected person
Epidemiology
Worldwide seroprevalence - 3%
>170 million people infected chronically
Prevalence of anti-HCV antibody in Ethiopians
Healthy Blood donors
-1.4%.
urban/rural communities(1993) -2%
patients with chronic hepatitis -21%.
cirrhosis of liver
-36%
HCC
-46%
Transmission
Sources of Infection
Injecting Drug Use and HCV
Transmission
Highly efficient
Contamination of drug paraphernalia, not just
needles and syringes
Rapidly acquired after initiation
30% prevalence after 3 years
>50% after 5 years
Four times more common than HIV
Posttransfusion Hepatitis C
% of Recipients Infected
30
All volunteer donors
HBsAg
25
20
15
Donor Screening for HIV Risk Factors
Anti-HIV
ALT/Anti-HBc
10
Anti-HCV
5
0
1965
Improved
HCV Tests
1970
1975
1980
1985
1990
1995
Year
Adapted from HJ Alter and Tobler and Busch, Clin Chem 1997
2000
Occupational Transmission of HCV
Inefficient by occupational exposures
Average incidence 1.8% following needle stick
from HCV-positive source
Associated with hollow-bore needles
Case reports of transmission from blood splash
to eye; one from exposure to non-intact skin
Prevalence 1-2% among health care workers
Lower than adults in the general population
10 times lower than for HBV infection
Perinatal Transmission of HCV
Transmission only from women HCV-RNA
positive at delivery
Average rate of infection 6%
Higher (17%) if woman co-infected with HIV
Role of viral titer unclear
No association with
Delivery method
Breastfeeding
Infected infants do well
Severe hepatitis is rare
Sexual Transmission of HCV
Partner studies
Low prevalence (1.5%) among long-term partners
infections might be due to common percutaneous exposures
(e.g., drug use), BUT
Male to female transmission more efficient
more indicative of sexual transmission
Occurs, but efficiency is low
Factors that facilitate transmission between partners
unknown (e.g., viral titer)
Accounts for 15-20% of acute and chronic infections in the
United States
Natural History of HCV Infection
Incubation period
Acute illness (jaundice)
Case fatality rate
Chronic infection
Chronic hepatitis
Cirrhosis
AgeMortality from CLD
related
Average 6-7 weeks
Range 2-26 weeks
Mild (<20%)
Low
60%-85%
10%-70%
<5%-20%
1%-5%
Serologic Pattern of Acute HCV Infection
with Recovery
antiHCV
Symptoms +/-
Titer
HCV RNA
ALT
Normal
0
1
2
3
4
Months
5
Time after
Exposure
6
1
2
3
Years
4
Serologic Pattern of Acute HCV Infection with
Progression to Chronic Infection
antiHCV
Symptoms +/-
Titer
HCV RNA
ALT
Normal
0
1
2
3
4
Months
5
Time after
Exposure
6
1
2
3
Years
4
Chronic Hepatitis C
Factors Promoting Progression or Severity
Increased alcohol intake
Age > 40 years at time of infection
HIV co-infection
Other
Male gender
Chronic HBV co-infection
Clinical Features
Acute Hepatitis (20%)
Jaundice
- 10-20%
Non specific sx- 20-30%
Chronic hepatitis
Most patients are asymptomatic
mild nonspecific symptoms
most frequent complaint is fatigue; other less
common manifestations include nausea,
anorexia, myalgia, arthralgia, weakness, and
weight loss
Extrahepatic manifestation of HCV
HEMATOLOGIC DISORDERS
Essential mixed cryoglobulinemia
Monoclonal gammopathies
Lymphoma
DIABETES MELLITUS
AUTOIMMUNE DISORDERS
Autoantibodies
Thyroid disease
Sialadenitis
Autoimmune idiopathic thrombocytopenic purpura
Myasthenia gravis
Sarcoidosis
Extrahepatic Manifestations of HCV
OCULAR DISEASE
RENAL DISEASE
DERMATOLOGIC DISEASE
Porphyria cutanea tarda
Leukocytoclastic vasculitis
Lichen planus
Necrolytic acral erythema
MUSCULOSKELETAL
MYOCARDITIS AND CARDIOMYOPATHY
NEUROCOGNITIVE DYSFUNCTION
Diagnosis
Indirect assay (EIAs)
Anti-HCV
Direct Assays
Qualitative- HCV RNA
Quantitative- HCV RNA levels
HCV Core Antigen Assay- EIA
HCV genotyping
Histopathology
Considered as the gold standard for establishing the
severity of the disease.
Two componentsNecroinflammatory changes
Stage of structural alterations
Exclusion of coexisting Disease
Determination of Rate of Progression
Guidance in Treatment decision-making
Scoring systems
Histology Activity Index(HAI)
METAVIR scoring system