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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