Maruf Aberra(MD) HEPATITIS C VIRUS. Virology RNA virus that belongs to the family flaviviruses; sole...
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Transcript of Maruf Aberra(MD) HEPATITIS C VIRUS. Virology RNA virus that belongs to the family flaviviruses; sole...
VirologyRNA 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
EpidemiologyWorldwide seroprevalence - 3%>170 million people infected chronicallyPrevalence 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%
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
0
5
10
15
20
25
30
1965 1970 1975 1980 1985 1990 1995 2000
Year
% o
f Rec
ipie
nts I
nfec
ted
All volunteer donors
HBsAg
Donor Screening for HIV Risk Factors
Anti-HIV
ALT/Anti-HBc
Anti-HCV
Improved HCV Tests
Adapted from HJ Alter and Tobler and Busch, Clin Chem 1997
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 InfectionNatural History of HCV Infection
Incubation periodIncubation period Average 6-7 Average 6-7 weeksweeks
Range 2-26 Range 2-26 weeksweeks
Acute illness (jaundice)Acute illness (jaundice) Mild (Mild (<<20%)20%)
Case fatality rateCase fatality rate LowLow
Chronic infectionChronic infection 60%-85%60%-85%
Chronic hepatitisChronic hepatitis 10%-70%10%-70%
CirrhosisCirrhosis <5%-20%<5%-20%
Mortality from CLDMortality from CLD 1%-5%1%-5%
Age-related
Serologic Pattern of Acute HCV Infection with Recovery
Symptoms +/-
Time after Exposure
Tite
ranti-HCV
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4YearsMonths
HCV RNA
Serologic Pattern of Acute HCV Infection with Progression to Chronic Infection
Symptoms +/-
Time after Exposure
Tite
ranti-HCV
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4YearsMonths
HCV RNA
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 FeaturesAcute 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 components-
Necroinflammatory 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