Hepatitis C virus (HCV) - MegaMicro

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Hepatitis C virus (HCV)

Micro > Virology > RNA viruses > Single Stranded RNA viruses > Flavivirus
Hepatitis C virus

Overview
  • Flavivirus, genus HepaceviridaessRNA
  • Enveloped
  • Icosahedral capsisd
  • Causes most cases of “non-A non-B” hepatitis
  • 6 genotypes – genotype predicts response to therapy
  • 1.0x1012 virions produced daily w/ rapid accumulation of mutations and formation of quasispecies (‘swarm’)... these constant mutations are helpful in escapting host immune system!

Epidemiology
  • High incidence of chronically infected (but asymptomatic) individuals promotes spread
  • Incidence peaked in late 1980’s and fell (due to screening of blood supply) until stabilizing in 2003
  • Transmission via blood and body fluids; IV drug users at highest risk
  • Sexual/vertical transmission is less common than w/ HBV
  • Little transfusion-related transmission in US now
  • Risk of needlestick ~3% (compare to HIV ~0.3% and Hepatitis B ~30%)

Pathogenesis and immunology
  • HCV is not cytotoxic
  • Vigorous CMI response increases chances of viral clearance (most people who are able to clear it do so within 3-4 months; the rest are stuck with it for a lifetime); humoral (Ab) response less important
  • Spontaneous clearance of virus occurs in a minority of those infected (most people   - 80% -  infected develop chronic infection)
  • High mutation rate à may help virus persist!
  • HIV infection accelerates complications of chronic hepatitis C
  •   
Clinical course
  • clinical hepatitis
  • may lead to end-stage liver disease
  • may lead to hepatocellular carcinoma
 
Diagnosis
    • Antibody (positive for both chronically infected and those with spontaneous clearance)
    • PCR of blood

Treatment
  • Older regimens based on interferon and ribabirin - associated with significant morbidity and low response rates
  • Newer "directly acting antivirals (DAAs) specifically target viral components
    • combination therapy required
    • General sequence is to treat for defined length of time and redraw Hep C PCR after completing therapy to document cure
    • DAAs are specific to HCV genotype and some HCV genomic polymorphisms
      • therefore is may be necessary to obtain testing for these determinants of success
    • Treatment is rapidly evolving and guidelines are regularly changing

Prevention
  • No vaccine available
  • Pre/post-exposure       Ig is NOT effective
  • Avoid exposure!
  •   
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