Viral hepatitis II Flashcards
Describe the morphology of HCV
- flavivirus
- +ssRNA
- seven genotypes
How did screening of HCV-infected donors affect the incidence of acute HCV?
Declines among transfusion recipients and decline among injection drug users
What tests are used to test for HCV in blood
2nd gen HCV Ab and RNA tests
What are the major targets for antiviral therapy in HCV?
NS3 (protease), NS5A, NS5B (RdRp)
Why is HCV challenging to make a vaccine in?
lots of variability between HCV genotypes + quasi species
Why is HCV bad? Epidemiology wise
- most acute infections become chronic
- leading indication for liver transplant
- most common blood-borne disease in NA and Western Europe
How is HCV transmitted?
- blood (safer now)
- IV drug abuse (most common)
- sexual transmisson
- vertical transmisson
How efficient is HCV transmisson?
very - contaminates drug paraphernalia, not just needles
Why is HCV bad health wise?
most acute HCV becomes chronic and it is not detected until cirrhosis begins usually
What was the therapy for HCV, what is now the therapy for HCV, is it curable?
was = Peg IFN and ribavirin
now = DAA –> cures
How was the mouse model of HCV developed?
Crossing Alb/uPA mice onto SCID background –> Alb-uPA/SCID mouse (must be homozygous) –> inject human hepatocytes into mouse spleen –> human hepatocytes migrate to liver –> transgenic mouse thats immunocomprimised and transplanted with human hepatocytes
Why did we get rid of IFN treatments for HCV?
IFN causes lots of side effects
What an ideal therapy for HCV?
- IFN free
- one-a-day dosing
- few or no side effects
- little or no resistance
- effective for all genotypes
Whats a current issue for HCV therapy?
- very costly
- trying to find carriers before it’s too late
What are the effects of curing HCV?
- reduces total mortality
- reduces liver-related mortality
- reduces liver cancer from HCV
- renders patients non infectious
Is HCV treatment increasing SVR more than new cases are reported? What does this imply?
No - need a vaccine
What are HCV vaccine challenges:
- viral diversity
- there was a vaccine clinical trial and it failed, so no clinical trails can happen until a vaccine is shown to have efficacy
Is there immunity to HCV?
yes - partial: reinfection with a different genotype have lower peak viremina, shorter duration of viremia, and reduced chronicity
Why is development of an HCV vaccine important?
cost effective, antivirals are very expensive
What is a CHIM study?
controlled human infection model: vaccinate volunteers and then infect with pathogen
Why are we able to do CHIM study with HCV?
because we have highly effective antivirals, cure chronic carriers
What is the HCV CHIM Aim?
to asses safety and efficacy of HCV vaccine candidates to prevent chronic HCV infection
Why must the reliability of the HCV inoculum be assesed in CHIM study?
- reliability of infectivity
- clinical course
- spontaneous clearnace rate
- curability
Describe the morphology of HDV
- env, viroid like
- circular ssRNA
- subviral agent
- can replicate autonomously
- requires HBV surface proteins for release and uptake
