Hepatitis Flashcards
how does viral replication of hepatitis C occur?
it has SUPER high levels of viral replication
it is highly error prone, and there is a “cloud” of quasispecies
it only exists in the cytoplasm and does not get integrated into nucleus/genome
how does HCV transmit?
what about vertical transmission?
what type of virus is it?
this is a single stranded RNA virus
parenteral transmission is most frequent
- 90% of new infections due to injecting drugs
there is a risk of sexual transmission, but it is quite low
the risk of vertical transmission is about 4% if mother has active replication (PCR demonstrates some virus in the blood)
is there any role for testing neonates for HCV? (if mother +)
not really, because there will be some transmission of the antibodies, therefore it will be falsely positive
what is the natural history of HCV infection?
about 25% will spontaneously clear the virus on first infection
the rest will have chronic infection
about 15% of total infected will develop cirrhosis after about 20 years
total lifetime risk is about 40%
only about 5% of the cirrhotics develop liver failure or cancer EACH YEAR
how does hep c kill hepatocytes?
it isn’t directly toxic.
it seems to lead to CTL killing of the cell
what is the role of liver biopsy in Hep C?
it is no longer a pre-req for treatment
it can be used to determine prognosis and relative need for treatment perhaps?
what is the goal of treatment in Hep C?
the goal is cure, which is actually “sustained virologic response”
this is no detectable disease 6 months after cessation of treatment
what are some factors that favour successful treatment?
genotype 2, 3 early stage disease IL28b cc genotype low viral load young, female, while, thing
what is the IL28b genotype?
this is a genotype that predicts response to treatment
the C/C genotype is best, and this was shown to be the same with different ethnicities
T/T is bad news though
how do we treat Hep C?
genotype 1 and 4: 48 weeks of Peg-interferon and ribavirin and a DAA (hep c protease inhibitor - teleprevir and boceprevir)
genotype 2 and 3: 24 weeks of Peg-IF and ribavirin. 48 weeks if already cirrhotic
what is peg-interferon?
the PEG stands for polyethylene glycol
it slows the absorption and metabolism
the interferon is the same drug as that released by immune system (LLs).
it has some sort of anti-viral action
What is ribavirin?
this is a nucleoside analogue
it doesn’t work as monotherapy
it is a potent teratogen - double contraception is required
it can cause haemolysis. this is important. is dose dependent
MOST COMMON SIDE EFFECT IS HAEMOLYTIC ANAEMIA! AAAAAHHHHH! DON’T FORGET THIS AGAIN!
what is the new agent sofobuvir?
this is an inhibitor of HCV RNA-dependent RNA polymerase
this is a super dooper effective anti-Hep C agent and has now been recommended as first line in the US
(not yet available in Australia)
what is the recurrence rate of Hep C in liver transplantation?
always
in 5 years post OLT 30 - 40% will have progressive liver disease
(this is a bad disease to have in the OLT)
what is the treatment protocol in HCV/HIV coinfection?
step 1 is to optimise HAART first, then treat the HCV
the HCV liver disease will progress rapidly and needs aggressive treatment
liver disease is actually the leading cause of mortality in these co-infected patients
