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
what type of virus is HBV?
what makes cure difficult?
is it more or less carcinogenic than other hep viruses?
it is a double stranded DNA virus
it has a high level of viraemia when active
it is super dooper infective
it integrates into the host genome making cure difficult
it is significantly more carcinogenic than other hepatitis viruses. It can cause cancer pre-cirrhosis c.f. HCV
what are the molecular pathogenetics of Hep B?
HBV isn’t usually cytopathic to hepatocytes
the HBeAg (the precore antigen) is essential for establishing persistent infection. This means that at the start of infection this MUST be present. Perhaps this suppresses the immune response
the liver disease is probably due to host immune responses
the HBV polymerase lacks proof reading function
what are the modes of transmission of HBV?
does age of infection make a difference to chronicity of infection?
perinatal in areas of high endemicity
sexual contact
blood products
organ transplant
unknown
IVDU
if someone is infected age 2 years = 5% chronic HBV
what are the treatment options in Hep B?
how do you choose between them?
immune modulating based treatment, using PEG-interferon
- for interferon to work, there needs to be active hepatitis - therefore, the ALT has to be elevated
- however, a severe flare can occur following introduction of interferon
OR
nucleoside analogues, primarily entecavir and tenofovir
why are we worried about viral resistance to entecavir and tenofovir?
these drugs both target DNA pol
that means that, theoretically, mutations could occur in a single area, that could lead to resistance.
however, this has yet to occur (as fair as we know)
why does Hep B treatment with nucleoside analogues need to be life long?
it’s because of the persistence of cccDNA in the infected cell’s nucleus
this is a circular bit of DNA that can be a template for future infection. Because it’s just chillin’ in the cell, it’s impossible for the body to completely eliminate it
this is less of an issue with interferon because there’s no single drug target (it just sort of stimulates an anti-viral activity in the body - i dunno, eh)
what is the risk of vertical transmission in HBV?
how do we treat/prevent?
this is a seriously infective virus. The risk is very high - around 90% if eAg+!
mode of delivery is of minor importance, suggesting it’s not about the blood exposure?
the baby should receive passive and active vaccination immediately (this is super effective)
the mother should be given tenofovir in the last trimester if there is a high viral load
is there any role for Hep B treatment in a patient about to receive immune suppression? (for example, about to undergo an HSCT or R-CHOP)
loss of immune control causes viral reactivation due to persistence of the cccDNA
then, when there is immune restoration, this can leads to a reconstitution illness (severe T cell mediated hepatitis)
at risk patients should have preemptive treatment with an anti-viral drug
what is the Hep D virus?
this is a co-infection with chronic HBV
it is a defective DNA virus that uses the HBV viral polymerase to replicate
there’s not very much in way of treatment although some people have tried PEG-interferon
