Infectious Causes of Hepatitis 2 Flashcards
What is the transmission of hepatitis B, C and D?
blood and blood derived body fluids - sexually transmitted and IV drug use
What type of infection is caused by hepatitis B, C and D?
chronic
For which hepatitis virus is there perinatal transmission?
hepatitis B - can be reduced but not eliminated with drug treatment
What proportion of regular IV drug users have hepatitis C?
50-60%
What is the structure of the hepatitis B virion?
virus particles have suface antigens, outer envelope (lipid bilayer) and inner capsid (the core structure) and contain an incomplete double strand of DNA - there are also not infectious particles made up purely of surface antigen
What are the different messenger RNAs that can be transcribed from the hepatitis B genome?
- the pregenomic RNA which codes for the core protein, the precore (HBeAg) and an enzyme for reverse transcription
- an RNA which codes for surface proteins
- another RNA which codes for non structural proteins involved in immune evasion and pathogenesis (protein X)
What restricts the level of mutation capable?
There is more than one reading frame
How does the hepatitis B virus replicate?
infects hepatocytes, DNA goes into nucleus where replication completes the gap to make a closed circular DNA episome, pregenomic RNA is transcribed, pregenomic RNA goes to the cytoplasm and forms a nucleocapsid which serves as a template for the genome via reverse transcription, produce core particles which can either re-enter the nucleus or leave the cell
Does hepatitis B replicate in intestinal mucosa?
No - only penetrates
What is the incubation period of hepatitis B?
on average 60-90 days
What percentage of patients under 5 will develop acute jaundice?
under 10%
What percentage of patients over 5 will develop acute jaundice?
30-50%
What percentage of patients under 5 will go on to develop a chronic infection?
30-90%
What percentage of patients over 5 will go on to develop a chronic infection?
15-25%
What are the two outcomes of an initial infection of hepatitis B?
resolution or chronic carrier state
What is the outcome of patients who are chronic carriers?
Can further progress to cirrhosis or can stabilise
What is the outcome of patients who develop cirrhosis?
Cirrhosis can maintain as compensated or can go into a decompensated cirrhosis
What is a possible outcome of cirrhosis?
liver cancer
In an acute infection what marks replication and presence of viral particles?
hepatitis B surface antigen and the presence of hepatitis B e antigen
What is the initial immune response?
IgM against the core protein
What is the immune response that develops?
IgG against the core protein
When do symptoms appear?
when the immune response begins
What demonstrates an immune response against the virus?
surface antibody
What stays at a sustained high level in chronic infection?
surface antigen and e antigen and core antibodies
What does a chronic infection lack?
antibodies to the surface and antibodies to the e antigen
What serological test shows that a patient is a chronic hepatitis B carrier?
positive for surface antigen
Which antibody to hepatitis B is present first - the core or the surface antibody?
The core antibody
What treatments can be used to prevent chronic hepatitis B from going to end stage liver disease?
cytokines (interferon) and antivirals (target replication)
What treatment is often required at end stage liver disease?
transplant
What causes hepatocellular carcinoma in hepatitis B infected patients?
partial integration of HBV genome disrupting normal DNA, repeated destruction and regeneration of hepatocytes accumulates mutations, and possible role of HBV-X gene
What is the surface antigen used to show in serological tests?
a general marker of infection
What is the surface antibody used to show in serological tests?
recovery and or immunity to HBV and also successful vaccination
What is the IgM core antibody used to show in serological tests?
marker of acute infection (rising titre)
What is the IgG core antibody used to show in serological tests?
marker of past or chronic infection (steady titre)
What is the e antigen used to show in serological tests?
indicates active replication - used to see if treatment is effective
What is the e antibody used to show in serological tests?
that the virus is no longer replicating
What does the HBV-DNA in serological tests show?
active replication - more accurate than hepatitis B e antigen
What antiviral drugs are available for HBV?
pegylated interferon alpha, nucleoside and nucleotide analogues and some new generation drugs
What does the pegylated mean?
better bioavailability
How do nucleoside and nucleotide analogues work?
they target polymerase function - but have low rates of viral clearance and get relapse after therapy stops
What is the difference between nucleoside and nucleotide analogues?
nucleotides have a phosphate added already to increase activity
What are 3TC and entecavir?
nucleoside analogues
What are adefovir and tenofovir?
nucleotide analogues
Is there a successful vaccine for hepatitis B?
yes - also works for hepatitis D
Can the vaccine be used post exposure?
yes
What is the hepatitis D virus?
It is an infectious virus particle encased in hepatitis B surface antigen which allows it to be taken up by hepatocytes
What type of genome is hepatitis D?
single stranded RNA
What is the core antigen for hepatitis D?
delta antigen
What is the clinical presentation of a co-infection of hepatitis B and D?
less severe acute disease with a low risk of chronic infection
What is the clinical presentation of a hepatitis B infection followed by a hepatitis D infection?
a chronic HDV infection with high risk of chronic liver disease
What family does the hepatitis C virus belong to?
flavivirus family
Is there a vaccine for hepatitis C?
No - instigates poor immune response
What is the genome of the hepatitis C virus?
single stranded linear + sense RNA
How does the hepatitis C virus make proteins in replication?
Protein encoded as a polyprotein which is cleaved by a protease
How does hepatitis C virus enter hepatocytes?
by associating with lipid
What happens after the hepatitis C enters the hepatocyte?
the RNA molecule goes to the ER where it is translated to structural and non structural proteins and then non structural proteins replicate the template to produce a lot of DNA
Why do a lot of mutations occur in hepatitis C?
because the replication machinery is error prone - an evasion strategy of the virus
What is the incubation period of hepatitis C?
6 weeks
What percentage of hepatitis C infections will lead to a chronic infection?
70%
What percentage of those infected with hepatitis C become chronic carriers?
70-90%
What are the outcome of a chronic hepatitis C infection?
cirrhosis, liver failure and carcinoma
What are the older drugs used to treat hepatitis C?
interferon alpha and ribavirin (a nucleoside inhibitor)
What are the disadvantages of the older drugs?
They have lots of side effects and are ineffective in many patients
What are teleprovir and boceprevir?
direct acting antivirals that inhibit proteases that cleaves up the polyprotein in the active forms
What other HCV specific life cycle inhibitors are available?
viral entry inhibitors, RNA translation inhibitors, replication inhibitors, assembly and release inhibitors
