L16. Hepatitis 2 (Chronic) Flashcards
What types of hepatitis virus cause chronic infection?
HBV, HCV and HDV
What are the sources of these chronic hepatitis viruses? How are they spread?
Source: Blood-Borne and in bodily fluids
Spread percutaneously and permucosally (sexual transmission, perinatal and IV drug use)
Does water and food sanitation have an impact on the spread of chronic hepatitis viruses?
NO
The prevention is by blood screening and modifying risk factor behaviour only.
Transmission is out of the hepatocytes into the blood (reverse to acute viruses)
What are the two forms of the Hepatitis B viral structure?
The INFECTIOUS form: double walled structure: outer envelope with surface antigen and inner capsid containing the genome
The NON-INFECTIOUS form: an incomplete filamentous form made up of the surface antigen
What is the purpose of the non-infectious filamentous form?
Because it is made up of the HBsAg (surface antigen) it is able to act as a decoy for antibodies against the virus to bind to it.
Describe the structure of the Hepatitis B genome
dsDNA
Circular - incomplete double strands
With repeated sequences called direct repeat (DR) regions
with genome has several RNA start sites and only one terminal site
Describe the replication of the Hepatitis B genome
Overlapping reading frames code for different proteins: core, surface, polymerase and other
The PRE-GENOMIC RNA is the most important and runs several loops around the DNA
Describe the pathogenesis of the hepatitis B virus
- Virus enters cells, release of core and genome
- Enters the nucleus and missing piece of DNA is repaired to a complete circle = covalently closed circular DNA (cccDNA)
- cccDNA episome is the template and undergoes reverser transcriptase (highly error prone) to produce several viral RNA including the pre-genomic RNA
- RNA and proteins leave nucleus into the cytoplasm and form the virus. This includes more reverse transcriptase to form the incomplete dsDNA loop for the next viral generation
Describe the life cycle of the hepatitis B virus
- Secreted in blood, semen and other blood exudates
- Penetrates the mucosal epithelium of new host
- Circulates in the blood and reaches the liver
- Infects and replicates in the hepatocytes
What is the Hepatitis B e-antigen an important indicator of?
Infectiousness
What is the incubation period of HBV?
60-90 days
What is the difference between ages in infection of HBV?
Young children have poorly formed immune systems and thus are more susceptible for chronic infection and spared from acute
Adults are susceptible to an acute infection (because of the immune response) and spared from chronic infection due to effective clearance
What is the difference in the serological courses of the acute vs. the chronic hepatitis B virus?
ACUTE:
HBsAg and HBeAg indicate presence of virus
HBeAg switches to anti-HBeAg
Levels of HBsAg decrease to baseline
Anti-HBc (core) levels increase and remain high (immunity)
CHRONIC:
HBsAg is present at much higher levels and stays high (no antigens against it are produced)
HBeAg doesn’t switch to Anti-HBeAg
What are some sequelae of chronic hepatitis B?
Cirrhosis
Liver failure
Primary hepatocellular carinoma (after 10-30 years)
What is the relationship between HBV and cancer?
100x higher risk of hepatocellular carcinoma if infected with HBV
About 2-10% of infected patients develop cancer
Repeated destruction and regeneration of hepatocytes increases the chance and accumulation of mutations