L16. Hepatitis 2 (Chronic) Flashcards

1
Q

What types of hepatitis virus cause chronic infection?

A

HBV, HCV and HDV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the sources of these chronic hepatitis viruses? How are they spread?

A

Source: Blood-Borne and in bodily fluids

Spread percutaneously and permucosally (sexual transmission, perinatal and IV drug use)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Does water and food sanitation have an impact on the spread of chronic hepatitis viruses?

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the two forms of the Hepatitis B viral structure?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the purpose of the non-infectious filamentous form?

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the structure of the Hepatitis B genome

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe the replication of the Hepatitis B genome

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe the pathogenesis of the hepatitis B virus

A
  1. Virus enters cells, release of core and genome
  2. Enters the nucleus and missing piece of DNA is repaired to a complete circle = covalently closed circular DNA (cccDNA)
  3. cccDNA episome is the template and undergoes reverser transcriptase (highly error prone) to produce several viral RNA including the pre-genomic RNA
  4. 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe the life cycle of the hepatitis B virus

A
  1. Secreted in blood, semen and other blood exudates
  2. Penetrates the mucosal epithelium of new host
  3. Circulates in the blood and reaches the liver
  4. Infects and replicates in the hepatocytes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the Hepatitis B e-antigen an important indicator of?

A

Infectiousness

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the incubation period of HBV?

A

60-90 days

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the difference between ages in infection of HBV?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the difference in the serological courses of the acute vs. the chronic hepatitis B virus?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are some sequelae of chronic hepatitis B?

A

Cirrhosis
Liver failure
Primary hepatocellular carinoma (after 10-30 years)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the relationship between HBV and cancer?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the two main classes of antiviral drugs used for HBV infections?

A

Interferon alpha (pegylated): for HBeAg positive carriers. Not highest effective rate and unpleasant therapy

Nucleoside and nucleotide analogs: don’t have the complete cyclic formation of the nucleotide/side and thus prevent elongation of the genome.

17
Q

Is there a vaccine available for hepatitis B?

A

Yes

It is an inactivated virus with an alum adjuvant that protects against both HBV and HDV

18
Q

What family does Hepatitis D belong to?

A

Deltavirus

19
Q

Describe the hepatitis D virus structure and genome

A

ssRNA genome
Rolling circle replication (self-complementary) and only makes 1 protein (the delta antigen)

It is inside a particle that has the HBsAg

20
Q

What is important about hepatitis D infection?

A

It only infects IN CONJUNCTION WITH HEPATITIS B because it is partly made by the HBsAg.

  1. Coinfection at the same time = severe acute disease (low risk of chronic infection)
  2. Superinfection of HDV onto HBV positive patients
    = chronic HDV infection with high risk of severe chronic liver disease
21
Q

What family does the HCV virus belong to?

A

Flavivirus

22
Q

Describe the HCV virus genome and structure

A

+ ssRNA virus
replicates without requiring being in the nucleus (has own mechanisms)

In a lipid envelope with lipid glyoproteins and lipid droplets

23
Q

Describe the replication process (intracellular pathogenesis) of the HCV virus

A

It enters the cell via endosomal means into hepatocytes and the endosome acidifies releasing the viral RNA. The RNA replicates in the cytoplasm through golgi for assembly before new viruses are formed

24
Q

The RNA polymerase of the +ssRNA is highly error prone. What is the implication of this?

A

There are many mutations that can occur and hence there is a large genome diversity capable of causing disease = very difficult for vaccine makers

25
Q

What is the incubation period of HCV?

A

6-7 weeks

26
Q

What percentage of people get chronically ill with hepatitis C?

A

70% (30% are able to clear the acute virus)

27
Q

What are the sequelae of chronic hepatitis C?

A

UP to 70-90% become chronic carriers

Liver fibrosis, cirrhosis, liver failure, cancer

28
Q

What drugs were used for hepatitis C?

A

Interferon alpha

Ribavirin (nucleoside analog)

29
Q

Describe the emergence of the Direct Acting Antivirals (DAA) for hepatitis C

A

Directly attack the specific viral enzymes and are proving to have relatively high efficacies

30
Q

What are some HVC specific life cycle inhibitors?

A
Viral entry inhibitors
HCV rna translation inhibitors
Post translational protein inhibitors (NS3-4A protease inhibitors)
HCV replication inhibitors
Viral assembly and release inhibitors
31
Q

What are the two phases of HCV treatment? (historically)

A

pre-2015 IFN based combination therapy

2015 onwards IFN-free combination therapy