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Molecular Basis of Disease > Hepatitis virus > Flashcards

Hepatitis virus Flashcards

1
Q

Why is the hepatitis virus historically important?

A

One of the only conditions that has lead to complete remission following therapy

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2
Q

What are the different types of Hepatitis virus?

A

A, B, C

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3
Q

How are the different Hepatitis viruses classified?

A

How they transmit

Type of nucleic acid

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4
Q

Hepatitis viruses are genetically linked

TRUE or FALSE

A

FALSE

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5
Q

Is the pathogenesis of hepatitis cytolytic?

A

No

It does not cause coughs or runny noses

Depends on the immune response to cause cell damage

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6
Q

How is HBA transmitted?

A

Water

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7
Q

How is HBV transmitted?

A

Blood

Mother to child - commonest

Sex

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8
Q

How is HCV transmitted?

A

Blood

Rarely transmitted through sex or from mother to child

Snorting drugs
Injections
Blood products

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9
Q

What is the pathogenesis of HBV?

A

Chronic

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10
Q

What is the pathogenesis of HCV?

A

Chronic

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11
Q

What is the pathogenesis HAV?

A

Self-limiting

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12
Q

What type of nucleic acid is found in HBV?

A

DNA

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13
Q

What type of nucleic acid is found in HCV?

A

RNA

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14
Q

What is the consequence of the chronicity of HBV and HCV?

A

Responsible for the immune mediated liver damage that leads to fibrosis and cancer

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15
Q

What is the consequence of the self-limiting property of HAV?

A

Individuals clear the virus, recover and have lasting immunity

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16
Q

How was hepatitis B discovered?

A

Electromyography

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17
Q

How was hepatitis A discovered?

A

Culture

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18
Q

How was hepatitis C discovered?

A

Blood from chimpances with non-Anon-B hepatitis was obtained

The total RNA and DNA was extracted

Genes were used to make complementary DNA (cDNA)

These were then inserted into eukaryotic bacteria, which used their replication machinery to clone the sequences

Antibodies from NANBH patients were obtained from the plasma

Scientists identified the sequences of DNA these antibodies bound to

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19
Q

What differentiates cDNA from normal DNA?

A

It has been modified by post-transcriptional modification to remove the introns

Only codes the exons

Contains a poly-A tail

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20
Q

What gene was identified to belong to the HCV?

A

5-1-1 clone

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21
Q

What type of nucleic acid is found in HCV?

A

Positively-stranded RNA

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22
Q

What year was the HCV genome discovered?

A

1993

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23
Q

What does the HCV genome code for?

A

Only codes for structural proteins

Including core and envelope proteins

And non-structural proteins

RNA polymerase, replication complex and serine proteases

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24
Q

What is a good target to knock out viral function?

A

RNA polymerase

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25
What percentage of acute hepatitis viruses become chronic?
80%
26
From the chronic infections, what percentage is associated with which level of fibrosis?
30% develop mild fibrosis 30% develop moderate fibrosis 20% develop severe fibrosis
27
What happens to the patients with chronic hepatitis that develop severe fibrosis?
They develop cirrhosis, which subsequently leads to cancer and death Some improve their condition and develop moderate fibrosis with normal life expectancies
28
What happens to the patients with moderate and mild fibrosis?
They go on to have normal life expectancies Some people with moderate fibrosis might develop severe fibrosis
29
What happens to the 20% of patients with acute hepatitis which do not develop chronic infections?
Resolution
30
Which factors affect the progression of cirrhosis?
Alcohol Weight Gender Age Onset of disease
31
How many people in the world are infected with Hepatitis C?
160 million people
32
What percentage of Hepatitis cases happen in Europe?
0.4-3.5%
33
Where are incidences of hepatitis higher?
In cities
34
How many major types of HCV exist?
6
35
How are the 6 different types of HCV differentiated?
Genetically
36
Why is it important to differentiate between the 6 different families of HCV?
Drugs might affect the different families in different ways Active sites are differently shaped
37
How are the 6 different HCV phylotypes arranged throughout the world?
There are clusters of different virus phylotypes throughout the world Prevalence depends on the behaviours typical for said area Areas with more injections and higher rates of intravenous drug users have higher rates
38
What are the two main strategies of treating HCV?
Boosting host immunity Direct antiviral agents
39
Examples of molecules boosting host immunity
Interpheron alpha
40
Examples of direct antiviral agents
Protease inhibitors Polymerase inhibitors Replication complex inhibitors
41
What was the outcome of boosting host immunity when first implemented to treat HCV?
Disappointing Only a 5% success rate Lots of side-effects
42
What was outcome of antiviral agents in HCV?
Higher success rates than boosting host immunity
43
What was the most successful treatment of HCV?
Combination therapy Boost the host immunity and direct antiviral agents
44
What drug changed HCV infections?
Polymerase inhibitors Have a 100% success rate
45
Why does HCV not develop resistance to polymerase inhibitors?
Because the selection pressure is so high that the mutation needed to gain resistance would render the virus non-viable
46
Characteristics of the HBV genome
Complex genome Genes overlap since there are no stop codons separating the genes Genes are encoded in one continuous cycle
47
How does the genome of the HBV affect its function?
Functions of the proteins encoded for by the hepatitis B overlap, much like the genome
48
How does HBV evade the immune system?
Some proteins encoded for by the genome help the virus evade the immune system Hepatitis B can reduce the expression of virus proteins once the body detects these in the immune system Hepatitis B forms reservoirs in its host by making circular complementary DNA strands in the nucleus, making it impossible for the host immunity to access these virus particles
49
How does Hepatitis B cause cancer?
Incorporates random sequences of DNA into the genome Affects the function of tumour suppression genes
50
What two markers are used to assess patients with chronic HBV infection?
HBV markers - HBsAg, anti-HBe, HBV DNA Liver disease markers - biochemical parameters (ALT). fibrosis markers (non-invasive markers of fibrosis, liver biopsies)
51
Which parameters are used to assess Hepatitis B infection?
1. Active or carrier state | 2. e antigen positive or negative
52
What are the three phases of chronic HBV infection with time?
HBeAg+ chronic hepatitis Inactive-carrier state HBeAg- chronic hepatitis
53
Describe the HBeAg+ stage of chronic HBV progression
There is immune tolerance to the virus Antigens for HBV are high Serum ALT levels are low since there is not a severe immune response mounted As the immune system reacts to the virus, the ALT levels rise as the hepatocytes are attacked by the immune system, as the virus injects its DNA into these cells Viral load decreases as a response
54
Describe the inactive-carrier stage of HBV progression
As the initial infection is cleared since the viral load is kept low, the cirrhosis goes back to normal Not present in all patients
55
Describe the HBeAg- stage of HBV progression
The immune reaction is re-established following immunosuppression that increases viral load The serum is negative for Hepatitis B antigens due to mutations to the viral genome The serum is positive for Hepatitis B antibodies
56
How many people die worldwide from HBV?
500 000
57
Why is HBV deadly?
Can lead to cirrhosis in chronic infection This is deadly if severe, since it leads to conditions like liver failure following decompensation and liver cancer
58
How many people are infected with HBV worldwide per year?
350 million
59
How many people in Europe are infected with HBV?
7000 - 8000 cases
60
What is the main goal for therapy of HBV?
Improve the quality of life and survival of patients by preventing the progression of the disease to cirrhosis, end-stage liver disease and death Therapies must cause a sustained suppression of HBV replication and reduce the histological activity of chronic hepatitis B
61
What is a factor that directly correlates with survival in HBV patients?
Prognosis of a HBV patient is related to the viral load The higher the HBV DNA level, the increased severity of cirrhosis and cancer present in patients
62
What are the three mechanisms by which HBV causes cancer?
Fibrosis and cirrhosis DNA integration Oncogenic proteins

Molecular Basis of Disease (28 decks)

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