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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
Q

What percentage of acute hepatitis viruses become chronic?

A

80%

26
Q

From the chronic infections, what percentage is associated with which level of fibrosis?

A

30% develop mild fibrosis

30% develop moderate fibrosis

20% develop severe fibrosis

27
Q

What happens to the patients with chronic hepatitis that develop severe fibrosis?

A

They develop cirrhosis, which subsequently leads to cancer and death

Some improve their condition and develop moderate fibrosis with normal life expectancies

28
Q

What happens to the patients with moderate and mild fibrosis?

A

They go on to have normal life expectancies

Some people with moderate fibrosis might develop severe fibrosis

29
Q

What happens to the 20% of patients with acute hepatitis which do not develop chronic infections?

A

Resolution

30
Q

Which factors affect the progression of cirrhosis?

A

Alcohol

Weight

Gender

Age

Onset of disease

31
Q

How many people in the world are infected with Hepatitis C?

A

160 million people

32
Q

What percentage of Hepatitis cases happen in Europe?

A

0.4-3.5%

33
Q

Where are incidences of hepatitis higher?

A

In cities

34
Q

How many major types of HCV exist?

A

6

35
Q

How are the 6 different types of HCV differentiated?

A

Genetically

36
Q

Why is it important to differentiate between the 6 different families of HCV?

A

Drugs might affect the different families in different ways

Active sites are differently shaped

37
Q

How are the 6 different HCV phylotypes arranged throughout the world?

A

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
Q

What are the two main strategies of treating HCV?

A

Boosting host immunity

Direct antiviral agents

39
Q

Examples of molecules boosting host immunity

A

Interpheron alpha

40
Q

Examples of direct antiviral agents

A

Protease inhibitors

Polymerase inhibitors

Replication complex inhibitors

41
Q

What was the outcome of boosting host immunity when first implemented to treat HCV?

A

Disappointing

Only a 5% success rate

Lots of side-effects

42
Q

What was outcome of antiviral agents in HCV?

A

Higher success rates than boosting host immunity

43
Q

What was the most successful treatment of HCV?

A

Combination therapy

Boost the host immunity and direct antiviral agents

44
Q

What drug changed HCV infections?

A

Polymerase inhibitors

Have a 100% success rate

45
Q

Why does HCV not develop resistance to polymerase inhibitors?

A

Because the selection pressure is so high that the mutation needed to gain resistance would render the virus non-viable

46
Q

Characteristics of the HBV genome

A

Complex genome

Genes overlap since there are no stop codons separating the genes

Genes are encoded in one continuous cycle

47
Q

How does the genome of the HBV affect its function?

A

Functions of the proteins encoded for by the hepatitis B overlap, much like the genome

48
Q

How does HBV evade the immune system?

A

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
Q

How does Hepatitis B cause cancer?

A

Incorporates random sequences of DNA into the genome

Affects the function of tumour suppression genes

50
Q

What two markers are used to assess patients with chronic HBV infection?

A

HBV markers - HBsAg, anti-HBe, HBV DNA

Liver disease markers - biochemical parameters (ALT). fibrosis markers (non-invasive markers of fibrosis, liver biopsies)

51
Q

Which parameters are used to assess Hepatitis B infection?

A
  1. Active or carrier state

2. e antigen positive or negative

52
Q

What are the three phases of chronic HBV infection with time?

A

HBeAg+ chronic hepatitis

Inactive-carrier state

HBeAg- chronic hepatitis

53
Q

Describe the HBeAg+ stage of chronic HBV progression

A

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
Q

Describe the inactive-carrier stage of HBV progression

A

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
Q

Describe the HBeAg- stage of HBV progression

A

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
Q

How many people die worldwide from HBV?

A

500 000

57
Q

Why is HBV deadly?

A

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
Q

How many people are infected with HBV worldwide per year?

A

350 million

59
Q

How many people in Europe are infected with HBV?

A

7000 - 8000 cases

60
Q

What is the main goal for therapy of HBV?

A

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
Q

What is a factor that directly correlates with survival in HBV patients?

A

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
Q

What are the three mechanisms by which HBV causes cancer?

A

Fibrosis and cirrhosis

DNA integration

Oncogenic proteins

Molecular Basis of Disease (28 decks)

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