Infectious Causes of Hepatitis 2

Question 1

What is the transmission of hepatitis B, C and D?

Answer 1

blood and blood derived body fluids - sexually transmitted and IV drug use

Question 2

What type of infection is caused by hepatitis B, C and D?

Answer 2

chronic

Question 3

For which hepatitis virus is there perinatal transmission?

Answer 3

hepatitis B - can be reduced but not eliminated with drug treatment

Question 4

What proportion of regular IV drug users have hepatitis C?

Answer 4

50-60%

Question 5

What is the structure of the hepatitis B virion?

Answer 5

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

Question 6

What are the different messenger RNAs that can be transcribed from the hepatitis B genome?

Answer 6

• 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)

Question 7

What restricts the level of mutation capable?

Answer 7

There is more than one reading frame

Question 8

How does the hepatitis B virus replicate?

Answer 8

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

Question 9

Does hepatitis B replicate in intestinal mucosa?

Answer 9

No - only penetrates

Question 10

What is the incubation period of hepatitis B?

Answer 10

on average 60-90 days

Question 11

What percentage of patients under 5 will develop acute jaundice?

Answer 11

under 10%

Question 12

What percentage of patients over 5 will develop acute jaundice?

Answer 12

30-50%

Question 13

What percentage of patients under 5 will go on to develop a chronic infection?

Answer 13

30-90%

Question 14

What percentage of patients over 5 will go on to develop a chronic infection?

Answer 14

15-25%

Question 15

What are the two outcomes of an initial infection of hepatitis B?

Answer 15

resolution or chronic carrier state

Question 16

What is the outcome of patients who are chronic carriers?

Answer 16

Can further progress to cirrhosis or can stabilise

Question 17

What is the outcome of patients who develop cirrhosis?

Answer 17

Cirrhosis can maintain as compensated or can go into a decompensated cirrhosis

Question 18

What is a possible outcome of cirrhosis?

Answer 18

liver cancer

Question 19

In an acute infection what marks replication and presence of viral particles?

Answer 19

hepatitis B surface antigen and the presence of hepatitis B e antigen

Question 20

What is the initial immune response?

Answer 20

IgM against the core protein

Question 21

What is the immune response that develops?

Answer 21

IgG against the core protein

Question 22

When do symptoms appear?

Answer 22

when the immune response begins

Question 23

What demonstrates an immune response against the virus?

Answer 23

surface antibody

Question 24

What stays at a sustained high level in chronic infection?

Answer 24

surface antigen and e antigen and core antibodies

Question 25

What does a chronic infection lack?

Answer 25

antibodies to the surface and antibodies to the e antigen

Question 26

What serological test shows that a patient is a chronic hepatitis B carrier?

Answer 26

positive for surface antigen

Question 27

Which antibody to hepatitis B is present first - the core or the surface antibody?

Answer 27

The core antibody

Question 28

What treatments can be used to prevent chronic hepatitis B from going to end stage liver disease?

Answer 28

cytokines (interferon) and antivirals (target replication)

Question 29

What treatment is often required at end stage liver disease?

Answer 29

transplant

Question 30

What causes hepatocellular carcinoma in hepatitis B infected patients?

Answer 30

partial integration of HBV genome disrupting normal DNA, repeated destruction and regeneration of hepatocytes accumulates mutations, and possible role of HBV-X gene

Question 31

What is the surface antigen used to show in serological tests?

Answer 31

a general marker of infection

Question 32

What is the surface antibody used to show in serological tests?

Answer 32

recovery and or immunity to HBV and also successful vaccination

Question 33

What is the IgM core antibody used to show in serological tests?

Answer 33

marker of acute infection (rising titre)

Question 34

What is the IgG core antibody used to show in serological tests?

Answer 34

marker of past or chronic infection (steady titre)

Question 35

What is the e antigen used to show in serological tests?

Answer 35

indicates active replication - used to see if treatment is effective

Question 36

What is the e antibody used to show in serological tests?

Answer 36

that the virus is no longer replicating

Question 37

What does the HBV-DNA in serological tests show?

Answer 37

active replication - more accurate than hepatitis B e antigen

Question 38

What antiviral drugs are available for HBV?

Answer 38

pegylated interferon alpha, nucleoside and nucleotide analogues and some new generation drugs

Question 39

What does the pegylated mean?

Answer 39

better bioavailability

Question 40

How do nucleoside and nucleotide analogues work?

Answer 40

they target polymerase function - but have low rates of viral clearance and get relapse after therapy stops

Question 41

What is the difference between nucleoside and nucleotide analogues?

Answer 41

nucleotides have a phosphate added already to increase activity

Question 42

What are 3TC and entecavir?

Answer 42

nucleoside analogues

Question 43

What are adefovir and tenofovir?

Answer 43

nucleotide analogues

Question 44

Is there a successful vaccine for hepatitis B?

Answer 44

yes - also works for hepatitis D

Question 45

Can the vaccine be used post exposure?

Answer 45

yes

Question 46

What is the hepatitis D virus?

Answer 46

It is an infectious virus particle encased in hepatitis B surface antigen which allows it to be taken up by hepatocytes

Question 47

What type of genome is hepatitis D?

Answer 47

single stranded RNA

Question 48

What is the core antigen for hepatitis D?

Answer 48

delta antigen

Question 49

What is the clinical presentation of a co-infection of hepatitis B and D?

Answer 49

less severe acute disease with a low risk of chronic infection

Question 50

What is the clinical presentation of a hepatitis B infection followed by a hepatitis D infection?

Answer 50

a chronic HDV infection with high risk of chronic liver disease

Question 51

What family does the hepatitis C virus belong to?

Answer 51

flavivirus family

Question 52

Is there a vaccine for hepatitis C?

Answer 52

No - instigates poor immune response

Question 53

What is the genome of the hepatitis C virus?

Answer 53

single stranded linear + sense RNA

Question 54

How does the hepatitis C virus make proteins in replication?

Answer 54

Protein encoded as a polyprotein which is cleaved by a protease

Question 55

How does hepatitis C virus enter hepatocytes?

Answer 55

by associating with lipid

Question 56

What happens after the hepatitis C enters the hepatocyte?

Answer 56

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

Question 57

Why do a lot of mutations occur in hepatitis C?

Answer 57

because the replication machinery is error prone - an evasion strategy of the virus

Question 58

What is the incubation period of hepatitis C?

Answer 58

6 weeks

Question 59

What percentage of hepatitis C infections will lead to a chronic infection?

Answer 59

70%

Question 60

What percentage of those infected with hepatitis C become chronic carriers?

Answer 60

70-90%

Question 61

What are the outcome of a chronic hepatitis C infection?

Answer 61

cirrhosis, liver failure and carcinoma

Question 62

What are the older drugs used to treat hepatitis C?

Answer 62

interferon alpha and ribavirin (a nucleoside inhibitor)

Question 63

What are the disadvantages of the older drugs?

Answer 63

They have lots of side effects and are ineffective in many patients

Question 64

What are teleprovir and boceprevir?

Answer 64

direct acting antivirals that inhibit proteases that cleaves up the polyprotein in the active forms

Question 65

What other HCV specific life cycle inhibitors are available?

Answer 65

viral entry inhibitors, RNA translation inhibitors, replication inhibitors, assembly and release inhibitors