Viral Hepatitis and Vaccines (Franco Falcone)

Question 1

What is Hepatitis?

Answer 1

Inflammation of the liver with various causes such as trauma, alcohol abuse. drug induced toxicity or viral infection.

Question 2

What is Liver Cirrhosis?

Answer 2

An advanced consequence of liver disease progression. It is characterised by fibrosis (tissue replaced with collagenous scars with no function) and regenerative nodules (attempts to repair damaged tissue).

Question 3

What is a common complication of cirrhosis?

Answer 3

Ascites - fluid retention in the abdominal cavity

Question 4

Which therapeutic option for liver cirrhosis is available?

Answer 4

Liver transplant is the only option because cirrhosis is irreversible.

Question 5

How does fibrosis occur?

Answer 5

Fibroblasts produce collagen which leads to formation of scars - they have no function and as a result lead to liver function reduction and associated symptoms.

Question 6

What is the cause of most hepatitis?

Answer 6

Viruses

Question 7

What are the types of viruses that cause viral hepatitis?

Answer 7

Hep A, B, C, D, E
HAV HBV HCV HDV HEV

Viral hepatitis can also be caused by other viruses such as Adenovirus, SARS, Ebola, Influenza and others but these viruses mainly cause other symptoms.

Question 8

What kind of infection do naked H viruses cause?

Answer 8

Naked viruses (HAV, HEV) lead to acute infections, whereas the enveloped viruses (HBV, HCV, HDV) cause persistent and chronic infections and have developed ways of evading immunity.

Question 9

How does the type of virus (enveloped v naked) affect their transmission?

Answer 9

Naked: oral fecal
Enveloped: blood another body fluids

Question 10

What are the symptoms of Hepatitis?

Answer 10

Jaundice / Icterus are the most characteristic of hepatitis symptoms.
Yellowing of the skin and eyes due to increased levels of bilirubin in the blood (a hemoglobin breakdown product).
Normally bilirubin is conjugated to form water soluble bilirubin diglucuronide in the healthy liver. In hepatitis this conjugation does not happen.

Question 11

When is jaundice a less common symptom?

Answer 11

In children 14 y/o or <

Question 12

Aside from jaundice, what are the other symptoms of hepatitis?

Answer 12

Fatigue 
Abdominal pain
Loss of appetite
Nausea and vomiting 
Dark urine

Question 13

Is HAV chronic or acute?

Answer 13

Acute; self-limiting

*Can result in fulminant (lightning) hepatitis and death in a small proportion of patients.

Question 14

What is a benefit of HAV once overcome?

Answer 14

Induces lifelong protection from reinfection

Question 15

How is HAV spread?

Answer 15

Mainly oral-fecal route; occurs worldwide and increased risk in poorly sanitised places.

Question 16

What is the structure of HAV like?

Answer 16

Non enveloped, SS(+)RNA
Spherical (pseudo-icosahedrical)
Classified within the picornavirus family.
Baltimore Group IV
VP1,2,3 are the polypeptides on the outer capsid

Question 17

How long does HBV stay in the body?

Answer 17

1-3 months (acute HBV)
6 months + (chronic HBV is less common)

In 20-25% patients with chronic HBV have progressive liver disease, leading to cirrhosis and around 10% will develop to liver cancer.

Question 18

How can HBV be transmitted?

Answer 18

Enveloped so transmitted in blood or body fluids
Sexually transmitted
Blood to blood contact (sharing needles or needle stick injuries)
Perinatal transmission from mother to child.

Question 19

What is the structure of HBV?

Answer 19

Enveloped, icosahedric capsid
A spherical, double-shelled structure, consisting of a lipid envelope containing HBsAg that surrounds an inner nucleocapsid composed of hepatitis B core antigen (HBcAg) complexed with virally encoded polymerase and the viral DNA genome.
HBV is one of few non-retroviral viruses that use reverse transcription as a part of its replication process.

Question 20

What Baltimore Group is HBV found in?

Answer 20

VII

dsDNA

Question 21

What is the incidence of HCV?

Answer 21

UK: 216,000 chronic hep C patients

87% are current or past injected drug users.

Question 22

What are the symptoms of HCV?

Answer 22

In most cases, hepatitis C causes no noticeable symptoms until the liver has been significantly damaged
Chronic liver disease progression in 70-75% of patient with Hep C - can lead to liver failure and/or cancer.

Question 23

Is there a vaccine for Hep C?

Answer 23

No

Question 24

How is HCV transmitted?

Answer 24

Enveloped so transmitted via blood or bodily fluids.
Usually transmitted blood-blood due to high concentrtion in the blood
Semen, vaginal fluid and saliva to a much lesser extent.

Question 25

What is the structure of HCV?

Answer 25

Enveloped, spherical, mature virions contain two virus-encoded membrane proteins (E1 and E2) in addition to capsid protein. Baltimore Group IV SS(+)RNA

Question 26

How can Hep C vary between places?

Answer 26

There are 11 genotypes of Hep C Genotypes 1,2,3 most widespread across Europe. Genotype 4 in Africa Genotype dictates the type of treatment needed.

Question 27

What are the treatment options for Hep C?

Answer 27

Current Tx: Combination of Ribavirin (oral nucleoside analogue) and Pegylated IFN-alpha (cytokine peptide). Treatment for 6-12 months Cure rate 20-40% only.

Question 28

What are the cautions with Ribavirin use?

Answer 28

Teratogenic - should not be used in pregnant women

Question 29

How does genotype affect treatment?

Answer 29

Ribavirin combined with pegylated INF-alpha Tx | 3x more effective in genotype 2 or 3 than in genotype 1

Question 30

What are the newer drugs available for Hep C treatment?

Answer 30

Boceprevir and Telaprevir (target HCV protease) Used for Genotype 1

Question 31

What type of virus is Hep D?

Answer 31

A defective virus / 'satellite' virus; it cannot exist on its own.

Question 32

What is needed for Hep D infection?

Answer 32

Co-infection with Hep B which provides the antigens needed for cell host cell attachment and infection. Once inside the cell HBV can replicate independently.

Question 33

What is the structure of HDV?

Answer 33

Enveloped, spherical | Membrane proteins originate from HBV helper virus.

Question 34

What Baltimore Group is HDV from?

Answer 34

V

Question 35

What is the significance of HDV?

Answer 35

The hepatitis delta virus relies on co-infection withHBV because it uses HBsAG as its own virion coat. Chronic HBV can lead to liver cancer

Question 36

Which Hepatitis Viruses can be vaccinated against?

Answer 36

Hep A and B

Question 37

What is the difference between active and passive vaccination?

Answer 37

Passive immunisation is the injection of pathogen-specific pooled human immunoglobulin (antibodies). Passive vaccination does not confer life long protection.

Question 38

What are live attenuated viruses?

Answer 38

``` Better. Viruses are grown in cultures and repeatedly passaged through rounds of culture. Viruses with low virulence are selected and these attenuated strains are reproduced in large quantities for vaccination. Immune response (similar to natural response) without causing full illness. Live vaccines avoided in immunocompromised oncology patients. ```

Question 39

How do inactivated vaccines cause protection?

Answer 39

Viruses are cultured and inactivated with formaldehyde. These vaccines have fewer side effects that live attenuated by the immune response elicited is less vigorous.

Question 40

What are subunit vaccines?

Answer 40

The safest method of vaccination Surface antigens are produced by recombinant DNA technologies. The recombinant proteins can be given alone or with up to 20 other proteins. The pathogen is not present so no risk to patients but the immune response is still evoked. HBV and Influenza vaccine.

Question 41

What kind of vaccine are flu vaccines / HBV vaccines?

Answer 41

Subunit vaccines.

Question 42

How can we vaccinate against HAV?

Answer 42

There is only one HAV serotype (but atleast 7 different genotypes) One strain vaccine can protect against all genotypes. Vaccine consists of inactivated whole viruses propagated in MRC-5 human lung fibroblast cell line.

Question 43

What three types of vaccine protect against HAV?

Answer 43

Monovalent vaccine which provides protection against HAV Combined HAV and HBV vaccine Combined HAV and typhoid fever vaccine

Question 44

What kind of vaccination can be given against HBV?

Answer 44

Subunit vaccine consisting of HBsAg adsorbed onto aluminium hydroxide adjuvant Prepared from yeast using recombinant DNA technology. Combined HAV and HBV vaccine Usually 3 doses with or without a booster

Question 45

When can HBV vaccine be given as Tx?

Answer 45

Vaccine is highly effective is given shortly after exposure e.g. needle stick injury