Microbiology 11 - Viral Hepatitis

Question 1

What type of virus is HepA?

Answer 1

Unenveloped
picornavirus, positive sense ssRNA genome

Question 2

Recall 2 RFs for Hep A transmission

Answer 2

1. Drinking from dodgy water supply
2. MSM

Question 3

HepA clinical course:

a) Incubation period
b) How long are you symptomatic for?
c) How long are you infectious for?
d) Is it acute or chronic?

Answer 3

Incubation period: 2-6 weeks

Symptomatic: 3-10 days prodrome of flu like illness –> 1-3 weeks of icteric state (jaundice, hepatomegaly, dark urine and pale stools)

Infectious: 2 weeks before symptom onset to 1 week after resolution of symptoms

–> advise to stay off work for a week after starting showing symptoms

ONLY ACUTE- can’t become chronic. Self-limiting.

Question 4

Hep A vaccine

Answer 4

HAV- Havrix. Need 2 doses of vaccine for full protection.

Type of vaccine: live attenuated and inactivated vaccines are available

Only available for certain at risk groups:

• GUM clinics- MSM are currently offered vaccinations
• Travel to high risk country
• Chronic liver disease - higher chance of severe disease
• Haemophilia
• People who inject drugs ‘PWID’
• Occupational risk:
  
  • lab
  • residential facilities
  • sewage work

Question 5

What is IgM positivity in HepA indicative of?

Answer 5

Current infection (or recent vaccination- but in thsi case ALT would not be raised)

Question 6

What is IgG positivity in HepA infection indicative of?

Answer 6

Past infection or vaccination

Question 7

What test is used to identify acute hepatitis A?

Answer 7

Anti-hepatitis A virus IgM

Question 8

What type of virus is HepB?

What is HBeAg?

Answer 8

DNA virus

Marker of infectivity

Question 9

How is HBV transmitted?

Is it more or less transmissible than HCV?

Answer 9

1. Sexual transmission
2. Parenteral:

• Blood products
• Blood transfusions
• IVDU
• tattoos
• needle stick

3. Vertical- Mother to baby

*MORE TRANSMISSIBLE than HCV (B is a B*tch)

Question 10

For how long does hepatitis B infection have to persist to be considered “chronic”?

What percentage of adults and children go on to develop chronic hepatitis if they have acute hepatitis?

Answer 10

6 months

Adults- 5-10% (because they have better immune system so can clear the infection more easily)

Children- 95%

Question 11

What is the incubation period for hepatitis B?

Answer 11

2-6 months - much longer than HepC

Question 12

What are the complications of chronic hepatitis B?

Answer 12

Cirrhosis
Hepatocellular carcinoma- high AFP

Question 13

Recall the stages of hepatitis B infection

Answer 13

1. Immune tolerant
2. Immune reactive
3. Inactive HBV carrier state
4. HBe antigen negative chronic HBV
5. HBs antigen negative phase

Question 14

What treatments are available for chronic hepatitis B? What is the main goal of treatment of Hepatitis B?

Answer 14

1. Interferon alpha

Pegylated Interferon (INF) Alpha 2a (subcut) – Direct antiviral effect + upregulates expression of MHC on cell surfaces

2. Lamivudine (nucleoside analogue)
3. Entecavir
   (nucleoside analogue)
4. Telbivudine
   (nucleoside analogue)
5. Tenofovir
   (nucleoTide analogue)

main goal of treatment is to prevent the progression to cirrhosis and HCC

Question 15

HepB serology table

Answer 15

Question 16

What does the hepatitis B vaccine contain?

Answer 16

Surface antigen

Question 17

Prevention of HepB

Answer 17

1. Vaccine

• routine immunisation at 2,3 and 4 months (6 in 1 vaccine)
• pre-exposure prophylaxis
• post exposure prophylaxis (eg following needle stick injury)
• pre and post exposure prophylaxis (accelerated schedule)

2. PMTCT

• If mom is HBsAg+ but HBeAg- : give baby HBV birth dose vaccine –> routine schedule
• If mom is HBsAg+ and HBeAg+ : give baby HBV birth dose vaccine + HBIG within 48 hours + routine HBV vaccine schedule

Question 18

What are the main routes of transmission of hepatitis C?

Answer 18

Blood products
MSM

Question 19

What % of people who get infected with hepatitis C go on to have chronic hep C?

Answer 19

60-80%

So much more than HepB!!

Question 20

What is the incubation period of hepatitis C?

Answer 20

2 - 6 weeks

Question 21

When do you make antibodies against HCV? What does anti-HCV positive mean?

Answer 21

*You only start making anti-HCV 4 weeks after the acute infection so it can take a while for them to show up + if you’re immunocompromised you might never make antibodies –> NOT RELIABLE marker of infection

If positive- you might have chronic HCV infection

If you see this, you should measure HCV RNA and viral load to see if they still have the infection as 20% of people might have cleared the infection!!

Question 22

What test is used to diagnose hep C infection?

Answer 22

HCV RNA

Question 23

What treatments are available for hepatitis C?

Answer 23

Initially interferon therapy (Peg INF ⍺ 2b/2a)

Now highly effective directly acting antivirals–> curative

3. NS3/4 protease inhibitors (-previrs, block translation): telaprevir, boceprevir, simeprevir, asunaprevir (learn one or two)
4. NS5A inhibitors (-asvirs, block release):
   ledipasvir, daclatasvir
5. Direct polymerase inhibitors (-buvirs,
   block replication): Sofosbuvir, dasabuvir

Question 24

Hepatitis D infection is always superimposed upon which type of infection?

Answer 24

Hepatitis B

Question 25

What is one particularly risky food for hepatitis E infection?

Answer 25

Wild boar \*\*undercooked pork\*\* \*\*also associated with shellfish\*\*

Question 26

What are the possible complications of hepatitis E infection?

Answer 26

Bell's palsy Guillain Barre

Question 27

What does HBV/HDV co-infection mean for the clinical course of infection?

Answer 27

Causes severe, acute infection, but very low chance of becoming chronic

Question 28

HepE genotypes

Answer 28

**Genotype 1+2** * ony human host * Genotype 1 can cause severe infection/high mortality in pregnant women * faeco-oral transmission * often contracted on holiday * brief, self-limiting **Genotype 3+4** * natural host is in swine, boar but humans are accidental hosts * can be contracted from eating dodgy sausages/meat on holiday * mostly asymptomatic

Question 29

Clinical course of HepE

Answer 29

**immunocompetent people:** acute and self limiting **immunocompromised patients:** 60% become chronic

Question 30

Which Hep virus is dangerous for pregnant women? what extra intestinal manifestation?

Answer 30

Hep E genotype 1 can cause severe fulminant liver failure in pregnant women thrombocytopaenia - can look similar to helpp syndrome

Question 31

Diagnosis of HepE

Answer 31

**Immunocompetent** * HepE IgM and IgG **Immunocompromised** * HepE RNA- as they may not mount a full immune response for it to be detected

Question 32

Which hepatitis virus is at risk of reactivating and when?

Answer 32

HepB is at risk of reactivating in immunocompromised individuals especially in those taking B cell depleting therapies such as rituximab

Question 33

What type of virus is hepatitis C?

Answer 33

Enveloped flavivirus, positive sense ssRNA genome

Question 34

Genotypes of HepC virus

Answer 34

``` Genotypes 1 (40-50% of HCV UK burden), 4, 5, and 6 – Treatment less successful ``` Genotypes 2 and 3 – (40-50% of HCV UK burden) Treatment more successful Most common in UK: 1,2,3

Question 35

What type of virus is Hep D virus?

Answer 35

Deltavirus, enveloped virus, negative sense, single-stranded circular RNA

Question 36

What type of virus is Hep E virus?

Answer 36

Unenveloped positive sense ssRNA genome

Question 37

What antibodies can be made in response to hepatitis B virus?

Answer 37

* IgM core antibody - only present in acute infection * IgG core antibody - present in acute and chronic infection (\*\*not sure why in acute...\_ * anti-HbS - only present if a) infection cleared or b) previous vaccination