Hepatitis C

Question 1

What genome does HepC have?

Answer 1

Positive sense, single strand RNA virus

Question 2

What is transmission of HepC solely through?

Answer 2

Contamination with infected blood

Question 3

What percent of HCV infections roughly are acute?

Answer 3

25% of infections

Question 4

What are 3 markers of acute infection?

Answer 4

1. Serum alanine aminotransferase (ALT)
2. HCV RNA
3. Anti-HCV (ELISA)

Question 5

What does ALT indicate?

Answer 5

Liver damage, indicates hepatocyte necrosis

Question 6

What is compensated cirrhosis?

Answer 6

Build up of scar tissue but doesn’t affect function of liver, so may be asymptomatic

Question 7

What is required for patients with severely decompensated cirrhosis and/or hepatocellular carcinoma?

Answer 7

Liver transplantation

Question 8

Why if you treat someone of HCV do they still have a high risk of developing liver cancer?

Answer 8

Gene expression patterns have changed

Question 9

What co-infections with HCV can you have?

Answer 9

HIV, HBV

Question 10

What does RIGI sense for HCV?

Answer 10

SsRNA, triggers anti viral state

Question 11

What does MDA5 sense?

Answer 11

Replicate intermediates

Question 12

How does HepC evade immune system?

Answer 12

Virion incorporates host proteins CD59 and CD55
Virion associates with lipoproteins

Question 13

What happens in chronic HCV infection to T cells?

Answer 13

Are functionally impaired, decreasing proliferation, cytokine production and cytolytic activity

Question 14

What does ribavirin as a treatment do?

Answer 14

Affects the synthesis of guanine, makes it less abundant in cells so that when you get genome replication, you are missing a lot of one of your bases to try generate more RNA

Question 15

What was the issue with using interferon and ribavirin together?

Answer 15

Got a lot of side effects, lots of people on this therapy couldn’t tolerate it

Question 16

What are the replication inhibitors?

Answer 16

DAA
Epclusa
Zepatier
Mavyret

Question 17

What are the 3 classes of DAAs (directly-acting antivirals)

Answer 17

NS3 inhibitors - NS3 forms protease, cleaves up polyprotein
NS5B inhibitors - RNA polymerase, interfere with production of proteins
NS5A inhibitors - NS5A is key player in assembly of viruses, so inhibiting this is a clever part of virus lifecycle being affected

Question 18

What should a HepC vaccine target?

Answer 18

Envelope proteins - elicits a neutralising Ab response
Non structural proteins - T cell response

Question 19

What are the HCV vaccine challenges?

Answer 19

Large genetic diversity of HCV species
Lack of robust in vivo models