Hepatitis C Virus

Question 1

What type of virus is Hep C

Answer 1

A flavivirus

Question 2

How long does seroconversion take

Answer 2

3-6 months

Question 3

How long is the latency of Hep C

Answer 3

2-9 weeks

Question 4

How many people are affected by Hep C

Answer 4

71 million
0.1% UK
1.4% US
14% Egypt

Question 5

What % of acute and chorinic hepatitis is caused by Hep C

Answer 5

20% Acute

70% Chronic

Question 6

What are the outcomes of Hep C Infection

Answer 6

10-30% Clear

70-90% get chronicn infection

Question 7

What are the soruces of Hep C Infection

Answer 7

60% IVDU
15% Sexual Contact
10% Unkown
10% Transfusion
4% Occupational
1% Household transmission

Question 8

How many genotypes of HCV are there

Answer 8

7

Question 9

What genotypes of HCV Are prevlanet where

Answer 9

1 - mainly Americas, Japan, Northern europe
3+6 = South and SW Asia
4+5 = Predominant in Africa
7 = rarely seeen in Africa byt not of clinical importance

Question 10

What % of hepatocytes are infected by HCV

Answer 10

5-19%

Question 11

What is teh half life of HCV

Answer 11

2-3 hours

Question 12

What is the structure of HCV

Answer 12

50nm diameter

9.6kb +ve sense RNA genome

Question 13

What does the polyprotein encode

Answer 13

Structure (Core , E1 and E2)
Non Structural (p7, NS2, NS3, NS4A, NS4B, NS5A, NS5B)

Question 14

Where does HCV Replicate t

Answer 14

The cytoplasm

Question 15

What are the receptors for HCV

Answer 15

E1/E2 bind to SR-B1 and CD81
Also Occludin and Claudin 1 important for binding
Also EGFR and ephrin type 2A receptor

Question 16

What proteases cleave the HCV polyprotein

Answer 16

Cellular Proteases - signalase

Viral proteases - NS2-NS3, NS3-NS4A

Question 17

How many proteins are there

Answer 17

10

Question 18

When does ALT peak

Answer 18

2 months –> coincides with a good T cell response

Question 19

How do the HCV proteins promote HCC

Answer 19

Core - inhibits apoptosis
NS3 - promotes cellular transformation
NS5A - contains a transactivation domain

Question 20

How do the HCV proteins perturb the IFN response

Answer 20

Core protein –> inhibits Stat1
NS5a –> generally attenuates IFN production
NS5a and E2 - inhibit PKR –> part of the innate response for binding and responding to dsRNA

Question 21

Where do ab target

Answer 21

The highly variables E2 region

Question 22

When are Ab generally detectable by

Answer 22

7-31 weeks –> however they are not maintained for life!

Question 23

How can persistent HCV infection trigger cell destution

Answer 23

Fas ligand induced apoptosis and TNF alpha and performin based mechanisms for cell destruction

Question 24

Why does HCV Persist the 3 hypothesis

Answer 24

1) Immune response too weak to clear infection once restablished
2) HCV Proteins suppress the immune response
3) VIral genetic variation

Question 25

What HCV Proteins supprress the viral imune response

Answer 25

NS3 - blocks IRF3 activation and IFN synthesis

NS5A - blocks PKR

Question 26

Polymorphisms in what gene promote HCV Clearnce

Answer 26

IL28B –> thsoe iwth C/C have a 2 fold higher chance of clearance than T/T

Question 27

Name the HCV Protease inhibitors and what they inhibit

Answer 27

Telaprevir and Boseprevir

Inhibit NS3/NS4A proteases –> WORK AGAINST GENOTYPE 1 –> incrases response rates to up to 70%

Question 28

What is the response to IFN-alpha and ribavarin

Answer 28

50%

Poor response ot type 1

Question 29

Cost of telprevir and boseprevir

Answer 29

£30,000 per person

Question 30

What is the NS5B Inhibitor

Answer 30

Sofosbuvir

Question 31

What is the NS5A inhibitor

Answer 31

Dalactavir

Question 32

Cost of NS5B inhibitor

Answer 32

£40,000