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Flashcards in Hepatitis C L16 Deck (19):
1

Which organisms does Hep C affect?

Humans

2

Hep C = ____1____ virus. Hep C therefore cannot integrate into host genome.

Hep B = ____2____ virus. Hep B can integrate into host genome (become part of it), allowing it to be reactivated in the future.

1. RNA

2. DNA

3

Over the course of a Hep C infection there will be substantial genetic drift of the viral genome.

Why?

Hep C is an RNA virus. The error prone nature of RNA replication (no mutation checking machinery with RNA) is the cause of the genetic drift (countless quasispecies).

4

Hep C is an incredibly resistant viral particle, can survive outside the body much longer than the average virus.

Hep C Genome

3 highly conserved areas:

  • 5’ UTR: initiating ___1___
  • Core: codes for ___2___ protein monomer
  • 3’ UTR: essential for RNA synthesis & packaging

1 hypervariable region: 

  • E1, E2 ___3___ proteins
  • Allows for evasion of host immunologic response

1. Translation

2. Capsid

3. Envelope

5

Hep C directly damages the ___1___ (by way of killing hepatocytes). Hep B is not itself toxic to the ___1___, it is the ______  2  ______ that causes the damage.

1. Liver

2. Immune response

6

How is Hep C transmitted? (3)

  • Direct blood or fluid exposure
    • e.g. Tattoos, ear piercings, acupuncture
  • Sexual activity
  • Perinatal transmission

7

Vast majority of HCV acute infections lead to ____1____ infections.

1. Chronic

8

HCV infection

In chronic phase, blood tests can look healthy due to ____1____ numbers of very well hidden viral particles.

In chronic phase, an HCV-specific ____2____ becomes present in the blood. Easiest screening test is to look for this ____2____.

1. Low

2. Antibody

9

Cirrhosis via viral hepatitis takes ~______ years

20

10

Antibody test = ?

Serology

11

Read

Hep C Diagnosis

  • HCV antibody is positive in patients who have been exposed to HCV and does NOT mean active infection
  • HCV RNA Positive indicate active infection
  • Majority will have raised ALT but some have normal ALT
  • In HCV Ab pos patients please remember to check for HBV and HIV

12

List some common adverse effects of HCV antiviral therapy. (10)

  • Flu-­‐like symptoms
  • Anaemia
  • Bone marrow suppression
  • Depression/anxiety
  • Infection
  • Insomnia / lethargy / fatigue
  • Thyroid dysfunction
  • Weight loss
  • Rashes
  • Nausea & vomiting

13

In last 5 years we have been able to use anti-virals that directly interfere with the virus (life-cycle etc.) compared to previously where we were only able to induce the ______  1  ______ to take action.

HCV Treatments

Protease Inhibitors       

  • Two protease inhibitors are licensed and approved by NICE for treatment of G1 HCV:
    • Telaprevir
    • Boceprevir
  • Inhibit the NS3/4A protease
  • Inhibit the HCV replication cycle
  • Cause rapid drop in viral load in Genotype 1 HCV
  • Rapid development of resistance so can not be used as monotherapy

1. Immune response

14

Big problem with the viral enzyme acting drugs is resistance.

Are likely to get resistant strains because each of these compounds are targeting a particular enzyme that is important for the ____1____ of the virus. Each enzyme has a single active site that the drug is targeting, so if a mutation effects the active site ____2____ then the drug will no longer work.

1. Replication

2. Shape

15

Read

Problems with protease inhibitors in treating HCV

  • Resistance
    • Patients need to comply with TDS regimen
    • Frequent testing of HCV RNA needed
    • Might reduce efficacy of future therapies
  • Side effects
    • More discontinuations
    • Rash with Telaprevir
    • Anaemia with Boceprevir
  • Drug-­‐Drug interactions
  • Cost

16

HCV Viral Genome Organisation

  • 9,400 nucleotides of ___1___-­sense RNA
  • 3010-­3,033 amino-acid polyprotein that is ___2___ into functionally distinct polypeptides after translation
  • RNA ___3___ is by an error-­prone RNA-dependent RNA polymerase

1. Positive

2. Cleaved

3. Replication

17

Describe the HCV virion. (2)

Size?

  • Enveloped viral particle
  • Icosahedral capsid

 

  • 40-­60 nm in diameter

18

When dealing with viruses you do not talk about cure, you talk about ______  _______  _______.

Sustained viral response

19

Ease of clearing HCV infection and action/drugs taken depend on the ______ of virus.

Genotype