Hepatitis C L16 Flashcards
Which organisms does Hep C affect?
Humans
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.
- RNA
- DNA
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).
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
- Translation
- Capsid
- Envelope
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.
- Liver
- Immune response
How is Hep C transmitted? (3)
- Direct blood or fluid exposure
- e.g. Tattoos, ear piercings, acupuncture
- Sexual activity
- Perinatal transmission
Vast majority of HCV acute infections lead to ____1____ infections.
- Chronic
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____.
- Low
- Antibody
Cirrhosis via viral hepatitis takes ~______ years
20
Antibody test = ?
Serology
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
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
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
- Immune response
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.
- Replication
- Shape
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
