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Hepatitis C - Coggle Diagram
Hepatitis C
Treatment options
Initially, very poor treatment and response rates. IFN alpha had a response rate of 5-20% and IFN + RBV had a supression rate of 40%
On top of that, poorly tolerated - thyroid dysfunction, depression, psychosis, bone marrow suppression and Flu-like symptoms (muscle aches and fatigue)
IFN Alpha: Contraindicated if neutrophil < 1.5 , platelets < 75,000/mm3 and severe depression.
Ribavirin: contraindicated if unstable CVD, poor renal function, anaemia and pregnancy (DNA analogue thus interfere with DNA synthesis - tetratogenic)
First Gen Direct Acting Antivirals (DAA): boceprevir, telaprevir and simeprevir
Targets the NS3/4 protease and only effective in G1 subtypes - But enzyme is similar to human protease thus many ADRs.
Max SVR = 60-85% in combo with peg-INF + RBV
Poorly tolerated, taken >48 weeks and extreme pill burden
Second Gen DDA: Sofosbuvir - a nucleoside analogue and a NS5B polymerase inhibitor. Highly potent and high barrier of resistance. Well tolerated and no food requirements. Pan-genotypic = effective in G1-4 subtypes
Care with renal impairment (no dose reduction required) and Amiodarone use causing severe bradycardia.
Combo Drugs
More specific and cleaner to use
NS3/4A inhibs: Glecaprevir and Vexilaprevir
NS5A inhibs Velpatasvir and Pilbrentasvir
NS5B Inhibs: Sofosbuvir
Harvoni (Sofosbuvir + Ledipasvir): Once daily dosing and 95% SVR in all genotypes.
First Line Combos:
**Epclusa (Velpatasvir + Sofosbuvir): Once daily 12 week course, effective in all genotypes and 99% SVR.
Maviret** (Glecaprevir + Pibrentasvir): Once daily 8 weeks course for all except G2 genotype. G2 genotype - 12 weeks course at 99% SVR.
Both well tolerated and equally effective. Epculsa slightly better in history of failure.
DDIs:
Maviret: P-gp inhib and substrate and a weak 3A4 inhib
Epculsa: P-gp and 2B6, 2C8 and 3A4 substrate, and requires acidic environment.
Second line combos:
Vosevi: (Sofosbuvir + Velpatasvir + Voxilparevir) - a combo of NS5B + NS5A and NS3 inhib designed as salvage therapy and used if first line DAA not responsive. Not used in DAA naive patients.
Vaccines
No vaccine for Hep C but the virus is cleared via the drugs. No immunity is developed thus re-infection is possible. The drugs only kills the virus.
Treatment goals
Eradicate the virus, cure or supress after 12 weeks of treatment.
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Classification
Similar to Hep B, the virus is a bloodborne virus. Spread via sharing needles/IV drug use, sexual contact, birth mother to child and needleprick in healthcare environment.
75-85% will develop chronic infection and only 15-25% will clear the infection within 6 months. Symptoms occur in only 20% of patients - dark urine, fatigue, anorexia, jaundice and ab pain.
Flavividae virus, has a rapid cell cycle, and rapid mutations. Many subtypes and mutations.
Prescribing
Was mainly gastroenterologist prescribing. Since the Turnbull Gov with the "Netflix" deal in 2016, GPs and general care works have been prescribing.
Shift in better access allows more people with Hep C to be treated, reducing prevalence in Aus and making medicine cheaper.
COVID 19 - due to lockdowns and limited availabilities, there has been a drop in clean needle sold, which can potentially increase share needle use and increase transmission