Hepatitis Drugs

Question 1

HBV Drugs

Answer 1

1st line Tx: Tenefovir (NA), Entecovir (NA), Peg IFN alpha

• NA: inhibit HBV DNA pol thereby inhibiting HBV DNA synth
• IFN: cytokines that induce signals inhibiting viral penetration, translocation, tscpt, protein processing, maturation and release (lots of side effects)
• NA are better tolerated and produce a higher but less rapid response rate than IFN BUT the response to NA may be less sustained after discontinuing the therapy than the response to IFN
• NA = oral, chronic therapy
• IFN = injections, finite therapy

Question 2

HBV Treatment Endpoints

Answer 2

1. Suppress HBV DNA to undetectable levels (PCR)
2. Seroconversion from HBeAG (+) to HBeAG(-)
3. Decrease in hepatic transaminase elevation

Question 3

HCV Treatment endpoints

Answer 3

• HCV eradication
• SVR as indicated by the absence of detectable viremia 6 mo. after completing tx
• All oral tx, well tolerated
• Nausea is a common side effect, take w/ food

Question 4

HCV Genotypes 2 + 3

Answer 4

Sofosbuvir + Ribavirin

• Sofosbuvir: NA that inhibits HCV RNA pol and NS5B
• Ribavirin: NA taht inhibits GTP synth. and viral mRNA capping, weight based
• 12 wks for HCV 2, 24 wks for HCV 3

Question 5

HCV Genotypes 1a, 1b + 4

Answer 5

1. Ledipasvir/Sofosbuvir (harvoni)- 12 wks
2. Paritaprevir/Ritonavir/ombitavir + 2 x daily Dasabuvir (Vikiera Pak)- 12 wks no cirrhosis, 24 wks cirrhosis
3. Sofosbuvir + Simeprivir +/- wt based ribavirin- 12-24 wks

• Ledipasvir + ombitasvir: inhibit HCV NS5A which inhibits viral assembly and replication
• Paritaprevir + simeprevir: inibits NS3/4A serine protease which inhibits processing of viral proteins
• Dasabuvir: non NA that inhibits NS5B pol.
• Ritonavir: boost for paritaprevir potency by inhibiting CYP3A4, no intrinsic anti HCV activity