Hepatitis Viruses: Ryan Flashcards
Destinguish ET from PT hepatitis and recall the etiological agents of each.
Enternally-transmitted (E-T)- HAV and HEV
Parenternally (IV, sexually)-transmitted (P-T)- HBV, HCV
Describe the signs and symptoms of hepatitis.
E-T: anorexia, malaise, fever, headache, jaundice. Pts are often infectious (fecal-oral) before they even present w/ symptoms.
P-T:
Describe the consequences of chronic hepatitis.
s
Describe the control of viral hepatitis.
Prevention: vaccine, screening of blood supplies for HBsAg, HBV DNA, and HBc abs.
E-T: no cure.
Vaccine prophylaxis available for HAV and HBV.
(Hav)rix- gamma globulin for children >2yo.
Twinrix (combo HAV and HBV) for adults.
HBV antivirals- only given to treat severe active infection: tenofovir (NRTI) and entecavir (NRTI) (both inhibit reverse transcriptase)
P-T: HCV treatable w/ Harvoni (Sofosbuvir + Ledispavir) x 12 months @ 1 pill/day ($1000/pill!)
HEV has a unique clinical course in pregnant women, unseen in the other hepatic viruses. Describe this.
1 in 5 fatality rate in pregnant women
Describe the utility of each of these diagnostic markers for HBV: HBsAg Anti-HBs HBeAg Anti-HBe Anti-HBc IgM Anti-HBc
HBsAg- ID of carriers or acutely affected persons
Anti-HBs- ID of persons who have had HBV infxn or vaccine
HBeAg- ID of those at incr. risk of transmission (capsid protein actively being made)
Anti-HBe- ID of HBsAg carriers at low risk of transmission
Anti-HBc- ID of persons w/ past infxn
IgM Anti-HBc- ID of acute or recent infxn
HBV serology:
What marker will you see in a vaccinee?
Anti-HBsAg
HBV serology:
What marker will you see in resolved acute infxn?
Anti-HBsAg and Anti-HBc (core antigen bc it was a real infxn)
HBV serology:
What marker will you see in a low risk carrier?
Anti-HBe, Anti-HBc (bc it was a real infxn)
HBV serology:
What marker will you see in a high risk carrier?
HBeAg, HBsAg, Anti-HBc
Compare and contrast serology between a pt who recovers from HDV infection vs. a pt who continues to have a chronic HDV infection.
Pt Recovers: anti-HBs high, anti-HDV low. HDV RNA and HBsAg levels gone from blood.
Chronic infxn: IgM anti-HDV low, total anti-HDV high. HDV RNA and HBsAg levels persist in blood. ALT levels never return to baseline (persistently elevated).
Before this date, we did not have effective screening methods for HCV in donated blood.
1992
Since the hepatitis (A-E) viruses are not cytolytic, most of the damage to hepatocytes is due to:
Our immune response (CD8+ T cells)
To a great extent, the older you are (>1yo) the greater/less your risk of experiencing chronic HCV hepatitis.
Less risk of chronic infxn w/ advancing age, particularly past 1 yo.
Describe the risk of hepatocellular carcinoma in pts infected w/ HCV.
1 in 25 will get HCC (4%)
That’s why it is so important to Dx and Tx!
List the NRTIs used to tx HBV.
Describe viral resistance to these drugs.
Tenofovir Entecavir Telbivudine Lamivudine Adefovir Emtricitabine
-these all require phosphorylation prior to being incorporated into DNA cycle, where they will cause chain termination
Resistance arises from mutations in the viral enzyme (reverse transcriptase), leading to decreased affinity of the drugs for their target.
Describe the rare toxicity of Tenofovir.
Explain its correlation w/ osteoporosis as well.
Renal tox.
Don’t give concurrently w/ other potentially renal toxic drugs or in pts w/ decr. renal fxn.
Antiretrovirals have been shown to increase bone turnover and decr. bone mineral density, possibly leading to osteoporosis. Rx Ca++ and Vit. D supplements when giving.
Describe the ironic toxicity of NRTIs and tests needed to monitor.
NRTIs can inhibit mitochondrial DNA polymerase as well. This can damage the liver. LFTs needed to monitor.
Which drug is effective against both HIV and HBV?
Tenofovir and emtricitabine (Truvada)
Describe how interferon works and why pt hate it.
Directly signals hepatocytes to block steps in viral replication.
Must be administered IV or IM
Causes flu-like symptoms.
BBW: Neuropsychiatric issues
Immune suppression, clotting dysfunction, hepatic and thyroid toxicity.
Describe the primary toxicity of Ribavirin.
Hemolytic anemia - 1 in 10 pts
Ribavirin, Bocepravir, and Telepravir show this ADE:
Male-mediated teratogenicity.
I’m gonna give you a suffix, you give me an MOA.
-previr
–I NS3 and NS4A (direct acting antiviral)
these proteins are involved in the post translational processing of the HCV polyprotein. Inhibition of these proteins inhibits viral protein maturation
I’m gonna give you a suffix, you give me an MOA.
-asvir
–I NS5A (direct acting antiviral) -(a)svir = NS5(A)
this protein is involved in the post translational processing of the HCV polyprotein. Inhibition of these proteins inhibits viral protein maturation
I’m gonna give you a suffix, you give me an MOA.
-buvir
–I NS5B (direct acting antiviral) -(b)uvir = NS5(B)
this protein is involved in the post translational processing of the HCV polyprotein. Inhibition of these proteins inhibits viral protein maturation
1st gen protease inhibitors:
Telepravir and bocepravir ADEs.
Both: n/d, fatigue, anemia, nausea
Telepravir: BBW serious rash - DRESS, TEN, SJS
2nd gen protease inhibitors:
Semeprevir
Peritaprevir
ADEs please.
Fatigue, photosens., GI tox, rash
NRTI ADEs please.
Generally well tolerated- fatigue, headaches
NNRTI ADEs please.
Generally well tolerated- fatigue, GI and dermal toxicity
