Hepatitis Viruses: Ryan

Question 1

Destinguish ET from PT hepatitis and recall the etiological agents of each.

Answer 1

Enternally-transmitted (E-T)- HAV and HEV

Parenternally (IV, sexually)-transmitted (P-T)- HBV, HCV

Question 2

Describe the signs and symptoms of hepatitis.

Answer 2

E-T: anorexia, malaise, fever, headache, jaundice. Pts are often infectious (fecal-oral) before they even present w/ symptoms.

P-T:

Question 3

Describe the consequences of chronic hepatitis.

Answer 3

s

Question 4

Describe the control of viral hepatitis.

Answer 4

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!)

Question 5

HEV has a unique clinical course in pregnant women, unseen in the other hepatic viruses. Describe this.

Answer 5

1 in 5 fatality rate in pregnant women

Question 6

Describe the utility of each of these diagnostic markers for HBV:
HBsAg
Anti-HBs
HBeAg
Anti-HBe
Anti-HBc
IgM Anti-HBc

Answer 6

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

Question 7

HBV serology:

What marker will you see in a vaccinee?

Answer 7

Anti-HBsAg

Question 8

HBV serology:

What marker will you see in resolved acute infxn?

Answer 8

Anti-HBsAg and Anti-HBc (core antigen bc it was a real infxn)

Question 9

HBV serology:

What marker will you see in a low risk carrier?

Answer 9

Anti-HBe, Anti-HBc (bc it was a real infxn)

Question 10

HBV serology:

What marker will you see in a high risk carrier?

Answer 10

HBeAg, HBsAg, Anti-HBc

Question 11

Compare and contrast serology between a pt who recovers from HDV infection vs. a pt who continues to have a chronic HDV infection.

Answer 11

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).

Question 12

Before this date, we did not have effective screening methods for HCV in donated blood.

Answer 12

1992

Question 13

Since the hepatitis (A-E) viruses are not cytolytic, most of the damage to hepatocytes is due to:

Answer 13

Our immune response (CD8+ T cells)

Question 14

To a great extent, the older you are (>1yo) the greater/less your risk of experiencing chronic HCV hepatitis.

Answer 14

Less risk of chronic infxn w/ advancing age, particularly past 1 yo.

Question 15

Describe the risk of hepatocellular carcinoma in pts infected w/ HCV.

Answer 15

1 in 25 will get HCC (4%)

That’s why it is so important to Dx and Tx!

Question 16

List the NRTIs used to tx HBV.

Describe viral resistance to these drugs.

Answer 16

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.

Question 17

Describe the rare toxicity of Tenofovir.

Explain its correlation w/ osteoporosis as well.

Answer 17

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.

Question 18

Describe the ironic toxicity of NRTIs and tests needed to monitor.

Answer 18

NRTIs can inhibit mitochondrial DNA polymerase as well. This can damage the liver. LFTs needed to monitor.

Question 19

Which drug is effective against both HIV and HBV?

Answer 19

Tenofovir and emtricitabine (Truvada)

Question 20

Describe how interferon works and why pt hate it.

Answer 20

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.

Question 21

Describe the primary toxicity of Ribavirin.

Answer 21

Hemolytic anemia - 1 in 10 pts

Question 22

Ribavirin, Bocepravir, and Telepravir show this ADE:

Answer 22

Male-mediated teratogenicity.

Question 23

I’m gonna give you a suffix, you give me an MOA.

-previr

Answer 23

–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

Question 24

I’m gonna give you a suffix, you give me an MOA.

-asvir

Answer 24

–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

Question 25

I’m gonna give you a suffix, you give me an MOA.

-buvir

Answer 25

–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

Question 26

1st gen protease inhibitors:

Telepravir and bocepravir ADEs.

Answer 26

Both: n/d, fatigue, anemia, nausea

Telepravir: BBW serious rash - DRESS, TEN, SJS

Question 27

2nd gen protease inhibitors:
Semeprevir
Peritaprevir
ADEs please.

Answer 27

Fatigue, photosens., GI tox, rash

Question 28

NRTI ADEs please.

Answer 28

Generally well tolerated- fatigue, headaches

Question 29

NNRTI ADEs please.

Answer 29

Generally well tolerated- fatigue, GI and dermal toxicity