Pharm: Hepatobiliary

Question 0

Why is HCV genotyping important?

Answer 0

To predict the likelihood of response to therapy. (Has no impact on the severity of liver injury.)

Question 1

Why is HCV subject to a high mutation rate?

Answer 1

The viral RNA-dependent RNA polymerase lacks proof-reading activity.

Question 2

What country has the highest prevalence of HCV?

Answer 2

Egypt (genotype 4).

Question 3

What profile has an increased risk of disease progression from HCV infection?

Answer 3

An older, obese, diabetic Caucasian or Hispanic male that smokes, drinks, has HBV, and is immunocompromized.

Question 4

What factors that influence the likelihood of response to therapy for HCV?

Answer 4

(1) genotype
(2) viral load
(3) viral kinetics on treatmne

Question 5

Until 2011, what was the standard of care for HCV infection?

Answer 5

Pegylated interferon alpha & ribavirin.

Question 6

What is the MoA of interferon alpha in the treatment of HCV?

Answer 6

(1) enhances MHC-1 expression
(2) amplifies Tc lymphocytes, NK cells
(3) enhances macrophage activity
(4) inhibits HCV attachment and uncoating
(5) activates cellular RNAses

Question 7

What are the adverse effects of interferon?

Answer 7

(1) influenza-like symptoms
(2) depression, suicidal ideation
(3) pancytopenia
(4) activation of autoimmune disease
(5) weight loss
(6) infection
(7) worsening of liver function in cirrhosis

Question 8

What is the MoA of ribavirin?

Answer 8

(1) inhibition of viral RNA polymerase
(2) induction of lethal mutations in HCV RNA
(3) GTP depletion
(4) favors Th1 response

Question 9

In treatment of HCV, what is required when prescribing ribavirin?

Answer 9

A concurrent interferon prescription. It improves to SVR from interferon treatment.

Question 10

What are adverse effects of ribavirin?

Answer 10

(1) non-immune hemolytic anemia
(2) rash
(3) dyspnea
(4) teratogenic
(5) contraindicated in chronic renal failure

Question 11

What is SVR?

Answer 11

Sustained viral response. It refers to the persistence of undetectable viral loads 6 months post-cessation of treatment.

Question 12

Which HCV genotype is most resistant to pegylated interferon + ribavirin therapy?

Answer 12

Genotype 1.

Question 13

J: These 2 drugs are HCV protease inhibitors used in the treatment of HCV since 2011.

Answer 13

What are telaprevir and boceprevir?

Question 14

What are adverse effects of HCV protease inhibitors?

Answer 14

(1) anemia
(2) rash
(3) dysgeusia
(4) anorectal discomfort
(5) drug-drug interaction with anti-retrovirals

Question 15

Besides improved SVR, what is a major goal of future HCV therapy?

Answer 15

Being interferon-free.

Question 16

What protein is secreted by actively replicating wild-type HBV?

Answer 16

HBeAg.

Question 17

What is the primary target in HBV therapies?

Answer 17

The viral DNA polymerase.

Question 18

What is a primary factor in determining whether HBV will progress to a chronic infection?

Answer 18

The degree of immune tolerance. More tolerance is worse (despite the fact that the immune response is primarily responsible for hepatic injury).

Question 19

What is suggested by a HBeAg-negative chronic HBV infection?

Answer 19

A precore mutation.

Question 20

What are indications for HBV treatment?

Answer 20

(1) elevated ALT
(2) elevated HBV DNA
(3) cirrhosis and detectable HBV DNA

Question 21

Why is HBeAg loss or seroconversion a desired endpoint of therapy?

Answer 21

(1) decreased risk of hepatic decompensation

(2) decreased risk of HCC

Question 22

What are disadvantages of using interferon for treatment of chronic HBV?

Answer 22

(1) high relapse rate in HBeAg negatives
(2) limited efficacy for high HBV DNA, low ALT
(3) side effects
(4) cannot used if liver is decompensated