Pharm: Hepatobiliary Flashcards
Why is HCV genotyping important?
To predict the likelihood of response to therapy. (Has no impact on the severity of liver injury.)
Why is HCV subject to a high mutation rate?
The viral RNA-dependent RNA polymerase lacks proof-reading activity.
What country has the highest prevalence of HCV?
Egypt (genotype 4).
What profile has an increased risk of disease progression from HCV infection?
An older, obese, diabetic Caucasian or Hispanic male that smokes, drinks, has HBV, and is immunocompromized.
What factors that influence the likelihood of response to therapy for HCV?
(1) genotype
(2) viral load
(3) viral kinetics on treatmne
Until 2011, what was the standard of care for HCV infection?
Pegylated interferon alpha & ribavirin.
What is the MoA of interferon alpha in the treatment of HCV?
(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
What are the adverse effects of interferon?
(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
What is the MoA of ribavirin?
(1) inhibition of viral RNA polymerase
(2) induction of lethal mutations in HCV RNA
(3) GTP depletion
(4) favors Th1 response
In treatment of HCV, what is required when prescribing ribavirin?
A concurrent interferon prescription. It improves to SVR from interferon treatment.
What are adverse effects of ribavirin?
(1) non-immune hemolytic anemia
(2) rash
(3) dyspnea
(4) teratogenic
(5) contraindicated in chronic renal failure
What is SVR?
Sustained viral response. It refers to the persistence of undetectable viral loads 6 months post-cessation of treatment.
Which HCV genotype is most resistant to pegylated interferon + ribavirin therapy?
Genotype 1.
J: These 2 drugs are HCV protease inhibitors used in the treatment of HCV since 2011.
What are telaprevir and boceprevir?
What are adverse effects of HCV protease inhibitors?
(1) anemia
(2) rash
(3) dysgeusia
(4) anorectal discomfort
(5) drug-drug interaction with anti-retrovirals
Besides improved SVR, what is a major goal of future HCV therapy?
Being interferon-free.
What protein is secreted by actively replicating wild-type HBV?
HBeAg.
What is the primary target in HBV therapies?
The viral DNA polymerase.
What is a primary factor in determining whether HBV will progress to a chronic infection?
The degree of immune tolerance. More tolerance is worse (despite the fact that the immune response is primarily responsible for hepatic injury).
What is suggested by a HBeAg-negative chronic HBV infection?
A precore mutation.
What are indications for HBV treatment?
(1) elevated ALT
(2) elevated HBV DNA
(3) cirrhosis and detectable HBV DNA
Why is HBeAg loss or seroconversion a desired endpoint of therapy?
(1) decreased risk of hepatic decompensation
(2) decreased risk of HCC
What are disadvantages of using interferon for treatment of chronic HBV?
(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
