Hepatobiliary Pharmacology Flashcards
T/F HepC viral RNA dependent RNAp lacks proofreading activity
T –> leads to a high mutation rate
Most common HCV genotype in US
genotype 1
% of people with acute phase who will get chronic HCV
85%
% of people with chronic HCV who get cirrhosis
20% over 20 years
Factors that increase progression of liver injury due to HCV
age >40, male, caucasian/hispanic, smoking, additional liver injury, immunocompromise
How do genotypes of HCV compare in tx response?
genotype 1 responds less than 2 and 3
Responsiveness to HCV tx? high viral load
less responsive
Responsiveness to HCV tx? age> 40
less responsive
Responsiveness to HCV tx? males
less responsive
Responsiveness to HCV tx? African Americans
less responsive
What genetic polymorphism is associated with less responsiveness to HCV tx?
IL28B
Gold standard response to HCV tx?
absence of detectable HCV at 6 months after therapy = sustained viral response (SVR) –> <1% chance of relapse at this point, 5x reduction in risk of HCC, elimination of decompensation risk
Traditional tx for HCV
peg interferon alpha + ribavirin
MOA of interferon in HCV
immune activation (MHC1 expression, tc/NK cell/macrophage activity) and potential direct antiviral activity (inhibition of attachment/uncoating/activation of RNAses)
Traditional tx for HCV
peg interferon alpha + ribavirin
MOA of interferon in HCV
immune activation (MHC1 expression, tc/NK cell/macrophage activity) and potential direct antiviral activity (inhibition of attachment/uncoating/activation of RNAses)
Adverse effects of interferon
flu-like symptoms, depression/suicidal ideation, pancytopenia, activation of autoimmune disease, weight loss, infection/cirrhosis, worsening of liver function
Ribavirin MOA
guanosine analogue –> inhibtion of viral RNAp, induction of lethal mutations in HCV, GTP depletion, modulation of tcell response, favoring Th1–> only works as combination tx by preventing relapse
Conceptual complication of monotherapy with specific antivirals
development of resistance –> use specific antivirals in combination therapy
e.g. Peg IFN + RBV + Boceprevir/Telaprevir
Adverse effects of viral protease inhibitors boceprevir/telaprevir
anemia, rash, dysgeusia, anorectal discomfort
Adverse effects of viral protease inhibitors boceprevir/telaprevir
anemia, rash, dysgeusia, anorectal discomfort
What does e antigen indicate in HBV?
that the virus is currently replicating (wild type only)
Why can’t we resolve HBV infection?
we can treat cytoplasmic processes but can’t get the viral DNA out once it’s been incorporated
How does HBV cause damage to hepatocytes?
mostly due to immune response –> degree of immune tolerance determines whether a chronic infection will develop
