Pharm for Viral Hepatitis Flashcards
What kind of genome does HCV have?
ssRNA
corrected (said ssDNA before. This was a typo. HBV is the only DNA hepatitis virus)
How are HCV gene products translated?
As a polyprotein.
What accounts for the high mutation rate in HCV?
viral RNA-dependent RNA polymerase lacks proofreading (like in HIV)
Does HCV genotype affect severity of liver injury?
No, but it does affect response to therapy.
Once a patient has cirrhosis, what’s the risk of progressing to HCC or decompensated cirrhosis?
5% / year
Factors that increase rate of progression to HCC / decompensated cirrhosis in HCV?
Age > 40 Male Caucasian/Hispanic Smoking Other liver injury (EtOH, HBV, etc) Immunocompromise
What does “on treatment viral kinetics” mean? Significance?
The rate at which viral load drops with therapy.
Faster drop predicts higher chance of sustained viral response (SVR).
What’s the definition of sustained viral response (SVR)? Significance?
Absence of detectable HCV 6mo after cessation of therapy.
SVR is in most cases a cure - chance of relapse after SVR is < 1%.
Additionally, risk of HCC is greatly reduced and risk of decompensation is almost eliminated.
Treatment for HCV prior to 2011?
PEGylated interferon-alpha (IFN) + ribavirin (RBV)
Potential MoAs of IFN?
Take-home points about it?
Immune activation - more MHC-I, more CTLs and NKs, more macrophage activity.
Direct antiviral activity - inhibits HCV attachment/uncoating, activation of RNAses.
Take-home points: Because IFN activates immune system it… 1. Makes you feel like crap. 2. Is less prone having HCV become resistant.
What affect does PEGylation of IFN have?
Increases half life - more sustained levels throughout therapy, and only needs to be given 1x/week.
Major adverse effects of IFN?
Flu-like symptoms
Depression, suicidial ideation
Pancytopenia
Activates autoimmune disease (eg. thyroiditis)
Cachexia
Increased bacterial infection risk (esp. cirrhosis)
Worsening of liver function (esp. in cirrhosis)
What’s the structure of ribavirin (RBV)?
What’s its MoA?
It’s a guanosine analogue that inhibits HCV’s RNA polymerase.
(also it induces mutations, depletes GTP, and makes T cell response favor Th1)
What’s the utility of RBV for HCV?
Useless on it own, but increases rate of SVR when given with IFN. (decreases rate of relapse)
Adverse effects of RBV?
Non-immune hemolytic anemia Rash Dyspnea Teratogenic -Also excreted renally and not dialyzable, so must be used with caution in pts with renal failure.
