B5.030 Viral Hepatitis Large Group Flashcards
tenofovir disoproxil mechanism
nucleotide analog of adenosine monophosphate and a reverse transcriptase inhibitor
tenofovir uses
inhibits viral reverse transcriptase of HIV and HBV
limited inhibition of human enzymes
lamivudine 3TC) mechanism
analogue of cytidine
antiretroviral medication
can inhibit both types of HIV reverse transcriptase and the reverse transcriptase of HBV
phosphorylated to active metabolites that compete for incorporation into viral DNA
use competitive inhibition and act as a chain terminator of DNA synthesis
lamivudine uses
used to prevent and treat HIV and chronic HBV (when other options are not possible)
downside to lamivudine
rapid resistance develops
30% after 2 years, 70% at 5 years
entecavir mechanism
deoxyguanosine analogue that inhibits reverse transcription, DNA replication and transcription in the viral replication process
adefovir dipivoxil mechanism
blocks reverse transcriptase
resistance doesn’t develop as quickly as with lamivudine
telbivudine mechanism
synthetic thymidine B-L-nucleoside analogue
intracellularly phosphorylated to the active triphosphate form, which competes with the natural substrate to inhibit HBV reverse transcriptase
reduces DNA replication by chain termination
combined HIV/HBV agents
tenofovir
lamivudine
chemical HBV agents
entecavir
adefovir dipivoxil
telbivudine
what is the function of IFN-a in HBV treatment
predominantly immunomodulatory effects
cytokine also exerts a limited direct antiviral effect
mechanism of IFN-a
binds to cellular receptor and activates secondary messengers, resulting in the production of multiple proteins that are important for the defense of the cell against viruses
immunomodulatory effects of IFN-a
enhancement of antigen presentation to immune system
activation of NK cells and other immune cells
production of cytokines
antiviral effects of IFN-a
degradation of viral mRNA
inhibition of viral protein synthesis
prevention of infection of cells
primary test for hep B screening
HBsAg
hep B viral load used for quantitative measure
what can be detected during acute hep B infections
anti-HBc IgM
what does anti-HBs in serum signify
protective antibody in those with prior infection or those who have been vaccinated
anti-HBc = had infection before
serology that characterizes chronic hep B
positive HBsAg
detectable HBV DNA levels for more than 6 months
why does hep D require hep B?
HBV provides HBsAg which is incorporated into the HDV membrane allowing the virus to infect hepatocytes
coinfection
susceptible anti-HBs-negative individual is infected with HDV and HBV
mostly leads to eradication of both viruses
superinfection
chronic HBV carrier is infected with HDV
most evolve to chronic HDV infection and hepatitis
chronic HDV infection worsens the preexisting HBV related liver damage
characterize HDV associated liver damage
necroinflammation
relentless deposition of collagen
cirrhosis and HCC possible
histo cells associated with HBV
ground glass hepatocytes
contain surface antigens in the ER
describe ground glass hepatocytes
abundance of ER among which viral particles of surface antigens accumulate
overloaded ER makes cytoplasm foggy/glassy
effect of alcohol on HCV
alcohol puts HCV patients at risk for more severe liver injury
alcohol promotes disease progression to cirrhosis and increases risk for liver cancer
moderate drinking may have some of these effects as well, but results are inconclusive
discuss HCV disease progression
15% resolve after acute infection
85% have chronic infection
of those with chronic infection, 20% get cirrhosis after 20ish years
cirrhosis can lead to ESLD (6%), HCC (4%), or LT/death (3-4%)
what factors can speed the progression of chronic HCV
HIV
HBV
alcohol
fatty liver
3 main pathological scoring systems used to assess histo disease grade in chronic hepatitis
Knodell (4 stages)
METAVIR (5 stages)
Ishack (6 stages)
common treatment for HCV
sofosbuvir
ledipsavir
ledipasvir mechanism
potent inhibitor of HCV NS5A
viral phosphoprotein that plays an important role in viral replication, assembly, and secretion
sofosbuvir mechanism
nucleotide analog inhibitor of HCV NS5B polymerase, the key enzyme mediating HCV RNA replication
mimics uridine nucleotide and acts as a chain terminator
