Hep C pathogenesis Flashcards
What are senescent cells?
Cells that don’t divide but aren’t dying.
What is juandice a result of?
Hepatocyte dysfunction, build up of bilirubin (yellow green colour)
In chornic HCV infection with an elevated ALT what could happen?
Cirrhosis in some cases which can also lead to hepatocellular carcinoma
In chronic HCV infection what happens to ALT levels?
They flucuate
What are other aspects of HCV pathogenesis?
Insulin resistance
Dysregulation of lipid metabolism/ steatosis
Hepatocellular carcinoma
How does HCV lead to diabetes?
HCV blocks glycogen synthesis and increases glucose production, reduces cytokines
What does the HCV core associate with?
Lipid droplets, lipid accumulation
How does HCV lead to steatosis (fatty liver)
Core and NS5A lead to lipid accumulation. Genotype specific, type 3 higher incidence
What viruses is hepatocellular carcinoma associated with?
HBV and HCV
How does HCC develop?
Hepacoytes which usually don’t divide proliferate, inflammation, increased cell turnover, oxidative DNA damage
What are molecular requirements for developing HCC
Decreased apoptosis - p53 and TGF-beta
Increased cell cycle- TGF-beta, Rb, growth factors
Inc. Vascularisation- Growth factors
Increased gene expression for cell adhesion and proliferation- Wnt-beta-catenin
HCV protein NS5A implicated in developining HCC
Apoptosis, cell cycle, gene expression
HCV protein NS3 implicated in developining HCC
Apoptosis
HCV protein Core implicated in developining HCC
Apoptosis, Cell cycle
HCV protein NS5B implicated in developining HCC
Cell cycle
How does HCV lead to HCC, what changes does it induce?
Epigenetic changes, chromatin remodelling
