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TOPIC: Understanding Hep C and the new DAAs

Understanding Hep C and the new DAAs 1 year 10 months ago #623

Hepatitis C is a virus, one of the most simple forms of "life".

The sole purpose of the virus is to reproduce itself. Here is an animated video of it's lifecycle:



Because it is so simple the virus alone does not have all the tools required to do this so it infects a cell and hijacks some of the machinery it finds there to make more mini me copies.

Hep C is quite badly named because it give the impression the virus only infects liver cells. It also infects many other cell types:

www.ncbi.nlm.nih.gov/pmc/articles/PMC3142522/

The virus itself consists of only 4 key parts:

  1. A single strand of RNA (this is the blueprint genetic code)
  2. The protein NS5B which is an RNA polymerase (it can make more viral RNA)
  3. Helper proteins like NS3, NS4 and NS5A
  4. Structural proteins that form the capsule to hold it all together (like the shell of an M&M chocolate)

To reproduce the virus needs to make some more of each of these 4 key parts that are then assembled into new viruses.

The DAA (Direct Acting Antiviral) treatments we use target parts 1-3

  1. Sofosbuvir is a pan genotypic RNA polymerase inhibitor
  2. Daclatasvir is a pan genotypic NS5A inhibitor
  3. Ledipasvir is an NS5A inhibitor
  4. Simeprevir is an NS3/4A inhibitor
  5. Ribavirin is a guanosine analog (fake DNA/RNA component)

Sofosbuvir is like turning the RNA photocopier off for all genotypes (pan genotypic)

Daclatasvir inhibits the NS5A in all genotypes, and Ledipasvir inhibits it well in GT1, GT4, GT6, ok in GT3 and not well in GT2 and GT5. Think of it like ripping out the electronics in that photocopier.

Simeprevir is similar to Daclatasvir/Ledipasvir but rips out a different bit of the controller.

All these treatments are targeted specifically at viral proteins so their impact on your body is minimal. They are like military snipers.

Ribavirin has many more side effects in that it is like using a machine gun to kill a mouse. It works but there is a lot of collateral damage. Ribavirin inserts a fake letter R into the viral RNA where their should be a G and renders it illegible (like a child scribbling on the blueprints or writing words with the wrong letters in them). Unfortunately it also does the same to you cells so any cell that needs to divide and multiply (like blood cells for example) is slowed down by the Ribavirin. So now you probably know why anaemia can be a problem - the Ribavirin slowed down you blood factory.
YMMV
Last Edit: 1 year 7 months ago by James-Freeman-facebook.
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Understanding Hep C and the new DAAs 1 year 10 months ago #641

  • Alsdad
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That is an absolutely brilliant explanation Doc. My seven year old would understand it, it's in such plain and clear language.
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Understanding Hep C and the new DAAs 1 year 10 months ago #651

  • Sirchinenge
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I'll be using this when I'm trying to explain Hep C in the future.
Sob/Dac from Oct 29 2015
Geno 1b
Fiberscan 9.9 Pre treatment
Fiberscan 7.4 week 10
VL 1.3 million pre treatment
Week 2.5 VL 96
Week 5.5 VL 17
Week 10 VL UD
SVR 3 UD
SVR 16 UD
Cured:
All liver functions in normal ranges.
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