Hello,

Sorry to hear you have relapsed

1) ?
2) Daclatasvir works for L31M, ledipasvir does not. ABT-493 is the NS3/4A inhibitor and ABT-530 is the NS5A and it is the current state of the art – but only available via a trial.
3) No, QUEST-1 was salvage of patients like you had failed V-pak (and other DAA regimens) http://www.infohep.org/Treatment-intensification-with-sofosbuvir-permits-cure-after-failure-of-previous-HCV-treatment/page/3014990/

On your skin red means more blood under here, so a liver spider elsewhere would be a red palm spot.

If you are well and your LFTs are good….

RELAPSE after four treatments!
HCV, G1b, F4, Child A-B!
Bad news! Mom has four treatments, the latter is Harvoni and she has relapsed!
First Treatment – 2000 Interferon / Ribavirin
Second Treatment – 2009 Peg Interferon / Ribavirin
Third treatment – 2015 Sovaldi / Ribavirin 24week
Fourth treatment – 2016 Harvoni 24week
Relapse!
Please give me advice what medicine to continue?

Hello Marilen,

Without knowing more details this advice should be viewed as generic.

There are several options to consider.

1) Wait for better drugs – this is unlikely to help as your mum is near the end
2) Do inexpensive maintenance therapy with say Sofosbuvir + Daclatasvir like we would do with HIV while we wait for better drugs. This might well be the best option
3) Do Sof+Dac or Sof+Led or Sof+Vel PLUS Ribavirin for 24 weeks
4) Look to do a curative 3 or 4 (or even 5) drug regimen. Options are things like Sof+Dac+Simeprevir or Asunaprevir, Viekira-pak + Sofosbuvir, Zepatier + Sofosbuvir and all with ? + Ribavirin

With Child’s Pugh A/B Viekira has a black box warning so it’s not a good option, but like I say, this is not a discussion that can be done via online posts and your budget needs to be considered. It looks like you are getting insurance coverage so funded Zepatier + Generic Sofosbuvir might be an option. The trial the underpins that is called C-SWIFT.

http://www.aidsmap.com/Treatment-intensification-with-sofosbuvir-permits-cure-after-failure-of-previous-HCV-treatment/page/3014995/

Here’s a list of all the things cirrhosis causes with pictures and diagrams

http://hepatitiscnewdrugresearch.com/physical-findings-suggestive-of-cirrhosisphotos.html

So happy for you Ariel. You are such an amazing positive person. I do hope you recover quickly from your dental work.

Hi Sven,

It is probably a side effect and the solution is to use some artificial saliva from the chemist until the meds finish when it should go away.

The medical term is xerostomia if you want to read all the health info about it, causes and treatments.

Hello SB

This is a good video:

[video]https://www.youtube.com/watch?v=fV-jhNQs_WE[/video]

1) Indefinitely, but the virus is not really alive. It is a piece of self assembling genetic code. “Floating around in the blood” it is assembled. On cell entry the envelope is shed and it “Falls to bits”, then there is replication/reassembly and exocytosis. There is a lot of waste. All the negative strands of RNA go to waste and are digested and recycled. A lot of the proteins suffer the same fate. The replicon unit has a lifespan of about 4 weeks (inhibited) but this is a half-life meaning it is an exponential decay over time with 1/2 at X units of time, 1/4 at 2 X units of time, 1/8 at 3 X units of time, etc
2) NS5B inhibition by Sofosbuvir is suicide inhibition – the sofosbuvir binds permanently rendering that replicon inactive. In time it will decay and be recycled. NS5A inhibition is transient, ie only while the drug is at a sufficient concentration, and it works by competing for space like a night club security person standing in a door blocking entry.
3) We use the Polymerase Chain Reaction to clone the HEP C RNA. We then look for specific target sequences in that RNA using probes that are like the mirror image of what we want to find.
4) Some membrane is used by the virus for it’s capsule. Cell death occurs when the body’s immune system recognises the infection and destroys the infected cell. This releases enzymes from inside liver cells like ALT/AST. Many cell lines (other than liver cells) are infected, thus the extra-hepatic manifestations
5) Harvoni is 2 things. Sofosbuvir suicide inhibiting NS5B and Ledipasvir competitively inhibiting NS5A. The drugs are well targeted at viral proteins but almost certainly bind to some host protiens and cause issues. These issues produce the side effects and depend on the genetics of the patient. The drug trials establish that we can successfully kill the virus without accidentally killing the patient. This is the trick with new drugs – get the effect desired without (too many) side effects.
6) Sofosbuvir is a pro-drug. It has no effect on anything and needs to be phosphorylated (twice) by CES1 and CatA to become the active metabolite GS-331007 which has a 1/2 life of 27 hours and exits via both the liver and renal (kidney) excretion – thus the problem with Sofosbuvir in renal failure patients.

I expect you may enjoy the detail in the European Medicines Agency Public Assessment Report:

http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/003850/WC500177996.pdf

Yes SVR rates improve with longer treatment and duration is in part an economic decision.

If I was F2 and GT2 and a past treatment failure I would take 24 weeks.

In GT1, which has better SVR rates but also better statistics, your SVR rate would be 94% with 12 weeks treatment and 99% with 24. For a government paying double for and extra 5% does not make good economic sense but for you…..

In GT3 SVR rates are lower – around 90% so you need all the help you can get.