TOPIC:

The new DAA medications do not require a lot of monitoring (unless Ribavirin is involved). Once you fall to UND (Undetectable) you will remain undetectable for the duration of treatment so further measurements are a waste of your time and money.

Here are some statistics about the % of people who will be <15 and/or undetectable at various points.

Week	% <15	% Undetectable
0	0	0
2	71	39
4	93	82
6	100	89
8	100	100
10	100	100
12	100	100

So the moral of the story is that once you are UND stop testing.

I am puzzled about this:-

The DAAs target the virus inside the hepatocyte and stop it replicating. So when all the hepatocytes are saturated with DAAs then replication of the virus should be stopped dead in its tracks. As most of the virus is in the blood, that should be the time it takes for all the blood to circulate through the liver. That would be <24 hours. So why does it actually take weeks to get to UND? What am I missing?

dt

dointime wrote: I am puzzled about this:-

The DAAs target the virus inside the hepatocyte and stop it replicating. So when all the hepatocytes are saturated with DAAs then replication of the virus should be stopped dead in its tracks. As most of the virus is in the blood, that should be the time it takes for all the blood to circulate through the liver. That would be <24 hours. So why does it actually take weeks to get to UND? What am I missing?

dt

Hi DT,
I think it has to do with detection of HCV in brain & CSF ( cerebral spinal fluid)
Maybe the virions that replicate outside of blood cells, like the brain tissue & CSF take much longer to kill? due to BB barrier ?
As I am not a medical researcher or MD this is just a pure speculation.
I don't have a link to this just picked it out from some of my old notes:

"The detection of HCV RNA in brain tissue, together with evidence to suggest independent viral evolution within the CNS, has suggested that the neurological symptoms reported in patients may result from direct infection of the brain. Recent advances in the tools available to study HCV have allowed researchers to address the question of whether HCV replicates in brain-derived cells. The recent observation that HCV can replicate in brain endothelial cells, and that neuroinflammation is a feature of HCV infection, may provide a mechanism for the neurological symptoms observed in a significant number of infected patients."

OMG!
I can't help myself from wanting to know the details even if they just make the picture more gruesome.

I was kinda theorising that maybe virions don't always snag a hepatocyte the first time around.
The reality will no doubt turn out to be stranger than anything I can imagine.
dt

There are probably questions none knows the answers to for certain at this moment, not even the experts, as HCV & it's treatments is very new on the scene. The science of Virology itself is also relatively new as compared to well established Bacteriology.

When I was first diagnosed 12 years ago, I studied & read everything I could about HCV, viruses, both in mainstream medical literature as well as looked & participated in naturopathic & complementary, alternative med. approach etc. for the next few years.
I even came across some great speculations & studies that HCV does not exists at all & was just Pharma manufactured propaganda in order to sell those expensive drugs & expensive tests, that was fun!
It all sounded very plausible to unscientific mind & I felt much better for a while after being convinced that this virus does not exists & it is just a fragment of some old mitochondria.etc.
I stopped reading anything about HCV soon after my first tx failed to cure me, I could not see the point of wasting time acquiring knowledge if all I ever wanted was a cure & not theories.

Now I just want the drugs & fast & be done with & start living again.

Interesting about the virus talking longer to eradicate from the brain. I have been reading about the Ebola nurse who is in the Royal Free in London. They eradicated the virus, she went back to her usual life then became ill again and readmitted to the Royal Free, Yesterday I read, that the Ebola isn't back, but she has contracted Meningitis. Their theory is that a few stray Ebola virus' remaining in her brain caused this. Thankfully, she is on the mend again now , although the Drs say she sill be with them for a long time yet before she is well again.

Exactly how I felt Jolie.

A question:
A friend was <15 at 4 weeks and <15 at 8 weeks. Tx naive, beginning v/l: 2.6 million. She is concerned she was not UND by week 8. Should she be?
Taking sof led/12 weeks.
Thanks,
Mike

<15 may mean UND.

This depend on field of linearity and analytical sensitivity. The test paper should have a note
fixhepc.com/forum/patient-stories/458-is...y.html?start=24#6495

She may need to do 24 weeks treatment the reason the majority stop at 12 weeks when
detected is they insurance will no loner pay.

At nearly six weeks my VL was 17 I've not done any bloods since and will do the next one
at close to week 10 I may need to do 24 weeks.

The facts are VL can and do go up and down during treatment even if your showing Detected at
week 12 you're not considered failed as 24 weeks post treatment is cured.

The chances are if you're UD from early on you'll remain so at 12 weeks

Sirchinenge wrote: She may need to do 24 weeks treatment the reason the majority stop at 12 weeks when
detected is they insurance will no loner pay.

At nearly six weeks my VL was 17 I've not done any bloods since and will do the next one
at close to week 10 I may need to do 24 weeks.

The facts are VL can and do go up and down during treatment even if your showing Detected at
week 12 you're not considered failed as 24 weeks post treatment is cured.

The chances are if you're UD from early on you'll remain so at 12 weeks

Hmm, this is what I thought - that even if you were still detected at 12wks, you may still achieve UND by 24?? A second course of treatment is unlikely to be an option for me.

Intuitively it is hard to see how <15 and detected can equate to cure and this was certainly my initial thought, but this was rapidly corrected by an expert:

fixhepc.com/forum/experts-corner/104-exp...-september-13th.html

2) The advice re prolongation of treatment based on HCV viral load monitoring is incorrect. There is no relationship between on-treatment monitoring and treatment outcome (assuming high level adherence, as in clinical trials). In fact, many patients in clinical trials have had "detectable" HCV RNA at end-of-treatment and still achieve sustained viral clearance. There is clearly no relationship between week 4 (or other timepoints) and sustained viral clearance, so extending treatment duration (as we did with interferon-based treatment) does not make sense in the interferon-free era, including in the case described below.

In the ION trials HCV RNA < 25 was used as the definition of success.

www.nejm.org/doi/full/10.1056/NEJMoa1402454#t=articleMethods

www.nejm.org/action/showImage?doi=10.105...EJMoa1402454&iid=t02

So according to the experts <15 (or <25) and detectable does not have any bearing on SVR. Undetectable is my favourite word but <15 is satisfactory.

Here is an interesting slide presentation suggesting the 1/2 life of the HCV RNA in mammalian cells may be quite long:

www.iapac.org/icvh/presentations/ICVH2013_Panel4_Soriano.pdf

Thanks very much for the confirmation on that, Dr James. So I guess seeing that 'UND' status pop up is (at least strictly clinically) isn't a requirement for SVR - but nice to have as a psychological factor. Why people feel the need to jump on extra treatment length, as some kind of "buffer" in case of relapse. To my mind if you attain UND at any point why would you think about extending tx?

Thank you all for your responses. I have never had the pleasure of being associated with such a bunch of caring, concerned folks.
There is a lot of goodness here.
Happy and Healthy New Year!
You are doing it Doc!
You and your bunch of merry pranksters .......
Mike

Hi zhuk Iam actually extenting my treatment because I started without updated fibroscan. Ive read that fibrosis can go up in one year. So just in case my condition was worse I will go to 20wks. Jill