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Hepatitis C Main Forums => Hepatitis C Research News & Studies => Topic started by: elias on December 01, 2016, 08:45:16 pm

Title: Where is the HCV after UNDETECT early in treatment?
Post by: elias on December 01, 2016, 08:45:16 pm
After HCV is found undetected early on in DAA treatment, it can at times relapse after treatment (or less commonly even during later phase of treatment). Leading to virological failure

Question: Where was the virus in the meantime, before it relapsed?

Was it really in the blood all along, just not at  a detectable level when that UNDETECT result was obtained?

Was it in some dormant phase inside the liver or other body tissue, impervious to the RNA test?

I'm trying to visualize the process of virological cure or failure.

Can someone clarify the above
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: Luna7 on December 01, 2016, 08:58:58 pm
After HCV is found undetected early on in DAA treatment, it can at times relapse after treatment (or less commonly even during later phase of treatment). Leading to virological failure

Question: Where was the virus in the meantime, before it relapsed?

Was it really in the blood all along, just not at  a detectable level when that UNDETECT result was obtained?

Was it in some dormant phase inside the liver or other body tissue, impervious to the RNA test?

I'm trying to visualize the process of virological cure or failure.

Can someone clarify the above

It is reported to hide in the upper left nostril, and that's why I sneezed frequently during treatment.
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: elias on December 01, 2016, 09:09:05 pm
i suspected as much, luna. thanks for confirming  :)
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: Luna7 on December 01, 2016, 09:11:09 pm
But on a less silly note, elias, I have wondered the very same thing.
The last test I had was at 4 weeks when I was undetected, and I can't seem to go back to the doctor to verify I've cleared.

I've wondered if the virus can hide out in the brain. A big part of my recovery was healing my blood-brain barrier, and I worried I might have trapped a live virus in there! :)

Also, I was losing weight along the way, changing my body composition, and wondering if that was hurting or helping in terms of the final removal of the virus.

I'm not sure I've heard your question addressed, and I kind of doubt anyone knows at this point, but could be fun to speculate.
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: Luna7 on December 01, 2016, 09:11:58 pm
i suspected as much, luna. thanks for confirming  :)

 ;D
I can't help it...I feel so silly tonight..
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: elias on December 01, 2016, 09:24:00 pm
How sad. We can send a man to the moon. Yet we still do not know how many angels can dance on the head  of a pin.

===============
The reason I'm asking about post-undetect virus is that I've used visualization to help me in the past. So why not now?   It is amazing how many in placebo control group have actual biological reactions.

================
In terms of getting your current viral load reading, is it that you're hesitant to have it done or that your doctor isn't available? If the latter, any doctor, even family practitioner can order the test for you. It doesnt require a specialist
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: Luna7 on December 01, 2016, 09:32:12 pm



The reason I'm asking about post-undetect virus is that I've used visualization to help me in the past. So why not now?   It is amazing how many in placebo control group have actual biological reactions.


One would think, from these frequent placebo effects that actually verify that people can heal themselves, that modern science would enhance this phenomenon.
Funny that.
Only the magic pill works.
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: Luna7 on December 01, 2016, 09:33:12 pm

In terms of getting your current viral load reading, is it that you're hesitant to have it done or that your doctor isn't available? If the latter, any doctor, even family practitioner can order the test for you. It doesnt require a specialist

Well, my doctor lied to me about how many tests I needed, saying insurance required excess testing. I called the insurance company to verify -- they insisted they did not require all the tests the doctor said I needed.
It's hard to go back and confront, tell her I know she lied.
I guess I need to find another doctor :(
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: elias on December 01, 2016, 09:41:15 pm
Quote
Only the magic pill works.

Possibly for clearing a virus  and a few other diseases , this might be true...
But even there, mind-set probably plays critical role because the pill might work in tandem with the host's immune system. I don't think science as we now know it has yet gotten a handle on how to enhance this. Possibly because its not quantifiable. Nor marketable..
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: elias on December 01, 2016, 09:45:13 pm
Quote
they insisted they did not require all the tests the doctor said I needed.

But would insurance cover such a test if done by say your family doctor or any general practitioner? That way you can get results and hopefully closure while looking for a new specialist?

I know they covered my viral load test when my family practitioner first ran it
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: Luna7 on December 01, 2016, 09:48:15 pm
But would insurance cover such a test if done by say your family doctor or any general practitioner? That way you can get results and hopefully closure while looking for a new specialist?

I know they covered my viral load test when my family practitioner first ran it

Yes, I think there's a lab here I can just walk in and request tests from.
I know I should :(
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: Luna7 on December 01, 2016, 09:50:48 pm
Possibly for clearing a virus  and a few other diseases , this might be true...
But even there, mind-set probably plays critical role because the pill might work in tandem with the host's immune system. I don't think science as we now know it has yet gotten a handle on how to enhance this. Possibly because its not quantifiable. Nor marketable..

I did positive visualization all the way through treatment, btw.
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: elias on December 01, 2016, 10:01:09 pm
Quote
I did positive visualization all the way through treatment, btw.

I was unable to do anything like that because deep down i did not believe the medication was really clearing anything. I have had this all my life, but didn't know it The 4-week undetected result this week convinced me I could get rid of it. So feeling more empowered. This is why I'd like some rough idea of what is I'm trying to clear myself of for the next few months.

Otherwise, intersection of liver and kidney meridians might just have to do...
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: Luna7 on December 01, 2016, 10:04:22 pm
I was unable to do anything like that because deep down i did not believe the medication was really clearing anything.

What caused you to not believe the medication could be clearing anything?
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: Luna7 on December 01, 2016, 10:07:03 pm
Well you know some people like to visualize some kind of war in their body, like dragons fighting the virus and such.
I always just focused on my good cells being healthier by the hour and not allowing anything that would hurt me to affect them.
I also trusted the medication was working to not allow the virus to replicate as well.
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: elias on December 01, 2016, 10:08:29 pm
partly the bizarre way by which im convinced i got this

partly because the virus was in me for so long..decades.. i assumed it had mutated into odd forms not addressed in the clinical trials

much of this was more subconscious than rational
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: elias on December 01, 2016, 10:12:31 pm
Well you know some people like to visualize some kind of war in their body, like dragons fighting the virus and such.
I always just focused on my good cells being healthier by the hour and not allowing anything that would hurt me to affect them.
I also trusted the medication was working to not allow the virus to replicate as well.

I dont go into the "dragonslayer" battle mode. More in terms of empowerment as you put forth. Matter of temperament I guess.

I'm trusting the medication more now, seeing it was able to clear it in a few weeks. The real hurdle is ahead though
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: Luna7 on December 01, 2016, 10:16:11 pm
partly the bizarre way by which im convinced i got this

partly because the virus was in me for so long..decades.. i assumed it had mutated into odd forms not addressed in the clinical trials

much of this was more subconscious than rational

I found myself getting very irrational during treatment at times, more so than preceding treatment.
There was a sense of my body being out of my control - I didn't know what was happening inside me and there was nothing I could do except for visualization and trying to remain calm and have some semblance of trust in the process.
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: Luna7 on December 01, 2016, 10:24:12 pm
I dont go into the "dragonslayer" battle mode. More in terms of empowerment as you put forth. Matter of temperament I guess.

I'm trusting the medication more now, seeing it was able to clear it in a few weeks. The real hurdle is ahead though

Yeah I remember waiting for the 3 months to pass, seemed like it never would on one level, but on another it seemed to fly by fast...
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: Lynn K on December 02, 2016, 11:00:14 pm
Sorry just skimmed the thread if the original question was answered i missed it

Anyway:

"Was it really in the blood all along, just not at  a detectable level when that UNDETECT result was obtained?"

Yes the test lists its LLOQ or its Lower Limit of Quantification that is the lowest quantity of virus the test can detect if it is present. So if you have less than say 15 IU/mL the test will say not detected.

But that is 15 IU of virus in every mL of blood on your body there are approximately 4.7 to 5.5 liters ( 4700 to 5500 mL) so not a lot of virus but enough to repopulate the viral load in an exponential way going from not detected at EOT back to prior treatment levels within weeks for those who relapse. This is why on treatment testing matters little and the only test that matters is the 12 week post to see if we really did get them all.
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: elias on December 03, 2016, 12:05:55 am
Thanks much Lynn:

That does explain a lot

Was wondering if it's also in the liver cells and if such infected cells aren't detected by the pcr? It's only measured in serum.

Also:

Does pcr detect only free viral particles or does it detect cell-bound virus as well?
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: Lynn K on December 03, 2016, 02:54:48 am
My assumption is the virus particles travel freely I the blood stream and are not hanging out some where secretly lurking. They have no intellect any more than grains of sand.

As they are just drawing a blood sample that is all being tested. I guess to test your assumption they could also do a liver biopsy at the same time to see if there are virus cells there.

I believe PCR describes the testing method found this:

"PCR stands for Polymerase Chain Reaction. It's a testing technique that can detect either DNA or RNA from any kind of organism, such as HIV, for example."

In my thinking it is mearly just too few virus cells for test to be able to detect. But this is way, way above my pay code. I am not a microbiologist by any stretch if the imagination. So pretty much that and 5 bucks and you can buy a cup of coffee. ;)
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: lporterrn on December 03, 2016, 02:36:19 pm
I am away and just checking in - looks like Lynn answered your question. Here is what I add- HCV replicates in the liver. The new meds prevent that replication. Picture this - the virus is replicating in liver - liver tries to stop that replication but meds stop it even more effectively and when the virus can't replicate it dies. Simultaneously, our circulation system circulates blood which picks up HCV in the liver - less will show up in the blood if the HCV in liver is dropping. HCV has to replicate to stay viable so when we get to nondetectable, it is pretty much the end of the game for Hép C.
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: Philadelphia on December 03, 2016, 04:08:40 pm
So you're saying  new DAAs are like birth control? Little chemical condoms designed to stop the virus having virii babies?
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: elias on December 03, 2016, 05:41:35 pm
Quote
Picture this - the virus is replicating in liver - liver tries to stop that replication but meds stop it even more effectively and when the virus can't replicate it dies. Simultaneously, our circulation system circulates blood which picks up HCV in the liver - less will show up in the blood if the HCV in liver is dropping. HCV has to replicate to stay viable so when we get to nondetectable, it is pretty much the end of the game for Hép C.

Thanks. This might help explain relapses even after the early UNDETECT during treatment. And why cirrhosis may make this more difficult. It does continue to have some presence in the liver. The real battleground is in the liver and resistance to viral replication mounted there. The meds act in tandem with the local resistance  and immune system to knock those off. Most often this succeeds nowadays. Though not always.

Do I have this mostly right?
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: Luna7 on December 03, 2016, 06:16:49 pm
So you're saying  new DAAs are like birth control? Little chemical condoms designed to stop the virus having virii babies?

Philadelphia, how did you know?
You're not supposed to, but I broke one of my pills apart and they were in there, little condoms.
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: dragonslayer on December 03, 2016, 06:19:23 pm
nope.. mine had IUDs.
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: Philadelphia on December 03, 2016, 10:34:53 pm
So Luna broke open a male pill and you broke open a female pill, dragonslayer!
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: elias on December 03, 2016, 10:50:33 pm
You need two layers of birth control here. Thats why they combine Sofosbuvir with another DAA. So both Luna and Dragonslayer are right. Condoms and IUD inside
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: Luna7 on December 03, 2016, 10:59:22 pm
We are all murderers.
I am deeply ashamed.
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: Mugwump on December 05, 2016, 12:35:38 am
After HCV is found undetected early on in DAA treatment, it can at times relapse after treatment (or less commonly even during later phase of treatment). Leading to virological failure

Question: Where was the virus in the meantime, before it relapsed?

Was it really in the blood all along, just not at  a detectable level when that UNDETECT result was obtained?

Was it in some dormant phase inside the liver or other body tissue, impervious to the RNA test?

I'm trying to visualize the process of virological cure or failure.

Can someone clarify the above
Fortunately HCV cannot live very long without reproducing in the body. The only place where it can reproduce is in an hepatocyte. So if there is any viable rna still waiting to reproduce then it will most likely be still in liver cells that have not been hit by the DAA drug quite yet.

The shape of mature virus encapsulation is how the rna is injected into an hepatocyte during an active infection with HCV. If this cycle of viral reproduction is somehow interrupted then the virus encapsulation is broken down over time in human blood largely by exposure to agents that disrupt the protein encapsulation.

It is possible that mature virus particles stay in places like the vitreous humor of the eyes and move only slowly back into the blood stream. But because the virus only lives encapsulated for a short time in the human body it must get to the liver with the shell intact or become inert rna and thus be discarded as useless material by the liver and other systems.

I hope this helps explain what is happening in a more understandable fashion. In essence the new drugs disrupt the reproductive cycle of the virus and also cleaves the rna strand and gives the body a chance to clear the huge numbers of virus particles that were circulating around waiting for a chance to latch on to an hepatocyte, inject the viral rna and complete the disease reproductive cycle.

It gives me the willies visualizing how insidious this tiny beast of a disease really was!! YUK

To a new happier life, free of the willies that once had a free ride in all our livers! 
eric 
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: elias on December 05, 2016, 01:22:18 am
Thanks so much, eric for taking the time to explain.

 I do wonder if after that on-treatment "undetected", the disruption of viral replication might be more governed by host immunity factors  and condition of the liver than in the time frame during which that early clearance is achieved. The latter is a fairly rapid process in most cases, compared to the former. It's in that later phase, which goes on for months, in which viral relapse, it if is to happen, does occur
Title: Re: Where is the HCV after UNDETECT early in treatment?
Post by: Lynn K on December 05, 2016, 01:28:40 am
All I know is almost everyone is not detected when tested at 4 weeks on treatment and there does not seem to be a correlation for those who are not. I have seen those who were treatment naive with no liver damage who were weakly detected on treatment. While I with genotype 1a, multiple treatment null responder with cirrhosis was not detected at week 4 on treatment so go figure....