Brain Fog? Good reason for it!

Molecular and bioinformatic evidence of hepatitis C virus evolution in brain.
Fishman SL, Murray JM, Eng FJ, Walewski JL, Morgello S, Branch AD.

Departments of 1Medicine, 2Pathology, and 3Neuroscience, Mount Sinai School of Medicine, New York, New York.

Background. @nbsp; Neurocognitive deficits in patients with hepatitis C virus (HCV) infection prompted a search for HCV in brain. Results. @nbsp; HCV was present in the brains of 7 (54%) of 13 patients with viremia, as determined by 5' UTR and E1 (envelope 1) gene analysis. Brain HCV RNA consensus sequences differed from those in plasma and liver in 4 (57%) of 7 patients. The quality of HCV RNA from postmortem brain and liver was assessed and demonstrated to be suitable for sequence analysis. Quasispecies analysis revealed that several mutations present in clones from >1 brain region were absent in clones from liver and plasma. Brain-specific mutations defined several families of related sequences. The patterns of brain-specific mutations in these families were consistent with the evolution of HCV RNA from a common ancestor. Single-nucleotide-polymorphism analysis confirmed that a prominent brain-specific mutation constituted 10% of HCV RNA in cerebellum and medulla but that this mutation was undetectable in the liver and plasma of the same patient. Conclusions. @nbsp; This study introduces novel methods for assessing RNA from postmortem samples. It increases the reported cases of HCV in the brain, provides the first E1 sequences from the brain, and contributes to the growing evidence that HCV replicates and evolves within the brain.

PMID: 18275278 [PubMed - in process]

Mike

[desrt]

Also may confirm why most who remain serum undetected still have recognizable RNA in specialized (compartmentalized) systems Whatever changes the virus makes to cross the blood/brain barrier leave it unviable elsewhere in the body

[alagirl]

I'd read an article about this before and was going to use it as evidence that people should treat early, rather than late, but then in the article I saw, the replication of Hepc was only happening in the brains of individuals who were also HIV positive.  I couln't find any that showed it was happening in people who weren't.

[mikesimon]

There is not mention in this abstract about HIV infection. Are you referring to another article? Mike

[DoubleDose]

Good article Mike!  Now we don't need to wonder too much about why we might feel slightly brain fogged, or fatigued and spacy after attaining the Holy Grail, the SVR!  
I have not met or heard from too many people over the years that claim to feel fully normal, or the way they felt before HCV, upon achieving SVR.  Maybe we have good reason for our post-tx funk.  If the virus is still hanging out in the brain, lymphocytes, and who knows what else.......we need a whole new generation of treatments, and testing that will identify just what is going on, and where!  

Of course this article does not surprise me one bit.  I have long suspected that the virus is replicating in lots of different tissues and compartments, and from the extra-hepatic symptoms, and intense localized problems associated with HCV I have also suspected that there are variants of the virus that adapt to different tissues or organs, as the above article stated regarding the brain infection.  I think that future testing, fine tuned to specific viral variants, will probably demonstrate that the virus is distributed in a variety of systems and tissues in the body, in addition to the blood and liver.

Add this article to the recently posted 'Salivary HCV infection" research, and you can anticipate what will likely be coming in future research studies.  We have been able to knock out (or knock down) the obvious, aggressive HCV viral infection carried by and in the blood, and grossly reproducing in the liver....but have we even yet begun to understand where else it lives, and how to address it?

Food for thought.

DoubleDose

[mikesimon]

I don't necessarily disagree with you but I will point out that this abstract centers around the brains of patients with viremia so I don't know what conclusions about SVR's brains can be drawn from it. The whole issue of occult HCV seems like a separate issue which may or may not be related to the notion that the virus replicates and/or mutates in the brain. I haven't seen any convincing evidence that occult HCV causes any detectable damage, aside from some elevation in liver enzymes and some degree of fibrosis - and those patients did not have spontaneous or treatment resolved HCV infections, from my vague recollection. I just found this interesting but not necessarily alarming for SVRs or people who've cleared without treatment. I just don't really have a strong opinion on the ramifications of this abstract. Mike

[jmjm530]

Thanks for posting.

Ala: I'd read an article about this before and was going to use it as evidence that people should treat early, rather than late,
-------------------------------------------------
You're making two assumptions here -- three really. First, that the HCV found in the brain has clinical implications, i.e there are symptons; second, that treatment will kill the HCV in the brain, with some studies (lympatic studies) suggest it may not; and third, that the overall benefit of treating early outweighs the risks of the treatment drugs.

DD: I have not met or heard from too many people over the years that claim to feel fully normal, or the way they felt before HCV, upon achieving SVR.  
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I agree generally with that statement (we've had some anecdotal polls here) in the terms you presented it -- those who treated. However, many have posted that they felt/feel quite normal before treating for HCV. In terms of brain function, this then begs the question is the culprit the HCV in the brain or the interferon itself. It appears that in those who felt fine before tx -- and not so fine after -- that the culprit is the interferon. Or if not the culprit, at least the catalyst.

[mikesimon]

Maybe we could inject interferon directly into our brain and kill 2 birds with one stone - our brain and the virus..... and quit fooling around. Or we could watch and wait.....I guess. This watching and waiting for new drugs seems to involve a significantly longer waiting period than some people had envisioned. Mike

[alagirl]

Mike - It probably was a different study, that's what I'm saying, I'm glad there are studies out there showing it in the brains of non HIV patients.  It makes my argument a bit stronger.

Aw Jim... inadvertently, you've made my argument for me.  If we can't kill HCV in the brain, then what better reason to treat early and kill the virus before it has a chance to infiltrate there. ;)

"Feeling normal" is not actually a good clinical measure of health, unfortunately.  Really, we need to have some studies of treaters vs. non-treaters and general health I suppose, or something of that nature.  I'm not certain exactly how that would be structured.  We know that ALL people infected with hepc for a certain period of time are at a fairly large risk for renal issues.  I haven't seen any studies done on individuals who have completed treatment treatment and their renal issues, but it would be an interesting study.  Since we know that treatment does help heal the liver, it would be interesting if it helped clear up renal issues as well.

[DoubleDose]

I agree with you.  Those are certainly open questions, and I am also conflicted over what is caused by the Interferon, and what is caused by the HCV.  The Interferon may well be a catalyst in many cases, or act as a sole cause of symptoms in others.  I still would bet that the HCV in the brain is what causes the many 'brain-fog' related symptoms in those who have not treated.  There has been lots of question about why HCV would be so symptomatic in some people who have little or no liver damage at all.

Often the answers have to do with suspected 'cytokine' responses in the body, causing these problems.  Well maybe there are cytokine responses in the brain, in response to the active HCV infection there.  OR, maybe the infection itself causes brain dysfunction and other problems.  The overwhelming fatigue in some HCV carriers often seems totally unrelated to liver damage, or length of infection, although it generally seems to worsen over decades.   Maybe this is due to direct viral action.  Along the same lines, what about the frequent salivary and Sjogren's Syndrome-like symptoms that develop in about 35% to 40% of those having HCV?  Could there be a direct viral action on the cells and tissues causing the problems, or could it be due to the cytokine response to the HCV viremia in these tissues?  Same questions with the arthralgia, and with gastric related symptoms.

We often forget some of the other interesting, and similar studies that have been published recently.  One study a year or two ago, in the Gastroenterology publication indicated research findings of HCV actively replicating in gastric fluids, and tissues.  Again, in fluids with no trace of blood, and clearly actively replicating.  Some of these studies get published, and then more or less forgotten.  I think they all provide clues to the behavior of this enigmatic virus.  

Some of us had severe, long term digestive and gastric issues over the decades before tx.  Most people seem to see those problems resolve after SVR, as did mine, and ChevyGal, etc.  Maybe it is easier to eradicate the virus in those areas, and fluids.  I think we need to have studies done on deceased SVR's in the future, to accurately determine if there is ongoing HCV replication in the brain, or any other compartments, after SVR.

Some people may wonder: why ask all these questions, but I think we don't get anywhere close to a real cure for HCV until we understand all these issues, and develop therapies to treat them successfully.  If they can 'kill' HCV in the liver, then I think they will develop methods to eradicate it in the brain, lymphatic system, or wherever else it might reside.  

I actually think that the more 'off the wall' questions that we all ask  (medical community included), the better our chances of finding long term health and peace of mind.

Thanks for your input Jim.  We have lots of unanswered questions still with HCV, but I guess like other areas of medicine, it comes slowly, and bit by bit.

DoubleDose

[Deb_c430]

That was an interesting article, very!  

I have read other articles about end stage liver cirrohis, that one  of the signs is a change in behaviour, anger, and  personality.  

It is often put in the same sentence as bloating, yellow eyes, and bleeding out.  

Double That is an interesting idea, and I agree we need to  look at all ascpects of this virus!   Like all other diseases, if the body works as a functioning machine so to speak, it stands to reason that all  things in some way connect.

I have nerve damage,  I could not lift my foot for a long time.   Well said Double and Mike.
Again interesting article.  Thanks for sharing it

Deb

[alagirl]

Seriously though, I think that treating early exposes people to lower amounts of interferon overall because they don't have to go through these second and third treatments with longer and higher doses.  On a FIRST TREATMENT I think it is worthwhile to do a pre-dose of pro-crit as Jim as suggested before tx for a couple of weeks, then I think doing a first dose with as strong a dose of ribavirin as recommended by one's doctor (not radically outside the SOC of course) keeping your procrit during treatment at a level that allows you to maintain tx without having to lower your ribavirin, and the SOC dose of interferon.

Also, I think, after reading a good many blogs and websites and medical sites even, that many people drop treatment the first time, or have their doctors discontinue them even, because their white blood cell count drops.  So I think a lot of people experience a partial first treatment that might have been a success except both they and their physician were afraid to press on in the face of a low white blood cell count, when in all actuality, people with HCV can handle the lower count, and neither they, nor their physicians, are educated to that.

[jmjm530]

Ala:  If we can't kill HCV in the brain, then what better reason to treat early and kill the virus before it has a chance to infiltrate there. ;)
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Now, that makes four assumptions. The fourth assuming that if  the virus invades the brain, it doesn't do it right away. I guess we'll have to agree to disagree on using this particular study as a reason for treating early -- or even treating for that matter.  Acute's btw are a different category than chonics which most here are  -- and a much stronger case can be made for acutes like yourself to treat with no liver damage.

------------------------------
MS:  This watching and waiting for new drugs seems to involve a significantly longer waiting period than some people had envisioned.

Many have seemed to found a nice compromise by jumping into the promising PI trials already. I know I'd be considering some of these trials if hadnt treated prior. The thing with "watch and wait" is it doesn't necessarily mean waiting for this new crop of drugs to come to market, as promising as they look. One might reasonably -- like Willing for example -- wait beyond the PI's for newer and even more effective treatments. On the other hand -- unless it's a relatively short-term strategy -- one should never just wait for something new unless the amount of liver damage warrants it. Where that point to jump in with what's a hand can be very individual.

DD,

You're quite welcome. While we don't always see eye-to-eye in how to assimilate some of these studies, I do (well at least usually :) ) appreciate what you bring to the table here. Questions do have to be asked.

-- Jim

[mikesimon]

Clinical trials have their own set of risks, as you well know. It is certainly not a panacea by any means. though it has apparently helped many achieve SVR. If one happens to be in the wrong arm it could be quite a different result. Mike

[DoubleDose]

I also must note that the apparent 'reason' for this research study (thankfully some researchers are asking hard questions) is in response to the neurocognitive dysfunction
found in HCV patients.  This brain dysfunction has been clearly shown over the years to not correlate with viral load, liver damage, or any other of the 'standard' issues that HCV is usually attributed to involve.

It really is about time that someone jumped in and did a definitive study to demonstrate just WHY we do have all these 'brain and cognitive' related issues.  It seemed obvious to many of us, for years, that the brain was a very likely site of active infection.  I will confidently predict that the virus will be additionally found to be alive and well (and actively reproducing) in many other tissues and organs, albeit at potentially much lower levels, and much more difficult to routinely detect. (enter the cellular immune response tests!!)
  
I would suspect that the virus is likely found in the major glands, possibly connective tissue, and we already know it can inhabit the salivary and gastric tissues, and now the brain, etc.  I think its just been a question of the "level of detectable infection", in most of these other tissues.  When you look really hard, with the right tools and tests, there it is.

I am in agreement that the active HCV virus loves the liver, and reproduces prodigiously in the blood, but those facts do not, and never have, precluded that the virus might not also concurrently occupy other 'friendly' tissues and organs, at different 'load' levels.  For someone to prematurely just conclude that these 'other infections' have no consequences is not very meaningful.

  If the brain infection, as a genetic variant of the blood/liver virus, as cited, is responsible for the brain related problems.....and then we are just now hearing about it???  It is only now being acknowledged as the likely culprit!!!   Can you even imagine how many more long term subtle changes are being provoked in our bodies by different versions of the HCV virus, occupying different tissues and organs???  Most of these suspected issues are only acknowledged as the culprits after they are proven by research studies.  Until they are proven, the medical community considers them of "no consequence"!  

Something to really consider.

DoubleDose

[mikesimon]

I wish I had a baseline (pre HCV) cognitive test against which to compare my current cognitive ability. I don't feel impaired but I would bet there are many here who'd disagree strongly with me about that. Mike

[DoubleDose]

Your comments below:

Ala:  If we can't kill HCV in the brain, then what better reason to treat early and kill the virus before it has a chance to infiltrate there. ;)
------------------
Now, that makes four assumptions. The fourth assuming that if  the virus invades the brain, it doesn't do it right away

My comment:

I agree about the "making assumptions" comment.  I would not be so quick to assume that the brain infection takes place long after the initial infection.  I could imagine a brain infection occuring pretty quickly after a general or acute infection, along with simultaneous lymphatic infection, etc.  We do not know nearly enough about these other"modes" of infection yet, to assume anything about them.  

I DO think we need to find out some things ASAP, like does the virus generally get eradicated after attaining SVR, or if not, how can we get at it during tx, to make sure that we don't continue on with a chronic viral brain infection, thinking we are cured because we have this SVR tag?

There are lots of controlled studies that could be conducted with HCV infected persons and control groups to look at brain related changes , both from an imaging standpoint, and a functional standpoint.  

Your comment about not making assumptions is important.  Today, too many doctors and laymen make untested assumptions about this virus all the time.

DoubleDose

[Deb_c430]

if the antibodies never leave your system,  and there is no  real cure, only a sort of lasting remission,  I think the more known the better.

[TnHepGuy_]

Good to see you, Mike - and thanks for posting this paper.

One thing I find interesting is that they only see it 7 of the 13 post-mortems. Begs the question: why not 100% - or 0%? Could the testing methodologies perhaps explain not finding in the rest of the subjects? If not, then what biological reasons could explain (e.g. - differing viral genetics between the patients, etc)?


David

[mikesimon]

Apparently according to this abstract, the virus doesn't universally infect the brain - 54% with this group. As to how long it takes to infect, that is too speculative for me to weigh in - whether it's rapid or slow.
I would GUESS that SVR likely inhibits replication wherever the virus replicates but I do not believe that every trace of the virus is necessarily eliminated upon SVR or that some replication doesn't go on. I have always believed that the damage from HCV that we are able to demonstrate is due to our immune response to the virus - that the virus by itself isn't cytopathic or, if it is cytopathic, it's effect is far less damaging than is our immune response to the virus. So, I would like to believe that SVRs are somewhat insulated from the type of damage that we know can result from the virus. HCV was found in my liver after SVR yet there was little damage and my ALT remains in the low teens. I think that a lot of SVRs would show HCV on biopsy but the liver damage that we see associated with HCV seems to be halted or significantly diminished once we reach SVR. So I am an optimist about SVR but not absolutely confident that we are totally in the clear. Mike

[Deb_c430]

agrees!

[mikesimon]

I posted my post before I read yours and it appears as though we were thinking along similar lines. It is always good to see you David - always. I hope all is well with you and your family.
Mike

[DoubleDose]

Hey I agree, SVR definitely confers some very good protections on us, and I am not begrudging the effort to get my SVR.  I do think there may be more systemic problems either from the 'compartmentalized' infection in HCV+ individuals, and maybe also in the SVR's, from this low level stuff.  And, even if the virus is not cytopathic itself, it may initiate some odd and pathological responses from the immune system, and the CNS.
So, I guess all that I am really saying is this:  let's find out what these other forms of infection really are capable of, whether brain infection, or persistent, latent HCV after resolution of the HCV chronic active infection.  And then let's see if other forms of therapy in the not too distant future, might be able to address some of these issues as well.

David, I also am intrigued by the percentage of brains having the virus.  Not 0% and not 100% but right in the middle.  To me, this warrants more study....where there's smoke there's fire.  What would cause half of the people to NOT have it in their brains?  Good questions from your end, and maybe finding out why this difference would answer some more questions.  

Deb, I agree, the more known the better is always a GOOD thing.  Some people don't like to hear threatening news, but it won't change anything by ignoring it.  The truth will out, as they say.  I think we can use the emerging research to better understand the virus, and develop better, targeted cures.

DoubleDose

[sfbaygirl]

I disagree that tx'ing earlier we can eliminate a need to do more interferon later. Many of us didn't find out we had Hep C for up to 30 years. Their first tx perhaps doesn't work, then they try another and another. Perhaps with a low VL, the first tx will be more successful and of course, RVR at week 4. But what about those non-responders on their first tx?  It doesn't seem to pan out that the earlier the better. Of course the eariler may be better, but not always. some that tx with a stage 0 or 1, go 48 weeks and relapse. Maybe they tx'ed as soon as they knew. So Ijust don't think the earlier the better is best for everyone.  I wish I knew before I tx'ed that interferon was going to effect me the way it did, but how would I know at first?  Same with non-responders. I am leery of doing another round of interferon even with the new drugs as a combo.

As far as brain fog, I didn't have it anywhere near what I had during tx. I think the interferon or the Riba had a huge effect on the awful fog I had. Now, off tx, I don't have it anywhere near what I had before.  It is hard to tell if some of it is from the Hep C, the ADD, or now the Lyrica I am on does to me. I know I am much less foggy now!

Linda

[Myown]

As far as the virus replicating in the brain,,,this goes back to what I had said to you about why I would think Pegintron might be better to use because its molecule is small enough to cross the BBB. I didn't read entire thread, maybe this was mentioned already.

But anyhow I read the the Alinia is a small molecule - whatever that means - how small, dunno, but I wonder it it can cross the BBB and if it has enough antiviral effect to zap the buggers in the brain ,,,,and I also wonder if the ribaviron crosses the BBB cause at least if it does,,at least we are getting something up there when not using Pegintron and using Pegasys.

I still wonder if I should do the second half of my tx with Pegintron - not asking you, just talking out loud ,,,,,(people with floating hepc particles in their brain talk out loud alot to themselves,,,j/k - no I'm not, its truuuuuue.)

[sfbaygirl]

If you are going to DD, why not do both pegintron and peg interferon?  That way you can cover both bases?  

[mikesimon]

I believe that arsenic also crosses the blood brain barrier. Mike

[Myown]

Yeah that was a theory of mine #4,001..... and I haven't gotten around to asking the doctor yet. My husband says me and the doctor cut up too much and I forget to ask him things. I don't forget to ask him things, I usually have a list, but the interferon split I did forget to ask.

I had mentioned that on forum a few times and could never understand why scripts arent't written like that. All doctors order one or the other from what I have always read,,,,but I guess thats cause they have their favorite for whatever reason:)

Okay gonna run. I told ya me and my husband are new to "Lost" series. Bought the first series and we like it. He is saying right now,,,"when are you going to get off that forum, I want to watch this so I can watch the Universe at 8 o'clock."  So see ya at 8 oclock for a little while if I am not tired... I don't want to watch the Universe.
MO

[Myown]

I believe that arsenic also crosses the blood brain barrier.
----------------------------------------------------------------------------------------------
Yes I think it does. Maybe I'll try it. I bet that will get every last viron. Thanks.

I wonder if it is bitter to taste. A pinch of sugar should do the trick - thanks again.

[working dog]

this stuff is all very interesting but i wonder if a lot of the brain fog we get on or off tx is from constantly being over tired..tired from an impaired liver that is being attacked by the hvc virus...i'm not on tx yet and have days when i feel pretty sharp..but most like now i don't so this post may mean nothing...billy

[Myown]

You definitely have a point and it probably applies to many. But for me,,, I have the brain fog but I am rarely tired - thank God. But my mind is really bad lately, very forgetful. Even my husband and mother  notices.

I love German Shepards. I have had shepards and also had a collie shepard mix which was an incredible dog - super smart. How many shepards do you have?

MO

[sfbaygirl]

We noticed you dont' get tired!  I wish I had your enegy!

[Mikkimoe]

Great observations - I for one know that many of my organs have been effected by this critter over the years - including my brain. I had to give up teaching last year due to the great fog ) and I'm not on tx yet - check out my journal for specifics.

Here is anarticle that seems to prove the theory as well: Done in Brazil

Research Article
The effect of early virological response in health-related quality of life in HCV-infected patients

Funded by:
Foundation for the Support of Research in the State of Bahia; Grant Number: 195712163383

Keywords
hepatitis C • interferon alpha • quality of life • depression


Abstract
Twenty-nine HCV-infected patients were treated with pegylated interferon alpha. Diagnosis was based on serum HCV RNA-PCR positive results and liver biopsy. All patients had elevated serum levels of alanine aminotransferase at the time of the study, but liver disease was compensated. Patients were evaluated at baseline treatment and after 4 and 12 weeks of antiviral treatment with the Medical Outcomes Study 36-item Short-Form Health Survey. The Mini-International Neuropsychiatric Interview was used to exclude previous or current psychiatric diagnoses. Both patients and psychiatrists were blind to the HCV RNA status, and serum HCV RNA test results only became available after the visit at week 12. After antiviral treatment, 16 patients (55.2%) were classified as nonresponders and 13 (44.8%) were classified as responders. When compared to nonresponders, responders had a greater improvement in the HRQOL scores for the mental health domain (P < .019). Differences in other domains were not significant. The present study confirms that active viral infection is one possible reason for the poor Health-Related Quality of Life in this population. J. Med. Virol. 80:419-423, 2008. © 2008 Wiley-Liss, Inc.

[Wassup]

Aside from all the normal things that healthy people have on their minds on a daily basis, lets look at what some/most of us HCVers have in addition: What's in store for me in the long run? Will I be able to work? for how long? What's this gunna cost, (not covered by my insurance)? How will my family deal with my health issues? Where will I find the time to squeeze medical appts.into what was already a maxed out schedule before dx'd? Will I lose my job,my home? How can I manage all this,when I'm sooo tired. How will I ever see this thing through?  I'm sure that the fears of everyone here are similar and many, more expansive than this partial list.

Then we speculate as to why we feel a little foggy in the brain. Why we forget to take a pill? Forget an appointment, a name that we knew as well as our own, just yesterday.

I haven't even started tx yet so I can't blame the interferon,  Perhaps the plethora of extra things to speculate, play some part in my malfunctioning brain activity.

I would also guess that having amonia (ammonia) in my blood, might not be healthy for cognitive activity.

The meds.my Dr. has me taking to alleviate the sx of HCV, might be fuzzing up my brain. Some days can't remember a three item grocery list.

If drinking alcohol itself, kills brain cells, wouldn't it make sense that a damaged liver, (unable to properly clean toxins out of my blood), would leave these toxins to circulate throught my body killing all sorts of cells?  

They say that a little bit of knowledge is a dangerous thing. I hope these speculations don't sound too redundant. If so, please forgive me. I mean well. Maybe this shoulda been posted in my Journal. Speculatively, Ant B

[Trish77]

Being the analytical person that I am, I want more definitive proof than that a mutated HCV strain is found in the brain to take the big leap that this is the cause of brain fog.  Unless it says so in other portions of the study, this one doesn't have anything to say about comparing the actual experience of brain fog in those persons found to have these mutations and those who don't.  

Mikkimoe, your article is an interesting addition to the mix, however it's talking the mental health of non-responders being not as good as that of responders.  If I hadn't responded to treatment and knew I had to do it again....compared with not ever having to go through that again...I'd have better or worse mental health on that issue alone.  I'd be more interested if they actually did a cellular sample from their brain somehow.  I'm not volunteering for that, however!!  Just saying.....

DD, the fact that persons with HCV continue to experience brain fog also doesn't warrant the huge leap that HCV cells continue to reside in the brain.  Considering how interferon/ribavirin impacts so many other health systems in the body of persons who have done tx and continue to have other issues, it's irresponsible to say that this is because of leftover HCV cells.  You seem to want to grasp at any straw that comes along to support this theory of yours.  

I don't deny that this is possible...that mutated HCV cells in the brain CAN cause an impact...but there really truly is hardly enough information in this particular excerpt to call this fact.  The only thing this bit of information allows is for us to entertain it as a possibility.  Considering that HCV can cause havoc with other organs and systems in our body, not beyond the realm of possibility.

Mike, I think I want to read that whole thing.  I'll try and look it up.  If you want to make it easy and post a link if you have one, I won't mind...otherwise, I'll take advantage of my pre-tx brain and put a bit of time into finding it.

VERY interesting discussion.   I want more proof though!!!!!  :)

Trish  

[Trish77]

Trish:  DD, the fact that persons with HCV continue to experience brain fog also doesn't warrant the huge leap that HCV cells continue to reside in the brain.
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To be clear, what I meant was.. those persons who have achieved SVR and yet continue to experience brain fog.  The ongoing impact of tx drugs is different for everyone and a very large factor to be considered here before leaping to the conclusion that it must be leftover HCV cells in the brain causing it.  I didn't say it wasn't possible but to me it's a reckless conclusion to come to without fully taking into account the impact of such potent drugs.

[beamishboy]

if ignorance is bliss-shouldn't our brainfog create a happy hepper?...personally,i believe major brainfog occurs during trx as a consequence of "the drugs"...after trx and SVR (in my own case) i am convinced that i am experiencing continued braineffects-cognitive impairmnt,depression,fatique&consequent anger issues (these effects **** me off,go figure)......so,how do we test for existence of virus in the brain without post-mortems or maybe,frontal labotomys?

[mikesimon]

Despite the title to the thread I really didn't make that leap myself - HCV in the brain = brain fog. I chose the title because I thought that it might intrigue people to take a look at the abstract. I found it interesting and thought provoking and it appears a few others did as well.
I disagree with you that DD was reckless or irresponsible. He didn't actually conclude anything more than there are issues he would like to see investigated. As we all know DD believes that the virus may have significant implications and inherent characteristics that have not been adequately studied or elucidated. This brief abstract can be interpreted to suggest that there may be some support here for his personal observations and opinions. I think that's basically all he said regarding this article.
To quote DD:
"So, I guess all that I am really saying is this:  let's find out what these other forms of infection really are capable of, whether brain infection, or persistent, latent HCV after resolution of the HCV chronic active infection.  And then let's see if other forms of therapy in the not too distant future, might be able to address some of these issues as well."
Here is the link. It is just the abstract and I do not have access to the entire article.

http://tiny.cc/ucdDH

Mike

[mikesimon]

This abstract may have been posted previously but I think it is relevant here. It should be somewhat encouraging to those worried about PMBCs serving as a reservoir for HCV once they've achieved SVR. Here is the abstract:

Clearance of hepatitis C virus RNA from the peripheral blood mononuclear cells of blood donors who spontaneously or therapeutically control their plasma viremia.
Bernardin F, Tobler L, Walsh I, Williams JD, Busch M, Delwart E.

Blood Systems Research Institute, San Francisco, CA.

We determined whether hepatitis C virus (HCV) RNA could be detected associated with peripheral blood mononuclear cells (PBMC) of seropositive blood donors who had spontaneously or therapeutically cleared their plasma viremia. Blood donor plasma viremia status was first determined with a highly sensitive transcription-mediated amplification (TMA) test performed in duplicate assays. PBMC from 69 aviremic and 56 viremic blood donors were then analyzed for the presence of HCV RNA with TMA adapted to detect viral RNA in PBMC and with a reverse transcription-nested polymerase chain reaction assay. PBMC-associated HCV RNA was detected in none of the 69 aviremic donors, including all 6 subjects with a sustained viral response following antiviral therapy. PBMC-associated HCV RNA was detected in 43 of the 56 viremic donors. The 13 viremic donors with no detectable PBMC-associated HCV RNA all had very low viral loads (6 positive only in 1 of 2 duplicate plasma TMA assays, 6 with viral loads below 100 HCV RNA copies/mL, and 1 with a viremia of 2700 HCV RNA copies/mL). The absence of detectable PBMC HCV RNA detection in all 69 aviremic donors reported here contrasts with prior studies, possibly as a result of the higher sensitivity of the TMA assay used to test for plasma viremia.....

Conclusion: Our results indicate that PBMC are unlikely to serve as a long-lived reservoir of HCV in aviremic subjects. (HEPATOLOGY 2008.).

PMID: 18220272 [PubMed - as supplied by publisher]
See: http://tiny.cc/cQATg

Mike

[Deb_c430]

I think knowledge is power,  and while all this  is still theory it is interesting to read and explore.  I also find it intriguing how opening one door often leads to another one that is closed.  

I do not see anything dangerous here, not to anyone participating in this conversation. It has all put out as theory and investigative.  

I have seen worse info given out here as gospel.  I am enjoying this conversation, thanks Mike again, dd, and all

Deb

[Trish77]

DD:  To: mikesimon, everyone
Good article Mike!  Now we don't need to wonder too much about why we might feel slightly brain fogged, or fatigued and spacy after attaining the Holy Grail, the SVR!  
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Mike:  I disagree with you that DD was reckless or irresponsible. He didn't actually conclude anything more than there are issues he would like to see investigated.
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The way I read it, Mike, right from the top he concluded that this article you posted was all the proof we need.  I think we DO need to wonder...and keep reading .. and researching....before we conclude that brain fog is due to residual HCV RNA mutations found in the brains of SOME persons who have had HCV .. but not all.  We don't even know the impact of such mutations, if any.  Still VERY much to keep wondering about.

DD....and perhaps I'm hitting a bit hard.  Perhaps you think out loud as you write your comments and you start from one premise and move to another.  As above.. you started out with the thought that this was definitive proof.. and yet in Mike's example, you end up saying.. "all I"m really saying is that we need to keep researching these things."  - (loose paraphrase there that shouldn't be in quotes, admittedly.) Well...that's not ALL you said, when you read the comments of yours that I quoted.  I'm just very leery of opening statements like the one I quoted of yours - jumping to erroneous conclusions leads away from vital truth and there is only enough information in this article to allow us to include another piece in the puzzle, not complete the puzzle.

Anyway....I don't want to split hairs too much here. I'm entitled to my opinion and I've stated it and taking my own knocks for my point of view. :)

I DO find these postings generate very worthwhile discussion and while I have some issue with how you present your opinions, DD, you ARE thought-provoking and the subsequent discussions are worthwhile and as Deb said, lead to opening many doors on other subjects as well.

Trish

[Trish77]

Mike: Despite the title to the thread I really didn't make that leap myself - HCV in the brain = brain fog. I chose the title because I thought that it might intrigue people to take a look at the abstract.
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You could write for the Globe and Mail in Canada with an approach like that. :)

[mikesimon]

I don't disagree with your opinion either. I think DD does write as he thinks and I do too. I try to have some idea of where I am going but I can drift a bit off course or simply change course. I hope we all realize that nothing written here - or perhaps anywhere, for that matter - is the absolute gospel. It's all just another's opinion of moonlight to me.
Michael

[mikesimon]

I don't disagree with your opinion either. I think DD does write as he thinks and I do too. I try to have some idea of where I am going but I can drift a bit off course or simply change course. I hope we all realize that nothing written here - or perhaps anywhere, for that matter - is the absolute gospel. It's all just another's opinion of moonlight to me.
Michael

[Forseegood]

hey, thanks for posting...

[pigeonca]

Aren't many symptoms (of name your disease) caused by the immune system rather than by the disease itself?  Example: the common cold.  So here's a theory: hcv isn't causing the problems; interferon is the culprit, whether it's the interferon your body makes in an unsuccessful attempt to fight the cooties, or the interferon you inject, which is stronger and causes stronger symptoms.

If there's residual virus after SVR, then your immune system is still overworking just to keep the virions from multiplying, and that's why you might feel foggy, tired and suffer from autoimmune issues.  Just a hunch - no science here.

[Trish77]

I don't disagree with your opinion either. I think DD does write as he thinks and I do too. I try to have some idea of where I am going but I can drift a bit off course or simply change course. I hope we all realize that nothing written here - or perhaps anywhere, for that matter - is the absolute gospel. It's all just another's opinion of moonlight to me.
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Guilty of the same myself.  'Nuff said.  

[DoubleDose]

Mike is right, I am often guilty of writing as I think, and I can often pursue two contradictory trains of thought somewhat simultaneously.  I guess I am reasoning through each line of thought, and also putting the idea out there for criticism.  So, I understand where you are coming from,  but....I don't ever want to come across as trying to say, with any authority, " this is the way it is!'   That is just not how I operate, and I don't have a need nor do I want to be the lecturer, or authority, at all.

  If my questions, theories, comments can provoke thought and discussion...then great.! That is the intention.  I don't make the statements lightly, but at the same time I am not saying"this is the truth!".  I just don't have any clear answers to much of this stuff, anymore than most of us.  I sometimes do think, though, that the medical experts dealing with HCV often speak as if, and I mean 'as if' they have clear cut, absolute answers to many of the subjects we often discuss.  I do not favor their 'dogmatic' approach, especially since there seems to be much contradictory research out there, on lots of relevant HCV matters, that the medical experts appear to already 'pronounced' to have definitively answered
I don't think that a large number of the doctors really have clear answers either, and in some cases, may have less insight regarding the more unknown, or unresearched aspects of this virus than we do. .Many of our members have studied, read about, observed, and followed the virus, and all its implications, from a very serious, personal, inductive and deductive level for many years.

  I think some of our suspiscions are likely to end up being more accurate than the 'edict-like' pronouncements handed down by the medical community over recent years....like:  "The virus is gone, eradicated, and there is no possibility for compartmentalized reproduction after SVR"....and I know we all have heard this...and many doctors still do say this....but the contradictory evidence is becoming somewhat overwhelming.

But I digress...I don't want to get too far off the immediate subject...but just to clarify the part of my initial statement that caused you some concerns, Here is what I said:

"Now we don't need to wonder too much about why we might feel slightly brain fogged, or fatigued and spacy after attaining the Holy Grail, the SVR!  "

So let me add as a preface: " Here is one possibility, as to why SVR's might feel brain fogged, etc. after SVR, along with the other possibilities...such as lots of interferon....permanent changes in the brain from prior HCV, or cytokine responses in the brain from the generalized blood HCV infection."  

I should have said what I said in the context of the additional possibilities, and I did not intend it to come across as "This is the only possibility for why this happens, and there are no other explanations"  That was definitely not my underlying belief, yet I can understand how you could easily take it that way.

So, if I do the same thing again in future comments (as I'm sure I will), be assured that I am never claiming absolute fact, or that I have the only answer....only that I am provoking your thought, and investigation into these possibilities!

Let's hope that some of the leading HCV researchers, and medical professionals also read this forum from time to time.  I would think that we provide enough material for them to consider, of any source out there.  I would LOVE to hear some of their replies.  AND to see some PROOF behind their answers!

All of you have a nice weekend and keep enjoying the forum!

DoubleDose

[DoubleDose]

Of course, your theory or hunch is the one that makes the most sense, and also explains why both SVR's and spontaneous clearers would experience more, and ofter worse, long term symptoms than many with active HCV infection.  One study that we read on the forum last week also attested to the fact that spontaneous clearers seem to have at least as many, if not more problems, than those with active infection (of course without the liver degradation).  This would most likely be attributed to the immune system constantly working to contain a minute, but persistent virus that is always trying to explode into a real infection.  

Look at someone with a serious influenza virus.  They may be ill for weeks, and have deathly powerful immune system reactions, making them feel extremely ill.  When they recover, they do not seem to have these lingering, or longterm symptoms that the SVR's, and spontaneous clearers do.  To me that indicates that the Flu sufferer has truly gotten rid of the virus, killed it off entirely, and their immune system returns to a normal state of equilibrium.  The HCV clearer, whether SVR or spontaneous, experiences an immune system that appears to be locked-in to an ongoing response pattern...thus generating autoimmune symptoms.  If it was all due to the use of external interferon, then the spontaneous clearers would have no longterm problems, since their own internal immune system did the work.  But, as we know, they DO have significant long term problems after clearance.  

So, as you speculate, the ongoing immune response is probably the culprit.  OR, if that is not the sole cause, then there may also be system dysfunction and immune system damage yet undiscovered by researchers, that are being caused by either compartmentalized HCV, or the low level persistent virus that remains in almost all persons after SVR.  Maybe a combination of both.

DoubleDose

[Trish77]

Here is an interesting article on this subject that hippygem referenced on the other side:

http://www.natap.org/2001/aug/evidence080501.htm

And another even more interesting article referenced within the above article (well it seems the first article is a report including the findings of this second perhaps):

http://www.natap.org/2000/ddw/rpt_11.htm

The overall conclusions from each of these seem to indicate that HCV does indeed cross the blood brain barrier and that HCV RNA resides in the brain in chronic HCV persons.  They also seem to conclude that there is noticeable cognitive impairment in chronic HCV persons.  They precluded those with intravenous drug use to eliminate that as a factor.  That makes the results more credible.  They also compared against HBV and "healthy" persons and found that the incidences of cognitive impairment of some kind are higher in chronic HCV persons.

However, the interesting finding, which should be of some comfort to those undergoing treatment and particularly to those achieving SVR, is that they found this improving after 12 weeks of treatment even and certainly for those achieving SVR.

For me this isn't conclusive, however definitely another interesting couple of pieces to the puzzle.  It remains to be seen why some continue to experience some sort of brain fog after SVR.   Apparently INF doesn't enter the brain but ribavirin does.  Another variable to consider when wondering about the post effects of treatment for those who continue to experience rage episodes, etc as some have posted here recently.  

More pieces to the puzzle.  Interested in other's interpretations of these articles.  I confess, it's not easy understanding all the terminology and getting a correct read on it.

Trish

[Trish77]

A bit of a delay in my response to you...I've been preoccupied. :)

Thank you for such a gracious and reasoned response.  I challenged you rather head-on and you took that well.  I respect that.  Having said that...expect me to continue to challenge you if you expect that you'll continue to talk in absolutes at times when they don't exist, regardless of your underlying intent. :)  It's nice to know that we can volley points of view back and forth, hard shots even at times..and out of all that we are closer to understanding truth if we are able to dialogue.  

You generate good discussions.  Much to learn.

Regards,

Trish

[Trish77]

Hm...let me correct myself here.  These articles indicate to me not that HCV RNA resides in the brain....but that HCV impacts cognitive reasoning in the brain which would seem to suggest, combined with other studies presented in this thread, that the possibility of HCV RNA residing in the brain exists and has some impact.  However...not enough information to positively conclude that, in my personal opinion.  Simply to add it as another possibility.