John,

I am so sorry to hear of your loss. What a difficult time you must have had. Thank you for sharing your painful story.

I had begun the conversations leading to the donation process after my son's accident as he was not expected to survive the night, but he did, and I did not realize how in-depth it would have become.

I think we need a universal response to this. As Mallani indicates, even in a single country such as AU, your luck depends on your location. There are so many, some even here, who wait for a life saving transplant. I know if I were the one in need, the immediacy of that need would transcend the possibility of exposure to almost any other type of illness. Especially a slow mover like HCV.

I agree, it will be a waste to exclude us. A heartbreaking and foolish waste too, unless there is something about this that I am not understanding. 

~ Rudi

Shortly after starting Tx in January, 2014, my younger sister passed away from a heart attack related to underlying advanced kidney disease. Not even aware she was an organ donor, I received a call the same evening that she passed away from a regional organ donation center. They asked me numerous questions for over an hour regarding her medical history, much of it based on her kidney disease and whether she had dialysis before she died. Apparently any type of needle exposure is a red flag or even sexual relations with a i.v. drug user could have excluded her from donation. I was told that HIV, Hep B and C would also rule out any organ donation. I asked about someone being SVR with Hep C and they told me that it didn't matter, they still would be excluded.  About two months ago, I got a letter thanking my family for the donation of her eyes that were used in a corneal transplant which is the first time I heard that any of her tissues were used.

The informant for the deceased needs to be prepared to answer specific questions regarding the deceased's general health before death, possible substance abuse, sexual experience including the number of partners and whether they or their partners used recreational i.v. drugs and other questions to ascertain possible contagious diseases from blood or other bodily fluids.

I am still listed as an organ donor, but have no idea if I were to die today that my Hep C experience automatically prohibits tissue use after death. The number of potential SVR donors should be increasing dramatically and it would be a waste to exclude our group from organ donations.

Hi Rudi,

As Lucinda Porter has said, it's OK to tick the organ donor box. Whether organs are used by a Transplant Centre seems to vary. It's quite odd, but some Centres in Australia will not use organs from HepC patients, whether SVR or not. Perhaps that will change.

The PM studies were all done before 2010, i.e. they predate the DAA SVR's. I haven't seen anything that changes the perception of SVR using DAA's. Obviously PM's are not done routinely- patients have to die from a sudden, unrelated event. Eventually someone will publish something about this. Cheers.

Thanks for the helpful link Tig.

This is a fresh frontier and Lucinda's guidelines were helpful as well as reflective that there is still much to be learned. When I googled this I couldn't find anything concrete. Hopefully some research $$ will be found for studies. 

She also touches on the life insurance issue, which is of great interest to me as my son is permanently disabled and I've always wanted to have a policy to provide for him. I will be on the hunt for an amenable insurer provided I am SVR.

Roo

Hi Rudi,

I found this PDF article published by Lucinda Porter, RN, that claims organ donation is allowed following SVR. I've also read other articles that state that its the decision of the transplant surgeon and recipient, but more and more often they are proceeding with it because the survival rates of the recipient is as high/long as those receiving organs never HCV infected. You can find several references via Google. Seems very interesting and is all new information for me too! I'm learning new things every day...

Tig

Hi Mallani,

Not to belabor your point, but just wondering, does this mean a person achieving SVR via DAA's can never sign up to be an organ donor? I don't mean to be dense but I'm thinking, if my organs could save a life, the person receiving them could later be treated for the Hep C. Better than dying for want of a heart, etc.?

Also, are the PM studies you reference predating DAA SVR's? Is there a chance Harvoni and or S/O treated folks could become blood/organ donors? I have always wanted to do this, and been thwarted first by not weighing enough, and then by Hep C. I would never want to cause anyone else to suffer, blood transfusions post child birth were likely how Hep C was introduced into my body, but I feel sad and a bit ashamed when I can't tic the donor box on my license, or have to sit out the blood drives.

Perhaps there is something in a pipeline that could allow us to one day become donors?

Thanks ~ Rudi

Hey Rubye & Malcolm

I think of this topic every so often and I agree, and think our immune can learn from being exposed to a drug that can possible awaken our associated neuropeptides.

I read a book about this called "The Molecules of Emotion" wrote by Candice Pert    

Pert was an internationally recognized pharmacologist who published over 250 scientific articles on peptides and their receptors and the role of these neuropeptides in the immune system. Her earliest work as a researcher involved the discovery of opiate receptors and the actions of receptors. She had an international reputation in the field of neuropeptide and receptor pharmacology, and chemical neuroanatomy. Pert also lectured worldwide on these and other subjects, including her theories on emotions and mind-body communication. Her popular book, Molecules of Emotion: Why You Feel the Way You Feel, (from Wikipedia)

The other area I think that would be important would be getting your blood moving on a regular basis by briskly walking or exercising enough to get our heart rate up for a 20 minute duration.

matt

Hmmm, that's so interesting that our auto immune system is teachable. I hope mine has learned enough to keep the virus at bay cause I sure am tired of it. And I hope for the same for everyone else here.

Hi Gary,

BJ is correct in his comments. You are also correct- the chance of relapse after SVR 12 or 24, is probably <0.5%.

The general consensus is that, after SVR, our autoimmune system 'learns' how to deal with the tiny amount of residual virus, which may surface from time to time.

This is why I do not use the term 'cured'. 'Successfully treated and controlled' is more appropriate. This is why we can never donate blood, and should remain vigilant about exposing our blood to others.

There have been several studies citing post-mortem results in post SVR patients. Residual virus has been found in virtually every tissue. Sobering thought, but don't worry about it. Cheers.

I'm not positive but that sounds about right.  It's just that they are still learning about this virus and they don't know for sure all the places it could be hiding. I think that once it's undetectable for an extended pd of time (or very low like you noted) that they have found the likely hood of it coming back is very very low.  does that make sense?

I'm not sure I understand this thread. I thought that if you reach SVR12 or SVR24 the chances of relapse were extremely small. Like less than 1%, am I wrong?

Gary

It was always my understanding that this virus hides all over the place. Its main goal is to survive and multiply and viruses are very adapt at playing "hide & seek".  I don't think even to this day, they know for sure all the places it hides. I was told that we need to continue treatment for such a long time because of this fact. The "treatment may initially kill of the most prolific of the virus - the ones  out in the open so to speak, and do it very quickly - which the treatment is designed to do so the virus can't replicate and make the treatment no longer effective.  I imagine thru trials they have found that the virus will creep up again as it comes out of hiding places and they've come up with a period of time we must continue on treatment to make sure all these buggers get annihilated. Even with today's treatments they still can't proclaim to be "cures" - because we can only get to a point where we can't detect any virus.  

This sentance from a previous post intrigue me about the Lymphatic System

---

One theory as to why it may act otherwise, is that hepatitis C hides out in the lymphatic system. 

---

 The Lymphatic system is the most unrecognized body systems that we know about. Because it has a lot to do with cleaning our wastes its becomes worth studing when we are in treatment and enduring chronic HCV. Check out this excerpt from an article and its link.

 The lymphatic system, or lymph system as it is also called, is a system made up of glands, lymph nodes, the spleen, thymus gland and tonsils. It bathes our bodys cells and carries the bodys cellular sewage away from the tissues to the blood, where it can be filtered by two of the bodys main detoxification organs: the liver and kidneys. This sewage is made up of the byproducts of our bodily processes, over-the-counter and prescription drugs, illicit drugs, cigarette toxins, other airborne pollutants, food additives, pesticides and other toxins.

Read more: http://www.care2.com/greenliving/11-ways-to-boost-your-lymphatic-system-for-great-health.html#ixzz3NM1QFVos

Also google the phrase -  "how to get your lymphatic system moving"

matt

Hi Rubye,

Nearly all of the virus will be wild-type. If left in peace, the virus exists in it's most efficient form, the wild-type. Each genotype has a preferred, most efficient structure. This is best able to enter cells and replicate. Variants will be formed but these mostly 'die-off'- it's survival of the fittest. Pre-treatment testing often shows some naturally occurring variants- the Q80K mutation is a good example. The current opinion seems to be that pre-treatment testing for polymorphisms is a waste of money. Cheers.

No, it's not a complicated answer at all and what you've explained makes a lot of sense to me. When I've asked about the possibility of the drugs being unable to kill off all the virus, thinking some may be tucked away in the tissues of the cirrhotic liver, most people simply answer that it replicates, implying that because it replicates all of it must be killed if some of it is killed. That just did not make sense to me. What you say here explains a lot. Thank you very much for taking the time to explain it Mal. 

The idea of the virus hiding in the brain or tissues explains why so many people relapse. Many don't have enough time with the drugs in their system it seems. Since I was only able to obtain 16 weeks of S/O and have cirrhosis I worry a bit about this. I don't get obsessed with it by any means. It just feels good to understand what is going on. Thank you again.

I just have one more question. If I have a 2.5 million viral load. Does that mean I have that many "copies" of some original virus contracted way back in the 70's when I was first diagnosed with non-A and non-B? Or are some copies and some mutated copies? 

Hi Rubye,

Your question isn't naive but it's not easy to answer.

Think about a course of antibiotics- these are usually taken for 5 days. We're dealing with bacteria, not our tricky virus. Some antibiotics (like penicillin) target the cell wall of bacteria, effectively killing them . Others (like the tetracyclines) interfere with the proteins in the bacterial cytoplasm, making growth and replication impossible. It takes time for the antibiotics to wipe out all the bacteria, and more time to perfuse and diffuse into tissues. Many patients do not take the full course of antibiotics, but stop when they feel better- often after a couple of days. This has allowed some bacteria to become resistant to certain drugs- they 'learn' how to protect themselves.

Our virus is very difficult. Being an RNA virus, when it replicates, it produces a family of viruses with slightly different chemical structure. An antiviral drug only works against a specific, original (wild-type) viral structure. This is why we need additional antivirals to combat the 'family'.

When we take an antiviral e.g. Sovaldi, it is quickly absorbed from the gut, changed to it's active form, and quickly reaches peak concentration in the blood. It then seeks out all the wild-type virus in the blood, effectively blocking them from replication. This possibly happens with just one dose.  However, up to half the virus is not in the blood, but in other tissues, mostly liver.  It takes time for the drug to diffuse/perfuse into the liver cells. This takes longer in those with liver fibrosis where blood perfusion is less. These patients also have a thick fibrous plate (limiting plate) between the blood vessels and liver cytoplasm.  So replication continues, and some of the new viral structures may be resistant to Sovaldi.  Again, this is where the extra antiviral will hopefully play its part.  The virus doesn't have to enter the blood.  It can spread directly from liver cell to liver cell.

As the title of this thread suggests, virus may be present in many body tissues.  Some tissues are very poorly perfused, so it will take longer for Sovaldi to reach any hidden virus.  Basically, it's a cat-and-mouse game, and nobody can predict how long it takes for the antiviral to track down all the virus.  Also nobody knows how effective the second or third antiviral is in dealing with the resistant viral copies.

It all comes back to the Clinical Trials. Various time frames were used in the Trials for each drug ( and drug combo)- 4 weeks, 8 weeks, 12 weeks, 24 weeks etc. The time we need to take each drug has been decided from these.

I know it's a complicated answer to a simple question. Sorry.

Rubye,

You have to remember that these drugs take time to perfuse throughout all body tissues. Once these medications have reached all tissues, the need to maintain extended exposure to it appears necessary to ensure the desired effect.

Tig

very impressive information and or questions you guys present.....

 sum pretty incredibly detailed minds who are very sharp reside here on this forum...

 theres a rumor that in sum book :) its says knowledge and wisdom are worth far more then money.....

The time thing is really very puzzling to me. If during tx, we have meds going through our system that stop replication of hcv, why can't they just do their job in one day. Why does it take 12 weeks or 24 weeks or how ever long? Are the drugs only able to kill so many hcv's a day? I realize this is a terribly naive question, but I have been wondering about this for quite awhile now. Do the drugs have to build up in our system to a certain saturation point before they do their job?

Hey all

The term latent virus is sometimes used in this discussion, Here is a excerpt from hepmag. 

Unlike HIV, hepatitis C does not form a latent reservoir, so technically if hepatitis C is nondetectable, it should remain that way. One theory as to why it may act otherwise, is that hepatitis C hides out in the lymphatic system. However, a study by Formann and colleagues found that although hepatitis C might be present in certain cells of someone with an SVR, there is no evidence that hepatitis C infection will recur.

Here's a link to a short article from Lucinda Porter

http://blogs.hepmag.com/lucindakporter/2014/07/hepatitis_c_treatmen_2.html

more to come

matt

Thanks Malcolm.

I have recently been wondering if that residual/trace HCV presence in some post-svr's will still be present in those treated with the newer medications.  Since these newer meds actually prevent replication by blocking virus assembly, their mode of action is different.  Just speculating...

 wow thats a pretty in depth answer Malcolm :)

great explanation... saved me a lot of looking around the net ....

i bet alot of people forget time to time that you are a doctor not to mention as i read in another post a  war veteran :)

mallani wrote:

---

Hi Matt,

You know that HCV has been found in virtually every tissue. Whether replication takes place is uncertain. The usual criteria for replication is the presence of negative strand HCV RNA in cells.

Only dedicated PCR tests can distinguish between positive and negative strand HCV RNA. Over the last few years, researchers have often failed to agree.

We know most replication takes place in hepatocytes. I think it is now accepted that replication may occur in peripheral blood monocytes, and probably in lymphoid tissue. Bone marrow cells, such as dendrocytes, are often mentioned.

As you say, Undetected means just that. No virus can be DETECTED in peripheral blood. It still may be present in tiny amounts, or be in monocytes, liver or other tissues. The good news is that the antiviral drugs will eventually seek them out. Cirrhotics may need extra time for this.

It has become increasing obvious that treatment stirs up our immune response, so we can cope with some residual virus even after treatment has finished. HCV RNA has been found in post-SVR patients, but this is no longer a concern. Cheers.

---

One of the most informative posts ever. Thanks Mal.

Hi Matt,

You know that HCV has been found in virtually every tissue. Whether replication takes place is uncertain. The usual criteria for replication is the presence of negative strand HCV RNA in cells.

Only dedicated PCR tests can distinguish between positive and negative strand HCV RNA. Over the last few years, researchers have often failed to agree.

We know most replication takes place in hepatocytes. I think it is now accepted that replication may occur in peripheral blood monocytes, and probably in lymphoid tissue. Bone marrow cells, such as dendrocytes, are often mentioned.

As you say, Undetected means just that. No virus can be DETECTED in peripheral blood. It still may be present in tiny amounts, or be in monocytes, liver or other tissues. The good news is that the antiviral drugs will eventually seek them out. Cirrhotics may need extra time for this.

It has become increasing obvious that treatment stirs up our immune response, so we can cope with some residual virus even after treatment has finished. HCV RNA has been found in post-SVR patients, but this is no longer a concern. Cheers.

 perfectly valid question....

i shall research and follow the clues to find the replication site or sites....

any1 would assumingly say it replicates in the liver.. because it attacks the liver but i bet its a little deeper then that...

keys and doors... find em

Have you ever wondered where the HCV replicates within your body?  I have asked multiple Doctors, read books that have made statements and heard other strange answers.

What do you think?  Where is the Virus Hiding?

It seems very important to recognized that the replication process takes place somewhere other that our blood. When a patient achieves UND status during treatment be it week 2, 4 ,6 its a great indicator that our body is responding correctly to the meds. But there is more to be accomplished, because many patients have relapsed after achieving UND. The drugs have to reach deep inside our bodies and our livers find the all sites that have active replication even the sometimes hard to reach sequestered areas. We know it can be done even with cirrhotics at a very high percentage if they are under treatment long enough. 

One of the very crucial things we learn from this is staying compliant to the dosing schedule or adherence. Seems obvious but its one of the reasons patients fail to achieve SVR 

I bring this thought up not to be fear mongering but to make us aware that achieving UND during treatment is just one of the steps towards a permanent cure. 

matt