thanks Malcolm

i wonder will they start considering VRVR (2w UND) as a factor for SVR outcome, same as they did with RVR. So many unknowns yet for long term SVR outcomes and scary stories about hcv leftovers in our bodies long after hcv replication stopped (or at least appears to be stopped). Was reading about other common latent virus coinfections that can affect SVR outcome (eg: common CMV coinfection http://www.ncbi.nlm.nih.gov/pubmed/21175794) and wondering can something else (beside destruction of hepatocytes and heavy coinfections like HIV) induce relapse of hcv at late stage of SVR.

Was amazed by the study of hcv patients reinfection with different hcv genotype and strange outcomes (both genotypes present in rare cases, but in most one genotype prevailed?), would be interesting if we could swap our hard treating genotypes for GT2 (without risk of having both genos)

best

Thanks Malcolm for the explanation.  It is important for SVR patients to understand this because it provides a motivation to still take care of one's body even after SVR (even though there are only a small percentage of patients in which the virus is reactivated after SVR.)

~

Carol

Carol, All this is interesting but not clinically relevant. It does explain why SVR's cannot donate blood, and should continue to take precautions like not sharing razors etc.  The continued viral replication may occur in hepatocytes, monocytes, macrophages and other cells. It's not significant as our body's immune system has 'learnt' how to limit the virus. As I've mentioned previously, post-mortems have shown HCV in many body tissues. As you probably know, HCV is not one virus, but a whole family of viruses with a very similar structure. These are the mutations that are found along with the most common structure ( called the wild-type virus). These mutations vary in their ability to replicate and enter cells. In time, the researchers will tell us whether the virus that persists is a dominant mutation, or the original 'wild-type' virus.

Hi Carol,

You got it!

Malcolm and Cinnamon Girl,

I think I am getting it, but let me know.  So, it's not that my husband's meds killed the viral particles, they just died off naturally due to their limited life span.  And the reason why his viral load is now undetectable is b/c the meds prevented those viral particles from reproducing.  Is this right?

~

Carol

Hi all,

Carol:  hope Jill's explanation has cleared things up. Remember a VL of 1.6 million i.u./cc means you have 20 billion viral particles circulating in your total blood volume. To replenish these, it is estimated that 1-2 trillion replications in hepatocytes must occur each day.

Loopy: Who knows what can trigger relapse. If the bodies immune system is compromised, the residual virus may re-activate. More research will be forthcoming. In the meantime, take our SVR and be grateful.

Zlikster: The stats on who will relapse after being Undet. at EOT are very sketchy. The most important predictor is the time it takes to become Undet. after start of treatment. Patients with an RVR have the lowest relapse rate. This outweighs age, weight,  fibrosis stage, IL28B status, viral load and type of treatment. Genotype is also important with Geno 2 having less chance of relapse, and Geno 1b has less chance of relapse than Geno 1a. Adherence to drug dosage is also mentioned, with the 80/80 rule being quoted ( you must be on 80% of the optimal dose for 80% of the time of treatment). This last one mostly referred to Peg and Riba. For the newer DAA's, this will soon be dropped ( and become 100/100).

I was given a 20% chance of relapse at EOT based on my RVR achievement. This was despite my cirrhosis, CT genotype, length of infection etc. I was told that would be 25% if I was Geno 1a. That's only my doc's experience.

Malcolm,

If in SVR patients the blood still contains tiny amounts of the Hep C virus, how could this be?  How is this small amount of replication still going on?

Hi Malcolm,

Thank you for the clarification. I must say your grand-daughter is very cute! :D

It is also confusing the data and information I have read on several papers that some people "relapse" years later with the same genotype. As only 10 million out of the 170 are registered as drug users, it leaves a big question mark as how they are re-infected. Anyway, the main thing is we all SVR.

Have a wonderful day. x

Carolinca wrote:

---

Hi Malcolm,

You stated in your post that the virus is not actually killed but is prevented from replicating.  This does not really make sense to me.  My husband's viral load before treatment was 1,600,000.  His viral load is now undetectable.  Therefore, it does seem to me that all of those viral particles were killed, or else they would have shown up in a current viral load test.

 

---

Hi Carol, to understand what Malcolm was saying you need to bear in mind that when someone is infected with Hep C there is a continuous turnover of virus particles going on, with new ones being produced and older ones naturally dying off because of their limited life span.  To put it simply, when a person like your husband is on treatment the effect of the medications is to interfere with the replication cycle and so prevent further viral reproduction from taking place, which naturally leads to a drop in the viral load.  Hope that helps!

Hi Malcolm,

You stated in your post that the virus is not actually killed but is prevented from replicating.  This does not really make sense to me.  My husband's viral load before treatment was 1,600,000.  His viral load is now undetectable.  Therefore, it does seem to me that all of those viral particles were killed, or else they would have shown up in a current viral load test.

~

Carol

Hi Malcolm

are there any stats of average relapses according to the liver damage, therapy length, GT, EOT +12w,+24w,+48, etc? I know EOT+12week is most critical period for relapses, but i have noticed people on this forum saying they had relapse EOT +24w and even 10years EOT?

just wondering how did they get that 1% as a stat?

cheers!

Hi Carol,

Not an easy question, so don't expect an easy reply.

Firstly, is our virus alive?  Many say it doesn't fit the definition of life. However, it has RNA and can replicate so let's assume it is alive. Each viral particle only has a 'lifespan' that lasts from a few hours to a few days.

Your hubby is on Interferon and Ribavirin.  Interferon has a complex action, stimulating the host response, interfering with HCV replication and preventing viral entry into cells. The action of Ribavirin is essentially unknown. Both drugs together may cause dramatic reduction in Viral Load. The virus is not actually 'killed' but is prevented from replicating. Replication usually only occurs in host cells ( hepatocytes), but whether the HCV can replicate in other host cells, such as blood monocytes , muscle cells etc, is still undecided. It can certainly enter such cells, and this may cause the non-hepatic manifestations of chronic HepC. .  The end result is that, for many patients (some Geno 1's and particularly Geno 2 and 3's), the virus becomes undetectable in the blood. For patients taking an Antiprotease, this is easier to explain, as the Antiprotease blocks viral replication, and the Peg and Riba destroy any drug-resistant mutations.

For patients with SVR, blood still contains tiny amounts of virus. Post-mortem results have shown virus in nerve, lymphoid, muscle, thyroid and other cells. Eventually we will find out whether this residual virus disappears over time ( years).

SVR is different from remission. Remission implies a disease is likely to reappear. In SVR, active infection only reappears in <1% of cases.

Hi Zlikster and Loopy,

We have hijacked Carol's thread so hope she doesn't mind.

Zlikster: All the things you mention affect the chances of achieving SVR. If SVR is attained, they are not important. I cannot find my best reference , but I include an older one which you may find interesting. It studies a large number of patients who completed Rx with Peg and Riba. All were Undet at EOT. 99% of relapses occurred in the first 12 weeks after EOT. Geno's 2/3 did slightly better than Geno1, dependent on the doses of Riba. There were no relapses between weeks 12 and 24, and after week 24, the chance of relapse was 1% after being followed for at least 3 years. The abstract from the Barcelona Conference last year, claimed 95% relapsed between weeks 4 and 8, and after week 12 and 24, the chance of relapse was again <1%. For that study, there was no statistical difference in relapse according to Genotype.

http://cid.oxfordjournals.org/content/49/9/1397.full

Loopy,

You are partly right. HCV is an RNA virus (Flavivirdae).  It doesn't combine with the host cell DNA and replicates in the cytoplasm of the host cell.  Many errors are made by the RNA polymerase leading to the many mutations that confuse our immune system.

HBV is a DNA virus (Hepadnavirus).  DNA is the storage for genetic codes. HBV combines with the host cell DNA and replicates in the nucleus. Because it can 'remember' what it 's structure is, it rarely makes mistakes (mutations). This stability is why vaccines are easy to make for many DNA viruses.

Herpes zoster and Herpes simplex are also DNA viruses. Because they combine with host cell DNA, this is why they can remain 'hidden' in nerve cells.  HCV can't do that.  It remains in the cytoplasm, and must replicate or die.  It may damage the host cell, but replication has only been proven in blood monocytes, which is probably why HCV  often has autoimmune disorders associated with it.

SVR '' relapse'' due to reinfection is a different story.   If an SVR patient shows up reinfected with a different Genotype, that's easy.  If the patient acquires it by say, sharing needles with the same person as before, he will turn up with the same Genotype and that's hard to include in statistics.   Complicated subject.

Zlikster, I misread your question. I do another post tomorrow with more details. It's bedtime here.

P.s. My new avatar is my cute grand-daughter, taken today.

Hi Caroline,

They now believe that the virus can be eradicated (cured). BUT, in some people the virus can remain hidden in damage or other organs and will return within a few months to a few years. This percentage is between 1-3% and very low. They're still not 100% sure if people become reinfected, but it in most cases the vl was so low they just couldn't detect it. Unless the body clears this naturally (15-30% of people,) we don't build a natural immunity and can become re-infected even with the same strain, hence the uncertainty. 

As the disease is newly recognized (90s), it is only recently they began to understand how the disease works. Hep C  affects the RNA rather than DNA like Hep B. This virus is a Hepacivirus a genus of the flavivridae family (dengue fever, yellow fever, West Nile fever etc). Now they understand how the disease replicates they have devised new drugs that are direct acting, breaking its ability to replicate. Hopefully this will reduce rates of people that don't successfully clear the virus for whatever reason.

Viruses are known to trick the immune system and hide in places hard to reach, one example is the Herpes viruses (Shingles, cold sores etc) that hide in the nerve endings. It is predicted that since the ground breaking work in understanding viral replication in H.I.V that within 10 years most of these diseases will be curable.

Hi,

So, when someone is on treatment, do the medications destroy the Hepatitis C virus or do they put it in remission somewhere in the body?