TOPIC:

Question One:

"What does this test mean?" This question is accompanied with test results such as:

HCV Viral Load (Log IU/mL) <1.18 NOT DETECTED

Answer: This is the very best news.

Undetectable means that hepatitis C is gone, and presumably all gone. The confusion over this test is because viral load tests don't measure down to zero. Further, viral load tests vary. For instance, the Abbott RealTime HCV assay (assay is a fancy word for a test that determines and measure the ingredients of something) measures down to 12 IU/mL in a 0.5 mL sample of blood. This means that if you have 12 IU/ml of hepatitis C (HCV RNA) in your blood, the test will detect it and count it. If you have less than 12, the test might not see it, and if it does, it won't be able to count it. .

Each test has its own detection range, some lower than others. The main thing is this:

"Not detected" = negative for hepatitis C
"Detected" or an actual number of how much HCV RNA you have = positive for hepatitis C

If you are concerned that you may have some residual HCV swimming around in your body, hoping to set up shop in your liver, rest assured, as this is quite unlikely. Hep C replicates a trillion times a day, so "not detected" might as well be zero. It is extremely unlikely that a small amount of HCV will remain alive in your body without having replicated to much higher amounts. In fact, viral load tends to replicate at much higher numbers when treatment fails.

Question Two:

I am on treatment with Harvoni. My pre-treatment viral load was X million. My week 4 (or week 8 or week 12) viral load came back detectable. I am devastated. Should I be?

Answer: No.

In the old days, back when treatment was long and used interferon, there were clear milestones that helped us know what our chances were of permanently clearing hepatitis C. Ignore all of that. New research funded the NIH Clinical Center showed that low levels of HCV RNA at the end of treatment are not predictive of treatment response among patients with hepatitis C virus treated with interferon-free regimens. (Clinical Infectious Diseases, March 2, 2015) In fact, low levels of HCV RNA detected at the end of treatment, and even post-therapy, do not signify treatment failure.

Here is a bit more information. Sidharthan and colleagues enrolled 114 subjects with chronic HCV/genotype 1 and no prior treatment. Six patients with detectable viral load at the end of treatment achieved a sustained virologic response (SVR12). You can read more about it: Utility of Hepatitis C Viral Load Monitoring on Directly Acting Antiviral Therapy - S Sreetha Sidharthan, et al.

The bottom line is that a detectable viral load at the end of treatment DOES NOT mean that treatment failed when using Harvoni-based treatment.

Important:
Don't despair if you have detectable virus during or at the end of HCV treatment.
Be sure your doctor doesn't stop treatment just because you have detectable HCV RNA. The HCV guidelines recommend viral load testing after 4 weeks of therapy and at 12 weeks following treatment completion. If quantitative HCV viral load is detectable at week 4 of treatment, repeat viral load testing at treatment week 6. If viral load has increased by greater than 10-fold on repeat testing at week 6 (or thereafter), then discontinuation of HCV treatment is recommended. There are no other recommendations to stop or extend therapy based on viral load results.

Here's my non-medical explanation of the difference between UND and < 15.

* Once we get down to a very small numbers of virus particles, it is no longer a question of medicine or even biology. It all comes down to chemistry, equilibria, and probabilities.

Anyway, I'm not a doctor, but I do know a bit about chemistry and biology, so here goes:

* Its important to remember that both quantitative and qualitative HCV RNA tests measure the amount of RNA from the virus in the bloodstream. They do not measure the number of actual virus particles (virions). The viral RNA is just one part of the package, so to speak.

* The qualitative test gives a yes/no answer, but a quantitative test gives a numerical count, unless it is less than about 15 units, in which case it is a yes/probably answer. But for someone on DAA treatment it is more like a "no" answer. Or more precisely, a "going to be no" answer. Confused? Don't be!

* We normally think of the virus as a solid particle, but in fact it is better to think of it as a population of particles. Some of them are useless, some of them are falling apart, and some of them are spontaneously re-assembling into new viral particles again. But most of the time they just fall apart naturally. Otherwise, they would be perfectly harmless. So when a blood test detects viral RNA, it is actually detecting bits of RNA from those particles that just by chance have fallen apart at the time of the test.

* Clearly, if there are no HCV virions present in the blood sample, then should be absolutely no HCV RNA present.

* But suppose you have just dropped a strategic nuclear warhead on a few trillion virions. Most of them will be absolutely destroyed (cut to shreds, vaporised, atomised, whatever).... But quite a few will only be cut to shreds and not vaporised. In other words, many of the viral fragments can persist for quite some time in the body (and so are still detectable), even though there is not enough of the right pieces to make new virus particles. So it is quite likely that very low but still "detactable" levels of HVC RNA can mean no viable virions left - or not enough viral fragments are left to be able to spontanously re-assemble again, which comes down to the same thing.

* On the other hand, maybe a few virions might survive the nuclear blast intact. But if you are down to just a very few, it is unlikely that there will be enough of them to replicate because a whole sequence of "chance" biological events have to take place in order for the virus to replicate successfully. And in order for that to happen, there needs to be enough copies of the virus (i.e. enough viable virions) in the first place so that all the necessary chance transfers and collisions and biological/chemical reactions can take place... And if you are down to just one virus particle, there is a very good chance that it will just fall apart and none of its components will ever arrive in the right place to re-assemble or to carry out the replication process. So once you are down to the last few stragglers, there is a good chance the virus will disappear naturally.

* And also don't forget that once infected, the body has developed antibodies which hunt down and destroy most of the virions on a daily basis... The problem with chronic HCV infection is that the speed of the hunt-and-destroy process is about the same as the speed of the virion replication rate, so the body never manages to clear the virus by itself. But the nuclear blast does not affect the antibody system. So again, very low but "detectable" HVC RNA means a high probability that the virus will clear because the antibodies are still busy with their (less than perfect) detect and destroy mission...

* This all means that it is quite possible to have "detectable" but very low (or even "unquantifiable") RNA tests all the way during treatment, and then only becoming "UND" several weeks or (even months) after the treatment has finished.

Me, me viral load was < 15 after 4 weeks. So I am pretty confident that I will eventually become "UND" in a quantatitive PCR test. But it is just a matter of time... Oops, I mean it is just a matter of chemical equilibria... and at the end of the day, this means just a matter of probabilities....

So to cut a long story short, my (non-medical) advice is also if you get to < 15, don't worry! You're well on the way to "UND"... But nobody can promise how long it will take...


www.questdiagnostics.com/testcenter/test...c=TH_HCV_RNA_QualTMA

www.hepatitis.va.gov/patient/hcv/diagnos...litative-testing.asp

www.researchgate.net/profile/Barbara_Reh...0cf240f04d0fbff3.pdf

Thanks Vororo, very well explained.




......it would seem young William learnt more at scuil than he lets on to his teacher.

splitdog wrote: The way I understand it, 'Quantitative' testing determines the actual number per ml of bloodborne virus. However, it is only accurate between 12 and 10,000,000. The 'Qualitative' testing is far more accurate, but can only determine present/not present. So you use quantitative to see how you're doing until <12, then do qualitative to see if it goes all the way down to undetected. (zero). Dr. Freeman?

Hey splitdog, pretty much. Check out the Doctor's cheat sheet link for a summation

Monitoring

Now the patient has access to the medications here is what monitoring on treatment looks like:

Baseline FBC, Cr&E, LFTs, Hep C Viral Load with reasonable currency + AFP and liver ultrasound for those with cirrhosis (looking for HCC)
4/52 into treatment FBC, Cr&E, LFTs, Hep C Viral Load
Repeat Viral Load at 4/52 intervals if not zero at 4/52
EOT (End Of Treatment) exit bloods

Hep C Viral Load can be quantitative (undetectable, <15, or 15-100,000,000) or qualitative (undetected/detected).

fixhepc.com/getting-treated/how-to-do-it/doctors.html


Thanks too for the great exposition Vovoro, very well explained

Thank you all. A lot of very useful information.

I have the next GP appointmnet in 2 weeks time and will get another blood test request. At that point I will be nearly 7 weeks.

I will possibly request Qualitative teast then.

fixhepc.com/forum/experts-corner/559-do-...d-if-below-lloq.html

Week 6 tomorrow.

Started to feel fatigue again and fall a sleep for an hour after work. All evening I spend on the sofa.

Lightheadedness still the issue, which I had before tx, but increased since starting tx.

Feel freezing all the time, starts from the legs and hands.

I plan to get my next blood test next week and will post my update here.

Hi Dan, I was just thinking about you and wondering how you were getting on.

Have you talked to a Dr re these side effects /symptoms?
Are you taking any supplements?

Sorry to hear you're suffering, Maybe you should get some time off work ? even a long weekend?
Get some rest.

It takes time m8 hang in there. 4 weeks next to no liver pain for me todays its back so I guess its just a roller coaster ride all the time

My doctor referred me to the neurologist, not sure when this will happen.

My next GP appointment is next week. I get the usual reply. Your blood test is normal. You need to clear your Hep C.

Emailed MonkMed few times after Christmas, but they are very slow to reply at the moment.


I started to get B complex twice a week from last week and Vit D from yesterday, just received it.

Have you started your tx LG?

Dan, have you shared with Dr treating you that you are in fact taking medication
for Hep C?

I emailed monk med and have had replies in a very timely fashion if you're planning on continuing
treatment with them as your provider you have to go through their process.

Apologies if I have both wrong.

Just wrote you a long post & the server was reset - Grrr
Do you check yr BP regularly? Ask nurse & or GP every time I'm there & they seem happy to take it.

Yes, I'm on tx, I've posted - So far so good, but early days yet.
Lower back pain returned, but I knew it would , all manageable. like you I get v tired in the evenings.
Mornings are great though.

Think Dan is on Twinvir Sirch

Hi Dan I have just been reading your blog thanks for your information about your tx so far I started yesterday on sof/led and am as skinny as too like LG and Zhuk
Re the BP are people in general getting this checked regularly and why? Mine has been all over the place since peg/inf and I take a low dose of coversyl to keep it kinda okay
Just wondering what the general advice is to us on these DAAs
My heart is feeling a tad excited but that's probably general excitement because I just started or is this also something people watch?
Sorry for all the questions trying to do this the very best I can and learning from other people helps us all I guess x
Thanks and wishing you well
Ariel

Sir
Yes, I told my GP that I'm on Twinvir and he agreed to monitor me. My hepatoligist appointment is only at the beginning of March, which will be 12 weeks and I told him in November, that I'm planning to get Generic tx.

I emailed Tim today as well, but didn't get a reply yet. As I said, before Christmas I was getting instant replies from them.