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TOPIC: How can the virus reappear after UND

How can the virus reappear after UND 6 years 3 months ago #10498

  • Dan
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Hi.

I wonder if anyone can give me an answer. On tx we all reach UND, which is the virus not detected, but how can some people relapse.

Where is the virus coming from?
Gen 1b, F1-F2. Naive.
Started Twinvir tx on 2 nd of December 2015 for 12 weeks.
Starting VL 400000, Alt 49/AST 44
1 week VL 29, ALT 44/AST 30.
4 weeks VL 12, ALT 33, Platelets 145, all other tests normal.
7 weeks VL Detected, ALT 28, all other normal
8 weeks UND, 12 week UND, 24 week SVR UND
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How can the virus reappear after UND 6 years 3 months ago #10502

  • Enkel
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Being UND doesn't mean that every virus is killed. some viruses reside deep in the body. Some viruses may hide. But this is not the case with the new treatment where many have been detected at EOT and still cured.
Male, Fibro F1. Geno 1b. ALT 67 before treatment Viral load 5 million. My huge viral load replicates in my nervous system as I suffer anxiety.
Started Twinvir 12/12/15.
Two weeks
ALT 17 at 2 weeks
Viral Load UND at 2 weeks
ALT 13.5 at 7 weeks EOT
ALT 10.5 at 15 weeks EOT
ALT 13 at 27 weeks EOT, VL UND, Cured
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How can the virus reappear after UND 6 years 3 months ago #10503

  • Sirchinenge
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Well, like I said in the previous thread, best I can see the majority who fail don't reach UD during
the 12 weeks they are usually 12 throughout then post treatment the virus is no longer being
suppressed via medications therefore it comes back.

There is a small percentage, I mean tiny who are UD during the 12 weeks and the virus also
comes back they don't know why, these treatments are new its gonna take some time to figure out
why some maybe resistant to treatment.

Lastly, they have being retreating those who fail with success it seems these people react better
to extra DAA.
Sob/Dac from Oct 29 2015
Geno 1b
Fiberscan 9.9 Pre treatment
Fiberscan 7.4 week 10
VL 1.3 million pre treatment
Week 2.5 VL 96
Week 5.5 VL 17
Week 10 VL UD
SVR 3 UD
SVR 16 UD
Cured:
All liver functions in normal ranges.
Last Edit: 6 years 3 months ago by Sirchinenge.
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How can the virus reappear after UND 6 years 3 months ago #10531

  • dointime
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best I can see the majority who fail don't reach UD during
the 12 weeks they are usually 12 throughout

I don't agree Sir. People do routinely reach UND without all the virus being gone. The PCR test just isn't sensitive enough to detect what's left. If we had a test that really could detect every virus then it would be much simpler. We'd know when we got the UND result that we could stop tx.

dt
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How can the virus reappear after UND 6 years 3 months ago #10536

  • Gaj
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Agree dt,

UND doesn't mean 'None there!', rather it is 'I can't see any?'.
and the test can't determine whether the RNA it can see is viable or not which is why some who are still detected at EOT go on to a SVR.
Then there is the question of whether some who 'relapsed' may have actually been reinfected post treatment?
G3a since '78 - Dx '12 - F4 (2xHCC)
24wk Tx - PEG/Riba/Dac 2013 relapsed
24wk Tx - Generic Sof/Dac/Riba 2015/16 relapsed
16wk Tx - 12/01/17 -> 03/05/17 NS3/NS5a + Generic Sof
SVR7 - 22/06/17 UND
SRV12 - 27/07/17 UND
SVR24 - 26/10/17 UND
:cheer: :cheer: :cheer:
Last Edit: 6 years 3 months ago by Gaj.
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How can the virus reappear after UND 6 years 3 months ago #10744

  • DrJames
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Viral load tests are imperfect.

There is very little viral RNA to to count it we use something called Polymerase Chain Reaction - this amplifies the quantity to something we can count.

The Lower Limit of Quantification (LLOQ) may be 30, 25, 15, 12 or 10 and virus that can be detected, but is at a lower level than this results in a <30 detected, <25 detected, ... <10 detected.

The Lower Limit of Detection (LLOD) is the smallest quantity that can be seen. A test with LLOQ <15 will have an LLOD of around <6 so RNA in the range 0-5 will come back as undetected.

When we see the rapid drop in HCV RNA this is all the easy stuff being killed. The problem is the mutants which are present in low levels. They are present in low levels because they don't grow as fast, but kill off all the faster growing stuff and you are left with the mutants.

Think of it like pulling all the plants out of a garden to leave raw earth. Pretty soon weeds take over the empty space.

So recurrence comes from hard to kill mutants that were present below the LLOD at the end of treatment. In other words the undetected was really "can't detect with the sensitivity required". For this reason we over treat everyone. 8 weeks Havoni for GT1 naive with low fibrosis gets at 121/123 SVR if the viral load is < 6 million to start with.

A high viral load is a negative predictor because it says 1) your body is not doing a good job killing it and 2) there are more virions, so more mutants.
YMMV
Last Edit: 6 years 3 months ago by DrJames.
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How can the virus reappear after UND 6 years 3 months ago #10745

  • isaing4
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Thanks Dr. James for your explanations!
Some mutants are hard to kill :woohoo:
Hope to kill them all! :evil:
HCV since I don't know. Diagnosed in 2010.
GT1b, F0/F1, VL 9M, ALT 44, AST 42, Tx naive,
started 12 wks Twinvir on 06.12.2015. Feeling great and grateful :)
virus not detected 06.02.2016 & SVR24
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Last Edit: 6 years 3 months ago by isaing4.
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How can the virus reappear after UND 6 years 3 months ago #10749

  • LondonGirl
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This has always been my instinct Dr F - and now you have given those little hardcore cells a name, 'The Mutants' :evil:

Wanting those mutants gone. I currently have flu, hope it doesn't make it harder to kill those evil mutants off.
GT1a Dec14 F2/8.7 VL 900000-2.5M
Jan16 Hepcivir-L MonkMed/Redemption
Baseline: VL 913575 Alt 76 Platelets low
Wk2 VL1157 Alt 23
DET Wk 8 VL 32 Alt19 'In the slow lane'
June16 Fibro 5.7 F0/1 LIF 1.5
Wk 11 VL<12 Alt 13 Det/Unq
Extending tx 12 wks Mylan Sofo/Dac MonkMed
Wk 14 VL <12 Det/Unq
Wk 16 VL UNDETECTED
Wk 22 + 4 Wks Sunprevir FixHepC
Wk 24 UNDETECTED Alt 13
Wk 12 post tx SVR12 Wk 26 SVR24
Thank-you Tim, Dr Debasis @ MonkMed & Dr Freeman @ Fix HepC
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How can the virus reappear after UND 6 years 3 months ago #10781

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Thanks Dr James
The test performed on me at Day 25 says measured in the assay range 30-100000000 and I came back as <30 but the doctor yesterday at the liver clinic called it "still detected" not UND yet?

I'm at week 5 now and have 7 to go with no liver damage and this first blood result is therefore good.

So my next path sheet handed to me is for the same clinic and the same requests
Does this mean it's always going to just come back <30 I am confused?

Or does this test somehow show up UND?
I'm attaching a screenshot of yesterday's result.
Thankyou James for this awesome medicine and your assistance with understanding this report
Ariel
Attachments:
Gen 1a
Peg/inf/riba 2012(!) stop @ Wk 43 potassium low +issues (rlps week 4 post tx, VL120,000) scnds eg. adenomas.
pre sof/led VL 240,000 Fibsc F0
Day 25 <30
Day 32 UND
Week 10 UND
EOT UND ALT11AST17GGT19
SVR4 UND ALT10 AST16 GGT13
SVR8 UND ALT <9 AST16 GGT15
SVR12 UND ALT14 AST19 GGT12 Bili 5
EOT +18 ALT13 AST20 GGT9 Bili 5
EOT +21 ALT11AST15
Cured SVR12
Dysplasia Adenomas RemvdAug '16
SVR24 UND ALT11AST16
ColonoscopyClear Nov17
LumpectomyClear ‘18
LithotripsyCytoscopyBiopsy 4/18
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How can the virus reappear after UND 6 years 3 months ago #11067

  • DrJames
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We discussed this privately but <30 mean old machine!

There is not an undetected or detected notation on this (which there is on most of the results)

Use a lab that does <15

The lower limit of detection is about <6 so anything in the range 0-5 will be undetected.

You need a real zero to clear but we can't measure that low, so we over treat by a working safe margin.

With GT1 for example SVR is typically 97% at 12 weeks (depends on your profile) but 99% at 24 weeks. To a government/insurance payer the extra 2% of not worth the extra 100% cost. If we just treated the 3% failures with 2 x the treatment length the cost only goes up 6% so it's a pretty logical decision to do 12 weeks and retreat failures for 106% when you weigh it up against spending 200% in the first instance to get there.

If you are privately paying you might reasonably decide that you would prefer 100:1 odds rather than 33:1 and opt for 24 weeks, but it is overkill for 97% and the last 12 weeks will be going into a body with no HCV.

Not an easy choice but you have to draw the line on treatment duration somewhere.
YMMV
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