Just Received Lab Results - Comments Welcome (and needed)

Profile:

Female
Age 51
Dx with Fibromyalgia in March 2005 (Symptomatic with fatigue, pain, sleep disurbance, lowered cognitive functioning since November 2004)

Was out of work last year for 12 weeks due to above symptoms and am currently out again since Oct 6 for 12 weeks - symptoms above have increased plus nausea, lack of appetite and weight loss (40 lbs) since May.

Learned of Hep C Infection after donating blood in August, 2006.

First visit with Infectious Disease Specialist October 23, 2006.
Following are the results of the Labs done that day:

Protein, Total, Serum    7.8
Albumin, Serum           4.4
Bilirubin, Total         0.5
Bilirubin, Direct        0.16
Alkaline Phosphatase, S   78
AST                       33
ALT                       35

Genotype 3
V/L 1,930,000

When I saw the specialist he told me that if I was Genotype 1a or 1b he would order a liver bx (I took this to mean that if it was any other type there would be no bx).

He also said if V/L was more than 2,000,000 - would treat, if less than 2,000,000 would not treat.  The V/L is very close to 2,000,000 so I don't know how he will interpret it.

I have been so prepared to come back as Geno 1a or 1b that I haven't even looked at Geno 3 so I'm off to do some research.  My next appt is November 20th.

Any information you all have would be very helpful!

[painterlady13]

In my opinion and mine only for what it is worth.... I think you really do need to have a biopsy to determine stage and grade of the disease.  1,2,3,or 4 all should.  you could have a low VL and still have stage 3 which would determine a need to treat asap. or a really high vl but still at stage 0 and be able to wait to treat for a year or 2.  others will chime in here that I am sure are more knowledgeable4 than I. But that is the info I have been told from my gastro and the liver specialist.

[LindyK]

So is V/L of 1,930,00 considered low or high.

[avidreader]

Viral load is not a good indicator or liver damage. Your viral load  can fluctuate quite a bit but don't really tell you what the virus is doing to your liver. Your ALT's and AST's (tests that measure liver enzyme/function) look great, but . . .

Most docs will biopsy Genotype 1's because the treatment is so long (minumum 48 weeks) and the odds on 'clearing' the virus are only 50/50. Genotype 1's and their docs have to do a kind of cost/benefit analysis on whether treatment is worth the risks associated with the meds. On the other hand, many doctors won't biopsy with other genotypes because the treatment time is shorter and the odds of treatment success are much better. Having said all of that, I would suggest that you find either a hepatoligist or a gastro doc who has lots of experience in treating HEP C to consult with before you make YOUR decision whether to treat or not. I would be skeptical of a doc who makes his treatment decisions based on viral load. Keep in mind that most internists and GP's don't have the time or ability to keep up to speed on the newest finding about Hep C and best practices and better treatments for treating this disease are still emerging. Good luck and stay in touch. There is a lot of good information on this board.

[Kalio1]

Viral Load Equivalents per Milliliter (EQ/ML)
Conversion to Logarithmic Form

(Viral Load is how many viral particles per ML of blood)

*[HCV-RNA (qPCR)-negative] is defined as less than 100 copies/ml of Hepatitis C
viral RNA as measured by the National Genetics Institute assay.

200,000 to 1,000,000 low

1,000,000 to 5,000,000 medium

5,000,000 to 25,000,000 high

above 25,000,000 very high

[GrandOak]

Demand bx and new doctor, preferably a Hepatologist.  (for Biopsy see: http://www.hivandhepatitis.com/hep_c/news/2005/011905_b.html)

Decision to tx is ultimately yours.  VL seems a bit high.  While VL does not mean much more than an indicator of whether tx is working for most HCV patients, such is not the case for Geno 3's.
(see: http://www.hcvadvocate.org/hepatitis/factsheets_pdf/genotype_FS.pdf)

[GrandOak]

It is my understanding that the value of VL is the same for Geno 3's as for the rest of the HCV genotypes.  This fact was greatly emphasized by my doctor last week when I was yanked from tx because mine went from 72 mil to 1.8 mil to 2.9 and finally to 4.4 mil when I was yanked.  But then I am a Geno 1a and as such VL is only a measure of whether a patient is a responder, rapid responder, nonresponder, relapser, etc. with respect to tx for my genotype.

[Kalio1]

I wanted to agree with Avid. Although 2's and 3's are often encouraged to tx due to their improved chances of clearing the virus on tx, they are not as often encouraged to have a biopsy because they are treating. At my doctor's facility, they encourage all those who do not treat, regardless of geno, to have a biopsy but 2 and 3's who do treat not to get one because it isn't needed to make a treatment decision and the risk isn't worth your desire to know liver condition. Hopefully your doctors will see it differently and give you a biopsy. Some here who are 3's did get them.
I am a geno 3a, and I also relapsed after 24 weeks of tx. Had I known by having a biopsy beforehand my liver condition, it would have changed the length of time I treated. As it is, I did the 24 weeks, relapsed and now am doing a year. If I had known my liver was as damaged as it is, I would have treated for a year the first time and possibly saved myself 6 months of tx. So when they say "you are going to treat so you dont need one" tell him yes you do need one and you need to know your liver condition because it will be part of the information you need to decide how long to treat.

[avidreader]

Perhaps I should have been clearer. I was talking about using pre-treatment viral loads as an indicator for treatment. Your results stongly indicate that you were not responding to treatment.  I would imagine that your doctor's decision to discontinue the treatment was based on not wanting to subject your body to the potential risks and damage that might be caused by a treatment and protocol that wasn't working anyway.

[friole]

I always give my VL in IU's (international units).  I don't know what everyone else speaks in if they don't put the reference down.  On my LabCorp tests, IU is about 40% of copies (eq)

Table 1: Conversion Chart

Assay Conversion Factor
Amplicor HCV Monitor v2.0 (manual procedure) 1 IU/mL = 0.9 copies/ml
Cobas Amplicor HCV Monitor v2.0 (semi-automated procedure) 1 IU/mL = 2.7 copies/ml
Versant HCV RNA 3.0 Quantitative Assay 1 IU/mL = 5.2 copies/ml
LCx
HCV RNA Quantitatiive Assay 1 IU/mL = 3.8 copies/ml
SuperQuant 1 IU/mL = 3.4 copies/ml

Viral load given in IU

Giving the viral load in IU probably soon will replace all other ways to express the viral load - until recently it was expressed most frequently  in eq or Meq. But at the moment and in old lab reports a wide variety of ways to give the viral load still can be found.

The IU = International Unit for the hepatitis C viral load is a unit more or less arbitrarily fixed. Labs now can take part in international comparison tests using a calibrated sample and thereby normalize their results to an international standard. So, in the future results from different laboratories should be directly comparable.

For converting numbers from eq to IU and vice versa, different labs use different conversion factors, in the range from 2 to 5 viruses per IU. If you do not know the factor that your lab uses, using a factor of three might be reasonable. That means: Viral loads given in eq/ml have to be divided by three to get the viral load in IU/ml. And, viral loads given in IU/ml have to be multiplied by three to get the result in eq/ml.

[friole]

Standard treatment for Genos 2 & 3 is to not get a biopsy because treatment is shorter.  However, there are a lot of good reasons to go ahead and get that biopsy.  We have seen a lot of relapses on this board for 2s and 3s.  The biopsy will indicate steatosis (fatty liver) and that is important.  A biopsy may help you make decisions later on in treatment.

Another "standard" for 2s and 3s is 800mg ribavirin.  I suggest you tell the doc you want weight based ribivirin.
frijole

[LindyK]

Thanks to everyone for your comments.  I really appreciate it.  The doctor I am seeing is in a group of Internists who all specialize in Infectious Diseases.  Should I still look for a hepatologist or a gasto doc?

The V/L on my lab results was:

1,930,000 IU/mL  and  log10 = 6.286

The doctor specificaly said if your V/L is more than 2,000,000 COPIES he would treat.

I hope this make things more clear about the V/L.

I'm still a little confused about the V/L but understand the importance of the bx and treatment time.

I am just gearing up for my strategy in dealing with this doc.  I have only had one experience with him but at that time he didn't seem real open to discussions.

Thanks for all your help!

[friole]

Everything you ever wanted to know about viral loads

http://janis7hepc.com/Viral_Loads.htm

I am surprised that your doctor would say he only treats those with copies over 2,000,000 (which you do have).  We have seen a lot of people here who have viral loads under 1,000,000 IU and have advanced liver disease.

My beginning viral load was about 1,520,000 IU (3.8 million copies).  I thought it was really high until I found this forum and saw loads into the 10's of millions.  In Clinical Care Options the doctor says there is little difference between 10 million and 1 million (that is a one log drop) and they show you charts as to how the Vl bounces around

http://www.clinicaloptions.com/hepatitis/treatment%20updates/hcv%20core%20curriculum.aspx

you will get so much information - in the form of a slide show - I think you find it very valuable.  It takes about 20 minutes to go thru it and I learned so much.  You have to register but it is free.  It is a sight for doctors to earn continuing education but open to anyone.
frijole

[LindyK]

Thanks for the links.

So as I figure it then, I have 4,825,000 Copies of the virus.  So if the doc says we will treat for 48 weeks (as opposed to 24 weeks) should I still insist on having a bx?

[Hepatitis Researcher]

At National Genetics the VL is always reported both in copies/ml as well as IU/ml. The conversion factor is 2.5.
If your VL is 2000000 IU,  it is 5 Million copies. That is quite high. NGi actually normally only measures up to 5 Million. Liver damage occurs over a wide range of VLs. Normal ALT is good, but not sufficient to rule out substantial fibrotic disease. There is a whole group of HCV patients with PNAL (Persistently Normal Alts) that is constantly discussed in HCV Hepatology and they have statistically a lower chance of disease progression, but for an individual patient this info is not very useful.

HCV normally progresses slowly. Knowing where you stand is important, also how fast are you progressing ( there are slow and fast fibrosers). In a few years combo treatments will be available with a clearly increased chance to become a SVR across all Genotypes.

Kalio, how low was your VL at your first and second treatment after four weeks.

At the NIh Hepatitis meeting in spring Jean Pawlotsky said that only IU should be used in the future. A storm of disagreement broke from the audience. If you can count something like people or viruses then give the real number - not an artificial pseudounit.

[Kalio1]

Just to reinforce what Friole is saying, my VL was 730,000 and I have cirrhosis. a biopsy was not recommended and only when I failed the first tx did I find out how damaged my liver was. I'd also encourage you to discuss Riba dosage with the others. I did 800 the first time and it should have been 1200.

VL is not a measure of liver damage, it tells you how much viremia is circulating in your serum and gives you a number when you start tx to go by so you can see when you reach undetectable status. Other than it's value in seeing if tx is working, it doesn't tell you much.

[friole]

Lindy, either way - 24 or 48, I would insist on the biopsy.  I think he will want to treat for 24 weeks, with the option to extend to 48.  The other thing to push for is a PCR at 4 weeks.  THat, to me, is imperative.  The standard is 12 weeks but ask him for one at 4 weeks and if he says no, check with your insurance company.  They should pay for it if the doctor orders it, and that 4 week PCR is a pretty good predictor.  Some with 2&3 have even shortened their treatment to 12 or 16 weeks if clear at 4 weeks.  

One mr thing to push for is sensitive testing.  Find out which lab is used - LabCorp and Quest are the two most popular. The most sensative Quest test is the Heptimax and the most sensitive LabCorp is the QuantaSure.

Good luck
frijole

[Hepatitis Researcher]

4 week testing with most sensitive tests is indeed critical.If you are negative then , your chances to become a SVR are very high.If you are not neg by week 12 chances are very low. The most sensitive test is Labcorps NGI Ultraqual ( LC# 140609) limit 2 Iu per ml. For dynamic range Labcorps NGI quantasure is slightly less sensitive, but gives you quant results 2- 2000000 IU/ml ( LC# 140639)

[friole]

You seem to really know of what you speak! Are you a researcher with NGI?  I think only IU's should be given for viral loads too but am really curious what copies are in the first place.  Is a copy one viron?  If so, why are conversions different with different lab test?

Now I really want to know the difference between those labcorp test.  My doctor lets me pick the one I want and I would like to know what to ask for next time (which will be my 6 month post PCR).   You said ......"The most sensitive test is Labcorps NGI Ultraqual ( LC# 140609) limit 2 Iu per ml. For dynamic range Labcorps NGI quantasure is slightly less sensitive, but gives you quant results 2- 2000000 IU/ml ( LC# 140639)"

So this means the NGI Ultraqual - a qualitative test - is more sensitive than the Quantasure which tests to 2??????  Please explain.
Thanks, frijole

[Kalio1]

First round, I was  UND by week 12, at that time a year ago I didn't know the importance of requesting testing at week 4. This round, I was clear by week 4. I did double doses of IFN for a month and 1600 riba a day for that month. Then I went to 1200 and regular IFN doses.

Got my fingers crossed for good news this spring!

How about you? Are you treating?

[friole]

Isn't hind site grand?  Right about now I am wishing I did those full 72!  You re definitely reight about the low viral loads and liver damage.  It is down right scarey.

[Kalio1]

What scares me is doctors saying this stuff to patients. That and it is pretty standard to not do biopsies on geno 2 and 3. that is a dumb stance, they should encourage all to have a biopsy (and hurry up with the noninvasive "biopsies")I think the patient risk of NOT having a biopsy is higher than if they do. Here they are, shocked they have this illness then the doctor fills them up with misinformation. If they don't do the research their health can suffer the consequences. To me judging by low viral load or low enzymes is very risky. Once a doctor has given a pateint incorrect or false info, then it is much harder to get them to listen to "the facts" because they trust in their doctors. Oh it frustrates me so! Had one of the many doctors I was seeing over my back surgeries and other various problems I had diagnosed me right I might have saved my liver some. Every one of them misdiagnosed my symptoms because my enzymes weren't HIGH. I had so many CBC's during that time, I had a PCP, a neurosurgeon, a pain control doctor and an ortho! I mean, come on guys! I had to get dang sick and happened to move to a new place and got a new doctor who was fresh out of med school and he finally caught it. I never had a VL over 730,000 nor did my enzymes go more than slightly over "normal"  So when people depend on those numbers, I think they do so at their own peril.

[friole]

I was clear at 56 weeks when I stopped (and have been clear since week 20).  My doc doesn't seem to have anything to say about the increased enzymes.  I guess, in the long scheme of things they aren't too high but for me they are.   I will know soon...

[Kalio1]

Good to hear that. I know other things can make them go up some too. I think they fluctuate some just normally. That must be stressful. Hang in there, it's probably nothing to worry about.

[jmjm530]

The good news is you're a geno 3 and not a geno 1. The not so good news is that the treatment decision protocol outlined by your doctor doesn't seem to make sense.

Viral load at any particular point in time is not associated with the amount of liver damage. A 2 million IU/ml is more of a mid-range load, neither high nor load. Also, keep in mind that some of today's viral load tests can be off as much as an entire log, which is perhaps one reason only a two-log move is considered significant.*

In regard to biopsy, some doctors will biopsy only geno 1's and some will suggest biopsy for all genotypes. Part of the reasoning is that some doctors feel all geno 2's and 3's should treat therefore why bother to biopsy? Counter arguments run that you might not want to treat with little or no fibrosis and that even if you decide to treat knowing your fibrosis stage can be useful information on how agressive you want to proceed with treatment. To me, this is a personal decision. I would definitely biopsy if I was inclined to wait. An alternative would be to get a Fibroscan in either Boston, NY or Miami, if available.

Unless you read your doctor incorrectly, my suggestion is to get a second opinion from a hepatologist (liver specialist) on treating that does not rest on your viral load.


*Source http://www.clinicaloptions.com/Hepatitis.aspx
(Dr. Shiffman Slide Presentation)

[Hepatitis Researcher]

You touched upon a very sensitive and important question.This very issue was just hotly debated with Dr. Lai ( from Hongkong) Dr. Gish, Dr. Perillo at a satellite symposium in Boston.
Dr. lai has seen many Asian patients with mildy elevated ALTs and fairly low VLs in HBv that had substantial liver damage and would not have been treated by the current guidelines. It was also clear that these guidelines - re mono/combo acceptable viral laod limits will need to change very soon. Also : What is a "normal" AST/ALT. Not more than 25 for a male!
Anyway if you are below 500 copies you might mainly need to watch the situation or maybe get a better test to see how low you really are. Plus 6monthly US screening, Alpha-fetoprotein. Never forget : Liver cancer kills more HBV  patients than end stage liver disease due to cirrhosis.
Age, stage of liver fibrosis are important considerations.
Also when it comes to treat patients with low viral loads, cost and drug toxicity are issues as well as resistance.

[Hepatitis Researcher]

You have a sharp eye for detail. I have cofounded NGI and am the inventor of all these tests. But now I am working on advanced treatment options for people with hepatitis, since many still fail to control their disease. I run into this site since I am trying to elucidate the " Alinia paradox" - the fact that this ( very available drug) has enormous in vitro potency - but only 50 % HCV negativity reported after 24 weeks in the Egypt study.Doctors in the US are using it on a few dozen patients " off label" for HCV.Was hoping to find some VL reports from people in this site.Then I saw all these questions here and thought to help a little, time permitting. Problem is, that the inherent complexity of the issues does not allow a realistic answer within the constraints given in this format.
A copy is a virion. Period. Conversions are different, because the standards that methods use are not from one source or method. Thats how the IU came into existence. To measure a standard itself is very hard.     Best if a patient sticks with one method or lab so differences are more meaningful. For HCV in the end what matters is to go UND BY THE MOST SENSITIVE TESTS FAST.Does that mean there is no more virus in the body at this time? Of course not. It means, that if you reduce your virus within four weeks to " negative" that the mechanism by which you block its replication is working well enough to reduce adaptive mutant formation AND that you will then further reduce your whole body burden of HCV ( now unmeasurable,BUT STILL IN YOU)( thats why you continue to treat and cannot stop right then!. This process of "invisible' further virus reduction must go on until you have nothing but a few copies of virus left that have been so poisened in their genomic information  by the Ribavirin that they cannot raise against some immune control by T cells and maybe some antibodies.

The difference between the two NGI tests I mentioned? One - "the quantasure" is a combo of the NGI superquant with the NGI ultraqual combined with a poisson distribution in case you fall neg on the quant and pos on the ultraqual ( if you are between 5 and 100 copies/ml). Confused? Only if you are very close to UND you need an ultraqual or quantasure , otherwise the superquant is all you need. If you want further details, happy to explain on the phone, no charge, is pro bono work.

[Kalio1]

Thank you so much for your informative post and the work you do for all of us with HCV in developing these tests.


There are a few that visit here who have taken Alinia, maybe if you put Alinia in your heading they might see it and share their info. with you.

[jboyhk]

I am an inactive carrier of Hep B but also carry the HepC antibodies 8 yrs ago.

After I was tested positive, I was also tested for genotype and viral load (one dr did VL the other genotype). The genotype came back 2b but the VL came back undetectable.

I have had VL tests over the past 8 yrs and always returned negative.

No dr has been able to explain to me how the genotype test could have come up 2b with undetectable virus.

Is it possible that there was some error in the lab? It was done in 1998 with Speciality Labs.

[willing]

interesting..accuracy and interpretation of HCV RNA amplification technology is a regular topic of discussion here. While the reliability of TMA over standard reverse-transcriptase PCR seems fairly well established (eg Germer'03, Desombere'05), the reliability of the  real-time  quantification of reverse-transcriptase PCR(eg, Radkowski'05 seems not to be generally accepted by physicians, notwithstanding endorsements like Halfon'06. As someone who works in this field do you have any reason to believe the real-time quantifications are suspect?

[jmjm530]

Thanks for the information. Don't want to pry, but since you more or less told us who you are, your credentials plus your interest in Alinia, sound very much like someone a recent poster referenced in terms of some sort of Fibroscan research in California. Several of us, including myself, have already had a Fibrosca at one of the U.S. trial centers and would be interested to hear more about your work, if you are involved and if appropriate.

Thanks for any information you may want to share.

-- Jim

[Hepatitis Researcher]

Its easy to give speculative answers to this question. What matters is this:
If you were repeatedly negative for HCV - hopefully with one of the ultrasensitive tests like the heptimax or ngis ultraqual - then there is little reason to worry beyond those general consideratons for any long term UND HCV or HBV patient.

The genotype test is done either by LINE probe asay or by sequencing - both of which require PCr amplification first to get enough material for amplification.
PCR can sometimes catch a single virion - I do this routinely with HBv virions - single copy PCR- and maybe specialty was having a lucky catch. Once you amplify with success you can genotype even a single virion, or in the case of HBV can determine resistance mutations as distributed in single virions.I call this "cloning by PCR".
But then maybe your "positive Genotype at specialty was just a lab artifact - these do happen.
What is your HBV - if any measured- viral load?

To willing; There are many PCR tests around, but the quantification accuracy depends basically on the accuracy of the inbuild standards. You dont measure the virus - you measure the blacknesss of a dot or the optical density or the fluorescent intensity - it is by comparison with the standard that has an intensity of its own that you calculate the VL.
In the lower range the real time PCRs get problematic in their quantitative accuracy. What matters most is the sensitivity cutoff which is higher in tests with inherent background. RNA/DNA preparation matters too. The Transcription mediated Amplification (TMA) is about as sensitive as NGIs ultraqual. There are many papers comparing many methods.Stick with a test for quantification and then use the ultrasensitive ones above to confirm "UND".

[jboyhk]

Thanks for your quick response as I know you are busy.

I currently live in Hong Kong, and have always been worried that the blood gets somehow degraded when its shipped to the US. 2 dr's here insist that is not likely as they get positive results back from many patients.

Yes, I have done the UltraQuant tests the last 3 yrs and have come undetectable in HepC.

Also I just recently got tested for the HepB ultraquant and got undetected <500 cps. (Previously they used the less sensitive tests that can be performed in Hong Kong).

But that genotype test result always bothered me, but it was done back in 1998. Back then the sensitivity of the tests was only <2000.

[Hepatitis Researcher]

You are well educated in hepatitis issues.I saw your exchange with kalio1 ( another thoughtful person)   re teatment length, fast response etc and many other comments of yours. You must realize that this forum shows, beyond the friendly compassion that people here have for each other, a sad and strong need to explore and have questions that strictly speaking only their doctor should answer.And the questions are often asked without all the info needed provided. It is a good idea to send them back to their Drs, with some added ammunition.
I focus on the question what can be done for people whose treatment failed and in HBV what is the best treatment in a particular case. In HBV we could help now- but the confusion in the medical community is great ( And worse in the insurance community). Quite an experience at the AASLDs satellite meetings!

Treatment of fibrosis is one important isuue. Here we might be able to slow progression of liver disease even if the virus cannot be eradicated. Difficult because approved therapies are not out yet. What about patients that cannot wait?
I am also interested in the effects of NAFLD on liver fibrosis progression and what we can do for this group to slow or stop fibrosis progression. For this purpose I obtained the very first fibroscan in the US, two years before Eugene got his (and I trained and got certified in Paris for this purpose). Strictly for research, since it is not FDA approved. You have to know how to use and interpret its readings however. Thus it might take a while before FDA approval is given since the original idea was to have the computer evaluate each of the 10-20 elastograms the machine generates.  When you had your Elastometry done were you fasting? Was it done at Dr. As lab in Boston?

[jboyhk]

Are you a believer that in HBV you should keep the virus levels as low as possible even if you have normal ALT/AST and E antigen negative?

My dr here, although treats hundreds of people with HBV, will only change his way of thinking if the recommened protocol is changed. He never wants to be ahead of the curve.

[jmjm530]

I certainly agree that nothing here should substitute for a treatment doctor who has not only the professional training but access to the patients complete medical records. Even non-treatment related information on the internet is often suspect and wrong. Unfortunately, if you've spent enough time here, you will come to understand that many of the doctors treating this difficult disease are also in need of more updated treatment information and frequently do their patients a disservice.

All we can do here is as you say, send folks back to their doctors with added ammunition which hopefully will add positively to the treatment equation. What both those being treated and what their doctors do with that information is another story. In some cases the best course seems to be to switch doctors but that's only a decision the person treating can make.

What do you tell someone who is a stage 3 or 4 with a three point hemoglobin drop in the first two weeks of treatment who is short of breath and ready to quit? I think suggesting they talk to their doctor about the rescue drug Procrit is a responsible thing to do. You'd be surprised how many doctors don't even use rescue drugs in spite of the recent studies. So what do you tell them when their doctor says he doesn't use them and is going to stop the riba instead? Many of us at this point suggest they consult with another doctor.

On a personal note, I've been to the very best doctors since the early 70's. I'm sure you're familiar with the late Dr. Sheila Sherlock. She reviewed my first biopsy slides. Dr. Sherlock is representative of the doctors I've seen. Still, there's still a lot of guessing even at the top. Dr. Sherlock was wrong on my prognosis -- she said it (called "chronic persistent hep then) would "burn out" in 5-7 years, and it just points out that everything has to be questioned. I think it prudent for everyone here to check and double-check all sources -- what they read here, what they read in other discussion groups, and even what their doctors tell them. I do.

-------
Regarding the scan. I was scanned twice, once during treatment and once five months post. I was never given instructions regarding fasting and frankly can't remember if I ate or didn't before the scan. First scan correlated with a very high stage 2 and the second with a low stage 2. I was also told there was no clinical benefit of scanning more than once a year. This appears different from the protocol a lady poster recently discussed which may or may not be used by your organization. I think she mentioned monthly scans.

I would be interested in your comments on both the fasting and the need for monthly scans. My understanding is that the U.S. trials are going very well and that FDA approval is around the corner, hopefully meaning we will have fibroscan devices more local in the not to distant future. I can certainly understand how useful a non-evasive device like Fibroscan would be to a researcher like yourself experimenting with a soup of different treatments like Alinia. After all, most people don't want a needle stuck into their liver every 6-12 months :)

Thanks for taking time out to participate in these discussions.

-- Jim

[jmjm530]

While you're here, I'd love to get your take on Mitchel Shiffman's slide presentation "Hepatitis C: Epidemiology, Diagnosis and Treatment" at the Clinical Care Options website. Specifically starting at slide #24 where he talks about the inherent variablity of quantitative HCV RNA assays.

If I understand him correctly, these assays can vary up to a log (1/2 log in either direction)for no other reason than testing variablity. Now, at very low numbers such as 10 IU/ml, a half log variation isn't very much, but let's say someone has a viral load of 600,000 IU/ml. A half log variance could mean their viral load actually is 3,000,000 IU/ml, or conversly much lower.

This type of variablity seems to have implications in determing pre-tx viral load and its implications. So if this variablity exists, how do so many studies seem to agree that pre-treatment viral load is a good predictor of response given this testing variablity? Using the above example again, how can 600,000 IU/ml be a useful cutoff point for low viral load given what appears to be such a variablity? Or does it just statitically work out that way with very large numbers of patients?

Hopefully, this link will take you to the presentation, otherwise you'll have to search under "Shiffman".
http://webcasting.clinicaloptions.com/p41111200/

Thanks again for your expert input.

-- Jim

[Eisbein]

Hopefully you stick around for a day or two.
You just might be the right person to ask.

We have several members here, myself included, who at some point during tx became PCR pos, after having been neg at prior PCR's.
I got a pos PCR at 20/IU using LabCorps HCV Quantasure Plus by Taqman (real time PCR technology, measuring down to 10 I/U.

I spoke to one of their big heads, don't think it's a good idea to mention names, but it starts with an S and ends n, and he insisted, that false pos are virtually impossible with this methodology.
But my doctor, who has devoted his life tx HepC patients (4000), insists that he has seen false pos with every lab, even the best.

Could you please comment. Is this contamination of the equipment?
On second thought this may NOT be such a good idea to ask you, an insider,LOL.


Anyway, after that questionable pos result I started using NGI QuantaSure, and occasionally Heptimax.

I am 9 month SVR, and not sure which qualitative test to pick from NGI's menu. My doctor also lets me pick my own.

Ina

[Kalio1]

Sorry I missed your posting of your enzymes until after I posted the above. Sorry about that, that is odd. What does the doctor say? Didn't you have a clear PCR post tx yet or am I mixing you up with someone else?

[jmjm530]

On a similar note, I heard from very well repected clinician/researcher that he stopped using Heptimax because of what he believed to be some false positives, I assume in the TMA portion of the test. Because of this, I switched from Heptimax to Quest's
HCV RNA Qualitative TMA using the Bayer Versant technology. Actually, I did both (Heptimax and Versant) the first time and then for my six-month post tx test only used the qualitative. Could you comment on false positives and/or accuracy of the quantitative TMA portion of Heptimax versus the HCV RNA qualitative. Both go down to 5 IU/ml. Thanks.

Ina,

Don't know if you saw my post below but broke down and had some soy sauce with my sushi last night :) Been off bread and hopefully all foods containing gluten for about a six days. Not sure if it's helping my stomach other than I'm losing some weight. LOL. Also, been thinking of seeing a doctor of TCM about some herbs for my post tx problems such as skin and digestion.

-- Jim

[Hepatitis Researcher]

RE CONTAMINATION; In the old days we used special pipettes, negative Air rooms and more gadgets to avoid post PCr product to prePCR testing material contamination. When I read that the Mayo clinic had just opened a facility with nice room separations neg, air etc for HCV I was smiling, because I had based NGI on the fundamental concept that there is only one way to really prevent postPCR contamination: Half a mile of city air in between labs, Zero contact between personnel, one way visitors only.
Labcorps Taqman test is not done at NGI and i do not know their precautions in any detail.
You are 9month post tx and neg so far on sensitive tests. That looks good. The proper test for you from NGI/Labcorps menu is LC# 140609 NGI HCV Ultraqual.

[Hepatitis Researcher]

Re Sheila Sherlock - yes - historical figure in Hepatology. Was that a chronic HCV biopsy she was looking at?( Sorry, dont know your personal hepatitis data) In Medicine, even the uttermost genius can only build upon the technology available around them. Sometimes it takes new technology to tackle critical problems, like e.g. to measure HCV in the blood of people. The hepatologist has to wait for a molecular biologist to develop such means - then a new world of testing, understanding and treating can unfold. I am deeply interested in the borderline issues of HCV and HBv  like intrafamiliar spread, stabiity of SVR, optimization of treatment approaches, speed of progression  etc. You are right that everything has to be questioned. But then who has the answers - often nobody -and action ( like some form of Tx) is still a pressing need.
When I spoke at the AASLD to the Echosens people - they are not yet aware for the need to be fasting for reproducible results. It is not part of the official protocol. What I found is the following ; In patients who had regression of fibrosis or cirrhosis it seems to matter more how engorged the liver is because some remnant fibrous strands might get pretensioned by the engorgement that follows a meal ( All the increased intestinal blood flow  has to go through the liver!) Then, when the elastic pulse wave hits along such a fibrous strand you get dramatic stiffness. The Fibroscan measures the speed with which this elastic wave propagates which can be very high if local remnant strands are hit. If the liver is relaxed, like in the fasting state, there is no pretensioning and the average collagen content of the parechyma determines wave velocity.

How often to scan: Easy answer to that one: When there is reason to fear that your fibrosis has intensified ( flare up etc) or hope that the treatment has reduced fibrosis you want to know where you stand. Severe fibrosis can develop in several month of intense hepatitis ( or take 20 years to develop in some) Thus it all depends on the circumstances that might have induced a change. Once a year is a good guess some might need more frequent intervals.

The issue of measurement variability in VLs is also important but difficult to discuss in this format. Quality control is the critical issue here and at NGI I introduced four independent PCrs for each sample at different cycle numbers to increase the reliability of quantitation.
Treatment decisions should not be made based on placements of Vl in the midrange. It is after all the inflammatory response to the presence of virus proteins  in the liver that causes the damage and stellate cell activation to increase collagen production and fibrosis which impedes diffusion in the Disse space making it harder for the liver to process the portal blood and the distortion in architecture of the lobulus. Vl is not linearly related to inflammation, although there are some connections - because the immune activation in the periphery is caused by virions travelling to these peripheral lymphnode sites.

[Eisbein]

Thank you for your response and suggestion.

Would you kindly clarify several issues.
Like you said,the NGI Quantasure # 140639 is made up of three portions...Super Quant, Ultra Qual, and Poisson.

I read that NGI was the only Lab in the US to get FDA approval for a test that was used in testing the National blood supply.
This FDA approved test was not approved for commercial use, but NGI uses the same approved methodology in it's Ultra qual, which is part of the Quantasure.
Did I understand this correctly?
Makes me feel better to know that I am having a test done that was sanctioned by the FDA.
-------------------------


Jim
I am beaten up from the biopsy today. I catch you another time at another post.
This thread is filling up, and it's best to leave room for researcher. When a visitor of this caliber comes by, we got to pick his brains before he silently disappears LOL.
He may be gone already.

Ina

[willing]

thanks for your reply, though perhaps I didn't put my question clearly. I was hoping you might give us some insight into a question that has been puzzling patients on this forum for some time. There is a growing discrepancy between on the one hand researchers who have reported detectable HCV RNA (+ and - strand) in liver, PBMC, macrophage and other cells extracted from patients who were UND in serum tests (either SVRs or treatment naive) and other researchers who dismiss such results as spurious/insignificant. There seem to be about a dozen recent papers in the former camp, including the Radkowski one linked above and others by Pham, Castillo, etc. The camp that is skeptical that serum-UND infection represents true infection seems to reflect prevailing opinion and includes prominent names in the field (eg Pawlotsky who you mentioned above).

Among the reasons given for dismissing serum-UND infection as true infection perhaps the most puzzling one, and the one I hoped you would give us your opinion on, is the reliability of the measurement protocols. The only differences seem to be that those reporting serum-UND infection examined cells rather than serum and that quantification was based on real-time PCR. However neither of these differences of themselves would seem to make their findings questionable. Perhaps the findings can be dismissed as contamination, but given the number of independent confirmations that seems an unlikely explanation. (Of course the "clinical significance" of serum-UND infection is a separate issue from its existence).

[jmjm530]

Thanks again for the info. Yes, SS was quite a figure, and I remember my hep doc at the time spoke of her in hallowed tones even though he was considered one of the best -- if not the best -- in this country. On good behavior I consider myself quite personable yet there seemed to be a wall of intimidation around the little lady that didn't allow you to speak unless spoken to. The slides, blood work, etc, she reviewed were for what was latter to be called hepatitis C, but in those days it was called "Chronic Persistent Hepatitis". The prevailing opinion then -- confirmed by SS -- was that if it Fibrosis didn't progress rapidly, the virus would burn out in 5-7 years. In my case, my initial biopsy was stage 0. Forgot if she was called in for my first or second biopsy but the thought was my fibrosis was not progressing therefore the outcome was good.
And, of course you are correct, one can not be held accountable for the technology of the day and I in no way meant to infer she made a mistake given the technology of the time -- as many doctors do, just read some of the posts here :) Bad analogy on my part.

Regarding some of the "Occult" and "Persistent" virus issues Willing discussed. I believe I have a good preview of your answer from your comments in the thread below "SVR for 4 years and now the Dragon is back". While I have not reserched this in the detail Willing has, I did discuss the issue with two well-known hepatologists I consulted with and I'll try and paraphrase what they said as best I can.

The first suggested that whatever viral particles were found were not fully "mature" -- my word -- and therefore of no real threat or consequence. The second questioned the actual methodology and said that none of these studies have been reproducable using methods commonly accepted. And of course, even in the other camp, almost all the studies have the disclaimer that no clinical significance has been demonstrated. I certainly don't pretend to have the answers on this and can only relate what I've been told so I'll leave it to the clinicians and researchers to battle it out and hopefully the future will tell more.

I added "DD" to the post which abreviates one of our member's moniker, "Double Dose". Double Dose is very intersted in intrafamiliar issues, specifically hepatitis-like symptomology within families where someone is HCV serum positive and the other symptomatic members are both serum and antibody negative.

Lastly, since you seem to be an outside of the box kinda guy, are you familiar with what I believe has been termed "pulse" therapy. It's where they administer peg and riba until the patient becomes non-detectible and then stop treatment immeditely be it one week, three weeks or twelve weeks. Then they monitor vl weekly and only start the peg and riba when vl is detectible. In theory this cycle is then repeated until SVR is attained although as of the last time I spoke to someone on this issue, no SVRs so far although apparently they have gotten people non-detectible for up to 3-4 months. My understanding is that these researchers feel that another agent in addition to peg and riba may be needed to prevent these relapses. The neat thing about this approach is that in theory it can potentially significantly limit the exposure to the treatment drugs and at the same time give the patient "rest" periods (when they're off the drugs) during treatment which from personal experience could be quite a relief both physcially and mentally. There was a study on this some time ago but most of the above was derived from a discussion with a clinician/researcher.

Thank you again for all your information and unique insights and like the others, hope you stick around.

Be well.

-- Jim

[jmjm530]

To complete my thought on SS, above. Again, the point was not to criticize her diagnosis but to point out that even the best clinicians/researchers are as you say bound by the knowlege and technology of the day. This is true today as it was then and I believe is frequenty overlooked. Medicine can get very arrogant at times (not talking about SS) only to be proved wrong a few years down the road. Maybe this is in part why those in the pro-occult camp are so skeptical of what is termed "SVR" and why those in let's say the anti-occult camp are so skeptical of the conclusions of the pro-camp :) Skepticism is good, because history shows it is necessary, especially in a fast moving field like Hep C.

-- Jim

[copyman]

hi and thanks for your contribution here. there has been much debate about the fibrosis serum marker tests. what is your opinion on the labcorp fibrosure test? how realible is this test in your opinion? i have read about being 80% accurate on the low and high end of F1 to F4 scale but wanted your opinion on it. thanks for you time.

[willing]

thanks for posting the reference to the "dragon is back" thread; I had missed that discussion (vey easy to do given the current volume!). Accepting the presence of virus notwithstanding serum-UND results, accompanied by "an effective HCV specific immune response that also persists and keeps that tiny amount in permanent check", seems a very different interpretation than arguing that "none of these studies have been reproducible using methods commonly accepted".  

Note that in the Maylin'06 LB9 study they only had liver tissue for 116 patients and detected HCV RNA in 2 using the standard commercially-available Versant Qual TMA. Thus my earlier question about the alleged unreliability of the real-time amplification  of  reverse-transcriptase PCR used by Pham, Radkowski and Castillo. Whether the percentage of serum-UND patients with actively replicating HCV in liver cells is 2% (LB9), 95% (Castillo'06) or 75% (Mike's surgeon) seems to come down to amplification technique.

Perhaps this seems like quibbling over many RNAs fragments can hide on the head of a pin, but I think the answers may have important clinical impact (selfishly, even for me).  Since "It is after all the inflammatory response" which may kill a number of us prematurely, immunomodulatory drugs may be more expedient than the battery of new drugs that seek to block viral replication by inhibiting the function of its various proteins (polymerase, protease, etc.). That is, it may be more expedient to learn to live with the virus and keep it in check than to try to eliminate it.

[TnHepGuy_]

Here's a new paper where they measure T-cell response and determine active replication via occult:

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17071928&query_hl=1&itool=pubmed_DocSum">Cellular immune responses associated with occult hepatitis C virus infection of the liver</a>

(from the paper):

"<i>These findings demonstrate that HCV-specific cellular immune responses are markers not only of previous exposure to and recovery from HCV but also of ongoing occult HCV infection.</i>"


TnHepGuy

[TnHepGuy_]

Here's a related paper from the same group (Castillo, Rodriguez-Inigo, Pardo, et al):

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=16847959">Virus-specific T-cell responses associated with hepatitis C virus (HCV) persistence in the liver after apparent recovery from HCV infection</a>

(from the paper):

"<i>In conclusion, HCV-specific T-cells are detectable in apparently recovered individuals in whom HCV RNA can persist in the liver indicating that HCV replication may be prolonged in the face of an insufficient or inadequate virus-specific CD4(+) and CD8(+) T-cell response.</i>"


TnHepGuy