Anti-Smooth Muscle Antibody and Other Tests

I'm still waiting for my first appointment with a specialist on 10/21 after being diagnosised with HCV nearly two weeks ago.  Here's my latest concern...

Last Friday, my family physician (FP) consulted with a local GI on the phone during my visit with her.  Although I didn't hear the conversation, my FP told me that the GI suggested that she order the following tests (in addition to PCR and genotyping):  anti-smooth muscle antibody; serum ANA; iron studies; sed (sp?) rate; and something else that I can't make out....anti-something-or-the-other Ab.

When I asked about this, my FP said that the GI told her that they were needed to determine if I even had "the kind of Hepatitis C that would respond to treatment."  My own research later led me to various sites on auto-immune Hepatitis C.  

Here's my question:  Are these tests standard for newly-diagnosed HCV patients?  Did any of you have them done to rule out auto-immune Hep C?  Should I be overly concerned about this?

Susan

[AtoGHepatitis]

If the Dr is testing for: "FP said that the GI told her that they were needed to determine if I even had "the kind of Hepatitis C that would respond to treatment."

he/she is testing for what genotype you have. Genotypes 1a, 1b, and 4 generally do not respond well to treatment, BUT, in many cases it does. Please remember that a response is known as a "sustained response" (SVR)... and it is better known as "Remission" and NOT a cure... the virus can return at any time. If you have a SVR, you should be tested yearly. Also, your Dr. may be testing you for viral load. This is how much virus you have per ml. of blood.
You can read about Genotype at:

http://hepcvets.com/genotype/toc.html

You can read about viral load at:

http://hepcvets.com/viral/toc.html

Good Luck,
Vikki
http://hepcvets.com

[ponygirl]

The more blood tests the better. I believe ANA is checking for auto-immune hep but there are other people here much more knowlegable. They also need to check thryroid levels and for other auto immune diseases such as rhematoid arthritis. Treatment can surface underlying problems we never knew we had and from what I understand thru careful monitoring during treatment they can avoid such things as blowing out thyroids. As you are going thru this process, ask for copies of all lab results. Write down all questions you may have B4 your appt. with specialist.

[britgirl]

I have to disagree. There is no reason to say "the virus could return at any time". How can that be? I have tested negative for the virus for a year since I finished treatment, and have been told I am cured. The hospital do not even want to see me for yearly blood tests. I am interested to know why you say what you do.

[DoubleDose]

I second your comments.  Current thinking among all the top Hepatologists and HCV Docs is that if you are undetected at the six month point AFTER finishing Tx, the virus is gone!  It is not in remission, since it is a virus, not a cancer...HCV virus does not go into a dormant state.  If there is any left, anywhere in your body after treatment ends, it will quickly begin the process of reproduction and regeneration usually to similar levels as before treatment.

Many docs now feel that even the three month post-Tx PCR gives a very high degree of probability of SVR, if the test shows undetected viral load.  There is no reason why the virus would 'sit around and wait' to return to full blood levels after discontinuation of Tx.  If you cleared ALL of the virus, from all areas of the body (Hepatocytes, Blood, Lymphatic System, etc)
during treatment, then you WILL achieve an SVR, or what most docs are now calling, a 'Cure'.

That DOES NOT necessarily mean that all previous liver damage, fibrosis, etc. are also automatically returned to normal 'pristine' state.  Some regress toward normal more so than others.  But what the SVR will do is prevent further progression of liver damage, and in best case scenarios will promote slow repair of some either minor or major degree of liver damage.

The SVR/Cure  vs. Remission issue is ultimately best understood by looking at the long term outcome for those who do indeed receive an undetected VL result six months post Tx.  Over 99% of these previously 'infected' individuals will never see the virus again in their systems.  Although they will always test positive to the HCV ANTIBODY test...which just means you ONCE had HCV virus in your system.

[MajNeni]

The only fly in the ointment is that even an SVR person can later get infected by a new HCV exposure... I think that can happen.  I don't think we get immunity to all genotypes, or even
"Our own" genotype, from getting the HCV virus out of our system once.  Someone please correct me if this is incorrect. Maj Neni

[mikesimon]

You're right. Mike

[willing]

personally, I'm going to consider myself cured, if I'm undetectable 3-month post tx, however, this being the real world there's always room for flies in the ointment. A large infb-2b-based retrospective <a href="http://www.natap.org/2001/aasld2/day22.htm">study</a> reported as high as 2.5% late relapse. It includes the quote:
" There were 5 patients who had HCV-RNA detected in their liver (not blood) in the 24 week post-treatment liver biopsy. These 5 patients were sustained responders so they had PCR negative in the blood. Two of the 5 subsequently relapsed".
Here's more <a href="http://www2.us.elsevierhealth.com/scripts/om.dll/serve?retrieve=/pii/S027091390300538X&nav=full">evidence</a> of virus lurking in tissue reservoirs - though these relapses occurrred before 24 weeks. I seem to remember one study reporting a relapse as late as 3-4 years but I can't find it so maybe I dreamt that.

Another, pegasys-based, reported <a href="http://www.natap.org/2001/aasld2/day24.htm"> <1%</a> late relapse.

Also, HCV-antibodies do not remain permanently detectable, but <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10802716&dopt=Abstract">fade away</a> over time. One study reported as early as 10 years. From one of susan400's posts it sounded as if her husband may have run into this.

[jonihs]

I wonder if these relapses were caused by the blood-brain barrier being breached. Are there any tests ongoing to prove or disprove that theory?

[Tosser]

That's scary. I don't know if I want to know about that or not.

[willing]

we don't yet know enough about how HCV enters a cell or how it replicates to be able to say which cell-types are susceptible to infectionan but - as we keep looking - the list of cell types that  can support replication gets longer and longer : hepatocytes, B cells, salivary and sweat cells, kidney cells, central -nervous system cells, intestinal mucosa cells, etc. Part of the puzzle of why tx works for some and not others is likely to be the fact that certain sequence variations make the virus more likely to infect certain cell-types (see for <a hef="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12532451&dopt=Abstract">example</a>.

The prevalence of CNS infection is higher than the relapse rate so there doesn't seem be any reason to worry that infection behind the blood-brain barrier is untreatable. Another part of tx success  puzzle is very likely to be the fact that some hcv variants are much more IFN resistant than others. There are at least two regions in the HCV genome that have confirmed association with IFN resistance (in fact one is called the "interferon-sensitivity-determining region" (ISDR)).

None of this is worth worrying about as far as I can tell - you can't change the HCV sequence(s) you've got. However it does suggest that individualized therapy based on the sequence of the virus you're carrying is not too far away.

[willing]

drats - forgot to include the above<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12532451&dopt=Abstract">link</a> .

[sugie]

If after you have cleared the virus, why do you have to continue full dose for 48 weeks genotype 1a???The virus may be lerking but with Pegasy, your system gets satuated and maybe that would be enough to keep it away??????With a maintainance dose,just hoping maybe I could start maybe feeling better sooner. My sides are getting harder and harder and afaid I won't make it. What do the study numbers say??I figure the drug company wants you to take as long as possible, some docs probably too. But what is the reality of the percentage of success per time and dose?Thanks for info.

[sugie]

Well, Maybe, Maybe not. How in heck can anyone do 78 weeks of this stuff??????It has effected major systems of my body and I am not undetected at 20 weeks. Sooooo, what are the odds of SVR after undetected at say 24? for a 48 week TX? How much better is it for 78?????I would love to just do enough but be sure it is enough.  I just think we all can't fit into the same time frame. I bet there are some markers or some way to tell when the torture is safe to end. By the way, what week are you on? Doing Pegasys?????and do you have to work? I am finding it very hard but have no choice but to keep going every day feeling like ****.

[DoubleDose]

The fallacy in your commentary is your saying 'once you have cleared', etc.  When you receive an 'undetectable' PCR result, generally from 4 weeks to 24 weeks after beginning therapy, you have not really 'CLEARED' the virus at all!  You are now merely at viral levels below the limits of current detection.  And that is only for the blood!  The virus may be at different/or higher levels for some time in your Liver (Hepatocytes), or possibly other reservoirs.  So you need to see the critical importance of maintaining long term dosing after your undetectable results, and also ideally not cutting back on dosing levels.  The dosing level is what produced the viral decline curve, and the lower the dose you end up doing, the longer it will take for true 'clearance' or eradication of the virus from your system.

The longer it took you to become undetected by PCR, generally the longer you must extend treatment in order to help assure final eradication (SVR).  Stopping early after undetected status, or cutting back dosage levels will assure you of either a breakthrough of the virus while on treatment, OR, a quick relapse after discontinuing Tx.  For Type 1's, if you are undetected fron 4 to 12 weeks into Tx, generally you must complete 48-52 weeks of total tx to have 80% odds of SVR.

If you become undetected from week 12 to week 24, many docs are now advising extended Tx in those cases, to 72 or 78 weeks total.  This shows some promise (in small studies) in upping SVR rates in these 'slow' responders.

Again, there is a huge difference between being 'undetected' by PCR, and fully 'Clearing' the HCV from one's body.  Hence the long follow-through periods for Type 1's after first undetected status. Stay with the program if you are undetected, and give it as long as you can tolerate.  You do not want a relapse....believe me.... it means starting over again and wasting much of your original efforts.  Discuss this issue with a good HCV doctor...because you do not want to squander a great opportunity for success.

[new-sojourn]

I can't beleive you even asked that question.  I was so sick I didn't even realize it.  The disease just slowly took over my whole life so silently and subtly I didn't relize how low my quality of life was.  1yr post-tx,svr or cured, it doesn't matter.  I feel like a com;letely different person, the person meant to inhabit my skin.

I was 24yrs infected, and I truly believe I will only continue to feel better.  And I mean in all ways-mentally, physically and spritually.

I don't think there are enough SVR's yet.  Look how many SVR's are on this board conpared to a year ago.  Only very broad generalizations can be drawn from a limited pool of responders.

[mikesimon]

Here's a recent article on obesity and it's effect on tx success.



                  
Obesity Predicts Poor Response to Hepatitis C Treatment

Laurie Barclay, MD

Medscape Medical News 2003.

[DoubleDose]

By the way, I am currently coming up to week #71, of a total 72 week tx program.  I have been on double dose Peg-Intron (3.0 mcg./kg) from week 1 up to week 53, along with 1,200 mg. Ribavirin up to week #53... i had to lower both at that point, going to 2.0 mcg./kg on the Peg-Intron, and 1000 mg/day of Riba, due to decreasing Hemo levels, in spite of being on Procrit almost from the beginning.

I have taken it week by week, and the first eight months were very difficult, with numerous debilitating side effects, it slowly became easier and more routine as time has gone by.  I
have managed to run an executive consulting firm during tx, and am the sole 'bread winner' for the family, with lots of school, and sports commitments.  It has been a struggle to say the least, but doable.  I see no other alternative!  Only SVR will satisfy me... I did a 15 month tx four years ago, and relapsed...so this time I want the best odds that I can get.
Why go through this only to have to confront the same tx AGAIN!

You do need to be undetected by sensitive PCR testing by 24 weeks at the latest...if not undetected at that point, your odds of success are less than 3%, if you become undetected at all.  You would need to go beyond 48-52 weeks if you become undetected by 24 weeks, since you are detected at 20 weeks.  Odds of SVR for late undetected Type 1's, (12 - 24 weeks becoming undetected) go down to the 35% to 50 % range, according to several large studies.

Smaller studies, using extended treatment (72 - 76 weeks) for late undetected Type 1's , have shown more like an 80% SVR rate for those that remain undetected throughout the 72 week tx, and keeping dosage reductions as minimal as medically possible.

I like 80% odds vs. 35% odds any day of the week, hence my extended tx.  My doc suggested it, and I could have stopped at 48 weeks, but we both read the studies, and knew the odds.  Again, why go through this if you are only going to give yourself 'low' odds of success.  If you do not become undetected very soon, (24 weeks) you and your doc. may wish to explore dosage increase, or doing a completely new round of Tx at adequate dosage levels to attain early PCR undetected status, ideally by 8 - 12 weeks.  Your doc can manage and medicate your side effects, using sleep aids, AD's, Procrit, Neupogen, or whatever is necessary to tolerate the tx.  I think that it slowly becomes easier as your body heals (when the virus is undetected) and after many months of becoming acclimated to the Inf. in your system.  Keep the Riba as high as called for, and watch the Hemo. and Thyroid levels...If you treat those issues as necessary during tx it often makes all the difference in the world...QOL wise.  I hope my comments are helpful, not discouraging, and cause you to consider going after your SVR with total conviction and confidence.

[new-sojourn]

I think this is an example of a perfect thread.  So many lately stray off into personal ******* w/real, imaginary or'puter friends and don't serve to heal.  Emotions run rampart releases chemicals so damaging to your liver that you might as well have a drink for the same damage.

We all have outside problems that will still be there when done w/tx.  

This fourm should ease peoples minds, not creat more turmoil.

The lack of long term data is what keeps some of us SVR's comin' back.  Unfortunatly, I see no survival rates for a SVR ESLD.  So I wonder if any do survive past 1-2yrs of dx & tx.  The average wait on a transplant list for livers is 23mo and most die waiting.  I'm 25mo since liver failure and 1yr post tx.

You could say I'm 'walkin' on egg shells", and as Warren Zevon suggested, I'm enjoying every sandwich.

[sugie]

I wonder, I am obese (but not morbid, 180/5'2") and still have a detectable viral load after shot 19. But I thought if you had a two log drop by week 12 it looked good and I did. 3,000,000 down to 55,000 to 4,100 now. Should I insist that meds be increased? I doubt I can take it but for the next month till shot 24, would it make any difference? And what to increase? shot amount or the copegus? I wondered when we started that Pegasys was made for folks 175 lbs.????? Any info. appreciated

[willing]

well...IMHO the chances of late relapse are so remote compared to non-response or relapse they certainly don't seem worth worrying about.  I haven't been too motivated to read up on post-tx QOL (but sure am looking forward to it!). Here's  a collection of recent <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=pubmed_pubmed&from_uid=12873820">studies </a> on QOL/cognitive-dysfunction and HCV. There's strong evidence indicating  fibrosis is likely to reverse after SVR, though slowly. I don't know whether the non-liver problems, such as the cognitive ones, also do( hope so ).

[DoubleDose]

Was the 55,000 result for your 12 week PCR or was the 4400 the 12 week result.
If it was the 55,000 at 12 weeks, then you did not have a 2-log drop.  That number would need to be 30,000 or less to meet the 2-log drop standard.  If the 4,400 was the vl at 12 weeks, then you are in good shape, and would have had close to a 3-log drop at 12 weeks.

If the 55,000 is indeed the 12 week PCR result, then your dosage is NOT adequate to provide any real chance of SVR in the future.  Those not reaching a 2-log or greated drop by week 12 had a miniscule probability ( less than 3%) of ultimate SVR, hence the reason that most docs and insurance companies will push to discontinue therapy if you don't meet the 12 week, 2-log criteria.

You are a responder it seems, but too slow  for practical purposes.  This may mean the need for higher dosing, more frequent dosing, an initial high-intensity induction phase,a different interferon (Peg-Intron,  Infergen, etc) or a combination of the above.  You just need to accelerate the decline curve, so that your body can ultimately clear all the HCV within a reasonable period of time (48 - 72 weeks depending on date of first undetected).  

If the smaller number (4400) was your 12 week PCR result, then you are in good shape, well on track, and only need to have an 'undetected' PCR by week 24, to have a good chance at long term eradication.  Read the research on viral kinetics, and decline curves, to better arm yourself for discussions with your doc.  You need the appropriate tx dosages to achieve the high probability decline rate for success.  Best of luck!

[DoubleDose]

Correction on my last post, I was referring to your 4,100 vl number, and mistakenly indicated 4,400.  Also, was the 4,100 vl result from the 19th week? or earlier?

Also, your question about Pegasys, and weight is a good one, since the FDA Pegasys documentation indicates that US based Type 1's had a lower SVR rate than the European patients did, ESPECIALLY heavier, US based Type 1's.  The dosing level may well be the problem in your case, but at this point no one knows for sure.  Roche certainly doesn't want to call attention to the inadequacies of their 'one-size only' dosing, especially in their new market, the US, which has been huge for them...so far.

I have to believe Roche will be preemptive in introducing flexible dosing, or similar modification, before Schering / Peg-Intron proves that their product is more effective for US based type 1's, in the upcoming, very large, head-to-head study being launched.

[mikesimon]

I just pasted that article form Medscape so I don't know anything more than what is in the article. I do know is that ribavirin (copegus) should probably be weight based. I don't know your dose but I would hope it is at least 1000 mg per day. I would think that according to the study the best thing you could do would be to lose some weight. As to your load drop: You would have had to be at 30,000 IU/ML or lower at week 12 to have achieved the 2 log drop. I would guess that if you do clear the idea of extended tx may be something to consider. Larger doses of both drugs may enhance your chances as well and I would speak tp your doctor about both approaches. Of course that depends on how you feel and how your blood chemistry looks. Best of luck to you. Mike

[Galen]

I have read in several different studies that Pegasys dosing was based on the assumption that the average patient weighs approximately 180#.  I always wondered how they came by one size fits all because from all that I have read before, many toxins, medications, and hormones have higher stores in people who are overweight.  That would mean, possibly, that a 180# man who is 5'11" would have a lower buildup of such toxins than a woman who is 5' tall at the same weight.  I do know that being overweight can make tx more difficult because of mitigating health factors.  What do you all think?