What do they mean by a false positive in regards to AMA testing?

I tested positive for AMA-M2 back in Oct. and it was a 68. I had a biopsy this past Jan. and it showed a fatty liver but no PBC. The liver Dr. Still wants to monitor my bloodwork and he wants to see me back in a year. I also had elevated alpha Feta protein and C-Reactive Protein. The pathology report mentioned that it could be early in disease process or where the biopsy was taken. Anyway, I feel like it hasn't been totally excluded completely and that I'm still waiting for the ball to drop. I had my GP retest my AMA M2 to see if it is still positive and it was 69.7, so still about the same. when the Dr. mentioned false positive my first thought was lab error. So, my question is could he mean false positive as in I carry the antibody but something else caused the elevation like the fatty liver etc. or is he referring to a lab error? What is he not telling me...maybe that it's only a matter of time or do some folks just carry the antibody and never get the disease. He did say that sometimes the tests were either .5% or 5% false positives not sure which, any advice would be appreciated. I've been feeling pretty sluggish as of late and not sure what to blame it on. Thanks!

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  • Hello Jean43.

    A false positive I take it regards to the AMA can mean that there isn't a good enough result as in a high titre (that is the measurement of the antibodies - titre) of the AMAs to be seen. In that case if a doctor is in any doubt a liver biopsy is normally taken. (I was diagnosed with PBC Dec 2010 on itching and at the time fatigue, abnormal liver function test and GGT and I had a high titre of AMAs.)

    You had a biopsy and normally a biopsy will show if a patient has PBC due to the cell changes apaprently. It doesn't matter about the sample site regarding PBC. In a patient with PBC though it is said a biopsy can show a stage of PBC it has cast doubt due to the fact that the liver is a large organ and it might be damaged in one area but not necessarily on the site where the biopsy was taken and vice-versa. A fatty liver can normally be shown on a scan and so can cirrhosis. (I did see a programme on tv late 2010, it was live on air with 2 men, one overweight who was found to have a fatty liver, the other was said to be a heavy drinker and he was shown to have cirrhosis.) Before the AMA blood test was devised, it was said the only way to know if a patient had PBC was for a biopsy to be performed. I'm not a doctor as you will know but this is what I've read about liver biopsies.

    It is possible that you might have a few AMAs but you might never go on to develop PBC. Did you by any chance ask what your bloods - the LFTs (liver function test) - showed. Were the results abnormal or normal. I expect any slight problems that occur in the liver can show abnormal or slightly abnormal LFTs. Certain medications can give an abnormal LFT result and patients tend to be checked at intervals whilst on certain medications.

    Interestingly I found out in 2010 when I was going through blood test after blood test that a bone problem can show abnormal LFTs and my GP said he was doing a test to check which it was that was causing the abnormal LFTs I had. Mine showed liver. The GP had to continue investigating as my LFTs were slowly climbing each check.

    I think any liver glitch can make one feel sluggish or fatigued. But in PBC, patients can also acquire a fatty liver.

    I expect your bloods are going to be monitored for the foreseeable future so if any changes take place it can be then discussed further.

  • I think you need to contact the PBC Foundation - there is a link to their site at the top of this page - and discuss this with one of their advisors. Even if they don't know the answer, they can tell you what you need to ask, in order to get an understanding of this.

    I'm afraid I don't know enough about the relevance of the alpha feta protein and C-reactive protein.

    When you talk about 'the elevation' do you mean that some of your liver function tests were elevated?

    +ve AMAs alone, are not - strictly - enough for a diagnosis of PBC. But if your lfts were elevated, as well as having AMAs, that is usually enough for a diagnosis.

    AMAs are strongly suggestive, or indicative of PBC, but not enough alone. Do you have symptoms of PBC?

    Sorry I can't be more help. I hope you get answers, soon. Meanwhile try not to worry, and be good to yourself.

  • Hi Peridot,

    Thanks for your response! I've been researching this since I found out that I had a positive titre and there's so much misinformation and or contradictory info that it makes it very confusing to get a clear answer. I feel like that in some ways it is similar to being told you carry the cancer gene for breast cancer and although you don't have at the moment it is very likely to develop in the future. I guess it's a case of the what if's. I know my titre isn't high as alot of you but I also have seen those who've gotten diagnosis of PBC with titres about my range or lower according to the lab that did mine a positive is anything over 25. I might be wrong but also doesn't a AMA titre usually run higher than an AMA-M2 antibody test because it tests for more than one mitochondrial antibody. I've never had the AMA test along with the M2 or the IGM test. As far as the LFT's they were elevated a few times and most of those were before my surgery for the removal of a parathyroid adenoma this past Sep. which not only causes raised calcium blood levels it can raise the ALP because it draws the calcium from the bones. Although, I had high ALP post surgery and it remains a high normal. My past experience with the calcium makes me wonder too since it would elevate from high normal to over the threshold into high for months that the GP actually thought it was my blood pressure meds that caused it. I doubted that it was the meds and sought a second opinion and went to an ENT specialist showed him the months of bloodwork and he ordered a scan and I was later diagnosed with a hyperparathyroid. Funny thing is I no longer have high blood pressure it was caused by the parathyroid. I also have an autoimmune thyroid (Hashimoto's) but it's subclinical and I'm not on any meds for it at the moment. They never did a GGT/GGTP to gather if the elevated ALP was bone or liver related. I did come across this in my liver disease book by Dr. Melissa Palmer "The level of AMA is reported in titers, such as a titre of 1:160 or 1:640. However, the level of the titre does not correlate with the severity of the disease nor is it significant in regard to prognosis. A titer of 1:40 may not be diagnostic of PBC and may disappear when blood tests are repeated. Rarely, people are discovered to have positive AMA yet lack all symptoms and have a normal AP and GGTP. It has been found that within approximately ten years, the development of symptoms and elevated AP levels occur." And one more item that I came across online "Blood tests to check for signs of autoimmune disease. An analysis of your blood may reveal anti-mitochondrial antibodies (AMAs). These antibodies almost never occur in people who don't have the disease, even if they have other liver disorders. Therefore, a positive AMA test is considered a very reliable indicator of the disease. However, a small percentage of people with primary biliary cirrhosis don't have AMAs." I believe that was Mayo Clinic's website. Although, in other sites and I don't have it in front me is that other autoimmune diseases can affect the AMA's. Even with liver biopsies my book says this "Because most liver diseases affect the entire organ uniformly, this tiny sample is usually representative of the entire liver and provides a complete story." However, other things I've read have mentioned sampling error's due to like you've said damage in one area and not exactly in another. Actually, my fatty liver didn't show up on the ultrasound except for that it was enlarged according to the liver DR. but I was told by the GP that it was all normal and I did read somewhere that fatty livers with over 30-33% fat in them show up on a scan. So confusing! Anyway, sorry to babble on...I was really hoping that the second AMA-M2 test was going to be negative so I could finally put it to rest. But it's usually never clear cut...is it? Thanks for listening and wishing you good health!

  • Hi GriityReads,

    Thank-you, I did go ahead and sign up although I've not been diagnosed and I'm from the US ...hope that's ok!

  • Hi Jean 43,

    I don't have anything official to do with the PBC F, but I'm sure they won't mind you joining even if you are in the US - although I guess emailing one of the advisors will be a better bet that phoning from the States!!

    I am very reluctant to take too much notice of any online info about PBC, even from fairly reliable sources like Mayo - it's an incredibly varied and complex condition, and they cannot cover all the variables in a brief 'info-piece'. Meanwhile, even recent books on the subject may have taken a few years to get to actual publication.

    Also, there is a lot of confusion about the issue of +ve AMAs. I have had +ve AMAs for about 23 years, with consistently healthy liver function tests and no symptoms of PBC, so AMAs are not a diagnosis.

    However, I don't have all the other things going on, that you have, so, 'badpiglet' (see comments below) is absolutely spot on when she suggests not reading too much into this 'false positive' reading, as your advisors will be checking out the whole, big picture.

    I know it's hard, but while you wait to see them, try to rest and relax, also try to treat yourself, and have some fun. Stress is the worst thing for all of these conditions, so the best thing to do is to look after yourself, live well, and enjoy life.

    I'm about to go for a walk on the beach in teeming rain, and watch the waves and clouds piling in!!

    Take care.

  • Hi GrittyReads, and Badpiglet,

    Just noticed your replies and I get what your saying and I agree that one has to be careful where they get their information and there are a lot of variables. I did go and look in the front pages of my book and the last time that it was revised was in 2004, so probably could be due for an update. I do always try to look at the date on the web page to make sure that it's not old stuff and Mayos listed 2014 and cited sources at bottom of page. I did come across this too recently and its dated as well but interesting nonetheless ncbi.nlm.nih.gov/pubmed/245... and goes against other things I've read, so I think I'm seriously done with it all. I guess I'll just write all these questions down and ask the Dr. about at next years appointment. Your right though it just isnt worth worrying about. Take care!

  • Hi Jean43,

    I think, if I understand it correctly, a false positive result when the labs test for various autoimmune diseases is as uncommon as you might think. I'm not 100% sure how much this applies to the M2 test specifically. Various factors can possibly affect results such as being elderly, recent illness, drugs taken. Also when a result is on the borderline. Your GP and consultant will be looking at your complete picture not just a single test in isolation.

    I definitely recommend talking to the PBC foundation - understanding tests and results is a complicated business and you don't want to worry yourself unnecessarily.

    There are some labs eg Derriford in Devon, that don't give an actual figure for the M2 test, just positive or negative.

  • Oops! missed out a word. Should read NOT as uncommon. Sorry!

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