Positive AMA, normal LFT - can fatigue be pbc related

[Jebweb]

12 years ago after abnormal LFT, was tested and confirmed positive for AMA. After a clear ultrasound and the return to normal LFT, was informed by consultant (only time have ever seen one) that there was a good possibility that I have pbc and that probably won't ever give me any problems and just to have regular LFT. I have not bothered to have LFT done very regularly but ones done recently are still within normal range with the exception of GGT levels which are a only slightly elevated from normal. I do presently (and have for a long time) suffered with fatigue and dry eyes and was wondering if this could be related to pbc or as my doctor thinks must be related to some other condition as my LFT are within normal limits. He is currently testing for other conditions as he believes that pbc is not to blame. Any thoughts would be appreciated.

[Val02]

Tiredness is definitely linked with PBC and many sufferers get dry eyes. I think both are autoimmune problems.

[Hidden]

Yes fatigue is part of PBC. In fact this alongside itching tend to be the commonest cause of a visit to see a doctor prior to going on the path to diagnose of PBC.

I was fatigued and itching back in 2010 when I went to see a GP. The fatigue didn't actually bother me as such, say that because I was working really long days and a lot of hours in a very demanding full-time job with no hols for 7 months, not 2 days off in a row in that time (due to it being retail and shop open 6 days per wk). It was the itching for me that got pretty intolerable and as a week and then a fortnight and another week went by I started to wonder what was up.

I had abnormal LFTs and a few other common blood abnormalities which you can get with a liver disorder so I had rechecks over the preceding months and then a scan (that looked normal) and then I saw the hospital doctor who took AMA (and ANA) blood checks. The AMA for me was positive and the ANA negative so I was informed along with the 2 symptons I had presented with many months prior that I had PBC.

Normally the AMA is the blood check that can verify more, sometimes not. In my case I got the diagnose this way.

[SC49]

It was tiredness, memory problems and palpitations that eventually took me to the doctor. I had other symptoms too but they were less problematic for me. I had been aware of memory problems and tiredness for months before I went to the doctor but I put them down to long hours at work and study. It was when I noticed they were not improved by a two week break that I thought that it might be more than overwork.

The blood tests showed raised liver enzymes, inflammation and possible infection. The enzymes continued to rise until I started on Urso when I was eventually diagnosed with PBC.

When I have tried to explain the extent of the memory problems and tiredness, my docs - including the consultant - have suggested that it is not PBC that causes those symptoms. Both have suggested that I have chronic fatigue syndrome. At this stage I have had to accept what they say (up to a point) but I can;t understand how they have arrived at their conclusion

Every piece of research or information that I have read has indicated that both tiredness and cognitive problems (and dry eyes) are common in people with PBC and that the severity of fatigue is not necessarily related the extent of liver damage or abnormalities in blood tests.

I can't decide if it's me - am i not describing my symptoms adequately? Or am I in denial ?

A lot of the literature about chronic fatigue syndrome suggests that people reject a diagnosis of chronic fatigue syndrome because of the implication that it is a mental - rather than physical - health condition. I have tried exercising more and I went to Cognitive Behavioural Therapy for a while. I took amitryptiline for a while but it made my brain even slower than usual (and believe me it was slow already!) I am still tired though and I still have an appalling memory and I can't concentrate on anything!

I am sorry that this is a long response - I think I am thinking out loud and trying to make sense of it myself

[mumofthree in reply to SC49]

Don't be too hard on yourself its not that you are not explaining yourself properly because we all seem to be coming up against the same problem of getting the so called specialists to take us seriously. If so many people are presenting with the same symptoms why is it so difficult for them to accept that there must be some link.

I get so tired I fall asleep at the drop of a hat and there's nothing I can do about it...its as if the energy just drains out of you. I have been known to nod off part way through having a conversation, luckily for me it has only happened in the company of my close family...How embarrassing would that be if it was with strangers or at work!! You just need to listen to your body. At one time I would beat myself up about things but now I don't...If I am tired I sleep sometimes a cat nap will suffice other times it may be a few hours but I wake up refreshed. If it takes me a couple of days to clean the house, so what!!

The worse thing for me is the lack of concentration and fuzzy head. I work part time and use a computer for up to 8 hours a day and have found that because my concentration span is so bad it takes me so much longer to do things. If I have to read lengthy documents my eyes go all funny and the writing dances on the screen so have to constantly stop, ending up reading the same thing over and over again before I can get the content into my head. Fortunately it has not affected my productivity enough that my boss has picked up on it.... but I am sure its only a matter of time. My memory is also pretty bad, I have to write myself notes and lists or I just forget.

You are not alone, many of us feel just as frustrated as you that we cannot get any one to take us seriously.

[judyt]

I, personally,consider that the people who deny fatigue and cognitive problems are those who are not blessed with an autoimmune disorder!! We hear it over and over again the same story that your autoimmune disorder whatever it is does not make you tired or affect your memory. I beg to disagree because everybody I know who has a disorder if some sort or another is complaining of fatigue.

[crundalite]

Hi

I too get very tired at times and fall asleep at the drop of a hat. On the other hand I often get spans of very poor sleep-which may exacerbate any tiredness.! I am also pretty active although sometimes I have to push myself. Ii is hard when doctors don't listen to what you are saying but at yours does at least seem to be investigating other possibilities which means he is trying! Should you feel that you are getting nowhere you could ask to see a gastro/hepatologist . Normal LFT's may not preclude PBC which can vary quite a lot and are only a snapshot after all. Good luck-tell us how you get on!

[SC49]

I slept through a performance of La Boheme - first live performance of an opera that I had ever been to and one that I had looked forward to for ages. I was told that it was very good

[Jebweb]

Thanks for your replies its good to hear your thoughts and experiences. Am not unduly worried by fatigue etc if related to pbc as LFT are normal. (Fortunately was able to give up work 8 years ago so can pace myself). However if it is not possible to get pbc symptoms with normal LFT (can anyone give a definitive answer on that) then I indeed need to look else where. It would help me to know that there is a reason for feeling like this otherwise you end up questioning yourself and the way you feel. Had another round of blood tests today (sad when you hope something shows up just to settle your mind)

[Wendom]

Hi I've had normal Lfts and had had positive Ama for 7 years I know of but I've had fatigue for longer than that and my consultant said I'm symptomatic for pbc he also said that fatigue is a big part of pbc snd that they used to transplant people early when it got too bad but he says they don't do that anymore because of the risks and lack of organs I have dry eyes and mouth lots if other symptoms too take care x

[rbwphd]

Hello fellow patients. I had a (+)ve AMA (anti-mitochondrial antibody), 3x the upper limit of normal on two occasions, 2 weeks apart after visiting my GP for abdominal pain and fatigue last summer. I did have a month-long bout of extreme fatigue with mildly elevated LFTs (liver function tests) 20 years ago (I am 53). AST and ALT (aspartate and alanine aminotransferase) values last year were elevated 5-fold the upper limit of normal and then returned to normal after discontinuing trazodone (an antidepressant used to treat insomnia). Abdominal CT (cat scan) was normal, there was no HAV, HBV or HCV infection (hepatitis A, B and C), normal LFTs and no physical symptoms other than the mild fatigue which subsided after 2 weeks. I had a cholycystectomy (gall bladder removal) for stones 4 years ago. I am a medical doctor and I don't think that I will get a liver biopsy unless my LFTs, particularly AP (alkaline phosphatase, marker of bile duct epithelium damage) elevates. I think that in my case it was a drug allergy that set this off. Again, I am not concerned unless the AP elevates. Just my two cents; I am not a liver specialist but my understanding after reading up extensively on the subject is that two of these criteria are needed to make a diagnosis: elevated AP, (+)ve AMA and/or a family history of autoimmune diseases. Having regular blood labs performed (yearly if healthy) is a good idea. Although I might have PBC, it would be a very slowly progressive form and at this point I am not worried. I hope this helps allay some fears.

Bob

[Keren]

Hi Bob,

I'm in the same boat (positve AMA + elevated IgM) - what do you make of the claim that the specificity of positive AMA is 98% for PBC? I guess we're all hoping we fall into the 2%, but the odds don't exactly work in our favour!

My biggest problem right now is that I'm also suffering from another as yet undiagnosed (but being investigated) musculoskeletal problem which is giving me widespread tendinitis and pain where I have tendon insertions - wrists, elbows, shoulders, neck, behind ears, all down my back, around my hips, knees, ankles and heels. I'm suspicious it's something in the spondyloarthritis family as I get low back pain when I sit or lie down which resolves when I get up and about. My neck also gives me regular misery. I was on a daily dose of 1000mg of naproxen to deal with the pain and stiffness which I found hugely helpful, but having had my AMA come back positive has freaked me out, so I've stopped them.

Obviously I don't want to live in agony, but I also don't want to shorten my life with NSAIDs. My doctor is deliberating over whether to refer me up to a liver specialist (even though my LFTs are currently normal) to try to decide where to go from here.

Oh, and I've also had Chronic Urticaria since 2007, so I take antihistimine daily. I think I fall into the 'patient with complex health problems' category.

Keren

[rbwphd in reply to Keren]

Hi Keren. Sorry to get back to you so late. I should make one correction to my last post; (+)ve AMA, elevated AP and (+)ve liver biopsy are the three criteria for diagnosing PBC, of which at least two are required. I have also read that a (+)ve AMA without one of the other lab results being (+)ve MIGHT be PBC and if it is, it is probably a very mild and slowly progressing form that might never make us sick. Specificity is used to RULE IN a condition but in this case it only rules in PBC with 98% certainty when at least one of the other two criteria I mentioned is positive.

The main side effect of naproxen is stomach upset and bleeding; it is probably one of the worst NSAIDs for this. However, there are other NSAIDs and other drugs used to treat spondyloarthritis (see drugs.com/condition/spondyl.... One class are the corticosteroids, such as prednisone. Another group are the disease-modifying anti-rheumatic drugs or DMARDs (i.e. methotrexate, azathioprine, chloroquine etc.) and these have worked well for sufferers of auto-immune disorders when NSAIDS and/or corticosteroids either don't work, cause allergy or are intolerable for the patient. Another class of drugs are the monoclonal antibodies or biological DMARDs (infliximab, etanercept, rituximab, etc.) which work by inhibiting a protein our bodies make called tumor necrosis factor or TNF which is instrumental in inflammation. These drugs are heavy duty; they are very expensive and can have some nasty side effects. They are usually used when the other therapies fail. Your GP would know more about the suitability of all these drug classes than I would since he/she knows your medical history.

Naproxen (an NSAID) is probably the least damaging of these drug classes and the reason you are taking it is because drugs like it are one of the first lines of treatment. After all, the central tenet of medicine is to "first do no harm". Unless you have an NSAID allergy (in which case you could not take any drug in that class), have a bleeding or cardiovascular problem or have elevated liver function tests, naproxen is probably OK.

Whether or not to go to a liver specialist is a tough call and I really couldn't advise anyone on that since that is not my forte. I decided not to go to one just yet because my liver enzyme profile, especially AP, has been normal and I haven't had any liver related symptoms such as pruritis (itching) or fatigue. In any case, with a normal AP the only way to know if you have PBC is with a liver biopsy and I think that I will wait on that one since in that case most of the time it would be stage 0 (no disease).

One last thing, since spondyloarthritis and chronic urticaria tend to be conditions of an autoimmune nature the addition of an elevated AMA might be part of a constellation of symptoms that are not necessarily PBC (remember the other 2%). If anything I would suggest you getting a liver and lipids panel every year at the least and especially be vigilant of an elevated AP for greater than 6 months. Also, if you don't have one yet, get yourself a rheumatologist that you like (must have good bedside manner!).

I hope this makes you worry less,

Bob

Charleston, WV

[Keren in reply to rbwphd]

Hi Bob,

Thanks very much for your extensive and thoughtful reply.

I live in the UK, and am going through investigations with rheumatology at the moment - I (unfortunately) saw a registrar on my first visit who had a bad bedside manner(!) and put all of my problems down to hypermobility. This was annoying and a bit bizarre, considering that I am only hypermobile in my thumbs and hips, and enthesitis is not an associated symptom of hypermobility. I'm going to go back and see a consultant in the next month or two once I've jumped through the PT and orthotics hoops.

Re: liver, I'm 38, so am fairly young on the PBC average age scale. I think I'd worry less if I was older and had normal LFTs, but it could be that I'm just in the early stages when most PBC patients are blissfully ignorant of their condition. It seems to be such a game of luck, and only time will tell which way my cards will fall. In the meantime, I'd like to do as little damage as possible.

I'm having problems with itching too. I initially thought it was stress related break-through itching from the chronic urticaria, but it's happening at night when I get too hot in bed, is keeping me awake, and is everywhere (head, abdo, arms, legs). It comes and goes, and some nights are definitely worse than others - I've woken up with blood on my sheets from broken skin. I take my antihistimine at night before I go to bed, and normally start getting urticaria wheals just before I take my next pill, so this does seem unrelated to that.

My GP has decided to refer me to a liver specialist to discuss pain management and also the viability of having a baby. In saying that, I'm not sure if I'm in any kind of fit state to either have or bring up a child, even though I'd dearly love to be a mother.

Hohum.

Thanks again,

Keren

[Keren in reply to Keren]

Oh, and this internalmedicinenews.com/sp... is another reason why I'm worried!

[milo2002 in reply to Keren]

There is research out there joint pain in PBC . I think autoimmune and rheumatology may be forward . Ask them to think about it

[rbwphd]

Hi Keren. My mother is from Lancs (Bolton) and I have an uncle and cousins in the UK. Getting back to PBC, the hepatologist will probably want to do a liver biopsy soon if the NHS hasn't overloaded his/her schedule and depending on how this person likes to treat PBC will probably put you on ursodiol after pathology confirms it. When I was a pathology resident in Philadelphia I never saw a case of PBC, just hepatitis C, alcoholic cirrhosis and a few other things. If I have PBC, being male makes it is a rare case indeed and since I was adopted I have no idea what my (biological) family history is.

Pregnancy can result in elevated AP which might obscure a worsening of PBC, however I have to say that I am far from being an expert on the subject. If you can get an obstetrician that you like (again, good bedside manner) and possibly an MFM (maternal-fetal medicine specialist, they work with high risk pregnancies) you may be in good stead for having a child. Another thing would be a social worker (do they use them is the UK?) to discuss access to these services. Here in the States there are a lot of folks with no insurance so they are used frequently in our hospitals to determine what kind of federal or state aid they can receive.

The main thing is to remain upbeat and avoid falling into a depressed state, since it is well known that depression can aggravate chronic illness and it is a significant risk factor for mortality in patients who have had an MI (heart attack). I am trying to get a family medicine residency here in WV but there are so few spots available and our government hasn't funded any extra training positions since 1997. We have a shortage of good docs, but I'm sure the situation is the same in the UK. I refuse to become bummed out and my wife, who is a retired police officer gives me lots of support. I think that is the main point, to have a good social support network and not to be alone in this whole thing.

Bob

[rainman in reply to rbwphd]

Bob,

I seem to be replying to an old thread, but if you get this, I would be curious to know if your status has changed. I am a 48 yr old man who just got news of positive AMA M2, an unexplained 15 year history of slightly elevated AST, and everything else normal, including ALP. I have no symptoms, but am planning a biopsy. I am nervous and just trying to learn all I can. I was encouraged that an educated medical professional in similar shoes felt comfortable sitting tight. Go Eagles, by the way.....

[breeski]

The same thing is happening to me right now. my lfts were elevated and then after 3 weeks went back to normal, but i was positive for ama. my gastro dr is saying it was prob a false positive or food poisoning. i am extremely tired all the time and insanely dry eyes- but my doctor has a "reason'' for all of my symptoms.. I'm not too worried since my enzymes are back to normal but it still sits in the back of my mind daily.