Maybe NOT PBC......perhaps Nodular Regenerative Hyperplasia?

[JennyCville]

Friends... I had my appointment Monday at NIH, the National Institute of Health. For those of you not in the US, this is our country's top hospital and research center. You have to be accepted into their program, because they only treat patients who meet the specific criteria for diseases they are studying. I was accepted because I have CVID (common variable immune deficiency) and PBC.  This is going to be long, because it was really, really eye opening, because my doctor doesn't necessarily buy the PBC diagnosis.

Let me first say that I was BLOWN AWAY by the NIH hepatologist I saw. He had literally memorized my biopsy slides and gave my husband and I a very detailed analysis

He explained that for most people, a positive mitochondrial antibody test (AMA) pretty much clinches a PBC diagnosis and many docs don't even bother to biopsy the liver. If you have a positive AMA...they just start treating you. A positive AMA is 25 +. Mine was 182~the highest my original Gastroenterologist had ever seen (and he didn't hesitate to tell me that and scare me to death). My liver biopsy in January supposedly confirmed the PBC diagnosis based on the damage they found- according to two specialists at Reston Hospital AND my insurance company used a "Best Docs" program and had some of the top doctors in the field of PBC read my slides and agreed wholeheartedly without question that it's PBC stage 2.

Except, Dr. Koh says...not quite. First of all, he said that with CVID patients, a positive antibody test doesn't clinch it...because we have the antibodies of thousands of people in our blood stream if we are on immunoglobulin therapy. (Each weekly infusion is a synthesis of 1000's of plasma donations). So in essence, a positive AMA in an immune deficient patient is just a maybe. And yes - my biopsy does have some features that are indicative of PBC...but it ALSO has features of Nodular Regenerative Hyperplasia. NRH is a liver disease that is the result of many infections, and many courses of antibiotics. It is a direct complication of CVID. And more people with CVID have NRH than PBC. Guess where the Center for NRH study is (for the WORLD.)  

You got it. NIH has the top NRH specialists working on their team.

None of the liver specialists who studied my biopsy slides until now had ever had a CVID patient, which is why they didn't even consider NRH as an option. And it's also really rare.

Now - the good (GREAT) news of yesterday is that they feel my liver damage is very early and hopefully we can prevent further damage. He was SO REASSURING about the staging. He said I'm "barely" a stage 2. Goosebumps of relief.

I have no idea whether NRH is "better" than PBC. Neither are fun....and both lead to really crappy things. But they do it differently. NRH causes portal hypertension which leads to strokes, horrible hemorrhage, and other stuff that made me stop googling it. It does NOT lead to Cirrhosis, whereas PBC does. leads to Cirrhosis. PBC is an autoimmune disease. NRH is a "complication" of infections and medication, not an autoimmune disease.

He reiterated over and over that we are just at the very beginning of a long relationship, that he would give me more info each time we meet, and that time will tell which liver diseases I actually have. He said that the biggest issue - by far - is my deficient immune system....out of control infections are my biggest enemy, as are certain medications. (I have chronic, debilitating urinary tract infections). He wants to keep me on my ursodiol for the liver disease and meet him back in a month. He said that each time they gather info on me it will become clearer where this is headed/what it is.  

 I have some combination of the following:

a) Primary Biliary Cirrhosis and Non Alcoholic Steato Hepatitis

b) Primary Biliary Cirrhosis, Non-Alcoholic Steato Hepatitis, AND Nodular Regnerative Hyperplasia

c) Nodular Regnerative Hyperplasia and Non Alcoholic Steato hepatitis.

He did feel that option "b" is a possibility - that I have both PBC and NRH. He will probably do a liver scope in the coming months to measure the pressure in my portal veins

I had a cardiac echo, CT scans of my chest/abdomen/pelvis, 20 vials of blood drawn, and a team of 6 doctors and nurse practitioners devoted just to me that day. The immunologists thinks that my pattern of infections is  incredible,but par for the course for someone with an immune deficiency. They are going to use the next few months to map my genes until they find out where things went wrong. Because it's genetic...I had a terrible bout of  Ecoli which triggered the CVID, but I always had the defective genes. Once they've mapped the genes,  they can actually go in and turn the defective genes off. 

Anyway, this is a lot of information to disperse, but I really believe that sharing our stories is so important, in the hopes that it might provide clues or ideas that could help others.

I am just so relieved to have people helping me who truly know what they are doing...my "regular" docs have admitted that they have no idea what to do with me.

Anyway, that's all for now.  If I didn't say it before, they are keeping me on the urso. 

Anyone on here have Nodular Regenerative Hyperplasia? 

Be well, friends.

 

[Junolee]

Wow.  Thank you.  I am looking forward to hearing how you are getting on. 

[butterflyEi]

Hi JennyCville

Thank you for sharing.  When you have something so rare it is great to find someone knowledgeable and helpful.  Let us know how you get on.

best wishes

[Twill]

Really impressed by the amount of information you got from the team of doctors.

Any information into PBC is well received.

I just wondered did you get any itching? which seems a major symptom of PBC for most people diagnosed with it.

Looking forward to your next blog

Look after yourself X

[JennyCville in reply to Twill]

I do have some itching...though it isn't terrible. It comes at night, and feels like painful "prickles".... 

[chynablue]

Jenny!  You went to NIH?!?  You are at celebrity status now.  Thanks for sharing with us.  This is great information!

[JennyCville in reply to chynablue]

chynablue...I know, right? It was my immune deficiency that bought my golden "ticket" in. It's absolutely amazing and HUGE. And we saw so many very, very sick people. I felt lucky, and scared at the same time, to be in the same place. 

[Belliver]

Wow! What an interesting experience you have had--- I'm so happy for you that you have had such a definitive doctor visit & described it so well. ( I have to spend a lot of time looking stuff up now!) Girl, you gonna be in all the medical journals, but keep us posted here! Have a great day!

[GrittyReads]

Hi,  I'm really pleased to hear that you finally seem to have been properly assessed and examined, and that final detailed diagnosis is in process.  Good luck with it all and thanks for giving such a detailed account of a new area.

However, I have to point out that AMAs   'on their own'   are not an absolute diagnostic criterion for PBC, even in cases quite separate from yours.  Some people just have AMAs ... the % of people in the UK (from blood donor records) is far higher than the much smaller % that eventually go on to develop PBC.   While AMAs are a strong indicator for PBC, and liver function tests, other checks,  medical history and family med history should also be assessed when AMAs are present  (and for many liver function tests will have to be done annually for the rest of life)  AMAs, on their own - regardless of the level of them - does not equal PBC. 

Eu/UK/US  formal diagnostic criteria require there to be:

AMAs,   and/or 

abnormal Liver functions tests,    and/or

biopsy evidence of PBC.

AMAs alone should not be assumed to mean PBC can be assumed.  Sorry to go on about it, but I was wrongly diagnosed for over 8 years, and it made some aspects of my life incredibly difficult, when there was no need for it. 

But so pleased that you finally have some answers.  do take care.

Gritty xx

[Hidden in reply to GrittyReads]

You are correct about the AMAs not necessarily indicating PBC, Gritty, it's the (AMA) M2 antigen complex, that is needed to diagnose PBC. Here is a link to the Mayo Clinic's page offering information about "Mitochondrial Antibodies (M2), Serum": mayomedicallaboratories.com...

[JennyCville in reply to Hidden]

You guys are awesome...thank you for setting us straight! I had a doc from the Washington University hospital liver department say that the AMA was a "clincher"....but this is why this board is so valuable. I am no expert, just trying to relay info as I get it.  Carry on, warriors!

[GrittyReads in reply to Hidden]

Hi DianneS,

Thanks for the link, but it is more complicated than the Mayo piece suggests.  Also, the research papers that the article cite are now pretty old, and it is a very general article.

When it says:

'positive results for antimitochondrial antibody (AMA) of M2 specificity are highly specific for PBC  ...'

that is true:  AMAs M2 are 'highly specific' for PBC, and other tests (liver function tests over 6 months, checking for PBC symptoms, general health assessment, family medical background, and checking for all other linked autoimmune conditions) should be done when a patient has M2 AMAs. 

Also, LFTs should be carried out for the rest of the patient's life, as PBC can develop (I've been having lfts for over 24 years now, with consistently perfect results).

But, the paper also says:

'A positive result for AMA of M2 specificity in a patient with clinical features of PBC is virtually diagnostic for this disease.'

So, the important bit there is 'with clinical features of PBC'.  It depends if there is more than just AMAs, even if they are M2 AMAs.

In my case, it has been known that I have had AMA M2 for over 24 years, and in that time I have always had perfect lfts and scans, with no symptoms or other 'clinical features of PBC', and with no other health problems that are linked to PBC.   

I worry, as too many consultants - who are not familiar with PBC (especially, it would seem, gastros) - are diagnosing PBC purely on the presence of AMAs.   The 'formal / official' diagnostic criteria for the Eu/UK/US,  stipulate more than just the presence of AMAs for a formal diagnosis of PBC.   For over 9 years, I was incorrectly diagnosed as having 'pre-symptomatic PBC' which caused havoc with insurance as that diagnosis does not officially exist ... and all I had was AMAs.  I had that diagnosis overturned last year, after seeing one of the country's leading PBC specialists.  I may still get PBC, and have lfts every year, but it would be ridiculous to go through life labelled with something that I don't have.

Jenny clearly has a lot of other things going on, but it would have been misleading if she had been labelled PBC, and investigations halted there.

I hope I'm not being too strident, but this AMA issue bothers me, as my misdiagnosis seriously messed up part of my life.  Do 'pm' me if you want to talk any more.

Take care,

Gritty x

[JennyCville in reply to GrittyReads]

Gritty...thank you for the clarification. And yes, I have "mysteries wrapped in enigmas" going on! I am so grateful that you haven't developed symptoms, and also that you have been a powerful advocate for yourself and others in your situation. Had I not fought for better care, I would have been left with inadequate care and even less information. Wishing you peace and good health!

[GrittyReads in reply to JennyCville]

Thanks Jenny, you take care, and do try to keep on enjoying life and being as stress-free as is possible in the circumstances.  Also, do let us know how you get on. 

Thanks also for your own strong stance, which has informed so many people on here, and - no doubt - caused quite a few Medics to learn a lot more!

Awesome.

[Hidden in reply to GrittyReads]

Yes, it a "very general article", as most of the Mayo Clinic's medical information pages are - which I think makes them more easily understood by the non-medical reader.

I posted the link purely in response to JennyCville's (quote):

 "He explained that for most people, a positive mitochondrial antibody test (AMA) pretty much clinches a PBC diagnosis and many docs don't even bother to biopsy the liver. If you have a positive AMA...they just start treating you.", 

to clarify that just a positive AMA was not indicative of PBC, but that it had to be AMA (M2) Serum. I didn't mention the LFTs or biopsy that are usually required for a diagnosis, as you had already covered them in your earlier post.

I can understand your angst about your misdiagnosis, based purely on your positive AMA result (I've read many of your other posts). I'm wondering now though, if we on the same page - when I read AMA, I'm thinking general AMA, not AMA (M2) which is more specific. Were you misdiagnosed with a positive AMA (M2) or just AMA? My diagnosis, 27 years ago, was based on elevated LFTs, AMA (M2) and fatigue, no biopsy until 6 months after diagnosis.

[JennyCville in reply to Hidden]

Sorry folks...the last thing I wanted was to provoke a debate over diagnoses. And my original diagnosis was based on elevated LFT's, positive AMA, and biospy.

[JennyCville in reply to JennyCville]

or rather...biopsy

[Hidden in reply to JennyCville]

Don't be sorry, debating is how we all learn about things. 

From what you have just written, re: elevated LFT's, positive AMA, and biopsy, I can see why a PBC diagnosis was made, so I will be more than interested in your final diagnosis. 

Take care. 

Di.

[GrittyReads in reply to JennyCville]

No, don't worry.  It's good to have these discussions, as we all learn so much from each other.   As I wasn't sure about whether you did also have raised lfts when dx, I didn't give you my full spiel.

Have a good weekend, take a break from this and have fun.

G xx

[GrittyReads in reply to Hidden]

Hi Dianne, 

Originally, back in 1992,  I was only told AMAs, different types or PBC ... never mentioned.  In fact I was not given a  diagnosis, just told to have annual lfts.  Then the same again 9 years ago, only this time I was given the false diagnosis.   Even 9 years ago, though, there just was not the info available, & I only found out about the different subtypes of AMA a few years ago.   I did ask my GP to check if I was M2, and I was ... I am(!), but still no symptoms, raised lfts or other signs.

I think most people are not told, and I find it alarming that  so many people are given a +ve diagnosis of PBC, with just AMAs; there have been folk on here who have been given Urso with AMAs only (M2 or not) and my consultant is completely opposed to that.

Mind you, you have raised an interesting point Dianne, so thanks.  I've realised that the info I have about the higher % of blood donors who are noted as having AMAs (compared to the small % of folk who go on to have/develop PBC) does not say if they are M2, or not.  Interesting.  I will find out ...

Take care,

Gritty

[Hidden in reply to GrittyReads]

I will definitely be interested in your findings. 

I agree with you on the issue of a diagnosis based only on the presence of a positive AMA result. I'm on a few Facebook PBC support groups and am continually amazed at how many 'newly' diagnosed people are added to the groups weekly, who claim they are AMA positive, have normal LFTs, none of the symptoms associated with PBC, and are still waiting to have a biopsy - here in Australia you have to have a least two of the three diagnostic criteria before PBC is considered.

Di

[Rockie]

JennyCville.  I am delighted for your sake that you are in the hands of such a good team of people who, I am positive, is going to help you. I also had goosebumps while reading this incredible story.   I live in South Africa, we have very good specialists, but sorry to say I have not yet met one that could give me any reassurance.  The one told me I need to see a super Specialist and he does not know such a specialist.  Good for you. I am holding thumbs. {Please keep us posted)

[MK3117]

Wow is right!!   Thank you for sharing and educating us.  It's amazing how much we can learn from each other, and now i have a few more questions for my hepatologist when I see him in a few weeks...  Please keep us in the know as you continue to your path.

[JennyCville]

Thanks, everyone...the more we know....it's like putting together a puzzle, or peeling away layers...

[JennyCville in reply to JennyCville]

And by the way...my AMA was the M2 variation of testing...just reread all of my dr's reports!

[YummyBear]

Thank you for such an enthralling and compelling account of your condition.  I am learning much and will be asking many questions at my next visit to the consultant in July.  I have gone around in circles with being told I have PBC, to not having PBC, but still nowhere nearer to having a firm diagnosis, except to say a fatty liver.  Bizarrely, having checked the many blood result print-outs, I have just noticed that I have never had a blood test for cholesterol in over a year ! 

[JennyCville]

YummyBear...I think the main thing I've learned is that this is an evolving process, and it's important to get the right people on your team. Many of us have been wrongly diagnosed, and badly informed. Will be praying that your appointment in July sheds light on your condition...and that it is as benign as possible!

[Pamela4475]

I may have it.... biopsy showed it but without fibrosis ... no pbc that I know of in the biopsy but really great response to urso...so I am at a stand still and continue urso with all normal labs now.... if anything I have stage 1 but very confused now

[Pamela4475]

My biopsy showed nrh but no pbc.... urso helped my labs to normal and I have plenty of pbc symptoms.... so I may have both.... does urso help the nrh?

[Pamela4475]

I was told that I had PBC and I did have the symptoms with elevated liver enzymes and forearm itching....as soon as ours was started my enzymes did better....Biopsy showed NRH but not really any PBC....I have moved and had to leave my favorite liver MD behind but am being picked up by liver instuitute of Dallas as they come to Amarillo Texas where I now live. Lets keep in touch...I feel lost and sometimes just afraid...I stopped googling it bc it was horrible....it is a very slow disease and one immunologist told me most people die with it but not from it.... I guess thats reassuring...we could still have both and all my AMAs 1 and 2 came back positive....keep in touch, Pam

[gwillistexas in reply to Pamela4475]

Pamela...may I ask if you see a dr from Methodist Liver Institute? There a few of them who come to Tyler once a month also. I saw one from there but I’m getting second opinion.

[Pamela4475 in reply to gwillistexas]

Yes that’s who they are setting me up with.....are they not to your liking?

[gwillistexas in reply to Pamela4475]

I was referred to Dr Mantry for consultation after my fibroscan indicated a little more fibrosis. I loved him. Great personality. But he prescribed 50,000 iu of Vit d a week and 10,000 iu of Vit a daily without checking my levels. I took it upon myself to have those labs done. Vit d was in perfect range. Vit a was low normal. No restrictions on my diet, which he said because my liver function was totally normal. So those things raised a flag with me. When a dr prescribes that high a dose of vitamins just because PBC patients have trouble absorbing and had no labs to back his decision, I don’t like it. He’s a great Dr. I have researched him thoroughly. I am seeing a hepatologist July 12th who is involved in that institute but left Methodist and opened private practice. He is still in Dallas but has signed contract with my hospital for a year and they hope to have him full time after that. I have also researched him extensively. He won Dr of the year In Dallas Magazine for the last several years and has been involved in PBC research. He has an excellent background.

[Pamela4475 in reply to gwillistexas]

Where is he located? I would not have taken that either

[gwillistexas in reply to Pamela4475]

Which Dr?

[Pamela4475 in reply to gwillistexas]

The doctor of the year one..... I wonder if he would see me in Dallas too?

[gwillistexas in reply to Pamela4475]

That is Dr Abdullah Mubarak

[gwillistexas in reply to Pamela4475]

I’m sure he would.

[Pamela4475 in reply to gwillistexas]

I could catch a flight there and fly back in the afternoon..... where are you located again?

[gwillistexas in reply to Pamela4475]

I’m in Tyler. About 2-2/12 hrs east of Plano. If you’d like, pm your email and I’ll send his info

[Pamela4475 in reply to gwillistexas]

That would be great.... I’m in Amarillo..... don’t know where that is in relation to me but will try and figure out how tonpm you.... are you on fb too?

[gwillistexas in reply to Pamela4475]

Yes I am. Gail Willis, Tyler, TX

[Pamela4475 in reply to gwillistexas]

See if I can send friend request

[gwillistexas in reply to Pamela4475]

I’ll watch for it.

[gwillistexas in reply to Pamela4475]

And messenger

[gwillistexas in reply to Pamela4475]

Look him up😊

[Pamela4475 in reply to gwillistexas]

Will do

[gwillistexas in reply to Pamela4475]

You won’t have to look him up, lol! I sent to you😊

[gwillistexas in reply to Pamela4475]

The hep I’m waiting to see is Abdullah Mubarak. He offices in Plano

[Pamela4475 in reply to gwillistexas]

Are they good doctors?

[gwillistexas in reply to Pamela4475]

I have no doubt they are very good at Methodist. They rank high in transplants. Probably some of the best.