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Non-responders

Hi

Just wondered how many of us are considered non-responders and are in the slightly over upper end of normal to around the 200 range of Alkaline Phosphatase who have stayed on Ursodiol only. How long have you been in this range? Have your symptoms advanced?

I am also AMA-negative. I was diagnosed last year in March via biopsy. My ALP went from above 400 to about 238 in the first few months on Ursodiol. In May this year it was around 180 then it went to 186. My blood test this week has it at 197. I am on 1000 Ursodiol. My hepatologist mentioned Ocaliva. I am not scheduled to see him until next year.

Of course having normal LFT s doesn’t mean that you won’t progress but it’s supposed to mean you have better chance of not progressing.

Also If you went obeticholic acid are you glad you did?

Linda

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Twojer...I have been on OCA 13 months. ALP dropped quickly. ALT & AST were each only few points above normal & quickly came back to normal. I went a year being glad I took OCA. But I found out in August, through fibroscan, my fibrosis increased slightly but enough I’m not pleased. My dr isn’t concerned but it’s not his liver. I’m still taking 5 mg daily & want to stop it. Will see hepatologist soon, I hope, & see what he wants to do. So at this point I can’t say yay or nay. Good luck.

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ThanksGwillistexas. I actually thought of you when I was writing my questions. 💗

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Oh, lol! You’re welcome. 😄

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Hi,

I've posted a lot lately so you may know what's happening on my end. I've been on URSO 2 years this month. My Alk-phos alone has fluctuated between 160-180. Everything else in normal range UNTIL last week. Ast, Alt and alk-phos are all up. I'm having labs again this coming week. I have an appt. with the PA on Friday. We're gonna talk about whatever my labs show and "Ocaliva." I'm nauseated now for 2 weeks, its slight nausea, and ever so often weird twinges of pain in my right upper quadrant through to my back. Ugh!

I'm guessing I'm a non responder 🙁. Looking to have a MR elastography. Found a facility that does have the software for their MRI machine in Kansas City MO. I get anxiety just thinking about the labs and the MRE. But I've never believed I was very early stage 0-1 as my hepatologist stated off my biopsy.

Stella❤

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Hi Stella

Yes I did see your posts. I had not as yet gotten my blood tests at the time. I was hoping they were down. But for whatever reason the ALP had gone back up. I am feeling downhearted. It seems like there is no rhyme or reason to this disease.

I keep trying to figure out whether some other medication or anything other than PBC might be impacting it. For instance I changed thyroid medication and my hematocrit was elevated.

I still hope to hear from our fellow PBC group to see if some of the non responders are still going strong on just Ursodiol.

Gwillistexas went on Ocaliva and has mixed feelings right now. You probably saw her post.

Linda

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Hi,

Boy do I know what you're feeling. I'm still having bouts of anxiety. I've just got to wrap my head around what's happening and do whatever I can to try to stabilize things. It just may be out of our control though. And that's exactly how I feel too, that there isn't a rhyme or reason.

Yes, I read her posts. I personally draw strength from gwillistexas ❤. Her attitude gives me hope that no matter what happens, I'm gonna get through it. Try to hang on.... they will figure something out for you. I wonder if anyone has tried Fibrates? I read those can help too. Don't know much about that though. My PA mentioned Fibrates.

Stella❤

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Ktltel...that’s very kind. Thank you🦋

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Responder/ non responder never clear where I sit with this, responder from UK-PBC say the ALP should be no higher than 1.67 of ULN ( upper limit of normal) My base line ALP 9 years ago on diagnosis was low compared to a lot of pbc’ers it was only 268 on Urso it dropped to 200/204 and fluctuated around that mark with the odd test reading as much as 240, all other tests in normal range. So could be considered a non responder on the ALP alone if your supposed to be 1.67 ULN after a year on urso. My lab ULN is 115 x by 1.67 = 192.05. But given all my other tests have remained normal my doctors had no cause for concern as the numbers stayed fairly stable and only fluctuated on the odd test over that period of time.

However,all this time I was not on the maximum dose of urso, I was only on 12mg per kg of weight.

Now two years ago, I lost weight and exercised which then put me on the maximum dose of 15mg of urso per kg of weight and within six months my ALP dropped. . So now my ALP is stable at 170/180, which are now in the responder range.

So you see if you need to respond in a year, who knows now, it’s to late to worry about however a recent shearwave elastography showed F0-F1 all tests are normal except the ALP at 170 , so after 9 years, all in all I’am doing okay. I think..... I feel okay so that’s what I’ll go by. I Hope this helps show some fluctuations are not always a cause for concern but getting checked and monitored is the best action to take.

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Candy

That is good that your ALP was so low on diagnosis. I’ve heard if they catch it early that it helps.

I went about 1 1/2 years before they decided I had PBC. I didn’t have the itch. I was tired sometime. I was negative—negative AMA, ANA, etc. in the meantime my ALP climbed from slightly above normal to well over 400–not as high as some—but higher than it could have been if the doctors had realized what it was. I finally had a biopsy which showed I had PBC.

Your experience makes me hope that perhaps it might be possible to fluctuate and yet not advance.

Thank you 💗

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I was diagnosed quite quickly, 5 months I didn’t go to the doctor with any symptoms it was an unrelated visit, but the alp was slightly raised, he said 99% sure I’d had glandular fever at some point as it was suddenly showing up in my blood tests. But he had a change of thought and to be on the safe side he sent me to specialist. Good job he did or it could be so different. I didn’t think that way at the time, I went to pieces when I was diagnosed thought I’d never see my children get married or have grand children, well I attended both weddings and have to grandchildren , whom come to stay on a sleep overs there is joy in life once again, but I also know how every little change or twinge can and still does sometimes send you in a spin. Take care.

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Candy12

I went through the same doom and gloom when I

was first diagnosed. I remembered reading about PBC and thinking “I can’t have this! How would I have it?”

And yes because of its erratic and unpredictable course I do pay attention maybe more than I should to new pains or fluctuating bloodwork. Your experience and others from this site as well as Robert’s (from PBC Foundation) information does give me hope.

🙂

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Hi Twojer

I have been on Urso for a year now and my levels have reduced lots, at diagnosis (ALP:789 GGT:1427 ALT: 459) but they are still too high (ALP: 280 GGT:369 ALT:223). My consultant confirmed this week that I need to start a second line treatment and that the two options are Bezafibrate and Ocaliva. He has started me on Bezafibrate this week as I suffer from itching and apparently Ocaliva can make this worse. Bezafibrate is not licensed for PBC but there have been positive results from clinical trials.

I am in the UK and my consultant told me that my hospital's policy was to use Bezafibrate over Ocaliva due to the recent research and not just because of cost. This makes me think that it may well be due to cost as I understand that Ocaliva is very expensive! It is hard to know what do for the best, should I have pushed harder to get Ocaliva or trust that the doctors know what they are doing.

I started on Bezafibrate this week and I have to go back in 3 months to see if I am responding.

The good thing is that there are alternatives to Urso now and we have options as non responders.

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Hi Twojer, I've been on urso since June 2015, was thought i was early stage at this point. ALP has never gone below 270. Last winter everything went up Alt and Ast were over 100 and ALP was over 900. A biopsy was done and i was diagnosed with borderline AIH. It was noted at biopsy i was actually stage 3 which was a bit o a shock! So now classed as non responder and on steroids and azathiprine for the AIH. For some reason unknown to the drs the PBC seems to respond to the steriods which apparently isn't normal. So for the time being I'm not getting a second line treatment and OCA has been ruled out as i have the itch. Bezafibrate has been discussed but won't be prescribed until the AIH is stable. I'm 47 and have been told disease progression is often quicker in younger patients.

Sandra

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Sandra

I am so sorry you have been dealing with so much. For whatever reason thank goodness the PBC seems to respond to the steroids.

It was enough of a shock for me to be diagnosed with PBC, a disease I had never heard of. No one seems to have the same experience with it and there is so much that is unknown.

Unknowns such as—Why me? How did I get it? I mean I know why with the attack on the bile ducts. What can I expect? What can help? With your particular experience— what caused everything to go up last winter? Etc etc The list seems endless.

There does seem to be a lot of research being done and hopefully we will all benefit.

Thank you for sharing your experience, Sandra. I will pray that your AIH is soon stable and that bezafibrate will be just what you need to stabilize.

Linda

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Hi Linda

I am classed as a nonresponder and alp was around 200 for a few years, I am currently on a clinical trial for the last year and half and my bloods a well within range. Currently at stage 3 fibroscan score of 16.3. Going to stay on this trial until it may be licenced.

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It’s interesting your classed as a non responder with ALP at 200, mine was that for years , were any of your other bloods out of range? Did they offer you OCA? I’ve just been reading a 2018 update on OCA, and it’s usefulness I’ll post it separately you may find it interesting.

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Wasn't offered oca still

Wasnt licenced when

I started this trial. All bloods were all out of range.

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Glad the trial seems to be working, and got your bloods back in range. Let’s hope they consider it a success and we get another medication.

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Kimphoebe

When you joined the clinical trial was your stage also 3 at that point? What about your fibroscan? Did you also stay on Ursodiol when you joined the trial?

May I ask what clinical trial you are participating in? How much longer will that trial run? Did you have symptoms like itching or right quadrant pain before starting the trial? If so did they improve?

All of this is encouraging. There seems to be a lot of new treatments that researchers are working on.

As a non-responder you were around the same level as I am. Some people who were at that level did not add anything else to it and were able to stay at that same levels. For others doctors/consultants are now suggesting adding Ocaliva or Bezofibrate. You seem to have found another positive addition with your trial.

Thanks for the hope!

Linda

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Jjones78

Thanks for answering. If you don’t mind my asking had your LFTs just suddenly gone up that high when they were discovered by a routine blood test or had you gone in because you were not feeling well? It took mine about a year and and a half to go from a little above normal to over 400. A biopsy confirmed it because I was AMA negative.

My doctor/consultant has mentioned Ocaliva. I am somewhat nervous about it because there are no long-term studies on it. I did mention Bezofibrate to him but he kind of discounted it. I did remember reading at least one large study that showed Bezofibrate has made a positive impact. There are several people on this site who have reported positive experience with Bezofibrate.

I was wondering what my doctor/consultant would do if I refused to take Ocaliva. Could I just stay fluctuating around that 1.67 times upper limit of normal ALP without adding a second treatment? Please let me know how you do on the Bezofibrate.

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Hi Twojer

I remember having raised LFTs after the birth of my son and being called back for follow up blood tests, but I never heard anything more about it so I didn't question it further. Fast forward 10 years (I hate going to the doctors!) and I eventually made an appointment as I had been suffering from severe fatigue and itching for over a year and that is when they ran blood tests and completely panicked when they saw how high my levels were. It is my own fault for not going sooner but I was 39, working full time in a stressful job and 2 boys to look after so I put how I was feeling down to stress. Plus everyone I speak to is always complains about how tired they are so I thought this was normal lol!

I will let you know how I respond to the Bezafibrate. My consultant had told me at a previous appointment that if my ALP went down to around 200 he wouldn't add a second line treatment. But I know others have started on Ocaliva at those levels. I guess you need to see if your ALP raises again and be guided by what your hepatologist says.

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Hi Twojer

I have been on OCA for 5 years as part of the long term safety extension arm of the trial. I was diagnosed at 38, partially responded for about 7 years, didn't realise how sick I was becoming - ALP 700 and feeling dreadful - as raising my 4 children & working as a nurse until my Dr recruited me into the OCA trial which has stabilised me . My Dr believes my liver would have failed without it so thus I am extremely grateful to be part of the trial. OCA is not available as yet in Australia where I live . I still take Urso as per my Drs instructions.

Best wishes from downunder

Karaliz

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Karaliz

What a positive testimonial for Ocaliva! I am so glad that you had such a positive result. How wonderful that your doctor was able to get you into the trial when you were so sick and that you were able to improve.

Do you mind telling me how much you are taking?

So happy for you!

Linda

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Hi Linda

I take 10 mgs daily ( took 5 for the first 6 months after being on placebo for a year which was then increased to 10.) I do have widespread cirrhosis which is compensated at present - have 6 monthly ultrasounds as cirrhotic livers are at increased risk of HCC. As I am only 53 with this level of liver damage, it is unlikely my liver will last my lifetime but my Dr says it has already lasted longer than he expected so who knows !! My basic general health is very good which has helped I think ☺️

I hope this is a bit useful Linda - I've had PBC for 15 years so tend not to use the forum as much as I did - although there was nothing like this support group when I was first diagnosed !

Take care

Karen

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Karaliz

I am especially glad that you took the time to talk about your experience. It helps to hear other people’s actual experiences and thoughts when looking at treatment options.

I always thought of myself as healthy until I was diagnosed with this disease. What a shocker! I think we settle down some after the initial jolt but it always seems to be present ready to loom up when least expected.

You ARE still young and it seems like there is more research and trials being done which might benefit us all. We just need to hang in there and stay positive. (Part of the talk I give to myself each day,some days are easier than others.

Best wishes for your basic good health to continue and your liver condition to remain stable!

Linda

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It's a pleasure Linda - I too find it very helpful to read of others experiences. Like you I received a dreadful shock to be told at 38 with 4 young children that I had an incurable autoimmune disease - I remember saying to the GP, how can I have a disease I've never heard of ?!

PBC was also played down quite a bit by the Drs I saw at diagnosis who described it as nothing much & repeated the rather meaningless mantra - " you'll die with it rather than from it" ... Once my liver became cirrhotic and the raft of associated symptoms became my close friends , the above sentiments rang hollow to say the least !!

However, this disease does give one time to plan for the future , ruminate , alter ones habits for the better and ultimately play the cards one has been dealt.

This then allows us to get on with living our lives as best and as meaningfully as we can - my philosophy for what it's worth !!

Karen

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Hi T , i’m on ursodoil for 30 yrs , have increased through the yrs , stay on it , it works for me , i’ve had ups and downs with my blood work

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Arlie

That is great!

Good to know that you have had ups and downs with your bloodwork but Ursodiol is still working for you after 30 years.

Thanks for letting me know. I feel encouraged.

Linda

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I think your liver enzymes fluctuate in time..my alt is just gone up 10 points this year hasn’t been down to what it was before..my next appointment is in December hope by that time my alt will drop🙏

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Hi Sachin1234,

I have heard that liver enzymes fluctuate, but it sure would be good to know why they do.

I think we newly diagnosed or nonresponders might be more concerned , but I’m thinking I would still be worried later on!

I am sorry your ALT has increased. I am sorry my ALP has increased. I am sorry I have it. I am sorry so little is still known about this disease. I am sorry any of us and our families has to deal with PBC. I am sorry we worry. Etc etc

But still there is hope. Research is ongoing and new drug trials are happening. Today the sun is shining and the fall colors on the trees outside are beautiful as they must be in Virginia also. Days like this make me forget I have PBC.

Please let me know how your December doctor visits goes. I have another blood test in December also. We will pray for drops. 😃

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Twojer...I was concerned in July, I think it was, because ALP went from 132 to 139. Robert posted that it is not uncommon for ALP to fluctuate as much as 15% and as long as it doesn’t continue increasing, is probably no concern. Mine dropped back down shortly. So who knows...

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Twojer...go to my post 4 months ago & you can read Roberts reply.

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Thanks gwillistexas I will! I am hoping it will drop back down. It had gone up a few points with the last blood tests but since the this one was up a little higher I knew I was getting into the definite nonresponder range.

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Twojer...if your ALP was 197 last test, I wouldn’t consider yourself a nonresponder just yet. Let your dr be your trusted guide on that 😊

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Gwillistexas

I thought it was actually pretty good when it went below 200 after about 14 months. Unfortunately even when it was 180 my hep was considering me a nonresponder. He said on my next visit (sometime after the first of the year) we would talk about Ocaliva.

I wanted to be prepared by knowing other people’s experience—on Ocaliva, on other things, and how many “nonresponders” might be still be in the UL of normal to slightly over 200 without having advanced using only Ursodiol.

So far i don’t itch and my scans all look normal. My biopsy said I was stage 1-2. I just don’t want to take anything that would advance PBC prematurely since I’m close to the transplant cutoff age.

Linda

Linda

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Twojer...none of us want to take anything that will cause or contribute to disease progression. Sad thing is, I think most drs give medication one year before they do a follow up fibroscan to see if medicine is working as they hope. A year is entirely too long to wait & see. Too much can happen in that year. If they see med didn’t do what was intended, you’re like “oh great! I’ve just possibly lost a year of my life!” Then the worries start back to square one. Sucks!

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You are AMA negative? That is one of the markers of PBC?? Confused. Your alkaline could be elevated due to other diseases?

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Hi Lawyers

Do you have PBC?

Below is from a PBC pamphlet available from PBC UK——

“How is PBC Diagnosed?

A diagnosis of PBC is usually dependent on two pieces of information being present:

• Abnormal liver biochemistry (also known as LFTs,

bloods or Liver Function Tests) usually involving raised

levels of Alkaline Phosphates and GGT

• Positive results in PBC specific antibodies (AMA or in

some cases ANA)

• Liver biopsy findings consistent with PBC (bile duct

damage)

In most cases, liver biochemistry and positive antibodies are enough to diagnose PBC. If there is any doubt about diagnosis, then a liver biopsy may be done.

Around 95% of those affected by PBC will have positive AMA (Antimitochondrial Antibodies). A smaller number of patients will have positive ANA (Antinuclear Antibodies).”

(This is me talking again)Most of the time if you have elevated AMA PLUS elevated liver function tests, especially ALP and it is from liver origin, they can usually diagnose PBC. (You can also have ALP from other areas like bone, but they look for primarily elevated ALP from the liver using blood tests)

Because I was AMA and ANA negative I had to have a biopsy to confirm the diagnosis. I did have elevated liver function tests.

As per the PBC pamphlet information only a small percentage of us test negative for AMA. You can obtain a lot of good information from the PBC UK website.

Linda

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I have PBC AIH CREST and Grovers disease. I am stage two. Judt had liver biopsy. I live in Charleston SC. I an well versed in the diseases. I also have positive ANA and AMA. Thank you for info. It is unusual not to elevated AMA but it does happen. Biopsy will show extent if damage to bile ducts etc. You are correct. Thank you again for all information. I have had since 1998 the AIH. PBC diagnoses just happened in June with new biopsy.

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Lawyers

Sorry I didn’t mean to send you stuff you already knew.

I was thinking somehow I may have swapped initials in one of my posts and alarmed you but I thought I’d better ask if you had PBC In case I gave too brief an answer. In the end I decided it would be better just to use the pamphlet. My apologies. It was easier to get it from the PBC site in case I said something incorrectly.

I had to have a liver biopsy to diagnose mine. While they were at it they decided what stage I might be in. The hard part was being AMA negative. It took a while for them to figure it out. I keep thinking maybe if I started Ursodiol earlier I would have been better off. They kept coming up with things that were even more horrible before the biopsy. I’ve heard it’s possible to go from AMA negative to positive over time.

Im sorry you’re dealing with so many different things. Some times there seems to be no end to things coming up.

Linda

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Mo worries. I understand. My ANA kept appearing and disappearing too. Sorry. Did not mean to come a across in a bad way. You were very kind. It gets frustrating. I no none with any of what we have except online which can be a blessing and a curse at the same time. Wishing you the best!!

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I was diagnosed in early 2017 based on abnormal blood tests at my routine checkup. ALP was in the 300s and AST and ALT were very high. First three months on Urso i saw positive response, then flattened. 9/2017 had biopsy confirming stage 0-1 pbc. Started Ocaliva 5 mg. Immediately had extremely positive results AST and ALT in normal range and ALP went to upper limit. But in March they started climbing again and i began to feel symptomatic. I went off a different medicine that i was on that might have been interfereing. AST and ALT are elevated but not worrisomely so but my ALP is still high in the 300s. I dont think the Ocaliva was a positive for me unfortunately as the improvement for me was only fleeting. Maybe I should not have started it until a full year on Urso. Anyway I just went for a second opinion and am going off of the URso for a month and then going to try another option probably a fibrate. I wish you the best of luck!

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Ottley3

I’m sorry it hadn’t been a smooth course for you. I was diagnosed in early 2017 also.

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Ottley 3

Sorry I didn’t get finished.....Thank you for sharing your experience with Ocaliva. I hope the fibrate works wonders. Let us hear how it is going for you.

Linda(Twojer)

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Thanks for sharing this information. The different LFTs are so confusing - all the numbers blur together after awhile. Apparently my ALT has persistently come down on URSO and is now at 91 but my ALK Phos and gamma GT are more stubborn. ALK Phos is around 430. I was worried that the ALK phos suggested AIH was not improving and I might be put back on steroids. As my consultant doesn't want to see me for another 4 months, I hope this means there are no concerns.

Thanks for your input; I think these liver conditions are all so fickle and the meds just have to be tinkered with until things seem to improve.

Did you have many side effects with Octavia?

Take care and hope you maintain at least a reasonable degree of health.

Jane

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Hi

Was diagnosed with PBC/AIH about a year ago after biopsy. Started on Urso and steroids but have been weaned off steroids. Vast improvement in all readings although ALP is still around 400 (was 1200 at diagnosis). Consultant is going to confer with hepatologist at Nottingham to consider whether my response to URSO is adequate. Your post has now got me thinking whether or not I am only a 'partial responder'. Not due to see GI for another 4 months but will ask whether or not I am a candidate for OCA.

Thanks for you post that has made me consider my own position. Hope all goes well with your treatment.

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Jane

Thank you for sharing your situation. So glad you’ve seen an improvement in your readings.

It’s strange but some doctors/consultants don’t seem too concerned once your liver function tests get in the below 200ALP range and others want to put you on something if your numbers aren’t normal after one year. I guess part of it is that the fibrates and OCA seem to bring down the liver test numbers and are now available.

Alas the irony is that even though your numbers normalize it doesn’t necessarily mean that the disease is not advancing. I just don’t want one of these other medicines to cause my PBC to advance because they don’t have enough reliable data on them yet.

Linda

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Twojer...Urso is an old original drug of probably 30 years. Robert will tell you they don’t know if the newer drugs have a positive impact until they’ve been around 20 years or so. Yes, Ocalvia is still in a trial but Urso was there at one time as well. If you’re not responding to Urso it’s worth giving another drug a chance.

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