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Passing along a research update from Dr. Eric Gershwin, Chief, Division of Rheumatology, Allergy and Clinical Immunology, Univ of California

I saw this yesterday on the Yahoo Groups / PBC Organization (US) and thought I'd pass along to those of you who like to stay current on research.

Dr. Gershwin's PBC Research Update

Despite major advances in the treatment of rheumatoid arthritis and other

autoimmune diseases through the use of biologic agents, there has been a

relative lack of effort and success in primary biliary cirrhosis (PBC). There

are several reasons for this. One reason is that there are a relatively

small number of affected people and thus industry is not as interested in

major investments of their time and money. In addition, there is also only a

handful of researchers who study mouse models of primary biliary cirrhosis.

Mouse models are a major tool and resource to apply new therapeutic

efforts that can ideally be applicable to humans. Our own group, and particularly

through the help of the PBCers, has been studying a mouse model in which

experimental animals are injected with a chemical that is very similar to

something found in cosmetics and some foods.

This compound is called 2-octynoic acid and we identified this putative

chemical as a possible risk factor for PBC following intensive studies with a

technique called quantitative structure activity relationships (QSAR) with

human PBC sera. In fact, the sera we used to identify this chemical was

given by many dozens of PBCers at the many local and regional meetings that

we held in Davis and throughout the West Coast, and even including the

meeting we had in Las Vegas several years ago. In any case, our laboratory

believes that there is a critical involvement of something called autoreactive

T cells. These cells lead to the destruction of bile duct cells, and we

have demonstrated that one such population of T cells, called CD8 T cells,

play an exceedingly important role.

Based on this information, we have been attempting to control the

activation of these T cells and prevent their movement into the liver of our mice

with PBC. We believe that by reducing the ability of these cells to become

abnormal, we will reduce liver inflammation. The following is a little bit

complicated but essentially the activation of these T cells requires two

critical signals. There is also, and very importantly, a receptor found on T

cells which is called cytotoxic T lymphocyte antigen 4 (CTLA4). The

ability to interrupt the function of CTLA4 has already been successfully used to

treat rheumatoid arthritis. We treated our mice to reduce the activation

of T cells by blocking this receptor. Importantly we have shown that

treatment with this compound called CTLA4-Ig, led to a significant reduction in

liver disease, including reducing the inflammation and the severity of the

bile duct injury.

Our data suggest that an experimental clinical trial with this drug is

warranted in humans and we hope it will become an impetus for other efforts at

newer biologic therapy. We are very excited about this result, not only

because of its potential for a clinical trial, but also it helps us

understand the mechanisms by which bile duct injury occurs in sufferers of PBC.

Our mouse work continues and we hope will continue to lead to advances in the

treatment of PBC.

M. Eric Gershwin M.D., M.A.C.P., M.A.C.R.

Distinguished Professor of Medicine

The Jack and Donald Chia Professor of Medicine

Chief, Division of Rheumatology, Allergy and Clinical Immunology

451 Health Sciences Dr. Suite 6510

University of California at Davis

Davis Calif 95616

9 Replies

Hello JennerLayne.

Though some of the information you transmitted was a bit technical in terminology to me, I did notice the mention of perhaps 'control the activiation of these T cells' mentioned. Well this is similar to what I have thought all along since diagnosis (Dec 2010).

Although no cure as yet for PBC I think the way forward would be to attempt to eradicate the antibodies that are continually causing the destruction of our bile ducts. Not sure if the information in more scientific terms on what you posted does mean the same as I have put in this paragraph.

I decided to tap in the 2-octynoic acid into Google to find out what it was. Information is a bit lax on it but I did find this:- 'Octanoic acid (caprylic acid) which has been doubly dehydrogenated at positions 2 and 3 to give the corresponding alkynoic acid. It is widely used in perfumes, lipstick, and many common food flavourings'.

Now reading the bit about being 'widely used' and what in, does really make me wonder. I've never worn make-up so lipstick is out but I do occasionally use perfume plus expect this acid has been disguised in food ingredients so it is anyone's guess there.

Thanks for posting. We never know, one day someone might stumble upon something that is the solution for PBC.


Thank you for this information. I have changed my diet over the past 7 months and decreased my numbers remarkably. I have elimated milk,eggs and meat. I am working on no more dairy. It made me very pleased to bring my score from 475 down to 206. My over all score is 14 down to 12. My other scores were normal. I am so happy. I hope there is a cure for this disease. I am starting to think diet. Best to all

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My gastro recommended going gluten free because I had so many digestive issues and upon DX last spring, I immediately cut gluten and changed my diet to less meat, less dairy and stopped most alcohol. My LFT's have dropped into the normal range and have remained there for several consecutive blood tests. I still have issues with fatigue, low VIT D, and joint and muscle aches, but feel I am moving in the right direction. I'll continue to post info as I find it, as I know some people love to read up on what's happening in the research world.


Thanks so much for your reply.


I'm in Minnesota and in process on bringing down my inflammatory markers. Will be seeing the doctor who is helping me this on Monday and will report back what I find. Please continue to share any relevent information on PBC, research, diets recommended, etc, etc Thank you all!!! I'm so happy to have found this site. I felt so alone, before.


Absolutely agree with you Saundrella this web site has helped me more than I can say , afraid my consultant told me there was nothing I could do to change anything except take Urso. I asked specifically about diet and he just shook his head.

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Hi Saundrella, I'm very interested to hear back from you on what you'll be doing to reduce your inflammatory markers. Thanks for sharing your experience. Abigail53 in Texas


Thanks for the posting, it does sound very interesting, hopefully this will eventually lead to a break through for PBC


Well, I went to the appointment on Monday and am more dubious than ever. First of all, this fellow is formally trained as a chiropractor. Typically, this is one field of medicine in which it's practitioners are likely to go into "functional medicine" taking course work which offers a protocal sanctioned by the ACCME (Accreditation Council for Continuing Medical Education). I looked into the requirements for study and one can take a five day course in "functional medicine" and begin to apply it, however, in order to get the accreditation, one must follow up the five day course with lectures in various, specific subjects required. The "functional medicine doctor", as this fellow referred to himself, did have the ACCME diploma and has been practicing for several years (13 years, I think). However, I'm not sold on the whole "functional medicine" approach in regard to bringing down inflammation slow down the disease process in PBC. I felt this doctor knew the material provided him very well. However, I question the promised outcome of the protocol, in my case, at least.

For instance, he tests for virus, antibodies, candida, gluten sensitivity, allergies, etc, etc, but when I ran this approach by my doctor at Mayo Clinic in Rochester, MN, he didn't want to outright discourage me, but he did offer some comments to make me think, more. First of all, bringing down the inflammation caused by each of different problems mentioned, in general, does not slow down the PBC inflammatory process, itself, because they are entirely separate issues. Also, when the "functional medicine" doctor discovers some bacteria or a hormonal imbalance and treats it, does he realize antibiotics and anti-fungals are metabolized in the liver and will cause further damage to it?!! Apparently not. And what about the bio-identical hormones he may use? Yes, they are natural, but do they not consist of yam and soy? I'm not sure about yams, but it seems to me I read they are not good for the liver. I know soy is not. Any antibiotic or anti-fungal is DEFINITELY not!! So, it seems, the cure is going to hurt my liver more than help it. Does this doctor know what he is doing, in advance, and is willing to do it, anyway, or does he simply not know all that much P'BC or the liver and that it can be damaged, further, especially once someone has already developed cirrhosis, as I have?!!

He charges 3-4 thousand dollars for his treatment plan (3-6 months, long) The six month plan is metabolic, alone, (diet, supplements, etc); the 3 month approach is metabolic and neurological. "Mind and body" sounds like a good approach to health and well-being, but his particular neurological exercises and laser treatments, not to mention chiropractic adjustments, just don't impress me. If fact, they disturb me more than anything else. I'm beginning to think my mind and body will come into balance as I eat right, think right and do the right things! It doesn't cost anything to hear someone tell you that!! So, while I may allow my daughter to go through his program to find out, specifically, what it's all about because I don't think it's going to hurt (having a "chronic fatigue syndrome" diagnosis), I don't think I dare go through it, myself. I just don't think this doctor knows enough about the PBC disease process and yet is very confident he can help me just as he says he's helped so many others and has the numbers to prove it. Like my Mayo doctor says, "It's a lot of money." and "They (researchers) have not found any correlation between bringing down inflammation in PBC and actually slowing down the PBC disease process". Inflammatory numbers, in general, don't seem to be correlate with the PBC disease process.

When one's liver enzymes are up, this indicates there is destruction of cells taking place but one does not have any means of knowing how much damage is occurring. The numbers don't tell you that, only that cells are dying. I don't know enough about this to comment further but the Mayo doctor was trying to tell me inflammation is not a good indication of what is going on within the liver, itself, if I understood him, correctly, that is. I don't know a whole lot about this but am interested in learning more.

I DO know by way of personal experience that when I bring my weight down, my pulse goes down and I feel better. I feel better when I exercise and eat right. I know when I eat too much, especially an overload of saturated fats, my liver feels congested. I know I cannot handle ANY alcohol. The alcohol from a mouthwash caused pain in my liver, so I never touch anything with alcohol in it.That's me, though, I cannot speak for anyone else.

I think I'm going to proceed by using my head instead of trusting anyone else too much. I'm actually afraid of putting myself in the hands of someone who is a chiropractor who may be looking for some means of increasing his income because business is slow. Maybe he does help other people. I'm not saying he doesn't. I'm just saying I don't feel I can trust him, at this point, to help me.

I wish I had something more hopeful to share with you as we're all in this, together. I may be further along than some of you but the good news for me is, though I already have cirrhosis, splenomegaly, low platelets, varices, etc, I have never itched except while pregnant, many years ago, nor do I have ascites,. My MELD score has held at 6 for several years, now. My fatigue is sometimes worse than others but, on the whole, I am very well-compensated. I haven't bled and, after being started on Urso 4 years ago, my LFTs returned to normal and have stayed down.... which is pretty unusual for someone who has already developed cirrhosis. Usually this sort of sustained, positive response occurs in the early stages of PBC. So one just never knows what their PBC is going to be like or what the future holds. For me, I have chosen to live as though I'm going to live forever after having made peace with the fact that I could have a bleed and die tomorrow (or get a living donor transplant from my daughter if I am not too advanced in age, by then). I refuse to let this disease process take down whatever is left of my life.

If someone has been thinking about some other way to bring down the inflammatory response in PBC, please let me know about it. I intend to talk, further, to this "functional medicine" doctor because he does seem very sincere, but he's going to have to clear a very high bar before I'd be willing to go with him. It concerns me that he hasn't anticipated any my concerns (if he knew all about these things) and addressed them before expecting me to climb on board.