Gaz,
Not trying to bust your bubble but with liver disease you best be making bread not beer unless you want to do more damage than what the PSC is doing.
Of course I know you were stating that lightheartedly. 
Mark
Mark,
All good points, and if I was the one with the disease, I would be more willing to put myself into a trial. But my baby? I wanted to try Vanco as soon as possible.
His heptologist seems to be very willing to accomodate the various tests at my request (probably to keep me off his backā¦lol).
There was supposed to be a clinical trial that his group (or maybe the hospital with whom his group works) was going to be participating in, but for some reason the facility was dropped.
Mark.
Just to clarify the ābeerā comment, as I do look after myself wellā¦ Yes it was just in humor. In addition to my ailments (Colitis and PSC) I am also coeliac, so bread, beer and all gluten went 7 years ago.
Basically the whole Australian economy hates residents like me for being unaustralianā¦ 
.
Good to know. With Humana my co-pay will be $800. a month. If I can figure out where to get this I will switch to United BCBS in 2019.
Hi Jtb,
I was referring to an older link on Vancomycin. You had mentioned you take Vancomycin and it helps you. I wanted to know about your experience and side effects if any, do you still take it, how do i get my doctor to prescibe me or do you know whom i can approach to try this out. My doctor is recommending a Liver transplant but i want to try alternatives before going for it as i understand PSC does reappear even after a transplant.
thank you.
Mike
Mike,
Regarding recurrence of PSC. Just for clarification, it does not always reappear and in fact recurrence rates have dropped at least in my part of the country. One of the things thatās helped this is to do the Rou-N-Y procedure hooking up the bile ducts directly into the colon and abandoning the common bile duct for that purpose, plus a regimen of Prednisone for at least a year after transplant. Hopefully you will not have to face recurrence, I certainly hope so.
Mark
Iāve been treating PSC with oral vanco for about 4.5 years now. When I started treatment I was being listed for transplant due to recurrent cholangitis (importantly, I likely did not have cirrhosis). While on the treatment my LFTs have returned to normal and Iāve been asymptomatic. I havenāt experienced any side effects. I was diagnosed with PSC 16 years ago when I was 19 years old and these last few years on vanco have been the healthiest of my adult life.
PSC is pretty rare and most doctors donāt spend the time to research the latest PSC studies. As a rare disease patient your job is to become a subject matter expert. If you are interested in attempting to treat PSC with oral vancomycin, know the existing vanco studies inside and out. Brief your doctor, provide the research, and be prepared to answer questions. What may help is to request this on a trial basis (3-4 months) emulating one of the existing protocols. Be prepared for rejection and try again elsewhere if needed.
Here are some case studies and trials to get you started. Also try to read all the vanco posts on this site and elsewhere (PSC facebook groups are another great resource). Please post If you have any questions. Iām a firm believer in trying everything else thatās possible before you start replacing hardware.
Stanford
Some background - http://sm.stanford.edu/archive/stanmed/2011spring/article6.html
Possible mechanism - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3565076/
Long-term treatment of 14 pediatrics - http://journals.lww.com/jpgn/Fulltext/2008/07000/Long_term_Treatment_of_Primary_Sclerosing.10.aspx
Trial that just wrapped up and we are waiting for results - https://clinicaltrials.gov/ct2/show/NCT01802073
Mayo/Lindor
http://www.medscape.com/viewarticle/780291
A long-term look at the patients in the above referenced trial - http://www.firstwordpharma.com/node/1385083
Case study
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5061664/
Iran
http://www.jgld.ro/wp/archive/y2016/n4/a7/
Mass General
Cal Poly
http://digitalcommons.calpoly.edu/cgi/viewcontent.cgi?article=1016&context=symposium
Here are some rPSC case studies:
-http://casereports.bmj.com/content/2017/bcr-2ā ā ā ā 65.full
-https://www.hindawi.com/journals/crit/2013/314292/
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Hi jtb,
Possibly it is all in the genesā¦ and PSC (and some other inflammatory diseases) could be genetic diseases. It looks like the FUT 2 gene could be the culprit for the PSC. The attachments explain the role of FUT 2 gene in regulating the bacteria in the intestines and its role played in the theory of the āleaky gutā. Maybe that would explain the dual role of the OV treatment: antibacterial and immunoregulator?
Did you come across this FUT 2 gene in your readings? Thanks. Daniela
PSC autoimune-2017-Clinical_Liver_Disease.pdf (284.7 KB)
FUT 2 gene and non secretor and and PSC.pdf (378.2 KB)
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FUT 2 has come up before in the facebook groups and IIRC we had patients with and without the gene.
I do believe that there is a genetic component to PSC but I take the very unorthodox view that PSC and PSC-IBD are not primarily autoimmune diseases, largely because of what OV treatment does to the gut. A few of us on treatment have sent samples to American Gut and the composition of gut bacteria on treatment is in theory very pro-inflammatory (non-PSC OV trials show similar gut microbiota). The results are that all of the normal bacteria, both gram positive and negative, are wiped out with an overgrowth of what are generally considered pathogenic, pro-inflammatory bacteria. There are some recent papers floating around reflecting on how certain gut bacteria influence the immune system. OV does everything wrong here, yet it still works.
In my opinion, a variant of PSC that is responsive to OV could be what was discovered here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4609469/. PSC could be an impaired ability to sulfate (make less toxic) the secondary bile acid, lithocholic acid (LCA). Levels of LCA correlate with outcome. Patients on high-dose urso were found to have higher than normal levels of LCA and were 2.3 times as likely to reach an end point (see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928060/). Patients taking OV were found to have little to no LCA (see https://www.ncbi.nlm.nih.gov/pubmed/24316517). This makes sense, OV kills the known bacteria that produce LCA (this bacteria converts CDCA and UDCA (urso) into LCA). In my opinion, PSC and PSC-IBD resolve on OV because the underlying cause of inflammation, unsulfated LCA, is no longer present.
We do have evidence of an autoimmune response and I believe this is a secondary effect caused by cholestasis/inflammation generally (studies have described such a response in the presence of bile acids and cholestasis alone).
This theory also may explain why PSC-UC tends to manifest differently than normal UC (near the small intestine vs further downstream). Unsulfated LCA tends to remain in interohepatic circulation compared to sulfated LCA that is eliminated. This unsulfated LCA is absorbed through the gut where PSC-UC often begins (ileum-cecum).
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Thks a lot jtb. The info is very interesting and it makes sense. Really appreciate the effort that you put into understanding the mechanism of this diseaseā¦Very helpful, thks a mill again. Daniela
jtb, I just came across this paper from 2003 re LCA and liver toxicity. The Discussion section of this paper is of particular interest.
Again, thks very much for pointing me to research in that direction. Daniela
Good stuff, Daniela. Feeding LCA is one of the animal models used to emulate PSC. Most critters arenāt naturally exposed to LCA and lack many of the mechanisms that humans have adapted for breaking it down into a less toxic form. Unless I missed something it sounds like they never figured out exactly why female vs male FXR-null mice produced a bunch of SULT2A1. For PSC patients, it seems like PXR stimulated SULT2A1 expression is broken. Is there some clever way we can work around this? The hormone DHEA expresses SULT2A1 through FXR, CAR, and PXR. Would incidental SULT2A1 expression in the liver and gut through PO DHEA sulfate LCA?
You got me going down the FUT2 rabbit hole. Hereās a good PSC specific study that was referenced in the paper you provided: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399030/. Whatās interesting is that the PSC non-secretors have higher levels of Firmicutes and lower levels of Proteobacteria than the PSC secretors. OV treatment has the opposite effect ā it eliminates nearly all Firmicutes (and gram negative Bacteroidetes, oddly) resulting in an overgrowth of Proteobacteria.
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Thanks for the information Mark. Which part of the country did you get your transplant done. I live in Illinois. I was recommended for the Liver transplant assessment which will start next week onwards. I will definitely discuss this procedure with my Hepa.
Thanks for the information jtb. This is a lot to absorb. How do you get your Vanco, is there a doctor you can refer me to? My Hepa gave me a -ve response and will not go for it. I needed to know what the protocol is to get started and how to get the prescription. I was diag in 2003 so time is ticking for me.
Mike,
I am from North Carolina and had my transplant at Duke Medical Center.
Mark
Mike, Iām not sure around Illinois. Reach out to some of the OV researchers such as Dr. Cox, Dr. Shamita Shah, Dr. Yinka Davies, or Dr. Lindor and see if they have any recommendations in your area.
Iām a patient of Dr. Rangnekar at the Georgetown Transplant Institute. He prescribes OV to his PSC patients on a case by case basis.
The Stanford folk have been prescribing this for 20+ years and recommend starting at 1500mg/day (500mg tid).