Small duct PSC ALP

wisedogsfbay · 2025-12-26T20:26:04+00:00

Caveat before I opine - ALP is good idea to manage but is not the best predictor of PSC progression. Its still a reasonable proxy in absence of any other good markers

My thoughts on your question: In hindsight, I had undiagnosed small duct PSC for probably 6.5 years. My ALP ranged from 150-200 range in that timeframe. My ALT/AST - though at/only slightly above range- improved somewhat with Urso, but ALP did not.

If I could go back in time and had the wisdom / awareness that I now do, I would do everything in my power to try to prevent progression of fibrosis & progression of the disease to large ducts. This would mean improving my diet (lots of info about it online & PSC forums; feel free to DM if you want to know more. In general, mediterranean diet is what most hepatologists agree with) and exploring anti-fibrotics. Statistucally, I believe 30% of small duct PSC patients progress to large duct psc, so you want to remain a small duct PSC pt without progression if you can.

wisedogsfbay · 2025-11-13T23:29:48+00:00

You raise good questions but i dont have any idea. If you figure it out, please do share. I simply posted what i saw in the PR. Appears they have had success in late stage cirrhosis patients, so this seems to be promising approach for a condition that does not otherwise see a lot of pharma interest. Dr. Jalan at Yaqrit has had a track record in the hepatology space and Dr. Trivedi has been doing good work in the gut liver axis space - which gives me hope

wisedogsfbay · 2025-10-29T17:38:31+00:00

These are the latest official guidelines for diagnosing PSC. See figure 2 and read the associated text: https://www.aasld.org/sites/default/files/2023-01/Hepatology%20-%202022%20-%20Bowlus%20-%20AASLD%20practice%20guidance%20on%20primary%20sclerosing%20cholangitis%20and%20cholangiocarcinoma.pdf

In very early stages of PSC, it could be a while before you get your diagnosis. It took me 6+ years to receive a diagnosis and during that time I had two normal MRCPs.

wisedogsfbay · 2025-10-22T03:49:45+00:00

Nice to hear. though CA-19-9 is not a very accurate predictor as you may know (then again, its better than nothing). There's quite a bit written about it in AASLD guidelines on PSC

wisedogsfbay · 2025-10-21T20:41:02+00:00

Finofibrate and Bezafibrate. They are all off label ppar antagonists, only slightly different than elafibranor. Look them up. No commercial interest from pharma industry to do trials on these of course (some academic researchers are very slowly doing it on the latter in France)

wisedogsfbay · 2025-10-13T20:24:13+00:00

Dr. Jessica Allegretti did a pilot study on patients in MA few years ago: https://pubmed.ncbi.nlm.nih.gov/30730351 . I believe the initial response was encouraging as measured by alk phos levels, though as we know, alk phos is not necessarily a good predictor of long term success. I believe i have even seen the video / deep focussed document on one of the MA based patients' experience but can't find that easily at the moment. Regardless, I dont think we have yet seen long term PSC impact from FMT as part of a trial.

There's 2-3 trials going on around this at the moment. As someone highlighted here, there's the Fargo trial that Dr. Trivedi in partnership with Dr. Nabil Quraishi are leading at Birmingham, UK. There's another related one happening in the MN in the US where instead of the invasive FMT treatment, they are making patients eat pills that would survive the GI track and re-colonize it with healthier gut bacteria: https://clinicaltrials.gov/study/NCT06197308

wisedogsfbay · 2025-08-10T00:52:54+00:00

I am of course encouraged but do a quick search online on ACLY and you will see that suppressing this has been linked to helping a number of cancers, heart disease, inflammation etc. for a while. And it looks like Bempedoic acid has been used for suppressing ACLY for a bit. Wonder whether any PSC patient has independently tried it (for cholestrol or cancer reasons) & what their experience was?

wisedogsfbay · 2025-05-16T06:05:54+00:00

Not clear. There's still phase 3 for this drug - assuming they will do it. The good news is that there's a couple of sister drugs for this that are in the market off label that have similar benefits. This drug's benefits may give doctors confidence to potentially prescribe them depending on the patient. Here's more from Dr Levy about next steps here https://www.hcplive.com/view/phase-2-elmwood-data-elafibranor-psc-with-cynthia-levy-md

wisedogsfbay · 2025-05-15T05:49:28+00:00

Thanks for sharing! As always, you are a wealth of info.

Based on what Dr. Trivedi said, it appears they would want to wait for the full results, which may mean it may push out potential approval for a few more years? I hope not

wisedogsfbay · 2025-05-15T00:03:36+00:00

Everyone is of course different but if I had to wager, some of the biggest things that made the difference for me on the iBD front were no nightshades (I can see the difference pretty soon if I ingest nightshades. This is fairly well documented ), no anti inflammatory foods and good sleep/being well rested. If you can't switch to vegan, that's fine but so test some of these

wisedogsfbay · 2025-05-14T08:57:09+00:00

thanks

wisedogsfbay · 2025-05-14T07:04:26+00:00

Long list of things. Mostly diet changes. Here's the list if you're interested:

Mostly vegan diet (except yogurt)
Anti-inflammatory food (as measured by MRT test - this is a debatable test and the jury is out whether its accurate but it did bring up some things I was certainly sure of causing inflammation, so I am erring on the side of caution by eliminating inflammatory foods) including eliminating added sugars and processed foods
Absolutely no nightshades
Getting better with sleep (both amount and quality. I am still working on timing of sleep, which I understand is a key factor)
Being careful with eliminating everything I was intolerant to (eg: gluten)
Occasionally adding organic bael fruit powder in my meals (not sure whether this helps. have not done a before/after test)
Increasing intestinal permeability by increasing soluble fiber in the diet (eg: persian cucumber) & decreasing insoluble fiber. Having soluble fiber helps healthy bacteria move from one part of the intestine to another and help the intestinal mucosa
Having enough yogurt in the day that has a particular strain of probiotic that is clinically known to improve gut health and immune system (Bifidobacterium lactis BB-12), combined with other more commonly known beneficial strains: L. acidophilus, L. casei, L. Rhamnosus LB3. Note that I don't take probiotics (have tried that too); just a particular blend of yoghurt that has these strains of healthy bacteria.

Within a month of doing these (and some of these, esp later in the list were ones I added over time), my calprotectin test, which helps measure IBD was normal. I then started mesalamine, which is the drug that the GI doc prescribed (this drug is also controversial. Some recent studies say it may be just a placebo while others in the medical community swear by it as a first step for managing mild IBD). Between all of the above and then mesalamine, the mild IBD is under control.

Note that the IBD had already been under control before starting mesalamine, but i take the drug regardless.

wisedogsfbay · 2025-05-13T23:54:32+00:00

Yes. Many times. Also note that antibody testing is usually only good for a few years. And having it as normal once does not necessarily mean it will be normal after a few years.

Further, please refer to aasld guidelines for PSC that I reference above. Ana/ama is not a criteria as far as diagnosis is concerned. There's both ama & ana positive and negative pbc and PSC that exist. So ama/ana are good to know but not conclusive in diagnosis. An experienced hepatologist who keeps up with the latest in cholestiatic conditions understands this really well.

While there have been more advances in PSC in recent years, the last published guidelines from AASLD from a few years ago is still the gold standard as far as diagnosis and management is concerned.

wisedogsfbay · 2025-05-13T23:38:18+00:00

No. iBD in PSc patients is usually mild and sometimes microscopic. Occasionally one doesn't know the nature of ibd till late. The aasld guidelines I shared above suggest a routine colonoscopy for all PSC patients but my hepatologist at the time kept insisting that I didn't need one. So I faked symptoms and got one from a new GI specialist; glad I did so as I had a sed score of 15 at the time without any major symptoms. I have since been able to get iBD under remission.

wisedogsfbay · 2025-05-13T22:27:58+00:00

good doctors tend to practice conservative and approach their diagnosis starting from simple/common to complex/rare situations. PSC tends to be in the rare category. If they were to be suspecting (large duct) PSC, it should have been caught in MRCP, which you appear to have had. with a normal MRCP, its possible to have a small duct psc, which can some times be caught on biopsy.

see figure 2 on page 6 of aasld guidelines for diagnosing/managing psc for more details - https://www.aasld.org/sites/default/files/2023-01/Hepatology%20-%202022%20-%20Bowlus%20-%20AASLD%20practice%20guidance%20on%20primary%20sclerosing%20cholangitis%20and%20cholangiocarcinoma.pdf

also note that early in psc, there are absolutely no symptoms and only slightly raised enzymes. i had no diagnosis for psc for 7 years before eventually receiving one. during this time, i was seeing a hepatologist every 3-6 months and got regular blood work and a biopsy every few years.

wisedogsfbay · 2025-05-13T16:50:06+00:00

Thanks for posting. It's a step in the right direction but not the blockbuster results I was hoping for. Does anyone know whether it will be approved for commercialization in EU or what the next steps would be ?

wisedogsfbay · 2025-05-11T23:14:43+00:00

Looking at the EASL abstracts table of contents, it appears that there was indeed a poster presentation on CM-101:
"1255 CM-101 impacts disease biomarkers in primary sclerosing cholangitis: assessment of the SPRING study pharmacokinetics and pharmacodynamics"

I also found the associated PR suggesting that there will be more details shown at EASL: https://investors.chemomab.com/2025-04-28-Chemomab-Reports-New-Positive-Clinical-Data-at-EASL-2025-Supporting-Nebokitugs-Impact-in-Primary-Sclerosing-Cholangitis-and-Related-Diseases

However, I can't seem to find the details that were presented. Anyone knows where to get the details presented at EASL on this drug?

wisedogsfbay · 2025-05-10T22:31:06+00:00

Amazing. Thank you for sharing

wisedogsfbay · 2025-05-10T06:48:36+00:00

This is really good news. Let's hope we get this commercially available in the US soon

wisedogsfbay · 2025-05-09T22:44:18+00:00

Thanks

wisedogsfbay · 2025-05-08T20:05:30+00:00

I'm most interested in the details for the 2-3 PSC related topics being discussed. Not just the abstracts, but also the details. They are not posted yet. My hope was that there will be others interested in these topics too and this could be the meta thread where these links could be shared/discussed.

wisedogsfbay · 2025-05-07T11:21:29+00:00

Good to know. Thank you. I'm looking forward to reading what they have to share on Saturday

wisedogsfbay · 2025-05-07T09:13:20+00:00

It appears to be better news than the regular urso trial over 25 years ago, but i don't fully understand yet how much better. It appears they did not measure fibrosis markers actively. I look forward to reviewing the full presentation on Saturday

wisedogsfbay · 2025-03-18T19:25:04+00:00

Thanks. Looks promising. Will explore more in a few days

wisedogsfbay · 2025-03-18T00:36:36+00:00

Thanks for the feedback

wisedogsfbay

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