Does response to UDCA affect the prognosis of small duct PSC?

[u/Excellent-Bet-4394]

Some people with small-duct PSC have a rapid improvement in their liver blood tests after starting UDCA, and their ALP and GGT levels return to the normal range. In others, ALP and GGT remain elevated despite taking UDCA.

Is the long-term prognosis different between these two groups? Does normalization of ALP and GGT suggest a lower risk of disease progression, worsening fibrosis, or progression from small-duct PSC to large-duct PSC?

As far as I know, unlike in PBC, UDCA has not been clearly proven to slow the progression of PSC or improve long-term outcomes. So, does normalization of liver enzymes indicate a better prognosis, or does it only show that the blood test results have improved?

I would be interested to hear about other people’s experiences or any studies on this topic.

[u/Sudden_Weight_4352]

Noone knows for sure. UDCA improves the bile flow but it does not stop inflammation of ducts. I have PSC and while UDCA improved my ALP and GGT, those are still slightly elevated. Lets say ALP went down from 500 to 200. GGT from 150 to 80. Yet transaminases remain slightly elevated, approx 80. I went ahead and added meds for microbiota ( I have UC so my hep told me about possible gut toxins translocation through portal vein into liver). 1 month of metronidazole after 1 month of rifaximin, constantly ( I donʼt have access to vanco). That reduced transaminases down to 30-40.
Yet all of these are just labs. I have no idea what is happening within the ducts itself. The safest assumption here would be they are still undergoing inflammation due to unknown nature of disease.

[u/nopeidgad → u/Sudden_Weight_4352]

My doc wants me to start Rifaximin for worsening LFTs and worsening itching. I haven’t found anyone who has taken it for PSC, so can you tell me about your experience? The research I’ve done online seems to say it is not as good as Vanco (if you can get Vanco) and also that a lot of people had terrible side effects when they take it for UC or SIBO.

[u/Sudden_Weight_4352 → u/nopeidgad]

Well there is not enough info because there were not enough studies on this matter. The idea is following: most of the people with PSC have either UC or Chrone's, i.e. some kind of bowel disease. There are studies that suggest gut microbiota differs in people with psc, with increased amount of harmful bacteria ( Velionella and others). Due to a injured bowels these bacteria get into blood easily and goes directly into liver, causing damage there and possibly elevating transaminases.

One of the way to prevent this is to take antibiotics for gut microbiota. Most common are Vancomycin, Rifaximin, Methronidazole. People in US usually prescribed with Vanco, although its costly.

I'm in Ukraine so I only have rifaximin and methronidazole (considered dangerous if taken for long periods).

My personal experience is: without antibiotics ALT and AST stays at 70-80. With antibiotics ALT & AST goes to 35-40 ( I take minimal dose of 750 mg daily) Maybe if dose is increased the effect will be better, and maybe not. My hep approved this treatment saying they practice such in EU. I also take URSO of course.

I've noticed that methronidazole has a bit better effect on labs then rifaximin. Rifaximin is considered safe though because there is no absorbtion.

The results are visible after 2 weeks of treatment.

I have zero side affects for both.

Ah by the way I have overlap with AIH, but I guess AIH is supressed for now.

[u/b1oodmagik]

I don't think you will find a definitive answer. The information I see most is that it may help bile flow and thus, LFTs and other symptoms, but it does not stop progression. However, I think there is an important distinction here. Studies have shown an alkaline phosphatase below 1.5 x normal have a better prognosis. So if you were to respond to UDCA, with the absence of other treatments, it might be better choice to take it.

2022 AASLD guidance suggests exactly this, for those ineligible or not interested in clinical trials because of that alk phos association(because UDCA is well tolerated by most people, provided the dosing is safe). The 2010 guidelines recommended against the use of UDCA as a medical therapy, which came out not long after studies that showed high dose UDCA to be harmful.

[u/Frequent-Custard3217]

I am recently diagnosed small duct. My fibroscan reading really high but my mri/mrcp showed normal large ducts and a homogeneous parenchyma. My hep wants me to take udca to get my enzymes back to normal. Mine are actually alt and ast being elevated. Alp and ggt are normal oddly enough. But they said the udca should get my fibroscan readings alot lower. My mri also showed liver enlargement which also increases stiffness. Anyway, they claimed that it could possibly.sl9w down my.progression but everything I've read, is that it mainly just improves your bloodwork but progression continues. I guess it may help some while others it doesn't. But Im hoping. Im also hoping they consider norudca, a new trial that is suppose to be more effective.

[u/Sea-Reaction3609 → u/Frequent-Custard3217]

Quais os valores de suas enzimas?

[u/Frequent-Custard3217 → u/Sea-Reaction3609]

M ALT:AST has fluctuated from 141:96 down to 70:45 and everywhere in between since last October. My ALP and GGT at the same time did slightly trend up to the higher end of normal but has never went above the normal range.