Why treat if it doesn't affect final outcome?

I have read that treatments like Urso can normalize liver numbers, but don’t affect life span or length of time before needing a liver. So why use it? Does it help improve quality of life? I am asking because this has been an option presented to me for my 14 year old son.

Some people believe that it has at least some, minor benefit (extending lifespan before transplant) for some subset of psc patients. Recent trials have not shown such effect, but it is plausible that some small effect exist.

Personally I dont use urso anymore as I do not believe it provides any real help (and it has been removed from psc treatment guidelines by major professional groups).

Have you considered using oral vanco? It has worked great and been used 20 years by few doctors to treat psc patients, especially children. It is in final, phase 3 clinical trial now. Hopefully thus leads to FDA approval and more widespread availability soon.

I can only share my own personal experience, but I basically had the same question when I read those same study results. A couple years ago, when I was 25 years old, for the first time in my life I experienced stomach pain in the upper right quadrant. I thought it was weird because I had never felt pain in that area ever, but here it was, and it wasn't going away. A quick internet search suggested gallbladder pain, which could be caused by stones. I waited for a few hours as the pain got worse, until I finally went to the ER, and as luck would have it the pain started going away right after I got there. I continued with the x-rays, ultrasounds, and whatever other scans they did, but they found no stones and with my pain gone, sent me on my way with for no explanation. For the next 18 months, I would experience this same pain no less than a dozen times, sometimes brief (a few hours) like that first time, but in most cases much worse. Each episode would usually go like this: severe stomach pain for up to 12 hours, followed by vomiting for another 24 hours, fatigue, and headache, dark urine, pale stools, then all-over-body itching for about a week. I called these "episodes" or "attacks" and I suffered through them for over a year before I finally decided to go to the ER again after we had moved, so this would be at a different hospital. Again no stones, but this time they found "sludge" in my gallbladder on the scans, so they admitted me and ordered a HIDA scan and MRI. MRI was fine. For HIDA, the dye is supposed to move from your liver to your gallbladder relatively quickly but mine was not moving at all. Not 2 hours later, not 4 hours later, it was still in my gallbladder. When they checked the following day it had finally moved, but it's not supposed to take that long. With my pain gone and symptoms gone, they dismissed me without much of an explanation. The theory at this time was a sphincter of oddi dysfunction. I was feeling better after that pretty bad episode, but it didn't last. The day after I got home from the hospital I was hit with more pain, then it went away, then another. Two attacks in 48 hours. Severe itching everywhere. The whites of my eyes were yellowI went to a doctor and explained everything and he called the gastroenterologist and told him I needed an ERCP asap, so we scheduled one for that weekend. At this point we still suspected sphincter of oddi but the GE explained that my ERCP looked like I had PSC. He prescribed me Urso. When I had another attack a few weeks later, he scheduled a colonoscopy to rule out IBD/Chron's and liver biopsy to confirm PSC. Colon was perfectly fine. Liver biopsy showed signs of cholestasis but was inconclusive? Not sure what that meant, but the GE said I was a mystery and he referred me to the lead hepatologist at the University of Michigan. Went there and explained everything, had another MRI done (fine again), and he said keep taking the Urso and get blood work every month. That was June 2014.

I took the urso for two weeks, all the while performing research and seeing things like the studies you mentioned, and I came to the same question. Why am I taking this if it doesn't help? I didn't really experience any side effects, but I was forgetting to take it, and that would cause me to stress out, and I just realized that this is kind of silly if it's not doing anything for me. So I stopped. I stopped taking Urso, I didn't get any blood work, and I kept the same type of diet I've had my adult life. I didn't change anything, and for whatever reason, my infections have stopped. In just two weeks it will be early June 2015, and it will be one year since my last infection. I have no idea why. I just kind of figured I would get blood work done the next time I got an infection. I was getting them every couple of months for a year and a half, then they stopped completely. I wish I knew why, and I'm knocking on wood whenever I think about it. For all I know, I could have an infection tomorrow or never again, I haven't the faintest idea what's going on with me, and I don't think anybody else does either.

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Our son is taking Urso. It has brought his liver numbers down to almost normal, however, the primary reason for use in my son's case is that some research has shown a possible added protection against colon cancer, which applies since he also has ulcerative colitis. Our son also takes azathioprine and is on Remicade as well, which can bring liver numbers down as well.

We have had two GI specialists actually have conflicting opinions on the Urso. The first that began treatment of our son was firmly against use of Urso, as he felt studies showed that not only did it not change final outcome, but a small subset of patients actually went to transplant faster than was expected while on it. The second specialist wholly disagreed, and said that from what he understood in research results was that the patients negatively affected by Urso had multiple other health issues, which made the results of the Urso studies less reliable in his thinking. He told us he puts all his PSC patients, and most UC patients on it. Then we had a third specialist, who is not really following our son's case but is part of the consultation group for our son, state that azathioprine is serving a "dual purpose" in helping both the colitis and the liver numbers, as she felt aza might delay time to transplant. ( I had never heard this before. No research was provided to back this up.) She also agreed with the use of Urso.

Pretty frustrating to not get consensus from the people who are the experts.

What sold Urso for us was the possibility of the added cancer protection, not the liver enzymes coming down. Our son experiences chronic pain of varying degrees, and it has continued both with and without Urso.

Hi Rivermouse,

the use of URSO is frequently debated among people with PSC. Some doctors have found that it doesn't provide any true benefit. Personally, I took URSO for an extended period of time. At that time, I was taking 3 pills/3x a day. It never lowered my liver numbers, nor reduced the itching.

In my opinion (and it is truly just my opinion), if the medication has a positive effect on the liver numbers, I would think that it has to provide at least some benefit to your son's overall health.

Although I know that many people have had no positive reaction to the medication, there are some that find it beneficial. My GI doesn't believe in prescribing it because she doesn't believe it works, but there is another doctor in her office that prescribes it regularly.

I don't think the medication causes issues (other than the fact that it is medication being processed by an already taxed liver), so you could always give it a try and see how he responds.

Good luck!

My doctor at Mayo said Urso generally improves your outlook to the extent your blookwork improves, but I know there is some debate around that. In my view...if my bloodwork improves, it certainly couldn't do me any harm so why not? I'm not on a high dose (high dose isn't good) and my values have improved meaningfully.

I think much of the debate around Urso is because the studies are don't show it to be clinically effective (ie the statistics don't support it). But it does improve liver values for some patients. An interesting idea is that PSC might be a collection of diseases that look similar, rather than one disease. As an analogy, we used to think that hepatitis was one disease but we later figured out that there are multiple types and each type is treated differently. If a treatment for one type was tested on patients across all types of hepatitis, it would be statistically ineffective. My doctor (he's a research type so it's his nature) mentioned this idea to me and it seems intuitive...he's speculating of course, but it seems like a good enough reason to give Urso a try.

I wouldn’t say that “it can’t hurt to take it”. One must measure the risks from the benefits…And the side effects that each individual might experience is to be considered also. My husband broke out in strange white bumps all over his body. One of the main US researchers was his doctor and he was not too keen on it a couple of years ago. Here are side effect to consider:
More common

Bladder pain
bloody or cloudy urine
difficult, burning, or painful urination
fast heartbeat
frequent urge to urinate
lower back or side pain
severe nausea
skin rash or itching over the entire body
stomach pain

Thank you everyone for the informative replies! My son hates taking pills. I really only want him on something if there is a pretty clear chance of a benefit. We are hoping to try Vanc soon. His Dr. Said he would contact Dr. Cox or Davies on our behalf since my emails and phone calls have not been returned. I think we would try the Urso if his itching gets to be o bad that he can’t handle it anymore-- until then, hopefully we can try the Vanc.

Hi Rivermouse,

I was diagnosed in 2011 with PSC at the age of 45. I've been treated with ursodiol ever since, and I am asymptomatic at this time. The information on the ultimate outcome of ursodiol treatment on PSC is scanty, conflicting and confusing. All I can say is that my enzymes and blood work has been within normal parameters since starting on this medication. I am not aware of any consistent information that ursodiol will cause a worsening of the condition, so my best advice would be to try the ursodiol, with the doctor's supervision, and if it doesn't help or if your son's condition worsens, you can always stop. I would try the lowest possible dose at first, then adjust as needed based on your son's response. Research is always advancing, and new options such as stem cell treatment will likely become available in the near future. Good luck, and I wish you all the best.

Urso has been used in PSC since years. There are indications that it works for about 10% of PSClers. There was a study in 2009 with a high (about double dose as normal) dosed Urso (by Lindor) in which more patients on high dose Urso had negative effects as those on placebo. Basing on that, the american guidlines were against Urso. And that's why a lot of doctors in US are against it. There was a study last year showing that if people stop Urso they are getting worse. The newest american guideline (April 2015) revised its strong position against Urso. Here is an extract:

UDCA has been the best studied of a number of potential treatments. A study of 105 patients using the dose of UDCA appropriate for patients with primary biliary cirrhosis (13–15 mg/kg/day) did show biochemical improvement but lack of evidence of clinical improvement (25). Subsequently, somewhat higher doses were tested and potential benefit was identified (43, 44). A large trial, which was nevertheless under enrolled, was reported from Scandinavia using a dose of 17–23 mg/kg/day. Biochemical improvement and important trends in clinical improvement were seen (45). The study enrolled only 63% of patients planned by power calculations; thus, the results were inconclusive. Recently, a large trial using a high dose of UDCA of 28–30 mg/kg/day was tested (46). Unfortunately, in this study the patients receiving the drug fared worse when compared with placebo, with substantially more adverse clinically important outcomes such as the need for transplantation and the development of varices. More recently, high doses of UDCA have been associated with an increased risk of colonic neoplasia in the settings of PSC and ulcerative colitis. At this point, no indication exists for using the higher doses of 28–30 mg/kg/day of UDCA (42).

More recently, several studies have shown that patients with PSC, who normalize liver biochemistries, whether this occurs spontaneously or more often with UDCA therapy, have a better prognosis. This has led some to revisit the issue of UCDA treatment for PSC; many practitioners are using a dose of ~20 mg/kg/day, although data from well-controlled clinical trials are lacking (47, 48, 49).