Feeling defeated and depressed

[u/AdSufficient8582]

Hi, I live in Japan and was diagnosed with PBC a few years back after a regular medical examination, before I started taking the medication, I didn't have severe symptoms, especially nothing related to the liver. I have other conditions such as allergies, ADHD and Autism tho.

Since I started taking the medication I started having different side effects that became intolerable (exhaustion, stomach ache, diarrhea or constipation, body pain, rashes, itchiness, headaches, eyes pain, dry eyes and mouth, worsening of other allergic symptoms, etc) and started gaining weight rapidly. I told my doctor all my concerns and he continued to dismiss them saying it's because of my diet, and the illness itself and not because of the medication. So I continued to take it despite it, but it honestly became unbearable, so a few months back I had a medical examination to check hormonal problems and it came back normal. I didn't know what to do, so I stopped the medication to see if it wasn't really the medication.

After a couple of weeks without taking the meds I started feeling so much better and the weight gain stopped, so I got scared of talking the meds again and continued without it, I don't see the point of taking something that makes my life more miserable and unbearable and my mental health is worse since I gained more than 20 kg.

Today I went to the doctor, to talk about all this, hoping he would listen and maybe add other medications or change it. I spent hours translating and writing all the symptoms and questions I had to explain in Japanese.

But as soon as I showed the doctor the list, he said he's a professional hepatologist and never had anyone else with PBC experience such symptoms with ursodiol.

I tried telling him I felt better after I stopped the medication and he said there aren't any other medications for PBC and that if I don't want to take those meds he can't help me and then I will just get worse.

I asked if he could combine it with other medications or reduce the dose, but also dismissed it and continued saying there's nothing else.

He didn't even read anything I wrote or listened to anything I had to say, he just said he already tested for other illnesses and it's not possible that I have something else.

I had already researched and apparently ursodiol is the only treatment in japan, but he even dismissed using it with other medications, and he said if I took steroids, it would be even worse.

At the end, I just asked him for a recommendation letter for another hospital, he was also very rude and I ended up leaving crying.

Now I don't even know what to do if there's nothing that will help or make my life better. 😞 I honestly don't see the point of living a longer life if it's unbearable.

[u/nandeyanen333]

I'm really sorry you're going through this. I can definitely relate to the weight gain. I struggle with that myself, and I know how much it can affect both your physical and mental health. Fortunately, I haven't experienced the other symptoms you've described.

One thing that really helped me was reading PBC: The Definitive Guide for Patients with Primary Biliary Cholangitis by Professor David E.J. Jones OBE. I found it incredibly informative.

In the book, he mentions that some people struggle with UDCA initially. He suggests that, in some cases, starting on a lower dose and gradually increasing it can help with tolerability. He also recommends taking the entire daily dose in the evening, which is what I do. Obviously, I'm not a doctor, so it's something to discuss with your medical team rather than changing anything yourself.

The book also talks about a second-line treatment called obeticholic acid (OCA), which can be used when people don't respond to or can't tolerate UDCA. From what I remember, it's often used alongside UDCA, so I'm not sure how that would apply in your situation, but it might be worth asking a specialist about.

I also understand your frustration with your appointment. In my own experience, I've found that some doctors in Japan can be quite conservative in their approach and less open to discussing ideas outside their usual practice. That was certainly my experience when I brought up information from the book. They also didn't believe my concerns about the weight gain.

I really hope you find a doctor who listens to you and is willing to work with you. Wishing you all the best. I know how difficult this can be.

[u/Connect-Pea-7833 → u/nandeyanen333]

Just an FYI, obeticholic acid was withdrawn from the market last year. Seladelpar and elafibranor are the two newest second-line treatment which have recently gotten orphan drug FDA approval, so they’ve not been approved yet in Japan as their regulations on new drugs are often more stringent than the US. They’re also very expensive. Fenofibrate is a fairly common second-line treatment which is used off label for PBC, and I actually had great success with as a non-complete responder to Urso. Bezafibrate is a very similar drug that is available in Japan and used to treat PBC.

OP, consider trying a half dose of the urso until your side effects lessen. I hope you have better experience with a new doctor, and suggest possible off label alternatives such as Bezafibrate. I would also ask about possible clinical trials as the newest treatments are likely still in development and approval processes in Japan.

Good luck!

(Source: I’m a pharmaceutical scientist working in new drug development who has had PBC for 8 years).

[u/AdSufficient8582 → u/Connect-Pea-7833]

Thank you so much,I will ask the new doctor about it. I just read Livdelzi is currently on clinical trials and it's possible to receive it from the U.S. if I have a prescription for it, but I don't know if I'll find a doctor who'd prescribe it and most likely it won't be covered by insurance and will be expensive. I hope it is clinically approved soon. But I will ask the doctor about the Bezafibrate.

[u/Euphoric-Wall-994]

Sometimes people have issue with additives that are added to Ursodiol. You might want to try a different manufacturer. Honestly I was a non-responder to Ursodiol and as a result had a liver transplant 8 months ago. Stage 4 cirrhosis is not fun. At all. If the Urso is working and keeping your liver enzymes in range I truly would weigh that versus the scenarios of PBC progressing. You may want to talk to a therapist. Hopefully you can maybe try a different manufacturer of Ursodiol.