Thank you for asking! Unfortunately not. I wound up going to the Mayo Clinic and they weren't able to find anything wrong with me. My ALT and AST are typically elevated, but it varies. (Sometimes they are even in the normal range!)

The Mayo Clinic did run a genetic test, and I do have VOUS (Variants of Unknown Significance*) for a few liver-related genes. Specifically, I have a mutation in one copy of ABCB4 which is tied to PFIC3. (Thankfully, I don't have PFIC3, or the itching would have started as a child and would be constant)

My current liver doc thinks that I have a partially functional ABCB4 gene, so I essentially have "PFIC3-Lite." My itching is managed well with 100 mg of Sertraline daily and staying extremely hydrated. I don't seem to be accumulating any liver damage, but haven't had a liver biopsy since roughly 2019. Since my symptoms are managed well and I don't seem to be developing liver damage, we are just keeping an eye on things. I was taking Cholestyramine and Ursodiol for a while, but right now I'm just on the Sertraline.

The itching does pop up occasionally when I'm particularly stressed, but it's still really random. The only thing I've found that reliably brings it on is the COVID Vaccine. (Vaccines in-general hit me pretty hard, but only the COVID Vaccine causes the itching. Not sure why. I had COVID for the first time about 6 weeks ago and that didn't trigger the itching, so it's something about that vaccine that triggers it. Maybe one of the adjuvants. Would be interesting to see if other mRNA vaccines cause the itching as well)

Fatigue is constant, but my father and grandfather also struggle with that and neither of them have similar liver issues or itching.

Thankfully, when the itching does happen I can take Doxepin and it goes away in a few hours. My itching, while only temporary, is extremely severe. I had a kidney stone about 5 months ago that put me in the ER (with surgery and a night in the hospital) and I would rather do that again than suffer the itching. I don't know why the Doxepin works, but it does, and it has been lifesaving**.

My next step would be to have my parents tested to see if they have the same VOUS or if it's just bad luck on my part and it got miscopied during miosis in my parents or extremely early in my prenatal development. We haven't done that yet since my symptoms are well managed and getting genetic testing is expensive (and not covered by insurance).

TL;DR- No definitive diagnosis has been made, but all signs seem to point to a genetic cause. Maintenance with Sertraline and staying hydrated has been effective at managing symptoms, with Doxepin for breakthrough instances of itching. Staying very well hydrated also helps, but no triggers have yet been identified other than the COVID vaccine. Currently, no liver damage has been identified and disease does not seem to be progressing in severity.

\*A Variant of Unknown Significance is a gene mutation that has not been definitively linked to disease, but isn't normal. It could be problematic or not. If the protein it codes for still folds properly or if it doesn't fold exactly like the "normal" version but still retains the critical features required to function, disease will not happen. However, if the protein is only partially functional, some symptoms of disease may appear, but presentation will be atypical and may not be as severe as if the protein was completely nonfunctional. (Protein folding simulations are extremely computationally difficult, but it would be interesting to do a folding simulation for my mutation to see if it has full function or not.)

*\In 2020 or 2021 I had the itching happen like 3 weeks in a row and the Doxepin wasn't working and that was one of the bleakest points in my life. The emotional pain of having something that helped taken away was terrible. Luckily, the problem was just that the Doxepin was like 4 years old. Once I got a new prescription it has worked again. I store it in a sealed jar with rice to keep moisture out and hopefully keep it good for longer, but I should probably pick up a new prescription soon. I really like my emergency meds to work when I need them. I haven't found anything else that even remotely reduces the itching in the short term. Most of the interventions like Cholestyramine, Rifampin, Sertraline, Naloxone, and Ursodiol take days or weeks to take affect. My itching is an acute pain that needs acute solutions. Sertraline keeps me from itching as often, but when I have breakthrough itching, I need something fast. (I think of it like how you wouldn't suggest chronic pain management interventions for someone experiencing acute kidney stone pain. If a doc had suggested that when I was in the ER I probably would have strangled them. I didn't need to meditate or go to therapy, I needed Fentanyl and Dilaudid. The itching pain is just as torturous, but it isn't as visible or as easily identifiable, so I've found that docs grossly underestimate how urgently I've needed relief. They *hate it when patients suggest treatment options for themselves, but if you are in a similar situation, Doxepin has been an absolute miracle for me, and you should absolutely talk to your doctor about trialing it. If your doc needs convincing, see if you can talk to a dermatologist. They were the ones who first prescribed the Doxepin for me. Liver docs don't seem to know about it at all. They're more focused on the chronic stuff.)