Thread by @ebtapper

What's the deal with ... Gilbert's syndrome?

Unconjugated bilirubin deserves its own #tweetorial

Featuring:
🟨Why?
🟨Is it bad or...PLOT TWIST...good!?
🟨What to do about it?
🏆The most 🍌🍌trials ever conducted

#livertwitter #meded #MedTwitter

1/

What is Gilbert's?

1⃣Healthy person gets labs. Bili 2.4, >80% indirect
2⃣Student studies all🌙, forgets 2 eat.
In AM,👀slightly 🟨

Turns out:
👉3% of🌎has bili>1.4mg/dL (fig1)

Many things⬆️indirect bili:
👉Only 1⃣ makes bili⬆️w/fasting (Fig2)

It's...

2/

GILBERT'S SYNDROME

Who?1⃣Described c1901. Hilarious paper
(🙏google translate, my🇨🇦franglish education)
Why?2⃣Familial⬇️UDPGT protein
(the thing that 'conjugates' bili)
Why?3⃣Base pair insertion in UGT1A1 promoter
(#TATAbox, the gene that makes UDPGT)

3/

But ...why is Gilbert's even a thing?
Why so common?

let's back up

Where does unconjugated bili come from?

1⃣Rusty🩸cells give up heme
2⃣Heme-oxygenase➡️Biliverdin➡️unconj bili
3⃣Liver takes bili➡️conjugates, dumps in bile
(👍fig from my old pal Sush Jangi)

4/

Biliverdin:
non-toxic,🚰soluble, 🟩pigment

Unconjugated Bilirubin:
toxic,🚫soluble,🟨pigment, needs energy 2make,
AND needs 2b conjugated 2b excreted

Why bother?
Why does every mammal make bilirubin?
Why is Gilbert's super common?

!!WHY!!

5/

Could unconjugated bilirubin...
...be good?

The birth of an idea:
In a 100% 🍌🍌 1938 paper:
🤔Hench saw improved RA symptoms after jaundice
💉So he injected ppl w/bili
😢No benefit

But!

Turns out bili IS an antioxidant with immunomodulating properties

6/

⬆️bilirubin levels or Gilbert mutation associated with

🫁⬇️resp disease
♥️⬇️heart disease
🦀⬇️cancer, particularly colon

and lower risks of RA, crohn's, lupus, and MS

Bring on the bili?

7/

Obviously too much bili is no good

1⃣+ immune associations lost when bili⬆️⬆️
2⃣Absent UDPGT? Keyword: Kernicterus.
That's crigler-najjar.
Type 1: Fatal without☀️therapy♾ or liver transplant
Type 2: 🤏UDPGT activity, induced by phenobarb

8/

Many things alter UDPGT activity

💊phenobarb induces
💊rifampin suppresses
🚬induces
🥃🍷induces, surprisingly

And the time has come!
The most🍌🍌🍌trial I have read

To prevent neonatal jaundice...
...🥃🍷was given to⬆️UDPGT activity in
... pregnant women

9/

If you find an isolated,⬆️unconjugated bili,
how do you congratulate the patient on their Gilbert's?

1⃣You could order the gene test
But then you'd have to wear a top hat qTuesday
Dont @ me. I dont make the rules

Or

2⃣you can follow these pathways (Fig1-2)

10/

This concludes a #tweetorial on Gilbert's!

Summary:
🟨Isolated hi indirect bili
🟨Common
🟨Unconjugated bili is antioxidant
🟨conjugation🔃by fasting, 💊🚬🥃
🟨A little extra bili may be good

Thank you for reading. Hope you enjoyed

11/11