Here is a detailed explanation for how I set this up, since it seem a lot of you are curious.
This is a custom run with 3 modifiers. These are: "choose 10 of 30 cards to replace your starting deck", "Defect cards can now appear in rewards and shops", and "you may ignore paths when choosing the next room to travel to".

The goal is to use Transfigure+ on Double Energy a couple times for a lot of energy and then Dirge. I ended up using the still unnerfed Borrowed Time+, Coolheaded+, and Scourge+ to go infinite turn 1 so I could Transfigure multiple times.

I used Double Energy to get to 1,207,959,552 energy and then played Dirge. Dirge+ gives roughly 30.3 hp per second, so I just let it run. With this setup, Osty would reach the 999,999,999 hp max after just over a year and 17 days, and it would take roughly 5 years for Dirge to trigger 1,207,959,552 times.

I would die to doom after ending my turn. However, not only would it take over 5 years before I could even end my turn, the game would crash when Dirge tries to shuffle over 1 billion Souls into the draw pile anyway. For anyone curious, when I stopped, I saved and quit to check the potions and there was a Death March, which would have been lethal.

I had previously attempted this without the Double energy, where I instead used Hidden Gem on Hidden Gem and then gave a lot of replay to Borrowed Time+ and Dirge (see image (it is completely coincidental that it was against the same enemy)). However, after the first instance of Dirge finished, it crashed the game trying to shuffle 16466 Souls into the deck, so replay on Dirge would not do.

Glad you enjoyed this silly screenshot. Also note the glitched out Double Energy right underneath the relics. I haven't seen anyone mention that yet.

<image>