Board Thread:Bug Reports/@comment-26520931-20160922121218/@comment-25101089-20160923131458

Alright, so it might be the quest giver actually disappearing instead of the icon just not being rendered? I've not seen that happening either, but if that is the cause, it should be easy enough to find and fix. If it happens again, you could try and find a crash report, which should have some sort of "skipping entity with id X" error log if the NPC is being removed somehow.

Or it may be as FEANOR said. Like any other entities, quest-givers belong to the chunk they're saved in, and so deleting that region file will delete the quest giver.