When might a pilot hand-fly a jet at cruise altitudes, and is it difficult?
For 747-100 and -200 aircraft at 35,000 ft and above, you can do it, but it's hard to keep the airplane within 100 feet of the assigned altitude, and you typically can't do that (or at least I couldn't) without practice. 200 foot altitude excursions were the norm when I first took control if I had not done it for a while. For the few first officers that accepted an invitation to try it, an initial 300 foot altitude excursion was typical when they first tried it, especially immediately after disengaging the autopilot.

I found the concentration required was very tiring. Ten minutes was typically enough to satisfy the urge.

Insofar as when you might want to do it, I found hand-flying produced a smoother ride in heavy to severe turbulence than the autopilot's turbulence mode, which tended to try to keep the assigned altitude and aircraft pitch too slavishly.