Agreed that 4-6 sector day without an A/p is fatiguing but the issue is more of having the capacity / time to brief rather than, in the original comment, of a Long Haul flight departing for a 10+h sector.
I have, and am sure will again, operated both short and long haul without A/p and undoubtedly the longer the flight the more fatigue becomes an issue, especially in weather and / or turbulence. That said if the A/p failed in flight I see no reason not to continue unless fuel becomes a factor in RVSM.