You would likely lose the ability to run most of the trails do to clearance issues unless you put more of a lift into the truck. Most full size pickups because of their length don’t have sufficient clearance to get over most of the rock obstacles. And then there are still some very tight areas.
With that being said there are some guys running larger trucks such as H1s and H2s and I know of one Ford Excursion on 42s. But he has the clearance.