If you guys have fairly new OE oxygen sensors (under 100K miles), run it! If they are old or aftermarket, they might screw up the virtual calculation and may cause driving issues or may not.
E85 is like cheap race gas, the motors love it! Put 5-6 tanks through the motor and the computers will fully adjust for it, even the transmission runs better in ours on that stuff.
There are no issues leaving it in your tank for a time, I've sat parked with only 5 gallons in the tank for over a month many times without issue. We have plastic tanks and everything else is made to come in contact with it in our fuel system.
It is an excellent cleanser so if that's what you want to do, who cares how much it costs. That's not the reason you're running it.
Driving around town and out to about a 50/50 mix of city and highway driving the 5.3 will burn a 1/2 gallon more per hour on E85 than 93 octane gasoline. On the highway, about a gallon more per hour.
These are my truck's stats since late 2017 and 220+ fill ups:
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