First off, Milk Thistle is probably not the greatest example as a recent 3rd party tested subset of products showed well over 80% of products NOT meeting label claims.
That said, the 4-hour protocol was introduced when multiple doses per day were employed to attenuate potential interaction. On a two-times per day protocol of oral PH/PS/DeS/AAS, the rationale centered on 4 hours to leave you up for 12 approximate hours.
In other words and a sheer example alone:
8am - 1st PH/PS/DeS/AAS (oral C17 alkylated) dose
12pm - 1st dose hepatoprotectant
4pm - 2nd PH/PS/DeS/AAS (oral C17 alkylated) dose
8pm - 2nd dose hepatoprotectant
Provided there are ANY other dosing protocols being employed, the direct hepatoprotectant setup would be modified accordingly. I have explained this setup (as well as presented the various lab work that offers rationale for it) thoroughly in many places on the web and I would invite you to check it out if the above doesn't seem clear.
Thanks for the interest,
D_