TWRA DOES NOT enforce the USCG regs that require a Captains License for guiding on all inland waters under their (USCG) jurisdiction. My understanding is that includes all navigable waters, but that would be a question for them. Your Clinch River IMO would fall under their regs.
I'm not sure how big of an enforcement priority it is for the Coast Guard to enforce the "six-pack" license. But, it is something that might come into play in the event of a lawsuit if the guide didn't have one as required. You can check with the USCG Group Ohio Valley on how and where to take the test.