I personally always think it comes down to the comic itself, and, first of all, you are never obliged to answer comments.
However, as someone who got barely any comments at all, I always try to answer all of them, even if it's just a "thank you" for a very non-descriptive comment. I didn't have negative comments so far (on my comics at least) but there it usually depends on how it is worded, what the commenter's intention probably was, and what mood I'm in that day. I usually try to understand where people are coming from if they have something negative/that doesn't align to my opinion to say. Thus I try to kind of ... make them understand where I'm coming from and what I think, or that they might even have a point.
If I'm enough in Fight Mode(TM) (which is most of the time) I also call out unnecessarily rude/inappropriate comments etc. - so far barely anyone got back at me but uuhhh yeah.
I'm generally just happy to just have intereaction with people about what I do so I just try my best. You can also always get back to comments later, and, especially if you get TONS of comments, you probably won't have time for that anyway.