I don’t know if it’s ever said, but I’ve always thought that the Uchiha clan was never able to retrieve Shisui’s body from the river. Why I think so? Because, if I remember correctly (I might be wrong tho), Kabuto says that Shisui was strong enough that he wanted to bring him back but was never able to find enough of his DNA for the Edo Tensei.
That means that Shisui either destroyed his body or he didn’t die and he stayed hidden somewhere.
But. What if the clan never found Shisui’s body because Danzō’s ROOT agents fished him from the Naka? Danzō kept him for a while to try and force Shisui to tell him where his other eye was, but when that didn’t happen he didn’t have a reason anymore to keep Shisui. He was probably in a very bad shape from his fall in the river and Danzō never really healed him, just keeping him alive enough to talk.
So, Danzō doesn’t have a reason to keep him anymore, right? But instead of simply killing him, he waits until after the Uchiha massacre and then gives Shisui to Orochimaru, because Shisui is now one of the last Uchihas and Danzō knows how obsessed Orochimaru is with the Sharingan, and even if Shisui doesn’t have one anymore Orochimaru can still use his body for experiments and Danzō gets to keeps Orochimaru as an ally.
And outside of the Sharingan, what’s another big thing Orochimaru is known for? Tenzo. The Mokuton. Shisui’ body is in a bad shape, Orochimaru probably knows that he won’t survive very long anyway so what does he have to lose? Besides, if I remember correctly, Orochimaru doesn’t know that his Mokuton experiment had one success until he faces Yamato years later, so he probably still think that it was a total fluke.
So he gets to work, he testes Shisui’s body over and over again to find the right way to introduce Hashirama’s cells and avoid a possible rejection, experimenting for days on end, finding sick amusement in the way Shisui suffers through it all, begging to be killed. Orochimaru has nothing to lose, Shisui will still die soon one way or the other but if he doesn’t? If he survives then Hashirama’s cells and their regenerative aspect will keep him alive, and Orochimaru will be able to experiment even more on him.
Of course, Shisui survives (I mean, if he were to die then this AU would stop here) and Orochimaru is ecstatic. He doesn’t give Shisui the Cursed Mark only because he doesn’t know how it would react with the Mokuton, and he doesn’t want to screw everything up once reaching this far. If he didn’t really care before, now he wants Shisui to stay alive. And he wants Itachi’s eyes to implant them in Shisui’s body so that he can create a strong vessel, because Orochimaru decides that he wants to take Shisui’s body with both the Mokuton and a strong Sharingan.
He doesn’t succeed, of course, Itachi wins against him and Orochimaru leaves the Akatsuki. Itachi doesn’t know about Shisui, no one knows about Shisui outside from Orochimaru and Kabuto, and no one finds out until Sasuke years later leaves Orochimaru with Team Taka.
And Imagine with me: Shisui still doesn’t have eyes, so Orochimaru orders Karin to teach him to sense chakra so that the Uchiha can still be useful in a way, so when Karin decides to follow Sasuke he brings Shisui with her.
And hear me out: after years of tortures, after years of agony, screaming and begging, eventually Shisui goes mute. He has screamed enough that his vocal cords are fucked up and not even the Mokuton can heal them anymore.
And when Karin takes Shisui with her, Sasuke doesn’t recognize him. And why should he? For him, Shisui is dead. And after years in Orochimaru’s hands Shisui would be unrecognizable, and at first Shisui doesn’t recognize Sasuke, either. He was kept mostly alone, outside from Orochimaru, Kabuto and Karin, because no one had to know who he was so he never heard anything about Sasuke following Orochimaru.
He does know about the massacre, Danzō would have told him just to see him suffer a bit more, but he doesn’t know that Sasuke is alive because Danzō didn’t tell him. He doesn’t know anything and maybe Karin doesn’t even know that Shisui is an Uchiha because maybe Orochimaru never told her and Shisui never thought it was important, after all the experiments and suffering going around saying that you’re an Uchiha is definitely not a top priority.
Maybe Karin doesn’t even know that his name is ‘Shisui’, maybe he just told her to call him 'Shi’, as in 'Death’ because he’s not Shisui anymore at this point, Shisui died that night in the Naka, he doesn’t deserve to keep that name anymore.
So Shisui finds out by chance that Sasuke is that Sasuke Uchiha, that his little cousin is still alive. I don’t really know how, but traveling with him and Team Taka he is bound to find out at some point.
But now that he knows, would Sasuke believe him if Shisui said who he really was? How would Shisui even explain all the shit that happened? He’s mute and blind, he’s only good as a sensor thanks to Karin and as a somehow good enough healer thanks to the curative chakra of the Mokuton, nothing more.
Shisui has no way of expressing himself, being blind he couldn’t even learn how to sign, he only remembers some of the ANBU signs but they are useless. He finds a way eventually, maybe he simply tries to write by letting his hand move through muscle memory and then show what he wrote to Karin so she can 'translate’ what he wrote in something legible, trying to re-write over and over again parts unreadable until Karin can read the whole story.
I mean, imagine Sasuke’s reaction. He wouldn’t believe it at first but Shisui wrote things only the real Shisui would know, imagine Sasuke finding out early about Danzō and what Konoha did, about why Shisui decided to kill himself. And Sasuke’s not stupid, he would probably make 2+2 about the massacre and about why Itachi left him alive, why Itachi wants so much to die by Sasuke’s hands.
And Sasuke doesn’t forgive Itachi, not fully, because he still killed the clan, he still slaughtered shinobi and civilians alike, women, men, old and young, he still mentally tortured Sasuke not once but twice, he still joined the Akatsuki and killed who knows how many people in its name, but now Sasuke knows that it’s not all Itachi’s fault. And he doesn’t know if he wants to kill Itachi anymore as much as before, because he wants Itachi’s part of the story first, Sasuke wants the whole truth and no more lies, because he thinks, after all he passed, to deserve it.