Piers Morgan said: RIP Alfie Evans. My deepest condolences to his parents, who fought so hard for their brave little boy.”
And thousands paid tribute on Alfie’s supporters page – Alfie’s Army – with tributes flooding the Facebook group.
Joanne Davies said: “Heartbreaking to wake up to this today, such a strong, brave, beautiful little boy…my hearts broken for you both. You did absolutely everything that you could, thinking of you all Tom & Kate.”
Edyta Craig said: “Fly high little Alfie. Such an incredible and beautiful boy. Absolutely heartbroken. Thinking of your amazing mummy and daddy.”
Leah Taylor said: “This has broke my heart waking to this, he was a true warrior and he gave it his all. I’m so sorry for your loss Kate and tom and beautiful little man, you flight high.”
Others also paid tribute on Twitter to the toddler, who was born in May 2016 and admitted to Alder Hey in the following December after suffering seizures. He had remained a patient ever since.
On Twitter, one user said: “RIP Alfie Evans. Sleep well little fella.”
Emma Johnston said: “Rest in peace sweet angel.”
@Oliveoyl60 said: “Huge condolences to the heartbroken parents of #AlfieEvans. Also huge respect and thanks for for the professionalism and care of staff at #AlderHey. RIP little man.”
In a statement, Alder Hey Children’s Hospital said: “We wish to express our heartfelt sympathy and condolences to ‘s family at this extremely distressing time.
“All of us feel deeply for Alfie, Kate, Tom and his whole family and our thoughts are with them.
“This has been a devastating journey for them and we would ask that their privacy and the privacy of staff at Alder Hey is respected.”
Mr Evans, 21 and Ms James, 20, had fought to take their son to a foreign hospital for treatment for a degenerative medical condition, but lost a final court appeal on Wednesday.
Doctors had removed Alfie’s life-support following a High Court judge’s ruling on Monday, however he continued to live.
His parents said that the youngster had defied doctors’ expectations and they took their case to the Court of Appeal, but the application to take him abroad was rejected.
The case has provoked strong feelings over whether judges, doctors or parents have the right to decide on a child’s life. Alfie’s parents have been backed by Pope Francis and Poland’s President Andrzej Duda.
The attention and emotion garnered by Alfie’s plight and his parents’ determined public campaign to get the treatment they believed he needed led to high tensions between supporters and staff at Alder Hey.
After accepting that their options had been exhausted, Alfie’s parents sought to build bridges with medical staff and pledged to work alongside doctors to give him “the dignity and comfort” he needed.
Mr Evans said: “We… thank Alder Hey staff at every level for their dignity and professionalism during what must be an incredibly difficult time for them too.
“Together we recognise the strains (that) recent events have put upon us all and we now wish for privacy for everyone concerned.”