Detective Chief Inspector Noel McHugh said O'Brien fled in October 2015 shortly after Josh Hanson, 21, was stabbed to death in a bar in Eastcote, north-west London.
"We really need people to keep up the momentum and keep their eyes open wherever they are in the world. Please don't be discouraged by the fact some potential sightings have been investigated and discounted — we want to hear from anyone and everyone who thinks they see O'Brien or has any information no matter how small. We could be a single phone call away from catching him," Det. Chief Insp. McHugh said on Thursday, October 11.
O'Brien, who is six feet tall, is known to have an interest in boxing, gyms and nightclubs and is an inveterate womanizer.
Pretended to Be Italian in Prague
O'Brien, who was 27 at the time of the incident, was arrested in Prague in October last year for an unrelated crime of assault and criminal damage but was released on bail and vanished after fooling the Czech police into believing he was an Italian called Enzo Mellonceli.
Detectives believe he is being helped by criminal associates who are providing him with money, false identities and fake documents to get across European borders.
Josh's mother Tracey, said the last three years had been "unimaginable" and she had not been able to grieve yet.
"I am asked ‘where do you get your strength from?' Every time I do an appeal, it takes a bit more from me and it hurts so badly. How long will I continue? Well, there will be no end, my family and I are going to get louder and more creative until we get justice for Josh," Mrs. Hanson said.
'Incredibly Distressing' For Murdered Man's Mother
"I struggle to look at the picture of Shane O'Brien…and for the past three years these images have taken over my life. It's incredibly distressing that today is the anniversary of Josh's murder and O'Brien is still at large. I find it astonishing how Europe's and now Interpol's most wanted man can be so elusive, or well networked, as the police say," she said.
A reward of £50,000 has been offered for information leading to the capture of O'Brien, who flew out of Britain on a private plane from Biggin Hill Airport in Kent in October 2015.
Mrs. Hanson spent Thursday, October 11, at London's Paddington station wearing a sandwich board with details of her son's murder on it.
Last Three Years Have Been 'Horrendous'
"For Josh's family, the last three years — more than 1,000 days and nights without Josh — have been horrendous. No words adequately describe the pain they are going through. His mum Tracey and sister Brooke have to live on a daily basis with the frustration and ongoing disappointment that as yet O'Brien evades capture," said Det. Chief Insp. McHugh.
O'Brien, who is originally from Ladbroke Grove in west London, was placed on Interpol's Most Wanted list in May 2018.
He has been reportedly seen in France, Spain, the Netherlands and Dubai but could be anywhere in the world.
Josh Hanson was stabbed in the neck in the early hours of the morning of October 11, 2015 at the RE bar in Eastcote. He died at the scene.
Witnesses said it was an unprovoked attack.