Clyne suffered the injury in Liverpool’s friendly with Borussia Dortmund in Indiana on Friday.
The 28-year-old right-back, who spent most of last season on loan at fellow Premier League side Bournemouth, was sidelined for most of the 2017/18 season with a back injury.
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He has not travelled with his teammates to New York for the final stop on the club’s US tour and has instead returned to the club’s Melwood training ground to begin his rehabilitation programme.
“What can I say other than how gutted we all are for Clyney,” Liverpool manager Jurgen Klopp told Liverpool’s website. “He was training and playing so well — he was in outstanding shape.
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“Clearly an injury of this nature isn’t a happy moment for any player, but the silver lining for him is that, according to the medical guys, it’s a straightforward ACL injury.”
Although Clyne is facing a prolonged period out of action, Liverpool’s medical team believe the nature of the injury should allow him a straightforward rehabilitation process.