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Liverpool suffered a second defeat in four days after Chelsea ended the Reds' hopes of winning a treble this season.
The Reds, who lost their first Premier League game in 44 matches when they were thrashed 3-0 in shocking fashion by Watford on Saturday, lost 2-0 at Stamford Bridge in the fifth round tie through goals from Willian and Ross Barkley.
It means that the Premier League runaway leaders will not be adding the FA Cup to their recent trophy successes.
Liverpool have been near-flawless for the majority of the campaign and are well on their way to winning a first league title for 30 years in record-breaking fashion.
But for the first time in the season they have looked like they are struggling, having now lost three of their last four games in all competitions and failing to find the net in the trio of defeats.
They created a series of clear-cut chances in the first half, including forcing Kepa Arrizabalaga into three brilliant consecutive saves, but their attacking intent petered out and the Anfield outfit were deserving of another defeat on the road.
Chelsea took the lead early into the first half after Adrian, the hero against Chelsea on penalties in the UEFA Super Cup in August, produced an absolute howler from Willian's effort.
The Blues sealed the win in the second courtesy of a sublime solo goal from boyhood Everton fan Barkley, booking Chelsea's place in the quarter final of this season's FA Cup.
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