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NPFL side Enyimba lost 4-1 to Pyramids FC of Egypt in the first leg of their CAF Confederation Cup quater-final tie in Cairo on Sunday.
Victor Mbaoma gave Enyimba the lead within a minute when he stole the ball from goalkeeper Sherif Ekramy.
The home team however rallied back with goals from Ramadan Robhi and Abdallah El Said in the first half.
Ibrahim Adel compounded the visitors woes with two more goals in the second half.
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The reverse fixture will take place next week Sunday with Enyimba needing to score three goals without conceding to advance into the semi-finals.
No Nigerian club have won the Confederation Cup since it was founded in 2004.