A Lautaro Martinez's first-half penalty sufficient for Inter Milan to clinch a 1-0 win over Rapid Vienna in Austria, with Irish teenager Ryan Nolan in the Inter squad.
The 19-year-old defender, who was born in Clare, was included in Luciano Spalletti’s 19-man match-day selection.
Spanish sides Sevilla, Valencia and Villarreal also tasted victory on the road, while Benfica, Club Brugge and Plzen have the upper hand heading into next week's second legs.
Napoli beat Zurich 3-1 in Switzerland. Napoli captain Lorenzo Insigne put the visitors ahead after 12 minutes as he capitalised on a dreadful mistake by keeper Yanick Brecher and Jose Callejon doubled their lead in the 21st when he slotted home from Kevin Malcuit's low cross.
Piotr Zielinski got the third 13 minutes from time before Benjamin Kololli grabbed a consolation from the penalty spot.
In the only tie featuring two teams who dropped down from the Champions League, visitors Benfica beat Galatasaray 2-1 after taking the lead in the 27th minute when Salvio converted a penalty given for handball.
Christian Luyindama equalised for the home side nine minutes into the second period but Benfica's top scorer Haris Seferovic clinched the win with a fine solo goal 10 minutes later.
It was also a good night for Spanish clubs, with Valencia, Sevilla and Villarreal winning away and Real Betis rescuing a last-gasp draw at Stade Rennes.
Alfonso Pedraza's goal after three minutes was enough to give Villarreal a 1-0 win over Sporting and maintain their unbeaten run in this year's competition.
Sevilla beat Lazio by the same scoreline in Rome thanks to Wissam Ben Yedder's close-range strike in the 22nd minute.
Real Betis were 2-0 down after 10 minutes at Rennes, a team making their first knockout round appearance in Europe.
The Spaniards got one back after 32 minutes through Giovani Lo Celso but Hatem Ben Arfa restored the home side's two-goal cushion right on halftime with a penalty.
Betis had the better of the second period and Sidnei made it 3-2 with a header before Mexican teenager Diego Lainez got the equaliser their pressure deserved just before the final whistle.
Plzen and Brugge got late goals for 2-1 home wins over Dinamo Zagreb and Salzburg respectively, while Shakhtar Donetsk twice recovered to draw 2-2 with visitors Eintracht Frankfurt.
Benjamin Verbic ensured Dynamo Kiev will head into their second leg clash with Olympiakos all square after they twice came from behind in Greece.
Ahmed Hassan put the home side ahead with just nine minutes gone and after Vitaliy Buyalskiy levelled, Gil Dias' thumping half-volley restored their lead only for Verbic to make it 2-2 with a minute remaining.
Russian side Krasnodar's game with visiting Bayer Leverkusen was goalless while Slavia Prague and Genk also failed to break the deadlock.
On Tuesday Fenerbahce beat Zenit 1-0.
The return legs take place on 21 February 21, except for Sevilla v Lazio, which is due to be played a day earlier.
