The match was as good as over inside the opening 27 minutes with Henrique, Gonzalo Higuain and Manolo Gabbiadini all on target for the Serie A side, with Duvan Zapata completing the rout in injury time.
Wolfsburg and Dnipro both enjoyed 2-0 home wins over Sporting Lisbon and Olympiacos respectively to hand themselves strong chances of progressing.
Bas Dost scored both goals for Bundesliga outfit Wolfsburg at the Volkswagen Arena, whilst Jaba Kankava and Ruslan Rotan scored within four second-half minutes to give Ukrainian side Dnipro control of their tie.
Club Brugge also hold a two-goal advantage going into the second leg of their clash with Aalborg following a 3-1 victory at the Nordjyske Arena.
Oulare and Lior Rafaelov netted in the first half for Club before Kenneth Petersen put through his own net on the hour, with Aalborg’s consolation coming via former Aston Villa striker Nicklas Helenius from the penalty spot.
Everton are knocking on the door of the last 16 following a stunning 4-1 victory over Young Boys thanks to a hat-trick from Romelu Lukaku.
Manager Roberto Martinez’s side suffered an early blow when Guillaume Hoarau gave the hosts a 10th-minute lead at the Stade de Suisse, only for Lukaku to haul the Toffees level 14 minutes later.
Seamus Coleman then fired Everton in front before the half-hour, with Lukaku increasing the advantage in the 39th and 58th minutes to set up what should be a routine second leg at Goodison Park next week.
Everton will be without John Stones for that match, though, after he was sent off for hauling back Hoarau in the area just after the hour, with the French striker sending the resultant penalty over the bar.
Zenit St Petersburg hold a slender 1-0 advantage over PSV Eindhoven courtesy of Hulk’s 63rd-minute strike at the Philips Stadion, whilst Italian sides Roma and Torino were both held at home by Feyenoord and Athletic Bilbao respectively.
Gervinho gave Roma the lead at the Stadio Olympico, only for Leytonstone-born Colin Kazim-Richards, who once played for Brighton, Sheffield United and Blackburn, to net his 10th goal of the season for the visitors.
At Torino, two first-half Maxi Lopez goals sandwiched strikes from Inaki Williams in the ninth minute and Carlos Gurpegi in the 73rd.
In the later kick-offs, Mario Balotelli scored his second winning goal for Liverpool in three matches??to give the Reds a narrow 1-0 lead to take to Besiktas next week.
In 2007 Liverpool hammered the Turkish side 8-0 in a Champions League clash,??but there was to be no repeat as Brendan Rodgers’ side managed only five shots??on target on this occasion.
The Anfield crowd had to wait until the 85th minute for the breakthrough, with??Balotelli converting from the spot after Jordan Ibe had been hacked down by??Ramon.
Spurs face a tough task in their second leg as they were held to a 1-1 draw at??White Hart Lane by Fiorentina.
Roberto Soldado volleyed home a sixth-minute opener – only his fifth goal of??the season – only for centre-back Jose Maria Basanta to equalise 30 minutes??later and give the visitors the edge for the return.
Celtic, meanwhile, produced a memorable performance to hold Inter Milan to a??3-3 draw at Celtic Park.
The Italian side roared into a two-goal lead inside 13 minutes with goals from??Xherdan Shaqiri – following a mistake from goalkeeper Craig Gordon – and Rodrigo??Palacio, only for Celtic to be back on level terms within 12 minutes.
Stuart Armstrong netted the first, with Hugo Campagnaro scoring an own goal 76??seconds later before Palacio pounced on another Gordon error on the stroke of??half-time.
But in the third minute of injury time John Guidetti gave Celtic a fighting??chance for next week’s second leg at the San Siro with his 12th goal of the??season, but first since the end of November.
Arkadiusz Milik’s 13th goal of the season was enough for Ajax to see off Legia??Warsaw at the Amsterdam ArenA, whilst Vicente Iborra made it two goals in two??games to see Sevilla home 1-0 at the Ramon Sanchez Pizjuan against Borussia??Moenchengladbach.
Guingamp and Villarreal also hold one-goal leads after both sides won 2-1 in??their first-leg matches with Dynamo Kiev and Salzburg respectively.
Despite Miguel Veloso giving Dynamo a 16th-minute lead at the Stade Municipal??de Roudourou, Guingamp struck back with two goals in four second-half minutes??from Claudio Beauvue and Mustapha Diallo.
In Spain, Ikenchukwu Uche scored his seventh goal of the season to give??Villarreal an early lead.
Although Jonatan Soriano scored from the spot just after the break, Denis??Cheryshev also made it seven for the campaign to give Villarreal the advantage??going into the return in Austria.
The only other game of the night saw Anderlecht held to a goalless draw at home??to Dinamo Moscow, who had Alexander Buttner sent off in the 75th minute.