The invention relates to a method for operating an internal combustion engine system (1) comprising: an internal combustion engine (2) provided with a plurality of cylinders (31-36), each of which being provided with an air inlet valve (31 a) and an exhaust gas valve (31b); a fuel supply system (20) configured to supply fuel to the cylinders (31-36); an air intake system (4) and an exhaust gas system (5); a turbocharging arrangement (6) comprising an intake air compressor (7) arranged in the air intake system (4) and an exhaust gas turbine (8) arranged in the exhaust gas system (5), wherein the intake air compressor (7) is operatively connected to the exhaust gas turbine (8); a controllable gas feeding device (9) arranged in the air intake system (4) downstream the intake air compressor (7); an exhaust gas aftertreatment system (18) arranged downstream the exhaust gas turbine (8); and a wastegate (13) arranged to allow exhaust gas to bypass the exhaust gas turbine (8), wherein the internal combustion engine system (1) is configured to allow operational deactivation of one or more cylinders (34-36) while one or more cylinders (31-33) are operationally active. The method comprises the steps of: determining (SI) whether a functional efficiency of the exhaust gas aftertreatment system (18) is or is about to fall below a threshold value, and when so: deactivating one or more of the cylinders (34-36); adapting a drive level of the gas feeding device (9) so as to establish a pressure in the air intake system (4) that is within a range suitable for operating remaining active cylinders (31-33); and opening the wastegate (13) to such a degree that at least 50% of the exhaust gas bypasses the exhaust gas turbine (8).