Considering the trend of legislative frameworks regarding transport sector and, specifically, Internal Combustion Engine (ICE) emissions; it was of interest to study Hydrogen as an alternative fuel since its peculiarity of being a fuel with no carbon atoms and thus not producing carbon mono/dioxide as combustion products. An inline 6 cylinders 13 liters Hydrogen Internal Combustion Engine is studied as an example of typical ICE adopted for on-road heavy duty vehicles. A mono dimensional thermo-fluid dynamic model is adopted to simulate the impact of Variable Valve Actuation (VVA) and Cylinder Deactivation (CDA) on engine performances with a focus on Brake Thermal Efficiency (BTE).