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The linewidth enhancement factor (LEF) describes the coupling between amplitude and phase fluctuations in a semiconductor laser, and has recently been shown to be a crucial component for frequency comb formation in addition to linewidth broadening. It necessarily arises from causality, as famously formulated by the Kramers-Kronig relation, in media with non-trivial dependence of the susceptibility on intensity variations. While thermal contributions are typically slow, and thus can often be excluded by suitably designing the dynamics of an experiment, the many quantum contributions are harder to separate. In order to understand and, ultimately, design the LEF to suitable values for frequency comb formation, soliton generation, or narrow laser linewidth, it is therefore important to systematically model all these effects. In this comprehensive work, we introduce a general scheme for computing the LEF, which we employ with a non-equilibrium Green's function model. This direct method, based on simulating the system response under varying optical intensity, and extracting the dependence of the susceptibility to intensity fluctuations, can include all relevant electronic effects and predicts the LEF of an operating quantum cascade laser to be in the range of 0.1 - 1, depending on laser bias and frequency. We also confirm that many-body effects, off-resonant transitions, dispersive (Bloch) gain, counter-rotating terms, intensity-dependent transition energy, and precise subband distributions all significantly contribute and are important for accurate simulations of the LEF.