Hepatic dysfunction after shock: Clinical parameters and biological pathways for therapeutic intervention

The prevalence of hepatic dysfunction was thought to be ≈ 1% in intensive care unit (ICU) patients, but is now being recognized to be > 10%. Mortality and length of ICU stay are directly affected by hepatic dysfunction, raising the need for a better understanding of this disorder in order to develop therapeutic options that go beyond the current practice of supportive care. The etiologies of hypoxic hepatitis are discussed, together with their differentiating physiological parameters. The liver's compensatory mechanisms are examined at the level of the microcirculation. The cytokine milieu and cells responsible are considered. Survival versus cell death by means of necrosis, apoptosis, or autophagy is determined by the interplay of intracellular pathways. Specific pathways discussed involve reactive oxygen species, Toll-like receptor 4, heme oxygenase, transcription factors such as nuclear factor-κB, mitogen-activated protein kinase and protein kinase B. From this basis, current and future therapeutic strategies are examined.