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Sepsis elicits profound changes in the concentrations of plasma proteins synthesized by liver parenchymal cells referred to as acute-phase proteins. Mechanisms controlling this orchestrated response include release of cytokines that induce acute-phase proteins, while other ‘house-keeping’ genes are downregulated.Although some acute-phase proteins help to control damage, functions of many other acute-phase reactants remain obscure. Changes in acute-phase gene expression are primarily subject to transcriptional regulation and can be comprehensively monitored by array techniques. Emerging evidence from such strategies implies that in addition to a ‘common host response’ also highly specific pathways are induced in specific disease contexts. Applying a systems biology approach to the integrated response of the hepatocyte to infection would suggest that the reprogramming of metabolic functions occurs in parallel with a severity-dependent disruption of phase I and II biotransformation and canalicular transport, that is, excretory failure. Although traditionally bilirubin serves to monitor excretion, emerging evidence suggests that bile acids indicate liver dysfunction with higher sensitivity and specificity.Sepsis induces reprogramming of the hepatic transcriptome. This includes induction of adaptive acute-phase proteins but also repression of phase I, II metabolism and transport with important implications for monitoring and pharmacotherapy.