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The liver is the largest visceral organ in the human body, performing many hundreds of functions that are critical for life. It is the site of metabolic processes, nutrient synthesis and storage, regulatory activities, and pathogen and xenobiotic defense processes. Models that recapitulate liver physiology are essential for predicting drug metabolism and toxicity as well as for understanding and treating diverse forms for disease. This chapter covers the utility and shortcomings of in vivo and in vitro liver models, with a focus on 3D models that mimic aspects of liver structure.

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