Allostasis in nonalcoholic fatty liver disease: implications for risk assessment

Allostasis, a concept of anticipatory physiological regulation in response to external and internal challenges, was originally developed in the context of neuroendocrinology and behavioral medicine. Allostasis preserves function under changing conditions by abandoning physiological set points and developing new ones. Allostatic load refers to the aggregate effect of adaptation throughout life, and corresponds to the wear and tear associated with this process. In response to chronic stress, allostatic load may accumulate faster than expected if sustained activation of regulatory systems exceeds optimum operating ranges; this results in increased risk of disease. Used in a broader sense, the allostatic model of adaptive responses, trade-offs, feed-forward cycles, and collateral damage provides a framework for assessing the involvement of environmental-genetic interactions and co-morbidities in the course of chronic disease and developing a comprehensive score for personalized risk prediction. The utility of this approach is illustrated for nonalcoholic fatty liver disease, a prevalent condition with common and less common outcomes.