Network Physiology of the Liver in Health and Disease

Liver plays a major role in metabolic and immunological processes in the body which makes it a hub in control of diverse physiological mechanisms in health and disease. Functional connectivity of the liver with other organs is well recognised by clinicians, given the fact that patients with liver failure exhibit multiple organ involvement. For example, chronic liver failure (cirrhosis) is characterised by portal hypertension, hepatorenal syndrome, encephalopathy, cardiomyopathy, hepatopulmonary syndrome, autonomic dysfunction, and an impaired immune response. Cirrhosis is hence a multi-systemic disease that affects the whole network of organ systems and not just metabolic function of the liver. Treatment of complications in such complex disorder is challenging as inhibition of a pathway in one subsystem may induce a paradoxical response in another, which may lead to less chance of adaptation and survival.

A dynamic networks approach to liver structure and functions, and to liver interactions with other organ systems represents a shift from the traditional reductionist paradigm, which considers involvement of distinct physiological components in the disease process separately. Although many organ-specific physiological mechanisms have been studied in detail in the last decades, none of these mechanisms work in isolation in patients with liver disease.

Fundamental research in the emerging field of Network Physiology has laid the foundation for understanding and quantifying global physiological behaviours that result from networked interactions across systems. An adaptive network approach can enable clinicians to determine prognosis and response to therapy based on novel integrative measures of emerging behaviours by taking in consideration the interactions among all physiological systems involved. It may also provide new insights into the fundamental mechanisms of organs interactions which enable us to treat liver disease or its complications. Although most researcher appreciate the need for a network approach to liver disease, currently there are no analytic and computational methods suitable for assessment of organ’s functional connectivity within the context of liver in health and disease.


This Research Topic aims to encourage researchers from different disciplines to share recent advances in empirical and modelling work on Network Physiology of the liver, spanning across a range of spatiotemporal scales from metabolic and cellular signalling processes to integrated organ systems interactions and the entire organism level. This articles collection will publish peer-reviewed original research and reviews.