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Group Head: Immunobiology of Chronic Liver Failure, Liver Sciences Research Synopsis: Patients with cirrhosis are predisposed to developing an infection which is frequently a precipitant of multiorgan failure and death. With poor outcomes following sepsis, the propagation of multidrug-resistant bacterial species and increasing waiting list mortality for liver transplantation, there is an urgent need for novel approaches to reducing the rate of infection. Paradoxically, these patients are characterised by heightened immune activity and rigorous inflammatory processes and are unable to contend with infection, suggesting that whilst these immune effectors are primed, their antibacterial effector functions are switched off. The precise mechanisms responsible for this phenomenon remain unknown but are suggestive of a skewed homeostatic balance between protective anti-pathogen immunity and host-induced immunopathology.

The aims of my research programme are to characterise the cellular and molecular mechanisms governing this predisposition to infection focusing on the intimate relationship between innate immune dysfunction and the gut-liver-brain axis. A dysfunctional gut microbiome plays a key role in patients with cirrhosis by influencing the rate of progression to terminal liver failure and a major goal for my group is to develop interventions which normalise the gut microbiome reducing the development of complications and liver failure. I consider myself at the forefront of this field of research and am a national and international key opinion leader on hepatic encephalopathy. I am the chief investigator of several key therapeutic clinical trials in the field including RIFSYS [NCT02019784] and PROFIT [NCT02862249].