Liver cirrhosis is considered as a public health concern, being the fourth cause of death in Europe. Patients with cirrhosis are in risk of clinically relevant complications that worsen their prognosis. Disease progression is associated with an immunological dysfunction promoting bacterial complications, which become frequently relevant during cirrhosis progression. This microbial cargo constantly reaches the liver through the portal circulation, so that the hepatic immune system continuously faces gut-derived antigens that require an efficient clearance.
Progressive and sustained liver damage pushes cirrhosis forward from a compensated towards a decompensated state, in which clinical complications arise and worsen patients’ prognosis. The dynamics of the immune response is then dissociated. On the one hand, progressive hepatocyte necrosis induces a hyper-activation of the systemic inflammatory response and the negative regulation of anti-inflammatory pathways. On the other hand, the increasing gut-derived antigenic burden compromises the immune surveillance activity and favors the exhaustion of immune cells functional capacity, leading to an immune deficient state (reduced phagocytic, respiratory burst and antimicrobial capacities, among others).
With this background, our group is focused on the comprehension of the local and systemic inflammatory response underlying cirrhosis progression, including gut-derived antigenic load arriving through the gut-liver axis, and neurocognitive complications facilitated by the liver-brain axis during decompensated stages of disease.
