Microalbuminuria, systemic inflammation, and multiorgan dysfunction in decompensated cirrhosis: evidence for a nonfunctional mechanism of hepatorenal syndrome

摘要

Multiorgan/system dysfunction or failure (MOD/F) is a frequent complication of severe acute diseases (i.e., sepsis, acute liver failure due to toxic or viral hepatitis or acute alcoholic hepatitis, acute pancreatitis, or severe trauma) that share a common pathophysiological mechanism consisting of massive release of inflammatory inducers [pathogen-associated molecular patterns (PAMPs) by bacteria and/or damage-associated molecular patterns (DAMPs) by injured tissue] [1]. These molecules cause intense and generalized activation of the innate immune system and systemic inflammation. In systemic circulation, there is leukocytosis and very high plasma levels of inflammatory cytokines, acute-phase proteins (C-reactive protein, fibrinogen, and ferritin), and markers of oxidative stress. In tissue and cells, there is increased infiltration by granulocytes and macrophages, increased production of reactive oxygen species (ROS) and nitrogen species, and overexpression of myriad inflammatory genes. Hyperacuteness, extreme severity, high associated mortality, and potential reversibility are the main characteristics of these diseases. Cardiocirculatory failure due to arterial vasodilation and left ventricular dysfunction and the associated organ hypoperfusion was the initial mechanism proposed to link systemic inflammation and multiorgan failure. However, there is now much evidence that inflammatory mediators and ROS have direct deleterious effects upon essential mechanisms of tissue homeostasis, including microcirculatory and mitochondrial function and cell death, which may produce organ failure in absence of impaired organ perfusion [2].