Störungen des angeborenen Immunsystems bei akuten und chronischen Lebererkrankungen

Abstract

Liver cirrhosis is a common disease causing great public-health concern because of the frequent complications requiring hospital care. Acute liver failure is also prone to several complications but is rare. One of the main complications for both acute and chronic liver diseases is infection, which regularly causes decompensation of cirrhosis, possibly leading to organ failure and death. This review focuses on innate immune function in cirrhosis, acute-on-chronic liver failure and acute liver failure. The known defects of Kupffer cells, neutrophils and monocytes are discussed, together with the pathophysiological importance of gut permeability, portal hypertension and intrinsic cellular defects, and the role of endotoxin, albumin, lipoproteins and toll-like receptors. Based on these different pathomechanisms, the available information on therapeutic strategies is presented. Antibiotic and probiotic treatment, nutritional support, artificial liver support, and experimental strategies such as inhibition of toll-like receptors and use of albumin and colony-stimulating factors are highlighted.

Ascites’ neutrophil function is significantly impaired in patients with decompensated cirrhosis but can be restored by autologous plasma incubation

“…In comparison to previous reports, the functional properties of blood neutrophils in cirrhosis were found to be less depressed in our cohort, which might be, however, partly explained by a relative underrepresentation of patients with heavily impaired liver function1823. Indeed, we could confirm a significantly reduced blood neutrophils oxidative burst rate when only patients with more advanced decompensation of the liver function (i.e.…”

Bench-to-beside review: Acute-on-chronic liver failure - linking the gut, liver and systemic circulation

“…Upon activation, Kupffer cells produce a great variety of inflammatory mediators such as cytokines, chemokines, oxygen-derived free radicals, eicosanoids, and lysosomal and proteolytic enzymes [10,12,13,18]. The massive release of local proinflammatory cytokines such as interleukin (IL)-1, IL-6, IL-17, IL-18, and tumor necrosis factor-alpha (TNFα) and the release of anti-inflammatory cytokines such as IL-4, IL-10, and IL-13 are considered causative in the subsequent development of SIRS and compensatory anti-inflammatory response syndrome (CARS) in acute and acute-on-chronic liver failure because of the overflow of these cytokines into the systemic circulation [25].…”

“…Albumin is known to have important detoxifying qualities such as scavenging free radicals and LPSs [10]. Third, in cirrhosis, there is evidence for a dysfunctional and hyporesponsive state of the innate immune system, a phenomenon that is known as immune paralysis [10,32]. This was also recently revealed in patients with ACLF [33].…”

“…The first evidence comes from clinical observations: infection is the reason for hospital admission in 15% to 35% of patients with cirrhosis, and 15% to 35% of the patients develop nosocomial infections in comparison with 5% to 7% in the general population [10]. Also, roughly one third of patients with advanced cirrhosis and culture-negative ascites exhibit bacterial DNA in circulation, which is closely correlated to the presence of intrahepatic and systemic endothelial dysfunction [47,48].…”

“…In reported literature, short-term mortality rates vary from 46% to 89% [10]. Mortality in ACLF is closely related to the development of SIRS in patients, irrespective of the severity of liver disease [3,11].…”