Serum levels of soluble Fas, nitric oxide and cytokines in acute decompensated cirrhotic patients

Abstract

AIM:To evaluate plasma levels of nitrite/nitrate (NOx), soluble Fas (sFas) antigen, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in patients with compensated and acute decompensated cirrhosis and to evaluate mediators causing acute decompensation in liver cirrhosis. METHODS:This prospective study was conducted in the medical intensive care unit of an academic tertiary center. Fifty-five patients with acute decompensation (gastrointestinal hemorrhage, encephalopathy, hydropic decompensation) and twenty-five patients with compensated liver cirrhosis were included. Blood samples were taken for analyses of sFas, Nox, IL-6, TNF-α. Liver enzymes and kidney functions were also tested. RESULTS:In patients with acute decompensation, plasma sFas levels were higher than in non-decompensated patients (15 305 ± 4646 vs 12 458 ± 4322 pg/mL, P < 0.05). This was also true for the subgroup of patients with alcoholic liver cirrhosis (P < 0.05). The other mediators were not different and none of the parameters predicted survival, except for ALT (alanine-aminotransferase). In patients with portal-hypertension-induced acute hemorrhage, NOx levels were significantly lower than in patients with other forms of decompensation (70.8 ± 48.3 vs 112.9 ± 74.9 pg/mL, P < 0.05). When NOx levels were normalized to creatinine levels, the difference disappeared. IL-6, TNF-α and sFas were not different between bleeders and non-bleeders. In decompensated patients sFas, IL-6 and NOx levels correlated positively with creatinine levels, while IL-6 levels were dependent on Child class. CONCLUSION:In acute decompensated cirrhotic patients sFas is increased, suggesting a role of apoptosis in this process and patients with acute bleeding have lower NOx levels. However, in this acute complex clinical situation, kidney function seems to have a predominant influence on mediator levels.

Increased intestinal macromolecular permeability and urine nitrite excretion associated with liver cirrhosis with ascites

“…For example, NO is a potent inducer of increased membrane permeability in the vascular endothelium and intestinal mucosa, possibly contributing to the accumulation of ascites and to bacterial translocation [31] . In the current study, although TNF-α was thought to induce NO synthesis (NOS) through the inducible NOS and endothelial NOS [32,33] , there was no significant correlation between TNF-α level and NO level in LC. This is the same to some studies, where such a relation could not be observed [34,35] .…”

Elevated nitric oxide and 3',5' cyclic guanosine monophosphate levels in patients with alcoholic cirrhosis

“…Our study, including only alcoholic patients of different Child classes, strengthens previous investigations and adds further information with respect to the second messenger cGMP and its relationship with the redox state of GSH. NO • or nitrite/nitrate measurements can be affected by creatinine levels, as demonstrated recently in acute decompensated cirrhotic patients [32] . In our clinical population, patients with Child C cirrhosis had elevated creatinine values compared to those with Child A cirrhosis, and this could also influence the results.…”

“…• synthesis and serum levels in various cirrhotic conditions [29][30][31][32] . Our study, including only alcoholic patients of different Child classes, strengthens previous investigations and adds further information with respect to the second messenger cGMP and its relationship with the redox state of GSH.…”

Acute-on-chronic liver failure: recent update

“…In ACLF, hepatocytes are exposed to chronically elevated concentrations of inflammatory cytokines, including interferon-g, TNF-α and interleukin (IL)-2 and IL-6. Depending on levels of proapoptotic or anti-apoptotic activity, inflammatory cytokines are able to stimulate both survival and apoptosis pathways and modulate the relative equilibrium of proand anti-apoptotic proteins, such as Bad and Bcl-2 respectively [57] . Apoptosis, or 'programmed cell death' is one of two main patterns of cell death; namely apoptosis and necrosis.…”