Soluble CD163 from activated macrophages predicts mortality in acute liver failure

University of California, San Diego, San Diego, California, United States
Journal of Hepatology (Impact Factor: 11.34). 12/2007; 47(5):671-6. DOI: 10.1016/j.jhep.2007.05.014
Source: PubMed


Soluble CD163 (sCD163) is a scavenger receptor shed in serum during inflammatory activation of macrophages. We investigated if sCD163 was increased and predicted outcome in acute liver failure (ALF).
Samples from 100 consecutive patients enrolled in the U.S. ALF Study Group for whom sera were available were collected on days 1 and 3, and clinical data were obtained prospectively. sCD163 levels were determined by ELISA.
The median level of sCD163 was significantly increased in ALF (21.1mg/l (range 3.6-74.9)) as compared to healthy controls (2.3mg/l (0.65-5.6), p<0.0001) and patients with stable liver cirrhosis (9.8mg/l (3.6-16.9), p=0.0002). sCD163 on day 1 correlated significantly with ALT, AST, bilirubin, and creatinine. sCD163 concentrations on day 3 were elevated in patients with fatal outcome of disease compared to spontaneous survivors, 29.0mg/l (7.2-54.0) vs. 14.6mg/l (3.5-67.2), respectively (p=0.0025). Patients that were transplanted had intermediate levels. Sensitivity and specificity at a cut-off level of 26mg/l was 62% and 81%, respectively.
Activated macrophages are involved in ALF resulting in a 10-fold increase in sCD163. A high level (>26mg/l) of sCD163 was significantly correlated with fatal outcome and might be used with other parameters to determine prognosis.

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Available from: Holger Jon Møller
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    • "These observations indicated that the deactivation and apoptosis of hepatic macrophages may be a potential link between inflammation and immunoparesis in ALF (Yang et al., 2013b). It is reported that during ALF, the activated KCs resulted in a significant increase in sCD163, which highly correlated with fatal outcome (Hiraoka et al., 2005;Møller et al., 2007).Mita et al. (2005)examined 24 patients with fulminant hepatic failure who underwent liver transplantation and discovered that FasL was expressed predominantly on liver macrophages, which contribute to the severe liver injury through Fas/FasL pathway. Activation of the immune coagulation system has been implicated in the pathogenesis of fulminant liver failure. "
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    • "Both markers remain elevated in ALF between day 1 and 3 following admission and levels correlate with severity of extra-hepatic complications and mortality. Serum levels of sCD163 were seen to diverge between day 1 and 3 in spontaneous survivors and those who died or required transplantation, with persisting macrophage activation indicative of poor prognosis [33]. Acetylated HMGB1 is secreted by monocytes and macrophages as a pro-inflammatory mediator, unlike the non-acetylated form that is more widely expressed and passively released by necrotic cells. "
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    • "Recently, several authors have reported the increased serum levels of macrophage­derived factors in patients with ALF, irrespective of the trigger, which suggests that activated macrophages play an important role in the progression of ALF [11–13]. Indeed, activation of macrophages and the subsequent release of proinflammatory mediators such as cytokines (e.g., tumor necrosis factor (TNF)-α), reactive oxygen species (ROS), and eicosanoids are considered to be an early step in the pathogenesis of liver damage, because they stimulate hepatic inflammation. "
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