Soluble CD163 from activated macrophages predicts mortality in acute liver failure

Abstract

Background/aims: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

Figures

Figure 1

A. Levels of soluble CD163 in patients with acute liver failure at day 1 and day 3 of enrolment compared to age- and sex-matched healthy controls. B. Levels of soluble CD163 in patients with acute liver failure at day 1 according to aetiology (Acetamin=Acetaminophen, drug hep=drug hepatitis, indeterm=indeterminate) compared to age- and sex-matched healthy controls. The box plots represent median and 25–75 percentiles. Upper and lower lines are the minimum and maximum values.

Figure 2

Levels of soluble CD163 in patients with acute liver failure in relation to survival (spont surv=patients with spontaneous survival, dead=patients who died without transplantation, transplant=patients who underwent liver transplantation). A. sCD163 measured at day 1, B. sCD163 measured at day 3, C. maximum value of sCD163 at day 1 and 3. The box plots represent median and 25–75 percentiles. Upper and lower lines are the minimum and maximum values.

Figure 3

Receiver operating characteristics (ROC) for the prediction of fatal outcome in patients with acute liver failure. A. sCD163 measured at day 1, B. sCD163 measured at day 3, C. maximum value of sCD163 at day 1 and 3. AUC=area under curve (95 % CI) (28).