Blood reelin levels in the progression of chronic liver disease

Background:

Reelin (RELN) is an extracellular matrix protein that was originally discovered as a crucial regulator in tissue architecture in the central nervous system. Recent findings indicate that RELN may play an important role in the organization of other organs as well, especially of the liver. Hepatic RELN expression was shown to be increased during the process of liver fibrosis, moreover there are hints that RELN acts as a tumor suppressor gene in the development of hepatocellular carcinoma (HCC). Against this background, the aim of our study was to explore alterations in blood RELN levels in patients with chronic liver diseases.

Methods:

We analyzed blood samples of patients with chronic hepatopathy of different etiologies without significant liver fibrosis (n = 25), with significant liver fibrosis (n = 36), with liver cirrhosis (n = 74), with liver cirrhosis and HCC (n = 26) as wells as of healthy controls (n = 15). We also compared blood samples from portal vein, liver vein and peripheral vein of patients with liver cirrhosis (gained during implantation of transjugular intrahepatic portosystemic shunt [TIPS]). Blood RELN concentrations were determined utilizing a human-RELN-specific enzyme-linked immunosorbent assay by Cloud-Clone Corp.®.

Results:

Blood RELN levels were significantly higher in patients with liver fibrosis or liver cirrhosis than in patients without liver fibrosis or healthy controls (13.2 ± 5.9 ng/ml vs. 18.7 ± 16.9 ng/ml, p = 0.032). Furthermore, patients with liver cirrhosis and HCC displayed significantly higher RELN concentrations compared to patients with liver cirrhosis without HCC (18.7 ± 16.9 ng/ml vs. 27.4 ± 12.8 ng/ml, p < 0.001). This effect was independent of liver function, assessed by the Child-Pugh stadium. We found no significant difference between RELN concentrations in portal vein, liver vein and peripheral veins (14.8 ± 13.1 ng/ml vs. 15.6 ± 14.0 ng/ml vs. 18.8 ± 14.9 ng/ml, p = 0.338).

Conclusions:

Changes in hepatic RELN expression in chronic liver disease are also reflected in alterations of blood RELN levels, which makes RELN a potential biomarker in this setting. The pathophysiological mechanisms underlying the changes in blood RELN levels are still under investigation. Further evaluation of RELN as a possible diagnostic marker is a promising task in hepatologic research.