Dynamic changes of soluble fibrinogen-like protein 2 in long term antiviral treatment of chronic hepatitis B

Objective To investigate the changes of peripheral blood expression levels of soluble fibrinogen-like protein 2 (sFGL2) in patients with chronic hepatitis B (CHB) before and after antiviral treatment. Methods From July 2013 to December 2014, initial CHB patients with entecavir antiviral therapy and healthy controls were enrolled. Clinical data at baseline and during follow-up were collected. Plasma levels of sFGL2 of all the included objects were measured by enzyme-linked immunosorbent assay (ELISA). All the patients received liver biopsy at baseline, and part of patients received a second liver biopsy at week 78 after treatment. The expression of sFGL2 in liver tissues were examined by immunohistochemistry. T test, Wilcoxon test and correlation analysis were performed for statistical analysis. Results A total of 71 CHB patients and 20 healthy controls were enrolled. At baseline, the level of plasma sFGL2 of CHB patients was significantly higher than healthy controls (105.6 μg/L (78.3 μg/L to 151.6 μg/L) vs 25.2 μg/L (18.8 μg/L to 34.3 μg/L), Z=-5.887, P<0.01). The plasma sFGL2 level of patients with liver cirrhosis was 146.0 μg/L (111.3 μg/L to 166.8 μg/L), which was higher than that of patients without liver cirrhosis (79.0 μg/L (65.4 μg/L to 107.4 μg/L)), and the difference was statistically significant (Z=-4.912, P<0.01). Plasma levels of sFGL2 were positively correlated with liver stiffness, liver inflammation and fibrosis stages (r=0.426, 0.240 and 0.655; all P<0.05). At 26 weeks and 52 weeks after treatment, the plasma levels of sFGL2 were 89.1 μg/L (69.8 μg/L to 125.5 μg/L) and 75.8 μg/L (53.4 μg/L to 98.9 μg/L), respectively, which gradually decreased compared with that at baseline (26 weeks vs baseline Z=-4.499, P<0.01; 52 weeks vs 26 weeks Z=-4.762, P<0.01). Furthermore, at baseline the number of sFGL2 positive cells in the liver tissue of liver cirrhosis group was 33.0±10.4, which was higher than that of non-liver cirrhosis group (17.6±6.7), and the difference was statistically significant (t=7.541, P<0.01). Compared with that at baseline (24.5±2.0), the number of sFGL2 positive cells in liver tissue at week 78 after treatment decreased (11.3±1.6), and the difference was statistically significant (t=11.980, P<0.01). Conclusion Plasma level of sFGL2 is closely correlated with the degree of liver inflammation and fibrosis in CHB, and the plasma level of sFGL2 significantly decreases after long-term antiviral therapy. Key words: sFGL2; Hepatitis B, chronic; Liver cirrhosis