Early Increased Ficolin‐2 Concentrations are Associated with Severity of Liver Inflammation and Efficacy of anti‐Viral Therapy in Chronic Hepatitis C Patients

Abstract

Ficolin-2 is a kind of human serum complement lectin with a structure similar to mannan-binding lectin (MBL), and it has been implicated in innate immunity. Recent studies have shown that complement pathway activation may contribute to hepatitis. However, the relationship between ficolin-2 and viral hepatitis remains largely elusive. The aim of this study was to determine the dynamics of ficolin-2 in patients with chronic hepatitis C. Forty nine patients who had not yet received therapy [24 patients with abnormal alanine aminotransferase (ALT) levels (>40 U/L) and 25 patients with normal ALT levels ( 40 U/L)], 28 patients with hepatitis C who received therapy for 2 weeks and 16 patients received therapy for a full month or longer were included in the study. A sandwich enzyme-linked immunosorbent assay (ELISA) was used to measure the ficolin-2 concentrations in all serum samples of patients and 42 healthy donors. We found the concentrations of ficolin-2 were significantly higher in chronic hepatitis C patients with abnormal ALT values than in chronic hepatitis C patients with normal ALT values and healthy controls. Ficolin-2 concentrations in chronic hepatitis C patients with abnormal ALT values were positively correlated with ALT levels (*P < 0.05). After therapy, the concentrations of ficolin-2 decreased and accompany with ALT and Hepatitis C virus (HCV) RNA levels. Then, we found ficolin-2 concentrations in rapid viral response (RVR) group decreased significantly (*P < 0.05), while in non-RVR group, ficolin-2 decreased slightly (P > 0.05). Our findings suggest that early increased ficolin-2 is highly correlated with hepatic inflammation and rapid viral response.

Ficolin-2 Inhibits Hepatitis C Virus Infection, whereas Apolipoprotein E3 Mediates Viral Immune Escape

“…Our previous data convincingly showed that HCV infection causes increased expression of ficolin-2 (18,40) and that increased ficolin-2 concentrations are associated with the efficacy of antiviral therapy in chronic hepatitis C patients (40). Our present data confirm that ficolin-2 blocks HCV infection of hepatocytes in vitro.…”

“…In a previous study, we found that an early increase of ficolin-2 was highly correlated with hepatic inflammation and a rapid viral response in chronic HCV patients (40). In the present study, we identify ficolin-2 as a new inhibitor of HCV entry.…”

“…Previous data, as well as our own, suggest that lipoproteins play an important role in HCV infection and that ApoE3 mediates immune escape from antiviral innate immunity, promoting HCV infection. This could explain why increased concentrations of ficolin-2 in HCV patients (40) still result in chronic infection. Proof-of-concept studies suggest that the HCV entry inhibitor ficolin-2 is a novel and promising antiviral innate immune molecule that increases the preventive and therapeutic arsenal against HCV infection.…”

“…In normal human serum, the IFN-a concentration is 2.25 6 0.88 pg/ml (43,46), whereas the therapeutic dose of IFN-a reaches the microgram level (180 mg/wk) in the clinical treatment of HCV (43,46), much higher than the normal level. The mean concentration of ficolin-2 in healthy controls is ∼4.67-6.0 mg/ml (18,40), and the EC 50 value of ficolin-2 against HCVcc-Huh7.5.1 cells at 72 h was 6.7 6 0.7 mg/ml. Thus, our data suggest that the ficolin-2 EC 50 is slightly higher than or close to the mean concentration of serum ficolin-2 in normal controls, which indicates that ficolin-2 is a more effective innate immune molecule against HCV and demonstrates potential as an effective drug against HCV.…”

Serum ficolin-2 concentrations are significantly changed in patients with hepatitis B virus infection and liver diseases

“…Recently, an increasing number of reports have shown that ficolin-2 can bind to viral glycoproteins and inhibit hepatitis C virus (HCV) and influenza virus infections (Pan et al, 2012;Zhao et al, 2014) and that abnormal ficolin-2 expression plays a crucial role in viral diseases (Hoang et al, 2011;Hu et al, 2013). However, the role of ficolin-2 and its dynamic changes over the course of and in the prognosis of CHB and HCC remain unclear.…”