Abstract
BackgroundClinical progression of HBV-related liver diseases is largely associated with the activity of HBV-specific T cells. Soluble fibrinogen-like protein 2 (sFGL2), mainly secreted by T cells, is an important effector molecule of the immune system.MethodssFGL2 levels were determined by ELISA assays in sera of 296 HBV patients clinically classified into the subgroups of acute hepatitis B (AHB), chronic hepatitis B (CHB), liver cirrhosis (LC), hepatocellular carcinoma (HCC) and patients with LC plus HCC. As control group, 158 healthy individuals were included. FGL2 mRNA was quantified by qRT-PCR in 32 pairs of tumor and adjacent non-tumor liver tissues.ResultssFGL2 levels were elevated in HBV patients compared to healthy controls (P < 0.0001). In the patient group, sFGL2 levels were increased in AHB compared to CHB patients (P = 0.017). sFGL2 levels were higher in LC patients compared to those without LC (P = 0.006) and were increased according to the development of cirrhosis as staged by Child-Pugh scores (P = 0.024). Similarly, HCC patients had increased sFGL2 levels compared to CHB patients (P = 0.033) and FGL2 mRNA was up-regulated in tumor tissues compared to adjacent non-tumor tissues (P = 0.043). In addition, sFGL2 levels were positively correlated with HBV-DNA loads and AST (Spearman’s rho = 0.21, 0.25 and P = 0.006, 0.023, respectively), but reversely correlated with platelet counts and albumin levels (Spearman’s rho = − 0.27, − 0.24 and P = 0.014, 0.033, respectively).ConclusionssFGL2 levels are induced by HBV infection and correlated with the progression and clinical outcome of HBV-related liver diseases. Thus, sFGL2 may serve as a potential indicator for HBV-related liver diseases.
Highlights
Clinical progression of Hepatitis B virus (HBV)-related liver diseases is largely associated with the activity of HBV-specific T cells
White blood cell counts were lower in patients with liver cirrhosis (LC) and patients with LC plus hepatocellular carcinoma (HCC) compared to chronic hepatitis B (CHB) and HCC patients (P < 0.001)
Increased Soluble fibrinogen-like protein 2 (sFGL2) levels were observed in patients with advanced liver diseases such as LC, HCC patients and those with both LC and HCC compared to CHB patients (P = 0.033, 0.006, and 0.001, respectively)
Summary
Clinical progression of HBV-related liver diseases is largely associated with the activity of HBV-specific T cells. HBV infection leads to a wide spectrum of liver diseases, including an asymptomatic carrier status, acute self-limiting and fulminant hepatitis, chronic hepatitis B (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC) [1]. HBV stimulates both the innate and adaptive immune systems to establish persistent infections and the liver injuries in chronic infection are associated with the activity of HBV-specific T cells [5]. Sequential transformation of normal hepatocytes to malignant cells during HCC development is associated with the immune response to HBV-infected liver cells, accumulated genetic alterations, and the interaction between the viral HBx protein with host signaling proteins [6]
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