Abstract
Interferon-stimulated gene 20 kDa protein (ISG20) with 3’ to 5’ exonuclease activity mainly targeting single-stranded RNA plays an important role in immune responses against various infectious pathogens, including hepatitis viruses. ISG20 levels were measured by ELISA assays in sera of 339 hepatitis B-virus (HBV) infected patients and 71 healthy individuals and were correlated with clinical and laboratory parameters. ISG20 mRNA was quantified by qRT-PCR in 30 pairs of hepatocellular carcinoma (HCC) tumour and adjacent non-tumour liver tissues. ISG20 levels were significantly elevated in HBV patients compared to healthy controls (P<0.0001). In the patient group, varying ISG20 levels were associated with different forms of HBV-related liver diseases. ISG20 levels were higher in patients with HCC compared to those without HCC (P<0.0001), and increased according to the stages of HCC (P<0.0001). ISG20 mRNA expression was up-regulated in tumour tissues compared to the expression in adjacent non-tumour tissues (P=0.017). Importantly, ISG20 levels were strongly correlated with the levels of AST, ALT, total and direct bilirubin among HCC patients (Pearson’s r = 0.43, 0.35, 0.34, 0.3; P<0.0001, respectively). Although differences between liver cirrhosis (LC) and non-LC patients were not observed, ISG20 levels were elevated according to the progression of cirrhosis in patients with LC plus HCC (P=0.005). In conclusions, ISG20 levels are induced by HBV infection and significantly associated with progression and clinical outcome of HBV-related liver diseases, especially in patients with HCC. ISG20 might be a potential indicator for liver injury and the clinical outcome in HBV-related HCC.
Highlights
Hepatitis B virus (HBV) infection affects approximately 257 million people worldwide and causes 887.000 deaths annually due to its complications
aspartate transaminase (AST) levels were higher among patients with liver cirrhosis (LC) compared to those without LC, while alanine transaminase (ALT) levels were higher in chronic hepatitis B (CHB) patients compared to the other groups (P
Our previous study has indicated the important role of ISG15 genetic variants and ISG15 serum levels in hepatitis B-virus (HBV) replication and the progression of HBV-related liver diseases [24]
Summary
Hepatitis B virus (HBV) infection affects approximately 257 million people worldwide and causes 887.000 deaths annually due to its complications. Regions with high prevalences of HBV infection include sub-Saharan Africa, Asia and some parts of the Americas, with infection rates in some regions being more than 8% of the population [1]. HBV infection is a leading cause of liver diseases, including acute self-limiting and fulminant hepatitis, chronic hepatitis B (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Rates of progression to LC in chronic HBV carriers are estimated to be 10% per year [2], and the risk of HCC development in chronic HBV carriers is 100-fold higher compared to HBV-negative individuals [3]. In patients with HBV-related LC, the 5-year cumulative occurrence of HCC is about 15% in highly endemic areas such as sub-Saharan Africa and Asia [2]. HCC can develop on the basis of chronic liver injury, inflammation, and cirrhosis through a complex of mechanisms, and the risk of HCC development in chronic HBV carriers is directly related to high levels of HBV replication in hepatocytes [3, 4]
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