Serum Decoy Receptor 3 Is a Useful Predictor for the Active Status of Chronic Hepatitis B in Hepatitis B e Antigen-Negative Patients

Abstract

Hepatitis B virus (HBV) infection is a global public health problem, because patients with chronic hepatitis B (CHB) may progress to liver cirrhosis and eventually evolve into hepatocellular carcinoma. Decoy receptor 3 (DcR3) is a soluble receptor of the tumor necrosis factor receptor superfamily, and has been implicated in anti-apoptotic and anti-inflammatory pathways. In this study, we explored the clinical value of serum DcR3 in predicting the active status of CHB in hepatitis B e antigen-negative patients (active HBeAg (−) CHB), which was determined with ELISA. The serum level of DcR3 in active HBeAg (−) CHB patients (1.92 ± 0.68 ng/ml) was higher than that in healthy controls (0.80 ± 0.25 ng/ml, p < 0.0001) and that in inactive status of HBeAg (−) CHB (inactive hepatitis B surface antigen carrier, HBsAg-IaC) patients (0.95 ± 0.26 ng/ml, p < 0.0001). DcR3 level was correlated with HBV DNA level (r = 0.819, p < 0.0001) and alanine transaminase level (ALT, r = 0.704, p < 0.0001) in active HBeAg (−) CHB patients. The area under the Receiver Operating Characteristics curve of DcR3 for detecting the active status of HBeAg (−) CHB patients was 0.914 (95% confidence interval, 0.851-0.977). The optimal cut-off value for DcR3 to predict active HBeAg (−) CHB was 1.22 ng/ml, which had a sensitivity of 87.5% and a specificity of 84.4%. These results suggest that serum DcR3 level may be useful for detecting HBeAg (−) CHB in the active stage, which requires medical treatment.

Role of TGFβ3-Smads-Sp1 axis in DcR3-mediated immune escape of hepatocellular carcinoma

“…In other words, DcR3 is easily detectable in the blood serum of patients, raising the possibility of using DcR3 as a biomarker for diagnosis, treatment and prognosis of some diseases. Therefore, in this study, DcR3 expression in serum was detected, showing that DcR3 in serum from HCC patients was higher than that in serum from humans without HCC, in keeping with the findings of Yanqiang Hou and Giorgos Bamias 33,34 . These observations indicate that DcR3 plays an important role in HCC progression and may serve as a valuable biomarker for monitoring HCC development in humans.…”

Elevated Serum Levels of the Antiapoptotic Protein Decoy-Receptor 3 Are Associated with Advanced Liver Disease

“…Interestingly, two recent studies may support this possible role of DcR3 in the inflammatory/fibrotic pathway. It was reported that DcR3 concentrations were increased in patients with primary biliary cirrhosis in both local and systemic levels when compared to healthy controls [21], while researchers from Japan suggest that sDcR3 values may be helpful in differentiating between active and inactive chronic hepatitis B in the subgroup of hepatitis B e antigen-negative patients [22]. Furthermore, in our study, within the population of patients with chronic hepatitis, the highest DcR3 values were seen in those with advanced Ishak scores in liver biopsy (i.e., with increasing levels of fibrosis).…”

Expression and Clinical Significance of Decoy Receptor 3 in Acute-on-Chronic Liver Failure

“…While the elevated DcR3 in ACLF is not reported previously, an increased DcR3 has been observed in patients with chronic HBV infection and is also suggested to be a useful noninvasive biomarker for discrimination of active hepatitis B from inactive HBV carriers [25] and a marker for liver fibrosis [26]. The pathophysiological value of increased DcR3 might be related with its function of modulating immune response, disrupting Fas signaling, and suppressing apoptosis.…”