Clinical Value of Plasma Secreted Frizzled-Related Protein 4 in the Chronic Hepatitis B Virus Infection: A Cross-sectional Study

Background: Secreted frizzled-related protein 4 (sFRP4) is elevated in hepatocellular carcinoma (HCC) patients, suggesting that it can be served as a candidate marker for diagnosing HCC. However, little is known about its role in the different stages of chronic hepatitis B virus (HBV) infection. Objectives: This study was conducted to explore the clinical value of plasma sFRP4 in the different stages of chronic HBV infection. Methods: A total of 303 patients with chronic HBV infection were enrolled in this cross-sectional study. They were classified into the chronic hepatitis B (CHB), liver cirrhosis (LC), HCC, and acute-on-chronic liver failure (ACLF) groups on admission. Additionally, 30 healthy subjects were included in the healthy control (HC) group. The clinical value of plasma sFRP4 in the different stages of chronic HBV infection was analyzed. Results: There were 54, 85, 105, 59, and 30 cases in the CHB, LC, HCC, ACLF, and HC groups, respectively. ACLF group had the highest plasma sFRP4 levels compared to the CHB, LC, and HCC groups (all P < 0.001), followed by the HCC and LC groups. LC and HCC groups were found with up-regulated sFRP4 than the CHB group (all P < 0.05). High levels of plasma sFRP4 were recognized as an independent risk factor for distinguishing patients with ACLF from patients with CHB and LC [adjusted odds ratio (OR):1.005, 95% confidence interval (CI): 1.000 - 1.010, P = 0.043], with the area under the receiver operating characteristic curve (AUC) of 0.790 (95% CI: 0.726 - 0.844, P < 0.001). However, in patients with ACLF, plasma sFRP4 levels in the deteriorated group were higher than in the improved group, with a marginally significant difference (P = 0.071). The AUC for predicting the 90 days prognosis in patients with ACLF was 0.640 (P = 0.064). Conclusions: Plasma sFRP4 might be a biomarker to reflect the progression of chronic HBV infection. However, it was not significantly related to the prognosis in patients with ACLF; we did not find this, which may be due to the small sample size.