Increased Serum Sphingosine-1-Phosphate Accompanied with Secretion of Hepatitis B Surface Antigen

Abstract

Background: Chronic Hepatitis B is a major public health problem worldwide and HBsAg loss is deemed a successful response to therapy, unfortunately, rarely achieved with present treatments. The alterations of S1P production and signaling have been widely reported to promote the survival of virus and documented quite differently in various viral infections, which may be associated with hepatitis B virus (HBV) infection. However, serum S1P as the simple indicator of S1P signaling has not been well characterized in HBV infection. \n \nMethods: We detected serum S1P in 82 hepatitis B patients and 65 other virus infections, retrospectively reviewed serological markers of HBV infection, S1P transporters and storage cells in peripheral blood. In order to avoid alterations of S1P caused by liver injury, hepatic lesions of all involved patients were excluded by ultrasound examination and liver\xa0function measure. ROC curve analysis was performed to define the diagnostic efficiency of S1P in hepatitis B. Student s t test and Pearson correlation analysis were used to investigate the association between serum S1P and individual diagnostic parameters.F \n \nFindings: S1P showed significantly higher level in HBV DNA-positive hepatitis B patients (29.68±1.25μM) than that in healthy subjects(2.96±0.21μM), however, no significances were presented in other virus infection like HCV. Serum S1P was mostly correlated with HBsAg(r=0.94, P＜0.0001) and 100% rose in HBsAg-positive HBV infection. AUC of serum S1P in diagnosis of hepatitis B was 0.9995 with 95% CI of 0.9981 to 1.001, and the score of 6.99 has the 100.0% sensitivity and 98.44% specificity, with very similar diagnostic efficacy to HBsAg. Moreover, other diagnostic parameters like albumin, liver damage and liver cancer didn’t significantly alter increased serum S1P caused by HBsAg production. \n \nInterpretation: Serum S1P is the first molecule found so far to be so tightly accompanied with HBsAg released into sera, which may evoke a promised resolution of HBsAg loss by targeting S1P signaling. In addition, serum S1P would play with HBsAg as a good biomarker to monitor the activity of HBV. \n \nFunding: The National Natural Science Foundation of China and Jinjihu talent training project of Suzhou Industrial Park, Suzhou, China. \n \nDeclaration of Interest: All other authors declare no competing interests. \n \nEthical Approval: Ethical approval was granted by the Ethical Committee of hospitals involved.