Serum Gasdermin-D and CHB-Related biochemical indicators as potential biomarkers for predicting the natural phases of Chronic HBV infection

Abstract Background: The adequate understanding and definition of chronic HBV (CHB) infection nature history remain vitally crucial to precisely antiviral treatment selection and prognosis evaluation. The existing biomarkers are insufficient to discriminate one from the complicated CHB nature phases immediately. Gasdermin-D, the pyroptosis executioner, was illustrated to mediate hepatocyte pyroptosis and participate in chronic HBV infection development. Methods: The 480 CHB infection consecutive patients, other chronic liver patients and HBV-infected cell platforms were enrolled in this project. GSDMD was calculated by Sandwich ELISA kits. CHB-related biochemical indicators SOD and LDH were measured by chemiluminescent immunoassay. The viral biomarkers were detected by immunofluorescence, western blot and real-time PCR. The correlation analysis, random forest analysis and receiver operating characteristic (ROC) curve were conducted to evaluate their value as biomarkers for predicting the CHB nature phases. Results: The prominent elevation of GSDMD was observed in CHB infection patients among other chronic liver diseases, and basically along with the progress of CHB infection nature course, as well as in vitro. The SOD and LDH also had significant differences in the four phases of CHB infection. Random forest analysis found GSDMD was the most associated variable in predicting CHB natural course, rather than SOD and LDH. The ROC analysis illustrated serum GSDMD as a single marker had the highest value in predicting HBeAg negative phases with an AUC of 0.772. The combination of serum GSDMD, SOD and LDH had the highest predictive values both in HBeAg positive and negative phases, with the AUCs of 0.875 and 0.887 respectively. Conclusions: Serum GSDMD had greater predictive performance in assessing HBeAg-negative CHB infection which may be related to the pyroptosis of HBV-infection hepatocytes. The combination of serum GSDMD, SOD and LDH may become novel potential biomarkers for auxiliary definitions of the natural course of CHB infection.