Abstract: Objective To investigate the role of RIPK3-mediated necroptosis in patients with HBV-related acute-on-chronic liver failure.Methods Total 140 subjects were recruited, including 40 patients with HBV related acute-on-chronic liver failure (HBV-ACLF), 40 patients with HBV-related liver cirrhosis (HBV-LC), 40 chronic hepatitis B patients (CHB), and 20 heathy controls. Serum RIPK3 levels were measured, and the correlation between ALT/AST with serum RIPK3 levels were analyzed.Results Serum RIPK3 levels in all patients with liver diseases [30.94 (0.00, 459.10) pg/mL], including HBV-ACLF, HBV-LC and CHB, were significantly higher than that in healthy controls [0.00 (0.00, 0.00) pg/mL] (P<0.0001). Moreover, serum RIPK3 levels gradually elevated as the severity of liver desease increased, especially in HBV-ACLF group [870.35 (337.80, 1426.97) pg/mL]. Significant positive correlation was found between serum RIPK3 and ALT levels (r=0.5804, P<0.0001), AST levels (r=0.8114, P<0.0001), TBIL (r=0.5388, P<0.0001), PT (r=0.5690, P<0.0001), as well as INR (r=0.5724, P<0.0001) in patients with liver disease.Conclusion Necroptosis, mediated by RIPK3, plays a significant role in HBV-ACLF.

Key words: Acute-on-chronic liver failure, Hepatitis B virus, Necroptosis, RIPK3