Abstract: Objective To investigate the expression of interleukin-35 (IL-35) in the natural course of chronic HBV infection and its correlation with viral load and liver biochemical parameters, and to evaluate its role in the management of chronic HBV infection so as to provide evidence for dynamic monitoring of the course of disease and reducing severity. Method 83 patients with chronic HBV infection were selected from the Department of Infectious Diseases of Shanghai Changhai Hospital from January 2015 to November 2020, including immune tolerance group (n=22), immune clearance group (n=29) and severe hepatitis group (n=32) according to the natural course of chronic HBV infection. 20 healthy people were chosen as control. The expression level of IL-35 in peripheral blood was detected by ELISA (enzyme linked immunosorbent assay), HBV DNA and transaminase were also detected meanwhile. Statistical analysis was performed using the Mann-Whitney U test between two groups, Kruskal-Wallis H test between multiple groups and correlation analysis. Result The IL-35 levels of chronic HBV infection and healthy people were 51.75 (9.9,96.5)pg/ml and 7.33 (3.35,8.76) pg/ml respectively, the difference was statistically significant (Z=-5.69, P<0.01). The natural course of chronic HBV infection was higher than that in healthy controls, and IL-35 expression was highest in severe hepatitis group [121.46 (68.98,213.44) pg/ml]. There was no significant correlation between IL-35 and HBV DNA (r=0.385, 0.392, -0.168, P>0.05). There was positive correlation between IL-35 and ALT in patients with severe hepatitis (ρ=0.543, P=0.045), and a good positive correlation between IL-35 and ALT or AST in patients with chronic HBV infection (ALT: r=0.684, P=0.001; AST: r=0.618, P=0.001). For each unit increase in serum IL-35, the likelihood of progression to severe hepatitis increased by 7.2%. The ROC curve of serum IL-35 level showed AUC was 0.9491 (95%CI: 0.9078-0.9905, P<0.01), cut off <50.95 pg/ml. Conclusion ①IL-35 is highly expressed in peripheral blood in the course of HBV chronic infection and is positively correlated with the degree of liver inflammation; ②IL-35 has important application value in clinical evaluation of hepatitis B patients. Dynamic monitoring of IL-35 level in peripheral blood can assist in evaluating patients’ immune status, and early antiviral treatment can reduce the incidence of severe hepatitis.

Key words: Hepatitis B virus, Chronic hepatitis B, Natural course of CHB, Interleukin-35, Severe hepatitis