High Expression of Interleukin-33/ST2 Predicts the Progression and Poor Prognosis in Chronic Hepatitis B Patients with Hepatic Flare.

Background: Interleukin-33 (IL-33), along with its receptor suppression of tumorigenicity 2 (ST2), is capable of regulating immune responses. Immunologically mediated events play a critical role in the acute phase of chronic hepatitis B (CHB) infection. The present study primarily aimed to determine whether the IL-33/ST2 axis could be used as a reliable biomarker to predict disease progression and prognosis.

Methods: The study included 130 cases of CHB, with 48 cases in stable condition, 50 cases of progression to hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF), and 32 cases of progression to HBV related pre-ACLF. The demographic data and laboratory test results were recorded and compared among the groups. The blood samples for the measurement of serum IL-33 and soluble ST2 (sST2) levels were collected at admission and evaluated twice using the ELISA method.

Results: The patients in which the disease progressed to HBV-ACLF had the highest serum IL-33 and sST2 levels among the three groups (p<0.001). The correlation analysis showed that the serum IL-33 levels were associated with the levels of ALT (r = 0.367, p<0.001), AST (r = 0.456, p<0.001) and the MELD score (r = 0.377, p = 0.001). The area under the curve (AUC) of IL-33 and sST2 levels for differentiation of disease progression were 0.861 (95% CI: 0.787-0.934, p<0.001) and 0.788 (95% CI: 0.692-0.884, p<0.001), respectively. The serum IL-33 levels combined with the MELD score had the highest 90-day mortality prediction efficiency, with an AUC of 0.918 (95% CI: 0.859-0.977, p<0.001), a sensitivity of 92.3%, and a specificity of 88.7%.

Conclusions: The IL-33/sST2 axis could be used to evaluate the progression and mortality in CHB patients with hepatic flare. The combinatorial use of multiple indicators could achieve the highest diagnostic and predictive accuracy.