Serum isthmin-1 levels in chronic hepatitis B: association with viral replication and hepatic dysfunction

Abstract

Introduction: Chronic hepatitis B virus (HBV) infection remains a major global health problem, underscoring the need for biomarkers that reflect viral replication and liver function. Isthmin-1 (ISM-1), an immunometabolic adipokine, has not been adequately studied in chronic HBV infection. This study evaluated serum ISM-1 levels in patients with chronic HBV to assess its potential as a complementary marker of viral activity and hepatic dysfunction.

Methodology: In this cross-sectional study, 100 patients with histologically mild chronic hepatitis B and 60 healthy controls were enrolled. Serum ISM-1 levels were measured using a commercial enzyme-linked immunosorbent assay (ELISA) kit alongside comprehensive virological and biochemical assessments.

Results: Serum ISM-1 concentrations were significantly lower in patients with chronic HBV than in healthy controls (102.74 ± 15.64 vs. 194.62 ± 187.59 pg/mL; p < 0.001). ISM-1 levels demonstrated a significant downward trend as HBV DNA categories increased (p = 0.001), indicating an inverse relationship with viral replication. Multiple linear regression identified direct bilirubin as a positive independent predictor of ISM-1 levels. ROC analysis showed moderate overall performance (AUC = 0.656); the marker exhibited a remarkably high sensitivity (97.0%) but limited specificity (38.7%).

Conclusions: Serum ISM-1 levels are significantly reduced in chronic HBV infection and are inversely associated with viral replication. The positive correlation with direct bilirubin may reflect an adaptive cellular response to hepatocellular stress rather than simple dysfunction. Despite its limited specificity, the high sensitivity of ISM-1 suggests that it could be a valuable complementary tool for monitoring disease progression and viral status in clinical practice.