HBV Dominance Is Associated With a Distinct Inflammatory Milieu in HBV/HCV Coinfection

Area of Science:

• Immunology
• Hepatology
• Virology

Background:

• Hepatitis B (HBV) and C (HCV) virus coinfection increases the risk of cirrhosis and hepatocellular carcinoma (HCC).
• Limited data exist on the immune system's response to HBV/HCV coinfection, particularly concerning dominance patterns and immune mediator expression.
• Understanding immune interactivity is crucial, especially as HBV reactivation can occur after HCV clearance.

Purpose of the Study:

• To investigate the immune interactivity between HCV and HBV in coinfected patients.
• To analyze patterns of soluble immune mediators (SIM) based on HBV and HCV dominance.
• To explore the impact of viral dominance on the inflammatory milieu and associated signaling pathways.

Main Methods:

• Cross-sectional study of 49 patients with chronic HBV and HCV coinfection.
• Measurement of 58 soluble immune mediators (SIM) in serum or plasma.
• Classification of patients into HBV dominance, HCV dominance, codominance, and no dominance groups.

Main Results:

• Distinct SIM expression patterns were observed across different dominance groups.
• HBV activity was associated with significantly higher SIM expression and an altered soluble inflammatory milieu (22 SIM altered, p < 0.05).
• Key affected pathways included JAK-STAT, IL-17 signaling, and Th17 cell differentiation, with inverse correlations found for CCL27/CTACK and SDF-1alpha with HCV-RNA.

Conclusions:

• Serological classification of dominance patterns in HBV/HCV coinfection reveals distinct soluble inflammatory profiles.
• Elevated HBV activity correlates with increased SIM expression, notably affecting the JAK-STAT and Th17/IL-17 axes.
• These immune alterations may play a role in the pathogenesis of liver fibrosis in coinfected individuals.