The balance of type 1 and type 2 immune responses in the contexts of hepatitis B infection and hepatitis D infection.

BACKGROUND: Hepatitis delta virus (HDV) infection is the most rapidly progressive chronic viral hepatitis. Little is understood about the immune responses to HDV.

AIM: To characterize the systemic immune environments of hepatitis B virus (HBV) and HDV patients at various disease stages.

METHODS: Evaluated 129 subjects; 53 HBV, 43 HDV, 33 healthy controls. HBV and HDV subjects were categorized by aspartate aminotransferase to platelet ratio index (APRI) into mild (APRI < 0.5), moderate, and severe (APRI > 1.0). Serum cytokines and immune markers were assessed at a single treatment-naïve time-point.

RESULTS: Type 1 cytokines are elevated in both HBV and HDV. Both groups show higher TNFa, IL-12p40, and CXCL9 when compared to controls (all p< 0.05). However, only HBV group displayed elevated IFNg compared to controls. Type 2 cytokines are elevated in HBV. HBV group shows higher IL-4, IL-13, and CCL26 compared to healthy controls and HDV. Chemokine CCL2 and CCL13 are lower in HDV. When assessing ratios, HDV displays higher IFNg/IL-4, TNFa/IL-4, and TNFa/IL-13 ratios than HBV and controls.

CONCLUSION: HBV and HDV subjects show similarly elevated type 1 cytokines. HDV subjects display relatively lower type 2 cytokines. These differences in the systemic immune environments, particularly the predominance of type 1 responses, may contribute to the comparatively rapid progression of HDV disease.

TRANSLATIONAL IMPACT: Characterization of the imbalance in type 1 and type 2 immunity unique HDV has the potential to provide immunological insights for designing therapeutic targets in HDV associated disease progression.