Microbial Translocation in the Context of Hepatitis B Infection and Hepatitis D Infection

Increased microbial translocation (MT) into the systemic circulation is associated with liver disease progression. Microbial translocation has yet to be completely defined in chronic hepatitis B virus (HBV) and chronic hepatitis delta virus (HDV).

The HBV and HDV patients display increased translocation of bacterial and fungal products into serum. An increased proportion of Gram-positive genera is associated with disease progression. Correlations of peptidoglycan with antimicrobial cytokines suggest that particular microbial classes may contribute to systemic inflammation and possibly disease progression.

Our aim was to characterize MT and associated immune response in chronic HBV and HDV at various stages of disease. Serum from 53 HBV, 43 HDV, and 36 healthy control (HC) subjects was obtained. Subjects were categorized by aspartate aminotransferase-to-platelet ratio index into mild (<0.5), moderate, and severe (>1.0) disease. Cytokines, microbial products, and microbial deoxyribonucleic acid (DNA) levels were assessed in a single treatment-naive time point for each patient. Next-generation sequencing identified bacterial species present within patient sera.

The HBV and HDV subjects display higher serum concentrations of Gram-negative (G-) bacterial lipopolysaccharide and fungal beta-glucan compared with HC (all P < .01). Gram-positive (G+) bacterial peptidoglycan is higher in HBV compared to HDV and HC (both P < .0001). Within both disease cohorts, peptidoglycan correlates with interleukin (IL)-1b, IL-8, IL-12p70, and IL-13 (all Spearman's rho >0.45; P < .05). Next-generation sequencing from 7 subjects with detectable serum bacterial DNA revealed changes in abundance of bacterial taxa and a higher proportion of Gram-positive genera in severe disease. Greater G+/G- taxa ratio is associated with higher cytokine levels and disease markers. Conclusions: The HBV and HDV patients display increased translocation of bacterial and fungal products into serum. An increased proportion of Gram-positive genera is associated with disease progression. Correlations of peptidoglycan with antimicrobial cytokines suggest that particular microbial classes may contribute to systemic inflammation and possibly disease progression.