Literature DB >> 35559125

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

Elizabeth C Townsend1, Grace Y Zhang1, Rabab Ali1, Pallavi Surana1, Marian Firke1, Mi Sun Moon1, Ma Ai Thanda Han1, Meital Gewirtz1, James A Haddad1, David E Kleiner2, Christopher Koh1, Theo Heller1.   

Abstract

Background: 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).
Methods: 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.
Results: 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. Published by Oxford University Press on behalf of Infectious Diseases Society of America 2020.

Entities:  

Keywords:  hepatitis B virus (HBV); hepatitis delta virus (HDV); immune responses; microbial translocation

Year:  2020        PMID: 35559125      PMCID: PMC9088508          DOI: 10.1093/ofid/ofaa496

Source DB:  PubMed          Journal:  Open Forum Infect Dis        ISSN: 2328-8957            Impact factor:   4.423


  39 in total

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