Journal of Hepatology
Volume 48, Issue 1 , Pages 61-67, January 2008

Presence of bacterial-DNA in cirrhosis identifies a subgroup of patients with marked inflammatory response not related to endotoxin

  • José M. González-Navajas

      Affiliations

    • CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
    • Unidad Hepática, Hospital General Universitario, Alicante, Spain
  • ,
  • Pablo Bellot

      Affiliations

    • Sección de Immunología, Hospital General Universitario, Alicante, Spain
  • ,
  • Rubén Francés

      Affiliations

    • CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
    • Unidad Hepática, Hospital General Universitario, Alicante, Spain
  • ,
  • Pedro Zapater

      Affiliations

    • CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
    • Laboratorio de Hemodinámica Hepática, Hospital Clínic, IDIBAPS, Barcelona, Spain
  • ,
  • Carlos Muñoz

      Affiliations

    • Servicio de Farmacología Clínica, Hospital General Universitario, Alicante, Spain
  • ,
  • Juan Carlos García-Pagán

      Affiliations

    • CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
    • Sección de Immunología, Hospital General Universitario, Alicante, Spain
  • ,
  • Sonia Pascual

      Affiliations

    • CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
    • Unidad Hepática, Hospital General Universitario, Alicante, Spain
  • ,
  • Miguel Pérez-Mateo

      Affiliations

    • Unidad Hepática, Hospital General Universitario, Alicante, Spain
  • ,
  • Jaime Bosch

      Affiliations

    • CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
    • Unidad Hepática, Hospital Clínic, IDIBAPS, Barcelona, Spain
  • ,
  • José Such

      Affiliations

    • CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
    • Unidad Hepática, Hospital General Universitario, Alicante, Spain
    • Corresponding Author InformationCorresponding author. Tel./fax: +34 965 938 345.

Received 31 May 2007; received in revised form 27 August 2007; accepted 29 August 2007. published online 19 October 2007.

Associate Editor: C. Merkel

Background/Aims

Serum lipopolysaccharide-binding protein and bacterial-DNA have been proposed as markers of bacterial translocation and this study aimed to evaluate the immune response registered by bacterial-DNA from Gram-positive and Gram-negative microorganisms and the effect on lipopolysaccharide-binding protein, to further investigate both markers.

Methods

Thirty-two patients were distributed into two groups according to the presence of bacterial-DNA, determined by broad-range PCR of 16SrRNA gene. Serum endotoxin, lipopolysaccharide-binding protein, cytokines and nitric oxide products were measured by ELISA.

Results

Serum endotoxin and lipopolysaccharide-binding protein were non-significantly higher in patients with bacterial-DNA than in those without bacterial-DNA. Regarding patients with bacterial-DNA from Gram-positive microorganisms (n=8), these levels were similar to those in patients without bacterial-DNA (n=16), and significantly lower than in patients with bacterial-DNA from Gram-negative bacteria. Tumour necrosis factor-alpha and interleukin-6 were significantly increased in patients with vs without bacterial-DNA (324.93±70.76 vs 134.91±34.58μg/mL; p<0.05; 294.96±87.48 vs 175.92±60.58μg/mL, p<0.05, respectively). Patients with bacterial-DNA from Gram-positive microorganisms also showed significantly higher levels for both cytokines than patients without bacterial-DNA, and similar to those in patients with bacterial-DNA from Gram-negative bacteria.

Conclusions

Patients with translocation of bacterial-DNA from Gram-positive microorganisms showed increased proinflammatory cytokines unrelated to endotoxin, which would not be detected by serum lipopolysaccharide-binding protein measurement.

Abbreviations: BT, bacterial translocation, LPS, lipopolysaccharide, LBP, LPS-binding protein, bactDNA, bacterial-DNA, TNF-α, tumour necrosis factor-alpha, IL6, interleukin 6, NO, nitric oxide, GNB, Gram-negative bacteria, GPC, Gram-positive cocci

Keywords: Bacterial translocation, Bacterial-DNA, Lipopolysaccharide-binding protein, Cytokine, Cirrhosis

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 The authors declare that they do not have anything to disclose regarding conflict of interest with respect to this manuscript.

PII: S0168-8278(07)00559-4

doi:10.1016/j.jhep.2007.08.012

Journal of Hepatology
Volume 48, Issue 1 , Pages 61-67, January 2008