Host response to translocated microbial products predicts outcomes of patients with HBV or HCV infection

Netanya G. Sandler, Christopher Koh, Annelys Roque, Jason L. Eccleston, Rebecca B. Siegel, Mary Demino, David E. Kleiner, Steven G. Deeks, T. Jake Liang, Theo Heller, Daniel C. Douek

Research output: Contribution to journalArticle

179 Citations (Scopus)

Abstract

Background & Aims: Chronic infection with hepatitis B or C virus (HBV or HCV) is a leading cause of cirrhosis by unknown mechanisms of pathogenesis. Translocation of gut microbial products into the systemic circulation might increase because of increased intestinal permeability, bacterial overgrowth, or impaired clearance of microbial products by Kupffer cells. We investigated whether the extent and progression of liver disease in patients with chronic HBV or HCV infection are associated with microbial translocation and subsequent activation of monocytes. Methods: In a retrospective study, we analyzed data from 16 patients with minimal fibrosis, 68 with cirrhosis, and 67 uninfected volunteers. We analyzed plasma levels of soluble CD14 (sCD14), intestinal fatty acid binding protein, and interleukin-6 by enzyme-linked immunosorbent assay, and lipopolysaccharide (LPS) by the limulus amebocyte lysate assay, at presentation and after antiviral treatment. Results: Compared with uninfected individuals, HCV- and HBV-infected individuals had higher plasma levels of LPS, intestinal fatty acid binding protein (indicating enterocyte death), sCD14 (produced upon LPS activation of monocytes), and interleukin-6. Portal hypertension, indicated by low platelet counts, was associated with enterocyte death (P =.045 at presentation, P <.0001 after therapy). Levels of sCD14 correlated with markers of hepatic inflammation (P =.02 for aspartate aminotransferase, P =.002 for ferritin) and fibrosis (P <.0001 for γ-glutamyl transpeptidase, P =.01 for alkaline phosphatase, P <.0001 for α-fetoprotein). Compared to subjects with minimal fibrosis, subjects with severe fibrosis at presentation had higher plasma levels of sCD14 (P =.01) and more hepatic CD14 + cells (P =.0002); each increased risk for disease progression (P =.0009 and P =.005, respectively). Conclusions: LPS-induced local and systemic inflammation is associated with cirrhosis and predicts progression to end-stage liver disease in patients with HBV or HCV infection.

Original languageEnglish (US)
JournalGastroenterology
Volume141
Issue number4
DOIs
StatePublished - Oct 2011
Externally publishedYes

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Fibrosis
Infection
Lipopolysaccharides
Fatty Acid-Binding Proteins
Enterocytes
Monocytes
Interleukin-6
Fetal Proteins
Inflammation
Horseshoe Crabs
End Stage Liver Disease
Kupffer Cells
gamma-Glutamyltransferase
Portal Hypertension
Ferritins
Aspartate Aminotransferases
Platelet Count
Hepatitis B virus
Hepacivirus
Antiviral Agents

Keywords

  • Hepatitis
  • Intestinal Fatty Acid Binding Protein
  • Microbial Translocation
  • Soluble CD14

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Sandler, N. G., Koh, C., Roque, A., Eccleston, J. L., Siegel, R. B., Demino, M., ... Douek, D. C. (2011). Host response to translocated microbial products predicts outcomes of patients with HBV or HCV infection. Gastroenterology, 141(4). https://doi.org/10.1053/j.gastro.2011.06.063

Host response to translocated microbial products predicts outcomes of patients with HBV or HCV infection. / Sandler, Netanya G.; Koh, Christopher; Roque, Annelys; Eccleston, Jason L.; Siegel, Rebecca B.; Demino, Mary; Kleiner, David E.; Deeks, Steven G.; Liang, T. Jake; Heller, Theo; Douek, Daniel C.

In: Gastroenterology, Vol. 141, No. 4, 10.2011.

Research output: Contribution to journalArticle

Sandler, NG, Koh, C, Roque, A, Eccleston, JL, Siegel, RB, Demino, M, Kleiner, DE, Deeks, SG, Liang, TJ, Heller, T & Douek, DC 2011, 'Host response to translocated microbial products predicts outcomes of patients with HBV or HCV infection', Gastroenterology, vol. 141, no. 4. https://doi.org/10.1053/j.gastro.2011.06.063
Sandler, Netanya G. ; Koh, Christopher ; Roque, Annelys ; Eccleston, Jason L. ; Siegel, Rebecca B. ; Demino, Mary ; Kleiner, David E. ; Deeks, Steven G. ; Liang, T. Jake ; Heller, Theo ; Douek, Daniel C. / Host response to translocated microbial products predicts outcomes of patients with HBV or HCV infection. In: Gastroenterology. 2011 ; Vol. 141, No. 4.
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abstract = "Background & Aims: Chronic infection with hepatitis B or C virus (HBV or HCV) is a leading cause of cirrhosis by unknown mechanisms of pathogenesis. Translocation of gut microbial products into the systemic circulation might increase because of increased intestinal permeability, bacterial overgrowth, or impaired clearance of microbial products by Kupffer cells. We investigated whether the extent and progression of liver disease in patients with chronic HBV or HCV infection are associated with microbial translocation and subsequent activation of monocytes. Methods: In a retrospective study, we analyzed data from 16 patients with minimal fibrosis, 68 with cirrhosis, and 67 uninfected volunteers. We analyzed plasma levels of soluble CD14 (sCD14), intestinal fatty acid binding protein, and interleukin-6 by enzyme-linked immunosorbent assay, and lipopolysaccharide (LPS) by the limulus amebocyte lysate assay, at presentation and after antiviral treatment. Results: Compared with uninfected individuals, HCV- and HBV-infected individuals had higher plasma levels of LPS, intestinal fatty acid binding protein (indicating enterocyte death), sCD14 (produced upon LPS activation of monocytes), and interleukin-6. Portal hypertension, indicated by low platelet counts, was associated with enterocyte death (P =.045 at presentation, P <.0001 after therapy). Levels of sCD14 correlated with markers of hepatic inflammation (P =.02 for aspartate aminotransferase, P =.002 for ferritin) and fibrosis (P <.0001 for γ-glutamyl transpeptidase, P =.01 for alkaline phosphatase, P <.0001 for α-fetoprotein). Compared to subjects with minimal fibrosis, subjects with severe fibrosis at presentation had higher plasma levels of sCD14 (P =.01) and more hepatic CD14 + cells (P =.0002); each increased risk for disease progression (P =.0009 and P =.005, respectively). Conclusions: LPS-induced local and systemic inflammation is associated with cirrhosis and predicts progression to end-stage liver disease in patients with HBV or HCV infection.",
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AU - Demino, Mary

AU - Kleiner, David E.

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