title: Host response to translocated microbial products predicts outcomes of patients with HBV or HCV infection.
abstract: OBJECTIVE
  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.
authors: Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Netanya G
authors: NG
authors: Sandler
authors: Christopher
authors: C
authors: Koh
authors: Annelys
authors: A
authors: Roque
authors: Jason L
authors: JL
authors: Eccleston
authors: Rebecca B
authors: RB
authors: Siegel
authors: Mary
authors: M
authors: Demino
authors: David E
authors: DE
authors: Kleiner
authors: Steven G
authors: SG
authors: Deeks
authors: T Jake
authors: TJ
authors: Liang
authors: Theo
authors: T
authors: Heller
authors: Daniel C
authors: DC
authors: Douek
mesh_terms: D018988:Bacterial Translocation; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D016923:Cell Death; D018450:Disease Progression; D058625:End Stage Liver Disease / Q000382:microbiology / Q000821:virology; D020895:Enterocytes / Q000382:microbiology / Q000473:pathology / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D050556:Fatty Acid-Binding Proteins / Q000097:blood; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000175:diagnosis / Q000276:immunology / Q000382:microbiology; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000175:diagnosis / Q000276:immunology / Q000382:microbiology; D054884:Host-Pathogen Interactions; D006801:Humans; D006975:Hypertension, Portal / Q000382:microbiology / Q000821:virology; D015850:Interleukin-6 / Q000097:blood; D007422:Intestines / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000821:virology*; D007728:Kupffer Cells / Q000382:microbiology / Q000821:virology; D008033:Limulus Test; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008070:Lipopolysaccharides / Q000097:blood; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000276:immunology / Q000382:microbiology / Q000821:virology*; D016015:Logistic Models; D008297:Male; D008396:Maryland; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000382:microbiology / Q000821:virology*; D016017:Odds Ratio; D012189:Retrospective Studies; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D050556:Fatty Acid-Binding Proteins; C508600:IL6 protein, human; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides