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PMID: 21726511 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural

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

Gastroenterology ·Vol. 141 ·No. 4 ·2011-10-00 ·Pages 1220-30, 1230.e1-3

Sandler NG, Koh C, Roque A, Eccleston JL, Siegel RB, Demino M, Kleiner DE, Deeks SG, Liang TJ, Heller T, Douek DC

Abstract

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. 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. 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). 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.

MeSH Terms
Bacterial Translocation Biomarkers/blood Biopsy Cell Death Disease Progression End Stage Liver Disease/microbiology,virology Enterocytes/microbiology,pathology,virology Enzyme-Linked Immunosorbent Assay Fatty Acid-Binding Proteins/blood Female Hepatitis B, Chronic/complications,diagnosis,immunology,microbiology Hepatitis C, Chronic/complications,diagnosis,immunology,microbiology Host-Pathogen Interactions Humans Hypertension, Portal/microbiology,virology Interleukin-6/blood Intestines/immunology,microbiology,pathology,virology Kupffer Cells/microbiology,virology Limulus Test Lipopolysaccharide Receptors/blood Lipopolysaccharides/blood Liver Cirrhosis/diagnosis,immunology,microbiology,virology Logistic Models Male Maryland Middle Aged Monocytes/immunology,microbiology,virology Odds Ratio Retrospective Studies Severity of Illness Index
Chemicals
Biomarkers Fatty Acid-Binding Proteins IL6 protein, human Interleukin-6 Lipopolysaccharide Receptors Lipopolysaccharides
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Sandler Netanya G
Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
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
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Article Info
Journal
Gastroenterology
Abbr.
Gastroenterology
ISSN
1528-0012
DOI
10.1053/j.gastro.2011.06.063
Published
2011-10-00
Epub
2011-00-02
Pages
1220-30, 1230.e1-3
Language
English
Region
United States
NLM ID
0374630
PMCID
PMC3186837
Subset
IM
Grants
NIAID NIH HHS · P01 AI076174 · United States
NIAID NIH HHS · P30 AI027763 · United States
Intramural NIH HHS · Z99 AI999999 · United States
NIAID NIH HHS · AI-76174 · United States
External Links
PubMed source DOI: 10.1053/j.gastro.2011.06.063 PMC Full Text View journal details
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