Host response to translocated microbial products predicts outcomes of patients with HBV or HCV infection
Open accessAbstract
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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The host response to translocated microbial products predicts outcomes also in patients with hepatitis B and C virus infections, indicating that bacterial translocation contributes to the progression of chronic liver injury not only in the presence of metabolic or alcoholic disease.
“Finally, the host response to translocated microbial products predicts outcomes also in patients with hepatitis B and C virus infections, indicating that bacterial translocation contributes to the progression of chronic liver injury not only in the presence of metabolic or alcoholic disease [241].”
From Gut-pancreas-liver Axis as a target for treatment of NAFLD/NASH (2020) · cites this paper as [241]
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- Authors
- Sandler, N. G., Koh, C., Roque, A., Eccleston, J. L., Siegel, R. B., Demino, M., Kleiner, D. E., Deeks, S. G., Liang, T. J., Heller, T., & Douek, D. C.
- Affiliations
- National Institutes of Health (US)
- San Francisco General Hospital (US)
- Corresponding author
- Heller, Theo
- Douek, Daniel C.
- ORCID
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2011-10
- Volume
- 141
- Issue
- 4
- Pages
- 1220-1230.e3
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC3186837
- OpenAlex
- W1978906150
- Cited by
- 307
- References
- 57
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 16 · 2023: 15 · 2022: 13 · 2021: 19 · 2020: 15 · 2019: 16 · 2018: 34 · 2017: 24 · 2016: 32 · 2015: 23 · 2014: 24 · 2013: 28 · 2012: 27
- FWCI
- 16.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99 AI999999)
- National Cancer Institute
- National Institute of Allergy and Infectious Diseases (AI 76174, Y99 AI999999, P01AI076174, P30AI027763)
- National Institute of Diabetes and Digestive and Kidney Diseases
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Medicine › Hepatology › Hepatitis C virus research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- microbial translocation, hepatitis B, hepatitis C, liver cirrhosis, lipopolysaccharide, soluble CD14, intestinal fatty acid binding protein, interleukin-6, portal hypertension, liver fibrosis, end-stage liver disease, Kupffer cells, monocyte activation, antiviral therapy, gut-liver axis
- MeSH terms
- Biopsy, Enzyme-Linked Immunosorbent Assay, Female, Humans, Hypertension, Portal, Intestines, Kupffer Cells, Limulus Test, Lipopolysaccharides, Liver Cirrhosis, Male, Maryland, Middle Aged, Monocytes, Retrospective Studies, Severity of Illness Index, Biomarkers, Interleukin-6, Logistic Models, Odds Ratio, Cell Death, Disease Progression, Lipopolysaccharide Receptors, Bacterial Translocation, Hepatitis B, Chronic, Hepatitis C, Chronic, Enterocytes, Fatty Acid-Binding Proteins, Host-Pathogen Interactions, End Stage Liver Disease
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