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Host Response to Translocated Microbial Products Predicts Outcomes of Patients with HBV or HCV infection.

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http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve & db=PubMed & dispmax=15 & list_\

uids=21731027,21416243,21726511,21735472,21735471,21735466,21725992,21725991,217\

25988,21723841,21723840,21728744,21723352,21722687,21722684 & dopt=AbstractPlus

Gastroenterology. 2011 Jul 1. [Epub ahead of print]

Host Response to Translocated Microbial Products Predicts Outcomes of Patients

with HBV or HCV infection.

Sandler NG, Koh C, Roque A, Eccleston JL, Siegel RB, Demino M, Kleiner DE, Deeks

SG, Liang TJ, Heller T, Douek DC.

Source

Human Immunology Section, Vaccine Research Center, National Institute of Allergy

and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD

20892.

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 (I-FABP),

and interleukin (IL)-6 by ELISA, 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, I-FABP (indicating enterocyte death), sCD14

(produced upon LPS activation of monocytes), and IL-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 AST, P=.002 for ferritin) and fibrosis

(P<.0001for gamma-glutamyl transpeptidase, P=.01 for alkaline phosphatase,

P<.0001 for alpha-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 are associated with cirrhosis and

predict progression to end-stage liver disease in patients with HBV or HCV

infection.

Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

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