Human immunodeficiency virus-related microbial translocation and progression of hepatitis C.
OBJECTIVE
Human immunodeficiency virus (HIV)-1 infection has been associated with enhanced microbial translocation, and microbial translocation is a mechanism through which alcohol and some enteric conditions cause liver disease. We hypothesized that HIV promotes liver disease by enhancing microbial translocation.


METHODS
We studied human cohorts in which hepatitis C virus (HCV) and HIV outcomes were carefully characterized.


RESULTS
HIV-related CD4(+) lymphocyte depletion was strongly associated with microbial translocation as indicated by elevated levels of circulating lipopolysaccharide (LPS), LPS-binding protein, soluble CD14, and fucose-binding lectin (AAL) reactive to immunoglobulin G specific for the alpha-galactose epitope and suppressed levels of endotoxin core antibodies (EndoCAb IgM) in HIV-infected subjects compared with the same persons before they had HIV infection and compared with HIV-uninfected subjects. The same measures of microbial translocation were strongly associated with HCV-related liver disease progression (cirrhosis), eg, LPS, odds ratio, 19.0 (P = .002); AAL, odds ratio, 27.8 (P < .0001); in addition, levels of LPS were elevated prior to recognition of cirrhosis.


CONCLUSIONS
Microbial translocation may be a fundamental mechanism through which HIV accelerates progression of chronic liver disease.
Balagopal
Ashwin
A
Division of Infectious Diseases, Viral Hepatitis Center, Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Philp
Frances H
FH
Astemborski
Jacquie
J
Block
Timothy M
TM
Mehta
Anand
A
Long
Ronald
R
Kirk
Gregory D
GD
Mehta
Shruti H
SH
Cox
Andrea L
AL
Thomas
David L
DL
Ray
Stuart C
SC
D000328:Adult; D018988:Bacterial Translocation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology* / Q000382:microbiology*; D006679:HIV Seropositivity; D019698:Hepatitis C, Chronic / Q000453:epidemiology / Q000276:immunology* / Q000382:microbiology*; D006801:Humans; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000276:immunology / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D015995:Prevalence