title: Liver stiffness is associated with monocyte activation in HIV-infected Ugandans without viral hepatitis.
abstract: A high prevalence of liver stiffness, as determined by elevated transient elastography liver stiffness measurement, was previously found in a cohort of HIV-infected Ugandans in the absence of chronic viral hepatitis. Given the role of immune activation and microbial translocation in models of liver disease, a shared immune mechanism was hypothesized in the same cohort without other overt causes of liver disease. This study examined whether HIV-related liver stiffness was associated with markers of immune activation or microbial translocation (MT). A retrospective case-control study of subjects with evidence of liver stiffness as defined by a transient elastography stiffness measurement ≥9.3 kPa (cases=133) and normal controls (n=133) from Rakai, Uganda was performed. Cases were matched to controls by age, gender, HIV, hepatitis B virus (HBV), and highly active antiretroviral therapy (HAART) status. Lipopolysaccharide (LPS), endotoxin IgM antibody, soluble CD14 (sCD14), C-reactive protein (CRP), and D-dimer levels were measured. Conditional logistic regression was used to estimate adjusted matched odds ratios (adjMOR) and 95% confidence intervals. Higher sCD14 levels were associated with a 19% increased odds of liver stiffness (adjMOR=1.19, p=0.002). In HIV-infected individuals, higher sCD14 levels were associated with a 54% increased odds of having liver stiffness (adjMOR=1.54, p<0.001); however, the opposite was observed in HIV-negative individuals (adjMOR=0.57, p=0.001). No other biomarker was significantly associated with liver stiffness, and only one subject was found to have detectable LPS. Liver stiffness in HIV-infected Ugandans is associated with increased sCD14 indicative of monocyte activation in the absence of viral hepatitis or microbial translocation, and suggests that HIV may be directly involved in liver disease.
authors.affiliation: Laboratory of Immunoregulation, NIAID, NIH, Baltimore, MD 21205, USA. aredd2@jhmi.edu
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Redd
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Wendel
authors.forename: Mary K
authors.initials: MK
authors.lastname: Grabowski
authors.forename: Ponsiano
authors.initials: P
authors.lastname: Ocama
authors.forename: Valerian
authors.initials: V
authors.lastname: Kiggundu
authors.forename: Francis
authors.initials: F
authors.lastname: Bbosa
authors.forename: Iga
authors.initials: I
authors.lastname: Boaz
authors.forename: Ashwin
authors.initials: A
authors.lastname: Balagopal
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Reynolds
authors.forename: Ronald H
authors.initials: RH
authors.lastname: Gray
authors.forename: David
authors.initials: D
authors.lastname: Serwadda
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Kirk
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.forename: Lara
authors.initials: L
authors.lastname: Stabinski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D054459:Elasticity Imaging Techniques; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000503:physiopathology*; D006525:Hepatitis, Viral, Human / Q000150:complications; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008099:Liver / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology*; D008103:Liver Cirrhosis / Q000209:etiology / Q000276:immunology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D012189:Retrospective Studies; D014454:Uganda; D055815:Young Adult
chemical_list: D018950:Lipopolysaccharide Receptors
references.citation: AIDS. 2010 Jun 19;24(10):1415-23
references.pmid: 20495440
references.citation: Clin Infect Dis. 2009 Apr 1;48(7):963-72
references.pmid: 19236273
references.citation: J Infect Dis. 2011 Mar 1;203(5):744-5; author reply 746
references.pmid: 21220777
references.citation: PLoS One. 2012;7(8):e41258
references.pmid: 22870212
references.citation: Gastroenterology. 2008 Jul;135(1):226-33
references.pmid: 18457674
references.citation: PLoS One. 2008 Jun 25;3(6):e2516
references.pmid: 18575590
references.citation: J Acquir Immune Defic Syndr. 2000 Jul 1;24(3):211-7
references.pmid: 10969344
references.citation: Antivir Ther. 2011;16(3):405-11
references.pmid: 21555823
references.citation: Clin Gastroenterol Hepatol. 2013 Mar;11(3):303-8.e1
references.pmid: 23142332
references.citation: Nat Med. 2006 Dec;12(12):1365-71
references.pmid: 17115046
references.citation: J Acquir Immune Defic Syndr. 2012 Dec 15;61(5):552-6
references.pmid: 22932319
references.citation: J Infect Dis. 2011 Mar 15;203(6):780-90
references.pmid: 21252259
references.citation: Infect Immun. 1998 May;66(5):2264-71
references.pmid: 9573116
references.citation: J Acquir Immune Defic Syndr. 2010 Aug;54(5):556-9
references.pmid: 20463585
references.citation: Clin Infect Dis. 2012 Jun;54(12):1806-13
references.pmid: 22460963
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 21;106(16):6718-23
references.pmid: 19357303
references.citation: AIDS. 2009 Nov 27;23(18):2397-404
references.pmid: 19773633