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. 2008 Jul;135(1):226-33.
doi: 10.1053/j.gastro.2008.03.022. Epub 2008 Mar 29.

Human immunodeficiency virus-related microbial translocation and progression of hepatitis C

Ashwin Balagopal  1 , Frances H Philp, Jacquie Astemborski, Timothy M Block, Anand Mehta, Ronald Long, Gregory D Kirk, Shruti H Mehta, Andrea L Cox, David L Thomas, Stuart C Ray
Affiliations

Human immunodeficiency virus-related microbial translocation and progression of hepatitis C

Ashwin Balagopal et al. Gastroenterology. 2008 Jul.

Abstract

Background & aims: 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.

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Conflict of interest statement

The authors have no financial conflicts of interest to report.

Figures

Figure 1a–e
Figure 1a–e
Increased microbial translocation and immune activation in HIV-infected subjects with stratified CD4+ lymphocyte counts compared to those without HIV infection. a. LPS, b. LBP, c. sCD14, d. AAL, and e. EndoCAb IgM was compared in 17 subjects with liver disease and 71 subjects without in the presence and absence of HIV infection. Each marker was measured in stored serum samples. Each point represents the value from one subject’s serum. P-values were generated by Wilcoxon Rank-Sum test procedure, and *p<0.05 was considered to be significant.
Figure 1a–e
Figure 1a–e
Increased microbial translocation and immune activation in HIV-infected subjects with stratified CD4+ lymphocyte counts compared to those without HIV infection. a. LPS, b. LBP, c. sCD14, d. AAL, and e. EndoCAb IgM was compared in 17 subjects with liver disease and 71 subjects without in the presence and absence of HIV infection. Each marker was measured in stored serum samples. Each point represents the value from one subject’s serum. P-values were generated by Wilcoxon Rank-Sum test procedure, and *p<0.05 was considered to be significant.
Figure 1a–e
Figure 1a–e
Increased microbial translocation and immune activation in HIV-infected subjects with stratified CD4+ lymphocyte counts compared to those without HIV infection. a. LPS, b. LBP, c. sCD14, d. AAL, and e. EndoCAb IgM was compared in 17 subjects with liver disease and 71 subjects without in the presence and absence of HIV infection. Each marker was measured in stored serum samples. Each point represents the value from one subject’s serum. P-values were generated by Wilcoxon Rank-Sum test procedure, and *p<0.05 was considered to be significant.
Figure 1a–e
Figure 1a–e
Increased microbial translocation and immune activation in HIV-infected subjects with stratified CD4+ lymphocyte counts compared to those without HIV infection. a. LPS, b. LBP, c. sCD14, d. AAL, and e. EndoCAb IgM was compared in 17 subjects with liver disease and 71 subjects without in the presence and absence of HIV infection. Each marker was measured in stored serum samples. Each point represents the value from one subject’s serum. P-values were generated by Wilcoxon Rank-Sum test procedure, and *p<0.05 was considered to be significant.
Figure 1a–e
Figure 1a–e
Increased microbial translocation and immune activation in HIV-infected subjects with stratified CD4+ lymphocyte counts compared to those without HIV infection. a. LPS, b. LBP, c. sCD14, d. AAL, and e. EndoCAb IgM was compared in 17 subjects with liver disease and 71 subjects without in the presence and absence of HIV infection. Each marker was measured in stored serum samples. Each point represents the value from one subject’s serum. P-values were generated by Wilcoxon Rank-Sum test procedure, and *p<0.05 was considered to be significant.
Figure 2
Figure 2
HCV seroconversion is not significantly associated with microbial translocation. Thirty-four persons had levels of microbial translocation markers drawn before and after acute HCV seroconversion. LPS levels were not different after seroconversion, as shown. Similar results were found for other microbial translocation markers.
Figure 3
Figure 3
HIV-related intestinal CD4+ lymphocyte depletion and microbial translocation contribute to HCV progression. An integrated model shows that microbial translocation is dependent on HIV-related CD4+ lymphocyte depletion. Microbial translocation is critical for the development of immune activation and AIDS, but liver disease develops only in HCV co-infection. Microbial translocation in the host with cirrhosis will lead to less clearance of bacterial products, and increased immune activation.
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References

    1. Weber R, Sabin CA, Friis-Moller N, et al. Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study. Arch Intern Med. 2006;166:1632–1641. - PubMed
    1. Goedert JJ, Eyster ME, Lederman MM, et al. End-stage liver disease in persons with hemophilia and transfusion- associated infections. Blood. 2002;100:1584–1589. - PubMed
    1. Thio CL, Seaberg EC, Skolasky RL, et al. HIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter AIDS Cohort Study (MACS) Lancet. 2002;360:1921–1926. - PubMed
    1. Smit-McBride Z, Mattapallil JJ, McChesney M, et al. Gastrointestinal T lymphocytes retain high potential for cytokine responses but have severe CD4(+) T-cell depletion at all stages of simian immunodeficiency virus infection compared to peripheral lymphocytes. J Virol. 1998;72:6646–6656. - PMC - PubMed
    1. Veazey RS, DeMaria M, Chalifoux LV, et al. Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science. 1998;280:427–431. - PubMed

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