Basic—Liver, Pancreas, and Biliary TractHuman Immunodeficiency Virus-Related Microbial Translocation and Progression of Hepatitis C
Section snippets
Study Population
For this investigation, subjects were chosen from 3 distinct ongoing cohorts in which liver disease, HIV infection, and HCV infection were carefully evaluated and serum specimens were archived at −80°C. All subjects provided informed consent for testing through a protocol approved by the committees on human research of the Johns Hopkins School of Medicine or Bloomberg School of Public Health.
Prevalent Liver Disease Group and Microbial Translocation Markers
A total of 88 HCV-infected persons had either cirrhosis or end-stage liver disease (17 cases) or clear evidence of minimal liver disease (71 controls). The mean age of subjects was 43.4 years at time of testing: 79.6% were male, 96.6% were African American, mean HCV RNA level was 12,928,360 IU/mL (7.1 log10), and 31.8% were HIV infected (Table 1). The associations of microbial translocation markers with factors such as age, sex, and alcohol use that might affect these markers and/or liver
Discussion
In this study, we confirmed that HIV-related CD4+ lymphocyte depletion was associated with microbial translocation and established a link between HIV-related microbial translocation and the severity of liver disease. These data suggest that microbial translocation may be a novel mechanism by which HIV accelerates liver disease.
The link between HIV and microbial translocation was already made by Brenchley et al.10 We confirm their cross-sectional analyses and extend these observations by finding
References (45)
- et al.
End-stage liver disease in persons with hemophilia and transfusion-associated infections
Blood
(2002) - et al.
HIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter AIDS Cohort Study (MACS)
Lancet
(2002) - et al.
Rapid mucosal CD4(+) T-cell depletion and enteropathy in simian immunodeficiency virus-infected rhesus macaques
Gastroenterology
(1999) Structural biology of the LPS recognition
Int J Med Microbiol
(2007)- et al.
TLRs, NLRs and RLRs: a trinity of pathogen sensors that cooperate in innate immunity
Trends Immunol
(2006) - et al.
Toll-like receptor 4 mediates inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells
Hepatology
(2003) - et al.
Total body irradiation and acute graft-versus-host disease: the role of gastrointestinal damage and inflammatory cytokines
Blood
(1997) - et al.
Probiotic effects on experimental graft-versus-host disease: let them eat yogurt
Blood
(2004) - et al.
Severity and correlates of liver disease in hepatitis C virus-infected injection drug users
Hepatology
(2002) - et al.
Simple and sensitive test for the determination of phenolic compounds in urine and its application to melanoma
J Invest Dermatol
(1975)
The influence of human immunodeficiency virus coinfection on chronic hepatitis C in injection drug users: a long-term retrospective cohort study
Hepatology
Clearance capacity of rat liver Kupffer, endothelial, and parenchymal cells
Gastroenterology
Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study
Arch Intern Med
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
Gastrointestinal tract as a major site of CD4+ T-cell depletion and viral replication in SIV infection
Science
Intrarectal transmission, systemic infection, and CD4(+) T-cell depletion in humanized mice infected with HIV-1
J Exp Med
Primary HIV-1 infection is associated with preferential depletion of CD4(+) T lymphocytes from effector sites in the gastrointestinal tract
J Exp Med
Severe CD4(+) T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy
J Virol
Microbial translocation is a cause of systemic immune activation in chronic HIV infection
Nat Med
Mechanisms of hepatic toxicity IIAlcoholic liver injury involves activation of Kupffer cells by endotoxin
Am J Physiol Gastrointest Liver Physiol
Development of a new, simple rat model of early alcohol-induced liver injury based on sensitization of Kupffer cells
Hepatology
TLR4 enhances TGF-beta signaling and hepatic fibrosis
Nat Med
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Supported by grants 1 R37DA004334, R01 2 DA012568, R01 DA016078, R01 DA013806, T32 AI07291, NCI R01CA120206, and U01CA084951.
Conflicts of interest: The authors have no financial conflicts of interest to report.