Human Immunodeficiency Virus-Related Microbial Translocation and Progression of Hepatitis C

Division of Infectious Diseases, Viral Hepatitis Center, Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Gastroenterology (Impact Factor: 16.72). 07/2008; 135(1):226-33. DOI: 10.1053/j.gastro.2008.03.022
Source: PubMed


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.
We studied human cohorts in which hepatitis C virus (HCV) and HIV outcomes were carefully characterized.
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.
Microbial translocation may be a fundamental mechanism through which HIV accelerates progression of chronic liver disease.

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Available from: Timothy Block, Nov 25, 2014
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    • "There is emerging evidence that successful antiviral treatment of HIV infection and HCV infection may reduce the risk of liver disease progression to cirrhosis and of its complications [1] [16]. Suppression of HIV replication , leading to immune restoration and reduction in systematic inflammation, may slow liver disease progression [17] [18] [19] [20] [21] [22]. As such, expert guidelines recommend antiretroviral therapy for most HIV/HCV coinfected persons, regardless of CD4 cell count [9] [23] [24]. "
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    ABSTRACT: Due to shared routes of transmission, acute and chronic infection with hepatitis C virus is common among persons living with HIV infection in many regions of the world. In the era of effective antiretroviral therapy, acute HCV infection has been increasingly recognized in HIV-infected persons, particularly men who have sex with men, and liver disease, including hepatocellular carcinoma, has emerged as a leading cause of morbidity and mortality in those with chronic HCV infection, particularly older adults with long-standing coinfection. Over the past decade, the foundation for the management of acute and chronic HCV infection has been interferon alfa. However, due the high burden of treatment-related side effects and low likelihood of sustained virologic response, the impact of treatment with peginterferon/ribavirin on the burden of HCV disease in has been limited. However, the anticipated availability of safe, tolerable and highly efficacious interferon-free, oral HCV direct-acting antiviral combination therapies promise to dramatically change the management of acute and chronic HCV infection in HIV-infected persons. Preliminary data from studies of such oral DAA regimens in HIV/HCV coinfected patients suggest that coinfection with HIV will not impair HCV cure with these regimens. Indeed, in the coming era of high effective oral HCV DAA treatments, the only special feature concerning treatment of acute and chronic HCV infection in HIV-infected patients may be drug interactions between the antiretroviral drugs for HIV infection and direct-acting antiviral drugs for HCV infection.
    Journal of Hepatology 11/2014; 61(1). DOI:10.1016/j.jhep.2014.08.006 · 11.34 Impact Factor
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    • "Heterosexual transmission of HIV among non-IDU sexual partners was also reported and is currently attracting increasing attention. Co-infection of HIV and HCV can result in liver cirrhosis and can increase HIV morbidity and mortality [12], [13]. Understanding the transmission routes of both HIV and HCV has significant indications for implementing anti-retroviral therapy. "
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    ABSTRACT: Background While many human immunodeficiency virus (HIV) studies have been performed in Liangshan, most were focused only on HIV infection and based on a sampling survey. In order to fully understand HIV and hepatitis C virus (HCV) prevalence and related risk factors in this region, this study implemented in 2009, included a survey, physical examination, HIV and HCV test in two towns. Methods All residents in two towns of the Butuo county were provided a physical examination and blood tests for HIV and HCV, and then followed by an interview for questionnaire. Results In total, 10,104 residents (92.4%) were enrolled and 9,179 blood samples were collected for HIV and HCV testing, 6,072 were from individuals >14 years old. The rates of HIV, HCV, and HIV/HCV co-infection were 11.4%, 14.0%, and 7.7%, respectively for >14-year-old residents. The 25–34 yr age group had the highest prevalence of HIV, HCV, and HIV/HCV co-infections, reaching 24.4%, 26.2% and 16.0%, respectively. Overall, males had a much higher prevalence of all infections than females (HIV: 16.3% vs. 6.8%, HCV: 24.6% vs. 3.9%, HIV/HCV co-infected: 14.7% vs. 1.1%, respectively; P = 0.000). Approximately half of intravenous drug users tested positive for HIV (48.7%) and 68.4% tested positive for HCV. Logistic regression analysis showed that five factors were significantly associated with HIV and HCV infection: gender (odds ratio [OR] = 5.8), education (OR = 2.29); occupation (student as reference; farmer: OR = 5.02, migrant worker: OR = 6.12); drug abuse (OR = 18.0); and multiple sexual partners (OR = 2.92). Knowledge of HIV was not associated with infection. Conclusion HIV and HCV prevalence in the Liangshan region is very serious and drug use, multiple sexual partners, and low education levels were the three main risk factors. The government should focus on improving education and personal health awareness while enhancing drug control programs.
    PLoS ONE 07/2014; 9(7):e101241. DOI:10.1371/journal.pone.0101241 · 3.23 Impact Factor
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    • "HIV infection of plasmacytoid dendritic cells causes persistent activation, resulting in excessive production of proapoptotic interferon (IFN)-í µí»¼, as well as immunosuppressive indoleamine-2,3-dioxygenase and transforming growth factor (TGF)-í µí»½ [4] [5] [6] [7] [8] [9] [10] [11] [12] [13]. In the case of monocytes/macrophages, translocation of microbial products , especially lipopolysaccharide and DNA, across the damaged intestinal epithelium, results in persistent systemic activation of these cells due to interaction with Toll-like receptors 4 and 9, as well as with cytosolic pathogen nucleic acid sensors [14] [15] [16] [17] [18] [19] [20] [21] [22] [23]. The resultant production of proinflammatory cytokines, especially TNF-í µí»¼, drives T-cell activation and activation-induced cell death [6] [21] [22]. "
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    ABSTRACT: Few studies have examined immune activation profiles in patients with advanced HIV-1 subtype C infection or assessed their potential to predict responsiveness to HAART. BioPlex, ELISA, and nephelometric procedures were used to measure plasma levels of inflammatory biomarkers in HIV-1 subtype C-infected patients sampled before and after 6 months of successful HAART (n = 20); in patients failing HAART (n = 30); and in uninfected controls (n = 8). Prior to HAART, CXCL9, CXCL10, β 2M, sTNF-R1, TGF- β 1, IFN- γ , IL-6, TNF, and sCD14 were significantly elevated in HIV-1-infected patients compared to controls (P < 0.01). All of these markers, with the exception of sTNF-R1, were also elevated in patients failing HAART (P < 0.05). The persistently elevated levels of CXCL9, CXCL10, and β 2M in patients failing therapy in the setting of a marked reduction in these markers in patients on successful HAART suggest that they may be useful not only to monitor immune activation during HAART, but also to distinguish between good and poor responders. In the case of sCD14 and TGF- β 1, the levels of these biomarkers remained persistently elevated despite HAART-induced virological suppression, a finding that is consistent with ongoing monocyte-macrophage activation, underscoring a potential role for adjuvant anti-inflammatory therapy.
    Mediators of Inflammation 04/2014; 2014:198413. DOI:10.1155/2014/198413 · 3.24 Impact Factor
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