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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    • "Human immunodeficiency virus (HIV) accelerates the progression of human hepatitis C virus (HCV)-related liver disease in HIV/HCV co-infected patients (Balagopal et al., 2008; Benhamou et al., 1999; Soto et al., 1997; Thein et al., 2008). In general, the mean time from HCV infection to development of cirrhosis is about 30 years in mono-HCV-infected individuals, but in HIV/HCV coinfected patients the time of onset becomes significantly shorter (Benhamou et al., 1999; Macías et al., 2009; Mohsen et al., 2003; Pineda et al., 2007; Soto et al., 1997) and the occurrence of cirrhosis becomes more frequent (Bonacini et al., 2001; Ioannou et al., 2013; Mohsen et al., 2003; Parodi et al., 2007) than in mono-HCVinfected patients. "
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    ABSTRACT: HIV/HCV co-infection is characterized by higher serum HCV RNA loads compared with HCV monoinfection. However, the relationship between HIV and HCV replication remains to be clarified. HIV Vpr has been shown to play an essential role in HIV replication. In this study, we aimed to explore the role of Vpr in HCV replication and pathogenesis. We therefore used the genotype 2a full-length HCV strain JFH1 infection system and the genotype 1b full-length HCV replicon OR6 cell line to analyze the effects of Vpr on HCV replication. We found that Vpr promoted HCV 5' UTR activity, HCV RNA replication and HCV protein expression in two HCV infection cell models. Additionally, lymphocyte-produced Vpr significantly induced HCV 5' UTR activity and HCV replication in hepatocytes. We also found that Vpr up-regulated the expression of miR-122 by stimulating its promoter activity. Furthermore, a miR-122 inhibitor suppressed the Vpr-mediated enhancement of both HCV 5' UTR activity and HCV replication. In summary,our results revealed that the Vpr-upregulated expression of miR-122 is closely related to the stimulation of HCV 5' UTR activity and HCV replication by Vpr,providing new evidence for how HIV interacts with HCV during HIV/HCV co-infection.
    Preview · Article · Apr 2015 · Journal of General Virology
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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.
    Preview · Article · Nov 2014 · Journal of Hepatology
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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.
    Full-text · Article · Jul 2014 · PLoS ONE
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