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Objetivos del portal de Epidemiología Molecular de Enfermedades Infecciosas (EMEI)Este portal de EMEI pretende ser una plataforma de divulgación:

- Científica en el área de la Epidemiología Molecular de Enfermedades Infecciosas aplicada a pacientes infectados por distintos microorganismos que producen infecciones víricas (SIDA, hepatitis C, etc.) ó infecciones bacterianas (sepsis, etc.).

- De las actividades científicas (artículos científicos, comunicaciones a congresos, etc.) realizadas por el grupo de investigación formado en torno al laboratorio de investigación de Coinfección HIV y Hepatitis, cuyo responsable es el Dr. Salvador Resino García

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EMEI- Últimos artículos científicos publicados:

  • A combined score of pro- and anti-inflammatory interleukins improves mortality prediction in severe sepsis. -

    A combined score of pro- and anti-inflammatory interleukins improves mortality prediction in severe sepsis.

    Cytokine. 2011 Dec 23;

    Authors: Andaluz-Ojeda D, Bobillo F, Iglesias V, Almansa R, Rico L, Gandía F, Resino S, Tamayo E, de Lejarazu RO, Bermejo-Martin JF

    Abstract
    Identification of patients at increased risk of death is dramatically important in severe sepsis. Cytokines have been widely assessed as potential biomarkers in this disease, but none of the cytokines studied has evidenced a sufficient specificity or sensitivity to be routinely employed in clinical practice. In this pilot study, we profiled 17 immune mediators in the plasma of 29 consecutively recruited patients with severe sepsis or septic shock, during the first 24h following admission to the ICU, by using a Bio-Plex Human Cytokine 17-Plex Panel (Bio-Rad). Patients were 66.1year old in average. Twelve patients of our cohort died during hospitalization at the ICU, eight of them in the first 72h due to multiorganic dysfunction syndrom (MODS). Levels in plasma of three pro-inflammatory mediators (IL-6, IL-8, MCP-1) and of an immunosuppressive one (IL-10) were higher in those patients with fatal outcome. We developed a combined score with those cytokines showing to better predict mortality in our cohort based on the results of Cox regression analysis. This way, IL-6, IL-8 and IL-10 were included in the score. Patients were split into two groups based on the percentile 75 (P75) of the plasma levels of these three interleukins. Those patients showing at least one interleukin value higher than P75 were given the value "1". Those patients showing IL-6, IL-8, IL-10 levels below P75 were given the value "0". Hazard ratios for mortality at day 3 and day 28th obtained with the combined score were 2-3-fold higher than those obtained with the individual interleukins values. In conclusion, we have described a combined cytokine score associated with a worse outcome in patients with sepsis, which may represent a new avenue to be explored for guiding treatment decisions in this disease.

    PMID: 22197776 [PubMed - as supplied by publisher]

  • High plasma CXCL10 levels are associated with HCV-genotype 1, and higher insulin resistance, fibrosis, and HIV viral load in HIV/HCV coinfected patients. -

    High plasma CXCL10 levels are associated with HCV-genotype 1, and higher insulin resistance, fibrosis, and HIV viral load in HIV/HCV coinfected patients.

    Cytokine. 2012 Jan;57(1):25-9

    Authors: Berenguer J, Fernandez-Rodríguez A, Jimenez-Sousa MA, Cosín J, Zarate P, Micheloud D, López JC, Miralles P, Catalán P, Resino S

    Abstract
    BACKGROUND: CXCL10 may contribute to the host immune response against the hepatitis C virus (HCV), liver disease progression, and response to HCV antiviral therapy. The aim of our study was to analyze the relationship among virological, immunological, and clinical characteristics with plasma CXCL10 levels in human immunodeficiency virus (HIV)/HCV-coinfected patients.
    METHODS: We carried out a cross-sectional study on 144 patients. CXCL10 and insulin were measured using an immunoassay kit. The degree of insulin resistance was estimated for each patient using the homeostatic model assessment (HOMA) method. Insulin resistance was defined as a HOMA index higher than or equal to 3.8. Aspartate aminotransferase (AST) to platelet ratio (APRI), FIB-4, Forns index, HGM1, and HGM2 were calculated.
    RESULTS: The variables associated with log(10) CXCL10 levels by univariate analysis were age (b=0.013; p=0.023), prior AIDS-defining condition (b=0.127; p=0.045), detectable plasma HIV viral load (b=0.092; p=0.006), log(10) HOMA (b=0.216; p=0.002), HCV-genotype 1 (b=0.114; p=0.071), and liver fibrosis assessed by all non-invasive indexes (log(10) APRI (b=0.296; p=0.001), log(10) FIB-4 (b=0.436; p<0.001), log(10) Forns index (b=0.591; p<0.001), log(10) HGM1 (b=0.351; p=0.021), and log(10) HGM2 (b=0.215; p=0.018)). However, in multivariate analysis, CXCL10 levels were only associated with HOMA, detectable plasma HIV viral load, HCV-genotype 1 and FIB-4 (R-square=0.235; p<0.001).
    CONCLUSION: Plasma CXCL10 levels were influenced by several characteristics of patients related to HIV and HCV infections, insulin resistance, and liver fibrosis, indicating that CXCL10 may play an important role in the pathogenesis of both HCV and HIV infections.

    PMID: 22136974 [PubMed - in process]

  • Early natural killer cell counts in blood predict mortality in severe sepsis. -

    Early natural killer cell counts in blood predict mortality in severe sepsis.

    Crit Care. 2011 Oct 21;15(5):R243

    Authors: Andaluz-Ojeda D, Iglesias V, Bobillo F, Almansa R, Rico L, Gandía F, Loma AM, Nieto C, Diego R, Ramos E, Nocito M, Resino S, Eiros JM, Tamayo E, de Lejarazu RO, Bermejo-Martin JF

    Abstract
    ABSTRACT: INTRODUCTION: Host immunity should play a principal role in determining both the outcome and recovery of patients with sepsis that originated from a microbial infection. Quantification of the levels of key elements of the immune response could have a prognostic value in this disease. METHODS: In an attempt to evaluate the quantitative changes in the status of immunocompetence in severe sepsis over time and its potential influence on clinical outcome, we monitored the evolution of immunoglobulins (Igs) (IgG, IgA and IgM), complement factors (C3 and C4) and lymphocyte subsets (CD4+ T cells, CD8+ T cells, B cells (CD19+) and natural killer (NK) cells (CD3-CD16+CD56+)) in the blood of 50 patients with severe sepsis or septic shock at day 1, day 3 and day 10 following admission to the ICU. RESULTS: Twenty-one patients died, ten of whom died within the 72 hours following admission to the ICU. The most frequent cause of death (n = 12) was multiorgan dysfunction syndrome. At day 1, survivors showed significantly higher levels of IgG and C4 than those who ultimately died. On the contrary, NK cell levels were significantly higher in the patients who died. Survivors exhibited a progressive increase from day 1 to day 10 on most of the immunological parameters evaluated (IgG, IgA, IgM, C3, CD4+, CD8+ T cells and NK cells). Multivariate Cox regression analysis, including age, sex, APACHE II score, severe sepsis or septic shock status and each one of the immunological parameters showed that NK cell counts at day 1 were independently associated with increased risk of death at 28 days (hazard ratio = 3.34, 95% CI = 1.29 to 8.64; P = 0.013). Analysis of survival curves provided evidence that levels of NK cells at day 1 (> 83 cells/mm3) were associated with early mortality. CONCLUSIONS: Our results demonstrate the prognostic role of NK cells in severe sepsis and provide evidence for a direct association of early counts of these cells in blood with mortality.

    PMID: 22018048 [PubMed - as supplied by publisher]

  • Reduction in Mycobacterial Disease Among Human Immunodeficiency Virus-infected Children in the Highly Active Antiretroviral Therapy Era (1997-2008). -

    Reduction in Mycobacterial Disease Among Human Immunodeficiency Virus-infected Children in the Highly Active Antiretroviral Therapy Era (1997-2008).

    Pediatr Infect Dis J. 2011 Oct 19;

    Authors: Jensen J, Alvaro-Meca A, Micheloud D, Díaz A, Resino S

    Abstract
    BACKGROUND:: Human immunodeficiency virus (HIV)-infected children are at increased risk of developing mycobacterial disease. The aim of this study was to estimate the change in mycobacterial disease rate in HIV-infected children and adolescents in the highly active antiretroviral therapy (HAART) era. METHODS:: We carried out a retrospective study. Data were obtained from the records of the minimum basic data set of hospitals in Spain from 1997 to 2008. The epidemiologic trends of mycobacterial diseases were evaluated through the following 3 calendar periods: early-period HAART (1997-1999), midperiod HAART (2000-2002), and late-period HAART (2003-2008). RESULTS:: We analyzed 1307 HIV-infected children and 5228 HIV-uninfected children. HIV-infected children had similar rate of tuberculosis (TB) and nontuberculous mycobacteria (NTM) disease, and they had an overall rate of mycobacterial disease higher than that of HIV-uninfected children (P < 0.001). In HIV-infected children, the highest rates were for pulmonary TB (15/42 [35.7%]) in the TB category and disseminated mycobacterium (9/42 [21.4%]) in the NTM category. The overall rate of mycobacterial disease (events per 1000 HIV-infected children-year) decreased from 1997-1999 to 2003-2008 (5.88-1.63, P = 0.007) and from 2000-2002 to 2003-2008 (4.20-1.63, P = 0.021). Furthermore, the rate of TB decreased from 1997-1999 to 2000-2002 (3.53-0.84, P = 0.016) and from 1997-1999 to 2003-2008 (3.53-1.31, P = 0.030), and the rate of NTM disease decreased from 2000-2002 to 2003-2008 (3.36-0.32, P = 0.002). CONCLUSIONS:: The rate of mycobacterial disease decreased among HIV-infected children in the HAART era, but the incidence of mycobacterial disease still remains higher than in the general population.

    PMID: 22016082 [PubMed - as supplied by publisher]

  • Direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza. -

    Direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza.

    BMC Infect Dis. 2011;11:232

    Authors: Almansa R, Anton A, Ramirez P, Martin-Loeches I, Banner D, Pumarola T, Xu L, Blanco J, Ran L, Lopez-Campos G, Martin-Sanchez F, Socias L, Loza A, Andaluz D, Maravi E, Gordón M, Gallegos MC, Fernandez V, León C, Merino P, Marcos MA, Gandía F, Bobillo F, Resino S, Eiros JM, Castro C, Mateo P, Gonzalez-Rivera M, Rello J, de Lejarazu RO, Kelvin DJ, Bermejo-Martin JF

    Abstract
    BACKGROUND: Severe disease caused by 2009 pandemic influenza A/H1N1virus is characterized by the presence of hypercytokinemia. The origin of the exacerbated cytokine response is unclear. As observed previously, uncontrolled influenza virus replication could strongly influence cytokine production. The objective of the present study was to evaluate the relationship between host cytokine responses and viral levels in pandemic influenza critically ill patients.
    METHODS: Twenty three patients admitted to the ICU with primary viral pneumonia were included in this study. A quantitative PCR based method targeting the M1 influenza gene was developed to quantify pharyngeal viral load. In addition, by using a multiplex based assay, we systematically evaluated host cytokine responses to the viral infection at admission to the ICU. Correlation studies between cytokine levels and viral load were done by calculating the Spearman correlation coefficient.
    RESULTS: Fifteen patients needed of intubation and ventilation, while eight did not need of mechanical ventilation during ICU hospitalization. Viral load in pharyngeal swabs was 300 fold higher in the group of patients with the worst respiratory condition at admission to the ICU. Pharyngeal viral load directly correlated with plasma levels of the pro-inflammatory cytokines IL-6, IL-12p70, IFN-γ, the chemotactic factors MIP-1β, GM-CSF, the angiogenic mediator VEGF and also of the immuno-modulatory cytokine IL-1ra (p < 0.05). Correlation studies demonstrated also the existence of a significant positive association between the levels of these mediators, evidencing that they are simultaneously regulated in response to the virus.
    CONCLUSIONS: Severe respiratory disease caused by the 2009 pandemic influenza virus is characterized by the existence of a direct association between viral replication and host cytokine response, revealing a potential pathogenic link with the severe disease caused by other influenza subtypes such as H5N1.

    PMID: 21880131 [PubMed - indexed for MEDLINE]

  • Soluble markers of inflammation are associated with Framingham scores in HIV-infected patients on suppressive antiretroviral therapy. -

    Soluble markers of inflammation are associated with Framingham scores in HIV-infected patients on suppressive antiretroviral therapy.

    J Infect. 2011 Nov;63(5):382-90

    Authors: Guzmán-Fulgencio M, Medrano J, Rallón N, Echeverria-Urabayen A, Miguel Benito J, Restrepo C, García-Álvarez M, Vispo E, San Roman J, Sánchez-Piedra C, Soriano V, Resino S

    Abstract
    OBJECTIVE: To evaluate the association between biomarkers of inflammation and endothelial dysfunction and Framingham scores (FS) for risk of coronary heart disease (FS-CHD), stroke (FS-Stroke) or any cardiovascular event (FS-CVE) in HIV-infected on suppressive highly active antiretroviral therapy (HAART).
    METHODS: A cross-sectional study was conducted in 73 HIV-infected patients and 23 healthy controls. Inflammatory molecules and endothelial dysfunction markers were measured using a multiplex immunoassay (plasminogen activator inhibitor type 1 (PAI-1), soluble TNF receptor type 1 (sTNF-R1), soluble CD40 ligand (sCD40L), soluble E-selectin (sE-selectin), soluble P-selectin (sP-selectin), soluble intercellular adhesion molecules (sICAM-1) and soluble vascular cell adhesion molecule (sVCAM-1). Outcome variables were FS-CHD ≥10%, FS-Stroke ≥5% and FS-CVE ≥10%.
    RESULTS: Significant differences (p < 0.05) were found comparing controls and HIV patients for PAI-1 (5.4 vs. 13.5 ng/dL), sTNF-R1 (0.85 vs. 1.09 ng/dL), sICAM-1 (529 vs. 858 ng/dL), sE-selectin (73.7 vs. 120 ng/dL), sP-selectin (676 vs. 1511 ng/dL) sCD40L (76 vs. 307 ng/dL), FS-CHD (4% vs. 7.8% L), FS-Stroke (2% vs. 2.8%) and FS-CVE (5% vs. 11%). In HIV-infected patients, the adjusted logistic regression analysis revealed that sTNF-R1 levels were significantly associated with increased FS-CHD>10% (OR: 11.51 (95% CI: 1.14; 115.84); p = 0.038) and FS-CVE (OR: 12.41 (95% CI: 1.25; 123.23); p = 0.031).
    CONCLUSIONS: HIV-infected patients show higher levels of soluble inflammatory and endothelial dysfunction markers than controls and have a two-fold increased FS of presenting coronary heart disease, stroke or cardiovascular events at 10 years. Furthermore, sTNF-R1 displayed the best association with FS of coronary heart disease and any cardiovascular event in our patients.

    PMID: 21855573 [PubMed - in process]

  • Diagnostic accuracy of the APRI, FIB-4, and the Forns index for predicting liver fibrosis in HIV/HCV-coinfected patients: a validation study. -

    Diagnostic accuracy of the APRI, FIB-4, and the Forns index for predicting liver fibrosis in HIV/HCV-coinfected patients: a validation study.

    J Infect. 2011 Nov;63(5):402-5

    Authors: Resino S, Asensio C, Bellón JM, Carmona R, Miralles P, López JC, Cosín J, Álvarez E, Berenguer J

    PMID: 21839774 [PubMed - in process]

  • European mitochondrial DNA haplogroups and metabolic disorders in HIV/HCV-coinfected patients on highly active antiretroviral therapy. -

    European mitochondrial DNA haplogroups and metabolic disorders in HIV/HCV-coinfected patients on highly active antiretroviral therapy.

    J Acquir Immune Defic Syndr. 2011 Dec 1;58(4):371-8

    Authors: Micheloud D, Berenguer J, Guzmán-Fulgencio M, Campos Y, García-Álvarez M, Catalán P, Cosín J, Miralles P, López JC, Resino S

    Abstract
    BACKGROUND: Mitochondrial DNA (mtDNA) haplogroups play an important role in susceptibility to metabolic disorders and cardiovascular disease.
    METHODS: We carried out a cross-sectional study in 248 HIV/hepatitis C virus-coinfected patients on highly active antiretroviral therapy to investigate whether mtDNA haplogroups had any influence on metabolic disorders. mtDNA genotyping was performed using the Sequenom MassARRAY platform. Insulin resistance (IR) was estimated using the homeostatic model assessment (HOMA) (HOMA ≥ 3.8), which was calculated as fasting plasma glucose (mmol/L) times fasting serum insulin (mU/L) divided by 22.5. A high atherogenic risk was assessed when the atherogenic index (AI) was ≥3.5. AI was calculated as total cholesterol (mg/dL) divided by HDL (mg/dL).
    RESULTS: The major haplogroup HV and haplogroup H had reduced odds ratios of IR (HOMA ≥ 3.8) [0.45 (95% CI: 0.24 to 0.85) and 0.36 (95% CI: 0.18 to 0.69), respectively], and high AI (AI ≥ 3.5) [0.44 (95% CI: 0.22 to 0.87) and 0.40 (95% CI: 0.19 to 0.80), respectively]. The major haplogroup U had increased odds of IR [2.66 (95% CI: 1.39 to 5.8)]. The major haplogroup JT and haplogroup T had increased odds of high AI [2.86 (95% CI: 1.29 to 6.33) and 4.01 (95%CI: 1.59 to 10.03), respectively]. Additionally, we found that patients belonging to the major haplogroup HV had lower values of serum hepatic growth factor and nerve growth factor, and higher values of adiponectin than patients belonging to the major haplogroup JT (P < 0.05).
    CONCLUSIONS: mtDNA haplogroups were associated with IR and atherogenic dyslipidemia; suggesting that mitochondrial genomics may play a significant role in metabolic disorders and cardiovascular diseases in HIV/hepatitis C virus-coinfected patients on highly active antiretroviral therapy.

    PMID: 21792063 [PubMed - indexed for MEDLINE]

  • European mitochondrial DNA haplogroups and liver fibrosis in HIV and hepatitis C virus coinfected patients. -

    European mitochondrial DNA haplogroups and liver fibrosis in HIV and hepatitis C virus coinfected patients.

    AIDS. 2011 Aug 24;25(13):1619-926

    Authors: García-Álvarez M, Guzmán-Fulgencio M, Berenguer J, Micheloud D, Campos Y, López JC, Cosín J, Miralles P, Alvarez E, Resino S

    Abstract
    BACKGROUND: HIV infection, hepatitis C virus (HCV) liver disease, and mitochondrial DNA (mtDNA) polymorphisms are three possibly interrelated factors that might be associated with progression of liver disease. The aim of this study was to investigate whether mtDNA haplogroups had any influence on liver fibrosis progression in HIV/HCV coinfected patients.
    METHODS: We carried out a cross-sectional study in 231 patients who were genotyped via Sequenom's MassARRAY platform (San Diego, California, USA). Liver fibrosis was estimated based on the METAVIR score. In each patient, fibrosis progression rate (FPR) was calculated by dividing the fibrosis stage (0-4) by the estimated duration of HCV infection in years.
    RESULTS: The cluster or major haplogroup HV was significantly associated with reduced odds ratios (OR) for advanced fibrosis [OR 0.35, 95% confidence interval (CI) 0.16-0.77, P = 0.009], cirrhosis (OR 0.16, 95% CI 0.04-0.60, P = 0.007), or high FPR (OR 0.43, 95% CI 0.21-0.84, P = 0.015). Within the major haplogroup HV, haplogroup H was significantly associated with an absence of advanced fibrosis (OR 0.40, 95% CI 0.18-0.91, P = 0.029), cirrhosis (OR 0.14, 95% CI 0.03-0.67, P = 0.014), or high FPR (OR 0.47, 95% CI 0.23-0.95, P = 0.035). We also found a significant association with increased odds of cirrhosis (OR 5.25, 95% CI 1.76-15.64, P = 0.003) in the closely related major haplogroup U.
    CONCLUSION: The mtDNA haplogroups HV and H were associated with slower fibrosis progression, and the haplogroup U was associated with faster fibrosis progression in HIV/HCV coinfected patients. These data suggest that mtDNA haplogroup may play a significant role in liver fibrogenesis during HCV infection.

    PMID: 21673559 [PubMed - indexed for MEDLINE]

  • Epidemiologic trends of cancer diagnoses among HIV-infected children in Spain from 1997 to 2008. -

    Epidemiologic trends of cancer diagnoses among HIV-infected children in Spain from 1997 to 2008.

    Pediatr Infect Dis J. 2011 Sep;30(9):764-8

    Authors: Alvaro-Meca A, Micheloud D, Jensen J, Díaz A, García-Alvarez M, Resino S

    Abstract
    BACKGROUND: The introduction of highly active antiretroviral therapy (HAART) has influenced the incidence of cancer in people with human immunodeficiency virus (HIV) infection. The aim of this study was to evaluate changes in the pattern of cancer rates in HIV-infected children on HAART during over a decade of follow-up.
    PATIENTS AND METHODS: We carried out a case-control study. Data were obtained from the records of the minimum basic data set of hospitals in Spain from 1999 to 2008. The epidemiologic trends of cancer diagnoses were evaluated through 3 calendar periods: early-period HAART: 1997-1999, midperiod HAART: 2000-2002, and late-period HAART: 2003-2008).
    RESULTS: HIV-infected children had higher rates of cancer diagnosis than HIV-negative children (P < 0.001) for both acquired immunodeficiency disease syndrome (AIDS)-defining malignancies (ADM) and non-AIDS-defining malignancies (non-ADM). The highest rates of cancer diagnosis in HIV-positive children were for non-Hodgkin lymphoma, malignant neoplasm of bone and articular cartilage, and Hodgkin lymphoma. When we compared the 3 calendar periods, we found that the rate of ADM diagnoses decreased (from 9.1 to 3.6 to 1.0 cancers per 1000 HIV-children/yr; P < 0.05) and that the rate of non-ADM diagnoses increased (from 0.6 to 5.0 to 8.7 cancers per 1000 HIV-children/yr; P < 0.05). Moreover, the overall rate of cancer diagnoses (ADM plus non-ADM) did not change during the study period (9.7, 8.7, and 9.7 cancers per 1000 HIV-children/yr).
    CONCLUSIONS: HIV-infected children had a dramatic decrease in the rate of ADM diagnoses and an increase in the rate of non-ADM diagnoses. The overall cancer diagnosis rate has not decreased during the past decade and the incidence of cancer still remains high in HIV-infected children in Spain.

    PMID: 21494172 [PubMed - indexed for MEDLINE]

  • High plasma fractalkine (CX3CL1) levels are associated with severe liver disease in HIV/HCV co-infected patients with HCV genotype 1. -

    High plasma fractalkine (CX3CL1) levels are associated with severe liver disease in HIV/HCV co-infected patients with HCV genotype 1.

    Cytokine. 2011 Jun;54(3):244-8

    Authors: García-Álvarez M, Berenguer J, Guzmán-Fulgencio M, Micheloud D, Catalán P, Muñoz-Fernandez MÁ, Alvarez E, Resino S

    Abstract
    BACKGROUND: Inappropriate persistence of chemokines expression in hepatitis C virus (HCV) infection can drive tissue damage, intrahepatic inflammation, and liver cell injury. The aim of study was to study the association of plasma fractalkine (CX3CL1) levels with fibrosis stage and necroinflammatory activity grade of liver biopsies in human immunodeficiency virus (HIV)/HCV co-infected patients with HCV genotype 1.
    METHODS: We carried out a cross-sectional study on 125 patients. Grading and staging of liver biopsies were carried out by METAVIR score. Plasma CX3CL1 was measured using an immunoassay kit.
    RESULTS: Patients with advanced fibrosis had higher CX3CL1 levels than those with mild or no fibrosis (p=0.010); and patients with severe activity grade had higher CX3CL1 levels than those with low activity grade (p=0.040). Plasma CX3CL1 levels were significantly associated with increased odds of significant fibrosis (odds ratio (OR): 3.47 (95% of confidence interval (95%CI): 1.04; 11.58)), advanced fibrosis (OR: 6.78 (95%CI: 1.70; 26.93)), and moderate necroinflammatory activity grade (OR: 4.09 (95%CI: 1.21; 13.87)). When we analyzed fibrosis stages and activity grades of METAVIR score together, we found a positive significant association of CX3CL1 levels with moderate activity grade/significant fibrosis (OR: 5.49 (95%CI: 1.46; 20.58)) and moderate activity grade/advanced fibrosis (OR: 8.99 (95%CI: 2.06; 39.23)).
    CONCLUSION: Plasma CX3CL1 levels were independently associated with several characteristics of severe liver disease in HIV/HCV coinfected patients with HCV-genotype 1, suggesting a role of CX3CL1 in the pathogenesis of HCV infection.

    PMID: 21463954 [PubMed - indexed for MEDLINE]

  • Soluble Fas and Fas ligand in HIV/HCV coinfected patients and impact of HCV therapy. -

    Soluble Fas and Fas ligand in HIV/HCV coinfected patients and impact of HCV therapy.

    Eur J Clin Microbiol Infect Dis. 2011 Oct;30(10):1213-21

    Authors: Guzmán-Fulgencio M, Berenguer J, García-Álvarez M, Micheloud D, C López J, Cosín J, Fernández de Castro I, Catalán P, Miralles P, Resino S

    Abstract
    The aim of this study was to evaluate the influence of clinical and epidemiological characteristics of 183 HIV/HCV coinfected patients and HCV clearance after antiviral treatment on serum sFas and sFasL levels. Thirty out of 183 patients underwent HCV antiviral therapy with IFN-α + RBV for a duration of 48 weeks. HCV genotype 1 and homeostasis model assessment for insulin resistance (HOMA-IR) had a significant positive relationship, and CD4+/μL had a significant negative relationship with sFas (R-square = 0.582; p < 0.001) and sFasL (R-square = 0.216; p < 0.001) in multivariate linear regression analysis. HCV genotype 1 was the only significant variable associated with the sFas/sFasL ratio (R-square = 0.201; p < 0.001). sFas and sFasL levels had positive significant correlations with serum sICAM-1, sVCAM-1, and HOMA levels (p < 0.05). Among patients on IFN-α + RBV therapy, 15 patients showed a sustained virologic response (SVR), while 15 patients were non-responders (NR). Patients with SVR had significant decreases in sFas (p = 0.008) and sFas/sFasL ratio (p = 0.002), while non-responders had a significant increase in sFasL values (p = 0.013). In conclusion, HCV genotype 1, high HOMA, and low CD4+/μL were associated with high serum levels of sFas and sFasL, which indicate higher levels of inflammation and, possibly, increased cardiovascular risk. Moreover, response to HCV antiviral therapy is known to reduce inflammation.

    PMID: 21442358 [PubMed - in process]

  • Sustained virological response to interferon-α plus ribavirin decreases inflammation and endothelial dysfunction markers in HIV/HCV co-infected patients. -

    Sustained virological response to interferon-α plus ribavirin decreases inflammation and endothelial dysfunction markers in HIV/HCV co-infected patients.

    J Antimicrob Chemother. 2011 Mar;66(3):645-9

    Authors: Guzmán-Fulgencio M, Berenguer J, de Castro IF, Micheloud D, López JC, Cosín J, Miralles P, Lorente R, Aldamiz-Echevarría T, Muñoz-Fernández MÁ, Resino S

    Abstract
    OBJECTIVES: Hepatitis C virus (HCV) antiviral therapy might lead to decreased chronic immune activation and endothelial dysfunction associated with cardiovascular risk. The aim was to evaluate the effect of HCV eradication on serum markers of inflammation and endothelial dysfunction markers in HIV/HCV co-infected patients.
    METHODS: We carried out a retrospective study of 69 HIV/HCV co-infected patients on interferon (IFN)-α plus ribavirin. In addition, 47 HIV-infected subjects were selected as a control group. A sustained virological response (SVR) was defined as an undetectable HCV viral load up to 24 weeks after the end of treatment. Tumour necrosis factor (TNF) receptor-1 (TNF-R1), soluble E-selectin (sE-selectin), soluble P-selectin (sP-selectin), soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured using a multiplex immunoassay kit.
    RESULTS: HIV/HCV co-infected patients had higher values of soluble TNF-R1 (sTNF-R1), sE-selectin and sICAM-1 than HIV mono-infected patients (P < 0.05). SVR patients had a decrease in sTNF-R1, sP-selectin, sE-selectin and sICAM-1 during anti-HCV treatment (P < 0.05) and, at the end of treatment, SVR patients had lower values of sTNF-R1, sE-selectin and sVCAM-1 than non-responder patients (P < 0.05), although the values of sTNF-R1, sP-selectin, sE-selectin and sICAM-1 remained higher than in HIV mono-infected patients (P < 0.05). Moreover, we found a significant positive relationship between an increase in sTNF-R1 and increases in sP-selectin, sE-selectin and sICAM-1 during anti-HCV therapy.
    CONCLUSIONS: Chronic hepatitis C infection induces alterations of markers of inflammation and endothelial dysfunction. Eradication of HCV, following IFN-α and ribavirin therapy, reduces immune activation as well as markers of inflammation and endothelial dysfunction.

    PMID: 21393232 [PubMed - indexed for MEDLINE]

  • Sustained virologic response decreases serum markers of angiogenesis, inflammation, and fibrosis in HIV/HCV-coinfected patients on hepatitis C virus therapy. -

    Sustained virologic response decreases serum markers of angiogenesis, inflammation, and fibrosis in HIV/HCV-coinfected patients on hepatitis C virus therapy.

    AIDS Patient Care STDS. 2011 Mar;25(3):131-3

    Authors: García-Álvarez M, Berenguer J, Micheloud D, Guzmán-Fulgencio M, Catalán P, López JC, Cosín J, Miralles P, Carrero-Gras A, Resino S

    PMID: 21294694 [PubMed - indexed for MEDLINE]

  • Cardiovascular risk markers are increased in HIV-infected children with lipodystrophy syndrome. -

    Cardiovascular risk markers are increased in HIV-infected children with lipodystrophy syndrome.

    J Infect. 2011 Mar;62(3):240-3

    Authors: Guzmán-Fulgencio M, Micheloud D, Lorente R, Bellón JM, Gomez MI, Gurbindo MD, León JA, Muñoz-Fernández MÁ, Resino S

    PMID: 21256862 [PubMed - indexed for MEDLINE]

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