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 entorno al laboratorio de EMEI cuyo responsable es el Dr. Salvador Resino García |
EMEI- Últimos artículos científicos publicados:
- Serum levels of adipokines in HIV/HCV co-infected patients and their association with insulin resistance and liver disease severity. -
Serum levels of adipokines in HIV/HCV co-infected patients and their association with insulin resistance and liver disease severity.
J Infect. 2010 Jul 2;
Authors: Fernández de Castro I, Berenguer J, Micheloud D, Guzmán-Fulgencio M, CosÃn J, Alvarez E, López JC, Miralles P, GarcÃa-Ãlvarez M, Resino S
PMID: 20728222 [PubMed - as supplied by publisher]
- Can serum hyaluronic acid replace simple non-invasive indexes to predict liver fibrosis in HIV/Hepatitis C coinfected patients? -
Related Articles Can serum hyaluronic acid replace simple non-invasive indexes to predict liver fibrosis in HIV/Hepatitis C coinfected patients?
BMC Infect Dis. 2010 Aug 19;10(1):244
Authors: Resino S, Bellon JM, Asensio C, Micheloud D, Miralles P, Vargas A, Catalan P, Lopez JC, Alvarez E, Cosin J, Lorente R, Munoz-Fernandez MA, Berenguer J
ABSTRACT: BACKGROUND: Hyaluronic acid (HA) serum levels correlate with the histological stages of liver fibrosis in hepatitis C virus (HCV) monoinfected patients, and HA alone has shown very good diagnostic accuracy as a non-invasive assessment of fibrosis and cirrhosis. The aim of this study was to evaluate serum HA levels as a simple non-invasive diagnostic test to predict hepatic fibrosis in HIV/HCV-coinfected patients and to compare its diagnostic performance with other previously published simple non-invasive indexes consisting of routine parameters (HGM-1, HGM-2, Forns, APRI, and FIB-4). METHODS: We carried out a cross-sectional study on 201 patients who all underwent liver biopsies and had not previously received interferon therapy. Liver fibrosis was determined via METAVIR score. The diagnostic accuracy of HA was assessed by area under the receiver operating characteristic curves (AUROCs). RESULTS: The distribution of liver fibrosis in our cohort was 58.2% with significant fibrosis (F[greater than or equal to]2), 31.8% with advanced fibrosis (F[greater than or equal to]3), and 11.4% with cirrhosis (F4). Values for the AUROC of HA levels corresponding to significant fibrosis (F[greater than or equal to]2), advanced fibrosis (F[greater than or equal to]3) and cirrhosis (F4) were 0.676, 0.772, and 0.863, respectively. The AUROC values for HA were similar to those for HGM-1, HGM-2, FIB-4, APRI, and Forns indexes. The best diagnostic accuracy of HA was found for the diagnosis of cirrhosis (F4): the value of HA at the low cut-off (1182 ng/mL) excluded cirrhosis (F4) with a negative predictive value of 99% and at the high cut-off (2400 ng/mL) confirmed cirrhosis (F4) with a positive predictive value of 55%. By utilizing these low and high cut-off points for cirrhosis, biopsies could have theoretically been avoided in 52.2% (111/201) of the patients. CONCLUSIONS: The diagnostic accuracy of serum HA levels increases gradually with the hepatic fibrosis stage. However, HA is better than other simple non-invasive indexes using parameters easily available in routine clinical practice only for the diagnosing of cirrhosis.
PMID: 20723207 [PubMed - as supplied by publisher]
- Hepatitis C virus infection is associated with endothelial dysfunction in HIV/hepatitis C virus coinfected patients. -
Related Articles Hepatitis C virus infection is associated with endothelial dysfunction in HIV/hepatitis C virus coinfected patients.
AIDS. 2010 Aug 24;24(13):2059-67
Authors: de Castro IF, Micheloud D, Berenguer J, Guzmán-Fulgencio M, Catalán P, Miralles P, Alvarez E, López JC, CosÃn J, Lorente R, Muñoz-Fernández MA, Resino S
OBJECTIVE: To quantify serum levels of intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) in HIV/HCV coinfected patients to examine their association with several clinical and epidemiological characteristics and the therapeutic responsiveness to interferon (IFN)-alpha and ribavirin therapy (IFN-alpha + RBV). DESIGN: Retrospective study. METHODS: We carried out a cross-sectional study with 183 IFN-alpha-naive patients on HAART, and 24 healthy controls. We also analyzed 30 out of 183 patients on IFN-alpha + RBV for the duration of 48 weeks. RESULTS: HIV/HCV coinfected patients had higher levels of sICAM-1 and sVCAM-1 than the healthy control group (P < 0.05). Patients with HCV-genotype 1, advanced fibrosis (F>or=3) or moderate to severe activity grade (A>or=2) had the highest values of sICAM-1 and sVCAM-1. When we carried out a multivariate analysis, we found a significant positive relationship between both HCV-genotype 1 and advanced fibrosis (F>or=3) with sICAM-1 (R = 0.549; P < 0.001); and a significant positive relationship between HCV-genotype 1 and advanced fibrosis (F>or=3) with sVCAM-1 (R = 0.624; P < 0.001). We also found a positive relationship of sICAM-1 or sVCAM-1 levels with transaminases and alkaline phosphatase circulation levels (P < 0.05). Nonresponder patients had higher sICAM-1 and sVCAM-1 serum levels, and patients with sustained virologic response had significantly lower levels of sICAM-1 (P = 0.001) and sVCAM-1 (P = 0.019). CONCLUSION: HIV and HCV coinfection induces alterations in sICAM-1 and sVCAM-1 serum levels, which were higher in patients with HCV-genotype 1 and advanced stage of HCV infection. However, response to IFN-alpha + RBV may reduce these cardiovascular risk markers.
PMID: 20616694 [PubMed - in process]
- Insulin Resistance Impairs Response to Interferon Plus Ribavirin in Patients Coinfected With HIV and Hepatitis C Virus. -
Related Articles Insulin Resistance Impairs Response to Interferon Plus Ribavirin in Patients Coinfected With HIV and Hepatitis C Virus.
J Acquir Immune Defic Syndr. 2010 Jun 23;
Authors: Ryan P, Resino S, Miralles P, CosÃn J, López JC, Moreno S, Catalán P, RamÃrez M, Gutiérrez I, Berenguer J
BACKGROUND/AIMS:: Controversy exists about whether insulin resistance (IR) affects response to treatment of hepatitis C. We evaluated the effect of IR on sustained virologic response (SVR) in HIV/hepatitis C virus (HCV)-coinfected patients treated with interferon plus ribavirin. METHODS:: We reviewed the clinical records of HIV/HCV-coinfected patients who received interferon plus ribavirin at our institution between July 2000 and March 2007. IR was defined as a homeostasis model assessment >/=3.8. SVR was defined as an undetectable HCV RNA at 24 weeks after the end of treatment. Efficacy was evaluated using an on-treatment (OT) analysis. Multivariate logistic regression analysis was used to evaluate factors associated with SVR. RESULTS:: During the study period, 218 patients were treated with interferon plus ribavirin; IR at baseline was available for 162 patients, and 134 were included in the OT analysis; HCV genotype (G) 1/4, 67%; F3-F4 fibrosis, 36%; IR 31%. SVR was achieved in 67 patients (50%) (79% in G 2/3 vs. 38% in G 1/4). IR was associated with a lower SVR [odds ratio (OR), 0.33; 95% confidence interval (CI): 0.15-0.72; P = 0.006). The independent variables related to SVR were genotype 2/3 (OR, 6.7; 95% CI: 2.71-16.98; P < 0.001), absence of IR at baseline (OR, 3.3; 95% CI: 1.36-8.26; P = 0.008), and nadir CD4 T-cell count (OR, 1.002; 95% CI: 1.00-1.00; P = 0.047). CONCLUSIONS:: Our data suggest that IR is an important determinant of SVR in HIV/HCV-coinfected patients treated with interferon plus ribavirin. Strategies to modify IR should be explored to enhance SVR during anti-HCV therapy.
PMID: 20577091 [PubMed - as supplied by publisher]
- Plasma interferon-gamma-inducible protein-10 can predict virologic response to hepatitis C virus therapy in HIV/HCV-coinfected patients with HCV genotype 1. -
Related Articles Plasma interferon-gamma-inducible protein-10 can predict virologic response to hepatitis C virus therapy in HIV/HCV-coinfected patients with HCV genotype 1.
J Acquir Immune Defic Syndr. 2010 Jun;54(2):219-20
Authors: Vargas A, Berenguer J, Ryan P, Catalán P, López JC, CosÃn J, Miralles P, Resino S
PMID: 20505475 [PubMed - indexed for MEDLINE]
- Adipokine profiles and lipodystrophy in HIV-infected children during the first 4 years on highly active antiretroviral therapy. -
Related Articles Adipokine profiles and lipodystrophy in HIV-infected children during the first 4 years on highly active antiretroviral therapy.
HIV Med. 2010 May 17;
Authors: Resino S, Micheloud D, Lorente R, Bellón JM, Navarro ML, Muñoz-Fernández MA
Objective The aim of the study was to evaluate the evolution of plasma adipokines and lipodystrophy in protease inhibitor-naïve vertically HIV-infected children on highly active antiretroviral therapy (HAART). Patients and methods We carried out a multicentre retrospective study of 27 children during 48 months on HAART. Every 3 months, CD4+ T-cells, CD8+ T-cells, viral load (VL), cholesterol, triglycerides, lipoproteins and adipokines were measured. Diagnoses of lipodystrophy were based on clinical examinations. Results We found hypercholesterolaemia (>200 mg/dL) in 9.5, 30.4, 21.7, 14.3 and 13.3% of the subjects at months 0, 12, 24, 36 and 48, respectively, and hypertriglyceridaemia (>170 mg/dL) in 14.3, 8.3, 13, 4.5 and 0% at the same time-points. During follow-up, and especially at the end of the study, we found an increase in plasma resistin levels and significant increases in total plasminogen activator inhibitor type 1, adiponectin, and leptin levels (P<0.05). We also observed slight increases in the leptin/adiponectin ratio, homeostatic model assessment, and C-peptide values during the first months of treatment followed by a moderate decrease or stabilization after 24 months on HAART. At the end of the study, 12 of the 27 children (44.4%) had lipodystrophy, 10 (37%) had lipoatrophy, and 11 (40.7%) had lipohypertrophy; and only three of the 27 children (11.1%) were diagnosed with lipoatrophy and lipohypertrophy with scores >/=2. Conclusions HIV-infected children showed an increase in serum adipokine levels, but this was not associated with the emergence of lipodystrophy during 48 months on HAART.
PMID: 20497248 [PubMed - as supplied by publisher]
- Increased Th1, Th17 and pro-fibrotic responses in hepatitis C-infected patients are down-regulated after 12 weeks of treatment with pegylated interferon plus ribavirin. -
Related Articles Increased Th1, Th17 and pro-fibrotic responses in hepatitis C-infected patients are down-regulated after 12 weeks of treatment with pegylated interferon plus ribavirin.
Eur Cytokine Netw. 2010 Jun 1;21(2):84-91
Authors: Jimenez-Sousa MA, Almansa R, de la Fuente C, Caro-Paton A, Ruiz L, Sanchez-AntolÃn G, Gonzalez JM, Aller R, Alcaide N, Largo P, Resino S, Ortiz de Lejarazu R, Bermejo-Martin JF
Hepatitis C virus causes significant morbidity and mortality worldwide. The infection induces up-regulation of cytokine and chemokines commonly linked to the development of cellular and pro-inflammatory antiviral responses. The current standard in hepatitis C treatment consists of combination regimens of pegylated interferon-alpha plus ribavirin. The impact of combined treatment in the host immune response is still poorly understood. In the present study, we profiled 27 cytokines, chemokines and growth factors involved in the innate and adaptive responses to the virus in the serum of 27 hepatitis C virus-infected patients, before and after 12 weeks of combined treatment, and compared them to 10 healthy controls. Hepatitis C virus infection induced not only the secretion of chemokines and cytokines participating in Th1 responses (MIP-1alpha, IP-10, TNF-alpha, IL-12p70, IL-2), but also cytokines involved in the development of Th17 responses (IL-6, IL-8, IL-9 and IL-17) and two pro-fibrotic factors (FGF-b, VEGF). The most important increases included MIP-1alpha (4.7-fold increase compared to the control group), TNF-alpha (3.0-fold), FGF-b (3.4-fold), VEGF (3.5-fold), IP-10 (3.6-fold), IL-17 (107.0-fold), IL-9 (7.5-fold), IL-12p70 (7.0-fold), IL-2 (5.6-fold) and IL-7 (5.6-fold). Combined treatment with pegylated interferon-alpha plus ribavirin down-modulated the secretion of key Th1 and Th17 pro-inflammatory mediators, and pro-fibrotic growth factors as early as 12 weeks after treatment initiation. MIP-1alpha, FGF-b, IL-17 decreased in a more dramatic manner in the group of responder patients than in the group of non-responders (fold-change in cEVR; fold-change in NcEVR): MIP-1alpha (4.72;1.71), FGF-b (4.54;1.21), IL-17 (107.1;1.8). Correlation studies demonstrated that the decreases in the levels of these mediators were significantly associated with each other, pointing to a coordinated effect of the treatment on their secretion (r coefficient; p value): [ FGF-b versus IL-17 (0.90; 0.00), IL-17 versus VEGF (0.88; 0.00), MIP-1alpha versus IL-17 (0.84;0.00), FGF-b versus MIP-1alpha (0.96;0.00), FGF-b versus IL-12p70 (0.90; 0.00), VEGF versus IL-12p70 (0.89; 0.00)]. Th17 immunity has been previously associated with autoimmune diseases and asthma, but this is the first work reporting a role for this profile in viral hepatitis. These results provide an opportunity to evaluate the impact of the treatment with Peg-INF-alpha and RBV on the prevention of immune-driven tissue damage in infected patients.
PMID: 20483710 [PubMed - in process]
- Hepatitis C virus (HCV) treatment uptake and changes in the prevalence of HCV genotypes in HIV/HCV-coinfected patients. -
Related Articles Hepatitis C virus (HCV) treatment uptake and changes in the prevalence of HCV genotypes in HIV/HCV-coinfected patients.
J Viral Hepat. 2010 Apr 27;
Authors: Medrano J, Resino S, Vispo E, Madejón A, Labarga P, Tuma P, MartÃn-Carbonero L, Barreiro P, Rodriguez-Novoa S, Jiménez-Nacher I, Soriano V
Summary. The efficacy of current hepatitis C therapy in HIV/HCV-coinfected patients is largely dependent on HCV genotype. The annual prevalence of HCV genotypes/subtypes and their influence on HCV clearance with antiviral treatment were examined in a dynamic cohort of HIV/HCV-coinfected patients followed up in Madrid since 2000. Patients entered the cohort at first visit and left the cohort when HCV clearance was achieved with HCV therapy or when follow-up was interrupted for any reason, including death. A total of 672 HIV/HCV-coinfected patients constituted the cohort. The mean follow-up time was 5.5 years, corresponding to 4108 patient-years. Mean age at entry was 37 years, and 73% were men and 86% were intravenous drug users. Overall distribution of HCV genotypes was as follows: 57.1% HCV-1 (1a: 29.2%, 1b: 20.4%, unknown: 7.6%), 1.3% HCV-2, 25.4% HCV-3 and 15.9% HCV-4. A total of 274 (40.8%) patients were treated with peginterferon-ribavirin, of whom 116 (42.3%) achieved HCV clearance following 1-3 courses of therapy. The proportion of HCV-1/4 rose from 71.7% in 2000 to 76.8% in 2008, whereas the proportion of HCV-2/3 fell from 28.1% in 2000 to 23.2% in 2008. The yearly prevalence increased for HCV-1 (R(2): 0.92, b: 0.59, P < 0.001) and HCV-4 (R(2): 0.77, b: 0.33, P < 0.005) and conversely diminished for HCV-3 (R(2): 0.94, b: -0.82, P < 0.001). In summary, the prevalence of HCV-1 and HCV-4 has increased over the last decade in HIV/HCV-coinfected patients, whereas conversely it has declined for HCV-3, in association with the wider use of HCV therapy (41%) in this population.
PMID: 20456635 [PubMed - as supplied by publisher]
- Association between lipodystrophy and leptin in human immunodeficiency virus-1-infected children receiving lopinavir/ritonavir-based therapy. -
Related Articles Association between lipodystrophy and leptin in human immunodeficiency virus-1-infected children receiving lopinavir/ritonavir-based therapy.
Pediatr Infect Dis J. 2010 Aug;29(8):774-7
Authors: Resino S, Palladino C, Lorente R, Micheloud D, Bellón JM, Larru B, Gutiérrez MD, de José MI, Polo R, Muñoz-Fernández MA,
Highly active antiretroviral therapy might lead to the development of dyslipidemia and lipodystrophy (LD) syndrome. We carried out a multicenter prospective study of 22 human immunodeficiency virus (HIV)-1-infected children treated during 48 months with lopinavir/ritonavir-based highly active antiretroviral therapy to evaluate the trend of serum lipids and adipokines. Increase in plasma leptin levels and leptin/adiponectin ratio was associated with LD. These adipokines may be surrogate markers of LD.
PMID: 20375850 [PubMed - in process]
- First evidence of a pro-inflammatory response to severe infection with influenza virus H1N1. -
Related Articles First evidence of a pro-inflammatory response to severe infection with influenza virus H1N1.
Crit Care. 2010;14(1):115
Authors: de Castro IF, Guzmán-Fulgencio M, GarcÃa-Alvarez M, Resino S
The great majority of infections caused by the pandemic variant of the influenza virus (nvH1N1) are self-limited, but a small percentage of patients develop severe symptoms requiring hospitalization. Bermejo-Martin and colleagues have presented a pilot study describing the differences in the early immune response for patients both mildly and severely infected with nvH1N1. Patients who develop severe symptoms after nvH1N1 infection showed Th1 and Th17 'hypercytokinemia', compared to mildly infected patients and healthy controls. The mediators involved with the Th1 and Th17 profiles are known to be involved in antiviral, pro-inflammatory and autoimmune responses. This is the first work reporting the association of a pro-inflamatory immune response with a severe pandemic infection, although it is likely that more studies are needed to understand the detrimental or beneficial roles these cytokines play in the evolution of mild and severe nvH1N1 infection.
PMID: 20236480 [PubMed - in process]
