Mercedes Márquez

Health-related quality of life in patients with primary Sjögren's syndrome: relationship with serum levels of proinflammatory cytokines

Objective: A cross-sectional study of 30 patients with primary Sjögrens syndrome (pSS) was performed to analyse the health-related quality of life and its relationship with serum levels of macrophage- and lymphocyte-derived cytokines. Patients and methods: Health-related quality of life was evaluated using the 36-item Short Form Health Survey (SF-36). Serum levels of interleukin (IL)-1β, IL-6, IL-10, tumour necrosis factor (TNF)-α, and gamma-interferon (γ-INF) were analysed by a sandwich immunoassay-based protein array system. Results: Each of the eight scales of the SF-36 evaluating quality of life, as well as the physical composite score (PCS) and the mental composite score (MCS), showed a decrease in pSS patients. Similarly, patients with pSS showed significantly increased concentrations of each of the five cytokines analysed, when compared with the healthy control group (n = 20). In pSS patients, a significant negative correlation was detected between serum levels of IL-6 and the PCS of the SF-36. Those patients with concentrations of IL-6 higher than those of the healthy controls showed a significantly lower score in the dimensions of bodily pain and physical functioning, and in the PCS. Conclusions: Patients with pSS showed increased levels of several macrophage- and lymphocyte-derived cytokines, indicating the existence of an immune activation state. Serum levels of one of these cytokines, IL-6, were correlated with poor quality of life in these individuals.

Prevalence of oxygen desaturation and use of oxygen at home in adults at sea level and at moderate altitude

The aim of this study was to determine the prevalence of oxygen desaturation in adults aged ≥40 yrs as altitude above sea level increases. A population-based, cross-sectional study with a multistage cluster sampling of 1,063 subjects from metropolitan Mexico City (Mexico; 2,240 m above sea level), 1,357 from Caracas (Venezuela; 950 m) and 943 from Montevideo (Uruguay; 35 m). The mean of six measurements of arterial oxygen saturation (SP,O2) was estimated using a pulse oximeter. Mean SP,O2 decreased with altitude. No subject from Montevideo had a mean SP,O2 ≤88%. Prevalence of subjects with SP,O2 ≤88%, a common criterion used for oxygen prescription, was 1.0% in Caracas and 6.0% in Mexico City. Additional predicting factors for hypoxaemia in multiple regression models were age, body mass index and a low forced expiratory volume in one second as a percentage of the predicted value. In Mexico City and Caracas, <10% of the hypoxaemic subjects reported use of domiciliary oxygen, whereas at least half of the subjects reporting use of oxygen at home had a resting SP,O2 >88%. In conclusion, the prevalence of hypoxaemia was closely related to altitude. Priorities for oxygen prescription must be defined in moderate altitudes because it is unfeasible to provide it to all subjects fulfilling the criteria commonly used.

Haemodynamic derangement in human immunodeficiency virus-infected patients with hepatitis C virus-related cirrhosis: the role of bacterial translocation.

Background and aims: Analysis of the influence of the effects of increased intestinal permeability on haemodynamic alterations in human immunodeficiency virus (HIV)‐infected patients with decompensated hepatitis C virus (HCV)‐related liver disease.

Influence of Genetic Polymorphisms of Tumor Necrosis Factor Alpha and Interleukin 10 Genes on the Risk of Liver Cirrhosis in HIV-HCV Coinfected Patients

Objective Analysis of the contribution of genetic (single nucleotide polymorphisms (SNP) at position -238 and -308 of the tumor necrosis factor alpha (TNF-α) and -592 of the interleukin-10 (IL-10) promotor genes) and of classical factors (age, alcohol, immunodepression, antirretroviral therapy) on the risk of liver cirrhosis in human immunodeficiency (HIV)-hepatitis C (HCV) virus coinfected patients. Patients and Methods Ninety one HIV-HCV coinfected patients (50 of them with chronic hepatitis and 41 with liver cirrhosis) and 55 healthy controls were studied. Demographic, risk factors for the HIV-HCV infection, HIV-related (CD4+ T cell count, antiretroviral therapy, HIV viral load) and HCV-related (serum ALT concentration, HCV viral load, HCV genotype) characteristics and polymorphisms at position -238 and -308 of the tumor necrosis factor alfa (TNF- α) and -592 of the interleukin-10 (IL-10) promotor genes were studied. Results Evolution time of the infection was 21 years in both patients’ groups (chronic hepatitis and liver cirrhosis). The group of patients with liver cirrhosis shows a lower CD4+ T cell count at the inclusion in the study (but not at diagnosis of HIV infection), a higher percentage of individuals with previous alcohol abuse, and a higher proportion of patients with the genotype GG at position -238 of the TNF-α promotor gene; polymorphism at -592 of the IL-10 promotor gene approaches to statistical significance. Serum concentrations of profibrogenic transforming growth factor beta1 were significantly higher in healthy controls with genotype GG at -238 TNF-α promotor gene. The linear regression analysis demonstrates that the genotype GG at -238 TNF-α promotor gene was the independent factor associated to liver cirrhosis. Conclusion It is stressed the importance of immunogenetic factors (TNF-α polymorphism at -238 position), above other factors previously accepted (age, gender, alcohol, immunodepression), on the evolution to liver cirrhosis among HIV-infected patients with established chronic HCV infections.

Immune activation response in chronic HIV-infected patients: influence of Hepatitis C virus coinfection.

Objectives We have analyzed the parameters (bacterial translocation, immune activation and regulation, presence of HCV coinfection) which could be implicated in an inappropriate immune response from individuals with chronic HIV infection. The influence of them on the evolution of CD4+ T cell count has been investigated. Patients and methods Seventy HIV-infected patients [monoinfected by HIV (n = 20), HCV-coinfected (with (n = 25) and without (n = 25) liver cirrhosis)] and 25 healthy controls were included. Median duration of HIV infection was 20 years. HIV- and HCV-related parameters, as well as markers relative to bacterial translocation, monocyte and lymphocyte activation and regulation were considered as independent variables. Dependent variables were the increase of CD4+ T cell count during the follow-up (12 months). Results Increased values of bacterial translocation, measured by lipopolysaccharide-binding protein, monocyte and lymphocyte activation markers and T regulatory lymphocytes were detected in HIV-monoinfected and HIV/HCV coinfected patients. Serum sCD14 and IL-6 were increased in HIV/HCV-coinfected patients with liver cirrhosis in comparison with those with chronic hepatitis or HIV-monoinfected individuals. Time with undetectable HIV load was not related with these parameters. The presence of cirrhosis was negatively associated with a CD4+ T cell count increase. Conclusion In patients with a chronic HIV infection, a persistent increase of lipopolysaccharide-binding protein and monocyte and lymphocyte modifications are present. HCV-related cirrhosis is associated with more elevated serum concentrations of monocyte-derived markers. Cirrhosis influences the continued immune reconstitution of these patients.

Gut epithelial barrier dysfunction in human immunodeficiency virus-hepatitis C virus coinfected patients: Influence on innate and acquired immunity

Even in cases where viral replication has been controlled by antiretroviral therapy for long periods of time, human immunodeficiency virus (HIV)-infected patients have several non-acquired immunodeficiency syndrome (AIDS) related co-morbidities, including liver disease, cardiovascular disease and neurocognitive decline, which have a clear impact on survival. It has been considered that persistent innate and acquired immune activation contributes to the pathogenesis of these non-AIDS related diseases. Immune activation has been related with several conditions, remarkably with the bacterial translocation related with the intestinal barrier damage by the HIV or by hepatitis C virus (HCV)-related liver cirrhosis. Consequently, increased morbidity and mortality must be expected in HIV-HCV coinfected patients. Disrupted gut barrier lead to an increased passage of microbial products and to an activation of the mucosal immune system and secretion of inflammatory mediators, which in turn might increase barrier dysfunction. In the present review, the intestinal barrier structure, measures of intestinal barrier dysfunction and the modifications of them in HIV monoinfection and in HIV-HCV coinfection will be considered. Both pathogenesis and the consequences for the progression of liver disease secondary to gut microbial fragment leakage and immune activation will be assessed.

THIS ARTICLE HAS BEEN RETRACTED: Haemodynamic derangement in human immunodeficiency virus-infected patients with hepatitis C virus-related cirrhosis: the role of bacterial translocation

Background and aims: Analysis of the influence of the effects of increased intestinal permeability on haemodynamic alterations in human immunodeficiency virus (HIV)‐infected patients with decompensated hepatitis C virus (HCV)‐related liver disease.

La valoración de RNA del virus de la hepatitis C realizada a las 12 semanas de finalizar el tratamiento predice la respuesta virológica sostenida en enfermos con coinfección por VIH y VHC

OBJECTIVE The aim of this study was to assess whether measurement of hepatitis C virus RNA (HCV-RNA) at 12 weeks post-treatment could predict sustained virological response (SVR) to antiviral therapy for chronic hepatitis C (pegylated interferon alfa-2a and ribavirin) in HIV-co-infected patients. PATIENTS AND METHODS HIV-HCV co-infected patients were included if they completed a full course of anti-HCV therapy, achieved an end-of-treatment response and complied with the week +12 and +24 post-treatment follow-up schedule for serum HCV-RNA determination (Real-time HCV (Abbott, Wiesbaden, Germany) (lower limit of detection, 12 IU/ml). RESULTS Forty out of 66 patients (61%) showed an end-of-treatment response. They were assessed in a follow-up visit at +12 and at +24 weeks post-treatment. Serum HCV-RNA was undetectable in 28 of them at +12 weeks, and 100% of these remained undetectable at 24 weeks post-treatment (the gold standard of (SVR). The positive predictive value was 100% (95% confidence interval, 98.21-100%). CONCLUSION Post-treatment follow-up to identify virological relapse could be shortened to 12 weeks, providing a new definition of sustained virological response.

THIS ARTICLE HAS BEEN RETRACTED: Haemodynamic derangement in human immunodeficiency virus-infected patients with hepatitis C virus-related cirrhosis: the role of bacterial translocation: Haemodynamic alterations in HIV/HCV cirrhotic patients

Background and aims: Analysis of the influence of the effects of increased intestinal permeability on haemodynamic alterations in human immunodeficiency virus (HIV)‐infected patients with decompensated hepatitis C virus (HCV)‐related liver disease.

OP25 Bacterial translocation and regulatory T lymphocytes in patients with liver cirrhosis

Introduction Increased prevalence of bacterial infectious diseases has been observed in cirrhotic patients, classically attributed to immunosuppression-associated liver cirrhosis. Conversely, advanced states of liver cirrhosis predispose to increased antigenic load. A possible role has been ascribed to the translocation of bacteria and endotoxins (lypopolysaccharide, LPS) from the gut. LPS increases the plasma levels of LPS-binding protein (LBP), the principal plasma protein responsible for transporting LPS to immune effector cells. High serum LBP has been proposed to identify a subset of cirrhotic patients with ascitis characterised by an activation of the immune cells to producer proinflammatory cytokines. Moreover, raised levels of circulating LBP or proinflammatory cytokines have been implicated in the endothelial activation and haemodynamic derangement observed in cirrhosis. A chronic antigenic stimulus will induce a monocyte and lymphocyte activation. Aim Intestinal permeability and bacterial translocation and their influence on T lymphocytes activation and differentiation in T reg were analysed in patients with compensated and decompensated liver cirrhosis. In particular, the regulation of T cell activation, mediated by co-stimulatory molecules, the expression of activation markers and the proportion of T CD4+ regulatory cells, as a function of bacterial translocation, were studied. Method 40 patients with liver cirrhosis, 20 of them without previous decompensation (CC) and 20 with ascetic decompensation (DC), and 20 healthy controls (HC) were studied. Bacterial translocation was analysed by serum concentrations of lypopolysacharide-binding protein (LBP). Membrane expression of co-stimulatory molecules (CD28), activation markers (CD25 and CD122) and proportion of T regulatory cells (defined as those CD4+CD25highintracellular FoxP3+) were studied by flow cytometry with specific antibodies. Values of the variables were expressed as median (interquartile range). Comparisons between variables were made by the Mann–Whitney U test. Associations between variables were analysed by the Pearsons correlation coefficient. Results Serum concentrations of LBP were significantly elevated in patients with compensated (7.7 (5.7–9.1 microg/ml) and decompensated (28.2 (10.7–40.6)) cirrhosis when compared with healthy controls (3.4 (2.7–4.2)) (p<0.001). Significantly higher concentrations of LBP were detected in those patients with higher portal hypertension. Those patients with decompensated cirrhosis shows an activation state characterised by increased percentages of CD25+ and CD122+ expression on CD4+ T cells. A decrease of CD28 expression was detected in T CD4+ lymphocytes from patients with decompensated cirrhosis (DC, 94% (89–98%); CC, 97% (92–98%); HC, 98 (96–99), DC vs HC: p=0.010). Moreover, T reg lymphocytes, expressed as a proportion of global T CD4+ cells, were significantly increased in patients with compensated and decompensated cirrhosis (DC, 14.7% (13.3–16.1%); CC, 10.3 (10.1–11.2); HC, 8.4 (7.2–8.7), p<0.001 in each case). A significant and positive correlation was detected between serum LBP concentration and percentage of CD4+ T reg (r=0.787, p<0.001). Conclusion Patients with liver cirrhosis, fundamentally those with previous decompensation, shows increased intestinal permeability and chronic systemic antigenic stimuli. As a response to those, T lymphocyte activation is detected. Probably as a mean to decrease the continuous antigenic stimuli, a diminution of co-stimulation and an expansion of suppressor populations are observed in them.