No abstract

During chronic inflammatory disorders, a persistent natural killer (NK) cell derangement is observed. While increased cell turnover is expected, little is known about whether and how NK-cell homeostatic balance is maintained. Here, flow cytometric analysis of peripheral blood mononuclear cells in chronic inflammatory disorders, both infectious and non-infectious, reveals the presence of a CD34+CD226(DNAM-1)brightCXCR4+ cell population displaying transcriptional signatures typical of common lymphocyte precursors and giving rise to NK-cell progenies with high expression of activating receptors and mature function and even to α/β T lymphocytes. CD34+CD226brightCXCR4+ cells reside in bone marrow, hardly circulate in healthy donors and are absent in cord blood. Their proportion correlates with the degree of inflammation, reflecting lymphoid cell turnover/reconstitution during chronic inflammation. These findings provide insight on intermediate stages of NK-cell development, a view of emergency recruitment of cell precursors, and upgrade our understanding and monitoring of chronic inflammatory conditions.

BackgroundIn recent years, Highly-Active Anti-Retroviral Therapies (HAARTs) have modified the Human Immunodeficiency Virus (HIV) life-cycle and the disease is now considered chronic. Consequently, a longitudinal and complex follow-up is now required for HIV positive patients during their lifetime. Moreover, patients often encounter various complications due to comorbidities, related to the immunodeficiency state and HAARTs’ side effects. Thus, HIV positive patients are involved in multicenter clinical trials (MCTs) to improve treatments and discover a preventive vaccine. Therefore, physicians require proper instruments to access comprehensive patient data for managing patients during follow-ups, and tools for data collection and analysis in MCTs.ObjectiveThe Ligurian HIV Clinical Network aims to provide physicians with a Web-tool to administrate HIV positive patients’ data within primary-care and to reuse the collected clinical information to perform MCTs in Northern Italy.MethodsThe key aspect of the system is a relational database which allows the storage of various types of clinical information (eg, related to HIV, cardiovascular, or hepatic diseases) in multiple formats. The modular design of the database permits a rapid insertion of new parameters without requiring any changes in the database structure. Furthermore, codes from biomedical ontologies controlled vocabularies (“Logical Observation Identifier Names and Codes”, and “International Classification of Diseases 9”) and ontologies (“Systematized Nomenclature of Medicine Clinical Terms”), units and normality ranges used by all partners participating in the project were collected to achieve a complete semantic interoperability. Accordingly, data can be automatically normalized through the z score formula and physicians can extract and correctly compare information with external statistical tools. Moreover, to respect patients’ privacy and legal issues, a local identifier, determined through an HASH cryptography algorithm, is assigned to each patient during the registration process. The database is managed by a user-friendly Web-platform which allows quick access to information during medical examinations and the reusing of the collected data for present and future MCTs. Furthermore, a bidirectional middleware was created in order to import/export information through HL7 messaging. Hence, data can be manually entered by physicians or automatically collected within HL7-compliant Hospital Information systems.ResultsPresently, the direct storage of patients’ information from the San Paolo Hospital (Savona, Italy), and San Martino and Galliera hospitals in Genoa is in a test phase. Currently, 8 centers of Infectious Diseases (located in Liguria and Piedmont) are participating in the project and almost 400 HIV positive patients have been recorded in the system. Patient data has been used for primary care and research purposes. Currently, there are 4 on-going MCTs and preliminary results have already been presented at International HIV congresses.ConclusionsThe ...

HIV infection induces remarkable expansion of CD8CD28CD127CD39 Treg cells, the frequency of which correlates with both clinical disease and signs of chronic immune cell activation. Monitoring their frequency in the circulation is a new marker of response to ART when effects on viremia and clinical response are not met.

Evaluation of a large series of patients chronically infected by HBV alone identified a significant proportion of patients who are actually untreated despite being potential candidates for antiviral therapy.

Background The development of direct-acting antivirals (DAA) for HCV has revolutionized the treatment of HCV, including its treatment in patients with HIV coinfection. The aim of this study was to compare the changes in liver function between coinfected and monoinfected patients with cirrhosis who achieved HCV eradication by DAA. Methods Patients with pre-treatment diagnosis of HCV liver cirrhosis, consecutively enrolled in the multicenter PITER cohort, who achieved a sustained virological response 12 weeks after treatment cessation (SVR12) were analysed. Changes in Child-Pugh (C-P) class and the occurrence of a decompensating event was prospectively evaluated after the end of DAA treatment. Cox regression analysis was used to evaluate factors independently associated with changes in liver function following viral eradication. Results We evaluated 1350 patients, of whom 1242 HCV monoinfected (median follow-up 24.7, range 6.8–47.5 months after viral eradication) and 108 (8%) HCV/HIV coinfected (median follow-up 27.1, range 6.0–44.6). After adjusting for age, sex, HCV-genotype, HBsAg positivity and alcohol use, HIV was independently associated with a more advanced liver disease before treatment (C-P class B/C vs A) (OR: 3.73, 95% CI:2.00–6.98). Following HCV eradication, C-P class improved in 17/20 (85%) coinfected patients (from B to A and from C to B) and in 53/82 (64.6%) monoinfected patients (from B to A) (p = 0.08). C-P class worsened in 3/56 coinfected (5.3%) (from A to B) and in 84/1024 (8.2%) monoinfected patients (p = 0.45) (from A to B or C and from B to C). Baseline factors independently associated with C-P class worsening were male sex (HR = 2.00; 95% CI = 1.18–3.36), platelet count < 100,000/μl (HR = 1.75; 95% CI 1.08–2.85) and increased INR (HR = 2.41; 95% CI 1.51–3.84). Following viral eradication, in 7 of 15 coinfected (46.6%) and in 61 of 133 (45.8%) monoinfected patients with previous history of decompensation, a new decompensating event occurred. A first decompensating event was recorded in 4 of 93 (4.3%) coinfected and in 53 of 1109 (4.8%) monoinfected patients (p = 0.83). Conclusions Improvement of liver function was observed following HCV eradication in the majority of patients with cirrhosis; however viral eradication did not always mean cure of liver disease in both monoinfected and coinfected patients with advanced liver disease.

The aim of this study was to determine the prevalence of hepatitis B virus (HBV) infection in an Italian region, Liguria (1,572,000 inhabitants), by means of a network of 12 referral centers for liver diseases. All patients with HBV surface antigen followed throughout 2006 were included. Personal data, infectious status with risk factors, other non-infectious risk factors for liver disease, clinical status, and treatment were the questionnaire. Four hundred forty-five patients (71% male) were evaluated. Their median age was 48 years (range 5-84), and 83.4% were of Italian origin. Community-acquired infection was the principal mode of HBV transmission (82.5%), followed by previous intravenous drug use (9.4%), perinatal transmission (6.3%), and transfusion-associated transmission (1.8%). Hepatitis B e-antigen was present in 20.4% of the patients, while co-infections with hepatitis D virus and/or hepatitis C virus and/or human immunodeficiency virus (HIV) were observed in 18.7% of the patients. Chronic active hepatitis was present in 62.5% of the patients, cirrhosis in 13.5%, hepatocellular carcinoma in 2.2%, and 21.8% of the patients were inactive carriers of HBV. In all, 42.5% of the patients were treated with interferon or lamivudine and/or adefovir-dipivoxil. Forty-nine patients were co-infected with HIV (86% on highly active antiviral therapy). Nevertheless, this study identified only 2.2% of the expected patients with HBV. Hence, it has to be reasoned that few potential infectious or treatable patients are referred to liver disease centers. HBV infection is still an underestimated health problem, and few potential infectious or treatable patients are referred to tertiary centers.

No abstract