122 results on '"Gianpiero D'Offizi"'
Search Results
2. Third dose of <scp>SARS‐CoV2 mRNA</scp> vaccination produces robust persistent cellular and humoral immune responses in liver transplant recipients
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Marzia Montalbano, Paola Piccolo, Raffaella Lionetti, Ubaldo Visco‐Comandini, Chiara Agrati, Germana Grassi, Silvia Meschi, Giulia Matusali, Federica Conte, Federica Angelone, Giuseppe Maria Ettorre, Nicola Guglielmo, Fabrizio Maggi, Massimo Francalancia, Tiziana Mereu, Vincenzo Puro, Enrico Girardi, and Gianpiero D'Offizi
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Hepatology - Published
- 2023
3. Evolution of SARS‐CoV‐2 variants of concern over a period of Delta and Omicron cocirculation, among patients hospitalized for COVID‐19 in an Italian reference hospital: Impact on clinical outcomes
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Annalisa Mondi, Ilaria Mastrorosa, Pierluca Piselli, Claudia Cimaglia, Giulia Matusali, Fabrizio Carletti, Giuseppina Giannico, Eugenia Milozzi, Elisa Biliotti, Silvia Di Bari, Pierangelo Chinello, Alessia Beccacece, Francesca Faraglia, Pietro Vittozzi, Silvia Mosti, Nardi Tetaj, Giulia Valeria Stazi, Carmela Pinnetti, Marta Camici, Alberto D'Annunzio, Alessandra Marani, Lavinia Fabeni, Eliana Specchiarello, Cesare Ernesto Maria Gruber, Alberta Villanacci, Sabrina Minicucci, Anna Rosa Garbuglia, Stefania Ianniello, Luisa Marchioni, Fabrizio Taglietti, Gianpiero D'Offizi, Fabrizio Palmieri, Emanuele Nicastri, Fabrizio Maggi, Francesco Vaia, Enrico Girardi, and Andrea Antinori
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Infectious Diseases ,Virology - Published
- 2023
4. Severe Acute Respiratory Syndrome Coronavirus 2 Monoclonal Antibody Combination Therapy in Patients With Coronavirus Disease 2019 and Primary Antibody Deficiency
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Laura Vincenzi, Isabella Quinti, Stefania Auria, Emanuele Nicastri, Francesco Cinetto, Eva Piano Mortari, Cinzia Milito, Ane Fernandez Salinas, Valentina Soccodato, Lichtner Miriam, Sara Terreri, Gianpiero D'Offizi, Rita Carsetti, and Federica Pulvirenti
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Good’ Syndrome ,Coronavirus disease 2019 (COVID-19) ,Combination therapy ,medicine.drug_class ,viruses ,Primary Immunodeficiency Diseases ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Antibodies, Viral ,Real-Time Polymerase Chain Reaction ,Monoclonal antibody ,Primary Antibody Deficiencies ,Antineoplastic Agents, Immunological ,Humans ,Immunology and Allergy ,Medicine ,In patient ,Prospective Studies ,skin and connective tissue diseases ,Prospective cohort study ,biology ,SARS-CoV-2 ,business.industry ,Brief Report ,Common variable immunodeficiency ,fungi ,Antibodies, Monoclonal ,COVID-19 ,Standard of Care ,medicine.disease ,Primary and secondary antibodies ,respiratory tract diseases ,COVID-19 Drug Treatment ,body regions ,Common Variable Immunodeficiency ,AcademicSubjects/MED00290 ,Infectious Diseases ,Immunology ,biology.protein ,Monoclonal antibodies ,business - Abstract
Background Previous reports highlighted the efficacy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific monoclonal antibodies (mAbs) against coronavirus disease 2019. Methods We conducted a prospective study on the clinical outcome and antiviral effects of mAbs added to standard of care therapy in SARS-CoV-2-infected patients with primary antibody defects. Results Median time of SARS-CoV-2 quantitative polymerase chain reaction (qPCR) positivity was shorter in 8 patients treated with mAbs (22 days) than in 10 patients treated with standard of care therapy only (37 days, P=.026). Median time of SARS-CoV-2 qPCR positivity from mAb administration was 10 days. Conclusions The SARS-CoV-2 mAbs treatment was effective and well tolerated in patients with primary antibody defects.
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- 2021
5. Aero-Medical Evacuation during SARS-CoV-2 Pandemic: Extraordinary Measure or Emerging Treatment Option?
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Domenico Benvenuto, Tommaso Ascoli Bartoli, Ambrogio Curtolo, Claudia Palazzolo, Serena Vita, Andrea Mariano, Laura Scorzolini, Giuseppe Ippolito, Luisa Marchioni, Federico Cerini, Gianpiero D’Offizi, Francesco Vaia, and Emanuele Nicastri
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General Medicine ,medical evacuation ,COVID-19 ,infectious diseases - Abstract
Aero-medical evacuation has been considered as a feasible and safe treatment option during COVID pandemic, particularly when the needs of affected patients exceed what local clinics and hospitals are supposed to provide. In this article, we analyzed the clinical course of 17 patients medically evacuated to the “L. Spallanzani” Institute in Rome, Italy from foreign countries, mainly Africa and Eastern Europe, who had COVID-19 pneumonia with, or without, coinfections such as malaria, HIV, tuberculosis and microbiologically confirmed sepsis syndrome. The aero-medical evacuation of patients with infectious diseases has become one of the greatest medical achievements we have reached during this pandemic; in fact, only two patients with life threatening coinfections have died. Although logistically difficult and cost consuming, medical evacuation should be considered as a treatment option more than a single extraordinary measure, especially among complex cases that require specific technical and human resources.
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- 2022
6. Role of the Immune System in Hepatocellular Carcinoma
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Chiara Taibi, Laura Vincenzi, and Gianpiero D’Offizi
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- 2022
7. Continuing our work: transplant surgery and surgical oncology in a tertiary referral COVID-19 center
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Giovanni Battista Levi Sandri, Gianpiero D'Offizi, Marco Colasanti, Mario Antonini, Giuseppe Maria Ettorre, Stefano Ferretti, Roberto Luca Meniconi, Andrea Laurenzi, Celeste Del Basso, Giammauro Berardi, and Nicola Guglielmo
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Male ,medicine.medical_specialty ,Time Factors ,Cirrhosis ,Referral ,Revised Cardiac Risk Index ,Pneumonia, Viral ,030230 surgery ,Systemic therapy ,law.invention ,Tertiary Care Centers ,03 medical and health sciences ,0302 clinical medicine ,law ,Surgical oncology ,Neoplasms ,Humans ,Medicine ,General surgery ,Pandemics ,Aged ,business.industry ,COVID-19 ,Outbreak ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Intensive care unit ,Liver Transplantation ,Surgery ,Transplantation ,Italy ,Surgical Procedures, Operative ,030220 oncology & carcinogenesis ,Female ,Original Article ,Coronavirus Infections ,business - Abstract
Background. COVID-19 is rapidly spreading worldwide. Healthcare systems are struggling to properly allocate resources while ensuring cure for diseases outside of the infection. The aim of this study was to demonstrate how surgical activity was affected by the virus outbreak and show the changes in practice in a tertiary referral COVID-19 center.Methods. The official bulletins of the Italian National Institute for the Infectious Diseases “L. Spallanzani” were reviewed to retrieve the number of daily COVID-19 patients. Records of consecutive oncological and transplant procedures performed during the outbreak were reviewed. Patients with a high probability of postoperative intensive care unit (ICU) admission were considered as high-risk and defined by an ASA score ≥ III and/or a Charlson Comorbidity Index (CCI) ≥ 6 and/or a Revised Cardiac Risk Index for Preoperative Risk (RCRI) ≥ 3.Results. 72 patients were operated including 12 (16.6%) liver (n=6) and kidney (n=6) transplantations. Patients had few comorbidities (26.3%), low ASA score (1.9±0.5), CCI (3.7±1.3) and RCRI (1.2±0.6) and had low risk of postoperative ICU admission. Few patients had liver cirrhosis (12.5%) or received preoperative systemic therapy (16.6%). 36 (50%) high risk surgical procedures were performed including major hepatectomies, pancreaticoduodenectomies, total gastrectomies, multivisceral resections and transplantations. Despite this, only 15 patients (20.8%) were admitted to the ICU.Conclusions. Only oncologic cases and transplantations were performed during the COVID-19 outbreak. Careful selection of patients allowed to perform major cancer surgeries and transplantations without further stressing hospital resources, meanwhile minimizing collateral damage to patients.
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- 2020
8. Incidence of Pneumothorax and Pneumomediastinum in 497 COVID-19 Patients with Moderate-Severe ARDS over a Year of the Pandemic: An Observational Study in an Italian Third Level COVID-19 Hospital
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Nardi, Tetaj, Gabriele, Garotto, Fabrizio, Albarello, Annelisa, Mastrobattista, Micaela, Maritti, Giulia Valeria, Stazi, Maria Cristina, Marini, Ilaria, Caravella, Manuela, Macchione, Giada, De Angelis, Donatella, Busso, Rachele, Di Lorenzo, Silvana, Scarcia, Anna, Farina, Daniele, Centanni, Joel, Vargas, Martina, Savino, Alessandro, Carucci, Andrea, Antinori, Fabrizio, Palmieri, Gianpiero, D'Offizi, Stefania, Ianniello, Fabrizio, Taglietti, Paolo, Campioni, Francesco, Vaia, Emanuele, Nicastri, Enrico, Girardi, Luisa, Marchioni, and Icu Covid-Study Group
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invasive mechanical ventilation ,medicine.medical_specialty ,ARDS ,pneumothorax ,medicine.medical_treatment ,barotrauma ,intensive care unit ,Article ,NO ,law.invention ,law ,medicine ,Intubation ,LS7_2 ,Pneumomediastinum ,COVID-19 waves ,LS7_9 ,pneumomediastinum ,business.industry ,Incidence (epidemiology) ,non-invasive ventilation ,COVID-19 ,subcutaneous emphysema ,General Medicine ,medicine.disease ,Intensive care unit ,Pneumothorax ,Emergency medicine ,Breathing ,Medicine ,medicine.symptom ,business ,human activities ,Subcutaneous emphysema - Abstract
(1) Background: COVID-19 is a novel cause of acute respiratory distress syndrome (ARDS). Indeed, with the increase of ARDS cases due to the COVID-19 pandemic, there has also been an increase in the incidence of cases with pneumothorax (PNX) and pneumomediastinum (PNM). However, the incidence and the predictors of PNX/PMN in these patients are currently unclear and even conflicting. (2) Methods: The present observational study analyzed the incidence of barotrauma (PNX/PNM) in COVID-19 patients with moderate–severe ARDS hospitalized in a year of the pandemic, also focusing on the three waves occurring during the year, and treated with positive-pressure ventilation (PPV). We collected demographic and clinical data. (3) Results: During this period, 40 patients developed PNX/PNM. The overall incidence of barotrauma in all COVID-19 patients hospitalized in a year was 1.6%, and in those with moderate–severe ARDS in PPV was 7.2% and 3.8 events per 1000 positive-pressure ventilator days. The incidence of barotrauma in moderate–severe ARDS COVID-19 patients during the three waves was 7.8%, 7.4%, and 8.7%, respectively. Treatment with noninvasive respiratory support alone was associated with an incidence of barotrauma of 9.1% and 2.6 events per 1000 noninvasive ventilator days, of which 95% were admitted to the ICU after the event, due to a worsening of respiratory parameters. The incidence of barotrauma of ICU COVID-19 patients in invasive ventilation over a year was 5.8% and 2.7 events per 1000 invasive ventilator days. There was no significant difference in demographics and clinical features between the barotrauma and non-barotrauma group. The mortality was higher in the barotrauma group (17 patients died, 47.2%) than in the non-barotrauma group (170 patients died, 37%), although this difference was not statistically significant (p = 0.429). (4) Conclusions: The incidence of PNX/PNM in moderate–severe ARDS COVID-19 patients did not differ significantly between the three waves over a year, and does not appear to be very different from that in ARDS patients in the pre-COVID era. The barotrauma does not appear to significantly increase mortality in COVID-19 patients with moderate–severe ARDS if protective ventilation strategies are applied. Attention should be paid to the risk of barotrauma in COVID-19 patients in noninvasive ventilation because the event increases the probability of admission to the intensive care unit (ICU) and intubation.
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- 2021
9. Phylogenetic and Phylodynamic Analyses of HCV Strains Circulating among Patients Using Injectable Drugs in Central Italy
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Claudia Minosse, Anna Rosa Garbuglia, Gianpiero D'Offizi, Daniela Nardozi, Ilaria Luzzitelli, Fiona McPhee, Chiara Taibi, Leonidas Salichos, and Maria Rosaria Capobianchi
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0301 basic medicine ,Microbiology (medical) ,QH301-705.5 ,Hepatitis C virus ,Population ,HCV genotypes ,Biology ,medicine.disease_cause ,phylogeny ,Microbiology ,molecular epidemiology ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,viral evolution ,0302 clinical medicine ,Phylogenetics ,Virology ,Genotype ,medicine ,Biology (General) ,education ,NS5B ,people who use drugs (PWUD) ,education.field_of_study ,Molecular epidemiology ,Phylogenetic tree ,virus diseases ,digestive system diseases ,030104 developmental biology ,chemistry ,Viral evolution ,030211 gastroenterology & hepatology ,hepatitis C virus (HCV) - Abstract
Approximately 71 million people worldwide are infected with the hepatitis C virus (HCV). Injectable drug use represents the most common route of transmission in Europe and other developed countries. We studied the molecular characteristics of the HCV infection among mono-infected people who used drugs (PWUD) in Italy. Among 208 PWUD with anti-HCV antibodies, 101 (48.6%) were HCV RNA-positive, the majority (47%) were infected with the HCV genotype (Gt)1a, followed by Gt3a (34.9%), Gt4 (9.1%), Gt1b (4.5%), and Gt2 (4.5%). Bayesian phylogenetic analyses of clustered HCV NS5B sequences from 66 HCV-positive PWUDs with available plasma samples indicated age and neighborhood proximity as the most common characteristics between closely related HCV strains. Population dynamics, as measured by a coalescent Bayesian skyline analysis, revealed an increase in HCV Gt1a infections from the mid-1980s to mid-1990s. While HCV Gt3a infections were first detected in the 1980s, patient numbers with this genotype subtype remained relatively constant. For both Gt1a and Gt3a, Birth–Death Bayesian Skyline analyses produced higher reproduction numbers post 2014. For earlier time intervals, slow growths were observed for both Gt1a and Gt3a with reproduction numbers (Re) of approximately 1. The evolutionary rates for Gt1a and Gt3a were estimated as 2.23 × 10−4 and 3.85 × 10−4, respectively.
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- 2021
10. Clinical and virological properties of hepatitis C virus genotype 4 infection in patients treated with different direct-acting antiviral agents
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Fiona McPhee, Barbara Bartolini, Claudia Minosse, Emanuela Giombini, Laura Loiacono, Marina Selleri, Stefano Cerilli, Maria Rosaria Capobianchi, Chiara Taibi, Anna Rosa Garbuglia, and Gianpiero D'Offizi
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0301 basic medicine ,medicine.medical_specialty ,Sofosbuvir ,viruses ,Hepatitis C virus ,Population ,Viral quasispecies ,Drug resistance ,medicine.disease_cause ,Gastroenterology ,deep sequencing ,03 medical and health sciences ,chemistry.chemical_compound ,Internal medicine ,Genotype ,medicine ,Pharmacology (medical) ,education ,NS5A ,NS5B ,Original Research ,resistance-associated substitution ,Pharmacology ,education.field_of_study ,virological failure ,business.industry ,virus diseases ,biochemical phenomena, metabolism, and nutrition ,hepatitis C virus genotype 4 ,digestive system diseases ,030104 developmental biology ,Infectious Diseases ,chemistry ,Infection and Drug Resistance ,identification ,population sequencing ,business ,RAS ,medicine.drug - Abstract
Claudia Minosse,1,* Marina Selleri,1,* Emanuela Giombini,1 Barbara Bartolini,1 Maria Rosaria Capobianchi,1 Stefano Cerilli,2 Laura Loiacono,2 Chiara Taibi,2 Gianpiero D’Offizi,2 Fiona McPhee,3 AnnaRosa Garbuglia1 1Department of Pre-clinical Research Epidemiology and Advanced Diagnostics, Laboratory of Virology, National Institute for Infectious Diseases “Lazzaro Spallanzani”– IRCCS, Rome, Italy; 2Clinical Department, Infectious Disease-Hepatology Unit, National Institute for Infectious Diseases, “Lazzaro Spallanzani” – IRCCS, Rome, Italy; 3Bristol-Myers Squibb Research and Development, Wallingford, CT, USA *These authors contributed equally to this work Background: The efficacy of direct-acting antivirals (DAAs) depends on the hepatitis C virus (HCV) genotype 4 (GT4) subtype which are used in the treatment of HCV. We aimed to retrospectively investigate the baseline prevalence of HCV NS5A and NS5B polymorphisms and their impact on virological outcome in GT4-infected patients treated with various DAA regimens.Patients and methods: Available plasma samples from HCV GT4-infected patients treated with different DAA regimens were analyzed at baseline and after treatment failure, where applicable. Sanger sequencing of patient-derived NS5A and NS5B regions was performed on all available samples, while ultradeep pyrosequencing (UDPS) of NS5A and NS5B regions was performed only on samples from treatment failures at different time points.Results: Sustained virological response (SVR) was achieved by 96% (48/50) of patients. Of 16 patients with baseline NS5A sequence, polymorphisms at amino acid positions associated with drug resistance were detected only at position 58: P58 (69.2%) and T58 (30.8%). Of 21 patients with baseline NS5B sequence, N142S was detected only in the two treatment failures, both with GT4d were treated with sofosbuvir (SOF)-based regimens, suggesting a potential involvement in SOF efficacy. Two patients (patient 1 [Pt1] and patient 2 [Pt2]) relapsed. In Pt1, NS5A-T56I and NS5A-Y93H/S emerged. In Pt2, NS5A-L28F emerged and a novel NS5B resistance-associated substitution (RAS), L204F, representing 1.5% of the viral population at baseline, enriched to 71% and 91.6% during and after treatment failure, respectively. UDPS of NS5B from Pt2 indicated a mixed infection of approximately 1:5, GT1a:GT4d, at baseline and GT4d during failure. Phylogenetic analysis of NS5A sequences indicated no clustering of HCV strains from patients achieving SVR vs patients who relapsed. The mean genetic distance in NS5A sequences was 5.8%, while a lower genetic distance (3.1%) was observed in NS5B sequences.Conclusion: Results from these analyses confirm the importance of UDPS in the analysis of viral quasispecies variability and the identification of novel RASs potentially associated with DAA treatment failure in HCV GT4-infected patients. Keywords: hepatitis C virus genotype 4, virological failure, population sequencing, deep sequencing, resistance-associated substitution, RAS, identification
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- 2018
11. Role of testosterone in SARS-CoV-2 infection: A key pathogenic factor and a biomarker for severe pneumonia
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Elisa Pianura, Lucia Ciavarella, Fabrizio Palmieri, Federica Di Stefano, Enrico Girardi, Emanuele Nicastri, Francesco Vaia, Stefano Curcio, Vincenzo Schininà, Roberto Baldelli, Andrea Antinori, Liliana Scarnecchia, Paolo Zuppi, Marta Camici, Giuseppe Ippolito, Luisa Marchioni, Carmela Pinnetti, Gianpiero D'Offizi, Roberta Gagliardini, Patrizia Lorenzini, Stefania Cicalini, and Nicola Petrosillo
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0301 basic medicine ,Microbiology (medical) ,Male ,medicine.medical_specialty ,Virulence Factors ,030106 microbiology ,Infectious and parasitic diseases ,RC109-216 ,gender imbalance ,Systemic inflammation ,Gastroenterology ,Article ,03 medical and health sciences ,severity markers ,0302 clinical medicine ,Sex hormone-binding globulin ,sexual hormones ,Internal medicine ,medicine ,Humans ,Sex hormones ,030212 general & internal medicine ,Viral shedding ,Testosterone ,biology ,business.industry ,SARS-CoV-2 ,Mortality rate ,Case-control study ,COVID-19 ,General Medicine ,Infectious Diseases ,Case-Control Studies ,testosterone ,androgen sensitivity ,biology.protein ,Biomarker (medicine) ,medicine.symptom ,business ,Biomarkers ,Hormone - Abstract
Objectives: To investigate the association between sex hormones and the severity of coronavirus disease 2019 (COVID-19). Furthermore, associations between sex hormones and systemic inflammation markers, viral shedding and length of hospital stay were studied. Design and methods: This case–control study included a total of 48 male patients with COVID-19 admitted to an Italian reference hospital. The 24 cases were patients with PaO2/FiO2 300 mmHg at all times and who may have required low-flow oxygen supplementation during hospitalization (mild COVID-19). For each group, sex hormones were evaluated on hospital admission. Results: Patients with severe COVID-19 (cases) had a significantly lower testosterone level compared with patients with mild COVID-19 (controls). Median total testosterone (TT) was 1.4 ng/mL in cases and 3.5 ng/mL in controls (P = 0.005); median bioavailable testosterone (BioT) was 0.49 and 1.21 in cases and controls, respectively (P = 0.008); and median calculated free testosterone (cFT) was 0.029 ng/mL and 0.058 ng/mL in cases and controls, respectively (P = 0.015). Low TT, low cFT and low BioT were correlated with hyperinflammatory syndrome (P = 0.018, P = 0.048 and P = 0.020, respectively) and associated with longer length of hospital stay (P = 0.052, P = 0.041 and P = 0.023, respectively). No association was found between sex hormone level and duration of viral shedding, or between sex hormone level and mortality rate. Conclusions: A low level of testosterone was found to be a marker of clinical severity of COVID-19.
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- 2021
12. Fibrogenic signals persist in DAA-treated HCV patients after sustained virological response
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Michela Terri, Veronica Bordoni, Tiziana Vescovo, Claudia Montaldo, Eleonora Tartaglia, Marco Tripodi, Flavia Trionfetti, Raffaele Strippoli, Veronica Riccioni, Chiara Agrati, Maria Giulia Prado, Cecilia Battistelli, and Gianpiero D'Offizi
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Cirrhosis ,liver fibrosis ,extracellular vesicles ,direct-acting antiviral (DAA) therapy ,Hepatology ,medicine.diagnostic_test ,biology ,Sustained Virologic Response ,business.industry ,Extracellular vesicle ,Cell Communication ,Hepacivirus ,medicine.disease ,Antiviral Agents ,Hepatitis C ,Virus ,Mass Spectrometry ,Liver disease ,Western blot ,Fibrosis ,microRNA ,Immunology ,medicine ,biology.protein ,Humans ,ACTA2 ,business - Abstract
Patients with HCV who achieve a sustained virological response (SVR) on direct-acting antiviral (DAA) therapy still need to be monitored for signs of liver disease progression. To this end, the identification of both disease biomarkers and therapeutic targets is necessary.Extracellular vesicles (EVs) purified from plasma of 15 healthy donors (HDs), and 16 HCV-infected patients before (T0) and after (T6) DAA treatment were utilized for functional and miRNA cargo analysis. EVs purified from plasma of 17 HDs and 23 HCV-infected patients (T0 and T6) were employed for proteomic and western blot analyses. Functional analysis in LX2 cells measured fibrotic markers (mRNAs and proteins) in response to EVs. Structural analysis was performed by qPCR, label-free liquid chromatography-mass spectrometry and western blot.On the basis of observations indicating functional differences (i.e. modulation of FN-1, ACTA2, Smad2/3 phosphorylation, collagen deposition) of plasma-derived EVs from HDs, T0 and T6, we performed structural analysis of EVs. We found consistent differences in terms of both miRNA and protein cargos: (i) antifibrogenic miR204-5p, miR181a-5p, miR143-3p, miR93-5p and miR122-5p were statistically underrepresented in T0 EVs compared to HD EVs, while miR204-5p and miR143-3p were statistically underrepresented in T6 EVs compared to HD EVs (p0.05); (ii) proteomic analysis highlighted, in both T0 and T6, the modulation of several proteins with respect to HDs; among them, the fibrogenic protein DIAPH1 was upregulated (LogTaken together, these results highlight structural EV modifications that are conceivably causal for long-term liver disease progression in patients with HCV despite DAA-mediated SVR.Direct-acting antivirals lead to virological cure in the majority of patients with chronic hepatitis C virus infection. However, the risk of liver disease progression or complications in patients with fibrosis and cirrhosis remains in some patients even after virological cure. Herein, we show that extracellular vesicle modifications could be linked to long-term liver disease progression in patients who have achieved virological cure; these modifications could potentially be used as biomarkers or treatment targets in such patients.
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- 2020
13. Factors Enhancing Treatment of Hepatitis C Virus-Infected Italian People Who Use Drugs: The CLEO-GRECAS Experience
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Giuseppe Cariti, Valerio Rosato, Giustino Parruti, Luca Rinaldi, Maria Antonietta Di Rosolini, Valeria Morbiducci, Lucio Cosco, Maria D'Antò, Emanuela Ciracì, Giovanni Garrucciu, Giorgio Barbarini, Massimo De Luca, Rodolfo Sacco, Riccardo Nevola, Pietro Gatti, Antonio Ascione, F. Benanti, Cecilia Cangiano, Paolo Maggi, Paolo Tundo, Gianpiero D'Offizi, Riccardo Guarisco, Giancarlo Gimignani, Michele Imparato, Fabio Bulla, Vincenzo Messina, G. Scifo, Ilaria Luzzitelli, Valeria Pace Palitti, Vito Di Marco, Francesco Di Lorenzo, Ernesto Claar, Antonio Izzi, Mariano Quartini, Tommaso Lupia, Umberto Vespasiani Gentilucci, Vincenzo Iovinella, Marco Di Stefano, Federica Sozio, Antonio Craxì, Rinaldi, Luca, Messina, Vincenzo, Di Marco, Vito, Iovinella, Vincenzo, Claar, Ernesto, Cariti, Giuseppe, Sacco, Rodolfo, De Luca, Massimo, Scifo, Gaetano, Gatti, Pietro, Barbarini, Giorgio, Pace Palitti, Valeria, Quartini, Mariano, Tundo, Paolo, D'Offizi, Gianpiero, Parruti, Giustino, di Rosolini, Maria Antonietta, Garrucciu, Giovanni, Cosco, Lucio, Benanti, Francesco, Gimignani, Giancarlo, Vespasiani Gentilucci, Umberto, Di Lorenzo, Francesco, D'Antò, Maria, Nevola, Riccardo, Lupia, Tommaso, Rosato, Valerio, Morbiducci, Valeria, Luzzitelli, Ilaria, Sozio, Federica, Di Stefano, Marco, Ciraci, Emanuela, Bulla, Fabio, Guarisco, Riccardo, Cangiano, Cecilia, Imparato, Michele, Maggi, Paolo, Ascione, Antonio, Craxì, Antonio, Izzi, Antonio, Rinaldi L., Messina V., Di Marco V., Iovinella V., Claar E., Cariti G., Sacco R., de Luca M., Scifo G., Gatti P., Barbarini G., Palitti V.P., Quartini M., Tundo P., D'Offizi G., Parruti G., di Rosolini M.A., Garrucciu G., Cosco L., Benanti F., Gimignani G., Gentilucci U.V., Di Lorenzo F., D'Anto M., Nevola R., Lupia T., Rosato V., Morbiducci V., Luzzitelli I., Sozio F., Di Stefano M., Ciraci E., Bulla F., Guarisco R., Cangiano C., Imparato M., Maggi P., Ascione A., Craxi A., and Izzi A.
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Adult ,Male ,Elbasvir ,medicine.medical_specialty ,Sofosbuvir ,Sustained Virologic Response ,Intention to Treat Analysi ,Substance-Related Disorders ,Hepatitis C virus ,medicine.disease_cause ,Antiviral Agents ,Medication Adherence ,03 medical and health sciences ,0302 clinical medicine ,Retrospective Studie ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Retrospective Studies ,Antiviral Agent ,Hepatology ,business.industry ,Gastroenterology ,virus diseases ,Glecaprevir ,Odds ratio ,Hepatitis C, Chronic ,Middle Aged ,Substance-Related Disorder ,Pibrentasvir ,digestive system diseases ,Intention to Treat Analysis ,Prospective Studie ,Grazoprevir ,Italy ,030220 oncology & carcinogenesis ,Cohort ,030211 gastroenterology & hepatology ,Female ,business ,medicine.drug ,Human - Abstract
INTRODUCTION: We assessed the performance of direct-acting antivirals (DAAs) in hepatitis C virus (HCV)-infected people who use drugs (PWUDs) in terms of sustained virological response (SVR) and adherence rates in comparison to a location-matched cohort of non-PWUD HCV patients. METHODS: All consecutive HCV RNA-positive PWUDs were enrolled between 2015 and 2019. All subjects underwent DAA treatment according to international guidelines and then followed, at least, up to 12 weeks after the end of treatment (SVR12). The SVR and adherence to treatment was compared with that of non-PWUD HCV patients observed at hepatological units of the CLEO platform. Intention-to-treat analysis was performed. RESULTS: A total of 1,786 PWUDs who were followed up were available for assessment. Most PWUDs (85.4%) were managed inside the specialized outpatient addiction clinics (SerDs). The overall SVR rate was 95.4%. The SerDs group achieved an SVR rate of 96.2% compared with 91.6% of the non-SerDs group (P < 0.001). Comparison with the non-SerDs group and the control HCV group showed a significant difference in the dropout rate (0.6% in the SerDs group versus 2.8% in the non-SerDs group and 1.2% in the control group; P < 0.001). At multivariate analysis, factors independently associated with SVR were use of the most recent regimens (elbasvir/grazoprevir, glecaprevir/pibrentasvir, and sofosbuvir/ velpatasvir; odds ratio: 3.126; P 5 0.000) and belonging to the SerDs group (odds ratio: 2.356; P 5 0.002). DISCUSSION: The performance of DAAs in PWUD is excellent, if 2 conditions are met: (i) that the latest generation drugs are used and (ii) that the patients are managed within the SerDs.
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- 2020
14. Postmortem Findings in Italian Patients With COVID-19: A Descriptive Full Autopsy Study of Cases With and Without Comorbidities
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Eleonora Lalle, Luisa Marchioni, Gianpiero D'Offizi, Franca Del Nonno, Daniele Colombo, Emanuele Nicastri, Fabrizio Palmieri, Gianluigi Biava, Delia Goletti, Mauro Piacentini, Nicola Petrosillo, Alimuddin Zumla, Giuseppe Ippolito, Roberta Nardacci, Antonino Di Caro, Laura Falasca, and Andrea Antinori
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Autopsy ,Comorbidity ,030204 cardiovascular system & hematology ,Kidney ,comorbidities ,03 medical and health sciences ,0302 clinical medicine ,autopsy ,Bone Marrow ,Major Article ,Medicine ,Immunology and Allergy ,Humans ,Vascular Diseases ,Respiratory system ,Pathological ,Lung ,Aged ,Aged, 80 and over ,business.industry ,SARS-CoV-2 ,COVID-19 ,Thrombosis ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,Infectious Diseases ,AcademicSubjects/MED00290 ,Italy ,Liver ,030220 oncology & carcinogenesis ,Female ,pathology ,Bone marrow ,business ,Spleen - Abstract
Background Descriptions of the pathological features of coronavirus disease-2019 (COVID-19) caused by the novel zoonotic pathogen severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emanate from tissue biopsies, case reports, and small postmortem studies restricted to the lung and specific organs. Whole-body autopsy studies of COVID-19 patients have been sparse. Methods To further define the pathology caused by SARS-CoV-2 across all body organs, we performed autopsies on 22 patients with COVID-19 (18 with comorbidities and 4 without comorbidities) who died at the National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS Hospital, Rome, Italy. Tissues from the lung, heart, liver, kidney, spleen, and bone marrow (but not the brain) were examined. Only lung tissues were subject to transmission electron microscopy. Results COVID-19 caused multisystem pathology. Pulmonary and cardiovascular involvement were dominant pathological features. Extrapulmonary manifestations included hepatic, kidney, splenic, and bone marrow involvement, and microvascular injury and thrombosis were also detected. These findings were similar in patients with or without preexisting medical comorbidities. Conclusions SARS-CoV-2 infection causes multisystem disease and significant pathology in most organs in patients with and without comorbidities., Autopsy findings in patients with COVID-19 showed deaths were due to cardiorespiratory failure, predominantly caused by acute lung injury, microvascular damage, and thrombosis. COVID-19 causes multisystem disease and significant pathology in most organs in patients with and without comorbidities.
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- 2020
15. COVID-19 Disease - Temporal Analyses of Complete Blood Count Parameters Over Course of Illness, and Relationship to Patient Demographics and Management Outcomes in Survivors and Non-Survivors: A Longitudinal Descriptive Cohort Study
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Simone Lanini, Chiara Montaldo, Emanuele Nicastri, Francesco Vairo, Chiara Agrati, Nicola Petrosillo, Paola Scognamiglio, Andrea Antinori, Vincenzo Puro, Antonino Di Caro, Gabriella De Carli, Assunta Navarra, Alessandro Agresta, Claudia Cimaglia, Fabrizio Palmieri, Gianpiero D’Offizi, Luisa Marchioni, Gary Pignac Kobinger, Markus Maeurer, Enrico Girardi, Maria Rosaria Capobianchi, Alimuddin Zumla, Franco Locatelli, and Giuseppe Ippolito
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medicine.medical_specialty ,COPD ,Hematology ,medicine.diagnostic_test ,Anemia ,business.industry ,Complete blood count ,Red blood cell distribution width ,medicine.disease ,Internal medicine ,medicine ,Anisocytosis ,Mean platelet volume ,business ,Cohort study - Abstract
Background: More detailed temporal analyses of complete (Full) blood count (CBC) parameters, their evolution and relationship to patient age, gender, co-morbidities and management outcomes in survivors and non-survivors with COVID-19 disease could help identify prognostic clinical biomarkers. Methods: From 29 January 2020 until 28 March 2020, we performed a longitudinal cohort study of COVID-19 inpatients at the Italian National Institute for Infectious Diseases, Rome, Italy. Nine CBC parameters as a continuous variable were studied [neutrophils, lymphocytes, monocytes, platelets, mean platelet volume, red blood cell count, haemoglobin concentration, mean red blood cell volume and red blood cell distribution width (RDW %)]. Model-based punctual estimates and difference between survivors and non-survivors, overall, and by co-morbidities, at specific times after symptoms, with relative 95% CI and P-values were obtained by marginal prediction and ANOVA-style joint tests. All analyses were carried out by STATA 15 statistical package. Main Findings: 379 COVID-19 patients [273 (72% were male; mean age was 61.67 (SD 15.60)] were enrolled and 1,805 measures per parameter were analysed. Neutrophil counts were on average significantly higher in non-survivors than in survivors (P 60 years(p=0.001). Age (p=0.042), obesity (p=0.002), chronic renal failure (p=0.002) and cardiovascular diseases (p=0.009) were independently associated with poor patient clinical outcome at 30 day after symptom onset. Interpretation: Increased neutrophil counts, reduced lymphocyte counts, higher median platelet volume, anemia with anisocytosis, in association with obesity, chronic renal failure, COPD, cardiovascular diseases and age >60 years predict poor prognosis in COVID19 patients. Funding Statement: Ricerca Corrente e Finalizzata Italy Ministry of Health, AIRC (IG2018-21880); Regione Lazio (Gruppi di ricerca, E56C18000460002). Declaration of Interests: The authors declare no competing interest. Ethics Approval Statement: This study was approved by the IRB of Italian National Institute for Infectious Diseases “Lazzaro Spallanzani” (INMI), in Rome (Italy).
- Published
- 2020
16. Early improvement of glycaemic control after virus clearance in patients with chronic hepatitis C and severe liver fibrosis: a cohort study
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Simone, Lanini, Barbara, Bartolini, Chiara, Taibi, Alessandro, Agresta, Anna Rosa, Garbuglia, Chiara, Montaldo, Raffaella, Pisapia, Gianpiero, D'Offizi, Paola, Scognamiglio, Maria Rosaria, Capobianchi, Alimuddin, Zumla, and Giuseppe, Ippolito
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Blood Glucose ,Cohort Studies ,Diabetes Complications ,Liver Cirrhosis ,Kinetics ,Rome ,Humans ,Hepacivirus ,Hepatitis C, Chronic ,Viral Load ,Antiviral Agents ,Retrospective Studies - Abstract
HCV has been recognized as the cause of chronic hepatitis C (CHC) since 1990. CHC is associated with progressive liver damage and extrahepatic conditions. Direct antiviral agents (DAAs), approved in 2014, have shown effectiveness in eradicating HCV in most patients. However, little is known about the effect of viral eradication on hepatic and extra-hepatic damage. We performed a historical cohort study of patients with HCV-related liver diseases who achieved SVR from March 2015 to October 2016 at INMI Lazzaro Spallanzani liver Unit in Rome (Italy). Repeated measures of glycaemia were analysed through a multilevel analysis framework to assess short time kinetics of blood glucose level at different times after therapy and for different levels of HCV viremia. The analysis included 205 patients. A model assessing temporal kinetics and variation of glycaemia according to HCV viremia provided evidence that blood glucose levels significantly dropped in patients with diabetes achieving SVR. Most of the variations occurred at 3-5 weeks of therapy (-17.96 mg/dL; p0.001) and in coincidence with HCV clearance (-13.92 mg/dL; p0.001). A weak, non-statistically significant reduction was observed in normoglycemic patients. Our study provides evidence that DAAs therapy may significantly improve glycaemic control in patients with CHC achieving SVR even when liver diseases are already established.
- Published
- 2019
17. The impact of the coronavirus disease 2019 pandemic on a central Italy transplant center
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Raffaella Lionetti, Marzia Montalbano, Laura Vincenzi, Giovanni Battista Levi Sandri, Giammauro Berardi, Ubaldo Visco Comandini, Giuseppe Maria Ettorre, Nicola Guglielmo, Adriano M. Pellicelli, and Gianpiero D'Offizi
- Subjects
medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Pneumonia, Viral ,Observational Study ,Economic shortage ,liver ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,law ,Health care ,Pandemic ,medicine ,Humans ,030212 general & internal medicine ,Intensive care medicine ,Pandemics ,business.industry ,Risk of infection ,COVID-19 ,General Medicine ,Intensive care unit ,Hospitals ,Liver Transplantation ,Italy ,030220 oncology & carcinogenesis ,Coronavirus Infections ,business ,COVID 19 ,Research Article ,transplantation - Abstract
Coronavirus disease 2019 (COVID-19) is challenging health care systems worldwide, raising the question of reducing the transplant program due to the shortage of intensive care unit beds and to the risk of infection in donors and recipients. We report the positive experience of a single Transplant Center in Rome, part of the National Institute for Infectious Diseases Lazzaro Spallanzani, one of the major national centers involved in the COVID-19 emergency.
- Published
- 2020
18. Virological response and resistance profile in HIV-1-infected patients starting darunavir-containing regimens
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Claudia Alteri, Daniele Armenia, Ada Bertoli, M. Andreoni, Gaetano Maffongelli, Andrea Antinori, Cristina Mussini, Vanni Borghi, Emanuele Nicastri, Federica Forbici, Domenico Di Carlo, Caterina Gori, Francesca Ceccherini-Silberstein, Mauro Zaccarelli, Mm Santoro, Massimo Giuliani, Gianpiero D'Offizi, Carmela Pinnetti, Stefania Cicalini, and Carlo Federico Perno
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Adolescent ,Anti-HIV Agents ,030106 microbiology ,virological response ,HIV Infections ,darunavir ,Drug resistance ,Gastroenterology ,Virological response ,Young Adult ,03 medical and health sciences ,darunavir dosage ,Interquartile range ,Internal medicine ,Drug Resistance, Viral ,medicine ,Humans ,Pharmacology (medical) ,Treatment Failure ,Viral ,Young adult ,Darunavir ,Ritonavir ,drug resistance ,business.industry ,Health Policy ,Middle Aged ,Viral Load ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,Surgery ,baseline viraemia ,Female ,HIV-1 ,Regimen ,Infectious Diseases ,business ,Viral load ,medicine.drug - Abstract
Objectives We evaluated the virological response in patients starting a regimen based on darunavir/ritonavir (DRV/r), which is currently the most widely used ritonavir-boosted protease inhibitor. Methods Data from 206 drug-naive and 327 PI-experienced patients starting DRV/r 600/100 mg twice daily (DRV600) or 800/100 mg once daily (DRV800) were examined. The probabilities of virological success (VS) and virological rebound (VR) were evaluated in survival analyses. Baseline DRV/r resistance and its evolution at failure were also examined. Results DRV600 was preferentially administered in patients with complex requirements (older age, higher viraemia, lower CD4 cell count and DRV/PI resistance) compared with DRV800. By 12 months, the probability of achieving VS was 93.2% and 84.3% in drug-naive and PI-experienced patients, respectively. The higher the baseline viraemia, the longer was the time required to achieve VS, both in drug-naive patients [>500 000 HIV-1 RNA copies/mL: median [interquartile range (IQR)] 6.1 (5.1–10.3) months; 100 000–500 000 copies/mL: median (IQR) 4.9 (3.8–6.1) months
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- 2016
19. Efficacy of sofosbuvir and ledipasvir in an HCV+ gastro-resected patient
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Gianpiero D’Offizi, C. Taibi, A. De Nicolò, Massimo Tempestilli, Antonio D'Avolio, Marzia Montalbano, and A. R. Garbuglia
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hepatitis C virus ,Ledipasvir ,medicine.medical_specialty ,ledipasvir ,Sofosbuvir ,sofosbuvir ,030226 pharmacology & pharmacy ,Virological response ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Chronic hepatitis ,Dose adjustment ,Gastro ,Internal medicine ,medicine ,Pharmacology (medical) ,Turning point ,Pharmacology ,business.industry ,gastrectomy ,Surgery ,Clinical Practice ,chemistry ,pharmacokinetics ,030211 gastroenterology & hepatology ,business ,medicine.drug - Abstract
SummaryWhat is known and objective The second-generation direct-acting antivirals represented the first major turning point for the eradication of HCV infection in almost all settings of patients. However, no data were available on use in gastro-resected patients. Case description We report on a gastrectomized patient with chronic hepatitis C infection. She was treated with sofosbuvir and ledipasvir (SOF/LDV) for 12 weeks, with measurement of blood levels of the drugs. She obtained sustained virological response at week 12 and 24 without dose adjustment. What is new and conclusion This case report can provide information useful for clinical practice in this set of patients and can open new perspectives in evaluating actual SOF/LDV bioavailability.
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- 2017
20. Effectiveness of new generation DAAs for HCV infection in a large cohort of Italian people who use drugs (PWID): the cleo-grecas real-world experience
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Vincenzo Messina, Vincenzo Iovinella, Ernesto Claar, Valerio Rosato, Massimo De Luca, Giorgio Barbarini, Giuseppe Cariti, Tommaso Lupia, Mariano Quartini, Gianpiero D’Offizi, Ilaria Luzzitelli, Giustino Parruti, Federica Sozio, Gaetano Scifo, Marco Distefano, Tundo Paolo, Francesco Benanti, Lucio Cosco, Fabio Bulla, Giancarlo Gimignani, Maria Antonietta Di Rosolini, Valeria Pace Palitti, Umberto Vespasiani Gentilucci, Antonio Ascione, Michele Imparato, Luca Rinaldi, Riccardo Nevola, Vito Di Marco, Antonio Craxì, Valeria Morbiducci, Francesco Di Lorenzo, Riccardo Guarisco, Rodolfo Sacco, and Antonio Izzi
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Hepatology - Published
- 2020
21. Long-Term Follow-Up of Acute Hepatitis B: New Insights in Its Natural History and Implications for Antiviral Treatment
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Maria Rosaria Capobianchi, Paola Zaccaro, Laura Vincenzi, Gianpiero D'Offizi, Claudia Minosse, Fabio Iacomi, Stefano Menzo, and Donatella Vincenti
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0301 basic medicine ,HBsAg ,medicine.medical_specialty ,lcsh:QH426-470 ,genotype ,Drug resistance ,Article ,Serology ,acute hepatitis ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Genotype ,Epidemiology ,Genetics ,HBV ,Medicine ,Seroconversion ,Genetics (clinical) ,business.industry ,Vaccination ,lcsh:Genetics ,030104 developmental biology ,Immunology ,030211 gastroenterology & hepatology ,business - Abstract
Acute hepatitis B infection (AHB) is still a common viral acute hepatitis worldwide. As vaccination, antiviral treatment, and immigration are bound to affect the epidemiological landscape of HBV infections, and some of its aspects need to be investigated: (1) the circulation of vaccine escape mutants and of primary drug resistant strains, (2) the change in HBV genotype prevalence, and (3) the clinical implications of AHB and the probability of chronification. The serological, virological, and clinical parameters of 75 patients, acutely infected by HBV, were gathered for a retrospective study. Long-term follow up, either to complete seroconversion or for up to five years, was possible for 44 patients. Sequence analysis of the reverse transcriptase/HBsAg and precore regions was performed to investigate the molecular epidemiology and pathogenesis of recent infections by HBV. Genotype distribution in AHB in Italian patients was radically different from that of chronic infections, with a dramatic increase of extra-European genotypes (A1, F), suggesting that a proportion of AHBs are currently related to imported strains. None of the documented infections occurred in vaccinated individuals, while HBsAg variants (potentially vaccine escape variants) were rare and less prevalent than in chronic infections. No drug resistant strains were observed. Spontaneous viral clearance occurred in all but three cases. Time to viral clearance was inversely proportional to liver damage, but HBsAg titer on day 28 and, better still, HBsAg decay from day 0 to day 28 after admission, were the best predictors of chronification. They are, thus, potentially useful to guide antiviral treatment to prevent chronic evolution.
- Published
- 2018
22. Significance of detectable HCV RNA below the limit of quantification in patients treated with DAAs using standard and ultrasensitive protocols
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Ubaldo Visco-Comandini, Maria Rosaria Capobianchi, Laura Loiacono, Raffaella Lionetti, Gianpiero D'Offizi, Marzia Montalbano, Daniele Lapa, Chiara Taibi, and Anna Rosa Garbuglia
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0301 basic medicine ,Male ,medicine.medical_specialty ,Sustained Virologic Response ,Hepacivirus ,Gastroenterology ,Viral Relapse ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,Virology ,Internal medicine ,Genotype ,medicine ,Humans ,In patient ,Retrospective Studies ,Detection limit ,Univariate analysis ,business.industry ,Hepatitis C, Chronic ,Viral Load ,030112 virology ,Discontinuation ,Regimen ,Infectious Diseases ,Treatment Outcome ,RNA, Viral ,030211 gastroenterology & hepatology ,Female ,Drug Monitoring ,business ,Viral load - Abstract
Predictive factors of HCV relapse after treatment with DAAs are poorly understood. In this study, we aimed to assess whether the residual viral load positivity observed during or at the end of treatment (EOT) has an impact on viral outcome. Blood samples were collected from 337 patients with genotypes (GT) 1a, 1b, 2, 3, and 4 HCV chronic infection, treated with DAAs to determine HCV RNA load by the Abbott RealTime HCV (ART) assay at treatment week (W) 4, at EOT, and 4, 12, 24 weeks after discontinuation. EOT and other samples with "detected
- Published
- 2018
23. Changing utilization of Stavudine (d4T) in HIV-positive people in 2006-2013 in the EuroSIDA study
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Massimo Galli, Vincent Soriano, Manuel Battegay, E. Mularska, AM Johnson, Viktar Mitsura, Bernard Hirschel, E. Simons, François Dabis, Josip Begovac, M. Gargiulo, Luigia Elzi, P. Vernazza, Thérèse Staub, Antoni Jou, Dan Turner, Fiona Mulcahy, Gatell Jm, Kamal Mansinho, G. Mateo, V. Ormaasen, Boron-Kaczmarska A. Boron-Kaczmarska, M. H. Losso, A Horban, Sonia Moreno, Rainer Weber, Christian Pradier, I. Bravo, Gianpiero D’Offizi, I. Yust, Michael Burke, Jens Nielsen, Magnus Gottfredsson, J Weber, Juergen K. Rockstroh, Juan González-Lahoz, Philippe Vanhems, N. Chentsova, G. Kyselyova, Markus Bickel, Christine Katlama, Nicola Gianotti, Irina Khromova, Roberto Esposito, Dalibor Sedláček, Gerd Fätkenheuer, Ladislav Machala, J. Kosmidis, Anders Sönnerborg, Anders Blaxhult, Francesco Mazzotta, S. Chaplinskas, Lars Østergaard, Cristina Tural, Anna Grzeszczuk, Shimon Pollack, Martin Fisher, E. Kravchenko, Marie-Luce Delforge, Claudine Duvivier, N. Vetter, Bruno Ledergerber, A. Vassilenko, Cristina Mussini, K. Kostov, E. Boffi, I. Zeltina, Danica Staneková, Pierre-Marie Girard, Robert Hemmer, L Caldeira, Robert Zangerle, Jan Gerstoft, Smidt Jelena Smidt, [No Value] Schmidt, Elżbieta Jabłonowska, M. Haouzi, G. Hassoun, P Francioli, Dénes Bánhegyi, M. Gutiérrez, Hans-Jürgen Stellbrink, Roger Paredes, A d'Arminio Monforte, O. Suetnov, T. Katzenstein, Robert Flisiak, Brygida Knysz, K. Wojcik, Jordi Puig, Baiba Rozentale, A. Gabbuti, Antonella Castagna, Olaf Degen, J van Lunzen, S. Servitskiy, D. Neau, Court Pedersen, Miłosz Parczewski, Jean-Paul Viard, Fernando Maltez, M. Kundro, D Podlekareva, Nathan Clumeck, G. Scullard, Leo Flamholc, Thomas Benfield, M. Larsen, Hansjakob Furrer, M. Mokráš, A. Thalme, M. Beniowski, I. Mazeu, G. Kutsyna, S De Wit, Peter Reiss, Vincenzo Vullo, Pere Domingo, Igor Karpov, Panagiotis Gargalianos, Ulrik Bak Dragsted, David Jilich, Elena Kuzovatova, Miriam Lichtner, E. Malolepsza, Anastasiia Kuznetsova, S. Buzunova, Matthias Cavassini, Pablo Labarga, A. B E Hansen, A. Maeland, Margaret A. Johnson, Djordje Jevtovic, J. Bruun, A Rakhmanova, Chloe Orkin, M. Pynka, V. Frolov, D. Duiculescu, AN Phillips, J Gasiorowski, Ole Kirk, V. Hadziosmanovic, P. Skinhøj, J. Tomazic, Maria A. Sambeat, R. Pristera, J. W. Goethe, G. Kronborg, Daniel Grint, Elzbieta Bakowska, L. N. Nielsen, A. Rakmanova, Claudio Arici, C. Taibi, Matti Ristola, J. M. Rodriguez, Miró Jm, Amanda Mocroft, H. Trocha, Jd Lundgren, Hila Elinav, Clifford Leen, E. Montesarchio, Eric Florence, Linos Vandekerckhove, Adriano Lazzarin, Jose Medrano, J. Perdios, Manuela Doroana, Brian Gazzard, Antonio Chirianni, Annalisa Ridolfo, A. Antinori, Johannes R. Bogner, Kai Zilmer, G. Xylomenos, Bonaventura Clotet, and H. Sambatakou
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Cart ,Rate ratio ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,parasitic diseases ,medicine ,Pharmacology (medical) ,030212 general & internal medicine ,Poisson regression ,0303 health sciences ,030306 microbiology ,business.industry ,Health Policy ,Stavudine ,medicine.disease ,Confidence interval ,3. Good health ,Infectious Diseases ,HIV-positive people ,Cohort ,symbols ,Lipodystrophy ,business ,Demography ,medicine.drug - Abstract
OBJECTIVES: The long-term side effects of stavudine (d4T) led to recommendations in 2009 to phase out use of this drug. We aimed to describe temporal patterns of d4T use across Europe. METHODS: Patients taking combination antiretroviral therapy (cART) in EuroSIDA with follow-up after 1 January 2006 were included in the study. cART was defined as d4T-containing [d4T plus at least two other antiretrovirals (ARVs) from any class] or non-d4T-containing (at least three ARVs from any class, excluding d4T). Poisson regression was used to describe temporal changes in the prevalence of d4T use and factors associated with initiating d4T. RESULTS: A total of 5850 patients receiving cART on 1 January 2006 were included in the current analysis, rising to 7768 patients on January 1 2013. During this time, the prevalence of d4T use fell from 11.2% to 0.7%, with an overall decline of 19% per 6 months [95% confidence interval (CI) 19-20%]. d4T use declined fastest in Northern Europe [26% (95% CI 23-29%) per 6 months], and slowest in Eastern Europe [17% (95% CI 16-19%) per 6 months]. In multivariable Poisson regression models, new d4T initiations decreased by 14% per 6 months [adjusted incidence rate ratio (aIRR) 0.86; 95% CI 0.80-0.91]. Factors associated with initiating d4T were residence in Eastern Europe (aIRR 4.31; 95% CI 2.17-9.98) versus other European regions and HIV RNA > 400 copies/mL (aIRR 3.11; 95% CI 1.60-6.02) versus HIV RNA < 400 copies/mL. CONCLUSIONS: d4T use has declined sharply since 2006 to low levels in most regions; however, a low but persistent level of d4T use remains in Eastern Europe, where new d4T initiations post 2006 are also more common. The reasons for the regional differences may be multifactorial, but it is important to ensure that all clinicians treating HIV-positive patients are aware of the potential harmful effects associated with d4T.
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- 2015
24. Dynamics of HCV genotype 4 resistance-associated variants during virologic escape with pIFN/RBV+daclatasvir: A case study using ultra deep pyrosequencing
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Barbara, Bartolini, Raffaella, Lionetti, Emanuela, Giombini, Catia, Sias, Chiara, Taibi, Marzia, Montalbano, Gianpiero, D'Offizi, D'Offizi, Gianpiero, Fiona, McPhee, Eric A, Hughes, Nannan, Zhou, Giuseppe, Ippolito, Anna Rosa, Garbuglia, and Maria R, Capobianchi
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Adult ,Pyrrolidines ,Daclatasvir ,Adolescent ,Genotype ,Hepatitis C virus ,Hepacivirus ,Viral quasispecies ,Viral Nonstructural Proteins ,Biology ,medicine.disease_cause ,Antiviral Agents ,Virology ,Drug Resistance, Viral ,Ribavirin ,medicine ,Humans ,Treatment Failure ,NS5A ,Haplotype ,Imidazoles ,Genetic Variation ,Valine ,Hepatitis C, Chronic ,Middle Aged ,Viral Load ,Infectious Diseases ,Carbamates ,Interferons ,Viral load ,Ultra deep pyrosequencing ,medicine.drug - Abstract
Background Daclatasvir (DCV) is an approved NS5A inhibitor with potent anti-HCV activity and broad genotype coverage. DCV resistance-associated variants (RAVs) have been described for patients infected with genotype (GT) 1, but increased GT4 prevalence in European countries as a result of immigration has boosted interest in this genotype. Objectives Establishment of NS5A variability in treatment-naive patients with HCV genotype 4 infection and a case study of the dynamics of resistance-associated variants in a virologic failure receiving pIFN/RBV + DCV, as assessed by ultra-deep sequencing. Study design Five treatment-naive GT4 patients (GT4a [n = 1], GT4d [n = 3], GT4o [n = 1]) were evaluated for inclusion in the COMMAND-4 study and treatment with pIFN/RBV ± DCV. Results Patient (Pt) 1 received pIFN/RBV; Pts2–4 received pIFN/RBV + DCV; Pt5 was a screening failure. Pt1 relapsed; Pt2 experienced breakthrough at Wk4; Pts3 and 4 achieved a sustained virologic response. No substitutions associated with DCV-resistance were detected at baseline. In terms of viremic time points for Pts1 and 2, the extent of NS5A diversity pre-treatment was not significantly related to viral load (r = −0568; p = 0.035). In Pt2, multiple substitutions associated with DCV-resistance were observed after breakthrough at NS5A amino acid positions 28, 31 and 93. These substitutions were frequently observed on the same haplotype (L28S + M31I = 55.52, 82.50, and 99.36% at Wk4, 8 and 9; L28S + M31I + Y93H = 11.77, 5.01 and Conclusions This is the first report to describe DCV-resistance in patients infected with GT4d, supporting a possible role for a recently described RAV (L28S), and presenting the dynamics of HCV quasispecies during therapy failure, with indications of changes of diversity and association of mutations.
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- 2015
25. Clinical and virological predictors of sustained response with an interferon-based simeprevir regimen for patients with chronic genotype 1 hepatitis C virus infection
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Gianpiero, D'Offizi, Calogero, Cammà, Chiara, Taibi, Michael, Schlag, Karin, Weber, Maria, Palma, Ralph, DeMasi, Katrien, Janssen, James, Witek, and Raffaella, Lionetti
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Adult ,Male ,Adolescent ,Genotype ,Interleukins ,Hepacivirus ,Hepatitis C, Chronic ,Middle Aged ,Young Adult ,Recurrence ,Simeprevir ,Albumins ,Ribavirin ,Humans ,RNA, Viral ,Female ,Interferons ,Aged - Abstract
Simeprevir plus peg-interferon/ribavirin (PR) is approved to treat chronic hepatitis C (HCV) genotype 1 (GT1) and GT4 infection. This study aimed to assess baseline and on-treatment the factors predictive of sustained virologic response 12-weeks post-treatment (SVR12) in patients receiving 12 weeks of simeprevir plus PR followed by 12 or 36 weeks of PR. Data from participants in four studies (QUEST-1, QUEST-2, ATTAIN and PROMISE) were pooled to examine the efficacy and safety of simeprevir+PR in HCV GT1 patients. The predictive power of baseline variables for SVR12 was assessed using univariate and multivariate logistic regression models while the relationship between early (Week 4) on-treatment response and SVR12 was analyzed by GT1 subtype and treatment experience. Data for 1160 patients were analyzed (overall SVR12: 71%). Baseline factors predictive of SVR12 were: IL28B CC genotype, GT1a/Q80K-negative, treatment-naïve/prior relapser, no cirrhosis, HCV-RNA ≤2,000,000IU/mL, albumin42g/L, platelets200x109 /L. Patients with HCV GT1b (86%), IL28B CC genotype (87%), and treatment-naïve patients (83%) were predicted to achieve the highest SVR12 rates and rates of rapid virologic response. Week 4 early on-treatment response identified treatment-naïve and prior relapse patients likely to achieve SVR12. Patients likely to respond to simeprevir+PR can be identified using baseline factors. Early on-treatment response predicts treatment success.
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- 2017
26. Treatment of Hepatitis C virus infection in Italy: A consensus report from an expert panel
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Carlo Federico Perno, Elisabetta Degasperi, Stefano Fagiuoli, Vincenza Calvaruso, Salvatore Petta, Raffaele Bruno, Alessia Ciancio, Giovanni Battista Gaeta, Giovanni Raimondo, Carlo Ferrari, Anna Linda Zignego, Massimo Andreoni, Massimo Puoti, Stefano Bonora, Giovanni Di Perri, Gloria Taliani, Pietro Andreone, Alfredo Alberti, Maurizia Rossana Brunetto, Vito Di Marco, Erica Villa, Sara Piovesan, Alessio Aghemo, Mauro Viganò, Francesca Ceccherini-Silberstein, Francesco Paolo Russo, Savino Bruno, Ugo Trama, Adriano M. Pellicelli, Antonio Craxì, Gianpiero D'Offizi, Piero Colombatto, Nicola Caporaso, Valeria Cento, Viganò, Mauro, Perno, Carlo Federico, Craxì, Antonio, Aghemo, Alessio, Alberti, Alfredo, Andreone, Pietro, Andreoni, Massimo, Bonora, Stefano, Brunetto, Maurizia Rossana, Bruno, Raffaele, Bruno, Savino, Calvaruso, Vincenza, Caporaso, Nicola, Ceccherini-Silberstein, Francesca, Cento, Valeria, Ciancio, Alessia, Colombatto, Piero, Degasperi, Elisabetta, Di Marco, Vito, Di Perri, Giovanni, D'offizi, Gianpiero, Fagiuoli, Stefano, Ferrari, Carlo, Gaeta, Giovanni Battista, Pellicelli, Adriano, Petta, Salvatore, Piovesan, Sara, Puoti, Massimo, Raimondo, Giovanni, Russo, Francesco Paolo, Taliani, Gloria, Trama, Ugo, Villa, Erica, Zignego, Anna Linda, Savino, Bruno, Vito, Marco, D'Offizi, Gianpiero, Russo, FRANCESCO PAOLO, Gaeta, G. B., Viganã², M., Perno, C., Craxi, A., Calvaruso, V, Di Marco, V, Petta, S, Vigano, M, Perno, C, Craxi, A, Aghemo, A, Alberti, A, Andreone, P, Andreoni, M, Bonora, S, Brunetto, M, Bruno, R, Bruno, S, Caporaso, N, Ceccherini-Silberstein, F, Cento, V, Ciancio, A, Colombatto, P, Degasperi, E, Di Perri, G, D'Offizi, G, Fagiuoli, S, Ferrari, C, Gaeta, G, Pellicelli, A, Piovesan, S, Puoti, M, Raimondo, G, Russo, F, Taliani, G, Trama, U, Villa, E, and Zignego, A
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Liver Cirrhosis ,Direct-acting antiviral agent ,Fibrosi ,Hepacivirus ,Chronic liver disease ,medicine.disease_cause ,Clinical knowledge ,Virological response ,0302 clinical medicine ,80 and over ,030212 general & internal medicine ,Chronic ,Antiviral treatment ,Cirrhosis ,Direct-acting antiviral agents ,Hepatitis C ,RAV ,Treatment failure ,Aged, 80 and over ,Gastroenterology ,Hepatology ,Middle Aged ,Viral Load ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,Italy ,Liver ,Combination ,030211 gastroenterology & hepatology ,Drug Therapy, Combination ,Human ,Adult ,medicine.medical_specialty ,Consensus ,Hepatitis C virus ,Liver Cirrhosi ,Consensu ,Antiviral Agents ,Unmet needs ,03 medical and health sciences ,Young Adult ,Drug Therapy ,Internal medicine ,medicine ,Humans ,Intensive care medicine ,Aged ,Antiviral Agent ,Hepaciviru ,Cirrhosi ,business.industry ,Hepatitis C, Chronic ,medicine.disease ,Virology ,Fibrosis ,Position paper ,business - Abstract
Hepatitis C virus (HCV) infection remains one of the main causes of chronic liver disease worldwide. The advent of direct-acting antivirals (DAAs) has significantly improved the course of patients with chronic HCV infection (CHC), due to the ability of these drugs to achieve high rates of sustained virological response (SVR). These exceedingly high rates of SVR and the excellent safety data have been confirmed in real life practice. Evolving guidelines have been issued by national and international scientific societies in accordance with the progression of clinical knowledge and the availability of new DAAs. These recommendations, however, may not be applied universally because of delays in drugs reimbursability in different countries and because some National Health Systems identify only patients with advanced disease as a treatment priority. Italy in this regard is a prototype about DAAs treatment of CHC patients. With the aim to assess the Italian treatment experience with DAAs and to respond to unmet needs in treatment optimization of antiviral therapy in specific settings of CHC patients, a group of Italian experts met in Stresa in February 2017. The summary of the considerations arising from this two-day meeting and some statements regarding a few open issues are reported in this position paper.
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- 2017
27. Laparoscopic liver resections in normal and cirrhotic livers: A retrospective analysis in a tertiary hepato-biliary unit
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Mario Antonini, Claudio Puoti, Marco Colasanti, Lidia Colace, Pierluca Piselli, Raffaella Lionetti, Roberto Santoro, Pasquale Lepiane, Giuseppe Maria Ettorre, Giovanni Vennarecci, Gianpiero D'Offizi, and Andrea Laurenzi
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Liver Cirrhosis ,Male ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Cirrhosis ,Laparoscopic liver resections ,Liver cirrhosis ,Aged ,Blood Loss, Surgical ,Case-Control Studies ,Female ,Hepatectomy ,Hepatitis C, Chronic ,Humans ,Laparoscopy ,Length of Stay ,Liver Neoplasms ,Middle Aged ,Retrospective Studies ,Tertiary Care Centers ,Treatment Outcome ,Postoperative Complications ,Gastroenterology ,Hepatology ,Liver resections ,Liver disease ,Blood loss ,Surgical ,Internal medicine ,medicine ,Retrospective analysis ,Blood Loss ,Chronic ,medicine.diagnostic_test ,business.industry ,Carcinoma ,Hepatocellular ,Hepatitis C ,medicine.disease ,Surgery ,Hepatocellular carcinoma ,business - Abstract
Liver surgery in patients with underlying liver disease results in higher mortality and morbidity rates compared to patients without underlying liver disease. Laparoscopy seems to have good results in patients with normal liver in terms of postoperative outcomes, but is more challenging in cirrhotic patients. Aim of this study was to evaluate the feasibility of laparoscopic liver resection both in normal and cirrhotic livers, and secondary endpoint was to compare the surgical results.We retrospectively evaluated 105 patients who underwent laparoscopic liver resection between November 2001 and January 2012. Candidates for laparoscopic liver resection were divided into two groups according to the presence or absence of an underlying liver disease.105 patients (52.4% males, median age 56.1 years) were enrolled, and 37.1% had liver cirrhosis. Hepatocellular carcinoma in hepatitis C virus-related cirrhosis (89.7%) and liver metastases (57.6%) were the main indications for surgery in patients with cirrhosis and non-cirrhotic livers, respectively. None of the patients died post-operatively. Cirrhotic patients had greater blood loss (100 vs 50 ml; p0.012) and longer hospital stays (6 vs 4 days; p0.031) compared to non-cirrhotics.Laparoscopic liver resections are safe and feasible procedures in both patients with cirrhotic and non-cirrhotic livers.
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- 2014
28. Determination of telaprevir in plasma of HCV-infected patients by HPLC-UV
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Pasquale Narciso, Tecla Gasperi, Marzia Montalbano, Gianpiero D'Offizi, Paolo Ascenzi, Leopoldo Paolo Pucillo, Massimo Tempestilli, Antonio D'Avolio, and Elisa Milano
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Analyte ,Chromatography ,medicine.diagnostic_test ,Elution ,Ribavirin ,Clinical Biochemistry ,Cell Biology ,Hepatitis C ,Pharmacology ,medicine.disease ,Biochemistry ,Telaprevir ,chemistry.chemical_compound ,chemistry ,Therapeutic drug monitoring ,Pegylated interferon ,Genetics ,medicine ,Molecular Biology ,Ammonium acetate ,medicine.drug - Abstract
Telaprevir is a direct acting antiviral agent, used with pegylated interferon and ribavirin for the management of chronic hepatitis C virus (HCV) genotype 1 infection, in patients not responding to therapy with pegylated interferon and ribavirin only. Although 75% of patients achieve a sustained virological response after treatment with telaprevir, adverse drug-drug interactions and undesirable events often occur. Therefore, telaprevir monitoring is pivotal to improve the management of HCV infection. Here, the first High-Performance Liquid Chromatography-Ultraviolet (HPLC-UV) method to quantify telaprevir in human plasma of HCV-genotype 1-infected patients is reported. The volume of the plasma sample was 700 μL. This method involved automated solid-phase extraction with Oasis HLB Cartridge 1 cc (divinylbenzene and N-vinylpyrrolidone). The extracted samples were reconstituted with 150 μL of 60/40 water/acetonitrile. Thirty microliters of these samples was injected into a HPLC-UV system, and the analytes were eluted on a X Terra(®) RP18 column (250 mm × 4.6 mm i.d.) with a particle size of 5 μm. The mobile phase (ammonium acetate buffer, 150 mM, pH 8.0, and methanol:acetonitrile 50:50) was delivered at 1.0 mL/min with linear gradient elution. The total run time for a single analysis was 16 min; telaprevir was detected by UV at 276 and 286 nm. The calibration curve was linear from 312.5 to 20,000 ng/mL (r(2) > 0.996). The absolute recovery of telaprevir ranged between 89 and 93% at concentrations of quality control samples of 800, 4,000, 8,000, and 16,000 ng/mL. Both precision and accuracy were always
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- 2013
29. Effectiveness of Paritaprevir/Ritonavir/Ombitasvir/Dasabuvir in Hemodialysis Patients With Hepatitis C Virus Infection and Advanced Liver Fibrosis: Case Reports
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Raffaella Lionetti, Gianpiero D'Offizi, Francesca Romana Ponziani, Laura Gianserra, Antonio Gasbarrini, Massimo Siciliano, Maurizio Pompili, and Caterina Pasquazzi
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Cyclopropanes ,Liver Cirrhosis ,Male ,030232 urology & nephrology ,medicine.disease_cause ,Gastroenterology ,Severity of Illness Index ,chemistry.chemical_compound ,0302 clinical medicine ,2-Naphthylamine ,Medicine ,Anilides ,Sulfonamides ,Dasabuvir ,Valine ,Hepatitis C ,Middle Aged ,Treatment Outcome ,Nephrology ,HCV ,030211 gastroenterology & hepatology ,Drug Therapy, Combination ,medicine.drug ,medicine.medical_specialty ,Macrocyclic Compounds ,Proline ,Hepatitis C virus ,Lactams, Macrocyclic ,Antiviral Agents ,03 medical and health sciences ,Renal Dialysis ,Internal medicine ,Humans ,Uracil ,therapy ,Ritonavir ,business.industry ,Ribavirin ,Settore MED/09 - MEDICINA INTERNA ,Hepatitis C, Chronic ,medicine.disease ,Ombitasvir ,Regimen ,chemistry ,Paritaprevir ,Immunology ,Kidney Failure, Chronic ,Carbamates ,business - Abstract
Hepatitis C virus infection is common among patients on hemodialysis therapy and is an important cause of morbidity and mortality. We investigated the safety and effectiveness of a paritaprevir/ritonavir/ombitasvir/dasabuvir regimen in a group of 10 patients on hemodialysis therapy with genotype 1a, 1b, or 4 hepatitis C virus infection who had predictors of unfavorable response, such as compensated cirrhosis (7 patients) or advanced fibrosis and failure of previous therapy (3 patients). The treatment, with or without ribavirin, was administered daily for 12 or 24 weeks. Clinical and virologic assessment was performed every 4 weeks during the treatment and at posttreatment weeks 4 and 12. All patients achieved a sustained virologic response at posttreatment week 12. 80% of patients reported at least one adverse event: fatigue and anemia of mild intensity were the most common; a single episode of moderate liver decompensation was observed. The paritaprevir/ritonavir/ombitasvir/dasabuvir antiviral regimen is effective and well tolerated in genotype 1 or 4 hepatitis C virus–infected patients on hemodialysis therapy with compensated cirrhosis and/or failure of previous treatments.
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- 2016
30. Evolutionary trends of resistance mutational patterns of HBV reverse transcriptase over years (2002-2012) of different treatment regimens: The legacy of lamivudine/adefovir combination treatment
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Donatella Vincenti, Stefano Menzo, Mariacarmela Solmone, Pierluca Piselli, Gianpiero D'Offizi, and Maria Rosaria Capobianchi
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0301 basic medicine ,Hepatitis B virus ,Guanine ,Genotype ,DNA Mutational Analysis ,Organophosphonates ,Drug resistance ,Biology ,medicine.disease_cause ,Antiviral Agents ,Evolution, Molecular ,03 medical and health sciences ,0302 clinical medicine ,Hepatitis B, Chronic ,Virology ,Drug Resistance, Viral ,medicine ,Adefovir ,Humans ,Treatment Failure ,Tenofovir ,Pharmacology ,Polymorphism, Genetic ,Adenine ,virus diseases ,Lamivudine ,RNA-Directed DNA Polymerase ,Entecavir ,Resistance mutation ,medicine.disease ,030112 virology ,Viral evolution ,DNA, Viral ,Mutation ,030211 gastroenterology & hepatology ,Drug Therapy, Combination ,Viral hepatitis ,Sequence Analysis ,medicine.drug - Abstract
Antiviral therapy has revolutionized treatment of chronic HBV infections. First generation compounds, lamivudine and adefovir, displayed a high rate of treatment failures, and have been replaced by more potent compounds with high genetic barrier to resistance. However, the evolution of the virus towards resistance due the use of first generation compounds may still provide useful information for a better management of current antivirals. A single center sequence database including 705 HBV reverse transcriptase sequences from patients failing antiviral treatments (2002-2012) has been statistically analyzed to highlight viral evolution in relationship to the use of antiviral compounds and to their associations/sequencing in those years. The influence of viral genotypes and polymorphisms on resistance-related mutational patterns was also investigated. This study documents how, after the first years of antiviral therapy, the use of adefovir as an add-on strategy allowed a consistent reduction treatment failures. It also documents the effects of the initial misuse of entecavir in lamivudine experienced patients. In the latest years, the correct use of entecavir and the introduction of tenofovir allowed further curbing of resistance-related treatment failures, which virtually disappeared. Furthermore, the study allows a better understanding of how viral genotype (A vs D) conditions specific mutational pathways to resistance against lamivudine and entecavir, and demonstrates that the use of adefovir in lamivudine experienced patients is associated to peculiar mutational patterns, in particular A181V + F/Y221L. Despite some concern may arise for patients previously treated with lamivudine/adefovir, in sequence or combination, where the virus may have developed a lower genetic barrier against resistance to tenofovir, the outlook of antiviral treatment of HBV infection should be quite optimistic.
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- 2016
31. P.09.4: Effectiveness of HCV Antiviral Treatment in Patients with Cirrhosis or Advanced Fibrosis and end-Stage Kidney Disease on Dialysis
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Antonio Gasbarrini, Massimo Siciliano, Caterina Pasquazzi, Laura Gianserra, Raffaella Lionetti, Maurizio Pompili, Francesca Romana Ponziani, and Gianpiero D’Offizi
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medicine.medical_specialty ,Cirrhosis ,Hepatology ,business.industry ,medicine.medical_treatment ,Gastroenterology ,medicine.disease ,Advanced fibrosis ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,030211 gastroenterology & hepatology ,In patient ,030212 general & internal medicine ,Antiviral treatment ,business ,End-stage kidney disease ,Dialysis - Published
- 2017
32. Effectiveness and safety of simeprevir-based regimens for hepatitis C in Italy
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Hamid Hasson, Maria Palma, Alessia Giorgini, Giovanni Battista Gaeta, Alessio Aghemo, Gianpiero D'Offizi, Roberta Termini, Barbara Menzaghi, Giuseppina Brancaccio, Gaeta, Giovanni Battista, Aghemo, Alessio, Menzaghi, Barbara, D'Offizi, Gianpiero, Giorgini, Alessia, Hasson, Hamid, Brancaccio, Giuseppina, Palma, Maria, and Termini, Roberta
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Adult ,Male ,Simeprevir ,medicine.medical_specialty ,Sustained Virologic Response ,Sofosbuvir ,Liver Cirrhosi ,Hepatitis C virus ,medicine.disease_cause ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Ribavirin ,Clinical endpoint ,Medicine ,030212 general & internal medicine ,Aged ,Antiviral Agent ,Hepaciviru ,business.industry ,General Medicine ,Hepatitis C ,Middle Aged ,medicine.disease ,Regimen ,Treatment Outcome ,Italy ,Tolerability ,chemistry ,Drug Therapy, Combination ,Female ,030211 gastroenterology & hepatology ,Cohort Studie ,business ,Human ,medicine.drug - Abstract
The combination of the direct-acting antivirals, simeprevir (SMV) and sofosbuvir (SOF), was the first highly efficacious interferon-free combination for treating patients with hepatitis C virus (HCV), and was widely used in Italy as a result. The aim of this study was to evaluate effectiveness and safety of SMV in Italian patients with HCV genotype (GT) 1 and 4 overall, by treatment regimen [SMV/SOF and SMV/SOF+ribavirin (RBV)], cirrhosis status, and GT (GT1a, GT1b, and GT4). An observational multicenter cohort study was conducted in 46 centers across Italy. Adult HCV + GT1 or GT4 patients, naive or treatment-experienced, with or without cirrhosis, who underwent treatment with a SMV-containing regimen from May to September 2015 were included. The primary endpoint was sustained virologic response (SVR), defined as undetectable serum HCV RNA levels 12 weeks after treatment end (SVR12). The secondary endpoints included duration of treatment, safety and tolerability of each treatment regimen, and SVR by treatment and according to response to previous treatment and fibrosis stage. The association between SVR and a subset of the most clinically relevant variables was investigated by a multivariate logistic regression analysis. A total of 349 HCV-positive patients treated with an SMV-based regimen were enrolled, of whom 342 received SMV/SOF ± RBV and were included in this analysis. Most patients (59.4%) were treatment-experienced and had cirrhosis (78.1%). In the group receiving SMV/SOF + RBV, most (63.1%) were treatment-experienced and 82.9% had cirrhosis. Three patients were lost to follow-up; 330 patients receiving SMV/SOF ± RBV (96.5%) were treated for 12 weeks. Overall, SVR12 was achieved by 324 patients [94.2%, 95% confidence interval (95% CI) 92–97]. When stratified by treatment and clinical and virologic characteristics, SVR12 was achieved by 77 of 79 [97.5% (95% CI 94.0–100.0)] and 247 of 263 [93.9% (95% CI 91.0–96.8)] patients receiving SMV/SOF and SMV/SOF + RBV, respectively; 132 of 139 (95.0%) naive versus 192/203 (94.6%) treatment-experienced patients; 250 of 267 (93.6%) cirrhotic and 56 of 62 (90.3%) HIV coinfected patients. SMV-based regimens were generally well tolerated. Adverse events leading to treatment discontinuations were not observed. A high proportion of patients treated with SMV/SOF-based regimens achieved SVR12 in this study. A high SVR12 rate was also achieved in patients with cirrhosis, treatment experience, and HUV coinfected patients.
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- 2018
33. A prospective multicentre study of the epidemiology and outcomes of bloodstream infection in cirrhotic patients
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Ivan Gentile, Jesús Rodríguez-Baño, Alia Eworo, Gloria Taliani, E. Nadal, M. Valerio, A. Beteta-Lopez, Christoph Schramm, Pierluigi Viale, Bruno Baršić, Cristina Badia, S. Ludovisi, Alberto Enrico Maraolo, Gabriella Verucchi, Elena Seminari, M. de Cueto, Maddalena Giannella, E. Boumis, S. Grieco, Pilar Retamar, Nazaret Cobos-Trigueros, Caterina Campoli, Emilio Bouza, Mauro Bernardi, Patrizia Burra, M. Varguvic, Sara K. Tedeschi, Esther Calbo, María Dolores González-Ripoll Navarro, N. Bar Sinai, Mario Venditti, Andreas Stallmach, Russell E. Lewis, Guglielmo Borgia, Patricia Muñoz, Antonio Riccardo Buonomo, Mical Paul, Gianpiero D'Offizi, Michele Bartoletti, Paolo Caraceni, M.A. Galan-Ladero, Mario Tumbarello, Manuela Merli, Marco Senzolo, G. Siccardi, R. Losito, A. Ottobrelli, E. Lopez Cortes, A. Rianda, Cristina Lucidi, Simone Ambretti, Nicola Petrosillo, M. Torrani Cerenzia, Tony Bruns, Bartoletti, M., Giannella, M., Lewis, R., Caraceni, P., Tedeschi, S., Paul, M., Schramm, C., Bruns, T., Merli, M, Cobos-Trigueros, N., Seminari, E., Retamar, P., Muñoz, P., Tumbarello, M., Burra, P., Torrani Cerenzia, M., Barsic, B., Calbo, E., Maraolo, A.E., Petrosillo, N., Galan-Ladero, M.A., D'Offizi, G., Bar Sinai, N., Rodríguez-Baño, J., Verucchi, G., Bernardi, M., Viale, P., Bartoletti, M, Giannella, M, Lewis, R, Caraceni, P, Tedeschi, S, Paul, M, Schramm, C, Bruns, T, Cobos-trigueros, N, Seminari, E, Retamar, P, Muñoz, P, Tumbarello, M, Burra, P, Torrani Cerenzia, M, Barsic, B, Calbo, E, Maraolo, Ae, Petrosillo, N, Galan-ladero, Ma, D'Offizi, G, Bar Sinai, N, Rodríguez-baño, J, Verucchi, G, Bernardi, M, Viale, P, Campoli, C, Siccardi, G, Ambretti, S, Stallmach, A, Venditti, M, Lucidi, C, Ludovisi, S, De Cueto, M, Navarro, Md, Lopez Cortes, E, Bouza, E, Valerio, M, Eworo, A, Losito, R, Senzolo, M, Nadal, E, Ottobrelli, A, Varguvic, M, Badia, C, Borgia, G, Gentile, I, Buonomo, Ar, Boumis, E, Beteta-lopez, A, Rianda, A, Taliani, G, and Grieco, S.
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Liver Cirrhosis ,Male ,Microbiology (medical) ,medicine.medical_specialty ,Multidrug-resistant pathogen ,Comorbidity ,Bloodstream infection ,Bacterial infections ,Bloodstream infections ,CLIF-SOFA ,Multidrug-resistant pathogens ,Logistic regression ,Liver cirrhosi ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Sepsis ,Internal medicine ,Epidemiology ,medicine ,Humans ,Prospective Studies ,030212 general & internal medicine ,Mortality ,Risk factor ,Intensive care medicine ,Prospective cohort study ,Aged ,Proportional hazards model ,business.industry ,Liver cirrhosis ,Infectious Diseases ,Mortality rate ,Hazard ratio ,Disease Management ,Drug Resistance, Microbial ,General Medicine ,Middle Aged ,Prognosis ,Patient Outcome Assessment ,Population Surveillance ,Female ,030211 gastroenterology & hepatology ,Bacterial infection ,business ,Cohort study - Abstract
ESGBIS/BICHROME Study Group: C. Campoli, G. Siccardi, S. Ambretti, A. Stallmach, M. Venditti, C. Lucidi, S. Ludovisi, M. De Cueto, M. D. Navarro, E. Lopez Cortes, E. Bouza, M. Valerio, A. Eworo, R. Losito, M. Senzolo, E. Nadal, A. Ottobrelli, M. Varguvic, C. Badia, G. Borgia, I. Gentile, A. R. Buonomo, E. Boumis, A. Beteta-Lopez, A. Rianda, G. Taliani, S. Grieco., [Objectives] To describe the current epidemiology of bloodstream infection (BSI) in patients with cirrhosis; and to analyse predictors of 30-day mortality and risk factors for antibiotic resistance., [Methods] Cirrhotic patients developing a BSI episode were prospectively included at 19 centres in five countries from September 2014 to December 2015. The discrimination of mortality risk scores for 30-day mortality were compared by area under the receiver operator risk and Cox regression models. Risk factors for multidrug-resistant organisms (MDRO) were assessed with a logistic regression model., [Results] We enrolled 312 patients. Gram-negative bacteria, Gram-positive bacteria and Candida spp. were the cause of BSI episodes in 53%, 47% and 7% of cases, respectively. The 30-day mortality rate was 25% and was best predicted by the Sequential Organ Failure Assessment (SOFA) and Chronic Liver Failure–SOFA (CLIF-SOFA) score. In a Cox regression model, delayed (>24 hours) antibiotic treatment (hazard ratio (HR) 7.58; 95% confidence interval (CI) 3.29–18.67; p < 0.001), inadequate empirical therapy (HR 3.14; 95% CI 1.93–5.12; p < 0.001) and CLIF-SOFA score (HR 1.35; 95% CI 1.28–1.43; p < 0.001) were independently associated with 30-day mortality. Independent risk factors for MDRO (31% of BSIs) were previous antimicrobial exposure (odds ratio (OR) 2.91; 95% CI 1.73–4.88; p < 0.001) and previous invasive procedures (OR 2.51; 95% CI 1.48–4.24; p 0.001), whereas spontaneous bacterial peritonitis as BSI source was associated with a lower odds of MDRO (OR 0.30; 95% CI 0.12–0.73; p 0.008)., [Conclusions] MDRO account for nearly one-third of BSI in cirrhotic patients, often resulting in delayed or inadequate empirical antimicrobial therapy and increased mortality rates. Our data suggest that improved prevention and treatment strategies for MDRO are urgently needed in the liver cirrhosis patients.
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- 2018
34. Lack of reduction of serum alphafetoprotein during treatment with direct antiviral agents predicts hepatocellular carcinoma development in a large cohort of patients with HCV-related cirrhosis
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C. Masetti, M. Lupo, Marzia Montalbano, Ubaldo Visco-Comandini, Valerio Giannelli, Elisabetta Teti, Raffaella Lionetti, A. Brega, Simona Francioso, Chiara Taibi, Massimo Siciliano, Antonio Picardi, Massimo Andreoni, Mario Angelico, Umberto Vespasiani Gentilucci, Giovanni Galati, Antonio Gasbarrini, Adriano M. Pellicelli, Gianpiero D'Offizi, Francesca Romana Ponziani, Chiara Dell'Unto, Maurizio Pompili, and Adriano De Santis
- Subjects
Male ,Serum ,0301 basic medicine ,Cirrhosis ,Sustained Virologic Response ,medicine.medical_treatment ,Liver transplantation ,Gastroenterology ,Liver disease ,0302 clinical medicine ,Aged, 80 and over ,Univariate analysis ,Incidence ,Liver Neoplasms ,Hepatitis C ,hepatocellular carcinoma ,Middle Aged ,Infectious Diseases ,Hepatocellular carcinoma ,Female ,030211 gastroenterology & hepatology ,alpha-Fetoproteins ,Alpha-fetoprotein ,alpha-fetoprotein ,direct-acting antiviral agents ,hepatitis C ,Adult ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Settore MED/17 - Malattie Infettive ,Antiviral Agents ,Risk Assessment ,03 medical and health sciences ,Virology ,Internal medicine ,medicine ,Humans ,neoplasms ,Aged ,Hepatology ,business.industry ,Hepatitis C, Chronic ,medicine.disease ,Fibrosis ,digestive system diseases ,Large cohort ,030104 developmental biology ,Paritaprevir ,business - Abstract
Risk of hepatocellular carcinoma (HCC) in hepatitis C virus cirrhotic patients treated with direct-acting antiviral agents (DAA) is still debating. We investigated it in a large cohort. The cohort comprised 1045 cirrhotic patients who completed treatment with DAA, with a median follow-up of 17.3 months after end of treatment (EOT), including 943 patients without history of HCC and 102 previously treated for HCC. The majority were men (59.9%), with compensated cirrhosis (88.8%), genotype 1b (44.7%). Univariate, multivariate analysis and Kaplan-Meier curves were performed to detect predictors of HCC in patients with and without reduction in alpha-fetoprotein (AFP) during treatment. SVR12 was 95.6%. HCC developed in 95 (9.9%), including 54 of 943 (5.7%) occurrent and 41 of 102 (39%) recurrent tumours. De novo were more often unifocal (P = 0.01) and curable (P = 0.03). AFP decreased from 16.1 ± 36.2 mg/dL (baseline) to 11.4 ± 55 mg/dL (EOT). At univariate analysis, predictors were a previous HCC, older age, higher model for end-stage liver disease, prolonged INR, lower platelets, baseline and EOT AFP, virological failure and no reduction in AFP during treatment. Kaplan-Meier curves showed lower incidence of HCC in patients showing any reduction in AFP (P = 0.001). Those with AFP
- Published
- 2018
35. The preventive phase I trial with the HIV-1 Tat-based vaccine
- Author
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Guido Palamara, Alessandra Latini, Giuseppe Tambussi, Paolo Monini, Adriano Lazzarin, Barbara Ensoli, Gianpiero D'Offizi, Maria Josè Ruiz Alvarez, Enrico Garaci, Barbara Collacchi, Massimo Giuliani, Arianna Scoglio, Aldo Di Carlo, Chiara Tassan Din, Marina Giulianelli, Maria Carta, Andrea Antinori, Pasquale Narciso, Stefania Bellino, Antonella Tripiciano, Olimpia Longo, Mauro Magnani, Fabrizio Ensoli, Valeria Fiorelli, Vittorio Francavilla, Angela Arancio, Giovanni Paniccia, and Raffaele Visintini
- Subjects
Adult ,Male ,T-Lymphocytes ,HIV Infections ,Interferon-gamma ,Immune system ,Acquired immunodeficiency syndrome (AIDS) ,Clinical endpoint ,medicine ,Humans ,AIDS Vaccines ,Immunity, Cellular ,General Veterinary ,General Immunology and Microbiology ,biology ,business.industry ,Public Health, Environmental and Occupational Health ,Middle Aged ,biology.organism_classification ,medicine.disease ,Virology ,Clinical trial ,Vaccination ,Infectious Diseases ,Immunization ,Immunology ,Lentivirus ,HIV-1 ,biology.protein ,Molecular Medicine ,Female ,Interleukin-4 ,Antibody ,business ,Epitope Mapping - Abstract
The native HIV-1 Tat protein was chosen as vaccine candidate for phase I clinical trials based on its role in the natural infection and AIDS pathogenesis, on the association of Tat-specific immune response with the asymptomatic stage as well as on its sequence conservation among HIV clades. A randomized, double blind, placebo-controlled phase I study (ISS P-001) was conducted in healthy adult volunteers without identifiable risk of HIV infection. Tat was administered 5 times monthly, subcute in alum or intradermic alone at 7.5 μg, 15 μg or 30 μg, respectively (ClinicalTrials.gov identifier: NCT00529698 ). Vaccination with Tat resulted to be safe and well tolerated (primary endpoint) both locally and systemically. In addition, Tat induced both Th1 and Th2 type specific immune responses in all subjects (secondary endpoint) with a wide spectrum of functional antibodies that are rarely seen in natural infection, providing key information for further clinical development of the Tat vaccine candidate.
- Published
- 2009
36. Parallel Conduction of the Phase I Preventive and Therapeutic Trials Based on the Tat Vaccine Candidate
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Vittorio Francavilla, Olimpia Longo, Adriano Lazzarin, A. Di Carlo, Mauro Magnani, Antonella Tripiciano, Guido Palamara, Fabrizio Ensoli, Angela Arancio, Giuseppe Tambussi, Marinella Giulianelli, Gianpiero D’Offizi, Paolo Monini, C. Tassan Din, Arianna Scoglio, Maria Carta, Giovanni Paniccia, Raffaele Visintini, Pasquale Narciso, Maria Elena Laguardia, Massimo Giuliani, Stefania Bellino, Andrea Antinori, Massimo Campagna, Barbara Ensoli, Valeria Fiorelli, and Barbara Collacchi
- Subjects
Adult ,medicine.medical_treatment ,Placebos ,Immune system ,Double-Blind Method ,Immunity ,medicine ,Humans ,Alum adjuvant ,Randomized Controlled Trials as Topic ,AIDS Vaccines ,Pharmacology ,Clinical Trials, Phase I as Topic ,biology ,business.industry ,Immunogenicity ,General Medicine ,Virology ,Vaccination ,Immunization ,Research Design ,Immunology ,HIV-1 ,biology.protein ,tat Gene Products, Human Immunodeficiency Virus ,Antibody ,business ,Adjuvant - Abstract
The native HIV-1 Tat protein was chosen as vaccine candidate for phase I clinical trials in both uninfected (ClinicalTrials.gov identifier: NCT00529698) and infected volunteers (ClinicalTrials.gov identifier: NCT00505401). The rationale was based on the role of Tat in the natural infection and AIDS pathogenesis, on the association of Tat-specific immune responses with the asymptomatic stage and slow-progression rate as well as on its sequence conservation among HIV clades (http://www.hiv1tat-vaccines.info/). The parallel conduction in the same clinical centers of randomized, double blind, placebo-controlled phase I studies both in healthy, immunologically competent adults and in HIV-infected, clinically asymptomatic, individuals represents a unique occasion to compare the vaccine-induced immune response in both the preventive and therapeutic setting. In both studies, the same lot of the native Tat protein was administered 5 times, every four weeks, subcute (SC) with alum adjuvant or intradermic (ID), in the absence of adjuvant, at 7.5 microg, 15 microg or 30 microg doses, respectively. The primary and secondary endpoints of these studies were the safety and immunogenicity of the vaccine candidate, respectively. The study lasted 52 weeks and monitoring was conducted for on additional 3 years. The results of both studies indicated that the Tat vaccine is safe and well tolerated both locally and systemically and it is highly immunogenic at all the dosages and by both routes of administration. Vaccination with Tat induced a balanced immune response in uninfected and infected individuals. In particular, therapeutic immunization induced functional antibodies and partially reverted the marked Th1 polarization of anti-Tat immunity seen in natural infection, and elicited a more balanced Th1/Th2 immune response. Further, the number of CD4 T cells correlated positively with anti-Tat antibody titers. Based on these results, a phase II study is ongoing in infected drug-treated individuals (http://www.hiv1tat-vaccines.info/).
- Published
- 2009
37. Differentiation of Monocytes Into CD1a− Dendritic Cells Correlates With Disease Progression in HIV-Infected Patients
- Author
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Nunzia Sanarico, Giulia Cappelli, Angelo Martino, Alessandra Sacchi, Gennaro De Libero, Vittorio Colizzi, Silvia Vendetti, Leopoldo Paolo Pupillo, Henri Chenal, Cristiana Cairo, Gianpiero D'Offizi, Sacchi, A., Cappelli, G., Cairo, C., Martino, A., Sanarico, N., D'Offizi, G., Pupillo, L. P., Chenal, H., Libero, G. D., Colizzi, V., and Vendetti, S.
- Subjects
CD4-Positive T-Lymphocytes ,Population ,Black People ,HIV Infections ,Biology ,Peripheral blood mononuclear cell ,Monocytes ,White People ,Antigens, CD1 ,Th2 Cells ,Immune system ,T-Lymphocyte Subsets ,Cell differentiation ,medicine ,Humans ,Macrophage ,Pharmacology (medical) ,education ,education.field_of_study ,integumentary system ,Monocyte ,Interleukin ,Cell Differentiation ,hemic and immune systems ,Dendritic Cells ,Dendritic cell ,Viral Load ,Interleukin-12 ,CD4 Lymphocyte Count ,Interleukin-10 ,AIDS ,Infectious Diseases ,medicine.anatomical_structure ,Monocyte differentiation ,Immunology ,Disease Progression ,Th1/Th2 cells ,Interleukin-4 ,Biomarkers ,Human - Abstract
Monocyte differentiation into dendritic cells (DCs) depends on microenvironmental conditions. In this study, the capacity of human monocytes to differentiate into mature DCs and their ability to induce an antiviral immune response was investigated in HIV-infected patients. In healthy subjects, monocytes differentiate into CD1a DCs in the presence of granulocyte macrophage colony-stimulating factor and interleukin (IL)-4 and matured in the presence of lipopolysaccharide. Here, we found that in 30% and 45% of HIV-infected white and African subjects, respectively, monocytes gave rise to a homogeneous CD1a DC population. In the patients who gave rise only to the CD1a DCs, this population spontaneously produced IL-10 but not IL-12, and induced a T helper 2-like immune response when cultured with human T cells isolated from cord blood mononuclear cells. In patients with monocytes differentiated into CD1a DCs, a high percentage of HIV-specific CD4 T cells producing IL-4 were seen in the peripheral blood. Furthermore, differentiation of monocytes into DCs with CD1a phenotype correlated with low CD4 T-cell counts and high viral loads in HIV-infected subjects. These results suggest that the differentiation of monocytes into CD1a DCs may be a phenotypic marker associated with progression of the disease. © 2007 Lippincott Williams & Wilkins, Inc.
- Published
- 2007
38. An IL-15 Dependent CD8 T Cell Response to Selected HIV Epitopes is Related to Viral Control in Early-Treated HIV-Infected Subjects
- Author
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Valerio Tozzi, Gianpiero D'Offizi, Filippo Martini, Roberto Paganelli, Alessandra Sacchi, Cristiana Gioia, Fabrizio Poccia, Angela Corpolongo, Pasquale Narciso, Ilaria Volpi, D'Offizi, G., Gioia, C., Corpolongo, A., Martini, F., Paganelli, R., Volpi, I., Sacchi, A., Tozzi, V., Narciso, P., and Poccia, F.
- Subjects
Adult ,Male ,Anti-HIV Agents ,HIV Antigens ,medicine.medical_treatment ,Immunology ,HIV Infections ,CD8-Positive T-Lymphocytes ,Virus Replication ,gag Gene Products, Human Immunodeficiency Virus ,Epitope ,Flow cytometry ,Epitopes ,Interferon-gamma ,03 medical and health sciences ,0302 clinical medicine ,Antiretroviral Therapy, Highly Active ,Humans ,Immunology and Allergy ,Medicine ,Cytotoxic T cell ,nef Gene Products, Human Immunodeficiency Virus ,Cytokine ,Interleukin-15 ,Pharmacology ,Immunodominant epitope ,medicine.diagnostic_test ,business.industry ,ELISPOT ,Maturative pattern ,Drug holiday ,Middle Aged ,Virology ,Peptide Fragments ,Recombinant Proteins ,In vitro ,Interleukin 15 ,030220 oncology & carcinogenesis ,HIV-1 ,Leukocytes, Mononuclear ,STI ,business ,Immunologic Memory ,CD8 T lymphocyte ,030215 immunology - Abstract
In some early-treated HIV+ patients, Structured Treatment Interruption (STI) is associated to spontaneous control of viral rebound. Thus, in this clinical setting, we analyzed the immunological parameters associated to viral control. Two groups of early treated patients who underwent STI were retrospectively defined, according to the ability to spontaneously control HIV replication (Controller and Non-controller). Plasma cytokine levels were analyzed by multiplex analysis. CD8 T cell differentiation was determined by polychromatic flow cytometry. Antigen-specific IFN-Γ production was analyzed by ELISpot and intracellular staining after stimulation with HIV-peptides. Long-term Elispot assays were performed in the presence or absence of IL-15. Plasma IL-15 was found decreased over a period of time in Non-Controller patients, whereas a restricted response to Gag (aa.167–202 and 265–279) and Nef (aa.86–100 and 111–138) immunodominant epitopes was more frequently observed in Controller patients. Interestingly, in two Non-Controller patients the CD8-mediated T cells response to immunodominant epitopes could be restored in vitro by IL-15, suggesting a major role of cytokine homeostasis on the generation of protective immunity. In early-treated HIV+ patients undergoing STI, HIV replication control was associated to CD8 T cell maturation and sustained IL-15 levels, leading to HIV-specific CD8 T cell responses against selected Gag and Nef epitopes.
- Published
- 2007
39. Short Communication: The 2005 Italian Quality Control Study for the Evaluation of CD4 Cells in Centers Involved in the Treatment of HIV Type 1 Patients
- Author
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Federico Martini, Crysoula Vlassi, Alessia Vitale, Enrico Girardi, Fernando Aiuti, Gianpiero D'Offizi, Bianca Mollicone, and Eleonora Cimini
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Reproducibility ,medicine.medical_specialty ,Cd4 t cell ,business.industry ,Immunology ,Human immunodeficiency virus (HIV) ,medicine.disease_cause ,medicine.disease ,Infectious Diseases ,Acquired immunodeficiency syndrome (AIDS) ,Absolute count ,Virology ,Internal medicine ,medicine ,Hiv patients ,Viral disease ,business - Abstract
We report the results of an external quality control program, including 17 Italian centers involved in the care of patients infected by HIV, to evaluate CD4 T cell count proficiency and reproducibility. The centers received two commercial stabilized blood preparations, one with “normal” and one with “low” CD4 T cell content. The centers were asked to process the samples two times, 1 week apart, with the same procedure used for samples from HIV patients. Most centers showed a good performance of CD4 frequency and absolute count determinations. In particular, the “low” sample was correctly analyzed by all centers; only two underestimated the “normal” sample CD4 frequency, and only one underestimated the CD4 absolute count by >100 CD4 cells/μl. Overall, our data suggest that most Italian laboratories provide reliable and reproducible results in evaluating CD4 T cells in HIV+ samples.
- Published
- 2007
40. Very low density lipoprotein and low density lipoprotein isolated from patients with hepatitis C infection induce altered cellular lipid metabolism
- Author
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Gianpiero D'Offizi, Carmine Mancone, Mariarosaria Napolitano, Alessandro Giuliani, Marco Tripodi, Tonino Alonzi, and Elena Bravo
- Subjects
Very low-density lipoprotein ,Lipid Metabolism Disorder ,Hepatitis C virus ,Lipid Metabolism Disorders ,Lipoproteins, VLDL ,Biology ,medicine.disease_cause ,chemistry.chemical_compound ,Virology ,medicine ,Humans ,Triglycerides ,Cholesterol ,Macrophages ,virus diseases ,Lipid metabolism ,Lipid Metabolism ,Hepatitis C ,Lipoproteins, LDL ,Infectious Diseases ,chemistry ,Low-density lipoprotein ,Cholesteryl ester ,lipids (amino acids, peptides, and proteins) ,Cholesterol Esters ,cholesteryl ester ,hepatitis c virus ,low-density lipoproteins ,triglyceride ,very low-density lipoproteins ,Lipoprotein - Abstract
Several abnormalities of lipid metabolism, including hypo-beta-lipoproteinemia and liver steatosis are associated with infection by hepatitis C virus (HCV). The aim of this study was to determine whether circulating lipoproteins of patients with HCV infection could directly cause alterations of lipid cellular metabolism. To this end the metabolic response of human monocyte-derived macrophages (HMDM) to very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL), measuring the cholesteryl ester (CE) and triglyceride (TG) production was analyzed. Lipoproteins were isolated from 18 patients infected with hepatitis C virus (HCV-VLDL and HCV-LDL) and from normal healthy donors (ct-VLDL and ct-LDL). In comparison to ct-lipoproteins, HCV-lipoproteins induced significant differences in HMDM CE and TG production. HCV-VLDL decreased CE and TG production; while HCV-LDL induced an increased TG synthesis. The present findings suggest that HCV infection modifies VLDL and LDL molecular composition, affecting cellular lipid metabolism, thus promoting intracellular lipid accumulation and hypo-beta-lipoproteinemia.
- Published
- 2007
41. Virological characterization of patients treated early is able to control HIV-1 replication after multiple cycles of structured therapy interruption
- Author
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Isabella Abbate, Gianpiero D’Offizi, Pasquale Narciso, S. Calcaterra, Chrysoula Vlassi, Angela Corpolongo, F. Martini, Maria Rosaria Capobianchi, and Gabriella Rozera
- Subjects
Adult ,Anti-HIV Agents ,HIV Infections ,Viremia ,Viral quasispecies ,Virus Replication ,Drug Administration Schedule ,Virus ,Antiretroviral Therapy, Highly Active ,Virology ,Replication (statistics) ,medicine ,Humans ,Phylogeny ,biology ,virus diseases ,Middle Aged ,Viral Load ,Provirus ,biology.organism_classification ,medicine.disease ,Infectious Diseases ,Viral replication ,DNA, Viral ,Lentivirus ,HIV-1 ,RNA, Viral ,Viral load - Abstract
This study aimed to define clinical and virological parameters associated with spontaneous control of HIV replication in patients having initiated HAART during primary HIV infection, who underwent structured therapy interruption by two protocols with either fixed or HIV viremia-guided scheme. At the end of the protocol all patients were changed to viremia-guided scheme and observed for 12 months (follow-up). Patients maintaining HIV viremia below the indications for resumption of HAART during the follow-up, were defined controllers, those who had to resume HAART were defined non-controllers. The following parameters were examined: pre-interruption therapy duration, CD4+, HIV RNA, proviral DNA, evolution of viral quasispecies. No specific advantage was conferred by either interruption of structured therapy in the proportion of controllers and non-controllers. Pre-HAART and zenith CD4+, pre-therapy interruption, HAART duration, but not pre-HAART HIV RNA, were significantly higher in controllers as compared to non-controllers. HIV RNA levels after the first interruption cycle of therapy were significantly lower in controllers than in non-controllers. Proviral DNA levels were also lower in controllers at this time point. HIV RNA and proviral DNA levels associated with the last interruption of therapy cycle were not different from those associated with the first cycle, and, in spite of multiple waves of virus rebound, very few gag quasispecies variants emerged in each patient. The data suggest that pre-treatment clinical parameters and virological events associated with the first viral rebound are crucial factors in determining the ability to control viral replication after multiple cycles of interruption of treatment. J. Med. Virol. 79: 1047–1054, 2007. © 2007 Wiley-Liss, Inc.
- Published
- 2007
42. Endocarditis and meningitis associated to nape piercing in a young female: a case report
- Author
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Andrea, Mariano, Raffaella, Pisapia, Amina, Abdeddaim, Chiara, Taibi, Alessia, Rianda, Laura, Vincenzi, and Gianpiero, D'Offizi
- Subjects
Adult ,Staphylococcus aureus ,Time Factors ,Bacteremia ,Endocarditis, Bacterial ,Staphylococcal Infections ,Anti-Bacterial Agents ,Meningitis, Bacterial ,Treatment Outcome ,Risk Factors ,Humans ,Drug Therapy, Combination ,Female ,Body Piercing ,Gentamicins ,Oxacillin - Abstract
Body piercing is a social phenomenon on the rise especially among young people. This procedure may be complicated by serious bacterial and viral infections. We report a case of Staphylococcus aureus infective endocarditis and meningitis arising from the site of a nape piercing, after its removal. A 21-year-old Italian female was admitted to hospital with neurological impairment and sepsis. A diagnosis of endocarditis associated with meningitis by S. aureus, complicated by septic emboli in the brain, retina, skin and kidney, was formulated on the basis of modified Duke's criteria. The likely port-of-entry was the site of a nape piercing, removed two months before. In view of the widespread practice of body piercing, provision of correct and timely information concerning the associated serious risks is now imperative. Such information should emphasise the option for antibiotic prophylaxis, and the importance of careful local hygiene, even after piercing removal.
- Published
- 2015
43. HCV NS3 quasispecies in liver and plasma and dynamics of telaprevir-resistant variants in breakthrough patients assessed by UDPS: A case study
- Author
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Emanuela Giombini, Anna Rosa Garbuglia, Barbara Bartolini, Marina Selleri, Raffaella Lionetti, Gianpiero D’Offizi, Maria Rosaria Capobianchi, and Chiara Taibi
- Subjects
Genotype ,Hepatitis C virus ,Hepacivirus ,Viral quasispecies ,Viral Nonstructural Proteins ,medicine.disease_cause ,Antiviral Agents ,Telaprevir ,Plasma ,Virology ,Drug Resistance, Viral ,medicine ,Humans ,Longitudinal Studies ,NS3 ,medicine.diagnostic_test ,biology ,Genetic Variation ,High-Throughput Nucleotide Sequencing ,Hepatitis C, Chronic ,Viral Load ,biology.organism_classification ,Infectious Diseases ,Liver ,Liver biopsy ,Viral load ,Oligopeptides ,medicine.drug - Abstract
The impact of pre-existing variants in hepatitis C virus (HCV) quasispecies, carrying resistance-associated mutations (RAMs), on the outcome of treatment with direct acting antiviral agents (DAA) is debated and it is complicated by the lack of knowledge of quasispecies distribution between the viral reservoir (liver) and the circulating compartment.To evaluate NS3 protease heterogeneity and presence of RAMs on baseline plasma and liver biopsy samples. Plasma dynamics were also analyzed during therapy and after its suspension. Study design Ultra-deep pyrosequencing (UDPS) was performed in two HCV genotype 1a patients who received telaprevir (TVR)-based therapy and developed treatment failure due to TVR-resistance.In both patients the baseline diversity of NS3 quasispecies in plasma was higher than in liver (183.6×10(-4) vs 47.8×10(-4) and 246.0×10(-4) vs 55.0×10(-4) nt substitution/site, respectively, p0.0001), but phylogenetic trees did not evidence compartmentalization between the two compartments. At baseline RAMs (i.e. V36A, T54A) were detected very low levels (range: 0.31-0.52%) in both specimen types. However, phylogenetic analyses revealed that the viral variants carrying these mutations at baseline were different from those that became fixed at breakthrough, when combined V36M+R155K, conferring high-level resistance to TVR, were observed. The frequency of resistance-associated variants declined after withdrawal of drug selective pressure.UDPS allowed extensive evaluation of quasispecies compartmentalization and of their dynamics after withdrawal of TVR. Plasma and liver NS3 quasispecies, including low level RAMs, do not show significant difference.
- Published
- 2015
44. The clinical significance of HCV core antigen detection during Telaprevir/Peg-Interferon/Ribavirin therapy in patients with HCV 1 genotype infection
- Author
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Daniele Lapa, Ubaldo Visco-Comandini, Raffaella Lionetti, Marzia Montalbano, Chiara Taibi, Paola Paci, Filippo Castiglione, Anna Rosa Garbuglia, Gianpiero D'Offizi, and Maria Rosaria Capobianchi
- Subjects
Male ,medicine.medical_specialty ,Genotype ,Alpha interferon ,Hepacivirus ,RVRrapid virological response ,Gastroenterology ,Antiviral Agents ,Sensitivity and Specificity ,HCVcore antigen ,Telaprevir ,EVRearly virological response ,Hepatitis C virus ,SVRsustained virological responseTelaprevir ,chemistry.chemical_compound ,Predictive Value of Tests ,Virology ,Internal medicine ,Ribavirin ,Medicine ,Humans ,Clinical significance ,Prospective Studies ,Prospective cohort study ,Adverse effect ,Antigens, Viral ,Aged ,business.industry ,Viral Core Proteins ,Interferon-alpha ,Hepatitis C, Chronic ,Middle Aged ,Regimen ,Infectious Diseases ,chemistry ,ROC Curve ,Predictive value of tests ,Immunology ,RNA, Viral ,Drug Therapy, Combination ,Female ,business ,Oligopeptides ,medicine.drug - Abstract
Direct-acting antiviral drugs (DAA) regimen improve the SVR rate. However, adverse effects often lead to therapy interruption. This underlines the importance to find some predictive parameters of response in order to consider the possibility of a shorter time of antiviral treatment in the appearance of adverse effects without affecting the success of the therapy.We aimed to examine the HCVAg kinetics in the early phase of treatment and its predictive value of SVR in patients undergoing TPV/Peg-IFN/RBV treatment.Twenty-three patients infected by HCV genotype 1 (1a n=11; 1b n=12) were included in this prospective study.At baseline the median Log of HCVAg concentration in RVR and EVR patients were 3.15 fmol/L and 3.45 fmol/L, respectively with no significant differences. The baseline median HCV-RNA to HCVAg ratio was 233.77, this ratio was significantly lower when measured on day 1 (27.52) and on day 6 (24.84) (p0.001). The two-tailed Fisher's exact test indicated that the SVR response is statistically significantly different in patients with detected HCVAg at week1 compared to patients with no detectable HCVAg (p=0.05). The sensitivity, specificity, and negative and positive predictive values (NPV, PPV) were 53.8, 87.5, 53.8 and 87.5%, respectively. The area under the ROC curve was 0.71 at day T6, the best cut-off of 3 fmol/L when evaluated with the HCVAg plasma concentration at day T6.Undetectable HCVAg in the early phase of TPV/Peg-IFN/RBV treatment could represent an important parameter for predicting SVR.
- Published
- 2015
45. Accumulation of dysfunctional effector CD8+T cells in the liver of patients with chronic HCV infection
- Author
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Roberto Tersigni, Giorgio Antonucci, Maria Antonella Longo, Gianpiero D'Offizi, Fabrizio Poccia, Guido Tocci, Oreste Lo Iacono, Chiara Agrati, Alessandra Oliva, Carla Nisii, and Massimo Tempestilli
- Subjects
Adult ,Male ,Pore Forming Cytotoxic Proteins ,CD3 ,Apoptosis ,CD8-Positive T-Lymphocytes ,Interferon-gamma ,Liver disease ,Immune system ,Humans ,Medicine ,Cytotoxic T cell ,Aged ,Membrane Glycoproteins ,Hepatology ,biology ,Perforin ,Tumor Necrosis Factor-alpha ,business.industry ,Degranulation ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,Acquired immune system ,Phenotype ,Liver ,Immunology ,biology.protein ,Female ,business ,CD8 ,Follow-Up Studies ,T-Lymphocytes, Cytotoxic - Abstract
Background/Aims Hepatitis C virus (HCV) causes a chronic infection that can lead to fibrosis and carcinoma. Immune responses mediated by cytotoxic T lymphocytes (CTLs) could be involved in viral clearance or persistence, and therefore in determining the course of the disease. Methods Intrahepatic and peripheral blood CD8+T cells were obtained from 32 HCV-chronically infected patients and analysed by flow-cytometry for surface markers of differentiation, IFNγ and TNFα production, degranulation capacity and perforin content, after CD3 triggering. Results were compared with those obtained from 13 patients with a non-viral liver disease. Results Intrahepatic CD8+T cells of HCV-infected patients, despite their phenotype of pre-terminally and terminally differentiated effectors (CCR7–CD45RA−/+), are poorly responsive to T cell receptor (TCR)-mediated stimulation compared with those obtained from uninfected subjects. This defect correlates with the severity of fibrosis, is more pronounced in patients with ALT 1.5×NU/ml, and is not evident after mitogen stimulation. Conclusions The present study describes the accumulation of hypo-responsive CD8+T cells in the liver of patients with chronic HCV infection. Understanding the mechanisms underlying this impairment may be helpful in the design of innovative strategies for HCV treatment.
- Published
- 2006
46. Liver Enzyme Elevation in Hepatitis C Virus (HCV)–HIV-Coinfected Patients Prior to and after Initiating HAART: Role of HCV Genotypes
- Author
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Marina Núñez, Gianpiero D'Offizi, Sergio Babudieri, Ivana Maida, Cinzia Selva, Giuliana Solinas, Pasqualino Narciso, L Fenu, and Maria Stella Mura
- Subjects
Adult ,Male ,Cellular immunity ,Genotype ,Hepatitis C virus ,Hepacivirus ,Immunology ,Population ,HIV Infections ,medicine.disease_cause ,Virus ,Flaviviridae ,Antiretroviral Therapy, Highly Active ,Virology ,Immunopathology ,medicine ,Humans ,education ,education.field_of_study ,biology ,virus diseases ,Alanine Transaminase ,Middle Aged ,biology.organism_classification ,Hepatitis C ,digestive system diseases ,Infectious Diseases ,Female ,Viral disease - Abstract
Transaminase elevation is frequently seen in hepatitis C virus (HCV)-HIV-coinfected patients receiving antiretroviral therapy (ART), representing an increase in the immune response against HCV and being one of the mechanisms proposed to be involved. There is a report claiming that HCV genotype 3 is an independent risk factor. Our objectives were to assess the incidence of liver toxicity in an HIV-HCV-coinfected population with relatively preserved cellular immunity, and the role of HCV genotypes in the elevation of liver enzymes, both at baseline and after initiating ART. All HIV(+) patients with positive anti-HCV serology and CD4(+) cell counts above 100/mm(3) who began triple ART were identified, and their HCV-RNA levels and HCV genotype were determined. Liver enzymes were determined at baseline and bimonthly during follow-up. Of anti-HCV patients 147 were included, 128 (87.1%) of whom had detectable plasma HCV-RNA. HCV-1 and HCV-4 genotypes were found to confer an increased probability of having at baseline transaminases within normal limits over the other genotypes. Severe transaminase elevations (grades 3 and 4) occurred in 5/124 patients (4.0%), all with high pre-HAART ALT and positive HCV-RNA levels. Multivariate analysis showed that patients with genotype HCV-3 had a 3.27 times higher risk of developing HAART-related transaminase elevations of any grade. In conclusion, subjects with the HCV-1 genotype more often had transaminases within normal limits at baseline. The incidence of severe transaminase elevation after initiating ART was very low (4%) in this HIV(+) population with relatively preserved cellular immunity. HCV genotype 3 was identified as a risk factor for the development of transaminase elevation of any grade.
- Published
- 2006
47. HIV-1 integrase genotyping is reliable and reproducible for routine clinical detection of integrase resistance mutations even in patients with low-level viraemia
- Author
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Alessandra Latini, Valentina Fedele, Carmela Pinnetti, Valentina Svicher, Claudia Alteri, A. Antinori, Francesca Ceccherini-Silberstein, Federica Forbici, Adriana Ammassari, D. Di Pinto, Emanuele Nicastri, Carlo Federico Perno, Ada Bertoli, M. Andreoni, Domenico Di Carlo, Lavinia Fabeni, Caterina Gori, Stefania Carta, Giulia Berno, Daniele Pizzi, Maria Mercedes Santoro, Roberta D'Arrigo, Loredana Sarmati, Gianpiero D’Offizi, and Daniele Armenia
- Subjects
Microbiology (medical) ,Adult ,Male ,Genotyping Techniques ,Mutation, Missense ,Viremia ,HIV Infections ,Drug resistance ,HIV Integrase ,Microbial Sensitivity Tests ,Biology ,INSTI ,Sensitivity and Specificity ,chemistry.chemical_compound ,Genotype ,medicine ,Humans ,Pharmacology (medical) ,Genotyping ,low-level viraemia ,Retrospective Studies ,Pharmacology ,drug resistance ,Elvitegravir ,Reproducibility of Results ,Middle Aged ,Viral Load ,Raltegravir ,medicine.disease ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,Virology ,Integrase ,dolutegravir ,Infectious Diseases ,chemistry ,Dolutegravir ,biology.protein ,HIV-1 ,elvitegravir ,HIV-1 genotyping ,Female ,integrase ,raltegravir ,medicine.drug - Abstract
Objectives Integrase drug resistance monitoring deserves attention because of the increasing number of patients being treated with integrase strand-transfer inhibitors. Therefore, we evaluated the integrase genotyping success rate at low-level viraemia (LLV, 51–1000 copies/mL) and resistance in raltegravir-failing patients. Methods An integrase genotypic resistance test (GRT) was performed on 1734 HIV-1 samples collected during 2006–13. Genotyping success rate was determined according to the following viraemia levels: 51–500, 501–1000, 1001–10 000, 10 001–100 000 and >100 000 copies/mL. The reproducibility of integrase GRT was evaluated in 41 plasma samples processed in duplicate in two reference centres. The relationship between LLV and resistance prevalence was evaluated in a subset of 120 raltegravir-failing patients. Results Overall, the integrase genotyping success rate was 95.7%. For viraemia levels 51–500 and 501–1000 copies/mL, the rate of success was 82.1% and 94.0%, respectively. GRT was reproducible, producing sequences with a high similarity and an equal resistance profile regardless of the sequencing centre or viraemia level. Resistance was detected both at LLV and at viraemia >1000 copies/mL (51–500 copies/mL = 18.2%; 501–1000 = 37.5%; 1001–10 000 = 53.7%; 10 001–100 000 = 30.0%; and >100 000 = 30.8%). At viraemia ≤500 copies/mL, Q148H/K/R and N155H had the same prevalence (9.1%), while the Y143C/H/R was completely absent. At early genotyping (within 3 months of raltegravir treatment), Q148H/K/R and N155H mutations were detected regardless of the viraemia level, while Y143C/H/R was observed only in samples with viraemia >1000 copies/mL. Conclusions Our findings prove the reliability of HIV-1 integrase genotyping and reinforce the concept that this assay may be useful in the management of failures even at LLV.
- Published
- 2014
48. Activation of Vγ9Vδ2 T cells by non-peptidic antigens induces the inhibition of subgenomic HCV replication
- Author
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Concetta Castilletti, Isabella Abbate, Maria Rosaria Capobianchi, Rafaella De Santis, Marco Tripodi, Tonino Alonzi, Gian Maria Fimia, Gianpiero D'Offizi, Fabrizio Poccia, Chiara Agrati, and Francesca Siepi
- Subjects
CBA cytometric bead assay ,FBS fetal bovine serum ,Lymphocyte Activation ,Virus Replication ,Zoledronic Acid ,Interleukin 21 ,Immunology and Allergy ,Cytotoxic T cell ,IL-2 receptor ,RT reverse transcription ,IFN-γ ,Bone Density Conservation Agents ,Diphosphonates ,ZAP70 ,Imidazoles ,NU neutralization unit ,virus diseases ,Receptors, Antigen, T-Cell, gamma-delta ,General Medicine ,Acquired immune system ,Hepatitis C ,medicine.anatomical_structure ,IPP isopentenyl pyrophosphate ,BrHPP bromohydrin pyrophosphate ,RNA, Viral ,T cell ,Immunology ,Biology ,γδ T cells ,Cell Line ,TNF tumor necrosis factor ,Interferon-gamma ,RANTES regulation on activation normal T expressed and secreted ,ZOL Zoledronate ,Antigen ,medicine ,Humans ,UNG uracil-N-glycosylase ,Antigens ,HBV hepatitis B virus ,Lymphokine ,Hepatitis C, Chronic ,Th1 Cells ,Virology ,Coculture Techniques ,digestive system diseases ,natural immunity ,HCV hepatitis C virus ,MIP1α/β macrophage inflammatory protein 1 α/β ,Original Research Papers - Abstract
Hepatitis C virus (HCV) has evolved complex strategies to evade host immune responses and establish chronic infection. Since human Vgamma9Vdelta2 T lymphocytes play a critical role in the immune response against viruses, we analyzed their antiviral functions on Huh7 hepatoma cells carrying the subgenomic HCV replicon (Rep60 cells). In a transwell culture system, Rep60 cells were co-cultured with either PBMCs or highly purified gammadelta T cells stimulated by non-peptidic antigens. Vgamma9Vdelta2 T cell activation was associated with a dramatic reduction of HCV RNA levels. Neutralizing antibodies targeting IFN-gamma revealed a critical role for this cytokine in the inhibition of HCV replication. Interestingly, drugs already in clinical use, such as Phosphostim and Zoledronate, known to activate gammadelta T cells, were shown to induce the inhibition of HCV replication mediated by Vgamma9Vdelta2 T cells of HCV patients. Our data suggest that the therapeutic activation of Vgamma9Vdelta2 T lymphocytes may represent an additional strategy to inhibit HCV replication and to restore a Th1-oriented immune response in HCV-infected patients.
- Published
- 2005
49. HLA-E Up-Regulation Induced by HIV Infection May Directly Contribute to CD94-Mediated Impairment of NK Cells
- Author
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Gianpiero D’Offizi, Federico Martini, Fabrizio Poccia, and Chiara Agrati
- Subjects
CD4-Positive T-Lymphocytes ,Cytotoxicity, Immunologic ,Cell number ,Immunology ,Cell ,Human immunodeficiency virus (HIV) ,HIV Infections ,Virus Replication ,medicine.disease_cause ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,HLA-E ,Downregulation and upregulation ,Antigens, CD ,HLA Antigens ,MHC class I ,medicine ,Humans ,Immunology and Allergy ,Lectins, C-Type ,Lymphocyte Count ,Pharmacology ,Innate immune system ,biology ,business.industry ,Histocompatibility Antigens Class I ,Up-Regulation ,Killer Cells, Natural ,medicine.anatomical_structure ,Case-Control Studies ,030220 oncology & carcinogenesis ,HIV-1 ,Hiv patients ,biology.protein ,business ,NK Cell Lectin-Like Receptor Subfamily D ,030215 immunology - Abstract
Alterations in NK cell numbers and function have been repeatedly shown during HIV infection. In this study, NK cell number and MHC class I expression on CD4+ T cells were studied in HIV patients at different stages of disease progression. An increased expression of HLA-E was seen on CD4+ T cells. In parallel, a reduced number of CD94+ NK cells was observed in advanced disease stages. Moreover, a decline in CD94 expression on NK cells was observed at the HIV replication peak in patients undergoing antiretroviral treatment interruption, suggesting a role of viral replication on NK cells alterations. In vitro HIV infection induced a rapid down-regulation of HLA-A,B,C expression, paralleled by an increased expression of HLA-E surface molecules, the formal ligands of CD94 NK receptors. HIV-infected HLA-E expressing cells were able to inhibit NK cell cytotoxicity through HLA-E expression, since cytotoxicity was restored by antibody masking experiments. These data indicate that the CD94/HLA-E interaction may contribute to NK cell dysfunction in HIV infection, suggesting a role of HIV replication in this process.
- Published
- 2005
50. Treatment failure to first-line direct antiviral (DAA) in HCV-related advanced liver disease: An Italian real-life urban setting
- Author
-
C.F. Perno, F. Chiesara, D. Di Paolo, V. Gerardi, Alessandra Moretti, Francesca Ceccherini-Silberstein, Anna Claudia Pellicelli, Valeria Cento, C. Masetti, Paolo Rossi, Francesco Santopaolo, M. Siciliano, Mario Angelico, L. Fondacaro, Martina Milana, Raffaella Lionetti, Ilaria Lenci, and Gianpiero D’Offizi
- Subjects
Liver disease ,medicine.medical_specialty ,Hepatology ,business.industry ,First line ,Internal medicine ,Gastroenterology ,medicine ,medicine.disease ,business ,Virology ,Treatment failure - Published
- 2016
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