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1. Link between persistent, unexplained gamma-glutamyltransferase elevation and porto-sinusoidal vascular disorder

Author

Nicola Pugliese, Francesca Romana Ponziani, Federica Cerini, Luca di Tommaso, Federica Turati, Marco Maggioni, Matteo Angelo Manini, Francesco Santopaolo, Cristiana Bianco, Chiara Masetti, Maria Cristina Giustiniani, Carlo La Vecchia, Luca Valenti, Luigi Terracciano, Mauro Viganò, and Alessio Aghemo

Subjects
PSVD, vascular liver disorder, GGT, non-cirrhotic portal hypertension, nodular regenerative hyperplasia, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: Porto-sinusoidal vascular disorder (PSVD) is a group of vascular disorders characterized by lesions involving portal venules and sinusoids, irrespective of the presence of portal hypertension. Liver biopsy is essential for diagnosis. In a single-center study, we demonstrated high rates of PSVD in patients with persistently elevated gamma-glutamyltransferase (GGT). This multicenter study aims to establish PSVD prevalence in a larger dataset of individuals with persistent and unexplained GGT elevation, and to identify associated risk factors. Methods: The study included all patients who underwent liver biopsy for persistent and unexplained GGT elevation in five Italian hepatology units between March 2015 and December 2021. Results: A total of 144 patients met the inclusion criteria. The majority were males (76/144, 52.8%) and mean age was 51.9 years (range 19-74). Only 12 (8.3%) had liver stiffness measurements (LSM) >10 kPa, while 7 (4.8%) had ultrasound evidence of portal hypertension. Histological findings were consistent with PSVD in 96 patients (67%). Alternative diagnoses were steatohepatitis in 13 (9%), sarcoidosis in 3 (2%) and congenital hepatic fibrosis in 3 (2%) patients. Histological findings were non-specific in 29 (20%) patients. PSVD was associated with male sex (odds ratio [OR] 2.60, 95% CI 1.13-5.99), LSM

Published
2024
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2. Hepatitis C Virus Infection in the Elderly in the Era of Direct-Acting Antivirals: Evidence from Clinical Trials and Real Life

Author

Nicola Pugliese, Davide Polverini, Ivan Arcari, Stella De Nicola, Francesca Colapietro, Chiara Masetti, Monica Ormas, Roberto Ceriani, Ana Lleo, and Alessio Aghemo

Subjects
HCV, antiviral therapy, elderly, drug–drug interactions, special populations, Medicine
Abstract

The introduction of direct-acting antiviral agents (DAAs) into clinical practice has revolutionized the therapeutic approach to patients with chronic hepatitis C virus (HCV) infection. According to the most recent guidelines, the first line of treatment for HCV infection involves the use of one of three pan-genotypic DAA combinations, sofosbuvir/velpatasvir (SOF/VEL), glecaprevir/pibrentasvir (GLE/PIB), and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX). These drugs have been shown to be effective and safe in numerous clinical trials and real-world studies, but special populations have been neglected. Among the special populations to be treated are elderly patients, whose numbers are increasing in clinical practice. The management of these patients can be challenging, in particular due to multiple comorbidities, polypharmacotherapy, and potential drug–drug interactions. This narrative review aims to summarize the current scientific evidence on the efficacy and safety of DAAs in the elderly population, both in clinical trials and in real-life settings. Although there is still a paucity of real-world data and no clinical trials have yet been conducted in the population aged ≥ 75 years old, some considerations about the efficacy and safety of DAAs in the elderly can be made based on the results of these studies. The pan-genotypic associations of DAAs appear to be as efficacious and safe in the elderly population as in the general population; this is both in terms of similar sustained virologic response (SVR) rates and similar frequencies of adverse events (AEs). However, further studies specifically involving this patient population would be necessary to confirm this evidence.

Published
2023
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3. Ursodeoxycholic Acid Does Not Improve COVID-19 Outcome in Hospitalized Patients

Author

Francesca Colapietro, Giovanni Angelotti, Chiara Masetti, Dana Shiffer, Nicola Pugliese, Stella De Nicola, Francesco Carella, Antonio Desai, Monica Ormas, Marta Calatroni, Paolo Omodei, Michele Ciccarelli, Stefano Aliberti, Francesco Reggiani, Michele Bartoletti, Maurizio Cecconi, Ana Lleo, Alessio Aghemo, and Antonio Voza

Subjects
UDCA, COVID-19, ACE2, Microbiology, QR1-502
Abstract

Ursodeoxycholic acid (UDCA) was demonstrated to reduce susceptibility to SARS-CoV-2 infection in vitro and improve infection course in chronic liver diseases. However, real-life evidence is lacking. We analyzed the impact of UDCA on COVID-19 outcomes in patients hospitalized in a tertiary center. Between January 2020 and January 2023, among 3847 patients consecutively hospitalized for COVID19, 57 (=UDCA group) were taking UDCA. The UDCA and the control groups (n = 3790) did not differ concerning comorbidities including diabetes mellitus type 2 (15.8% vs. 12.8%) and neoplasia (12.3% vs. 9.4%). Liver diseases and vaccination rate were more common in the UDCA group (14.0% vs. 2.5% and 54.4% vs. 30.2%, respectively). Overall mortality and CPAP treatment were 22.8 % and 15.7% in the UDCA, and 21.3% and 25.9% in the control group. Mortality was similar (p = 0.243), whereas UDCA was associated with a lower rate of CPAP treatment (OR = 0.76, p < 0.05). Treatment with UDCA was not an independent predictor of survival in patients hospitalized for COVID-19.

Published
2023
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4. Correction: Sarcopenia as a predictor of survival in patients undergoing bland transarterial embolization for unresectable hepatocellular carcinoma.

Author

Ezio Lanza, Chiara Masetti, Gaia Messana, Riccardo Muglia, Nicola Pugliese, Roberto Ceriani, Ana Lleo de Nalda, Lorenza Rimassa, Guido Torzilli, Dario Poretti, Felice D'Antuono, Letterio Salvatore Politi, Vittorio Pedicini, Alessio Aghemo, and Humanitas HCC Multidisciplinary Group

Subjects
Medicine, Science
Abstract

[This corrects the article DOI: 10.1371/journal.pone.0232371.].

Published
2020
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5. Sarcopenia as a predictor of survival in patients undergoing bland transarterial embolization for unresectable hepatocellular carcinoma.

Author

Ezio Lanza, Chiara Masetti, Gaia Messana, Riccardo Muglia, Nicola Pugliese, Roberto Ceriani, Ana Lleo de Nalda, Lorenza Rimassa, Guido Torzilli, Dario Poretti, Felice D'Antuono, Letterio Salvatore Politi, Vittorio Pedicini, Alessio Aghemo, and Humanitas HCC Multidisciplinary Group

Subjects
Medicine, Science
Abstract

Sarcopenia has been associated with lower overall survival in patients with cirrhosis and hepatocellular carcinoma (HCC) undergoing surgical resection, TACE, TARE, or transplantation. This monocentric study evaluated the prognostic significance of sarcopenia in patients affected by HCC who received bland transarterial embolization (TAE) therapy, by analyzing its impact on survival and treatment-related complications. All consecutive patients who underwent the 1st TAE between March 1st 2011 and July 1st 2019 in our Institution were retrospectively studied. To evaluate sarcopenia, the skeletal muscle index (SMI) was calculated by normalizing the cross-sectional muscle area at the level of L3 on an abdominal CT scan prior to embolization (cm2) by patient height (m2). SMI cut-off values for sarcopenia were considered ≤ 39 cm2/m2 for women and ≤55 cm2/m2 for men. Data about age, gender, body mass index (BMI), underlying liver disease, liver function, MELD score, Child-Pugh score, multifocal disease, performance status, previous interventions, length of stay (LOS), complications after the procedure, readmission rate within 30 days, survival time from TAE and total number and type of TAE received following the first procedure were collected. From 2011 to 2019, 142 consecutive patients underwent 305 TAEs. Observation time ranged from 1.4 to 100.5 months (median 20.1 SD = 22). Sarcopenia at baseline was present in 121 (85%) patients. Overall 87 (61.2%) patients died during follow-up with survival rates at 1-, 2-, 3-, 4-, and 5-year of 71%, 41%, 22%, 16% and 11% respectively. After multivariate analysis sarcopenia (HR = 2.22, p = 0.046), previous ablation/resection (HR = 0.51, p = 0.005) and multifocal disease (HR = 1.84, p = 0.02) were associated with reduced survival. Sarcopenia did not influence the safety of TAE in terms of LOS (2 days vs 1.5 days, p = 0.2), early complications rate (8% vs 5%, p = 0.5) and readmission rate within 30 days (7% vs 5%, p = 0.74). Sarcopenia, estimated by the L3SMI method, is an emerging prognostic factor in patients with HCC undergoing bland TAE therapy as it is associated with increased mortality, without impairing the safety of the locoregional treatment. Measures to ameliorate the SMI, such as nutritional support and physical exercise, should be evaluated in clinical trials for HCC patients receiving liver embolization to determine their impact on overall survival.

Published
2020
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6. Gallstone disease is associated with more severe liver damage in patients with non-alcoholic fatty liver disease.

Author

Anna Ludovica Fracanzani, Luca Valenti, Maurizio Russello, Luca Miele, Cristina Bertelli, Alessandro Bellia, Chiara Masetti, Consuelo Cefalo, Antonio Grieco, Giulio Marchesini, and Silvia Fargion

Subjects
Medicine, Science
Abstract

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and gallstone disease (GD) are both highly prevalent in the general population and associated with obesity and insulin resistance. We aimed to evaluate the prevalence of GD in a cross sectional study of NAFLD patients and to define whether the presence of GD is associated with diabetes and predicts more severe liver disease. METHODOLOGY/PRINCIPAL FINDINGS: We merged databases of four Liver Units, comprising 524 consecutive biopsy-proven NAFLD (373 males) observed between January 2003 and June 2010. GD was diagnosed in 108 (20%), and 313 cases (60%) were classified by liver biopsy as nonalcoholic steatohepatitis (NASH). The GD subgroup was characterized by a significantly higher prevalence of females, prediabetes/diabetes, abdominal obesity and metabolic syndrome, older age, higher BMI, fasting glucose, HOMA-IR and lower ALT. The prevalence of GD progressively increased with advancing fibrosis and with the severity of necroinflammatory activity (p for trend = 0.0001 and = 0.01, respectively), without differences in the severity of steatosis. At multivariate analysis GD was associated with female gender (OR 1.37, 95% CI 1.04-1.8), age (OR 1.027, 95% CI1.003-1.05), fasting glucose (OR 1.21, 95% CI 1.10-1.33) and NASH (OR 1.40,95% CI 1.06-1.89), whereas ALT levels were associated with a lower GD risk (OR 0.98, 95% CI 0.97-0.99). When subjects with cirrhosis were excluded from analysis, the association between GD and fasting glucose, female gender, and NASH was maintained. CONCLUSION: Patients with NAFLD have a high prevalence of GD, which characterizes subjects with altered glucose regulation and more advanced liver disease.

Published
2012
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7. Hepatic and pulmonary involvement in a patient with PR3-ANCA vasculitis following SARS-CoV-2 vaccination: A case report

Author

Antonio Tonutti, Edoardo Simonetta, Anna Stainer, Giulia Suigo, Maria De Santis, Carlo Selmi, Chiara Masetti, Ana Lleo, Luigi Maria Terracciano, Stefano Aliberti, and Francesco Amati

Subjects
Rheumatology
Abstract

We here report the first case of anti-proteinase 3–positive anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis following the severe acute respiratory syndrome coronavirus 2 Pfizer-BioNTech vaccine presenting with prominent liver involvement and alveolar haemorrhage. Two weeks after vaccination, a 49-year-old man developed inflammatory arthralgias and hypertransaminasaemia. Two months later, fever and haemoptysis appeared; the patient tested positive for anti-proteinase 3 autoantibodies. High-dose steroids and rituximab were started, and complete remission was achieved. Systemic autoimmune diseases, including ANCA-associated vasculitis, should always be considered in the differential diagnosis of hypertransaminasaemia, especially when the clinical context is suspicious.

Published
2023
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9. Safety of current antiviral drugs for chronic hepatitis B

Author

Chiara Masetti, Nicola Pugliese, Alessio Aghemo, and Mauro Viganò

Subjects
Carcinoma, Hepatocellular, Hepatitis B, Chronic, Treatment Outcome, Liver Neoplasms, Humans, Pharmacology (medical), General Medicine, Tenofovir, Antiviral Agents
Abstract

Oral nucleos(t)ide analogues (NUCs) are recommended as first-line therapy for chronic hepatitis B (CHB) due to higher HBV-DNA suppression rates and safety profile. Long-term treatment with NUCs is often necessary to achieve durable viral suppression.This review provides an overview of the long-term safety data that have become available since entecavir (ETV) and tenofovir disoproxil fumarate (TDF) were first approved, and recent data on tenofovir alafenamide (TAF) in patients with CHB.NUCs generally show remarkable safety in patients taking them for long periods. Nevertheless, renal and bone toxicity may occur in a minority of patients on TDF therapy. These effects have been overcome by the recent release of TAF. Moreover, the currently available data do not allow firm conclusions on the superiority of TDF on ETV about hepatocellular carcinoma (HCC) risk reduction. Observational studies involving more homogeneous cohorts are therefore needed; furthermore, long-term studies assessing the impact of TAF on this important topic are warranted.

Published
2022

11. Myosteatosis Is Not Associated with Complications or Survival in HCC Patients Undergoing Trans Arterial Embolization

Author

Chiara Masetti, Nicola Pugliese, Ludovica Lofino, Francesca Colapietro, Roberto Ceriani, Ana Lleo, Dario Poretti, Vittorio Pedicini, Stella De Nicola, Guido Torzilli, Lorenza Rimassa, Alessio Aghemo, and Ezio Lanza

Subjects
hepatocellular carcinoma, sarcopenia, myosteatosis, trans-arterial embolization, locoregional therapy, General Medicine
Abstract

Alterations in nutritional status, in particular sarcopenia, have been extensively associated with a poor prognosis in cirrhotic patients regardless of the etiology of liver disease. Less is known about the predictive value of myosteatosis, defined as pathological fat infiltration into the skeletal muscle. We retrospectively analyzed a cohort of 151 cirrhotic patients with unresectable hepatocellular carcinoma (HCC) who underwent their first trans-arterial embolization (TAE) between 1 March 2011 and 1 July 2019 at our Institution. Clinical and biochemical data were collected. Sarcopenia was assessed using the L3-SMI method while myosteatosis with a dedicated segmentation suite (3D Slicer), using a single slice at an axial plane located at L3 and calculating the IMAC (Intramuscular Adipose Tissue Content Index). The sex-specific cut-off values for defining myosteatosis were IMAC > −0.44 in males and >−0.31 in females. In our cohort, 115 (76%) patients were included in the myosteatosis group; 128 (85%) patients had a coexistent diagnosis of sarcopenia. Patients with myosteatosis were significantly older and showed higher BMI than patients without myosteatosis. In addition, male gender and alcoholic- or metabolic-related cirrhosis were most represented in the myosteatosis group. Myosteatosis was not associated with a different HCC burden, length of hospitalization, complication rate, and readmission in the first 30 days after discharge. Overall survival was not influenced by the presence of myosteatosis.

Published
2022
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12. Outcome of Sars-COV-2-related thyrotoxicosis in survivors of Covid-19: a prospective study

Author

Elisa Carlani, Francesca Motta, Gaia Pellegatta, Vincenzo Craviotto, Francesco Reggiani, Angelo Dipasquale, Stéphanie Baggio, Walter Vena, Paolo Colombo, Mattia Nigro, Lorenzo Maria Canziani, Francesca Puggioni, Federica Tordato, Mauro Chiarito, Franca Barbic, Antonio Desai, Lorenzo Calabro', Maddalena Casana, Hayato Kurihara, Elena Azzolini, Fabio Procopio, Carlo Fedeli, Enrico Marrano, Marta Calatroni, Michele Ciccarelli, Federico Sicoli, Antonio Voza, Paola Morelli, Enrico Brunetta, Marta Pellegrino, Mario Borroni, Silvia Paiardi, Paola Maria Magnoni, Ferdinando Loiacono, Giacomo Maria Guidelli, ELOISA FRANCHI, Chiara Masetti, Andrea Gerardo Antonio Lania, CLAUDIO ANGELINI, Paola GALIMBERTI, Vittorio Pedicini, Elisabetta Lavezzi, Federica Mrakic Sposta, Paolo Dario Omodei, Elena Generali, SALVATORE BADALAMENTI, and ALESSANDRO PIZZOCARO

Subjects
Male, medicine.medical_specialty, endocrine system, Thyroiditis, endocrine system diseases, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Thyrotropin, 030209 endocrinology & metabolism, Trab, Gastroenterology, Hyperthyroidism, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Thyroid peroxidase, Internal medicine, Medicine, Humans, Euthyroid, Prospective Studies, Survivors, Prospective cohort study, Autoantibodies, Thyroid, biology, business.industry, SARS-CoV-2, COVID-19, Middle Aged, medicine.disease, Thyroxine, medicine.anatomical_structure, Thyrotoxicosis, 030220 oncology & carcinogenesis, SARS-CoV2, biology.protein, Thyroglobulin, Female, Original Article, Thyroid function, business
Abstract

Purpose To evaluate the post- coronavirus disease-19 (COVID-19) outcome of thyroid function in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related thyrotoxicosis. Methods This was a single-center prospective study involving 29 patients (11 females, 18 males; median age 64 years, range: 43–85) with thyrotoxicosis diagnosed after hospitalization for COVID-19 and then followed-up for a median period of 90 days (range: 30–120) after hospital discharge. At follow-up, patients were evaluated for serum thyrotropin (TSH), free-thyroxine (FT4), free-triiodiothyronine (FT3), TSH receptor antibodies (TRAb), thyroglobulin antibodies (TgAb), thyroperoxidase antibodies (TPOAb) and ultrasonographic thyroid structure. Results After recovery of COVID-19, serum TSH values significantly increased (P

Published
2021

13. Frequent NS5A and multiclass resistance in almost all HCV genotypes at DAA failures: What are the chances for second-line regimens?

Author

Velia Chiara Di Maio, Valeria Cento, Marianna Aragri, Stefania Paolucci, Teresa Pollicino, Nicola Coppola, Bianca Bruzzone, Valeria Ghisetti, Maurizio Zazzi, Maurizia Brunetto, Ada Bertoli, Silvia Barbaliscia, Silvia Galli, William Gennari, Fausto Baldanti, Giovanni Raimondo, Carlo Federico Perno, Francesca Ceccherini-Silberstein, Pietro Andreone, Massimo Andreoni, Mario Angelico, Sergio Babudieri, Giorgio Barbarini, Vincenzo Boccaccio, Lucio Boglione, Matteo Bolis, Stefano Bonora, Vanni Borghi, Giuseppina Brancaccio, Savino Bruno, Pierluigi Cacciatore, Vincenza Calvaruso, Nicola Caporaso, Antonio Ciaccio, Alessia Ciancio, Piero Colombatto, Raffaele Cozzolongo, Antonio Craxì, Cecilia D'Ambrosio, Gabriella D'Ettorre, Andrea De Luca, Antonio Di Biagio, Giovanni Di Perri, Simona Francioso, Giovanni Battista Gaeta, Alessia Giorgini, Antonio Grieco, Guido Gubertini, Roberto Gulminetti, Lara Lambiase, Ilaria Lenci, Miriam Lichtner, Ivana Maida, Simona Marenco, Letizia Marinaro, Renato Maserati, Chiara Masetti, Michela Melis, Elisa Meregalli, Valeria Micheli, Filomena Morisco, Fosca Niero, Laura Ambra Nicolini, Valeria Pace Palitti, Maurizio Paoloni, Giustino Parruti, Caterina Pasquazzi, Adriano Pellicelli, Ennio Polilli, Maria Laura Ponti, Massimo Puoti, Maria Rendina, Giuliano Rizzardini, Barbara Rossetti, Tina Ruggiero, Vincenzo Sangiovanni, Mario Starace, Laura Sticchi, Pierluigi Tarquini, Pierluigi Toniutto, Vincenzo Vullo, Di Maio VC, Cento V, Aragri M, Paolucci S, Pollicino T3, Coppola N4, Bruzzone B5, Ghisetti V6, Zazzi M7, Brunetto M8, Bertoli A1, Barbaliscia S1, Galli S9, Gennari W10, Baldanti F2, Raimondo G3, Perno CF1, Ceccherini-Silberstein F11, Andreone P, Andreoni M, Angelico M, Babudieri S, Barbarini G, Boccaccio V, Boglione L, Bolis M, Bonora S, Borghi V, Brancaccio G, Bruno S, Cacciatore P, Calvaruso Vincenza, Caporaso N, Ciaccio A, Ciancio A, Colombatto P, Cozzolongo R, Craxì Antonio, D'Ambrosio C, D'Ettorre G, De Luca A, Di Biagio A, Di Perri G, Francioso S, Gaeta GB, Giorgini A, Grieco A, Gubertini G, Gulminetti R, Lambiase L, Lenci I, Lichtner M, Maida I, Marenco S, Marinaro L, Maserati R, Masetti C, Melis M, Meregalli E, Micheli V, Morisco F, Niero F, Nicolini LA, Palitti VP, Paoloni M, Parruti G, Pasquazzi C, Pellicelli A, Polilli E, Ponti ML, Puoti M, Rendina M, Rizzardini G, Rossetti B, Ruggiero T, Sangiovanni V, Starace M, Sticchi L, Tarquini P, Toniutto P, Vullo V., Di Maio, Vc, Cento, V, Aragri, M, Paolucci, S, Pollicino, T, Coppola, N, Bruzzone, B, Ghisetti, V, Zazzi, M, Brunetto, M, Bertoli, A, Barbaliscia, S, Galli, S, Gennari, W, Baldanti, F, Raimondo, G, Perno, Cf, Ceccherini-Silberstein, F., Andreone P, Andreoni, M, Angelico, M, Babudieri, S, Barbarini, G, Boccaccio, V, Boglione, L, Bolis, M, Bonora, S, Borghi, V, Brancaccio, G, Bruno, S, Cacciatore, P, Calvaruso, V, Caporaso, N, Ciaccio, A, Ciancio, A, Colombatto, P, Cozzolongo, R, Craxì, A, D'Ambrosio, C, D'Ettorre, G, De Luca, A, Di Biagio, A, Di Perri, G, Francioso, S, Gaeta, Gb, Giorgini, A, Grieco, A, Gubertini, G, Gulminetti, R, Lambiase, L, Lenci, I, Lichtner, M, Maida, I, Marenco, S, Marinaro, L, Maserati, R, Masetti, C, Melis, M, Meregalli, E, Micheli, V, Morisco, F, Niero, F, Nicolini, La, Palitti, Vp, Paoloni, M, Parruti, G, Pasquazzi, C, Pellicelli, A, Polilli, E, Ponti, Ml, Puoti, M, Rendina, M, Rizzardini, G, Rossetti, B, Ruggiero, T, Sangiovanni, V, Starace, M, Sticchi, L, Tarquini, P, Toniutto, P, Vullo, V., Di Maio, V, Perno, C, Ceccherini-Silberstein, F, Andreone, P, Craxi, A, Gaeta, G, Nicolini, L, Palitti, V, Ponti, M, and Vullo, V

Subjects
0301 basic medicine, medicine.medical_specialty, hepacivirus, HCV RAS, Treatment outcome, Drug Resistance, HCV genotypes, Drug resistance, Biology, NS5A, 03 medical and health sciences, 0302 clinical medicine, Second line, drug resistance viral, humans, retreatment, treatment outcome, antiviral agents, hepatitis c chronic, Internal medicine, Drug Resistance, Viral, Humans, Retreatment, Treatment Outcome, Antiviral Agents, Hepacivirus, Hepatitis C, Chronic, medicine, Viral, Chronic, Hepatology, Hepatitis C, Settore MED/07 - Microbiologia e Microbiologia Clinica, medicine.disease, Virology, Hepatology, HCV, NS5A, 030104 developmental biology, HCV, 030211 gastroenterology & hepatology
Published
2018

14. Régénération naturelle de Pin pignon (Pinus pinea L.) dans la Pineta Granducale di Alberese. (Parco Naturale della Maremma, Toscana, Italie)

Author

Maurizio Mencuccini and Chiara Masetti

Subjects
Pinus pinea L, Parco Naturale della Maremma, natural regeneration, demography, animal structures, Ecology, fungi, Environmental factor, food and beverages, Forestry, Natural regeneration, medicine.disease_cause, complex mixtures, Parc naturel de la Maremma, régénération naturelle, démographie, Geography, medicine, Ecology, Evolution, Behavior and Systematics
Abstract

In an uneven-aged stand, the stone pine natural regeneration process was studied. Seed dispersal was abundant only under pine canopies. Rate and amount of germinations depended on meteorological conditions and on the presence of shrub cover. Seedling survival during the first two years was depressed by shrub cover, but summer droughts had an overwhelming effect. The presence of such interactions between pine seedling and understorey species populations suggest that past management practices of the pinewood (shrub and tree cutting, game management) affected the probabilities of stone pine seedling recruitment : social, economical and technical evolution of these practices probably changed forest micro-environmental conditions and, consequently, reduced the abundance of stone pine natural regeneration., Nous avons étudié quelques aspects de la régénération naturelle du Pin pignon dans une pinède sur la côte de la mer Tyrrhénienne en Toscane. La production de graine est généralement bonne. Environ 90 % des graines tombent sous le feuillage des arbres-mères. Le couvert arbustif d’un côté permet la germination de nombreuses plantules, mais de l’autre, empêche leur survie. La sécheresse au cours de l’été réduit fortement la survie des plantules pendant les deux premières années. A partir des années 40, l’évolution de l’étage arbustif, qui était auparavant éliminé, peut avoir modifié les conditions de la pinède, ce qui a sûrement altéré les possibilités d’implantation et survie des plantules de Pin pignon., Masetti Chiara, Mencuccini Maurizio. Régénération naturelle de Pin pignon (Pinus pinea L.) dans la Pineta Granducale di Alberese. (Parco Naturale della Maremma, Toscana, Italie). In: Ecologia mediterranea, tome 17,1991. pp. 103-118.

Published
1991
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15. DECLINE OF PREVALENCE OF RESISTANCE ASSOCIATED SUBSTITUTIONS TO NS3 AND NS5A INHIBITORS AT DAA- FAILURE IN HEPATITIS C VIRUS IN ITALY OVER THE YEARS 2015 TO 2018

Author

Aasld, American Association For The Study Of Liver Diseases, Barbara, Rossetti, Redi, David, Velia Chiara Di Maio, Marianna, Aragri, Stefania, Paolucci, Paglicci, Lorenzo, Chiara, Masetti, Bianca, Bruzzone, Carmine, Minichini, FRANCESCA MONTAGNANI, Valeria, Micheli, Simona, Landonio, Giacomo Zanelli, Elisabetta, Degasperi, Renato, Maserati, Ivana, Maida, Annapaola, Callegaro, Silvia, Barbaliscia, Ada, Bertoli, Claudio, Paternoster, Simona, Marenco, Filomena, Morisco, Vincenza, Calvaruso, Gloria, Taliani, Massimo, Puoti, Giovanni, Cenderello, Adriano De Santis, Miriam, Lichtner, Nicola, Coppola, Roberto, Gulminetti, Valeria, Cento, Maria, Rendina, Elisabetta, Teti, Giustino, Parruti, Tina, Ruggiero, Valeria, Ghisetti, Caterina, Pasquazzi, Laura Ambra Nicolini, Vincenzo, Vullo, Adriano, Pellicelli, Tullio, Prestileo, Raffaele, Cozzolongo, Vincenzo, Sangiovanni, Marco, Biolato, Ilaria, Lenci, Anna, Licata, Antonio, Ciaccio, Valeria Pace Palitti, Alessia, Giorgini, Giuseppe, Cariti, Alessia, Ciancio, Alessio, Aghemo, Vanni, Borghi, Pietro, Andreone, Brunetto, Maurizia R., Teresa, Pollicino, Teresa Antonia Santantonio, Nunzia, Cuomo, Cinzia, Caudai, Sergio, Babudieri, Pietro, Lampertico, Giovanni Battista Gaeta, Giovanni, Raimondo, Massimo, Andreoni, Giuliano, Rizzardini, Mario, Angelico, Carlo Federico Perno, Antonio, Craxì, Maurizio Zazzi, Francesca Ceccherini Silberstein, and and HCV Virology Italian Resistance Network (Vironet C)

16. Multiclass HCV resistance to direct-acting antiviral failure in real-life patients advocates for tailored second-line therapies

Author

Di Maio, Velia C., Cento, Valeria, Lenci, Ilaria, Aragri, Marianna, Rossi, Piera, Barbaliscia, Silvia, Melis, Michela, Verucchi, Gabriella, Magni, Carlo F., Teti, Elisabetta, Bertoli, Ada, Antonucci, Francescopaolo, Bellocchi, Maria C., Micheli, Valeria, Masetti, Chiara, Landonio, Simona, Francioso, Simona, Santopaolo, Francesco, Pellicelli, Adriano M., Calvaruso, Vincenza, Gianserra, Laura, Siciliano, Massimo, Romagnoli, Dante, Cozzolongo, Raffaele, Grieco, Antonio, Vecchiet, Jacopo, Morisco, Filomena, Merli, Manuela, Brancaccio, Giuseppina, Di Biagio, Antonio, Loggi, Elisabetta, Mastroianni, Claudio Maria, Pace Palitti, Valeria, Tarquini, Pierluigi, Puoti, Massimo, Taliani, Gloria, Sarmati, Loredana, Picciotto, Antonino, Vullo, Vincenzo, Caporaso, Nicola, Paoloni, Maurizio, Pasquazzi, Caterina, Rizzardini, Giuliano, Parruti, Giustino, Craxì, Antonio, Babudieri, Sergio, Andreoni, Massimo, Angelico, Mario, Perno, Carlo F., Ceccherini Silberstein, Francesca, Mariani, R., Iapadre, N., Grimaldi, A., Cozzolongo, R., Andreone, P., Verucchi, G., Menzaghi, B., Quirino, T., Pisani, V., Torti, MARIA CHIARA, Vecchiet, J., Bruzzone, B., De Maria, A., Marenco, S., Nicolini, L. A., Viscoli, C., Casinelli, K., Delle Monache, M., Lichtner, Miriam, Aghemo, A., Boccaccio, V., Bruno, S., Cerrone, M., Colombo, M., D'Arminio Monforte, A., Danieli, E., Donato, F., Gubertini, G., Lleo, A., Magni, C. F., Mancon, A., Monico, S., Niero, F., Russo, M. L., Gnocchi, M., Orro, A., Milanesi, L., Baldelli, E., Bertolotti, M., Borghi, V., Mussini, C., Brancaccio, G., Gaeta, G. B., Lembo, V., Sangiovanni, V., Di Marco, V., Mazzola, A., Petta, S., D'Amico, E., Cacciatore, P., Consorte, A., Pieri, A., Polilli, E., Sozio, F., Antenucci, F., Aragri, M., Baiocchi, L., Barbaliscia, S., Biliotti, Elisa, Biolato, M., Carioti, L., Ceccherini Silberstein, F., Cerasari, G., Cerva, C., Ciotti, M., D'Ambrosio, C., D'Ettorre, G., De Leonardis, F., De Sanctis, A., Di Maio, V. C., Di Paolo, D., Furlan, Caterina, Gallo, P., Gasbarrini, A., Giannelli, V., Grieco, S., Lambiase, L., Lattanzi, B., Lenci, I., Lula, R., Malagnino, V., Manuelli, M., Miglioresi, L., Milana, M., Moretti, A., Nosotti, L., Palazzo, Donatella, Pellicelli, A., Romano, M., Sarrecchia, C., Sforza, D., Sorbo, M. C., Spaziante, M., Svicher, V., Tisone, G., Vespasiani Gentilucci, U., D'Adamo, G., Mangia, A., Maida, I., Mura, M. S., Falconi, L., Di Giammartino, D., Di Maio, V., Cento, V., Lenci, I., Aragri, M., Rossi, P., Barbaliscia, S., Melis, M., Verucchi, G., Magni, C., Teti, E., Bertoli, A., Antonucci, F., Bellocchi, M., Micheli, V., Masetti, C., Landonio, S., Francioso, S., Santopaolo, F., Pellicelli, A., Calvaruso, V., Gianserra, L., Siciliano, M., Romagnoli, D., Cozzolongo, R., Grieco, A., Vecchiet, J., Morisco, F., Merli, M., Brancaccio, G., Di Biagio, A., Loggi, E., Mastroianni, C., Pace Palitti, V., Tarquini, P., Puoti, M., Taliani, G., Sarmati, L., Picciotto, A., Vullo, V., Caporaso, N., Paoloni, M., Pasquazzi, C., Rizzardini, G., Parruti, G., Craxã¬, A., Babudieri, S., Andreoni, M., Angelico, M., Perno, C., Ceccherini-Silberstein, F., Mariani, R., Iapadre, N., Grimaldi, A., Andreone, P., Menzaghi, B., Quirino, T., Pisani, V., Torti, C., Bruzzone, B., De Maria, A., Marenco, S., Nicolini, L., Viscoli, C., Casinelli, K., Delle Monache, M., Lichtner, M., Aghemo, A., Boccaccio, V., Bruno, S., Cerrone, M., Colombo, M., D'Arminio Monforte, A., Danieli, E., Donato, F., Gubertini, G., Lleo, A., Mancon, A., Monico, S., Niero, F., Russo, M., Gnocchi, M., Orro, A., Milanesi, L., Baldelli, E., Bertolotti, M., Borghi, V., Mussini, C., Gaeta, G., Lembo, V., Sangiovanni, V., DI MARCO, V., Mazzola, A., Petta, S., D'Amico, E., Cacciatore, P., Consorte, A., Pieri, A., Polilli, E., Sozio, F., Antenucci, F., Baiocchi, L., Biliotti, E., Biolato, M., Carioti, L., Cerasari, G., Cerva, C., Ciotti, M., D'Ambrosio, C., D'Ettorre, G., De Leonardis, F., De Sanctis, A., Di Paolo, D., Furlan, C., Gallo, P., Gasbarrini, A., Giannelli, V., Grieco, S., Lambiase, L., Lattanzi, B., Lula, R., Malagnino, V., Manuelli, M., Miglioresi, L., Milana, M., Moretti, A., Nosotti, L., Palazzo, D., Romano, M., Sarrecchia, C., Sforza, D., Sorbo, M., Spaziante, M., Svicher, V., Tisone, G., Vespasiani-Gentilucci, U., D'Adamo, G., Mangia, A., Maida, I., Mura, M., Falconi, L., Di Giammartino, D., Di Maio, V, Cento, V, Lenci, I, Aragri, M, Rossi, P, Barbaliscia, S, Melis, M, Verucchi, G, Magni, C, Teti, E, Bertoli, A, Antonucci, F, Bellocchi, M, Micheli, V, Masetti, C, Landonio, S, Francioso, S, Santopaolo, F, Pellicelli, A, Calvaruso, V, Gianserra, L, Siciliano, M, Romagnoli, D, Cozzolongo, R, Grieco, A, Morisco, F, Merli, M, Brancaccio, G, Di Biagio, A, Loggi, E, Mastroianni, C, Pace Palitti, V, Tarquini, P, Puoti, M, Taliani, G, Sarmati, L, Picciotto, A, Vullo, V, Caporaso, N, Paoloni, M, Pasquazzi, C, Rizzardini, G, Parruti, G, Craxì, A, Babudieri, S, Andreoni, M, Angelico, M, Perno, C, Ceccherini-Silberstein, F, Velia C. Di Maio, Valeria Cento, Ilaria Lenci, Marianna Aragri, Piera Rossi, Silvia Barbaliscia, Michela Meli, Gabriella Verucchi, Carlo F. Magni, Elisabetta Teti, Ada Bertoli, Francesco Paolo Antonucci, Maria C. Bellocchi, Valeria Micheli, Chiara Masetti, Simona Landonio, Simona Francioso, Francesco Santopaolo, Adriano M. Pellicelli, Vincenza Calvaruso, Laura Gianserra, Massimo Siciliano, Dante Romagnoli, Raffaele Cozzolongo, Antonio Grieco, Jacopo Vecchiet, Filomena Morisco, Manuela Merli, Giuseppina Brancaccio, Antonio Di Biagio, Elisabetta Loggi, Claudio M. Mastroianni, Valeria Pace Palitti, Pierluigi Tarquini, Massimo Puoti, Gloria Taliani, Loredana Sarmati, Antonino Picciotto, Vincenzo Vullo, Nicola Caporaso, Maurizio Paoloni, Caterina Pasquazzi, Giuliano Rizzardini, Giustino Parruti, Antonio Craxì, Sergio Babudieri, Massimo Andreoni, Mario Angelico, Carlo F. Perno, Francesca Ceccherini-Silberstein, for the HCV Italian Resistance Network Study Group: [.., P. Andreone, E. Loggi, G. Verucchi, ], Di Maio, Velia C., Cento, Valeria, Lenci, Ilaria, Aragri, Marianna, Rossi, Piera, Barbaliscia, Silvia, Melis, Michela, Verucchi, Gabriella, Magni, Carlo F., Teti, Elisabetta, Bertoli, Ada, Antonucci, Francescopaolo, Bellocchi, Maria C., Micheli, Valeria, Masetti, Chiara, Landonio, Simona, Francioso, Simona, Santopaolo, Francesco, Pellicelli, Adriano M., Calvaruso, Vincenza, Gianserra, Laura, Siciliano, Massimo, Romagnoli, Dante, Cozzolongo, Raffaele, Grieco, Antonio, Vecchiet, Jacopo, Morisco, Filomena, Merli, Manuela, Brancaccio, Giuseppina, Di Biagio, Antonio, Loggi, Elisabetta, Mastroianni, Claudio M., Pace Palitti, Valeria, Tarquini, Pierluigi, Puoti, Massimo, Taliani, Gloria, Sarmati, Loredana, Picciotto, Antonino, Vullo, Vincenzo, Caporaso, Nicola, Paoloni, Maurizio, Pasquazzi, Caterina, Rizzardini, Giuliano, Parruti, Giustino, Craxã¬, Antonio, Babudieri, Sergio, Andreoni, Massimo, Angelico, Mario, Perno, Carlo F., Ceccherini-Silberstein, Francesca, Nicolini, L. A., Magni, C. F., Russo, M. L., Gaeta, G. B., Di Marco, V., Di Maio, V. C., Sorbo, M. C., Mura, M. S., Di Maio, Velia C, Magni, Carlo F, Bellocchi, Maria C, Pellicelli, Adriano M, Mastroianni, Claudio M, Craxì, Antonio, Perno, Carlo F, and Ceccherini Silberstein, Francesca

Subjects
Male, 0301 basic medicine, hepatitis C virus, Sustained Virologic Response, Sofosbuvir, Hepacivirus, Drug Resistance, resistance-associated substitutions, Viral Nonstructural Proteins, VARIANTS, NS5A, medicine.disease_cause, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Recurrence, INFECTION, antiviral therapy, Medicine, hepatitis C viru, Viral, Treatment Failure, Chronic, direct-acting antivirals, resistance test, hepatology, biology, GENOTYPE 1, virus diseases, Middle Aged, Settore MED/07 - Microbiologia e Microbiologia Clinica, Hepatitis C, Italy, Combination, Interferon, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, Author Keywords:antiviral therapy, RIBAVIRIN, Sequence Analysis, Human, medicine.drug, medicine.medical_specialty, Daclatasvir, Genotype, Hepatitis C virus, Antiviral Agents, LONG-TERM PERSISTENCE, DACLATASVIR, 03 medical and health sciences, Drug Therapy, Aged, Drug Resistance, Viral, Hepatitis C, Chronic, Humans, Interferons, Mutation, Ribavirin, Sequence Analysis, DNA, Hepatology, TREATMENT-NAIVE, Internal medicine, Antiviral Agent, resistance-associated substitution, direct-acting antiviral, Hepaciviru, resistance test KeyWords Plus:HEPATITIS-C VIRUS, business.industry, Viral Nonstructural Protein, DNA, biology.organism_classification, Clinical trial, 030104 developmental biology, SOFOSBUVIR, chemistry, Sequence Analysi, Immunology, business
Abstract

Background & Aims: Despite the excellent efficacy of direct-acting antivirals (DAA) reported in clinical trials, virological failures can occur, often associated with the development of resistance-associated substitutions (RASs). This study aimed to characterize the presence of clinically relevant RASs to all classes in real-life DAA failures. Methods: Of the 200 virological failures that were analyzed in 197 DAA-treated patients, 89 with pegylated-interferon+ribavirin (PegIFN+RBV) and 111 without (HCV-1a/1b/1g/2/3/4=58/83/1/6/24/25; 56.8% treatment experienced; 65.5% cirrhotic) were observed. Sanger sequencing of NS3/NS5A/NS5B was performed by home-made protocols, at failure (N= 200) and whenever possible at baseline (N= 70). Results: The majority of the virological failures were relapsers (57.0%), 22.5% breakthroughs, 20.5% non-responders. RAS prevalence varied according to IFN/RBV use, DAA class, failure type and HCV genotype/subtype. It was 73.0% in IFN group vs 49.5% in IFN free, with the highest prevalence of NS5A-RASs (96.1%), compared to NS3-RASs (75.9% with IFN, 70.5% without) and NS5B-RASs (66.6% with IFN, 20.4% without, in sofosbuvir failures). In the IFN-free group, RASs were higher in breakthrough/non-responders than in relapsers (90.5% vs 40.0%, P= 2 DAA classes showed multiclass resistance, including 11/11 NS3+NS5A failures. Furthermore, 20.0% of patients had baseline-RASs, which were always confirmed at failure. Conclusions: In our failure setting, RAS prevalence was remarkably high in all genes, with a partial exception for NS5B, whose limited resistance is still higher than previously reported. This multiclass resistance advocates for HCV resistance testing at failure, in all three genes for the best second-line therapeutic tailoring.

Published
2017
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