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1. COVID-19 in liver transplant recipients: incidence, hospitalization and outcome in an Italian prospective double-centre study

Author

Maria Guarino, Valentina Cossiga, Ilaria Loperto, Ilaria Esposito, Rosanna Ortolani, Andrea Fiorentino, Giuseppina Pontillo, Lucia De Coppi, Valentina Cozza, Alfonso Galeota Lanza, Giovanni Giuseppe Di Costanzo, Francesco Paolo Picciotto, and Filomena Morisco

Subjects
Medicine, Science
Abstract

Abstract Liver transplant (LT) recipients are vulnerable to SARS-CoV-2-infection (COVID-19), due to immunosuppression and comorbidities. This study aimed to evaluate the impact of COVID-19 on LT recipients compared to general population in the Campania region. In this prospective double-centre study, we enrolled all consecutive adult LT recipients with confirmed SARS-CoV-2-infection. Data were collected at diagnosis of COVID-19 and during follow-up and compared with the regional population. Thirty LT recipients (3.28%) developed SARS-CoV-2-infection (76.66% male, median age 62.61 years). Sixteen (53.33%) were symptomatic. Common symptoms were fever, cough, fatigue, and anosmia. Twenty-five (83.33%) were outpatients, 5 (16.66%) required hospitalization (6.66% admitted to Intensive Care Unit, 6.62% developed Acute Respiratory Distress Syndrome and 6.66% died). Immunosuppressors were in 3 (10%) patients. Incidence rate of COVID-19 was similar between LT patients and general population (3.28% vs 4.37%, p = 0.142) with higher rate of symptoms in LT patients (53.33% vs 15.87%, p

Published
2022
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2. COVID-19 and Fatty Liver Disorders

Author

Maria Guarino, Valentina Cossiga, Francesco Maria Cutolo, Maria Rosaria Attanasio, Raffaele Lieto, and Filomena Morisco

Subjects
NAFLD, MAFLD, COVID-19, obesity, fibrosis, telemedicine, Medicine
Abstract

In late 2019, the world was shaken by the COVID-19 pandemic. Severe Acute Respiratory Syndrome Coronavirus—2 (SARS-CoV-2) infection became one of the main causes of illness and hospitalization worldwide, especially in subjects with metabolic comorbidities such as obesity, diabetes, or liver disease. This scenario crosses with the metabolic liver disorders’ “pandemic”, caused by the exponential spreading of non-alcoholic fatty liver disease, which is now the most prevalent cause of chronic liver disease (CLD). The aim of this review is to analyze the key factors of the relationship between COVID-19 and the spectrum of fatty liver disorders (FLD), in terms of molecular mechanisms and clinical presentation which can predict a more severe course of the infection. In addition, this review will face the change in management of FLD during pandemics, with a central role of telemedicine, and the role of other interventions in preventing and treating severe infection in these subjects.

Published
2023
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3. Safety and Immunogenicity of Anti-SARS-CoV-2 Booster Dose in Patients with Chronic Liver Disease

Author

Valentina Cossiga, Mario Capasso, Maria Guarino, Ilaria Loperto, Stefano Brusa, Francesco Maria Cutolo, Maria Rosaria Attanasio, Raffaele Lieto, Giuseppe Portella, and Filomena Morisco

Subjects
COVID-19, SARS-CoV-2, chronic liver disease, vaccine, cirrhosis, Medicine
Abstract

The low response to vaccines is a well-known problem in cirrhosis. We evaluated the safety and immunogenicity of booster doses in patients with chronic liver disease (CLD), comparing the humoral response in cirrhotic vs. non-cirrhotic patients, and the impact of different factors on immune response. From September 2021 to April 2022, outpatients with CLD who completed the primary vaccination course and the booster dose against SARS-CoV-2 were enrolled. Blood samples were collected after second and third doses for detecting anti-spike protein IgG. We enrolled 340 patients; among them, 91 subjects were cirrhotic. After primary vaccination course, 60 (17.6%) patients did not develop a positive antibody titer, without significant differences between cirrhotic and non-cirrhotic patients (p = 0.076); most of them (88.3%) developed it after booster dose. At multivariable analysis, factors associated with higher humoral response after booster dose were only porto-sinusoidal vascular disorder (p = 0.007) as an etiology of CLD and the use of the mRNA-1273 vaccine (p = 0.001). In conclusion, in patients with CLD, a booster dose against SARS-CoV-2 induces an excellent immunogenicity and leads to an adequate antibody response. Cirrhosis is not associated with a worse humoral response, compared to patients with non-cirrhotic CLD.

Published
2023
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4. Incidence and risk factors of early HCC occurrence in HCV patients treated with direct acting antivirals: a prospective multicentre study

Author

Luca Rinaldi, Alessandro Perrella, Maria Guarino, Massimo De Luca, Guido Piai, Nicola Coppola, Pia Clara Pafundi, Fortunato Ciardiello, Morena Fasano, Erika Martinelli, Giovanna Valente, Riccardo Nevola, Caterina Monari, Lucia Miglioresi, Barbara Guerrera, Massimiliano Berretta, Ferdinando Carlo Sasso, Filomena Morisco, Antonio Izzi, and Luigi Elio Adinolfi

Subjects
HCC, Direct acting antivirals, HCV cirrhosis, Immune-surveillance, Medicine
Abstract

Abstract Background An unexpected increased HCC recurrence and occurrence rate among HCV patients treated with direct acting antivirals combination has been reported. Aim of the study was the evaluation of early HCC occurrence rate and its risk factors in a HCV infected population, treated with direct-acting-antivirals. Methods According to the Italian ministerial guidelines for direct-acting-antivirals treatment, 1022 consecutive HCV patients treated with direct-acting-antivirals were enrolled. Patients either with active HCC at imaging or history of previous treated HCC, HBV or HIV co-infection, or liver transplant recipients were excluded. The SVR, defined as the persistent absence of detectable serum HCV-RNA 12 weeks after the end of treatment (SVR12), was assessed for all enrolled patients. Abdominal ultrasound was performed before starting antiviral therapy, and repeated every 6 months. HCC was diagnosed according to the international guidelines. Patients showing either nodular patterns suggestive of HCC or with uncertain dynamic vascular behaviour were excluded from a further follow-up. Results Nine hundred and eighty-five patients completed the 48 weeks follow-up after the end of treatment. A Sofosbuvir-based regimen was administered in the 74.9% of patients, among whom, the 71.6% underwent a simultaneous Ribavirin administration. A sustained virological response at 12 weeks off treatment was documented in 966 patients (98.2%). During the post treatment follow-up HCC was detected in 35 patients, with a cumulative incidence rate of the 3.55%. At multivariate analysis, four variables resulted independently associated with HCC development, both in a cirrhosis based and a class B Child based model, respectively: cirrhosis/class B Child, therapeutic schedule including Sofosbuvir without Ribavirin, liver stiffness values, male gender and presence of diabetes. A multivariate analysis performed on Child A cirrhotic patients, showed that Sofosbuvir based therapeutic treatment without Ribavirin had a HCC occurrence 5.7 higher than Ribavirin-based schedules with or without Sofosbuvir (p

Published
2019
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5. Gender and Autoimmune Liver Diseases: Relevant Aspects in Clinical Practice

Author

Federica Invernizzi, Marta Cilla, Silvia Trapani, Maria Guarino, Valentina Cossiga, Martina Gambato, Maria Cristina Morelli, Filomena Morisco, Patrizia Burra, and Annarosa Floreani

Subjects
gender, autoimmune liver diseases, autoimmune hepatitis primary biliary cirrhosis, primary sclerosing cholangitis, overlap syndromes, liver transplant, Medicine
Abstract

Autoimmune liver diseases (AILDs) include autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis. The etiologies of AILD are not well understood but appear to involve a combination of genetic and environmental factors. AILDs commonly affect young individuals and are characterized by a highly variable clinical course. These diseases significantly influence quality of life and can progress toward liver decompensation or the onset of hepatocellular or cholangiocarcinoma; a significant number of patients eventually progress to end-stage liver disease, requiring liver transplantation. In this review, we focus on the sex characteristics and peculiarities of AILD patients and highlight the relevance of a sex-specific analysis in future studies. Understanding the sex differences underlying AILD immune dysregulation may be critical for developing more effective treatments.

Published
2022
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6. Sarcopenia in chronic advanced liver diseases: A sex-oriented analysis of the literature

Author

Federica Invernizzi, Lucia Lapenna, Valentina Cossiga, Ilaria Lenci, C. Becchetti, Filomena Morisco, Alberto Zanetto, Patrizia Burra, Luisa Pasulo, Maria Guarino, Bruna Lavezzo, and Manuela Merli

Subjects
Liver Cirrhosis, Male, Sarcopenia, medicine.medical_specialty, Carcinoma, Hepatocellular, medicine.medical_treatment, Liver transplantation, Chronic liver disease, Muscle mass, Liver disease, Quality of life, Internal medicine, gender, medicine, sex, Humans, Retrospective Studies, Hepatology, business.industry, Incidence (epidemiology), Liver Neoplasms, Gastroenterology, musculoskeletal system, medicine.disease, body regions, Hepatocellular carcinoma, Quality of Life, Female, 610 Medizin und Gesundheit, liver disease, business, human activities, sarcopenia
Abstract

Sarcopenia, defined as progressive and generalized loss of muscle mass and strength, is common in chronic liver disease. It significantly impacts the quality of life and increases the risk of liver-related complications and mortality in cirrhotic patients. Moreover, recent studies showed a negative impact of sarcopenia on patients awaiting liver transplantation (LT), on post-LT outcomes, and on response to hepatocellular carcinoma therapies. Data about the influence of sex on the incidence, prevalence, diagnosis and treatment of sarcopenia in chronic liver diseases are poor and conflicting. The aims of this review of the literature are to define sex differences in sarcopenic cirrhotic patients and to highlight the necessity of a sex stratified analysis in future studies. This analysis of the literature showed that most of the studies are retrospective, with a higher prevalence of sarcopenia in males, probably due to anatomical differences between the sexes. Moreover, diagnostic criteria for sarcopenia are different between studies, as there is not a defined cut-off and, as a consequence, no comparable results. In conclusion, sex seems to have an impact on sarcopenia, and future studies must accurately investigate its role in identifying and treating high-risk patients, reducing the negative impact of sarcopenia on the survival and quality of life of cirrhotic patients.

Published
2022

7. Coffee prevents fatty liver disease induced by a high-fat diet by modulating pathways of the gut–liver axis

Author

Paola Vitaglione, Giovanna Mazzone, Vincenzo Lembo, Giuseppe D'Argenio, Antonella Rossi, Maria Guido, Marcella Savoia, Federico Salomone, Ilario Mennella, Francesca De Filippis, Danilo Ercolini, Nicola Caporaso, and Filomena Morisco

Subjects
Non-alcoholic steatohepatitis, Metabolic syndrome, Gut permeability, Gut microbiota, Polyphenols, Nutrition. Foods and food supply, TX341-641, Medicine
Abstract

Coffee consumption is inversely associated with the risk of non-alcoholic fatty liver disease (NAFLD). A gap in the literature still exists concerning the intestinal mechanisms that are involved in the protective effect of coffee consumption towards NAFLD. In this study, twenty-four C57BL/6J mice were divided into three groups each receiving a standard diet, a high-fat diet (HFD) or an HFD plus decaffeinated coffee (HFD+COFFEE) for 12 weeks. Coffee supplementation reduced HFD-induced liver macrovesicular steatosis (P

Published
2019
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8. Hepatitis B vaccine coverage and risk factors for lack of vaccination in subjects with HBsAg negative liver cirrhosis in Italy: still, much work should be done

Author

Massimo Marignani, R. Fontana, Maria Cristina Vinci, Tommaso Stroffolini, Alessia Ciancio, Evangelista Sagnelli, Guido Colloredo, Anna Lombardi, Luigina Ferrigno, Filomena Morisco, Sergio Babudieri, Stroffolini, T., Lombardi, A., Ciancio, A., Fontana, R., Colloredo, G., Marignani, M., Vinci, M., Morisco, F., Babudieri, S., Ferrigno, L., and Sagnelli, E.

Subjects
Male, HBsAg, medicine.medical_specialty, Vaccination Coverage, Cirrhosis, Hepatitis B vaccine, Lack of vaccination, Chronic liver disease, Hbsag negative, Surveys and Questionnaires, Internal medicine, Humans, Medicine, Hepatitis B Vaccines, Aged, Hepatology, business.industry, Gastroenterology, Middle Aged, HB vaccine, medicine.disease, Vaccination, Cross-Sectional Studies, Italy, Immunization, Liver cirrhosis, Etiology, Female, business
Abstract

Background: in Italy, Hepatitis-B-vaccine is advised and provided free-of-charge for subjects with chronic liver disease (CLD), including liver cirrhosis. Aims: to evaluate HB-vaccine-coverage and variables associated with lack of vaccination in cirrhotic patients with particular attention to cirrhosis' etiology. Methods: cirrhotic patients of any etiology (excluding HBsAg+) referring to 8 tertiary-centers were prospectively enrolled for a-six-months-period in 2019. Subjects were asked if they received HB-vaccine previously. Multiple-logistic-regression-analysis was performed to identify independent predictors of lack of vaccination. Results: 731 cases were recruited. Overall-vaccine-coverage was 16.3% (23.7% in those younger than 65y, 10.0% in those older than 64y; p64 y (OR: 4.27; CI 95%: 2.52-7.24), educational level

Published
2021

9. Effectiveness of SARS-CoV-2 vaccination in liver transplanted patients: The debate is open!

Author

Ilaria Esposito, Alessandro Furno, Valentina Cossiga, Maria Guarino, and Filomena Morisco

Subjects
2019-20 coronavirus outbreak, COVID-19 Vaccines, Hepatology, Coronavirus disease 2019 (COVID-19), SARS-CoV-2, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine.medical_treatment, Vaccination, COVID-19, Immunosuppression, Liver transplantation, Virology, Liver, medicine, Humans, business, Letter to the Editor
Published
2022

10. Incidence of DAA failure and the clinical impact of retreatment in real-life patients treated in the advanced stage of liver disease: Interim evaluations from the PITER network.

Author

Loreta A Kondili, Giovanni Battista Gaeta, Maurizia Rossana Brunetto, Alfredo Di Leo, Andrea Iannone, Teresa Antonia Santantonio, Adele Giammario, Giovanni Raimondo, Roberto Filomia, Carmine Coppola, Daniela Caterina Amoruso, Pierluigi Blanc, Barbara Del Pin, Liliana Chemello, Luisa Cavalletto, Filomena Morisco, Laura Donnarumma, Maria Grazia Rumi, Antonio Gasbarrini, Massimo Siciliano, Marco Massari, Romina Corsini, Barbara Coco, Salvatore Madonia, Marco Cannizzaro, Anna Linda Zignego, Monica Monti, Francesco Paolo Russo, Alberto Zanetto, Marcello Persico, Mario Masarone, Erica Villa, Veronica Bernabucci, Gloria Taliani, Elisa Biliotti, Luchino Chessa, Maria Cristina Pasetto, Pietro Andreone, Marzia Margotti, Giuseppina Brancaccio, Donatella Ieluzzi, Guglielmo Borgia, Emanuela Zappulo, Vincenza Calvaruso, Salvatore Petta, Loredana Falzano, Maria Giovanna Quaranta, Liliana Elena Weimer, Stefano Rosato, Stefano Vella, and Edoardo Giovanni Giannini

Subjects
Medicine, Science
Abstract

Few data are available on the virological and clinical outcomes of advanced liver disease patients retreated after first-line DAA failure.To evaluate DAA failure incidence and the retreatment clinical impact in patients treated in the advanced liver disease stage.Data on HCV genotype, liver disease severity, and first and second line DAA regimens were prospectively collected in consecutive patients who reached the 12-week post-treatment and retreatment evaluations from January 2015 to December 2016 in 23 of the PITER network centers.Among 3,830 patients with advanced fibrosis (F3) or cirrhosis, 139 (3.6%) failed to achieve SVR. Genotype 3, bilirubin levels >1.5mg/dl, platelet count

Published
2017
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11. Sex difference in the interaction of alcohol intake, hepatitis B virus, and hepatitis C virus on the risk of cirrhosis.

Author

Tommaso Stroffolini, Evangelista Sagnelli, Angelo Andriulli, Guido Colloredo, Caterina Furlan, Giovanni Battista Gaeta, Filomena Morisco, Mario Pirisi, Floriano Rosina, Caterina Sagnelli, Antonina Smedile, Piero Luigi Almasio, and EPACRON study group

Subjects
Medicine, Science
Abstract

The joint effect of the interaction of alcohol intake, hepatitis B virus (HBV) and hepatitis C virus (HCV) on the risk of cirrhosis is still unexplored because a large sample size is required for this investigation.Evaluation of interaction of HBV, HCV and alcohol abuse on the risk of cirrhosis.We analysed 12,262 consecutive patients with chronic liver disease of various aetiologies referring to 95 Italian liver units in 2001 or 2014. To evaluate the interaction between alcohol abuse, HBV infection, and HCV infection, patients unexposed to either factors were used as reference category. Adjustment for BMI and age was done by multiple logistic regression analysis.Females were older than males (p

Published
2017
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12. Surveillance for hepatocellular carcinoma with a 3-months interval in 'extremely high-risk' patients does not further improve survival

Author

Filippo Pelizzaro, Giulia Peserico, Marco D'Elia, Nora Cazzagon, Francesco Paolo Russo, Alessandro Vitale, Edoardo G. Giannini, Manuela Piccinnu, Gian Ludovico Rapaccini, Maria Di Marco, Eugenio Caturelli, Marco Zoli, Rodolfo Sacco, Giuseppe Cabibbo, Fabio Marra, Andrea Mega, Filomena Morisco, Antonio Gasbarrini, Gianluca Svegliati-Baroni, Francesco Giuseppe Foschi, Andrea Olivani, Alberto Masotto, Gerardo Nardone, Giovanni Raimondo, Francesco Azzaroli, Gianpaolo Vidili, Filippo Oliveri, Franco Trevisani, Fabio Farinati, Maurizio Biselli, Paolo Caraceni, Francesca Garuti, Annagiulia Gramenzi, Andrea Neri, Valentina Santi, Fabio Piscaglia, Francesco Tovoli, Alessandro Granito, Luca Muratori, Francesca Benevento, Elton Dajti, Giovanni Marasco, Federico Ravaioli, Alberta Cappelli, Rita Golfieri, Cristina Mosconi, Matteo Renzulli, Angela Imondi, Anna Sartori, Barbara Penzo, Elisa Pinto, Ester Marina Cela, Antonio Facciorusso, Valentina Cacciato, Edoardo Casagrande, Alessandro Moscatelli, Gaia Pellegatta, Nicoletta De Matthaeis, Gloria Allegrini, Valentina Lauria, Giorgia Ghittoni, Giorgio Pelecca, Fabrizio Chegai, Fabio Coratella, Mariano Ortenzi, Gabriele Missale, Alessandro Inno, Fabiana Marchetti, Anita Busacca, Calogero Cammà, Vincenzo Di Martino, Giacomo Emanuele Maria Rizzo, Maria Stella Franzè, Carlo Saitta, Assunta Sauchella, Vittoria Bevilacqua, Alberto Borghi, Andrea Casadei Gardini, Fabio Conti, Anna Chiara Dall'aglio, Giorgio Ercolani, Federica Mirici, Claudia Campani, Chiara Di Bonaventura, Stefano Gitto, Pietro Coccoli, Antonio Malerba, Maria Guarino, Maurizia Brunetto, Veronica Romagnoli, Pelizzaro, F., Peserico, G., D'Elia, M., Cazzagon, N., Russo, F. P., Vitale, A., Giannini, E. G., Piccinnu, M., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Sacco, R., Cabibbo, G., Marra, F., Mega, A., Morisco, F., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F. G., Olivani, A., Masotto, A., Nardone, G., Raimondo, G., Azzaroli, F., Vidili, G., Oliveri, F., Trevisani, F., Farinati, F., Biselli, M., Caraceni, P., Garuti, F., Gramenzi, A., Neri, A., Santi, V., Piscaglia, F., Tovoli, F., Granito, A., Muratori, L., Benevento, F., Dajti, E., Marasco, G., Ravaioli, F., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Imondi, A., Sartori, A., Penzo, B., Pinto, E., Cela, E. M., Facciorusso, A., Cacciato, V., Casagrande, E., Moscatelli, A., Pellegatta, G., De Matthaeis, N., Allegrini, G., Lauria, V., Ghittoni, G., Pelecca, G., Chegai, F., Coratella, F., Ortenzi, M., Missale, G., Inno, A., Marchetti, F., Busacca, A., Camma, C., Di Martino, V., Rizzo, G. E. M., Franze, M. S., Saitta, C., Sauchella, A., Bevilacqua, V., Borghi, A., Casadei Gardini, A., Conti, F., Dall'Aglio, A. C., Ercolani, G., Mirici, F., Campani, C., Di Bonaventura, C., Gitto, S., Coccoli, P., Malerba, A., Guarino, M., Brunetto, M., Romagnoli, V., Pelizzaro, Filippo, Peserico, Giulia, D'Elia, Marco, Cazzagon, Nora, Russo, Francesco Paolo, Vitale, Alessandro, Giannini, Edoardo G., Piccinnu, Manuela, Rapaccini, Gian Ludovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Sacco, Rodolfo, Cabibbo, Giuseppe, Marra, Fabio, Mega, Andrea, Morisco, Filomena, Gasbarrini, Antonio, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, Olivani, Andrea, Masotto, Alberto, Nardone, Gerardo, Raimondo, Giovanni, Azzaroli, Francesco, Vidili, Gianpaolo, Oliveri, Filippo, Trevisani, Franco, Farinati, Fabio, Biselli, Maurizio, Caraceni, Paolo, Garuti, Francesca, Gramenzi, Annagiulia, Neri, Andrea, Santi, Valentina, Piscaglia, Fabio, Tovoli, Francesco, Granito, Alessandro, Muratori, Luca, Benevento, Francesca, Dajti, Elton, Marasco, Giovanni, Ravaioli, Federico, Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Imondi, Angela, Sartori, Anna, Penzo, Barbara, Pinto, Elisa, Cela, Ester Marina, Facciorusso, Antonio, Cacciato, Valentina, Casagrande, Edoardo, Moscatelli, Alessandro, Pellegatta, Gaia, De Matthaeis, Nicoletta, Allegrini, Gloria, Lauria, Valentina, Ghittoni, Giorgia, Pelecca, Giorgio, Chegai, Fabrizio, Coratella, Fabio, Ortenzi, Mariano, Missale, Gabriele, Inno, Alessandro, Marchetti, Fabiana, Busacca, Anita, Cammà, Calogero, Di Martino, Vincenzo, Rizzo, Giacomo Emanuele Maria, Franzè, Maria Stella, Saitta, Carlo, Sauchella, Assunta, Bevilacqua, Vittoria, Borghi, Alberto, Casadei Gardini, Andrea, Conti, Fabio, Dall'aglio, Anna Chiara, Ercolani, Giorgio, Mirici, Federica, Campani, Claudia, Di Bonaventura, Chiara, Gitto, Stefano, Coccoli, Pietro, Malerba, Antonio, Guarino, Maria, Brunetto, Maurizia, and Romagnoli, Veronica

Subjects
medicine.medical_specialty, Carcinoma, Hepatocellular, Survival, Hepatocellular carcinoma, Cancer stage, Surveillance interval, Internal medicine, medicine, Humans, Propensity Score, Survival analysis, High risk patients, Hepatology, business.industry, Liver Neoplasms, Settore MED/09 - MEDICINA INTERNA, Gastroenterology, Patient survival, medicine.disease, Survival Analysis, Propensity score matching, Survival Analysi, Liver cancer, business, Median survival, Human
Abstract

Background An enhanced surveillance schedule has been proposed for cirrhotics with viral etiology, who are considered at extremely high-risk of hepatocellular carcinoma (HCC). Aims We compared the 3- and 6-months surveillance interval, evaluating cancer stage at diagnosis and patient survival. Methods Data of 777 HBV and HCV cirrhotic patients with HCC diagnosed under a 3-months (n = 109, 3MS group) or a 6-months (n = 668, 6MS group) surveillance were retrieved from the Italian Liver Cancer database. Survival in the 3MS group was considered as observed and adjusted for lead-time bias, and survival analysis was repeated after a propensity score matching. Results The 3-months surveillance interval neither reduced the share of patients diagnosed outside the Milano criteria, nor increased their probability to receive curative treatments. The median survival of 6MS patients (55.0 months [45.9–64.0]) was not significantly different from the observed (47.0 months [35.0–58.9]; p = 0.43) and adjusted (44.9 months [33.4–56.4]; p = 0.30) survival of 3MS patients. A propensity score analysis confirmed the absence of a survival advantage for 3MS patients. Conclusions A tightening of surveillance schedule does not increase the diagnosis of early-stage tumors, the feasibility of curative treatments and the survival. Therefore, we should maintain the 6-months interval in the surveillance of viral cirrhotics.

Published
2022

13. Development and Validation of a New Prognostic System for Patients with Hepatocellular Carcinoma.

Author

Fabio Farinati, Alessandro Vitale, Gaya Spolverato, Timothy M Pawlik, Teh-la Huo, Yun-Hsuan Lee, Anna Chiara Frigo, Anna Giacomin, Edoardo G Giannini, Francesca Ciccarese, Fabio Piscaglia, Gian Lodovico Rapaccini, Mariella Di Marco, Eugenio Caturelli, Marco Zoli, Franco Borzio, Giuseppe Cabibbo, Martina Felder, Rodolfo Sacco, Filomena Morisco, Elisabetta Biasini, Francesco Giuseppe Foschi, Antonio Gasbarrini, Gianluca Svegliati Baroni, Roberto Virdone, Alberto Masotto, Franco Trevisani, Umberto Cillo, and ITA.LI.CA study group

Subjects
Medicine
Abstract

Prognostic assessment in patients with hepatocellular carcinoma (HCC) remains controversial. Using the Italian Liver Cancer (ITA.LI.CA) database as a training set, we sought to develop and validate a new prognostic system for patients with HCC.Prospective collected databases from Italy (training cohort, n = 3,628; internal validation cohort, n = 1,555) and Taiwan (external validation cohort, n = 2,651) were used to develop the ITA.LI.CA prognostic system. We first defined ITA.LI.CA stages (0, A, B1, B2, B3, C) using only tumor characteristics (largest tumor diameter, number of nodules, intra- and extrahepatic macroscopic vascular invasion, extrahepatic metastases). A parametric multivariable survival model was then used to calculate the relative prognostic value of ITA.LI.CA tumor stage, Eastern Cooperative Oncology Group (ECOG) performance status, Child-Pugh score (CPS), and alpha-fetoprotein (AFP) in predicting individual survival. Based on the model results, an ITA.LI.CA integrated prognostic score (from 0 to 13 points) was constructed, and its prognostic power compared with that of other integrated systems (BCLC, HKLC, MESIAH, CLIP, JIS). Median follow-up was 58 mo for Italian patients (interquartile range, 26-106 mo) and 39 mo for Taiwanese patients (interquartile range, 12-61 mo). The ITA.LI.CA integrated prognostic score showed optimal discrimination and calibration abilities in Italian patients. Observed median survival in the training and internal validation sets was 57 and 61 mo, respectively, in quartile 1 (ITA.LI.CA score ≤ 1), 43 and 38 mo in quartile 2 (ITA.LI.CA score 2-3), 23 and 23 mo in quartile 3 (ITA.LI.CA score 4-5), and 9 and 8 mo in quartile 4 (ITA.LI.CA score > 5). Observed and predicted median survival in the training and internal validation sets largely coincided. Although observed and predicted survival estimations were significantly lower (log-rank test, p < 0.001) in Italian than in Taiwanese patients, the ITA.LI.CA score maintained very high discrimination and calibration features also in the external validation cohort. The concordance index (C index) of the ITA.LI.CA score in the internal and external validation cohorts was 0.71 and 0.78, respectively. The ITA.LI.CA score's prognostic ability was significantly better (p < 0.001) than that of BCLC stage (respective C indexes of 0.64 and 0.73), CLIP score (0.68 and 0.75), JIS stage (0.67 and 0.70), MESIAH score (0.69 and 0.77), and HKLC stage (0.68 and 0.75). The main limitations of this study are its retrospective nature and the intrinsically significant differences between the Taiwanese and Italian groups.The ITA.LI.CA prognostic system includes both a tumor staging-stratifying patients with HCC into six main stages (0, A, B1, B2, B3, and C)-and a prognostic score-integrating ITA.LI.CA tumor staging, CPS, ECOG performance status, and AFP. The ITA.LI.CA prognostic system shows a strong ability to predict individual survival in European and Asian populations.

Published
2016
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14. Incidence of HCC recurrence after DAA treatment for HCV in a multicentre Italian cohort study

Author

Nicola Caporaso, Angelo Salomone Megna, Maria Guarino, Filomena Morisco, Nicola Coppola, Federica Morando, Marco Guarracino, Anna Sessa, Luca Rinaldi, Andrea Aglitti, Dario Bruzzese, Giovan Giuseppe Di Costanzo, Guarino, Maria, Giuseppe Di Costanzo, Giovan, Bruzzese, Dario, Sessa, Anna, Guarracino, Marco, Rinaldi, Luca, Aglitti, Andrea, Salomone Megna, Angelo, Morando, Federica, Coppola, Nicola, Caporaso, Nicola, and Morisco, Filomena

Subjects
medicine.medical_specialty, Complementary and alternative medicine, business.industry, Internal medicine, Incidence (epidemiology), medicine, Pharmaceutical Science, Pharmacology (medical), medicine.disease, business, Obesity, Cohort study
Published
2020

15. Migratory flow and hepatitis delta infection in Italy: A new challenge at the beginning of the third millennium

Author

Tommaso Stroffolini, Alessia Ciancio, Caterina Furlan, Maria Vinci, Rosanna Fontana, Maurizio Russello, Guido Colloredo, Filomena Morisco, Nicola Coppola, Sergio Babudieri, Luigina Ferrigno, Caterina Sagnelli, Evangelista Sagnelli, Giulia Verzon, Arianna Latanza, Viviana Picciotto, Grazia Anna Niro, Rosa Grazia Benigno, Giuseppina Pontillo, Vincenzo Messina, Vito Fiore, Stroffolini, T., Ciancio, A., Furlan, C., Vinci, M., Fontana, R., Russello, M., Colloredo, G., Morisco, F., Coppola, N., Babudieri, S., Ferrigno, L., Sagnelli, C., and Sagnelli, E.

Subjects
Male, HBsAg carriers, Cirrhosis, Multivariate analysis, viruses, Emigrants and Immigrants, 03 medical and health sciences, 0302 clinical medicine, Virology, Prevalence, Advanced disease, Humans, Medicine, Multiple logistic regression analysis, Hepatitis Antibodies, 030212 general & internal medicine, Hepatology, HDV infection, HDV infection endemicity, business.industry, HEPATITIS DELTA, virus diseases, Mean age, Middle Aged, biochemical phenomena, metabolism, and nutrition, medicine.disease, Hepatitis D, HBsAg carrier, Infectious Diseases, Italy, Female, 030211 gastroenterology & hepatology, Hbsag carrier, Hepatitis Delta Virus, business, Demography
Abstract

In Italy, HDV infection endemicity has greatly decreased overtime. Migratory flow may change this scenario as migrants often come from high HDV endemicity areas. Here, we studied characteristics of HDV infection in Italy, particularly addressed to the birth area of subjects. Chronic HBsAg carriers consecutively referring to 9 units in Italy prospectively enrolled for a six-month period in 2019 were tested for anti-HDV by ELISA. Multiple logistic regression analysis was performed to identify anti-HDV positivity independent predictors. A total of 894 HBsAg-positive subjects were enrolled. Of them, 786 (87.9%) were tested for anti-HDV. Anti-HDV overall prevalence was 9.9% (6.4% in Italian natives and 26.4% in non-natives; P&nbsp

Published
2020

16. The association between education level and chronic liver disease of any etiology

Author

Evangelista Sagnelli, Filomena Morisco, Maurizio Russello, Sergio Babudieri, Caterina Sagnelli, Caterina Furlan, Mariantonietta Pisaturo, Mario Pirisi, Piero Luigi Almasio, Antonina Smedile, Tommaso Stroffolini, Stroffolini, T., Sagnelli, E., Sagnelli, C., Morisco, F., Babudieri, S., Furlan, C., Pirisi, M., Russello, M., Smedile, A., Pisaturo, M., Almasio, P. L., Stroffolini T., Sagnelli E., Sagnelli C., Morisco F., Babudieri S., Furlan C., Pirisi M., Russello M., Smedile A., Pisaturo M., and Almasio P.L.

Subjects
Liver Cirrhosis, medicine.medical_specialty, Cirrhosis, Alcohol Drinking, Liver Cirrhosi, Disease, 030204 cardiovascular system & hematology, Educational setting, Chronic liver disease, Logistic regression, Chronic disease, 03 medical and health sciences, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Internal medicine, HBV, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Stage (cooking), Association (psychology), business.industry, Liver Diseases, Liver Disease, Fatty liver, Middle Aged, medicine.disease, Italy, HCV, Etiology, Liver disorder, Alcohol, business, Human, Liver disorders
Abstract

Background The potential link between educational level and chronic liver diseases (CLD) were explored using the mortality records of liver cirrhosis, which lack accuracy and are unable to identify the different etiological factors of liver cirrhosis. Information on the association of low educational level with the severity of CLD is lacking. Aim To evaluate the potential association linking education level to etiology and clinical stage of CLD cases. Methods Consecutive enrolment of 11,107 subjects with CLD aged≥18 years prospectively recruited in two national surveys in 2001 and 2014 at one of the participating Italian liver units throughout the country. Subjects were pooled in two groups: low education level (less than high school) and high education level (completed high school or beyond). The association of demographic, etiological, and clinical stage of subjects with educational level was assessed using logistic regression analysis. In the analysis low educational level was the outcome variable. Results A total of 11,107 subjects born in Italy (mean age 55.5 years, sex ratio 1.5) were evaluated. Multiple logistic regression analysis shows that chronic HCV infection (O.R.1,38:95%,C.I.1.23-1.55), risky alcohol intake (O.R.1.96;95%,C.I.1.73-2.21) and liver cirrhosis (O.R.1.65;95%,C.I.1.46-1.85) all resulted independently associated with less than a completed high school education. HBV infection resulted independently associated with high education level (O.R.0.74;95%,C.I.0.64-0.86), reflecting changes in HBV modes of transmission in recent decades. No association was found with CLD related to non-alcoholic fatty liver disease (O.R.1.03;95%, C.I.0.81-1.30). Conclusions These findings show an independent association linking education level with viruses and alcohol-related CLD. Low educational level is associated with the severity of CLD.

Published
2020

17. Evaluation of the Effect Derived from Silybin with Vitamin D and Vitamin E Administration on Clinical, Metabolic, Endothelial Dysfunction, Oxidative Stress Parameters, and Serological Worsening Markers in Nonalcoholic Fatty Liver Disease Patients

Author

Rosa Di Sarno, Stefania Lama, Antonietta Gerarda Gravina, Alessandro Federico, Mario Masarone, Carmelina Loguercio, Marcello Persico, Marcello Dallio, Valentina Cossiga, Concetta Tuccillo, Paola Stiuso, Filomena Morisco, Federico, A., Dallio, M., Masarone, M., Gravina, A. G., Di Sarno, R., Tuccillo, C., Cossiga, V., Lama, S., Stiuso, P., Morisco, F., Persico, M., and Loguercio, C.

Subjects
Male, 0301 basic medicine, Aging, Chronic liver disease, Biochemistry, Gastroenterology, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Nonalcoholic fatty liver disease, Vitamin E, Vitamin D, Endothelial dysfunction, Endothelial Cell, lcsh:Cytology, General Medicine, Middle Aged, Liver, Homeostatic model assessment, Cytokines, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, Human, Research Article, Adult, medicine.medical_specialty, Article Subject, 03 medical and health sciences, Insulin resistance, Internal medicine, medicine, Vitamin D and neurology, Humans, lcsh:QH573-671, Cytokine, Aged, business.industry, Body Weight, Endothelial Cells, Oxidative Stre, Biomarker, Cell Biology, medicine.disease, Oxidative Stress, 030104 developmental biology, Silybin, Insulin Resistance, Metabolic syndrome, business, Transient elastography, Biomarkers
Abstract

Nowadays, the nonalcoholic fatty liver disease represents the main chronic liver disease in the Western countries, and the correct medical therapy remains a big question for the scientific community. The aim of our study was to evaluate the effect derived from the administration for six months of silybin with vitamin D and vitamin E (RealSIL 100D®) on metabolic markers, oxidative stress, endothelial dysfunction, and worsening of disease markers in nonalcoholic fatty liver disease patients. We enrolled 90 consecutive patients with histological diagnosis of nonalcoholic fatty liver disease and 60 patients with diagnosis of reflux disease (not in therapy) as healthy controls. The nonalcoholic fatty liver disease patients were randomized into two groups: treated (60 patients) and not treated (30 patients). We performed a nutritional assessment and evaluated clinical parameters, routine home tests, the homeostatic model assessment of insulin resistance, NAFLD fibrosis score and fibrosis-4, transient elastography and controlled attenuation parameter, thiobarbituric acid reactive substances, tumor necrosis factor α, transforming growth factor β, interleukin-18 and interleukin-22, matrix metalloproteinase 2, epidermal growth factor receptor, insulin growth factor-II, cluster of differentiation-44, high mobility group box-1, and Endocan. Compared to the healthy controls, the nonalcoholic fatty liver disease patients had statistically significant differences for almost all parameters evaluated at baseline (p<0.05). Six months after the baseline, the proportion of nonalcoholic fatty liver disease patients treated that underwent a statistically significant improvement in metabolic markers, oxidative stress, endothelial dysfunction, and worsening of disease was greater than not treated nonalcoholic fatty liver disease patients (p<0.05). Even more relevant results were obtained for the same parameters by analyzing patients with a concomitant diagnosis of metabolic syndrome (p<0.001). The benefit that derives from the use of RealSIL 100D could derive from the action on more systems able to advance the pathology above all in that subset of patients suffering from concomitant metabolic syndrome.

Published
2019

18. Acute Delta Hepatitis in Italy spanning three decades (1991-2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Author

Tommaso, Stroffolini, Filomena, Morisco, Luigina, Ferrigno, Giuseppina, Pontillo, Giuseppina, Iantosca, Valentina, Cossiga, Simonetta, Crateri, Maria Elena Tosti, Valeria, Alfonsi, Franca, D'Angelo, Zotti, Carla Maria, Rainero, Erika, Marengo, Noemi, Silvana, Malaspina, Angela, Gallone, Annalisa, Castella, Maria Teresa Galati, Annamaria, Scala, Paolo, Castagna, Virginia, Silano, Sebastiano, D'Agosta, Maria Grazia Tacca, Silvia, Iodice, Vilma, Corvi, Maurizio, Oddone, Daniela, Rivetti, Paola, Ravaschietto, Franco, Giovanetti, Teresa, Cappello, Alessandro, Smaniotto, Mario, Ruffier, Marina, Verardo, Maria, Gramegna, Sabrina, Senatore, Danilo, Cereda, Annalisa, Donadini, Carla, Nespoli, Livia, Trezzi, Giorgio, Gennati, Angelo, Monteverdi, Liana, Boldori, Franco Paolo Tortorella, Paola Elvira Merlini, Davide Di Caterina, Marino, Faccini, Anna, Lamberti, Eva, Rossetti, Rita, Brugnoli, Giulia, Mainardi, Alessandra, Vezzoli, Daniela, Caso, Milena, Testa, Alice, Erba, Paola, Senegaglia, Annamaria, Spagna, Silvia, Lodola, Marcello, Tirani, Enza, Giompapa, Luigi Guido Roveri, Gabriele, Guardigli, Vanna, Scalvinoni, Silvia, Spertini, Sabine, Gamper, Andrea, Grünfelder, Barbara, Ploner, Verena, Runggatscher, Silvia, Molinaro, Maria Grazia Zuccali, Silvia, Franchini, Francesca, Russo, Francesca, Zanella, Donatella, Rizzato, Graziella, Carpene, Nadia, Lamonato, Emanuela, Destefani, Alessandra Dal Zotto, Rita Dal Zotto, Paola, Casagrande, Felice, Foglia, Gemma, Zorzi, Ester, Chermaz, Liana, Gava, Luigi, Nicolardi, Lorena, Pavanetto, Cecilia, Battiston, Francesco De Grandi, Laura, Rizzato, Michele, Tonon, Elisabetta, Cannizzo, Maurizio, Foroni, Laura, Colucci, Monica, Barbieri, Rosanna, Ledri, Tolinda, Gallo, Giulio, Rocco, Rossana, Stacul, Ariella, Breda, Andrea, Iob, Simonetta, Micossi, Oriana, Feltrin, Giuseppina, Caernelos, Marco, Mela, Virna, Frumento, Anna, Opisso, Alessandro, Cuccu, Giorgio, Zoppi, Patrizia, Torracca, Armanda, Capellini, Francesco, Maddalo, Giovanna, Mattei, Claudio, Gualanduzzi, Erika, Massimiliani, Anna Rita Sacchi, Laura, Gardenghi, Anna Rosa Gianninoni, Elena Dalle Donne, Roberto, Rangoni, Annalisa, Califano, Chiara, Reali, Emilia, Biguzzi, Barbara, Bondi, Anna, Pecci, Bianca Maria Borrini, Lucia, Pecori, Emanuela, Balocchini, Costanza, Pierozzi, Rosa, Luzzoli, Paola, Marchini, Lara, Lucchesi, Alberto, Tomasi, Elisabetta, Raso, Nadia, Olimpi, Cristiana, Berti, Francesca, Matarazzo, Nicoletta, Galletti, Laura, Puppa, Marinella, Frasca, Alessandro, Barbieri, Chiara, Cinughi, Maria, Bandini, Iorio, Lezzi, Fabrizia, Verdelli, Renzo, Paradisi, Rita, Bindi, Cinzia Monica Sansone, Maria, Rosati, Federica, Zacchini, Simonetta, Baretti, Rossella, Cecconi, Chiara, Staderini, Poalo, Filidei, Elisabetta, Alfaroli, Franco, Barghini, Marina, Cadoni, Anna, Tosti, Giovannini, G, Giovanni, Piattellini, Alessandra, Buscosi, Anna, Pasquale, Carla, Ciani, Maria Claudia Paoloni, Franco, Santocchia, Maria Laura Proietti, Daniel, Fiacchini, Dzenana, Hazurovic, Maria Sole Giamprini, Katia, Gatti, Jacqueline Van Will, Alfredo, Vaccaro, Maria Margherita Sbarbati, Alessandra, Amelio, Daniela, Cimini, Vania, Moroni, Daniela, Francoletti, Federica, Scaccia, Elisabetta, Branchesi, Selena, Saracino, Catia, Mezzanotte, Susanna, Cimica, Vita, Vitale, Franca, Laici, Irene, Petrelli, Barbara, Airini, Gabriella, Passarini, Lucia, Ruffini, Anna Maria Lambertucci, Annarita, Mogetta, Francesca, Cioccoloni, Giuseppe, Ciarrocchi, Marina, Pistolesi, Erika, Fratello, Francesca, Picciotti, Claudio, Angelini, Paola, Scognamiglio, Francesco, Vairo, Andreina, Ercole, Antonio Salvatore Maglietta, Fabrizio, Magrelli, Fabrizio, Perrelli, Carlo, Cerocchi, Paolo, Grillo, Cristina, Vazzoler, Maria Rosaria Loffredo, Alessio, Pendenza, Maria Rosaria Nappi, Paola, Bueti, Luigi, Santucci, Franca, Mangiagli, Donatella, Varrenti, Silvia, Aquilani, Pietro, Dionette, Daniela, Corpolongo, Giuseppe Di Luzio, Manuela Di Giacomo, Enrico, Giansanti, Cristiana, Mancini, Claudio, Turchi, Carla, Granchelli, Graziella, Soldato, Felesina, D'Eugenio, Ida, Albanesi, Maria Antonietta Ferrara, Annarita, Citarella, Elena, Fossi, Rosa, Alfieri, Milena, Scotto, Anna Luisa Caiazzo, Rosa, Prato, Maria, Chironna, Domenico, Martinelli, Francesca, Fortunato, Maria Giovanna Cappelli, Daniela, Loconsole, Anna, Morea, Giulia Del Matto, Raffaele, Angelillis, Marcello, Antonazzo, Valerio, Aprile, Grazia Maria Avella, Roberta, Cambria, Giovanni, Caputi, Rosati, Cipriani, Carlo De Santis, Francesco, Desiante, Marisa, Ferraro, Vera, Laforgia, Antonino, Madaro, Maria Giuseppina Maluccio, Anna Maria Matera, Stefania, Menolascina, Giuseppina, Moffa, Maria, Nesta, Rita, Olivieri, Onofrio, Pagone, Pasquale, Pedote, Rosella, Squicciarini, Stefano, Termite, Viviana, Vitale, Francesco, Negrone, Manuela, Maldini, Giovanni, Laugello, Teresa, Russo, Anna Domenica Mignuoli, Giuseppe, Afflitto, Benedetto, Caroleo, Maria, Montesanti, Vincenzo De Giorgio, Antonio, Maradei, Rocco Cataldo Romeo, Francesca, Scrivano, Elisa, Lazzarino, Vittoria, Surace, Antonella, Giordano, Alessandro, Bisbano, Anita, Arcuri, Ida, Valentini, Rossana, Mangione, Valentina, Meli, Mario, Cuccia, Elena, Longhitano, Fiorenzo, Delogu, Donatella, Fracasso, Maria Vittoria Marceddu, Antonina, Puggioni, Maria Valentina Eugenua Marras, Rita, Serpi, Simonetta, Santus, Valentina, Marras, Stroffolini, Tommaso, Morisco, Filomena, Ferrigno, Luigina, Pontillo, Giuseppina, Iantosca, Giuseppina, Cossiga, Valentina, Crateri, Simonetta, and Tosti, Maria Elena

Subjects
Adult, Male, medicine.medical_specialty, HBsAg, Hepatitis B virus, viruses, Population, hepatitis delta, medicine.disease_cause, Virology, Internal medicine, Epidemiology, medicine, Humans, hepatitis B vaccination, education, Hepatitis, education.field_of_study, Hepatitis B Surface Antigens, Hepatology, business.industry, Immunization Programs, Incidence (epidemiology), virus diseases, biochemical phenomena, metabolism, and nutrition, medicine.disease, Hepatitis B, Hepatitis D, Vaccination, Infectious Diseases, surveillance, epidemiology, Female, Hepatitis Delta Virus, business, Viral hepatitis
Abstract

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p

Published
2021

19. Risk stratification of HCC occurrence after HCV eradication: a complicate plot of risk factors related and unrelated to the previous viral disease

Author

Nicola Caporaso, Filomena Morisco, Valentina Cossiga, Maria Guarino, Cossiga, Valentina, Guarino, Maria, Morisco, Filomena, and Caporaso, Nicola

Subjects
Oncology, medicine.medical_specialty, Cirrhosis, business.industry, Hepatitis C virus, Cancer, medicine.disease_cause, medicine.disease, digestive system diseases, 03 medical and health sciences, Editorial, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Hepatocellular carcinoma, Risk stratification, medicine, 030211 gastroenterology & hepatology, Viral disease, Risk factor, business
Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second most frequent cause of cancer-related death worldwide. Hepatitis C virus (HCV) infection is one of leading cause of cirrhosis, that is the strongest risk factor for the development of HCC in Western countries (1,2).

Published
2020

20. Impact of the Sars-Cov-2 Pandemic on Gastroenterology Units in Italy: a National Survey

Author

Edoardo Savarino, S. Sferrazza, Bruno Annibale, Patrizia Burra, Lorenzo Fuccio, A. Repici, Santino Marchi, Gianluca Ianiro, Gaetano Cristian Morreale, Luigi Ricciardiello, Antonio Benedetti, M Maida, Domenico Alvaro, Manuele Furnari, Filomena Morisco, and Alessandro Vitello

Subjects
medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Health professionals, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Gastroenterology, ULTRASOUND PROCEDURES, Internal medicine, Pandemic, medicine, Observational study, business, Personal protective equipment
Abstract

Aims This is a prospective observational web-based survey aimed to assess the impact of SARS-CoV-2 pandemic onGastroenterology Units in Italy. Methods All members of the Italian Society of Gastroenterology (SIGE) were invited to answer a 39-point multiple-choiceweb-based survey between March 30 thand April 7 th2020. Results Data of 121 hospitals from all 20 Italian regions were analyzed. Overall, 10.7 % of Gastroenterology divisions havebeen converted to COVID Units. Outpatients consultations, endoscopic and ultrasound procedures were limited to urgenciesand oncology indications in 85.1 %, 96.2 % and 72.2 % of Units, respectively, and 46.7 % of Units suspended the screeningfor colorectal cancer.In order to guarantee the ordinary follow-up of outpatients, 83/121 (68.6 %) divisions activated aremote consultancy service (63.9 % by phone, 31.3 % by email, 4.8 % by video). Overall, 112/121 (92.6 %) GI Units issued and followed a specific protocol for the management of patients with suspectedor confirmed SARS-CoV-2 infection. The 72.2 % of the staff received proper training for the use of personal protective equipment, although 45.5 % did not havesufficient devices for an adequate replacement. With regard to PPE availability, N95/FFP2-3 masks were available in 91/121 (75.2 %), surgical masks in 115/121 (95.0 %),gloves in 117/121 (96.7 %), disposable gown in 100/121 (82.6 %), hairnet in 104/121 (85.9 %), goggles in 78/121 (64.5 %)and boots in 57/121 (47.1 %) of divisions. Finally, in 41/121 GI divisions (33.9 %) there was at least one healthcare professional who got infected, in a total of 132subjects, of which 121/132 from divisions not-converted to COVID Units and 75/132 from high-prevalence areas. Conclusions Substantial changes of practice and reduction of procedures have been recorded in the entire country duringthe first wave of the pandemic. The long-term impact of such modifications is difficult to estimate but potentially very riskyfor many digestive diseases.

Published
2021

21. Performance of the model for end-stage liver disease score for mortality prediction and the potential role of etiology

Author

Roberto Miraglia, Matteo Garcovich, Giulia Tosetti, Nicola Caporaso, Agostino Colli, Antonio Rampoldi, Ioannis Petridis, Stella De Nicola, Angelo Andriulli, Marcello Dallio, Giovanni Perricone, G. Gobbo, Filomena Morisco, Antonio Gasbarrini, Pietro Pozzoni, Giuseppe Malizia, Angelo Vanzulli, Gennaro D'Amico, Gianluca Svegliati Baroni, Angelo Luca, Francesco Salerno, Mario D'Amico, Manuela Merli, Luca S. Belli, Vincenzo La Mura, Luchino Chessa, A. Iacobellis, Giuseppe Tarantino, Marco Solcia, Cristiano Sgrazzutti, Lorenzo Ridola, Luigi Maruzzelli, Alessandro Federico, Aldo Airoldi, Luigi Addario, Riccardo Volpes, Massimo Primignani, D'Amico, G., Maruzzelli, L., Airoldi, A., Petridis, I., Tosetti, G., Rampoldi, A., D'Amico, M., Miraglia, R., De Nicola, S., La Mura, V., Solcia, M., Volpes, R., Perricone, G., Sgrazzutti, C., Vanzulli, A., Primignani, M., Luca, A., Malizia, G., Federico, A., Dallio, M., Andriulli, A., Iacobellis, A., Addario, L., Garcovich, M., Gasbarrini, A., Chessa, L., Salerno, F., Gobbo, G., Merli, M., Ridola, L., Baroni, G. S., Tarantino, G., Caporaso, N., Morisco, F., Pozzoni, P., Colli, A., Belli, L. S., D'Amico, Gennaro, Maruzzelli, Luigi, Airoldi, Aldo, Petridis, Ioanni, Tosetti, Giulia, Rampoldi, Antonio, D'Amico, Mario, Miraglia, Roberto, De Nicola, Stella, La Mura, Vincenzo, Solcia, Marco, Volpes, Riccardo, Perricone, Giovanni, Sgrazzutti, Cristiano, Vanzulli, Angelo, Primignani, Massimo, D'Angelo, Luca, Malizia, Giuseppe, Federico, Alessandro, Dallio, Marcello, Andriulli, Angelo, Iacobellis, Angelo, Addario, Luigi, Garcovich, Matteo, Gasbarrini, Antonio, Chessa, Luchino, Salerno, Francesco, Gobbo, Giulia, Merli, Manuela, Ridola, Lorenzo, Baroni, Gianluca Svegliati, Tarantino, Giuseppe, Caporaso, Nicola, Morisco, Filomena, Pozzoni, Pietro, Colli, Agostino, Belli, Luca Saverio, D'Amico, G, Maruzzelli, L, Airoldi, A, Petridis, I, Tosetti, G, Rampoldi, A, D'Amico, M, Miraglia, R, De Nicola, S, La Mura, V, Solcia, M, Volpes, R, Perricone, G, Sgrazzutti, C, Vanzulli, A, Primignani, M, Luca, A, Malizia, G, Federico, A, Dallio, M, Andriulli, A, Iacobellis, A, Addario, L, Garcovich, M, Gasbarrini, A, Chessa, L, Salerno, F, Gobbo, G, Merli, M, Ridola, L, Baroni, G, Tarantino, G, Caporaso, N, Morisco, F, Pozzoni, P, Colli, A, and Belli, L

Subjects
Adult, medicine.medical_specialty, Cirrhosis, Time Factors, medicine.medical_treatment, Validation Studies as Topic, Models, Biological, Severity of Illness Index, Cohort Studies, End Stage Liver Disease, Liver disease, Model for End-Stage Liver Disease, clinical prediction rule, Internal medicine, Post-hoc analysis, Medicine, Humans, Mortality, Aged, Hepatology, business.industry, cirrhosis, Middle Aged, medicine.disease, Prognosis, MELD, body regions, Italy, Cohort, Etiology, TIPS, Steatohepatitis, business, Transjugular intrahepatic portosystemic shunt, cirrhosi, Follow-Up Studies
Abstract

Background & Aims Although the discriminative ability of the model for end-stage liver disease (MELD) score is generally considered acceptable, its calibration is still unclear. In a validation study, we assessed the discriminative performance and calibration of 3 versions of the model: original MELD-TIPS, used to predict survival after transjugular intrahepatic portosystemic shunt (TIPS); classic MELD-Mayo; and MELD-UNOS, used by the United Network for Organ Sharing (UNOS). We also explored recalibrating and updating the model. Methods In total, 776 patients who underwent elective TIPS (TIPS cohort) and 445 unselected patients (non-TIPS cohort) were included. Three, 6 and 12-month mortality predictions were calculated by the 3 MELD versions: discrimination was assessed by c-statistics and calibration by comparing deciles of predicted and observed risks. Cox and Fine and Grey models were used for recalibration and prognostic analyses. Results In the TIPS/non-TIPS cohorts, the etiology of liver disease was viral in 402/188, alcoholic in 185/130, and non-alcoholic steatohepatitis in 65/33; mean follow-up±SD was 25±9/19±21 months; and the number of deaths at 3-6-12 months was 57-102-142/31-47-99, respectively. C-statistics ranged from 0.66 to 0.72 in TIPS and 0.66 to 0.76 in non-TIPS cohorts across prediction times and scores. A post hoc analysis revealed worse c-statistics in non-viral cirrhosis with more pronounced and significant worsening in the non-TIPS cohort. Calibration was acceptable with MELD-TIPS but largely unsatisfactory with MELD-Mayo and -UNOS whose performance improved much after recalibration. A prognostic analysis showed that age, albumin, and TIPS indication might be used to update the MELD. Conclusions In this validation study, the performance of the MELD score was largely unsatisfactory, particularly in non-viral cirrhosis. MELD recalibration and candidate variables for an update to the MELD score are proposed. Lay summary While the discriminative performance of the model for end-stage liver disease (MELD) score is credited to be fair to good, its calibration, the correspondence of observed to predicted mortality, is still unsettled. We found that application of 3 different versions of the MELD in 2 independent cirrhosis cohorts yielded largely imprecise mortality predictions particularly in non-viral cirrhosis. Thus, we propose a recalibration and suggest candidate variables for an update to the model.

Published
2021

22. Changes in hepatocellular carcinoma aggressiveness characteristics with an increase in tumor diameter

Author

Giovanni Raimondo, Alberto Masotto, Edoardo G. Giannini, Filippo Oliveri, Fabio Piscaglia, Francesco Giuseppe Foschi, Giuseppe Cabibbo, Gianpaolo Vidili, Francesco Azzaroli, Gian Ludovico Rapaccini, Antonio Gasbarrini, Rodolfo Sacco, Franco Trevisani, Gerardo Nardone, Maria Di Marco, Fabio Marra, Brian I. Carr, Eugenio Caturelli, Andrea Mega, Marco Zoli, Filomena Morisco, Vito Guerra, Gianluca Svegliati-Baroni, Fabio Farinati, Gabriele Missale, Rossella Donghia, Carr B.I., Guerra V., Donghia R., Farinati F., Giannini E.G., Piscaglia F., Rapaccini G.L., Di Marco M., Caturelli E., Zoli M., Sacco R., Cabibbo G., Marra F., Mega A., Morisco F., Gasbarrini A., Svegliati-Baroni G., Foschi F.G., Missale G., Masotto A., Nardone G., Raimondo G., Azzaroli F., Vidili G., Oliveri F., Trevisani F., Carr, B. I., Guerra, V., Donghia, R., Farinati, F., Giannini, E. G., Piscaglia, F., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Sacco, R., Cabibbo, G., Marra, F., Mega, A., Morisco, F., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F. G., Missale, G., Masotto, A., Nardone, G., Raimondo, G., Azzaroli, F., Vidili, G., Oliveri, F., and Trevisani, F.

Subjects
Male, Cancer Research, Pathology, medicine.medical_specialty, Carcinoma, Hepatocellular, Prognosi, Settore MED/12 - GASTROENTEROLOGIA, Clinical Biochemistry, size, Pathology and Forensic Medicine, evolution, medicine, Humans, Prospective Studies, HCC, Tumor size, business.industry, Liver Neoplasms, Carcinoma, Settore MED/09 - MEDICINA INTERNA, Hepatocellular, Middle Aged, Prognosis, medicine.disease, Portal vein thrombosis, trend, Oncology, Liver Neoplasm, Hepatocellular carcinoma, Female, business, Human
Abstract

Background: Hepatocellular carcinoma prognosis depends on both liver and tumor determinants, especially on maximum tumor diameter, multifocality, and presence of portal vein thrombosis, despite apparently complete tumor removal by resection or liver transplantation. Aims: To examine parameters of hepatocellular carcinoma aggressiveness as tumor size increases. Methods: A large hepatocellular carcinoma database was examined for trends in serum alpha-fetoprotein and the percentage of patients with macroscopic portal vein thrombosis or tumor multifocality. Results: A total of 13,016 hepatocellular carcinoma patients were identified having full tumor and survival data. Of these, 76.56% were male and 23.44% were female, with a median age of 64.4 years. We found that as the maximum tumor diameter increased, there was a significant trend for increased alpha-fetoprotein levels ( PConclusions: The greater fold-increases in alpha-fetoprotein and portal vein thrombosis compared with increases in maximum tumor diameter imply that hepatocellular carcinoma characteristics may change with increasing size to a more aggressive phenotype, suggesting that follow-up tumor sampling might be useful, in addition to baseline tumor sampling, for optimal therapeutic choices to be made.

Published
2021

23. Clinical features and comorbidity pattern of HCV infected migrants compared to native patients in care in Italy: A real-life evaluation of the PITER cohort

Author

Maria Giovanna Quaranta, Luigina Ferrigno, Xhimi Tata, Franca D'Angelo, Marco Massari, Carmine Coppola, Elisa Biliotti, Alessia Giorgini, Diletta Laccabue, Alessia Ciancio, Pier Luigi Blanc, Marzia Margotti, Donatella Ieluzzi, Maurizia Rossana Brunetto, Francesco Barbaro, Francesco Paolo Russo, Ilaria Beretta, Giulia Morsica, Gabriella Verucchi, Annalisa Saracino, Massimo Galli, Loeta A. Kondili, Cesare Mazzaro, Manuela Bertola, Ornella Schioppa, Antonio Benedetti, Laura Schiadà, Monica Cucco, Andrea Giacometti, Laura Brescini, Sefora Castelletti, Alessandro Fiorentini, Gioacchino Angarano, Michele Milella, Alfredo Di Leo, Maria Rendina, Fulvio Salvatore D'abramo, Chiara Lillo, Andrea Iannone, Mariano Piazzolla, Lorenzo Badia, Fabio Piscaglia, Francesca Benevento, Ilaria Serio, Francesco Castelli, Serena Zaltron, Angiola Spinetti, Silvia Odolini, Raffaele Bruno, Mario Mondelli, Luchino Chessa, Martina Loi, Carlo Torti, Chiara Costa, Maria Mazzitelli, Vincenzo Pisani, Vincenzo Scaglione, Enrico Maria Trecarichi, Anna Linda Zignego, Monica Monti, Francesco Madia, Letizia Attala, Piera Pierotti, Elena Salomoni, Elisa Mariabelli, Teresa Antonia Santantonio, Serena Rita Bruno, Ester Marina Cela, Matteo Bassetti, Giovanni Mazzarello, Anna Ida Alessandrini, Antonio Di Biagio, Laura Ambra Nicolini, Giovanni Raimondo, Roberto Filomia, Alessio Aghemo, Rossella Meli, Adriano Lazzarin, Stefania Salpietro, Anna Ludovica Fracanzani, Erika Fatta, Rosa Lombardi, Pietro Lampertico, Marta Borghi, Roberta D'ambrosio, Elisabetta Degasperi, Massimo Puoti, Chiara Baiguera, Federico D'amico, Maria Vinci, Maria Grazia Rumi, Massimo Zuin, Paola Zermiani, Pietro Andreone, Paolo Caraceni, Valeria Guarneri, Erica Villa, Veronica Bernabucci, Laura Bristot, Maria Luisa Paradiso, Guglielmo Migliorino, Alessandra Gambaro, Giuseppe Lapadula, Anna Spolti, Alessandro Soria, Pietro Invernizzi, Antonio Ciaccio, Martina LucÀ, Federica Malinverno, Laura Ratti, Daniela Caterina Amoruso, Federica Pisano, Ferdinando Scarano, Laura Staiano, Filomena Morisco, Valentina Cossiga, Ivan Gentile, Antonio Riccardo Buonomo, Maria Foggia, Emanuela Zappulo, Alessandro Federico, Marcello Dallio, Nicola Coppola, Caterina Sagnelli, Salvatore Martini, Caterina Monari, Gerardo Nardone, Costantino Sgamato, Liliana Chemello, Luisa Cavalletto, Daniela Sterrantino, Alberto Zanetto, Paola Zanaga, Giuseppina Brancaccio, Antonio Craxì, Salvatore Petta, Vincenza Calvaruso, Luciano Crapanzano, Salvatore Madonia, Marco Cannizzaro, Erica Maria Bruno, Anna Licata, Simona Amodeo, Adele Rosaria Capitano, Carlo Ferrari, Elisa Negri, Alessandra Orlandini, Marco Pesci, Roberto Gulminetti, Layla Pagnucco, Giustino Parruti, Paola Di Stefano, Barbara Coco, Romina Corsini, Elisa Garlassi, Massimo Andreoni, Elisabetta Teti, Carlotta Cerva, Lorenzo Baiocchi, Giuseppe Grassi, Antonio Gasbarrini, Maurizio Pompili, Martina De Siena, Gloria Taliani, Martina Spaziante, Marcello Persico, Mario Masarone, Andrea Aglitti, Gemma Calvanese, Marco Anselmo, Pasqualina De Leo, Monica Marturano, Giorgio Maria Saracco, Quaranta M.G., Ferrigno L., Tata X., D'Angelo F., Massari M., Coppola C., Biliotti E., Giorgini A., Laccabue D., Ciancio A., Blanc P.L., Margotti M., Ieluzzi D., Brunetto M.R., Barbaro F., Russo F.P., Beretta I., Morsica G., Verucchi G., Saracino A., Galli M., Kondili L.A., Mazzaro C., Bertola M., Benedetti A., Schiada L., Cucco M., Giacometti A., Brescini L., Castelletti S., Fiorentini A., Angarano G., Milella M., Leo A.D., Rendina M., Salvatore D'ABRAMO F., Lillo C., Iannone A., Piazzolla M., Badia L., Piscaglia F., Benevento F., Serio I., Castelli F., Zaltron S., Spinetti A., Odolini S., Bruno R., Mondelli M., Chessa L., Loi M., Torti C., Costa C., Mazzitelli M., Pisani V., Scaglione V., Trecarichi E.M., Zignego A.L., Monti M., Madia F., Attala L., Pierotti P., Salomoni E., Mariabelli E., Santantonio T.A., Bruno S.R., Cela E.M., Bassetti M., Mazzarello G., Alessandrini A.I., Biagio A.D., Nicolini L.A., Raimondo G., Filomia R., Aghemo A., Meli R., Lazzarin A., Salpietro S., Fracanzani A.L., Fatta E., Lombardi R., Lampertico P., Borghi M., D'ambrosio R., Degasperi E., Puoti M., Baiguera C., D'AMICO F., Vinci M., Rumi M.G., Zuin M., Zermiani P., Andreone P., Caraceni P., Guarneri V., Villa E., Bernabucci V., Bristot L., Paradiso M.L., Migliorino G., Gambaro A., Lapadula G., Spolti A., Soria A., Invernizzi P., Ciaccio A., LucA M., Malinverno F., Ratti L., Amoruso D.C., Pisano F., Scarano F., Staiano L., Morisco F., Cossiga V., Gentile I., Buonomo A.R., Foggia M., Zappulo E., Federico A., Dallio M., Coppola N., Sagnelli C., Martini S., Monari C., Nardone G., Sgamato C., Chemello L., Cavalletto L., Sterrantino D., Zanetto A., Zanaga P., Brancaccio G., Craxi A., Petta S., Calvaruso V., Crapanzano L., Madonia S., Cannizzaro M., Bruno E.M., Licata A., Amodeo S., Capitano A.R., Ferrari C., Negri E., Orlandini A., Pesci M., Gulminetti R., Pagnucco L., Parruti G., Stefano P.D., Coco B., Corsini R., Garlassi E., Andreoni M., Teti E., Cerva C., Baiocchi L., Grassi G., Gasbarrini A., Pompili M., Siena M.D., Taliani G., Spaziante M., Persico M., Masarone M., Aglitti A., Calvanese G., Anselmo M., Leo P.D., Marturano M., Saracco G.M., Quaranta, M, Ferrigno, L, Tata, X, D'Angelo, F, Massari, M, Coppola, C, Biliotti, E, Giorgini, A, Laccabue, D, Ciancio, A, Blanc, P, Margotti, M, Ieluzzi, D, Brunetto, M, Barbaro, F, Russo, F, Beretta, I, Morsica, G, Verucchi, G, Saracino, A, Galli, M, Kondili, L, Mazzaro, C, Bertola, M, Benedetti, A, Schiada, L, Cucco, M, Giacometti, A, Brescini, L, Castelletti, S, Fiorentini, A, Angarano, G, Milella, M, Leo, A, Rendina, M, Salvatore D'ABRAMO, F, Lillo, C, Iannone, A, Piazzolla, M, Badia, L, Piscaglia, F, Benevento, F, Serio, I, Castelli, F, Zaltron, S, Spinetti, A, Odolini, S, Bruno, R, Mondelli, M, Chessa, L, Loi, M, Torti, C, Costa, C, Mazzitelli, M, Pisani, V, Scaglione, V, Trecarichi, E, Zignego, A, Monti, M, Madia, F, Attala, L, Pierotti, P, Salomoni, E, Mariabelli, E, Santantonio, T, Bruno, S, Cela, E, Bassetti, M, Mazzarello, G, Alessandrini, A, Biagio, A, Nicolini, L, Raimondo, G, Filomia, R, Aghemo, A, Meli, R, Lazzarin, A, Salpietro, S, Fracanzani, A, Fatta, E, Lombardi, R, Lampertico, P, Borghi, M, D'Ambrosio, R, Degasperi, E, Puoti, M, Baiguera, C, D'Amico, F, Vinci, M, Rumi, M, Zuin, M, Zermiani, P, Andreone, P, Caraceni, P, Guarneri, V, Villa, E, Bernabucci, V, Bristot, L, Paradiso, M, Migliorino, G, Gambaro, A, Lapadula, G, Spolti, A, Soria, A, Invernizzi, P, Ciaccio, A, Luca, M, Malinverno, F, Ratti, L, Amoruso, D, Pisano, F, Scarano, F, Staiano, L, Morisco, F, Cossiga, V, Gentile, I, Buonomo, A, Foggia, M, Zappulo, E, Federico, A, Dallio, M, Coppola, N, Sagnelli, C, Martini, S, Monari, C, Nardone, G, Sgamato, C, Chemello, L, Cavalletto, L, Sterrantino, D, Zanetto, A, Zanaga, P, Brancaccio, G, Craxi, A, Petta, S, Calvaruso, V, Crapanzano, L, Madonia, S, Cannizzaro, M, Bruno, E, Licata, A, Amodeo, S, Capitano, A, Ferrari, C, Negri, E, Orlandini, A, Pesci, M, Gulminetti, R, Pagnucco, L, Parruti, G, Stefano, P, Coco, B, Corsini, R, Garlassi, E, Andreoni, M, Teti, E, Cerva, C, Baiocchi, L, Grassi, G, Gasbarrini, A, Pompili, M, Siena, M, Taliani, G, Spaziante, M, Persico, M, Masarone, M, Aglitti, A, Calvanese, G, Anselmo, M, Leo, P, Marturano, M, Saracco, G, Quaranta, M. G., Ferrigno, L., Tata, X., D'Angelo, F., Massari, M., Coppola, C., Biliotti, E., Giorgini, A., Laccabue, D., Ciancio, A., Blanc, P. L., Margotti, M., Ieluzzi, D., Brunetto, M. R., Barbaro, F., Russo, F. P., Beretta, I., Morsica, G., Verucchi, G., Saracino, A., Galli, M., Kondili, L. A., Mazzaro, C., Bertola, M., Benedetti, A., Schiada, L., Cucco, M., Giacometti, A., Brescini, L., Castelletti, S., Fiorentini, A., Angarano, G., Milella, M., Leo, A. D., Rendina, M., Salvatore D'ABRAMO, F., Lillo, C., Iannone, A., Piazzolla, M., Badia, L., Piscaglia, F., Benevento, F., Serio, I., Castelli, F., Zaltron, S., Spinetti, A., Odolini, S., Bruno, R., Mondelli, M., Chessa, L., Loi, M., Torti, C., Costa, C., Mazzitelli, M., Pisani, V., Scaglione, V., Trecarichi, E. M., Zignego, A. L., Monti, M., Madia, F., Attala, L., Pierotti, P., Salomoni, E., Mariabelli, E., Santantonio, T. A., Bruno, S. R., Cela, E. M., Bassetti, M., Mazzarello, G., Alessandrini, A. I., Biagio, A. D., Nicolini, L. A., Raimondo, G., Filomia, R., Aghemo, A., Meli, R., Lazzarin, A., Salpietro, S., Fracanzani, A. L., Fatta, E., Lombardi, R., Lampertico, P., Borghi, M., D'Ambrosio, R., Degasperi, E., Puoti, M., Baiguera, C., D'Amico, F., Vinci, M., Rumi, M. G., Zuin, M., Zermiani, P., Andreone, P., Caraceni, P., Guarneri, V., Villa, E., Bernabucci, V., Bristot, L., Paradiso, M. L., Migliorino, G., Gambaro, A., Lapadula, G., Spolti, A., Soria, A., Invernizzi, P., Ciaccio, A., Luca, M., Malinverno, F., Ratti, L., Amoruso, D. C., Pisano, F., Scarano, F., Staiano, L., Morisco, F., Cossiga, V., Gentile, I., Buonomo, A. R., Foggia, M., Zappulo, E., Federico, A., Dallio, M., Coppola, N., Sagnelli, C., Martini, S., Monari, C., Nardone, G., Sgamato, C., Chemello, L., Cavalletto, L., Sterrantino, D., Zanetto, A., Zanaga, P., Brancaccio, G., Craxi, A., Petta, S., Calvaruso, V., Crapanzano, L., Madonia, S., Cannizzaro, M., Bruno, E. M., Licata, A., Amodeo, S., Capitano, A. R., Ferrari, C., Negri, E., Orlandini, A., Pesci, M., Gulminetti, R., Pagnucco, L., Parruti, G., Stefano, P. D., Coco, B., Corsini, R., Garlassi, E., Andreoni, M., Teti, E., Cerva, C., Baiocchi, L., Grassi, G., Gasbarrini, A., Pompili, M., Siena, M. D., Taliani, G., Spaziante, M., Persico, M., Masarone, M., Aglitti, A., Calvanese, G., Anselmo, M., Leo, P. D., Marturano, M., and Saracco, G. M.

Subjects
Male, HCV genotypes, Ethnic group, Linked-to-care patient, Comorbidity, Hepacivirus, Logistic regression, medicine.disease_cause, Comorbidities, Direct acting antivirals, HCV Cohort, Linked-to-care patients, Aged, Antiviral Agents, Coinfection, Female, Hepatitis C, Chronic, Humans, Italy, Middle Aged, Transients and Migrants, 0302 clinical medicine, Medicine, Chronic, Gastroenterology, virus diseases, Hepatitis C, Life evaluation, 030220 oncology & carcinogenesis, Cohort, 030211 gastroenterology & hepatology, Comorbiditie, Human, Hepatitis C virus, Settore MED/12 - GASTROENTEROLOGIA, 03 medical and health sciences, Disease severity, Antiviral Agent, Hepaciviru, Hepatology, business.industry, Settore MED/09 - MEDICINA INTERNA, medicine.disease, digestive system diseases, Direct acting antiviral, business, Demography
Abstract

Background: Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort. Methods: Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used. Results: Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both groups, whereas genotype 4 was more prevalent in migrants (p < 0.05). Liver disease severity and sustained virologic response (SVR) were similar. A higher prevalence of comorbidities was reported for natives compared to migrants (p < 0.05). Liver disease progression cofactors (HBsAg, HIV coinfection, alcohol abuse, potential metabolic syndrome) were present in 39.1% and 47.1% (p > 0.05) of migrants and natives who eradicated HCV, respectively. Conclusion: Compared to natives, HCV-infected migrants in care have different demographics, HCV genotypes, viral coinfections and comorbidities and similar disease severity, SVR and cofactors for disease progression after HCV eradication. A periodic clinical assessment after HCV eradication in Italians and migrants with cofactors for disease progression is warranted.

Published
2021

24. Metabolic-associated fatty liver disease (MAFLD) in coeliac disease

Author

Valentina Cossiga, Anna Alisi, Nicola Imperatore, Maria Guarino, Simona Ricciolino, Antonio Rispo, Raffaella Tortora, Filomena Morisco, Andrea Fiorentino, Anna Testa, Rispo, A., Imperatore, N., Guarino, M., Tortora, R., Alisi, A., Cossiga, V., Testa, A., Ricciolino, S., Fiorentino, A., and Morisco, F.

Subjects
medicine.medical_specialty, Waist, Population, MAFLD, Disease, Gastroenterology, Coeliac disease, metabolic syndrome, Diet, Gluten-Free, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Non-alcoholic Fatty Liver Disease, Internal medicine, medicine, steatosis, Humans, education, Retrospective Studies, education.field_of_study, Hepatology, business.industry, Fatty liver, nutritional and metabolic diseases, medicine.disease, digestive system diseases, Celiac Disease, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Waist Circumference, Metabolic syndrome, Steatosis, business, coeliac disease
Abstract

BACKGROUND AND AIMS Coeliac disease (CD) is considered a high-risk condition for developing non-alcoholic fatty liver disease (NAFLD) and other related metabolic disorders, particularly after commencing gluten-free diet (GFD). Recently, a new concept of metabolic-associated fatty liver disease (MAFLD) has been proposed to overcome the limitations of NAFLD definition. This study aimed at exploring the prevalence of NAFLD and MAFLD in CD patients at the time of CD diagnosis and after 2 years of GFD. Furthermore, we evaluated the role of PNPLA3 rs738409 in the development of NAFLD and MAFLD in the same population. METHODS We retrospectively enrolled all newly diagnosed CD patients who underwent clinical, laboratory and ultrasonography investigations both at diagnosis and after 2 years of follow-up. Moreover, a PNPLA3 rs738409 genotyping assay was performed. RESULTS Of 221 newly diagnosed CD patients, 65 (29.4%) presented NAFLD at CD diagnosis, while 32 (14.5%) met the criteria for MAFLD (k = 0.57). There were no significant differences between NAFLD and MAFLD, except for the higher rate of insulin resistance (IR) of MAFLD patients (75% vs 33.8%, P

Published
2021

25. Coffee Restores Expression of lncRNAs Involved in Steatosis and Fibrosis in a Mouse Model of NAFLD

Author

Salvatore Piro, Stefania Di Mauro, Alessandra Scamporrino, Maria Guido, Rosaria Maria Pipitone, Agnese Filippello, Valentina Cossiga, Roberta Malaguarnera, Francesco Purrello, Federico Salomone, Vincenzo Lembo, Filomena Morisco, Stefania Grimaudo, Di Mauro, Stefania, Salomone, Federico, Scamporrino, Alessandra, Filippello, Agnese, Morisco, Filomena, Guido, Maria, Lembo, Vincenzo, Cossiga, Valentina, Pipitone, Rosaria Maria, Grimaudo, Stefania, Malaguarnera, Roberta, Purrello, Francesco, Piro, Salvatore, and Pipitone, Rosaria

Subjects
lncRNA, Liver Cirrhosis, Male, medicine.medical_specialty, Gm16551, H19, NAFLD, coffee, Animals, Coffee, Disease Models, Animal, Fatty Liver, Gene Expression, Liver, Mice, Mice, Inbred C57BL, Non-alcoholic Fatty Liver Disease, RNA, Long Noncoding, Coenzyme A, Circadian clock, Biology, Inbred C57BL, Article, chemistry.chemical_compound, Downregulation and upregulation, Fibrosis, Settore BIO/13 - Biologia Applicata, Internal medicine, medicine, TX341-641, Messenger RNA, Nutrition and Dietetics, Nutrition. Foods and food supply, Animal, Fatty liver, nutritional and metabolic diseases, medicine.disease, Endocrinology, chemistry, Lipogenesis, Disease Models, RNA, Long Noncoding, Steatosis, Food Science
Abstract

Background and aim: Coffee intake exerts protective effects against non-alcoholic fatty liver disease (NAFLD), although without fully cleared mechanisms. In this study we aimed to assess whether coffee consumption may influence the expression of long non-coding RNAs (lncRNAs) in the liver. Methods: C57BL/6J mice were fed a 12-week standard diet (SD), high-fat diet (HFD) or HFD plus decaffeinated coffee solution (HFD + coffee). Expression of specific lncRNAs involved in NAFLD was analyzed by real-time PCR. For the most differentially expressed lncRNAs, the analysis was also extended to their mRNA targets. Results: Decaffeinated coffee intake reduced body weight gain, prevented NAFLD, lowered hyperglycemia and hypercholesterolemia. NAFLD was associated with lower hepatic expression of Gm16551, a lncRNA inhibiting de novo lipogenesis, and higher expression of H19, a lncRNA promoting fibrogenesis. Coffee intake restored Gm16551 to levels observed in lean mice and downregulated gene expression of its targets acetyl coenzyme A carboxylase 1 and stearoyl coenzyme A desaturase 1. Furthermore, coffee consumption markedly decreased hepatic expression of H19 and of its target gene collagen alpha-1(I) chain; consistently, in mice fed HFD + coffee liver expression of αSMA protein returned to levels of mice fed SD. Expression of lncRNA involved in circadian clock such as fatty liver-related lncRNA 1 (FLRL1) and fatty liver-related lncRNA 2 (FLRL2) were upregulated by HFD and were also modulated by coffee intake. Conclusion. Hepatoprotective effects of coffee may be depending on the modulation of lncRNAs involved in key pathways of NAFLD onset and progression.

Published
2021

26. An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs

Author

Heather J. Cordell, James J. Fryett, Kazuko Ueno, Rebecca Darlay, Yoshihiro Aiba, Yuki Hitomi, Minae Kawashima, Nao Nishida, Seik-Soon Khor, Olivier Gervais, Yosuke Kawai, Masao Nagasaki, Katsushi Tokunaga, Ruqi Tang, Yongyong Shi, Zhiqiang Li, Brian D. Juran, Elizabeth J. Atkinson, Alessio Gerussi, Marco Carbone, Rosanna Asselta, Angela Cheung, Mariza de Andrade, Aris Baras, Julie Horowitz, Manuel A.R. Ferreira, Dylan Sun, David E. Jones, Steven Flack, Ann Spicer, Victoria L. Mulcahy, Jinyoung Byan, Younghun Han, Richard N. Sandford, Konstantinos N. Lazaridis, Christopher I. Amos, Gideon M. Hirschfield, Michael F. Seldin, Pietro Invernizzi, Katherine A. Siminovitch, Xiong Ma, Minoru Nakamura, George F. Mells, Andrew Mason, Catherine Vincent, Gang Xie, Jinyi Zhang, Andrea Affronti, Piero L. Almasio, Domenico Alvaro, Pietro Andreone, Angelo Andriulli, Francesco Azzaroli, Pier Maria Battezzati, Antonio Benedetti, MariaConsiglia Bragazzi, Maurizia Brunetto, Savino Bruno, Vincenza Calvaruso, Vincenzo Cardinale, Giovanni Casella, Nora Cazzagon, Antonio Ciaccio, Barbara Coco, Agostino Colli, Guido Colloredo, Massimo Colombo, Silvia Colombo, Laura Cristoferi, Carmela Cursaro, Lory Saveria Crocè, Andrea Crosignani, Daphne D’Amato, Francesca Donato, Gianfranco Elia, Luca Fabris, Stefano Fagiuoli, Carlo Ferrari, Annarosa Floreani, Andrea Galli, Edoardo Giannini, Ignazio Grattagliano, Pietro Lampertico, Ana Lleo, Federica Malinverno, Clara Mancuso, Fabio Marra, Marco Marzioni, Sara Massironi, Alberto Mattalia, Luca Miele, Chiara Milani, Lorenzo Morini, Filomena Morisco, Luigi Muratori, Paolo Muratori, Grazia A. Niro, Sarah O’Donnell, Antonio Picciotto, Piero Portincasa, Cristina Rigamonti, Vincenzo Ronca, Floriano Rosina, Giancarlo Spinzi, Mario Strazzabosco, Mirko Tarocchi, Claudio Tiribelli, Pierluigi Toniutto, Luca Valenti, Maria Vinci, Massimo Zuin, Hitomi Nakamura, Seigo Abiru, Shinya Nagaoka, Atsumasa Komori, Hiroshi Yatsuhashi, Hiromi Ishibashi, Masahiro Ito, Kiyoshi Migita, Hiromasa Ohira, Shinji Katsushima, Atsushi Naganuma, Kazuhiro Sugi, Tatsuji Komatsu, Tomohiko Mannami, Kouki Matsushita, Kaname Yoshizawa, Fujio Makita, Toshiki Nikami, Hideo Nishimura, Hiroshi Kouno, Hirotaka Kouno, Hajime Ota, Takuya Komura, Yoko Nakamura, Masaaki Shimada, Noboru Hirashima, Toshiki Komeda, Keisuke Ario, Makoto Nakamuta, Tsutomu Yamashita, Kiyoshi Furuta, Masahiro Kikuchi, Noriaki Naeshiro, Hironao Takahashi, Yutaka Mano, Seiji Tsunematsu, Iwao Yabuuchi, Yusuke Shimada, Kazuhiko Yamauchi, Rie Sugimoto, Hironori Sakai, Eiji Mita, Masaharu Koda, Satoru Tsuruta, Hiroshi Kamitsukasa, Takeaki Sato, Naohiko Masaki, Tatsuro Kobata, Nobuyoshi Fukushima, Yukio Ohara, Toyokichi Muro, Eiichi Takesaki, Hitoshi Takaki, Tetsuo Yamamoto, Michio Kato, Yuko Nagaoki, Shigeki Hayashi, Jinya Ishida, Yukio Watanabe, Masakazu Kobayashi, Michiaki Koga, Takeo Saoshiro, Michiyasu Yagura, Keisuke Hirata, Atsushu Tanaka, Hajime Takikawa, Mikio Zeniya, Masanori Abe, Morikazu Onji, Shuichi Kaneko, Masao Honda, Kuniaki Arai, Teruko Arinaga-Hino, Etsuko Hashimoto, Makiko Taniai, Takeji Umemura, Satoru Joshita, Kazuhiko Nakao, Tatsuki Ichikawa, Hidetaka Shibata, Satoshi Yamagiwa, Masataka Seike, Koichi Honda, Shotaro Sakisaka, Yasuaki Takeyama, Masaru Harada, Michio Senju, Osamu Yokosuka, Tatsuo Kanda, Yoshiyuki Ueno, Kentaro Kikuchi, Hirotoshi Ebinuma, Takashi Himoto, Michio Yasunami, Kazumoto Murata, Masashi Mizokami, Kazuhito Kawata, Shinji Shimoda, Yasuhiro Miyake, Akinobu Takaki, Kazuhide Yamamoto, Katsuji Hirano, Takafumi Ichida, Akio Ido, Hirohito Tsubouchi, Kazuaki Chayama, Kenichi Harada, Yasuni Nakanuma, Yoshihiko Maehara, Akinobu Taketomi, Ken Shirabe, Yuji Soejima, Akira Mori, Shintaro Yagi, Shinji Uemoto, Egawa H, Tomohiro Tanaka, Noriyo Yamashiki, Sumito Tamura, Yasuhiro Sugawara, Norihiro Kokudo, Naga Chalasani, Vel Luketic, Joseph Odin, Kapil Chopra, Goncalo Abecasis, Michael Cantor, Giovanni Coppola, Aris Economides, Luca A. Lotta, John D. Overton, Jeffrey G. Reid, Alan Shuldiner, Christina Beechert, Caitlin Forsythe, Erin D. Fuller, Zhenhua Gu, Michael Lattari, Alexander Lopez, Thomas D. Schleicher, Maria Sotiropoulos Padilla, Karina Toledo, Louis Widom, Sarah E. Wolf, Manasi Pradhan, Kia Manoochehri, Ricardo H. Ulloa, Xiaodong Bai, Suganthi Balasubramanian, Leland Barnard, Andrew Blumenfeld, Gisu Eom, Lukas Habegger, Alicia Hawes, Shareef Khalid, Evan K. Maxwell, William Salerno, Jeffrey C. Staples, Marcus B. Jones, Lyndon J. Mitnaul, Richard Sturgess, Christopher Healey, Andrew Yeoman, Anton VJ. Gunasekera, Paul Kooner, Kapil Kapur, V. Sathyanarayana, Yiannis Kallis, Javaid Subhani, Rory Harvey, Roger McCorry, Paul Rooney, David Ramanaden, Richard Evans, Thiriloganathan Mathialahan, Jaber Gasem, Christopher Shorrock, Mahesh Bhalme, Paul Southern, Jeremy A. Tibble, David A. Gorard, Susan Jones, George Mells, Victoria Mulcahy, Brijesh Srivastava, Matthew R. Foxton, Carole E. Collins, David Elphick, Mazn Karmo, Francisco Porras-Perez, Michael Mendall, Tom Yapp, Minesh Patel, Roland Ede, Joanne Sayer, James Jupp, Neil Fisher, Martyn J. Carter, Konrad Koss, Jayshri Shah, Andrzej Piotrowicz, Glyn Scott, Charles Grimley, Ian R. Gooding, Simon Williams, Judith Tidbury, Guan Lim, Kuldeep Cheent, Sass Levi, Dina Mansour, Matilda Beckley, Coral Hollywood, Terry Wong, Richard Marley, John Ramage, Harriet M. Gordon, Jo Ridpath, Theodore Ngatchu, Vijay Paul Bob Grover, Ray G. Shidrawi, George Abouda, L. Corless, Mark Narain, Ian Rees, Ashley Brown, Simon Taylor-Robinson, Joy Wilkins, Leonie Grellier, Paul Banim, Debasish Das, Michael A. Heneghan, Howard Curtis, Helen C. Matthews, Faiyaz Mohammed, Mark Aldersley, Raj Srirajaskanthan, Giles Walker, Alistair McNair, Amar Sharif, Sambit Sen, George Bird, Martin I. Prince, Geeta Prasad, Paul Kitchen, Adrian Barnardo, Chirag Oza, Nurani N. Sivaramakrishnan, Prakash Gupta, Amir Shah, Chris DJ. Evans, Subrata Saha, Katharine Pollock, Peter Bramley, Ashis Mukhopadhya, Stephen T. Barclay, Natasha McDonald, Andrew J. Bathgate, Kelvin Palmer, John F. Dillon, Simon M. Rushbrook, Robert Przemioslo, Chris McDonald, Andrew Millar, Cheh Tai, Stephen Mitchell, Jane Metcalf, Syed Shaukat, Mary Ninkovic, Udi Shmueli, Andrew Davis, Asifabbas Naqvi, Tom JW. Lee, Stephen Ryder, Jane Collier, Howard Klass, Matthew E. Cramp, Nichols Sharer, Richard Aspinall, Deb Ghosh, Andrew C. Douds, Jonathan Booth, Earl Williams, Hyder Hussaini, John Christie, Steven Mann, Douglas Thorburn, Aileen Marshall, Imran Patanwala, Aftab Ala, Julia Maltby, Ray Matthew, Chris Corbett, Sam Vyas, Saket Singhal, Dermot Gleeson, Sharat Misra, Jeff Butterworth, Keith George, Tim Harding, Andrew Douglass, Harriet Mitchison, Simon Panter, Jeremy Shearman, Gary Bray, Michael Roberts, Graham Butcher, Daniel Forton, Zahid Mahmood, Matthew Cowan, Debashis Das, Chin Lye Ch’ng, Mesbah Rahman, Gregory C.A. 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A., Overton, J. D., Reid, J. G., Shuldiner, A., Beechert, C., Forsythe, C., Fuller, E. D., Gu, Z., Lattari, M., Lopez, A., Schleicher, T. D., Padilla, M. S., Toledo, K., Widom, L., Wolf, S. E., Pradhan, M., Manoochehri, K., Ulloa, R. H., Bai, X., Balasubramanian, S., Barnard, L., Blumenfeld, A., Eom, G., Habegger, L., Hawes, A., Khalid, S., Maxwell, E. K., Salerno, W., Staples, J. C., Jones, M. B., Mitnaul, L. J., Sturgess, R., Healey, C., Yeoman, A., Gunasekera, A. V., Kooner, P., Kapur, K., Sathyanarayana, V., Kallis, Y., Subhani, J., Harvey, R., Mccorry, R., Rooney, P., Ramanaden, D., Evans, R., Mathialahan, T., Gasem, J., Shorrock, C., Bhalme, M., Southern, P., Tibble, J. A., Gorard, D. A., Jones, S., Mells, G., Mulcahy, V., Srivastava, B., Foxton, M. R., Collins, C. E., Elphick, D., Karmo, M., Porras-Perez, F., Mendall, M., Yapp, T., Patel, M., Ede, R., Sayer, J., Jupp, J., Fisher, N., Carter, M. J., Koss, K., Shah, J., Piotrowicz, A., Scott, G., Grimley, C., Gooding, I. 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S., Kia, R., Gee, I., Keld, R., Ransford, R., Gotto, J., Millson, C., Cordell H.J., Fryett J.J., Ueno K., Darlay R., Aiba Y., Hitomi Y., Kawashima M., Nishida N., Khor S.-S., Gervais O., Kawai Y., Nagasaki M., Tokunaga K., Tang R., Shi Y., Li Z., Juran B.D., Atkinson E.J., Gerussi A., Carbone M., Asselta R., Cheung A., de Andrade M., Baras A., Horowitz J., Ferreira M.A.R., Sun D., Jones D.E., Flack S., Spicer A., Mulcahy V.L., Byan J., Han Y., Sandford R.N., Lazaridis K.N., Amos C.I., Hirschfield G.M., Seldin M.F., Invernizzi P., Siminovitch K.A., Ma X., Nakamura M., Mells G.F., Mason A., Vincent C., Xie G., Zhang J., Affronti A., Almasio P.L., Alvaro D., Andreone P., Andriulli A., Azzaroli F., Battezzati P.M., Benedetti A., Bragazzi M., Brunetto M., Bruno S., Calvaruso V., Cardinale V., Casella G., Cazzagon N., Ciaccio A., Coco B., Colli A., Colloredo G., Colombo M., Colombo S., Cristoferi L., Cursaro C., Croce L.S., Crosignani A., D'Amato D., Donato F., Elia G., Fabris L., Fagiuoli S., Ferrari C., Floreani A., Galli A., Giannini E., Grattagliano I., Lampertico P., Lleo A., Malinverno F., Mancuso C., Marra F., Marzioni M., Massironi S., Mattalia A., Miele L., Milani C., Morini L., Morisco F., Muratori L., Muratori P., Niro G.A., O'Donnell S., Picciotto A., Portincasa P., Rigamonti C., Ronca V., Rosina F., Spinzi G., Strazzabosco M., Tarocchi M., Tiribelli C., Toniutto P., Valenti L., Vinci M., Zuin M., Nakamura H., Abiru S., Nagaoka S., Komori A., Yatsuhashi H., Ishibashi H., Ito M., Migita K., Ohira H., Katsushima S., Naganuma A., Sugi K., Komatsu T., Mannami T., Matsushita K., Yoshizawa K., Makita F., Nikami T., Nishimura H., Kouno H., Ota H., Komura T., Nakamura Y., Shimada M., Hirashima N., Komeda T., Ario K., Nakamuta M., Yamashita T., Furuta K., Kikuchi M., Naeshiro N., Takahashi H., Mano Y., Tsunematsu S., Yabuuchi I., Shimada Y., Yamauchi K., Sugimoto R., Sakai H., Mita E., Koda M., Tsuruta S., Kamitsukasa H., Sato T., Masaki N., Kobata T., Fukushima N., Ohara Y., Muro T., Takesaki E., Takaki H., Yamamoto T., Kato M., Nagaoki Y., Hayashi S., Ishida J., Watanabe Y., Kobayashi M., Koga M., Saoshiro T., Yagura M., Hirata K., Tanaka A., Takikawa H., Zeniya M., Abe M., Onji M., Kaneko S., Honda M., Arai K., Arinaga-Hino T., Hashimoto E., Taniai M., Umemura T., Joshita S., Nakao K., Ichikawa T., Shibata H., Yamagiwa S., Seike M., Honda K., Sakisaka S., Takeyama Y., Harada M., Senju M., Yokosuka O., Kanda T., Ueno Y., Kikuchi K., Ebinuma H., Himoto T., Yasunami M., Murata K., Mizokami M., Kawata K., Shimoda S., Miyake Y., Takaki A., Yamamoto K., Hirano K., Ichida T., Ido A., Tsubouchi H., Chayama K., Harada K., Nakanuma Y., Maehara Y., Taketomi A., Shirabe K., Soejima Y., Mori A., Yagi S., Uemoto S., H E., Tanaka T., Yamashiki N., Tamura S., Sugawara Y., Kokudo N., Chalasani N., Luketic V., Odin J., Chopra K., Abecasis G., Cantor M., Coppola G., Economides A., Lotta L.A., Overton J.D., Reid J.G., Shuldiner A., Beechert C., Forsythe C., Fuller E.D., Gu Z., Lattari M., Lopez A., Schleicher T.D., Padilla M.S., Toledo K., Widom L., Wolf S.E., Pradhan M., Manoochehri K., Ulloa R.H., Bai X., Balasubramanian S., Barnard L., Blumenfeld A., Eom G., Habegger L., Hawes A., Khalid S., Maxwell E.K., Salerno W., Staples J.C., Jones M.B., Mitnaul L.J., Sturgess R., Healey C., Yeoman A., Gunasekera A.V., Kooner P., Kapur K., Sathyanarayana V., Kallis Y., Subhani J., Harvey R., McCorry R., Rooney P., Ramanaden D., Evans R., Mathialahan T., Gasem J., Shorrock C., Bhalme M., Southern P., Tibble J.A., Gorard D.A., Jones S., Mells G., Mulcahy V., Srivastava B., Foxton M.R., Collins C.E., Elphick D., Karmo M., Porras-Perez F., Mendall M., Yapp T., Patel M., Ede R., Sayer J., Jupp J., Fisher N., Carter M.J., Koss K., Shah J., Piotrowicz A., Scott G., Grimley C., Gooding I.R., Williams S., Tidbury J., Lim G., Cheent K., Levi S., Mansour D., Beckley M., Hollywood C., Wong T., Marley R., Ramage J., Gordon H.M., Ridpath J., Ngatchu T., Bob Grover V.P., Shidrawi R.G., Abouda G., Corless L., Narain M., Rees I., Brown A., Taylor-Robinson S., Wilkins J., Grellier L., Banim P., Das D., Heneghan M.A., Curtis H., Matthews H.C., Mohammed F., Aldersley M., Srirajaskanthan R., Walker G., McNair A., Sharif A., Sen S., Bird G., Prince M.I., Prasad G., Kitchen P., Barnardo A., Oza C., Sivaramakrishnan N.N., Gupta P., Shah A., Evans C.D., Saha S., Pollock K., Bramley P., Mukhopadhya A., Barclay S.T., McDonald N., Bathgate A.J., Palmer K., Dillon J.F., Rushbrook S.M., Przemioslo R., McDonald C., Millar A., Tai C., Mitchell S., Metcalf J., Shaukat S., Ninkovic M., Shmueli U., Davis A., Naqvi A., Lee T.J., Ryder S., Collier J., Klass H., Cramp M.E., Sharer N., Aspinall R., Ghosh D., Douds A.C., Booth J., Williams E., Hussaini H., Christie J., Mann S., Thorburn D., Marshall A., Patanwala I., Ala A., Maltby J., Matthew R., Corbett C., Vyas S., Singhal S., Gleeson D., Misra S., Butterworth J., George K., Harding T., Douglass A., Mitchison H., Panter S., Shearman J., Bray G., Roberts M., Butcher G., Forton D., Mahmood Z., Cowan M., Ch'ng C.L., Rahman M., Whatley G.C.A., Wesley E., Mandal A., Jain S., Pereira S.P., Wright M., Trivedi P., Gordon F.H., Unitt E., Palejwala A., Austin A., Vemala V., Grant A., Higham A.D., Brind A., Mathew R., Cox M., Ramakrishnan S., King A., Whalley S., Fraser J., Thomson S.J., Bell A., Wong V.S., Kia R., Gee I., Keld R., Ransford R., Gotto J., Millson C., Medical Research Council (MRC), LiveR North, Cordell, H, Fryett, J, Ueno, K, Darlay, R, Aiba, Y, Hitomi, Y, Kawashima, M, Nishida, N, Khor, S, Gervais, O, Kawai, Y, Nagasaki, M, Tokunaga, K, Tang, R, Shi, Y, Li, Z, Juran, B, Atkinson, E, Gerussi, A, Carbone, M, Asselta, R, Cheung, A, de Andrade, M, Baras, A, Horowitz, J, Ferreira, M, Sun, D, Jones, D, Flack, S, Spicer, A, Mulcahy, V, Byan, J, Han, Y, Sandford, R, Lazaridis, K, Amos, C, Hirschfield, G, Seldin, M, Invernizzi, P, Siminovitch, K, Ma, X, Nakamura, M, Mells, G, Mason, A, Vincent, C, Xie, G, Zhang, J, Affronti, A, Almasio, P, Alvaro, D, Andreone, P, Andriulli, A, Azzaroli, F, Battezzati, P, Benedetti, A, Bragazzi, M, Brunetto, M, Bruno, S, Calvaruso, V, Cardinale, V, Casella, G, Cazzagon, N, Ciaccio, A, Coco, B, Colli, A, Colloredo, G, Colombo, M, Colombo, S, Cristoferi, L, Cursaro, C, Croce, L, Crosignani, A, D'Amato, D, Donato, F, Elia, G, Fabris, L, Fagiuoli, S, Ferrari, C, Floreani, A, Galli, A, Giannini, E, Grattagliano, I, Lampertico, P, Lleo, A, Malinverno, F, Mancuso, C, Marra, F, Marzioni, M, Massironi, S, Mattalia, A, Miele, L, Milani, C, Morini, L, Morisco, F, Muratori, L, Muratori, P, Niro, G, O'Donnell, S, Picciotto, A, Portincasa, P, Rigamonti, C, Ronca, V, Rosina, F, Spinzi, G, Strazzabosco, M, Tarocchi, M, Tiribelli, C, Toniutto, P, Valenti, L, Vinci, M, Zuin, M, Nakamura, H, Abiru, S, Nagaoka, S, Komori, A, Yatsuhashi, H, Ishibashi, H, Ito, M, Migita, K, Ohira, H, Katsushima, S, Naganuma, A, Sugi, K, Komatsu, T, Mannami, T, Matsushita, K, Yoshizawa, K, Makita, F, Nikami, T, Nishimura, H, Kouno, H, Ota, H, Komura, T, Nakamura, Y, Shimada, M, Hirashima, N, Komeda, T, Ario, K, Nakamuta, M, Yamashita, T, Furuta, K, Kikuchi, M, Naeshiro, N, Takahashi, H, Mano, Y, Tsunematsu, S, Yabuuchi, I, Shimada, Y, Yamauchi, K, Sugimoto, R, Sakai, H, Mita, E, Koda, M, Tsuruta, S, Kamitsukasa, H, Sato, T, Masaki, N, Kobata, T, Fukushima, N, Ohara, Y, Muro, T, Takesaki, E, Takaki, H, Yamamoto, T, Kato, M, Nagaoki, Y, Hayashi, S, Ishida, J, Watanabe, Y, Kobayashi, M, Koga, M, Saoshiro, T, Yagura, M, Hirata, K, Tanaka, A, Takikawa, H, Zeniya, M, Abe, M, Onji, M, Kaneko, S, Honda, M, Arai, K, Arinaga-Hino, T, Hashimoto, E, Taniai, M, Umemura, T, Joshita, S, Nakao, K, Ichikawa, T, Shibata, H, Yamagiwa, S, Seike, M, Honda, K, Sakisaka, S, Takeyama, Y, Harada, M, Senju, M, Yokosuka, O, Kanda, T, Ueno, Y, Kikuchi, K, Ebinuma, H, Himoto, T, Yasunami, M, Murata, K, Mizokami, M, Kawata, K, Shimoda, S, Miyake, Y, Takaki, A, Yamamoto, K, Hirano, K, Ichida, T, Ido, A, Tsubouchi, H, Chayama, K, Harada, K, Nakanuma, Y, Maehara, Y, Taketomi, A, Shirabe, K, Soejima, Y, Mori, A, Yagi, S, Uemoto, S, H, E, Tanaka, T, Yamashiki, N, Tamura, S, Sugawara, Y, Kokudo, N, Chalasani, N, Luketic, V, Odin, J, Chopra, K, Abecasis, G, Cantor, M, Coppola, G, Economides, A, Lotta, L, Overton, J, Reid, J, Shuldiner, A, Beechert, C, Forsythe, C, Fuller, E, Gu, Z, Lattari, M, Lopez, A, Schleicher, T, Padilla, M, Toledo, K, Widom, L, Wolf, S, Pradhan, M, Manoochehri, K, Ulloa, R, Bai, X, Balasubramanian, S, Barnard, L, Blumenfeld, A, Eom, G, Habegger, L, Hawes, A, Khalid, S, Maxwell, E, Salerno, W, Staples, J, Jones, M, Mitnaul, L, Sturgess, R, Healey, C, Yeoman, A, Gunasekera, A, Kooner, P, Kapur, K, Sathyanarayana, V, Kallis, Y, Subhani, J, Harvey, R, Mccorry, R, Rooney, P, Ramanaden, D, Evans, R, Mathialahan, T, Gasem, J, Shorrock, C, Bhalme, M, Southern, P, Tibble, J, Gorard, D, Jones, S, Srivastava, B, Foxton, M, Collins, C, Elphick, D, Karmo, M, Porras-Perez, F, Mendall, M, Yapp, T, Patel, M, Ede, R, Sayer, J, Jupp, J, Fisher, N, Carter, M, Koss, K, Shah, J, Piotrowicz, A, Scott, G, Grimley, C, Gooding, I, Williams, S, Tidbury, J, Lim, G, Cheent, K, Levi, S, Mansour, D, Beckley, M, Hollywood, C, Wong, T, Marley, R, Ramage, J, Gordon, H, Ridpath, J, Ngatchu, T, Bob Grover, V, Shidrawi, R, Abouda, G, Corless, L, Narain, M, Rees, I, Brown, A, Taylor-Robinson, S, Wilkins, J, Grellier, L, Banim, P, Das, D, Heneghan, M, Curtis, H, Matthews, H, Mohammed, F, Aldersley, M, Srirajaskanthan, R, Walker, G, Mcnair, A, Sharif, A, Sen, S, Bird, G, Prince, M, Prasad, G, Kitchen, P, Barnardo, A, Oza, C, Sivaramakrishnan, N, Gupta, P, Shah, A, Evans, C, Saha, S, Pollock, K, Bramley, P, Mukhopadhya, A, Barclay, S, Mcdonald, N, Bathgate, A, Palmer, K, Dillon, J, Rushbrook, S, Przemioslo, R, Mcdonald, C, Millar, A, Tai, C, Mitchell, S, Metcalf, J, Shaukat, S, Ninkovic, M, Shmueli, U, Davis, A, Naqvi, A, Lee, T, Ryder, S, Collier, J, Klass, H, Cramp, M, Sharer, N, Aspinall, R, Ghosh, D, Douds, A, Booth, J, Williams, E, Hussaini, H, Christie, J, Mann, S, Thorburn, D, Marshall, A, Patanwala, I, Ala, A, Maltby, J, Matthew, R, Corbett, C, Vyas, S, Singhal, S, Gleeson, D, Misra, S, Butterworth, J, George, K, Harding, T, Douglass, A, Mitchison, H, Panter, S, Shearman, J, Bray, G, Roberts, M, Butcher, G, Forton, D, Mahmood, Z, Cowan, M, Ch'Ng, C, Rahman, M, Whatley, G, Wesley, E, Mandal, A, Jain, S, Pereira, S, Wright, M, Trivedi, P, Gordon, F, Unitt, E, Palejwala, A, Austin, A, Vemala, V, Grant, A, Higham, A, Brind, A, Mathew, R, Cox, M, Ramakrishnan, S, King, A, Whalley, S, Fraser, J, Thomson, S, Bell, A, Wong, V, Kia, R, Gee, I, Keld, R, Ransford, R, Gotto, J, Millson, C, Cordell HJ, Fryett JJ, Ueno K, Darlay R, Aiba Y, Hitomi Y, Kawashima M, Nishida N, Khor SS, Gervais O, Kawai Y, Nagasaki M, Tokunaga K, Tang R, Shi Y, Li Z, Juran BD, Atkinson EJ, Gerussi A, Carbone M, Asselta R, Cheung A, de Andrade M, Baras A, Horowitz J, Ferreira MAR, Sun D, Jones DE, Flack S, Spicer A, Mulcahy VL, Byan J, Han Y, Sandford RN, Lazaridis KN, Amos CI, Hirschfield GM, Seldin MF, Invernizzi P, Siminovitch KA, Ma X, Nakamura M, Mells GF, PBC Consortia, Canadian PBC Consortium, Chinese PBC Consortium, Italian PBC Study Group, Japan-PBC-GWAS Consortium, US PBC Consortium, UK-PBC Consortium, and Calvaruso V. .

Subjects
Liver Cirrhosis, ALSPAC, ERN RARE-LIVER, Genomic co-localization, Network-based in silico drug efficacy screening, UK-PBC, 0301 basic medicine, Candidate gene, Genome-Wide Association Study, Humans, Liver Cirrhosis, Biliary, Italian PBC Study Group, LD SCORE REGRESSION, Japan-PBC-GWAS Consortium, Genome-wide association study, Locus (genetics), Disease, SUSCEPTIBILITY, PBC, Chronic liver disease, Bioinformatics, GENETIC ASSOCIATION, 1117 Public Health and Health Services, 03 medical and health sciences, 0302 clinical medicine, UK-PBC Consortium, Genotype, Medicine, Genetic association, Science & Technology, Gastroenterology & Hepatology, Hepatology, business.industry, Biliary, Chinese PBC Consortium, 1103 Clinical Sciences, medicine.disease, PBC Consortia, 030104 developmental biology, Meta-analysis, ERN RARE LIVER, 030211 gastroenterology & hepatology, US PBC Consortium, Canadian PBC Consortium, business, Life Sciences & Biomedicine, Human
Abstract

[BACKGROUND & AIMS] Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intra-hepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. [METHODS] We combined new and existing genotype data for 10, 516 cases and 20, 772 controls from five European and two East Asian cohorts. [RESULTS] We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57th genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, each having key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, Jak-STAT signalling, and differentiation of TH1 and TH17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some well-established in the treatment of other autoimmune disorders. [CONCLUSIONS] This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders. [Lay summary] Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10, 516 people with PBC and 20, 772 healthy individuals recruited in Canada, China, Italy, Japan, UK, or USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these ‘candidate genes’ to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC., 原発性胆汁性胆管炎のゲノムワイド関連解析 --国際メタ解析による新規疾患感受性遺伝子と治療薬候補の同定--. 京都大学プレスリリース. 2021-06-28.

Published
2021

27. PNPLA3, TM6SF2, and MBOAT7 Influence on Nutraceutical Therapy Response for Non-alcoholic Fatty Liver Disease: A Randomized Controlled Trial

Author

Marcello Dallio, Carmelina Loguercio, Filomena Morisco, Alessandro Federico, Concetta Tuccillo, Mario Masarone, Marcello Persico, Mario Romeo, Dallio, M., Masarone, M., Romeo, M., Tuccillo, C., Morisco, F., Persico, M., Loguercio, C., Federico, A., Dallio, Marcello, Masarone, Mario, Romeo, Mario, Tuccillo, Concetta, Morisco, Filomena, Persico, Marcello, Loguercio, Carmelina, and Federico, Alessandro

Subjects
Medicine (General), medicine.medical_specialty, medicine.medical_treatment, Context (language use), nutraceutics, Gastroenterology, law.invention, R5-920, Insulin resistance, Randomized controlled trial, genome wide association studie, law, Oral administration, Internal medicine, insulin resistance, medicine, TBARS, Vitamin D and neurology, genetics, Original Research, systemic inflammation, business.industry, Vitamin E, Fatty liver, nutritional and metabolic diseases, nutraceutic, General Medicine, genome wide association studies, medicine.disease, Medicine, genetic, business
Abstract

Introduction: PNPLA3, TM6SF2, and MBOAT7 genes play a crucial role in non-alcoholic fatty liver disease (NAFLD) development and worsening. However, few data are available on their treatment response influence. The aim of this trial is to explore the effect derived from silybin-phospholipids complex (303 mg of silybin-phospholipids complex, 10 μg of vitamin D, and 15 mg of vitamin E twice a day for 6 months) oral administration in NAFLD patients carrying PNPLA3-rs738409, TM6SF2-rs58542926, or MBOAT7-rs641738 genetic variants.Materials and Methods: In all, 92 biopsy-proven NAFLD patients were grouped in 30 NAFLD wild type controls, 30 wild type treated patients, and 32 mutated treated ones. We assessed glycemia (FPG), insulinemia, HOMA-IR, aspartate and alanine aminotransferases (AST, ALT), C-reactive protein (CRP), thiobarbituric acid reactive substance (TBARS), stiffness, controlled attenuation parameter (CAP), dietary daily intake, and physical activity at baseline and end of treatment.Results: The wild-type treated group showed a significant improvement of FPG, insulinemia, HOMA-IR, ALT, CRP, and TBARS (p < 0.05), whereas no improvements were recorded in the other two study groups. NAFLD wild type treated patients showed higher possibilities of useful therapeutic outcome (p < 0.01), obtained from the prescribed therapeutic regimen, independently from age, sex, comorbidities, medications, CAP, and stiffness in comparison to the mutated group.Discussion: The assessed mutations are independently associated with no response to a silybin-based therapeutic regimen and could be considered as useful predictive markers in this context.Clinical Trial Registry Number:www.ClinicalTrials.gov, identifier: NCT04640324.

Published
2021

28. Risk Factors for Liver Decompensation and HCC in HCV-Cirrhotic Patients after DAAs: A Multicenter Prospective Study

Author

Maria Guarino, Mariarita Cannavò, Tommaso Stroffolini, Filomena Morisco, Alessandro Federico, Rosa G. Benigno, Marcello Dallio, Paola Begini, Flavia Lucia Lombardo, Massimo Marignani, Giuseppina Pontillo, Morisco, Filomena, Federico, Alessandro, Marignani, Massimo, Cannavò, Mariarita, Pontillo, Giuseppina, Guarino, Maria, Dallio, Marcello, Begini, Paola, Benigno, Rosa G, Lombardo, Flavia L, Stroffolini, Tommaso, Morisco, F., Federico, A., Marignani, M., Cannavo, M., Pontillo, G., Guarino, M., Dallio, M., Begini, P., Benigno, R. G., Lombardo, F. L., and Stroffolini, T.

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, Cirrhosis, Independent predictor, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, Liver stiffness, Internal medicine, Medicine, Liver decompensation, HCC, Prospective cohort study, RC254-282, DAA, liver decompensation, business.industry, Proportional hazards model, cirrhosis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, virus diseases, DAAs, medicine.disease, digestive system diseases, liver stiffness, 030104 developmental biology, Oncology, HCV, 030211 gastroenterology & hepatology, business, cirrhosi
Abstract

Background: Prospective studies on predictors of liver-related events in cirrhotic subjects achieving SVR after DAAs are lacking. Methods: We prospectively enrolled HCV cirrhotic patients in four Italian centers between November 2015 and October 2017. SVR and no-SVR cases were compared according to the presence or absence of liver-related events during a 24-month follow-up. Independent predictors of liver-related events were evaluated by Cox regression analysis. Results: A total of 706 subjects started DAAs therapy. SVR was confirmed in 687 (97.3%). A total of 61 subjects (8.9%) in the SVR group and 5 (26.3%) in the no-SVR group had liver-related events (p &lt, 0.03). The incidence rate x 100 p/y was 1.6 for HCC, 1.7 for any liver decompensation, and 0.5 for hepatic death. Baseline liver stiffness (LSM) ≥ 20 kPa (HR 4.0, 95% CI 1.1–14.1) and genotype different from 1 (HR 7.5, 95% CI 2.1–27.3) were both independent predictors of liver decompensation. Baseline LSM &gt, 20 KPa (HR 7.2, 95% CI 1.9–26.7) was the sole independent predictor of HCC. A decrease in liver stiffness (Delta LSM) by at least 20% at the end of follow-up was not associated with a decreased risk of liver-related events. Conclusion: Baseline LSM ≥ 20 kPa identifies HCV cirrhotic subjects at higher risk of liver-related events after SVR.

Published
2021

29. Low influenza vaccination coverage in subjects with liver cirrhosis. An alert waiting for winter season 2020-2021 during the COVID-19 pandemic

Author

Evangelista Sagnelli, Tommaso Stroffolini, Anna Lombardi, Maria Cristina Vinci, Sergio Babudieri, Luigina Ferrigno, Filomena Morisco, Alessia Ciancio, Grazia Anna Niro, Guido Colloredo, Massimo Marignani, Stroffolini, T., Lombardi, A., Ciancio, A., Niro, G. A., Colloredo, G., Marignani, M., Vinci, M., Morisco, F., Babudieri, S., Ferrigno, L., and Sagnelli, E.

Subjects
Liver Cirrhosis, Male, influenza viru, Pediatrics, medicine.medical_specialty, Cirrhosis, Vaccination Coverage, SARS coronavirus, Coronavirus disease 2019 (COVID-19), influenza virus, 03 medical and health sciences, 0302 clinical medicine, Virology, Pandemic, Epidemiology, Influenza, Human, Prevalence, Medicine, Humans, vaccines, 030212 general & internal medicine, Pandemics, Aged, SARS coronaviru, business.industry, SARS-CoV-2, Vaccination, COVID-19, Odds ratio, Middle Aged, medicine.disease, Confidence interval, Infectious Diseases, Logistic Models, Influenza Vaccines, Etiology, 030211 gastroenterology & hepatology, Female, Seasons, business
Abstract

We have evaluated flu vaccine coverage and variables associated with the lack of vaccination in cirrhotic subjects with particular attention to the cirrhosis etiology. Cirrhotic subjects consecutively referring to eight Italian centers were prospectively enrolled for a 6-month period in 2019. Subjects were asked if they had received a flu vaccine in the last 12 months. Multiple logistic regression analysis was performed to identify independent predictors of lack of vaccination. A total of 818 cases were recruited. The overall vaccine coverage was 39.6% (26.9% in those younger than 65 years and 51.9% in those older than 64 years; p < 0.001). Age < 65 years (odds ratio [OR] = 2.38; 95% confidence interval [CI] = 1.68–3.36), alcoholic etiology (OR = 2.40; 95% CI = 1.49–3.85), birth abroad (OR = 2.7; 95% CI = 1.10–6.61), and residence in South/Sardinia island (OR = 1.66; 95% CI = 1.14–2.42) all resulted independent predictors of the likelihood of lack of vaccination. The lack of information regarding the vaccine as the reason for no vaccination was reported by 71.4% of foreigners and by 34.7% of natives (p < 0.001). In conclusion, much work still should be done to improve coverage among groups at higher risk of lack of vaccination identified in this survey. The ongoing SARS-CoV-2 pandemic may represent one more alert for improving seasonal flu vaccine coverage to avoid further stress to the National Health System.

Published
2020

30. Rapid 'breath-print' of liver cirrhosis by proton transfer reaction time-of-flight mass spectrometry. A pilot study.

Author

Filomena Morisco, Eugenio Aprea, Vincenzo Lembo, Vincenzo Fogliano, Paola Vitaglione, Giovanna Mazzone, Luca Cappellin, Flavia Gasperi, Stefania Masone, Giovanni Domenico De Palma, Riccardo Marmo, Nicola Caporaso, and Franco Biasioli

Subjects
Medicine, Science
Abstract

UnlabelledThe aim of the present work was to test the potential of Proton Transfer Reaction Time-of-Flight Mass Spectrometry (PTR-ToF-MS) in the diagnosis of liver cirrhosis and the assessment of disease severity by direct analysis of exhaled breath. Twenty-six volunteers have been enrolled in this study: 12 patients (M/F 8/4, mean age 70.5 years, min-max 42-80 years) with liver cirrhosis of different etiologies and at different severity of disease and 14 healthy subjects (M/F 5/9, mean age 52.3 years, min-max 35-77 years). Real time breath analysis was performed on fasting subjects using a buffered end-tidal on-line sampler directly coupled to a PTR-ToF-MS. Twelve volatile organic compounds (VOCs) resulted significantly differently in cirrhotic patients (CP) compared to healthy controls (CTRL): four ketones (2-butanone, 2- or 3- pentanone, C8-ketone, C9-ketone), two terpenes (monoterpene, monoterpene related), four sulphur or nitrogen compounds (sulfoxide-compound, S-compound, NS-compound, N-compound) and two alcohols (heptadienol, methanol). Seven VOCs (2-butanone, C8-ketone, a monoterpene, 2,4-heptadienol and three compounds containing N, S or NS) resulted significantly differently in compensate cirrhotic patients (Child-Pugh A; CP-A) and decompensated cirrhotic subjects (Child-Pugh B+C; CP-B+C). ROC (Receiver Operating Characteristic) analysis was performed considering three contrast groups: CP vs CTRL, CP-A vs CTRL and CP-A vs CP-B+C. In these comparisons monoterpene and N-compound showed the best diagnostic performance.ConclusionsBreath analysis by PTR-ToF-MS was able to distinguish cirrhotic patients from healthy subjects and to discriminate those with well compensated liver disease from those at more advanced severity stage. A breath-print of liver cirrhosis was assessed for the first time.

Published
2013
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31. Overview of Immune Checkpoint Inhibitors Therapy for Hepatocellular Carcinoma, and The ITA.LI.CA Cohort Derived Estimate of Amenability Rate to Immune Checkpoint Inhibitors in Clinical Practice

Author

Edoardo G. Giannini, Andrea Aglitti, Mauro Borzio, Martina Gambato, Maria Guarino, Massimo Iavarone, Quirino Lai, Giovanni Battista Levi Sandri, Fabio Melandro, Filomena Morisco, Francesca Romana Ponziani, Maria Rendina, Francesco Paolo Russo, Rodolfo Sacco, Mauro Viganò, Alessandro Vitale, Franco Trevisani, on behalf of the Associazione Italiana per lo Studio del Fegato (AISF) HCC Special Interest Group, Giannini, Edoardo, Aglitti, Andrea, Borzio, Mauro, Gambato, Martina, Guarino, Maria, Iavarone, Massimo, Lai, Quirino, Levi Sandri, Giovanni, Melandro, Fabio, Morisco, Filomena, Ponziani, Francesca, Rendina, Maria, Russo, Francesco, Sacco, Rodolfo, Viganò, Mauro, Vitale, Alessandro, Trevisani, Franco, and Edoardo G. Giannini, Andrea Aglitti, Mauro Borzio, Martina Gambato, Maria Guarino, Massimo Iavarone, Quirino Lai, Giovanni Battista Levi Sandri, Fabio Melandro, Filomena Morisco, Francesca Romana Ponziani, Maria Rendina, Francesco Paolo Russo, Rodolfo Sacco, Mauro Viganò, Alessandro Vitale, Franco Trevisani, Associazione Italiana per lo Studio del Fegato (AISF) HCC Special Interest Group

Subjects
0301 basic medicine, Cancer Research, medicine.medical_treatment, check-point inhibitors, immunotherapy, liver disease, outcome, Ipilimumab, Review, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Cancer immunotherapy, Atezolizumab, medicine, Ticilimumab, business.industry, Immunotherapy, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Immune checkpoint, Check-point inhibitor, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer research, Nivolumab, business, Tremelimumab, medicine.drug
Abstract

Despite progress in our understanding of the biology of hepatocellular carcinoma (HCC), this tumour remains difficult-to-cure for several reasons, starting from the particular disease environment where it arises—advanced chronic liver disease—to its heterogeneous clinical and biological behaviour. The advent, and good results, of immunotherapy for cancer called for the evaluation of its potential application also in HCC, where there is evidence of intra-hepatic immune response activation. Several studies advanced our knowledge of immune checkpoints expression in HCC, thus suggesting that immune checkpoint blockade may have a strong rationale even in the treatment of HCC. According to this background, initial studies with tremelimumab, a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor, and nivolumab, a programmed cell death protein 1 (PD-1) antibody, showed promising results, and further studies exploring the effects of other immune checkpoint inhibitors, alone or with other drugs, are currently underway. However, we are still far from the identification of the correct setting, and sequence, where these drugs might be used in clinical practice, and their actual applicability in real-life is unknown. This review focuses on HCC immunobiology and on the potential of immune checkpoint blockade therapy for this tumour, with a critical evaluation of the available trials on immune checkpoint blocking antibodies treatment for HCC. Moreover, it assesses the potential applicability of immune checkpoint inhibitors in the real-life setting, by analysing a large, multicentre cohort of Italian patients with HCC.

Published
2019

32. A hyper-glycosylation of HBV surface antigen correlates with HBsAg-Negativity at immunosuppression-driven HBV reactivation in vivo and hinders HBsAg recognition in vitro

Author

Francesca Ceccherini-Silberstein, Carlotta Cerva, Ada Bertoli, Carlo Federico Perno, Massimo Marignani, Miriam Lichtner, Aldo Marrone, L. Colagrossi, Jens Verheyen, Valentina Svicher, Katia Yu La Rosa, N. Iapadre, Constance Delaugerre, L. Piermatteo, Massimo Levrero, Sarah Maylin, Marianna Aragri, Nicola Coppola, Loredana Sarmati, Stefano Aquaro, A. Battisti, Romina Salpini, Laura Belloni, Massimo Andreoni, Mario Angelico, Patrizia Saccomandi, Filomena Morisco, Salpini, R., Piermatteo, L., Battisti, A., Colagrossi, L., Aragri, M., Rosa, K. Y. L., Bertoli, A., Saccomandi, P., Lichtner, M., Marignani, M., Maylin, S., Delaugerre, C., Morisco, F., Coppola, N., Marrone, A., Iapadre, N., Cerva, C., Aquaro, S., Angelico, M., Sarmati, L., Andreoni, M., Verheyen, J., Ceccherini-Silberstein, F., Levrero, M., Perno, C. F., Belloni, L., Svicher, V., Salpini, Romina, Piermatteo, Lorenzo, Battisti, Arianna, Colagrossi, Luna, Aragri, Marianna, Yu La Rosa, Katia, Bertoli, Ada, Saccomandi, Patrizia, Lichtner, Miriam, Marignani, Massimo, Maylin, Sarah, Delaugerre, Constance, Morisco, Filomena, Coppola, Nicola, Marrone, Aldo, Iapadre, Nerio, Cerva, Carlotta, Aquaro, Stefano, Angelico, Mario, Sarmati, Loredana, Andreoni, Massimo, Verheyen, Jen, Ceccherini-Silberstein, Francesca, Levrero, Massimo, Federico Perno, Carlo, Belloni, Laura, and Svicher, Valentina

Subjects
0301 basic medicine, Male, HBsAg, Glycosylation, lcsh:QR1-502, Medizin, medicine.disease_cause, lcsh:Microbiology, HBV, HBV reactivation, N-linked glycosylation, 0302 clinical medicine, biology, virus diseases, Middle Aged, Infectious Diseases, 030211 gastroenterology & hepatology, Female, Antibody, Hepatitis B virus, Article, Cell Line, 03 medical and health sciences, Antigen, In vivo, Virology, medicine, Humans, Hepatitis B Antibodies, Aged, Immune Evasion, Hepatitis, Immunosuppression Therapy, Hepatitis B Surface Antigens, business.industry, medicine.disease, In vitro, Settore MED/17, digestive system diseases, 030104 developmental biology, Reinfection, Mutation, biology.protein, Virus Activation, business
Abstract

Immune-suppression driven Hepatitis B Virus (HBV)-reactivation poses serious concerns since it occurs in several clinical settings and can result in severe forms of hepatitis. Previous studies showed that HBV strains, circulating in patients with HBV-reactivation, are characterized by an enrichment of immune-escape mutations in HBV surface antigen (HBsAg). Here, we focused on specific immune-escape mutations associated with the acquisition of N-linked glycosylation sites in HBsAg (NLGSs). In particular, we investigated profiles of NLGSs in 47 patients with immunosuppression-driven HBV-reactivation and we evaluated their impact on HBsAg-antigenicity and HBV-replication in vitro. At HBV-reactivation, despite a median serum HBV-DNA of 6.7 [5.3&ndash, 8.0] logIU/mL, 23.4% of patients remained HBsAg-negative. HBsAg-negativity at HBV-reactivation correlated with the presence of &gt, 1 additional NLGSs (p &lt, 0.001). These NLGSs are located in the major hydrophilic region of HBsAg (known to be the target of antibodies) and resulted from the single mutation T115N, T117N, T123N, N114ins, and from the triple mutant S113N+T131N+M133T. In vitro, NLGSs strongly alter HBsAg antigenic properties and recognition by antibodies used in assays for HBsAg-quantification without affecting HBsAg-secretion and other parameters of HBV-replication. In conclusion, additional NLGSs correlate with HBsAg-negativity despite HBV-reactivation, and hamper HBsAg-antigenicity in vitro, supporting the role of NGSs in immune-escape and the importance of HBV-DNA for a proper diagnosis of HBV-reactivation.

Published
2020

33. Use of Telemedicine for chronic liver disease at a single care center during the COVID-19 pandemic: Prospective observational study

Author

Andrea Fiorentino, Giuseppina Pontillo, Valentina Cossiga, Maria Guarino, Filomena Morisco, Guarino, M., Cossiga, V., Fiorentino, A., Pontillo, G., and Morisco, F.

Subjects
Male, 020205 medical informatics, 02 engineering and technology, Telehealth, Chronic liver disease, Disease Outbreaks, 0302 clinical medicine, Health care, Pandemic, 0202 electrical engineering, electronic engineering, information engineering, Ambulatory Care, Medicine, Prospective Studies, Referral and Consultation, Disease Outbreak, Liver Diseases, lcsh:Public aspects of medicine, Liver Disease, Telemedicine, Hospitalization, Italy, Liver, lcsh:R858-859.7, 030211 gastroenterology & hepatology, Female, Medical emergency, Coronavirus Infections, Human, Pneumonia, Viral, Health Informatics, lcsh:Computer applications to medicine. Medical informatics, Chronic disease, 03 medical and health sciences, Betacoronavirus, Hospital, Ambulatory care, Humans, Pandemics, Original Paper, Modalities, Hepatology, Betacoronaviru, business.industry, SARS-CoV-2, Coronavirus Infection, COVID-19, lcsh:RA1-1270, medicine.disease, Prospective Studie, Observational study, business, Delivery of Health Care
Abstract

Background The COVID-19 outbreak has overwhelmed and altered health care systems worldwide, with a substantial impact on patients with chronic diseases. The response strategy has involved implementing measures like social distancing, and care delivery modalities like telemedicine have been promoted to reduce the risk of transmission. Objective The aim of this study was to analyze the benefits of using telemedicine services for patients with chronic liver disease (CLD) at a tertiary care center in Italy during the COVID-19–mandated lockdown. Methods From March 9 to May 3, 2020, a prospective observational study was conducted in the Liver Unit of the University Hospital of Naples Federico II to evaluate the impact of (1) a fully implemented telemedicine program, partially restructured in response to COVID-19 to include video consultations; (2) extended hours of operation for helpline services; and (3) smart-working from home to facilitate follow-up visits for patients with CLD while adhering to social distancing regulations. Results During the lockdown in Italy, almost 400 visits were conducted using telemedicine; only patients requiring urgent care were admitted to a non–COVID-19 ward of our hospital. Telemedicine services were implemented not only for follow-up visits but also to screen patients prior to hospital admission and to provide urgent evaluations during complications. Of the nearly 1700 patients with CLD who attended a follow-up visit at our Liver Unit, none contracted COVID-19, and there was no need to alter treatment schedules. Conclusions Telemedicine was a useful tool for following up patients with CLD and for reducing the impact of the COVID-19 pandemic. This system of health care delivery was appreciated by patients since it gave them the opportunity to be in contact with physicians while respecting social distancing rules.

Published
2020

34. The bisphenol a induced oxidative stress in non-alcoholic fatty liver disease male patients: A clinical strategy to antagonize the progression of the disease

Author

Mario Masarone, Alessandro Federico, Filomena Morisco, Mario Romeo, Antonietta Gerarda Gravina, Concetta Tuccillo, Carmelina Loguercio, Sonia Errico, Marcello Persico, Nadia Diano, Paola Stiuso, Marcello Dallio, Federico, A., Dallio, M., Gravina, A. G., Diano, N., Errico, S., Masarone, M., Romeo, M., Tuccillo, C., Stiuso, P., Morisco, F., Persico, M., and Loguercio, C.

Subjects
Adult, Male, medicine.medical_specialty, endocrine system, Antioxidant, Health, Toxicology and Mutagenesis, medicine.medical_treatment, Cancer biology, lcsh:Medicine, medicine.disease_cause, Article, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Phenols, Internal medicine, Vitamin D and neurology, TBARS, Humans, Medicine, Obesity, Benzhydryl Compounds, Benzhydryl Compound, urogenital system, business.industry, Vitamin E, lcsh:R, Fatty liver, Public Health, Environmental and Occupational Health, Oxidative Stre, Middle Aged, medicine.disease, Oxidative Stress, Endocrinology, Italy, Liver, 030220 oncology & carcinogenesis, Homeostatic model assessment, 030211 gastroenterology & hepatology, business, Oxidative stress, hormones, hormone substitutes, and hormone antagonists, Human, Non-alcoholic fatty liver disease
Abstract

Introduction: Bisphenol A (BPA) exposure has been correlated to non-alcoholic fatty liver disease (NAFLD) development and progression. We investigated, in a clinical model, the effects of the administration of 303 mg of silybin phospholipids complex, 10 g of vitamin D, and 15 mg of vitamin E (RealSIL, 100D, IBI-Lorenzini, Aprilia, Italy) in male NAFLD patients exposed to BPA on metabolic, hormonal, and oxidative stress-related parameters. Methods: We enrolled 32 male patients with histologic diagnosis of NAFLD and treated them with Realsil 100D twice a day for six months. We performed at baseline clinical, biochemical, and food consumption assessments as well as the evaluation of physical exercise, thiobarbituric acid reactive substances (TBARS), plasmatic and urinary BPA and estrogen levels. The results obtained were compared with those of healthy control subjects and, in the NAFLD group, between baseline and the end of treatment. Results: A direct proportionality between TBARS levels and BPA exposure was shown (p &lt, 0.0001). The therapy determined a reduction of TBARS levels (p = 0.011), an improvement of alanine aminotransferase, aspartate aminotransferase, insulinemia, homeostatic model assessment insulin resistance, C reactive protein, tumor necrosis factor alpha (p &lt, 0.05), an increase of conjugated BPA urine amount, and a reduction of its free form (p &lt, 0.0001, p = 0.0002). Moreover, the therapy caused an increase of plasmatic levels of the native form of estrogens (p = 0.03). Conclusions: We highlighted the potential role of BPA in estrogen oxidation and oxidative stress in NAFLD patients. The use of Realsil 100D could contribute to fast BPA detoxification and to improve cellular antioxidant power, defending the integrity of biological estrogen-dependent pathways.

Published
2020

35. Plasma phospholipid dysregulation in patients with cystathionine-β synthase deficiency

Author

Mattia Chiesa, Filomena Capasso, Filomena Morisco, Susanna Fiorelli, Elena Tremoli, Matteo Nicola Dario Di Minno, Andrea Anesi, Viviana Cavalca, Gualtiero I. Colombo, Benedetta Porro, Roberta Clara Orsini, Sonia Eligini, Alessandro Di Minno, F. Cirillo, Di Minno, A., Anesi, A., Chiesa, M., Cirillo, F., Colombo, G. I., Orsini, R. C., Capasso, F., Morisco, F., Fiorelli, S., Eligini, S., Cavalca, V., Tremoli, E., Porro, B., and Di Minno, M. N. D.

Subjects
Adult, Male, medicine.medical_specialty, Settore CHIM/01 - CHIMICA ANALITICA, Spectrometry, Mass, Electrospray Ionization, Homocysteine, Endocrinology, Diabetes and Metabolism, S-adenosylhomocysteine, Medicine (miscellaneous), 030209 endocrinology & metabolism, Homocystinuria, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Plasma untargeted lipidomics, Internal medicine, Lipidomics, medicine, Humans, Plasma untargeted lipidomic, Phosphatidylethanolamine-N-methyltransferase, Chromatography, High Pressure Liquid, Phospholipids, Aged, Dyslipidemias, chemistry.chemical_classification, Nutrition and Dietetics, S-adenosylmethionine, biology, Chemistry, Lysophosphatidylethanolamine, Lipidome, Middle Aged, medicine.disease, Cystathionine beta synthase, Endocrinology, Phosphatidylethanolamine N-methyltransferase, Case-Control Studies, biology.protein, lipids (amino acids, peptides, and proteins), Female, Cardiology and Cardiovascular Medicine, Biomarkers, Polyunsaturated fatty acid
Abstract

Background & aims: Patients with cystathionine β-synthase deficiency (CBSD) exhibit high circulating levels of homocysteine and enhanced lipid peroxidation. We have characterized the plasma lipidome in CBSD patients and related lipid abnormalities with reactions underlying enhanced homocysteine levels. Methods and results: Using an ultra-high-performance liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry method, plasma lipids were determined with an untargeted lipidomics approach in 11 CBSD patients and 11 matched healthy subjects (CTRL). Compared to CTRL, CBSD patients had a higher medium and long-chain polyunsaturated fatty acids (PUFA) content in phosphatidylethanolamine (PE) and lysophosphatidylethanolamine (LPE) species (p < 0.02), and depletion of phosphatidylcholine (PC; p = 0.02) and of lysophosphatidylcholine (LPC; p = 0.003) species containing docosahexaenoic acid (DHA), suggesting impaired phosphatidylethanolamine-N-methyltransferase (PEMT) activity. PEMT converts PE into PC using methyl group by S-adenosylmethionine (SAM) thus converted in S-adenosylhomocysteine (SAH). Whole blood SAM and SAH concentrations by liquid chromatography tandem mass spectrometry were 1.4-fold (p = 0.015) and 5.3-fold (p = 0.003) higher in CBSD patients than in CTRL. A positive correlation between SAM/SAH and PC/PE ratios (r = 0.520; p = 0.019) was found. Conclusions: A novel biochemical abnormality in CBSD patients consisting in depletion of PC and LPC species containing DHA and accumulation of PUFA in PE and LPE species is revealed by this lipidomic approach. Changes in plasma SAM and SAH concentrations are associated with such phospholipid dysregulation. Given the key role of DHA in thrombosis prevention, depletion of PC species containing DHA in CBSD patients provides a new direction to understand the poor cardiovascular outcome of patients with homocystinuria.

Published
2020

36. Modeling the time-related fluctuations of AFP and PIVKA-II serum levels in patients with cirrhosis undergoing surveillance for hepatocellular carcinoma

Author

G. Ricco, Patrizia Pontisso, Mario Plebani, Chiara Cosma, Maurizia Rossana Brunetto, Alessandra Biasiolo, Ferruccio Bonino, Giorgio Bedogni, Filippo Oliveri, Filomena Morisco, Daniela Cavallone, Maria Guarino, Ricco, G., Cosma, C., Bedogni, G., Biasiolo, A., Guarino, M., Pontisso, P., Morisco, F., Oliveri, F., Cavallone, D., Bonino, F., Plebani, M., and Brunetto, M. R.

Subjects
Liver Cirrhosis, Male, Cancer Research, Cirrhosis, Chronic liver disease, Severity of Illness Index, Gastroenterology, 0302 clinical medicine, Reference Values, Liver Neoplasms, AFP, biomarkers, cirrhosis, hepatocellular carcinoma, PIVKA-II, surveillance, General Medicine, Middle Aged, Prognosis, Oncology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Disease Progression, biomarker, Female, Prothrombin, 030211 gastroenterology & hepatology, alpha-Fetoproteins, medicine.medical_specialty, Carcinoma, Hepatocellular, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, Biomarkers, Tumor, Genetics, medicine, Humans, In patient, Protein Precursors, neoplasms, Aged, Retrospective Studies, business.industry, Retrospective cohort study, medicine.disease, digestive system diseases, Biological Variation, Population, ROC Curve, Etiology, business, Biological variability, cirrhosi
Abstract

BACKGROUND: The time-related variability of HCC biomarkers has not been investigated so far. OBJECTIVE: To assess the changes of alpha-fetoprotein (AFP) and protein induced by vitamin-K absence/antagonist-II (PIVKA-II) in patients with HCC (HCC+) as compared to patients without HCC (HCC-). METHODS: AFP and PIVKA-II were measured by a single laboratory using an automated chemiluminescent-enzyme-immunoassay (Fujirebio Inc., Tokyo, Japan) in 1163 sera of 418 cirrhotics (31.1% HBV, 58.6% HCV, 10.3% non-viral etiology) undergoing ultrasound HCC surveillance. The mean (range) number of effective time-points available for analysis was 2.8 (2.0 to 3.0); 124 patients with HCC were matched with 294 who remained HCC free for at least 12 months after the last specimen. AFP and PIVKA-II changes were estimated over time by means of a random-effect generalized least squares (RE-GLS) regression model under the missingness at random assumption. RESULTS: Patients with and without HCC had comparable chronic liver disease etiology and staging. AFP/PIVKA-II median (25th; 75th percentile) values at the latest time-point were 4.2 (2.6; 8.6) ng/mL/32 (25; 42) mAU/mL in HCC- and 8.4 (4.4; 32.1) ng/mL/66 (32; 192) mAU/mL in HCC+ (p< 0.001). Log10AFP and log10PIVKA-II time-changes differed in HCC+ and HCC- patients. In HCC+ patients, both log10AFP and log10PIVKA-II showed an increasing trend over time. In HCC- patients, log10PIVKA-II variations were minimal as compared to log10AFP variations. The percent increase of log10AFP at 6 months vs. baseline was 11% (95%CI 5 to 17%) and 5% (95%CI 1 to 8%) for log10PIVKA-II in HCC+vs. HCC- patients. CONCLUSIONS: The present retrospective study of the biological variability of AFP and PIVKA-II suggests that their time-related changes may serve as potential predictors of HCC. This topic needs to be addressed by longitudinal studies.

Published
2020

37. Liver resection is always a good choice for hepatocellular carcinoma (HCC) patients regardless of Barcelona Clinic Liver Cancer (BCLC) stage: the therapeutic hierarchy

Author

Nicola Caporaso, Filomena Morisco, Maria Guarino, Guarino, Maria, Caporaso, Nicola, and Morisco, Filomena

Subjects
Oncology, medicine.medical_specialty, Hierarchy, business.industry, MEDLINE, General Medicine, medicine.disease, BCLC Stage, Resection, Text mining, Internal medicine, Hepatocellular carcinoma, medicine, Liver cancer, business
Published
2020

38. Impact of the COVID-19 pandemic on Gastroenterology Divisions in Italy: A national survey

Author

Lorenzo Fuccio, Edoardo Savarino, Luigi Ricciardiello, Bruno Annibale, Gianluca Ianiro, Patrizia Burra, Antonio Benedetti, Filomena Morisco, Alessandro Vitello, Manuele Furnari, Marcello Maida, Santino Marchi, Domenico Alvaro, Alessandro Repici, Sandro Sferrazza, Gaetano Cristian Morreale, Maida M., Sferrazza S., Savarino E., Ricciardiello L., Repici A., Morisco F., Furnari M., Fuccio L., Morreale G.C., Vitello A., Burra P., Marchi S., Annibale B., Benedetti A., Alvaro D., Ianiro G., Maida, M., Sferrazza, S., Savarino, E., Ricciardiello, L., Repici, A., Morisco, F., Furnari, M., Fuccio, L., Morreale, G. C., Vitello, A., Burra, P., Marchi, S., Annibale, B., Benedetti, A., Alvaro, D., and Ianiro, G.

Subjects
medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Health Personnel, Pneumonia, Viral, Gastroenterology, Article, Covid 19, pandemic, gastrenterology, Tertiary Care Centers, Betacoronavirus, Hospital, ULTRASOUND PROCEDURES, Country level, Internal medicine, Surveys and Questionnaires, Pandemic, Health care, medicine, Humans, Viral, Survey, Pandemics, Personal protective equipment, Personal Protective Equipment, Infection Control, Hepatology, Betacoronaviru, business.industry, SARS-CoV-2, Coronavirus Infection, COVID-19, Impact, Coronavirus Infections, Hospitals, Italy, Outbreak, Endoscopy, Pneumonia, Intensive Care Units, Emergency Service, Hospital, business, Healthcare system, Human
Abstract

Background In Italy, the spread of the COVID-19 pandemic has stressed the entire healthcare system and required a huge re-organization of many Divisions, including those of Gastroenterology. Aims to assess the impact of COVID-19 pandemic on Gastroenterology Divisions across Italy. Methods All members of the Italian Society of Gastroenterology (SIGE) were invited to answer a web-based survey. Results Data of 121 hospitals from all 20 Italian regions were analyzed. Overall, 10.7% Gastroenterology Divisions have been converted to Covid Units. Outpatients consultations, endoscopic and ultrasound procedures were limited to urgencies and oncology indications in 85.1%, 96.2% and 72.2% of Units, respectively, and 46.7% of them suspended the screening for colorectal cancer. Moreover, 72.2% of the staff received a training for use of personal protective equipment, although 45.5% did not have sufficient devices for adequate replacement. Overall, 132 healthcare workers in 41 Gastroenterology Divisions were found to be infected. Conclusion This is the first study to evaluate, at a country level, the impact of COVID-19 outbreak on Gastroenterology Divisions. Substantial changes of practice and reduction of procedures have been recorded in the entire country. The long-term impact of such modifications is difficult to estimate but potentially very risky for many digestive diseases.

Published
2020

39. On-treatment serum albumin level can guide long-term treatment in patients with cirrhosis and uncomplicated ascites

Author

Alessandro Federico, M. Colpani, Paolo Caraceni, Marco Domenicali, Manuel Tufoni, L. Simone, A Alberti, Giovanni Raimondo, A. Risso, Antonietta Sticca, Salvatore Piano, Anna Visani, Francesco Salerno, Giacomo Laffi, Piera Rossi, Paolo Angeli, F. Fidone, Pierluigi Toniutto, Vincenza Calvaruso, Silvia Nardelli, Aldo Airoldi, Sara Massironi, Stefania Gioia, A. Roncadori, Marco Marzioni, Nicola Caporaso, N.M. Castellaneta, Stefano Fagiuoli, Francesco Giuseppe Foschi, Raffaele Cozzolongo, Maria Rendina, Irene Cacciola, Oliviero Riggio, Sergio Neri, Raffaella Viganò, Ferdinando Giannone, Chiara Mazzarelli, Maria Marsico, Giovanni Parrella, Riccardo Guarisco, Chiara Elia, F. Levantesi, M. Cavallin, Alida Andrealli, A. Pecchioli, Loredana Prestianni, Rosanna De Marco, T Gabbani, Elga Neri, S. Boccia, Arianna Lanzi, Giacomo Zaccherini, Marcello Dallio, Giovanni Perricone, Giorgio Ballardini Natascia Celli, Francesco Auriemma, Federica Mirici Cappa, Agnese Antognoli, Annalisa Tortora, Gianfranco Elia, R. Bringiotti, Francesco De Leonardis, Marcello Vangeli, Agostino Rizzotto, Dario Conte, Manuela Merli, Francesca Capretti, Mauro Bernardi, Chiara Pasquale, Pietro Leo, D. Maiorca, M. Zappimbulso, Filomena Morisco, Vincenzo Sangiovanni, Maurizio Baldassarre, Lucia Cesarini, Gianluca Svegliati-Baroni, Maria Guarino, Carmelina Loguercio, Alessandra Galioto, Antonio Mastroianni, Giorgio Maria Saracco, Antonio Gasbarrini, G. Magini, Alba Kostandini, Carlo Alessandria, Josè Petruzzi, Vito Di Marco, Silvano Fasolato, Elisa Negri, Fabio Pugliese, Mario Angelico, Daniela Campion, Caraceni P., Tufoni M., Zaccherini G., Riggio O., Angeli P., Alessandria C., Neri S., Foschi F.G., Levantesi F., Airoldi A., Simone L., Svegliati-Baroni G., Fagiuoli S., Laffi G., Cozzolongo R., Di Marco V., Sangiovanni V., Morisco F., Toniutto P., Gasbarrini A., De Marco R., Piano S., Nardelli S., Elia C., Roncadori A., Baldassarre M., Bernardi M., Domenicali M., Giannone F.A., Antognoli A., Merli M., Pasquale C., Gioia S., Fasolato S., Sticca A., Campion D., Risso A., Saracco G.M., Prestianni L., Fidone F., Maiorca D., Rizzotto A., Cappa F.M., Lanzi A., Neri E., Visani A., Mastroianni A., Perricone G., Alberti A.B., Cesarini L., Mazzarelli C., Vangeli M., Vigano R., Marzioni M., Capretti F., Kostandini A., Magini G., Colpani M., Gabbani T., Marsico M., Zappimbulso M., Petruzzi J., Calvaruso V., Parrella G., Caporaso N., Auriemma F., Guarino M., Pugliese F., Tortora A., Leo P., Angelico M., De Leonardis F., Pecchioli A., Rossi P., Raimondo G., Cacciola I., Elia G., Negri E., Dallio M., Loguercio C., Federico A., Conte D., Massironi S., Natascia Celli G.B., Rendina M., Bringiotti R., Castellaneta N.M., Salerno F., Boccia S., Guarisco R., Galioto A., Cavallin M., Andrealli A., Caraceni, P., Tufoni, M., Zaccherini, G., Riggio, O., Angeli, P., Alessandria, C., Neri, S., Foschi, F. G., Levantesi, F., Airoldi, A., Simone, L., Svegliati-Baroni, G., Fagiuoli, S., Laffi, G., Cozzolongo, R., Di Marco, V., Sangiovanni, V., Morisco, F., Toniutto, P., Gasbarrini, A., De Marco, R., Piano, S., Nardelli, S., Elia, C., Roncadori, A., Baldassarre, M., Bernardi, M., Domenicali, M., Giannone, F. A., Antognoli, A., Merli, M., Pasquale, C., Gioia, S., Fasolato, S., Sticca, A., Campion, D., Risso, A., Saracco, G. M., Prestianni, L., Fidone, F., Maiorca, D., Rizzotto, A., Cappa, F. M., Lanzi, A., Neri, E., Visani, A., Mastroianni, A., Perricone, G., Alberti, A. B., Cesarini, L., Mazzarelli, C., Vangeli, M., Vigano, R., Marzioni, M., Capretti, F., Kostandini, A., Magini, G., Colpani, M., Gabbani, T., Marsico, M., Zappimbulso, M., Petruzzi, J., Calvaruso, V., Parrella, G., Caporaso, N., Auriemma, F., Guarino, M., Pugliese, F., Tortora, A., Leo, P., Angelico, M., De Leonardis, F., Pecchioli, A., Rossi, P., Raimondo, G., Cacciola, I., Elia, G., Negri, E., Dallio, M., Loguercio, C., Federico, A., Conte, D., Massironi, S., Natascia Celli, G. B., Rendina, M., Bringiotti, R., Castellaneta, N. M., Salerno, F., Boccia, S., Guarisco, R., Galioto, A., Cavallin, M., Andrealli, A., Caraceni, P, Tufoni, M, Zaccherini, G, Riggio, O, Angeli, P, Alessandria, C, Neri, S, Foschi, F, Levantesi, F, Airoldi, A, Simone, L, Svegliati-Baroni, G, Fagiuoli, S, Laffi, G, Cozzolongo, R, Di Marco, V, Sangiovanni, V, Morisco, F, Toniutto, P, Gasbarrini, A, De Marco, R, Piano, S, Nardelli, S, Elia, C, Roncadori, A, Baldassarre, M, Bernardi, M, Domenicali, M, Giannone, F, Antognoli, A, Merli, M, Pasquale, C, Gioia, S, Fasolato, S, Sticca, A, Campion, D, Risso, A, Saracco, G, Prestianni, L, Fidone, F, Maiorca, D, Rizzotto, A, Cappa, F, Lanzi, A, Neri, E, Visani, A, Mastroianni, A, Perricone, G, Alberti, A, Cesarini, L, Mazzarelli, C, Vangeli, M, Vigano, R, Marzioni, M, Capretti, F, Kostandini, A, Magini, G, Colpani, M, Gabbani, T, Marsico, M, Zappimbulso, M, Petruzzi, J, Calvaruso, V, Parrella, G, Caporaso, N, Auriemma, F, Guarino, M, Pugliese, F, Tortora, A, Leo, P, Angelico, M, De Leonardis, F, Pecchioli, A, Rossi, P, Raimondo, G, Cacciola, I, Elia, G, Negri, E, Dallio, M, Loguercio, C, Federico, A, Conte, D, Massironi, S, Natascia Celli, G, Rendina, M, Bringiotti, R, Castellaneta, N, Salerno, F, Boccia, S, Guarisco, R, Galioto, A, Cavallin, M, and Andrealli, A

Subjects
Male, 0301 basic medicine, Cirrhosis, ascites, complications, liver cirrhosis, serum albumin, survival, Serum albumin, Survival, Logistic regression, Gastroenterology, Biomarkers, Pharmacological, Ascites, Complications, 0302 clinical medicine, Medicine, biology, Middle Aged, Intention to Treat Analysis, Treatment Outcome, Ascite, Female, 030211 gastroenterology & hepatology, Drug Monitoring, medicine.symptom, medicine.medical_specialty, Settore MED/12 - GASTROENTEROLOGIA, Serum Albumin, Human, 03 medical and health sciences, Serum albumin level, Predictive Value of Tests, Internal medicine, Post-hoc analysis, Humans, In patient, Biological Products, Cirrhosi, Hepatology, business.industry, Albumin, medicine.disease, Long-Term Care, Survival Analysis, 030104 developmental biology, biology.protein, business, Complication
Abstract

Background & Aims: The ANSWER study reported that long-term albumin administration in patients with cirrhosis and uncomplicated ascites improves survival. During treatment, serum albumin increased within a month and remained stable thereafter. In this post hoc analysis, we aimed to determine whether on-treatment serum albumin levels could guide therapy. Methods: Logistic regression was used to assess the association between baseline serum albumin and mortality, as well as to determine on-treatment factors associated with mortality and to predict the achievement of a given on-treatment serum albumin level. Survival was assessed by Kaplan-Meier estimates and second-order polynomial regression. Patients whose on-treatment serum albumin remained below normal were compared with a subset of patients from the control arm matched by principal score. Results: Baseline serum albumin was closely associated with 18-month mortality in untreated patients; albumin treatment almost effaced this relationship. On-treatment serum albumin and MELD-Na at month 1 were the sole independent variables associated with mortality. Second-order polynomial regression revealed that survival improved in parallel with increased 1-month on-treatment serum albumin. Kaplan-Meier estimations showed that any value of 1-month on-treatment serum albumin (0.1 g/dl intervals) in the range 2.5–4.5 g/dl discriminated patient survival. In the normal range of serum albumin, the best discriminant value was 4.0 g/dl. Compared to untreated patients, survival even improved in patients whose on-treatment serum albumin remained below normal. Conclusion: Baseline serum albumin per se should not guide the decision to start albumin therapy. Conversely, 1-month on-treatment serum albumin levels are strongly associated with outcomes and could guide the use of albumin – 4.0 g/dl being the target threshold. However, even patients whose serum albumin remains below normal benefit from long-term albumin administration. Lay summary: The ANSWER study has shown that long-term albumin administration improves survival and prevents the occurrence of major complications in patients with cirrhosis and ascites. This study shows that the achievement of these beneficial effects is related to a significant increase in serum albumin concentration. Even though the best results follow the achievement of a serum albumin concentration of 4 g/dl, a survival benefit is also achieved in patients who fail to normalise serum albumin.

Published
2020

40. Eradication of HCV in Renal Transplant Recipients and Its Effects on Quality of Life

Author

Pasquale Buonanno, L. Donnarumma, Silvia Camera, Lucia Ferreri, Massimo Sabbatini, Filomena Morisco, Ivana Capuano, Nicola Caporaso, Sabbatini, Massimo, Capuano, Ivana, Camera, Silvia, Ferreri, Lucia, Buonanno, Pasquale, Donnarumma, Laura, Caporaso, Nicola, and Morisco, Filomena

Subjects
Adult, Male, medicine.medical_specialty, Article Subject, Sofosbuvir, Immunology and Microbiology (all), lcsh:Medicine, Renal function, Hepacivirus, 030230 surgery, Antiviral Agents, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Liver stiffness, Internal medicine, Ribavirin, Hcv hepatitis, medicine, Humans, Aged, Antiviral Agent, Hepaciviru, Biochemistry, Genetics and Molecular Biology (all), Proteinuria, General Immunology and Microbiology, business.industry, lcsh:R, General Medicine, Hepatitis C, Chronic, Middle Aged, Hepatitis C, Kidney Transplantation, Regimen, Treatment Outcome, Italy, chemistry, Renal transplant, Quality of Life, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, medicine.symptom, business, Human, medicine.drug
Abstract

Background. The use of direct antiviral agents (DAA) has radically modified the course of HCV hepatitis in renal patients. Aim of this study was to assess the effects of HCV eradication on quality of life (QOL) in renal transplant recipients (RTR), measured by CLDQ and SF-36. Methods. Sixteen RTR with well preserved GFR (mean: 60.3±19.3 ml/min) and chronic HCV infection with moderate liver stiffness (9.3±1.7 kPa) were given a sofosbuvir-based regimen for 12 weeks and had a 1 year follow-up. Results. At end of treatment (EOT) a complete viral clearance was observed in all the patients, with normalization of most laboratory data and a consistent reduction in liver stiffness. All these parameters remained stable after 1 year, as well as renal function and proteinuria. Questionnaire data showed consistent amelioration in different “emotional” domains at EOT, which persisted after 1 year and were associated with a globally improved QOL, although there was no change in most of the “physical” domains in both questionnaires. One patient under ribavirin developed an acute anemia and withdrew from the study, but no further adverse episode was observed throughout the study. Conclusions. Our data, while confirming the efficacy of oral DAA, show that HCV infection represents a heavy psychological burden in renal transplant recipients, greatly alleviated by viral eradication, which determines a significant improvement in QOL that represents an important outcome in management of all transplant recipients. This trial is registered with ISRCTN97560076.

Published
2018

41. Dietary supplementation of vitamin D prevents the development of western diet‐induced metabolic, hepatic and cardiovascular abnormalities in rats

Author

Carmine Morisco, G. Mazzone, Maria D'Armiento, Carmine Del Giudice, Antonella Rossi, Giuseppe D'Argenio, Nicola Caporaso, Bruno Trimarco, Vincenzo Lembo, Filomena Morisco, Mazzone, Giovanna, Morisco, Carmine, Lembo, Vincenzo, D’Argenio, Giuseppe, D’Armiento, Maria, Rossi, Antonella, Giudice, Carmine Del, Trimarco, Bruno, Caporaso, Nicola, and Morisco, Filomena

Subjects
0301 basic medicine, Vitamin, insulin, medicine.medical_specialty, medicine.medical_treatment, vitamin D, 030204 cardiovascular system & hematology, Diabete, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, cardiovascular disease, Internal medicine, Diabetes mellitus, Western diet, HOMA, medicine, Vitamin D and neurology, Dietary supplementation, business.industry, Insulin, Gastroenterology, Fructose, Original Articles, medicine.disease, western diet, 030104 developmental biology, Endocrinology, Oncology, chemistry, business
Abstract

The western diet high in fat and fructose may cause metabolic disorders and cardiovascular diseases.To evaluate whether long-term daily vitamin DThree groups of rats were fed for 6 months with standard diet (SD), western diet (WD) or WD containing 23 IU/day/rat vitamin DSixty-one per cent of hepatocytes in WD rats had steatotic vacuoles compared with just 27% in rats on a WD plus vitamin DIn animal models of liver and cardiovascular metabolic damage, the supplementation of vitamin D

Published
2018

42. The interpretation of liver function tests in pregnancy

Author

Filomena Morisco, Valentina Cossiga, Maria Guarino, Guarino, M., Cossiga, V., and Morisco, F.

Subjects
HELLP syndrome, Physiology, Transaminase, Acute fatty liver of pregnancy, Cholestasis, Liver Function Tests, Pregnancy, medicine, Humans, Liver injury, medicine.diagnostic_test, business.industry, Liver Function Test, Liver Disease, Liver Diseases, Gastroenterology, medicine.disease, Haemolysis, Pregnancy Complications, Cholestasi, Female, Liver function tests, business, Cholestasis of pregnancy, Human
Abstract

Abnormal liver tests occur in 3-5% of pregnancies and show many different causes. Although alterations of liver enzymes could be a physiological phenomenon, it may also reflect potential severe liver injury, necessitating further assessment and accurate management. The work-up has to consider liver diseases specific of pregnancy and non pregnancy-related liver damage (coincidental and pre-existing to pregnancy). Pre-existing liver diseases during pregnancy are relatively uncommon, as pregnant women are generally young and healthy. Liver diseases unique to pregnancy are intrahepatic cholestasis of pregnancy, the HELLP syndrome (haemolysis, elevated liver enzymes, low platelets) and acute fatty liver of pregnancy. These disorders may result in foetal distress, severe liver damage and sometime hepatic failure; for these reasons the diagnostic work-up and treatment must be very fast. This review focuses on the management of pregnant women with altered liver function tests. Furthermore, the main liver diseases specific of pregnancy are described.

Published
2019

43. Adherence to Barcelona Clinic Liver Cancer guidelines in field practice: Results of Progetto Epatocarcinoma Campania

Author

Luigi Elio Adinolfi, Giorgio de Stefano, Raffaella Tortora, Angelo Salomone Megna, Vincenzo De Girolamo, Maria Guarino, Marcello Persico, Giovanni Battista Gaeta, Nicola Coppola, Francesco Izzo, Vincenzo Messina, Giuseppe D'Adamo, Gerardo Nardone, Giovan Giuseppe Di Costanzo, Carmine Coppola, Guido Piai, Filomena Morisco, and Giampiero Francica

Subjects
medicine.medical_specialty, Multivariate analysis, Hepatology, business.industry, Gastroenterology, medicine.disease, Thrombosis, digestive system diseases, BCLC Stage, Surgery, Portal vein thrombosis, 03 medical and health sciences, 0302 clinical medicine, Field practice, 030220 oncology & carcinogenesis, Internal medicine, medicine, 030211 gastroenterology & hepatology, Liver function, Stage (cooking), Liver cancer, business
Abstract

Background The BCLC algorithm is the standard system for clinical management of HCC. Data on adherence to this therapeutic paradigm are scarce. Aims This field-practice study aimed to provide a description of HCC cirrhotic patients in Southern Italy, to evaluate the adherence to BCLC guidelines and its impact on patients’ survival. Methods We analyzed the region-wide Italian database of Progetto Epatocarcinoma Campania, which includes data of HCC cirrhotic patients, prospectively collected from January 2013 to December 2015 in 16 regional centers. Results Overall 1008 HCC patients were enrolled: 70.6% patients received therapies recommended by BCLC algorithm, while 29.4% underwent different treatments. Among patients who were treated in adherence to guidelines, a higher rate of diagnosis on surveillance programs, better liver function, lower rate of AFP >200ng/ml, more early stage and monofocal HCC, lower frequency of nodules >5cm, portal vein thrombosis and metastases were observed. The overall survival was evaluated according to HCC stage and no differences between group and patients managed differently were found. The multivariate analysis showed that non-adherence to treatment guidelines was independently associated to the BCLC stage B, Child-Pugh classes B-C, and to the presence of neoplastic thrombosis and metastases. Conclusion Adherence to BCLC algorithm in field-practice was high in early and end stage HCC patients, but it was poor in intermediate and advanced patients.

Published
2018

44. Prevalence of and risk factors for HBV infection in a metropolitan Southern Italian area: Evidence for the effectiveness of universal Hepatitis B vaccination

Author

Tommaso Stroffolini, Flavia Lucia Lombardo, Ilaria Loperto, Silvia Camera, Filomena Morisco, Nicola Caporaso, L. Donnarumma, Valentina Cossiga, Maria Guarino, Morisco, Filomena, Stroffolini, Tommaso, Lombardo, Flavia Lucia, Guarino, Maria, Camera, Silvia, Cossiga, Valentina, Donnarumma, Laura, Loperto, Ilaria, and Caporaso, Nicola

Subjects
Adult, Male, HBsAg, medicine.medical_specialty, Pediatrics, Epidemiology, Population, Logistic regression, 03 medical and health sciences, 0302 clinical medicine, Residence Characteristics, Risk Factors, Seroepidemiologic Studies, Poverty Areas, Prevalence, Humans, Medicine, 030212 general & internal medicine, Cities, Hepatitis B Antibodies, education, Socioeconomic status, education.field_of_study, Hepatitis B Surface Antigens, Hepatology, business.industry, Vaccination, Age Factors, Gastroenterology, Middle Aged, Hepatitis B, medicine.disease, Italy, Social Class, Educational Status, Female, 030211 gastroenterology & hepatology, Residence, Risk factor, business, Demography
Abstract

Available data on HBV prevalence in Italy are outdated and assessed with studies conducted in small towns. We aimed to evaluate prevalence of and risk factors for HBV infection in the metropolitan area of Naples, 24 years after the introduction of mass vaccination campaign against Hepatitis B in Italy.A random systematic sample of the adult general population of Naples was selected from the register of 3 general practitioners in 3 different socio-economic districts. Independent predictors of the likelihood of HBV infection were identified by logistic regression analysis.Among 900 selected subjects, 772 (85.8%) participated in the study. The overall HBsAg and anti-HBc prevalences were 1.7% and 14.4%, respectively. Both markers were more likely detected in the district at low socioeconomic status than in those at medium-high status (p0.01). Anti-HBc prevalence linearly increased from 0% in subjects 30 years old or younger to 28.0% in those older than 60 years of age (p0.01). At multivariate analysis, age60 years (OR3.38; 95%CI:1.98-5.74), low socioeconomic district of residence (OR3.26; 95%CI:1.72-6.18), and low educational qualification (OR2.73; 95%CI:1.45-5.16) were independent predictors of anti-HBc positivity.Differences in socioeconomic conditions have played a major role in the past spread of HBV infection in Naples. Hepatitis B vaccination has resulted very effectively in preventing HBV infection, regardless of the district of residence, as none of the subjects in the vaccinated cohorts was exposed to the infection.

Published
2017

45. AF.90 RISK FACTORS FOR LIVER DECOMPENSATION AND HCC IN HCV-CIRRHOTIC PATIENTS AFTER DAAS: A MULTICENTER PROSPECTIVE STUDY

Author

M. Cannavò, L. Pignata, Tommaso Stroffolini, Marcello Dallio, Massimo Marignani, Giuseppina Pontillo, Flavia Lucia Lombardo, Filomena Morisco, Alessandro Federico, M. Capasso, Valentina Cossiga, Michele Pier Luca Guarino, Paola Begini, and R. Benigno

Subjects
medicine.medical_specialty, Hepatology, business.industry, Internal medicine, Gastroenterology, medicine, Liver decompensation, Prospective cohort study, business
Published
2021

46. AF.93 COVID-19 IN LIVER TRANSPLANT RECIPIENTS: AN ITALIAN CASE-CONTROL DOUBLE-CENTER STUDY

Author

Michele Pier Luca Guarino, M. Capasso, V. Cozza, L. De Coppi, Valentina Cossiga, Ilaria Loperto, F.P. Picciotto, R. Ortolani, I. Esposito, Giuseppina Pontillo, Andrea Fiorentino, Filomena Morisco, G.G. Di Costanzo, and L. Pignata

Subjects
2019-20 coronavirus outbreak, Pediatrics, medicine.medical_specialty, Hepatology, Coronavirus disease 2019 (COVID-19), Liver, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Gastroenterology, medicine, Center (algebra and category theory), business, Abstracts of the 27th National Congress of Digestive Diseases 2021 – FISMAD
Published
2021

48. T06.01.9 THE BISPHENOL A INDUCED WORSENING OF NON-ALCOHOLIC FATTY LIVER DISEASE: A CLINICAL STRATEGY TO ANTAGONIZE THE PROGRESSION OF THE DISEASE

Author

Carla Nicolucci, Sonia Errico, Marcello Dallio, Nadia Diano, Mario Masarone, Concetta Tuccillo, R. Di Sarno, Antonietta Gerarda Gravina, Marcello Persico, Carmela Loguercio, Paola Stiuso, Alessandro Federico, and Filomena Morisco

Subjects
medicine.medical_specialty, Bisphenol A, Hepatology, business.industry, Fatty liver, Gastroenterology, Non alcoholic, Disease, medicine.disease, chemistry.chemical_compound, chemistry, Internal medicine, medicine, business
Published
2020

49. The Combination of Berberine, Tocotrienols and Coffee Extracts Improves Metabolic Profile and Liver Steatosis by the Modulation of Gut Microbiota and Hepatic miR-122 and miR-34a Expression in Mice

Author

G. Mazzone, Claudia Miele, Iolanda Veneruso, Nicola Caporaso, Paola Mirra, Valentina Cossiga, Filomena Morisco, Vincenzo Lembo, Valeria D'Argenio, Alessia Leone, Francesco Beguinot, Cecilia Nigro, Maria Guido, Cossiga, V., Lembo, V., Nigro, C., Mirra, P., Miele, C., D'Argenio, V., Leone, A., Mazzone, G., Veneruso, I., Guido, M., Beguinot, F., Caporaso, N., and Morisco, F.

Subjects
Male, 0301 basic medicine, Berberis, Berberine, gut microbiome, Coffea, Arecaceae, Gut flora, Mice, Liver disease, chemistry.chemical_compound, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, MiR-122, Nutrition and Dietetics, biology, Tocotrienols, digestive, oral, and skin physiology, food and beverages, miR-122, Liver, 030220 oncology & carcinogenesis, lipids (amino acids, peptides, and proteins), miR-34a, medicine.medical_specialty, Berberis aristata, Diet, High-Fat, Article, metabolic syndrome, 03 medical and health sciences, Insulin resistance, NAFLD, Internal medicine, medicine, MiR‐122, Animals, Humans, Plant Extracts, Gut microbiome, Metabolic syndrome, MiR‐34a, nutritional and metabolic diseases, medicine.disease, biology.organism_classification, Gastrointestinal Microbiome, Disease Models, Animal, MicroRNAs, 030104 developmental biology, Endocrinology, Gene Expression Regulation, chemistry, Dysbiosis, Insulin Resistance, Steatosis, Food Science
Abstract

Non-alcoholic-fatty liver disease (NAFLD) is spreading worldwide. Specific drugs for NAFLD are not yet available, even if some plant extracts show beneficial properties. We evaluated the effects of a combination, composed by Berberis Aristata, Elaeis Guineensis and Coffea Canephora, on the development of obesity, hepatic steatosis, insulin-resistance and on the modulation of hepatic microRNAs (miRNA) levels and microbiota composition in a mouse model of liver damage. C57BL/6 mice were fed with standard diet (SD, n = 8), high fat diet (HFD, n = 8) or HFD plus plant extracts (HFD+E, n = 8) for 24 weeks. Liver expression of miR-122 and miR-34a was evaluated by quantitativePCR. Microbiome analysis was performed on cecal content by 16S rRNA sequencing. HFD+E-mice showed lower body weight (p &lt, 0.01), amelioration of insulin-sensitivity (p = 0.021), total cholesterol (p = 0.014), low-density-lipoprotein-cholesterol (p &lt, 0.001), alanine-aminotransferase (p = 0.038) and hepatic steatosis compared to HFD-mice. While a decrease of hepatic miR-122 and increase of miR-34a were observed in HFD-mice compared to SD-mice, both these miRNAs had similar levels to SD-mice in HFD+E-mice. Moreover, a different microbial composition was found between SD- and HFD-mice, with a partial rescue of dysbiosis in HFD+E-mice. This combination of plant extracts had a beneficial effect on HFD-induced NAFLD by the modulation of miR-122, miR-34a and gut microbiome.

Published
2021

50. Systematic review: interferon-free regimens for patients with HCV-related Child C cirrhosis

Author

A. Amoruso, Nicola Caporaso, Grazia Anna Niro, N. Andriulli, Michele Pier Luca Guarino, Monica Greco, M. Librandi, Antonio Massimo Ippolito, Maria Rosa Valvano, Filomena Morisco, Angelo Andriulli, A. Iacobellis, Guarino, Maria, Morisco, Filomena, Valvano, M. R, Ippolito, A. M, Librandi, M, Andriulli, N, Greco, M, Amoruso, A, Iacobellis, A, Niro, G, Caporaso, Nicola, and Andriulli, A.

Subjects
Liver Cirrhosis, Ledipasvir, Simeprevir, medicine.medical_specialty, Cirrhosis, Daclatasvir, Sofosbuvir, Hepatitis C virus, medicine.disease_cause, Antiviral Agents, 03 medical and health sciences, chemistry.chemical_compound, Liver disease, 0302 clinical medicine, Internal medicine, medicine, Humans, Protease Inhibitors, Pharmacology (medical), Hepatology, business.industry, Ribavirin, Gastroenterology, medicine.disease, Hepatitis C, Surgery, chemistry, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Interferons, business, medicine.drug
Abstract

SummaryBackground It is unclear whether the efficacy and long-term outcome of treating patients with hepatitis C virus (HCV)-positive cirrhosis with the new protease inhibitors will extend to those with Child C cirrhosis. Aim To assess the effectiveness of the interferon-free regimens in Child C cirrhotic patients with HCV infection. Methods A systematic Medline search was conducted to retrieve studies describing the treatment of Child C patients with direct-acting agents. Citations from identified studies were cross-referenced and abstracts from European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Disease (AASLD) meetings were checked. Extracted data were evaluated using a meta-analysis to calculate a weighted response rate. Results Seven full-text records and two conference abstracts were retained for analysis from the 649 records identified. Data from an Italian real-life trial were also interrogated. Information on treatment outcome was available for 228 of the 240 Child C patients evaluated in the 10 trials. Overall, the weighted mean sustained virological response (SVR12) was 74.9% (95% CI: 65.6–82.4%). Neither duration of treatment (24 or 12 weeks), nor addition of ribavirin influenced these rates. The weighted SVR12 was 65.4% (95% CI: 46.8–80.2) after sofosbuvir/simeprevir, 76.0% (95% CI: 54.4–89.3%) after sofosbuvir/daclatasvir and 83.0% (95% CI: 73.4–89.6) after sofosbuvir/ledipasvir. Some studies did not provide information on the rate of post-treatment relapse or functional improvement. However, in those studies that did provide such data, a relapse was documented in 12.1% of patients and an improvement of ≥2 points on the model for end-stage liver disease (MELD) score in 61.1% of patients. Conclusion The improvement in MELD scores strongly suggests HCV-positive patients with Child C cirrhosis should be treated with these agents.

Published
2017

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