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104 results on '"Gianluca, Svegliati-Baroni"'

1. Global prevalence of metabolic dysfunction-associated fatty liver disease-related hepatocellular carcinoma: A systematic review and meta-analysis

Author

Harry Crane, Guy D. Eslick, Cameron Gofton, Anjiya Shaikh, George Cholankeril, Mark Cheah, Jian-Hong Zhong, Gianluca Svegliati-Baroni, Alessandro Vitale, Beom Kyung Kim, Sang Hoon Ahn, Mi Na Kim, Simone I Strasser, and Jacob George

Subjects
fatty liver, hepatocellular carcinoma, epidemiology, prevalence, metabolic syndrome, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background/Aims The global proportion of hepatocellular carcinoma (HCC) attributable to metabolic dysfunction-associated fatty liver disease (MAFLD) is unclear. The MAFLD diagnostic criteria allows objective diagnosis in the presence of steatosis plus defined markers of metabolic dysfunction, irrespective of concurrent liver disease. We aimed to determine the total global prevalence of MAFLD in HCC cohorts (total-MAFLD), including the proportion with MAFLD as their sole liver disease (single-MAFLD), and the proportion of those with concurrent liver disease where MAFLD was a contributary factor (mixed-MAFLD). Methods This systematic review and meta-analysis included studies systematically ascertaining MAFLD in HCC cohorts, defined using international expert panel criteria including ethnicity-specific BMI cut-offs. A comparison of clinical and tumour characteristics was performed between single-MAFLD, mixed-MAFLD, and non-MAFLD HCC. Results 22 studies (56,565 individuals with HCC) were included. Total and single-MAFLD HCC prevalence was 48.7% (95% confidence interval [CI] 34.5–63.0%) and 12.4% (95% CI 8.3–17.3%), respectively. In HCC due to chronic hepatitis B, C, and alcohol-related liver disease, mixed-MAFLD prevalence was 40.0% (95% CI 30.2–50.3%), 54.1% (95% CI 40.4–67.6%) and 64.3% (95% CI 52.7–75.0%), respectively. Mixed-MAFLD HCC had significantly higher likelihood of cirrhosis and lower likelihood of metastatic spread compared to single-MAFLD HCC, and a higher platelet count and lower likelihood of macrovascular invasion compared to non-MAFLD HCC. Conclusions MAFLD is common as a sole aetiology, but more so as a co-factor in mixed-aetiology HCC, supporting the use of positive diagnostic criteria.

Published
2024
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2. Hypoalbuminemia and Risk of Portal Vein Thrombosis in Cirrhosis

Author

Giuseppe, Palasciano, Felicia, D’Alitto, Ostilio, Palmieri Vincenzo, Daniela, Santovito, Dario, Di Michele, Giuseppe, Croce, David, Sacerdoti, Silvia, Brocco, Silvano, Fasolato, Lara, Cecchetto, Giancarlo, Bombonato, Michele, Bertoni, Tea, Restuccia, Paola, Andreozzi, Livia, Liguori Maria, Francesco, Perticone, Benedetto, Caroleo, Maria, Perticone, Orietta, Staltari, Roberto, Manfredini, Alfredo, De Giorgi, Maurizio, Averna, Antonina, Giammanco, Alessandro, Granito, Irene, Pettinari, Sara, Marinelli, Luigi, Bolondi, Lorenzo, Falsetti, Aldo, Salvi, Emanuele, Durante-Mangoni, Flavio, Cesaro, Vincenza, Farinaro, Enrico, Ragone, Ignazio, Morana, Angelo, Andriulli, Antonio, Ippolito, Angelo, Iacobellis, Grazia, Niro, Antonio, Merla, Giovanni, Raimondo, Sergio, Maimone, Irene, Cacciola, Doriana, Varvara, Davide, Drenaggi, Silvia, Staffolani, Antonio, Picardi, Umberto, Vespasiani-Gentilucci, Giovanni, Galati, Paolo, Gallo, Giovanni, Davì, Cosima, Schiavone, Francesca, Santilli, Claudio, Tana, Anna, Licata, Maurizio, Soresi, Battista, Bianchi Giovanni, Isabella, Carderi, Antonio, Pinto, Antonino, Tuttolomondo, Giovanni, Ferrari, Paolo, Gresele, Tiziana, Fierro, Olivia, Morelli, Giacomo, Laffi, Giulio, Romanelli Roberto, Umberto, Arena, Cristina, Stasi, Antonio, Gasbarrini, Matteo, Gargovich, Assunta, Zocco Maria, Laura, Riccardi, Elena, Ainora Maria, William, Capeci, Pio, Martino Giuseppe, Lorenzo, Nobili, Maurizio, Cavallo, Pierluigi, Frugiuele, Antonio, Greco, Antonello, Pietrangelo, Paolo, Ventura, Chiara, Cuoghi, Matteo, Marcacci, Gaetano, Serviddio, Gianluigi, Vendemiale, Rosanna, Villani, Ruggiero, Gargano, Gianpaolo, Vidili, Valentina, Di Cesare, Maristella, Masala, Giuseppe, Delitala, Pietro, Invernizzi, Giovanni, Di Minno, Antonella, Tufano, Francesco, Purrello, Graziella, Privitera, Alessandra, Forgione, Valentina, Curigliano, Marco, Senzolo, Kryssia Isabel, Rodríguez-Castro, Gianluigi, Giannelli, Carla, Serra, Sergio, Neri, Pietro, Pignataro, Mario, Rizzetto, Wilma, Debernardi Venon, Gianluca, Svegliati Baroni, Gaetano, Bergamaschi, Michela, Masotti, Filippo, Costanzo, Roberto, Corazza Gino, Hugh, Caldwell Stephen, Francesco, Angelico, Ben Maria, Del, Laura, Napoleone, Licia, Polimeni, Marco, Proietti, Valeria, Raparelli, Francesco, Romiti Giulio, Eleonora, Ruscio, Andrea, Severoni, Giovanni, Talerico, Filippo, Toriello, Annarita, Vestri, Cangemi, Roberto, Raparelli, Valeria, Talerico, Giovanni, Basili, Stefania, and Violi, Francesco

Published
2024
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3. Oesophageal varices predict complications in compensated advanced non-alcoholic fatty liver disease

Author

Grazia Pennisi, Marco Enea, Mauro Viganò, Filippo Schepis, Victor de Ledinghen, Annalisa Berzigotti, Vincent Wai-Sun Wong, Anna Ludovica Fracanzani, Giada Sebastiani, Carmen Lara-Romero, Elisabetta Bugianesi, Gianluca Svegliati-Baroni, Fabio Marra, Alessio Aghemo, Luca Valenti, Vincenza Calvaruso, Antonio Colecchia, Gabriele Di Maria, Claudia La Mantia, Huapeng Lin, Yuly P. Mendoza, Nicola Pugliese, Federico Ravaioli, Manuel Romero-Gomez, Dario Saltini, Antonio Craxì, Vito Di Marco, Calogero Cammà, and Salvatore Petta

Subjects
varices, NAFLD, cACLD, liver decompensation, Portal Vein Thrombosis, baveno, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: We aimed to evaluate the impact of oesophageal varices (OV) and their evolution on the risk of complications of compensated advanced chronic liver disease (cACLD) caused by non-alcoholic fatty liver disease (NAFLD). We also assessed the accuracy of non-invasive scores for predicting the development of complications and for identifying patients at low risk of high-risk OV. Methods: We performed a retrospective assessment of 629 patients with NAFLD-related cACLD who had baseline and follow-up oesophagogastroduodenoscopy and clinical follow-up to record decompensation, portal vein thrombosis (PVT), and hepatocellular carcinoma. Results: Small and large OV were observed at baseline in 30 and 15.9% of patients, respectively. The 4-year incidence of OV from absence at baseline, and that of progression from small to large OV were 16.3 and 22.4%, respectively. Diabetes and a ≥5% increase in BMI were associated with OV progression. Multivariate Cox regression revealed that small (hazard ratio [HR] 2.24, 95% CI 1.47–3.41) and large (HR 3.86, 95% CI 2.34–6.39) OV were independently associated with decompensation. When considering OV status and trajectories, small (HR 2.65, 95% CI 1.39–5.05) and large (HR 4.90, 95% CI 2.49–9.63) OV at baseline and/or follow-up were independently associated with decompensation compared with the absence of OV at baseline and/or follow-up. The presence of either small (HR 2.8, 95% CI 1.16–6.74) or large (HR 5.29, 95% CI 1.96–14.2) OV was also independently associated with incident PVT. Conclusion: In NAFLD-related cACLD, the presence, severity, and evolution of OV stratify the risk of developing decompensation and PVT. Impact and implications: Portal hypertension is the main driver of liver decompensation in chronic liver diseases, and its non-invasive markers can help risk prediction. The presence, severity, and progression of oesophageal varices stratify the risk of complications of non-alcoholic fatty liver disease. Easily obtainable laboratory values and liver stiffness measurement can identify patients at low risk for whom endoscopy may be withheld, and can also stratify the risk of liver-related complications.

Published
2023
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5. Landscape of alcohol-related hepatocellular carcinoma in the last 15 years highlights the need to expand surveillance programs

Author

Nicola Reggidori, Laura Bucci, Valentina Santi, Benedetta Stefanini, Lorenzo Lani, Davide Rampoldi, Giorgia Ghittoni, Fabio Farinati, Alberto Masotto, Bernardo Stefanini, Andrea Mega, Elisabetta Biasini, Francesco Giuseppe Foschi, Gianluca Svegliati-Baroni, Angelo Sangiovanni, Claudia Campani, Giovanni Raimondo, Gianpaolo Vidili, Antonio Gasbarrini, Ciro Celsa, Mariella Di Marco, Edoardo G. Giannini, Rodolfo Sacco, Maurizia Rossana Brunetto, Francesco Azzaroli, Donatella Magalotti, Filomena Morisco, Gian Ludovico Rapaccini, Gerardo Nardone, Alessandro Vitale, Franco Trevisani, Maurizio Biselli, Paolo Caraceni, Annagiulia Gramenzi, Francesca Benevento, Alessandro Granito, Luca Muratori, Fabio Piscaglia, Francesco Tovoli, Gloria Allegrini, Calogero Cammà, Giuseppe Cabibbo, Carmelo Marco Giacchetto, Paolo Giuffrida, Maria Vittoria Grassini, Mauro Grova, Gabriele Rancatore, Caterina Stornello, Valentina Adotti, Tancredi Li Cavoli, Fabio Marra, Martina Rosi, Vittoria Bevilacqua, Alberto Borghi, Lucia Napoli, Fabio Conti, G.L. Frassineti, Maria Teresa Migliano, Nicoletta de Matthaeis, Francesca Romana Ponziani, Gabriele Missale, Andrea Olivani, Mario Capasso, Valentina Cossiga, Maria Guarino, Ester Marina Cela, Antonio Facciorusso, Camilla Graziosi, Valentina Lauria, Giorgio Pelecca, Marta Schirripa, Fabrizio Chegai, Armando Raso, Alessio Bozzi, Maria Stella Franzè, Carlo Saitta, Assunta Sauchella, Elton Dajti, Federico Ravaioli, Maria Corina Plaz Torres, Giulia Pieri, Filippo Oliveri, Gabriele Ricco, Veronica Romagnoli, Alessandro Inno, Fabiana Marchetti, Pietro Coccoli, Antonio Malerba, Alberta Cappelli, Rita Golfieri, Cristina Mosconi, and Matteo Renzulli

Subjects
Hepatocellular carcinoma, Alcohol abuse, ITA.LI.CA staging system, Metabolic dysfunction-associated fatty liver disease, Surveillance programs, Oesophageal varices, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: Alcohol abuse and metabolic disorders are leading causes of hepatocellular carcinoma (HCC) worldwide. Alcohol-related aetiology is associated with a worse prognosis compared with viral agents, because of the lower percentage of patients diagnosed with HCC under routine surveillance and a higher burden of comorbidity in alcohol abusers. This study aimed to describe the evolving clinical scenario of alcohol-related HCC over 15 years (2006–2020) in Italy. Methods: Data from the Italian Liver Cancer (ITA.LI.CA) registry were used: 1,391 patients were allocated to three groups based on the year of HCC diagnosis (2006–2010; 2011–2015; 2016–2020). Patient characteristics, HCC treatment, and overall survival were compared among groups. Survival predictors were also investigated. Results: Approximately 80% of alcohol-related HCCs were classified as cases of metabolic dysfunction-associated fatty liver disease. Throughout the quinquennia,

Published
2023
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6. The Italian data on SARS-CoV-2 infection in transplanted patients support an organ specific immune response in liver recipients

Author

Maria Rendina, Michele Barone, Chiara Lillo, Silvia Trapani, Lucia Masiero, Paolo Trerotoli, Francesca Puoti, Luigi Giovanni Lupo, Francesco Tandoi, Salvatore Agnes, Antonio Grieco, Enzo Andorno, Simona Marenco, Edoardo Giovanni Giannini, Umberto Baccarani, Pierluigi Toniutto, Amedeo Carraro, Antonio Colecchia, Matteo Cescon, Maria Cristina Morelli, Umberto Cillo, Patrizia Burra, Paolo Angeli, Michele Colledan, Stefano Fagiuoli, Luciano De Carlis, Luca Belli, Paolo De Simone, Paola Carrai, Fabrizio Di Benedetto, Nicola De Maria, Giuseppe Maria Ettorre, Valerio Giannelli, Salvatore Gruttadauria, Riccardo Volpes, Sveva Corsale, Vincenzo Mazzaferro, Sherrie Bhoori, Renato Romagnoli, Silvia Martini, Giorgio Rossi, Lucio Caccamo, Maria Francesca Donato, Massimo Rossi, Stefano Ginanni Corradini, Marco Spada, Giuseppe Maggiore, Giuseppe Tisone, Ilaria Lenci, Giovanni Vennarecci, Raffaella Tortora, Marco Vivarelli, Gianluca Svegliati Baroni, Fausto Zamboni, Laura Mameli, Silvio Tafuri, Simona Simone, Loreto Gesualdo, Massimo Cardillo, and Alfredo Di Leo

Subjects
COVID-19, liver transplantation, solid organ transplant, immunotolerance, microchimerism, Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionThe study of immune response to SARSCoV-2 infection in different solid organ transplant settings represents an opportunity for clarifying the interplay between SARS-CoV-2 and the immune system. In our nationwide registry study from Italy, we specifically evaluated, during the first wave pandemic, i.e., in non-vaccinated patients, COVID-19 prevalence of infection, mortality, and lethality in liver transplant recipients (LTRs), using non-liver solid transplant recipients (NL-SOTRs) and the Italian general population (GP) as comparators.MethodsCase collection started from February 21 to June 22, 2020, using the data from the National Institute of Health and National Transplant Center, whereas the data analysis was performed on September 30, 2020.To compare the sex- and age-adjusted distribution of infection, mortality, and lethality in LTRs, NL-SOTRs, and Italian GP we applied an indirect standardization method to determine the standardized rate.ResultsAmong the 43,983 Italian SOTRs with a functioning graft, LTRs accounted for 14,168 patients, of whom 89 were SARS-CoV-2 infected. In the 29,815 NL-SOTRs, 361 cases of SARS-CoV-2 infection were observed. The geographical distribution of the disease was highly variable across the different Italian regions. The standardized rate of infection, mortality, and lethality rates in LTRs resulted lower compared to NL-SOTRs [1.02 (95%CI 0.81-1.23) vs. 2.01 (95%CI 1.8-2.2); 1.0 (95%CI 0.5-1.5) vs. 4.5 (95%CI 3.6-5.3); 1.6 (95%CI 0.7-2.4) vs. 2.8 (95%CI 2.2-3.3), respectively] and comparable to the Italian GP.DiscussionAccording to the most recent studies on SOTRs and SARS-CoV-2 infection, our data strongly suggest that, in contrast to what was observed in NL-SOTRs receiving a similar immunosuppressive therapy, LTRs have the same risk of SARS-CoV-2 infection, mortality, and lethality observed in the general population. These results suggest an immune response to SARS-CoV-2 infection in LTRS that is different from NL-SOTRs, probably related to the ability of the grafted liver to induce immunotolerance.

Published
2023
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7. Perspective on the Role of Gut Microbiome in the Treatment of Hepatocellular Carcinoma with Immune Checkpoint Inhibitors

Author

Ludovico Abenavoli, Michele Montori, Gianluca Svegliati Baroni, Maria Eva Argenziano, Francesca Giorgi, Giuseppe Guido Maria Scarlata, Francesca Ponziani, and Emidio Scarpellini

Subjects
immunotherapy, checkpoint inhibitors, gut microbiota, fecal microbiota transplantation, Medicine (General), R5-920
Abstract

Background and Objectives: Hepatocellular carcinoma (HCC) is the leading cause of liver cancer worldwide and has a high mortality rate. Its incidence has increased due to metabolic-associated liver disease (MAFLD) epidemics. Liver transplantation and surgery remain the most resolute measures. Despite the optimistic use of multi-kinase inhibitors, namely sorafenib, the co-existence of chronic liver disease made the response rate low in these patients. Immune checkpoint inhibitors (ICIs) have become a promising hope for certain advanced solid tumors and, also, for advanced HCC. Unfortunately, a large cohort of patients with HCC fail to respond to immunotherapy. Materials and Methods: We conducted a narrative search on the main medical databases for original articles, reviews, meta-analyses, randomized clinical trials, and case series using the following keywords and acronyms and their associations: hepatocellular carcinoma, immunotherapy, checkpoint inhibitors, gut microbiota, and fecal microbiota transplantation. Results: ICIs are a promising and sufficiently safe treatment option for HCC. In detail, they have significantly improved survival and prognosis in these patients vs. sorafenib. Although there are several highlighted mechanisms of resistance, the gut microbiota signature can be used both as a response biomarker and as an effect enhancer. Practically, probiotic dose-finding and fecal microbiota transplantation are the weapons that can be used to increase ICI’s treatment-response-reducing resistance mechanisms. Conclusion: Immunotherapy has been a significant step-up in HCC treatment, and gut microbiota modulation is an effective liaison to increase its efficacy.

Published
2023
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8. The Role of Transjugular Intrahepatic Portosystemic Shunt (TIPS) in Treating Portal Hypertension in Patients with Hepatocellular Carcinoma

Author

Daniele Balducci, Michele Montori, Federico De Blasio, Alessandro Di Bucchianico, Maria Eva Argenziano, Gianluca Svegliati Baroni, and Emidio Scarpellini

Subjects
transjugular intrahepatic portosystemic shunt, hepatocellular carcinoma, locoregional therapy, systemic therapy, liver surgery, Medicine (General), R5-920
Abstract

Liver cancer is very frequent, and hepatocellular carcinoma (HCC) accounts for the majority of liver cancer cases. Its growing incidence has been greatly affected by the increasing prevalence of metabolic-associated fatty liver disease (MAFLD). The latter is a new epidemic in our era. In fact, HCC is often generated from noncirrhotic liver and its treatment benefits from surgical and nonsurgical approaches, potentially bridged by transjugular intrahepatic portosystemic shunt (TIPS) use. TIPS use is an effective treatment for portal hypertension complications, but its application in patients with HCC and clinically significant portal hypertension (CSPH) remains controversial due to concerns about tumor rupture, dissemination, and increased toxicity. The technical feasibility and safety of TIPS use in HCC patients have been evaluated in several studies. Despite concerns about intraprocedural complications, retrospective studies have shown high success rates and low complication rates in TIPS placement for HCC patients. TIPS use in combination with locoregional treatments, such as transarterial chemoembolization (TACE) or transarterial radioembolization (TARE), has been explored as a treatment option for HCC patients with portal hypertension. These studies have shown improved survival rates in patients undergoing TIPS in combination with locoregional treatments. However, the efficacy and toxicity of TACE in combination with TIPS use require careful evaluation, as changes in venous and arterial flow can affect treatment outcomes and complications. The results from studies evaluating the impact of TIPS on systemic therapy and surgical options are also promising. In conclusion, the TIPS is a sufficiently safe, useful item available for physicians treating complications of portal hypertension. Moreover, a TIPS can be used in combination with locoregional therapy in HCC patients. Systemic chemotherapy can also benefit of the use of TIPS placement. A complex interplay affects TIPS use with surgery. The latter needs further data. The TIPS is a useful and safe add-on treatment, changing the natural course of HCC progression. Its use is regulated by a sophisticated physiologic and pathophysiologic flow of evidence.

Published
2023
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9. Time-Varying mHAP-III Is the Most Accurate Predictor of Survival in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization

Author

Claudia Campani, Alessandro Vitale, Gabriele Dragoni, Umberto Arena, Giacomo Laffi, Umberto Cillo, Edoardo G. Giannini, Francesco Tovoli, Gian Ludovico Rapaccini, Maria Di Marco, Eugenio Caturelli, Marco Zoli, Rodolfo Sacco, Giuseppe Cabibbo, Andrea Mega, Maria Guarino, Antonio Gasbarrini, Gianluca Svegliati-Baroni, Francesco Giuseppe Foschi, Elisabetta Biasini, Alberto Masotto, Gerardo Nardone, Giovanni Raimondo, Francesco Azzaroli, Gianpaolo Vidili, Maurizia Rossana Brunetto, Fabio Farinati, Franco Trevisani, and Fabio Marra

Subjects
barcelona clinic liver cancer, italica staging system, albi grade, mesiah, cancer of the liver italian program, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Introduction: The prognosis of patients undergoing transarterial chemoembolization (TACE) is extremely variable, and a confounding factor is that TACE is often repeated several times. We retrospectively evaluated the accuracy of different prognostic scores and staging systems in estimating overall survival (OS) in patients with hepatocellular carcinoma (HCC). Methods: An analysis considering prognostic models as time-varying variables was performed, calculating OS from the time of TACE to the time of the subsequent treatment. Total follow-up time for each patient was therefore split into several observation times accounting for each TACE procedure. Values of the likelihood ratio test (LRT) and Akaike information criterion (AIC) were used to compare different systems. Univariable and multivariable analyses were conducted to identify additional factors predictive of OS. We analyzed 1,610 TACE performed in 1,058 patients recorded in the Italian Liver Cancer database from 2008 through 2016. Results: The median OS of the enrolled patients was 41 months. According to LRT χ2 and AIC values based on the time-varying analysis, mHAP-III achieved the best values (41.72 and 4,625.49, respectively, p < 0.0001), indicating the highest predictive performance compared with all other scores (HAP, mHAP-II, ALBI, and pALBI) and staging systems (MELD, ITALICA, CLIP, MESH, MESIAH, JIS, HKLC, and BCLC). In the multivariable Cox proportional hazards model, mHAP-III maintained an independent effect on OS (hazard ratio 1.31, 95% CI: 1.10–1.55, p < 0.0001). Time-varying age, alcoholic etiology, radiologic response to TACE, and performing ablation or surgery after TACE were additional significant variables resulting from the multivariable model. Conclusion: An innovative time-varying analysis revealed that mHAP-III was the most accurate model in predicting OS in patients with HCC undergoing TACE. Other clinical pre- and post-TACE variables were also found to be relevant for this prediction.

Published
2021
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10. Transarterial Chemoembolization for Hepatocellular Carcinoma in Clinical Practice: Temporal Trends and Survival Outcomes of an Iterative Treatment

Author

Filippo Pelizzaro, Selion Haxhi, Barbara Penzo, Alessandro Vitale, Edoardo G. Giannini, Vito Sansone, Gian Ludovico Rapaccini, Maria Di Marco, Eugenio Caturelli, Donatella Magalotti, Rodolfo Sacco, Ciro Celsa, Claudia Campani, Andrea Mega, Maria Guarino, Antonio Gasbarrini, Gianluca Svegliati-Baroni, Francesco Giuseppe Foschi, Andrea Olivani, Alberto Masotto, Gerardo Nardone, Giovanni Raimondo, Francesco Azzaroli, Gianpaolo Vidili, Maurizia Rossana Brunetto, Franco Trevisani, and Fabio Farinati

Subjects
hepatocellular carcinoma, transarterial chemoembolization, survival, iterative treatment, therapeutic hierarchy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

BackgroundTransarterial chemoembolization (TACE) is one of the most frequently applied treatments for hepatocellular carcinoma (HCC) worldwide. In this study, we aimed at evaluating whether and how TACE application and repetition, as well as the related outcome, have changed over the last three decades in Italy.MethodsData of 7,184 patients with HCC were retrieved from the Italian Liver Cancer (ITA.LI.CA) database. Patients were divided according to the period of diagnosis in six cohorts: P1 (1988–1993), P2 (1994–1998), P3 (1999–2004), P4 (2005–2009), P5 (2010–2014), and P6 (2015–2019). All the analyses were repeated in the overall patient population and in Barcelona Clinic Liver Cancer (BCLC) B patients, who are the subgroup of HCC patients originally supposed to receive TACE according to guidelines. TACE was defined as either the first or the main (more effective) treatment.ResultsThe proportion of patients receiving TACE as first or main therapy declined over time, and less than 50% of BCLC B patients were treated with chemoembolization from P3 onward. Conversely, TACE was widely used even outside the intermediate stage. Survival of TACE-treated patients progressively increased from P1 to P6. Although TACE was performed only once in the majority of patients, there was an increasing proportion of those receiving 2 or ≥3 treatments sessions over time. The overall survival (OS) of patients undergoing repeated treatments was significantly higher compared to those managed with a single TACE (median OS 40.0 vs. 65.0 vs. 71.8 months in 1, 2, and ≥3 TACE groups, respectively; p < 0.0001). However, after a first-line TACE, the adoption of curative therapies provided longer survival than repeating TACE (83.0 vs. 42.0 months; p < 0.0001), which in turn was associated with better outcomes compared to systemic therapies or best supportive care (BSC).ConclusionsDespite a decline in the percentage of treated patients over time, TACE has still an important role in the management of HCC patients. The survival of TACE-treated patients gradually improved over time, probably due to a better patient selection. Iterative TACE is effective, but an upward shift to curative therapies provides better outcomes while transition to systemic therapies and BSC leads to a worse prognosis.

Published
2022
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11. Combination Treatment with Hydroxytyrosol and Vitamin E Improves NAFLD-Related Fibrosis

Author

Nadia Panera, Maria Rita Braghini, Annalisa Crudele, Antonella Smeriglio, Marzia Bianchi, Angelo Giuseppe Condorelli, Rebecca Nobili, Libenzio Adrian Conti, Cristiano De Stefanis, Gessica Lioci, Fabio Gurrado, Donatella Comparcola, Antonella Mosca, Maria Rita Sartorelli, Vittorio Scoppola, Gianluca Svegliati-Baroni, Domenico Trombetta, and Anna Alisi

Subjects
NAFLD, fibrosis, antioxidants, PIIINP, NOX2, Nutrition. Foods and food supply, TX341-641
Abstract

Non-alcoholic fatty liver disease (NAFLD)-related liver fibrosis results in the encapsulation of injured liver parenchyma by a collagenous scar mainly imputable to hepatic stellate cells’ activation. Approved pharmacological treatments against NAFLD-related fibrosis are still lacking, but natural compounds such as hydroxytyrosol (HXT) and vitamin E (VitE), are emerging as promising therapeutic opportunities. In this study, the potential anti-fibrotic effect of HXT + VitE combination therapy was investigated in vitro and in vivo. In particular, tumor growth factor (TGF)-β-activated LX-2 cells as an in vitro model, and carbon tetrachloride plus a Western diet as a mice model were employed. The effect of HXT + VitE on fibrosis was also investigated in children with biopsy-proven NAFLD. Our results demonstrated that HXT + VitE caused a reduction of proliferation, migration, contractility, and expression of pro-fibrogenic genes in TGF-β-activated LX-2 cells. HXT + VitE treatment also antagonized TGF-β-dependent upregulation of pro-oxidant NOX2 by interfering with nuclear translocation/activation of SMAD2/3 transcription factors. The mouse model of NAFLD-related fibrosis treated with HXT + VitE showed a marked reduction of fibrosis pattern by histology and gene expression. Accordingly, in children with NAFLD, HXT + VitE treatment caused a decrease of circulating levels of PIIINP and NOX2 that was supported over time. Our study suggests that HXT + VitE supplementation may improve NAFLD-related fibrosis.

Published
2022
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12. Farnesoid X Receptor, Bile Acid Metabolism, and Gut Microbiota

Author

Hideki Mori, Gianluca Svegliati Baroni, Marco Marzioni, Francesca Di Nicola, Pierangelo Santori, Luca Maroni, Ludovico Abenavoli, and Emidio Scarpellini

Subjects
farnesoid X receptor, bile acids metabolism, gut microbiota, dysbiosis, liver steatosis, Microbiology, QR1-502
Abstract

Obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD) are characterized by the concepts of lipo- and glucotoxicity. NAFLD is characterized by the accumulation of different lipidic species within the hepatocytes. Bile acids (BA), derived from cholesterol, and conjugated and stored in the gallbladder, help the absorption/processing of lipids, and modulate host inflammatory responses and gut microbiota (GM) composition. The latter is the new “actor” that links the GI tract and liver in NAFLD pathogenesis. In fact, the discovery and mechanistic characterization of hepatic and intestinal farnesoid X receptor (FXR) shed new light on the gut–liver axis. We conducted a search on the main medical databases for original articles, reviews, meta-analyses of randomized clinical trials, and case series using the following keywords, their acronyms, and their associations: farnesoid X receptor, bile acids metabolism, gut microbiota, dysbiosis, and liver steatosis. Findings on the synthesis, metabolism, and conjugation processes of BAs, and their action on FXR, change the understanding of NAFLD physiopathology. In detail, BAs act as ligands to several FXRs with GM modulation. On the other hand, the BAs pool is modulated by GM, thus, regulating FXRs functioning in the frame of liver fat deposition and fibrosis development. In conclusion, BAs passed from their role of simple lipid absorption and metabolism agents to messengers between the gut and liver, modulated by GM.

Published
2022
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13. Potential feasibility of atezolizumab-bevacizumab therapy in patients with hepatocellular carcinoma treated with tyrosine-kinase inhibitors

Author

Benedetta Stefanini, Laura Bucci, Valentina Santi, Nicola Reggidori, Davide Rampoldi, Lorenzo Lani, Alessandro Granito, Angelo Sangiovanni, Giuseppe Cabibbo, Fabio Farinati, Claudia Campani, Francesco Giuseppe Foschi, Gianluca Svegliati-Baroni, Giovanni Raimondo, Antonio Gasbarrini, Andrea Mega, Elisabetta Biasini, Rodolfo Sacco, Filomena Morisco, Eugenio Caturelli, Gianpaolo Vidili, Francesco Azzaroli, Edoardo G. Giannini, Gian Ludovico Rapaccini, Maurizia Rossana Brunetto, Alberto Masotto, Gerardo Nardone, Mariella Di Marco, Donatella Magalotti, Franco Trevisani, Maurizio Biselli, Paolo Caraceni, Annagiulia Gramenzi, Francesco Tovoli, Luca Muratori, Francesca Benevento, Gloria Allegrini, Calogero Cammà, Ciro Celsa, Paolo Giuffrida, Caterina Stornello, Mauro Grova, Carmelo Marco Giacchetto, Gabriele Rancatore, Maria Vittoria Grassini, Valentina Adotti, Stefano Gitto, Fabio Marra, Martina Rosi, Vittoria Bevilacqua, Alberto Borghi, Andrea Casadei Gardini, Fabio Conti, Anna Chiara Dall'Aglio, Giorgio Ercolani, Federica Mirici, Nicoletta de Matthaeis, Francesca Romana Ponziani, Gabriele Missale, Andrea Olivani, Maria Guarino, Valentina Cossiga, Mario Capasso, Ester Marina Cela, Antonio Facciorusso, Valentina Lauria, Giorgia Ghittoni, Giorgio Pelecca, Fabrizio Chegai, Fabio Coratella, Mariano Ortenzi, Serena Dell'Isola, Maria Stella Franzè, Carlo Saitta, Assunta Sauchella, Elton Dajti, Federico Ravaioli, Giulia Pieri, Maria Corina Plaz Torres, Filippo Oliveri, Gabriele Ricco, Veronica Romagnoli, Alessandro Inno, Fabiana Marchetti, Pietro Coccoli, Antonio Malerba, Alberta Cappelli, Rita Golfieri, Cristina Mosconi, null Matteo Renzulli, Stefanini, B., Bucci, L., Santi, V., Reggidori, N., Rampoldi, D., Lani, L., Granito, A., Sangiovanni, A., Cabibbo, G., Farinati, F., Campani, C., Foschi, F. G., Svegliati-Baroni, G., Raimondo, G., Gasbarrini, A., Mega, A., Biasini, E., Sacco, R., Morisco, F., Caturelli, E., Vidili, G., Azzaroli, F., Giannini, E. G., Rapaccini, G. L., Brunetto, M. R., Masotto, A., Nardone, G., Di Marco, M., Magalotti, D., Trevisani, F., Biselli, M., Caraceni, P., Gramenzi, A., Tovoli, F., Muratori, L., Benevento, F., Allegrini, G., Camma, C., Celsa, C., Giuffrida, P., Stornello, C., Grova, M., Giacchetto, C. M., Rancatore, G., Grassini, M. V., Adotti, V., Gitto, S., Marra, F., Rosi, M., Bevilacqua, V., Borghi, A., Gardini, A. C., Conti, F., Dall'Aglio, A. C., Ercolani, G., Mirici, F., de Matthaeis, N., Ponziani, F. R., Missale, G., Olivani, A., Guarino, M., Cossiga, V., Capasso, M., Cela, E. M., Facciorusso, A., Lauria, V., Ghittoni, G., Pelecca, G., Chegai, F., Coratella, F., Ortenzi, M., Dell'Isola, S., Franze, M. S., Saitta, C., Sauchella, A., Dajti, E., Ravaioli, F., Pieri, G., Torres, M. C. P., Oliveri, F., Ricco, G., Romagnoli, V., Inno, A., Marchetti, F., Coccoli, P., Malerba, A., Cappelli, A., Golfieri, R., Mosconi, C., Matteo, Renzulli, Stefanini, Benedetta, Bucci, Laura, Santi, Valentina, Reggidori, Nicola, Rampoldi, Davide, Lani, Lorenzo, Granito, Alessandro, Sangiovanni, Angelo, Cabibbo, Giuseppe, Farinati, Fabio, Campani, Claudia, Foschi, Francesco Giuseppe, Svegliati-Baroni, Gianluca, Raimondo, Giovanni, Gasbarrini, Antonio, Mega, Andrea, Biasini, Elisabetta, Sacco, Rodolfo, Morisco, Filomena, Caturelli, Eugenio, Vidili, Gianpaolo, Azzaroli, Francesco, Giannini, Edoardo G, Rapaccini, Gian Ludovico, Brunetto, Maurizia Rossana, Masotto, Alberto, Nardone, Gerardo, Di Marco, Mariella, Magalotti, Donatella, and Trevisani, Franco

Subjects
Atezolizumab-bevacizumab, Clinical Trials as Topic, Antineoplastic Combined Chemotherapy Protocol, Carcinoma, Hepatocellular, Systemic therapy, Hepatology, Hepatocellular carcinoma, Tirosin-kinase inhibitor, Liver Neoplasms, Gastroenterology, Bevacizumab, Feasibility Studie, Tyrosine, Human
Abstract

Background: The combination of atezolizumab-bevacizumab has been proven to be superior to sorafenib for the treatment of unresectable hepatocellular carcinoma not amenable to locoregional treatments, be-coming the standard of care of systemic therapy.Aim: This study aimed at assessing real-world feasibility of atezolizumab-bevacizumab in patients treated with tyrosine-kinase inhibitors.Methods: Among 1447 patients treated with tyrosine-kinase inhibitors from January 2010 to December 2020, we assessed the percentage of those potentially eligible to atezolizumab-bevacizumab (according to IMbrave-150 trial criteria), and the overall survival of eligible and non-eligible patients.Results: 422 (29%) patients were qualified for atezolizumab-bevacizumab therapy. The main exclusion causes were Child-Pugh class and Performance Status. Adopting the more permissive inclusion criteria of SHARP trial, 535 patients became eligible. The median overall survival of tyrosine-kinase inhibitors patients was 14.9 months, longer in eligible patients than in their counterpart due to better baseline liver function and oncological features.Conclusion: Real-world data indicate that less than one-third of hepatocellular carcinoma patients treated with tyrosine-kinase inhibitors are potentially eligible to atezolizumab-bevacizumab according to the reg-istration trial criteria. These patients have a longer survival than the non-eligible ones. If the selection criteria of atezolizumab-bevacizumab trial are maintained in clinical practice, tyrosine-kinase inhibitors will remain the most used systemic therapy for hepatocellular carcinoma patients.(c) 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Published
2022

14. A multi-society Delphi consensus statement on new fatty liver disease nomenclature

Author

Mary E, R, Jeffrey V, L, Vlad, R, Sven M, F, Arun J, S, Fasiha, K, Diana, R, Manal F, A, Quentin M, A, Juan Pablo, A, Marco, A, Ramon, B, Ulrich, B, Jerome, B, Elisabetta, B, Christopher, B, Graciela E, C, Abhijit, C, Helena, C, Donna, C, Kenneth, C, Mohamed, E, Samuel, K, Wayne, E, Jiangao, F, Samer, G, Cynthia D, G, Stephen A, H, Seung Up, K, Bart, K, Marko, K, Kris, K, Florence, L, Rohit, L, Robert, M, Timothy R, M, Elisabeth, P, Michael, R, Manuel, R, Marcelo, S, Shivaram Prasad, S, Silvia C, S, C Wendy, S, Dina, T, Luca, V, Miriam B, V, Vincent, W, Stavra, X, Yusuf, Y, Zobair, Y, Ansley, H, Marcela, V, Newsome, NVeeral Ajmeral, P, Alazawi, W, Alkhatry, M, Alkhouri, N, Allen, A, Allison, M, Alswat, K, R Alvares-da-Silva, M, Alves-Bezerra, M, J Armstrong, M, Arufe, D, Aschner, P, Baffy, G, Bansal, M, Bedossa, P, Belfort, R, Berg, T, Berzigotti, A, Betel, M, Bianco, C, Brass, C, L Brosgart, C, Matthews Brunt, E, Buti, M, Caldwell, S, Carr, R, Casanovas, T, Castera, L, Caussy, C, Cerda, E, Chalasani, N, Kheong Chan, W, Charatcharoenwitthaya, P, Charlton, M, Cheung, A, Chiodi, D, Chung, R, Cohen, D, Corey, K, P Cotrim, H, Crespo, J, Dassanayake, A, Davidson, N, De Knegt, R, De Ledinghen, V, Demir, M, Diaz, S, Mae Diehl, A, Dimmig, B, Dirchwolf, M, Duseja, A, Dvorak, K, Ekstedt, M, El Wakil, R, Lucía Ferraz, M, Friedman, S, Fuchs, M, Gastaldelli, A, Geerts, A, Geier, A, Girala, M, Goh, G, Goossens, N, Graupera, I, Hagström, H, Henry, Z, Hunyady, B, Hutchison, A, Isaacs, S, Jornayvaz, F, Kemp, C, Kile, D, Kim, W, Kleiner, D, Kohli, R, Kugelmas, M, Lavine, J, Lazo, M, Leite, N, Lozano, A, Luukkonen, P, Macedo, P, Mansour, D, Mantzoros, C, Marchesini, G, Marciano, S, Martinez, K, Vladimirova Mateva, L, M Mato, J, Mccary, A, Miele, L, Mikolasevic, I, Miller, V, Moreno, R, Moylan, C, Nakajima, A, Charles Nault, J, Norris, S, Noureddin, M, P Oliveira, C, Ong, A, Padilla, M, Pais, R, Panduro, A, K Panigrahi, M, Papatheodoridis, G, Pelusi, S, Pérez, M, Perez Escobar, J, Perseghin, G, Pessoa, M, Petta, S, Pinzani, M, Platon Lupsor, M, Rabiee, A, Romeo, S, Rotman, Y, Rowe, I, Salupere, R, Satapathy, S, M Schattenberg, J, Schaufert, W, Schnabl, B, Seim, L, Serfaty, L, Shapiro, D, K Singal, A, Skladany, L, Stefan, N, Stine, J, Sundaram, S, Svegliati-Baroni, G, Szabo, G, Tacke, F, Tanwandee, T, Targher, G, Terrault, N, Tetri, B, Thiele, M, Tisthammer, B, Torre Delgadillo, A, Trauner, M, Tsochatzis, E, Van Kleef, L, Van Mil, S, Vanwagner, L, Antonio Velarde Ruiz Velasco, J, Vesterhus, M, Vilar-Gomez, E, Watt, K, Wattacheril, J, Wilkins, F, Willemse, J, Zekry, A, Zelber-Sagi, S, Rinella, Mary E, Lazarus, Jeffrey V, Ratziu, Vlad, Francque, Sven M, Sanyal, Arun J, Kanwal, Fasiha, Romero, Diana, Abdelmalek, Manal F, Anstee, Quentin M, Arab, Juan Pablo, Arrese, Marco, Bataller, Ramon, Beuers, Ulrich, Boursier, Jerome, Bugianesi, Elisabetta, Byrne, Christopher, Castro Narro, Graciela E, Chowdhury, Abhijit, Cortez-Pinto, Helena, Cryer, Donna, Cusi, Kenneth, El-Kassas, Mohamed, Klein, Samuel, Eskridge, Wayne, Fan, Jiangao, Gawrieh, Samer, Guy, Cynthia D, Harrison, Stephen A, Kim, Seung Up, Koot, Bart, Korenjak, Marko, Kowdley, Kris, Lacaille, Florence, Loomba, Rohit, Mitchell-Thain, Robert, Morgan, Timothy R, Powell, Elisabeth, Roden, Michael, Romero-Gómez, Manuel, Silva, Marcelo, Singh, Shivaram Prasad, Sookoian, Silvia C, Spearman, C Wendy, Tiniakos, Dina, Valenti, Luca, Vos, Miriam B, Wai-Sun Wong, Vincent, Xanthakos, Stavra, Yilmaz, Yusuf, Younossi, Zobair, Hobbs, Ansley, Villota-Rivas, Marcela, Philip NVeeral Ajmeral, William Alazawi, Maryam Alkhatry, Naim Alkhouri, Alina Allen, Michael Allison, Khalid Alswat, Mario R Alvares-da-Silva, Michele Alves-Bezerra, Matthew J Armstrong, Diego Arufe, Pablo Aschner, Gyorgy Baffy, Meena Bansal, Pierre Bedossa, Renata Belfort, Thomas Berg, Annalisa Berzigotti, Michael Betel, Cristiana Bianco, Clifford Brass, Carol L Brosgart, Elizabeth Matthews Brunt, Maria Buti, Steve Caldwell, Rotonya Carr, Teresa Casanovas, Laurent Castera, Cyrielle Caussy, Eira Cerda, Naga Chalasani, Wah Kheong Chan, Phunchai Charatcharoenwitthaya, Michael Charlton, Amanda Cheung, Daniela Chiodi, Ray Chung, David Cohen, Kathleen Corey, Helma P Cotrim, Javier Crespo, Anuradha Dassanayake, Nicholas Davidson, Robert De Knegt, Victor De Ledinghen, Münevver Demir, Sebastian Diaz, Anna Mae Diehl, Bruce Dimmig, Melisa Dirchwolf, Ajay Duseja, Karel Dvorak, Mattias Ekstedt, Reda El Wakil, María Lucía Ferraz, Scott Friedman, Michael Fuchs, Amalia Gastaldelli, Anja Geerts, Andreas Geier, Marcos Girala, George Goh, Nicolas Goossens, Isabel Graupera, Hannes Hagström, Zachary Henry, Bela Hunyady, Alan Hutchison, Scott Isaacs, François Jornayvaz, Cynthia Kemp, Denise Kile, Won Kim, David Kleiner, Rohit Kohli, Marcelo Kugelmas, Joel Lavine, Mariana Lazo, Nathalie Leite, Adelina Lozano, Panu Luukkonen, Paula Macedo, Dina Mansour, Christos Mantzoros, Giulio Marchesini, Sebastián Marciano, Kim Martinez, Lyudmila Vladimirova Mateva, Jose M Mato, Alexis McCary, Luca Miele, Ivana Mikolasevic, Veronica Miller, Rosalba Moreno, Cynthia Moylan, Atsushi Nakajima, Jean Charles Nault, Suzanne Norris, Mazen Noureddin, C P Oliveira, Arlin Ong, Martín Padilla, Raluca Pais, Arturo Panduro, Manas K Panigrahi, George Papatheodoridis, Serena Pelusi, Marlene Pérez, Juanita Perez Escobar, Gianluca Perseghin, Mario Pessoa, Salvatore Petta, Massimo Pinzani, Monica Platon Lupsor, Atoosa Rabiee, Stefano Romeo, Yaron Rotman, Ian Rowe, Riina Salupere, Sanjaya Satapathy, Jörn M Schattenberg, Wendy Schaufert, Bernd Schnabl, Lynn Seim, Lawrence Serfaty, David Shapiro, Ashwani K Singal, Lubomir Skladany, Norbert Stefan, Jonathan Stine, Shikha Sundaram, Gianluca Svegliati-Baroni, Gyonzgi Szabo, Frank Tacke, Tawesak Tanwandee, Giovanni Targher, Norah Terrault, Brent Tetri, Maja Thiele, Baron Tisthammer, Aldo Torre Delgadillo, Michael Trauner, Emmanuel Tsochatzis, Laurens Van Kleef, Saskia Van Mil, Lisa VanWagner, Jose Antonio Velarde Ruiz Velasco, Mette Vesterhus, Eduardo Vilar-Gomez, Kymberly Watt, Julia Wattacheril, Fonda Wilkins, José Willemse, Amany Zekry, Shira Zelber-Sagi, Mary E, R, Jeffrey V, L, Vlad, R, Sven M, F, Arun J, S, Fasiha, K, Diana, R, Manal F, A, Quentin M, A, Juan Pablo, A, Marco, A, Ramon, B, Ulrich, B, Jerome, B, Elisabetta, B, Christopher, B, Graciela E, C, Abhijit, C, Helena, C, Donna, C, Kenneth, C, Mohamed, E, Samuel, K, Wayne, E, Jiangao, F, Samer, G, Cynthia D, G, Stephen A, H, Seung Up, K, Bart, K, Marko, K, Kris, K, Florence, L, Rohit, L, Robert, M, Timothy R, M, Elisabeth, P, Michael, R, Manuel, R, Marcelo, S, Shivaram Prasad, S, Silvia C, S, C Wendy, S, Dina, T, Luca, V, Miriam B, V, Vincent, W, Stavra, X, Yusuf, Y, Zobair, Y, Ansley, H, Marcela, V, Newsome, NVeeral Ajmeral, P, Alazawi, W, Alkhatry, M, Alkhouri, N, Allen, A, Allison, M, Alswat, K, R Alvares-da-Silva, M, Alves-Bezerra, M, J Armstrong, M, Arufe, D, Aschner, P, Baffy, G, Bansal, M, Bedossa, P, Belfort, R, Berg, T, Berzigotti, A, Betel, M, Bianco, C, Brass, C, L Brosgart, C, Matthews Brunt, E, Buti, M, Caldwell, S, Carr, R, Casanovas, T, Castera, L, Caussy, C, Cerda, E, Chalasani, N, Kheong Chan, W, Charatcharoenwitthaya, P, Charlton, M, Cheung, A, Chiodi, D, Chung, R, Cohen, D, Corey, K, P Cotrim, H, Crespo, J, Dassanayake, A, Davidson, N, De Knegt, R, De Ledinghen, V, Demir, M, Diaz, S, Mae Diehl, A, Dimmig, B, Dirchwolf, M, Duseja, A, Dvorak, K, Ekstedt, M, El Wakil, R, Lucía Ferraz, M, Friedman, S, Fuchs, M, Gastaldelli, A, Geerts, A, Geier, A, Girala, M, Goh, G, Goossens, N, Graupera, I, Hagström, H, Henry, Z, Hunyady, B, Hutchison, A, Isaacs, S, Jornayvaz, F, Kemp, C, Kile, D, Kim, W, Kleiner, D, Kohli, R, Kugelmas, M, Lavine, J, Lazo, M, Leite, N, Lozano, A, Luukkonen, P, Macedo, P, Mansour, D, Mantzoros, C, Marchesini, G, Marciano, S, Martinez, K, Vladimirova Mateva, L, M Mato, J, Mccary, A, Miele, L, Mikolasevic, I, Miller, V, Moreno, R, Moylan, C, Nakajima, A, Charles Nault, J, Norris, S, Noureddin, M, P Oliveira, C, Ong, A, Padilla, M, Pais, R, Panduro, A, K Panigrahi, M, Papatheodoridis, G, Pelusi, S, Pérez, M, Perez Escobar, J, Perseghin, G, Pessoa, M, Petta, S, Pinzani, M, Platon Lupsor, M, Rabiee, A, Romeo, S, Rotman, Y, Rowe, I, Salupere, R, Satapathy, S, M Schattenberg, J, Schaufert, W, Schnabl, B, Seim, L, Serfaty, L, Shapiro, D, K Singal, A, Skladany, L, Stefan, N, Stine, J, Sundaram, S, Svegliati-Baroni, G, Szabo, G, Tacke, F, Tanwandee, T, Targher, G, Terrault, N, Tetri, B, Thiele, M, Tisthammer, B, Torre Delgadillo, A, Trauner, M, Tsochatzis, E, Van Kleef, L, Van Mil, S, Vanwagner, L, Antonio Velarde Ruiz Velasco, J, Vesterhus, M, Vilar-Gomez, E, Watt, K, Wattacheril, J, Wilkins, F, Willemse, J, Zekry, A, Zelber-Sagi, S, Rinella, Mary E, Lazarus, Jeffrey V, Ratziu, Vlad, Francque, Sven M, Sanyal, Arun J, Kanwal, Fasiha, Romero, Diana, Abdelmalek, Manal F, Anstee, Quentin M, Arab, Juan Pablo, Arrese, Marco, Bataller, Ramon, Beuers, Ulrich, Boursier, Jerome, Bugianesi, Elisabetta, Byrne, Christopher, Castro Narro, Graciela E, Chowdhury, Abhijit, Cortez-Pinto, Helena, Cryer, Donna, Cusi, Kenneth, El-Kassas, Mohamed, Klein, Samuel, Eskridge, Wayne, Fan, Jiangao, Gawrieh, Samer, Guy, Cynthia D, Harrison, Stephen A, Kim, Seung Up, Koot, Bart, Korenjak, Marko, Kowdley, Kris, Lacaille, Florence, Loomba, Rohit, Mitchell-Thain, Robert, Morgan, Timothy R, Powell, Elisabeth, Roden, Michael, Romero-Gómez, Manuel, Silva, Marcelo, Singh, Shivaram Prasad, Sookoian, Silvia C, Spearman, C Wendy, Tiniakos, Dina, Valenti, Luca, Vos, Miriam B, Wai-Sun Wong, Vincent, Xanthakos, Stavra, Yilmaz, Yusuf, Younossi, Zobair, Hobbs, Ansley, Villota-Rivas, Marcela, Philip NVeeral Ajmeral, William Alazawi, Maryam Alkhatry, Naim Alkhouri, Alina Allen, Michael Allison, Khalid Alswat, Mario R Alvares-da-Silva, Michele Alves-Bezerra, Matthew J Armstrong, Diego Arufe, Pablo Aschner, Gyorgy Baffy, Meena Bansal, Pierre Bedossa, Renata Belfort, Thomas Berg, Annalisa Berzigotti, Michael Betel, Cristiana Bianco, Clifford Brass, Carol L Brosgart, Elizabeth Matthews Brunt, Maria Buti, Steve Caldwell, Rotonya Carr, Teresa Casanovas, Laurent Castera, Cyrielle Caussy, Eira Cerda, Naga Chalasani, Wah Kheong Chan, Phunchai Charatcharoenwitthaya, Michael Charlton, Amanda Cheung, Daniela Chiodi, Ray Chung, David Cohen, Kathleen Corey, Helma P Cotrim, Javier Crespo, Anuradha Dassanayake, Nicholas Davidson, Robert De Knegt, Victor De Ledinghen, Münevver Demir, Sebastian Diaz, Anna Mae Diehl, Bruce Dimmig, Melisa Dirchwolf, Ajay Duseja, Karel Dvorak, Mattias Ekstedt, Reda El Wakil, María Lucía Ferraz, Scott Friedman, Michael Fuchs, Amalia Gastaldelli, Anja Geerts, Andreas Geier, Marcos Girala, George Goh, Nicolas Goossens, Isabel Graupera, Hannes Hagström, Zachary Henry, Bela Hunyady, Alan Hutchison, Scott Isaacs, François Jornayvaz, Cynthia Kemp, Denise Kile, Won Kim, David Kleiner, Rohit Kohli, Marcelo Kugelmas, Joel Lavine, Mariana Lazo, Nathalie Leite, Adelina Lozano, Panu Luukkonen, Paula Macedo, Dina Mansour, Christos Mantzoros, Giulio Marchesini, Sebastián Marciano, Kim Martinez, Lyudmila Vladimirova Mateva, Jose M Mato, Alexis McCary, Luca Miele, Ivana Mikolasevic, Veronica Miller, Rosalba Moreno, Cynthia Moylan, Atsushi Nakajima, Jean Charles Nault, Suzanne Norris, Mazen Noureddin, C P Oliveira, Arlin Ong, Martín Padilla, Raluca Pais, Arturo Panduro, Manas K Panigrahi, George Papatheodoridis, Serena Pelusi, Marlene Pérez, Juanita Perez Escobar, Gianluca Perseghin, Mario Pessoa, Salvatore Petta, Massimo Pinzani, Monica Platon Lupsor, Atoosa Rabiee, Stefano Romeo, Yaron Rotman, Ian Rowe, Riina Salupere, Sanjaya Satapathy, Jörn M Schattenberg, Wendy Schaufert, Bernd Schnabl, Lynn Seim, Lawrence Serfaty, David Shapiro, Ashwani K Singal, Lubomir Skladany, Norbert Stefan, Jonathan Stine, Shikha Sundaram, Gianluca Svegliati-Baroni, Gyonzgi Szabo, Frank Tacke, Tawesak Tanwandee, Giovanni Targher, Norah Terrault, Brent Tetri, Maja Thiele, Baron Tisthammer, Aldo Torre Delgadillo, Michael Trauner, Emmanuel Tsochatzis, Laurens Van Kleef, Saskia Van Mil, Lisa VanWagner, Jose Antonio Velarde Ruiz Velasco, Mette Vesterhus, Eduardo Vilar-Gomez, Kymberly Watt, Julia Wattacheril, Fonda Wilkins, José Willemse, Amany Zekry, and Shira Zelber-Sagi

Abstract

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panellists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms “nonalcoholic” and “fatty” were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction–associated steatotic liver disease (MASLD). There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction–associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction–associated steatotic liver disease, who consume greater amounts of alcohol per week (140–350 g/wk and 210–420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and non-stigmati

Published
2023

15. A multi-society Delphi consensus statement on new fatty liver disease nomenclature

Author

Rinella, Mary E, Lazarus, Jeffrey V, Ratziu, Vlad, Francque, Sven M, Sanyal, Arun J, Kanwal, Fasiha, Romero, Diana, Abdelmalek, Manal F, Anstee, Quentin M, Arab, Juan Pablo, Arrese, Marco, Bataller, Ramon, Beuers, Ulrich, Boursier, Jerome, Bugianesi, Elisabetta, Byrne, Christopher, Castro Narro, Graciela E, Chowdhury, Abhijit, Cortez-Pinto, Helena, Cryer, Donna, Cusi, Kenneth, El-Kassas, Mohamed, Klein, Samuel, Eskridge, Wayne, Fan, Jiangao, Gawrieh, Samer, Guy, Cynthia D, Harrison, Stephen A, Kim, Seung Up, Koot, Bart, Korenjak, Marko, Kowdley, Kris, Lacaille, Florence, Loomba, Rohit, Mitchell-Thain, Robert, Morgan, Timothy R, Powell, Elisabeth, Roden, Michael, Romero-Gómez, Manuel, Silva, Marcelo, Singh, Shivaram Prasad, Sookoian, Silvia C, Spearman, C Wendy, Tiniakos, Dina, Valenti, Luca, Vos, Miriam B, Wong, Vincent Wai-Sun, Xanthakos, Stavra, Yilmaz, Yusuf, Younossi, Zobair, Hobbs, Ansley, Villota-Rivas, Marcela, Newsome, Philip NVeeral Ajmeral, William Alazawi, Maryam Alkhatry, Naim Alkhouri, Alina Allen, Michael Allison, Khalid Alswat, Mario R Alvares-da-Silva, Michele Alves-Bezerra, Matthew J Armstrong, Diego Arufe, Pablo Aschner, Gyorgy Baffy, Meena Bansal, Pierre Bedossa, Renata Belfort, Thomas Berg, Annalisa Berzigotti, Michael Betel, Cristiana Bianco, Clifford Brass, Carol L Brosgart, Elizabeth Matthews Brunt, Maria Buti, Steve Caldwell, Rotonya Carr, Teresa Casanovas, Laurent Castera, Cyrielle Caussy, Eira Cerda, Naga Chalasani, Wah Kheong Chan, Phunchai Charatcharoenwitthaya, Michael Charlton, Amanda Cheung, Daniela Chiodi, Ray Chung, David Cohen, Kathleen Corey, Helma P Cotrim, Javier Crespo, Anuradha Dassanayake, Nicholas Davidson, Robert De Knegt, Victor De Ledinghen, Münevver Demir, Sebastian Diaz, Anna Mae Diehl, Bruce Dimmig, Melisa Dirchwolf, Ajay Duseja, Karel Dvorak, Mattias Ekstedt, Reda El Wakil, María Lucía Ferraz, Scott Friedman, Michael Fuchs, Amalia Gastaldelli, Anja Geerts, Andreas Geier, Marcos Girala, George Goh, Nicolas Goossens, Isabel Graupera, Hannes Hagström, Zachary Henry, Bela Hunyady, Alan Hutchison, Scott Isaacs, François Jornayvaz, Cynthia Kemp, Denise Kile, Won Kim, David Kleiner, Rohit Kohli, Marcelo Kugelmas, Joel Lavine, Mariana Lazo, Nathalie Leite, Adelina Lozano, Panu Luukkonen, Paula Macedo, Dina Mansour, Christos Mantzoros, Giulio Marchesini, Sebastián Marciano, Kim Martinez, Lyudmila Vladimirova Mateva, Jose M Mato, Alexis McCary, Luca Miele, Ivana Mikolasevic, Veronica Miller, Rosalba Moreno, Cynthia Moylan, Atsushi Nakajima, Jean Charles Nault, Suzanne Norris, Mazen Noureddin, C P Oliveira, Arlin Ong, Martín Padilla, Raluca Pais, Arturo Panduro, Manas K Panigrahi, George Papatheodoridis, Serena Pelusi, Marlene Pérez, Juanita Perez Escobar, Gianluca Perseghin, Mario Pessoa, Salvatore Petta, Massimo Pinzani, Monica Platon Lupsor, Atoosa Rabiee, Stefano Romeo, Yaron Rotman, Ian Rowe, Riina Salupere, Sanjaya Satapathy, Jörn M Schattenberg, Wendy Schaufert, Bernd Schnabl, Lynn Seim, Lawrence Serfaty, David Shapiro, Ashwani K Singal, Lubomir Skladany, Norbert Stefan, Jonathan Stine, Shikha Sundaram, Gianluca Svegliati-Baroni, Gyonzgi Szabo, Frank Tacke, Tawesak Tanwandee, Giovanni Targher, Norah Terrault, Brent Tetri, Maja Thiele, Baron Tisthammer, Aldo Torre Delgadillo, Michael Trauner, Emmanuel Tsochatzis, Laurens Van Kleef, Saskia Van Mil, Lisa VanWagner, Jose Antonio Velarde Ruiz Velasco, Mette Vesterhus, Eduardo Vilar-Gomez, Kymberly Watt, Julia Wattacheril, Fonda Wilkins, José Willemse, Amany Zekry, Shira Zelber-Sagi, Mary E, R, Jeffrey V, L, Vlad, R, Sven M, F, Arun J, S, Fasiha, K, Diana, R, Manal F, A, Quentin M, A, Juan Pablo, A, Marco, A, Ramon, B, Ulrich, B, Jerome, B, Elisabetta, B, Christopher, B, Graciela E, C, Abhijit, C, Helena, C, Donna, C, Kenneth, C, Mohamed, E, Samuel, K, Wayne, E, Jiangao, F, Samer, G, Cynthia D, G, Stephen A, H, Seung Up, K, Bart, K, Marko, K, Kris, K, Florence, L, Rohit, L, Robert, M, Timothy R, M, Elisabeth, P, Michael, R, Manuel, R, Marcelo, S, Shivaram Prasad, S, Silvia C, S, C Wendy, S, Dina, T, Luca, V, Miriam B, V, Vincent, W, Stavra, X, Yusuf, Y, Zobair, Y, Ansley, H, Marcela, V, Newsome, NVeeral Ajmeral, P, Alazawi, W, Alkhatry, M, Alkhouri, N, Allen, A, Allison, M, Alswat, K, R Alvares-da-Silva, M, Alves-Bezerra, M, J Armstrong, M, Arufe, D, Aschner, P, Baffy, G, Bansal, M, Bedossa, P, Belfort, R, Berg, T, Berzigotti, A, Betel, M, Bianco, C, Brass, C, L Brosgart, C, Matthews Brunt, E, Buti, M, Caldwell, S, Carr, R, Casanovas, T, Castera, L, Caussy, C, Cerda, E, Chalasani, N, Kheong Chan, W, Charatcharoenwitthaya, P, Charlton, M, Cheung, A, Chiodi, D, Chung, R, Cohen, D, Corey, K, P Cotrim, H, Crespo, J, Dassanayake, A, Davidson, N, De Knegt, R, De Ledinghen, V, Demir, M, Diaz, S, Mae Diehl, A, Dimmig, B, Dirchwolf, M, Duseja, A, Dvorak, K, Ekstedt, M, El Wakil, R, Lucía Ferraz, M, Friedman, S, Fuchs, M, Gastaldelli, A, Geerts, A, Geier, A, Girala, M, Goh, G, Goossens, N, Graupera, I, Hagström, H, Henry, Z, Hunyady, B, Hutchison, A, Isaacs, S, Jornayvaz, F, Kemp, C, Kile, D, Kim, W, Kleiner, D, Kohli, R, Kugelmas, M, Lavine, J, Lazo, M, Leite, N, Lozano, A, Luukkonen, P, Macedo, P, Mansour, D, Mantzoros, C, Marchesini, G, Marciano, S, Martinez, K, Vladimirova Mateva, L, M Mato, J, Mccary, A, Miele, L, Mikolasevic, I, Miller, V, Moreno, R, Moylan, C, Nakajima, A, Charles Nault, J, Norris, S, Noureddin, M, P Oliveira, C, Ong, A, Padilla, M, Pais, R, Panduro, A, K Panigrahi, M, Papatheodoridis, G, Pelusi, S, Pérez, M, Perez Escobar, J, Perseghin, G, Pessoa, M, Petta, S, Pinzani, M, Platon Lupsor, M, Rabiee, A, Romeo, S, Rotman, Y, Rowe, I, Salupere, R, Satapathy, S, M Schattenberg, J, Schaufert, W, Schnabl, B, Seim, L, Serfaty, L, Shapiro, D, K Singal, A, Skladany, L, Stefan, N, Stine, J, Sundaram, S, Svegliati-Baroni, G, Szabo, G, Tacke, F, Tanwandee, T, Targher, G, Terrault, N, Tetri, B, Thiele, M, Tisthammer, B, Torre Delgadillo, A, Trauner, M, Tsochatzis, E, Van Kleef, L, Van Mil, S, Vanwagner, L, Antonio Velarde Ruiz Velasco, J, Vesterhus, M, Vilar-Gomez, E, Watt, K, Wattacheril, J, Wilkins, F, Willemse, J, Zekry, A, Zelber-Sagi, S, and Vincent Wai-Sun, W

Subjects
steatotic liver disease, MASLD, alcohol, steatohepatiti, MetALD, NASH, nonalcoholic, Delphi, Fatty liver disease, NAFLD, cardiometabolic, nomenclature, mafld, type 2 diabetes, MED/13 - ENDOCRINOLOGIA
Abstract

Unlabelled: The principal limitations of the terms nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature and/or definition. Methods: A modified Delphi process was led by three large pan-national liver associations. Consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. Results: A total of 236 panellists from 56 countries participated in four online surveys and two hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83% and 78%, respectively. 74% of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms 'non-alcoholic' and 'fatty' were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease (SLD) was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). There was consensus to change the definition to include the presence of at least one of five cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic SLD. A new category, outside pure MASLD, termed MetALD was selected to describe those with MASLD who consume greater amounts of alcohol per week (140 to 350g/week and 210 to 420g/week for females and males respectively). Conclusions: The new nomenclature and diagnostic criteria are widely supported, non-stigmatising and can improve awareness and patient identification.

Published
2023

16. Gut-Pancreas-Liver Axis as a Target for Treatment of NAFLD/NASH

Author

Gianluca Svegliati-Baroni, Bárbara Patrício, Gessica Lioci, Maria Paula Macedo, and Amalia Gastaldelli

Subjects
non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, type-2 diabetes, gut-pancreas-liver axis, incretins, lipid metabolism, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Non-alcoholic fatty liver disease (NAFLD) represents the most common form of chronic liver disease worldwide. Due to its association with obesity and diabetes and the fall in hepatitis C virus morbidity, cirrhosis in NAFLD is becoming the most frequent indication to liver transplantation, but the pathogenetic mechanisms are still not completely understood. The so-called gut-liver axis has gained enormous interest when data showed that its alteration can lead to NAFLD development and might favor the occurrence of non-alcoholic steatohepatitis (NASH). Moreover, several therapeutic approaches targeting the gut-pancreas-liver axis, e.g., incretins, showed promising results in NASH treatment. In this review, we describe the role of incretin hormones in NAFLD/NASH pathogenesis and treatment and how metagenomic/metabolomic alterations in the gut microbiota can lead to NASH in the presence of gut barrier modifications favoring the passage of bacteria or bacterial products in the portal circulation, i.e., bacterial translocation.

Published
2020
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17. Corrigendum to ‘Non-alcoholic fatty liver disease in adults 2021: A clinical practice guideline of the Italian Association for the Study of the Liver (AISF), the Italian Society of Diabetology (SID) and the Italian Society of Obesity (SIO)’ Nutrition, Metabolism and Cardiovascular diseases volume 32 issue 1 (2022) 1-16

Author

Giulio Marchesini, Elisabetta Bugianesi, Patrizia Burra, Fabio Marra, Luca Miele, Anna Alisi, Piero Vajro, Mario Masarone, Salvatore Petta, Marcello Persico, Gianluca Svegliati-Baroni, Luca Valenti, Massimo Federici, Francesco Purrello, Ferdinando Carlo Sasso, Giovanni Targher, Luca Busetto, Maria Letizia Petroni, Ferruccio Santini, Calogero Cammà, and Agostino Colli

Subjects
Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Cardiology and Cardiovascular Medicine
Published
2023

18. [YIA] Interaction between Glutathione S-transferase P and Nrf2 transcription factor in mouse hepatocarcinoma: a molecular and physical characterization

Author

Desirée, Bartolini, primary, Gabriele, Galeazzi, additional, Anna Maria, Stabile, additional, Fabio, Gurrato, additional, Gessica, Lioci, additional, Alessandra, Pistilli, additional, Gabriele, Di Sante, additional, Anna, Migni, additional, Mario, Rende, additional, Gianluca, Svegliati-Baroni, additional, and Francesco, Galli, additional

Published
2022
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20. Corrigendum to 'Non-alcoholic fatty liver disease in adults 2021: A clinical practice guideline of the Italian Association for the Study of the Liver (AISF), the Italian Society of Diabetology (SID) and the Italian Society of Obesity (SIO)' [Dig Liver Dis 54 (2022) 170–182]

Author

Giulio Marchesini, Elisabetta Bugianesi, Patrizia Burra, Fabio Marra, Luca Miele, Anna Alisi, Piero Vajro, Mario Masarone, Salvatore Petta, Marcello Persico, Gianluca Svegliati-Baroni, Luca Valenti, Massimo Federici, Francesco Purrello, Ferdinando Carlo Sasso, Giovanni Targher, Luca Busetto, Maria Letizia Petroni, Ferruccio Santini, Calogero Cammà, and Agostino Colli

Subjects
Hepatology, Gastroenterology
Published
2023

22. 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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23. HDL cholesterol protects from liver injury in mice with intestinal specific LXRα activation

Author

Gessica Lioci, Chiara Rychlicki, Maurizio Parola, Gianluca Svegliati-Baroni, Valentina D'Oria, Erica Novo, Marco Marzioni, Claudia Bocca, Debora Maria Giordano, Anna Alisi, Nadia Panera, Cristiano De Stefanis, Luca Maroni, Fabio Gurrado, Luciano Trozzi, and I. Pierantonelli

Subjects
high-density lipoproteins, medicine.medical_specialty, Kupffer Cells, Inflammation, liver X receptors, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Fibrosis, Internal medicine, medicine, Animals, Liver X receptor, Liver injury, Hepatology, Cholesterol, Cholesterol, HDL, fibrosis, Reverse cholesterol transport, M2 Macrophage, medicine.disease, Mice, Inbred C57BL, inflammation, Endocrinology, Liver, chemistry, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, medicine.symptom, Steatosis
Abstract

Background and aims Liver X receptors (LXRs) exert anti-inflammatory effects even though their hepatic activation is associated with hypertriglyceridemia and hepatic steatosis. Selective induction of LXRs in the gut might provide protective signal(s) in the aberrant wound healing response that induces fibrosis during chronic liver injury, without hypertriglyceridemic and steatogenic effects. Methods Mice with intestinal constitutive LXRα activation (iVP16-LXRα) were exposed to intraperitoneal injection of carbon tetrachloride (CCl4 ) for 8 weeks, and in vitro cell models were used to evaluate the beneficial effect of high-density lipoproteins (HDL). Results After CCl4 treatment, the iVP16-LXRα phenotype showed reduced M1 macrophage infiltration, increased expression M2 macrophage markers, and lower expression of hepatic pro-inflammatory genes. This anti-inflammatory effect in the liver was also associated with decreased expression of hepatic oxidative stress genes and reduced expression of fibrosis markers. iVP16-LXRα exhibited increased reverse cholesterol transport in the gut by ABCA1 expression and consequent enhancement of the levels of circulating HDL and their receptor SRB1 in the liver. No hepatic steatosis development was observed in iVP16-LXRα. In vitro, HDL induced a shift from M1 to M2 phenotype of LPS-stimulated Kupffer cells, decreased TNFα-induced oxidative stress in hepatocytes and reduced NF-kB activity in both cells. SRB1 silencing reduced TNFα gene expression in LPS-stimulated KCs, and NOX-1 and IL-6 in HepG2. Conclusions Intestinal activation of LXRα modulates hepatic response to injury by increasing circulating HDL levels and SRB1 expression in the liver, thus suggesting this circuit as potential actionable pathway for therapy.

Published
2020

24. Characteristics and survival of patients with primary biliary cholangitis and hepatocellular carcinoma

Author

Edoardo G. Giannini, Giulia Pieri, Sara Labanca, Maria Corina Plaz Torres, Antonio Gasbarrini, Elisabetta Biasini, Claudia Campani, Nora Cazzagon, Francesco Giuseppe Foschi, Andrea Mega, Alberto Masotto, Giovanni Raimondo, Gian Ludovico Rapaccini, Rodolfo Sacco, Eugenio Caturelli, Maria Guarino, Francesco Tovoli, Gianpaolo Vidili, Maurizia Rossana Brunetto, Gerardo Nardone, Gianluca Svegliati-Baroni, Donatella Magalotti, Francesco Azzaroli, Giuseppe Cabibbo, Maria Di Marco, Angelo Sangiovanni, Franco Trevisani, Maurizio Biselli, Paolo Caraceni, Annagiulia Gramenzi, Francesca Benevento, Alessandro Granito, Luca Muratori, Fabio Piscaglia, Federica Bertellini, Fabio Farinati, Giorgio Palano, Filippo Pelizzaro, Barbara Penzo, Elisa Pinto, Gloria Allegrini, Calogero Cammà, Ciro Celsa, Paolo Giuffrida, Caterina Stornello, Mauro Grova, Carmelo Marco Giacchetto, Gabriele Rancatore, Maria Vittoria Grassini, Valentina Adotti, Stefano Gitto, Fabio Marra, Martina Rosi, Vittoria Bevilacqua, Alberto Borghi, Andrea Casadei Gardini, Fabio Conti, Lucia Napoli, Marco Domenicali, Maria Teresa Migliano, Nicoletta de Matthaeis, Francesca Romana Ponziani, Andrea Olivani, Gabriele Missale, Valentina Cossiga, Mario Capasso, Filomena Morisco, Ester Marina Cela, Antonio Facciorusso, Valentina Lauria, Giorgia Ghittoni, Giorgio Pelecca, Fabrizio Chegai, Fabio Coratella, Mariano Ortenzi, Serena Dell'Isola, Maria Stella Franzè, Carlo Saitta, Assunta Sauchella, Elton Dajti, Federico Ravaioli, Filippo Oliveri, Gabriele Ricco, Veronica Romagnoli, Alessandro Inno, Fabiana Marchetti, Pietro Coccoli, Antonio Malerba, Alberta Cappelli, Rita Golfieri, Cristina Mosconi, Matteo Renzulli, Giannini, Edoardo G, Pieri, Giulia, Labanca, Sara, Plaz Torres, Maria Corina, Gasbarrini, Antonio, Biasini, Elisabetta, Campani, Claudia, Cazzagon, Nora, Foschi, Francesco Giuseppe, Mega, Andrea, Masotto, Alberto, Raimondo, Giovanni, Rapaccini, Gian Ludovico, Sacco, Rodolfo, Caturelli, Eugenio, Guarino, Maria, Tovoli, Francesco, Vidili, Gianpaolo, Brunetto, Maurizia Rossana, Nardone, Gerardo, Svegliati-Baroni, Gianluca, Magalotti, Donatella, Azzaroli, Francesco, Cabibbo, Giuseppe, Di Marco, Maria, Sangiovanni, Angelo, Trevisani, Franco, Giannini, E. G., Pieri, G., Labanca, S., Plaz Torres, M. C., Gasbarrini, A., Biasini, E., Campani, C., Cazzagon, N., Foschi, F. G., Mega, A., Masotto, A., Raimondo, G., Rapaccini, G. L., Sacco, R., Caturelli, E., Guarino, M., Tovoli, F., Vidili, G., Brunetto, M. R., Nardone, G., Svegliati-Baroni, G., Magalotti, D., Azzaroli, F., Cabibbo, G., Di Marco, M., Sangiovanni, A., Trevisani, F., Biselli, M., Caraceni, P., Gramenzi, A., Benevento, F., Granito, A., Muratori, L., Piscaglia, F., Bertellini, F., Farinati, F., Palano, G., Pelizzaro, F., Penzo, B., Pinto, E., Allegrini, G., Camma, C., Celsa, C., Giuffrida, P., Stornello, C., Grova, M., Giacchetto, C. M., Rancatore, G., Grassini, M. V., Adotti, V., Gitto, S., Marra, F., Rosi, M., Bevilacqua, V., Borghi, A., Gardini, A. C., Conti, F., Napoli, L., Domenicali, M., Migliano, M. T., de Matthaeis, N., Ponziani, F. R., Olivani, A., Missale, G., Cossiga, V., Capasso, M., Morisco, F., Cela, E. M., Facciorusso, A., Lauria, V., Ghittoni, G., Pelecca, G., Chegai, F., Coratella, F., Ortenzi, M., Dell'Isola, S., Franze, M. S., Saitta, C., Sauchella, A., Dajti, E., Ravaioli, F., Oliveri, F., Ricco, G., Romagnoli, V., Inno, A., Marchetti, F., Coccoli, P., Malerba, A., Cappelli, A., Golfieri, R., Mosconi, C., and Renzulli, M.

Subjects
Male, Carcinoma, Hepatocellular, Cholestatic liver disease, Outcome, Surveillance, Survival, Treatment, Hepatology, Prognosi, Liver Cirrhosis, Biliary, Risk Factor, Settore MED/12 - GASTROENTEROLOGIA, Liver Neoplasms, Gastroenterology, Prognosis, Risk Factors, Humans, Female, Human, Aged
Abstract

Background: Comprehensive and contemporary data pertaining large populations of patients with Primary Biliary Cholangitis (PBC) and hepatocellular carcinoma (HCC) are missing. Aim: To describe main characteristics and outcome of PBC patients with HCC diagnosed in the new millennium. Methods: Analysing the Italian Liver Cancer registry we identified 80 PBC patients with HCC diagnosed after the year 2000, and described their clinical characteristics, access to treatment and survival. Results: Median age of patients was 71 years and 50.0% were males. Cirrhosis was present in 86.3% of patients, being well-compensated in 58.0%. Median HCC diameter was smaller in patients under surveillance (2.6vs 4.0cm, P=0.007). Curative treatment, feasible in 50.0% of patients, was associated with improved survival compared to palliative and supportive care (42vs 33vs 6 months, P

Published
2022

25. 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

26. Global multi-stakeholder endorsement of the MAFLD definition

Author

Nahum Méndez-Sánchez, Elisabetta Bugianesi, Robert G Gish, Frank Lammert, Herbert Tilg, Mindie H Nguyen, Shiv K Sarin, Núria Fabrellas, Shira Zelber-Sagi, Jian-Gao Fan, Gamal Shiha, Giovanni Targher, Ming-Hua Zheng, Wah-Kheong Chan, Shlomo Vinker, Takumi Kawaguchi, Laurent Castera, Yusuf Yilmaz, Marko Korenjak, C Wendy Spearman, Mehmet Ungan, Melissa Palmer, Mortada El-Shabrawi, Hans-Juergen Gruss, Jean-François Dufour, Anil Dhawan, Heiner Wedemeyer, Jacob George, Luca Valenti, Yasser Fouad, Manuel Romero‐Gomez, Mohammed Eslam, Maria Lorena Abate, Bahaa Abbas, Ahmed Amr Abbassy, Waleed Abd El Ghany, Amira Abd Elkhalek, Emad Abd ElMajeed, Mohammad Abdalgaber, Mohamed AbdAllah, Marwa Abdallah, Nourhan Abdallah, Shereen Abdelaleem, Yasser Abdelghani, Wael Abdelghany, Safaa Mohamed Abdelhalim, Wafaa Abdelhamid, Nehal Abdelhamid, Nadia A. Abdelkader, Elsayed Abdelkreem, Aly Mohamed Abdelmohsen, Awny Ali Abdelrahman, Sherief M Abd-elsalam, Doaa Abdeltawab, Abdulbaset Abduh, Nada Abdulhakam, Maheeba Abdulla, Navid Abedpoor, Ludovico Abenavoli, Fredrik Åberg, Omala Ablack, Mostafa Abo elftouh, Yousry Esam-Eldin Abo-Amer, Ashraf Aboubkr, Alaa Aboud, Amr M. Abouelnaga, Galal A. Aboufarrag, Ashraf Aboutaleb, Leticia Abundis, Gupse Adalı, Enrique Adames, Leon Adams, Danjuma Adda, Noor Adel, Nada Adel, Muhammad Adel Sayed, Taiba Jibril Afaa, Nawal Afredj, Gulnara Aghayeva, Alessio Aghemo, Carlos A. Aguilar-Salinas, Golo Ahlenstiel, Walid Ahmady, Wafaa Ahmed, Amira Ahmed, Samah Nasser Ahmed, Heba Mostafa Ahmed, Rasha Ahmed, Elmar Aigner, Mesut Akarsu, Maisam Akroush, Umit Akyuz, Mamun Al Mahtab, Tahani Al Qadiri, Yusriya Al Rawahi, Razzaq AL rubaee, Muna Al Saffar, Shahinul Alam, Zaid Al-Ani, Agustín Albillos, Mohamed Alboraie, Said Al-Busafi, Mohamed Al-Emam, Jawaher Alharthi, Kareem Ali, Basma Abdelmoez Ali, Mohammad Ali, Raja Affendi Raja Ali, Anna Alisi, Ali Raad AL-Khafaji, Maryam Alkhatry, Rocio Aller, Yahya Almansoury, Khalid Al-Naamani, Alaa Alnakeeb, Anna Alonso, Saleh A. Alqahtani, Leina Alrabadi, Khalid Alswat, Mahir Altaher, Turki Altamimi, Jose Altamirano, Mario R. Alvares-da-Silva, Elsragy Adel M. Aly, Amgad Alzahaby, Ahmed Alzamzamy, Keisuke Amano, Maysa A. Amer, Mona A. Amin, Sayed A. Amin, Ashraf A. Amir, Javier Ampuero, Noha Anas, Pietro Andreone, Soa Fy Andriamandimby, Mahmoud Anees, Peltec Angela, Manal Antonios, Wael Arafat, Jose Moreno Araya, Juan Armendariz-Borunda, Matthew J. Armstrong, Hassan Ashktorab, Patricia Aspichueta, Fathia Assal, Mira Atef, Dina Attia, Hoda Atwa, Reham Awad, Mohyeldeen Abd Elaziz Awad, Sally Awny, Obafemi Awolowo, Yaw Asante Awuku, Ibrahim Ayada, Than Than Aye, Sherif Ayman, Hedy Ayman, Hesham Ayoub, Hosny M. Azmy, Romiro P. Babaran, Omneya Badreldin, Ahmed Badry, İbrahim Halil Bahçecioğlu, Amira Bahour, Jiajia Bai, Yasemin Balaban, Muthuswamy Balasubramanyam, Khaled Bamakhrama, Jesus M Banales, Babu Bangaru, Jianfeng Bao, Jorge Suazo Barahona, Salma Barakat, Sandra Maria Barbalho, Bikwa Barbra, Beatriz Barranco, Francisco Barrera, Ulrich Baumann, Shamardan Bazeed, Eva Bech, Aourarh Benayad, Andreas Benesic, David Bernstein, Fernando Bessone, Susie Birney, Cyrille Bisseye, Martin Blake, Bilal Bobat, Leonilde Bonfrate, Dmitry S Bordin, Francisco Bosques-Padilla, Jerome Boursier, Boushab Mohamed Boushab, David Bowen, Patricia Medina Bravo, Paul N Brennan, Bisi Bright, Ilse Broekaert, Xabier Buque, Diego Burgos-Santamaría, Julio Burman, Luca Busetto, Chris D. Byrne, Patricia Anne I. Cabral-Prodigalidad, Guillermo Cabrera-Alvarez, Wei Cai, Francesca Cainelli, Ali Riza Caliskan, Ali Canbay, Ana Cano-Contreras, Hai-Xia Cao, Zhujun Cao, Andres Carrion, Francesca Carubbi, Teresa Casanovas, Marlen Ivón Castellanos Fernández, Jin Chai, Siew Pheng Chan, Phunchai Charatcharoenwitthaya, Norberto Chavez-Tapia, Kazuaki Chayama, Jinjun Chen, Lin Chen, Zhong-Wei Chen, Huiting Chen, Sui-Dan Chen, Qiang Chen, Yaxi Chen, Gang Chen, En-Quang Chen, Fei Chen, Pei-Jer Chen, Robert Cheng, Wendy Cheng, Jack Tan Wei Chieh, Imad Chokr, Evangelos Cholongitas, Ashok Choudhury, Abhijit Chowdhury, Evaristus Sunday Chukwudike, Stefano Ciardullo, Michelle Clayton, Karine Clement, Marie Michelle Cloa, Cecilia Coccia, Cristina Collazos, Massimo Colombo, Arif Mansur Cosar, Helma Pinchemel Cotrim, Joris Couillerot, Alioune Coulibaly, Gonzalo Crespo, Javier Crespo, Maria Cruells, Ian Homer Y. Cua, Hesham K. 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Dwawhi, Sho Eiketsu, Doaa El Amrousy, Ahmed El Deeb, Ghada El Deriny, Hesham Salah El Din, Salwa El Kamshishy, Mohamed El Kassas, Maissa El Raziky, Osama A Elagamy, Wafaa Elakel, Dina Elalfy, Hanaa Elaraby, Heba ElAwady, Reda Elbadawy, Hanaa Hassan Eldash, Manal S. Eldefrawy, Carol Lezama Elecharri, Amel Elfaramawy, Mohammed Elfatih, Mahmoud Elfiky, Mohamed Elgamsy, Mohamed Elgendy, Mohamed A. El-Guindi, Nagi Elhussieny, Ahmed Maher Eliwa, Zeineb Elkabbany, Hesham El-Khayat, Nehal M. El-Koofy, Alaa Elmetwalli, Amr Elrabat, Fathiya El-Raey, Fatma Elrashdy, Medhat Elsahhar, Esraa M. Elsaid, Shimaa Elsayed, Hany Elsayed, Aly Elsayed, Amr M. Elsayed, Hamdy Elsayed, Magdy El-Serafy, Ahmed M. Elsharkawy, Reem Yehia Elsheemy, Eman Elsayed Elshemy, Sara Elsherbini, Naglaa Eltoukhy, Reda Elwakil, Ola Emad, Shaimaa Emad, Mohamed Embabi, Ilkay Ergenç, Tatiana Ermolova, Gamal Esmat, Doaa M. 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Icaza-Chávez, Sahar Idelbi, Ramazan Idilman Idilman, Mayumi Ikeda, Giuseppe Indolfi, Federica Invernizzi, Iram Irshad, Hasan Mohamed Ali Isa, Natacha Jreige Iskandar, Abdulrahman Ismaiel, Mariam Ismail, Zulkifli Ismail, Faisal Ismail, Hideki Iwamoto, Kathryn Jack, Rachael Jacob, Fuad Jafarov, Wasim Jafri, Helen Jahshan, Prasun K Jalal, Ligita Jancoriene, Martin Janicko, Hiruni Jayasena, Meryem Jefferies, Vivekanand Jha, Fanpu Ji, Yaqiu Ji, Jidong Jia, Changtao Jiang, Ni Jiang, Zong-zhe Jiang, Xing Jin, Yi Jin, Xu Jing, Qian Jingyu, Maia Jinjolava, FX Himawan Haryanto Jong, Alina Jucov, Ibecheole Julius, Mona Kaddah, Yoshihiro Kamada, Abobakr kamal, Enas Mohamed Kamal, Ashraf Sayed Kamel, Jia-Horng Kao, Maja Karin, Thomas Karlas, Mohammad Kashwaa, Leolin Katsidzira, Eda Kaya, M.Azzam Kayasseh, Bernadette Keenan, Caglayan Keklikkiran, William Keml, Deia K. Khalaf, Rofida Khalefa, Sherin Khamis, Doaa Khater, Hamed khattab, Anatoly Khavkin, Olga Khlynova, Nabil Khmis, Nazarii Kobyliak, Apostolos Koffas, Kazuhiko Koike, Kenneth Y.Y. Kok, Tomas Koller, Narcisse Patrice Komas, Nataliya V. Korochanskaya, Yannoula Koulla, Shunji Koya, Colleen Kraft, Bledar Kraja, Marcin Krawczyk, Mohammad Shafi Kuchay, Anand V Kulkarni, Ashish Kumar, Manoj Kumar, Sulaiman Lakoh, Philip Lam, Ling Lan, Naomi F. Lange, Kamran Bagheri Lankarani, Nicolas Lanthier, Kateryna Lapshyna, Sameh A. Lashen, Konang Nguieguia Justine Laure, Leonid Lazebnik, Didier Lebrec, Samuel S. Lee, Way Seah Lee, Yeong Yeh Lee, Diana Julie Leeming, Nathalie Carvalho Leite, Roberto Leon, Cosmas Rinaldi Adithya Lesmana, Junfeng Li, Qiong Li, Jun Li, Yang-Yang Li, Yufang Li, Lei Li, Min Li, Yiling li, Huiqing Liang, Tang Lijuan, Seng Gee Lim, Lee-Ling Lim, Shumei Lin, Han-Chieh Lin, Rita Lin, Rania Lithy, Yaru Liu, Yuanyuan Liu, Xin Liu, Wen-Yue Liu, Shourong Liu, Ken Liu, Tian Liu, Amedeo Lonardo, Mariana Bravo López, Eva López-Benages, Patricio Lopez-Jaramillo, Huimin Lu, Lun Gen Lu, Yan Lu, John Lubel, Rashid Lui, Iulianna Lupasco, Elena Luzina, Xiao-Hui Lv, Kate Lynch, Hong-Lei Ma, Mariana Verdelho Machado, Nonso Maduka, Katerina Madzharova, Russellini Magdaong, Sanjiv Mahadeva, Amel Mahfouz, Nik Ritza Kosai Nik Mahmood, Eman Mahmoud, Mohamed Mahrous, Rakhi Maiwall, Ammar Majeed, Avik Majumdar, Loey Mak, Madiha M Maklouf, Reza Malekzadeh, Claudia Mandato, Alessandra Mangia, Jake Mann, Hala Hussien Mansour, Abdellah Mansouri, Alessandro Mantovani, Jun qian Mao, Flor Maramag, Giulio Marchesini, Claude Marcus, Rui António Rocha Tato Marinho, Maria L Martinez-Chantar, Antonieta A. Soares Martins, Rana Marwan, Karen Frances Mason, Ghadeer Masoud, Mohamed Naguib Massoud, Maria Amalia Matamoros, Rosa Martín Mateos, Asmaa Mawed, Jean Claude Mbanya, Charles Mbendi, Lone McColaugh, Duncan McLeod, Juan Francisco Rivera Medina, Ahmed Megahed, Mai Mehrez, Iqbal Memon, Shahin Merat, Randy Mercado, Ahmed Mesbah, Taoufik Meskini, Mayada Metwally, Rasha Metwaly, Lei Miao, Eileen Micah, Luca Miele, Vladimir Milivojevic, Tamara Milovanovic, Yvonne L. Mina, Milan Mishkovik, Amal Mishriki, Tim Mitchell, Alshaimaa Mohamed, Mona Mohamed, Sofain Mohamed, Shady Mohammed, Ahmed Mohammed, Viswanathan Mohan, Sara Mohie, Aalaa Mokhtar, Reham Moniem, Mabel Segura Montilla, Jose Antonio Orozco Morales, María María Sánchez Morata, Jose Maria Moreno-Planas, Silvia Morise, Sherif Mosaad, Mohamed Moselhy, Alaa Mohamed Mostafa, Ebraheem Mostafa, Nezha Mouane, Nasser Mousa, Hamdy Mahfouz Moustafa, Abeer Msherif, Kate Muller, Christopher Munoz, Ana Beatriz Muñoz-Urribarri, Omar Alfaro Murillo, Feisul Idzwan Mustapha, Emir Muzurović, Yehia Nabil, Shaymaa Nafady, Ayu Nagamatsu, Atsushi Nakajima, Dan Nakano, Yuemin Nan, Fabio Nascimbeni, Mirella S. Naseef, Nagwa Nashat, Taran Natalia, Francesco Negro, Alexander V. 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Peltekian, Xuebin Peng, Liang Peng, Ying Peng, Rahul Pengoria, Martina Perez, José Luis Pérez, Norma Marlene Pérez, Marcello Persico, Mário Guimarães Pessoa, Salvatore Petta, Mathew Philip, Maria Corina Plaz Torres, Naveen Polavarapu, Jaime Poniachik, Piero Portincasa, Chunwen Pu, Tuğrul Pürnak, Edhie Purwanto, Xiaolong Qi, Xingshun Qi, Zibing Qian, Zhao Qiang, Zengpei Qiao, Liang Qiao, Alberto Queiroz, Atoosa Rabiee, Manal Radwan, Alain Marcel Rahetilahy, Yasmin Ramadan, Dina Ramadan, Anis Safura Ramli, Grant A. Ramm, Ao Ran, Ivan Rankovic, Huiying RAO, Sara Raouf, Sayantan Ray, Nancy Reau, Ahmed Refaat, Thomas Reiberger, Jose M Remes-Troche, Eira Cerda Reyes, Ben Richardson, Ezequiel Ridruejo, Sergio Riestra Jimenez, Ibrahim Rizk, Stuart Roberts, Juan Pablo Roblero, Jorge Alberto Prado Robles, Don Rockey, Manuel Rodríguez, Heriberto Rodríguez Hernández, Eva Román, Fernando Gomes Romeiro, Stefano Romeo, Jose Miguel Rosales-Zabal, Georgina R. 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Xu, A, Xu, C, Yan, H, Yang, J, Yang, R, Yang, Y, Yang, Q, Yang, N, Yao, J, Yara, J, Yaras, S, Yilmaz, N, Younes, R, Younes, H, Young, S, Youssef, F, Yu, Y, Yu, M, Yuan, J, Yue, Z, Yuen, M, Yun, W, Yurukova, N, Zakaria, S, Zaky, S, Zaldastanishvili, M, Zapata, R, Zare, N, Zerem, E, Zeriban, N, Zeshuai, X, Zhang, H, Zhang, X, Zhang, Y, Zhang, W, Zhang, Z, Zhao, J, Zhao, R, Zhao, H, Zheng, C, Zheng, Y, Zheng, R, Zheng, T, Zheng, K, Zhou, X, Zhou, Y, Zhou, H, Zhou, L, Zhu, L, Zhu, Y, Zhu, P, Ziada, E, Ziring, D, Ziyi, L, Zou, S, Zou, Z, Zou, H, Zuart Ruiz, R, and Global Multi-Stakeholder Consensus on the Redefinition of Fatty Liver Disease

Subjects
Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], Hepatology, Non-alcoholic Fatty Liver Disease, NAFLD, consensu, Gastroenterology, MAFLD, definition, Humans, MAFLD, NAFLD, Human medicine
Abstract

Contains fulltext : 252162.pdf (Publisher’s version ) (Closed access)

Published
2022

27. Rare ATG7 genetic variants predispose patients to severe fatty liver disease

Author

Guido A. Baselli, Oveis Jamialahmadi, Serena Pelusi, Ester Ciociola, Francesco Malvestiti, Marco Saracino, Luigi Santoro, Alessandro Cherubini, Paola Dongiovanni, Marco Maggioni, Cristiana Bianco, Federica Tavaglione, Annalisa Cespiati, Rosellina M. Mancina, Roberta D’Ambrosio, Valentina Vaira, Salvatore Petta, Luca Miele, Umberto Vespasiani-Gentilucci, Alessandro Federico, Jussi Pihlajamaki, Elisabetta Bugianesi, Anna L. Fracanzani, Helen L. Reeves, Giorgio Soardo, Daniele Prati, Stefano Romeo, Luca VC. Valenti, Vittorio Borroni, Antonio Liguori, Luisa Ronzoni, Melissa Tomasi, Angela Lombardi, Mahnoosh Ostadreza, Elia Casirati, Ilaria Marini, Silvia Maier, Chiara Rosso, Gianluca Svegliati Baroni, Carlo Santaniello, Marcello Dallio, Baselli, Guido A, Jamialahmadi, Ovei, Pelusi, Serena, Ciociola, Ester, Malvestiti, Francesco, Saracino, Marco, Santoro, Luigi, Cherubini, Alessandro, Dongiovanni, Paola, Maggioni, Marco, Bianco, Cristiana, Tavaglione, Federica, Cespiati, Annalisa, Mancina, Rosellina M, D'Ambrosio, Roberta, Vaira, Valentina, Petta, Salvatore, Miele, Luca, Vespasiani-Gentilucci, Umberto, Federico, Alessandro, Pihlajamaki, Jussi, Bugianesi, Elisabetta, Fracanzani, Anna L, Reeves, Helen L, Soardo, Giorgio, Prati, Daniele, Romeo, Stefano, and Valenti, Luca Vc

Subjects
Inflammation, Liver Cirrhosis, autophagy, Hepatology, Biopsy, NAFLD, NASH, autophagy, genetics, liver fibrosis, Carcinoma, Liver Neoplasms, NASH, Hepatocellular, Autophagy-Related Protein 7, NAFLD, genetics, liver fibrosis, Humans, Liver, Carcinoma, Hepatocellular, Non-alcoholic Fatty Liver Disease, genetic
Abstract

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disorders and has a strong heritable component. The aim of this study was to identify new loci that contribute to severe NAFLD by examining rare variants.Methods: We performed whole-exome sequencing in in-dividuals with NAFLD and advanced fibrosis or hepatocellular carcinoma (n = 301) and examined the enrichment of likely pathogenic rare variants vs. the general population. This was followed by validation at the gene level.Results: In patients with severe NAFLD, we observed an enrichment of the p.P426L variant (rs143545741 C>T; odds ratio [OR] 5.26, 95% CI 2.1-12.6; p = 0.003) of autophagy-related 7 (ATG7), which we characterized as a loss-of-function, vs. the general population, and an enrichment in rare variants affecting the catalytic domain (OR 13.9; 95% CI 1.9-612; p = 0.002). In the UK Biobank cohort, loss-of-function ATG7 variants increased the risk of cirrhosis and hepatocellular carcinoma (OR 3.30; 95% CI 1.1-7.5 and OR 12.30, 95% CI 2.6-36, respectively; p C) was also associated with severe NAFLD in the clinical cohort (OR 1.7; 95% CI 1.2-2.5; p = 0.003), predisposed to hepatocellular ballooning (p = 0.007) evolving to fibrosis in the Liver biopsy cohort (n = 2,268), and was associated with liver injury in the UK Biobank (aspartate aminotransferase levels, p

Published
2022

28. Epidemiological trends and trajectories of MAFLD-associated hepatocellular carcinoma 2002-2033: The ITA.LI.CA database

Author

Alessandro, Vitale, Gianluca, Svegliati-Baroni, Alessio, Ortolani, Monica, Cucco, Giulio V, Dalla Riva, Edoardo G, Giannini, Fabio, Piscaglia, Gianludovico, Rapaccini, Mariella, Di Marco, Eugenio, Caturelli, Marco, Zoli, Rodolfo, Sacco, Giuseppe, Cabibbo, Fabio, Marra, Andrea, Mega, Filomena, Morisco, Antonio, Gasbarrini, Francesco Giuseppe, Foschi, Gabriele, Missale, Alberto, Masotto, Gerardo, Nardone, Giovanni, Raimondo, Francesco, Azzaroli, Gianpaolo, Vidili, Filippo, Oliveri, Filippo, Pelizzaro, Rafael, Ramirez Morales, Umberto, Cillo, Franco, Trevisani, Luca, Miele, Giulio, Marchesini, Fabio, Farinati, Alessandro, Di Bucchianico, Vitale, A., Svegliati-Baroni, G., Ortolani, A., Cucco, M., Dalla Riva, G. V., Giannini, E. G., Piscaglia, F., Rapaccini, G., Di Marco, M., Caturelli, E., Zoli, M., Sacco, R., Cabibbo, G., Marra, F., Mega, A., Morisco, F., Gasbarrini, A., Foschi, F. G., Missale, G., Masotto, A., Nardone, G., Raimondo, G., Azzaroli, F., Vidili, G., Oliveri, F., Pelizzaro, F., Ramirez Morales, R., Cillo, U., Trevisani, F., Miele, L., Marchesini, G., Farinati, F., Alessandro Vitale, Gianluca Svegliati-Baroni, Alessio Ortolani, Monica Cucco, Giulio V Dalla Riva, Edoardo G Giannini, Fabio Piscaglia, Gianludovico Rapaccini, Mariella Di Marco, Eugenio Caturelli, Marco Zoli, Rodolfo Sacco, Giuseppe Cabibbo, Fabio Marra, Andrea Mega, Filomena Morisco, Antonio Gasbarrini, Francesco Giuseppe Foschi, Gabriele Missale, Alberto Masotto, Gerardo Nardone, Giovanni Raimondo, Francesco Azzaroli, Gianpaolo Vidili, Filippo Oliveri, Filippo Pelizzaro, Rafael Ramirez Morales, Umberto Cillo, Franco Trevisani, Luca Miele, Giulio Marchesini, Fabio Farinati, Vitale, Alessandro, Svegliati-Baroni, Gianluca, Ortolani, Alessio, Cucco, Monica, Dalla Riva, Giulio V, Giannini, Edoardo G, Piscaglia, Fabio, Rapaccini, Gianludovico, Di Marco, Mariella, Caturelli, Eugenio, Zoli, Marco, Sacco, Rodolfo, Cabibbo, Giuseppe, Marra, Fabio, Mega, Andrea, Morisco, Filomena, Gasbarrini, Antonio, Foschi, Francesco Giuseppe, Missale, Gabriele, Masotto, Alberto, Nardone, Gerardo, Raimondo, Giovanni, Azzaroli, Francesco, Vidili, Gianpaolo, Oliveri, Filippo, Pelizzaro, Filippo, Ramirez Morales, Rafael, Cillo, Umberto, Trevisani, Franco, Miele, Luca, Marchesini, Giulio, and Farinati, Fabio

Subjects
Male, Settore MED/12 - Gastroenterologia, Carcinoma, Hepatocellular, Liver Neoplasms, nonalcoholic steatohepatitis, Gastroenterology, hepatocellular carcinoma, digestive system diseases, Non-alcoholic Fatty Liver Disease, Risk Factors, Humans, neoplasms
Abstract

BackgroundMetabolic dysfunction-associated fatty liver disease (MAFLD) represents a new inclusive definition of the whole spectrum of liver diseases associated to metabolic disorders. The main objective of this study was to compare patients with MAFLD and non-MAFLD with hepatocellular carcinoma (HCC) included in a nationally representative cohort.MethodsWe analysed 6882 consecutive patients with HCC enrolled from 2002 to 2019 by 23 Italian Liver Cancer centres to compare epidemiological and future trends in three subgroups: pure, single aetiology MAFLD (S-MAFLD); mixed aetiology MAFLD (metabolic and others, M-MAFLD); and non-MAFLD HCC.ResultsMAFLD was diagnosed in the majority of patients with HCC (68.4%). The proportion of both total MAFLD and S-MAFLD HCC significantly increased over time (from 50.4% and 3.6% in 2002–2003, to 77.3% and 28.9% in 2018–2019, respectively, pConclusionsThe prevalence of MAFLD HCC in Italy is rapidly increasing to cover the majority of patients with HCC. Despite a less favourable cancer stage at diagnosis, patients with MAFLD HCC have a lower risk of HCC-related death, suggesting reduced cancer aggressiveness.

Published
2021

29. Mild impact of SARS-CoV-2 infection on the entire population of liver transplant recipients: the experience of an Italian Centre based in a high-risk area

Author

Federico Mocchegiani, Marco Vivarelli, and Gianluca Svegliati Baroni

Subjects
2019-20 coronavirus outbreak, Entire population, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), SARS-CoV-2, Questionnaire, business.industry, medicine.medical_treatment, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Covid 19, Immunosuppression, Liver transplantation, Virology, Surgery, Risk area, Pandemic, Medicine, business, Letter to the Editor, Liver transplant
Published
2020

30. Pathophysiology of Non Alcoholic Fatty Liver Disease

Author

Salvatore Petta, Amalia Gastaldelli, Eleni Rebelos, Elisabetta Bugianesi, Piergiorgio Messa, Luca Miele, Gianluca Svegliati-Baroni, Luca Valenti, and Ferruccio Bonino

Subjects
fatty liver, insulin resistance, free fatty acids, cholesterol, adiponectin, leptin, insulin, glucagon, glucagon-like peptide 1, ghrelin, irisin, selenoprotein P, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

The physiopathology of fatty liver and metabolic syndrome are influenced by diet, life style and inflammation, which have a major impact on the severity of the clinicopathologic outcome of non-alcoholic fatty liver disease. A short comprehensive review is provided on current knowledge of the pathophysiological interplay among major circulating effectors/mediators of fatty liver, such as circulating lipids, mediators released by adipose, muscle and liver tissues and pancreatic and gut hormones in relation to diet, exercise and inflammation.

Published
2016
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31. Comparison of point shear wave elastography and transient elastography in the evaluation of patients with NAFLD

Author

Giulio Argalia, Claudio Ventura, Niccolò Tosi, Daniele Campioni, Corrado Tagliati, Marianna Tufillaro, Monica Cucco, Gianluca Svegliati Baroni, and Andrea Giovagnoni

Subjects
Liver Cirrhosis, Male, Liver, ROC Curve, Non-alcoholic Fatty Liver Disease, Biopsy, Elasticity Imaging Techniques, Humans, Radiology, Nuclear Medicine and imaging, General Medicine, Prospective Studies, Fibrosis
Abstract

To compare point shear wave elastography (pSWE, ElastPQ®) and transient elastography (TE) with Liver Biopsy in order to evaluate fibrosis stage in non-alcoholic fatty liver disease (NAFLD).Our prospective study from September 2017 to October 2020 included 50 consecutively enrolled patients with NAFLD (52.2 ± 13.0 years, 32 male). All patients underwent clinical evaluation, B-mode ultrasound, pSWE, TE and liver biopsy in a single evaluation. The clinical, laboratory and liver biopsy data were compared with liver stiffness (LS) measurement obtained with pSWE and TE. TE and pSWE diagnostic accuracy for the diagnosis of the different fibrosis stages were evaluated using the area under receiver operating characteristic curve (AUROC).Only fibrosis stage was independently associated with TE and pSWE. The median liver stiffness measurement for fibrosis stages F0, F1, F2, F3, and F4 using TE was 4.8 (4.7-6.1) kPa, 5.5 (4.4-7.3) kPa, 7.7 (6.1-9.1) kPa, 9.9 (8.8-13.8) kPa, and 20.2 kPa, respectively. The corresponding median liver stiffness measurement using pSWE was 4.2 (4.0-4.8) kPa, 4.7 (4.2-5.8) kPa, 5.1 (4.1-6.9) kPa, 8.5 (5.2-13.3), and 15.1 kPa, respectively. The AUROC of TE for diagnosis of fibrosis stage F1, ≥ F2, ≥ F3, and F4 were 0.795, 0.867, 0.927, and 0.990, respectively. The corresponding AUROC of pSWE was 0.717, 0.733, 0.908, and 1.000, respectively. No association was observed with other histological parameters.TE was significantly better than pSWE for the diagnosis of fibrosis stage ≥ F2. No statistically significant differences were found between TE and pSWE AUROC of fibrosis stage ≥ F1, ≥ F3, and F4.

Published
2021

32. Non-alcoholic fatty liver disease in adults 2021: A clinical practice guideline of the Italian Association for the Study of the Liver (AISF), the Italian Society of Diabetology (SID) and the Italian Society of Obesity (SIO)

Author

Giulio Marchesini, Elisabetta Bugianesi, Patrizia Burra, Fabio Marra, Luca Miele, Anna Alisi, Piero Vajro, Mario Masarone, Salvatore Petta, Marcello Persico, Gianluca Svegliati-Baroni, Luca Valenti, Massimo Federici, Francesco Purrello, Ferdinando Carlo Sasso, Giovanni Targher, Luca Busetto, Maria Letizia Petroni, Ferruccio Santini, Calogero Cammà, Agostino Colli, Marchesini G., Bugianesi E., Burra P., Marra F., Miele L., Alisi A., Vajro P., Masarone M., Petta S., Persico M., Svegliati-Baroni G., Valenti L., Federici M., Purrello F., Sasso F.C., Targher G., Busetto L., Petroni M.L., Santini F., Camma C., Colli A., Marchesini, G., Bugianesi, E., Burra, P., Marra, F., Miele, L., Alisi, A., Vajro, P., Masarone, M., Petta, S., Persico, M., Svegliati-Baroni, G., Valenti, L., Federici, M., Purrello, F., Sasso, F. C., Targher, G., Busetto, L., Petroni, M. L., Santini, F., Camma, C., and Colli, A.

Subjects
Male, Adult, Endocrinology, Diabetes and Metabolism, Settore MED/12 - GASTROENTEROLOGIA, Medicine (miscellaneous), Settore MED/09, Guideline, Guidelines, Guidelines, NAFLD, NASH, Non-alcoholic Fatty Liver Disease, Medical, NAFLD, Humans, Obesity, Societies, Medical, Patient Care Team, Nutrition and Dietetics, NASH, Delivery of Health Care, Sudden Infant Death, Hepatology, Gastroenterology, Disease Management, Female, Italy, Psychiatry and Mental health, Clinical Psychology, Cardiology and Cardiovascular Medicine, Societies, Human
Abstract

Nonalcoholic fatty liver disease (NAFLD) is a common and emerging liver disease in adults, paralleling the epidemic of obesity and diabetes, and leading to worrisome events (hepatocellular carcinoma and end-stage liver disease). In the last years, mounting evidence added insights about epidemiology, natural history, diagnosis and lifestyle-based or drug treatment of NAFLD. In this rapidly evolving scenario, members of the Associazione Italiana per lo Studio del Fegato (AISF), the Società Italiana di Diabetologia (SID) and the Società Italiana dell'Obesità (SIO) reviewed current knowledge on NAFLD. The quality of the published evidence is graded, and practical recommendations are made following the rules and the methodology suggested in Italy by the Centro Nazionale per l'Eccellenza delle cure (CNEC) and Istituto Superiore di Sanità (ISS). Whenever possible, recommendations are placed within the context the Italian Healthcare system, with reference to specific experience and local diagnostic and management resources. Level of evidence: Level of evidence of recommendations for each PICO question were reported according to available evidence.

Published
2021

33. Anticoagulation and Vessel Recanalization in Cirrhotic Patients with Splanchnic Vein Thrombosis: A Multidisciplinary 'Real Life' Experience

Author

Serena Rupoli, Alessandro Fiorentini, Erika Morsia, Gianluca Svegliati-Baroni, Giorgia Micucci, Luca Maroni, Kimberly Blaine Garvey, Alessandra Riva, Lidia Da Lio, Antonio Benedetti, Massimo Offidani, Attilio Olivieri, and Tarantino Giuseppe

Subjects
Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Multivariate analysis, Cirrhosis, Endocrinology, Diabetes and Metabolism, Hemorrhage, Esophageal and Gastric Varices, Cohort Studies, splanchnic vein thrombosis, Internal medicine, medicine, Humans, Pharmacology (medical), Endoscopy, Digestive System, Prospective Studies, Splanchnic Circulation, Aged, Original Research, Aged, 80 and over, Venous Thrombosis, anticoagulant therapy, business.industry, Incidence (epidemiology), cirrhosis, Public Health, Environmental and Occupational Health, Anticoagulants, Hematology, General Medicine, Middle Aged, medicine.disease, Thrombosis, Vascular Health and Risk Management, Splanchnic vein thrombosis, Cardiology, multidisciplinary approach, Female, vessel recanalization, Liver function, Cardiology and Cardiovascular Medicine, business, Complication, Cohort study
Abstract

Serena Rupoli,1 Alessandro Fiorentini,1 Erika Morsia,1 Gianluca Svegliati-Baroni,2 Giorgia Micucci,1 Luca Maroni,2 Kimberly Blaine Garvey,1 Alessandro Fiorentini Snr,3 Alessandra Riva Snr,4 Lidia Da Lio,5 Antonio Benedetti,2 Massimo Offidani,1 Attilio Olivieri,1 Tarantino Giuseppe2 1Clinica Ematologica, Dipartimento di Medicina Interna, Ancona, Italy; 2SOD Clinica di Gastroenterologia, Epatologia ed Endoscopia Digestiva d’Urgenza, Ancona, Italy; 3SOD Malattie Infettive emergenti e degli immunodepressi, Ospedali Riuniti Ancona, Ancona, Italy; 4SOD Clinica Malattie Infettive tropicali, parassitologia, epatiti croniche, Ancona, Italy; 5SOD Medicina di Laboratorio, Ospedali Riuniti Ancona, Ancona, ItalyCorrespondence: Erika MorsiaClinica Ematologica, Ospedali Riuniti Ancona, via Conca 71, 60126, ItalyEmail erika.morsia@ospedaliriuniti.marche.itBackground and Aim: Splanchnic vein thrombosis (SVT) is a potentially life-threatening complication of liver cirrhosis. This study aimed to evaluate the impact of a multi-disciplinary approach and early anticoagulation therapy (AT) on bleeding/thrombotic events, recanalization rates and outcome of cirrhotic patients with SVT.Methods: This is a single-center, registry-based cohort study. Over 17 years, 149 SVT patients were enrolled and prospectively evaluated. Regarding cirrhotic-SVT, a pre-specified algorithm, guiding initial posology of AT and follow-up visits schedule, was performed. Major bleeding (MB), thrombotic events, functional liver scores and all cause-mortality were investigated. Efficacy of AT was evaluated by radiological imaging.Results: In cirrhotic-SVT, the incidence rate of MB was 8.4 per 100 patient-year (95% CI, 3.83– 15.97), while the incidence rate of thrombosis was 5.6 per 100 patient-year (95% CI, 2.05– 12.2). In incidental SVT treated with AT, MB incidence was 6.5 per 100 patient-year (95% CI: 2.8– 12.82), while in symptomatic SVT was 2.2 per 100 patient-year (95% CI: 0.25– 8.02). All thrombotic recurrences occurred in incidental SVT (7.7 per 100 patient-years; 95% CI, 3.71– 14.26). Overall survival was significantly higher in patients who had at least a partial recanalization (p < 0.01) and partial/total recanalization was independently associated with improved MELD score at multivariate analysis (HR 2.62, 95% CI 1.1– 6.47, p = 0.03).Conclusion: In cirrhotic SVT patients, partial or total resolution of thrombosis ameliorates liver function and is associated with higher overall survival. A multidisciplinary approach together with radiological follow-up at pre-fixed time improves patient selection and monitoring.Keywords: splanchnic vein thrombosis, cirrhosis, anticoagulant therapy, vessel recanalization, multidisciplinary approach

Published
2021

35. 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

36. 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

37. Identification of clinical phenotypes and related survival in patients with large hccs

Author

Rossella Donghia, Antonio Gasbarrini, Giovanni Raimondo, Elisabetta Biasini, Francesco Giuseppe Foschi, Gianpaolo Vidili, Maria Guarino, Andrea Mega, Marco Zoli, Rodolfo Sacco, Fabio Farinati, Brian I. Carr, Gianluca Svegliati-Baroni, Ciro Celsa, Eugenio Caturelli, Edoardo G. Giannini, Vito Guerra, Gian Ludovico Rapaccini, Maria Di Marco, Gerardo Nardone, Franco Trevisani, Claudia Campani, Luca Muratori, Francesco Azzaroli, Maurizia Rossana Brunetto, Alberto Masotto, Carr B.I., Guerra V., Donghia R., Farinati F., Giannini E.G., Muratori L., Rapaccini G.L., Di Marco M., Caturelli E., Zoli M., Sacco R., Celsa C., Campani C., Mega A., Guarino M., Gasbarrini A., Svegliati-Baroni G., Foschi F.G., Biasini E., Masotto A., Nardone G., Raimondo G., Azzaroli F., Vidili G., Brunetto M.R., Trevisani F., Carr, B. I., Guerra, V., Donghia, R., Farinati, F., Giannini, E. G., Muratori, L., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Sacco, R., Celsa, C., Campani, C., Mega, A., Guarino, M., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F. G., Biasini, E., Masotto, A., Nardone, G., Raimondo, G., Azzaroli, F., Vidili, G., Brunetto, M. R., and Trevisani, F.

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, PVT, Settore MED/12 - GASTROENTEROLOGIA, Serum albumin, lcsh:RC254-282, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, Platelet, HCC, neoplasms, Survival rate, biology, business.industry, Proportional hazards model, Albumin, Hazard ratio, Settore MED/09 - MEDICINA INTERNA, Multifocality, large, phenotypes, multifocality, albumin, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, digestive system diseases, Portal vein thrombosis, Large, Phenotypes, Phenotype, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, biology.protein, business
Abstract

Background. Hepatocellular carcinoma (HCC) factors, especially maximum tumor diameter (MTD), tumor multifocality, portal vein thrombosis (PVT), and serum alpha-fetoprotein (AFP), influence survival. Aim. To examine patterns of tumor factors in large HCC patients. Methods. A database of large HCC patients was examined. Results. A multiple Cox proportional hazard model on death identified low serum albumin levels and the presence of PVT and multifocality, with each having a hazard ratio ≥2.0. All combinations of these three parameters were examined in relation to survival. Using univariate Cox analysis, the combination of albumin &gt, 3.5 g/dL and the absence of both PVT and multifocality had the best survival rate, while all combinations that included the presence of PVT had poor survival and hazard ratios. We identified four clinical phenotypes, each with a distinct median survival: patients with or without PVT or multifocality plus serum albumin ≥3.5 (g/dL), with each subgroup displaying high (≥100 IU/mL) or low (&lt, 100 IU/mL) blood AFP levels. Across a range of MTDs, we identified only two significant trends, blood AFP and platelets. Conclusions. Patients with large HCCs have distinct phenotypes and survival, as identified by the combination of PVT, multifocality, and blood albumin levels.

Published
2021

38. The pathophysiology of gut–liver connection

Author

Luca Maroni, Francesca Fianchi, Luca Miele, and Gianluca Svegliati Baroni

Subjects
Intestinal permeability, biology, Bile acid, Chemistry, medicine.drug_class, Settore MED/12 - GASTROENTEROLOGIA, Context (language use), Lipid metabolism, Gut flora, medicine.disease, biology.organism_classification, digestive system, Cell biology, N/A, Nonalcoholic fatty liver disease, medicine, Dysbiosis, Lipid digestion
Abstract

The physiological functions of the liver and the intestine are intimately connected by tightly regulated mechanisms. The liver secretes bile acids in the intestine, which are fundamental in lipid digestion but also regulate the composition of the gut microbiota. In turn, the intestine regulates the synthesis of bile acids by a feedback loop based on the FXR/FGF-19 axis, and secretes in the blood stream a number of incretins that participate in glucose and lipid metabolism, at least in part by modulating hepatic functions. Moreover, alteration of the gut permeability induced by a variety of factors (including dysbiosis) deeply influences the quantity and quality of metabolites and bacterial products that reach the liver via the portal blood and modulate hepatic molecular pathways. The dysregulation of the gut–liver axis plays therefore a crucial role in the pathogenesis of many metabolic diseases, and is actively studied in the context of nonalcoholic fatty liver disease (NAFLD). Strategies aiming at restoring intestinal permeability, modulating dysbiosis, or influencing molecular pathways involved in the regulation of the gut–liver axis have actively been investigated as potential new therapies for NAFLD. In the present chapter, the physiopathological bases of the “leaky gut hypothesis” and their relevance to the development of NAFLD will be presented in details. Moreover, current knowledge on incretins and bile acid pathway modulation in NAFLD will be discussed.

Published
2021

39. Time-Varying mHAP-III Is the Most Accurate Predictor of Survival in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization

Author

Francesco Giuseppe Foschi, Gianpaolo Vidili, Andrea Mega, Antonio Gasbarrini, Marco Zoli, Edoardo G. Giannini, Rodolfo Sacco, Alessandro Vitale, Francesco Tovoli, Giacomo Laffi, Maria Di Marco, Giovanni Raimondo, Gianluca Svegliati-Baroni, Claudia Campani, Francesco Azzaroli, Fabio Farinati, Umberto Arena, Fabio Marra, Gabriele Dragoni, Alberto Masotto, Franco Trevisani, Maurizia Rossana Brunetto, Giuseppe Cabibbo, Elisabetta Biasini, Gian Ludovico Rapaccini, Eugenio Caturelli, Gerardo Nardone, Maria Guarino, Umberto Cillo, Campani, C., Vitale, A., Dragoni, G., Arena, U., Laffi, G., Cillo, U., Giannini, E. G., Tovoli, F., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Sacco, R., Cabibbo, G., Mega, A., Guarino, M., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F. G., Biasini, E., Masotto, A., Nardone, G., Raimondo, G., Azzaroli, F., Vidili, G., Brunetto, M. R., Farinati, F., Trevisani, F., Marra, F., Campani C., Vitale A., Dragoni G., Arena U., Laffi G., Cillo U., Giannini E.G., Tovoli F., Rapaccini G.L., Di Marco M., Caturelli E., Zoli M., Sacco R., Cabibbo G., Mega A., Guarino M., Gasbarrini A., Svegliati-Baroni G., Foschi F.G., Biasini E., Masotto A., Nardone G., Raimondo G., Azzaroli F., Vidili G., Brunetto M.R., Farinati F., Trevisani F., and Marra F.

Subjects
ALBI grade, Barcelona Clinic Liver Cancer, Cancer of the Liver Italian Program, ITALICA staging system, MESIAH, medicine.medical_specialty, lcsh:RC254-282, Gastroenterology, Internal medicine, Medicine, In patient, Radiologic Response, Settore MED/12 - Gastroenterologia, Original Paper, Hepatology, business.industry, Proportional hazards model, Confounding, Hazard ratio, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Oncology, Hepatocellular carcinoma, Akaike information criterion, business, Liver cancer
Abstract

Introduction: The prognosis of patients undergoing transarterial chemoembolization (TACE) is extremely variable, and a confounding factor is that TACE is often repeated several times. We retrospectively evaluated the accuracy of different prognostic scores and staging systems in estimating overall survival (OS) in patients with hepatocellular carcinoma (HCC). Methods: An analysis considering prognostic models as time-varying variables was performed, calculating OS from the time of TACE to the time of the subsequent treatment. Total follow-up time for each patient was therefore split into several observation times accounting for each TACE procedure. Values of the likelihood ratio test (LRT) and Akaike information criterion (AIC) were used to compare different systems. Univariable and multivariable analyses were conducted to identify additional factors predictive of OS. We analyzed 1,610 TACE performed in 1,058 patients recorded in the Italian Liver Cancer database from 2008 through 2016. Results: The median OS of the enrolled patients was 41 months. According to LRT χ2 and AIC values based on the time-varying analysis, mHAP-III achieved the best values (41.72 and 4,625.49, respectively, p < 0.0001), indicating the highest predictive performance compared with all other scores (HAP, mHAP-II, ALBI, and pALBI) and staging systems (MELD, ITALICA, CLIP, MESH, MESIAH, JIS, HKLC, and BCLC). In the multivariable Cox proportional hazards model, mHAP-III maintained an independent effect on OS (hazard ratio 1.31, 95% CI: 1.10–1.55, p < 0.0001). Time-varying age, alcoholic etiology, radiologic response to TACE, and performing ablation or surgery after TACE were additional significant variables resulting from the multivariable model. Conclusion: An innovative time-varying analysis revealed that mHAP-III was the most accurate model in predicting OS in patients with HCC undergoing TACE. Other clinical pre- and post-TACE variables were also found to be relevant for this prediction.

Published
2021

40. List of contributors

Author

Giada Alterini, Gabrio Bassotti, Massimo Bellini, Teodora Surdea Blaga, Corrado Blandizzi, Stefano Brillanti, Francesco Bronzini, Rocchina Colucci, Dan L. Dumitrascu, Charlotte D’Mello, Francesca Fianchi, Matteo Fornai, Andrea Galli, Simona Grad, Yong-Ku Kim, Anna-Lena Laguna de la Vera, Luca Maroni, Luca Miele, Stefano Milani, Waltraud Pfeilschifter, Andrei V. Pop, Sandip Samanta, Giulia Scalese, Carola Severi, Debbie L. Shawcross, Cheolmin Shin, Cristina Stasi, Gianluca Svegliati Baroni, Mark G. Swain, Jonel Trebicka, Paolo Usai Satta, and Christoph Welsch

Published
2021

41. Predictors of worse prognosis in young and middle-aged adults hospitalized with covid-19 pneumonia: A multi-center italian study (covid-under50)

Author

Alessandro Zanforlin, Antonella Caminati, Susanna Contucci, Donatella Amico, Marina Saetta, Martina Bonifazi, Lara Letizia Latini, Umberto Zuccon, Edlira Skrami, Saverio Cinti, Sara Lococo, Elisabetta Balestro, Giampietro Marchetti, Floriano Bonifazi, Venerino Poletti, Flavia Carle, Stefano Gasparini, Francesco Bini, Sara Piciucchi, Alessandro Di Marco Berardino, Federico Mei, Claudia Ravaglia, Gianluca Svegliati-Baroni, Lina Zuccatosta, Mario Tamburrini, Sara Tomassetti, Piero Candoli, Guido Levi, Vincenzo Menditto, and Sergio Harari

Subjects
Pediatrics, medicine.medical_specialty, Population, lcsh:Medicine, 030209 endocrinology & metabolism, Comorbidity, Article, 03 medical and health sciences, 0302 clinical medicine, Mechanical ventilation, Diabetes mellitus, Internal medicine, medicine, 030212 general & internal medicine, Obesity, Mortality, education, Asthma, education.field_of_study, business.industry, Predictors, lcsh:R, COVID-19, Retrospective cohort study, General Medicine, Pneumonia, medicine.disease, Pulmonology, Young people, business, Body mass index
Abstract

Obesity as well as metabolic and cardiovascular comorbidities are established, significant predictors of worse prognosis in the overall COVID-19 population, but limited information is available on their roles in young and middle-aged adults (aged ≤ 50 years). The main objectives of the present Italian multi-center study were to describe clinical characteristics and role of selected prognostic predictors in a large cohort of young and middle-aged hospitalized patients. Nine pulmonology units, across north and center of Italy, were involved in this retrospective study. Comorbidities were classified according to their known or potential association with COVID-19. A total of 263 subjects were included. The prevalence of obesity was 25.9%, mechanical ventilation (MV) was needed in 27.7%, and 28 in-hospital deaths occurred (10.6%). Obesity and older age were the only independent, significant predictors for MV. Comorbidities, such as hypertension, diabetes, asthma, and increased D-dimer levels were significantly associated with higher mortality risk, regardless of age, body mass index, and MV. Obesity in young and middle-aged adults is a strong predictor of a more complicated COVID-19, without, however, evidence of a significant effect on in-hospital mortality. Selected comorbidities, including hypertension, diabetes and asthma, significantly impact survival even in a younger population, suggesting the need for prompt recognition of these conditions.

Published
2021

42. Liver Cirrhosis Complications Management at the Emergency Department

Author

Ludovico Abenavoli, Gianluca Svegliati-Baroni, Emidio Scarpellini, Francesco Luzza, Tiziana Larussa, Valeria Santori, Carmelo Luigiano, and Dan L. Dumitrascu

Subjects
Liver Cirrhosis, medicine.medical_specialty, Cirrhosis, medicine.medical_treatment, Liver transplantation, Esophageal and Gastric Varices, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Spontaneous bacterial peritonitis, Internal medicine, Ascites, medicine, Upper gastrointestinal, Humans, Hepatic encephalopathy, Pharmacology, business.industry, General Medicine, Emergency department, Variceal hemorrhage, medicine.disease, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, medicine.symptom, business, Emergency Service, Hospital, Gastrointestinal Hemorrhage
Abstract

Background and Aims: Liver cirrhosis (LC) of any origin has always been a source of several emergencies for physicians working at the Emergency Department (ER). LC patients can present with several complications that are sometimes difficult to recognize and treat. Thus, we reviewed the literature evidence for the diagnosis and management of several LC related emergencies. Methods: We conducted a search on the main medical databases for papers, reviews, metanalyses, case series, and RCTs using the following keywords and their associations: liver cirrhosis, variceal hemorrhage, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, hepato-renal syndrome, emergency. Results: Main LC emergencies are upper gastrointestinal hemorrhage, decompensated ascites and spontaneous bacterial peritonitis, hepatic encephalopathy, hepato-renal syndrome. Their management is partly medical and interventional. Very often, the final cure of some complications, such as hepato-renal syndrome, is represented by liver transplantation. Conclusions: Although LC prevalence is going to fall in the following years, due to HBV and HCV optimized treatments, its complications represent a significant admission percentage at the ER and challenge for physicians’ skills.

Published
2020

43. Liver transplantation in hepatocellular carcinoma after tumour downstaging (XXL): a randomised, controlled, phase 2b/3 trial

Author

Marco Bongini, Vincenzo Mazzaferro, Silvia Martini, Michele Colledan, Gianluca Svegliati Baroni, Massimo Rossi, Enrico Regalia, Maria Grazia Lucà, Stefano Ginanni Corradini, Mauro Salizzoni, Stefano Fagiuoli, Rosalba Miceli, Stefano Di Sandro, Maria Flores, Mario Angelico, Riccardo Volpes, S. Mirabella, Salvatore Gruttadauria, Luca S. Belli, Giuseppe Tisone, Riccardo De Carlis, Sherrie Bhoori, Luigi Mariani, Carlo Sposito, Davide Citterio, B. Antonelli, Renato Romagnoli, Massimo Iavarone, Marco Vivarelli, Massimo De Giorgio, Luciano De Carlis, Michele Droz dit Busset, Mazzaferro, V, Citterio, D, Bhoori, S, Bongini, M, Miceli, R, De Carlis, L, Colledan, M, Salizzoni, M, Romagnoli, R, Antonelli, B, Vivarelli, M, Tisone, G, Rossi, M, Gruttadauria, S, Di Sandro, S, De Carlis, R, Lucà, M, De Giorgio, M, Mirabella, S, Belli, L, Fagiuoli, S, Martini, S, Iavarone, M, Svegliati Baroni, G, Angelico, M, Ginanni Corradini, S, Volpes, R, Mariani, L, Regalia, E, Flores, M, Droz Dit Busset, M, and Sposito, C

Subjects
Sorafenib, Adult, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Adolescent, medicine.medical_treatment, Milan criteria, Liver transplantation, 03 medical and health sciences, Young Adult, 0302 clinical medicine, liver transplant, HCC, Internal medicine, medicine, Humans, Survival rate, Aged, Neoplasm Staging, business.industry, Carcinoma, Liver Neoplasms, Hepatocellular, Middle Aged, medicine.disease, Liver Transplantation, Transplantation, Survival Rate, Case-Control Studies, Female, Follow-Up Studies, Neoplasm Recurrence, Local, Neoplasm Recurrence, Oncology, Local, Response Evaluation Criteria in Solid Tumors, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Liver function, business, medicine.drug
Abstract

Summary Background Indications for liver transplantation for hepatocellular carcinoma are evolving and so-called expanded criteria remain debated. Locoregional therapies are able to downstage hepatocellular carcinoma from beyond to within the Milan criteria. We aimed to investigate the efficacy of liver transplantation after successful hepatocellular carcinoma downstaging. Methods We did an open-label, multicentre, randomised, controlled trial designed in two phases, 2b and 3, at nine Italian tertiary care and transplantation centres. Patients aged 18–65 years with hepatocellular carcinoma beyond the Milan criteria, absence of macrovascular invasion or extrahepatic spread, 5-year estimated post-transplantation survival of at least 50%, and good liver function (Child-Pugh A-B7) were recruited and underwent tumour downstaging with locoregional, surgical, or systemic therapies according to multidisciplinary decision. After an observation period of 3 months, during which sorafenib was allowed, patients with partial or complete responses according to modified Response Evaluation Criteria in Solid Tumors were randomly assigned (1:1) by an interactive web-response system to liver transplantation or non-transplantation therapies (control group). A block randomisation (block size of 2), stratified by centre and compliance to sorafenib treatment, was applied. Liver transplantation was done with whole or split organs procured from brain-dead donors. The control group received sequences of locoregional and systemic treatment at the time of demonstrated tumour progression. The primary outcomes were 5-year tumour event-free survival for phase 2b and overall survival for phase 3. Analyses were by intention to treat. Organ allocation policy changed during the course of the study and restricted patient accrual to 4 years. This trial is registered with ClinicalTrials.gov , NCT01387503 . Findings Between March 1, 2011, and March 31, 2015, 74 patients were enrolled. Median duration of downstaging was 6 months (IQR 4–11). 29 patients dropped out before randomisation and 45 were randomly assigned: 23 to the transplantation group versus 22 to the control group. At data cutoff on July 31, 2019, median follow-up was 71 months (IQR 60–85). 5-year tumour event-free survival was 76·8% (95% CI 60·8–96·9) in the transplantation group versus 18·3% (7·1–47·0) in the control group (hazard ratio [HR] 0·20, 95% CI 0·07–0·57; p=0·003). 5-year overall survival was 77·5% (95% CI 61·9–97·1) in the transplantation group versus 31·2% (16·6–58·5) in the control group (HR 0·32, 95% CI 0·11–0·92; p=0·035). The most common registered grade 3–4 serious adverse events were hepatitis C virus recurrence (three [13%] of 23 patients) and acute transplant rejection (two [9%]) in the transplantation group, and post-embolisation syndrome (two [9%] of 22 patients) in the control group. Treatment-related deaths occurred in four patients: two (8%) of 23 patients in the transplantation group (myocardial infarction and multi-organ failure) versus two (9%) of 22 patients in the control group (liver decompensation). Interpretation Although results must be interpreted with caution owing to the early closing of the trial, after effective and sustained downstaging of eligible hepatocellular carcinomas beyond the Milan criteria, liver transplantation improved tumour event-free survival and overall survival compared with non-transplantation therapies Post-downstaging tumour response could contribute to the expansion of hepatocellular carcinoma transplantation criteria. Funding Italian Ministry of Health.

Published
2020

44. Predictors of Worse Prognosis in Young Adults Hospitalized with COVID-19 Pneumonia: A Multi-Center Italian Study (COVID-UNDER50)

Author

Marina Saetta, Martina Bonifazi, Lara Letizia Latini, Saverio Cinti, Guido Levi, Venerino Poletti, Sergio Harari, Sara Piciucchi, Giampietro Marchetti, Sara Lococo, Gianluca Svegliati Baroni, Umberto Zuccon, Piero Candoli, Federico Mei, Floriano Bonifazi, Sara Tomassetti, Stefano Gasparini, Francesco Bini, Alessandro Di Marco Berardino, Mario Tamburrini, Vincenzo G Menditto, Alessandro Zanforlin, Antonella Caminati, Lina Zuccatosta, Susanna Contucci, Elisabetta Balestro, Flavia Carle, Edlira Skrami, Claudia Ravaglia, and Donatella Amico

Subjects
Pediatrics, medicine.medical_specialty, education.field_of_study, business.industry, Medical record, Population, Retrospective cohort study, medicine.disease, Comorbidity, Informed consent, Cohort, Medicine, Young adult, business, education, Body mass index
Abstract

Background: Obesity as well as metabolic and cardiovascular comorbidities are established, significant predictors of worse prognosis in overall COVID-19 population, but limited information are available on their specific roles in young adults (aged ≤ 50 years). The main objectives of the present Italian multi-center study were to describe clinical characteristics, and role of selected prognostic predictors, in particular obesity, in a large cohort of young hospitalized patients with COVID-19 pneumonia. Methods: Nine Pulmonology Units, across North and Centre of Italy, were involved in this retrospective study. Demographic and clinical characteristics as well as radiological features were registered for all cases. Comorbidity were classified according to their known or potential association with COVID-19. Findings: A total of 263 subjects were included. The prevalence of obesity was 25.9%, mechanical ventilation (MV) was needed in 73 patients (27.7%), and 28 in-hospital deaths occurred (10.6%). Obesity and older age were the only significant predictors for MV in a full model adjusted for comorbidities and markers of severity. Pre-existing comorbidities, such as hypertension, diabetes and asthma, and increased D-dimer level were significantly associated with higher mortality risk, regardless of age, body mass index, and MV. Interpretation: Obesity in young adults is, per se, a strong, independent, predictor of a more complicated COVID-19, without, however, influencing in-hospital mortality. On the other hand, selected comorbidities, mainly hypertension, diabetes and asthma, significantly impact survival even in a young population, and prompt recognition of these conditions as well as a closer surveillance of this subgroup are highly recommended. Funding: none. Declaration of Interests: Prof. Bonifazi reports speaker fees from Boehringer Ingelheim and Roche, outside the submitted work; Dr. Harari reports personal fees from Roche, grants and personal fees from Actelion and Boehringer Ingelheim, outside the submitted work. Ethics Approval Statement: Anonymized data of patients included in the study cohort were retrospectively collected from electronic medical records. The study protocol complies to the ethical guidelines of the 1975 Declaration of Helsinki and it was notified and approved by the coordinator ethics committee (n. 2020131) and by each local ethics committee and the need for patient’s informed consent was waived.

Published
2020

45. Research Strands in Dermatology and Gastroenterology Units of Department of Clinical and Molecular Sciences in Polytechnic Marche University

Author

Annamaria Offidani, I. Pierantonelli, Laura Schiadà, Antonio Benedetti, Antonio Di Sario, Emanuela Martina, Anna Campanati, Luca Maroni, Paola Sassaroli, Marco Marzioni, Gianluca Svegliati-Baroni, Oriana Simonetti, Emanuele Bendia, and Giuseppe Tarantino

Subjects
Helicobacter pylori infection, medicine.medical_specialty, integumentary system, business.industry, Non alcoholic, Disease, Alopecia areata, medicine.disease, Gastroenterology, Inflammatory bowel disease, Dermatology, Internal medicine, Psoriasis, Cutaneous melanoma, medicine, business, Pyoderma gangrenosum
Abstract

As examples of crucial interface organs gut and skin show more similarities than differences, therefore it is unsurprising that several gut pathologies have skin comorbidities, and vice versa. The relationship between gut and skin, referred as the “gut-skin axis”, is one of the most intriguing area of emerging research. However the complex interactions between skin and gut are far from to be completely elucidated, since neither mainstream gastroenterology nor dermatology research have systematically investigated the ‘gut-skin axis’. In the last years several clinical researches conducted jointly by Dermatology and Gastroenterology Unit of Department of Clinical and Molecular Sciences of Polytechnic Marche University have progressively contributed to give useful data to delineate the molecular mechanisms underlying the relationship between skin and gut. In the meantime, the improvement in the knowledge of pathogenic links between different disease involving skin and gastro-intestinal tract has contributed to increase the scientific cooperation between gastroenterologists and dermatologists, by feeding the research strands. Herein the results of several studies focusing on pathogenic relationship between gastrointestinal disorders as inflammatory bowel disease, non alcoholic fatty liver disease, helicobacter pylori infection and dermatologic disease like psoriasis, pyoderma gangrenosum, chronic spontaneous urticaria, suppurative hidradenitis and alopecia areata have been reported. Moreover results emerging from several other research lines involving gastroenterological and dermatological Unit independently, and focusing on cutaneous melanoma, wound healing, mesenchymal stem cells, and antimicrobial molecules are described.

Published
2020

46. 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

47. Lack of NLRP3-inflammasome leads to gut-liver axis derangement, gut dysbiosis and a worsened phenotype in a mouse model of NAFLD

Author

Chiara Rychlicki, I. Pierantonelli, C. Pinto, C. Saponaro, Amalia Gastaldelli, Saverio Cinti, Samuele De Minicis, Gianluca Svegliati-Baroni, Valeria Manghina, Marco Marzioni, Luciano Trozzi, Emma Buzzigoli, E. Mingarelli, Sergio Uzzau, Melania Gaggini, Laura Agostinelli, Antonio Giordano, Debora Maria Giordano, Loris Sartini, and Cristina Fraumene

Subjects
0301 basic medicine, medicine.medical_specialty, Cirrhosis, Adipose tissue, lcsh:Medicine, Biology, Article, 03 medical and health sciences, Internal medicine, medicine, lcsh:Science, Liver injury, Multidisciplinary, Intestinal permeability, Fatty liver, lcsh:R, Inflammasome, medicine.disease, 3. Good health, 030104 developmental biology, Endocrinology, Immunology, TLR4, lcsh:Q, Dysbiosis, medicine.drug
Abstract

Non-Alcoholic Fatty Liver Disease (NAFLD) represents the most common form of chronic liver injury and can progress to cirrhosis and hepatocellular carcinoma. A “multi-hit” theory, involving high fat diet and signals from the gut-liver axis, has been hypothesized. The role of the NLRP3-inflammasome, which senses dangerous signals, is controversial. Nlrp3−/− and wild-type mice were fed a Western-lifestyle diet with fructose in drinking water (HFHC) or a chow diet. Nlrp3−/−-HFHC showed higher hepatic expression of PPAR γ2 (that regulates lipid uptake and storage) and triglyceride content, histological score of liver injury and greater adipose tissue inflammation. In Nlrp3−/−-HFHC, dysregulation of gut immune response with impaired antimicrobial peptides expression, increased intestinal permeability and the occurrence of a dysbiotic microbiota led to bacterial translocation, associated with higher hepatic expression of TLR4 (an LPS receptor) and TLR9 (a receptor for double-stranded bacterial DNA). After antibiotic treatment, gram-negative species and bacterial translocation were reduced, and adverse effects restored both in liver and adipose tissue. In conclusion, the combination of a Western-lifestyle diet with innate immune dysfunction leads to NAFLD progression, mediated at least in part by dysbiosis and bacterial translocation, thus identifying new specific targets for NAFLD therapy.

Published
2017

48. Nonalcoholic fatty liver disease impairs the cytochrome P-450-dependent metabolism of α-tocopherol (vitamin E)

Author

Roberta Galarini, Chiara Rychlicki, Angelo Russo, Guido Bellezza, Francesco Galli, Angelo Sidoni, Desirée Bartolini, Pierangelo Torquato, Carolina Barola, Gianluca Svegliati-Baroni, and Danilo Giusepponi

Subjects
Male, 0301 basic medicine, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, Palmitic Acid, Fatty Acids, Nonesterified, Biochemistry, Palmitic acid, chemistry.chemical_compound, Endocrinology, Non-alcoholic Fatty Liver Disease, Nonalcoholic fatty liver disease, Vitamin E, PPAR-γ, Tocopherol, Nutrition and Dietetics, NASH, food and beverages, Hep G2 Cells, Diabetes and Metabolism, Liver, lipids (amino acids, peptides, and proteins), Diet, Carbohydrate Loading, Sterol Regulatory Element Binding Protein 1, Vitamin, medicine.medical_specialty, Fructose, Biology, Diet, High-Fat, Hydroxylation, SREBP, 03 medical and health sciences, NAFLD, Internal medicine, medicine, Animals, Humans, Cytochrome P450 Family 4, Molecular Biology, Lipid metabolism, Metabolism, medicine.disease, Mice, Inbred C57BL, PPAR gamma, 030104 developmental biology, Gene Expression Regulation, chemistry, Diet, Western, Alpha-tocopherol, CYP4F2, alpha-Tocopherol, Oleic Acid
Abstract

This study aims to investigate in in vivo and in vitro models of nonalcoholic fatty liver disease (NAFLD) the enzymatic metabolism of α-tocopherol (vitamin E) and its relationship to vitamin E-responsive genes with key role in the lipid metabolism and detoxification of the liver. The experimental models included mice fed a high-fat diet combined or not with fructose (HFD+F) and HepG2 human hepatocarcinoma cells treated with the lipogenic agents palmitate, oleate or fructose. CYP4F2 protein, a cytochrome P-450 isoform with proposed α-tocopherol ω-hydroxylase activity, decreased in HFD and even more in HFD+F mice liver; this finding was associated with increased hepatic levels of α-tocopherol and decreased formation of the corresponding long-chain metabolites α-13-hydroxy and α-13-carboxy chromanols. A decreased expression was also observed for PPAR-γ and SREBP-1 proteins, two vitamin E-responsive genes with key role in lipid metabolism and CYP4F2 gene regulation. A transient activation of CYP4F2 gene followed by a repression response was observed in HepG2 cells during the exposure to increasing levels of the lipogenic and cytotoxic agent palmitic acid; such gene repression effect was further exacerbated by the co-treatment with oleic acid and α-tocopherol and was also observed for PPAR-γ and the SREBP isoforms 1 and 2. Such gene response was associated with increased uptake and ω-hydroxylation of α-tocopherol, which suggests a minor role of CYP4F2 in the enzymatic metabolism of vitamin E in HepG2 cells. In conclusion, the liver metabolism and gene response of α-tocopherol are impaired in experimental NAFLD.

Published
2017

49. Fibronectin Type III Domain–Containing Protein 5 rs3480 A>G Polymorphism, Irisin, and Liver Fibrosis in Patients With Nonalcoholic Fatty Liver Disease

Author

I. Pierantonelli, Debora Maria Giordano, Luca Valenti, Vito Di Marco, Massimiliano Ruscica, Calogero Cammà, Chiara Rychlicki, Gianluca Svegliati-Baroni, Marica Meroni, Marco Maggioni, Silvia Fargion, Salvatore Petta, Antonio Craxì, Nicola Ferri, Rosaria Maria Pipitone, Anna Ludovica Fracanzani, Stefania Grimaudo, Paola Dongiovanni, Daniela Cabibi, Petta, S., Valenti, L., Svegliati-Baroni, G., Ruscica, M., Pipitone, R., Dongiovanni, P., Rychlicki, C., Ferri, N., Cammà, C., Fracanzani, A., Pierantonelli, I., Di Marco, V., Meroni, M., Giordano, D., Grimaudo, S., Maggioni, M., Cabibi, D., Fargion, S., and Craxì, A.

Subjects
Liver Cirrhosis, Male, 0301 basic medicine, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Severity of Illness Index, Biochemistry, Gastroenterology, Mice, Endocrinology, Non-alcoholic Fatty Liver Disease, Fibrosis, Nonalcoholic fatty liver disease, Odds Ratio, Prospective Studies, Carbon Tetrachloride, medicine.diagnostic_test, Reverse Transcriptase Polymerase Chain Reaction, Hep G2 Cells, Middle Aged, FNDC5, Liver, Liver biopsy, Female, Adult, medicine.medical_specialty, In Vitro Techniques, Diet, High-Fat, Real-Time Polymerase Chain Reaction, Polymorphism, Single Nucleotide, 03 medical and health sciences, Diabetes mellitus, Internal medicine, Myokine, Hepatic Stellate Cells, medicine, Animals, Humans, FNDC5, IRISIN, NAFLD, Genetic Predisposition to Disease, business.industry, Biochemistry (medical), medicine.disease, digestive system diseases, Fibronectins, 030104 developmental biology, Case-Control Studies, Hepatic stellate cell, Steatosis, business
Abstract

Context Contrasting data have been reported on the role of irisin, a novel myokine encoded by the fibronectin type III domain-containing protein 5 (FNDC5) gene, in nonalcoholic fatty liver disease (NAFLD) pathogenesis. We tested in patients with suspected nonalcoholic steatohepatitis (NASH) the association of FNDC5 variants, hepatic expression, and circulating irisin with liver damage (F2 to F4 fibrosis as main outcome). We also investigated whether irisin modulates hepatocellular fat accumulation and stellate cell activation in experimental models. Methods We considered 593 consecutive patients who underwent liver biopsy for suspected NASH and 192 patients with normal liver enzymes and without steatosis. FNDC5 rs3480 and rs726344 genotypes were assessed by 5' nuclease assays. Hepatic irisin expression was evaluated in mice fed a high-fat diet or treated with CCl4. The effect of irisin was evaluated in fat-laden HepG2 hepatocytes and in hepatic stellate cells (HSCs). Results In patients at risk for NASH [odds ratio (OR) = 0.64, 95% confidence interval (CI), 0.47 to 0.87; P = 0.005], and more so in the high-risk subgroup of those with impaired fasting glucose/diabetes (OR = 0.44, 95% CI, 0.26 to 0.74; P = 0.002), the rs3480 A>G variant was independently associated with protection from F2 to F4 fibrosis. Irisin is expressed in human activated HSC, where it mediated fibrogenic actions and collagen synthesis, and is overexpressed in NAFLD patients with F2 to F4 fibrosis and CCl4-treated mice. However, Irisin does not affect fat accumulation in HepG2 and is not induced by high-fat-diet-inducing NAFLD. Conclusions The FNDC5 rs3480 variant is associated with protection from clinically significant fibrosis in patients with NAFLD, while irisin expression is correlated with the severity of NAFLD and may be involved in extracellular matrix deposition. These data suggest that irisin is involved in regulation of hepatic fibrogenesis.

Published
2017

50. Mechanisms for increased risk of diabetes in chronic liver diseases

Author

Ramy Youne, Fabrizia Carli, Monica Cucco, Amalia Gastaldelli, Chiara Rosso, Elisabetta Bugianesi, Melania Gaggini, Chiara Barbieri, and Gianluca Svegliati-Baroni

Subjects
Blood Glucose, endocrine system, medicine.medical_specialty, endocrine system diseases, medicine.medical_treatment, Glucose Tolerance Test, Humans, Insulin, Diabetes Mellitus, Type 2, Insulin Resistance, Non-alcoholic Fatty Liver Disease, Chronic liver disease, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Diabetes mellitus, Internal medicine, medicine, Diabetes Mellitus, Glucose tolerance test, Hepatology, medicine.diagnostic_test, business.industry, Fatty liver, nutritional and metabolic diseases, medicine.disease, 3. Good health, 030220 oncology & carcinogenesis, Liver biopsy, 030211 gastroenterology & hepatology, Steatosis, business, hormones, hormone substitutes, and hormone antagonists, Type 2
Abstract

OBJECTIVE Patients with chronic liver disease (CLD), both non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC), are at high risk of diabetes (T2D), but mechanisms are still unknown. Muscle/liver insulin resistance (IR) and pancreatic dysfunction are the major metabolic defects leading to T2D. However, if the risk of T2D in CLD patients is because of reduced insulin response and/or to IR, and the impact of liver histology has not been investigated. DESIGN We studied 220 non-T2D patients with chronic liver disease (129 NAFLD, BMI = 27.3 kg/m2 ; 91 CHC, BMI = 25.0 kg/m2 ) that received a 75-gram oral glucose tolerance test (OGTT) with the measurement of glucose and insulin concentrations for 2 hours, glucose tolerance (NGT vs IGT) and liver biopsy. The results were compared to 26 controls (CT-NGT, BMI = 25.6 kg/m2 ). We evaluated peripheral insulin sensitivity (OGIS), OGTT-insulin response (ΔAUC-I/ΔAUC-G) and disposition-index (DI = OGIS∙ΔAUC-I/ΔAUC-G) for the risk to develop T2D. RESULTS NAFLD had increased muscle IR (associated to NASH, steatosis and fibrosis), higher than in CHC or CT-NGT (OGIS = 8.9 vs 11.3 and 10.5 mL/min kg, P < .0001). In NAFLD, OGTT-insulin response (ΔAUC-I/ΔAUC-G) was the highest while it was significantly decreased in CHC (2.2 vs 1.1 and 1.6, NAFLD vs. CHC and CT-NGT, P < .005). The highest T2D risk (low DI) was observed in CHC-IGT (7.5), CHC-NGT (13.5) and NAFLD-IGT (10.8) vs CT-NGT (14.9, all P < .0001), but not in NAFL-NGT or NASH-NGT. CONCLUSION We observed an increased T2D risk in NAFLD-IGT, CHC-IGT and CHC-NGT mainly because of reduced OGTT-insulin response, while insulin response in NAFLD-NGT compensates the IR thus maintaining normal glycaemia.

Published
2019

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