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1. Oesophageal varices predict complications in compensated advanced non-alcoholic fatty liver disease

Author

Ministero dell'Istruzione e del Merito, Fonds de Recherche du Québec, Pennisi, Grazia, Enea, Marco, Viganò, Mauro, Schepis, Filippo, Ledinghen, Victor de, Berzigotti, Annalisa, Wai-Sun Wong, Vincent, Fracanzani, Anna Ludovica, Sebastiani, Giada, Lara-Romero, Carmen, Bugianesi, Elisabetta, Svegliati-Baroni, Gianluca, Marra, Fabio, Aghemo, Alessio, Valenti, Luca, Calvaruso, Vincenza, Colecchia, Antonio, Di Maria, Gabriele, La Mantia, Claudia, Lin, Huapeng, Mendoza, Yuly, Pugliese, Nicola, Ravaioli, Federico, Romero-Gómez, Manuel, Saltini, Dario, Craxi, Antonio, Di Marco, Vito, Cammà, Calogero, Petta, Salvatore, Ministero dell'Istruzione e del Merito, Fonds de Recherche du Québec, Pennisi, Grazia, Enea, Marco, Viganò, Mauro, Schepis, Filippo, Ledinghen, Victor de, Berzigotti, Annalisa, Wai-Sun Wong, Vincent, Fracanzani, Anna Ludovica, Sebastiani, Giada, Lara-Romero, Carmen, Bugianesi, Elisabetta, Svegliati-Baroni, Gianluca, Marra, Fabio, Aghemo, Alessio, Valenti, Luca, Calvaruso, Vincenza, Colecchia, Antonio, Di Maria, Gabriele, La Mantia, Claudia, Lin, Huapeng, Mendoza, Yuly, Pugliese, Nicola, Ravaioli, Federico, Romero-Gómez, Manuel, Saltini, Dario, Craxi, Antonio, Di Marco, Vito, Cammà, Calogero, and Petta, Salvatore more...

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. more...

Published
2023

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

Author

Pelizzaro, Filippo, Haxhi, Selion, Penzo, Barbara, Vitale, Alessandro, Giannini, Edoardo G, Sansone, Vito, Rapaccini, Gian Ludovico, Di Marco, Maria Teresa, Caturelli, Eugenio, Magalotti, Donatella, Sacco, Rodolfo, Celsa, Ciro, Campani, Claudia, Mega, Andrea, Guarino, Maria, Gasbarrini, Antonio, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, Olivani, Andrea, Masotto, Alberto, Nardone, Gerardo, Raimondo, Giovanni, Azzaroli, Francesco, Vidili, Gianpaolo, Brunetto, Maurizia Rossana, Trevisani, Franco, Farinati, Fabio, Rapaccini, Gian Ludovico (ORCID:0000-0002-6467-857X), Di Marco, Maria, Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), Pelizzaro, Filippo, Haxhi, Selion, Penzo, Barbara, Vitale, Alessandro, Giannini, Edoardo G, Sansone, Vito, Rapaccini, Gian Ludovico, Di Marco, Maria Teresa, Caturelli, Eugenio, Magalotti, Donatella, Sacco, Rodolfo, Celsa, Ciro, Campani, Claudia, Mega, Andrea, Guarino, Maria, Gasbarrini, Antonio, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, Olivani, Andrea, Masotto, Alberto, Nardone, Gerardo, Raimondo, Giovanni, Azzaroli, Francesco, Vidili, Gianpaolo, Brunetto, Maurizia Rossana, Trevisani, Franco, Farinati, Fabio, Rapaccini, Gian Ludovico (ORCID:0000-0002-6467-857X), Di Marco, Maria, and Gasbarrini, Antonio (ORCID:0000-0002-7278-4823) more...

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 rol more...

Published
2022

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

Author

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 Teresa, 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, Rapaccini, Gian Ludovico (ORCID:0000-0002-6467-857X), Di Marco, Maria, Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), 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 Teresa, 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, Rapaccini, Gian Ludovico (ORCID:0000-0002-6467-857X), Di Marco, Maria, and Gasbarrini, Antonio (ORCID:0000-0002-7278-4823) more...

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. (C) 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. more...

Published
2022

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

Author

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 Teresa, Sangiovanni, Angelo, Trevisani, Franco, Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), Rapaccini, Gian Ludovico (ORCID:0000-0002-6467-857X), Di Marco, Maria, 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 Teresa, Sangiovanni, Angelo, Trevisani, Franco, Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), Rapaccini, Gian Ludovico (ORCID:0000-0002-6467-857X), and Di Marco, Maria more...

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 (2.6 vs 4.0 cm, P = 0.007). Curative treatment, feasible in 50.0% of patients, was associated with improved survival compared to palliative and supportive care (42 vs 33 vs 6 months, P<0.0001). Surveillance was associated with a non-significant improved survival (36 vs 23 months), likely due to similar rate of curative treatment in patients under (51.4%) and outside surveillance (42.6%). Conclusions: PBC patients with HCC are often elderly males with well-preserved liver function. Feasibility of curative treatment is high and associated with improved prognosis. Description of these patients may help focus surveillance to identify earlier tumours, increase their curability, and improve prognosis. more...

Published
2022

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

Author

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, Farinati, Fabio, Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), Miele, Luca (ORCID:0000-0003-3464-0068), 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, Farinati, Fabio, Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), and Miele, Luca (ORCID:0000-0003-3464-0068) more...

Abstract

Background Metabolic 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. Methods We 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. Results MAFLD 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, p<0.001). In Italy S-MAFLD HCC is expected to overcome M-MAFLD HCC in about 6 years. Patients with S-MAFLD HCC were older, more frequently men and less frequently cirrhotic with clinically relevant portal hypertension and a surveillance-related diagnosis. They had more frequently large tumours and extrahepatic metastases. After weighting, and compared with patients with non-MAFLD, S-MAFLD and M-MAFLD HCC showed a significantly lower overall (p=0.026, p=0.004) and HCC-related (p<0.001, for both) risk of death. Patients with S-MAFLD HCC showed a significantly higher risk of non-HCC-related death (p=0.006). Conclusions The 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. more...

Published
2021

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

Author

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

Abstract

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 downsta more...

Published
2020

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

Author

Caraceni, Paolo, Tufoni, Manuel, Zaccherini, Giacomo, Riggio, Oliviero, Angeli, Paolo, Alessandria, Carlo, Neri, Sergio, Foschi, Francesco G, Levantesi, Fabio, Airoldi, Aldo, Simone, Loredana, Svegliati-Baroni, Gianluca, Fagiuoli, Stefano, Laffi, Giacomo, Cozzolongo, Raffaele, Di Marco, Vito, Sangiovanni, Vincenzo, Morisco, Filomena, Toniutto, Pierluigi, Gasbarrini, Antonio, De Marco, Rosanna, Piano, Salvatore, Nardelli, Silvia, Elia, Chiara, Roncadori, Andrea, Baldassarre, Maurizio, Bernardi, Mauro, Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), Caraceni, Paolo, Tufoni, Manuel, Zaccherini, Giacomo, Riggio, Oliviero, Angeli, Paolo, Alessandria, Carlo, Neri, Sergio, Foschi, Francesco G, Levantesi, Fabio, Airoldi, Aldo, Simone, Loredana, Svegliati-Baroni, Gianluca, Fagiuoli, Stefano, Laffi, Giacomo, Cozzolongo, Raffaele, Di Marco, Vito, Sangiovanni, Vincenzo, Morisco, Filomena, Toniutto, Pierluigi, Gasbarrini, Antonio, De Marco, Rosanna, Piano, Salvatore, Nardelli, Silvia, Elia, Chiara, Roncadori, Andrea, Baldassarre, Maurizio, Bernardi, Mauro, and Gasbarrini, Antonio (ORCID:0000-0002-7278-4823) more...

Abstract

N/A

Published
2020

8. Recommendations for Management and Treatment of Nonalcoholic Steatohepatitis

Author

Ratziu, Vlad, Ghabril, Marwan, Romero-Gómez, Manuel, Svegliati-Baroni, Gianluca, Ratziu, Vlad, Ghabril, Marwan, Romero-Gómez, Manuel, and Svegliati-Baroni, Gianluca

Abstract

The prevalence of nonalcoholic liver disease (NAFLD) is increasing worldwide in conjunction with the epidemic increase in obesity and metabolic risk factors. Consequently, NAFLD has become a leading indication for liver transplantation. Although genetic factors play an important role in the pathogenesis of NAFLD, detrimental lifestyle trends favoring a calorically unrestricted diet rich in carbohydrates and unsaturated fat, prolonged sedentary periods or limited physical activity have major metabolic implications. In aggregate these physiological dysregulations constitute the main risk factors for the metabolic syndrome and NAFLD. The cornerstone of the treatment of NAFLD, is lifestyle changes, including modifications to diet and physical activity, to reduce body weight and liver fat, however adherence is notoriously poor and the epidemic of NAFLD continues to grow unimpeded. In the face of this unmet clinical need, the pharmacologic therapy of NAFLD has been expanding as the varied mechanistic pathways of NAFLD are elucidated. Beyond these approaches to treating NAFLD, the prevention of other liver diseases is additionally important. Chief among these is alcoholic liver disease, and heavy use is detrimental irrespective of underlying NAFLD. However, the impact of mild to moderate alcohol use in patients with mild or nonadvanced forms NAFLD is undefined. This article summarizes the results of the International Liver Transplantation Society consensus meeting on NAFLD in liver transplantation. It describes the available evidence and provides consensus guidance on the lifestyle and pharmacologic therapies of NAFLD, and the consensus position on alcohol use in patients with NAFLD. more...

Published
2019

9. Restaging Patients With Hepatocellular Carcinoma Before Additional Treatment Decisions: A Multicenter Cohort Study

Author

Vitale, Alessandro, Farinati, Fabio, Noaro, Giulia, Burra, Patrizia, Pawlik, Timothy M., Bucci, Laura, Giannini, Edoardo G., Faggiano, Chiara, Ciccarese, Francesca, Rapaccini, Gian Lodovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Cabibbo, Giuseppe, Virdone, Roberto, Marra, Fabio, Felder, Martina, Morisco, Filomena, Benvegnù, Luisa, Gasbarrini, Antonio, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, Olivani, Andrea, Masotto, Alberto, Nardone, Gerardo, Colecchia, Antonio, Fornari, Fabio, Marignani, Massimo, Vicari, Susanna, Bortolini, Emanuela, Cozzolongo, Raffaele, Grasso, Alessandro Giovanni, Aliberti, Camillo, Bernardi, Mauro, Frigo, Anna Chiara, Borzio, Mauro, Trevisani, Franco, Cillo, Umberto, Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), Vitale, Alessandro, Farinati, Fabio, Noaro, Giulia, Burra, Patrizia, Pawlik, Timothy M., Bucci, Laura, Giannini, Edoardo G., Faggiano, Chiara, Ciccarese, Francesca, Rapaccini, Gian Lodovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Cabibbo, Giuseppe, Virdone, Roberto, Marra, Fabio, Felder, Martina, Morisco, Filomena, Benvegnù, Luisa, Gasbarrini, Antonio, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, Olivani, Andrea, Masotto, Alberto, Nardone, Gerardo, Colecchia, Antonio, Fornari, Fabio, Marignani, Massimo, Vicari, Susanna, Bortolini, Emanuela, Cozzolongo, Raffaele, Grasso, Alessandro Giovanni, Aliberti, Camillo, Bernardi, Mauro, Frigo, Anna Chiara, Borzio, Mauro, Trevisani, Franco, Cillo, Umberto, and Gasbarrini, Antonio (ORCID:0000-0002-7278-4823) more...

Abstract

Prognostic assessment of patients with hepatocellular carcinoma (HCC) at the time of diagnosis remains controversial and becomes even more complex at the time of restaging when new variables need to be considered. The aim of the current study was to evaluate the prognostic utility of restaging patients before proceeding with additional therapies for HCC. Two independent Italian prospective databases were used to identify 1,196 (training cohort) and 648 (validation cohort) consecutive patients with HCC treated over the same study period (2008-2015) who had complete restaging before decisions about additional therapies. The performance of the Italian Liver Cancer (ITA.LI.CA) prognostic score at restaging was compared with that of the Barcelona Clinic Liver Cancer, Hong Kong Liver Cancer, and Cancer of the Liver Italian Program systems. A multivariable Cox survival analysis was performed to identify baseline, restaging, or dynamic variables that were able to improve the predictive performance of the prognostic systems. At restaging, 35.3% of patients maintained stable disease; most patients were either down-staged by treatment (27.2%) or had disease progression (37.5%). The ITA.LI.CA scoring system at restaging demonstrated the best prognostic performance in both the training and validation cohorts (c-index 0.707 and 0.722, respectively) among all systems examined. On multivariable analysis, several variables improved the prognostic ability of the ITA.LI.CA score at restaging, including progressive disease after the first treatment, Model for End-Stage Liver Disease at restaging, and choice of nonsurgical treatment as additional therapy. A new ITA.LI.CA restaging model was created that demonstrated high discriminative power in both the training and validation cohorts (c-index 0.753 and 0.745, respectively). Conclusion: Although the ITA.LI.CA score demonstrated the best prognostic performance at restaging, other variables should be considered to improve the prognostic a more...

Published
2018

10. Utility of Tumor Burden Score to Stratify Prognosis of Patients with Hepatocellular Cancer: Results of 4759 Cases from ITA.LI.CA Study Group

Author

Vitale, Alessandro, Lai, Quirino, Farinati, Fabio, Bucci, Laura, Giannini, Edoardo G., Napoli, Lucia, Ciccarese, Francesca, Rapaccini, Gian Lodovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Cabibbo, Giuseppe, Virdone, Roberto, Marra, Fabio, Felder, Martina, Morisco, Filomena, Benvegnù, Luisa, Gasbarrini, Antonio, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, Missale, Gabriele, Masotto, Alberto, Nardone, Gerardo, Colecchia, Antonio, Bernardi, Mauro, Trevisani, Franco, Pawlik, Timothy M., Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), Vitale, Alessandro, Lai, Quirino, Farinati, Fabio, Bucci, Laura, Giannini, Edoardo G., Napoli, Lucia, Ciccarese, Francesca, Rapaccini, Gian Lodovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Cabibbo, Giuseppe, Virdone, Roberto, Marra, Fabio, Felder, Martina, Morisco, Filomena, Benvegnù, Luisa, Gasbarrini, Antonio, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, Missale, Gabriele, Masotto, Alberto, Nardone, Gerardo, Colecchia, Antonio, Bernardi, Mauro, Trevisani, Franco, Pawlik, Timothy M., and Gasbarrini, Antonio (ORCID:0000-0002-7278-4823) more...

Abstract

Background: Dichotomous models like Milan Criteria represent the routinely used tools for predicting the outcome of patients with hepatocellular carcinoma (HCC). However, a paradigm shift from a dichotomous to continuous prognostic stratification should represent a good strategy for improving the prediction process. Recently, the tumor burden score (TBS) has been proposed for selecting patients with colorectal liver metastases. To date, TBS has not been validated in a large HCC population. The main objective of this study was to evaluate the prognostic power of TBS in an HCC population treated with different curative and palliative modalities. Methods: Prospectively collected data from consecutive HCC patients managed in 24 institutions participating in the ITA.LI.CA group between Jan 2002 and Mar 2015 were analyzed (n = 4759). A sub-analysis focused on 3909 patients with the radiological evidence of vascular invasion or metastatic disease was also performed. Results: TBS demonstrated the best discriminative ability when compared to MC and other tumor-specific scores. At multivariable Cox regression analysis, TBS was an independent risk factor of overall survival, with a 6% increased risk for patient death for each point increase in TBS. At survival analysis, when TBS â ¥ 8 was connected with MELD â ¥ 15 and alpha-fetoprotein â ¥ 1000 ng/mL, patients presenting all these three risk factors presented the worst results (p value < 0.0001). Conclusions: Survival prediction of HCC patients was very well done using TBS model, even stratifying the population in relation to the presence of metastases and/or vascular invasion. TBS model was the best in terms of discriminatory ability and goodness of fit when compared with other continuous or binary variables. Its incorporation in a model composed by tumor- and liver function-related variables further increases its survival prediction. more...

Published
2018

11. Hepatic decompensation is the major driver of death in HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma

Author

Cabibbo, Giuseppe, Petta, Salvatore, Barbara, Marco, Attardo, Simona, Bucci, Laura, Farinati, Fabio, Giannini, Edoardo G., Negrini, Giulia, Ciccarese, Francesca, Rapaccini, Gian Ludovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Virdone, Roberto, Marra, Fabio, Mega, Andrea, Morisco, Filomena, Benvegnã1, Luisa, Gasbarrini, Antonio, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, Olivani, Andrea, Masotto, Alberto, Nardone, Gerardo, Colecchia, Antonio, Persico, Marcello, Craxã¬, Antonio, Trevisani, Franco, Cammã&nbsp, Calogero, Rapaccini, GL (ORCID:0000-0002-6467-857X), Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), Cabibbo, Giuseppe, Petta, Salvatore, Barbara, Marco, Attardo, Simona, Bucci, Laura, Farinati, Fabio, Giannini, Edoardo G., Negrini, Giulia, Ciccarese, Francesca, Rapaccini, Gian Ludovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Virdone, Roberto, Marra, Fabio, Mega, Andrea, Morisco, Filomena, Benvegnã1, Luisa, Gasbarrini, Antonio, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, Olivani, Andrea, Masotto, Alberto, Nardone, Gerardo, Colecchia, Antonio, Persico, Marcello, Craxã¬, Antonio, Trevisani, Franco, Cammã&nbsp, Calogero, Rapaccini, GL (ORCID:0000-0002-6467-857X), and Gasbarrini, Antonio (ORCID:0000-0002-7278-4823) more...

Abstract

Background & Aims Assessment of long-term outcome is required in hepatitis C virus (HCV)-infected patients with cirrhosis, who have been successfully treated for Barcelona Clinic Liver Cancer (BCLC) stage A hepatocellular carcinoma (HCC). However, problems arise due to the lack of models accounting for early changes during follow-up. The aim of this study was to estimate the impact of early events (HCC recurrence or hepatic decompensation within 12 months of complete radiological response) on 5-year overall survival (OS) in a large cohort of patients with HCV and cirrhosis, successfully treated HCC. Methods A total of 328 consecutive Caucasian patients with HCV-related cirrhosis and BCLC stage 0/A HCC who had complete radiological response after curative resection or thermal ablation were prospectively recruited to this study. Primary endpoint of the study was 5-year OS. Independent baseline and time-dependent predictors of 5-year OS were identified by Cox model. Results The observed 5-year survival rate was 44%. The observed HCC early recurrence and early hepatic decompensation rate were 21% and 10%, respectively. Early hepatic decompensation (Hazard Ratio [HR] 7.52; 95% confidence intervals (CI): 1.23–13.48) and HCC early recurrence as time-dependent covariates (HR 2.50; 95%CI: 1.23–5.05), presence of esophageal varices at baseline (HR 1.66; 95% CI: 1.02–2.70) and age (HR 1.04; 95% CI: 1.02–1.07) were significantly associated with the 5-year OS. Conclusion Survival in HCV-infected patients with cirrhosis and successfully treated HCC is influenced by early hepatic decompensation. Our study indirectly suggests that direct-acting antiviral agents could improve OS of HCC patients through long-term preservation of liver function, resulting in a lower cirrhosis-related mortality and a greater change of receiving curative treatments. Lay summary Survival in hepatitis C virus (HCV) infected patients with cirrhosis and successfully treated hepatocell more...

Published
2017

12. Hepatocellular carcinoma recurrence in patients with curative resection or ablation: impact of HCV eradication does not depend on the use of interferon

Author

Petta, S., Cabibbo, G., Barbara, M., Attardo, S., Bucci, L., Farinati, F., Giannini, E. G., Tovoli, F., Ciccarese, F., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Virdone, R., Marra, F., Felder, M., Morisco, F., Benvegnù, L., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F. G., Olivani, A., Masotto, A., Nardone, G., Colecchia, A., Persico, M., Boccaccio, V., Craxì, A., Bruno, S., Trevisani, F., Cammà, C, Biselli, Maurizio, Caraceni, Paolo, Cucchetti, Alessandro, Domenicali, Marco, Piscaglia, Fabio, Gramenzi, Annagiulia, Granito, Alessandro, Magalotti, Donatella, Serra, Carla, Negrini, Giulia, Napoli, L., Napoli, Lucia, Salvatore, Veronica, Benevento, Francesca, Gazzola, Alessia, Murer, Francesca, Pozzan, Caterina, Vanin, Veronica, Moscatelli, Alessandro, Pellegatta, Gaia, Picciotto, Antonino, Savarino, Vincenzo, Delpoggio, Paolo, Olmi, Stefano, De Matthaeis, Nicoletta, Balsamo, Claudia, Vavassori, Elena, Roselli, Paola, Dell’Isola, Serena, Ialungo, Anna Maria, Rastrelli, Elena, Rini, Francesca, Costantino, Andrea, Affronti, Andrea, Affronti, Marco, Mascari, Marta, Mega, Andrea, Pompili, Maurizio, Rinninella, Emanuele, Mismas, Valeria, Dall’Aglio, Anna Chiara, Feletti, Valentina, Lanzi, Arianna, Cappa, Federica Mirici, Neri, Elga, Stefanini, Giuseppe Francesco, Tamberi, Stefano, Biasini, Elisabetta, Missale, Gabriele, Guarino, Maria, Ortolani, Alessio, Chiaramonte, Maria, Marchetti, Fabiana, Valerio, Matteo, Aburas, Sami, Inghilesi, Andrea L., Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Coccoli, Piero, Zamparelli, Marco Sanduzzi, Petta, Salvatore, Cabibbo, Giuseppe, Barbara, Marco, Attardo, Simona, Bucci, Laura, Farinati, Fabio, Giannini, Edoardo G., Tovoli, Francesco, Ciccarese, Francesca, Rapaccini, Gian Lodovico, Dimarco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Virdone, Roberto, Marra, Fabio, Felder, Martina, Morisco, Filomena, Benvegnù, Luisa, Gasbarrini, Antonio, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, Olivani, Andrea, Masotto, Alberto, Nardone, Gerardo, Colecchia, Antonio, Persico, Marcello, Boccaccio, Vincenzo, Craxì, Antonio, Bruno, Savino, Trevisani, Franco, Cammà, Calogero, Rapaccini, G. L. (ORCID:0000-0002-6467-857X), Gasbarrini, A. (ORCID:0000-0002-7278-4823), Pompili, Maurizio (ORCID:0000-0001-6699-7980), Rinninella, Emanuele (ORCID:0000-0002-9165-2367), Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), Petta, S., Cabibbo, G., Barbara, M., Attardo, S., Bucci, L., Farinati, F., Giannini, E. G., Tovoli, F., Ciccarese, F., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Virdone, R., Marra, F., Felder, M., Morisco, F., Benvegnù, L., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F. G., Olivani, A., Masotto, A., Nardone, G., Colecchia, A., Persico, M., Boccaccio, V., Craxì, A., Bruno, S., Trevisani, F., Cammà, C, Biselli, Maurizio, Caraceni, Paolo, Cucchetti, Alessandro, Domenicali, Marco, Piscaglia, Fabio, Gramenzi, Annagiulia, Granito, Alessandro, Magalotti, Donatella, Serra, Carla, Negrini, Giulia, Napoli, L., Napoli, Lucia, Salvatore, Veronica, Benevento, Francesca, Gazzola, Alessia, Murer, Francesca, Pozzan, Caterina, Vanin, Veronica, Moscatelli, Alessandro, Pellegatta, Gaia, Picciotto, Antonino, Savarino, Vincenzo, Delpoggio, Paolo, Olmi, Stefano, De Matthaeis, Nicoletta, Balsamo, Claudia, Vavassori, Elena, Roselli, Paola, Dell’Isola, Serena, Ialungo, Anna Maria, Rastrelli, Elena, Rini, Francesca, Costantino, Andrea, Affronti, Andrea, Affronti, Marco, Mascari, Marta, Mega, Andrea, Pompili, Maurizio, Rinninella, Emanuele, Mismas, Valeria, Dall’Aglio, Anna Chiara, Feletti, Valentina, Lanzi, Arianna, Cappa, Federica Mirici, Neri, Elga, Stefanini, Giuseppe Francesco, Tamberi, Stefano, Biasini, Elisabetta, Missale, Gabriele, Guarino, Maria, Ortolani, Alessio, Chiaramonte, Maria, Marchetti, Fabiana, Valerio, Matteo, Aburas, Sami, Inghilesi, Andrea L., Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Coccoli, Piero, Zamparelli, Marco Sanduzzi, Petta, Salvatore, Cabibbo, Giuseppe, Barbara, Marco, Attardo, Simona, Bucci, Laura, Farinati, Fabio, Giannini, Edoardo G., Tovoli, Francesco, Ciccarese, Francesca, Rapaccini, Gian Lodovico, Dimarco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Virdone, Roberto, Marra, Fabio, Felder, Martina, Morisco, Filomena, Benvegnù, Luisa, Gasbarrini, Antonio, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, Olivani, Andrea, Masotto, Alberto, Nardone, Gerardo, Colecchia, Antonio, Persico, Marcello, Boccaccio, Vincenzo, Craxì, Antonio, Bruno, Savino, Trevisani, Franco, Cammà, Calogero, Rapaccini, G. L. (ORCID:0000-0002-6467-857X), Gasbarrini, A. (ORCID:0000-0002-7278-4823), Pompili, Maurizio (ORCID:0000-0001-6699-7980), Rinninella, Emanuele (ORCID:0000-0002-9165-2367), and Gasbarrini, Antonio (ORCID:0000-0002-7278-4823) more...

Abstract

Background: In HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma (HCC), the time to HCC recurrence and the effects of sustained viral eradication (SVR) by interferon (IFN)-based or IFN-free regimens on HCC recurrence remain unclear. Aim: To perform an indirect comparison of time to recurrence (TTR) in patients with successfully treated early HCC and active HCV infection with those of patients with SVR by IFN-based and by IFN-free regimens. Methods: We evaluated 443 patients with HCV-related cirrhosis and Barcelona Clinic Liver Cancer Stage A/0 HCC who had a complete radiological response after curative resection or ablation. Active HCV infection was present in 328, selected from the Italian Liver Cancer group cohort; 58 patients had SVR achieved by IFN-free regimens after HCC cure, and 57 patients had SVR achieved by IFN-based regimens after HCC cure. Individual data of patients in the last two groups were extracted from available publications. Results: TTR by Kaplan–Meier curve was significantly lower in patients with active HCV infection compared with those with SVR both by IFN-free (P = 0.02) and by IFN-based (P < 0.001) treatments. TTR was similar in patients with SVR by IFN-free or by IFN-based (P = 0.49) strategies. Conclusion: In HCV-infected, successfully treated patients with early HCC, SVR obtained by IFN-based or IFN-free regimens significantly reduce tumour recurrence without differences related to the anti-viral strategy used. more...

Published
2017

13. The evolutionary scenario of hepatocellular carcinoma in Italy: an update

Author

Bucci, Laura, Garuti, Francesca, Lenzi, Barbara, Pecorelli, Anna, Farinati, Fabio, Giannini, Edoardo G., Granito, Alessandro, Ciccarese, Francesca, Rapaccini, Gian Lodovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Cammà, Calogero, Virdone, Roberto, Marra, Fabio, Felder, Martina, Morisco, Filomena, Benvegnù, Luisa, Gasbarrini, Antonio, Svegliati Baroni, Gianluca, Foschi, Francesco Giuseppe, Missale, Gabriele, Masotto, Alberto, Nardone, Gerardo, Colecchia, Antonio, Bernardi, Mauro, Trevisani, Franco, Biselli, Maurizio, Caraceni, Paolo, Cucchetti, Alessandro, Domenicali, Marco, Gramenzi, Annagiulia, Magalotti, Donatella, Napoli, Lucia, Negrini, Giulia, Piscaglia, Fabio, Serra, Carla, Tovoli, Francesco, Marafatto, Filippo, Murer, Francesca, Peserico, Giulia, Pozzan, Caterina, Vanin, Veronica, Moscatelli, Alessandro, Pellegatta, Gaia, Picciotto, Antonino, Savarino, Vincenzo, Poggio, Paolo Del, Olmi, Stefano, De Matthaeis, Nicoletta, Balsamo, Claudia, Vavassori, Elena, Roselli, Paola, Dell’Isola, Serena, Ialungo, Anna Maria, Rastrelli, Elena, Barcellona, Maria Rosa, Cabibbo, Giuseppe, Costantino, Andrea, Maida, Marcello, Affronti, Andrea, Mega, Andrea, Rinninella, Emanuele, Mismas, Valeria, Dall’Aglio, Anna Chiara, Feletti, Valentina, Lanzi, Arianna, Cappa, Federica Mirici, Neri, Elga, Stefanini, Giuseppe Francesco, Tamberi, Stefano, Biasini, Elisabetta, Porro, Emanuela, Guarino, Maria, Gemini, Stefano, Schiadà, Laura, Chiaramonte, Maria, Marchetti, Fabiana, Valerio, Matteo, Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Coccoli, Piero, Zamparelli, Marco Sanduzzi, Aburas, Sami, Inghilesi, Andrea Lorenzo, Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), Rinninella, Emanuele (ORCID:0000-0002-9165-2367), Bucci, Laura, Garuti, Francesca, Lenzi, Barbara, Pecorelli, Anna, Farinati, Fabio, Giannini, Edoardo G., Granito, Alessandro, Ciccarese, Francesca, Rapaccini, Gian Lodovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Cammà, Calogero, Virdone, Roberto, Marra, Fabio, Felder, Martina, Morisco, Filomena, Benvegnù, Luisa, Gasbarrini, Antonio, Svegliati Baroni, Gianluca, Foschi, Francesco Giuseppe, Missale, Gabriele, Masotto, Alberto, Nardone, Gerardo, Colecchia, Antonio, Bernardi, Mauro, Trevisani, Franco, Biselli, Maurizio, Caraceni, Paolo, Cucchetti, Alessandro, Domenicali, Marco, Gramenzi, Annagiulia, Magalotti, Donatella, Napoli, Lucia, Negrini, Giulia, Piscaglia, Fabio, Serra, Carla, Tovoli, Francesco, Marafatto, Filippo, Murer, Francesca, Peserico, Giulia, Pozzan, Caterina, Vanin, Veronica, Moscatelli, Alessandro, Pellegatta, Gaia, Picciotto, Antonino, Savarino, Vincenzo, Poggio, Paolo Del, Olmi, Stefano, De Matthaeis, Nicoletta, Balsamo, Claudia, Vavassori, Elena, Roselli, Paola, Dell’Isola, Serena, Ialungo, Anna Maria, Rastrelli, Elena, Barcellona, Maria Rosa, Cabibbo, Giuseppe, Costantino, Andrea, Maida, Marcello, Affronti, Andrea, Mega, Andrea, Rinninella, Emanuele, Mismas, Valeria, Dall’Aglio, Anna Chiara, Feletti, Valentina, Lanzi, Arianna, Cappa, Federica Mirici, Neri, Elga, Stefanini, Giuseppe Francesco, Tamberi, Stefano, Biasini, Elisabetta, Porro, Emanuela, Guarino, Maria, Gemini, Stefano, Schiadà, Laura, Chiaramonte, Maria, Marchetti, Fabiana, Valerio, Matteo, Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Coccoli, Piero, Zamparelli, Marco Sanduzzi, Aburas, Sami, Inghilesi, Andrea Lorenzo, Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), and Rinninella, Emanuele (ORCID:0000-0002-9165-2367) more...

Abstract

Background & Aims: Epidemiology of hepatocellular carcinoma is changing worldwide. This study aimed at evaluating the changing scenario of aetiology, presentation, management and prognosis of hepatocellular carcinoma in Italy during the last 15 years. Methods: Retrospective analysis of the ITA.LI.CA (Italian Liver Cancer) database including 5192 hepatocellular carcinoma patients managed in 24 centres from 2000 to 2014. Patients were divided into three groups according to the date of cancer diagnosis (2000–2004, 2005–2009 and 2010–2014). Results: The main results were as follows: (i) progressive patient aging; (ii) progressive expansion of non-viral cases and, namely, of “metabolic” hepatocellular carcinomas; (iii) increasing proportion of hepatocellular carcinoma diagnosed during a correct (semi-annual) surveillance programme; (iv) favourable cancer stage migration; (v) increased use of radiofrequency ablation to the detriment of percutaneous ethanol injection; (vi) improved outcomes of ablative and transarterial treatments; (vii) improved overall survival (adjusted for the lead time in surveyed patients), particularly after 2009, of both viral and non-viral patients presenting with an early- or intermediate-stage hepatocellular carcinoma. Conclusions: During the last 15 years several aetiological and clinical features of hepatocellular carcinoma patients have changed, as their management. The observed improvement of overall survival was owing both to the wider use of semi-annual surveillance, expanding the proportion of tumours that qualified for curative treatments, and to the improved outcome of loco-regional treatments. more...

Published
2017

14. Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: A multicenter prospective study

Author

Piscaglia, Fabio, Svegliati Baroni, Gianluca, Barchetti, Andrea, Pecorelli, Anna, Marinelli, Sara, Tiribelli, Claudio, Bellentani, Stefano, Pompili, Maurizio, Pompili, Maurizio (ORCID:0000-0001-6699-7980), Piscaglia, Fabio, Svegliati Baroni, Gianluca, Barchetti, Andrea, Pecorelli, Anna, Marinelli, Sara, Tiribelli, Claudio, Bellentani, Stefano, Pompili, Maurizio, and Pompili, Maurizio (ORCID:0000-0001-6699-7980) more...

Abstract

Nonalcoholic fatty liver disease (NAFLD) represents the hepatic manifestation of metabolic syndrome and may evolve into hepatocellular carcinoma (HCC). Only scanty clinical information is available on HCC in NAFLD. The aim of this multicenter observational prospective study was to assess the clinical features of patients with NAFLD-related HCC (NAFLD-HCC) and to compare them to those of hepatitis C virus (HCV)-related HCC. A total of 756 patients with either NAFLD (145) or HCV-related chronic liver disease (611) were enrolled in secondary care Italian centers. Survival was modeled according to clinical parameters, lead-time bias, and propensity analysis. Compared to HCV, HCC in NAFLD patients had a larger volume, showed more often an infiltrative pattern, and was detected outside specific surveillance. Cirrhosis was present in only about 50% of NAFLD-HCC patients, in contrast to the near totality of HCV-HCC. Regardless of tumor stage, survival was significantly shorter (P = 0.017) in patients with NAFLD-HCC, 25.5 months (95% confidence interval 21.9-29.1), than in those with HCV-HCC, 33.7 months (95% confidence interval 31.9-35.4). To eliminate possible confounders, a propensity score analysis was performed, which showed no more significant difference between the two groups. Additionally, analysis of patients within Milan criteria submitted to curative treatments did not show any difference in survival between NAFLD-HCC and HCV-HCC (respectively, 38.6 versus 41.0 months, P = nonsignificant) Conclusions: NAFLD-HCC is more often detected at a later tumor stage and could arise also in the absence of cirrhosis, but after patient matching, it has a similar survival rate compared to HCV infection; a future challenge will be to identify patients with NAFLD who require more stringent surveillance in order to offer the most timely and effective treatment. (Hepatology 2016;63:827-838) more...

Published
2016

15. Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: A multicenter prospective study

Author

Piscaglia, Fabio, Svegliati Baroni, Gianluca, Barchetti, Andrea, Pecorelli, Anna, Marinelli, Sara, Tiribelli, Claudio, Bellentani, Stefano, Grieco, Antonio, Grieco, Antonio (ORCID:0000-0002-0544-8993), Piscaglia, Fabio, Svegliati Baroni, Gianluca, Barchetti, Andrea, Pecorelli, Anna, Marinelli, Sara, Tiribelli, Claudio, Bellentani, Stefano, Grieco, Antonio, and Grieco, Antonio (ORCID:0000-0002-0544-8993) more...

Abstract

Nonalcoholic fatty liver disease (NAFLD) represents the hepatic manifestation of metabolic syndrome and may evolve into hepatocellular carcinoma (HCC). Only scanty clinical information is available on HCC in NAFLD. The aim of this multicenter observational prospective study was to assess the clinical features of patients with NAFLD-related HCC (NAFLD-HCC) and to compare them to those of hepatitis C virus (HCV)-related HCC. A total of 756 patients with either NAFLD (145) or HCV-related chronic liver disease (611) were enrolled in secondary care Italian centers. Survival was modeled according to clinical parameters, lead-time bias, and propensity analysis. Compared to HCV, HCC in NAFLD patients had a larger volume, showed more often an infiltrative pattern, and was detected outside specific surveillance. Cirrhosis was present in only about 50% of NAFLD-HCC patients, in contrast to the near totality of HCV-HCC. Regardless of tumor stage, survival was significantly shorter (P = 0.017) in patients with NAFLD-HCC, 25.5 months (95% confidence interval 21.9-29.1), than in those with HCV-HCC, 33.7 months (95% confidence interval 31.9-35.4). To eliminate possible confounders, a propensity score analysis was performed, which showed no more significant difference between the two groups. Additionally, analysis of patients within Milan criteria submitted to curative treatments did not show any difference in survival between NAFLD-HCC and HCV-HCC (respectively, 38.6 versus 41.0 months, P = nonsignificant) Conclusions: NAFLD-HCC is more often detected at a later tumor stage and could arise also in the absence of cirrhosis, but after patient matching, it has a similar survival rate compared to HCV infection; a future challenge will be to identify patients with NAFLD who require more stringent surveillance in order to offer the most timely and effective treatment. (Hepatology 2016;63:827-838) more...

Published
2016

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

Author

Farinati, Fabio, Vitale, Alessandro, Spolverato, Gaya, Pawlik, Timothy M., Huo, Teh-La, Lee, Yun-Hsuan, Frigo, Anna Chiara, Giacomin, Anna, Giannini, Edoardo G., Ciccarese, Francesca, Piscaglia, Fabio, Rapaccini, Gian Ludovico, Di Marco, Mariella, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Cabibbo, Giuseppe, Felder, Martina, Sacco, Rodolfo, Morisco, Filomena, Biasini, Elisabetta, Foschi, Francesco Giuseppe, Gasbarrini, Antonio, Svegliati Baroni, Gianluca, Virdone, Roberto, Masotto, Alberto, Trevisani, Franco, Cillo, Umberto, Rapaccini, Gian Ludovico (ORCID:0000-0002-6467-857X), Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), Farinati, Fabio, Vitale, Alessandro, Spolverato, Gaya, Pawlik, Timothy M., Huo, Teh-La, Lee, Yun-Hsuan, Frigo, Anna Chiara, Giacomin, Anna, Giannini, Edoardo G., Ciccarese, Francesca, Piscaglia, Fabio, Rapaccini, Gian Ludovico, Di Marco, Mariella, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Cabibbo, Giuseppe, Felder, Martina, Sacco, Rodolfo, Morisco, Filomena, Biasini, Elisabetta, Foschi, Francesco Giuseppe, Gasbarrini, Antonio, Svegliati Baroni, Gianluca, Virdone, Roberto, Masotto, Alberto, Trevisani, Franco, Cillo, Umberto, Rapaccini, Gian Ludovico (ORCID:0000-0002-6467-857X), and Gasbarrini, Antonio (ORCID:0000-0002-7278-4823) more...

Abstract

Background: 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. Methods and Findings: 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 pati more...

Published
2016

17. Practice guidelines for the treatment of hepatitis C: recommendations from an AISF/SIMIT/SIMAST Expert Opinion Meeting.

Author

Prati, Daniele, Gasbarrini, Antonio, Mazzotta, Francesco, Sagnelli, Evangelista, Carosi, Giampiero, Abrescia, Nicola, Alberti, Alfredo, Ambu, Silvia, Andreone, Piero, Andriulli, Angelo, Angelico, Mario, Antonucci, Giorgio, Ascione, Antonio, Belli, Luca Saverio, Bruno, Raffaele, Bruno, Savino, Burra, Patrizia, Cammà, Calogero, Caporaso, Nicola, Cariti, Giuseppe, Cillo, Umberto, Coppola, Nicola, Craxì, Antonio, De Luca, Andrea, De Martin, Eleonora, Di Marco, Vito, Fagiuoli, Stefano, Ferrari, Carlo, Gaeta, Giovanni Battista, Galli, Massimo, Grieco, Antonio, Grossi, Paolo, Licata, Anna, Maida, Ivana, Mangia, Alessandra, Marino, Nicoletta, Maserati, Renato, Missale, Gabriele, Mondelli, Mario, Nasta, Paola, Niro, Grazia, Persico, Marcello, Petrelli, Enzo, Picciotto, Antonio, Piscaglia, Fabio, Pollicino, Teresa, Puoti, Claudio, Puoti, Massimo, Raimondo, Giovanni, Rumi, Maria Grazia, Santantonio, Teresa, Smedile, Antonina, Squadrito, Giovanni, Svegliati Baroni, Gianluca, Taliani, Gloria, Tavio, Marcello, Toti, Mario, Bonino, Ferruccio, Brunetto, Maurizia Rossana, Cacopardo, Bruno, Caremani, Marcello, Cauda, Roberto, Colombo, Massimo, Di Perri, Giovanni, Donato, Francesca, Farci, Patrizia, Fattovich, Giovanna, Filice, Gaetano, Ghinelli, Florio, Guadagnino, Vincenzo, Lazzarin, Adriano, Levrero, Massimo, Licata, Giuseppe, Orani, Anna, Paffetti, Amerigo, Pastore, Giuseppe, Piccinino, Felice, Pizzigallo, Eligio, Pontisso, Patrizia, Portelli, Vincenzo, Rizzetto, Mario, Rossi, Alessandro, Stroffolini, Tommaso, Ubaldi, Enzo, Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), De Luca, Andrea (ORCID:0000-0002-8311-6935), Grieco, Antonio (ORCID:0000-0002-0544-8993), Cauda, Roberto (ORCID:0000-0002-1498-4229), Prati, Daniele, Gasbarrini, Antonio, Mazzotta, Francesco, Sagnelli, Evangelista, Carosi, Giampiero, Abrescia, Nicola, Alberti, Alfredo, Ambu, Silvia, Andreone, Piero, Andriulli, Angelo, Angelico, Mario, Antonucci, Giorgio, Ascione, Antonio, Belli, Luca Saverio, Bruno, Raffaele, Bruno, Savino, Burra, Patrizia, Cammà, Calogero, Caporaso, Nicola, Cariti, Giuseppe, Cillo, Umberto, Coppola, Nicola, Craxì, Antonio, De Luca, Andrea, De Martin, Eleonora, Di Marco, Vito, Fagiuoli, Stefano, Ferrari, Carlo, Gaeta, Giovanni Battista, Galli, Massimo, Grieco, Antonio, Grossi, Paolo, Licata, Anna, Maida, Ivana, Mangia, Alessandra, Marino, Nicoletta, Maserati, Renato, Missale, Gabriele, Mondelli, Mario, Nasta, Paola, Niro, Grazia, Persico, Marcello, Petrelli, Enzo, Picciotto, Antonio, Piscaglia, Fabio, Pollicino, Teresa, Puoti, Claudio, Puoti, Massimo, Raimondo, Giovanni, Rumi, Maria Grazia, Santantonio, Teresa, Smedile, Antonina, Squadrito, Giovanni, Svegliati Baroni, Gianluca, Taliani, Gloria, Tavio, Marcello, Toti, Mario, Bonino, Ferruccio, Brunetto, Maurizia Rossana, Cacopardo, Bruno, Caremani, Marcello, Cauda, Roberto, Colombo, Massimo, Di Perri, Giovanni, Donato, Francesca, Farci, Patrizia, Fattovich, Giovanna, Filice, Gaetano, Ghinelli, Florio, Guadagnino, Vincenzo, Lazzarin, Adriano, Levrero, Massimo, Licata, Giuseppe, Orani, Anna, Paffetti, Amerigo, Pastore, Giuseppe, Piccinino, Felice, Pizzigallo, Eligio, Pontisso, Patrizia, Portelli, Vincenzo, Rizzetto, Mario, Rossi, Alessandro, Stroffolini, Tommaso, Ubaldi, Enzo, Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), De Luca, Andrea (ORCID:0000-0002-8311-6935), Grieco, Antonio (ORCID:0000-0002-0544-8993), and Cauda, Roberto (ORCID:0000-0002-1498-4229) more...

Abstract

It is increasingly clear that a tailored therapeutic approach to patients with hepatitis C virus infection is needed. Success rates in difficult to treat and low-responsive hepatitis C virus patients are not completely satisfactory, and there is the need to optimise treatment duration and intensity in patients with the highest likelihood of response. In addition, the management of special patient categories originally excluded from phase III registration trials needs to be critically re-evaluated. This article reports the recommendations for the treatment of hepatitis C virus infection on an individual basis, drafted by experts of three scientific societies. more...

Published
2010