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1. LIVER DISEASE & SICKLE CELL DISEASE: AUTOIMMUNE HEPATITIS MORE THAN A COINCIDENCE; A SYSTEMATIC LITERATURE REVIEW.

Author

Kelvin Lynch, Andrea Mega, Andrea Piccin, Massimo Daves, and Helen Fogarty

Subjects
Sickle Cell, Autoimmune, Liver Disease, Hepaitits, Steroids, Vaso-occlusive Crisis, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

• In patients with SCD, chronic liver damage is a common manifestation. More than 50% of SCD patients have elevated liver enzymes. Common underlying aetiologies include sickle cell hepatic crisis, viral hepatitis, sickle cell intrahepatic cholestasis and hepatic sequestration in the acute setting, and cholelithiasis and iron overload in the chronic setting. Autoimmune hepatitis (AIH) is a rare disease that appears to occur more commonly in the sickle cell disease (SCD) population than in the general population. There are many schools of thought as to why this is the case, including the phosphatidylserine hypothesis, the heme inflammatory hypothesis, the complement generation hypothesis, and the transfusion alloimmunization hypothesis. • • Due to the natural history of the two illnesses, SCD is almost always diagnosed first in cases of dual pathology. Symptoms such as jaundice, fatigue, and abdominal pain are common in SCD, as are abnormal liver function tests (LFTs). These abnormalities, attributed to the other more frequent liver involvements in SCD, can lead to delays in AIH diagnosis in this population. • Corticosteroids, sometimes with other immunosuppressive agents, such as azathioprine, are the cornerstone of acute AIH treatment (4). However, corticosteroid use in the SCD population has been shown to carry an increased risk of vaso-occlusive crises (1, 5), providing a treatment dilemma. • • The following is a review of AIH in the SCD population, where we explore the pathophysiology behind the association between the two disorders, discuss an approach to investigating abnormal LFTs in SCD, and examine treatment options in this population with co-existing diseases.

Published
2023
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2. 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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3. Predictors of solid extra-hepatic non-skin cancer in liver transplant recipients and analysis of survival: A long-term follow-up study

Author

Stefano Gitto, Paolo Magistri, Luca Marzi, Nicolò Mannelli, Nicola De Maria, Andrea Mega, Giovanni Vitale, Giovanna Valente, Francesco Vizzutti, Erica Villa, Fabio Marra, Pietro Andreone, Margherita Falcini, Barbara Catellani, Gian Piero Guerrini, Valentina Serra, Stefano Di Sandro, Roberto Ballarin, Guido Piai, Filippo Schepis, Marzia Margotti, Carmela Cursaro, Paolo De Simone, Stefania Petruccelli, Paola Carrai, Paolo Forte, Claudia Campani, Heinz Zoller, and Fabrizio Di Benedetto

Subjects
Liver transplant, Cancer, Aging, Diabetes, Metabolic syndrome, Specialties of internal medicine, RC581-951
Abstract

Introduction and objectives: De novo malignancies represent an important cause of death for liver transplant recipients. Our aim was to analyze predictors of extra-hepatic non-skin cancer (ESNSC) and the impact of ESNSC on the long-term outcome. Patients: We examined data from patients transplanted between 2000 and 2005 and followed-up in five Italian transplant clinics with a retrospective observational cohort study. Cox Regression was performed to identify predictors of ESNSC. A 1:2 cohort sub-study was developed to analyze the impact of ESNSC on 10-year survival. Results: We analyzed data from 367 subjects (median follow-up: 15 years). Patients with ESNSC (n = 47) more often developed post-LT diabetes mellitus (DM) (57.4% versus 35,9%, p = 0.004). At multivariate analysis, post-LT DM independently predicted ESNSC (HR 1.929, CI 1.029-3.616, p = 0.040). Recipients with ESNSC showed a lower 10-year survival than matched controls (46,8% versus 68,1%, p = 0.023). Conclusions: Post-LT DM seems to be a relevant risk factor for post-LT ESNSC. ESNSC could have a noteworthy impact on the long-term survival of LT recipients.

Published
2022
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4. 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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5. Role of Etiology in Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Counterfactual Event-Based Mediation Analysis

Author

Rodolfo Sacco, Daryl Ramai, Raffaella Tortora, Giovan Giuseppe di Costanzo, Michela Emma Burlone, Mario Pirisi, Piera Federico, Bruno Daniele, Marianna Silletta, Paolo Gallo, Caterina Cocuzza, Maurizio Russello, Giuseppe Cabibbo, Gabriele Rancatore, Silvia Cesario, Gianluca Masi, Luca Marzi, Andrea Mega, Alessandro Granito, Giulia Pieri, Edoardo G. Giannini, Rosa Paolillo, Gennaro Gadaleta-Caldarola, Vincenzo Dadduzio, Guido Giordano, Luca Giacomelli, Simonetta Papa, Matteo Renzulli, Marcello Maida, Michele Ghidini, Mauro Borzio, and Antonio Facciorusso

Subjects
HCC, survival, progression, liver cancer, mediation analysis, viral etiology, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background: Whether the etiology of underlying liver disease represents a prognostic factor in patients with hepatocellular carcinoma (HCC) treated with lenvatinib is still a matter of debate. This study investigates whether the viral etiology of HCC plays a prognostic role in overall survival (OS). Methods: Data derived from a multicenter series of 313 HCC patients treated with lenvatinib between 2019 and 2022 were analyzed. Actuarial survival estimates were computed using the Kaplan–Meier method and compared with the log-rank test. We performed an event-based counterfactual mediation analysis to estimate direct (chronic inflammation and immunosuppression), indirect (tobacco smoking, alcohol use, illicit drug abuse with injections), and the total effect of viral etiology on OS. Results were expressed as hazard ratio (HR) and 95% CI. Results: Median OS was 21 months (95% CI: 20–23) in the group with other etiologies and 15 months (14–16) in the group with viral etiology (p < 0.0001). The total effect of viral etiology was associated with OS (HR 2.76, 1.32–5.21), and it was mainly explained by the pure direct effect of viral etiology (HR 2.74, 1.15–4.45). By contrast, its total indirect effect was not associated with poorer survival (HR 1.05, 0.82–2.13). These results were confirmed when considering tobacco, alcohol consumption, or injection drug abuse as potential mediators. Median progression-free survival was 9 months (8–10) in patients with other etiologies and 6 months (5–7) in patients with viral etiology (p < 0.0001). No difference in terms of adverse event rate was observed between the two groups. Conclusions: Patients affected by HCC with nonviral etiology treated with lenvatinib exhibit longer survival than those with viral etiology. This finding may have relevance in the treatment decision-making process.

Published
2023
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6. 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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7. Impact and Novel Perspective of Immune Checkpoint Inhibitors in Patients with Early and Intermediate Stage HCC

Author

Luca Marzi, Andrea Mega, Stefano Gitto, Filippo Pelizzaro, Andreas Seeber, and Gilbert Spizzo

Subjects
targeted therapy, locoregional treatment, immunotherapy, multimodality therapy, immune checkpoint inhibitors, hepatocellular carcinoma, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Surgery and radiofrequency ablation remain the gold standard to achieve cure in patients with hepatocellular carcinoma (HCC). After a decade in which only sorafenib was available for advanced and metastatic HCC, the emergence of other molecularly targeted drugs and immune checkpoint inhibitors (ICIs) has significantly improved the patients` prognosis. In particular, the use of ICIs has shown promising results and has revolutionized the treatment algorithm in HCC patients. Indeed, preclinical and clinical data have documented a high density of immunosuppressive cells and an increased expression of the programmed death-1 (PD-1) receptor and cytotoxic T-cell associated protein-4 (CTLA-4) in HCC. However, despite these observations, no validated biomarker is available and the molecular groundwork responsible for response to ICIs remains elusive. The anti-CTLA4 monoclonal antibody tremelimumab and the anti-PD-1 monoclonal antibodies nivolumab and pembrolizumab were the first ICIs to be tested in HCC. Recently, the combination of the anti-programmed death-ligand 1 (PD-L1) inhibitor atezolizumab and the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab demonstrated an improvement in patient outcome compared to sorafenib, becoming the standard of care in the frontline setting of advanced disease. Other immunotherapeutic agents such as pembrolizumab or the combination nivolumab-ipilimumab have shown promising results that have to be confirmed in phase III studies. Currently, the combination of different ICIs (i.e., ipilimumab, durvalumab) and anti-angiogenic agents (i.e., regorafenib, lenvatinib) is currently being tested in several trials and will hopefully revolutionize the treatment of HCC. To date, numerous studies are underway evaluating ICIs in adjuvant and neoadjuvant settings to improve survival in early and intermediate stages. Thus, this review focuses on the rationale for ICIs and their potential use for early or intermediate HCC stages.

Published
2022
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8. 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

9. A Nomogram-Based Prognostic Model for Advanced Hepatocellular Carcinoma Patients Treated with Sorafenib: A Multicenter Study

Author

Giovanni Marasco, Francesco Poggioli, Antonio Colecchia, Giuseppe Cabibbo, Filippo Pelizzaro, Edoardo Giovanni Giannini, Sara Marinelli, Gian Ludovico Rapaccini, Eugenio Caturelli, Mariella Di Marco, Elisabetta Biasini, Fabio Marra, Filomena Morisco, Francesco Giuseppe Foschi, Marco Zoli, Antonio Gasbarrini, Gianluca Svegliati Baroni, Alberto Masotto, Rodolfo Sacco, Giovanni Raimondo, Francesco Azzaroli, Andrea Mega, Gianpaolo Vidili, Maurizia Rossana Brunetto, Gerardo Nardone, Luigina Vanessa Alemanni, Elton Dajti, Federico Ravaioli, Davide Festi, Franco Trevisani, and on behalf of the Italian Liver Cancer (ITA.LI.CA.) Group

Subjects
sorafenib, hepatocellular carcinoma, survival, prognosis, cohort study, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Among scores and staging systems used for HCC, none showed a good prognostic ability in patients with advanced HCC treated with Sorafenib. We aimed to evaluate predictive factors of overall survival (OS) and drug response in HCC patients undergoing Sorafenib included in the Italian Liver Cancer (ITA.LI.CA.) multicenter cohort. Patients in the ITA.LI.CA database treated with Sorafenib and updated on 30 June 2019 were included. Demographic and clinical data before starting Sorafenib treatment were considered. For the evaluation of predictive factors for OS, a time-dependent Cox proportional hazard model was used. A total of 1107 patients were included in our analysis. The mean age was 64.3 years and 81.7% were male. Most patients were staged as BCLC B (205, 18.9%) or C (706, 65.1%). The median time of Sorafenib administration was 4 months (interquartile range (IQR) 2–12), and the median OS was 10 months (IQR: 4–20). A total of 263 patients (33.8%) out of 780 with available evaluation experienced objective tumoral response to Sorafenib. The Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (hazard ratio (HR) 1.284), maximum tumoral diameter (HR 1.100), plasma total bilirubin (HR 1.119), aspartate amino transferase assessed as multiple of the upper normal value (HR 1.032), alpha-fetoprotein ≥200 ng/mL (HR 1.342), hemoglobin (HR 0.903) and platelet count (HR 1.002) were associated with OS at multivariate Cox regression analysis. Drug response was predicted by maximum tumoral diameter and platelet count. A novel prognostic nomogram for patients undergoing Sorafenib is hereby proposed. The novelty introduced is the comprehensive patient’s assessment using common markers of patient’s general status, liver damage and function and HCC biology. Further studies are required to test its accuracy and provide external validation.

Published
2021
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10. Food and Nutrition in the Pathogenesis of Liver Damage

Author

Andrea Mega, Luca Marzi, Michael Kob, Andrea Piccin, and Annarosa Floreani

Subjects
xenobiotics, micronutrients, P450 enzymes, vitamins, herbs, red vine, Nutrition. Foods and food supply, TX341-641
Abstract

The liver is an important organ and plays a key role in the regulation of metabolism and in the secretion, storage, and detoxification of endogenous and exogenous substances. The impact of food and nutrition on the pathophysiological mechanisms of liver injury represents a great controversy. Several environmental factors including food and micronutrients are involved in the pathogenesis of liver damage. Conversely, some xenobiotics and micronutrients have been recognized to have a protective effect in several liver diseases. This paper offers an overview of the current knowledge on the role of xenobiotics and micronutrients in liver damage.

Published
2021
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11. Identification of Clinical Phenotypes and Related Survival in Patients with Large HCCs

Author

Brian I. Carr, Vito Guerra, Rossella Donghia, Fabio Farinati, Edoardo G. Giannini, Luca Muratori, Gian Ludovico Rapaccini, Maria Di Marco, Eugenio Caturelli, Marco Zoli, Rodolfo Sacco, Ciro Celsa, Claudia Campani, 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, and Franco Trevisani

Subjects
HCC, large, phenotypes, PVT, multifocality, albumin, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
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 >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 (

Published
2021
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12. Surveillance as Determinant of Long-Term Survival in Non-Transplanted Hepatocellular Carcinoma Patients

Author

Filippo Pelizzaro, Alessandro Vitale, Anna Sartori, Andrea Vieno, Barbara Penzo, Francesco Paolo Russo, Anna Chiara Frigo, Edoardo G Giannini, Manuela Piccinnu, Gian Ludovico Rapaccini, Maria Di Marco, Eugenio Caturelli, Marco Zoli, Rodolfo Sacco, Ciro Celsa, Fabio Marra, Andrea Mega, Maria Guarino, Antonio Gasbarrini, Gianluca Svegliati-Baroni, Francesco Giuseppe Foschi, Andrea Olivani, Alberto Masotto, Pietro Coccoli, Giovanni Raimondo, Francesco Azzaroli, Gianpaolo Vidili, Maurizia Rossana Brunetto, Franco Trevisani, Fabio Farinati, and on behalf of ITA.LI.CA Study Group

Subjects
hepatocellular carcinoma, long-term survival, surveillance, cancer stage, treatment, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Purpose: We aimed at assessing the impact of surveillance on long-term survival in HCC patients. Methods: From the ITA.LI.CA database, we selected 1028 cases with long (≥5 years, LS group) and 2721 controls with short-term survival (p < 0.0001), and had more favorable baseline characteristics. Surveillance was an independent predictor of LS (OR = 1.413, 95% CI 1.195–1.671; p < 0.0001). The observed and the lead-time corrected survival of surveilled patients were significantly longer compared to the survival of not surveilled patients (p < 0.0001 and p = 0.0008, respectively). In IPW adjusted populations, no survival differences were demonstrated between the two groups (p = 0.30). Conclusions: Surveillance, increasing early-stage diagnosis and applicability of curative treatments, is a fundamental determinant of long-term survival in HCC patients. A wide implementation of surveillance programs should be pursued in order to improve HCC patients’ prognosis.

Published
2021
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14. 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

15. 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

17. 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

18. Hepatitis C virus eradication with direct‐acting antiviral improves insulin resistance

Author

E. Franceschet, L. Marzi, Federica De Marchi, Patrizia Burra, Martina Gambato, Francesco Paolo Russo, Fabio Farinati, Heinz Zoller, I. Bortoluzzi, Benedikt Schaefer, Ramona Al Zoairy, Alberto Zanetto, Annarosa Floreani, Erica Nicola Lynch, and Andrea Mega

Subjects
Male, medicine.medical_specialty, Cirrhosis, Sustained Virologic Response, Hepatitis C virus, medicine.medical_treatment, Hepacivirus, Assessment index, medicine.disease_cause, Antiviral Agents, Tertiary care, Gastroenterology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Virology, Internal medicine, Diabetes mellitus, Diabetes Mellitus, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Aged, diabetes, Hepatology, business.industry, cirrhosis, Insulin, DAAs, Hepatitis C, Chronic, Middle Aged, medicine.disease, Treatment Outcome, Infectious Diseases, Liver, HCV, Elasticity Imaging Techniques, Female, 030211 gastroenterology & hepatology, Interferons, Insulin Resistance, business, Direct acting
Abstract

Sustained virological response (SVR) after interferon-based therapy is associated with improvement of insulin resistance (IR) in HCV-infected patients. Few data are available in the direct-acting antivirals (DAAs) era, especially in cirrhotic patients. We prospectively evaluated the long-term effect of DAAs on IR. Patients treated with DAAs between May 2015 and December 2016 in 3 tertiary care centres were recruited. Patients with diabetes were excluded. Biochemical and virological data were collected at baseline, 12/24/48 weeks (W) after the end of therapy (EOT). Presence of IR was defined by a 'homeostasis model assessment index for IR' [HOMA-IR])> 2.5. Liver fibroscan was performed at baseline, at 24/48W after EOT. Hundred and thirty-eight patients were enrolled (mean age 58 years, M/F 85/53, GT1 61%, 68.8% cirrhotic). Sixty-eight patients (94/138) had IR. Patients with IR had significantly higher stiffness than patients without it (23 ± 12 vs 15 ± 8; P < .0001). SVR12 was achieved in 135 (98%) patients, and 124 (90%) patients reached the 48W post-EOT. At this time point, the percentage of patients with IR significantly decreased to 49% (P = 0,01). HOMA-IR was significantly lower than baseline (1.8 vs 3; P < .001), and this was related to a significant reduction of insulin level (11.7 ± 6.3 vs 16.4 ± 8.3). High BMI was associated with a significantly lower probability of achieving a non-IR status at 24W (P = .05) and 48W (P = .03).In conclusion, SVR following DAAs led to a significant reduction of IR, even in patients with cirrhosis. Nevertheless, IR can persist after the achievement of SVR, especially in patients with high BMI.

Published
2019

19. 'Will Artificial Intelligence Unveil Hepatocellular Carcinoma?'

Author

Andrea Mega, Padova Explora-Research, Alessandra Andreotti, Andrea Piccin, L. Marzi, and Fabio Vittadello

Subjects
Oncology, medicine.medical_specialty, Liver disease, business.industry, Internal medicine, Hepatocellular carcinoma, medicine, General Medicine, medicine.disease, business, GeneralLiterature_MISCELLANEOUS
Abstract

Dear Editor, due to continuous implementing of medical devices physicians are dealing with tremendous amount of data and clinical...

Published
2021

20. Food and Nutrition in the Pathogenesis of Liver Damage

Author

Annarosa Floreani, Michael Kob, Andrea Mega, Andrea Piccin, and L. Marzi

Subjects
Physiology, red vine, Review, Protective Agents, Pathogenesis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Detoxification, medicine, Humans, Nutritional Physiological Phenomena, xenobiotics, TX341-641, P450 Enzymes, Liver damage, spices, Liver injury, Nutrition and Dietetics, business.industry, Nutrition. Foods and food supply, Liver Diseases, P450 enzymes, herbs, medicine.disease, Micronutrient, vitamins, Liver, chemistry, 030220 oncology & carcinogenesis, micronutrients, 030211 gastroenterology & hepatology, Xenobiotic, business, Food Science
Abstract

The liver is an important organ and plays a key role in the regulation of metabolism and in the secretion, storage, and detoxification of endogenous and exogenous substances. The impact of food and nutrition on the pathophysiological mechanisms of liver injury represents a great controversy. Several environmental factors including food and micronutrients are involved in the pathogenesis of liver damage. Conversely, some xenobiotics and micronutrients have been recognized to have a protective effect in several liver diseases. This paper offers an overview of the current knowledge on the role of xenobiotics and micronutrients in liver damage.

Published
2021

21. 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

22. 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

23. 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

25. Pre-transplant diabetes predicts atherosclerotic vascular events and cardiovascular mortality in liver transplant recipients: a long-term follow-up study

Author

Tiziana Olivieri, Nicola De Maria, Gian Piero Guerrini, Andrea Mega, Heinz Zoller, Paolo Magistri, Giovanna Valente, Paolo De Simone, Laura Turco, Erica Villa, Stefano Gitto, Guido Piai, Paolo Forte, Stefano Di Sandro, Fabio Marra, Valentina Serra, Giuseppe Tarantino, Giacomo Laffi, Paola Carrai, Margherita Falcini, Francesco Vizzutti, Edoardo Borelli, Stefania Petruccelli, Roberto Ballarin, Margherita Marocchi, Giovanni Vitale, Rachele Puntili, Fabrizio Di Benedetto, L. Marzi, Filippo Schepis, and Pietro Andreone

Subjects
medicine.medical_specialty, Multivariate analysis, Cardiovascular risk factors, Diabetes mellitus, Metabolic syndrome, Follow-Up Studies, Humans, Retrospective Studies, Risk Factors, Cardiovascular Diseases, Diabetes Mellitus, Liver Transplantation, Disease, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Internal Medicine, Medicine, 030212 general & internal medicine, Risk factor, Survival analysis, Proportional hazards model, business.industry, medicine.disease, medicine.symptom, business, Weight gain
Abstract

Background Early after surgery, liver transplant (LT) recipients often develop weight gain. Metabolic disorders and cardiovascular disease represent main drivers of morbidity and mortality. Our aim was to identify predictors of atherosclerotic vascular events (AVE) and to assess the impact of AVE on the long-term outcome. Methods We retrospectively analyzed data from patients transplanted between 2000 and 2005 and followed-up in five Italian transplant clinics. Cox Regression analysis was performed to identify predictors of AVE, global mortality, and cardiovascular mortality. Survival analysis was performed using the Kaplan-Meier method. Results We analyzed data from 367 subjects during a median follow-up of 14 years. Thirty-seven post-LT AVE were registered. Patients with AVE more frequently showed pre-LT diabetes mellitus (DM) (48.6 vs 13.9%, p=0.000). In the post-LT period, patients with AVE satisfied criteria of metabolic syndrome in 83.8% vs. 36.7% of subjects without AVE (p=0.000). At multivariate analysis, pre-LT DM independently predicted AVE (HR 2.250, CI 4.848-10.440, p=0.038). Moreover, both pre-LT DM and AVE strongly predicted cardiovascular mortality (HR 5.418, CI 1.060-29.183, p=0.049, and HR 86.097, CI 9.510-779.480, p=0.000, respectively). Conclusions Pre-LT DM is the main risk factor for post-LT AVE. Pre-LT DM and post-LT AVE are strong, long-term predictors of cardiovascular mortality. Patients with pre-LT DM should obtain a personalized follow-up for prevention or early diagnosis of AVE.

Published
2020

27. Observational retrospective study of vascular modulator changes during treatment in essential thrombocythemia

Author

Mario Plebani, Clemens Feistritzer, Dino Veneri, Andrea Piccin, Enrica Pacquola, Ciaran Murphy, Michele Gottardi, Filippo Gherlinzoni, Muriel Van Schilfgaarde, Martin Langes, Irene Pusceddu, Luigi Marcheselli, Andrea Mega, Günther Gastl, Michael Steurer, Omar Perbellini, Martina Tauber, Elisa Piva, Mauro Krampera, Daisy Corvetta, Guido Mazzoleni, Angela Maria Di Pierro, Roberto Gambato, and Elva Eakins

Subjects
Male, 030204 cardiovascular system & hematology, Pharmacology, Adrenomedullin, Essential, 0302 clinical medicine, Cell-Derived Microparticles, Hydroxyurea, Thrombocythemia, Platelet, essential thrombocythemia, Endothelin-1, General Medicine, Middle Aged, Pathophysiology, vascular modulator changes, medicine.anatomical_structure, Female, Public Health, medicine.drug, Thrombocythemia, Essential, Blood Platelets, Endothelium, Nitric Oxide, Aged, Aspirin, Case-Control Studies, Endothelium, Vascular, Humans, Quinazolines, Retrospective Studies, Public Health, Environmental and Occupational Health, Biochemistry (medical), 03 medical and health sciences, Vascular, Physiology (medical), medicine, essential thrombocythemia, vascular modulator changes, anagrelide, aspirin, Platelet-poor plasma, Essential thrombocythemia, business.industry, Environmental and Occupational Health, Anagrelide, medicine.disease, Endothelin 1, Immunology, anagrelide, business, 030215 immunology
Abstract

Essential thrombocythemia (ET) patients are at risk of developing thrombotic events. Qualitative platelet (PLT) abnormalities and activation of endothelial cells (ECs) and PLTs are thought to be involved. Microparticles (MPs) can originate from PLTs (PMPs), ECs (EMPs), or red cells (RMPs). Previous studies have indicated that MPs contribute to ET pathophysiology. Endothelial modulators (eg, nitric oxide [NO], adrenomedullin [ADM], and endothelin-1 [ET-1]) are also involved in the pathophysiology of this condition. We hypothesized that treatments for reducing PLT count might also indirectly affect MP generation and endothelial activity by altering endothelial modulator production. The rationale of this study was that hydroxyurea (HU), a cytostatic drug largely used in ET, induces the production of a potent vasoactive agent NO in ECs. An observational retrospective study was designed to investigate the relationship between MPs, NO, ADM, and ET-1 in ET patients on treatment with HU, anagrelide (ANA), aspirin (ASA), and a group of patients before treatment. A total of 63 patients with ET diagnosis: 18 on HU + ASA, 15 on ANA + ASA, 19 on ASA only, and 11 untreated patients, and 18 healthy controls were included in this study. Blood samples were analyzed for MP (absolute total values) and functional markers (percentage values) by flow cytometry. PLT-derived MPs were studied using CD61, CD62P, CD36, and CD63, whereas endothelial-derived MPs were studied using CD105, CD62E, and CD144. Endothelial modulator markers (NO, ADM, and ET-1) were measured by ELISA. Total MP count was higher in the group treated with ANA + ASA (P 0.01). MP markers modified in ET patients returned to levels of healthy controls following treatment, in particular, in patients on ANA treatment. NO and ADM values were higher in the HU group (P 0.001). HU and ANA treatment also affected MP production in a cell origin-specific manner. HU and ANA, although acting via different pathways, have similar final effects. For instance, HU causes vasodilatation by increasing NO and ADM levels, whereas ANA impairs vasoconstriction by reducing ET-1. In conclusion, therapy with HU cytostatic drugs and ANA can reduce PLT count in ET, and also affect endothelial modulatory agents, with HU sustaining vasodilation and prothrombotic MP concentration, whereas ANA decreases vasoconstriction.

Published
2016

28. Years of life that could be saved from prevention of hepatocellular carcinoma

Author

Andrea Costantino, Marcello Maida, Fabio Farinati, Laura Schiadà, Stefano Tamberi, Alessandro Moscatelli, Elena Rastrelli, Maria Chiaramonte, Paolo Poggio, Gianluca Svegliati Baroni, Matteo Renzulli, Fabio Piscaglia, Filomena Morisco, Paola Roselli, Roberto Virdone, Anna Maria Lalungo, Matteo Ravaioli, E.G. Giannini, Anna Chiara Dall’Aglio, Antonio Daniele Pinna, Elena Vavassori, Fabiana Marchetti, Eugenio Caturelli, Marco Domenicali, Calogero Cammà, Giulia Bosco, Carla Serra, Claudia Balsamo, Donatella Magalotti, Gian Ludovico Rapaccini, Valeria Mismas, S. Gemini, Stefano Olmi, Alberto Masotto, V. Feletti, Francesca Murer, Gaia Pellegatta, Maria Rosa Barcellona, A. Gazzola, Andrea Mega, Luigi Bolondi, Paolo Caraceni, Laura Bucci, Rita Golfieri, Annagiulia Gramenzi, Francesca Ciccarese, Rodolfo Sacco, Cristina Mosconi, Franco Borzio, Emanuele Rinninella, M. Di Marco, Alberta Cappelli, Marco Zoli, V. Vanin, Luisa Benvegnù, Mauro Bernardi, Emanuela Porro, Matteo Valerio, A. Pecorelli, Antonino Picciotto, Federica Mirici Cappa, Martina Felder, Elisabetta Biasini, Antonio Gasbarrini, Maurizio Biselli, Alessandro Cucchetti, Gabriele Missale, L. Venerandi, Serena Dell'Isola, Franco Trevisani, Elga Neri, Vincenzo Savarino, Maria Guarino, C. Pozzan, Giuseppe Cabibbo, F.G. Foschi, Giuseppe Francesco Stefanini, Arianna Lanzi, Andrea Affronti, Cucchetti, A, Trevisani, F, Bucci, L, Ravaioli, M, Farinati, F, Giannini, E. G, Ciccarese, F, Piscaglia, F, Rapaccini, G. L, Di Marco, M, Caturelli, E, Zoli, M, Borzio, F, Sacco, R, Maida, M, Felder, M, Morisco, Filomena, Gasbarrini, A, Gemini, S, Foschi, F. G, Missale, G, Masotto, A, Affronti, A, Bernardi, M, Pinna, A. D., Giannini, Eg, Rapaccini, Gl, Morisco, F, Foschi, Fg, Pinna, AD, Italian Liver Cancer (ITA.LI.CA.) Group, Bolondi, L, Biselli, M, Caraceni, P, Domenicali, M, Gramenzi, A., Cucchetti, A., Trevisani, F., Bucci, L., Ravaioli, M., Farinati, F., Giannini, E. G., Ciccarese, F., Piscaglia, F., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Maida, M., Felder, M., Morisco, F., Gasbarrini, A., Gemini, S., Foschi, F. G., Missale, G., Masotto, A., Affronti, A., Bernardi, M., Bolondi, L., Biselli, M., Caraceni, P., Domenicali, M., Magalotti, D., Pecorelli, A., Serra, C., Venerandi, L., Gazzola, A., Murer, F., Pozzan, C., Vanin, V., Del Poggio, P., Olmi, S., Balsamo, C., Vavassori, E., Benvegnu, L., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Bosco, G., Roselli, P., Dell'Isola, S., Lalungo, A. M., Rastrelli, E., Moscatelli, A., Pellegatta, G., Picciotto, A., Savarino, V., Barcellona, M. R., Camma, C., Cabibbo, G., Costantino, A., Virdone, R., Mega, A., Rinninella, E., Mismas, V., Dall'Aglio, A. C., Feletti, V., Lanzi, A., Cappa, F. M., Neri, E., Stefanini, G. F., Tamberi, S., Biasini, E., Porro, E., Guarino, M., Baroni, G. S., Schiada, L., Chiaramonte, M., Marchetti, F., and Valerio, M.

Subjects
Registrie, Male, Pediatrics, Databases, Factual, Hepatocellular carcinoma, 0302 clinical medicine, prevention, 80 and over, Secondary Prevention, Pharmacology (medical), Prospective Studies, Registries, Young adult, Prospective cohort study, Secondary prevention, Aged, 80 and over, education.field_of_study, Liver Neoplasms, Gastroenterology, Disease Management, Middle Aged, Primary Prevention, diagnosi, Italy, Liver Neoplasm, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Human, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, Adolescent, Population, life expentancy, Milan criteria, 03 medical and health sciences, Databases, Young Adult, Life Expectancy, medicine, Humans, Aged, education, Factual, Hepatology, business.industry, Carcinoma, Settore MED/09 - MEDICINA INTERNA, Hepatocellular, medicine.disease, Surgery, Prospective Studie, Years of potential life lost, Life expectancy, business
Abstract

Summary Background Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. Aim To assess how many years of life are lost after HCC diagnosis. Methods Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. Results Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18–61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986–1999, to 10.7 in 2000–2006 and 7.4 years in 2007–2014. Currently, an HCC diagnosis when a single tumour

Published
2016

30. Insulin resistance improvement after effective Hepatitis C virus eradication and its role on the onset of complications of advanced liver disease

Author

Alberto Zanetto, Andrea Mega, I. Bortoluzzi, Alberto Ferrarese, S.S. Sciarrone, Martina Gambato, Francesco Paolo Russo, Patrizia Burra, Fabio Farinati, and E. Franceschet

Subjects
Liver disease, medicine.medical_specialty, Insulin resistance, Hepatology, business.industry, Hepatitis C virus, Internal medicine, Gastroenterology, medicine, medicine.disease, business, medicine.disease_cause
Published
2018

31. Sex hormone profile and endometrial cancer risk in primary biliary cirrhosis: a case-control study

Author

Fabio Farinati, Mario Plebani, Vincenzo Baldo, Andrea Mega, P. Grella, Annarosa Floreani, and Delia M. Paternoster

Subjects
Adult, medicine.medical_specialty, Gastroenterology, Endometrium, Primary biliary cirrhosis, Sex hormone-binding globulin, Risk Factors, Sex Hormone-Binding Globulin, Internal medicine, medicine, Humans, Prospective Studies, Risk factor, Gonadal Steroid Hormones, skin and connective tissue diseases, Prospective cohort study, Testosterone, Aged, biology, medicine.diagnostic_test, Liver Cirrhosis, Biliary, business.industry, Endometrial cancer, Body Weight, Obstetrics and Gynecology, Middle Aged, medicine.disease, Endometrial Neoplasms, Endocrinology, Reproductive Medicine, Case-Control Studies, biology.protein, Regression Analysis, Female, business, Body mass index, Endometrial biopsy
Abstract

To investigate the sex hormone profile and endometrial histology in primary biliary cirrhosis (PBC).A prospective case-control study. Twenty-two females with PBC and 22 sex- and age-matched healthy controls underwent complete gynaecological examination including endometrial biopsy and a sex hormone serological profile including: oestrone, 17-beta oestradiol, testosterone, progesterone, dehydroepiandrosterone sulphate (DHEA-S) and sex hormone binding protein (SHBG). The sex hormone profile was evaluated with respect to the body mass index (BMI), anthropometric measurements and endometrial histological/cytological patterns in each case. Statistical analysis was done with the chi-squared method, Student's t-test for unpaired data, linear regression analysis, Spearman's rank correlation test and stepwise multiple regression analysis.The BMI was comparable in the two groups, while PBC cases had significantly smaller subscapular, waist, bicipital, tricipital and calf fold measurements than controls. Testosterone serum levels were significantly lower in PBC cases than in controls (0.9+/-0.6 versus 1.4+/-0.7 mmol/l, P0.03), whereas SHBG was significantly higher than in controls (88.6+/-72.1 versus 63.6+/-27.6, P0.005). No significant differences between the two groups were found for oestrone, 17-beta oestradiol, DHEA-S, and progesterone levels. No difference patterns were observed in endometrial histological/cytological patterns. Multiple regression analysis identified SHBG as an independent variable associated with PBC.Changes in sex hormone profile are secondary to hepatic dysfunction in PBC. Females with PBC do not appear to carry a higher risk of endometrial cancer.

Published
2002

34. Effects of alendronate sodium on severe osteodystrophy in postmenopausal patients with primary biliary cirrhosis: a pilot study

Author

Giovanni Luisetto, L. Tizian, Andrea Mega, Remo Naccarato, Andrea Buda, and Annarosa Floreani

Subjects
Pharmacology, medicine.medical_specialty, Bone disease, business.industry, Alendronic acid, Osteoporosis, medicine.disease, Gastroenterology, Surgery, Alendronate Sodium, Osteopenia, Primary biliary cirrhosis, Tolerability, Internal medicine, medicine, Pharmacology (medical), Osteodystrophy, business, medicine.drug
Abstract

Osteodystrophy is a major complication in primary biliary cirrhosis (PBC) and a significant problem for patients who require a liver transplant. Treatment for osteodystrophy has yet to be standardized. The goal of this pilot study was to assess the efficacy and tolerability of alendronate sodium, a potent specific inhibitor of osteoclast-mediated bone resorption. The study comprised 15 post-menopausal PBC patients (mean age, 64.25 ± 8.77 years) with severe osteodystrophy. Four patients had histologic stage II disease, 8 stage III, and 3 stage IV. All patients had a T score below 2, indicating a fracture risk of 60%. All patients received two courses of alendronate sodium (10 mg/d for 3 months, separated by a 2-month interval). The following variables were assessed at baseline and after 10 months: bone mineral density (BMD) (by dual-energy x-ray absorptiometry in the lumbar spine), calcium, sodium, potassium, creatinine, 25-hydroxyvitamin D, parathyroid hormone, and osteocalcin. No patients dropped out of the study, and therapy was well tolerated by all patients. At the end of treatment, BMD increased significantly compared with baseline (0.714 ± 0.115 g/cm 2 vs 0.740 ± 0.108 g/cm 2 ). Although not statistically significant, a trend toward an increase in serum osteocalcin levels (1.4 ± 1.5 ng/mL vs 2.6 ± 1.4 ng/mL) was evident. These preliminary findings suggest that alendronate sodium may be helpful in treating severe osteodystrophy in postmenopausal patients with PBC. Larger, controlled trials using long-term treatment with alendronate sodium are needed to establish the efficacy and safety of this drug.

Published
1998

35. P.1.331: SURVIVAL OF PATIENTS WITH HEPATOCELLULAR CARCINOMA: AN OBSERVATIONAL HOSPITAL-BASED STUDY

Author

Andrea Mega, Martin F, M. Felder, H. Pernthaler, R. Carella, M. Battisti-matscher, S. Amplatz, A. Frena, G. Bonatti, F. Chilovi, F. Ferro, T. Haglmueller, and F. Di Fede

Subjects
Oncology, Hospital based study, medicine.medical_specialty, Hepatology, business.industry, Hepatocellular carcinoma, Internal medicine, Gastroenterology, medicine, Observational study, medicine.disease, business
Published
2011

36. Bone metabolism and gonad function in male patients undergoing liver transplantation: a two-year longitudinal study

Author

Stefano Fagiuoli, Patrizia Boccagni, Remo Naccarato, Patrizia Burra, Andrea Mega, Vincenzo Baldo, Giovanni Luisetto, L. Tizian, Annarosa Floreani, Floreani, A, Mega, A, Tizian, L, Burra, P, Boccagni, P, Baldo, V, Fagiuoli, S, Naccarato, R, and Luisetto, G

Subjects
Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Bone density, Bone disease, Bone metabolism, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Osteoporosis, Urology, Liver transplantation, Bone and Bones, Liver disease, Bone Density, Internal medicine, Testis, medicine, Humans, Testosterone, Osteodystrophy, Longitudinal Studies, Bone mineral, business.industry, Osteoporosi, Luteinizing Hormone, Middle Aged, medicine.disease, Transplantation, Endocrinology, Parathyroid Hormone, Gonad function, Follicle Stimulating Hormone, business
Abstract

Osteodystrophy is a major complication of end-stage liver disease, especially in postmenopausal women. Our aim in this study was to evaluate bone metabolism and gonad function in men undergoing orthotopic liver transplantation (OLTx). Twenty-three consecutive men (mean age 48±13 years) evaluated for OLTx were studied, assessing the following parameters at baseline and 3, 6, 12 and 24 months after OLTx: lumbar spine (L2-L4) bone mineral density (BMD), parathyroid hormone (PTH), osteocalcin (BGP), 25-hydroxyvitamin D (25OHD), free testosterone (FT) and gonadotropins (FSH, LH). At baseline, 12 patients (52%) had a T-score

Published
2001

37. Is osteoporosis a peculiar association with primary biliary cirrhosis?

Author

Mario Plebani, Patrizia Burra, Annarosa Floreani, Giovanni Luisetto, Valentina Camozzi, Andrea Mega, and Vincenzo Baldo

Subjects
Adult, Liver Cirrhosis, medicine.medical_specialty, Population, Osteoporosis, Gastroenterology, Bone remodeling, Risk Factors, Internal medicine, Prevalence, medicine, Vitamin D and neurology, Humans, education, Bone mineral, education.field_of_study, Univariate analysis, Liver Cirrhosis, Biliary, business.industry, General Medicine, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, Osteopenia, Endocrinology, Brief Reports, Female, business
Abstract

AIM: (1) To compare the prevalence of osteoporosis (t-score ≤ -2.5 SD) between stage IV PBC patients, and two groups of age- and sex-matched controls: one with hepatitis C virus (HCV)-related cirrhosis, and the other one consisting of a group of healthy subjects from the general population; (2) to identify the main risk factors for the development of bone loss. METHODS: Thirty-five stage IV PBC patients (mean age 52.5 ± 10 years), 49 females with HCV-related cirrhosis (mean age 52.9 ± 5.8 years) and 33 healthy females (mean age 51.8 ± 2.22 years) were enrolled in the study. Bone metabolism was evaluated by measuring serum calcium corrected for serum albumin (Ca corr.), 25-hydroxy vitamin D (25-OH vit D), parathyroid hormone, osteocalcin. Bone mineral density (BMD) was assessed at the lumbar spine by dual-photon X-ray absorptiometry. RESULTS: Osteoporosis was present in 5/35 PBC patients (14.2%) and in 7/49 HCV-related cirrhotic patients (14.3%), without any statistical difference between the two groups. Among healthy control subjects, none had osteoporosis. No difference was found between the three groups in serum parameters of bone metabolism. Univariate analysis showed that menopausal state and low BMI were significantly correlated with osteoporosis. Multivariate regression analysis showed that menopausal status, BMI < 23, and old age were independent variables significantly correlated with osteoporosis. CONCLUSION: PBC in itself has no negative influence on BMD. End-stage liver disease patients carry a disease-specific risk for osteoporosis, but have an effective risk of bone loss in relation to individual potential risk for each patient. A practical message should be taken into account, that is, every effort should be made to prevent osteoporosis when a patient has simple osteopenia, or if it is a woman in or near menopausal age.

Published
2005

39. Is osteopenia a peculiar association with primary biliary cirrhosis (PBC)?

Author

Vincenzo Baldo, Andrea Mega, Giovanni Luisetto, Valentina Camozzi, Patrizia Burra, A. Floreani, and Mario Plebani

Subjects
Osteopenia, medicine.medical_specialty, Primary biliary cirrhosis, Hepatology, business.industry, Internal medicine, Gastroenterology, medicine, business, medicine.disease
Published
2002

40. Bone metabolism in male subjects undergoing liver transplantation(OLTx)

Author

L. Tizian, Patrizia Burra, Giovanni Luisetto, Andrea Mega, Patrizia Boccagni, Annarosa Floreani, Remo Naccarato, Vincenzo Baldo, and Stefano Fagiuoli

Subjects
medicine.medical_specialty, Hepatology, business.industry, Internal medicine, medicine.medical_treatment, medicine, Liver transplantation, business, Gastroenterology, Bone remodeling
Published
2000

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