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2. The Influence of Additional Treatments on the Survival of Patients Undergoing Transarterial Radioembolization (TARE)

Author

Quartuccio, Natale, primary, Ialuna, Salvatore, additional, Scalisi, Daniele, additional, D’Amato, Fabio, additional, Barcellona, Maria Rosa, additional, Bavetta, Maria Grazia, additional, Fusco, Giorgio, additional, Bronte, Enrico, additional, Musso, Emma, additional, Bronte, Fabrizio, additional, Picciotto, Viviana, additional, Carroccio, Antonio, additional, Verderame, Francesco, additional, Malizia, Giuseppe, additional, Cistaro, Angelina, additional, La Gattuta, Fabio, additional, and Moreci, Antonino Maria, additional

Published
2024
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3. The Influence of Additional Treatments, Injected Activity and Mean Dose to the Tumor on the Overall Survival of Patients Undergoing Transarterial Radioembolization (TARE)

Author

Quartuccio, Natale, primary, Ialuna, Salvatore, additional, Scalisi, Daniele, additional, D'Amato, Fabio, additional, Barcellona, Maria Rosa, additional, Bavetta, Maria Grazia, additional, Fusco, Giorgio, additional, Bronte, Enrico, additional, Musso, Emma, additional, Bronte, Fabrizio, additional, Picciotto, Viviana, additional, Carroccio, Antonio, additional, Verderame, Francesco, additional, Malizia, Giuseppe, additional, Cistaro, Angelina, additional, La Gattuta, Fabio, additional, and Moreci, Antonino Maria, additional

Published
2024
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4. Cost-effectiveness analysis of personalised versus standard dosimetry for selective internal radiation therapy with TheraSphere in patients with hepatocellular carcinoma

Author

Rognoni, Carla, primary, Barcellona, Maria Rosa, additional, Bargellini, Irene, additional, Bavetta, Maria Grazia, additional, Bellò, Marilena, additional, Brunetto, Maurizia, additional, Carucci, Patrizia, additional, Cioni, Roberto, additional, Crocetti, Laura, additional, D’Amato, Fabio, additional, D’Amico, Mario, additional, Deagostini, Simona, additional, Deandreis, Désirée, additional, De Simone, Paolo, additional, Doriguzzi, Andrea, additional, Finessi, Monica, additional, Fonio, Paolo, additional, Grimaldi, Serena, additional, Ialuna, Salvatore, additional, Lagattuta, Fabio, additional, Masi, Gianluca, additional, Moreci, Antonio, additional, Scalisi, Daniele, additional, Virdone, Roberto, additional, and Tarricone, Rosanna, additional

Published
2022
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5. Curative therapies are superior to standard of care (transarterial chemoembolization) for intermediate stage hepatocellular carcinoma

Author

Pecorelli, Anna, Lenzi, Barbara, Gramenzi, Annagiulia, Garuti, Francesca, Farinati, Fabio, Giannini, Edoardo G., Ciccarese, Francesca, Piscaglia, Fabio, Rapaccini, Gian Lodovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Cabibbo, Giuseppe, Felder, Martina, Morisco, Filomena, Gasbarrini, Antonio, Baroni, Gianluca Svegliati, Foschi, Francesco G., Biasini, Elisabetta, Masotto, Alberto, Virdone, Roberto, Bernardi, Mauro, Trevisani, Franco, Bolondi, Luigi, Biselli, Maurizio, Bucci, Laura, Caraceni, Paolo, Cucchetti, Alessandro, Domenicali, Marco, Magalotti, Donatella, Serra, Carla, Venerandi, Laura, Giacomin, Anna, Maddalo, Gemma, Pozzan, Caterina, Vani, Veronica, Poggio, Paolo Del, Olmi, Stefano, Balsamo, Claudia, Vavassori, Elena, Benvegnù, Luisa, Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Bosco, Giulia, Roselli, Paola, DellʼIsola, Serena, Ialungo, Anna Maria, Bruzzone, Linda, Picciotto, Antonino, Marenco, Simona, Risso, Domenico, Sammito, Giorgio, Savarino, Vincenzo, Cammà, Calogero, Maida, Marcello, Costantino, Andrea, Barcellona, Maria Rosa, Affronti, Andrea, Mega, Andrea, Rinninella, Emanuele, Mismas, Valeria, Cappa, Federica Mirici, DallʼAglio, Anna Chiara, Feletti, Valentina, Lanzi, Arianna, Neri, Elga, Stefanini, Giuseppe Francesco, Tamberi, Stefano, Missale, Gabriele, Porro, Emanuela, Guarino, Maria, Gemini, Stefano, and Schiadà, Laura

Published
2017
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6. 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, and Inghilesi, Andrea Lorenzo

Published
2017
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7. Years of life that could be saved from prevention of hepatocellular carcinoma

Author

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., Pinna, A. D., Bolondi, Luigi, Biselli, Maurizio, Caraceni, Paolo, Domenicali, Marco, Gramenzi, Annagiulia, Magalotti, Donatella, Pecorelli, Anna, Serra, Carla, Venerandi, Laura, Gazzola, Alessia, Murer, Francesca, Pozzan, Caterina, Vanin, Veronica, Poggio, Paolo Del, Olmi, Stefano, Balsamo, Claudia, Vavassori, Elena, Benvegnù, Luisa, Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Bosco, Giulia, Roselli, Paola, DellʼIsola, Serena, Lalungo, Anna Maria, Rastrelli, Elena, Moscatelli, Alessandro, Pellegatta, Gaia, Picciotto, Antonino, Savarino, Vincenzo, Barcellona, Maria Rosa, Virdone, Roberto, Mega, Andrea, Rinninella, Emanuele, Mismas, Valeria, DallʼAglio, Anna Chiara, Feletti, Valentina, Lanzi, Arianna, Cappa, Federica Mirici, Neri, Elga, Stefanini, Giuseppe Francesco, Tamberi, Stefano, Guarino, Maria, Baroni, Gianluca Svegliati, Schiadà, Laura, Chiaramonte, Maria, Marchetti, Fabiana, and Valerio, Matteo

Published
2016
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8. Comparison between alcohol- and hepatitis C virus-related hepatocellular carcinoma: clinical presentation, treatment and outcome

Author

Bucci, L., Garuti, F., Camelli, V., Lenzi, B., 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., Trevisani, F., Bolondi, Luigi, Biselli, Maurizio, Caraceni, Paolo, Cucchetti, Alessandro, Domenicali, Marco, Gramenzi, Annagiulia, Magalotti, Donatella, Pecorelli, Anna, Serra, Carla, Venerandi, Laura, Gazzola, Alessia, Murer, Francesca, Pozzan, Caterina, Vanin, Veronica, Poggio, Paolo Del, Olmi, Stefano, Balsamo, Claudia, Vavassori, Elena, Benvegnù, Luisa, Capelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Roselli, Paola, Isola, Serena, Ialungo, Anna Maria, Rastrelli, Elena, Moscatelli, Alessandro, Pelagatta, Gaia, Picciotto, Antonino, Savarino, Vincenzo, Barcellona, Maria Rosa, Cammà, Calogero, Cabibbo, Giuseppe, Costantino, Andrea, Virdone, Roberto, Mega, Andrea, Rinninella, Emanuele, Mismas, Valeria, DallʼAglio, Anna Chiara, Feletti, Valentina, Lanzi, Arianna, Cappa, Federica Mirici, Neri, Elga, Stefanini, Giuseppe Francesco, Tamberi, Stefano, Biasini, Elisabetta, Porro, Emanuela, Guarino, Maria, Baroni, Gianluca Svegliati, Schiadà, Laura, Chiaramonte, Maria, Marchetti, Fabiana, and Valerio, Matteo

Published
2016
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9. Correlation between LDH levels and response to sorafenib in HCC patients: an analysis of the ITA.LI.CA database

Author

Sacco, Rodolfo, Mismas, Valeria, Granito, Alessandro, Musettini, Gianna, Masi, Gianluca, Caparello, Chiara, Vivaldi, Caterina, Felder, Martina, Bresci, Giampaolo, Fornaro, Lorenzo, Trevisani, Franco, Bernardi, Mauro, Bolondi, Luigi, Piscaglia, Fabio, Zoli, Marco, Biselli, Maurizio, Caraceni, Paolo, Cucchetti, Alessandro, Domenicali, Marco, Frigerio, Marta, Erroi, Virginia, Garuti, Francesca, Gramenzi, Annagiulia, Lenzi, Barbara, Magalotti, Donatella, Pecorelli, Anna, Venerandi, Laura, Farinati, Fabio, Giacomin, Anna, Vanin, Veronica, Pozzan, Caterina, Maddalo, Gemma, Ciccarese, Francesca, Del Poggio, Paolo, Olmi, Stefano, Di Marco, Mariella, Balsamo, Claudia, Di Nolfo, Maria Anna, Vavassori, Elena, Alberti, Alfredo, Benvegnã¹, Luisa, Gatta, Angelo, Gios, Maurizio, Golfieri, Rita, Giampalma, Emanuela, Mosconi, Cristina, Renzulli, Matteo, Rapaccini, Gian Lodovico, Bosco, Giulia, Caturelli, Eugenio, Roselli, Paola, Dell’isola, Serena, Ialungo, Anna Maria, Giannini, Edoardo G., Risso, Domenico, Marenco, Simona, Bruzzone, Linda, Savarino, Vincenzo, Picciotto, Antonino, Chiaramonte, Maria, Cabibbo, Giuseppe, Cammã , Calogero, Maida, Marcello, Di Martino, Arezia, Barcellona, Maria Rosa, Mega, Andrea, Gasbarrini, Antonio, Rinninella, Emanuele, Rotella, Virginia, Ginanni, Barbara, Foschi, Francesco Giuseppe, Lanzi, Arianna, Stefanini, Giuseppe Francesco, Dall’aglio, Anna Chiara, Cappa, Federica Mirici, Neri, Elga, Bassi, Paolo, Zanotti, Miriam, Missale, Gabriele, Biasini, Elisabetta, Porro, Emanuela, Morisco, Filomena, Guarino, Maria, Baroni, Gianluca Svegliati, Schiadã , Laura, Gemini, Stefano, Borzio, Francesco, Virdone, Roberto, Rodolfo Sacco, Valeria Misma, Alessandro Granito, Gianna Musettini, Gianluca Masi, Chiara Caparello, Caterina Vivaldi, Martina Felder, Giampaolo Bresci, Lorenzo Fornaro, for the Italian Liver Cancer (ITA.LI.CA) group: [.., Franco Trevisani, Mauro Bernardi, Luigi Bolondi, Fabio Piscaglia, Marco Zoli, Maurizio Biselli, Paolo Caraceni, Alessandro Cucchetti, Marco Domenicali, Marta Frigerio, Virginia Erroi, Francesca Garuti, Annagiulia Gramenzi, Barbara Lenzi, Donatella Magalotti, Anna Pecorelli, Laura Venerandi, Rita Golfieri, Emanuela Giampalma, Cristina Mosconi, Matteo Renzulli, and ]

Subjects
Oncology, Male, Pathology, Cancer Research, Clinical Biochemistry, Drug Resistance, L-Lactate dehydrogenase, Biomarkers, HCC, LDH, Sorafenib, Aged, Antineoplastic Agents, Biomarkers, Tumor, Carcinoma, Hepatocellular, Drug Resistance, Neoplasm, Female, Humans, Kaplan-Meier Estimate, L-Lactate Dehydrogenase, Liver Neoplasms, Middle Aged, Niacinamide, Phenylurea Compounds, ROC Curve, Retrospective Studies, Treatment Outcome, 2734, Antineoplastic Agent, Retrospective Studie, Neoplasm, Tumor, Liver Neoplasm, Hepatocellular carcinoma, Human, medicine.drug, Phenylurea Compound, medicine.medical_specialty, Sorafenib treatment, Pathology and Forensic Medicine, Text mining, Internal medicine, medicine, Carcinoma, neoplasms, business.industry, Retrospective cohort study, Hepatocellular, Biomarker, medicine.disease, digestive system diseases, business
Abstract

Background Lactate dehydrogenase (LDH) is a predictor of clinical outcome in hepatocellular carcinoma (HCC) patients. However, its predictive role in the clinical outcomes of sorafenib treatment has been poorly documented. The correlation between LDH levels and clinical outcomes in HCC patients treated with sorafenib and included in the nationwide Italian database ITA.LI.CA was investigated here. Patients and Methods The ITA.LI.CA database contains data for 5,136 HCC patients. All patients treated with sorafenib treatment and with available LDH values were considered. Overall survival (OS) and time to progression (TTP) were compared in patients with LDH levels above and below a defined threshold, determined through an ROC analysis. An explorative analysis investigated the relationship between the variation of LDH levels during treatment and response to sorafenib. Results Baseline LDH levels were available for 97 patients. The most accurate cutoff value for LDH concentration was 297 U/L. Patients with LDH values above (n=45) and below (n=52) this threshold showed equal OS (12.0 months) and TTP (4.0 months) values. Data on LDH levels during sorafenib treatment were reported for 10 patients. LDH values decreased in 3 patients (mean difference = -219 U/L) who also reported a prolonged OS and TTP versus those with unmodified/increased LDH (OS: NE (not evaluated) vs. 8.0 months, p=0.0083; TTP: 19.0 vs. 3.0 months, p=0.008). Conclusions The clinical benefits of sorafenib do not seem to be influenced by baseline LDH. According to the results of an explorative analysis, however, a decreased LDH concentration during sorafenib might be associated with improved clinical outcomes.

Published
2015

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

Author

Cucchetti, A, Trevisani, F., Bucci, L., Ravaioli, M., Farinati, F., Giannini, E. G., Ciccarese, F., Piscaglia, F., Rapaccini, Gian Ludovico, Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Maida, M., Felder, M., Morisco, F., Gasbarrini, Antonio, Gemini, S., Foschi, F. G., Missale, G., Masotto, A., Affronti, A., Bernardi, M., Pinna, A. D., Bolondi, Luigi, Biselli, Maurizio, Caraceni, Paolo, Domenicali, Marco, Gramenzi, Annagiulia, Magalotti, Donatella, Pecorelli, Anna, Serra, Carla, Venerandi, Laura, Gazzola, Alessia, Murer, Francesca, Pozzan, Caterina, Vanin, Veronica, Del Poggio, Paolo, Olmi, Stefano, Balsamo, Claudia, Vavassori, Elena, Benvegnù, Luisa, Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Bosco, Giulia, Roselli, Paola, Dell'Isola, Serena, Lalungo, Anna Maria, Rastrelli, Elena, Moscatelli, Alessandro, Pellegatta, Gaia, Picciotto, Antonino, Savarino, Vincenzo, Barcellona, Maria Rosa, Cammà, Calogero, Cabibbo, Giuseppe, Costantino, Andrea, Virdone, Roberto, 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, Baroni, Gianluca Svegliati, Schiadà, Laura, Chiaramonte, Maria, Marchetti, Fabiana, Valerio, Matteo, Rapaccini, Gian Ludovico (ORCID:0000-0002-6467-857X), Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), Rinninella, Emanuele (ORCID:0000-0002-9165-2367), Cucchetti, A, Trevisani, F., Bucci, L., Ravaioli, M., Farinati, F., Giannini, E. G., Ciccarese, F., Piscaglia, F., Rapaccini, Gian Ludovico, Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Maida, M., Felder, M., Morisco, F., Gasbarrini, Antonio, Gemini, S., Foschi, F. G., Missale, G., Masotto, A., Affronti, A., Bernardi, M., Pinna, A. D., Bolondi, Luigi, Biselli, Maurizio, Caraceni, Paolo, Domenicali, Marco, Gramenzi, Annagiulia, Magalotti, Donatella, Pecorelli, Anna, Serra, Carla, Venerandi, Laura, Gazzola, Alessia, Murer, Francesca, Pozzan, Caterina, Vanin, Veronica, Del Poggio, Paolo, Olmi, Stefano, Balsamo, Claudia, Vavassori, Elena, Benvegnù, Luisa, Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Bosco, Giulia, Roselli, Paola, Dell'Isola, Serena, Lalungo, Anna Maria, Rastrelli, Elena, Moscatelli, Alessandro, Pellegatta, Gaia, Picciotto, Antonino, Savarino, Vincenzo, Barcellona, Maria Rosa, Cammà, Calogero, Cabibbo, Giuseppe, Costantino, Andrea, Virdone, Roberto, 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, Baroni, Gianluca Svegliati, Schiadà, Laura, Chiaramonte, Maria, Marchetti, Fabiana, Valerio, Matteo, Rapaccini, Gian Ludovico (ORCID:0000-0002-6467-857X), Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), and Rinninella, Emanuele (ORCID:0000-0002-9165-2367)

Abstract

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 <2 cm results in 3.7 years-of-life lost while the diagnosis when a single tumour ≥2 cm or 2/3 nodules still within the Milan criteria, results in 5.0 years-of-life lost, representing the loss of only approximately 5.5% and 7.2%, respectively, of the entire lifespan from birth. Conclusions: Hepatocellular carcinoma occurrence results in the loss of a considerable number of years-of-life, especially for younger patients. In recent years, the increased possibility of effectively treating this tumour has improved life expectancy, thus reducing years-of-life lost.

Published
2016

11. PNPLA3 GG Genotype and Carotid Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease

Author

Petta, Salvatore, primary, Valenti, Luca, additional, Marchesini, Giulio, additional, Di Marco, Vito, additional, Licata, Anna, additional, Cammà, Calogero, additional, Barcellona, Maria Rosa, additional, Cabibi, Daniela, additional, Donati, Benedetta, additional, Fracanzani, Anna, additional, Grimaudo, Stefania, additional, Parrinello, Gaspare, additional, Pipitone, Rosaria Maria, additional, Torres, Daniele, additional, Fargion, Silvia, additional, Licata, Giuseppe, additional, and Craxì, Antonio, additional

Published
2013
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13. Association Between PNPLA3 rs738409 C>G Variant and Liver-Related Outcomes in Patients with Non-alcoholic Fatty Liver Disease

Author

Stefania Grimaudo, Maria Rosa Barcellona, Federica Spatola, Antonio Craxì, Roberta Boemi, Rosaria Maria Pipitone, Aurora Giannetti, Grazia Pennisi, Marco Enea, Vito Di Marco, Salvatore Petta, Ciro Celsa, Giulio Marchesini, Calogero Cammà, Grimaudo, Stefania, Pipitone, Rosaria Maria, Pennisi, Grazia, Celsa, Ciro, Cammà, Calogero, Di Marco, Vito, Barcellona, Maria Rosa, Boemi, Roberta, Enea, Marco, Giannetti, Aurora, Spatola, Federica, Marchesini, Giulio, Craxì, Antonio, Petta, Salvatore, Grimaudo S., Pipitone R.M., Pennisi G., Celsa C., Camma C., Di Marco V., Barcellona M.R., Boemi R., Enea M., Giannetti A., Spatola F., Marchesini G., Craxi A., and Petta S.

Subjects
Liver Cancer, medicine.medical_specialty, Cirrhosis, Carcinoma, Hepatocellular, Genotype, Gastroenterology, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Internal medicine, Nonalcoholic fatty liver disease, medicine, Humans, Decompensation, Genetic Predisposition to Disease, Prospective Studies, Prospective cohort study, Hepatology, Proportional hazards model, business.industry, Prognostic Factor, Risk Factor, Hazard ratio, Liver Neoplasms, Membrane Proteins, Long-Term Outcome, Lipase, medicine.disease, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, business, Liver cancer
Abstract

Background & Aims Patients with nonalcoholic fatty liver disease (NAFLD) have an increased risk for liver-related complications, such as decompensation, hepatocellular carcinoma (HCC), and death; the severity of liver fibrosis and metabolic comorbidities are the main risk factors. A single nucleotide polymorphism in patatin-like phospholipase domain-containing-3 (PNPLA3) gene is associated with higher prevalence of liver damage and HCC, but there are no data from prospective studies of outcomes of patients with this polymorphism. We investigated whether the common rs738409 variant in PNPLA3 gene associates with the occurrence of liver-related events and death in a large cohort of patients with NAFLD. Methods We followed 471 consecutive individuals at a hospital in Italy with a diagnosis of NAFLD based on histologic factors or a diagnosis of compensated NAFLD-related cirrhosis based on clinical factors for at least 6 months, from March 2004 through December 2018. We collected data on the occurrence of hepatic and extrahepatic outcomes, including decompensation and HCC, cardiovascular events and extrahepatic cancers, and overall and liver-related death. We detected the rs738409 G>C polymorphism in DNA from patient blood samples using the TaqMan assay. Results During a median follow-up time of 64.6 months (range 6.1–175 months) 26 cases of decompensation, 13 HCCs, and 16 deaths (12 liver-related) were recorded. All liver-related events, including liver-related death, occurred in patients with F3 fibrosis or cirrhosis. The prevalence of PNPLA3 rs738409 GG, GT, and TT genotypes was 31.8%, 45.6%, and 22.6%, respectively. After adjusting for clinical, metabolic, and histologic risk factors, PNPLA3 C>G variant was associated with a higher risk of decompensation (hazard ratio [HR], 2.10; 95% CI, 1.03–4.29; P = .04), HCC (HR, 2.68; 95% CI, 1.01–7.26; P = .04), and liver-related death (HR, 3.64; 95% CI, 1.18–11.2; P = .02) by multivariate Cox regression analysis. In the subgroup of 162 patients with F3 fibrosis or cirrhosis, we confirmed the independent association between the PNPLA3 variant and decompensation (HR, 2.00; 95% CI, 1.01–3.97; P = .04), HCC (HR, 2.66; 95% CI, 1.02–7.13; P = .04), and liver-related death (HR, 3.64, 95% CI, 1.18–11.2; P = .02). We found no association between PNPLA3 genotype and cardiovascular events, extrahepatic cancers, or overall mortality. Conclusions Patients with NAFLD carrying PNPLA3 rs738409 G>C variant are at higher risk of liver-related events and death.

Published
2020

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