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1. Patterns of treatment and costs of intermediate and advanced hepatocellular carcinoma management in four Italian centers

Author

Colombo GL, Cammà C, Attili AF, Ganga R, Gaeta GB, Brancaccio G, Franzini JM, Volpe M, and Turchetti G

Subjects
Therapeutics. Pharmacology, RM1-950
Abstract

Giorgio Lorenzo Colombo,1 Calogero Cammà,2 Adolfo Francesco Attili,3 Roberto Ganga,4 Giovanni Battista Gaeta,5 Giuseppina Brancaccio,5 Jean Marie Franzini,6 Marco Volpe,6 Giuseppe Turchetti7 1Department of Drug Sciences, University of Pavia, Pavia, Italy; 2Section of Gastroenterology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy; 3Department of Clinical Medicine, University of Rome (La Sapienza) Rome, Italy; 4Clinical Medicine Division, Ospedale Brotzu, Cagliari, Italy; 5Viral Hepatitis Unit, Second University, Naples, Italy; 6Business Integration Partners S.p.A., Milan, Italy; 7Scuola Superiore Sant’Anna, Pisa, Italy Background: Hepatocellular carcinoma (HCC) is a severe health condition associated with high hospitalizations and mortality rates, which also imposes a relevant economic burden.Purpose: The aim of the present survey is to investigate treatment strategies and related costs for HCC in the intermediate and advanced stages of the disease. Patients and methods: The survey was conducted in four Italian centers through structured interviews with physicians. Information regarding the stage of disease, treatments performed, and related health care resource consumption was included in the questionnaire. Direct health care cost per patient associated with the most relevant treatments such as sorafenib, transarterial chemoembolization (TACE), and transarterial radioembolization (TARE) was evaluated.Results: Between 2013 and 2014, 285 patients with HCC were treated in the four participating centers; of these, 80 were in intermediate stage HCC (Barcelona Clinic Liver Cancer Classification [BCLC] B), and 57 were in the advanced stage of the disease (BCLC C). In intermediate stage HCC, the most frequent first-line treatment was TACE (63%) followed by sorafenib (15%), radiofrequency ablation (14%), and TARE (1.3%). In the advanced stage of HCC, the most frequently used first-line therapy was sorafenib (56%), followed by best supportive care (21%), TACE (18%), and TARE (3.5%). The total costs of treatment per patient amounted to €12,214.54 with sorafenib, €13,418.49 with TACE, and €26,106.08 with TARE. Both in the intermediate and in the advanced stage of the disease, variability in treatment patterns among centers was observed.Conclusion: The present analysis raises for the first time the awareness of the overall costs incurred by the Italian National Healthcare System for different treatments used in intermediate and advanced HCC. Further investigations would be important to better understand the effective health care resource usage. Keywords: disease costs, drugs cost, transarterial embolization, sorafenib

Published
2015

2. Italy GIDEON final analysis Sorafenib-treated patients: prognostic value of baseline characteristics and staging systems

Author

D'Angelo, S, Lorusso, V, Piras, MR, Sansonno, D, Benedetti, A, Montesarchio, V, Attili, AF, Frustaci, S, Barni, S, Pirisi, M, Carpani, D, Magini, G, Daniele, B., GIANNITRAPANI, Lydia, D'Angelo, S, Lorusso, V, Piras, MR, Sansonno, D, Giannitrapani, L, Benedetti, A, Montesarchio, V, Attili, AF, Frustaci, S, Barni, S, Pirisi, M, Carpani, D, Magini, G, and Daniele, B

Subjects
Settore MED/09 - Medicina Interna, HCC, Sorafenib, clinical practice
Published
2014

3. HCC management with Sorafenib and TACE: Italian experience from GIDEON (Global Investigational Of Therapeutic Decisions in HCC and of its Treatment with Sorafenib)

Author

Lorusso, V, Germano, D, Zolfino, MT, Sansonno, D, Benedetti, A, Montesarchio, V, Attili, AF, Frustaci, S, Gasbarrini, A, Cillo, U, Carpani, D. Picciotto A, D’Angelo S., MONTALTO, Giuseppe, Lorusso, V, Germano, D, Zolfino, MT, Sansonno, D, Montalto, G, Benedetti, A, Montesarchio, V, Attili, AF, Frustaci, S, Gasbarrini, A, Cillo, U, and Carpani, D Picciotto A, D’Angelo S

Subjects
Hepatocellular carcinoma, Sorafenib, Management
Published
2014

4. Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort

Author

GUARD C, Study Group, Hassanein, T, Bakalos, G, Ahlers, S, Shiffman, Ml, Tallarico, L, Reddy, Kr, Orlandini, A, Ferenci, P, Derbala, M, Coppola, C, Foster, Gr, Basho, J, Shabanaj, G, Harxhi, A, Debzi, N, Afredj, N, Guessab, N, Mahindad, N, Mahiou, H, Aissaoui, M, Al Qameesh, J, Al Ghandoor, Z, Assene, C, Bastens, B, Brixko, C, Cool, M, De Galocsy, C, Delwaide, J, George, C, Laukens, P, Lefebvre, V, Mulkay, Jp, Nevens, F, Servais, B, Van Vlierberghe, H, Horsmans, Y, Henrion, J, Sprengers, D, Michielsen, P, Bourgeois, S, Lasser, L, Langlet, P, Robaeys, G, Martinet, Jp, Warzee, P, Hoste, P, Reynaert, H, Juriens, I, Decaestecker, J, Van Der Meersch, F, Janssens, F, Ahmetagic, S, Verhaz, A, Bevanda, M, Calkic, L, Ibrahimpasic, N, Mesihovic, R, Mello, Ce, Ruiz, Fj, Martins Junior, E, Ferraz, Ml, Silva, G, Mendes, C, Lyra, A, Silva, Mh, Gomide, G, Fernandes, Jc, Pereira, P, Correa, Mc, Teixeira, R, Yousry, A, Hanno, A, Gabr, M, Omar, A, Esmat, G, Karatapanis, S, Nikolopoulou, V, Giannoulis, G, Manolakopoulos, S, Elefsiniotis, I, Drakoulis, C, Dimitroulopoulos, D, Kanatakis, S, Ketikoglou, I, Mimidis, K, Evgenidis, N, Akriviades, E, Vafiadi Zoubouli, I, Tsianos, E, Mela, M, Orfanou, E, Mousoulis, G, Karagiannis, I, Manesis, E, Varga, M, Nemesánszky, E, Fried, K, Schuller, J, Szalay, F, Lengyel, G, Tornai, I, Banyai, T, Lesch, M, Nagy, I, Gervain, J, Tusnadi, A, Schneider, F, Szentgyörgyi, L, Hunyady, B, Vincze, A, Tolvaj, G, Varkonyi, I, Makkai, E, Enyedi, J, Racz, I, Hausinger, P, Váczi, Z, Patai, Á, Ozsvár, Z, Lakner, L, Ribiczey, P, Bhalla, A, Somani, S, Luaia, R, Rao, P, Philip, M, Lawate, P, Nagral, A, Sood, A, Parikh, S, Merat, S, Nassiri Toosi, M, Alavian, Sm, Zali, Mr, Daryani, Ne, Drenaggi, D, Attili, Af, Bandiera, F, Bassi, P, Bellati, G, Bellantani, S, Brunetto, MAURIZIA ROSSANA, Bruno, S, Castelli, F, Castellacci, R, Cattelan, Am, Colombo, M, Craxi, A, D'Angelo, S, Colombo, S, Demelia, L, Di Perri, G, Di Giacomo, A, Ferrari, C, Francisci, D, Casinelli, K, Ganga, R, Costa, C, Mangia, A, Russo, Fp, Matarazzo, F, Mazzella, G, Mazzeo, M, Memoli, M, Montalbano, M, Montalto, G, Pieri, A, Passariello, N, Picciotto, A, Pietrangelo, A, Pirisi, M, Quirino, T, Raimondo, G, Rapaccini, Gl, Rizzardini, G, Rizzetto, M, Russello, M, Sabusco, G, Santantonio, T, Soardo, G, Amedea, A, Verucchi, G, Vinelli, F, Zignego, Al, Zuin, M, Ascione, A, Vinci, M, Pigozzi, Mg, Tundo, P, Saracco, Gm, Amoroso, P, Andreoni, M, Colletta, C, Erne, E, Megna, As, Biglino, A, Chiriaco, P, Foti, G, Spinzi, G, D'Amico, E, Paik, Sw, Ahn, Sh, Lee, Yn, Kim, Y, Yang, J, Han, Sy, Varghese, R, Al Gharabally, A, Askar, H, Sharara, A, Yaghi, C, Rached, Aa, Houmani, Z, Zaarour, F, Dohaibi, A, Ivanovski, L, Joksimovic, N, Abbas, Z, Memon, S, Mohsin, A, Masood, S, Hashmi, Z, Halota, W, Deron, Z, Mazur, W, Flisiak, R, Lipczynski, A, Musialik, J, Piekarska, A, Augustyniak, K, Baka Cwierz, B, Simon, K, Gietka, A, Berak, H, Sieklucki, J, Radowska, D, Szlauer, B, Piekos, T, Olszok, I, Jablkowski, M, Orszulak, G, Warakomska, I, Aleixo, Mj, Valente, C, Macedo, G, Sarmento Castro, R, Roxo, F, Faria, T, Mansinho, K, Velez, J, Ramos, Jp, Guerreiro, H, Alberto, S, Monteverde, C, Serejo, F, Peixe, P, Malhado, J, Curescu, M, Streinu Cercel, A, Caruntu, F, Livia, H, Preotescu, L, Arama, V, Ancuta, I, Gheorghe, L, Stanciu, C, Trifan, A, Acalovschi, M, Andreica, V, Pascu, O, Lencu, M, Sporea, I, Olteanu, D, Ionita Radu, F, Fierbinteanu Braticevici, C, Motoc, A, Silaghi, R, Musat, M, Coman, F, Stan, M, Cijevschi, C, Miftode, E, Delic, D, Jesic, R, Nozic, D, Svorcan, P, Fabri, M, Konstantinovic, L, Pelemis, M, Jankovic, G, Todorovic, Z, Nagorni, A, Kupcova, V, Skladany, L, Szantova, M, Krkoska, D, Jarcuska, P, Schreter, I, Oltman, M, Bocakova, J, Bunganic, I, Holoman, J, Giguere, A, Abdou, A. M., Basic (bio-) Medical Sciences, Gastroenterology, Laboratory of Molecullar and Cellular Therapy, Liver Cell Biology, Michielsen, Peter, GUARD-C Study Group, Graham R. Foster, Carmine Coppola, Moutaz Derbala, Peter Ferenci, Alessandra Orlandini, K. Rajender Reddy, Ludovico Tallarico, Mitchell L. Shiffman, Silke Ahler, Georgios Bakalo, Tarek Hassanein, GUARD-C Study Group: [.., Davide Drenaggi, Adolfo Francesco Attili, Franco Bandiera, Paolo Bassi, Giorgio Bellati, Stefano Bellantani, Maurizia Brunetto, Savino Bruno, Francesco Castelli, Roberto Castellacci, Anna Maria Cattelan, Massimo Colombo, Antonio Craxi, Salvatore D'angelo, Silvia Colombo, Luigi Demelia, Giovanni Di Perri, Antonio Di Giacomo, Carlo Ferrari, Daniela Francisci, Katia Casinelli, Roberto Ganga, Chiara Costa, Alessandra Mangia, Francesco Paolo Russo, Filippo Matarazzo, Giuseppe Mazzella, Maurizio Mazzeo, Massimo Memoli, Marzia Montalbano, Giuseppe Montalto, Alessandro Pieri, Nicola Passariello, Antonio Picciotto, Antonello Pietrangelo, Mario Pirisi, Tiziana Quirino, Giovanni Raimondo, Gian Ludovico Rapaccini, Giuliano Rizzardini, Mario Rizzetto, Maurizio Russello, Giuseppe Sabusco, Teresa Santantonio, Giorgio Soardo, Alessandri Amedea, Gabriella Verucchi, Francesco Vinelli, Anna Linda Zignego, Massimo Zuin, Antonio Ascione, Maria Vinci, Maria Graziella Pigozzi, Paolo Tundo, Giorgio Maria Saracco, Pietro Amoroso, Massimo Andreoni, Cosimo Colletta, Elke Erne, Angelo Salomone Megna, Alberto Biglino, Piergiorgio Chiriaco, Giuseppe Foti, Giancarlo Spinzi, Emilio D'amico, …], Foster G.R., Coppola C., Derbala M., Ferenci P., Orlandini A., Reddy K.R., Tallarico L., Shiffman M.L., Ahlers S., Bakalos G., Hassanein T., Basho J., Shabanaj G., Harxhi A., Debzi N., Afredj N., Guessab N., Mahindad N., Mahiou H., Aissaoui M., Al Qameesh J., Al Ghandoor Z., Assene C., Bastens B., Brixko C., Cool M., De Galocsy C., Delwaide J., George C., Laukens P., Lefebvre V., Mulkay J.-P., Nevens F., Servais B., Van Vlierberghe H., Horsmans Y., Henrion J., Sprengers D., Michielsen P., Bourgeois S., Lasser L., Langlet P., Robaeys G., Martinet J.-P., Warzee P., Hoste P., Reynaert H., Juriens I., Decaestecker J., Van Der Meersch F., Janssens F., Ahmetagic S., Verhaz A., Bevanda M., Calkic L., Ibrahimpasic N., Mesihovic R., Mello C.E., Ruiz F.J., Junior E.M., Ferraz M.L., Silva G., Mendes C., Lyra A., Silva M.H., Gomide G., Fernandes J.C., Pereira P., Correa M.C., Teixeira R., Yousry A., Hanno A., Gabr M., Omar A., Esmat G., Karatapanis S., Nikolopoulou V., Giannoulis G., Manolakopoulos S., Elefsiniotis I., Drakoulis C., Dimitroulopoulos D., Kanatakis S., Ketikoglou I., Mimidis K., Evgenidis N., Akriviades E., Vafiadi-Zoubouli I., Tsianos E., Mela M., Orfanou E., Mousoulis G., Karagiannis I., Manesis E., Varga M., Nemesanszky E., Fried K., Schuller J., Szalay F., Lengyel G., Tornai I., Banyai T., Lesch M., Nagy I., Gervain J., Tusnadi A., Schneider F., Szentgyorgyi L., Hunyady B., Vincze A., Tolvaj G., Varkonyi I., Makkai E., Enyedi J., Racz I., Hausinger P., Vaczi Z., Patai A., Ozsvar Z., Lakner L., Ribiczey P., Bhalla A., Somani S., Luaia R., Rao P., Philip M., Lawate P., Nagral A., Sood A., Parikh S., Merat S., Nassiri-Toosi M., Alavian S.-M., Zali M.R., Daryani N.E., Drenaggi D., Attili A.F., Bandiera F., Bassi P., Bellati G., Bellantani S., Brunetto M., Bruno S., Castelli F., Castellacci R., Cattelan A.M., Colombo M., Craxi A., D'angelo S., Colombo S., Demelia L., Di Perri G., Di Giacomo A., Ferrari C., Francisci D., Casinelli K., Ganga R., Costa C., Mangia A., Russo F.P., Matarazzo F., Mazzella G., Mazzeo M., Memoli M., Montalbano M., Montalto G., Pieri A., Passariello N., Picciotto A., Pietrangelo A., Pirisi M., Quirino T., Raimondo G., Rapaccini G.L., Rizzardini G., Rizzetto M., Russello M., Sabusco G., Santantonio T., Soardo G., Amedea A., Verucchi G., Vinelli F., Zignego A.L., Zuin M., Ascione A., Vinci M., Pigozzi M.G., Tundo P., Saracco G.M., Amoroso P., Andreoni M., Colletta C., Erne E., Megna A.S., Biglino A., Chiriaco P., Foti G., Spinzi G., D'amico E., Paik S.W., Ahn S.-H., Lee Y.N., Kim Y., Yang J., Han S.Y., Varghese R., Al Gharabally A., Askar H., Sharara A., Yaghi C., Abou Rached A., Houmani Z., Zaarour F., Dohaibi A., Ivanovski L., Joksimovic N., Abbas Z., Memon S., Mohsin A., Masood S., Hashmi Z., Halota W., Deron Z., Mazur W., Flisiak R., Lipczynski A., Musialik J., Piekarska A., Augustyniak K., Baka-Cwierz B., Simon K., Gietka A., Berak H., Sieklucki J., Radowska D., Szlauer B., Piekos T., Olszok I., Jablkowski M., Orszulak G., Warakomska I., Aleixo M.J., Valente C., Macedo G., Sarmento-Castro R., Roxo F., Faria T., Mansinho K., Velez J., Ramos J.P., Guerreiro H., Alberto S., Monteverde C., Serejo F., Peixe P., Malhado J., Curescu M., Streinu-Cercel A., Caruntu F., Livia H., Preotescu L., Arama V., Ancuta I., Gheorghe L., Stanciu C., Trifan A., Acalovschi M., Andreica V., Pascu O., Lencu M., Sporea I., Olteanu D., Ionita-Radu F., Fierbinteanu-Braticevici C., Motoc A., Silaghi R., Musat M., Coman F., Stan M., Cijevschi C., Miftode E., Delic D., Jesic R., Nozic D., Svorcan P., Fabri M., Konstantinovic L., Pelemis M., Jankovic G., Todorovic Z., Nagorni A., Kupcova V., Skladany L., Szantova M., Krkoska D., Jarcuska P., Schreter I., Oltman M., Bocakova J., Bunganic I., Holoman J., Giguere A., Abdou A.M.S., UCL - SSS/IREC-Institut de recherche expérimentale et clinique, UCL - SSS/IREC/GAEN-Pôle d'Hépato-gastro-entérologie, and UCL - (SLuc) Service de gastro-entérologie

Subjects
Genetics and Molecular Biology (all), Male, Chronic Hepatitis, Hepacivirus, Ribavirin/adverse effects, Asthenia/chemically induced, Polyethylene Glycol, Biochemistry, Polyethylene Glycols, Body Mass Index, Chronic Liver Disease, 0302 clinical medicine, Neutropenia/chemically induced, Interferon-alpha/adverse effects, Medicine, Chronic, lcsh:Science, Liver Diseases, virus diseases, Antiviral Agents/adverse effects, Cohort, Science & Technology - Other Topics, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Cohort study, Human, medicine.medical_specialty, Alpha interferon, Gastroenterology and Hepatology, Antiviral Agents, Microbiology, Dose-Response Relationship, 03 medical and health sciences, Pharmacotherapy, Hepatitis C, Chronic/drug therapy, Dose Prediction Methods, Drug Therapy, Anemia/chemically induced, Humans, Hemoglobin, Aged, Medicine and health sciences, Biochemistry, Genetics and Molecular Biology (all), Hepaciviru, Science & Technology, Dose-Response Relationship, Drug, Flaviviruses, lcsh:R, Organisms, Biology and Life Sciences, Proteins, medicine.disease, digestive system diseases, chemistry, Agricultural and Biological Sciences (all), Withholding Treatment, Asthenia, Immunology, Proportional Hazards Model, lcsh:Q, Human medicine, RNA viruses, Physiology, lcsh:Medicine, Peginterferon-alfa, Polyethylene Glycols/adverse effects, Adult, Anemia, Cohort Studies, Female, Hepatitis C, Chronic, Host-Pathogen Interactions, Interferon-alpha, Middle Aged, Neutropenia, Outcome Assessment (Health Care), Proportional Hazards Models, RNA, Viral, Recombinant Proteins, Ribavirin, Medicine (all), chemistry.chemical_compound, Outcome Assessment, Health Care, Medicine and Health Sciences, 030212 general & internal medicine, Viral, Pathology and laboratory medicine, Multidisciplinary, biology, Hepatitis C virus, Pharmaceutics, Hepatitis C, Hematology, Recombinant Protein, Outcome Assessment (Health Care)/methods, Medical microbiology, Host-Pathogen Interaction, Multidisciplinary Sciences, Physiological Parameters, Research Design, Combination, Viruses, Drug, Pathogens, Host-Pathogen Interactions/drug effects, Research Article, Clinical Research Design, Research and Analysis Methods, Internal medicine, Recombinant Proteins/adverse effects, RNA, Viral/blood, Antiviral Agent, business.industry, Body Weight, Hepacivirus/drug effects, Viral pathogens, biology.organism_classification, Hepatitis viruses, Microbial pathogens, RNA, Adverse Events, Cohort Studie, business
Abstract

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA

Published
2015

7. A Simplified Psychometric Evaluation for the Diagnosis of Minimal Hepatic Encephalopathy

Author

Riggio, O, Ridola, L, Pasquale, C, Pentassuglio, I, Nardelli, S, Moscucci, F, Trezza, M, Merli, M, Attili, Af, Montagnese, Sara, Amodio, Piero, and Merkel, Carlo

Subjects
Male, medicine.medical_specialty, Psychometrics, liver cirrhosis, hepatic encephalopathy, minimal hepatic encephalopathy, Logistic regression, Gastroenterology, Liver disease, Model for End-Stage Liver Disease, mild cognitive impairment, Internal medicine, medicine, Humans, Hepatic encephalopathy, Aged, Aged, 80 and over, Validation group, Hepatology, Proportional hazards model, business.industry, psychometric evaluation, Middle Aged, medicine.disease, Surgery, Relative risk, Female, business, Psychometric tests, Follow-Up Studies
Abstract

Background & Aims The psychometric hepatic encephalopathy score (PHES), which includes 5 psychometric tests, is a standard for the diagnosis of minimal hepatic encephalopathy (HE). We investigated whether a simplified PHES (SPHES) is as useful as the whole PHES. Methods The PHES was determined for 79 cirrhotic patients (the training group), who were followed up for the development of overt HE. Backward logistic regression was performed by eliminating stepwise variables—removal did not impair regression. A separate series of 65 patients was used as a validation group. Results The PHES was abnormal in 45 patients. The SPHES, determined from the digit symbol, serial dotting, and line tracing tests, did not differ significantly from the full PHES; 24 of the 79 patients developed overt HE. The likelihood of developing overt HE was higher among patients with an abnormal PHES (log-rank P = .003) or SPHES ( P = .004). By using Cox regression and model for end-stage liver disease scores to analyze data from patients with previous HE and transjugular intrahepatic portosystemic shunts, PHES (relative risk, 4.16; P = .003) and SPHES (relative risk, 3.70; P = .004) were the only variables associated with the development of overt HE. The accuracy of the SPHES was confirmed in the validation group. Conclusions A simplified PHES is as good as the PHES in diagnosing minimal HE and in predicting the occurrence of overt HE.

Published
2011

9. Role of body mass index in the prediction of all cause mortality in over 62000 men and women. The Italian RIFLE Pooling Project

Author

SECCARECCIA F, LANTI M, MENOTTI A, SCANGA M, THE RIFLE RESEARCH GROUP, FARCHI G, CONTI S, MARENCO G, FALCHERO M, FERRARIO M, CESANA GC, TENCONI MT, MUSSI A, DOBRILLA G, DE PETRIS G, ANGELINI GP, OCKOLICSANYI L, TOSO S, AMBROSIO GB, BITTOLO BON G, ALESSANDRINI P, FERUGLIO GA, VANUZZO D, CARULLI N, SALVIOLI GF, GADDI A, D'ADDARO S, ALVISI V, BUZZELLI GP, GIACCHI M, LAURENZI M, SPAGNOLO A, RICCI G, ANTONINI R, ANGELICO F, LALLONI L, ATTILI AF, URBINATI GC, GIAMPAOLI S, MANCINI M, PANICO S, FARINARO E, ALBANO O, MISCIAGNA G, MUNTONI S, STABILINI L, AVELLONE G, DI GARBO G., DEVOTI, Gabriele, Seccareccia, F, Lanti, M, Menotti, A, Scanga, M, THE RIFLE RESEARCH, Group, Farchi, G, Conti, S, Marenco, G, Falchero, M, Ferrario, M, Cesana, Gc, Tenconi, Mt, Mussi, A, Devoti, Gabriele, Dobrilla, G, DE PETRIS, G, Angelini, Gp, Ockolicsanyi, L, Toso, S, Ambrosio, Gb, BITTOLO BON, G, Alessandrini, P, Feruglio, Ga, Vanuzzo, D, Carulli, N, Salvioli, Gf, Gaddi, A, D'Addaro, S, Alvisi, V, Buzzelli, Gp, Giacchi, M, Laurenzi, M, Spagnolo, A, Ricci, G, Antonini, R, Angelico, F, Lalloni, L, Attili, Af, Urbinati, Gc, Giampaoli, S, Mancini, M, Panico, S, Farinaro, E, Albano, O, Misciagna, G, Muntoni, S, Stabilini, L, Avellone, G, and DI GARBO, G.

Published
1998

10. Electrocardiographic Minnesota Code findings predicting short-term mortality in asymptomatic subjects. The Italian RIFLE Pooling Project (Risk Factors and Life Expectancy)

Author

MENOTTI A, SECCARECCIA F, THE RIFLE RESEARCH GROUP, LANTI M, FARCHI G, CONTI S, DIMA F, SCANGA M, MARENCO G, FALCHERO M, FERRARIO M, CESANA GC, TENCONI MT, LADDOMADA MS, DOBRILLA G, DE PETRIS G, ANGELINI GP, OCKOLICSANYI L, TOSO S, AMBROSIO GB, BITTOLO BON G, ALESSANDRINI P, FERUGLIO GA, VANUZZO D, CARULLI N, SALVIOLI GF, GADDI A, D'ADDATO S, ALVISI V, BUZZELLI GP, GIACCHI M, LAURENZI M, SPAGNOLO A, RICCI G, ANTONINI R, ANGELICO F, LALLONI L, ATTILI AF, URBINATI GC, GIAMPAOLI S, MANCINI M, PANICO S, FARINARO E, ALBANO O, MISCIAGNA G, MUNTONI S, STABILINI L, AVELLONE G, DI GARBO G. ., DEVOTI, Gabriele, Menotti, A, Seccareccia, F, THE RIFLE RESEARCH, Group, Lanti, M, Farchi, G, Conti, S, Dima, F, Scanga, M, Marenco, G, Falchero, M, Ferrario, M, Cesana, Gc, Tenconi, Mt, Laddomada, M, Devoti, Gabriele, Dobrilla, G, DE PETRIS, G, Angelini, Gp, Ockolicsanyi, L, Toso, S, Ambrosio, Gb, BITTOLO BON, G, Alessandrini, P, Feruglio, Ga, Vanuzzo, D, Carulli, N, Salvioli, Gf, Gaddi, A, D'Addato, S, Alvisi, V, Buzzelli, Gp, Giacchi, M, Laurenzi, M, Spagnolo, A, Ricci, G, Antonini, R, Angelico, F, Lalloni, L, Attili, Af, Urbinati, Gc, Giampaoli, S, Mancini, M, Panico, S, Farinaro, E, Albano, O, Misciagna, G, Muntoni, S, Stabilini, L, Avellone, G, and DI GARBO, G. .

Published
1997

11. Syndrome X: prevalence in a large population-based study

Author

LIU J, TREVISAN M, MENOTTI A, THE RIFLE RESEARCH GROUP, LANTI M, FARCHI G, CONTI S, SECCARECCIA F, DIMA F, SCANGA M, MARENCO G, FALCHERO M, FERRARIO M, CESANA GC, TENCONI MT, LADDOMADA MS, DOBRILLA G, DE PETRIS G, ANGELINI GP, OCKOLICSANYI L, TOSO S, AMBROSIO GB, BITTOLO BON G, ALESSANDRINI P, FERUGLIO GA, VANUZZO D, CARULLI N, SALVIOLI GF, GADDI A, D'ADDARO S, ALVISI V, BUZZELLI GP, GIACCHI M, LAURENZI M, SPAGNOLO A, RICCI G, ANTONINI R, ANGELICO F, LALLONI L, ATTILI AF, URBINATI GC, GIAMPAOLI S, MANCINI M, PANICO S, FARINARO E, ALBANO O, MISCIAGNA G, MUNTONI S, STABILINI L, AVELLONE G, DI GARBO G. ., DEVOTI, Gabriele, Liu, J, Trevisan, M, Menotti, A, THE RIFLE RESEARCH, Group, Lanti, M, Farchi, G, Conti, S, Seccareccia, F, Dima, F, Scanga, M, Marenco, G, Falchero, M, Ferrario, M, Cesana, Gc, Tenconi, Mt, Laddomada, M, Devoti, Gabriele, Dobrilla, G, DE PETRIS, G, Angelini, Gp, Ockolicsanyi, L, Toso, S, Ambrosio, Gb, BITTOLO BON, G, Alessandrini, P, Feruglio, Ga, Vanuzzo, D, Carulli, N, Salvioli, Gf, Gaddi, A, D'Addaro, S, Alvisi, V, Buzzelli, Gp, Giacchi, M, Laurenzi, M, Spagnolo, A, Ricci, G, Antonini, R, Angelico, F, Lalloni, L, Attili, Af, Urbinati, Gc, Giampaoli, S, Mancini, M, Panico, S, Farinaro, E, Albano, O, Misciagna, G, Muntoni, S, Stabilini, L, Avellone, G, and DI GARBO, G. .

Published
1997

13. Mean levels and distributions of some cardiovascular risk factors in Italy in the 1970's and the 1980's. The Italian RIFLE Pooling Project. Risk Factors and Life Expectancy

Author

MENOTTI A, SECCARECCIA F, LANTI M, THE RIFLE PROJECT RESEARCH GROUP, FARCHI G, CONTI S, DIMA F, SCANGA M, MARENCO G, FALCHERO M, IDEO G, PODDA M, FERRARIO M, CESANA GC, TENCONI MT, MUSSI A, DOBRILLA G, DE PETRIS G, ANGELINI GP, OCKOLICSANYI L, TOSO S, AMBROSIO GB, BITTOLO BON G, ALESSANDRINI P, FERUGLIO GA, VANUZZO D, CARULLI N, SALVIOLI GF, GADDI A, D'ADDARO S, ALVISI V, BUZZELLI GP, GIACCHI M, LAURENZI M, SPAGNOLO A, RICCI G, ANTONINI R, ANGELICO F, LALLONI L, ATTILI AF, URBINATI GC, GIAMPAOLI S, MANCINI M, PANICO S, FARINARO E, ALBANO O, MISCIAGNA G, MUNTONI S, STABILINI L, AVELLONE G, DI GARBO G. ., DEVOTI, Gabriele, Menotti, A, Seccareccia, F, Lanti, M, THE RIFLE PROJECT RESEARCH, Group, Farchi, G, Conti, S, Dima, F, Scanga, M, Marenco, G, Falchero, M, Ideo, G, Podda, M, Ferrario, M, Cesana, Gc, Tenconi, Mt, Mussi, A, Devoti, Gabriele, Dobrilla, G, DE PETRIS, G, Angelini, Gp, Ockolicsanyi, L, Toso, S, Ambrosio, Gb, BITTOLO BON, G, Alessandrini, P, Feruglio, Ga, Vanuzzo, D, Carulli, N, Salvioli, Gf, Gaddi, A, D'Addaro, S, Alvisi, V, Buzzelli, Gp, Giacchi, M, Laurenzi, M, Spagnolo, A, Ricci, G, Antonini, R, Angelico, F, Lalloni, L, Attili, Af, Urbinati, Gc, Giampaoli, S, Mancini, M, Panico, S, Farinaro, E, Albano, O, Misciagna, G, Muntoni, S, Stabilini, L, Avellone, G, and DI GARBO, G. .

Published
1995

14. The prediction of coronary heart disease mortality as a function of major risk factors in over 30000 men in the Italian RIFLE Pooling Project. A comparison with the MRFIT primary screenees

Author

MENOTTI A, FARCHI G, SECCARECCIA F, THE RIFLE RESEARCH GROUP, CONTI S, GIAMPAOLI S, LANTI M, MARIOTTI S, SCANGA M, MARENCO G, FALCHERO M, IDEO G, PODDA M, FERRARIO M, CESANA GC, TENCONI MT, LADDOMADA MS, DOBRILLA G, DE PETRIS G, ANGELINI GP, OCKOLICSANYI L, TOSO S, AMBROSIO GB, BITTOLO BON G, ALESSANDRINI P, FERUGLIO GA, VANUZZO D, CARULLI N, SALVIOLI GF, GADDI A, D'ADDARO S, ALVISI V, BUZZELLI GP, GIACCHI M, LAURENZI M, SPAGNOLO A, RICCI G, ANTONINI R, ANGELICO F, LALLONI L, ATTILI AF, URBINATI GC, MANCINI M, PANICO S, FARINARO E, ALBANO O, MISCIAGNA G, MUNTONI S, STABILINI L, AVELLONE G, DI GARBO G. ., DEVOTI, Gabriele, Menotti, A, Farchi, G, Seccareccia, F, THE RIFLE RESEARCH, Group, Conti, S, Giampaoli, S, Lanti, M, Mariotti, S, Scanga, M, Marenco, G, Falchero, M, Ideo, G, Podda, M, Ferrario, M, Cesana, Gc, Tenconi, Mt, Laddomada, M, Devoti, Gabriele, Dobrilla, G, DE PETRIS, G, Angelini, Gp, Ockolicsanyi, L, Toso, S, Ambrosio, Gb, BITTOLO BON, G, Alessandrini, P, Feruglio, Ga, Vanuzzo, D, Carulli, N, Salvioli, Gf, Gaddi, A, D'Addaro, S, Alvisi, V, Buzzelli, Gp, Giacchi, M, Laurenzi, M, Spagnolo, A, Ricci, G, Antonini, R, Angelico, F, Lalloni, L, Attili, Af, Urbinati, Gc, Mancini, M, Panico, S, Farinaro, E, Albano, O, Misciagna, G, Muntoni, S, Stabilini, L, Avellone, G, and DI GARBO, G. .

Published
1994

15. Presentation of the RIFLE Project Risk Factors and Life Expectancy

Author

THE RIFLE RESEARCH GROUP, MENOTTI A, FARCHI G, CONTI S, GIAMPAOLI S, LANTI M, MARIOTTI S, SCANGA M, SECCARECCIA F, SPAGNOLO A, VERDECCHIA A, DI CARLO G, DIMA F, MARENCO G, FALCHERO M, IDEO G, PODDA M, FERRARIO M, CESANA GC, TENCONI MT, LADDOMADA MS, DOBRILLA G, DE PETRIS G, ANGELINI GP, OCKOLICSANYI L, TOSO S, AMBROSIO GB, TASSO S, BITTOLO BON G, ALESSANDRINI P, FERUGLIO GA, VANUZZO D, CARULLI N, SALVIOLI GF, GADDI A, D'ADDATO S, DESCOVICH GC, DORMI A, BARBARA L, ALVISI V, BUZZELLI GP, GIACCHI M, LAURENZI M, RICCI G, ANTONINI R, ANGELICO F, LALLONI L, ATTILI AF, URBINATI GC, MANCINI M, PANICO S, FARINARO E, ALBANO O, MISCIAGNA G, MUNTONI S, STABILINI L, AVELLONE G, DI GARBO G. ., DEVOTI, Gabriele, THE RIFLE RESEARCH, Group, Menotti, A, Farchi, G, Conti, S, Giampaoli, S, Lanti, M, Mariotti, S, Scanga, M, Seccareccia, F, Spagnolo, A, Verdecchia, A, DI CARLO, G, Dima, F, Marenco, G, Falchero, M, Ideo, G, Podda, M, Ferrario, M, Cesana, Gc, Tenconi, Mt, Laddomada, M, Devoti, Gabriele, Dobrilla, G, DE PETRIS, G, Angelini, Gp, Ockolicsanyi, L, Toso, S, Ambrosio, Gb, Tasso, S, BITTOLO BON, G, Alessandrini, P, Feruglio, Ga, Vanuzzo, D, Carulli, N, Salvioli, Gf, Gaddi, A, D'Addato, S, Descovich, Gc, Dormi, A, Barbara, L, Alvisi, V, Buzzelli, Gp, Giacchi, M, Laurenzi, M, Ricci, G, Antonini, R, Angelico, F, Lalloni, L, Attili, Af, Urbinati, Gc, Mancini, M, Panico, S, Farinaro, E, Albano, O, Misciagna, G, Muntoni, S, Stabilini, L, Avellone, G, and DI GARBO, G. .

Published
1993

17. A new highly effective short-term therapy schedule for Helicobacter pylori eradication

Author

Zullo, A, Rinaldi, V, Winn, S, Meddi, P, Lionetti, R, Hassan, Cesare, Ripani, C, Tomaselli, G, and Attili, Af

Subjects
Oral, Adult, Male, Settore MED/12 - GASTROENTEROLOGIA, PATHOGENESIS, TINIDAZOLE, Administration, Oral, Antitrichomonal Agents, Penicillins, REGIMENS, LANSOPRAZOLE, Drug Administration Schedule, Helicobacter Infections, OMEPRAZOLE PLUS CLARITHROMYCIN, TRIPLE-THERAPY, DUODENAL-ULCER, INFECTION, AMOXICILLIN, LANSOPRAZOLE, PATHOGENESIS, COMBINATION, TINIDAZOLE, REGIMENS, Clarithromycin, INFECTION, Humans, Stomach Ulcer, OMEPRAZOLE PLUS CLARITHROMYCIN, COMBINATION, Aged, Helicobacter pylori, Middle Aged, Anti-Ulcer Agents, Anti-Bacterial Agents, Treatment Outcome, Administration, Patient Compliance, Drug Therapy, Combination, Female, DUODENAL-ULCER, TRIPLE-THERAPY, Omeprazole, AMOXICILLIN
Abstract

Although triple therapy regimens suggested in the Current European guidelines give fairly good results, several studies have reported an unsatisfactory Helicobacter pylori eradication rate (80%).To evaluate the efficacy of a new short-term treatment sequence on H. pylori eradication.A total of 52 patients with H. pylori infection and either non-ulcer dyspepsia (34 patients) or peptic ulcer (18 patients) were enrolled to receive a 10-day therapy: omeprazole 20 mg b.d. plus amoxycillin 1 g b.d. for the first 5 days, followed by omeprazole 20 mg b.d., clarithromycin 500 mg b.d. and tinidazole 500 mg b.d. for the remaining 5 days. H. pylori infection at entry was assessed by rapid urease test and histology on biopsies from the antrum and the corpus. Bacterial eradication was assessed by endoscopy (peptic ulcer patients) or 13C urea breath test (non-ulcer dyspepsia patients) 4-6 weeks after therapy had ended.All patients completed the study. H. pylori eradication was achieved in all but one patient, with an eradication rate of 98% (95% CI: 94.3-100) with intention-to-treat analysis. Patient compliance was good (consumption of prescribed drugs95%) for all but one patient, who took the triple therapy regimen for 4 days instead of 5 days. No major side-effects were reported but three (6%) patients complained of mild side-effects.The use of this 'five plus five' therapy schedule as an initial treatment for H. pylori deserves further investigation.

Published
2000

18. Helicobacter pylori eradication with proton pump inhibitor – based triple therapies and re – treatment with ranitidine bismuth citrate – based triple therapy

Author

Rinaldi, V, Zullo, A, De Francesco, V, Hassan, Cesare, Winn, S, Stoppino, V, Faleo, D, and Attili, Af

Subjects
Adult, Male, Adolescent, Settore MED/12 - GASTROENTEROLOGIA, TINIDAZOLE, Ranitidine, DISEASE, Helicobacter Infections, INFECTION, QUADRUPLE THERAPY, Humans, OMEPRAZOLE PLUS CLARITHROMYCIN, OMEPRAZOLE PLUS CLARITHROMYCIN, QUADRUPLE THERAPY, ULCER PATIENTS, INFECTION, CURE, METRONIDAZOLE, AMOXICILLIN, 100-PERCENT, TINIDAZOLE, DISEASE, Aged, CURE, 100-PERCENT, Helicobacter pylori, Proton Pump Inhibitors, Proton Pumps, Middle Aged, Histamine H2 Antagonists, METRONIDAZOLE, Drug Therapy, Combination, Female, Bismuth, AMOXICILLIN, ULCER PATIENTS
Abstract

It has been suggested that short-term triple therapy comprising a proton pump inhibitor, plus clarithromycin and amoxycillin be used as first choice in treating H. pylori infection, while eradication failure patients should be further treated with a quadruple therapy. Nevertheless, conflicting results have been reported using these treatment regimens in different countries.A total of 278 patients with H. pylori infection were randomised to receive one-week triple therapy, comprising clarithromycin 500 mg b.d., amoxycillin 1 g b.d., and either omeprazole 20 mg b.d. (OAC; 90 patients), or pantoprazole 40 mg b.d. (PAC; 95 patients), or lansoprazole 30 mg b.d. (LAC; 93 patients). H. pylori infection at entry, and eradication 4-6 weeks after therapy had ended, were assessed by rapid urease test and histology on biopsies from the antrum and the corpus. When eradication did not occur, patients were given a 2-week treatment comprising ranitidine bismuth citrate 400 mg b.d., tetracycline 500 mg t.d.s. and tinidazole 500 mg b.d. (RBTT). Eradication in these patients was assessed 4-6 weeks after conclusion of treatment by a further endoscopy.Six patients were lost to the follow-up. At the end of the first course of treatment, the overall H. pylori eradication rate was 78% (95% CI: 73-83) and 79% (95% CI: 75-84) at 'intention-to-treat' (ITT) and 'per protocol' (PP) analysis, respectively, without any statistically significant difference between treatment regimens, although a trend for better results with the omeprazole combination was observed. Moreover, H. pylori eradication was achieved in 82% (95% CI: 75-97) (ITT) and 86% (95% CI: 69-94) (PP) of 38 patients re-treated with RBTT regimen.Our data found that this short-term triple therapy is not a satisfactory treatment (80% eradication rate) for H. pylori infection. The 2-week triple therapy used as re-treatment in eradication failure patients yielded more promising results.

Published
1999

21. Factors associated with gallstone disease in the MICOL experience

Author

Attili, Af, Capocaccia, R, Carulli, Nicola, Festi, D, Roda, E, Barbara, L, Capocaccia, L, Menotti, A, Okolicsanyi, L, Ricci, G, Lalloni, L, Mariotti, S, Sama, C, Scafato, E, the MICOL Group, and Roncucci, Luca

Subjects
obesity, diabetes, gallstones, risk factors, gender, cholesterolemia
Published
1997

22. Helicobacter pylori density and cagA status in cirrhotic patients: a case-control study

Author

Zullo, A, Sanchez Mete, L, Hassan, Cesare, Diana, F, Festuccia, F, Attili, Af, Morini, S., Zullo, A, Sanchez Mete, L, Hassan, Cesare, Diana, F, Festuccia, F, Attili, Af, and Morini, S.

Abstract

Despite a similar Helicobacter pylori prevalence, peptic ulcer is more frequent in cirrhotic patients than in controls. We evaluated whether cirrhotic patients had an increased bacterial density and/or a higher prevalence of H. pylori cagA-positive strains than controls.

Published
2004

24. Helicobacter pylori diagnosis in patients with liver cirrhosis

Author

Sanchez Mete, L, Zullo, A, Hassan, Cesare, Rinaldi, V, Magno, M, Festuccia, F, Morini, S, Attili, Af, Magno, Ms, Sanchez Mete, L, Zullo, A, Hassan, Cesare, Rinaldi, V, Magno, M, Festuccia, F, Morini, S, Attili, Af, and Magno, Ms

Abstract

In cirrhotics, Helicobacter pylori infection is the major cause of peptic lesions, which are an important cause of upper intestinal haemorrhage in these patients. However, some diagnostic methods are not accurate for H. pylori detection in cirrhotics.

Published
2003

26. Gastric epithelial cell proliferation in patients with liver cirrhosis

Author

Zullo, A, Romiti, Anita, Rinaldi, V, Vecchione, A, Hassan, Cesare, Winn, S, Tomao, S, Attili, Af, Zullo, A, Romiti, Anita, Rinaldi, V, Vecchione, A, Hassan, Cesare, Winn, S, Tomao, S, and Attili, Af

Abstract

An increased risk for gastric cancer in patients with liver cirrhosis has recently been reported. This study was performed in order to determine gastric epithelial cell proliferation in cirrhotic patients and to evaluate the role of congestive gastropathy (CG) and Helicobacter pylori infection in this process. Thirty-six cirrhotic patients and 18 controls were enrolled in the study. All patients underwent endoscopy and three biopsies were performed in the antrum and three in the gastric body. The presence of H. pylori infection was assessed by a rapid urease test and histology. The antral biopsies were used for gastric cell proliferation assessment by an immunohistochemical analysis (Ki-67). There was no significant difference in epithelial cell proliferation between cirrhotics and controls. Gastric proliferation values were higher in patients with H. pylori infection compared with uninfected patients, both in cirrhotic (P = 0.003) and in control groups (P = 0.06). Among the cirrhotic group, we found a progressive increase in gastric cell proliferation values related to the degree of CG, the highest values being observed in cirrhotic patients with severe CG. Moreover, cirrhotics with both severe CG and H. pylori infection had the highest proliferation values when compared with all other subgroups. In conclusion, this study found that: (1) CG significantly affects epithelial cell proliferation in gastric mucosa in cirrhotic patients, (2) H. pylori infection plays a similar role in gastric cell proliferation in both cirrhotic and non-cirrhotic patients, and (3) CG and H. pylori could act synergistically in this process.

Published
2001

29. Ascorbic acid and intestinal metaplasia in the stomach: a prospective, randomized study

Author

Zullo, A, Rinaldi, V, Hassan, Cesare, Diana, F, Winn, S, Castagna, G, Attili, Af, Zullo, A, Rinaldi, V, Hassan, Cesare, Diana, F, Winn, S, Castagna, G, and Attili, Af

Abstract

Intestinal type metaplasia plays a role in intestinal type gastric carcinoma development. Ascorbic acid demonstrates a protective effect against gastric carcinogenesis, due to its ability to inactivate oxygen free-radicals as well as its nitrite-scavenging effects.

Published
2000

30. Clinical and histologic predictors of Helicobacter pylori infection recurrence

Author

Zullo, A, Rinaldi, V, Hassan, Cesare, Taggi, F, Giustini, M, Winn, S, Castagna, G, Attili, Af, Zullo, A, Rinaldi, V, Hassan, Cesare, Taggi, F, Giustini, M, Winn, S, Castagna, G, and Attili, Af

Abstract

Factors influencing Helicobacter pylori infection recurrence still have not been fully clarified. The aim of this study was to determine whether, after eradication of H. pylori, any clinical or histologic features could yield information on infection relapse. We enrolled in the study 72 patients successfully treated for H. pylori infection by either dual (n = 49) or triple (n = 23) therapy. H. pylori eradication was defined as a negative bacterial finding by rapid urease test and histologic assessment at least 4 weeks after cessation of therapy. Upon eradication, gastritis grading was performed and patients were asked to return for an endoscopic control 6-8 months later. The recurrence of H. pylori infection was observed in 12 of 72 (16.7%) patients. The infection recurrence rate resulted significantly higher in nonulcer dyspepsia patients (p = 0.01 ) and in women (p = 0.03), whereas infection relapse did not differ between patients treated with dual or triple therapy. There was a strong (p = 0.0001 ) relationship between the persistence of chronic active gastritis after H. pylori eradication and recurrence of infection, whereas gastritis grade and metaplasia were not related to recurrence. In conclusion, this study found that H. pylori infection recurrence after successful dual or triple therapy is fairly high and that gastroduodenal disease, gender, and gastritis activity seem to affect infection relapse.

Published
2000

31. Reflux oesophagitis after Helicobacter pylori treatment

Author

Rinaldi, V, Morini, S, Zullo, A, Hassan, Cesare, De Francesco, V, Faleo, D, Attili, Af, Rinaldi, V, Morini, S, Zullo, A, Hassan, Cesare, De Francesco, V, Faleo, D, and Attili, Af

Abstract

N/A

Published
2000

33. Helicobacter pylori infection, plasma ammonia levels, and psychometric testing in cirrhotic patients

Author

Zullo, A, Rinaldi, V, Meddi, P, Hassan, Cesare, Winn, S, Attili, Af, Zullo, A, Rinaldi, V, Meddi, P, Hassan, Cesare, Winn, S, and Attili, Af

Abstract

The role of Helicobacter pylori (H. pylori) infection as a cause of hepatic encephalopathy is still debated. This study focused on the relationship between H. pylori, plasma ammonia levels, and intellectual function in cirrhotic patients.

Published
1999

34. Helicobacter pylori and plasma ammonia levels in cirrhotics: role of urease inhibition by acetohydroxamic acid

Author

Zullo, A, Rinaldi, V, Hassan, Cesare, Folino, S, Winn, S, Pinto, G, Attili, Af, Zullo, A, Rinaldi, V, Hassan, Cesare, Folino, S, Winn, S, Pinto, G, and Attili, Af

Abstract

The role of Helicobacter pylori as a cause of hyperammonaemia in cirrhotics has still not been fully clarified. This study was aimed at evaluating the effect of acute Helicobacter pylori urease inhibition by oral acetohydroxamic acid administration on blood ammonia levels in cirrhotic patients.

Published
1998

35. Gastric pathology in cholecystectomy patients: role of Helicobacter pylori and bile reflux

Author

Zullo, A, Rinaldi, V, Hassan, Cesare, Lauria, V, Attili, Af, Zullo, A, Rinaldi, V, Hassan, Cesare, Lauria, V, and Attili, Af

Abstract

The data regarding the role of Helicobacter pylori infection in patients with bile reflux are conflicting. Bile reflux is often observed after cholecystectomy. This study focuses on the role of H. pylori in gastric pathology of patients who had undergone cholecystectomy. Eighty-seven consecutive patients were included in the study. An upper gastrointestinal endoscopy was performed, and biopsy specimens were taken in the antrum, incisura angularis, and in the gastric body. The presence of bile reflux in gastric fluid at endoscopic examination was recorded. The overall H. pylori infection rate was 62%, with no difference between patients with (59.7%) and without (64%) endoscopic bile reflux (p = 0.67). The intestinal metaplasia rate in gastric mucosa was significantly higher in patients with both H. pylori and bile reflux than in patients without infection and bile reflux (36.4% vs. 5.6%, p = 0.02). Moreover, the mean number of years after cholecystectomy in patients with intestinal metaplasia was significantly higher than in those without metaplasia (21.1 +/- 7 vs. 11.5 +/- 8 years, p < 0.0001), whereas mean age did not differ significantly between groups (60.3 +/- 12 vs. 55.8 +/- 11 years, p = 0.14). Furthermore, we found four cases of gastric cancer, three with H. pylori infection. The mean number of years after cholecystectomy was significantly higher in patients with gastric cancer than in other patients (21.8 +/- 4 vs. 12.2 +/- 8 years, p = 0.009). This study found that H. pylori infection is frequent in cholecystectomized patients, also in the presence of endoscopic bile reflux. Bile reflux seems to act synergistically with H. pylori infection on gastric pathology.

Published
1998

41. Incidence of gallstone disease in Italy: Results from a multicenter, population-based Italian study (the MICOL project)

Author

Claudia Sama, Adolfo Francesco Attili, Ada Dormi, Paolo Pazzi, Paola Loria, Davide Festi, Antonio Colecchia, Enrico Roda, Tommaso Staniscia, Giuseppe Mazzella, S. Capodicasa, Festi D, Dormi A, Capodicasa S, Staniscia T, Attili AF, Loria P, Pazzi P, Mazzella G, Sama C, Roda E, and Colecchia A.

Subjects
Adult, Male, Abdominal pain, medicine.medical_specialty, Epidemiology, Cross-sectional study, Population, Pain, Disease, Population based, Gallstones, Body Mass Index, abdominal pain, body mass index, cholecystectomy, epidemiology, gallstone disease, incidence, prevalence, ultrasonography, Clinical Research, Risk Factors, Gallstone disease, Prevalence, Medicine, Humans, Cholecystectomy, education, Ultrasonography, Incidence, Body mass index, Aged, education.field_of_study, business.industry, Incidence (epidemiology), INCIDENCE OF GALLSTONE ITALY, CHOLESTEROL GALLSTONE, Gastroenterology, Age Factors, General Medicine, RISK FACTOR FOR GALLSTONE, Middle Aged, medicine.disease, Surgery, Cross-Sectional Studies, Multicenter study, Italy, Female, business, Demography
Abstract

AIM: To evaluate gallstone incidence and risk factors in a large population-based study. METHODS: Gallstone incidence and risk factors, were evaluated by structured questionnaire and physical examination, respectively, in 9611 of 11 109 (86.5%) subjects who were gallstone-free at the cross-sectional study. RESULTS: Six centers throughout Italy enrolled 9611 subjects (5477 males, 4134 females, aged 30-79 years), 9517 of whom were included into analysis: 424 subjects (4.4%) had gallstones and 61 (0.6%) had been cholecystectomized yielding a cumulative incidence of 0.67% per year (0.66% in males, 0.81% in females). Increasing age, a high body mass index (BMI), a history of diabetes, peptic ulcer and angina, and low cholesterol and high triglyceride levels were identified as risk factors in men while, in females, the only risk factors were increasing age and a high BMI. Increasing age and pain in the right hypocondrium in men and increasing age in females were identified as predictors of gallstones. Pain in the epigastrium/right hypocondrium was the only symptom related to gallstones; furthermore, some characteristics of pain (forcing to rest, not relieved by bowel movements) were significantly associated with gallstones. No correlation was found between gallstone characteristics and clinical manifestations, while increasing age in men and increasing age and BMI in females were predictors of pain. CONCLUSION: Increasing age and BMI represent true risk factors for gallstone disease (GD); pain in the right hypocondrium and/or epigastrium is confirmed as the only symptom related to gallstones.

Published
2008

42. Influence of tauroursodeoxycholic and taurodeoxycholic acids on hepatic metabolism and biliary secretion of phosphatidylcholine in the isolated rat liver

Author

Mario Angelico, G. B. Gaeta, A. Di Biase, Marie Francoise Tripodi, Alfredo Cantafora, Adolfo Francesco Attili, R. Utili, S. Ginanni Corradini, Domenico Alvaro, Alvaro, D, Angelico, M, Cantafora, A, DI BIASE, A, Gaeta, Giovanni Battista, GINANNI CORRADINI, S, Tripodi, Mf, Attili, Af, and Utili, Riccardo

Subjects
Male, medicine.medical_specialty, Phospholipid secretion, Hepatic metabolism, Tauroursodeoxycholate, Taurooleoxycholate, Liver perfusion, Inbred Strains, Biophysics, Phospholipid, Hepatic metabolism, Tauroursodeoxycholate, Taurooleoxycholate, In Vitro Techniques, Biology, Chenodeoxycholic Acid, Biochemistry, Animals, Carbon Radioisotopes, Taurochenodeoxycholic Acid, Perfusion, Taurodeoxycholic Acid, Rats, Rats, Inbred Strains, Triglycerides, Bile, Deoxycholic Acid, Liver, Phosphatidylcholines, chemistry.chemical_compound, Endocrinology, Phosphatidylcholine, Internal medicine, medicine, Secretion, Diacylglycerol kinase, Phosphatidylethanolamine, Settore MED/12 - Gastroenterologia, Phospholipid secretion, Metabolism, Liver perfusion, chemistry, Specific activity, Drug metabolism
Abstract

Studies were carried out using an isolated rat liver system to define: the contribution of exogenous phosphatidylcholine (PC) to biliary phospholipid secretion; and its hepatic metabolism during perfusion of the livers with conjugated bile salts with different hydrophilic/hydrophobic properties. A tracer dose of sn-1-palmitoyl-sn-2-[14C]linoleoylPC was injected as a bolus into the recirculating liver perfusate, under constant infusion of 0.75 mumol/min of tauroursodeoxycholate or taurodeoxycholate. The effects on bile flow, biliary lipid secretion, 14C disappearance from the perfusate and its appearance in bile, as well as hepatic and biliary biotransformation were determined. With both the bile salts, about 40% of the [14C]PC was taken up by the liver from the perfusate over 100 min. During the same period less than 2% of the given radioactivity was secreted into bile. More than 95% of the 14C recovered in bile was located within the identical injected PC molecular species. The biliary secretion of labeled as well as unlabeled PC, however, was significantly higher in livers perfused with taurodeoxycholate than tauroursodeoxycholate, while the reverse was observed with respect to bile flow and total bile salt secretion. The exogenous PC underwent extensive hepatic metabolization which appeared to be influenced by the type of bile salt perfusing the liver. After 2 h perfusion, the liver radioactivity was found, in decreasing order, in PC, triacylglycerol, phosphatidylethanolamine and diacylglycerol. In addition, the specific activity of triacylglycerol was significantly higher in tauroursodeoxycholate than in taurodeoxycholate-perfused livers (P less than 0.025), while the reverse was true for the specific activity of hepatic PC (P less than 0.01). Because taurodeoxycholate and tauroursodeoxycholate showed opposite effects on both biliary lipid secretion and hepatic PC biotransformations, we conclude that the hepatic metabolism of glycerolipids is influenced by the physiochemical properties of bile salts.

Published
1986

43. Impact of new DAA therapy on real clinical practice: a multicenter region-wide cohort study.

Author

Lanini S, Scognamiglio P, Mecozzi A, Lombardozzi L, Vullo V, Angelico M, Gasbarrini A, Taliani G, Attili AF, Perno CF, De Santis A, Puro V, Cerqua F, D'Offizi G, Pellicelli A, Armignacco O, Mennini FS, Siciliano M, Girardi E, Panella V, and Ippolito G

Subjects
Adult, Aged, Aged, 80 and over, Cohort Studies, Drug Therapy, Combination, Drugs, Investigational therapeutic use, Female, Follow-Up Studies, Hepatitis C, Chronic complications, Humans, Liver Cirrhosis complications, Liver Cirrhosis drug therapy, Liver Cirrhosis virology, Male, Middle Aged, Antiviral Agents therapeutic use, Hepatitis C, Chronic drug therapy, Therapies, Investigational methods
Abstract

Background: Management of chronic hepatitis C (CHC) has significantly accelerated in the last few years. Currently, second generation direct acting antivirals (DAAs) promise clearance of infection in most of patients. Here we present the results of the first analysis carried out on data of Lazio clinical network for DAAs., Methods: The study was designed as a multicenter cohort: a) to assess the evolution of treatment during the first 24 months of the activity of the Clinical Network; b) to report overall efficacy of treatments; c) to analyze potential factors associated with lack of virological response at 12 weeks after therapy (SVR12); d) to evaluate the variation of ALT at baseline and 12 weeks after therapy in those who achieved SVR12 in comparison to those who did not. Analyses of efficacy were carried out with multilevel mixed effect logistic regression model. ALT temporal variation was assessed by mixed effect model mixed models with random intercept at patient's level and random slope at the level of the time; i.e. either before or after therapy., Results: Between 30 December 2014 and 31 December 2016 5279 patients started a DAA treatment; of those, 5127 (in 14 clinical centers) had completed the 12-week follow-up. Overall proportion of SVR12 was 93.41% (N = 4780) with no heterogeneity between the 14 clinical centers. Interruption as the consequence of severe side effect was very low (only 23 patients). Unadjusted analysis indicates that proportion of SVR12 significantly changes according to patient's baseline characteristics, however after adjusting for potential confounders only adherence to current guidelines, stage of liver diseases, gender, transplant and HIV status were independently associated with the response to therapy. Analysis of ALT temporal variation showed that ALT level normalized in most, but not, all patients who achieved SVR12., Conclusion: Our study confirmed the extraordinary efficacy of DAAs outside clinical trials. The advantage of DAAs was particularly significant for those patients who were previously considered as difficult-to-treat and did not have treatment options before DAAs era. Intervention based on network of select centers and prioritization of patients according to diseases severity was successful. Further studies are needed to establish whether clearance of HCV after DAAs therapy can arrest or even revert liver fibrosis in non-cirrhotic patients and/or improve life quality and expectancy in those who achieve SVR12 with cirrhosis.

Published
2018
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44. Prognostic ability of BCLC-B Subclassification in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.

Author

Biolato M, Gallusi G, Iavarone M, Cabibbo G, Racco S, De Santis A, Corte CD, Maida M, Attili AF, Sangiovanni A, Cammà C, La Torre G, Gasbarrini A, and Grieco A

Subjects
Aged, Aged, 80 and over, Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular pathology, Female, Humans, Italy, Kaplan-Meier Estimate, Liver Neoplasms mortality, Liver Neoplasms pathology, Male, Middle Aged, Multivariate Analysis, Predictive Value of Tests, Proportional Hazards Models, Retrospective Studies, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome, Carcinoma, Hepatocellular therapy, Chemoembolization, Therapeutic adverse effects, Chemoembolization, Therapeutic mortality, Decision Support Techniques, Liver Neoplasms therapy, Neoplasm Staging methods
Abstract

Prognostic ability of BCLC-B Subclassification in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization Background and aims. A subclassification system for intermediate hepatocellular carcinoma (HCC) was recently proposed to optimize treatment allocation. The aim of this study was to assess the prognostic ability of that substaging proposal., Patients and Methods: This is a retrospective multicenter cohort study including patients with intermediate HCC treated with transarterial chemoembolization (TACE). Predictors of survival were identified using the Cox proportional regression model., Results: 289 Barcelona Clinic Liver Cancer (BCLC) B patients were included. Median overall survival of the whole cohort was 23 months (C.I. 95% 20.2- 25.8). Child A status (H.R. 1.35, C.I. 95% 1.02-1.78) and tumour burden beyond the up-to-seven criterion (H.R. 1.39, C.I. 95% 1.07- 1.80) were independent prognostic factors for overall survival on multivariate analysis. Analysis of the substages showed that median survival was 33.0 months for B1 stage (n = 81), 20.8 months for B2 stage (n = 106), 16.1 months for B3 stage (n = 24), 22.2 months for B4 stage (n = 42) and 15.0 months for quasi-C stage (n = 36). Regarding the discriminatory ability of the substaging proposal, the log rank test showed a significant survival difference for B1vs. B4 (p = 0.003) and B1 vs. Quasi-C (p = 0.039) and a trend for B1 vs. B2 (p = 0.05) and B1 vs. B3 (p = 0.05)., Conclusions: Apart from substage B1, BCLC-B subclassification does not discriminate perfectly patients treated with TACE. Also some patients in substage B4 can benefit from TACE.

Published
2018
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45. Endoscopic ultrasound-guided drainage of a post-hepatectomy abscess using a lumen-apposing self-expandable metal stent with electrocautery-enhanced delivery system.

Author

Attili F, Dang S, Rimbaș M, Di Maurizio L, Ettorre GM, Attili AF, and Larghi A

Subjects
Abdominal Abscess etiology, Aged, Drainage methods, Electrocoagulation instrumentation, Endosonography, Hepatectomy adverse effects, Humans, Male, Ultrasonography, Interventional, Abdominal Abscess surgery, Drainage instrumentation, Self Expandable Metallic Stents
Published
2016
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46. Woodchuck hepatitis virus core gene deletions and proliferative responses of peripheral blood mononuclear cells stimulated by an immunodominant epitope: a viral immune escape in the woodchuck model of chronic hepatitis B?

Author

Taffon S, Kondili LA, Giuseppetti R, Ciccaglione AR, Pulimanti B, Attili AF, Rapicetta M, and D'Ugo E

Subjects
Animals, Disease Models, Animal, Female, Gene Deletion, Hepatitis B Virus, Woodchuck physiology, Hepatitis B virus genetics, Hepatitis B virus immunology, Hepatitis B virus physiology, Hepatitis B, Chronic physiopathology, Hepatitis B, Chronic virology, Humans, Immune Evasion, Leukocytes, Mononuclear cytology, Leukocytes, Mononuclear virology, Male, Viral Core Proteins metabolism, Cell Proliferation, Hepatitis B Virus, Woodchuck genetics, Hepatitis B Virus, Woodchuck immunology, Hepatitis B, Chronic immunology, Immunodominant Epitopes immunology, Leukocytes, Mononuclear immunology, Marmota virology, Viral Core Proteins genetics
Abstract

Marmota monax and its natural infection by woodchuck hepatitis virus (WHV) could be used as a predictive model for evaluating mechanisms of viral persistence during chronic hepatitis B virus (HBV) infection. The aim of this study was to investigate the presence of viral variants in the core gene of chronically WHV-infected woodchucks that showed two different patterns of peripheral blood mononuclear cells' (PBMCs') responses after stimulation with a specific WHV core peptide. Sequences' analysis of the WHV core region from eight WHV chronically infected woodchucks have been performed after in vitro stimulation with an immunodominant epitope of the WHV core protein (amino acids [aa] 96-110). Following this stimulation, positive PBMC responses at each point of follow-up were observed for four animals (group A), and weak immune responses at one or a few points of follow-up were observed for the remaining four animals (group B). The WHV core gene sequences contained amino acid deletions (aa 84-126, aa 84-113) in three of four group A animals and in none of group B animals. In the group A animals, the same deletions were observed in liver specimens and in two of four tumor specimens. Hepatocellular carcinoma (HCC) was diagnosed in all group A animals and in one group B animal. In conclusion, internal deletions in the core region correlated with a sustained PBMC response to the immunogenic peptide (96-110) of the core protein. A possible role of this relationship in hepatocarcinogenesis could be hypothesized; however, this needs to be investigated in patients with chronic HBV infection. The evaluation of virus-specific T-cell responses and T-cell epitopes that are possibly related to the mechanisms of viral evasion should be further investigated in order to design combined antiviral and immune approaches to control chronic HBV infection.

Published
2015
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47. Transplantation of human fetal biliary tree stem/progenitor cells into two patients with advanced liver cirrhosis.

Author

Cardinale V, Carpino G, Gentile R, Napoletano C, Rahimi H, Franchitto A, Semeraro R, Nuti M, Onori P, Berloco PB, Rossi M, Bosco D, Brunelli R, Fraveto A, Napoli C, Torrice A, Gatto M, Venere R, Bastianelli C, Aliberti C, Salvatori FM, Bresadola L, Bezzi M, Attili AF, Reid L, Gaudio E, and Alvaro D

Subjects
Aged, Antigens, Neoplasm metabolism, Biliary Tract cytology, Cell Adhesion Molecules metabolism, Epithelial Cell Adhesion Molecule, Female, Hepatic Artery, Humans, Male, Fetal Tissue Transplantation methods, Liver Cirrhosis therapy, Stem Cell Transplantation methods
Abstract

Background: Efforts to identify cell sources and approaches for cell therapy of liver diseases are ongoing, taking into consideration the limits recognized for adult liver tissue and for other forms of stem cells. In the present study, we described the first procedure of via hepatic artery transplantation of human fetal biliary tree stem cells in patients with advanced cirrhosis., Methods: The cells were immune-sorted from human fetal biliary tree by protocols in accordance with current good manufacturing practice (cGMP) and extensively characterized. Two patients with advanced liver cirrhosis (Child-Pugh C) have been submitted to the procedure and observed through a 12 months follow-up., Results: The resulting procedure was found absolutely safe. Immuno-suppressants were not required, and the patients did not display any adverse effects correlated with cell transplantation or suggestive of immunological complications. From a clinical point of view, both patients showed biochemical and clinical improvement during the 6 month follow-up and the second patient maintained a stable improvement for 12 months., Conclusion: This report represents proof of the concept that the human fetal biliary tree stem cells are a suitable and large source for cell therapy of liver cirrhosis. The isolation procedure can be carried out under cGMP conditions and, finally, the infusion procedure is easy and safe for the patients. This represents the basis for forthcoming controlled clinical trials.

Published
2014
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48. Recipient perioperative cholesterolaemia and graft cholesterol metabolism gene expression predict liver transplant outcome.

Author

Ginanni Corradini S, Siciliano M, Parlati L, Molinaro A, Cantafora A, Poli E, Mennini G, Melandro F, Vestri AR, Merli M, Bianco P, Corsi A, Toniutto P, Bitetto D, Falleti E, Attili AF, Berloco P, and Rossi M

Subjects
Cholesterol metabolism, Creatinine blood, Female, Humans, Italy, Liver Transplantation statistics & numerical data, Male, Middle Aged, Multivariate Analysis, Perioperative Period, Proprotein Convertase 9, Proprotein Convertases metabolism, Prospective Studies, Receptors, LDL metabolism, Regression Analysis, Retrospective Studies, Reverse Transcriptase Polymerase Chain Reaction, Serine Endopeptidases metabolism, Treatment Outcome, Cholesterol blood, Liver Cirrhosis surgery, Liver Transplantation methods, RNA, Messenger metabolism
Abstract

Background & Aims: We analysed for the first time whether recipient perioperative serum total cholesterol (sTC) concentration is associated with liver transplantation outcome., Methods: We studied noncholestatic cirrhotics submitted to primary deceased-donor liver transplantation in a prospective group (n=140) from Rome and in a validation retrospective cohort (n=157) from Udine, Italy. Pre-ischaemia and post-reperfusion cholesterol metabolism gene mRNA was measured by RT-PCR in 74 grafts of the study group., Results: At Cox regression analysis, independently from confounders including recipient MELD score, the recipient pre-operative sTC pooled quintiles 2-5, compared with the lowest quintile showed HR (95% CI) and significances for overall graft loss (GL) of 0.215 (0.104-0.444) P<0.001 in the study group and 0.319 (0.167-0.610) P=0.001 in the validation cohort. Analysing sTC as a continuous variable, the risk of overall GL for every 10-mg/dl decrease in pre-operative sTC increased by 13% and by 9% in the study group and in the validation cohort respectively. In the study group, independent associations at multivariate analyses were: (a) high graft pre-ischaemia expression of INSIG-1, which indicates hepatocellular cholesterol depletion, with post-reperfusion graft necrosis; (b) GL with inadequate graft post-reperfusion response to cholesterol depletion, shown by a failure to reduce the PCSK9 to LDLR expression ratio; (c) GL with a relative increase of sTC on post-operative day-7, selectively because of the LDL fraction, which indirectly suggests poor cholesterol uptake from blood., Conclusions: Low recipient pre-transplant sTC concentration, its post-operative day-7 increase and a genetically determined low graft cholesterol availability predict poor liver transplant outcome., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Published
2014
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49. Hepatocellular carcinoma in cirrhotic patients with transjugular intrahepatic portosystemic shunt: a retrospective case-control study.

Author

De Santis A, Iegri C, Kondili L, Riggio O, Salvatori FM, Catalano C, Di Martino M, Bassanelli C, Lupo M, Lucatelli P, and Attili AF

Subjects
Aged, Carcinoma, Hepatocellular diagnostic imaging, Case-Control Studies, Female, Follow-Up Studies, Humans, Hypertension, Portal etiology, Hypertension, Portal therapy, Incidence, Liver Neoplasms diagnostic imaging, Male, Middle Aged, Retrospective Studies, Severity of Illness Index, Survival Rate, Ultrasonography, Carcinoma, Hepatocellular epidemiology, Liver Cirrhosis complications, Liver Neoplasms epidemiology, Population Surveillance, Portasystemic Shunt, Transjugular Intrahepatic mortality
Abstract

Background: An association between Transjugular Intrahepatic Porto-Systemic Shunt (TIPS) and the development of hepatocellular carcinoma in patients with cirrhosis has been suggested, but not confirmed., Aim: To evaluate the potential role of TIPS in hepatocellular carcinoma development., Methods: We performed a retrospective case-control study among patients with cirrhosis; all cases had undergone TIPS placement. Cases and controls were followed as outpatients at a single liver care centre in the same timeframe., Results: Overall, 101 patients with cirrhosis (mean age 58 ± 9 years, 64.3% male) were included in each group. Median duration of follow-up was 56.7 months (range 8.2-174.5) for TIPS patients and 67.8 months (range 8.3-183.1) for controls (p=0.08). In both groups 94% of patients had Child-Pugh Class A or B cirrhosis. The cumulative incidence of hepatocellular carcinoma at 1, 3, 5, and 10 years was 2%, 7%, 18%, and 46% among TIPS patients, and 3%, 10%, 19%, and 39% among controls (log rank test p=0.19). Compared to controls, hepatocellular carcinoma nodules in TIPS patients were more frequently situated in the right lobe (p<0.05)., Conclusions: TIPS does not seem to increase the risk of hepatocellular carcinoma in patients with Child-Pugh Class A or B cirrhosis; for these patients ultrasound surveillance should not be modified., (Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Published
2014
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50. PNPLA3 I148M (rs738409) genetic variant and age at onset of at-risk alcohol consumption are independent risk factors for alcoholic cirrhosis.

Author

Burza MA, Molinaro A, Attilia ML, Rotondo C, Attilia F, Ceccanti M, Ferri F, Maldarelli F, Maffongelli A, De Santis A, Attili AF, Romeo S, and Ginanni Corradini S

Subjects
Adult, Age of Onset, Genotype, Humans, Incidence, Italy, Kaplan-Meier Estimate, Linear Models, Models, Genetic, Proportional Hazards Models, Retrospective Studies, Risk Factors, Alcohol Drinking epidemiology, Lipase genetics, Liver Cirrhosis, Alcoholic epidemiology, Liver Cirrhosis, Alcoholic genetics, Membrane Proteins genetics, Mutation, Missense genetics
Abstract

Background & Aims: Environmental and genetic factors contribute to alcoholic cirrhosis onset. In particular, age at exposure to liver stressors has been shown to be important in progression to fibrosis in hepatitis C individuals. However, no definite data on the role of age at onset of at-risk alcohol consumption are available. Moreover, patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M (rs738409) variant has been associated with alcoholic cirrhosis, but only in cross-sectional studies. The aim of this study was to investigate the role of age at onset of at-risk alcohol consumption and PNPLA3 I148M variant on alcoholic cirrhosis incidence., Methods: A total of 384 at-risk alcohol drinkers were retrospectively examined. The association among age at onset of at-risk alcohol consumption, PNPLA3 I148M variant and cirrhosis incidence was tested., Results: A higher incidence of alcoholic cirrhosis was observed in individuals with an older (≥24 years) compared with a younger (<24) age at onset of at-risk alcohol consumption (P-value < 0.001). Moreover, PNPLA3 148M allele carriers showed an increased incidence of cirrhosis (P-value < 0.001). Both age at onset of at-risk alcohol consumption and PNPLA3 148M allele were independent risk factors for developing cirrhosis (H.R. (95% C.I.): 2.76 (2.18-3.50), P-value < 0.001; 1.53(1.07-2.19), P-value = 0.021 respectively). The 148M allele was associated with a two-fold increased risk of cirrhosis in individuals with a younger compared with an older age at onset of at-risk alcohol consumption (H.R. (95% C.I.): 3.03(1.53-6.00) vs. 1.61(1.09-2.38)., Conclusions: Age at onset of at-risk alcohol consumption and PNPLA3 I148M genetic variant are independently associated with alcoholic cirrhosis incidence., (© 2013 The Authors. Liver International published by John Wiley & Sons Ltd.)

Published
2014
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