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3. Pegylated interferon α plus ribavirin for the treatment of chronic hepatitis C: A multicentre independent study supported by the Italian Drug Agency

Author

Rosina F, Tosti ME, Borghesio E, Masocco M, Mele A, Coppola C, Milella M, Borgia G, Andreone P, Koch M, Zignego AL, Romano M, Carrara M, Almasio PL, Azzola E, Nardone G, Benedetti A, Carosi G, Mazzotta F, Sagnelli E, Rizzetto M, for the AIFA Study Group, Italian Association for the Study of the Liver, Italian Society for Infectious, Tropical Diseases, Italian Association of Hospital Gastroenterologists, Italian Society of Gastroenterology, LOGUERCIO, Carmelina, Rosina, F, Tosti, Me, Borghesio, E, Masocco, M, Mele, A, Coppola, C, Milella, M, Borgia, G, Andreone, P, Koch, M, Zignego, Al, Romano, M, Carrara, M, Almasio, Pl, Azzola, E, Nardone, G, Benedetti, A, Carosi, G, Mazzotta, F, Sagnelli, E, Rizzetto, M, for the AIFA Study, Group, Italian Association for the Study of the, Liver, Italian Society for, Infectiou, Tropical, Disease, Italian Association of Hospital, Gastroenterologist, Italian Society of, Gastroenterology, and Loguercio, Carmelina

Published
2014

6. PEG-IFN for hepatitis C in clinical practice

Author

Rosina F., Tosti M. E., Borghesio E., Mele A., Minoli G., Gasbarrini A., Pallone f., Carosi G., Mazzotta F., Rizzetto M., the AIFA Study Group, FEDERICO, Alessandro, Rosina, F., Tosti, M. E., Borghesio, E., Mele, A., Minoli, G., Gasbarrini, A., Pallone, F., Carosi, G., Mazzotta, F., Rizzetto, M., the AIFA Study, Group, and Federico, Alessandro

Published
2009

7. Pegylated interferon α plus ribavirin for the treatment of chronic hepatitis C: A multicentre independent study supported by the Italian Drug Agency

Author

Rosina, F, Tosti, Me, Borghesio, E, Masocco, M, Mele, A, Coppola, C, Milella, M, Borgia, G, Andreone, P, Koch, M, Zignego, Al, Romano, M, Carrara, M, Almasio, Pl, Azzola, E, Nardone, G, Benedetti, A, Carosi, G, Mazzotta, F, Sagnelli, E, Rizzetto, M, AIFA Study Group, Italian Association for the Study of the Liver, Italian Society for Infectious, Tropical, Diseases, Italian Association of Hospital Gastroenterologists, Italian Society of Gastroenterology, Italian Association for the Study of the Liver AISF, Tropical Diseases SIMIT, Italian Association of Hospital Gastroenterologists AIGO, and Contini, Carlo

Subjects
Peg-interferon/ribavirin, therapy, chronic hepatitis C, hepatitis C virus genotype cC, NO
Published
2014

8. Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis

Author

Liu, X, Invernizzi, P, Lu, Y, Kosoy, R, Bianchi, I, Podda, M, Xu, C, Xie, G, Macciardi, F, Selmi, C, Lupoli, S, Shigeta, R, Ransom, M, Lleo, A, Lee, A, Mason, A, Myers, R, Peltekian, K, Ghent, C, Bernuzzi, F, Zuin, M, Rosina, F, Borghesio, E, Floreani, A, Lazzari, R, Niro, G, Andriulli, A, Muratori, L, Muratori, P, Almasio, P, Andreone, P, Margotti, M, Brunetto, M, Coco, B, Alvaro, D, Bragazzi, M, Marra, F, Pisano, A, Rigamonti, C, Colombo, M, Marzioni, M, Benedetti, A, Fabris, L, Strazzabosco, M, Portincasa, P, Palmieri, V, Tiribelli, C, Croce, L, Bruno, S, Rossi, S, Vinci, M, Prisco, C, Mattalia, A, Toniutto, P, Picciotto, A, Galli, A, Ferrari, C, Colombo, S, Casella, G, Morini, L, Caporaso, N, Colli, A, Spinzi, G, Montanari, R, Gregersen, P, Heathcote, E, Hirschfield, G, Siminovitch, K, Amos, C, Gershwin, M, Seldin, M, INVERNIZZI, PIETRO, Lee, AT, Mason, AL, Myers, RP, Peltekian, KM, Ghent, CN, Bernuzzi, Francesca Veronica, Almasio, PL, Bragazzi, MC, STRAZZABOSCO, MARIO, Palmieri, VO, Gregersen, PK, Heathcote, EJ, Hirschfield, GM, Siminovitch, KA, Amos, CI, Gershwin, ME, Seldin, MF, Liu, X, Invernizzi, P, Lu, Y, Kosoy, R, Bianchi, I, Podda, M, Xu, C, Xie, G, Macciardi, F, Selmi, C, Lupoli, S, Shigeta, R, Ransom, M, Lleo, A, Lee, A, Mason, A, Myers, R, Peltekian, K, Ghent, C, Bernuzzi, F, Zuin, M, Rosina, F, Borghesio, E, Floreani, A, Lazzari, R, Niro, G, Andriulli, A, Muratori, L, Muratori, P, Almasio, P, Andreone, P, Margotti, M, Brunetto, M, Coco, B, Alvaro, D, Bragazzi, M, Marra, F, Pisano, A, Rigamonti, C, Colombo, M, Marzioni, M, Benedetti, A, Fabris, L, Strazzabosco, M, Portincasa, P, Palmieri, V, Tiribelli, C, Croce, L, Bruno, S, Rossi, S, Vinci, M, Prisco, C, Mattalia, A, Toniutto, P, Picciotto, A, Galli, A, Ferrari, C, Colombo, S, Casella, G, Morini, L, Caporaso, N, Colli, A, Spinzi, G, Montanari, R, Gregersen, P, Heathcote, E, Hirschfield, G, Siminovitch, K, Amos, C, Gershwin, M, Seldin, M, INVERNIZZI, PIETRO, Lee, AT, Mason, AL, Myers, RP, Peltekian, KM, Ghent, CN, Bernuzzi, Francesca Veronica, Almasio, PL, Bragazzi, MC, STRAZZABOSCO, MARIO, Palmieri, VO, Gregersen, PK, Heathcote, EJ, Hirschfield, GM, Siminovitch, KA, Amos, CI, Gershwin, ME, and Seldin, MF

Abstract

A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 × 10−11, odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 × 10−10, OR = 1.63) and 17q12-21 (P = 1.7 × 10−10, OR = 1.38).

Published
2010

9. Prolonged treatment (2 years) with different doses (3 versus 6 MU) of interferon alpha-2b for chronic hepatitis type C. Results of a multicenter randomized trial

Author

Saracco, Giorgio Maria, Borghesio, E., Mesina, P., Solinas, A., Spezia, C., Macor, F., Gallo, Vittorio, Chiandussi, L., Donada, C., Donadon, V., Spirito, F., Masaracco, G., Gallo, V., Mangia, A., Andriulli, A., Verme, G., and Rizzetto, M.

Subjects
Male, Dose-Response Relationship, Drug, Genotype, Interferon-alpha, Hepacivirus, Interferon alpha-2, Middle Aged, Antiviral Agents, Hepatitis C, Severity of Illness Index, Recombinant Proteins, Treatment Outcome, Predictive Value of Tests, Chronic Disease, Humans, RNA, Viral, Female, Viremia
Abstract

To examine the effect of prolonged treatment with different doses of interferon alpha-2b on the relapse rate in patients with chronic hepatitis C.One hundred and seventy-one patients with non-cirrhotic chronic hepatitis C were enrolled in an Italian multicenter trial. All patients were treated for 3 months with 3,000,000 Units (3 MU) of interferon alpha-2b given subcutaneously three times a week (t.i.w.). Patients with abnormal alanine aminotransferase (ALT) values were given 6 MU of interferon for an additional 3 months. If ALT remained persistently abnormal, therapy was then suspended. If ALT levels were normal, therapy was continued (6 MU t.i.w.) for an additional 18 months (total=2 years). Patients with normal ALT were randomly assigned to two groups, one receiving 3 MU and the other receiving 6 MU t.i.w. for an additional 21 months (total=2 years). Follow-up continued for 2 years after therapy withdrawal.Seven patients stopped treatment during the first 3 months. Of the remaining 164 patients, 76 (46%) showed abnormal ALT levels after 3 months of therapy: 11 of these (14%) normalized ALT values when given 6 MU and a sustained response was maintained in eight during the follow-up. Overall, 54 and 34 patients were allocated respectively to the groups receiving the 3 MU and 6 MU long-term treatment. At the end of therapy, 35/54 patients of the group 3 MU and 21/34 patients of the group 6 MU showed normal ALT levels (65% vs 62%, p=N.S.). After 2 years of follow-up, 24/35 (69%) patients of the group 3 MU and 16/21 (76%) of the group 6 MU were still in remission (p=N.S.). In an intention-to-treat analysis, 48/171 (28%) patients showed a long-term response (normal ALT values, HCV-RNA negative). About 65% of the sustained responders showed low baseline viremia compared with 33% of non-responders (p=0.005) while genotype 1b was more frequently found among non-responders than in long-term responders (84% vs 25%, p=0.0001).About 14% of patients who do not respond to a 3-month course of 3 MU of interferon normalize ALT levels when given 6 MU. In prolonged treatment, there is no significant difference between 3 and 6 MU in inducing a sustained response. Patients with low baseline viremia and genotype 2a respond significantly better to prolonged interferon therapy than highly viremic patients with genotype 1b.

Published
1997

13. OC.09.4: RELATIONSHIP OF GENETIC VARIATIONS OF THE GENE CODING FOR THE HUMAN EQUILIBRATIVE NUCLEOSIDE TRANSPORTER-1 (HENT1) WITH PROTEIN EXPRESSION AND RESPONSE TO TREATMENT IN CHRONIC HEPATITIS C

Author

Tarabra, E., primary, Framarin, L., additional, Actis, G.C., additional, Bocca, C., additional, Baiocchi, L., additional, Borghesio, E., additional, Tappero, G., additional, Carenzi, S., additional, Berrutti, M., additional, Ciancio, A., additional, Tabone, M., additional, Picciotto, A., additional, Grasso, A., additional, Artioli, S., additional, Rizzi, R., additional, Vecchi, E., additional, Strona, S., additional, Fazio, V., additional, Pistone, C., additional, Cassano, V., additional, Predebon, S., additional, Tibaudi, D., additional, and Rosina, F., additional

Published
2011
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19. RELATIONSHIP BETWEEN C/T_13910 POLYMORPHISM INVOLVED IN THE ADULT LACTASE PERSISTENCE AND RISK OF COLORECTAL CANCER IN THE ITALIAN POPULATION

Author

Tarabra, E., primary, Pazienza, P., additional, Borghesio, E., additional, Biava, A., additional, Tappero, G., additional, Framarin, L., additional, Actis, G., additional, Castellino, F., additional, Leone, N., additional, De Paolis, P., additional, Comandone, A., additional, Rosina, F., additional, and Ayoubi, M., additional

Published
2009
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21. MTHFR C677T AND A1298C POLYMORPHISMS AND SPORADIC COLORECTAL CARCINOMA RISK IN A COHORT OF ITALIAN PATIENTS

Author

Actis, G., primary, Pazienza, P., additional, Parziale, A., additional, Cicilano, M., additional, Tappero, G., additional, Tarabra, E., additional, Chiaramello, S., additional, Ayoubi, M., additional, Framarin, L., additional, Biava, A., additional, Borghesio, E., additional, De Paolis, P., additional, Comandone, A., additional, Castellino, F., additional, and Rosina, F., additional

Published
2009
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22. PEG-IFN FOR HEPATITIS C IN CLINICAL PRACTICE

Author

Rosina, F., primary, Tosti, M.E., additional, Borghesio, E., additional, Mele, A., additional, Minoli, G., additional, Gasbarrini, A., additional, Pallone, F., additional, Carosi, G., additional, Mazzotta, F., additional, and Rizzetto, M., additional

Published
2009
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24. la reinfezione virale nel post -trapianto

Author

Smedile, Antonina, Brunetto, M. R., Marzano, A, Ottobrelli, A, Abate, Maria Lorena, Borghesio, E, Durazzo, Marilena, Verme, G, and Rizzetto, Mario

Published
1992

25. Xantogranuloma necrobiotico

Author

Tomasini, C, Aloi, F, Depaoli, M, Borghesio, E, Carucci, P, and Durazzo, Marilena

Published
1992

29. Pegylated interferon α plus ribavirin for the treatment of chronic hepatitis C: A multicentre independent study supported by the Italian Drug Agency

Author

Rosina, Floriano, Tosti, Maria Elena, Borghesio, Elisabetta, Masocco, Maria, Mele, Alfonso, Coppola, Carmine, Milella, Michele, Borgia, Guglielmo, Andreone, Pietro, Koch, Maurizio, Zignego, Anna Linda, Romano, Mario, Carrara, Maurizio, Almasio, Piero Luigi, Azzola, Emilio, Nardone, Gerardo, Benedetti, Antonio, Carosi, Giampiero, Mazzotta, Francesco, Sagnelli, Evangelista, Rizzetto, Mario, Mascolo, M. C., Cursaro, C., Scuteri, A., Crespi, C., Gianstefani, A., Ranieri, J., Monti, M., Corti, G., Blanc, P. L., Baragli, F., Bellentani, S., Gasbarrini, A., Pompili, M., Mecenate, F., Picardi, A., Vespasiani, U., Nosotti, Null, Null, A. Picardi, Ricci, G. L., Paffetti, A., Mastropietro, C., Moretti, A., Spagnolo, A. L., Puoti, C., Bellis, L., Regazzetti, A., Maffezzini, E., Pietrangelo, A., Abbati, G., Borghi, A., Sardini, C., Raimondo, G., Scribano, L., Martines, D., Svegliati Baroni, G., Faraci, G., Schi anchi, S., Fornaciari, G., Massari, M., Fabris, P., Bertin, T., Salvagnini, M., Madonia, S., Calì, A., Civitavecchia, G., Pirisi, M., Smirne, C., Andreoletti, M., Morisco, F., Caporaso, N., Gentile, I., Brancaccio, G., Gaeta, G. B., Liberti, A., Iannece, M. D., Rocco, A., Federico, A., Loguercio, C., Riegler, G., Esposito, P., Fargion, S., Fatta, E., Masutti, F., Bonaventura, M. E., Autolitano, A., Russello, M., Bellia, A., Toniutto, P., Bitetto, D., Pasulo, L., Lucà, M. G., Grattagliano, I., Palasciano, G., Romagno, D., Giannelli, G., Napoli, N., Plattella, M. S., Cassano, P., Gobbo, G., Monti, V., Raspanti, A., Cuccorese, Null, Colombo, A. E., Mandelli, G., Spinzi, G. C., Floridia, Null, Messina, V., Bonfante, S., Bellissima, P., Toti, M., Vecchiet, J., Falasca, K., Portelli, V., Stefano, G. De, Pietromatera, G., Viganò, P., Re, T., Andreoni, M., Null, G. Raineri, Grossi, P. A., Caputo, S., Cassola, G., Feasi, M., Biagio, A. Di, Nicolini, LAURA AMBRA, Giannini, EDOARDO GIOVANNI, Corbo, M., Foti, G., Kunkar, A., Caterini, L., Migliorini, D., Chiodera, A., Calleri, G., Spezia, C., Framarin, L., Null, M. Berrutti, Ciancio, A., Baiguera, C., Puoti, M., Vento, S., Contini, C., Boccia, S., Casiraghi, M. A., Simone, L., Tacconi, D., Caremani, M., Almi, P., Chimenti, M., Cosco, Null, Messeri, D., Esperti, F. C., Lomonaco, L., Pazzi, P., Fornari, F., Comparato, G., Casetti, T., Foschi, F. G., Samori, A., Ferretti, E., Marin, R., Campo, N., Testa, R., Rizzo, S., Rosina, F, Tosti, ME, Borghesio, E, Masocco, M, Mele, A, Coppola, C, Milella, M, Borgia, G, Andreone, P, Koch, M, Zignego, AL, Romano, M, Carrara, M, Almasio, PL, Azzola, E, Nardone, G, Benedetti, A, Carosi, G, Mazzotta, F, Sagnelli, E, Rizzetto, M, Rosina, F., Tosti, M. E., Borghesio, E., Masocco, M., Mele, A., Coppola, C., Milella, M., Borgia, Guglielmo, Andreone, P., Koch, M., Zignego, A. L., Romano, M., Carrara, M., Almasio, P. L., Azzola, E., Nardone, GERARDO ANTONIO PIO, Benedetti, A., Carosi, G., Mazzotta, F., Sagnelli, E., Rizzetto, M., Aifa, Aisf, Simit, Aigo, Sige, Gentile, Ivan, Morisco, Filomena, Et, Al, Floriano Rosina, Maria Elena Tosti, Elisabetta Borghesio, Maria Masocco, Alfonso Mele, Carmine Coppola, Michele Milella, Guglielmo Borgia, Pietro Andreone, Maurizio Koch, Anna Linda Zignego, Mario Romano, Maurizio Carrara, Piero Luigi Almasio, Emilio Azzola, Gerardo Nardone, Antonio Benedetti, Giampiero Carosi, Francesco Mazzotta, Evangelista Sagnelli, and Mario Rizzetto

Subjects
Registrie, Male, Cirrhosis, medicine.disease_cause, Polyethylene Glycol, Gastroenterology, Polyethylene Glycols, chemistry.chemical_compound, Hepatitis Viruses, Hepatitis Viruse, Prospective Studies, Viral, Registries, Chronic, Prospective cohort study, Drug Carrier, Drug Carriers, Settore MED/12 - Gastroenterologia, Medicine (all), Recombinant Protein, Middle Aged, Hepatitis C, Recombinant Proteins, Treatment Outcome, Italy, Combination, RNA, Viral, Population study, Drug Therapy, Combination, Female, Human, medicine.medical_specialty, Genotype, Hepatitis C virus, Alpha interferon, Ribavirin, Sustained virological response (SVR), Treatment, Antiviral Agents, Follow-Up Studie, Hepatology, Drug Therapy, Internal medicine, medicine, Humans, Antiviral Agent, business.industry, Interferon-alpha, HCV therapy, Hepatitis C, Chronic, medicine.disease, Clinical trial, Prospective Studie, chemistry, Immunology, RNA, Follow-Up Studies, business
Abstract

a b s t r a c t Background: Data on the efficacy of Peg-interferon/ribavirin therapy for chronic hepatitis C are mostly derived from treatment of selected patients enrolled in clinical trials. This study aimed to assess the effectiveness of Peg-interferon/ribavirin therapy in “real world” chronic hepatitis C patients in Italy. Methods: Independent observational multicentre study including consecutive patients receiving Peginterferon/ribavirin in the 18 months before (retrospective phase) and after (prospective phase) the start of the study. Results: 4176 patients were eligible. The final study population consisted of 2051 patients in the retrospective and 2073 in the prospective phase. Sustained virological response was achieved by 1036 patients (50.5%) during the retrospective phase: 325 were genotypes 1/4 (34.1%) and 684 were genotypes 2/3 (67.2%) and by 800 patients (38.6%) during the prospective phase: 300 were genotypes 1/4 (28.4%) and 473 were genotypes 2/3 (51.5%). During multivariate analysis genotypes 2/3 were significantly associated with higher sustained virological response rates; cirrhosis and -glutamil-transpeptidase >2 times the normal limit were associated with poorer response. Conclusions: The response to Peg-interferon/ribavirin therapy in “real world” clinical practice is distinctly lower than in registration trials. The difference in response rates was more pronounced among easy-totreat than among difficult-to-treat hepatitis C virus genotypes.

Published
2014

30. Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis

Author

Massimo Zuin, Antonio Benedetti, Pierluigi Toniutto, Vincenzo Palmieri, Peter K. Gregersen, Cristina Rigamonti, Christopher I. Amos, Paolo Muratori, Barbara Coco, Francesca Bernuzzi, Piero Luigi Almasio, Renzo Montanari, Maurizia Rossana Brunetto, Fabio Macciardi, Andrea Galli, Pietro Andreone, Cameron N. Ghent, Yue Lu, Luca Fabris, Gideon M. Hirschfield, Marzia Margotti, Michael Ransom, Ilaria Bianchi, Agostino Colli, Carlo Selmi, Giancarlo Spinzi, Lory Saveria Crocè, S. Bruno, Gang Xie, Mario Strazzabosco, Claudio Tiribelli, Xiangdong Liu, Grazia Anna Niro, E. Jenny Heathcote, Russell Shigeta, Katherine A. Siminovitch, Elisabetta Borghesio, Nicola Caporaso, M. Eric Gershwin, Andrew Mason, Maria Vinci, Mauro Podda, Robert P. Myers, Fabio Marra, Cleofe Prisco, Lorenzo Morini, Roman Kosoy, Alberto Mattalia, Michael F. Seldin, Chun Xu, Maria Consiglia Bragazzi, Piero Portincasa, Roberta Lazzari, Giovanni Casella, Sonia Rossi, Marco Marzioni, Silvia Colombo, Domenico Alvaro, Luigi Muratori, Sara Lupoli, Carlo Ferrari, Annette Lee, Annarosa Floreani, Yan Lu, Floriano Rosina, Angelo Andriulli, Massimo Colombo, Antonio Picciotto, Kevork M. Peltekian, Ana Lleo, Alessandro Pisano, Pietro Invernizzi, Liu, X, Invernizzi, P, Lu, Y, Kosoy, R, Bianchi, I, Podda, M, Xu, C, Xie, G, Macciardi, F, Selmi, C, Lupoli, S, Shigeta, R, Ransom, M, Lleo, A, Lee, AT, Mason, AL, Myers, RP, Peltekian, KM, Ghent, CN, Bernuzzi, F, Zuin, M, Rosina, F, Borghesio, E, Floreani, A, Lazzari, R, Niro, G, Andriulli, A, Muratori, L, Muratori, P, Almasio, PL, Andreone, P, Margotti, M, Brunetto, M, Coco, B, Alvaro, D, Bragazzi, MC, Marra, F, Pisano, A, Rigamonti, C, Colombo, M, Marzioni, M, Benedetti, A, Fabris, L, Strazzabosco, M, Portincasa, P, Palmieri, VO, Tiribelli, C, Croce, L, Bruno, S, Rossi, S, Vinci, M, Prisco, C, Mattalia, A, Toniutto, P, Picciotto, A, Galli, A, Ferrari, C, Colombo, S, Casella, G, Morini, L, Caporaso, N, Colli, A, Spinzi, G, Montanari, R, Gregersen, PK, Heathcote, EJ, Hirschfield, GM, Siminovitch, KA, Amos, CI, Gershwin, ME, Seldin, MF, Lee, At, Mason, Al, Myers, Rp, Peltekian, Km, Ghent, Cn, Almasio, Pl, Bragazzi, Mc, Palmieri, Vo, Caporaso, Nicola, Gregersen, Pk, Heathcote, Ej, Hirschfield, Gm, Siminovitch, Ka, Amos, Ci, Gershwin, Me, Seldin, M. F., Lee, A, Mason, A, Myers, R, Peltekian, K, Ghent, C, Almasio, P, Bragazzi, M, Palmieri, V, Gregersen, P, Heathcote, E, Hirschfield, G, Siminovitch, K, Amos, C, Gershwin, M, Seldin, M, X., Liu, P., Invernizzi, Y., Lu, R., Kosoy, I., Bianchi, M., Podda, C., Xu, G., Xie, F., Macciardi, C., Selmi, S., Lupoli, R., Shigeta, M., Ransom, A., Lleo, A. T., Lee, A. L., Mason, R. P., Myer, K. M., Peltekian, C. N., Ghent, F., Bernuzzi, M., Zuin, F., Rosina, E., Borghesio, A., Floreani, R., Lazzari, G., Niro, A., Andriulli, L., Muratori, P., Muratori, P. L., Almasio, P., Andreone, M., Margotti, M., Brunetto, B., Coco, D., Alvaro, M. C., Bragazzi, F., Marra, A., Pisano, C., Rigamonti, M., Colombo, M., Marzioni, A., Benedetti, L., Fabri, M., Strazzabosco, P., Portincasa, V. O., Palmieri, Tiribelli, Claudio, Croce', Saveria, S., Bruno, S., Rossi, M., Vinci, C., Prisco, A., Mattalia, P., Toniutto, A., Picciotto, A., Galli, C., Ferrari, S., Colombo, G., Casella, L., Morini, N., Caporaso, A., Colli, G., Spinzi, R., Montanari, P. K., Gregersen, E. J., Heathcote, G. M., Hirschfield, K. A., Siminovitch, C. I., Amo, M. E., Gershwin, M. F., Seldin, Liu X, Invernizzi P, Lu Y, Kosoy R, Bianchi I, Podda M, Xu C, Xie G, Macciardi F, Selmi C, Lupoli S, Shigeta R, Ransom M, Lleo A, Lee AT, Mason AL, Myers RP, Peltekian KM, Ghent CN, Bernuzzi F, Zuin M, Rosina F, Borghesio E, Floreani A, Lazzari R, Niro G, Andriulli A, Muratori L, Muratori P, Almasio PL, Andreone P, Margotti M, Brunetto M, Coco B, Alvaro D, Bragazzi MC, Marra F, Pisano A, Rigamonti C, Colombo M, Marzioni M, Benedetti A, Fabris L, Strazzabosco M, Portincasa P, Palmieri VO, Tiribelli C, Croce L, Bruno S, Rossi S, Vinci M, Prisco C, Mattalia A, Toniutto P, Picciotto A, Galli A, Ferrari C, Colombo S, Casella G, Morini L, Caporaso N, Colli A, Spinzi G, Montanari R, Gregersen PK, Heathcote EJ, Hirschfield GM, Siminovitch KA, Amos CI, Gershwin ME, and Seldin MF.

Subjects
Liver Cirrhosis, Oncology, Canada, medicine.medical_specialty, Cirrhosis, European Continental Ancestry Group, LOCI, PRIMARY BILIARY CIRRHOSIS, GENOME WIDE ASSOCIATION, Genome-wide association study, Locus (genetics), genetics, Genome, Genome-Wide Association Study, Humans, Interferon Regulatory Factors, Liver Cirrhosi, Biology, Biliary, Meta-Analysis as Topic, Odds Ratio, White People, Article, Alleles, Canada, European Continental Ancestry Group, primary biliary cirrhosi, Primary biliary cirrhosis, Meta-Analysis as Topic, MED/12 - GASTROENTEROLOGIA, IL12A, Internal medicine, Odds Ratio, Genetics, medicine, Humans, Allele, genome, genetics, Genome, Genome-Wide Association Study, Humans, Interferon Regulatory Factors, Liver Cirrhosis, Alleles, primary biliary cirrhosis, genome-wide meta-analyses, Liver Cirrhosis, Biliary, Biliary, Odds ratio, medicine.disease, Interferon Regulatory Factors, Cohort, Genome-Wide Association Study
Abstract

A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 × 10−11, odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 × 10−10, OR = 1.63) and 17q12-21 (P = 1.7 × 10−10, OR = 1.38).

Published
2010

31. LCT-13910C>T polymorphism-associated lactose malabsorption and risk for colorectal cancer in Italy.

Author

Tarabra E, Pazienza P, Borghesio E, Actis GC, Tappero G, Framarin L, Ayoubi M, Castellino F, Leone N, Sansoè G, De Paolis P, Comandone A, and Rosina F

Subjects
Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Colorectal Neoplasms epidemiology, Colorectal Neoplasms genetics, Female, Genotype, Humans, Incidence, Italy epidemiology, Lactase metabolism, Lactose Intolerance complications, Lactose Intolerance enzymology, Male, Middle Aged, Prognosis, Retrospective Studies, Risk Factors, Colorectal Neoplasms etiology, DNA, Neoplasm genetics, Lactase genetics, Lactose Intolerance genetics, Polymorphism, Genetic
Abstract

Background: The activity of epithelial lactase (LCT) associates with a polymorphism 13910 bp upstream the LCT-encoding gene (LCT-13910C>T). The relationship between LCT-13910C>T polymorphism and risk for colorectal cancer is unclear., Aims: We examined the relationship between the LCT-13910C>T polymorphism causing lactose intolerance and risk for colorectal cancer/polyps onset in the Italian population., Patients and Methods: 793 subjects (306 with colorectal cancer, 176 with polyps and 311 controls) were genotyped for the LCT-13910C>T variant by TaqMan real time-PCR., Results: Lactose malabsorption linked to the CC genotype did not associate with an increased risk for either colorectal cancer (OR=1.041; 95% CI=0.751-1.442; p=0.868) or polyps (OR=0.927; 95% CI=0.630-1.363; p=0.769). There was no association with colorectal cancer/polyps site. 60% of the subjects overall bore the CC genotype., Conclusion: In the Italian population the LCT-13910C>T polymorphism is not associated to the risk for colorectal cancer or polyps., (Copyright 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Published
2010
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32. Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis.

Author

Liu X, Invernizzi P, Lu Y, Kosoy R, Lu Y, Bianchi I, Podda M, Xu C, Xie G, Macciardi F, Selmi C, Lupoli S, Shigeta R, Ransom M, Lleo A, Lee AT, Mason AL, Myers RP, Peltekian KM, Ghent CN, Bernuzzi F, Zuin M, Rosina F, Borghesio E, Floreani A, Lazzari R, Niro G, Andriulli A, Muratori L, Muratori P, Almasio PL, Andreone P, Margotti M, Brunetto M, Coco B, Alvaro D, Bragazzi MC, Marra F, Pisano A, Rigamonti C, Colombo M, Marzioni M, Benedetti A, Fabris L, Strazzabosco M, Portincasa P, Palmieri VO, Tiribelli C, Croce L, Bruno S, Rossi S, Vinci M, Prisco C, Mattalia A, Toniutto P, Picciotto A, Galli A, Ferrari C, Colombo S, Casella G, Morini L, Caporaso N, Colli A, Spinzi G, Montanari R, Gregersen PK, Heathcote EJ, Hirschfield GM, Siminovitch KA, Amos CI, Gershwin ME, and Seldin MF

Subjects
Canada, Genome, Genome-Wide Association Study, Humans, Interferon Regulatory Factors, Liver Cirrhosis, Biliary, Meta-Analysis as Topic, Odds Ratio, Alleles, White People genetics
Abstract

A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 x 10(-11), odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 x 10(-10), OR = 1.63) and 17q12-21 (P = 1.7 x 10(-10), OR = 1.38).

Published
2010
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33. Sequential versus concomitant administration of ribavirin and interferon alfa-n3 in patients with chronic hepatitis C not responding to interferon alone: results of a randomized, controlled trial.

Author

Sostegni R, Ghisetti V, Pittaluga F, Marchiaro G, Rocca G, Borghesio E, Rizzetto M, and Saracco G

Subjects
Adolescent, Adult, Antiviral Agents adverse effects, Antiviral Agents therapeutic use, Drug Administration Schedule, Drug Therapy, Combination, Forecasting, Hepacivirus genetics, Hepatitis C, Chronic pathology, Hepatitis C, Chronic virology, Humans, Interferon-alpha adverse effects, Middle Aged, RNA, Viral analysis, Recombinant Proteins, Retreatment, Ribavirin adverse effects, Ribavirin therapeutic use, Treatment Outcome, Antiviral Agents administration & dosage, Hepatitis C, Chronic drug therapy, Interferon-alpha administration & dosage, Interferon-alpha therapeutic use, Ribavirin administration & dosage
Abstract

We conducted a three-arm, randomized trial in 96 patients with chronic hepatitis C who did not respond to interferon alfa to compare treatments. Group 1 (33 patients) received ribavirin alone (1,000 mg/daily for 6 months) followed by interferon alfa n-3 alone (3 MU thrice weekly for 6 months); group 2 (33 patients) received ribavirin plus interferon alfa n-3 for 6 months at the above doses; and group 3 (30 patients) received interferon alfa n-3 alone (3 MU thrice weekly for 6 months). At the end of treatment, 3 patients (10%) in group 1, 13 (41%) in group 2, and 5 (17%) in group 3 had normal alanine transaminase (ALT) levels (group 2 vs. groups 1 and 3, P = .008). After 6 months of follow-up, only 4 patients (12.5%) in group 2 still had normal ALT values (P = .03). At the end of therapy, hepatitis C virus (HCV) RNA was no longer detectable by polymerase chain reaction in 4 (13%), 9 (27%), and 2 (7%) patients, respectively, in groups 1, 2, and 3 (P = NS). Six months posttherapy, only 5 (15%) patients in group 2 were still HCV RNA negative (P = .02). At the time of follow-up liver biopsy, performed 6 months after the end of treatment, a significant improvement of the necroinflammatory scores was observed among group 2 patients (P = .01) but not in the other two groups. Side effects reflected the profile of each drug as monotherapy; mild hemolytic anemia was the most frequent side effect caused by ribavirin. In conclusion, concomitant administration of ribavirin and interferon alfa n-3 was significantly superior to the sequential schedule or interferon alfa n-3 monotherapy in inducing a sustained response in patients with chronic hepatitis C who had not responded to interferon alone. However, combination therapy at the dose and duration adopted in this study is capable of modifying the natural course of the disease in only a minority of these patients.

Published
1998
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34. Serum immunoglobulin M antibody to hepatitis D as a surrogate marker of hepatitis D in interferon-treated patients and in patients who underwent liver transplantation.

Author

Borghesio E, Rosina F, Smedile A, Lagget M, Niro MG, Marinucci G, and Rizzetto M

Subjects
Adult, Female, Hepatitis B Surface Antigens analysis, Hepatitis D diagnosis, Humans, Interferon alpha-2, Male, Middle Aged, Recombinant Proteins, Antibodies, Viral blood, Hepatitis D therapy, Hepatitis Delta Virus immunology, Immunoglobulin M blood, Interferon-alpha therapeutic use, Liver Transplantation
Abstract

The kinetics of the immunoglobulin (Ig) M type antibody to the hepatitis D virus (IgM anti-HD) were investigated in hepatitis B surface antigen (HBsAg) carriers with chronic hepatitis D treated with interferon (IFN) and in patients with terminal hepatitis delta virus (HDV) cirrhosis who underwent liver transplantation. The IgM antibody disappeared in each of 8 patients who responded to IFN therapy with the persistent normalization of aminotransferases and with the clearance of serum HBsAg and HDV-RNA. The IgM reactivity did not decline in the 45 treated patients who did not respond to the cytokine or who experienced a relapse after responding while on therapy. The antibody rapidly disappeared from serum post-transplantation in each of 10 examined patients with HDV who underwent transplantation. In 5 patients who underwent transplantation and who became reinfected with HDV, the antibody remained undetectable during the early reinfection phase, as marked by HDV replication and by the absence of liver damage; however, it rapidly raised to pre-transplantation levels with the recurrence of hepatitis D (HD) in the liver graft. Monomeric 7S IgM anti-HD predominated over pentameric 19S antibody in each of the two patients examined for IgM anti-HD molecular species. The IgM antibody to HDV raises in response to HDV-induced damage and represents a valid surrogate marker of liver damage which is immunopathologically related to HDV infection. Besides providing diagnostic information, it provides the best predictor of impending resolution of chronic HDV disease, whether spontaneous or IFN-induced.

Published
1998
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35. Anti-neutrophil cytoplasmic antibodies in inflammatory bowel disease: do they recognize different subsets of a heterogeneous disease?

Author

Castellino F, Rosina F, Bansi DS, Bauducci M, Touscoz GA, Giorda L, Borghesio E, Bessone MP, Astegiano M, and Musso A

Subjects
Adult, Antibodies, Antineutrophil Cytoplasmic, Biomarkers analysis, Colitis, Ulcerative diagnosis, Crohn Disease diagnosis, Diagnosis, Differential, Enzyme-Linked Immunosorbent Assay, Epitopes, Female, Fluorescent Antibody Technique, Indirect, Humans, Immunoblotting, Male, Sensitivity and Specificity, Autoantibodies analysis, Colitis, Ulcerative immunology, Crohn Disease immunology
Abstract

Objective: To evaluate the prevalence of anti-neutrophil cytoplasmic antibodies in a series of patients with inflammatory bowel disease, the discriminatory value of these antibodies in differentiating between ulcerative colitis and Crohn's disease, their antigen specificity and their correlation with epidemiological and clinical variables., Methods: Serum anti-neutrophil cytoplasmic antibodies were evaluated by indirect immunofluorescence and immunoblotting using neutrophils isolated from peripheral blood and by enzyme-linked immunosorbent assays (ELISAs) using proteinase 3 and myeloperoxidase as antigens., Results: Anti-neutrophil cytoplasmic antibodies were detected by immunofluorescence in 43 (39.8%) of 108 patients with ulcerative colitis, in 11 (11.9%) of 92 patients with Crohn's disease (P < 0.001) and 5 (6.8%) of 73 control patients. The predominant pattern was perinuclear staining around neutrophil nuclei (44 of 59, 75%); a homogeneous cytoplasmic staining was present in 15 (25%) of 59 sera, mainly among Crohn's disease and control patients. The ELISAs gave no positive results. Recognition of proteins of relative molecular masses 27,000 and 49,000 at immunoblotting was common to ulcerative colitis, Crohn's disease and control sera. The proteins of relative molecular masses 32,000 and 106,000 were recognized exclusively by 11% of anti-neutrophil-positive ulcerative colitis sera. No significant correlation was found between the presence of anti-neutrophil cytoplasmic antibodies and the demographic and clinical characteristics of the patients., Conclusion: Anti-neutrophil cytoplasmic antibodies are detectable in a large proportion of patients with ulcerative colitis, but their prevalence in a limited proportion of patients with Crohn's disease reduces their discriminatory capability. The persistence of anti-neutrophil cytoplasmic antibodies after total colectomy and the absence of a correlation between the activity of the disease and the presence or titre of these antibodies support the hypothesis that anti-neutrophil cytoplasmic antibodies are not simply an epiphenomenon of colonic inflammation.

Published
1995

36. [Immunoblotting in the diagnosis of chronic viral hepatitis].

Author

Cozzolongo R, Bauducci M, Giannuzzi V, Ragnini F, Borghesio E, Cuppone R, Martinotti R, Manghisi OG, and Rosina F

Subjects
Humans, Sensitivity and Specificity, Hepatitis B diagnosis, Hepatitis C diagnosis, Hepatitis D diagnosis, Hepatitis, Chronic diagnosis, Immunoblotting methods
Published
1995

37. Heterogeneity of liver-kidney microsomal autoantibodies in chronic hepatitis C and D virus infection.

Author

Durazzo M, Philipp T, Van Pelt FN, Lüttig B, Borghesio E, Michel G, Schmidt E, Loges S, Rizzetto M, and Manns MP

Subjects
Animals, Antibodies, Anti-Idiotypic blood, Antibody Specificity, Chronic Disease, Enzyme-Linked Immunosorbent Assay, Female, Hepatitis C blood, Hepatitis D blood, Humans, Immunoglobulin G blood, Male, Rats, Autoantibodies blood, Hepatitis C immunology, Hepatitis D immunology
Abstract

Background/aims: Anti-liver-kidney microsomal (LKM) autoantibodies occur in a proportion of patients with chronic hepatitis C and D infections. Because of different immunofluorescence patterns, antibodies in hepatitis C and D were termed LKM-1 and LKM-3, respectively. The aim of the present study was to evaluate the different specificities of LKM-1 and LKM-3 antibodies., Methods: Forty-nine samples of LKM-1 sera and 16 samples of LKM-3 sera were studied for reactivity against rat and human liver microsomal proteins by immunofluorescence, enzyme-linked immunosorbent assay, and Western blot., Results: Thirty-four percent of the LKM-1 sera reacted with 50-kilodalton cytochrome P4502D6 in Western blot. In addition, a proportion of the sera recognized either a 59- or 70-kilodalton antigen, and 45% of the sera did not react in Western blot. Recently, the major LKM-3 antigen was identified as an autoepitope expressed on uridine diphosphate-glucuronosyltransferases (UGT). Seven LKM-3-positive sera reacted with recombinant rabbit family one UGT. None of the anti-LKM-1-positive hepatitis C sera reacted with UGT. Antibody reactivity against liver microsomal proteins in enzyme-linked immunosorbent assay ended when antigens were pretreated with sodium dodecyl sulfate, confirming that antibodies recognize conformational epitopes., Conclusions: LKM-1 antibodies in hepatitis C are more heterogeneous and react with different antigens compared with LKM-3 antibodies in hepatitis D.

Published
1995
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38. [A case of hepatocarcinoma preceded by several years by "isolated" increase in alphafetoprotein].

Author

Durazzo M, Borghesio E, Regge D, Milone PA, and Rizzetto M

Subjects
Carcinoma, Hepatocellular blood, Humans, Liver Neoplasms blood, Male, Middle Aged, Time Factors, Carcinoma, Hepatocellular diagnosis, Liver Neoplasms diagnosis, alpha-Fetoproteins analysis
Abstract

Hepatocarcinoma (HCC), the most frequent malignant hepatic neoplasia, is sometimes difficult to diagnose at an early stage since the symptoms may be attributed to concomitant hepatic cirrhosis. The assay of alpha-fetoprotein associated with an ultrasound examination of the hepatic parenchyma is an important screening tool for high-risk patients. Ultrasound examination is considered the most sensitive method and alpha-fetoprotein is a supplementary diagnostic tool. Elevated alpha-fetoprotein only occasionally precedes morphological anomalies and even in these cases the neoplastic aspect emerges within a short period of time. The case reported here illustrates the "astronomic" increase of alpha-fetoprotein in a high-risk patient for HCC (positive HBsAg cirrhosis) without the manifest appearance of any instrumental or histological data confirming the presence of the tumour for two years. When the tumour was identified in instrumental tests it had spread throughout the entire hepatic parenchyma in a form which could no longer be treated using any form of therapy. The case reported here emphasizes the diagnostic value of alphafetoprotein in high-risk patients for HCC, even in the prolonged absence of all other data regarding neoplastic transformation.

Published
1992

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