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1. Trends in chronic hepatitis B virus infection in Italy over a 10-year period: Clues from the nationwide PITER and MASTER cohorts toward elimination

Author

Brancaccio, G, Coco, B, Nardi, A, Quaranta, M, Tosti, M, Ferrigno, L, Cacciola, I, Messina, V, Chessa, L, Morisco, F, Milella, M, Barbaro, F, Ciancio, A, Russo, F, Coppola, N, Blanc, P, Claar, E, Verucchi, G, Puoti, M, Zignego, A, Chemello, L, Madonia, S, Fagiuoli, S, Marzano, A, Ferrari, C, Lampertico, P, Di Marco, V, Craxì, A, Santantonio, T, Raimondo, G, Brunetto, M, Gaeta, G, Kondili, L, Pasulo, L, Coppola, C, Pisano, F, Romano, M, Porcu, C, Bottalico, I, Cossiga, V, Tata, X, Sagnelli, C, Pierotti, P, Degasperi, E, Rosato, V, Badia, L, Ieluzzi, D, Monti, M, Bavetta, M, Cavalletto, L, Toniutto, P, Fornasiere, E, Colecchia, A, Ferrarese, A, Nardone, G, Rocco, A, Viganò, M, Foschi, F, Conti, F, Morsica, G, Salpietro, S, Torti, C, Costa, C, Federico, A, Dallio, M, Giorgini, A, Anselmo, M, De Leo, P, Zaltron, S, Cambianica, A, Piscaglia, F, Serio, I, Schivazappa, S, Mastroianni, A, Chidichimo, L, Massari, M, Mazzaro, C, Marrone, A, D'Amore, F, D'Offizi, G, Licata, A, Niro, G, Pollicino, T, Aghemo, A, Brancaccio G., Coco B., Nardi A., Quaranta M. G., Tosti M. E., Ferrigno L., Cacciola I., Messina V., Chessa L., Morisco F., Milella M., Barbaro F., Ciancio A., Russo F. P., Coppola N., Blanc P., Claar E., Verucchi G., Puoti M., Zignego A. L., Chemello L., Madonia S., Fagiuoli S., Marzano A., Ferrari C., Lampertico P., Di Marco V., Craxì A., Santantonio T. A., Raimondo G., Brunetto M. R., Gaeta G. B., Kondili L. A., Pasulo L., Coppola C., Pisano F., Romano M., Porcu C., Bottalico I. F., Cossiga V., Tata X., Sagnelli C., Pierotti P., Degasperi E., Rosato V., Badia L., Ieluzzi D., Monti M., Bavetta M. G., Cavalletto L., Toniutto P., Fornasiere E., Colecchia A., Ferrarese A., Nardone G., Rocco A., Viganò M., Foschi F. G., Conti F., Morsica G., Salpietro S., Torti C., Costa C., Federico A., Dallio M., Giorgini A., Anselmo M., De Leo P., Zaltron S., Cambianica A., Piscaglia F., Serio I., Schivazappa S., Mastroianni A., Chidichimo L., Massari M., Mazzaro C., Marrone A., D'Amore F. M., D'Offizi G., Licata A., Niro G. A., Pollicino T., Aghemo A., Brancaccio, G, Coco, B, Nardi, A, Quaranta, M, Tosti, M, Ferrigno, L, Cacciola, I, Messina, V, Chessa, L, Morisco, F, Milella, M, Barbaro, F, Ciancio, A, Russo, F, Coppola, N, Blanc, P, Claar, E, Verucchi, G, Puoti, M, Zignego, A, Chemello, L, Madonia, S, Fagiuoli, S, Marzano, A, Ferrari, C, Lampertico, P, Di Marco, V, Craxì, A, Santantonio, T, Raimondo, G, Brunetto, M, Gaeta, G, Kondili, L, Pasulo, L, Coppola, C, Pisano, F, Romano, M, Porcu, C, Bottalico, I, Cossiga, V, Tata, X, Sagnelli, C, Pierotti, P, Degasperi, E, Rosato, V, Badia, L, Ieluzzi, D, Monti, M, Bavetta, M, Cavalletto, L, Toniutto, P, Fornasiere, E, Colecchia, A, Ferrarese, A, Nardone, G, Rocco, A, Viganò, M, Foschi, F, Conti, F, Morsica, G, Salpietro, S, Torti, C, Costa, C, Federico, A, Dallio, M, Giorgini, A, Anselmo, M, De Leo, P, Zaltron, S, Cambianica, A, Piscaglia, F, Serio, I, Schivazappa, S, Mastroianni, A, Chidichimo, L, Massari, M, Mazzaro, C, Marrone, A, D'Amore, F, D'Offizi, G, Licata, A, Niro, G, Pollicino, T, Aghemo, A, Brancaccio G., Coco B., Nardi A., Quaranta M. G., Tosti M. E., Ferrigno L., Cacciola I., Messina V., Chessa L., Morisco F., Milella M., Barbaro F., Ciancio A., Russo F. P., Coppola N., Blanc P., Claar E., Verucchi G., Puoti M., Zignego A. L., Chemello L., Madonia S., Fagiuoli S., Marzano A., Ferrari C., Lampertico P., Di Marco V., Craxì A., Santantonio T. A., Raimondo G., Brunetto M. R., Gaeta G. B., Kondili L. A., Pasulo L., Coppola C., Pisano F., Romano M., Porcu C., Bottalico I. F., Cossiga V., Tata X., Sagnelli C., Pierotti P., Degasperi E., Rosato V., Badia L., Ieluzzi D., Monti M., Bavetta M. G., Cavalletto L., Toniutto P., Fornasiere E., Colecchia A., Ferrarese A., Nardone G., Rocco A., Viganò M., Foschi F. G., Conti F., Morsica G., Salpietro S., Torti C., Costa C., Federico A., Dallio M., Giorgini A., Anselmo M., De Leo P., Zaltron S., Cambianica A., Piscaglia F., Serio I., Schivazappa S., Mastroianni A., Chidichimo L., Massari M., Mazzaro C., Marrone A., D'Amore F. M., D'Offizi G., Licata A., Niro G. A., Pollicino T., and Aghemo A.

Abstract

Objectives: The study measures trends in the profile of patients with chronic hepatitis B virus linked to care in Italy. Methods: A cross-sectional, multicenter, observational cohort (PITER cohort) of consecutive patients with hepatitis B surface antigen (HBsAg) over the period 2019-2021 from 46 centers was evaluated. The reference was the MASTER cohort collected over the years 2012-2015. Standard statistical methods were used. Results: The PITER cohort enrolled 4583 patients, of whom 21.8% were non-Italian natives. Compared with those in MASTER, the patients were older and more often female. The prevalence of hepatitis B e antigen (HBeAg) declined (7.2% vs 12.3; P <0.0001) and that of anti-hepatitis D virus (HDV) remained stable (9.3% vs 8.3%). In both cohorts, about 25% of the patients had cirrhosis, and those in the PITER cohort were older. HBeAg-positive was 5.0% vs 12.6% (P <0.0001) and anti-HDV positive 24.8% vs 17.5% (P <0.0017). In the logistic model, the variables associated with cirrhosis were anti-HDV-positive (odds ratio = 10.08; confidence interval 7.63-13.43), age, sex, and body mass index; the likelihood of cirrhosis was reduced by 40% in the PITER cohort. Among non-Italians, 12.3% were HBeAg-positive (vs 23.4% in the MASTER cohort; P <0.0001), and 12.3% were anti-HDV-positive (vs 11.1%). Overall, the adherence to the European Association for the Study of the Liver recommendations for antiviral treatment increased over time. Conclusion: Chronic hepatitis B virus infection appears to be in the process of becoming under control in Italy; however, HDV infection is still a health concern in patients with cirrhosis and in migrants.

Published
2023

4. Resistance analysis and treatment outcomes in hepatitis C virus genotype 3-infected patients within the Italian network VIRONET-C

Author

Di Maio, V, Barbaliscia, S, Teti, E, Fiorentino, G, Milana, M, Paolucci, S, Pollicino, T, Morsica, G, Starace, M, Bruzzone, B, Gennari, W, Micheli, V, Yu La Rosa, K, Foroghi, L, Calvaruso, V, Lenci, I, Polilli, E, Babudieri, S, Aghemo, A, Raimondo, G, Sarmati, L, Coppola, N, Pasquazzi, C, Baldanti, F, Parruti, G, Perno, C, Angelico, M, Craxi, A, Andreoni, M, Ceccherini-Silberstein, F, Andreone, P, Aragri, M, Bertoli, A, Boeri, E, Brancaccio, G, Brunetto, M, Callegaro, A, Cenderello, G, Cento, V, Ciaccio, A, Ciancio, A, Cuomo, N, De Santis, A, Di Biagio, A, Di Marco, V, Di Perri, G, Di Stefano, M, Gaeta, G, Ghisetti, V, Gulminetti, R, Lampertico, P, Landonio, S, Lichtner, M, Lleo, A, Maida, I, Marenco, S, Masetti, C, Mastroianni, C, Minichini, C, Milano, E, Monno, L, Novati, S, Pace Palitti, V, Paternoster, C, Pellicelli, A, Pieri, A, Puoti, M, Rizzardini, G, Ruggiero, T, Rossetti, B, Sangiovanni, V, Santantonio, T, Taliani, G, Toniutto, P, Vullo, V, Zazzi, M, Di Maio V. C., Barbaliscia S., Teti E., Fiorentino G., Milana M., Paolucci S., Pollicino T., Morsica G., Starace M., Bruzzone B., Gennari W., Micheli V., Yu La Rosa K., Foroghi L., Calvaruso V., Lenci I., Polilli E., Babudieri S., Aghemo A., Raimondo G., Sarmati L., Coppola N., Pasquazzi C., Baldanti F., Parruti G., Perno C. F., Angelico M., Craxi A., Andreoni M., Ceccherini-Silberstein F., Andreone P., Aragri M., Bertoli A., Boeri E., Brancaccio G., Brunetto M., Callegaro A. P., Cenderello G., Cento V., Ciaccio A., Ciancio A., Cuomo N., De Santis A., Di Biagio A., Di Marco V., Di Perri G., Di Stefano M. A., Gaeta G. B., Ghisetti V., Gulminetti R., Lampertico P., Landonio S., Lichtner M., Lleo A., Maida I., Marenco S., Masetti C., Mastroianni C., Minichini C., Milano E., Monno L., Novati S., Pace Palitti V., Paternoster C., Pellicelli A., Pieri A., Puoti M., Rizzardini G., Ruggiero T., Rossetti B., Sangiovanni V., Santantonio T., Taliani G., Toniutto P., Vullo V., Zazzi M., Di Maio, V, Barbaliscia, S, Teti, E, Fiorentino, G, Milana, M, Paolucci, S, Pollicino, T, Morsica, G, Starace, M, Bruzzone, B, Gennari, W, Micheli, V, Yu La Rosa, K, Foroghi, L, Calvaruso, V, Lenci, I, Polilli, E, Babudieri, S, Aghemo, A, Raimondo, G, Sarmati, L, Coppola, N, Pasquazzi, C, Baldanti, F, Parruti, G, Perno, C, Angelico, M, Craxi, A, Andreoni, M, Ceccherini-Silberstein, F, Andreone, P, Aragri, M, Bertoli, A, Boeri, E, Brancaccio, G, Brunetto, M, Callegaro, A, Cenderello, G, Cento, V, Ciaccio, A, Ciancio, A, Cuomo, N, De Santis, A, Di Biagio, A, Di Marco, V, Di Perri, G, Di Stefano, M, Gaeta, G, Ghisetti, V, Gulminetti, R, Lampertico, P, Landonio, S, Lichtner, M, Lleo, A, Maida, I, Marenco, S, Masetti, C, Mastroianni, C, Minichini, C, Milano, E, Monno, L, Novati, S, Pace Palitti, V, Paternoster, C, Pellicelli, A, Pieri, A, Puoti, M, Rizzardini, G, Ruggiero, T, Rossetti, B, Sangiovanni, V, Santantonio, T, Taliani, G, Toniutto, P, Vullo, V, Zazzi, M, Di Maio V. C., Barbaliscia S., Teti E., Fiorentino G., Milana M., Paolucci S., Pollicino T., Morsica G., Starace M., Bruzzone B., Gennari W., Micheli V., Yu La Rosa K., Foroghi L., Calvaruso V., Lenci I., Polilli E., Babudieri S., Aghemo A., Raimondo G., Sarmati L., Coppola N., Pasquazzi C., Baldanti F., Parruti G., Perno C. F., Angelico M., Craxi A., Andreoni M., Ceccherini-Silberstein F., Andreone P., Aragri M., Bertoli A., Boeri E., Brancaccio G., Brunetto M., Callegaro A. P., Cenderello G., Cento V., Ciaccio A., Ciancio A., Cuomo N., De Santis A., Di Biagio A., Di Marco V., Di Perri G., Di Stefano M. A., Gaeta G. B., Ghisetti V., Gulminetti R., Lampertico P., Landonio S., Lichtner M., Lleo A., Maida I., Marenco S., Masetti C., Mastroianni C., Minichini C., Milano E., Monno L., Novati S., Pace Palitti V., Paternoster C., Pellicelli A., Pieri A., Puoti M., Rizzardini G., Ruggiero T., Rossetti B., Sangiovanni V., Santantonio T., Taliani G., Toniutto P., Vullo V., and Zazzi M.

Abstract

Aim: This study aimed to investigate the role of resistance-associated substitutions (RASs) to direct-acting-antivirals (DAAs) in HCV genotype 3 (GT3). Methods: Within the Italian VIRONET-C network, a total of 539 GT3-infected patients (417 DAA-naïve and 135 DAA-failures, of them, 13 at both baseline and failure) were analysed. Sanger sequencing of NS3/NS5A/NS5B was performed following home-made protocols. Results: The majority of patients were male (79.4%), 91.4% were injection drug users, 49.3% were cirrhotic and 13.9% were HIV co-infected. Phylogenetic analysis classified sequences as GT3a-b-g-h (98%-0.4%-0.2%-1.2%) respectively. Overall, 135 patients failed a DAA regimen: sofosbuvir (SOF)/daclatasvir (DCV) or velpatasvir (VEL)±ribavirin (RBV) (N = 91/15) and glecaprevir (G)/pibrentasvir (P) (N = 9). Moreover, 14.8% of patients were treated with suboptimal regimens for GT3: 3D ± RBV (Paritaprevir/r + Ombitasvir+Dasabuvir, N = 15), SOF + Simeprevir (SIM) (N = 1) or SOF/Ledipasvir (LDV) ± RBV (N = 4). RAS prevalence was 15.8% in DAA-naïve patients. At failure, 81.5% patients showed at least one RAS: 11/25 (44.0%) in NS3, 109/135 (80.7%) in NS5A, 7/111 (6.3%) in NS5B SOF-failures. In NS5A-failures, Y93H RAS was the most prevalent (68.5% vs 5.1% DAA-naïve, P <.001) followed by A30K (12.7% vs 2.8% in DAA-naïve, P <.001). Analysing baseline samples, a higher prevalence of NS5A-RASs was observed before treatment in DAA-failures (5/13, 38.5%) vs DAA-naïves (61/393, 15.5%, P =.04). Regarding 228 DAA-naïve patients with an available outcome, 93.9% achieved a SVR. Interestingly, patients with baseline Y93H and/or A30K had SVR rate of 72.2% vs 95.7% for patients without NS5A-RASs (P =.002). Conclusions: In this real-life GT3 cohort, the majority of failures harboured resistant variants carrying NS5A-RASs, the most frequent being Y93H. The presence of natu

Published
2021

6. Co-circulation of SARS-CoV-2 Alpha and Gamma variants in Italy, February and March 2021

Author

Stefanelli, P., Trentini, F., Guzzetta, G., Marziano, V., Mammone, A., Schepisi, M. S., Poletti, P., Grane, C. M., Manica, M., del Manso, M., Andrianou, X., Ajelli, M., Rezza, G., Brusaferro, S., Merler, S., Di Martino, A., Ambrosio, L., Lo Presti, A., Fiore, S., Fabiani, C., Benedetti, E., Di Mario, G., Facchini, M., Puzelli, S., Calzoletti, L., Fontana, S., Venturi, G., Fortuna, C., Marsili, G., Amendola, A., Stuppia, L., Savini, G., Picerno, A., Lopizzo, T., Dell'Edera, D., Minchella, P., Greco, F., Viglietto, G., Atripaldi, L., Limone, A., D'Agaro, P., Licastro, D., Pongolini, S., Sambri, V., Dirani, G., Zannoli, S., Affanni, P., Colucci, M. E., Capobianchi, M. R., Icardi, G., Bruzzone, B., Lillo, F., Orsi, A., Pariani, E., Baldanti, F., Molecolare, U. V., Gismondo, M. R., Maggi, F., Caruso, A., Ceriotti, F., Boniotti, M. B., Barbieri, I., Bagnarelli, P., Menzo, S., Garofalo, S., Scutella, M., Pagani, E., Collini, L., Ghisetti, V., Brossa, S., Ru, G., Bozzetta, E., Chironna, M., Parisi, A., Rubino, S., Serra, C., Piras, G., Coghe, F., Vitale, F., Tramuto, F., Scalia, G., Palermo, C. I., Mancuso, G., Pollicino, T., Di Gaudio, F., Vullo, S., Reale, S., Cusi, M. G., Rossolini, G. M., Pistello, M., Mencacci, A., Camilloni, B., Severini, S., Di Benedetto, M., Terregino, C., Monne, I., Biscaro, V., Stefanelli P, Trentini F, Guzzetta G, Marziano V, Mammone A, Sane Schepisi M, Poletti P, Molina Grané C, Manica M, Del Manso M, Andrianou X, Ajelli M, Rezza G, Brusaferro S, Merler S, Vitale F, Tramuto F, Stefanelli P., Trentini F., Guzzetta G., Marziano V., Mammone A., Sane Schepisi M., Poletti P., Molina Grane C., Manica M., Del Manso M., Andrianou X., Ajelli M., Rezza G., Brusaferro S., Merler S., Sambri V, and (membro del COVID-19 National Microbiology Surveillance Study Group)

Subjects
Epidemiology, SARS-CoV-2, Public Health, Environmental and Occupational Health, COVID-19, co-circulation, lineage, SARS-CoV-2 variant of concern, transmissibility, Humans, Italy, Models, Theoretical, Settore MED/42 - Igiene Generale E Applicata, SARS-COV-2 VARIANT OF CONCERN, CO-CIRCULATION, LINEAGE, TRANSMISSIBILITY, HUMANS, ITALY, MODELS, THEORETICAL, COVID-19, SARS-COV-2, Theoretical, Models, Virology, Human
Abstract

Background Several SARS-CoV-2 variants of concern (VOC) have emerged through 2020 and 2021. There is need for tools to estimate the relative transmissibility of emerging variants of SARS-CoV-2 with respect to circulating strains. Aim We aimed to assess the prevalence of co-circulating VOC in Italy and estimate their relative transmissibility. Methods We conducted two genomic surveillance surveys on 18 February and 18 March 2021 across the whole Italian territory covering 3,243 clinical samples and developed a mathematical model that describes the dynamics of co-circulating strains. Results The Alpha variant was already dominant on 18 February in a majority of regions/autonomous provinces (national prevalence: 54%) and almost completely replaced historical lineages by 18 March (dominant across Italy, national prevalence: 86%). We found a substantial proportion of the Gamma variant on 18 February, almost exclusively in central Italy (prevalence: 19%), which remained similar on 18 March. Nationally, the mean relative transmissibility of Alpha ranged at 1.55–1.57 times the level of historical lineages (95% CrI: 1.45–1.66). The relative transmissibility of Gamma varied according to the assumed degree of cross-protection from infection with other lineages and ranged from 1.12 (95% CrI: 1.03–1.23) with complete immune evasion to 1.39 (95% CrI: 1.26–1.56) for complete cross-protection. Conclusion We assessed the relative advantage of competing viral strains, using a mathematical model assuming different degrees of cross-protection. We found substantial co-circulation of Alpha and Gamma in Italy. Gamma was not able to outcompete Alpha, probably because of its lower transmissibility.

Published
2022

7. Update of the statements on biology and clinical impact of occult hepatitis B virus infection

Author

Raimondo, G, Locarnini, S, Pollicino, T, Levrero, M, Zoulim, F, Lok, A, Allain, J, Berg, T, Bertoletti, A, Brunetto, M, Bruno, R, Chen, D, Coppola, N, Cornberg, M, Craxi, A, Dandri, M, Di Marco, V, Ferrari, C, Gaeta, G, Glebe, D, Guidotti, L, Kramvis, A, Lampertico, P, Li, C, Liang, J, Marzano, A, Michalak, T, Pawlotsky, J, Prati, D, Puoti, M, Samuel, D, Soriano, V, Squadrito, G, Sureau, C, Trepo, C, Yuen, M, Raimondo G., Locarnini S., Pollicino T., Levrero M., Zoulim F., Lok A. S., Allain J. -P., Berg T., Bertoletti A., Brunetto M. R., Bruno R., Chen D. -S., Coppola N., Cornberg M., Craxi A., Dandri M., Di Marco V., Ferrari C., Gaeta G. B., Glebe D., Guidotti L. G., Kramvis A., Lampertico P., Li C., Liang J., Marzano A., Michalak T. I., Pawlotsky J. -M., Prati D., Puoti M., Samuel D., Soriano V., Squadrito G., Sureau C., Trepo C., Yuen M. -F., Raimondo, G, Locarnini, S, Pollicino, T, Levrero, M, Zoulim, F, Lok, A, Allain, J, Berg, T, Bertoletti, A, Brunetto, M, Bruno, R, Chen, D, Coppola, N, Cornberg, M, Craxi, A, Dandri, M, Di Marco, V, Ferrari, C, Gaeta, G, Glebe, D, Guidotti, L, Kramvis, A, Lampertico, P, Li, C, Liang, J, Marzano, A, Michalak, T, Pawlotsky, J, Prati, D, Puoti, M, Samuel, D, Soriano, V, Squadrito, G, Sureau, C, Trepo, C, Yuen, M, Raimondo G., Locarnini S., Pollicino T., Levrero M., Zoulim F., Lok A. S., Allain J. -P., Berg T., Bertoletti A., Brunetto M. R., Bruno R., Chen D. -S., Coppola N., Cornberg M., Craxi A., Dandri M., Di Marco V., Ferrari C., Gaeta G. B., Glebe D., Guidotti L. G., Kramvis A., Lampertico P., Li C., Liang J., Marzano A., Michalak T. I., Pawlotsky J. -M., Prati D., Puoti M., Samuel D., Soriano V., Squadrito G., Sureau C., Trepo C., and Yuen M. -F.

Abstract

In October 2018 a large number of international experts with complementary expertise came together in Taormina to participate in a workshop on occult hepatitis B virus infection (OBI). The objectives of the workshop were to review the existing knowledge on OBI, to identify issues that require further investigation, to highlight both existing controversies and newly emerging perspectives, and ultimately to update the statements previously agreed in 2008. This paper represents the output from the workshop.

Published
2019

8. Frequent NS5A and multiclass resistance in almost all HCV genotypes at DAA failures: What are the chances for second-line regimens?

Author

Di Maio, V, Cento, V, Aragri, M, Paolucci, S, Pollicino, T, Coppola, N, Bruzzone, B, Ghisetti, V, Zazzi, M, Brunetto, M, Bertoli, A, Barbaliscia, S, Galli, S, Gennari, W, Baldanti, F, Raimondo, G, Perno, C, Ceccherini-Silberstein, F, Andreone, P, Andreoni, M, Angelico, M, Babudieri, S, Barbarini, G, Boccaccio, V, Boglione, L, Bolis, M, Bonora, S, Borghi, V, Brancaccio, G, Bruno, S, Cacciatore, P, Calvaruso, V, Caporaso, N, Ciaccio, A, Ciancio, A, Colombatto, P, Cozzolongo, R, Craxi, A, D'Ambrosio, C, D'Ettorre, G, De Luca, A, Di Biagio, A, Di Perri, G, Francioso, S, Gaeta, G, Giorgini, A, Grieco, A, Gubertini, G, Gulminetti, R, Lambiase, L, Lenci, I, Lichtner, M, Maida, I, Marenco, S, Marinaro, L, Maserati, R, Masetti, C, Melis, M, Meregalli, E, Micheli, V, Morisco, F, Niero, F, Nicolini, L, Palitti, V, Paoloni, M, Parruti, G, Pasquazzi, C, Pellicelli, A, Polilli, E, Ponti, M, Puoti, M, Rendina, M, Rizzardini, G, Rossetti, B, Ruggiero, T, Sangiovanni, V, Starace, M, Sticchi, L, Tarquini, P, Toniutto, P, Vullo, V, Di Maio V. C., Cento V., Aragri M., Paolucci S., Pollicino T., Coppola N., Bruzzone B., Ghisetti V., Zazzi M., Brunetto M., Bertoli A., Barbaliscia S., Galli S., Gennari W., Baldanti F., Raimondo G., Perno C. F., Ceccherini-Silberstein F., Andreone P., Andreoni M., Angelico M., Babudieri S., Barbarini G., Boccaccio V., Boglione L., Bolis M., Bonora S., Borghi V., Brancaccio G., Bruno S., Cacciatore P., Calvaruso V., Caporaso N., Ciaccio A., Ciancio A., Colombatto P., Cozzolongo R., Craxi A., D'Ambrosio C., D'Ettorre G., De Luca A., Di Biagio A., Di Perri G., Francioso S., Gaeta G. B., Giorgini A., Grieco A., Gubertini G., Gulminetti R., Lambiase L., Lenci I., Lichtner M., Maida I., Marenco S., Marinaro L., Maserati R., Masetti C., Melis M., Meregalli E., Micheli V., Morisco F., Niero F., Nicolini L. A., Palitti V. P., Paoloni M., Parruti G., Pasquazzi C., Pellicelli A., Polilli E., Ponti M. L., Puoti M., Rendina M., Rizzardini G., Rossetti B., Ruggiero T., Sangiovanni V., Starace M., Sticchi L., Tarquini P., Toniutto P., Vullo V., Di Maio, V, Cento, V, Aragri, M, Paolucci, S, Pollicino, T, Coppola, N, Bruzzone, B, Ghisetti, V, Zazzi, M, Brunetto, M, Bertoli, A, Barbaliscia, S, Galli, S, Gennari, W, Baldanti, F, Raimondo, G, Perno, C, Ceccherini-Silberstein, F, Andreone, P, Andreoni, M, Angelico, M, Babudieri, S, Barbarini, G, Boccaccio, V, Boglione, L, Bolis, M, Bonora, S, Borghi, V, Brancaccio, G, Bruno, S, Cacciatore, P, Calvaruso, V, Caporaso, N, Ciaccio, A, Ciancio, A, Colombatto, P, Cozzolongo, R, Craxi, A, D'Ambrosio, C, D'Ettorre, G, De Luca, A, Di Biagio, A, Di Perri, G, Francioso, S, Gaeta, G, Giorgini, A, Grieco, A, Gubertini, G, Gulminetti, R, Lambiase, L, Lenci, I, Lichtner, M, Maida, I, Marenco, S, Marinaro, L, Maserati, R, Masetti, C, Melis, M, Meregalli, E, Micheli, V, Morisco, F, Niero, F, Nicolini, L, Palitti, V, Paoloni, M, Parruti, G, Pasquazzi, C, Pellicelli, A, Polilli, E, Ponti, M, Puoti, M, Rendina, M, Rizzardini, G, Rossetti, B, Ruggiero, T, Sangiovanni, V, Starace, M, Sticchi, L, Tarquini, P, Toniutto, P, Vullo, V, Di Maio V. C., Cento V., Aragri M., Paolucci S., Pollicino T., Coppola N., Bruzzone B., Ghisetti V., Zazzi M., Brunetto M., Bertoli A., Barbaliscia S., Galli S., Gennari W., Baldanti F., Raimondo G., Perno C. F., Ceccherini-Silberstein F., Andreone P., Andreoni M., Angelico M., Babudieri S., Barbarini G., Boccaccio V., Boglione L., Bolis M., Bonora S., Borghi V., Brancaccio G., Bruno S., Cacciatore P., Calvaruso V., Caporaso N., Ciaccio A., Ciancio A., Colombatto P., Cozzolongo R., Craxi A., D'Ambrosio C., D'Ettorre G., De Luca A., Di Biagio A., Di Perri G., Francioso S., Gaeta G. B., Giorgini A., Grieco A., Gubertini G., Gulminetti R., Lambiase L., Lenci I., Lichtner M., Maida I., Marenco S., Marinaro L., Maserati R., Masetti C., Melis M., Meregalli E., Micheli V., Morisco F., Niero F., Nicolini L. A., Palitti V. P., Paoloni M., Parruti G., Pasquazzi C., Pellicelli A., Polilli E., Ponti M. L., Puoti M., Rendina M., Rizzardini G., Rossetti B., Ruggiero T., Sangiovanni V., Starace M., Sticchi L., Tarquini P., Toniutto P., and Vullo V.

Published
2018

9. Frequency of somatic mutations in TERT promoter, TP53 and CTNNB1 genes in patients with hepatocellular carcinoma from Southern Italy

Author

Lombardo, D., Saitta, C., Giosa, D., Di Tocco, F. C., Musolino, C., Caminiti, G., Chines, V., Franze, M. S., Alibrandi, A., Navarra, G., Raimondo, G., and Pollicino, T.

Subjects
Somatic mutations, Hepatocellular carcinoma, CTNNB1 gene, TP53 gene, TERT promoter, Activating protein 2 transcription factor, Activating protein 2 transcription factor, CTNNB1 gene, Hepatocellular carcinoma, Somatic mutations,TERT promoter, TP53 gene
Published
2020

10. DECLINE OF PREVALENCE OF RESISTANCE ASSOCIATED SUBSTITUTIONS TO NS3 AND NS5A INHIBITORS AT DAA- FAILURE IN HEPATITIS C VIRUS IN ITALY OVER THE YEARS 2015 TO 2018

Author

Redi, D., Rossetti, B., Di Maio, V. C., Aragri, M., Paolucci, S., Masetti, C., Paglicci, L., Bruzzone, B., Minichini, C., FRANCESCA MONTAGNANI, Micheli, V., Landonio, S., Degasperi, E., Giacomo Zanelli, Maserati, R., Maida, I., Callegaro, A. P., Barbaliscia, S., Bertoli, A., Paternoster, C., Marenco, S., Morisco, F., Calvaruso, V., Taliani, G., Puoti, M., Cenderello, G., Santis, A., Lichtner, M., Coppola, N., Gulminetti, R., Cento, V., Rendina, M., Teti, E., Parruti, G., Ruggiero, T., Ghisetti, V., Pasquazzi, C., Nicolini, L. A., Vullo, V., Pellicelli, A., Prestileo, T., Cozzolongo, R., Sangiovanni, V., Biolato, M., Lenci, I., Licata, A., Ciaccio, A., Pace Palitti, V., Giorgini, A., Cariti, G., Ciancio, A., Aghemo, A., Borghi, V., Andreone, P., Brunetto, M., Pollicino, T., Santantonio, T., Cuomo, N., Caudai, C., Babudieri, S., Lampertico, P., Gaeta, G. B., Raimondo, G., Andreoni, M., Rizzardini, G., Angelico, M., Perno, C. F., Craxì, A., Maurizio Zazzi, Ceccherini- Silberstein, F., and on behalf of HCV Virology Italian Resistance Network (Vironet C)

Published
2019

12. Free episomal and integrated HBV DNA in HBsAg-negative patients with intrahepatic cholangiocarcinoma

Author

Pollicino, T, Musolino, C, Saitta, C, Tripodi, G, Lanza, M, Raffa, G, Tocco, F, Raggi, C, Bragazzi, M, Barbera, A, Navarra, G, Invernizzi, P, Alvaro, D, Raimondo, G, Pollicino, Teresa, Musolino, Cristina, Saitta, Carlo, Tripodi, Gianluca, Lanza, Marika, Raffa, Giuseppina, Tocco, Francesca Casuscelli di, Raggi, Chiara, Bragazzi, Maria Consiglia, Barbera, Adalberto, Navarra, Giuseppe, Invernizzi, Pietro, Alvaro, Domenico, Raimondo, Giovanni, Pollicino, T, Musolino, C, Saitta, C, Tripodi, G, Lanza, M, Raffa, G, Tocco, F, Raggi, C, Bragazzi, M, Barbera, A, Navarra, G, Invernizzi, P, Alvaro, D, Raimondo, G, Pollicino, Teresa, Musolino, Cristina, Saitta, Carlo, Tripodi, Gianluca, Lanza, Marika, Raffa, Giuseppina, Tocco, Francesca Casuscelli di, Raggi, Chiara, Bragazzi, Maria Consiglia, Barbera, Adalberto, Navarra, Giuseppe, Invernizzi, Pietro, Alvaro, Domenico, and Raimondo, Giovanni

Abstract

There is evidence that chronic hepatitis B virus (HBV) infection is associated with an increased risk of intrahepatic cholangiocarcinoma (ICC) development, and it has been hypothesized an etiological role of HBV in the development of this tumor. Very little is known about occult HBV infection (OBI) in ICC. Aims of the study were to investigate the OBI prevalence and to characterize the HBV molecular status at intrahepatic level in OBI-positive cases with ICC. Frozen liver tumor specimens from 47 HBV surface-antigen-negative patients with ICC and 41 paired non-tumor liver tissues were tested for OBI by 4 different HBV-specific nested PCR. Covalently closed circular HBV DNA (HBV cccDNA) and viral integrations were investigated in OBI-positive cases. HBV DNA was detected in tumor and/or non-tumor specimens from 29/47 (61.7%) ICC patients. HBV cccDNA was found in tissues from 5/17 (34.5%) cases examined. HBV integration was detected in 4/10 (40%) tumor tissues tested and involved HBx and HBV-core gene sequences in 3 and 1 cases, respectively. Viral integration occurred: (a) 9,367 nucleotides upstream of the cat-eye-syndrome critical region protein-5-isoform coding sequence; (b) within the cystinosin isoform-1-precursor gene; (c) within the thromboxane-A-synthase-1 gene; (d) within the ATPase phospholipid transporting 9B gene. Occult HBV infection is highly prevalent in patients with ICC. Both free viral genomes and integrated HBV DNA can be present in these cases. These results suggest an involvement of HBV in the carcinogenic process leading to ICC development even in cases with occult infection.

Published
2019

13. AISF position paper on liver transplantation and pregnancy: Women in Hepatology Group, Italian Association for the Study of the Liver (AISF)

Author

Burra, P, Rodríguez-Castro, K, Guarino, M, Morisco, F, Villa, E, Mazzella, G, Women in Hepatology Group, Italian Association for the Study of the Liver (AISF) (Alisi, A, Balsano, C, Bernabucci, V, Berzigotti, A, Brunetto, M, Bugianesi, E, Calvaruso, V, Cariani, E, Coco, B, Colle, I, Critelli, R, De Martin, E, Del Buono, M, Fabregat, I, Faillaci, F, Fattovich, G, Floreani, A, Garcia-Tsao, G, Housset, C, Karampatou, A, Lei, B, Mangia, A, Martinez-Chantar, Ml, Milosa, F, Nasta, P, Ozben, T, Pollicino, T, Ponti, Ml, Pontisso, P, Reeves, H, Rendina, M, Rodríguez-Castro, Ki, Sagnelli, C, Sebastiani, Giulia, Smedile, A, Taliani, G, Vandelli, C, Vanni, E, Vukotic, R, Zignego, Al), Alisi A, Balsano C, Bernabucci V, Berzigotti A, Brunetto M, Bugianesi E, Burra P, Calvaruso V, Cariani E, Coco B, Colle I, Critelli R, De Martin E, Del Buono M, Fabregat I, Faillaci F, Fattovich G, Floreani A, Garcia-Tsao G, Housset C, Karampatou A, Lei B, Mangia A, Martinez-Chantar ML, Milosa F, Morisco F, Nasta P, Ozben T, Pollicino T, Ponti ML, Pontisso P, Reeves H, Rendina M, Rodríguez-Castro KI, Sagnelli C, Sebastiani G, Smedile A, Taliani G, Vandelli C, Vanni E, Villa E, Vukotic R, Zignego AL, Burra P, Rodríguez-Castro K, Guarino M, Morisco F, Villa E, Mazzella G., Alisi, A, Balsano, C, Bernabucci, V, Berzigotti, A, Brunetto, M, Bugianesi, E, Burra, P, Calvaruso, V, Cariani, E, Coco, B, Colle, I, Critelli, R, De Martin, E, Del Buono, M, Fabregat, I, Faillaci, F, Fattovich, G, Floreani, A, Garcia-Tsao, G, Housset, C, Karampatou, A, Lei, B, Mangia, A, Martinez-Chantar, Ml, Milosa, F, Morisco, F, Nasta, P, Ozben, T, Pollicino, T, Ponti, Ml, Pontisso, P, Reeves, H, Rendina, M, Rodríguez-Castro, Ki, Sagnelli, C, Sebastiani, G, Smedile, A, Taliani, G, Vandelli, C, Vanni, E, Vukotic, R, Zignego, Al, Rodríguez-Castro, K, Guarino, M, Villa, E, Mazzella, G., Garcia Tsao, G, Martinez Chantar, Ml, Morisco, Filomena, Rodríguez Castro, Ki, Rodríguez Castro, K, Guarino, Maria, Alisi, Anna, Balsano, Clara, Bernabucci, Veronica, Berzigotti, Annalisa, Brunetto, Maurizia, Bugianesi, Elisabetta, Burra, Patrizia, Calvaruso, Vincenza, Cariani, Elisabetta, Coco, Barbara, Colle, Isabelle, Critelli, Rosina, De Martin, Eleonora, Del Buono, Mariagrazia, Fabregat, Isabel, Faillaci, Francesca, Fattovich, Giovanna, Floreani, Annarosa, Garcia-tsao, Guadalupe, Housset, Chantal, Karampatou, Aimilia, Lei, Barbara, Mangia, Alessandra, Martinez-chantar, Maria Luz, Milosa, Fabiola, Nasta, Paola, Ozben, Tomri, Pollicino, Teresa, Ponti, Maria Laura, Pontisso, Patrizia, Reeves, Helen, Rendina, Maria, Rodrã­guez-castro, Kryssia Isabel, Sagnelli, Caterina, Sebastiani, Giada, Smedile, Antonella, Taliani, Gloria, Vandelli, Carmen, Vanni, Ester, Villa, Erica, Vukotic, Ranka, Zignego, Anna Linda, Rodrã­guez-castro, Kryssia, and Mazzella, Giuseppe

Subjects
Risk Assessment, Fertility, Immunosuppression, Liver transplantation, Pregnancy, Immunosuppressive Agent, Medical, Hepatology, Gastroenterology, Humans, Obstetric Labor Complication, Societies, Medical, Postpartum Period, Pregnancy Outcome, Contraception, Female, Italy, Obstetric Labor Complications, Practice Guidelines as Topic, Pregnancy Complications, Immunosuppressive Agents, Liver Transplantation, Pregnancy Complication, surgical procedures, operative, Societies, Human
Abstract

After the first successful pregnancy in a liver transplant recipient in 1978, much evidence has accumulated on the course, outcomes and management strategies of pregnancy following liver transplantation. Generally, liver transplantation restores sexual function and fertility as early as a few months after transplant. Considering that one third of all liver transplant recipients are women, that approximately one-third of them are of reproductive age (18-49 years), and that 15% of female liver transplant recipients are paediatric patients who have a >70% probability of reaching reproductive age, the issue of pregnancy after liver transplantation is rather relevant, and obstetricians, paediatricians, and transplant hepatologists ever more frequently encounter such patients. Pregnancy outcomes for both the mother and infant in liver transplant recipients are generally good, but there is an increased incidence of preterm delivery, hypertension/preeclampsia, foetal growth restriction, and gestational diabetes, which, by definition, render pregnancy in liver transplant recipients a high-risk one. In contrast, the risk of congenital anomalies and the live birth rate are comparable to those of the general population. Currently there are still no robust guidelines on the management of pregnancies after liver transplantation. The aim of this position paper is to review the available evidence on pregnancy in liver transplant recipients and to provide national Italian recommendations for clinicians caring for these patients. (C) 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Published
2016

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

Author

Prati, D, Gasbarrini, A, Mazzotta, F, Sagnelli, E, Carosi, G, Abrescia, N, Alberti, Alfredo, Ambu, S, Andreone, P, Andriulli, A, Angelico, M, Antonucci, G, Ascione, A, Belli, Ls, Bruno, R, Bruno, S, Burra, Patrizia, Camma, C, Caporaso, N, Cariti, G, Cillo, U, Coppola, N, Craxi, A, DE LUCA, A, DE MARTIN, E, DI MARCO, V, Fagiuoli, S, Ferrari, C, Gaeta, Gb, Galli, M, Grieco, A, Grossi, P, Licata, A, Maida, I, Mangia, A, Marino, N, Maserati, R, Missale, G, Mondelli, M, Nasta, P, Niro, G, Persico, M, Petrelli, E, Picciotto, A, Piscaglia, F, Pollicino, T, Puoti, C, Puoti, M, Raimondo, G, Rumi, Mg, Santantonio, T, Smedile, A, Squadrito, G, Baroni, Gs, Taliani, G, Tavio, M, Toti, M, Bonino, F, Brunetto, Mr, Cacopardo, B, Caremani, M, Cauda, R, Colombo, M, DI PERRI, G, Donato, F, Farci, P, Fattovich, G, Filice, G, Ghinelli, F, Guadagnino, V, Lazzarin, A, Levrero, M, Licata, G, Orani, A, Paffetti, A, Pastore, G, Piccinino, F, Pizzigallo, E, Pontisso, Patrizia, Portelli, V, Rizzetto, M, Rossi, A, Stroffolini, T, Ubaldi, E, Santantanio, T, Alberti, A., Antonucci, Gf, Craxi, A., Prati D, Gasbarrini A, Mazzotta F, Sagnelli E, Carosi G, Abrescia N, Alberti A, Ambu S, Andreone P, Andriulli A, Angelico M, Antonucci GF, Ascione A, Belli LS, Bruno R, Bruno S, Burra P, Cammà, C, Caporaso N, Cariti G, Cillo U, Coppola N, Craxì, A, De Luca A, De Martin E, Di Marco, V, Fagiuoli S, Ferrari C, Gaeta GB, Galli M, Grieco A, Grossi P, Licata, A, Maida I, Mangia A, Marino N, Maserati R, Missale G, Mondelli M, Nasta P, Niro G, Persico M, Petrelli E, Picciotto A, Piscaglia F, Pollicino T, Prati D, Puoti C, Puoti M, Raimondo G, Rumi MG, Sagnelli E, Santantonio T, Smedile A, Squadrito G, Baroni GS, Taliani G, Tavio M, Toti M, Bonino F, Brunetto MR, Cacopardo B, Caremani M, Cauda R, Colombo M, Di Perri G, Donato F, Farci P, Fattovich G, Filice G, Ghinelli F, Guadagnino V, Lazzarin A, Levrero M, Licata G, Orani A, Paffetti A, Pastore G, Piccinino F, Pizzigallo E, Pontisso P, Portelli V, Rizzetto M, Rossi A, Stroffolini T, Ubaldi E., Italian Association for the Study of the Liver, Italian Society of Infectious, Tropical Disease, Italian Society for the Study of Sexually Transmitted Diseases: Prati D., Gasbarrini A., Mazzotta F., Sagnelli E., Carosi G., Abrescia N., Alberti A., Ambu S., Andreone P., Andriulli A., Angelico M., Antonucci G.F., Ascione A., Belli L.S., Bruno R., Bruno S., Burra P., Cammà C., Caporaso N., Cariti G., Cillo U., Coppola N., Craxì A., De Luca A., De Martin E., Di Marco V., Fagiuoli S., Ferrari C., Gaeta G.B., Galli M., Grieco A., Grossi P., Licata A., Maida I., Mangia A., Marino N., Maserati R., Missale G., Mondelli M., Nasta P., Niro G., Persico M., Petrelli E., Picciotto A., Piscaglia F., Pollicino T., Puoti C., Puoti M., Raimondo G., Rumi M.G., Santantonio T., Smedile A., Squadrito G., Baroni G.S., Taliani G., Tavio M., Toti M., Bonino F., Brunetto M.R., Cacopardo B., Caremani M., Cauda R., Colombo M., Di Perri G., Donato F., Farci P., Fattovich G., Filice G., Ghinelli F., Guadagnino V., Lazzarin A., Levrero M., Licata G., Orani A., Paffetti A., Pastore G., Piccinino F., Pizzigallo E., Pontisso P., Portelli V., Rizzetto M., Rossi A., Stroffolini T., Ubaldi E., Prati, D, Gasbarrini, A, Mazzotta, F, Sagnelli, E, Carosi, G, Abrescia, N, Alberti, A, Ambu, S, Andreone, P, Andriulli, A, Angelico, M, Antonucci, G, Ascione, A, Belli, L, Bruno, R, Bruno, S, Burra, P, Caporaso, N, Cariti, G, Cillo, U, Coppola, N, De Luca, A, De Martin, E, Fagiuoli, S, Ferrari, C, Gaeta, G, Galli, M, Grieco, A, Grossi, P, Maida, I, Mangia, A, Marino, N, Maserati, R, Missale, G, Mondelli, M, Nasta, P, Niro, G, Persico, M, Petrelli, E, Picciotto, A, Piscaglia, F, Pollicino, T, Puoti, C, Puoti, M, Raimondo, G, Rumi, M, Santantonio, T, Smedile, A, Squadrito, G, Baroni, G, Taliani, G, Tavio, M, Toti, M, Bonino, F, Brunetto, M, Cacopardo, B, Caremani, M, Cauda, R, Colombo, M, Di Perri, G, Donato, F, Farci, P, Fattovich, G, Filice, G, Ghinelli, F, Guadagnino, V, Lazzarin, A, Levrero, M, Licata, G, Orani, A, Paffetti, A, Pastore, G, Piccinino, F, Pizzigallo, E, Pontisso, P, Portelli, V, Rizzetto, M, Rossi, A, Stroffolini, T, and Ubaldi, E

Subjects
Liver Cirrhosis, ANTIVIRAL TREATMENT, Human immunodeficiency virus (HIV), HIV Infections, Hepacivirus, ANTIVIRAL THERAPY, PEGYLATED INTERFERON-ALPHA-2B, LIVER-TRANSPLANTATION, PEGINTERFERON ALPHA-2A, HIV-INFECTED PATIENTS, VIRUS-COINFECTED PATIENTS, RAPID VIROLOGICAL RESPONSE, Antiviral therapy, medicine.disease_cause, Gastroenterology, Polyethylene Glycols, HBV, guidelines, Acute hepatitis, Chronic hepatitis, Settore MED/12 - Gastroenterologia, liver transplantation, Hepatitis C, Recombinant Proteins, acute hepatitis, antiviral therapy, chronic hepatitis, cirrhosis, elderly patients, hbv, hcv, hdv, hiv, CLINICAL PRACTICE GUIDELINES, Cirrhosis, HCV, Drug Therapy, Combination, Antiviral therapy Acute hepatitis Chronic hepatitis,Cirrhosis, Elderly patients, HBV, HCV, HDV, HIV Liver transplantation, Elderly patient, Acute hepatiti, medicine.medical_specialty, Genotype, Alpha interferon, Interferon alpha-2, CHRONIC HEPATITIS C, Antiviral Agents, Hepatitis B, Chronic, Internal medicine, HDV, Drug Resistance, Viral, Ribavirin, medicine, Humans, Cirrhosi, Hepatology, business.industry, Settore MED/09 - MEDICINA INTERNA, Interferon-alpha, HIV, Hepatitis C, Chronic, medicine.disease, Elderly patients, Family medicine, Expert opinion, Chronic hepatiti, business
Abstract

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

Published
2010

18. Hepatitis B Virus (HBV) maintains its pro-oncogenic properties in case of occult HBV infection

Author

Pollicino, T, Squadrito, G, Cerenzia, G, Cacciola, I, Raffa, G, Craxi, A, Farinati, F, Missale, G, Smedile, A, Tiribelli, Claudio, Villa, E, Raimondo, G., Pollicino, T, Squadrito, G, Cerenzia, G, Cacciola, I, Raffa, G, Craxi, A, Farinati, F, Missale, G, Smedile, A, Tiribelli, Claudio, Villa, E, and Raimondo, G.

Subjects
Hepatocellular/virology* DNA, Viral/analysis Female Genome, Chronic/complications* Humans Liver/virology Liver Neoplasms/virology* Male Middle Aged Transcription, Aged Carcinoma, Hepatocellular/virology* DNA, Viral/analysis Female Genome, Viral Hepatitis B virus/genetics Hepatitis B virus/physiology* Hepatitis B, Chronic/complications* Humans Liver/virology Liver Neoplasms/virology* Male Middle Aged Transcription, Genetic Virus Replication, Aged Carcinoma, Viral Hepatitis B virus/genetics Hepatitis B virus/physiology* Hepatitis B, Genetic Virus Replication
Abstract

BACKGROUND AND AIMS: Occult hepatitis B virus (HBV) infection is characterized by persistence of HBV DNA into the tissue of hepatitis B surface antigen-negative individuals. The clinical relevance of this peculiar infection is still under debate. In particular, the impact of occult HBV infection in cases of hepatocellular carcinoma (HCC) is uncertain. We investigated the prevalence and molecular status of occult HBV in patients with HCC. METHODS: We tested tumor tissues from 107 patients with HCC and the corresponding nontumor liver tissue from 72 of these patients for HBV DNA. We also examined liver specimens from 192 patients with chronic hepatitis. All cases were hepatitis B surface antigen negative. Covalently closed circular HBV genomes, HBV transcripts, and viral integrated forms were investigated in cases of HCC found positive for occult HBV. RESULTS: Viral DNA was detected in 68 of 107 cases of HCC (63.5%) and in 63 of 192 cases of chronic hepatitis (32.8%) (P < 0.0001; odds ratio, 3.6; 95% confidence interval, 2.2-5.9). The significant association of occult HBV with HCC was irrespective of age, sex, and contemporary hepatitis C virus infection. Both integrated viral DNA and covalently closed circular HBV genomes were detected in patients with occult HBV. Moreover, the presence of free HBV genomes was associated with persistence of viral transcription and replication. CONCLUSIONS: Our findings provide clear evidence that occult HBV is a risk factor for development of HCC and show that the potential mechanisms whereby overt HBV might induce tumor formation are mostly maintained in cases of occult infection.

Published
2004

19. IL28B genotype, differential expression of intrahepatis interferon-stimulated genes and response to PEG-IFN and ribavirin therapy in an Italian prospective cohort of genotype 1 hepatitis C patients in 'real life'

Author

Testoni, B, Scisciani, C, Grimaudo, S, Maimone, S, Pollicino, T, Di Marco, V, Gaeta, Gb, Fattovich, Giovanna, Santantonio, T, Raimondo, G, Craxì, A, and Levriero, M.

Subjects
chronic hepatitis C, HCV genotype 1, response to interferon therapy, IL-28B genotype, intrahepatic interferon stimulated genes
Published
2012

29. Longitudinal evaluation reveals a complex spectrum of virological profiles in hepatitis B virus/Hepatitis C virus coinfected patients

Author

Raimondo, G, Brunetto, Mr, Pontisso, P, Smedile, A, Maina, Am, Saitta, C, Squadrito, G, AND ASSOCIAZIONE ITALIANA STUDIO FEGATO AISF COOPERATIVE GROUP OLIVERO A, TONO N., Rosina, F, Sartori, M, Colombo, M, Lampertico, P, Fargion, S, Rossini, A, Fattovich, Giovanna, Ruvoletto, Mg, Villano, M, Croc, L, Picciotto, A, Ferrari, C, Missale, G, Zignego, Al, Moscato, G, Toti, M, Levriero, M, Puoti, C, Caporaso, N, Morisco, F, Gaeta, Gb, Piccinino, F, Sagnelli, E, Persico, M, Andriulli, A, Niro, Ga, Dentico, P, Pastore, G, Santantonio, T, Crax, A, DI MARCO, V, Cacopardo, B, Bruno, S, Smedile, V, Aiello, A, Brancatelli, S, Costantino, L, Pollicino, T, and Raffa, G.

Subjects
hepatitis B, hepatitis c, coinfection, virological profile
Published
2006

32. Regulated expression of vascular cell adhesion molecule-1 in human malignant melanoma

Author

Jonjic N, Martìn-Padura I, Pollicino T, Bernasconi S, Jílek P, Bigotti A, Mortarini R, Anichini A, Parmiani G, and Colotta F

Subjects
Transcription, Genetic, Cells, Molecular Sequence Data, Vascular Cell Adhesion Molecule-1, Polymerase Chain Reaction, Monocytes, Genetic, Vascular, Tumor Cells, Cultured, Humans, Northern, Endothelium, Melanoma, Cells, Cultured, Neoplastic, Phagocytes, Cultured, Base Sequence, Blotting, Tumor Necrosis Factor-alpha, DNA, DNA, Neoplasm, Base Sequence, Blotting, Northern, Cell Adhesion Molecules, Cells, Cultured, DNA, Neoplasm, Endothelium, Vascular, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, Melanoma, Molecular Sequence Data, Monocytes, Phagocytes, Polymerase Chain Reaction, Transcription, Genetic, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha, Vascular Cell Adhesion Molecule-1, Blotting, Northern, Immunohistochemistry, Tumor Cells, Gene Expression Regulation, Neoplastic, Gene Expression Regulation, Neoplasm, Endothelium, Vascular, Transcription, Cell Adhesion Molecules, Regular Articles
Abstract

Expression of the endothelial adhesion molecule VCAM-1 was studied in human malignant melanoma lines by flow cytometry. Clones 2/4 and 2/14 (derived from the same lesion) had appreciable levels of VCAM-1 expression, whereas clone 2/21 and the lines A2058, Mel24, and A375 were negative. Clone 2/14 was selected for further analysis. Exposure to tumor necrosis factor (TNF) markedly augmented VCAM-1 on melanoma cells. Surface VCAM-1 was associated with expression of specific transcripts that were augmented by TNF. Analysis by reverse transcriptase and polymerase chain reaction using appropriate primers revealed that TNF-stimulated melanoma cells expressed both 7 and 6 immunoglobulin domain transcripts with predominance of the longer species. Tumor necrosis factor--stimulated melanoma cells bound more VLA-4-expressing cells (melanoma and monocytes) than resting tumor cells and anti-VCAM-1 monoclonal antibodies significantly inhibited binding, thus suggesting that surface VCAM-1 on melanoma is functional. Analysis of melanoma tissue sections demonstrated that VCAM-1 is not a marker of transformation of melanocytes because it can be detected in benign nevi. Although, unlike ICAM-1, VCAM-1 is not correlated with tumor progression, its expression in a fraction of primary melanomas indicates that it may play a role in regulating host immune response and homotypic interactions in some malignant melanomas.

Published
1992

36. Declino delle Sostituzioni associate a resistenza (RAS) ad inibitori di NS3 ed NS5A al fallimento con DAA nel virus dell’epatite C in Italia negli anni 2015-2018

Author

Paglicci, L., Redi, D., Rossetti, B., Di Maio, V. C., Aragri, M., Paolucci, S., Masetti, C., Bruzzone, B., Minichini, C., FRANCESCA MONTAGNANI, Micheli, V., Landonio, S., Degasperi, E., Giacomo Zanelli, Maserati, R., Maida, I., Callegaro, A. P., Barbaliscia, S., Bertoli, A., Paternoster, C., Marenco, S., Morisco, F., Calvaruso, V., Taliani, G., Puoti, M., Cenderello, G., Santis, A., Lichtner, M., Coppola, N., Gulminetti, R., Cento, V., Rendina, M., Teti, E., Parruti, G., Ruggiero, T., Ghisetti, V., Pasquazzi, C., Nicolini, L. A., Vullo, V., Pellicelli, A., Prestileo, T., Cozzolongo, R., Sangiovanni, V., Biolato, M., Lenci, I., Licata, A., Ciaccio, A., Pace Palitti, V., Giorgini, A., Cariti, G., Ciancio, A., Aghemo, A., Borghi, V., Andreone, P., Brunetto, M., Pollicino, T., Santantonio, T., Cuomo, N., Caudai, C., Babudieri, S., Lampertico, P., Gaeta, G. B., Raimondo, G., Andreoni, M., Rizzardini, G., Angelico, M., Perno, C. F., Craxì, A., Maurizio Zazzi, and Ceccherini-Silberstein, F.

37. Trends in chronic hepatitis B virus infection in Italy over a 10-year period: Clues from the nationwide PITER and MASTER cohorts toward elimination

Author

Giuseppina Brancaccio, Barbara Coco, Alessandra Nardi, Maria Giovanna Quaranta, Maria Elena Tosti, Luigina Ferrigno, Irene Cacciola, Vincenzo Messina, Luchino Chessa, Filomena Morisco, Michele Milella, Francesco Barbaro, Alessia Ciancio, Francesco Paolo Russo, Nicola Coppola, Pierluigi Blanc, Ernesto Claar, Gabriella Verucchi, Massimo Puoti, Anna Linda Zignego, Liliana Chemello, Salvatore Madonia, Stefano Fagiuoli, Alfredo Marzano, Carlo Ferrari, Pietro Lampertico, Vito Di Marco, Antonio Craxì, Teresa Antonia Santantonio, Giovanni Raimondo, Maurizia R. Brunetto, Giovanni Battista Gaeta, Loreta A. Kondili, Luisa Pasulo, Carmine Coppola, Federica Pisano, Mariarosaria Romano, Carmen Porcu, Irene Francesca Bottalico, Valentina Cossiga, Xhimi Tata, Caterina Sagnelli, Piera Pierotti, Elisabetta Degasperi, Valerio Rosato, Lorenzo Badia, Dontella Ieluzzi, Monica Monti, Maria Grazia Bavetta, Luisa Cavalletto, Pierluigi Toniutto, Ezio Fornasiere, Antonio Colecchia, Alberto Ferrarese, Gerardo Nardone, Alba Rocco, Mauro Viganò, Francesco Giuseppe Foschi, Fabio Conti, Giulia Morsica, Stefania Salpietro, Carlo Torti, Chiara Costa, Alessandro Federico, Marcello Dallio, Alessia Giorgini, Marco Anselmo, Pasqualina De Leo, Serena Zaltron, Anna Cambianica, Fabio Piscaglia, Ilaria Serio, Simona Schivazappa, Antonio Mastroianni, Luciana Chidichimo, Marco Massari, Cesare Mazzaro, Aldo Marrone, Francesca Maria D'Amore, Gianpiero D'Offizi, Anna Licata, Grazia Anna Niro, Teresa Pollicino, Alessio Aghemo, Brancaccio, G., Coco, B., Nardi, A., Quaranta, M. G., Tosti, M. E., Ferrigno, L., Cacciola, I., Messina, V., Chessa, L., Morisco, F., Milella, M., Barbaro, F., Ciancio, A., Russo, F. P., Coppola, N., Blanc, P., Claar, E., Verucchi, G., Puoti, M., Zignego, A. L., Chemello, L., Madonia, S., Fagiuoli, S., Marzano, A., Ferrari, C., Lampertico, P., Di Marco, V., Craxi, A., Santantonio, T. A., Raimondo, G., Brunetto, M. R., Gaeta, G. B., Kondili, L. A., Pasulo, L., Coppola, C., Pisano, F., Romano, M., Porcu, C., Bottalico, I. F., Cossiga, V., Tata, X., Sagnelli, C., Pierotti, P., Degasperi, E., Rosato, V., Badia, L., Ieluzzi, D., Monti, M., Bavetta, M. G., Cavalletto, L., Toniutto, P., Fornasiere, E., Colecchia, A., Ferrarese, A., Nardone, G., Rocco, A., Vigano, M., Foschi, F. G., Conti, F., Morsica, G., Salpietro, S., Torti, C., Costa, C., Federico, A., Dallio, M., Giorgini, A., Anselmo, M., De Leo, P., Zaltron, S., Cambianica, A., Piscaglia, F., Serio, I., Schivazappa, S., Mastroianni, A., Chidichimo, L., Massari, M., Mazzaro, C., Marrone, A., D'Amore, F. M., D'Offizi, G., Licata, A., Niro, G. A., Pollicino, T., Aghemo, A., Brancaccio, G, Coco, B, Nardi, A, Quaranta, M, Tosti, M, Ferrigno, L, Cacciola, I, Messina, V, Chessa, L, Morisco, F, Milella, M, Barbaro, F, Ciancio, A, Russo, F, Coppola, N, Blanc, P, Claar, E, Verucchi, G, Puoti, M, Zignego, A, Chemello, L, Madonia, S, Fagiuoli, S, Marzano, A, Ferrari, C, Lampertico, P, Di Marco, V, Craxì, A, Santantonio, T, Raimondo, G, Brunetto, M, Gaeta, G, Kondili, L, Pasulo, L, Coppola, C, Pisano, F, Romano, M, Porcu, C, Bottalico, I, Cossiga, V, Tata, X, Sagnelli, C, Pierotti, P, Degasperi, E, Rosato, V, Badia, L, Ieluzzi, D, Monti, M, Bavetta, M, Cavalletto, L, Toniutto, P, Fornasiere, E, Colecchia, A, Ferrarese, A, Nardone, G, Rocco, A, Viganò, M, Foschi, F, Conti, F, Morsica, G, Salpietro, S, Torti, C, Costa, C, Federico, A, Dallio, M, Giorgini, A, Anselmo, M, De Leo, P, Zaltron, S, Cambianica, A, Piscaglia, F, Serio, I, Schivazappa, S, Mastroianni, A, Chidichimo, L, Massari, M, Mazzaro, C, Marrone, A, D'Amore, F, D'Offizi, G, Licata, A, Niro, G, Pollicino, T, and Aghemo, A

Subjects
Microbiology (medical), Infectious Diseases, Epidemiology, Hepatitis Delta, Migrant, General Medicine, Chronic, Hepatitis B, Migrants, Hepatitis control
Abstract

Objectives: The study measures trends in the profile of patients with chronic hepatitis B virus linked to care in Italy. Methods: A cross-sectional, multicenter, observational cohort (PITER cohort) of consecutive patients with hepatitis B surface antigen (HBsAg) over the period 2019-2021 from 46 centers was evaluated. The reference was the MASTER cohort collected over the years 2012-2015. Standard statistical methods were used. Results: The PITER cohort enrolled 4583 patients, of whom 21.8% were non-Italian natives. Compared with those in MASTER, the patients were older and more often female. The prevalence of hepatitis B e antigen (HBeAg) declined (7.2% vs 12.3; P

Published
2023

38. Update of the statements on biology and clinical impact of occult hepatitis B virus infection

Author

Ding-Shinn Chen, Thomas Berg, Giovanni Battista Gaeta, Alfredo Marzano, Luca G. Guidotti, Vito Di Marco, Massimo Levrero, Antonio Craxì, Anna Kramvis, Anna S. Lok, Nicola Coppola, Giovanni Raimondo, Jean-Michel Pawlotsky, Teresa Pollicino, Dieter Glebe, Man-Fung Yuen, Didier Samuel, Maurizia Rossana Brunetto, Antonio Bertoletti, Daniele Prati, Massimo Puoti, Thomas I. Michalak, Jake Liang, Vincent Soriano, Pietro Lampertico, Raffaele Bruno, Fabien Zoulim, Christian Trepo, Chengyao Li, Camille Sureau, Stephen Locarnini, Giovanni Squadrito, C. Ferrari, Markus Cornberg, Jean-Pierre Allain, Maura Dandri, Department of Internal Medicine, University of Messina, Victorian Infectious Diseases Reference Laboratory, Center for Life Nanoscience/IIT@Sapienza [Rome, Italy] (CLNS@SAPIENZA Roma), Instituto Italiano di Tecnologia [Rome, Italy], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Division of Gastroenterology, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Division of Transfusion Medicine, University of Cambridge [UK] (CAM), Department of Medical Biochemistry, Uni, Institute of Infectious and Tropical Diseases, Università degli Studi di Pavia, European XFEL GmbH (XFEL), European XFEL GmbH, Department of Gastroenterology, Hepatology and Endocrinology (MHH), Hannover Medical School [Hannover] (MHH), Università degli studi di Palermo - University of Palermo, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Infectious Diseases Dept, University of Naples Federico II, I Gastroenterology Unit, Department of Medicine, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Case Western Reserve University [Cleveland], Centre National de Référence Virus des hépatites B, C et Delta, Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Transfusion Medicine and Hematology, Alessandro Manzoni Hospital, Department of infectious Diseases, Hôpital Paul Brousse, Institut National de la Transfusion Sanguine [Paris] (INTS), Immunité muqueuse et vaccination, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Raimondo, G, Locarnini, S, Pollicino, T, Levrero, M, Zoulim, F, Lok, A, Allain, J, Berg, T, Bertoletti, A, Brunetto, M, Bruno, R, Chen, D, Coppola, N, Cornberg, M, Craxi, A, Dandri, M, Di Marco, V, Ferrari, C, Gaeta, G, Glebe, D, Guidotti, L, Kramvis, A, Lampertico, P, Li, C, Liang, J, Marzano, A, Michalak, T, Pawlotsky, J, Prati, D, Puoti, M, Samuel, D, Soriano, V, Squadrito, G, Sureau, C, Trepo, C, Yuen, M, Raimondo G., Locarnini S., Pollicino T., Levrero M., Zoulim F., Lok A.S., Allain J.-P., Berg T., Bertoletti A., Brunetto M.R., Bruno R., Chen D.-S., Coppola N., Cornberg M., Craxi A., Dandri M., Di Marco V., Ferrari C., Gaeta G.B., Glebe D., Guidotti L.G., Kramvis A., Lampertico P., Li C., Liang J., Marzano A., Michalak T.I., Pawlotsky J.-M., Prati D., Puoti M., Samuel D., Soriano V., Squadrito G., Sureau C., Trepo C., Yuen M.-F., Raimondo, G., Locarnini, S., Pollicino, T., Levrero, M., Zoulim, F., Lok, A. S., Allain, J. -P., Berg, T., Bertoletti, A., Brunetto, M. R., Bruno, R., Chen, D. -S., Coppola, N., Cornberg, M., Craxi, A., Dandri, M., Di Marco, V., Ferrari, C., Gaeta, G. B., Glebe, D., Guidotti, L. G., Kramvis, A., Lampertico, P., Li, C., Liang, J., Marzano, A., Michalak, T. I., Pawlotsky, J. -M., Prati, D., Puoti, M., Samuel, D., Soriano, V., Squadrito, G., Sureau, C., Trepo, C., and Yuen, M. -F.

Subjects
0301 basic medicine, Occult HBV infection, Hepatitis B virus, medicine.medical_specialty, Carcinoma, Hepatocellular, Hepatocellular carcinoma, Hbv reactivation, MEDLINE, HBV reactivation, OBI, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, HBV S variant, Risk Factors, medicine, Humans, Hepatitis B Antibodies, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, Hepatitis B Surface Antigens, Hepatology, HBV cccDNA, Liver Neoplasms, virus diseases, HBV S variants, HBV transmission, Hepatitis B, medicine.disease, Occult, digestive system diseases, 3. Good health, 030104 developmental biology, Liver, DNA, Viral, 030211 gastroenterology & hepatology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

In October 2018 a large number of international experts with complementary expertise came together in Taormina to participate in a workshop on occult hepatitis B virus infection (OBI). The objectives of the workshop were to review the existing knowledge on OBI, to identify issues that require further investigation, to highlight both existing controversies and newly emerging perspectives, and ultimately to update the statements previously agreed in 2008. This paper represents the output from the workshop.

Published
2019

39. Ficolin-2 Plasma Level Assesses Liver Fibrosis in Non-Alcoholic Fatty Liver Disease

Author

Pablo J. Giraudi, Noel Salvoza, Deborah Bonazza, Carlo Saitta, Daniele Lombardo, Biagio Casagranda, Nicolò de Manzini, Teresa Pollicino, Giovanni Raimondo, Claudio Tiribelli, Silvia Palmisano, Natalia Rosso, Giraudi, P. J., Salvoza, N., Bonazza, D., Saitta, C., Lombardo, D., Casagranda, B., de Manzini, N., Pollicino, T., Raimondo, G., Tiribelli, C., Palmisano, S., and Rosso, N.

Subjects
Liver Cirrhosis, Blood-based test, Fibrosi, Biopsy, Liver Cirrhosi, Liver fibrosis, Omics, Catalysis, Inorganic Chemistry, Blood-based tests, Discovery strategy, Non-alcoholic Fatty Liver Disease, Lectins, Omic, Humans, Obesity, Morbid, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, In silico, Organic Chemistry, Liver fibrosi, Biomarker, General Medicine, Biomarkers, Non-alcoholic fatty liver disease, Fibrosis, Liver, Obesity, Morbid, Computer Science Applications, biomarkers, in silico, non-alcoholic fatty liver disease, discovery strategy, omics, blood-based tests, obesity, liver fibrosis, Lectin, Human
Abstract

Fibrosis is the strongest predictor for disease-specific mortality in non-alcoholic fatty liver diseases (NAFLD), but the need for liver biopsy limits its diagnosis. We assessed the performance of plasma ficolin-2 (FCN-2) as a biomarker of fibrosis identified by an in silico discovery strategy. Two hundred and thirty-five morbidly obese (MO) subjects with biopsy-proven NAFLD stratified by fibrosis stage (F0, n = 44; F1, n = 134; F2, n = 46; F3/F4, n = 11) and 40 cirrhotic patients were enrolled. The cohort was subdivided into discovery (n = 76) and validation groups (n = 159). The plasma level of FCN-2 and other candidate markers was determined. FCN-2 was inversely correlated with the stage of liver fibrosis (ρ = −0.49, p < 0.001) independently of steatosis (p = 0.90), inflammation (p = 0.57), and ballooning (p = 0.59). In the global cohort, FCN-2 level decreased significantly in a stepwise fashion from F0/F1 (median 4753 ng/mL) to F2–F3–F4 (2760 ng/mL) and in cirrhotic subjects (1418 ng/mL). The diagnostic performance of FCN-2 in detecting F ≥ 2 was higher than other indexes (APRI, FIB-4) (AUROC 0.82, 0.68, and 0.6, respectively). The accuracy improved when combined with APRI score and HDL values (FCNscore, AUROC 0.85). Overall, the FCN-2 plasma level can accurately discriminate liver fibrosis status (minimal vs. moderate/advanced) significantly improving the fibrosis diagnostic algorithms.

Published
2022

40. IFN-α inhibits HBV transcription and replication in cell culture and in humanized mice by targeting the epigenetic regulation of the nuclear cccDNA minichromosome.

Author

Belloni L, Allweiss L, Guerrieri F, Pediconi N, Volz T, Pollicino T, Petersen J, Raimondo G, Dandri M, Levrero M, Belloni, Laura, Allweiss, Lena, Guerrieri, Francesca, Pediconi, Natalia, Volz, Tassilo, Pollicino, Teresa, Petersen, Joerg, Raimondo, Giovanni, Dandri, Maura, and Levrero, Massimo

Abstract

HBV infection remains a leading cause of death worldwide. IFN-α inhibits viral replication in vitro and in vivo, and pegylated IFN-α is a commonly administered treatment for individuals infected with HBV. The HBV genome contains a typical IFN-stimulated response element (ISRE), but the molecular mechanisms by which IFN-α suppresses HBV replication have not been established in relevant experimental systems. Here, we show that IFN-α inhibits HBV replication by decreasing the transcription of pregenomic RNA (pgRNA) and subgenomic RNA from the HBV covalently closed circular DNA (cccDNA) minichromosome, both in cultured cells in which HBV is replicating and in mice whose livers have been repopulated with human hepatocytes and infected with HBV. Administration of IFN-α resulted in cccDNA-bound histone hypoacetylation as well as active recruitment to the cccDNA of transcriptional corepressors. IFN-α treatment also reduced binding of the STAT1 and STAT2 transcription factors to active cccDNA. The inhibitory activity of IFN-α was linked to the IRSE, as IRSE-mutant HBV transcribed less pgRNA and could not be repressed by IFN-α treatment. Our results identify a molecular mechanism whereby IFN-α mediates epigenetic repression of HBV cccDNA transcriptional activity, which may assist in the development of novel effective therapeutics. [ABSTRACT FROM AUTHOR]

Published
2012
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41. Free episomal and integrated HBV DNA in HBsAg-negative patients with intrahepatic cholangiocarcinoma

Author

Maria Consiglia Bragazzi, Giuseppina Raffa, Teresa Pollicino, Gianluca Tripodi, Domenico Alvaro, Chiara Raggi, Marika Lanza, Francesca Casuscelli di Tocco, Adalberto Barbera, C. Musolino, Giuseppe Navarra, Pietro Invernizzi, Carlo Saitta, Giovanni Raimondo, Pollicino, T, Musolino, C, Saitta, C, Tripodi, G, Lanza, M, Raffa, G, Tocco, F, Raggi, C, Bragazzi, M, Barbera, A, Navarra, G, Invernizzi, P, Alvaro, D, and Raimondo, G

Subjects
0301 basic medicine, Liver tumor, hepatitis B viru, HBV DNA integration, medicine.disease_cause, Virus, 03 medical and health sciences, 0302 clinical medicine, MED/12 - GASTROENTEROLOGIA, intrahepatic cholangiocarcinoma, covalently closed circular HBV DNA, hepatitis B virus, occult HBV Infection, medicine, Intrahepatic Cholangiocarcinoma, Hepatitis B virus, business.industry, virus diseases, cccDNA, medicine.disease, Virology, digestive system diseases, HBx, 030104 developmental biology, Oncology, Cystinosin, 030220 oncology & carcinogenesis, business, Nested polymerase chain reaction, Research Paper
Abstract

There is evidence that chronic hepatitis B virus (HBV) infection is associated with an increased risk of intrahepatic cholangiocarcinoma (ICC) development, and it has been hypothesized an etiological role of HBV in the development of this tumor. Very little is known about occult HBV infection (OBI) in ICC. Aims of the study were to investigate the OBI prevalence and to characterize the HBV molecular status at intrahepatic level in OBI-positive cases with ICC. Frozen liver tumor specimens from 47 HBV surface-antigen-negative patients with ICC and 41 paired non-tumor liver tissues were tested for OBI by 4 different HBV-specific nested PCR. Covalently closed circular HBV DNA (HBV cccDNA) and viral integrations were investigated in OBI-positive cases. HBV DNA was detected in tumor and/or non-tumor specimens from 29/47 (61.7%) ICC patients. HBV cccDNA was found in tissues from 5/17 (34.5%) cases examined. HBV integration was detected in 4/10 (40%) tumor tissues tested and involved HBx and HBV-core gene sequences in 3 and 1 cases, respectively. Viral integration occurred: (a) 9,367 nucleotides upstream of the cat-eye-syndrome critical region protein-5-isoform coding sequence; (b) within the cystinosin isoform-1-precursor gene; (c) within the thromboxane-A-synthase-1 gene; (d) within the ATPase phospholipid transporting 9B gene. Occult HBV infection is highly prevalent in patients with ICC. Both free viral genomes and integrated HBV DNA can be present in these cases. These results suggest an involvement of HBV in the carcinogenic process leading to ICC development even in cases with occult infection.

Published
2019

42. Frequent NS5A and multiclass resistance in almost all HCV genotypes at DAA failures: What are the chances for second-line regimens?

Author

Velia Chiara Di Maio, Valeria Cento, Marianna Aragri, Stefania Paolucci, Teresa Pollicino, Nicola Coppola, Bianca Bruzzone, Valeria Ghisetti, Maurizio Zazzi, Maurizia Brunetto, Ada Bertoli, Silvia Barbaliscia, Silvia Galli, William Gennari, Fausto Baldanti, Giovanni Raimondo, Carlo Federico Perno, Francesca Ceccherini-Silberstein, Pietro Andreone, Massimo Andreoni, Mario Angelico, Sergio Babudieri, Giorgio Barbarini, Vincenzo Boccaccio, Lucio Boglione, Matteo Bolis, Stefano Bonora, Vanni Borghi, Giuseppina Brancaccio, Savino Bruno, Pierluigi Cacciatore, Vincenza Calvaruso, Nicola Caporaso, Antonio Ciaccio, Alessia Ciancio, Piero Colombatto, Raffaele Cozzolongo, Antonio Craxì, Cecilia D'Ambrosio, Gabriella D'Ettorre, Andrea De Luca, Antonio Di Biagio, Giovanni Di Perri, Simona Francioso, Giovanni Battista Gaeta, Alessia Giorgini, Antonio Grieco, Guido Gubertini, Roberto Gulminetti, Lara Lambiase, Ilaria Lenci, Miriam Lichtner, Ivana Maida, Simona Marenco, Letizia Marinaro, Renato Maserati, Chiara Masetti, Michela Melis, Elisa Meregalli, Valeria Micheli, Filomena Morisco, Fosca Niero, Laura Ambra Nicolini, Valeria Pace Palitti, Maurizio Paoloni, Giustino Parruti, Caterina Pasquazzi, Adriano Pellicelli, Ennio Polilli, Maria Laura Ponti, Massimo Puoti, Maria Rendina, Giuliano Rizzardini, Barbara Rossetti, Tina Ruggiero, Vincenzo Sangiovanni, Mario Starace, Laura Sticchi, Pierluigi Tarquini, Pierluigi Toniutto, Vincenzo Vullo, Di Maio VC, Cento V, Aragri M, Paolucci S, Pollicino T3, Coppola N4, Bruzzone B5, Ghisetti V6, Zazzi M7, Brunetto M8, Bertoli A1, Barbaliscia S1, Galli S9, Gennari W10, Baldanti F2, Raimondo G3, Perno CF1, Ceccherini-Silberstein F11, Andreone P, Andreoni M, Angelico M, Babudieri S, Barbarini G, Boccaccio V, Boglione L, Bolis M, Bonora S, Borghi V, Brancaccio G, Bruno S, Cacciatore P, Calvaruso Vincenza, Caporaso N, Ciaccio A, Ciancio A, Colombatto P, Cozzolongo R, Craxì Antonio, D'Ambrosio C, D'Ettorre G, De Luca A, Di Biagio A, Di Perri G, Francioso S, Gaeta GB, Giorgini A, Grieco A, Gubertini G, Gulminetti R, Lambiase L, Lenci I, Lichtner M, Maida I, Marenco S, Marinaro L, Maserati R, Masetti C, Melis M, Meregalli E, Micheli V, Morisco F, Niero F, Nicolini LA, Palitti VP, Paoloni M, Parruti G, Pasquazzi C, Pellicelli A, Polilli E, Ponti ML, Puoti M, Rendina M, Rizzardini G, Rossetti B, Ruggiero T, Sangiovanni V, Starace M, Sticchi L, Tarquini P, Toniutto P, Vullo V., Di Maio, Vc, Cento, V, Aragri, M, Paolucci, S, Pollicino, T, Coppola, N, Bruzzone, B, Ghisetti, V, Zazzi, M, Brunetto, M, Bertoli, A, Barbaliscia, S, Galli, S, Gennari, W, Baldanti, F, Raimondo, G, Perno, Cf, Ceccherini-Silberstein, F., Andreone P, Andreoni, M, Angelico, M, Babudieri, S, Barbarini, G, Boccaccio, V, Boglione, L, Bolis, M, Bonora, S, Borghi, V, Brancaccio, G, Bruno, S, Cacciatore, P, Calvaruso, V, Caporaso, N, Ciaccio, A, Ciancio, A, Colombatto, P, Cozzolongo, R, Craxì, A, D'Ambrosio, C, D'Ettorre, G, De Luca, A, Di Biagio, A, Di Perri, G, Francioso, S, Gaeta, Gb, Giorgini, A, Grieco, A, Gubertini, G, Gulminetti, R, Lambiase, L, Lenci, I, Lichtner, M, Maida, I, Marenco, S, Marinaro, L, Maserati, R, Masetti, C, Melis, M, Meregalli, E, Micheli, V, Morisco, F, Niero, F, Nicolini, La, Palitti, Vp, Paoloni, M, Parruti, G, Pasquazzi, C, Pellicelli, A, Polilli, E, Ponti, Ml, Puoti, M, Rendina, M, Rizzardini, G, Rossetti, B, Ruggiero, T, Sangiovanni, V, Starace, M, Sticchi, L, Tarquini, P, Toniutto, P, Vullo, V., Di Maio, V, Perno, C, Ceccherini-Silberstein, F, Andreone, P, Craxi, A, Gaeta, G, Nicolini, L, Palitti, V, Ponti, M, and Vullo, V

Subjects
0301 basic medicine, medicine.medical_specialty, hepacivirus, HCV RAS, Treatment outcome, Drug Resistance, HCV genotypes, Drug resistance, Biology, NS5A, 03 medical and health sciences, 0302 clinical medicine, Second line, drug resistance viral, humans, retreatment, treatment outcome, antiviral agents, hepatitis c chronic, Internal medicine, Drug Resistance, Viral, Humans, Retreatment, Treatment Outcome, Antiviral Agents, Hepacivirus, Hepatitis C, Chronic, medicine, Viral, Chronic, Hepatology, Hepatitis C, Settore MED/07 - Microbiologia e Microbiologia Clinica, medicine.disease, Virology, Hepatology, HCV, NS5A, 030104 developmental biology, HCV, 030211 gastroenterology & hepatology
Published
2018

43. Neoangiogenesis-related genes are hallmarks of fast-growing hepatocellular carcinomas and worst survival. Results from a prospective study

Author

Mariagrazia Del Buono, Paola Loria, Teresa Pollicino, Stefano Colopi, Elena Bertolini, Guido Marzocchi, Stefano Ballestri, Cristian Caporali, Calogero Cammà, Barbara Lei, Aimilia Karampatou, Gianluigi Giannelli, Fabiola Milosa, Erica Villa, Giuseppe Cabibbo, Marco Enea, Elena Turola, Rosina Maria Critelli, Umberto Cillo, Giorgio Enrico Gerunda, Patrizia Pontisso, Nicola De Maria, María L. Martínez-Chantar, Paola Todesca, Luisa Losi, Livia Maccio, Filippo Schepis, Villa E., Critelli R., Lei B., Marzocchi G., Camma C., Giannelli G., Pontisso P., Cabibbo G., Enea M., Colopi S., Caporali C., Pollicino T., Milosa F., Karampatou A., Todesca P., Bertolini E., Maccio L., Martinez-Chantar M.L., Turola E., Dal Buono M., De Maria N., Ballestri S., Schepis F., Loria P., Gerunda G.E., Losi L., and Cillo U.

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Time Factors, Carcinoma, Hepatocellular, Time Factor, Microarray, Hepatocellular carcinoma, molecular carcinogenesis, Gastroenterology, liver imaging, HEPATOCELLULAR CARCINOMA, LIVER IMAGING, MOLECULAR CARCINOGENESIS, MOLECULAR ONCOLOGY, Aged, Aged, 80 and over, Disease Progression, Female, Humans, Liver Neoplasms, Middle Aged, Neovascularization, Pathologic, Prospective Studies, Survival Rate, Tumor Burden, Medicine (all), 03 medical and health sciences, molecular oncology, 0302 clinical medicine, Hepatocellular carcinoma, liver imaging, molecular carcinogenesis, molecular oncology, Internal medicine, medicine, Carcinoma, Doubling time, Prospective cohort study, Survival rate, business.industry, Proportional hazards model, medicine.disease, Prospective Studie, 030104 developmental biology, Quartile, Liver Neoplasm, 030220 oncology & carcinogenesis, business, Human
Abstract

Objective The biological heterogeneity of hepatocellular carcinoma (HCC) makes prognosis difficult. We translate the results of a genome-wide high-throughput analysis into a tool that accurately predicts at presentation tumour growth and survival of patients with HCC.Design Ultrasound surveillance identified HCC in 78 (training set) and 54 (validation set) consecutive patients with cirrhosis. Patients underwent two CT scans 6 weeks apart (no treatment in-between) to determine tumour volumes (V-0 and V-1) and calculate HCC doubling time. Baseline-paired HCC and surrounding tissue biopsies for microarray study (Agilent Whole Human Genome Oligo Microarrays) were also obtained. Predictors of survival were assessed by multivariate Cox model.Results Calculated tumour doubling times ranged from 30 to 621 days (mean, 107 +/- 91 days; median, 83 days) and were divided into quartiles: = 111 days (n= 19). Median survival according to doubling time was significantly lower for the first quartile versus the others (11 vs 41 months, 42, and 47 months, respectively) (p< 0.0001). A five-gene transcriptomic hepatic signature including angiopoietin-2 (ANGPT2), delta-like ligand 4 (DLL4), neuropilin (NRP)/tolloid (TLL)-like 2 (NETO2), endothelial cell-specific molecule-1 (ESM1), and nuclear receptor subfamily 4, group A, member 1 (NR4A1) was found to accurately identify rapidly growing HCCs of the first quartile (ROC AUC: 0.961; 95% CI 0.919 to 1.000; p< 0.0001) and to be an independent factor for mortality (HR: 3.987; 95% CI 1.941 to 8.193, p< 0.0001).Conclusions The hepatic five-gene signature was able to predict HCC growth in individual patient and the consequent risk of death. This implies a role of this molecular tool in the future therapeutic management of patients with HCC.

Published
2015

44. Current epidemiology of HCV in Sicily: the RESIST-HCV model

Author

F. Ceccherini-Silbertein, Walter Mazzucco, Rosanna Cusimano, Giovanni Squadrito, S. Petta, Rosalba Amodio, Bruno Cacopardo, G. Raimondo, Teresa Pollicino, Francesco Vitale, F. Cartabellotta, C. Cammà, Vincenza Calvaruso, Antonio Craxì, S Mazzola, V. Di Marco, G. Scifo, Maurizio Russello, Di Marco, V, Cartabellotta, F, Mazzucco, W, Calvaruso, V, Petta, S, Mazzola, S, Cusimano, R, Amodio, R, Scifo, G, Russello, M, Cacopardo, B, Squadrito, G, Raimondo, G, Pollicino, T, Ceccherini-Silbertein, F, Vitale, F, Camma, C, and Craxi, A

Subjects
medicine.medical_specialty, Hepatology, Resist, business.industry, Epidemiology, Gastroenterology, medicine, HCV treatment, Current (fluid), clinical surveillance, business, Intensive care medicine, epidemiology of HCV
Abstract

Background: Real-world data to guide hepatitis C virus (HCV)- related public health initiatives and linkage to care of patients are lacking in our region. Aims: To describe the epidemiological features of a large cohort of patients with chronic HCV infection from Sicily included in a regional network aimed at DAA treatment (RESIST-HCV). Methods: Demographic and clinical data were recorded on a web-based platform before starting treatment with DAAs. Gender, year of birth, HCV genotype, co-infections, stages of liver disease and co-morbidities were analyzed. Chi-square with Yates correc- tion was appliedto assess the differences between cohorts. Results: Overall, 15,270 patients were registered on the HCV- RESIST platform from March 2015 to March 2019. The analysis of demographic and viral features showed a clear-cut bimodal distribution, defining two cohorts of patients. The first (cohort 1) includes 9.939 patients (65%) born between the years 1930 and 1959, while the second (cohort 2) included 5.331 patients (35%) born between 1960 and 1999. When comparing the two cohorts, cohort 1 had a higher rate of infection with HCV Gt 1b or 2 (90% vs 47%; p

Published
2019

45. Transcriptional regulation of miR-224 upregulated in human HCCs by NFκB inflammatory pathways

Author

Melchiorre Cervello, Giuseppe Montalto, Paolo D'Onorio De Meo, Rossana De Iaco, Francesca Guerrieri, V. Schinzari, Natalia Pediconi, Giovanni Raimondo, C. Scisciani, Massimo Levrero, Teresa Pollicino, Stefania Vossio, Scisciani, C., Vossio, S., Guerrieri, F., Schinzari, V., De Iaco, R., D'Onorio De Meo, P., Cervello, M., Montalto, G., Pollicino, T., Raimondo, G., Levrero, M., and Pediconi, N.

Subjects
Lipopolysaccharides, Liver Cirrhosis, Male, Carcinoma, Hepatocellular, Transcription, Genetic, Liver Cirrhosi, Lipopolysaccharide, Biology, Cell Movement, Cell Line, Tumor, microRNA, Transcriptional regulation, Humans, NF kappa B, HCC, mir-224, nfκb, hcc, mirnas, transcription, Transcription factor, Lymphotoxin-alpha, miRNA, Aged, Hepatology, miRNAs, miR-224, Transcription, Tumor Necrosis Factor-alpha, Liver Neoplasms, NF-kappa B, MicroRNA, HCCS, Middle Aged, NFKB1, Up-Regulation, MicroRNAs, IκBα, Liver, Liver Neoplasm, Case-Control Studies, Immunology, Cancer research, Tumor necrosis factor alpha, Female, Signal transduction, Case-Control Studie, NFκB, Human, Signal Transduction
Abstract

Background & Aims: miR-224 is up-regulated in human HCCs as compared to both paired peri-tumoral cirrhotic tissues and cirrhotic livers without HCC. Here, we have cloned the miR-224 regulatory region and characterized its transcriptional regulation by the NFκB-dependent inflammatory pathways. Methods: Mature miRNA expression was evaluated by a 2 step stem-loop real-time RT-PCR. The recruitment of polymerase II and transcription factors on the pre-miR-224 promoter has been assessed by ChIPSeq and ChIP. Results: We found miR-224 levels strongly up-regulated in both peri-tumoral cirrhotic livers and HCC samples as compared to normal livers. In silico analysis of the putative miR-224 promoter revealed multiple NFκB sites. We showed that LTα and TNFα activate transcription from the miR-224 promoter and of endogenous miR-224 expression in HCC cell lines, whereas the expression of miR-224 target API5 was reduced. Exogenously expressed p65/RelA activates the miR-224 promoter and a dominant negative form of IκBα (IκBSR) represses it. ChIP analysis showed that p65/NFκB is recruited on the miR-224 promoter and that its binding sharply increases after exposure to LPS, TNFα, and LTα. Altogether these findings link the inflammatory signals to NFκB-mediated activation of miR-224 expression. An antago-miR specific for miR-224 blocked LPS and LTα stimulated HCC cells migration and invasion. Conversely, the IKK inhibitor BMS-345541 blocks pre-miR-224-induced cellular migration and invasion. Conclusions: Our results identify p65/NFκB as a direct transcriptional regulator of miR-224 expression and link miR-224 up-regulation with the activation of the LPS, LTα, and TNFα inflammatory pathways and cell migration/invasion in HCC. © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Published
2012

46. Treatment of chronic hepatitis B: update of the recommendations from the 2007 Italian Workshop

Author

Teresa Pollicino, Massimo Colombo, Alfredo Marzano, Pietro Lampertico, Giovanni Raimondo, Francesco Mazzotta, Maurizia Rossana Brunetto, Giampiero Carosi, Mario Rizzetto, Mario Toti, Giovanni Battista Gaeta, Felice Piccinino, Giuseppe Pastore, Evangelista Sagnelli, Vito Di Marco, Daniele Prati, Massimo Levrero, Carlo Ferrari, Antonio Craxì, Massimo Puoti, Alfredo Alberti, Antonina Smedile, Gaetano Filice, Raffaele Bruno, Teresa Santantonio, Giuseppe Cariti, Carosi, G, Rizzetto, M, Alberti, A, Cariti, G, Colombo, M, Craxi, A, Filice, G, Levrero, M, Mazzotta, F, Pastore, G, Piccinino, F, Prati, D, Raimondo, G, Sagnelli, E, Toti, M, Brunetto, M, Bruno, R, Di Marco, V, Ferrari, C, Gaeta, GB, Lampertico, P, Marzano, A, Pollicino, T, Puoti, M, Santantonio, T, Smedile, A, Craxì, A, Gaeta, Giovanni Battista, and Smedile, A.

Subjects
Liver Cirrhosis, medicine.medical_specialty, Hepatitis B virus, Cirrhosis, Carcinoma, Hepatocellular, Organophosphonates, chronic hepatitis B, The Italian recommendations for the therapy of hepatitis B, Tenofovir, Adefovir, Cirrhosis, Telbivudine, Lamivudine, Entecavir, medicine.disease_cause, Antiviral Agents, adefovir, cirrhosis, entecavir, hbv, lamivudine, telbivudine, tenofovir, Hepatitis B, Chronic, Internal medicine, Telbivudine, medicine, Adefovir, HBV, Humans, Stage (cooking), Tenofovir, Hepatology, business.industry, Adenine, Liver Neoplasms, Gastroenterology, Lamivudine, Entecavir, medicine.disease, Virology, Italy, Hepatocellular carcinoma, Reverse Transcriptase Inhibitors, Interferons, business, medicine.drug
Abstract

The Italian recommendations for the therapy of hepatitis B virus (HBV)-related disease were issued in 2008. Subsequently in 2008 the nucleotide analogue (NA) Tenofovir was approved for antiviral treatment. The introduction of this important new drug has called for the current guidelines update, which includes some additional revisions: (a) the indication for therapy is extended to mild liver fibrosis and the indication for treatment is graded as “possible”, “optional” or “mandatory” according to the fibrosis stage; (b) two different treatment strategies are described: first line definite duration treatment with interferon, long-term treatment of indefinite duration with NA; (c) the indication to follow either strategy is also based on the stage of liver fibrosis; (d) virological monitoring is modified to include the definitions of failure and of sustained virological response to interferon therapy; (e) the recommendation to use HBV DNA assays with high sensitivity and wide linear ranges is underlined (f) guidelines on post-treatment follow-up after finite treatment with NA, potential side effects of therapy and non-virological monitoring are defined; (g) definitions and treatment of patients without optimal response to NA are reported; (f) treatment and monitoring of compensated or decompensated cirrhosis and hepatocellular carcinoma are updated.

Published
2011

47. Occult hepatitis B virus infection and hepatocellular carcinoma development in patients with chronic hepatitis C

Author

Massimo Levrero, Antonio Craxì, Giovanni Raimondo, Teresa Pollicino, Raimondo, G, Pollicino, T, Levrero, M, and Craxi, A

Subjects
Hepatitis B virus, medicine.medical_specialty, Hepatology, medicine.diagnostic_test, business.industry, Hepatitis C, medicine.disease_cause, medicine.disease, Gastroenterology, Occult, Chronic hepatitis, Internal medicine, Hepatocellular carcinoma, Biopsy, medicine, Carcinoma, HBV, In patient, Occult Hepatitis B Virus Infection, Prevalence, business
Published
2011

48. Replicative and Transcriptional Activities of Hepatitis B Virus in Patients Coinfected with Hepatitis B and Hepatitis Delta Viruses▿ †

Author

Giuseppina Raffa, Giovanni Squadrito, Angela Alibrandi, Irene Cacciola, Teresa Santantonio, Giovanni Raimondo, Giovanni Battista Gaeta, Giuseppe Colucci, Chiara Calvi, Giuliano Iannello, Teresa Pollicino, Massimo Levrero, Pollicino, T, Raffa, G, Santantonio, T, Gaeta, Giovanni Battista, Iannello, G, Alibrandi, A, Squadrito, G, Cacciola, I, Calvi, C, Colucci, G, Levrero, M, and Raimondo, G.

Subjects
Male, HBsAg, Hepatitis D, Chronic, Transcription, Genetic, viruses, Biopsy, HBV DNA, HDV RNA, covalently closed circular DNA (cccDNA), HBV INFECTION NATURAL-HISTORY, HBV DNA SEQUENCE ANALYSIS, medicine.disease_cause, Virus Replication, Polymerase Chain Reaction, biology, virus diseases, cccDNA, Hepatitis B, Middle Aged, Hepatitis D, Genome Replication and Regulation of Viral Gene Expression, Liver, RNA, Viral, Female, Hepatitis D virus, DNA, Circular, Hepatitis Delta Virus, Adult, Hepatitis B virus, Adolescent, Immunology, Molecular Sequence Data, Microbiology, Base Sequence, DNA, Viral, Hepatitis B, Chronic, Humans, Viremia, Young Adult, Hepatitis B virus PRE beta, Virology, medicine, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, medicine.disease, digestive system diseases, Hepadnaviridae, Insect Science
Abstract

Hepatitis B virus (HBV) and hepatitis delta virus (HDV) interplay was investigated by examining liver and serum samples from 21 coinfected and 22 HBV-monoinfected patients with chronic liver disease. Different real-time PCR assays were applied to evaluate intrahepatic amounts of HBV DNA, covalently closed circular DNA (cccDNA), pregenomic RNA (pgRNA), pre-S/S RNAs, and HDV RNA. Besides HBV DNA and HDV RNA levels, HBsAg concentrations in the sera were also determined. HDV-coinfected cases showed significantly lower median levels of serum HBV DNA (−5 log), intrahepatic relaxed-circular DNA (−2 log), and cccDNA (−2 log) than those of HBV-monoinfected cases. Interestingly, pgRNA and pre-S/S RNA amounts were significantly lower (both −1 log) in HDV-positive patients, whereas serum HBsAg concentrations were comparable between the two patient groups. Pre-S/S RNA and HBsAg amounts per cccDNA molecule were higher in HDV-positive patients (3-fold and 1 log, respectively), showing that HBV replication was reduced, whereas synthesis of envelope proteins was not specifically decreased. The ratios of cccDNA to intracellular total HBV DNA showed a larger proportion of cccDNA molecules in HDV-positive cases. For these patients, both intrahepatic and serum HDV RNA amounts were associated with cccDNA but not with HBsAg or HBV DNA levels. Finally, HBV genomes with large deletions in the basal core promoter/precore region were detected in 5/21 HDV-positive patients but in no HDV-negative patients and were associated with lower viremia levels. These findings provide significant information about the interference exerted by HDV on HBV replication and transcription activities in the human liver.

Published
2010

49. Statements from the Taormina expert meeting on occult hepatitis B virus infection

Author

Didier Samuel, Jean-Pierre Allain, Maurizia Rossana Brunetto, Daniel Shouval, Giovanni Squadrito, Thomas I. Michalak, Massimo Colombo, Ding-Shinn Chen, Giovanni Raimondo, Giovanni Battista Gaeta, Antonio Craxì, Marie Annick Buendia, Massimo Levrero, Daniele Prati, Massimo Puoti, Jean-Michel Pawlotsky, Christian Trepo, Alessandro Zanetti, Antonina Smedile, Erica Villa, Stephen Locarnini, Fabien Zoulim, Francesco Donato, Mario U. Mondelli, Carlo Ferrari, Wolfram H. Gerlich, Teresa Pollicino, Hans Will, RAIMONDO G, ALLAIN JP, BRUNETTO MR, BUENDIA MA, CHEN DS, COLOMBO M, CRAXI' A, DONATO F, FERRARI C, GAETA GB, GERLICH WH, LEVRERO M, LOCARNINI S, MICHALAK T, MONDELLI MU, PAWLOTSKY JM, POLLICINO T, PRATI D, PUOTI M, SAMUEL D, SHOUVAL D, SMEDILE A, SQUADRITO G, TRÉPO C, VILLA E, WILL H, ZANETTI AR, and ZOULIM F

Subjects
HBV, guidelines, media_common.quotation_subject, viral hepatitis, Occult hepatitis B virus infection OBI, Seropositive OBI and Seronegative OBI, medicine.disease_cause, Occult hepatitis B virus, molecular detection of HBV DNA, HBV transmission, Viral genetics, medicine, media_common, Hepatitis B virus, False OBI, Clinical impact of OBI, Diagnosis of OBI and epidemiological aspects, Hepatology, Art, Occult hepatitis B infection, Occult, Virology, Humanities
Abstract

Giovanni Raimondo*, Jean-Pierre Allain, Maurizia R. Brunetto, Marie-Annick Buendia, Ding-Shinn Chen, Massimo Colombo, Antonio Craxi, Francesco Donato, Carlo Ferrari, Giovanni B. Gaeta, Wolfram H. Gerlich, Massimo Levrero, Stephen Locarnini, Thomas Michalak, Mario U. Mondelli, Jean-Michel Pawlotsky, Teresa Pollicino, Daniele Prati, Massimo Puoti, Didier Samuel, Daniel Shouval, Antonina Smedile, Giovanni Squadrito, Christian Trepo, Erica Villa, Hans Will, Alessandro R. Zanetti, Fabien Zoulim

Published
2008

50. Occult hepatitis B virus infection

Author

Massimo Levrero, Giovanni Squadrito, Claudio Tiribelli, Mario U. Mondelli, Antonio Craxì, Teresa Pollicino, Fabio Farinati, Clara Balsano, Giovanni Raimondo, Raimondo, G, Balsano, C, Craxi, A, Farinati, F, Levrero, M, Mondelli, M, Pollicino, T, Squadrito, G, and Tiribelli, Claudio

Subjects
Male, ACUTE VIRAL-HEPATITIS, POSTTRANSFUSION HEPATITIS, HBV SURFACE-ANTIGEN, Comorbidity, HBV genome, HBsAg-negative, liver DNA, liver disease, medicine.disease_cause, Severity of Illness Index, SEROLOGICAL MARKERS, TRANSPLANT RECIPIENTS, HEPATITIS C VIRUS, HEPATOCELLULAR-CARCINOMA, CHRONIC LIVER-DISEASE, POLYMERASE CHAIN-REACTION, occult hepatitis B virus infection, Liver disease, Chronic/diagnosis* Hepatitis B, Differential Disease Progression Female Hepatitis B Surface Antigens/analysis* Hepatitis B, hbsag-negative, hbv genome, liver disease, liver dna, Incidence, Hepatocellular/diagnosis Carcinoma, Liver Neoplasms, Gastroenterology, Hepatitis C, Hepatitis B, Prognosis, Chronic/epidemiology* Humans Incidence Liver Neoplasms/diagnosis Liver Neoplasms/epidemiology* Male Prognosis Risk Assessment Severity of Illness Index, Carcinoma, Hepatocellular/diagnosis Carcinoma, Hepatocellular/epidemiology* Comorbidity DNA, Viral/analysis Diagnosis, Differential Disease Progression Female Hepatitis B Surface Antigens/analysis* Hepatitis B, Chronic/diagnosis* Hepatitis B, Chronic/epidemiology* Humans Incidence Liver Neoplasms/diagnosis Liver Neoplasms/epidemiology* Male Prognosis Risk Assessment Severity of Illness Index, Hepatocellular carcinoma, Disease Progression, Female, Carcinoma, Hepatocellular, Risk Assessment, Diagnosis, Differential, Hepatitis B, Chronic, Viral/analysis Diagnosis, medicine, Humans, Risk factor, Hepatitis B virus, Hepatitis B Surface Antigens, Hepatology, business.industry, Carcinoma, medicine.disease, Occult, Virology, Hepatocellular/epidemiology* Comorbidity DNA, Viral replication, Immunology, DNA, Viral, business
Abstract

Many studies have shown that hepatitis B virus infection may also occur in hepatitis B surface antigen-negative patients. This occult infection has been identified both in patients with cryptogenic liver disease and in patients with hepatitis C virus-related chronic hepatitis, and much evidence suggests that it may be a risk factor of hepatocellular carcinoma development. However several aspects of this occult infection remain unclear such as its prevalence and the factor(s) involved in the lack of circulating hepatitis B surface antigen. Moreover, it is uncertain whether the occult hepatitis B virus infection may contribute to chronic liver damage, considering that it is usually associated with a suppressed viral replication. Evidence and hypotheses concerning this fascinating field of bio-medical research are reviewed.

Published
2000

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