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9. Regorafenib Efficacy After Sorafenib in Patients With Recurrent Hepatocellular Carcinoma After Liver Transplantation: A Retrospective Study

Author

Iavarone, Massimo, primary, Invernizzi, Federica, additional, Ivanics, Tommy, additional, Mazza, Stefano, additional, Zavaglia, Claudio, additional, Sanduzzi‐Zamparelli, Marco, additional, Fraile‐López, Miguel, additional, Czauderna, Carolin, additional, Di Costanzo, Giovanni, additional, Bhoori, Sherrie, additional, Pinter, Matthias, additional, Manini, Matteo Angelo, additional, Amaddeo, Giuliana, additional, Yunquera, Ainhoa Fernandez, additional, Piñero, Federico, additional, Blanco Rodríguez, Maria Jose, additional, Anders, Margarita, additional, Aballay Soteras, Gabriel, additional, Villadsen, Gerda Elisabeth, additional, Yoon, Peter Daechul, additional, Cesarini, Lucia, additional, Díaz‐González, Álvaro, additional, González‐Diéguez, Maria Luisa, additional, Tortora, Raffaella, additional, Weinmann, Arndt, additional, Mazzaferro, Vincenzo, additional, Romero Cristóbal, Mario, additional, Crespo, Gonzalo, additional, Regnault, Helene, additional, De Giorgio, Massimo, additional, Varela, Maria, additional, Prince, Rebecca, additional, Scudeller, Luigia, additional, Donato, Maria Francesca, additional, Wörns, Marcus‐Alexander, additional, Bruix, Jordi, additional, Sapisochin, Gonzalo, additional, Lampertico, Pietro, additional, and Reig, Maria, additional

Published
2021
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10. Regorafenib Efficacy After Sorafenib in Patients With Recurrent Hepatocellular Carcinoma After Liver Transplantation: A Retrospective Study

Author

Iavarone, Massimo, Invernizzi, Federica, Ivanics, Tommy, Mazza, Stefano, Zavaglia, Claudio, Sanduzzi‐Zamparelli, Marco, Fraile‐López, Miguel, Czauderna, Carolin, Di Costanzo, Giovanni, Bhoori, Sherrie, Pinter, Matthias, Manini, Matteo Angelo, Amaddeo, Giuliana, Yunquera, Ainhoa Fernandez, Piñero, Federico, Blanco Rodríguez, Maria Jose, Anders, Margarita, Aballay Soteras, Gabriel, Villadsen, Gerda Elisabeth, Yoon, Peter Daechul, Cesarini, Lucia, Díaz‐González, Álvaro, González‐Diéguez, Maria Luisa, Tortora, Raffaella, Weinmann, Arndt, Mazzaferro, Vincenzo, Romero Cristóbal, Mario, Crespo, Gonzalo, Regnault, Helene, De Giorgio, Massimo, Varela, Maria, Prince, Rebecca, Scudeller, Luigia, Donato, Maria Francesca, Wörns, Marcus‐Alexander, Bruix, Jordi, Sapisochin, Gonzalo, Lampertico, Pietro, Reig, Maria, Iavarone, Massimo, Invernizzi, Federica, Ivanics, Tommy, Mazza, Stefano, Zavaglia, Claudio, Sanduzzi‐Zamparelli, Marco, Fraile‐López, Miguel, Czauderna, Carolin, Di Costanzo, Giovanni, Bhoori, Sherrie, Pinter, Matthias, Manini, Matteo Angelo, Amaddeo, Giuliana, Yunquera, Ainhoa Fernandez, Piñero, Federico, Blanco Rodríguez, Maria Jose, Anders, Margarita, Aballay Soteras, Gabriel, Villadsen, Gerda Elisabeth, Yoon, Peter Daechul, Cesarini, Lucia, Díaz‐González, Álvaro, González‐Diéguez, Maria Luisa, Tortora, Raffaella, Weinmann, Arndt, Mazzaferro, Vincenzo, Romero Cristóbal, Mario, Crespo, Gonzalo, Regnault, Helene, De Giorgio, Massimo, Varela, Maria, Prince, Rebecca, Scudeller, Luigia, Donato, Maria Francesca, Wörns, Marcus‐Alexander, Bruix, Jordi, Sapisochin, Gonzalo, Lampertico, Pietro, and Reig, Maria

Published
2021
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12. Hepatocellular carcinoma recurrence after direct-acting antiviral therapy: an individual patient data meta-analysis

Author

Sapena, Victor, primary, Enea, Marco, additional, Torres, Ferran, additional, Celsa, Ciro, additional, Rios, Jose, additional, Rizzo, Giacomo Emanuele Maria, additional, Nahon, Pierre, additional, Mariño, Zoe, additional, Tateishi, Ryosuke, additional, Minami, Tatsuya, additional, Sangiovanni, Angelo, additional, Forns, Xavier, additional, Toyoda, Hidenori, additional, Brillanti, Stefano, additional, Conti, Fabio, additional, Degasperi, Elisabetta, additional, Yu, Ming-Lung, additional, Tsai, Pei-Chien, additional, Jean, Kevin, additional, El Kassas, Mohamed, additional, Shousha, Hend Ibrahim, additional, Omar, Ashraf, additional, Zavaglia, Claudio, additional, Nagata, Hiroko, additional, Nakagawa, Mina, additional, Asahina, Yasuhiro, additional, Singal, Amit G, additional, Murphy, Caitlin, additional, Kohla, Mohamed, additional, Masetti, Chiara, additional, Dufour, Jean-François, additional, Merchante, Nicolas, additional, Cavalletto, Luisa, additional, chemello, liliana LC, additional, POL, Stanislas, additional, Crespo, Javier, additional, Calleja, Jose Luis, additional, Villani, Rosanna, additional, Serviddio, Gaetano, additional, Zanetto, Alberto, additional, Shalaby, Sarah, additional, Russo, Francesco Paolo, additional, Bielen, Rob, additional, Trevisani, Franco, additional, Cammà, Calogero, additional, Bruix, Jordi, additional, Cabibbo, Giuseppe, additional, and Reig, Maria, additional

Published
2021
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17. Regorafenib improves survival after sorafenib treatment in patients with recurrent hepatocellular carcinoma after liver transplantation, compared to best supportive care

Author

Iavarone, Massimo, primary, Invernizzi, Federica, additional, Zavaglia, Claudio, additional, Zamparelli, Marco Sanduzzi, additional, Fraile, Miguel, additional, Czauderna, Carolin, additional, Di Costanzo, Giuseppe, additional, Bhoori, Sherrie, additional, Pinter, Matthias, additional, Manini, Matteo Angelo, additional, Amaddeo, Giuliana, additional, Fernandez, Ainhoa, additional, Pinero, Federico, additional, Blanco Rodriguez, Maria Jose, additional, Anders, Maria Margarita, additional, Aballay Soteras, Gabriel Alejandro, additional, Villadsen, Gerda Elisabeth, additional, Cesarini, Lucia, additional, Mazza, Stefano, additional, Díaz-Gonzázlez, Álvaro, additional, Gonzalez Dieguez, Maria Luisa, additional, Tortora, Raffaella, additional, Weinmann, Arndt, additional, Mazzaferro, Vincenzo, additional, Romero, Mario, additional, Crespo, Gonzalo, additional, Regnault, Helene, additional, De Giorgio, Massimo, additional, Varela, Maria, additional, Donato, Maria Francesca, additional, Worns, Marcus-Alexander, additional, Bruix, Jordi, additional, Lampertico, Pietro, additional, and Reig, María, additional

Published
2020
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18. Pulmonary Resection for Metastasis of Hepatocellular Carcinoma Recurring After Liver Transplant: An Italian Multicenter Experience

Author

Invenizzi, Federica, primary, Iavarone, Massimo, additional, Donato, Maria Francesca, additional, Mazzucco, Alessandra, additional, Torre, Massimo, additional, Conforti, Serena, additional, Rimessi, Arianna, additional, Zavaglia, Claudio, additional, Schiavon, Marco, additional, Comacchio, Giovanni, additional, Rea, Federico, additional, Boetto, Riccardo, additional, Cillo, Umberto, additional, Dondossola, Daniele, additional, De Carlis, Luciano, additional, Lampertico, Pietro, additional, Nosotti, Mario, additional, and Mendogni, Paolo, additional

Published
2020
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20. Liver transplantation for HCV cirrhosis: Improved survival in recent years and increased severity of recurrent disease in female recipients: Results of a long term retrospective study

Author

Belli, Luca S., Burroughs, Andrew K., Burra, Patrizia, Alberti, Alberto B., Samonakis, Dimitrios, Cammà, Calogero, Carlis, Luciano De, Minola, Ernesto, Quaglia, Alberto, Zavaglia, Claudio, Vangeli, Marcello, Patch, David, Dhillon, Amar, Cillo, Umberto, Guido, Maria, Fagiuoli, Stefano, Giacomoni, Alessandro, Slim, Omar A., Airoldi, Aldo, Boninsegna, Sara, Davidson, Brian R., Rolles, Keith, and Pinzello, Giovambattista

Published
2007
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23. Clinical outcome indicators in chronic hepatitis B and C: A primer for value‐based medicine in hepatology

Author

Strazzabosco, Mario, primary, Cortesi, Paolo A., additional, Conti, Sara, additional, Okolicsanyi, Stefano, additional, Rota, Matteo, additional, Ciaccio, Antonio, additional, Cozzolino, Paolo, additional, Fornari, Carla, additional, Gemma, Marta, additional, Scalone, Luciana, additional, Cesana, Giancarlo, additional, Fabris, Luca, additional, Colledan, Michele, additional, Fagiuoli, Stefano, additional, Ideo, Gaetano, additional, Zavaglia, Claudio, additional, Perricone, Giovanni, additional, Munari, Luca M., additional, Mantovani, Lorenzo G., additional, and Belli, Luca S., additional

Published
2019
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24. FRI-376-Early treatment with sorafenib and mTOR inhibitor in recurrent hepatocellular carcinoma after liver transplantation: Safety and survival

Author

Invernizzi, Federica, primary, Iavarone, Massimo, additional, Zavaglia, Claudio, additional, Mazza, Stefano, additional, Maggi, Umberto, additional, cesarini, lucia, additional, Antonelli, Barbara, additional, Airoldi, Aldo, additional, Manini, Matteo Angelo, additional, Sangiovanni, Angelo, additional, Rossi, Giorgio, additional, Donato, Maria Francesca, additional, Belli, Luca Saverio, additional, and Lampertico, Pietro, additional

Published
2019
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25. Hepatocellular carcinoma recurrence after direct-acting antiviral therapy: an individual patient data meta-analysis

Author

Sapena, Victor, Enea, Marco, Torres, Ferran, Celsa, Ciro, Rios, Jose, Rizzo, Giacomo Emanuele Maria, Nahon, Pierre, Mariño, Zoe, Tateishi, Ryosuke, Minami, Tatsuya, Sangiovanni, Angelo, Forns, Xavier, Toyoda, Hidenori, Brillanti, Stefano, Conti, Fabio, Degasperi, Elisabetta, Yu, Ming-Lung, Tsai, Pei-Chien, Jean, Kevin, El Kassas, Mohamed, Shousha, Hend Ibrahim, Omar, Ashraf, Zavaglia, Claudio, Nagata, Hiroko, Nakagawa, Mina, Asahina, Yasuhiro, Singal, Amit G, Murphy, Caitlin, Kohla, Mohamed, Masetti, Chiara, Dufour, Jean-Francois, Merchante, Nicolas, Cavalletto, Luisa, chemello, liliana LC, POL, Stanislas, Crespo, Javier, Calleja, Jose Luis, Villani, Rosanna, Serviddio, Gaetano, Zanetto, Alberto, Shalaby, Sarah, Russo, Francesco Paolo, Bielen, Rob, Trevisani, Franco, Cammà, Calogero, Bruix, Jordi, Cabibbo, Giuseppe, and Reig, Maria

Abstract

ObjectiveThe benefit of direct-acting antivirals (DAAs) against HCV following successful treatment of hepatocellular carcinoma (HCC) remains controversial. This meta-analysis of individual patient data assessed HCC recurrence risk following DAA administration.DesignWe pooled the data of 977 consecutive patients from 21 studies of HCV-related cirrhosis and HCC, who achieved complete radiological response after surgical/locoregional treatments and received DAAs (DAA group). Recurrence or death risk was expressed as HCC recurrence or death per 100 person-years (100PY). Propensity score-matched patients from the ITA.LI.CA. cohort (n=328) served as DAA-unexposed controls (no-DAA group). Risk factors for HCC recurrence were identified using random-effects Poisson.ResultsRecurrence rate and death risk per 100PY in DAA-treated patients were 20 (95% CI 13.9 to 29.8, I2=74.6%) and 5.7 (2.5 to 15.3, I2=54.3), respectively. Predictive factors for recurrence were alpha-fetoprotein logarithm (relative risk (RR)=1.11, 95% CI 1.03 to 1.19; p=0.01, per 1 log of ng/mL), HCC recurrence history pre-DAA initiation (RR=1.11, 95% CI 1.07 to 1.16; p<0.001), performance status (2 vs 0, RR=4.35, 95% CI 1.54 to 11.11; 2 vs 1, RR=3.7, 95% CI 1.3 to 11.11; p=0.01) and tumour burden pre-HCC treatment (multifocal vs solitary nodule, RR=1.75, 95% CI 1.25 to 2.43; p<0.001). No significant difference was observed in RR between the DAA-exposed and DAA-unexposed groups in propensity score-matched patients (RR=0.64, 95% CI 0.37 to 1.1; p=0.1).ConclusionEffects of DAA exposure on HCC recurrence risk remain inconclusive. Active clinical and radiological follow-up of patients with HCC after HCV eradication with DAA is justified.

Published
2022
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31. HLA typing in chronic type B, D and C hepatitis

Author

Zavaglia, Claudio, Bortolon, Cristina, Ferrioli, Gabriella, Rho, Anna, Mondazzi, Luca, Bottelli, Riccardo, Ghessi, Alberto, Gelosa, Franco, Iamoni, Gianmaria, and Ideo, Gaetano

Published
1996

33. Clinical outcome indicators in chronic hepatitis B and C: A primer for value‐based medicine in hepatology.

Author

Strazzabosco, Mario, Cortesi, Paolo A., Conti, Sara, Okolicsanyi, Stefano, Rota, Matteo, Ciaccio, Antonio, Cozzolino, Paolo, Fornari, Carla, Gemma, Marta, Scalone, Luciana, Cesana, Giancarlo, Fabris, Luca, Colledan, Michele, Fagiuoli, Stefano, Ideo, Gaetano, Zavaglia, Claudio, Perricone, Giovanni, Munari, Luca M., Mantovani, Lorenzo G., and Belli, Luca S.

Subjects
CHRONIC hepatitis B, DELPHI method, LIVER diseases
Abstract

Background & Aims: Chronic liver diseases (CLDs) are major health problems that require complex and costly treatments. Liver‐specific clinical outcome indicators (COIs) able to assist both clinicians and administrators in improving the value of care are presently lacking. The Value‐Based Medicine in Hepatology (VBMH) study aims to fill this gap, devising and testing a set of COIs for CLD, that could be easily collected during clinical practice. Here we report the COIs generated and recorded for patients with HBV or HCV infection at different stages of the disease. Methods / Results: In the first phase of VBMH study, COIs were identified, based on current international guidelines and literature, using a modified Delphi method and a RAND 9‐point appropriateness scale. In the second phase, COIs were tested in an observational, longitudinal, prospective, multicentre study based in Lombardy, Italy. Eighteen COIs were identified for HBV and HCV patients. Patients with CLD secondary to HBV (547) or HCV (1391) were enrolled over an 18‐month period and followed for a median of 4 years. The estimation of the proposed COIs was feasible in the real‐word clinical practice and COI values compared well with literature data. Further, the COIs were able to capture the impact of new effective treatments like direct‐acting antivirals (DAAs) in the clinical practice. Conclusions: The COIs efficiently measured clinical outcomes at different stages of CLDs. While specific clinical practice settings and related healthcare systems may modify their implementation, these indicators will represent an important component of the tools for a value‐based approach in hepatology and will positively affect care delivery. [ABSTRACT FROM AUTHOR]

Published
2020
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34. AS150 - Regorafenib improves survival after sorafenib treatment in patients with recurrent hepatocellular carcinoma after liver transplantation, compared to best supportive care

Author

Iavarone, Massimo, Invernizzi, Federica, Zavaglia, Claudio, Zamparelli, Marco Sanduzzi, Fraile, Miguel, Czauderna, Carolin, Di Costanzo, Giuseppe, Bhoori, Sherrie, Pinter, Matthias, Manini, Matteo Angelo, Amaddeo, Giuliana, Fernandez, Ainhoa, Pinero, Federico, Blanco Rodriguez, Maria Jose, Anders, Maria Margarita, Aballay Soteras, Gabriel Alejandro, Villadsen, Gerda Elisabeth, Cesarini, Lucia, Mazza, Stefano, Díaz-Gonzázlez, Álvaro, Gonzalez Dieguez, Maria Luisa, Tortora, Raffaella, Weinmann, Arndt, Mazzaferro, Vincenzo, Romero, Mario, Crespo, Gonzalo, Regnault, Helene, De Giorgio, Massimo, Varela, Maria, Donato, Maria Francesca, Worns, Marcus-Alexander, Bruix, Jordi, Lampertico, Pietro, and Reig, María

Published
2020
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39. Influence of immunogenetic background on the outcome of recurrent hepatitis C after liver transplantation

Author

Belli, Luca Saverio, Zavaglia, Claudio, Alberti, Alberto Battista, Poli, Francesca, Rondinara, Gianfranco, Silini, Enrico, Taioli, Emanuela, De Carlis, Luciano, Scalamogna, Mario, Forti, Domenico, Pinzello, Giovambattista, Idèo, Gaetano, Belli, L, Zavaglia, C, Alberti, A, Poli, F, Rondinara, G, Silini, E, Taioli, E, De Carlis, L, Scalamogna, M, Forti, D, Pinzello, G, and Idèo, G

Subjects
Allele, Adult, Male, Hepatology, Histocompatibility Antigens Class I, Histocompatibility Antigens Class II, Middle Aged, Hepatitis C, Liver Transplantation, Immunogenetic, Postoperative Complications, Gene Frequency, Recurrence, Multivariate Analysis, Disease Progression, Immunogenetics, Humans, Female, Postoperative Complication, Multivariate Analysi, Alleles, Human
Abstract

In immunocompetent patients, specific human leukocyte antigen (HLA) class II alleles have been associated with the severity of hepatitis C virus (HCV)-related disease, in particular, HLA-DRBI* 1 I has been found to exert a protective effect. The authors have analyzed the role of HLA class I and II alleles in determining the frequency, timing, and progression of histologically proven recurrent hepatitis C in 89 patients who underwent a liver transplant for HCV-related cirrhosis. In addition, the influence of HLA mismatch between donor and recipient, HCV genotype, and use of steroid pulses was also evaluated. Median patient follow up was 35 months (range 4-119). HLA-DRBI typing was performed by genomic analysis in all cases. Liver biopsies were obtained routinely and at least at yearly intervals. Histologically proven recurrent hepatitis was observed in 46 patients (52%), 10 patients progressing to stage 5-6 fibrosis in most cases within 2 years after transplant. By univariate analysis, 3 variables, HLA-B14, HLA-DRB1*04, and HLA-DRB1 donor/recipient mismatch, showed a significant effect on time to recurrent hepatitis C disease. These parameters were included in a multivariate regression model along with HCV genotype, treatment with steroid pulses and DRB1*11. HLA-B14, HLA-DRBI*04, and HLA-DRBI donor/recipient mismatch were confirmed to provide a significant and independent contribution to the risk of hepatitic disease recurrence. As for the severity of the disease, none of the 10 patients with stage 5-6 hepatitis carried the HLA- DRBI*11 allele, in line with what was observed in nontransplant subjects. Our results suggest that in posttransplant recurrent hepatitis C, immunogenetic factors are relevant in determining HCV infection outcome

Published
2000

41. Liver transplantation for HCV cirrhosis: Improved survival in recent years and increased severity of recurrent disease in female recipients: Results of a long term retrospective study

Author

Belli, L, Burroughs, A, Burra, P, Alberti, A, Samonakis, D, Cammà, C, De Carlis, L, Minola, E, Quaglia, A, Zavaglia, C, Vangeli, M, Patch, D, Dhillon, A, Cillo, U, Guido, M, Fagiuoli, S, Giacomoni, A, Slim, O, Airoldi, A, Boninsegna, S, Davidson, B, Rolles, K, Pinzello, G, Belli, Luca S., Burroughs, Andrew K., Burra, Patrizia, Alberti, Alberto B., Samonakis, Dimitrios, Cammà, Calogero, De Carlis, Luciano, Minola, Ernesto, Quaglia, Alberto, Zavaglia, Claudio, Vangeli, Marcello, Patch, David, Dhillon, Amar, Cillo, Umberto, Guido, Maria, Fagiuoli, Stefano, Giacomoni, Alessandro, Slim, Omar A., Airoldi, Aldo, Boninsegna, Sara, Davidson, Brian R., Rolles, Keith, Pinzello, Giovambattista, Belli, L, Burroughs, A, Burra, P, Alberti, A, Samonakis, D, Cammà, C, De Carlis, L, Minola, E, Quaglia, A, Zavaglia, C, Vangeli, M, Patch, D, Dhillon, A, Cillo, U, Guido, M, Fagiuoli, S, Giacomoni, A, Slim, O, Airoldi, A, Boninsegna, S, Davidson, B, Rolles, K, Pinzello, G, Belli, Luca S., Burroughs, Andrew K., Burra, Patrizia, Alberti, Alberto B., Samonakis, Dimitrios, Cammà, Calogero, De Carlis, Luciano, Minola, Ernesto, Quaglia, Alberto, Zavaglia, Claudio, Vangeli, Marcello, Patch, David, Dhillon, Amar, Cillo, Umberto, Guido, Maria, Fagiuoli, Stefano, Giacomoni, Alessandro, Slim, Omar A., Airoldi, Aldo, Boninsegna, Sara, Davidson, Brian R., Rolles, Keith, and Pinzello, Giovambattista

Abstract

In recent years, a worsening outcome of hepatitis C virus (HCV)-positive recipients and a faster progression of recurrent disease to overt cirrhosis have been reported. Our aims were to 1) assess patient survival and development of severe recurrent disease (Ishak fibrosis score > 3) in different transplant years; and 2) model the effects of pre- and post-liver transplantation (LT) variables on the severity of recurrent disease. A multicenter retrospective analysis was conducted on 502 consecutive HCV-positive transplant recipients between January 1990 and December 2002. Protocol liver biopsies were obtained at 1, 3, 5, 7, and 10 yr post-LT ir almost 90% of the patients. All 502 patients were included in the overall survival analysis, while only the 354 patients with a follow-up longer than 1 yr were considered for the analysis of predictors of disease progression. The overall Kaplan-Meier survival rates were 78.7%, 66.3%, and 58.6%, at 12, 60, and 120 months, respectively, and a trend for a better patient survival over the years emerged from all 3 centers. The cumulative probability of developing HCV-related recurrent severe fibrosis (Ishak score 4-6) in the cohort of 354 patients who survived at least 1 yr remained unchanged over the years. Multivariate analysis indicated that older donors (P = 0.0001) and female gender of recipient (P = 0.02) were the 2 major risk factors for the development of severe recurrent disease, while the adoption of antilymphocytic preparations was associated with a less aggressive course (P = 0.03). Two of these prognostic factors, donor age and recipient gender, are easily available before LT and their combination showed an important synergy, such that a female recipient not only had a much higher probability of severe recurrent disease than a male recipient but her risk increased with the increasing age of the donor, reaching almost 100% when the age of the donor was 60 or older. In conclusion, a trend for a better patient survival

Published
2007

42. HLA-DRB1 donor-recipient mismatch affects the outcome of hepatitis C disease recurrence after liver transplantation

Author

Belli, L, Burra, P, Poli, F, Alberti, A, Silini, E, Zavaglia, C, Fagiuoli, S, Prando, D, Espadas De Arias, A, Boninsegna, S, Tinelli, C, Scalamogna, M, De Carlis, L, Pinzello, G, Belli, Luca Saverio, Burra, Patrizia, Poli, Francesca, Alberti, Alberto Battista, Silini, Enrico, Zavaglia, Claudio, Fagiuoli, Stefano, Prando, Daniela, Espadas De Arias, Alejandro, Boninsegna, Sara, Tinelli, Carmine, Scalamogna, Mario, De Carlis, Luciano, Pinzello, Giovambattista, Belli, L, Burra, P, Poli, F, Alberti, A, Silini, E, Zavaglia, C, Fagiuoli, S, Prando, D, Espadas De Arias, A, Boninsegna, S, Tinelli, C, Scalamogna, M, De Carlis, L, Pinzello, G, Belli, Luca Saverio, Burra, Patrizia, Poli, Francesca, Alberti, Alberto Battista, Silini, Enrico, Zavaglia, Claudio, Fagiuoli, Stefano, Prando, Daniela, Espadas De Arias, Alejandro, Boninsegna, Sara, Tinelli, Carmine, Scalamogna, Mario, De Carlis, Luciano, and Pinzello, Giovambattista

Abstract

Background & Aims: This study extends our previously reported observations that various immunological factors are associated with the occurrence of histologically proven recurrent hepatitis C. The two specific issues investigated were to confirm the associations of MHC alleles and donor/recipient mismatch with the occurrence of recurrent hepatitis C in an independent cohort of newly transplanted patients and to look for immunologic and nonimmunologic variables affecting the severity of the recurrent disease. Methods: Two separate cohorts of consecutive patients were studied: a look-back cohort (LC) of 120 patients and a cohort for studying the disease progression (CSDP) of 190 patients. Protocol liver biopsies were obtained at least 1, 3, 5, 7, and 10 years after liver transplantation (LT). Results: A fully mismatched donor/recipient pair at the DRB1 locus was confirmed to be associated with both the recurrence of histologic hepatitis in the LC (59% vs 23%, P = .0002) and its progression beyond stage 3 in the CSPD (71.4% vs 39.3%, P = .0003). Relevant immunologic and nonimmunologic variables were included into a multivariate Cox proportional model and three variables, namely, donor age, full HLA-DRB1 donor-recipient mismatch, and HLA B14, resulted in independent risk factors for the development of severe fibrosis. Conclusion: This study provides evidence that DRB1 donor-recipient mismatch affects both the occurrence and progression of recurrent hepatitis C disease. This information is clinically relevant as it may help to better allocate organs and to recognize patients at risk for progression so that specific interventions can be implemented. © 2006 by the American Gastroenterological Association Institute

Published
2006

45. Influence of immunogenetic background on the outcome of recurrent hepatitis C after liver transplantation

Author

Belli, L, Zavaglia, C, Alberti, A, Poli, F, Rondinara, G, Silini, E, Taioli, E, De Carlis, L, Scalamogna, M, Forti, D, Pinzello, G, Idèo, G, Belli, Luca Saverio, Zavaglia, Claudio, Alberti, Alberto Battista, Poli, Francesca, Rondinara, Gianfranco, Silini, Enrico, Taioli, Emanuela, De Carlis, Luciano, Scalamogna, Mario, Forti, Domenico, Pinzello, Giovambattista, Idèo, Gaetano, Belli, L, Zavaglia, C, Alberti, A, Poli, F, Rondinara, G, Silini, E, Taioli, E, De Carlis, L, Scalamogna, M, Forti, D, Pinzello, G, Idèo, G, Belli, Luca Saverio, Zavaglia, Claudio, Alberti, Alberto Battista, Poli, Francesca, Rondinara, Gianfranco, Silini, Enrico, Taioli, Emanuela, De Carlis, Luciano, Scalamogna, Mario, Forti, Domenico, Pinzello, Giovambattista, and Idèo, Gaetano

Abstract

In immunocompetent patients, specific human leukocyte antigen (HLA) class II alleles have been associated with the severity of hepatitis C virus (HCV)-related disease, in particular, HLA-DRBI* 1 I has been found to exert a protective effect. The authors have analyzed the role of HLA class I and II alleles in determining the frequency, timing, and progression of histologically proven recurrent hepatitis C in 89 patients who underwent a liver transplant for HCV-related cirrhosis. In addition, the influence of HLA mismatch between donor and recipient, HCV genotype, and use of steroid pulses was also evaluated. Median patient follow up was 35 months (range 4-119). HLA-DRBI typing was performed by genomic analysis in all cases. Liver biopsies were obtained routinely and at least at yearly intervals. Histologically proven recurrent hepatitis was observed in 46 patients (52%), 10 patients progressing to stage 5-6 fibrosis in most cases within 2 years after transplant. By univariate analysis, 3 variables, HLA-B14, HLA-DRB1*04, and HLA-DRB1 donor/recipient mismatch, showed a significant effect on time to recurrent hepatitis C disease. These parameters were included in a multivariate regression model along with HCV genotype, treatment with steroid pulses and DRB1*11. HLA-B14, HLA-DRBI*04, and HLA-DRBI donor/recipient mismatch were confirmed to provide a significant and independent contribution to the risk of hepatitic disease recurrence. As for the severity of the disease, none of the 10 patients with stage 5-6 hepatitis carried the HLA- DRBI*11 allele, in line with what was observed in nontransplant subjects. Our results suggest that in posttransplant recurrent hepatitis C, immunogenetic factors are relevant in determining HCV infection outcome

Published
2000

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