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1. Long‐term outcomes of direct acting antivirals in post‐transplant advanced hepatitis C virus recurrence and fibrosing cholestatic hepatitis

Author

Vukotic, R., Conti, F., Fagiuoli, S., Morelli, M. C., Pasulo, L., Colpani, M., Foschi, F. G., Berardi, S., Pianta, P., Mangano, M., Donato, M. F., Malinverno, F., Monico, S., Tamè, M., Mazzella, G., Belli, L. S., Viganò, R., Carrai, P., Burra, P., Russo, F. P., Lenci, I., Toniutto, P., Merli, M., Loiacono, L., Iemmolo, R., Degli Antoni, A. M., Romano, A., Picciotto, A., Rendina, M., and Andreone, P.

Published
2017
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2. Aging and gallstone disease

Author

Lirussi, F., Nassuato, G., Passera, D., Toso, S., Iemmolo, R. M., Okolicsanyi, L., Capocaccia, L., editor, Ricci, G., editor, Angelico, F., editor, Angelico, M., editor, Attili, A. F., editor, and Lalloni, L., editor

Published
1991
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3. The Italian compassionate use of sofosbuvir in HCV patients waitlisted for liver transplantation: A national real-life experience

Author

Martini, S, Donato, M, Mazzarelli, C, Rendina, M, Visco-Comandini, U, Fili, D, Gianstefani, A, Fagiuoli, S, Melazzini, M, Montilla, S, Pani, L, Petraglia, S, Russo, P, Trotta, M, Carrai, P, Caraceni, P, Angeli, P, Ballardini, G, Bernabucci, V, Bhoori, S, Burra, P, Civolani, A, D'Offizi, G, Felder, M, Gaeta, G, Ganga, R, Ginanni Corradini, S, Iemmolo, R, Lenci, I, Lionetti, R, Montalbano, M, Morelli, M, Picciotto, A, Sapere, C, Serviddio, G, Tame, M, Verucchi, G, Zignego, A, Martini S., Donato M. F., Mazzarelli C., Rendina M., Visco-Comandini U., Fili D., Gianstefani A., Fagiuoli S., Melazzini M., Montilla S., Pani L., Petraglia S., Russo P., Trotta M. P., Carrai P., Caraceni P., Angeli P., Ballardini G., Bernabucci V., Bhoori S., Burra P., Civolani A., D'Offizi G., Felder M., Gaeta G. B., Ganga R., Ginanni Corradini S., Iemmolo R. M., Lenci I., Lionetti R., Montalbano M., Morelli M. C., Picciotto A., Sapere C., Serviddio G., Tame M., Verucchi G., Zignego A. L., Martini, S, Donato, M, Mazzarelli, C, Rendina, M, Visco-Comandini, U, Fili, D, Gianstefani, A, Fagiuoli, S, Melazzini, M, Montilla, S, Pani, L, Petraglia, S, Russo, P, Trotta, M, Carrai, P, Caraceni, P, Angeli, P, Ballardini, G, Bernabucci, V, Bhoori, S, Burra, P, Civolani, A, D'Offizi, G, Felder, M, Gaeta, G, Ganga, R, Ginanni Corradini, S, Iemmolo, R, Lenci, I, Lionetti, R, Montalbano, M, Morelli, M, Picciotto, A, Sapere, C, Serviddio, G, Tame, M, Verucchi, G, Zignego, A, Martini S., Donato M. F., Mazzarelli C., Rendina M., Visco-Comandini U., Fili D., Gianstefani A., Fagiuoli S., Melazzini M., Montilla S., Pani L., Petraglia S., Russo P., Trotta M. P., Carrai P., Caraceni P., Angeli P., Ballardini G., Bernabucci V., Bhoori S., Burra P., Civolani A., D'Offizi G., Felder M., Gaeta G. B., Ganga R., Ginanni Corradini S., Iemmolo R. M., Lenci I., Lionetti R., Montalbano M., Morelli M. C., Picciotto A., Sapere C., Serviddio G., Tame M., Verucchi G., and Zignego A. L.

Abstract

Background & Aims: This study aimed to assess the real-life clinical and virological outcomes of HCV waitlisted patients for liver transplantation (LT) who received sofosbuvir/ribavirin (SOF/R) within the Italian compassionate use program. Methods: Clinical and virological data were collected in 224 patients with decompensated cirrhosis and/or hepatocellular carcinoma (HCC) receiving daily SOF/R until LT or up a maximum of 48 weeks. Results: Of 100 transplanted patients, 51 were HCV-RNA negative for >4 weeks before LT (SVR12: 88%) and 49 negative for <4 weeks or still viraemic at transplant: 34 patients continued treatment after LT (bridging therapy) (SVR12: 88%), while 15 stopped treatment (SVR12: 53%). 98 patients completed SOF/R without LT (SVR12: 73%). In patients with advanced decompensated cirrhosis (basal MELD ≥15 and/or C-P ≥B8), a marked improvement of the scores occurred in about 50% of cases and almost 20% of decompensated patients without HCC reached a condition suitable for inactivation and delisting. Conclusions: These real-life data indicate that in waitlisted patients: (i) bridging antiviral therapy can be an option for patients still viraemic or negative <4 weeks at LT; and (ii) clinical improvement to a condition suitable for delisting can occur even in patients with advanced decompensated cirrhosis.

Published
2018

7. Long-term outcomes of direct acting antivirals in post-transplant advanced hepatitis C virus recurrence and fibrosing cholestatic hepatitis

Author

Vukotic, R, Conti, F, Fagiuoli, S, Morelli, M, Pasulo, L, Colpani, M, Foschi, F, Berardi, S, Pianta, P, Mangano, M, Donato, M, Malinverno, F, Monico, S, Tame, M, Mazzella, G, Belli, L, Vigano, R, Carrai, P, Burra, P, Russo, F, Lenci, I, Toniutto, P, Merli, M, Loiacono, L, Iemmolo, R, Degli Antoni, A, Romano, A, Picciotto, A, Rendina, M, Andreone, P, Vukotic R., Conti F., Fagiuoli S., Morelli M. C., Pasulo L., Colpani M., Foschi F. G., Berardi S., Pianta P., Mangano M., Donato M. F., Malinverno F., Monico S., Tame M., Mazzella G., Belli L. S., Vigano R., Carrai P., Burra P., Russo F. P., Lenci I., Toniutto P., Merli M., Loiacono L., Iemmolo R., Degli Antoni A. M., Romano A., Picciotto A., Rendina M., Andreone P., Vukotic, R, Conti, F, Fagiuoli, S, Morelli, M, Pasulo, L, Colpani, M, Foschi, F, Berardi, S, Pianta, P, Mangano, M, Donato, M, Malinverno, F, Monico, S, Tame, M, Mazzella, G, Belli, L, Vigano, R, Carrai, P, Burra, P, Russo, F, Lenci, I, Toniutto, P, Merli, M, Loiacono, L, Iemmolo, R, Degli Antoni, A, Romano, A, Picciotto, A, Rendina, M, Andreone, P, Vukotic R., Conti F., Fagiuoli S., Morelli M. C., Pasulo L., Colpani M., Foschi F. G., Berardi S., Pianta P., Mangano M., Donato M. F., Malinverno F., Monico S., Tame M., Mazzella G., Belli L. S., Vigano R., Carrai P., Burra P., Russo F. P., Lenci I., Toniutto P., Merli M., Loiacono L., Iemmolo R., Degli Antoni A. M., Romano A., Picciotto A., Rendina M., and Andreone P.

Abstract

Long-term functional outcomes of sofosbuvir-based antiviral treatment were evaluated in a cohort study involving 16 Italian centres within the international compassionate use programme for post-transplant hepatitis C virus (HCV) recurrence. Seventy-three patients with cirrhosis (n=52) or fibrosing cholestatic hepatitis (FCH, n=21) received 24-week sofosbuvir with ribavirin±pegylated interferon or interferon-free sofosbuvir-based regimen with daclatasvir/simeprevir+ribavirin. The patients were observed for a median time of 103 (82-112) weeks. Twelve of 73 (16.4%) died (10 non-FCH, 2 FCH) and two underwent re-LT. Sustained virological response was achieved in 46 of 66 (69.7%): 31 of 47 (66%) non-FCH and 15 of 19 (79%) FCH patients. All relapsers were successfully retreated. Comparing the data of baseline with last follow-up, MELD and Child-Turcotte-Pugh scores improved both in non-FCH (15.3±6.5 vs 10.5±3.8, P<.0001 and 8.4±2.1 vs 5.7±1.3, P<.0001, respectively) and FCH (17.3±5.9 vs 10.1±2.8, P=.001 and 8.2±1.6 vs 5.5±1, P=.001, respectively). Short-treatment mortality was higher in patients with baseline MELD≥25 than in those with MELD<25 (42.9% vs 4.8%, P=.011). Long-term mortality was 53.3% among patients with baseline MELD≥20 and 7.5% among those with MELD<20 (P<.0001). Among deceased patients 75% were Child-Turcotte-Pugh class C at baseline, while among survivors 83.9% were class A or B (P<.0001). Direct acting antivirals-based treatments for severe post-transplant hepatitis C recurrence, comprising fibrosing cholestatic hepatitis, significantly improve liver function, even without viral clearance and permit an excellent long-term survival. The setting of severe HCV recurrence may require the identification of “too-sick-to-treat patients” to avoid futile treatments.

Published
2017

8. The Italian compassionate use of sofosbuvir observational cohort study for the treatment of recurrent hepatitis C: clinical and virological outcomes

Author

Carrai, P, Morelli, C, Cordone, G, Romano, A, Tame, M, Lionetti, R, Pietrosi, G, Lenci, I, Piai, G, Russo, F, Coppola, C, Melazzini, M, Montilla, S, Pani, L, Petraglia, S, Russo, P, Trotta, M, Martini, S, Toniutto, P, Bandiera, F, Bhoori, S, Brillanti, S, Burra, P, Corsale, S, De Luca, A, Fagiuoli, S, Fattovich, G, Fava, G, Felder, M, Forte, P, Galeota-Lanza, A, Gitto, S, Grieco, A, Grossi, P, Ialungo, A, Iemmolo, R, Loiacono, L, Mangia, A, Merli, M, Piacentini, A, Pellicelli, A, Rigamonti, C, Gabriella, V, Zignego, A, Carrai P., Morelli C., Cordone G., Romano A., Tame M., Lionetti R., Pietrosi G., Lenci I., Piai G., Russo F. P., Coppola C., Melazzini M., Montilla S., Pani L., Petraglia S., Russo P., Trotta M. P., Martini S., Toniutto P., Bandiera F., Bhoori S., Brillanti S., Burra P., Corsale S., De Luca A., Fagiuoli S., Fattovich G., Fava G., Felder M., Forte P., Galeota-Lanza A., Gitto S., Grieco A., Grossi P., Ialungo A. M., Iemmolo R. M., Loiacono L., Mangia A., Merli M., Piacentini A., Pellicelli A., Rigamonti C., Gabriella V., Zignego A. L., Carrai, P, Morelli, C, Cordone, G, Romano, A, Tame, M, Lionetti, R, Pietrosi, G, Lenci, I, Piai, G, Russo, F, Coppola, C, Melazzini, M, Montilla, S, Pani, L, Petraglia, S, Russo, P, Trotta, M, Martini, S, Toniutto, P, Bandiera, F, Bhoori, S, Brillanti, S, Burra, P, Corsale, S, De Luca, A, Fagiuoli, S, Fattovich, G, Fava, G, Felder, M, Forte, P, Galeota-Lanza, A, Gitto, S, Grieco, A, Grossi, P, Ialungo, A, Iemmolo, R, Loiacono, L, Mangia, A, Merli, M, Piacentini, A, Pellicelli, A, Rigamonti, C, Gabriella, V, Zignego, A, Carrai P., Morelli C., Cordone G., Romano A., Tame M., Lionetti R., Pietrosi G., Lenci I., Piai G., Russo F. P., Coppola C., Melazzini M., Montilla S., Pani L., Petraglia S., Russo P., Trotta M. P., Martini S., Toniutto P., Bandiera F., Bhoori S., Brillanti S., Burra P., Corsale S., De Luca A., Fagiuoli S., Fattovich G., Fava G., Felder M., Forte P., Galeota-Lanza A., Gitto S., Grieco A., Grossi P., Ialungo A. M., Iemmolo R. M., Loiacono L., Mangia A., Merli M., Piacentini A., Pellicelli A., Rigamonti C., Gabriella V., and Zignego A. L.

Abstract

Direct antivirals are available for treating recurrent hepatitis C (RHC). This study reported outcomes of 424 patients with METAVIR F3–F4 RHC who were treated for 24 weeks with sofosbuvir/ribavirin and followed for 12 weeks within the Italian sofosbuvir compassionate use program. In 55 patients, daclatasvir or simeprevir were added. Child–Pugh class and model of end stage liver disease (MELD) scores were evaluated at baseline and 36 weeks after the start of therapy. The sustained viral response (SVR) was 86.7% (316/365) in patients who received sofosbuvir/ribavirin and 98.3% (58/59) in patients who received a second antiviral (P < 0.01). In patients treated with sofosbuvir/ribavirin, a significant difference in SVR was observed between patients diagnosed with METAVIR F4 (211/250; 84.4%), METAVIR F3 (95/105; 90.5%) and fibrosing cholestatic hepatitis (10/10; 100%) (P = 0.049). A significant association was found between patients who worsened from Child–Pugh class A and who experienced viral relapse (4/26 vs. 8/189, P = 0.02). In patients with a baseline MELD score <15, a significant association was found between maintaining a final MELD score <15 and the achievement of SVR (187/219 vs. 6/10, P = 0.031). This real-world study indicates that sofosbuvir/ribavirin treatment for 24 weeks was effective, and the achievement of SVR was associated with a reduced probability of developing worsening liver function.

Published
2017

9. Prevention of hepatitis C recurrence by bridging sofosbuvir/ribavirin from pre- to post-liver transplant: A real-life strategy

Author

Donato, M. F., Morelli, C., Romagnoli, R., Invernizzi, F., Mazzarelli, C., Iemmolo, R. M., Montalbano, M., Lenci, I., Bhoori, S., Pieri, G., Berardi, S., Caraceni, P., Martini, S., Angeli, P., Belli, L. S., Bernabucci, V., Malinverno, F., Monico, S., Ottobrelli, A., Romano, A., Strona, S., Tame, M. R., Visco-Comandini, U., Cavenago, M., De Carlis, L., Di Benedetto, F., Dondossola, D., Ettorre, G. M., Mazzaferro, V., Montin, U., Pinna, A. D., Rossi, G., Salizzoni, M., Tisone, G., Donato, Maria Francesca, Morelli, Cristina, Romagnoli, Renato, Invernizzi, Federica, Mazzarelli, Chiara, Iemmolo, Rosa Maria, Montalbano, Marzia, Lenci, Ilaria, Bhoori, Sherrie, Pieri, Giulia, Berardi, Sonia, Caraceni, Paolo, Martini, Silvia, Donato, M, Morelli, C, Romagnoli, R, Invernizzi, F, Mazzarelli, C, Iemmolo, R, Montalbano, M, Lenci, I, Bhoori, S, Pieri, G, Berardi, S, Caraceni, P, Martini, S, Angeli, P, Belli, L, Bernabucci, V, Malinverno, F, Monico, S, Ottobrelli, A, Romano, A, Strona, S, Tamè, M, Visco-Comandini, U, Cavenago, M, De Carlis, L, Di Benedetto, F, Dondossola, D, Ettorre, G, Mazzaferro, V, Montin, U, Pinna, A, Rossi, G, Salizzoni, M, and Tisone, G

Subjects
Liver Cirrhosis, Male, Sofosbuvir, Sustained Virologic Response, Hepatocellular carcinoma, medicine.medical_treatment, Hepacivirus, Liver transplantation, medicine.disease_cause, hepatitis C, hepatocellular carcinoma, liver transplant, sofosbuvir therapy, virological response, Adult, Aged, Antiviral Agents, Carcinoma, Hepatocellular, Drug Therapy, Combination, Female, Hepatitis C, Humans, Italy, Liver Neoplasms, Middle Aged, Postoperative Period, Preoperative Period, Recurrence, Retrospective Studies, Ribavirin, Liver Transplantation, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Sofosbuvir therapy, Retrospective Studie, Liver transplant, Virological response, Liver Neoplasm, 030220 oncology & carcinogenesis, Combination, 030211 gastroenterology & hepatology, Viral hepatitis, Human, medicine.drug, medicine.medical_specialty, Liver Cirrhosi, Hepatitis C virus, 03 medical and health sciences, Hepatology, Drug Therapy, Internal medicine, medicine, Antiviral Agent, Hepaciviru, business.industry, Carcinoma, Hepatocellular, medicine.disease, Settore MED/18, Surgery, Regimen, chemistry, business
Abstract

Background and aims Hepatitis C virus (HCV) reinfection following liver transplant (LT) is associated with reduced graft and patients survival. Before transplant, Sofosbuvir/Ribavirin (SOF/R) treatment prevents recurrent HCV in 96% of those patients achieving viral suppression for at least 4 weeks before transplant. We evaluated whether a bridging SOF-regimen from pre to post-transplant is safe and effective to prevent HCV recurrence in those patients with less than 4 week HCV-RNA undetectability at the time of transplant. Material and Methods From July 2014 SOF/R was given in 233 waitlisted HCV cirrhotics with/without hepatocellular carcinoma (HCC) within an Italian Compassionate Program. One-hundred were transplanted and 31 patients (31%) treated by SOF/R bridging therapy were studied Results LT indication in bridge subgroup was HCC in 22 and decompensated cirrhosis in 9. HCV-genotype was 1/4 in 18 patients. SOF 400 mg/day and R (median dosage 800 mg/day) were given for a median of 35 days before LT. At transplant time, 19 patients were still HCV-RNA positive (median HCV-RNA 58 IU/ml). One recipient had a virological breakthrough at week 4 post-transplant; one died, on treatment, 1-month post-transplant for sepsis and 29/31 achieved a 12-week sustained virological response (94%). Acute cellular rejection occurred in 4 recipients. On September 2016, 30 recipients (97%) are alive with a median follow-up of 18 months (range 13-25). Conclusions In patients with suboptimal virological response at LT a bridging SOF/R regimen helps avoiding post-transplant graft reinfection. This article is protected by copyright. All rights reserved.

Published
2017

13. Prevalent use of Combined Prophylaxis of Hepatitis B after liver transplantation in Italy: Results of a national survey in a large cohort

Author

Marzano, A, Andreone, P, Boccagni, P, Burra, P, Caneschi, F, Conoscitore, P, Coppola, C, De Carlis, L, Fagiuoli, S, Forte, P, Gaeta, G, Iemmolo, R, Suffredini, A, Mazzola, M, Merli, M, Parrilli, G, Piai, G, Piras, M, Salizzoni, M, Tamè, M, Tisone, G, Toniutto, P, Vennarecci, G, Volpes, R, Zamboni, F, Caccamo, L, Bertuzzo, V, Bongiovanni, A, Brin-Dicci, G, Cocchis, D, Ettorre, G, Gianni, E, Giusto, M, Lenisa, I, Lucà, M, Mameli, L, Mangoni, I, Manini, M, Paoli, S, Russo, F, Staiano, L, Stornaiuolo, G, Toti, L, Valente, G, Vukotic, R, Marzano, Alfredo, Andreone, Pietro, Boccagni, Patrizia, Burra, Patrizia, Caneschi, Francesco, Conoscitore, Pasquale F., Coppola, Carmine, De Carlis, Luciano, Fagiuoli, Stefano, Forte, Paolo, Gaeta, Giovanni B., Iemmolo, Rosa M., Suffredini, Anna Lotti, Mazzola, Michele, Merli, Manuela, Parrilli, Gianpaolo, Piai, Guido, Piras, Maria R., Salizzoni, Mauro, Tamè, Mariarosa, Tisone, Giuseppe, Toniutto, Pierluigi, Vennarecci, Giovanni, Volpes, Riccardo, Zamboni, Fausto, Caccamo, Lucio, Bertuzzo, Valentina R., Bongiovanni, Assunta S., Brin-Dicci, Gaetano, Cocchis, Donatella, Ettorre, Giuseppe M., Gianni, Elena, Giusto, Michela, Lenisa, Ilaria, Lucà, Maria G., Mameli, Laura, Mangoni, Iacopo, Manini, Matteo A., Paoli, Serena, Russo, Francesco P., Staiano, Laura, Stornaiuolo, Gianfranca, Toti, Luca, Valente, Giovanna, Vukotic, Ranka, Marzano, A, Andreone, P, Boccagni, P, Burra, P, Caneschi, F, Conoscitore, P, Coppola, C, De Carlis, L, Fagiuoli, S, Forte, P, Gaeta, G, Iemmolo, R, Suffredini, A, Mazzola, M, Merli, M, Parrilli, G, Piai, G, Piras, M, Salizzoni, M, Tamè, M, Tisone, G, Toniutto, P, Vennarecci, G, Volpes, R, Zamboni, F, Caccamo, L, Bertuzzo, V, Bongiovanni, A, Brin-Dicci, G, Cocchis, D, Ettorre, G, Gianni, E, Giusto, M, Lenisa, I, Lucà, M, Mameli, L, Mangoni, I, Manini, M, Paoli, S, Russo, F, Staiano, L, Stornaiuolo, G, Toti, L, Valente, G, Vukotic, R, Marzano, Alfredo, Andreone, Pietro, Boccagni, Patrizia, Burra, Patrizia, Caneschi, Francesco, Conoscitore, Pasquale F., Coppola, Carmine, De Carlis, Luciano, Fagiuoli, Stefano, Forte, Paolo, Gaeta, Giovanni B., Iemmolo, Rosa M., Suffredini, Anna Lotti, Mazzola, Michele, Merli, Manuela, Parrilli, Gianpaolo, Piai, Guido, Piras, Maria R., Salizzoni, Mauro, Tamè, Mariarosa, Tisone, Giuseppe, Toniutto, Pierluigi, Vennarecci, Giovanni, Volpes, Riccardo, Zamboni, Fausto, Caccamo, Lucio, Bertuzzo, Valentina R., Bongiovanni, Assunta S., Brin-Dicci, Gaetano, Cocchis, Donatella, Ettorre, Giuseppe M., Gianni, Elena, Giusto, Michela, Lenisa, Ilaria, Lucà, Maria G., Mameli, Laura, Mangoni, Iacopo, Manini, Matteo A., Paoli, Serena, Russo, Francesco P., Staiano, Laura, Stornaiuolo, Gianfranca, Toti, Luca, Valente, Giovanna, and Vukotic, Ranka

Abstract

BACKGROUND: Prophylaxis of hepatitis B after liver transplantation with antiviral(s) and immunoglobulins effciently protect the majority of recipients; however recent experiences suggest a decline of HBsag-positive candidates and the use of hepatitis B immunoglobulin-free schedules. MetHoDs: this national survey evaluated the epidemiology and clinical results of hepatitis B prophylaxis among 10,365 liver transplants performed in 25 years in 13 italian centers. RESULTS: With a percentage of 22, 2260 procedures were performed in HBsAg-positive recipients and 714 out of 1080 anti-HBc-positive grafts were used in HBsag-negative recipients; a total of 2974 patients (29%) were considered at risk of hepatitis B after liver transplantation. similar rates (18% of HBsag-positive candidates and 15% of anti-HBc-positive grafts) were registered in the last collected year. combined prophylaxis with Hepatitis B immunoglobulins remained prevalent among centers and was effective in 96% of HBsag-positive recipients and in 94% of HBsag-negative recipients of anti-HBc-positive grafts. CONCLUSIONS: Data from this survey confrm: the excellent results of combined prophylaxis; the past and persistent use of Hepatitis B immunoglobulin-on and only rare-off prophylactic regimens, in contrast with the newest reports; the increasing use of anti-HBc-positive grafts; the past and present high prevalence of HBsag-positive recipients, due to an increase in candidates with either hepatocellular carcinoma and Hepatitis Delta Virus coinfection in the last years

Published
2018

14. Prevention of hepatitis C recurrence by bridging sofosbuvir/ribavirin from pre- to post-liver transplant: A real-life strategy

Author

Donato, M, Morelli, C, Romagnoli, R, Invernizzi, F, Mazzarelli, C, Iemmolo, R, Montalbano, M, Lenci, I, Bhoori, S, Pieri, G, Berardi, S, Caraceni, P, Martini, S, Angeli, P, Belli, L, Bernabucci, V, Malinverno, F, Monico, S, Ottobrelli, A, Romano, A, Strona, S, Tamè, M, Visco-Comandini, U, Cavenago, M, De Carlis, L, Di Benedetto, F, Dondossola, D, Ettorre, G, Mazzaferro, V, Montin, U, Pinna, A, Rossi, G, Salizzoni, M, Tisone, G, Donato, Maria Francesca, Morelli, Cristina, Romagnoli, Renato, Invernizzi, Federica, Mazzarelli, Chiara, Iemmolo, Rosa Maria, Montalbano, Marzia, Lenci, Ilaria, Bhoori, Sherrie, Pieri, Giulia, Berardi, Sonia, Caraceni, Paolo, Martini, Silvia, Angeli, Paolo, Belli, Luca Saverio, Bernabucci, Veronica, Malinverno, Federica, Monico, Sara, Ottobrelli, Antonio, Romano, Antonietta, Strona, Silvia, Tamè, Maria Rosa, Visco-Comandini, Ubaldo, Cavenago, Margherita, De Carlis, Luciano, Di Benedetto, Fabrizio, Dondossola, Daniele, Ettorre, Giuseppe Maria, Mazzaferro, Vincenzo, Montin, Umberto, Pinna, Antonio Daniele, Rossi, Giorgio, Salizzoni, Mauro, Tisone, Giuseppe, Donato, M, Morelli, C, Romagnoli, R, Invernizzi, F, Mazzarelli, C, Iemmolo, R, Montalbano, M, Lenci, I, Bhoori, S, Pieri, G, Berardi, S, Caraceni, P, Martini, S, Angeli, P, Belli, L, Bernabucci, V, Malinverno, F, Monico, S, Ottobrelli, A, Romano, A, Strona, S, Tamè, M, Visco-Comandini, U, Cavenago, M, De Carlis, L, Di Benedetto, F, Dondossola, D, Ettorre, G, Mazzaferro, V, Montin, U, Pinna, A, Rossi, G, Salizzoni, M, Tisone, G, Donato, Maria Francesca, Morelli, Cristina, Romagnoli, Renato, Invernizzi, Federica, Mazzarelli, Chiara, Iemmolo, Rosa Maria, Montalbano, Marzia, Lenci, Ilaria, Bhoori, Sherrie, Pieri, Giulia, Berardi, Sonia, Caraceni, Paolo, Martini, Silvia, Angeli, Paolo, Belli, Luca Saverio, Bernabucci, Veronica, Malinverno, Federica, Monico, Sara, Ottobrelli, Antonio, Romano, Antonietta, Strona, Silvia, Tamè, Maria Rosa, Visco-Comandini, Ubaldo, Cavenago, Margherita, De Carlis, Luciano, Di Benedetto, Fabrizio, Dondossola, Daniele, Ettorre, Giuseppe Maria, Mazzaferro, Vincenzo, Montin, Umberto, Pinna, Antonio Daniele, Rossi, Giorgio, Salizzoni, Mauro, and Tisone, Giuseppe

Abstract

Background & Aims: Hepatitis C virus (HCV) re-infection following liver transplant (LT) is associated with reduced graft and patient survival. Before transplant, Sofosbuvir/ Ribavirin (SOF/R) treatment prevents recurrent HCV in 96% of those patients achieving viral suppression for at least 4 weeks before transplant. We evaluated whether a bridging SOF-regimen from pre- to post-transplant is safe and effective to prevent HCV recurrence in those patients with less than 4 weeks of HCV-RNA undetectability at the time of transplant. Methods: From July 2014 SOF/R was given in 233 waitlisted HCV cirrhotics with/ without hepatocellular carcinoma (HCC) within an Italian Compassionate Program. One hundred patients were transplanted and 31 patients (31%) treated with SOF/R bridging therapy were studied. Results: Liver transplant indication in bridge subgroup was HCC in 22 and decompensated cirrhosis in 9. HCV-genotype was 1/4 in 18 patients. SOF 400 mg/day and R (median dosage 800 mg/day) were given for a median of 35 days before LT. At transplant time, 19 patients were still HCV-RNA positive (median HCV-RNA 58 IU/mL). One recipient had a virological breakthrough at week 4 post-transplant; one died, on treatment, 1-month post-transplant for sepsis and 29/31 achieved a 12-week sustained virological response (94%). Acute cellular rejection occurred in three recipients. On September 2016, 30 recipients (97%) were alive with a median follow-up of 18 months (range 13-25). Conclusions: In patients with suboptimal virological response at LT, a bridging SOF/R regimen helps avoiding post-transplant graft reinfection.

Published
2017

16. Treatment of hepatitis C recurrence is less successful in female than in male liver transplant recipients

Author

Giannelli, V, Giusto, M, Farcomeni, A, Ponziani, F, Pompili, M, Viganò, R, Iemmolo, R, Donato, M, Rendina, M, Toniutto, P, Pasulo, L, Morelli, M, De Martin, E, Miglioresi, L, DI PAOLO, D, Fagiuoli, S, Merli, M, Belli, L, Gerunda, G, Montalti, R, Di Benedetto, F, De Ruvo, N, Rigamonti, C, Colombo, M, Rossi, G, Fornasiere, E, Di Leo, A, Castellaneta, N, Lupo, L, Nemeo, V, Bringiotti, R, Zappimbulso, M, Vero, V, Colpani, M, Cescon, M, Bertuzzo, V, Pinna, A, Visco Comandini, U, Antonucci, G, Ettorre, G, Burra, P, Senzolo, M, Ginanni, C, Mennini, G, Rossi, M, Angelico, M, Tisone, G, Gasbarrini, A, Giannelli, V, Giusto, M, Farcomeni, A, Ponziani, F, Pompili, M, Viganò, R, Iemmolo, R, Donato, M, Rendina, M, Toniutto, P, Pasulo, L, Morelli, M, De Martin, E, Miglioresi, L, Di Paolo, D, Fagiuoli, S, Merli, M, Giannelli, Valerio, Giusto, Michela, Farcomeni, Alessio, Ponziani, Francesca R, Pompili, Maurizio, Viganò, Raffaella, Iemmolo, Rosa Maria, Donato, Maria F, Rendina, Maria, Toniutto, Pierluigi, Pasulo, Luisa, Morelli, Maria Cristina, De Martin, Eleonora, Miglioresi, Lucia, Di Paolo, Daniele, Fagiuoli, Stefano, Merli, Manuela, Montalti, Roberto, Giannelli V., Giusto M., Farcomeni A., Ponziani F.R., Pompili M., Viganò R., Iemmolo R.M., Donato M.F., Rendina M., Toniutto P., Pasulo L., Morelli M.C., De Martin E., Miglioresi L., Di Paolo D., Fagiuoli S., Merli M., Belli L., Gerunda G.E., Montalti R., Di Benedetto F., De Ruvo N., Rigamonti C., Colombo M., Rossi G., Fornasiere E., Di Leo A., Castellaneta N.M., Lupo L., Nemeo V., Bringiotti R., Zappimbulso M., Vero V., Colpani M., Cescon M., Bertuzzo V., Pinna A.D., Visco-Comandini U., Antonucci G., Ettorre G.M., Burra P., Senzolo M., Ginanni C.S., Mennini G., Rossi M., Angelico M., Tisone G., and Gasbarrini A.

Subjects
Adult, Male, antiviral treatment, Sex Factor, Hepacivirus, Polyethylene Glycol, Antiviral Agents, Settore MED/01 - Statistica Medica, Polyethylene Glycols, Sex Factors, INTERFERON THERAPY, Retrospective Studie, Recurrence, Ribavirin, gender, Humans, adherence, HCV, liver transplant, hepatitis c, Aged, Retrospective Studies, Antiviral Agent, Settore MED/12 - Gastroenterologia, Hepaciviru, liver transplantation, Settore MED/09 - MEDICINA INTERNA, HCV recurrence, liver transplantation, virus diseases, HEPATITIS C VIRUS, Interferon-alpha, Hepatitis C, Chronic, Middle Aged, Viral Load, hcv, hepatitis c virus, digestive system diseases, Liver Transplantation, Treatment Outcome, Patient Compliance, RNA, Viral, Female, HCV recurrence, Human
Abstract

It has been recently suggested that the risk of graft loss after liver transplantation (LT) may increase in female HCV patients. The aim of the study was to examine gender differences in HCV therapy tolerance and outcome in LT patients treated for HCV recurrence. A retrospective study was conducted on liver recipients with HCV recurrence, who were given antiviral therapy from 2001 to 2009 in 12 transplant centers in Italy. Sustained virological response (SVR), adherence-to-therapy, and side effects were evaluated. A multivariate logistic regression model was used after adjusting for possible confounders. The data regarding 342 treated patients were analyzed. SVR was reported in 38.8% of patients. At baseline, male and female did not differ in HCV viral load, histology, or rate of diabetes. SVR was lower in females than in males (29.5% vs. 42.1%; P=0.03). Adherence-to-therapy was also lower in females than in males 43.4% vs. 23.8%; P=0.001); anemia was the main reason for lower adherence. In a multivariate analysis in patients Genotype1, female gender (P

Published
2012

17. The Persistence of HCV Replication Is Associated with an Increased Mortality Rate in HCV Recurrent Transplant Patients: Results from the AISF-RECOLT-C Group

Author

Rendina, M., Castellaneta, N. M., Fagiuoli, Stefano, Ponziani, F., Vigano, R., Iemmolo, R. M., Donato, M. F., Toniutto, P., Pasulo, L., Morelli, M. C., Burra, Patrizia, Miglioresi, L., Giannelli, V., Paolo, D. D., Leo, A. D., Rendina, M, Castellaneta, N, Fagiuoli, S, Ponziani, F, Vigano, R, Iemmolo, R, Donato, M, Toniutto, P, Pasulo, L, Morelli, M, Burra, P, Miglioresi, L, Giannelli, V, Paolo, D, and Leo, A

Subjects
HCV replication, mortality, transplant patients
Published
2011

18. Cirrosi Biliare Primitiva

Author

Iemmolo, R. M., Fabris, Luca, Cadamuro, Massimiliano, Strazzabosco, M., Okolicsanyi, L, Peracchia, A, Roncoroni, L, Iemmolo, R, Fabris, L, Cadamuro, M, and Strazzabosco, M

Subjects
MED/12 - GASTROENTEROLOGIA, fegato, infiammazione, Cirrosi Biliare Primitiva
Published
2008

20. Recipient female gender is a risk factor for graft loss after liver transplantation for chronic hepatitis C: Evidence from the prospective Liver Match cohort

Author

Belli, L, Romagnoli, R, Nardi, A, Marianelli, T, Donato, F, Corradini, S, Iemmolo, R, Morelli, C, Pasulo, L, Rendina, M, De Martin, E, Ponziani, F, Volpes, R, Strazzabosco, M, Angelico, M, STRAZZABOSCO, MARIO, ANGELICO, MARIO, Belli, L, Romagnoli, R, Nardi, A, Marianelli, T, Donato, F, Corradini, S, Iemmolo, R, Morelli, C, Pasulo, L, Rendina, M, De Martin, E, Ponziani, F, Volpes, R, Strazzabosco, M, Angelico, M, STRAZZABOSCO, MARIO, and ANGELICO, MARIO

Abstract

Background: Female gender has been reported to be a risk factor for graft loss after liver transplantation for hepatitis C virus (HCV)-related cirrhosis but evidence is limited to retrospective studies. Aims: To investigate the impact of recipient gender and donor/recipient gender mismatch on graft outcome. Methods: We performed a survival analysis of a cohort of 1530 first adult transplants enrolled consecutively in Italy between 2007 and 2009 and followed prospectively. After excluding possible confounding factors (fulminant hepatitis, human immunodeficiency virus co-infection, non-viremic anti-HCV positive subjects), a total of 1394 transplant recipients (604 HCV-positive and 790 HCV-negative) were included. Results: Five-year graft survival was significantly reduced in HCV-positive patients (64% vs 76%, p= 0.0002); Cox analysis identified recipient female gender (HR = 1.44, 95% CI 1.03-2.00, p= 0.0319), Mayo clinic End stage Liver Disease score (every 10 units, HR = 1.25, 95% CI 1.03-1.50; p= 0.022), portal thrombosis (HR = 2.40, 95% CI 1.20-4.79, p= 0.0134) and donor age (every 10 years, HR = 1.14, 95% CI 1.05-1.24, p= 0.0024) as independent determinants of graft loss. All additional mortality observed among female recipients was attributable to severe HCV recurrence. Conclusions. This study unequivocally shows that recipient female gender unfavourably affects the outcome of HCV-infected liver grafts.

Published
2015

21. From meetings

Author

Arias, I. M., Jezequel, A. M., Berg, P. A., Gatta, A., Angeli, P., Galanti, B., Gaeta, G. B., Gallo, C., Giusti, G., Pourcel, C., Zignego, A. L., Bréchot, C., Cantley, L., Rizzetto, M., Mazzanti, R., Moscarella, S., Gentilini, P., Buzzelli, G., Smorlesi, C., Dattolo, P., Focardi, G. P., Laffi, G., Meacci, E., Marra, F., Gentilini, P., Reynolds, T. B., Arroyo, V., Haupert, G. T., Gerbes, A. L., Gentilini, P., Varticovski, L., Villari, N., Bartoletti, S., Strazzabosco, M., Muraca, M., Venuti, M., Varotto, A., Iemmolo, R. M., Fragasso, A., Passera, D., Okolicsanyi, L., Capocaccia, L., Ariosto, F., Merli, M., Riggio, O., Romiti, A., Pagliaro, L., D’Amico, G., Traina, M., Montalbano, L., Gatto, G., Pisa, R., Maisano, S., Politi, F., Colletti, P., Tiné, F., Barbara, L., Corinaldesi, R., De Giorgio, R., Stanghellini, V., Scuro, L. A., Vantini, I., Dobrilla, G., Amplatz, S., Naccarato, R., Di Mario, F., Blasi, A., Mangiameli, A., Bianchi Porro, G., Petrillo, M., Forgac, M. D., Donowitz, M., Rood, R. P., Wesolek, J. H., Emmer, E., Cohen, M., McCullen, J., Braithwaite, R. S., Sharp, G. W. G., Murer, H., Ward, H. D., and Pereira, M. E. A.

Published
1988
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24. Fibrosis Progression in Non Responders to Antiviral Treatment (AT) in HCV Recurrence Following Liver Transplantation (LT): An Italian Multicenter Retrospective Study

Author

DE MARTIN, Eleonora, Senzolo, Marco, Francesca, P. R., Pasulo, L., Vigano, R., Belli, L., Donato, F., Angelico, M., Paolo, D. D., Rendina, M., Miglioresi, L., Grazi, G. L., Morelli, M., Toniutto, P., Merli, M., Giannelli, V., Castellaneta, N. M., Marino, M., Iemmolo, R. M., Gerunda, G. E., Villa, E., Gasbarrini, A., Fagiuoli, S., and Burra, Patrizia

Published
2010

29. Treatment of genotype-1 hepatitis C recurrence after liver transplant improves survival in both sustained responders and relapsers

Author

Ponziani, F, Milani, A, Gasbarrini, A, Zaccaria, R, Viganò, R, Iemmolo, R, Donato, M, Rendina, M, Toniutto, P, Pasulo, L, Cescon, M, Burra, P, Miglioresi, L, Merli, M, Paolo, D, Fagiuoli, S, Pompili, M, Ponziani FR, Milani A, Gasbarrini A, Zaccaria R, Viganò R, Iemmolo RM, Donato MF, Rendina M, Toniutto P, Pasulo L, Cescon M, Burra P, Miglioresi L, Merli M, Paolo DD, Fagiuoli S, Pompili M, Ponziani, F, Milani, A, Gasbarrini, A, Zaccaria, R, Viganò, R, Iemmolo, R, Donato, M, Rendina, M, Toniutto, P, Pasulo, L, Cescon, M, Burra, P, Miglioresi, L, Merli, M, Paolo, D, Fagiuoli, S, Pompili, M, Ponziani FR, Milani A, Gasbarrini A, Zaccaria R, Viganò R, Iemmolo RM, Donato MF, Rendina M, Toniutto P, Pasulo L, Cescon M, Burra P, Miglioresi L, Merli M, Paolo DD, Fagiuoli S, and Pompili M

Abstract

The aim of this study was to evaluate the factors affecting the response to treatment and how it could affect survival in a large series of genotype-1 HCV-transplanted patients. Three-hundred and twenty six genotype-1 HCV patients were enrolled. One hundred and ninety-six patients (60.1%) were nonresponders and 130 (39.9%) showed negative HCV-RNA at the end of treatment. Eighty-four of them (25.8%) achieved sustained virological response, while 46 (14.1%) showed viral relapse. Five-year cumulative survival was significantly worse in nonresponders (76.4%) compared with sustained viral response (93.2) or relapsers (94.9%). Sustained responders and relapsers were therefore considered as a single 'response group' in further analysis. Pretreatment variables significantly associated with virological response at multivariate regression analysis were the absence of ineffective pretransplant antiviral therapy, the recurrence of HCV-hepatitis more than 1 year after transplant, an histological grading ≥4 at pretreatment liver biopsy, a pretreatment HCV-RNA level <1.2 × 106IU/ml, and the absence of diabetes. As expected, also on-treatment variables (rapid and early virological response) were significantly associated to the response to antiviral treatment. In conclusion, this study shows that postliver transplant antiviral treatment results in beneficial effect on survival not only in sustained responders but also in relapsers.

Published
2013

30. Liver-kidney-transplantation in type 1 primary hyperoxaluria: description and comments on a case

Author

Giovanni Gambaro, Lidestri, V., Gerunda, G. E., Zavan, M. C., Iemmolo, R. M., Rigotti, P., Naso, A., Antonello, A., and D Angelo, A.

Subjects
Male, Adolescent, Hyperoxaluria, Primary, Humans, Kidney Failure, Chronic, Kidney Transplantation, Liver Transplantation
Abstract

Primary hyperoxaluria leads to oxalosis, a systemic illness with fatal prognosis in uremic youngsters because of systemic complications.A 14-year old boy with primary type 1 hyperoxaluria who had a long-lasting history of nephrolithiasis and passed from normal renal function to end-stage renal disease within 7 months. MEASUREMENT of alanine: glyoxylate aminotransferase (AGT) catalytic activity in the liver biopsy disclosed very low activity which was not. responsive to pyridoxin., thus the patient entered onto a priority national waiting list for liver-kidney transplantation and a week later received a combined transplant. In order to increase body clearance of oxalate, the patient underwent medical treatment to increase urine oxalate solubility (sodium and potassium citrate oral therapy, magnesium supplementation and increase of diuresis) and intensive dialysis both before and after transplantation.The medical approach to the treatment of this rare illness is discussed. Since the major risk for the grafted kidney is related to the oxalate burden, i.e. oxalate deposition from the body deposits to the kidney that becomes irreversibly damaged, treatment consists of increasing the body clearance of oxalate both by increasing oxalate solubility in the urine and with intensive dialysis performed both before and after combined transplantation. To the same extent (by limiting body oxalate deposits), a relatively early (native GFR 20-25 ml/minute) transplantation is advisable.

Published
2000

31. Prognostic value of EEG spectral analysis in cirrhotic patients

Author

Amodio, Piero, Petteno, E., Marchetti, P., DEL PICCOLO, Franco, Iemmolo, R. M., Destro, C., Casagrande, F., Angeli, Paolo, Gerunda, GIORGIO ENRICO, Montagnese, Sara, Pellegrini, Andrea, Musto, C., and Gatta, Angelo

Subjects
Liver cirrhosis, hepatic encephalopathy, Q-EEG
Published
2000

32. Prognostic value of hypozincemia in cirrhotic patients

Author

Amodio, Piero, Marchetti, P., DEL PICCOLO, Franco, Petteno, E., Angeli, Paolo, Craighero, R., Iemmolo, R., Casagrande, F., CAREGARO NEGRIN, Lorenza, Merkel, Carlo, Pellegrini, Andrea, and Gatta, Angelo

Subjects
zinc
Published
2000

33. The persistence of HCV replication is associated with an increased mortality rate in HCV recurrent transplant patients: Results from the AISF-RECOLT-C group

Author

Rendina, M, Castellaneta, N, Fagiuoli, S, Ponziani, F, Vigano, R, Iemmolo, R, Donato, M, Toniutto, P, Pasulo, L, Morelli, M, Burra, P, Miglioresi, L, Giannelli, V, Paolo, D, Leo, A, M. Rendina, N. M. Castellaneta, S. Fagiuoli, F. Ponziani, R. Vigano, R. M. Iemmolo, M. F. Donato, P. Toniutto, L. Pasulo, M. C. Morelli, P. Burra, L. Miglioresi, V. Giannelli, D. D. Paolo, A. D. Leo, Rendina, M, Castellaneta, N, Fagiuoli, S, Ponziani, F, Vigano, R, Iemmolo, R, Donato, M, Toniutto, P, Pasulo, L, Morelli, M, Burra, P, Miglioresi, L, Giannelli, V, Paolo, D, Leo, A, M. Rendina, N. M. Castellaneta, S. Fagiuoli, F. Ponziani, R. Vigano, R. M. Iemmolo, M. F. Donato, P. Toniutto, L. Pasulo, M. C. Morelli, P. Burra, L. Miglioresi, V. Giannelli, D. D. Paolo, and A. D. Leo

Published
2011

34. Acute and chronic rejection during interferon therapy in HCV recurrent transplant patients: Results from the AISF-RECOLT-C group

Author

Rendina, M, Castellaneta, N, Fagiuoli, S, Ponziani, F, Vigano, R, Iemmolo, R, Donato, M, Toniutto, P, Pasulo, L, Morelli, M, Burra, P, Miglioresi, L, Giannelli, V, Paolo, D, Leo, A, M. Rendina, N. M. Castellaneta, S. Fagiuoli, F. Ponziani, R. Vigano, R. M. Iemmolo, M. F. Donato, P. Toniutto, L. Pasulo, M. C. Morelli, P. Burra, L. Miglioresi, V. Giannelli, D. D. Paolo, A. D. Leo, Rendina, M, Castellaneta, N, Fagiuoli, S, Ponziani, F, Vigano, R, Iemmolo, R, Donato, M, Toniutto, P, Pasulo, L, Morelli, M, Burra, P, Miglioresi, L, Giannelli, V, Paolo, D, Leo, A, M. Rendina, N. M. Castellaneta, S. Fagiuoli, F. Ponziani, R. Vigano, R. M. Iemmolo, M. F. Donato, P. Toniutto, L. Pasulo, M. C. Morelli, P. Burra, L. Miglioresi, V. Giannelli, D. D. Paolo, and A. D. Leo

Published
2011

36. Svr To Antiviral Therapy Is Highly Protective Against Liver-related Death In Patients With Hcv Recurrence On the Graft After Liver Transplantation (lt)

Author

Rendina, M, Castellaneta, N, Fagiuoli, S, Burra, P, Vigano, R, Iemmolo, R, Donato, M, Toniutto, P, Pasulo, L, Morelli, M, Miglioresi, L, Merli, M, Angelico, M, Gasbarrini, A, Leo, A, M. Rendina, N. M. Castellaneta, S. Fagiuoli, P. Burra, R. Vigano, R. M. Iemmolo, M. F. Donato, P. Toniutto, L. Pasulo, M. C. Morelli, L. Miglioresi, M. Merli, M. Angelico, A. Gasbarrini, A. D. Leo, Rendina, M, Castellaneta, N, Fagiuoli, S, Burra, P, Vigano, R, Iemmolo, R, Donato, M, Toniutto, P, Pasulo, L, Morelli, M, Miglioresi, L, Merli, M, Angelico, M, Gasbarrini, A, Leo, A, M. Rendina, N. M. Castellaneta, S. Fagiuoli, P. Burra, R. Vigano, R. M. Iemmolo, M. F. Donato, P. Toniutto, L. Pasulo, M. C. Morelli, L. Miglioresi, M. Merli, M. Angelico, A. Gasbarrini, and A. D. Leo

Published
2010

37. Cirrosi Biliare Primitiva

Author

Okolicsanyi, L, Peracchia, A, Roncoroni, L, Iemmolo, R, Fabris, L, Cadamuro, M, Strazzabosco, M, Iemmolo, RM, CADAMURO, MASSIMILIANO, STRAZZABOSCO, MARIO, Okolicsanyi, L, Peracchia, A, Roncoroni, L, Iemmolo, R, Fabris, L, Cadamuro, M, Strazzabosco, M, Iemmolo, RM, CADAMURO, MASSIMILIANO, and STRAZZABOSCO, MARIO

Published
2008

38. Lo zinco nell’encefalopatia subclinica

Author

Marchetti, P. G., Amodio, Piero, DEL PICCOLO, Franco, Pettenò, E., Angeli, Paolo, Iemmolo, R. M., Casagrande, F., CAREGARO NEGRIN, Lorenza, Merkel, Carlo, Nardi, T., Milazzo, D., Musto, C., and Gatta, Angelo

Published
1998

44. Timing of reinfection and mechanisms of hepatocellular damage in transplanted hepatitis C virus-reinfected liver

Author

Ballardini, G, De Raffele, E, Groff, P, Bioulac Sage, P, Grassi, A, Ghetti, S, Susca, M, Strazzabosco, M, Bellusci, R, Iemmolo, R, Grazi, G, Zauli, D, Cavallari, A, Bianchi, F, STRAZZABOSCO, MARIO, Iemmolo, RM, Bianchi, FB, Ballardini, G, De Raffele, E, Groff, P, Bioulac Sage, P, Grassi, A, Ghetti, S, Susca, M, Strazzabosco, M, Bellusci, R, Iemmolo, R, Grazi, G, Zauli, D, Cavallari, A, Bianchi, F, STRAZZABOSCO, MARIO, Iemmolo, RM, and Bianchi, FB

Abstract

Pathogenic mechanisms and dynamics of hepatitis C virus (HCV) reinfection in orthotopic liver transplantation (OLT) are poorly defined. This study focuses on these aspects by studying 55 frozen biopsy specimens from transplant recipients with various histological diagnoses obtained from 4 days to 4 years post-OLT and 10 patients with HCV-related chronic hepatitis. The percentage of HCV-infected hepatocytes, number and distribution of CD8 and natural killer cells, and rates of hepatocellular apoptosis and proliferation were quantified by immunohistochemistry. HCV antigens were detected in 37% of biopsy specimens obtained within 20 days and 90% of biopsy specimens obtained from 21 days to 6 months after OLT. The number of HCV-infected hepatocytes was never less than 40% in acute hepatitis specimens and never greater than 30% in the other cases. Hepatocellular apoptosis was high in biopsy specimens of acute hepatitis and moderate in those from transplant recipients with normal histological characteristics, but still greater than in specimens of chronic active hepatitis. Proliferation correlated significantly with apoptosis. Lymphocyte infiltration was high and similar among cases of acute hepatitis, chronic hepatitis, and rejection. These data: (1) show that the detection of liver HCV antigens is sensitive enough to be used in clinical practice as a diagnostic tool to detect infection of the transplanted liver and might be useful, combined with conventional histological evaluation to detect hepatitic damage, for therapeutic decision making; (2) suggest direct cytotoxicity of HCV, as well as immunologic mechanisms possibly prevalent in chronic hepatitis and rejection, at least in the phase of acute massive liver infection; and (3) show that hepatocellular apoptosis and regeneration might be active enough to lead to replacement of the entire transplanted liver in 2 weeks

Published
2002

46. Cerebral aspergillosis in a liver transplant recipient: a case report of long-term survival after combined treatment with liposomal amphotericin B and surgery

Author

Iemmolo, R, Rossanese, A, Rotilio, A, Mattisi, G, Gerunda, G, Merenda, R, Neri, D, Crepaldi, G, Strazzabosco, M, Iemmolo, RM, Gerunda, GE, STRAZZABOSCO, MARIO, Iemmolo, R, Rossanese, A, Rotilio, A, Mattisi, G, Gerunda, G, Merenda, R, Neri, D, Crepaldi, G, Strazzabosco, M, Iemmolo, RM, Gerunda, GE, and STRAZZABOSCO, MARIO

Abstract

Cerebral aspergillosis is a life-threatening complication in liver transplant recipients, with mortality rates approaching 100%; treatment with amphotericin B is of limited efficacy because of its poor distribution in the cerebrospinal fluid and its systemic side effects. We report the case of a liver transplant recipient who developed recurrent cerebral Aspergillus fumigatus infection, and was successfully treated by combined surgical excision of the lesion and administration of liposomal amphotericin B. This first report of long-term complication-free survival in a liver transplant recipient suggests that therapy with liposomal amphotericin B may reduce the risk of recurrence of cerebral aspergillosis in these immunocompromised patients

Published
1998

47. Pathophysiology of the biliary epithelium

Author

Alvaro, D, Benedetti, A, Strazzabosco, M, Spirlì, C, Zsembery, A, Granato, A, Fabris, L, Cavestro, G, Iemmolo, R, Okolicsanyi, L, Crepaldi, G, STRAZZABOSCO, MARIO, Cavestro, GM, Iemmolo, RM, Crepaldi, G., Alvaro, D, Benedetti, A, Strazzabosco, M, Spirlì, C, Zsembery, A, Granato, A, Fabris, L, Cavestro, G, Iemmolo, R, Okolicsanyi, L, Crepaldi, G, STRAZZABOSCO, MARIO, Cavestro, GM, Iemmolo, RM, and Crepaldi, G.

Published
1997

48. Epstein-Barr virus-associated post-transplant lympho-proliferative disease of donor origin in liver transplant recipients

Author

Strazzabosco, M, Corneo, B, Iemmolo, R, Menin, C, Gerunda, G, Bonaldi, L, Merenda, R, Neri, D, Poletti, A, Montagna, M, Del Mistro, A, Faccioli, A, D'Andrea, E, Iemmolo, RM, Faccioli, AM, D'Andrea, E., Strazzabosco, M, Corneo, B, Iemmolo, R, Menin, C, Gerunda, G, Bonaldi, L, Merenda, R, Neri, D, Poletti, A, Montagna, M, Del Mistro, A, Faccioli, A, D'Andrea, E, Iemmolo, RM, Faccioli, AM, and D'Andrea, E.

Abstract

BACKGROUND/AIMS: Post-transplant lymphoproliferative disease, a potential complication of solid organ transplantation, occurs in about 3% of orthotopic liver transplant recipients. We report the genetic and virological characterization of two cases of post-transplant lymphoproliferative disease that occurred early (4 and 6 months) after orthotopic liver transplant as large-cell non-Hodgkin's lymphomas located at the hepatic hilum. METHODS: Lymphomatous tissues were analyzed for clonality and presence of Epstein-Barr virus (EBV) sequences by Southern blot, polymerase chain reaction, and in situ hybridization techniques. RESULTS: The tumors in both cases were sustained by a clonal proliferation of B lymphocytes containing type A EBV DNA. Moreover, in situ hybridization with a digoxigenin-labeled EBV-specific probe evidenced a strong nuclear signal in most of the neoplastic cells. DNA microsatellite analysis at three different loci detected alleles of donor origin in both tumor samples, suggesting that the neoplastic B cells were of donor origin. CONCLUSIONS: EBV-infected donor B lymphocytes might be responsible for intragraft post-transplant lymphoproliferative disease in orthotopic liver transplant recipients. As 20 to 30% of post-transplant lymphomas involve the graft itself, donor-derived post-transplant lymphoproliferative disease might be more frequent than presently appreciated. Prospective studies are needed to assess its real incidence and identify possible risk factors

Published
1997

49. Effect of Silibinin on biliary lipid composition. Experimental and clinical study

Author

Nassuato, G, Iemmolo, R, Strazzabosco, M, Lirussi, F, Deana, R, Francesconi, M, Muraca, M, Passera, D, Fragasso, A, Orlando, R, Iemmolo, RM, Francesconi, MA, Orlando, R., Nassuato, G, Iemmolo, R, Strazzabosco, M, Lirussi, F, Deana, R, Francesconi, M, Muraca, M, Passera, D, Fragasso, A, Orlando, R, Iemmolo, RM, Francesconi, MA, and Orlando, R.

Abstract

The effect of Silymarin, a natural flavonoid, on biliary lipid composition, was studied in rats and humans. Bile flow, biliary cholesterol, phospholipid and total bile salt concentrations were measured in 23 control rats and in 27 rats treated with Silibinin, the active component of Silymarin, at the dose of 100 mg/kg body weight i.p. (n = 21) or 50 mg/kg body weight i.p. (n = 6) for 7 days. Biliary cholesterol and phospholipid concentrations were significantly reduced after the higher Silibinin dose (60.9 and 72.9% of the control values), whereas bile flow and biliary total bile salt concentration were unchanged. After the lower Silibinin dose all parameters remained unchanged. Total liver cholesterol content was not affected by Silibinin. On the other hand, in vitro determination of rat liver microsomal 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity showed a significant dose-dependent inhibition by Silibinin (0.5-8 mg/kg). Biliary lipid composition was also assayed in four gallstone and in 15 cholecystectomized patients before and after Silymarin (420 mg per day for 30 days) or placebo administration. In both groups, biliary cholesterol concentrations were reduced after Silymarin treatment and the bile saturation index significantly decreased accordingly. These data suggest that Silibinin-induced reduction of biliary cholesterol concentration both in humans and in rats might be, at least in part, due to a decreased synthesis of liver cholesterol

Published
1991

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