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Safety and efficacy of ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in patients over 65 years with HCV genotype 1 cirrhosis

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Abstract

Purpose

To analyse safety and efficacy of treatment based on ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in the sub-group of GT1 patients older than 65 years.

Methods

We collected data extracted from the ABACUS compassionate-use nationwide Italian programme, in patients with cirrhosis due to hepatitis C virus (HCV) Genotype-1 (GT1) or 4 and at high risk of decompensation. GT1-HCV-infected patients received once-daily ombitasvir/paritaprevir, with the pharmacokinetic enhancer ritonavir (25/150/100 mg) and twice-daily dasabuvir (250 mg) plus Ribavirin (RBV) (OBV/PTV/r + DSV + RBV) for 12 (GT1b) or 24 (GT1a) weeks. Endpoints were to evaluate safety and efficacy, the latter defined as HCV RNA negative 12 weeks after the end of treatment (SVR12).

Results

Patients who suffered any adverse event (AE) were 74/240 (30.8%); 13/240 (5.4%) discontinued the treatment. A multivariate analysis found albumin < 3.5 g/dL (OR 2.04: 95% CI 1.0–4.2, p < 0.05) and hypertension (OR 4.6: 95% CI 2.3–9.2, p < 0.001) as variables independently associated with AE occurrence. The SVR12 was 95% (228/240). Multivariate analysis identified baseline bilirubin < 2 mg/dL (OR 4.9: 95% CI 1.17–20.71, p = 0.029) as the only variable independently associated with SVR12.

Conclusion

Our findings suggest that OBV/PTV/r + DSV + RBV is safe and effective in real-life use in patients with compensated cirrhosis, HCV-GT1 infection, and age over 65.

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Abbreviations

DAAs:

Direct-acting antivirals

OBV/PTV/r + DSV:

Ombitasvir, paritaprevir, ritonavir + dasabuvir

RBV:

Ribavirin

HCV:

Hepatitis C virus

GT1:

Genotype 1

SVR12:

Sustained virological response at 12 weeks after the end of treatment

LC:

Liver cirrhosis

HCC:

Hepatocellular carcinoma

AIFA:

Agenzia Italiana del Farmaco

AISF:

Associazione Italiana per lo Studio del Fegato

CTP:

Child–Turcotte–Pugh

INR:

International normalized ratio

AE:

Adverse event

CTCAE:

Common terminology criteria for adverse events

ITT:

Intention to treat

BMI:

Body mass index

eGFR:

Estimated glomerular filtration rate

MELD:

Model for end-stage liver disease

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Acknowledgements

The ABACUS Study Group: Giuseppe Abbati, Alfredo Alberti, Pietro Andreone, Massimo Andreoni, Paolo Angeli, Mario Angelico, Gioacchino Angarano, Debora Angrisani, Andrea Antinori, Cinzia Antonini, Ivo Avancini, Michele Barone, Raffaele Bruno, Antonio Benedetti, Veronica Bernabucci, Pier Blanc, Chiara Boarini, Nicola Boffa, Lucio Boglione, Vanni Borghi, Guglielmo Borgia, Giuseppina Brancaccio, Maurizia Brunetto, Irene Cacciola, Paolo Calabrese, Vincenza Calvaruso, Davide Campagnolo, Benedetta Canovari, Nicola Caporaso, Franco Capra, Giada Carolo, Giovanni Cassola, Francesco Castelli, Roberto Cauda, Francesca Ceccherini Silberstein, Roberto Cecere, Luchino Chessa, Alessandro Chiodera, Antonio Chirianni, Alessia Ciancio, Serena Cima, Barbara Coco, Massimo Colombo, Nicola Coppola, Giampaolo Corti, Lucio Cosco, Silvia Corradori, Raffaele Cozzolongo, Antonio Cristaudo, Elena Danieli, Antonella D’Arminio Monforte, Marco delle Monache, Paolo Del Poggio, Andrea de Luca, Chiara Dentone, Antonio Di Biagio, Alfredo Di Leo, Giovanni Di Perri, Marco Di Stefano, Giampiero D’Offizi, Francesca Donato, Emanuele Durante, Elke Erne, Stefano Fagiuoli, Katia Falasca, Alessandro Federico, Martina Felder, Carlo Ferrari, Giovanni Battista Gaeta, Roberto Ganga, Pietro Gatti, Vania Giacomet, Andrea Giacometti, Alice Gianstefani, Maria Giordani, Alessia Giorgini, Antonio Grieco, Michele Guerra, Roberto Gulminetti, Donatella Ieluzzi, Michele Imparato, Valentina Iodice, Silvia La Monica, Adriano Lazzarin, Marco Lenzi, Massimo Levrero, Myriam Lichtner, Raffaella Lionetti, Carmela Lo Guercio, Salvatore Madonna, Silvia Magnani, Ivana Maida, Massimo Marignani, Aldo Marrone, Fabio Marsetti, Silvia Martini, Mario Masarone, Renato Maserati, Claudio Maria Mastroianni, Massimo Memoli, Barbara Menzaghi, Manuela Merli, Luca Miele, Michele Milella, Mario Mondelli, Marzia Montalbano, Monica Monti, Olivia Morelli, Filomena Morisco, Gaetano Nardone, Sergio Novara, Giovanna Onnelli, Mirella Onofrio, Simona Paganin, Luca Pani, Maria Rita Parisi, Giustino Parruti, Caterina Pasquazzi, Luisa Pasulo, Carlo Federico Perno, Marcello Persico, Guido Piai, Antonino Picciotto, Grazielle Marie Pigozzi, Sara Piovesan, Maria Chiara Piras, Massimo Pirisi, Anna Maria Piscaglia, Laura Ponti, Domenico Potenza, Cecilia Pravadelli, Mariano Quartini, Tiziana Quirino, Giovanni Raimondo, Gian Ludovico Rapaccini, Maria Rendina, Giuliano Rizzardini, Mario Rizzetto, Salvatore Rizzo, Dante Romagnoli, Antonietta Romano, Cristina Rossi, Maria Grazia Rumi, Maurizio Russello, Francesca Paolo Russo, Maria Luisa Russo, Domenico Ettore Sansonno, Teresa Antonia Santantonio, Giorgio Saracco, Anna Maria Schimizzi, Gaetano Serviddio, Filomena Simeone, Attilio Solinas, Alessandro Soria, Marco Tabone, Gloria Taliani, Giuseppe Tarantino, Pierluigi Tarquini, Marcello Tavio, Antonio Termite, Elisabetta Teti, Pierluigi Toniutto, Carlo Torti, Paolo Tundi, Giacomo Vecchiet, Gabriella Verucchi, Umberto Vespasiani Gentilucci, Maria Vinci, Vincenzo Vullo, Teresa Zolfino, and Massimo Zuin.

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Authors and Affiliations

  1. Department of Medicine, Centre for Liver Disease, Buon Consiglio-Fatebenefratelli Hospital, Via Manzoni 220, 80123, Naples, Italy

    Antonio Ascione & Luca Fontanella

  2. Liver Unit, AORN Cardarelli, Naples, Italy

    Massimo De Luca

  3. Italian Medicines Agency (AIFA), Rome, Italy

    Mario Melazzini, Simona Montilla & Maria Paola Trotta

  4. Department of Gastroenterology, DiBiMIS, University of Palermo, Palermo, Italy

    Salvatore Petta & Antonio Craxì

  5. Division of Infectious Diseases, AO Niguarda Ca’ Granda Hospital, Milan, Italy

    Massimo Puoti

  6. III U.O.C. P.O. Cotugno, AORN Ospedali dei Colli, Naples, Italy

    Vincenzo Sangiovanni

  7. Infectious Diseases Unit, AORN Caserta, Caserta, Italy

    Vincenzo Messina

  8. Humanitas University and IRCCS Clinical Institute Humanitas, Rozzano, Milan, Italy

    Savino Bruno

  9. Infectious Disease, Cotugno Hospital, AORN Ospedali dei Colli, Naples, Italy

    Antonio Izzi

  10. Gastroenterology Unit, Department of Internal Medicine, AOU Policlinico of Modena, Modena, Italy

    Erica Villa

  11. UO Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Hospital Maggiore Policlinico of Milan, Milan, Italy

    Alessio Aghemo

  12. Interdepartmental Centre for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

    Anna Linda Zignego

  13. Unit of Infectious Diseases and Hepatology, AOU of Parma, Parma, Italy

    Alessandra Orlandini

  14. Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome, Italy

    Antonio Gasbarrini

  15. Clinic of Gastroenterology and Hepatology, Università Politecnica delle Marche, Ancona, Italy

    Marco Marzioni

  16. Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy

    Edoardo G. Giannini

Authors
  1. Antonio Ascione
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  2. Massimo De Luca
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  3. Mario Melazzini
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  4. Simona Montilla
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  6. Salvatore Petta
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  9. Vincenzo Messina
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  11. Antonio Izzi
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Consortia

For the ABACUS Study Group

  • Giuseppe Abbati
  • , Alfredo Alberti
  • , Pietro Andreone
  • , Massimo Andreoni
  • , Paolo Angeli
  • , Mario Angelico
  • , Gioacchino Angarano
  • , Debora Angrisani
  • , Andrea Antinori
  • , Cinzia Antonini
  • , Ivo Avancini
  • , Michele Barone
  • , Raffaele Bruno
  • , Antonio Benedetti
  • , Veronica Bernabucci
  • , Pier Blanc
  • , Chiara Boarini
  • , Nicola Boffa
  • , Lucio Boglione
  • , Vanni Borghi
  • , Guglielmo Borgia
  • , Giuseppina Brancaccio
  • , Maurizia Brunetto
  • , Irene Cacciola
  • , Paolo Calabrese
  • , Vincenza Calvaruso
  • , Davide Campagnolo
  • , Benedetta Canovari
  • , Nicola Caporaso
  • , Franco Capra
  • , Giada Carolo
  • , Giovanni Cassola
  • , Francesco Castelli
  • , Roberto Cauda
  • , Francesca Ceccherini Silberstein
  • , Roberto Cecere
  • , Luchino Chessa
  • , Alessandro Chiodera
  • , Antonio Chirianni
  • , Alessia Ciancio
  • , Serena Cima
  • , Barbara Coco
  • , Massimo Colombo
  • , Nicola Coppola
  • , Giampaolo Corti
  • , Lucio Cosco
  • , Silvia Corradori
  • , Raffaele Cozzolongo
  • , Antonio Cristaudo
  • , Elena Danieli
  • , Antonella D’Arminio Monforte
  • , Marco delle Monache
  • , Paolo Del Poggio
  • , Andrea de Luca
  • , Chiara Dentone
  • , Antonio Di Biagio
  • , Alfredo Di Leo
  • , Giovanni Di Perri
  • , Marco Di Stefano
  • , Giampiero D’Offizi
  • , Francesca Donato
  • , Emanuele Durante
  • , Elke Erne
  • , Stefano Fagiuoli
  • , Katia Falasca
  • , Alessandro Federico
  • , Martina Felder
  • , Carlo Ferrari
  • , Giovanni Battista Gaeta
  • , Roberto Ganga
  • , Pietro Gatti
  • , Vania Giacomet
  • , Andrea Giacometti
  • , Alice Gianstefani
  • , Maria Giordani
  • , Alessia Giorgini
  • , Antonio Grieco
  • , Michele Guerra
  • , Roberto Gulminetti
  • , Donatella Ieluzzi
  • , Michele Imparato
  • , Valentina Iodice
  • , Silvia La Monica
  • , Adriano Lazzarin
  • , Marco Lenzi
  • , Massimo Levrero
  • , Myriam Lichtner
  • , Raffaella Lionetti
  • , Carmela Lo Guercio
  • , Salvatore Madonna
  • , Silvia Magnani
  • , Ivana Maida
  • , Massimo Marignani
  • , Aldo Marrone
  • , Fabio Marsetti
  • , Silvia Martini
  • , Mario Masarone
  • , Renato Maserati
  • , Claudio Maria Mastroianni
  • , Massimo Memoli
  • , Barbara Menzaghi
  • , Manuela Merli
  • , Luca Miele
  • , Michele Milella
  • , Mario Mondelli
  • , Marzia Montalbano
  • , Monica Monti
  • , Olivia Morelli
  • , Filomena Morisco
  • , Gaetano Nardone
  • , Sergio Novara
  • , Giovanna Onnelli
  • , Mirella Onofrio
  • , Simona Paganin
  • , Luca Pani
  • , Maria Rita Parisi
  • , Giustino Parruti
  • , Caterina Pasquazzi
  • , Luisa Pasulo
  • , Carlo Federico Perno
  • , Marcello Persico
  • , Guido Piai
  • , Antonino Picciotto
  • , Grazielle Marie Pigozzi
  • , Sara Piovesan
  • , Maria Chiara Piras
  • , Massimo Pirisi
  • , Anna Maria Piscaglia
  • , Laura Ponti
  • , Domenico Potenza
  • , Cecilia Pravadelli
  • , Mariano Quartini
  • , Tiziana Quirino
  • , Giovanni Raimondo
  • , Gian Ludovico Rapaccini
  • , Maria Rendina
  • , Giuliano Rizzardini
  • , Mario Rizzetto
  • , Salvatore Rizzo
  • , Dante Romagnoli
  • , Antonietta Romano
  • , Cristina Rossi
  • , Maria Grazia Rumi
  • , Maurizio Russello
  • , Francesca Paolo Russo
  • , Maria Luisa Russo
  • , Domenico Ettore Sansonno
  • , Teresa Antonia Santantonio
  • , Giorgio Saracco
  • , Anna Maria Schimizzi
  • , Gaetano Serviddio
  • , Filomena Simeone
  • , Attilio Solinas
  • , Alessandro Soria
  • , Marco Tabone
  • , Gloria Taliani
  • , Giuseppe Tarantino
  • , Pierluigi Tarquini
  • , Marcello Tavio
  • , Antonio Termite
  • , Elisabetta Teti
  • , Pierluigi Toniutto
  • , Carlo Torti
  • , Paolo Tundi
  • , Giacomo Vecchiet
  • , Gabriella Verucchi
  • , Umberto Vespasiani Gentilucci
  • , Maria Vinci
  • , Vincenzo Vullo
  • , Teresa Zolfino
  •  & Massimo Zuin

Corresponding author

Correspondence to Antonio Ascione.

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The authors declare that they have no competing interest.

Additional information

The members of the ABACUS Study Group are listed in Acknowledgements.

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Ascione, A., De Luca, M., Melazzini, M. et al. Safety and efficacy of ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in patients over 65 years with HCV genotype 1 cirrhosis. Infection 46, 607–615 (2018). https://doi.org/10.1007/s15010-018-1157-x

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