Incidence of DAA failure and the clinical impact of retreatment in real-life patients treated in the advanced stage of liver disease: Interim evaluations from the PITER network

Loreta A Kondili, Giovanni Battista Gaeta, Maurizia Rossana Brunetto, Alfredo Di Leo, Andrea Iannone, Teresa Antonia Santantonio, Adele Giammario, Giovanni Raimondo, Roberto Filomia, Carmine Coppola, Daniela Caterina Amoruso, Pierluigi Blanc, Barbara Del Pin, Liliana Chemello, Luisa Cavalletto, Filomena Morisco, Laura Donnarumma, Maria Grazia Rumi, Antonio Gasbarrini, Massimo SicilianoMarco Massari, Romina Corsini, Barbara Coco, Salvatore Madonia, Marco Cannizzaro, Anna Linda Zignego, Monica Monti, Francesco Paolo Russo, Alberto Zanetto, Marcello Persico, Mario Masarone, Erica Villa, Veronica Bernabucci, Gloria Taliani, Elisa Biliotti, Luchino Chessa, Maria Cristina Pasetto, Pietro Andreone, Marzia Margotti, Giuseppina Brancaccio, Donatella Ieluzzi, Guglielmo Borgia, Emanuela Zappulo, Vincenza Calvaruso, Salvatore Petta, Loredana Falzano, Liliana Elena Weimer, Stefano Rosato, Stefano Vella, Edoardo Giovanni Giannini

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

BACKGROUND: Few data are available on the virological and clinical outcomes of advanced liver disease patients retreated after first-line DAA failure.

AIM: To evaluate DAA failure incidence and the retreatment clinical impact in patients treated in the advanced liver disease stage.

METHODS: Data on HCV genotype, liver disease severity, and first and second line DAA regimens were prospectively collected in consecutive patients who reached the 12-week post-treatment and retreatment evaluations from January 2015 to December 2016 in 23 of the PITER network centers.

RESULTS: Among 3,830 patients with advanced fibrosis (F3) or cirrhosis, 139 (3.6%) failed to achieve SVR. Genotype 3, bilirubin levels >1.5mg/dl, platelet count <120,000/mm3 and the sofosbuvir+ribavirin regimen were independent predictors of failure by logistic regression analysis. The failure rate was 7.6% for patients treated with regimens that are no longer recommended or considered suboptimal (sofosbuvir+ribavirin or simeprevir+sofosbuvir±ribavirin), whereas 1.4% for regimens containing sofosbuvir combined with daclatasvir or ledipasvir or other DAAs. Of the patients who failed to achieve SVR, 72 (51.8%) were retreated with a second DAA regimen, specifically 38 (52.7%) with sofosbuvir+daclatasvir, 27 (37.5%) with sofosbuvir+ledipasvir, and 7 (9.7%) with other DAAs ±ribavirin. Among these, 69 (96%) patients achieved SVR12 and 3 (4%) failed. During a median time of 6 months (range: 5-14 months) between failure and the second DAA therapy, the Child-Pugh class worsened in 12 (16.7%) patients: from A to B in 10 patients (19.6%) and from B to C in 2 patients (10.5%), whereas it did not change in the remaining 60 patients. Following the retreatment SVR12 (median time of 6 months; range: 3-12 months), the Child-Pugh class improved in 17 (23.6%) patients: from B to A in 14 (19.4%) patients, from C to A in 1 patient (1.4%) and from C to B in 2 (2.9%) patients; it remained unchanged in 53 patients (73.6%) and worsened in 2 (2.8%) patients. Of patients who were retreated, 3 (4%) had undergone OLT before retreatment (all reached SVR12 following retreatment) and 2 (2.8%) underwent OLT after having achieved retreatment SVR12. Two (70%) of the 3 patients who failed to achieve SVR12 after retreatment, and 2 (2.8%) of the 69 patients who achieved retreatment SVR12 died from liver failure (Child-Pugh class deteriorated from B to C) or HCC complications.

CONCLUSIONS: Failure rate following the first DAA regimen in patients with advanced disease is similar to or lower than that reported in clinical trials, although the majority of patients were treated with suboptimal regimens. Interim findings showed that worsening of liver function after failure, in terms of Child Pugh class deterioration, was improved by successful retreatment in about one third of retreated patients within a short follow-up period; however, in some advanced liver disease patients, clinical outcomes (Child Pugh class, HCC development, liver failure and death) were independent of viral eradication.

Original languageEnglish
Pages (from-to)e0185728
JournalPLoS One
Volume12
Issue number10
DOIs
Publication statusPublished - 2017

Fingerprint

Retreatment
liver diseases
Liver
Liver Diseases
incidence
Incidence
Ribavirin
Platelets
Bilirubin
Regression analysis
Deterioration
Logistics
liver failure
Liver Failure
Sofosbuvir
Fibrosis
Genotype

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents/administration & dosage
  • Drug Therapy, Combination
  • Female
  • Hepatitis C/drug therapy
  • Humans
  • Incidence
  • Liver Diseases/drug therapy
  • Male
  • Middle Aged
  • Prospective Studies

Cite this

Incidence of DAA failure and the clinical impact of retreatment in real-life patients treated in the advanced stage of liver disease : Interim evaluations from the PITER network. / Kondili, Loreta A; Gaeta, Giovanni Battista; Brunetto, Maurizia Rossana; Di Leo, Alfredo; Iannone, Andrea; Santantonio, Teresa Antonia; Giammario, Adele; Raimondo, Giovanni; Filomia, Roberto; Coppola, Carmine; Amoruso, Daniela Caterina; Blanc, Pierluigi; Del Pin, Barbara; Chemello, Liliana; Cavalletto, Luisa; Morisco, Filomena; Donnarumma, Laura; Rumi, Maria Grazia; Gasbarrini, Antonio; Siciliano, Massimo; Massari, Marco; Corsini, Romina; Coco, Barbara; Madonia, Salvatore; Cannizzaro, Marco; Zignego, Anna Linda; Monti, Monica; Russo, Francesco Paolo; Zanetto, Alberto; Persico, Marcello; Masarone, Mario; Villa, Erica; Bernabucci, Veronica; Taliani, Gloria; Biliotti, Elisa; Chessa, Luchino; Pasetto, Maria Cristina; Andreone, Pietro; Margotti, Marzia; Brancaccio, Giuseppina; Ieluzzi, Donatella; Borgia, Guglielmo; Zappulo, Emanuela; Calvaruso, Vincenza; Petta, Salvatore; Falzano, Loredana; Weimer, Liliana Elena; Rosato, Stefano; Vella, Stefano; Giannini, Edoardo Giovanni.

In: PLoS One, Vol. 12, No. 10, 2017, p. e0185728.

Research output: Contribution to journalArticle

Kondili, LA, Gaeta, GB, Brunetto, MR, Di Leo, A, Iannone, A, Santantonio, TA, Giammario, A, Raimondo, G, Filomia, R, Coppola, C, Amoruso, DC, Blanc, P, Del Pin, B, Chemello, L, Cavalletto, L, Morisco, F, Donnarumma, L, Rumi, MG, Gasbarrini, A, Siciliano, M, Massari, M, Corsini, R, Coco, B, Madonia, S, Cannizzaro, M, Zignego, AL, Monti, M, Russo, FP, Zanetto, A, Persico, M, Masarone, M, Villa, E, Bernabucci, V, Taliani, G, Biliotti, E, Chessa, L, Pasetto, MC, Andreone, P, Margotti, M, Brancaccio, G, Ieluzzi, D, Borgia, G, Zappulo, E, Calvaruso, V, Petta, S, Falzano, L, Weimer, LE, Rosato, S, Vella, S & Giannini, EG 2017, 'Incidence of DAA failure and the clinical impact of retreatment in real-life patients treated in the advanced stage of liver disease: Interim evaluations from the PITER network', PLoS One, vol. 12, no. 10, pp. e0185728. https://doi.org/10.1371/journal.pone.0185728
Kondili, Loreta A ; Gaeta, Giovanni Battista ; Brunetto, Maurizia Rossana ; Di Leo, Alfredo ; Iannone, Andrea ; Santantonio, Teresa Antonia ; Giammario, Adele ; Raimondo, Giovanni ; Filomia, Roberto ; Coppola, Carmine ; Amoruso, Daniela Caterina ; Blanc, Pierluigi ; Del Pin, Barbara ; Chemello, Liliana ; Cavalletto, Luisa ; Morisco, Filomena ; Donnarumma, Laura ; Rumi, Maria Grazia ; Gasbarrini, Antonio ; Siciliano, Massimo ; Massari, Marco ; Corsini, Romina ; Coco, Barbara ; Madonia, Salvatore ; Cannizzaro, Marco ; Zignego, Anna Linda ; Monti, Monica ; Russo, Francesco Paolo ; Zanetto, Alberto ; Persico, Marcello ; Masarone, Mario ; Villa, Erica ; Bernabucci, Veronica ; Taliani, Gloria ; Biliotti, Elisa ; Chessa, Luchino ; Pasetto, Maria Cristina ; Andreone, Pietro ; Margotti, Marzia ; Brancaccio, Giuseppina ; Ieluzzi, Donatella ; Borgia, Guglielmo ; Zappulo, Emanuela ; Calvaruso, Vincenza ; Petta, Salvatore ; Falzano, Loredana ; Weimer, Liliana Elena ; Rosato, Stefano ; Vella, Stefano ; Giannini, Edoardo Giovanni. / Incidence of DAA failure and the clinical impact of retreatment in real-life patients treated in the advanced stage of liver disease : Interim evaluations from the PITER network. In: PLoS One. 2017 ; Vol. 12, No. 10. pp. e0185728.
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title = "Incidence of DAA failure and the clinical impact of retreatment in real-life patients treated in the advanced stage of liver disease: Interim evaluations from the PITER network",
abstract = "BACKGROUND: Few data are available on the virological and clinical outcomes of advanced liver disease patients retreated after first-line DAA failure.AIM: To evaluate DAA failure incidence and the retreatment clinical impact in patients treated in the advanced liver disease stage.METHODS: Data on HCV genotype, liver disease severity, and first and second line DAA regimens were prospectively collected in consecutive patients who reached the 12-week post-treatment and retreatment evaluations from January 2015 to December 2016 in 23 of the PITER network centers.RESULTS: Among 3,830 patients with advanced fibrosis (F3) or cirrhosis, 139 (3.6{\%}) failed to achieve SVR. Genotype 3, bilirubin levels >1.5mg/dl, platelet count <120,000/mm3 and the sofosbuvir+ribavirin regimen were independent predictors of failure by logistic regression analysis. The failure rate was 7.6{\%} for patients treated with regimens that are no longer recommended or considered suboptimal (sofosbuvir+ribavirin or simeprevir+sofosbuvir±ribavirin), whereas 1.4{\%} for regimens containing sofosbuvir combined with daclatasvir or ledipasvir or other DAAs. Of the patients who failed to achieve SVR, 72 (51.8{\%}) were retreated with a second DAA regimen, specifically 38 (52.7{\%}) with sofosbuvir+daclatasvir, 27 (37.5{\%}) with sofosbuvir+ledipasvir, and 7 (9.7{\%}) with other DAAs ±ribavirin. Among these, 69 (96{\%}) patients achieved SVR12 and 3 (4{\%}) failed. During a median time of 6 months (range: 5-14 months) between failure and the second DAA therapy, the Child-Pugh class worsened in 12 (16.7{\%}) patients: from A to B in 10 patients (19.6{\%}) and from B to C in 2 patients (10.5{\%}), whereas it did not change in the remaining 60 patients. Following the retreatment SVR12 (median time of 6 months; range: 3-12 months), the Child-Pugh class improved in 17 (23.6{\%}) patients: from B to A in 14 (19.4{\%}) patients, from C to A in 1 patient (1.4{\%}) and from C to B in 2 (2.9{\%}) patients; it remained unchanged in 53 patients (73.6{\%}) and worsened in 2 (2.8{\%}) patients. Of patients who were retreated, 3 (4{\%}) had undergone OLT before retreatment (all reached SVR12 following retreatment) and 2 (2.8{\%}) underwent OLT after having achieved retreatment SVR12. Two (70{\%}) of the 3 patients who failed to achieve SVR12 after retreatment, and 2 (2.8{\%}) of the 69 patients who achieved retreatment SVR12 died from liver failure (Child-Pugh class deteriorated from B to C) or HCC complications.CONCLUSIONS: Failure rate following the first DAA regimen in patients with advanced disease is similar to or lower than that reported in clinical trials, although the majority of patients were treated with suboptimal regimens. Interim findings showed that worsening of liver function after failure, in terms of Child Pugh class deterioration, was improved by successful retreatment in about one third of retreated patients within a short follow-up period; however, in some advanced liver disease patients, clinical outcomes (Child Pugh class, HCC development, liver failure and death) were independent of viral eradication.",
keywords = "Adult, Aged, Aged, 80 and over, Antiviral Agents/administration & dosage, Drug Therapy, Combination, Female, Hepatitis C/drug therapy, Humans, Incidence, Liver Diseases/drug therapy, Male, Middle Aged, Prospective Studies",
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year = "2017",
doi = "10.1371/journal.pone.0185728",
language = "English",
volume = "12",
pages = "e0185728",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "10",

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TY - JOUR

T1 - Incidence of DAA failure and the clinical impact of retreatment in real-life patients treated in the advanced stage of liver disease

T2 - Interim evaluations from the PITER network

AU - Kondili, Loreta A

AU - Gaeta, Giovanni Battista

AU - Brunetto, Maurizia Rossana

AU - Di Leo, Alfredo

AU - Iannone, Andrea

AU - Santantonio, Teresa Antonia

AU - Giammario, Adele

AU - Raimondo, Giovanni

AU - Filomia, Roberto

AU - Coppola, Carmine

AU - Amoruso, Daniela Caterina

AU - Blanc, Pierluigi

AU - Del Pin, Barbara

AU - Chemello, Liliana

AU - Cavalletto, Luisa

AU - Morisco, Filomena

AU - Donnarumma, Laura

AU - Rumi, Maria Grazia

AU - Gasbarrini, Antonio

AU - Siciliano, Massimo

AU - Massari, Marco

AU - Corsini, Romina

AU - Coco, Barbara

AU - Madonia, Salvatore

AU - Cannizzaro, Marco

AU - Zignego, Anna Linda

AU - Monti, Monica

AU - Russo, Francesco Paolo

AU - Zanetto, Alberto

AU - Persico, Marcello

AU - Masarone, Mario

AU - Villa, Erica

AU - Bernabucci, Veronica

AU - Taliani, Gloria

AU - Biliotti, Elisa

AU - Chessa, Luchino

AU - Pasetto, Maria Cristina

AU - Andreone, Pietro

AU - Margotti, Marzia

AU - Brancaccio, Giuseppina

AU - Ieluzzi, Donatella

AU - Borgia, Guglielmo

AU - Zappulo, Emanuela

AU - Calvaruso, Vincenza

AU - Petta, Salvatore

AU - Falzano, Loredana

AU - Weimer, Liliana Elena

AU - Rosato, Stefano

AU - Vella, Stefano

AU - Giannini, Edoardo Giovanni

PY - 2017

Y1 - 2017

N2 - BACKGROUND: Few data are available on the virological and clinical outcomes of advanced liver disease patients retreated after first-line DAA failure.AIM: To evaluate DAA failure incidence and the retreatment clinical impact in patients treated in the advanced liver disease stage.METHODS: Data on HCV genotype, liver disease severity, and first and second line DAA regimens were prospectively collected in consecutive patients who reached the 12-week post-treatment and retreatment evaluations from January 2015 to December 2016 in 23 of the PITER network centers.RESULTS: Among 3,830 patients with advanced fibrosis (F3) or cirrhosis, 139 (3.6%) failed to achieve SVR. Genotype 3, bilirubin levels >1.5mg/dl, platelet count <120,000/mm3 and the sofosbuvir+ribavirin regimen were independent predictors of failure by logistic regression analysis. The failure rate was 7.6% for patients treated with regimens that are no longer recommended or considered suboptimal (sofosbuvir+ribavirin or simeprevir+sofosbuvir±ribavirin), whereas 1.4% for regimens containing sofosbuvir combined with daclatasvir or ledipasvir or other DAAs. Of the patients who failed to achieve SVR, 72 (51.8%) were retreated with a second DAA regimen, specifically 38 (52.7%) with sofosbuvir+daclatasvir, 27 (37.5%) with sofosbuvir+ledipasvir, and 7 (9.7%) with other DAAs ±ribavirin. Among these, 69 (96%) patients achieved SVR12 and 3 (4%) failed. During a median time of 6 months (range: 5-14 months) between failure and the second DAA therapy, the Child-Pugh class worsened in 12 (16.7%) patients: from A to B in 10 patients (19.6%) and from B to C in 2 patients (10.5%), whereas it did not change in the remaining 60 patients. Following the retreatment SVR12 (median time of 6 months; range: 3-12 months), the Child-Pugh class improved in 17 (23.6%) patients: from B to A in 14 (19.4%) patients, from C to A in 1 patient (1.4%) and from C to B in 2 (2.9%) patients; it remained unchanged in 53 patients (73.6%) and worsened in 2 (2.8%) patients. Of patients who were retreated, 3 (4%) had undergone OLT before retreatment (all reached SVR12 following retreatment) and 2 (2.8%) underwent OLT after having achieved retreatment SVR12. Two (70%) of the 3 patients who failed to achieve SVR12 after retreatment, and 2 (2.8%) of the 69 patients who achieved retreatment SVR12 died from liver failure (Child-Pugh class deteriorated from B to C) or HCC complications.CONCLUSIONS: Failure rate following the first DAA regimen in patients with advanced disease is similar to or lower than that reported in clinical trials, although the majority of patients were treated with suboptimal regimens. Interim findings showed that worsening of liver function after failure, in terms of Child Pugh class deterioration, was improved by successful retreatment in about one third of retreated patients within a short follow-up period; however, in some advanced liver disease patients, clinical outcomes (Child Pugh class, HCC development, liver failure and death) were independent of viral eradication.

AB - BACKGROUND: Few data are available on the virological and clinical outcomes of advanced liver disease patients retreated after first-line DAA failure.AIM: To evaluate DAA failure incidence and the retreatment clinical impact in patients treated in the advanced liver disease stage.METHODS: Data on HCV genotype, liver disease severity, and first and second line DAA regimens were prospectively collected in consecutive patients who reached the 12-week post-treatment and retreatment evaluations from January 2015 to December 2016 in 23 of the PITER network centers.RESULTS: Among 3,830 patients with advanced fibrosis (F3) or cirrhosis, 139 (3.6%) failed to achieve SVR. Genotype 3, bilirubin levels >1.5mg/dl, platelet count <120,000/mm3 and the sofosbuvir+ribavirin regimen were independent predictors of failure by logistic regression analysis. The failure rate was 7.6% for patients treated with regimens that are no longer recommended or considered suboptimal (sofosbuvir+ribavirin or simeprevir+sofosbuvir±ribavirin), whereas 1.4% for regimens containing sofosbuvir combined with daclatasvir or ledipasvir or other DAAs. Of the patients who failed to achieve SVR, 72 (51.8%) were retreated with a second DAA regimen, specifically 38 (52.7%) with sofosbuvir+daclatasvir, 27 (37.5%) with sofosbuvir+ledipasvir, and 7 (9.7%) with other DAAs ±ribavirin. Among these, 69 (96%) patients achieved SVR12 and 3 (4%) failed. During a median time of 6 months (range: 5-14 months) between failure and the second DAA therapy, the Child-Pugh class worsened in 12 (16.7%) patients: from A to B in 10 patients (19.6%) and from B to C in 2 patients (10.5%), whereas it did not change in the remaining 60 patients. Following the retreatment SVR12 (median time of 6 months; range: 3-12 months), the Child-Pugh class improved in 17 (23.6%) patients: from B to A in 14 (19.4%) patients, from C to A in 1 patient (1.4%) and from C to B in 2 (2.9%) patients; it remained unchanged in 53 patients (73.6%) and worsened in 2 (2.8%) patients. Of patients who were retreated, 3 (4%) had undergone OLT before retreatment (all reached SVR12 following retreatment) and 2 (2.8%) underwent OLT after having achieved retreatment SVR12. Two (70%) of the 3 patients who failed to achieve SVR12 after retreatment, and 2 (2.8%) of the 69 patients who achieved retreatment SVR12 died from liver failure (Child-Pugh class deteriorated from B to C) or HCC complications.CONCLUSIONS: Failure rate following the first DAA regimen in patients with advanced disease is similar to or lower than that reported in clinical trials, although the majority of patients were treated with suboptimal regimens. Interim findings showed that worsening of liver function after failure, in terms of Child Pugh class deterioration, was improved by successful retreatment in about one third of retreated patients within a short follow-up period; however, in some advanced liver disease patients, clinical outcomes (Child Pugh class, HCC development, liver failure and death) were independent of viral eradication.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antiviral Agents/administration & dosage

KW - Drug Therapy, Combination

KW - Female

KW - Hepatitis C/drug therapy

KW - Humans

KW - Incidence

KW - Liver Diseases/drug therapy

KW - Male

KW - Middle Aged

KW - Prospective Studies

U2 - 10.1371/journal.pone.0185728

DO - 10.1371/journal.pone.0185728

M3 - Article

C2 - 28977040

VL - 12

SP - e0185728

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 10

ER -