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: Interim evaluations from the PITER network
AU - Calvaruso, Vincenza
AU - Petta, Salvatore
AU - Rosato, Stefano
AU - Biliotti, Elisa
AU - Andreone, Pietro
AU - Amoruso, Daniela Caterina
AU - Masarone, Mario
AU - Brunetto, Maurizia Rossana
AU - Blanc, Pierluigi
AU - Russo, Francesco Paolo
AU - Gaeta, Giovanni Battista
AU - Ieluzzi, Donatella
AU - Del Pin, Barbara
AU - Giammario, Adele
AU - Villa, Erica
AU - Corsini, Romina
AU - Donnarumma, Laura
AU - Filomia, Roberto
AU - Vella, Stefano
AU - Gasbarrini, Antonio
AU - Zappulo, Emanuela
AU - Madonia, Salvatore
AU - Zanetto, Alberto
AU - Siciliano, Massimo
AU - Chessa, Luchino
AU - Di Leo, Alfredo
AU - Gasbarrini, Antonio
AU - Pasetto, Maria Cristina
AU - Cannizzaro, Marco
AU - Raimondo, Giovanni
AU - Rumi, Maria Grazia
AU - Santantonio, Teresa Antonia
AU - Siciliano, Massimo
AU - Brancaccio, Giuseppina
AU - Quaranta, Maria Giovanna
AU - Quaranta, Maria Giovanna
AU - Margotti, Marzia
AU - Cavalletto, Luisa
AU - Kondili, Loreta A.
AU - Coco, Barbara
AU - Falzano, Loredana
AU - Morisco, Filomena
AU - Weimer, Liliana Elena
AU - Iannone, Andrea
AU - Chemello, Liliana
AU - Coppola, Carmine
AU - Rumi, Maria Grazia
AU - Massari, Marco
AU - Zignego, Anna Linda
AU - Taliani, Gloria
AU - Borgia, Guglielmo
AU - Giannini, Edoardo Giovanni
AU - Persico, Marcello
AU - Monti, Monica
AU - Bernabucci, Veronica
AU - Raimondo, Giovanni
PY - 2017
Y1 - 2017
N2 - BackgroundFew data are available on the virological and clinical outcomes of advanced liver disease patients retreated after first-line DAA failure.AimTo evaluate DAA failure incidence and the retreatment clinical impact in patients treated in the advanced liver disease stage.MethodsData 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.ResultsAmong 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/mm(3) 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.ConclusionsFailure 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 - BackgroundFew data are available on the virological and clinical outcomes of advanced liver disease patients retreated after first-line DAA failure.AimTo evaluate DAA failure incidence and the retreatment clinical impact in patients treated in the advanced liver disease stage.MethodsData 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.ResultsAmong 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/mm(3) 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.ConclusionsFailure 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 - 80 and over; Antiviral Agents; Drug Therapy
KW - Adult; Aged; Aged
KW - Combination; Female; Hepatitis C; Humans; Incidence; Liver Diseases; Male; Middle Aged; Prospective Studies; Biochemistry
KW - Genetics and Molecular Biology (all); Agricultural and Biological Sciences (all)
KW - 80 and over; Antiviral Agents; Drug Therapy
KW - Adult; Aged; Aged
KW - Combination; Female; Hepatitis C; Humans; Incidence; Liver Diseases; Male; Middle Aged; Prospective Studies; Biochemistry
KW - Genetics and Molecular Biology (all); Agricultural and Biological Sciences (all)
UR - http://hdl.handle.net/10447/247551
UR - http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0185728&type=printable
M3 - Article
VL - 12
SP - e0185728-
JO - PLoS One
JF - PLoS One
SN - 1932-6203
ER -