PMID- 25311757 OWN - NLM STAT- MEDLINE DCOM- 20151223 LR - 20150407 IS - 1365-2893 (Electronic) IS - 1352-0504 (Linking) VI - 22 IP - 5 DP - 2015 May TI - Undetectable HCV-RNA at treatment-week 8 results in high-sustained virological response in HCV G1 treatment-experienced patients with advanced liver disease: the International Italian/Spanish Boceprevir/Peginterferon/Ribavirin Name Patients Program. PG - 469-80 LID - 10.1111/jvh.12342 [doi] AB - In many countries, first-generation protease inhibitors (PIs)/peginterferon/ribavirin (P/R) still represent the only treatment option for HCV-infected patients. Subjects with advanced disease and previous failure to P/R urgently need therapy, but they are under-represented in clinical trials. All treatment-experienced F3/4 Metavir patients who received boceprevir (BOC)+P/R in the Italian-Spanish Name Patient Program have been included in this study. Multivariate logistic regression analysis (MLR) was used to identify baseline and on-treatment predictors of SVR and adverse events (AEs). Four hundred and sixteen patients, mean age 57.7 (range 25-78 years), 70% males, 69.5% (289/416) F4, 14% (41/289) Child-Pugh class A6, 24% (70/289) with varices and 42% (173/416) prior null responders to P/R, were analysed. Overall, SVR rate (all 381 patients who received one dose of BOC) was 49%, (58% in F3, 45% in F4, 61% in relapsers, 51% in partial, 38% in null responders, and 72% in subjects with undetectable HCV-RNA at treatment-week (TW)8. Among patients with TW8 HCV-RNA >/= 1000 IU/L, SVR was 8% (negative predictive value = 92%). Death occurred in 3 (0.8%) patients, while decompensation and infections were observed in 2.9% and 11%, respectively. At MLR, SVR predictors were TW4 HCV-RNA >/= 1log10 -decline from baseline, undetectable TW8 HCV-RNA, prior relapse, albumin levels >/=3.5 g/dL and platelet counts >/=100 000/muL. Metavir F4, Child-Pugh A6, albumin, platelets, age and female gender were associated with serious and haematological AEs. Among treatment-experienced patients with advanced liver disease eligible for IFN-based therapy, TW8 HCV-RNA characterised the subset with either high or poor likelihood of achieving SVR. Using TW8 HCV-RNA as a futility rule, BOC/P/R appears to have a favourable benefit-risk profile. CI - (c) 2014 John Wiley & Sons Ltd. FAU - Bruno, S AU - Bruno S AD - AO Fatebenefratelli e Oftalmico, Milano, Italy. FAU - Bollani, S AU - Bollani S FAU - Zignego, A L AU - Zignego AL FAU - Pascasio, J M AU - Pascasio JM FAU - Magni, C AU - Magni C FAU - Ciancio, A AU - Ciancio A FAU - Caremani, M AU - Caremani M FAU - Mangia, A AU - Mangia A FAU - Marenco, S AU - Marenco S FAU - Piovesan, S AU - Piovesan S FAU - Chemello, L AU - Chemello L FAU - Babudieri, S AU - Babudieri S FAU - Moretti, A AU - Moretti A FAU - Gea, F AU - Gea F FAU - Colletta, C AU - Colletta C FAU - Perez-Alvarez, R AU - Perez-Alvarez R FAU - Forns, X AU - Forns X FAU - Larrubia, J R AU - Larrubia JR FAU - Arenas, J AU - Arenas J FAU - Crespo, J AU - Crespo J FAU - Calvaruso, V AU - Calvaruso V FAU - Ceccherini Silberstein, F AU - Ceccherini Silberstein F FAU - Maisonneuve, P AU - Maisonneuve P FAU - Craxi, A AU - Craxi A FAU - Calleja, J L AU - Calleja JL CN - Italian and Spanish (IAS)-BoC Study Group LA - eng PT - Journal Article PT - Observational Study DEP - 20141014 PL - England TA - J Viral Hepat JT - Journal of viral hepatitis JID - 9435672 RN - 0 (Antiviral Agents) RN - 0 (Interferon-alpha) RN - 0 (RNA, Viral) RN - 49717AWG6K (Ribavirin) RN - 89BT58KELH (N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide) RN - 9DLQ4CIU6V (Proline) SB - IM MH - Adult MH - Aged MH - Antiviral Agents/*therapeutic use MH - Drug Therapy, Combination/methods MH - Female MH - Hepacivirus/isolation & purification MH - Hepatitis C, Chronic/*drug therapy/virology MH - Humans MH - Interferon-alpha/*therapeutic use MH - Italy MH - Male MH - Middle Aged MH - Proline/*analogs & derivatives/therapeutic use MH - RNA, Viral/*blood MH - Ribavirin/*therapeutic use MH - Spain MH - Treatment Outcome MH - *Viral Load OTO - NOTNLM OT - IFN-based therapy OT - boceprevir OT - cirrhosis OT - first-generation protease inhibitors OT - hepatitis C FIR - Di Marco, V IR - Di Marco V FIR - Monti, M IR - Monti M FIR - Rizzardini, G IR - Rizzardini G FIR - Landonio, S IR - Landonio S FIR - Rizzetto, M IR - Rizzetto M FIR - Lapini, L E IR - Lapini L FIR - Piazzolla, V IR - Piazzolla V FIR - Picciotto, A IR - Picciotto A FIR - Alberti, A IR - Alberti A FIR - Cavaletto, L IR - Cavaletto L FIR - Koch, M IR - Koch M FIR - Massari, M IR - Massari M FIR - Muratori, L IR - Muratori L FIR - Cipriano, V IR - Cipriano V FIR - Montineri, A IR - Montineri A FIR - Iacobello, C IR - Iacobello C FIR - Fangazio, S IR - Fangazio S FIR - Pirisi, M IR - Pirisi M FIR - Colombo, A IR - Colombo A FIR - Bellati, G IR - Bellati G FIR - Mazzotta, F IR - Mazzotta F FIR - Pierotti, P IR - Pierotti P FIR - Traverso, A IR - Traverso A FIR - Serviddio, G IR - Serviddio G FIR - Russello, M IR - Russello M FIR - Santantonio, T IR - Santantonio T FIR - Drenaggi, D IR - Drenaggi D FIR - Marchionne, E IR - Marchionne E FIR - Zuin, M IR - Zuin M FIR - Delliponti, M IR - Delliponti M FIR - Farina, F IR - Farina F FIR - Andreone, P IR - Andreone P FIR - Scuteri, A IR - Scuteri A FIR - Galli, M IR - Galli M FIR - Giannini, E G IR - Giannini E FIR - Nerli, A IR - Nerli A FIR - Carbonai, S IR - Carbonai S FIR - Coppola, N IR - Coppola N FIR - Montalbano, M IR - Montalbano M FIR - Portelli, V IR - Portelli V FIR - Di Biagio, A IR - Di Biagio A FIR - Nicolini, L A IR - Nicolini L FIR - Mastroianni, C IR - Mastroianni C FIR - Madonia, S IR - Madonia S FIR - Licata, A IR - Licata A FIR - Montalto, G IR - Montalto G FIR - Giannitrapani, L IR - Giannitrapani L FIR - Mondelli, M IR - Mondelli M FIR - Pellicelli, A IR - Pellicelli A FIR - Toniutto, P IR - Toniutto P FIR - Borgia, G IR - Borgia G FIR - Gentile, I IR - Gentile I FIR - De Luca, M IR - De Luca M FIR - Di Costanzo, G G IR - Di Costanzo G FIR - Corti, G IR - Corti G FIR - Cento, V IR - Cento V FIR - Sousa, M IR - Sousa M FIR - Delgado, M B IR - Delgado M FIR - De la Revilla, J IR - De la Revilla J FIR - Navarro, J M IR - Navarro J FIR - Barcena, R IR - Barcena R FIR - Romero-Gomez, M IR - Romero-Gomez M FIR - Fernandez-Rodriguez, C M IR - Fernandez-Rodriguez C FIR - Narvaez, I IR - Narvaez I FIR - Erdozain, J C IR - Erdozain J FIR - Molina, E IR - Molina E FIR - Fernandez, I IR - Fernandez I FIR - Cuenca, B IR - Cuenca B FIR - Planas, R IR - Planas R FIR - Garcia-Samaniego, J IR - Garcia-Samaniego J FIR - Ladero, J M IR - Ladero J FIR - Gonzalez, J M IR - Gonzalez J FIR - Serra, M A IR - Serra M FIR - Castellote, I IR - Castellote I FIR - Sola, R IR - Sola R FIR - Anton, T IR - Anton T FIR - Ryan, I IR - Ryan I FIR - Gonzalez, F IR - Gonzalez F FIR - Martinez, E IR - Martinez E FIR - Portu, J IR - Portu J EDAT- 2014/10/15 06:00 MHDA- 2015/12/24 06:00 CRDT- 2014/10/15 06:00 PHST- 2014/07/16 00:00 [received] PHST- 2014/09/03 00:00 [accepted] PHST- 2014/10/15 06:00 [entrez] PHST- 2014/10/15 06:00 [pubmed] PHST- 2015/12/24 06:00 [medline] AID - 10.1111/jvh.12342 [doi] PST - ppublish SO - J Viral Hepat. 2015 May;22(5):469-80. doi: 10.1111/jvh.12342. Epub 2014 Oct 14.