***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: The optimal retreatment strategy for patients chronically infected with hepatitis C virus who experience virologic failure after treatment with direct‐acting antiviral – based therapies remains unclear . In this multicenter , open‐label , phase 2 study , we evaluated the efficacy and safety of a fixed‐dose combination of sofosbuvir‐velpatasvir ( 400 mg/100 mg ) plus weight‐adjusted ribavirin administered for 24 weeks in patients who did not achieve sustained virologic response after prior treatment with direct‐acting antiviral regimens that included the nucleotide analogue nonstructural protein 5B inhibitor sofosbuvir plus the nonstructural protein 5A inhibitor velpatasvir with or without the nonstructural protein 3/4A protease inhibitor voxilaprevir . The primary efficacy endpoint was the proportion of patients achieving sustained virologic response at 12 weeks after the cessation of treatment . In total , 63 of 69 ( 91 % ; 95 % confidence interval , 82%‐97 % ) patients achieved sustained virologic response at 12 weeks , including 36 of 37 ( 97 % ; 95 % confidence interval , 86%‐100 % ) patients with hepatitis C virus genotype 1 infection , 13 of 14 ( 93 % ; 95 % confidence interval , 66%‐100 % ) patients with genotype 2 infection , and 14 of 18 ( 78 % ; 95 % confidence interval , 52%‐94 % ) patients with genotype 3 infection . Most adverse events were of mild or moderate severity . The most frequently reported adverse events were fatigue , nausea , headache , insomnia , and rash . One patient ( 1 % ) with genotype 1a infection discontinued all study drugs due to an adverse event ( irritability ) . Conclusion : Retreatment of patients who previously failed direct‐acting antiviral – based therapies  with sofosbuvir‐velpatasvir plus ribavirin for 24 weeks was well tolerated and effective , particularly those with hepatitis C virus genotype 1 or 2 infection . ( Hepatology 2017;66:1083‐1089 ) BACKGROUND Interferon-based treatment is not suitable for many patients with hepatitis C virus ( HCV ) infection because of contraindications such as psychiatric illness , and a high burden of adverse events . We assessed the efficacy and safety of an interferon-free regimen -- a fixed-dose combination of the nucleotide polymerase inhibitor sofosbuvir ( 400 mg ) and the HCV NS5A inhibitor ledipasvir ( 90 mg ) , with and without ribavirin -- in patients with genotype-1 hepatitis C infection who were treatment-naive or previously treated with a protease-inhibitor regimen . METHODS For this open-label study , we enrolled 100 adult patients ( > 18 years ) with HCV infection at a centre in the USA between Nov 2 , 2012 , and Dec 21 , 2012 . In cohort A , we used a computer-generated sequence to r and omly assign ( 1:1:1 ; stratified by HCV genotype [ 1a vs 1b ] ) 60 non-cirrhotic , treatment-naive patients to receive sofosbuvir plus ledipasvir for 8 weeks ( group 1 ) , sofosbuvir plus ledipasvir and ribavirin for 8 weeks ( group 2 ) , or sofosbuvir plus ledipasvir for 12 weeks ( group 3 ) . In cohort B , we r and omly allocated ( 1:1 ; stratified by genotype and presence or absence of cirrhosis ) 40 patients who previously had virological failure after receiving a protease inhibitor regimen to receive sofosbuvir plus ledipasvir for 12 weeks ( group 4 ) or sofosbuvir plus ledipasvir and ribavirin for 12 weeks ( group 5 ) . 22 ( 55 % ) of 40 patients in cohort B had compensated cirrhosis . The primary endpoint was sustained virological response 12 weeks after treatment ( SVR12 ) , analysed by intention to treat . This study is registered with Clinical Trials.gov , number NCT01329978 . FINDINGS In cohort A , SVR12 was achieved by 19 ( 95 % ) of 20 patients ( 95 % CI 75 - 100 ) in group 1 , by 21 ( 100 % ) of 21 patients ( 84 - 100 ) in group 2 , and by 18 ( 95 % ) of 19 patients ( 74 - 100 ) in group 3 . In cohort B , SVR12 was achieved by 18 ( 95 % ) of 19 patients ( 74 - 100 ) in group 4 and by all 21 ( 100 % ) of 21 patients ( 84 - 100 ) in group 5 . Two patients had viral relapse ; one patient was lost to follow-up after achieving sustained virological response 8 weeks after treatment . The most common adverse events were nausea , anaemia , upper respiratory tract infection , and headache . One patient in group five had a serious adverse event of anaemia , thought to be related to ribavirin treatment . INTERPRETATION These findings suggest that the fixed-dose combination of sofosbuvir-ledipasvir alone or with ribavirin has the potential to cure most patients with genotype-1 HCV , irrespective of treatment history or the presence of compensated cirrhosis . Further clinical trials are needed to establish the best treatment duration and to further assess the contribution of ribavirin . FUNDING Gilead Sciences BACKGROUND The once-daily , ribavirin-free , pangenotypic , direct-acting antiviral regimen , glecaprevir coformulated with pibrentasvir , has shown high rates of sustained virological response in phase 2 and 3 studies . We aim ed to assess the efficacy and safety of 12 weeks of coformulated glecaprevir and pibrentasvir in patients with hepatitis C virus ( HCV ) infection and compensated cirrhosis . METHODS We did this single-arm , open-label , multicentre phase 3 study at 40 sites in Belgium , Canada , Germany , South Africa , Spain , and the USA . We enrolled patients aged 18 years or older with HCV genotype 1 , 2 , 4 , 5 , or 6 infection and compensated cirrhosis . Patients were either HCV treatment-naive or had not responded to treatment with interferon or pegylated interferon with or without ribavirin , or sofosbuvir plus ribavirin with or without pegylated interferon . Oral glecaprevir ( 300 mg ) coformulated with pibrentasvir ( 120 mg ) was administered once daily for 12 weeks . The primary efficacy endpoint was sustained virological response at post-treatment week 12 ( HCV RNA < 15 IU/mL ) . We assessed efficacy and safety in all patients who received at least one dose of study drug ( intention-to-treat population ) . This study is registered with Clinical Trials.gov , number NCT02642432 . FINDINGS Between Dec 7 , 2015 , and May 4 , 2016 , we enrolled 146 patients with compensated cirrhosis , of whom 48 ( 33 % ) had genotype 1a HCV infection , 39 ( 27 % ) had genotype 1b infection , 34 ( 23 % ) had genotype 2 infection , 16 ( 11 % ) had genotype 4 infection , two ( 1 % ) had genotype 5 infection , and seven ( 5 % ) had genotype 6 infection . 12 weeks after treatment , 145 patients ( 99 % , 95 % CI 98 - 100 ) achieved sustained virological response , with one ( 1 % ) relapse at post-treatment week 8 . We recorded 101 ( 69 % ) adverse events , of which 65 ( 64 % ) were mild . The most common adverse events were fatigue ( n=28 [ 19 % ] ) and headache ( n=20 [ 14 % ] ) . 11 ( 8 % ) patients had serious adverse events , none of which were deemed related to study drugs . No patients had elevations in alanine aminotransferase and no patients prematurely discontinued treatment because of adverse events . INTERPRETATION Our results show that 99 % of patients treated with once-daily glecaprevir plus pibrentasvir achieved a sustained virological response at 12 weeks . Furthermore , this drug regimen had a favourable safety profile in previously treated or untreated patients with chronic HCV genotype 1 , 2 , 4 , 5 , or 6 infection and compensated cirrhosis . These findings could help simplify treatment algorithms and reduce treatment burden . FUNDING AbbVie Glecaprevir ( nonstructural protein 3/4A protease inhibitor ) and pibrentasvir ( nonstructural protein 5A inhibitor ) ( G/P ) , a coformulated once‐daily , all oral , ribavirin (RBV)‐free , direct‐acting antiviral regimen , was evaluated for safety and efficacy in hepatitis C virus genotype 2 (GT2)–infected Japanese patients , including those with compensated cirrhosis . CERTAIN‐2 is a phase 3 , open‐label , multicenter study assessing the safety and efficacy of G/P ( 300/120 mg ) once daily in treatment‐naive and interferon ± RBV treatment – experienced Japanese patients without cirrhosis but with GT2 infection . Patients were r and omized 2:1 to receive 8 weeks of G/P ( arm A ) or 12 weeks of sofosbuvir ( 400 mg once daily ) + RBV ( 600‐1000 mg weight‐based , twice daily ) ( arm B ) . The primary endpoint was noninferiority of G/P compared to sofosbuvir + RBV by assessing sustained virologic response at posttreatment week 12 ( SVR12 ) among patients in the intent‐to‐treat population . SVR12 was also assessed in treatment‐naive and  interferon ± RBV  treatment‐experienced patients with GT2 infection and compensated cirrhosis who received G/P for 12 weeks in the CERTAIN‐1 study . A total of 136 patients were enrolled in CERTAIN‐2 . SVR12 was achieved by 88/90 ( 97.8 % ) patients in arm A and 43/46 ( 93.5 % ) patients in arm B. No patient in arm A experienced virologic failure , while 2 did in arm B. The primary endpoint was achieved . In CERTAIN‐1 , 100 % ( 18/18 ) of GT2‐infected patients with compensated cirrhosis achieved SVR12 . Treatment‐emergent serious adverse events were experienced by 2 patients without cirrhosis in each arm and no patient with cirrhosis . Conclusion : The results demonstrate high efficacy and favorable tolerability of G/P in GT2‐infected Japanese patients . ( Hepatology 2018;67:505‐513 ) The phase 2 , open-label ACCORDION ( Clinical Trials.gov : NCT02349048 ) study investigated the efficacy , safety and pharmacokinetics of a 6- or 8-week regimen of simeprevir , daclatasvir and sofosbuvir in treatment-naïve patients with chronic hepatitis C virus ( HCV ) genotype ( GT ) 1 infection and either early-stage fibrosis or compensated cirrhosis . Patients were assigned to treatment groups according to their fibrosis stage . Early-stage fibrosis : simeprevir 150 mg , daclatasvir 60 mg , sofosbuvir 400 mg once daily for 6 weeks ; compensated cirrhosis : same regimen for 8 weeks . The primary endpoint was sustained virologic response 12 weeks after the end of treatment ( SVR12 ) . Safety , tolerability and pharmacokinetics of simeprevir , daclatasvir and sofosbuvir were investigated . Sixty-eight patients were treated ( 6-week group : n = 59 ; 8-week group : n = 9 ) . SVR12 was achieved by 86.4 % ( 51/59 ) of patients with early-stage fibrosis and by 100 % ( 9/9 ) of patients with cirrhosis . The main reason for not achieving SVR12 in the 6-week group was viral relapse ( 11.9 % ; 7/59 ) . One patient had on-treatment failure due to an early withdrawal ( lost to follow-up due to incarceration ) . One patient with SVR12 in the 6-week group had a late viral relapse at post-treatment week 24 . No clinical ly significant drug-drug interactions were observed . Adverse events were reported in 63.2 % of patients ( 43/68 ) and were mainly grade 1/2 . None of these led to treatment discontinuation . The 3 direct-acting antiviral regimens of simeprevir , daclatasvir and sofosbuvir were safe and well tolerated in treatment-naïve , HCV GT1-infected patients 
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Personalised strategies ( 100 % vs 87.6 % ; p<0.001 ) and therapy shortened according to ≥3 host/viral factors ( 92.9 % vs 81.4 % or 87.2 % for 1 or 2 host/viral factors , respectively ; p=0.008 ) offer higher SVR rates when shortening therapy .
Conclusions : Treatment optimisation for individuals with multiple predictors of treatment failure can offer high SVR rates .