***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: 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 Treatment options are limited for patients infected by hepatitis C virus ( HCV ) with advanced liver disease . We assessed the safety and efficacy of ledipasvir , sofosbuvir , and ribavirin in patients with HCV genotype 1 or 4 and advanced liver disease . METHODS We did an open-label study at 34 sites in Europe , Canada , Australia , and New Zeal and . Cohort A included patients with Child-Turcotte-Pugh class B ( CTP-B ) or CTP-C cirrhosis who had not undergone liver transplantation . Cohort B included post-transplantation patients who had either no cirrhosis ; CTP-A , CTP-B , or CTP-C cirrhosis ; or fibrosing cholestatic hepatitis . Patients in each group were r and omly assigned ( 1:1 ) using a computer-generated r and omisation sequence to receive 12 or 24 weeks of ledipasvir ( 90 mg ) and sofosbuvir ( 400 mg ) once daily ( combination tablet ) , plus ribavirin ( 600 - 1200 mg daily ) . The primary endpoint was the proportion of patients achieving a sustained virological response 12 weeks after treatment ( SVR12 ) . All patients who received at least one dose of study drug were included in the safety analysis and all patients who received at least one dose of study drug and did not undergo liver transplantation during treatment were included in the efficacy analyses . Estimates of SVR12 and relapse rates and their two-sided 90 % CI ( Clopper-Pearson method ) were provided . This exploratory phase 2 study was not powered for formal comparisons among treatment groups ; no statistical hypothesis testing was planned or conducted . The trial is registered with EudraCT ( number 2013 - 002802 - 30 ) and Clinical Trials.gov ( number NCT02010255 ) . FINDINGS Between Jan 14 , 2014 , and Aug 19 , 2014 , 398 patients were screened . Of 333 patients who received treatment , 296 had genotype 1 HCV and 37 had genotype 4 HCV . In cohort A , among patients with genotype 1 HCV , SVR12 was achieved by 20 ( 87 % , 90 % CI 70 - 96 ) of 23 CTP-B patients with 12 weeks of treatment ; 22 ( 96 % , 81 - 100 ) of 23 CTP-B patients with 24 weeks of treatment ; 17 ( 85 % , 66 - 96 ) of 20 CTP-C patients ( 12 weeks treatment ) ; and 18 ( 78 % , 60 - 91 ) of 23 CTP-C patients ( 24 weeks treatment ) . In cohort B , among patients with genotype 1 HCV , SVR12 was achieved by 42 ( 93 % , 84 - 98 ) of 45 patients without cirrhosis ( 12 weeks treatment ) ; 44 ( 100 % , 93 - 100 ) of 44 patients without cirrhosis ( 24 weeks treatment ) ; 30 ( 100 % , 91 - 100 ) of 30 CTP-A patients ( 12 weeks treatment ) ; 27 ( 96 % , 84 - 100 ) of 28 CTP-A patients ( 24 weeks treatment ) ; 19 ( 95 % , 78 - 100 ) of 20 CTP-B patients ( 12 weeks treatment ) ; 20 ( 100 % , 86 - 100 ) of 20 CTP-B patients ( 24 weeks treatment ) ; one ( 50 % , 3 - 98 ) of two CTP-C patients ( 12 weeks treatment ) ; and four ( 80 % , 34 - 99 ) of five CTP-C patients ( 24 weeks treatment ) . All five patients with fibrosing cholestatic hepatitis achieved SVR12 ( 100 % , 90 % CI 55 - 100 ) . Among all patients with genotype 4 HCV , SVR12 was achieved by 14 ( 78 % , 56 - 92 ) of 18 patients ( 12 weeks treatment ) and 16 ( 94 % , 75 - 100 ) of 17 patients ( 24 weeks treatment ) . Seven patients ( 2 % ) discontinued ledipasvir-sofosbuvir prematurely due to adverse events . 17 patients died , mainly from complications of hepatic decompensation . INTERPRETATION Ledipasvir-sofosbuvir and ribavirin provided high rates of SVR12 for patients with advanced liver disease , including those with decompensated cirrhosis before or after liver transplantation . FUNDING Gilead Sciences BACKGROUND Hepatitis C virus ( HCV ) genotype 4 accounts for about 13 % of global HCV infections . Because interferon-containing treatments for genotype 4 infection have low efficacy and poor tolerability , an unmet need exists for effective all-oral regimens . We examined the efficacy and safety of an all-oral interferon-free regimen of ombitasvir , an NS5A inhibitor , and paritaprevir ( ABT-450 ) , an NS3/4A protease inhibitor dosed with ritonavir ( ombitasvir plus paritaprevir plus ritonavir ) , given with or without ribavirin . METHODS In this multicentre ongoing phase 2b , r and omised , open-label combination trial ( PEARL-I ) , patients were recruited from academic , public , and private hospitals and clinics in France , Hungary , Italy , Pol and , Romania , Spain , Turkey , and the USA . Eligible participants were aged 18 - 70 years with non-cirrhotic , chronic HCV genotype 4 infection ( documented ≥6 months before screening ) and plasma HCV RNA levels higher than 10,000 IU/mL. Previously untreated ( treatment-naive ) patients were r and omly assigned ( 1:1 ) by computer-generated r and omisation lists to receive once-daily ombitasvir ( 25 mg ) plus paritaprevir ( 150 mg ) plus ritonavir ( 100 mg ) with or without weight-based ribavirin for 12 weeks . Previously treated ( treatment-experienced ) patients who had received pegylated interferon plus ribavirin all received the ribavirin-containing regimen . The primary endpoint was a sustained virological response ( HCV RNA < 25 IU/mL ) 12 weeks after the end of treatment ( SVR12 ) . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT01685203 . FINDINGS Between Aug 14 , 2012 , and Nov 19 , 2013 , 467 patients with HCV infection were screened , of whom 174 were infected with genotype 4 . 135 patients were r and omly assigned to treatment and received at least one dose of study medication ; 86 patients were treatment-naive , of whom 44 received ombitasvir plus paritaprevir plus ritonavir and 42 received ombitasvir plus paritaprevir plus ritonavir with ribavirin , and 49 treatment-experienced patients received the ribavirin-containing regimen . In previously untreated patients , SVR12 rates were 100 % ( 42/42 [ 95 % CI 91·6 - 100 ] ) in the ribavirin-containing regimen and 90·9 % ( 40/44 [ 95 % CI 78·3 - 97·5 ] ) in the ribavirin-free regimen . No statistically significant differences in SVR12 rates were noted between the treatment-naive groups ( mean difference -9·16 % [ 95 % CI -19·61 to 1·29 ] ; p=0·086 ) . All treatment-experienced patients achieved SVR12 ( 49/49 ; 100 % [ 95 % CI 92·7 - 100 ] ) . In the ribavirin-free group , two ( 5 % ) of 42 treatment-naive patients had virological relapse , and one ( 2 % ) of 44 had virological breakthrough ; no virological failures were recorded in the ribavirin-containing regimen . The most common adverse event was headache ( 14 [ 29 % ] of 49 treatment-experienced patients and 14 [ 33 % ] of 42 treatment-naive patients ) . No adverse event-related discontinuations or dose interruptions of study medications , including ribavirin , were noted , and only four patients ( 4 % ) of 91 receiving ribavirin required dose modification for haemoglobin less than 100 g/L or anaemia . INTERPRETATION An interferon-free regimen of ombitasvir plus paritaprevir plus ritonavir with or without ribavirin achieved high sustained virological response rates at 12 weeks after the end of treatment and was generally well tolerated , with low rates of anaemia and treatment discontinuation in non-cirrhotic previously untreated and previously treated patients with HCV genotype 4 infection . FUNDING AbbVie BACKGROUND & AIMS Direct-acting antiviral agents have improved treatment outcomes for patients with hepatitis C virus ( HCV ) infection ; however , head-to-head comparisons are limited . The C-EDGE Head-2-Head Study compared the safety and efficacy of elbasvir/grazoprevir ( EBR/GZR ) with sofosbuvir plus pegylated interferon/ribavirin ( SOF/PR ) in patients with HCV infection . METHODS This was a r and omized , open-label , phase III trial . Two hundred fifty-seven patients with HCV 
    Output:
    
Conclusions Second-generation DAAs presented several advantages : virologic response values higher than the average achieved by previous IFN-based therapies , reduced treatment duration , and the possibility of different combinations of therapies to meet patient needs .
Thus , IFN-free therapies appear to be valuable alternatives for the treatment of chronic hepatitis