***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 The worldwide prevalence of chronic hepatitis C virus ( HCV ) infection is estimated to be approaching 200 million people . Current therapy relies upon a combination of pegylated interferon-α and ribavirin , a poorly tolerated regimen typically associated with less than 50 % sustained virological response rate in those infected with genotype 1 virus . The development of direct-acting antiviral agents to treat HCV has focused predominantly on inhibitors of the viral enzymes NS3 protease and the RNA-dependent RNA polymerase NS5B . Here we describe the profile of BMS-790052 , a small molecule inhibitor of the HCV NS5A protein that exhibits picomolar half-maximum effective concentrations ( EC50 ) towards replicons expressing a broad range of HCV genotypes and the JFH-1 genotype 2a infectious virus in cell culture . In a phase I clinical trial in patients chronically infected with HCV , administration of a single 100-mg dose of BMS-790052 was associated with a 3.3 log10 reduction in mean viral load measured 24 h post-dose that was sustained for an additional 120 h in two patients infected with genotype 1b virus . Genotypic analysis of sample s taken at baseline , 24 and 144 h post-dose revealed that the major HCV variants observed had substitutions at amino-acid positions identified using the in vitro replicon system . These results provide the first clinical validation of an inhibitor of HCV NS5A , a protein with no known enzymatic function , as an approach to the suppression of virus replication that offers potential as part of a therapeutic regimen based on combinations of HCV inhibitors BACKGROUND & AIMS Fibrosing cholestatic hepatitis ( FCH ) is a life-threatening disorder that develops in patients with recurrent hepatitis C virus ( HCV ) infection after liver transplantation . Until recently , therapeutic options have been limited . We evaluated the efficacy and safety of sofosbuvir- and daclatasvir-based regimens . METHODS We analyzed data from 23 patients with FCH who participated in a prospect i ve cohort study in France and Belgium of the effects of antiviral agents in patients with recurrence of HCV infection after liver transplantation , from October 2013 through April 2014 . Most of the patients had genotype 1 infections that had not responded to previous treatment ; 4 patients also were infected with human immunodeficiency virus . Eight patients ( 37 % ) had ascites and 15 patients ( 65 % ) had bilirubin levels greater than 100 mmol/L ; their median serum level of HCV RNA was 7 log IU/mL. The median time between transplantation and treatment initiation was 5 months . Subjects were given either sofosbuvir and daclatasvir ( n = 15 ) or sofosbuvir and ribavirin ( n = 8) for 24 weeks . The primary outcome was complete clinical response ( survival without re-transplantation , bilirubin level < 34 μmol/L , and no ascites or hepatic encephalopathy 36 weeks after treatment began ) . RESULTS All patients survived , without re-transplantation , until week 36 . Rapid and dramatic improvements in clinical status were observed . The patients ' median bilirubin concentration decreased from 122 μmol/L at baseline to a normal value at week 12 of treatment . Twenty-two patients ( 96 % ) had a complete clinical response at week 36 . Despite the low rate of rapid virologic response , 22 patients ( 96 % ) achieved a sustained virologic response at week 12 . The only relapse of HCV infection occurred in a patient with human immunodeficiency virus infection who received sofosbuvir and ribavirin . Tolerance was satisfactory , with no grade 3 or 4 adverse events related to sofosbuvir or daclatasvir and no significant interactions among drugs . CONCLUSIONS Sofosbuvir therapy with daclatasvir or ribavirin leads to major clinical improvement and high rates of sustained virologic response at week 12 in most patients with recurrence of HCV infection and FCH after liver transplantation . Clinical Trial.gov no : NCT01944527 BACKGROUND All-oral combination therapy is desirable for patients with chronic hepatitis C virus ( HCV ) infection . We evaluated daclatasvir ( an HCV NS5A replication complex inhibitor ) plus sofosbuvir ( a nucleotide analogue HCV NS5B polymerase inhibitor ) in patients infected with HCV genotype 1 , 2 , or 3 . METHODS In this open-label study , we initially r and omly assigned 44 previously untreated patients with HCV genotype 1 infection and 44 patients infected with HCV genotype 2 or 3 to daclatasvir  at a dose of 60 mg orally once daily plus sofosbuvir at a dose of 400 mg orally once daily , with or without ribavirin , for 24 weeks . The study was exp and ed to include 123 additional patients with genotype 1 infection who were r and omly assigned to daclatasvir plus sofosbuvir , with or without ribavirin , for 12 weeks ( 82 previously untreated patients ) or 24 weeks ( 41 patients who had previous virologic failure with telaprevir or boceprevir plus peginterferon alfa-ribavirin ) . The primary end point was a sustained virologic response ( an HCV RNA level of < 25 IU per milliliter ) at week 12 after the end of therapy . RESULTS Overall , 211 patients received treatment . Among patients with genotype 1 infection , 98 % of 126 previously untreated patients and 98 % of 41 patients who did not have a sustained virologic response with HCV protease inhibitors had a sustained virologic response at week 12 after the end of therapy . A total of 92 % of 26 patients with genotype 2 infection and 89 % of 18 patients with genotype 3 infection had a sustained virologic response at week 12 . High rates of sustained virologic response at week 12 were observed among patients with HCV subtypes 1a and 1b ( 98 % and 100 % , respectively ) and those with CC and non-CC IL28B genotypes ( 93 % and 98 % , respectively ) , as well as among patients who received ribavirin and those who did not ( 94 % and 98 % , respectively ) . The most common adverse events were fatigue , headache , and nausea . CONCLUSIONS Once-daily oral daclatasvir plus sofosbuvir was associated with high rates of sustained virologic response among patients infected with HCV genotype 1 , 2 , or 3 , including patients with no response to prior therapy with telaprevir or boceprevir . ( Funded by Bristol-Myers Squibb and Pharmasset ( Gilead ) ; A1444040 Clinical Trials.gov number , NCT01359644 . ) Chronic hepatitis C virus ( HCV ) infection with advanced cirrhosis or post‐liver transplantation recurrence represents a high unmet medical need with no approved therapies effective across all HCV genotypes . The open‐label ALLY‐1 study assessed the safety and efficacy of a 60‐mg once‐daily dosage of daclatasvir ( pan‐genotypic NS5A inhibitor ) in combination with sofosbuvir at 400 mg once daily ( NS5B inhibitor ) and ribavirin at 600 mg/day for 12 weeks with a 24‐week follow‐up in two cohorts of patients with chronic HCV infection of any genotype and either compensated/decompensated cirrhosis or posttransplantation recurrence . Patients with on‐treatment transplantation were eligible to receive 12 additional weeks of treatment immediately after transplantation . The primary efficacy measure was sustained virologic response at posttreatment week 12 ( SVR12 ) in patients with a genotype 1 infection in each cohort . Sixty patients with advanced cirrhosis and 53 with posttransplantation recurrence were enrolled ; HCV genotypes 1 ( 76 % ) , 2 , 3 , 4 , and 6 were represented . Child‐Pugh classifications in the advanced cirrhosis cohort were 20 % A , 53 % B , and 27 % C. In patients with cirrhosis , 82 % ( 95 % confidence interval [ CI ] , 67. 
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CONCLUSION SOF+DCV±RBV regimen is of high efficacy and tolerability in LT recipients with HCV infection