***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: IMPORTANCE The efficacy of directly acting antiviral agents in interferon-free regimens for the treatment of chronic hepatitis C infections needs to be evaluated in different population s. OBJECTIVE To determine the efficacy and safety of sofosbuvir with weight-based or low-dose ribavirin among a population with unfavorable treatment characteristics . DESIGN , SETTING , AND PATIENTS Single-center , r and omized , 2-part , open-label phase 2 study involving 60 treatment-naive patients with hepatitis C virus ( HCV ) genotype 1 enrolled at the National Institutes of Health ( October 2011-April 2012 ) . INTERVENTIONS In the study 's first part , 10 participants with early to moderate liver fibrosis were treated with 400 mg/d of sofosbuvir and weight-based ribavirin for 24 weeks . In the second part , 50 participants with all stages of liver fibrosis were r and omized 1:1 to receive 400 mg of sofosbuvir with either weight-based or low-dose 600 mg/d of ribavirin for 24 weeks . MAIN OUTCOMES AND MEASURES The primary study end point was the proportion of participants with undetectable HCV viral load 24 weeks after treatment completion ( sustained virologic response of 24 weeks [ SVR24 ] ) . RESULTS In the first part of the study , 9 participants ( 90 % ; 95 % CI , 55%-100 % ) achieved SVR24 . In the second part , 7 participants ( 28 % ) in the weight-based group and 10 ( 40 % ) in the low-dose group relapsed after treatment completion leading to SVR24 rates of 68 % ( 95 % CI , 46%-85 % ) in the weight-based group and 48 % ( 95 % CI , 28%-69 % ; P = .20 ) in the low-dose group . Twenty individuals participated in a pharmacokinetic-viral kinetic sub study , which demonstrated a slower loss rate of infectious virus in relapsers than in participants who achieved SVR ( clearance , 3.57/d vs 5.60/d ; P = .009 ) . The most frequent adverse events were headache , anemia , fatigue , and nausea . There were 7 grade 3 events including anemia , neutropenia , nausea , hypophosphatemia , and cholelithiasis or pancreatitis . No one discontinued treatment due to adverse events . CONCLUSION AND RELEVANCE In a population of patients with a high prevalence of unfavorable traditional predictors of treatment response , a 24-week regimen of sofosbuvir and weight-based or low-dose ribavirin result ed in SVR24 rates of 68 % and 48 % , respectively . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01441180 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 . ) OBJECTIVES Case series constitute a weak form of evidence for effectiveness of health technologies . However , for a variety of reasons , such studies may be included in health technology assessment s. There are no clear criteria for assessing the quality of case series . We carried out an empirical investigation of the association between outcome frequency and method ological characteristics in a sample of health technology assessment s. METHODS Systematic review s of functional endoscopic sinus surgery for nasal polyps , spinal cord stimulation for chronic back pain , and percutaneous transluminal coronary angioplasty and coronary artery bypass grafting for chronic stable angina were identified as containing more than forty case series . Data were extracted by one review er and checked by a second on population characteristics , outcomes , and the following method ological features : sample size , prospect ive/retrospective approach , consecutive recruitment , multi- or single-center organization , length of follow-up , independence of outcome measurement , and date of publication . Association between method ological features and outcome were explored in univariate and multivariate analyses using parametric and nonparametric tests and robust regression or analysis of variance/ analysis of covariance , as appropriate . RESULTS Included review s contained between forty-two and seventy-six case series studies , involving 5 to 172,283 participants . Reporting of method ological features was poor and limited the analyses . In general , we found little evidence of any association between method ological characteristics and outcome . Sample size is used as an inclusion criterion in many review s of'case series but was consistently shown to have no relationship to outcome in all analyses . A prospect i ve approach was not associated with outcome . Insufficient data were available to explore consecutive recruitment . Mixed results were shown for length of follow-up , independence of outcome measurement , and publication date . CONCLUSIONS We found little evidence to support the use of many of the factors included in tools used for quality assessment of case series . Importantly , we found no relationship between study size and outcome across the four examples studied . Isolated examples of a potentially important relationship between other method ological factors and outcome were shown , for example , blinding of outcome measurement , but these examples were not shown consistently across the small number of examples studied . Further research into the determinants of quality in case series studies is required to support health technology assessment Background High baseline levels of IP-10 predict a slower first phase decline in HCV RNA and a poor outcome following interferon/ribavirin therapy in patients with chronic hepatitis C. Several recent studies report that single nucleotide polymorphisms ( SNPs ) adjacent to IL28B predict spontaneous resolution of HCV infection and outcome of treatment among HCV genotype 1 infected patients . Methods and Findings In the present study , we correlated the occurrence of variants at three such SNPs ( rs12979860 , rs12980275 , and rs8099917 ) with pretreatment plasma IP-10 and HCV RNA throughout therapy within a phase III treatment trial ( HCV-DITTO ) involving 253 Caucasian patients . The favorable SNP variants ( CC , AA , and TT , respectively ) were associated with lower baseline IP-10 ( P = 0.02 , P = 0.01 , P = 0.04 ) and were less common among HCV genotype 1 infected patients than genotype 2/3 ( P<0.0001 , P<0.0001 , and P = 0.01 ) . Patients carrying favorable SNP genotypes had higher baseline viral load than those carrying unfavorable variants ( P = 0.0013 , P = 0.029 , P = 0.0004 respectively ) . Among HCV genotype 1 infected carriers of the favorable C , A , or T alleles , IP-10 below 150 pg/mL significantly predicted a more pronounced reduction of HCV RNA from day 0 to 4 ( first phase decline ) , which translated into increased rates of RVR ( 62 % , 53 % , and 39 % ) and SVR ( 85 % , 76 % , and 75 % respectively ) among homozygous carriers with baseline IP-10 below 150 pg/mL. In multivariate analyses of genotype 1-infected patients , baseline IP-10 and C genotype at rs12979860 independently predicted the first phase viral decline and RVR , which in turn independently predicted SVR . Conclusions Concomitant assessment of pretreatment IP-10 and IL28B-related SNPs augments the prediction of the first phase decline in HCV RNA , RVR , and final therapeutic outcome Black Americans ( blacks ) have a high prevalence of chronic hepatitis C virus ( HCV ) infection and respond poorly to therapy with interferon alfa-based regimens , but they have been underrepresented in clinical trials . The aim of this study was to assess the rate of sustained virological response ( SVR ) to peginterferon alfa-2a ( 40 kd ) in combination with ribavirin in black patients chronically infected with HCV genotype 1 . In a prospect i ve , multicenter , open-label trial , 78 black and 28 white American interferon-naïve patients were enrolled to receive once weekly subcutaneous injections of 180 microg peginterferon alfa-2a plus oral ribavirin ( 1000 mg/d for patients weighing less than 75 kg and 1200 mg/d for patients weighing 75 kg or more ) for 48 weeks . Pre- and post-treatment liver biopsies were evaluated for necroinflammation and fibrosis . SVR , defined as undetectable ( < 50 IU/mL ) HCV RNA , was 26 % in the black group and 39 % in the white group . Although the SVR rate was lower in blacks than in whites , the SVR of 26 % represents an improvement over previously reported SVR rates from smaller , retrospective studies of black patients . We also observed improvement in fibrosis in 25 % of the black patients . No unexpected adverse events occurred . In conclusion , this prospect i ve study evaluating responses of black patients with chronic hepatitis C to  peginterferon alfa-2a/ribavirin has demonstrated that treatment can be safely offered to such individuals with reasonable antiviral and histological benefit BACKGROUND Several small studies have reported a lower response rate to interferon alfa among black patients with chronic hepatitis C infection than among white patients . The increased prevalence of infection with hepatitis C virus ( HCV ) genotype 1 , which has a lower response rate than other genotypes , has been suggested as the cause . METHODS We treated 100 black patients and 100 non-Hispanic white patients with chronic hepatitis C with peginterferon alfa-2b and ribavirin for 48 weeks . Enrollment was controlled so that the two groups had similar proportions of patients with genotype 1 infection . The primary end point was a sustained virologic response , which was defined as a negative test for serum HCV RNA six months after the completion of therapy . RESULTS In both cohorts , 98 percent of patients had genotype 1 infection . The rate of sustained virologic response was higher among non-Hispanic white patients than among black patients ( 52 percent vs.19 percent , P<0.001 ) . The black patients also had significantly lower rates of virologic response at 12 weeks and at the end of treatment . Multivariable analyses examining sociodemographic and clinical characteristics found that black race was the only variable significantly associated with the difference in response rate . CONCLUSIONS Black patients with chronic hepatitis C have a lower rate of response to treatment with peginterferon alfa-2b and ribavirin than non-Hispanic white patients , a difference that is not explained by differences in the viral genotype BACKGROUND The st and ard treatment for hepatitis C virus ( HCV ) infection is interferon , which 
    Output:
    
A trend was seen for an association between RVR and baseline IP-10 for genotype 4 , while no association was found for genotype 2 and 3 .
We found indications of a possible association between baseline IP-10 level and virological responses in patients with CHC genotype 1 and 4