***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: Nearly 10 % of kidney transplant recipients in Western countries have chronic hepatitis C virus ( HCV ) infection ( 1 ) . The higher HCV prevalence in kidney transplant recipients than in the general population is a direct consequence of the association between HCV infection and kidney impairment as well as an increased risk for HCV infection acquired during hemodialysis or from blood transfused before routine HCV screening ( 2 , 3 ) . Chronic HCV infection increases the risk for end-stage renal disease  ( 47 ) and , in kidney transplant patients , is associated with higher graft loss and mortality rates ( 810 ) . Treatment with interferon regimens has been limited because of the increased risk for interferon-mediated graft rejection and relatively low efficacy , result ing in an unacceptable riskbenefit ratio ( 8 , 11 ) . Direct-acting antiviral agents ( DAAs ) were developed that are highly effective against all HCV genotypes and seemed to be safe and effective in clinical trials as well as in studies of immunocompromised patients , such as orthotopic liver transplant recipients with HCV infection . Interest in using DAAs to treat HCV infection in kidney transplant patients has increased ; however , data regarding their use in this population are very limited ( 3 , 12 , 13 ) . In 2 small studies , treatment with a combination of DAAs for 12 weeks led to high rates of sustained virologic response ( SVR ) in kidney transplant recipients , with no significant adverse events or graft rejection noted ( 14 , 15 ) . In clinical trials , the fixed-dose combination of ledipasvir and sofosbuvir given for 12 or 24 weeks provided SVR rates ranging from 93 % to 99 % in treatment-naive and -experienced patients with HCV genotype 1 , 4 , 5 , or 6 infection ( 1620 ) . European and North American guidelines recommend as first-line options treatment with ledipasvirsofosbuvir for 12 weeks , along with ribavirin for patients without cirrhosis or with ribavirin for those with cirrhosis , or for 24 weeks without ribavirin in patients with cirrhosis who are intolerant or have a contraindication to ribavirin ( 21 , 22 ) . The high efficacy observed with fixed-dose ledipasvirsofosbuvir , even when not administered with ribavirin , represents a critical advantage for treating patients with impaired kidney function , avoiding the need for complicated ribavirin dosing strategies and assessment of ribavirin blood concentration . In addition , the lack of significant drugdrug interactions between ledipasvirsofosbuvir and immunosuppressant drugs and the absence of a clinical ly relevant effect of hepatic dysfunction on drug pharmacokinetics support its use in treating HCV recurrence after liver transplantation ( 23 , 24 ) . On the basis of these encouraging data , we conducted the first multinational , r and omized , controlled study to make an exploratory comparison of the efficacy and safety of 12 and 24 weeks of ledipasvirsofosbuvir without ribavirin in kidney transplant patients with chronic HCV genotype 1 or 4 infection . Supplement . Study Protocol Methods Setting and Participants Patients were enrolled at 5 clinical sites in 4 European countries : Italy , France , Austria , and Germany . Eligible patients were aged 18 years or older ; had chronic HCV genotype 1 or 4 infection , with plasma HCV RNA levels of 15 IU/mL or greater ; and had received a kidney transplant at least 6 months before the baseline study visit . Patients with compensated cirrhosis were eligible , with cirrhosis defined as a METAVIR score of 4 or an Ishak score of 5 or greater by biopsy , a FibroScan ( Echosens ) value greater than 12.5 kPa , or a FibroTest ( BioPredictive ) score greater than 0.75 plus an aspartate aminotransferaseplatelet ratio index greater than 2 . Patients were excluded from participation if they had a body mass index less than 18 kg/m2 ; decompensated liver disease ( that is , presence of ascites , encephalopathy , or variceal hemorrhage ) ; an electrocardiogram with clinical ly significant abnormalities ; HIV infection ; hepatitis B virus infection ; creatinine clearance less than 40 mL/min , as calculated by the CockcroftGault equation ; an albumin level lower than 30 g/L ; an international normalized ratio greater than 1.5 times the upper limit of normal ( unless the patient had hemophilia or was stable while receiving an anticoagulant regimen affecting international normalized ratio ) ; a hemoglobin level lower than 100 g/L ; a platelet level of 50109 cells/L or less ; a direct bilirubin level greater than 1.5 times the upper limit of normal , except for patients with Gilbert syndrome ; and an alanine aminotransferase , aspartate aminotransferase , or alkaline phosphatase level greater than 10 times the upper limit of normal . All patients provided written informed consent before undertaking any study -related procedures . Study Design Patients were r and omly assigned 1:1 to receive either 12 or 24 weeks of treatment with a fixed-dose combination of ledipasvir ( 90 mg ) and sofosbuvir ( 400 mg ) once daily by means of an integrated Web response system ( Bracket ) . A statistician employed by the sponsor generated the r and omization code by using SAS version 9.2 ( SAS Institute ) . R and omization was stratified by genotype , treatment history ( treatment naive or experienced ) , and the presence or absence of cirrhosis . Investigators , patients , and trial personnel were not blinded to treatment assignment . The study protocol was approved by each institution 's review board or ethics committee before study initiation . The study was conducted in accordance with the International Conference on Harmonisation ( ICH ) Good Clinical Practice Guidelines and the Declaration of Helsinki . All authors had access to the study data and review ed and approved the final manuscript before journal su bmi ssion . Study Assessment s Plasma HCV RNA was analyzed by using the COBAS AmpliPrep/COBAS TaqMan HCV Test , v2.0 ( Roche Molecular Systems ) , with a lower limit of quantification ( LLOQ ) of 15 IU/mL. Hepatitis C virus genotype and subtype were determined by using the Versant HCV Genotype INNO-LiPA 2.0 assay ( Siemens ) . An interleukin-28B genotype test was done through polymerase chain reaction amplification and sequencing of the rs12979860 single-nucleotide polymorphism . Plasma sample s for viral sequencing were collected at the same time points as those for HCV RNA levels . Deep sequencing of the NS5A and NS5B regions of the HCV RNA with MiSeq technology ( DDL Diagnostic Laboratory ) was performed on sample s collected from all patients at baseline and on posttreatment sample s from all patients with virologic failure . The result ing sequences were compared with reference sequences to determine the prevalence of resistance-associated substitutions ( RASs ) and the association of RASs with virologic outcomes . Resistance-associated substitutions present at more than 15 % of sequence reads are reported . Adverse events were recorded from day 1 of treatment until 30 days after the last dose ; serious adverse events and adverse events related to protocol -m and ated procedures were collected from screening through the last day of follow-up ( posttreatment week 24 ) or 30 days after the last dose . The data included reported adverse events as well as the results of physical examinations and clinical laboratory tests , vital signs , and electrocardiogram recordings . Treatment-emergent clinical and laboratory adverse events were summarized by using the Medical Dictionary for Regulatory Activities ( MedDRA ) , version 19.0 ( the MedDRA trademark is owned by the International Federation of Pharmaceutical Manufacturers and Associations on behalf of the ICH ) . Virologic relapse was defined as HCV RNA at the LLOQ or higher during the posttreatment period in a patient who had HCV RNA less than the LLOQ at the end of treatment . End Points and Statistical Analysis The primary efficacy end point was the percentage of patients with HCV RNA less than the LLOQ 12 weeks after stopping the study drug ( SVR12 ) . In the primary efficacy analysis , the SVR12 rate was calculated with a 2-sided 95 % exact CI by using the ClopperPearson method ( 25 ) . Patients with missing HCV RNA values at posttreatment week 12 who had posttreatment HCV RNA values less than the LLOQ before and after the missing posttreatment week 12 value were assumed to have achieved SVR12 . This study was exploratory in nature ; no inferential statistics or statistical comparisons were planned . The primary safety end point was any adverse event leading to permanent discontinuation of the study drug . We used SAS , version 9.2 , for all statistical analyses . Role of the Funding Source The sponsor design ed and conducted the study in collaboration with the principal investigators , collected the data , and monitored the study conduct . Results Study Population Of 130 patients screened , 16 ( 12.3 % ) were excluded : 11 did not meet eligibility criteria , 2 withdrew consent , and 3 were excluded because of existing clinical ly significant medical conditions ( atrial fibrillation , planned heart surgery , and hyponatremia with a urinary tract infection ) . A total of 114 patients were enrolled and treated at 5 sites in 4 European countries between 7 November 2014 and 16 June 2015 ( Appendix Figure ) . Overall , 94 % of the patients were white and 58 % were male ( Table 1 ) . Most were treatment naive ( 69 % ) , did not have cirrhosis ( 85 % ) , and had genotype 1 infection ( 91 % ) . Of the patients with genotype 1 infection , 75 % had genotype 1b infection . Appendix Figure . Patient disposition . LDVSOF = ledipasvirsofosbuvir . Table 1 . Demographic and Baseline Characteristics * Efficacy Ledipasvirsofosbuvir treatment result ed in rapid HCV RNA suppression ( Table 2 ) . By week 4 , 102 of 114 patients ( 89 % ) had HCV RNA less than the LLOQ ( with target not detectable in 68 % ) . By week 8 , all 113 evaluable patients ( 100 % [ excluding 1 patient in the 12-week group who discontinued study treatment at week 4 because of a serious adverse event ] ) had HCV RNA less than the LLOQ ( with target not detectable in 112 of 113 [ 99 % ] ) . At the end of treatment , BACKGROUND Chronic hepatitis C virus ( HCV ) infection is more prevalent among patients who have chronic kidney disease than among those who do not have the disease . Patients with chronic kidney disease who also have HCV infection are at higher risk for progression to end‐stage renal disease than those who have chronic kidney disease without HCV infection . Patients with both HCV infection and advanced chronic kidney disease have limited treatment options . METHODS We conducted a multicenter , open‐label , phase 3 trial to evaluate the efficacy and safety of treatment with the combination of the NS3/4A protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir for 12 weeks in adults who had HCV genotype 1 , 2 , 3 , 4 , 5 , or 6 infection and also had compensated liver disease ( with or without cirrhosis ) with severe renal impairment , dependence on dialysis , or both . Patients had stage 4 or 5 chronic kidney disease and either had received no previous treatment for HCV infection or had received previous treatment with interferon or pegylated interferon , ribavirin , sofosbuvir , or a combination of these medications . The primary end point was a sustained virologic response 12 weeks after the end of treatment . RESULTS Among the 104 patients enrolled in the trial , 52 % had genotype 1 infection , 16 % had genotype 2 infection , 11 % had genotype 3 infection , 19 % had genotype 4 infection , and 2 % had genotype 5 or 6 infection . The sustained virologic response rate was 98 % ( 102 of 104 patients ; 95 % confidence interval , 95 to 100 ) . No patients had virologic failure during treatment , and no patients had a virologic relapse after the end of treatment . Adverse events that were reported in at least 10 % of the patients were pruritus , fatigue , and nausea . Serious adverse events were reported in 24 % of the patients . Four patients discontinued the trial treatment prematurely because of adverse events ; three of these patients had a sustained virologic response . CONCLUSIONS Treatment with glecaprevir and pibrentasvir for 12 weeks result ed in a high rate of sustained virologic response in patients with stage 4 or 5 chronic kidney disease and HCV infection . ( Funded by AbbVie ; Clinical Trials.gov number , NCT02651194 . Well‐tolerated , ribavirin‐free , pangenotypic hepatitis C virus ( HCV ) treatments for transplant recipients remain a high priority . Once‐daily glecaprevir/pibrentasvir demonstrates high rates of sustained virologic response at 12 weeks posttreatment ( SVR12 ) across all major HCV genotypes ( GTs ) . This trial evaluated the safety and effic 
    Output:
    
Acute HCV infection in hemodialysis units is identified by monitoring liver biochemical test results for increases above baseline , which may suggest acute HCV infection and prompt testing for HCV viremia several months before EIA testing shows positive results .