***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: UNLABELLED Successful treatment of chronic HCV with  peginterferon ( PEGIFN ) and ribavirin ( RVN ) is often limited by anemia . We performed the present study to determine if utilizing epoetin alpha ( EPO ) with or without a higher dose of RVN could enhance sustained virologic response ( SVR ) . We r and omized 150 treatment-naive patients with chronic HCV genotype 1 into 3 treatment groups : ( 1 ) PEGIFN alpha-2b ( 1.5 microg/kg/week ) + weight-based RVN ( WBR ) 13.3 mg/kg/day ( 800 to 1400 mg/day ) ; ( 2 ) PEGIFN alpha-2b + WBRVN + EPO ( 40,000 U/week ) ; or ( 3 ) PEGIFN alpha-2b + higher dose WBR 15.2 mg/kg/day ( 1000 to 1600 mg/day ) + EPO . We initiated EPO at the onset of therapy to maintain the hemoglobin between 12 and 15 g/dL. When required , we reduced RVN by 200-mg steps . African Americans compose 36 % of the population . A significantly smaller percentage of group 2 patients had a decline in hemoglobin to less than 10 g/dL ( 9 % versus 34 % ; P < 0.05 ) and required that the RVN dose be reduced ( 10 % versus 40 % ; P < 0.05 ) compared to group 1 patients . Despite this , SVR was similar in these groups ( 19 % to 29 % ) . SVR was significantly greater ( P < 0.05 ) in group 3 patients ( 49 % ) . This result ed from a significant decline ( P < 0.05 ) in relapse rate ; only 8 % versus 38 % for groups 1 and 2 . CONCLUSION We conclude that using EPO in all subjects at the initiation of PEGIFN and RVN treatment will not enhance SVR given the same starting dose of RVN . In contrast , a higher starting dose of RVN was associated with a lower relapse rate and higher rate of SVR BACKGROUND In patients with chronic infection with hepatitis C virus ( HCV ) genotype 1 , treatment with peginterferon alfa and ribavirin for 48 weeks results in rates of sustained virologic response of 40 to 50 % . Telaprevir is a specific inhibitor of the HCV serine protease and could be of value in HCV treatment . METHODS A total of 334 patients who had chronic infection with HCV genotype 1 and had not been treated previously were r and omly assigned to receive one of four treatments involving various combinations of telaprevir ( 1250 mg on day 1 , then 750 mg every 8 hours ) , peginterferon alfa-2a ( 180 microg weekly ) , and ribavirin ( dose according to body weight ) . The T12PR24 group ( 81 patients ) received telaprevir , peginterferon alfa-2a , and ribavirin for 12 weeks , followed by peginterferon alfa-2a and ribavirin for 12 more weeks . The T12PR12 group ( 82 patients ) received telaprevir , peginterferon alfa-2a , and ribavirin for 12 weeks . The T12P12 group ( 78 patients ) received telaprevir and peginterferon alfa-2a without ribavirin for 12 weeks . The PR48 ( control ) group ( 82 patients ) received peginterferon alfa-2a and ribavirin for 48 weeks . The primary end point , a sustained virologic response ( an undetectable HCV RNA level 24 weeks after the end of therapy ) , was compared between the control group and the combined T12P12 and T12PR12 groups . RESULTS The rate of sustained virologic response for the T12PR12 and T12P12 groups combined was 48 % ( 77 of 160 patients ) , as compared with 46 % ( 38 of 82 ) in the PR48 ( control ) group ( P=0.89 ) . The rate was 60 % ( 49 of 82 patients ) in the T12PR12 group ( P=0.12 for the comparison with the PR48 group ) , as compared with 36 % ( 28 of 78 patients ) in the T12P12 group ( P=0.003 ; P=0.20 for the comparison with the PR48 group ) . The rate was significantly higher in the T12PR24 group ( 69 % [ 56 of 81 patients ] ) than in the PR48 group ( P=0.004 ) . The adverse events with increased frequency in the telaprevir-based groups were pruritus , rash , and anemia . CONCLUSIONS In this phase 2 study of patients infected with HCV genotype 1 who had not been treated previously , one of the three telaprevir groups had a significantly higher rate of sustained virologic response than that with st and ard therapy . Response rates were lowest with the regimen that did not include ribavirin . ( Clinical Trials.gov number , NCT00372385 . Background The conventional antiviral treatment of chronic hepatitis related to hepatitis C virus ( HCV ) often leads to anemia . In this case , it is necessary to reduce ribavirin dose or stop treatment , thus reducing the rate of sustained virological response . Aim We investigated whether epoetin alpha administration improves treatment adherence and leads to higher percentage of response at the end of therapy and sustained virological response . Methods Two hundred and fourteen individuals with genotype 1b HCV-related chronic hepatitis underwent treatment with pegylated (peg)-interferon alpha-2A  180 μg once weekly and ribavirin 1,000–1,200 mg/day ; 174 were responders . Forty individuals completed treatment with no hemoglobin reduction ; 134 developed anemia during therapy . Anemic responders were distributed r and omly into two groups : group 1 continued therapy with epoetin alpha addiction ; group 2 continued antiviral therapy with ribavirin reduction only . Results Patients in group 1 achieved better control of hemoglobin levels ( 13.8 ± 1.2 g/dl at the end of therapy ) than tthose in group 2 ( 11.5 ± 0.8 g/dl ) . Sustained virological response was 59.7 % in group 1 compared with 34.4 % in group 2 ( p < 0.01 ) . Conclusions In patients with 1b HCV-related chronic hepatitis who develop anemia during antiviral treatment , administration of epoetin alpha increases hemoglobin levels and the end-of-treatment rate and sustains virological response by improving treatment adherence BACKGROUND In patients with chronic infection with hepatitis C virus ( HCV ) genotype 1 who do not have a sustained response to therapy with peginterferon-ribavirin  , outcomes after retreatment are suboptimal . Boceprevir , a protease inhibitor that binds to the HCV nonstructural 3 ( NS3 ) active site , has been suggested as an additional treatment . METHODS To assess the effect of the combination of boceprevir and peginterferon-ribavirin for retreatment of patients with chronic HCV genotype 1 infection , we r and omly assigned patients ( in a 1:2:2 ratio ) to one of three groups . In all three groups , peginterferon alfa-2b and ribavirin were administered for 4 weeks ( the lead-in period ) . Subsequently , group 1 ( control group ) received placebo plus peginterferon-ribavirin for 44 weeks ; group 2 received boceprevir plus peginterferon-ribavirin for 32 weeks , and patients with a detectable HCV RNA level at week 8 received placebo plus peginterferon-ribavirin for an additional 12 weeks ; and group 3 received boceprevir plus peginterferon-ribavirin for 44 weeks . RESULTS A total of 403 patients were treated . The rate of sustained virologic response was significantly higher in the two boceprevir groups ( group 2 , 59 % ; group 3 , 66 % ) than in the control group ( 21 % , P<0.001 ) . Among patients with an undetectable HCV RNA level at week 8 , the rate of sustained virologic response was 86 % after 32 weeks of triple therapy and 88 % after 44 weeks of triple therapy . Among the 102 patients with a decrease in the HCV RNA level of less than 1 log(10 ) IU per milliliter at treatment week 4 , the rates of sustained virologic response were 0 % , 33 % , and 34 % in groups 1 , 2 , and 3 , respectively . Anemia was significantly more common in the boceprevir groups than in the control group , and erythropoietin was administered in 41 to 46 % of boceprevir-treated patients and 21 % of controls . CONCLUSIONS The addition of boceprevir to peginterferon-ribavirin result ed in significantly higher rates of sustained virologic response in previously treated patients with chronic HCV genotype 1 infection , as compared with peginterferon-ribavirin alone . ( Funded by Schering-Plough [ now Merck ] ; HCV RESPOND-2 Clinical Trials.gov number , NCT00708500 . ) Pegylated interferon ( peg‐IFN ) and ribavirin ( RBV ) are effective in eradicating the hepatitis C virus in more than half of patients . However , anemia arising from RBV‐induced hemolysis can prompt dose reductions and lower sustained virologic response ( SVR ) rates . In early clinical trials , Viramidine ( VRD , renamed taribavirin ) , an RBV prodrug , was associated with less anemia and VRD given at 600 mg twice daily ( BID ) appeared to provide the best safety with comparable efficacy to RBV . The phase III Viramidine 's Safety and Efficacy versus Ribavirin 1 ( ViSER1 ) study r and omized 972 treatment‐naïve patients with chronic hepatitis C to fixed‐dose VRD ( 600 mg BID ) or weight‐based RBV ( 1000 or 1200 mg/day ) , each given with peg‐IFN alfa‐2b at 1.5 μg/kg/week . The primary efficacy endpoint was SVR rate , and the primary safety endpoint was hemoglobin ( Hb ) event rate ( percent of patients with Hb < 10 g/dL or at least a 2.5‐g/dL decrease from baseline ) . SVR rates were 37.7 % with VRD ( 244/647 ) and 52.3 % with RBV ( 170/325 ) . Thus , the ViSER1 study failed to demonstrate the primary noninferiority efficacy endpoint . Significantly fewer patients had Hb events with VRD ( 353/647 ; 54.6 % ) compared to those with RBV ( 272/325 ; 83.7 % ) ( P < 0.001 ) , and significantly fewer developed anemia ( Hb < 10 g/dL ) with VRD ( 34/647 ; 5.3 % ) compared to those with RBV ( 76/325 ; 23.5 % ) ( P < 0.001 ) . Conclusion : Fixed doses of VRD failed to demonstrate noninferiority to RBV in producing SVR rates . The incidence of anemia was approximately four‐fold significantly lower with VRD than with RBV . These results suggest fixed‐dose VRD given 600 mg BID is insufficient to treat patients with chronic hepatitis C ; a weight‐based dosing trial of viramidine is currently under way . ( HEPATOLOGY 2009 . Dose reductions of pegylated interferon alpha and ribavirin may be avoided by using growth factors . This phase II clinical trial assesses the dose , efficacy and safety of darbepoetin alpha and filgrastim for treatment of anaemia and neutropenia associated with combination therapy for hepatitis C virus ( HCV ) . Chronic hepatitis C patients ( n = 101 ) received pegylated interferon alpha-2b ( 1.5 mug/kg once weekly ) and ribavirin ( 800 - 1400 mg once daily ) . Patients with anaemia [ haemoglobin ( Hb ) < /= 10.5 g/dL ] received darbepoetin alpha ( 3 mug/kg once every 2 weeks ) ; the dose was titrated to achieve a Hb level of 12.0 g/dL. Patients with neutropenia [ absolute neutrophil count ( ANC ) < /= 0.75 x 10(9)/L ] received filgrastim with the dose titrated from 150 mug QW to 300 mug thrice weekly to maintain ANC > /= 0.75 x 10(9)/L and < 10 x 10(9)/L. During antiviral therapy , 52 % of patients required darbepoetin alpha , filgrastim or both . Hb at the time of darbepoetin alpha initiation was 10.2 + 
    Output:
    
Ribavirin dose reductions have been recommended in the package inserts for the pegylated interferon products and studies have demonstrated the need for maintenance of 80 % of the initial ribavirin dose to achieve optimal sustained virologic response ( SVR ) with dual therapy .
The use of erythropoietin-stimulating agents has been shown to be effective for anemia caused by peginterferon and ribavirin without compromising SVR rates .
Limited data have been published regarding the management of anemia with triple therapy ; however , efficacy studies for boceprevir and telaprevir have used ribavirin dose reduction and erythropoietin-stimulating agents to successfully manage anemia .
CONCLUSIONS : Anemia is a common adverse event associated with the use of ribavirin , and , more recently , the new HCV protease inhibitors .