***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 Only 15 to 20 percent of patients with chronic hepatitis C have a sustained virologic response to interferon therapy . We compared the efficacy and safety of recombinant interferon alfa-2b alone with those of a combination of interferon alfa-2b and ribavirin for the initial treatment of patients with chronic hepatitis C. METHODS We r and omly assigned 912 patients with chronic hepatitis C to receive st and ard-dose interferon alfa-2b alone or in combination with ribavirin ( 1000 or 1200 mg orally per day , depending on body weight ) for 24 or 48 weeks . Efficacy was assessed by measurements of serum hepatitis C virus ( HCV ) RNA and serum aminotransferases and by liver biopsy . RESULTS The rate of sustained virologic response ( defined as an undetectable serum HCV RNA level 24 weeks after treatment was completed ) was higher among patients who received combination therapy for either 24 weeks ( 70 of 228 patients , 31 percent ) or 48 weeks ( 87 of 228 patients , 38 percent ) than among patients who received interferon alone for either 24 weeks ( 13 of 231 patients , 6 percent ) or 48 weeks ( 29 of 225 patients , 13 percent ) ( P<0.001 for the comparison of interferon alone with both 24 weeks and 48 weeks of combination treatment ) . Among patients with HCV genotype 1 infection , the best response occurred in those who were treated for 48 weeks with interferon and ribavirin .  Histologic improvement was more common in patients who were treated with combination therapy for either 24 weeks ( 57 percent ) or 48 weeks ( 61 percent ) than in those who were treated with interferon alone for either 24 weeks ( 44 percent ) or 48 weeks ( 41 percent ) . The drug doses had to be reduced and treatment discontinued more often in patients who were treated with combination therapy . CONCLUSIONS In patients with chronic hepatitis C , initial therapy with interferon and ribavirin was more effective than treatment with interferon alone BACKGROUND / AIMS Interferon-alpha plus ribavirin seem to be more efficacious than interferon monotherapy in chronic hepatitis C. In a multicenter r and omized trial , we evaluated the efficacy of this association for interferon-alpha resistant chronic hepatitis C. METHODS Fifty patients who were non-responders to recombinant or lymphoblastoid interferon-alpha were r and omized to receive either ribavirin ( 800 mg/day ) plus leucocytic interferon-alpha ( 3 mega units thrice weekly ) or the same dose of interferon-alpha alone , for 6 months . Effects of therapy were evaluated by serum aminotransferase and hepatitis C virus RNA levels and control liver biopsies . RESULTS At the end of treatment , aminotransferase levels become normal in 9/26 patients receiving combination therapy ( 35 % [ confidence interval , 16 % to 53 % ] ) and in 2/24 receiving interferon-alpha alone ( 8 % [ confidence interval , -3 % to 19 % ] ) ( p = 0.03 ) . Aminotransferase normalization was never associated with hepatitis C virus RNA clearance . All patients with normal aminotransferase relapsed after discontinuation of therapy . At the end of treatment , mean hepatitis C virus RNA levels significantly decreased only in the group receiving combination therapy , but returned to pretreatment values 6 months thereafter . No histological improvement was observed in either group . CONCLUSIONS There is no indication for treatment with interferon-alpha at the dose of 3 mega units thrice weekly plus 800 mg/day of ribavirin for 6 months in chronic hepatitis C resistant to interferon-alpha CONTEXT R and omized trials with adequate sample size offer an opportunity to assess the safety of new medications in a controlled setting ; however , generalizable data on drug safety reporting are sparse . OBJECTIVE To scrutinize the completeness of safety reporting in r and omized trials .  DESIGN , SETTING , AND PATIENTS Survey of safety reporting in 192 r and omized drug trials 7 diverse topics with sample sizes of at least 100 patients and at least 50 patients in a study arm ( N = 130074 patients ) . Trial reports were identified from comprehensive meta-analyses in 7 medical areas . MAIN OUTCOME MEASURES Adequate reporting of specific adverse effects and frequency and reasons for withdrawals due to toxic effects ; article space allocated to safety reporting and predictors of such reporting . RESULTS Severity of clinical adverse effects and laboratory-determined toxicity was adequately defined in only 39 % and 29 % of trial reports , respectively . Only 46 % of trials stated the frequency of specific reasons for discontinuation of study treatment due to toxicity . For these 3 parameters , there was significant heterogeneity in rates of adequate reporting across topics ( P = .003 , P<.001 , and P = .02 , respectively ) . Overall , the median space allocated to safety results was 0.3 page . A similar amount of space was devoted to contributor names and affiliations ( P = .16 ) . On average , the percentage of space devoted to safety in the results section was 9.3 % larger in trials involving dose comparisons than in those that did not ( P<.001 ) and 3.8 % smaller in trials reporting statistically significant results for efficacy outcomes ( P = .047 ) . CONCLUSIONS The quality and quantity of safety reporting vary across medical areas , study design s , and setting s but they are largely inadequate . Current st and ards for safety reporting in r and omized trials should be revised to address this inadequacy BACKGROUND A sustained virological response ( SVR ) rate of 41 % has been achieved with interferon alfa-2b plus ribavirin therapy of chronic hepatitis C. In this r and omised trial , peginterferon alfa-2b plus ribavirin was compared with interferon alfa-2b plus ribavirin . METHODS 1530 patients with chronic hepatitis C were assigned interferon alfa-2b ( 3 MU subcutaneously three times per week ) plus ribavirin 1000 - 1200 mg/day orally , peginterferon alfa-2b 1.5 microg/kg each week plus 800 mg/day ribavirin , or peginterferon alfa-2b 1.5 microg/kg per week for 4 weeks then 0.5 microg/kg per week plus ribavirin 1000 - 1200 mg/day for 48 weeks . The primary endpoint was the SVR rate ( undetectable hepatitis C virus [ HCV ] RNA in serum at 24-week follow-up ) . Analyses were based on patients who received at least one dose of study medication . FINDINGS The SVR rate was significantly higher ( p=0.01 for both comparisons ) in the higher-dose peginterferon group ( 274/511 [ 54 % ] ) than in the lower-dose peginterferon ( 244/514 [ 47 % ] ) or interferon ( 235/505 [ 47 % ] ) groups . Among patients with HCV genotype 1 infection , the corresponding SVR rates were 42 % ( 145/348 ) , 34 % ( 118/349 ) , and 33 % ( 114/343 ) . The rate for patients with genotype 2 and 3 infections was about 80 % for all treatment groups . Secondary analyses identified bodyweight as an important predictor of SVR , prompting comparison of the interferon regimens after adjusting ribavirin for bodyweight ( mg/kg ) . Side-effect profiles were similar between the treatment groups . INTERPRETATION In patients with chronic hepatitis C , the most effective therapy is the combination of peginterferon alfa-2b 1.5 microg/kg per week plus ribavirin . The benefit is mostly achieved in patients with HCV genotype 1 infections BACKGROUND Interferon alfa is the only effective treatment for patients with chronic hepatitis C. Forty percent of patients have an initial response to this therapy , but most subsequently relapse . We compared the effect of interferon alone with that of interferon plus oral ribavirin for relapses of chronic hepatitis C. METHODS We studied 345 patients with chronic hepatitis C who relapsed after interferon treatment . A total of 173 patients were r and omly assigned to receive st and ard-dose recombinant interferon alfa-2b concurrently with ribavirin ( 1000 to 1200 mg orally per day , depending on body weight ) for six months , and 172 patients were assigned to receive interferon and placebo . RESULTS At the completion of treatment , serum levels of hepatitis C virus ( HCV ) RNA were undetectable in 141 of the 173 patients who were treated with interferon and ribavirin and in 80 of the 172 patients who were treated with interferon alone ( 82 percent vs. 47 percent , P<0.001 ) . Serum HCV RNA levels remained undetectable 24 weeks after the end of treatment in 84 patients ( 49 percent ) in the combination-therapy group , but in only 8 patients ( 5 percent ) in the interferon group ( P<0.001 ) . Sustained normalization of serum alanine aminotransferase concentrations and histologic improvement were highly correlated with virologic response . Base-line serum HCV RNA levels of 2 x 10(6 ) copies per milliliter or less were associated with higher rates of response in both treatment groups . Viral genotypes other than type 1 were associated with sustained responses only in the combination-therapy group . Combined therapy caused a predictable fall in hemoglobin concentrations but otherwise had a safety profile similar to that of interferon alone . CONCLUSIONS In patients with chronic hepatitis C who relapse after treatment with interferon , therapy with interferon and oral ribavirin results in higher rates of sustained virologic , biochemical , and histologic response than treatment with interferon alone BACKGROUND Only 15 - 20 % of patients with chronic hepatitis C achieve a sustained virological response with interferon therapy . The aim of this study was to compare the efficacy and safety of interferon alpha2b in combination with oral ribavirin with interferon alone , for treatment of chronic infection with hepatitis C virus ( HCV ) . METHODS 832 patients aged 18 years or more with chronic HCV who had not been treated with interferon or ribavirin  , were enrolled and r and omly allocated one of three regimens : 3 mega units ( MU ) interferon alpha2b three times a week plus 1000 - 1200 mg ribavirin per day for 48 weeks ; 3 MU interferon alpha2b three times a week plus 1000 - 1200 mg ribavirin per day for 24 weeks ; or 3 MU interferon alpha2b three times a week and placebo for 48 weeks . All patients were assessed for safety , tolerance , and efficacy at the end of weeks 1 , 2 , 4 , 6 , and 8 , and every 4 weeks during treatment . After treatment was completed patients were followed up on weeks 4 , 8 , 12 , and 24 . The primary endpoint was loss of detectable HCV-RNA ( serum HCV-RNA < 100 copies/mL ) at week 24 after treatment . FINDINGS Sustained virological response at 24 weeks after treatment , was found in 119 ( 43 % ) of the 277 patients treated for 48 weeks with the combination regimen , 97 ( 35 % ) of the 277 patients treated for 24 weeks with the combination regimen ( p = O.055 ) , and 53 ( 19 % ) of the 278 patients treated for 48 weeks with interferon alone ( p<0.001 vs both combination regimens , intention-to-treat analysis ) . Logistic regression identified five independent factors significantly associated with response : genotype 2 or 3 , viral load less than 2 million copies/mL , age 40 years or less , minimal fibrosis stage , and female sex . Among patients with fewer than three of these factors the odds ratio of sustained response was 2.6 ( 95 % Cl 1.4 - 4.8 ; p=0.002 ) for the 48 week combination regimen compared with 24 weeks of the combination regimen . Discontinuation of therapy for adverse events was more frequent with combination ( 19 % ) and monotherapy ( 13 % ) given for 48 weeks than combination therapy given for 24 weeks ( 8 % ) . INTERPRETATION An interferon alpha2b plus ribavirin combination is more effective than 48 weeks of interferon alpha2b monotherapy and has an acceptable safety profile . Patients with few favourable factors benefit more from extending the duration of combination therapy to 48 weeks Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must 
    Output:
    
Combination therapy also significantly improved liver histologic response .
The effects on quality of life are unclear .
However , combination therapy significantly increased the risk of hematological , dermatological , gastrointestinal , and several other types of adverse events .
In conclusion , the effect of ribavirin plus interferon on viral clearance may lead to reduced mortality and morbidity in patients with chronic hepatitis C infection .
However , combination therapy is associated with increased risk for adverse events