***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: Interferon has been shown to be an effective treatment for some patients with chronic hepatitis C. In this study , the value of retreatment of nonresponders to interferon was investigated . Thirty-eight patients with hepatitis C virus (HCV)-RNA-positive chronic hepatitis C virus (HCV)-RNA-positive chronic hepatitis C who had been treated with betainterferon but still showed an alanine aminotransferase ( ALT ) level>50 KU upon completion of therapy were retreated with  alpha-interferon . Eight patients ( 21.1 % ) had normalization of ALT levels after interferon retreatment were studied . Of 16 patients with transient  HCV-RNA  negativity 1 month after the initial interferon therapy , 7 ( 43.8 % ) had a complete response , with normalization of ALT levels and undetectable HCV-RNA , more than 6 months after interferon retreatment . On the other h and , of the 22 patients with  HCV-RNA activity 1 month after the initial interferon therapy , only 1 ( 4.5 % ) had a complete response . Multivariate analysis , using a multiple logistic model , indicated that a complete response to readministration of interferon was most strongly correlated to transient negative conversion for HCV-RNA after the initial course of treatment BACKGROUND AND AIM Interferon-alpha treatment of chronic hepatitis C is beneficial in only 20 - 30 % of patients . This study evaluates if combination therapy with Interferon-alfa plus ribavirin is effective in inducing a response in patients who did not respond to , or relapsed after , a st and ard Interferon-alfa treatment . PATIENTS AND METHODS A total of 88 patients , 49 non-responders and 39 relapsers to previous Interferon-alfa therapy , were r and omized to receive either natural Interferon-alfa ( 6 MU t.i.w . ) plus ribavirin ( 1000 mg/daily ) or natural Interferon-alfa alone ( 6 MU t.i.w . ) for 6 months . All were followed for 12 months after stopping therapy . Serum aminotransferase levels were assessed monthly and HCV RNA was evaluated by RT-PCR ( Amplicor , Roche ) at end of therapy and the end of follow-up . RESULTS After treatment , a higher response rate defined as return to normal of aminotransferases and absence of serum HCV RNA was observed among patients treated with Interferon-alfa-ribavirin : 4/28 ( 14 % ) vs 1/21 ( 5 % ) non-responder patients and 9/19 ( 47 % ) vs 5/20 ( 25 % ) in the relapsers group . At the end of follow-up , a sustained response was found only in the combination treatment group : 4 % and 32 % in non-responder and relapser patients , respectively . CONCLUSIONS Our results suggest that retreatment with natural Interferon-alfa plus ribavirin is more effective than Interferon-alfa alone in increasing the response rate in patients with chronic hepatitis C who relapse after a previous st and ard IFN treatment whereas it is less effective in non-responder patients The aim of this study was to eluci date indicator of interferon ( IFN ) therapy for reducing hepatocellular carcinoma ( HCC ) in chronic hepatitis C patients without eradicating hepatitis C virus ( HCV ) RNA during IFN therapy . Inclusion criteria were biopsy-proven chronic hepatitis or liver cirrhosis , IFN period for more than 1.5 years and persistently positive HCV-RNA during IFN therapy . Two hundred thirty-six patients satisfied above criteria were treated with IFN for 1.5 - 5 years ( median 1.8 years , mean 2 years ) . Mean age was 55.1 years and male was 145 ( 61 % ) . Eighty-one ( 34 % ) patients had severe fibrosis of the liver . These patients were prospect ively monitored about HCC after the termination of IFN therapy . We regarded biochemical response ( BR ) as normalization of serum aminotransferase and alpha-fetoprotein for more than 1 year during IFN therapy . Cumulative rate of development of HCC after the termination of IFN therapy was 9.1 % at 5th year and 26.5 % at 10th year . Cox proportional analysis showed that HCC development after the termination of IFN therapy occurred when histological staging was advanced ( P < 0.0001 ) and BR was not achieved ( P = 0.009 ) , age was > 60 years ( P = 0.026 ) . The relative risk of HCC development in patients with BR was 0.36 compared with patients without BR . The attainment of BR during IFN therapy is effective in reducing hepatocarcinogenesis for patients with chronic HCV infection Interferon-alpha ( IFN ) monotherapy results in sustained virological clearance in a minority of patients with chronic hepatitis C. The aim of this study was to assess the effect of a reinforced regimen combining ribavirin and high-dose IFN for 48 weeks compared with a nonreinforced regimen combining a st and ard IFN regimen and ribavirin for 24 weeks in nonresponders with chronic hepatitis C. A total of 231 patients with chronic hepatitis C and previous nonresponse to IFN monotherapy were r and omized . The reinforced group ( n = 114 ) received IFN-2b 6 million units ( MU ) thrice weekly ( TIW ) and ribavirin for 48 weeks , and the nonreinforced group ( n = 117 ) received IFN-2b 3 MU TIW and ribavirin for 24 weeks . The main outcome measure was a sustained virological response , defined as negative serum hepatitis C virus (HCV)-RNA 24 weeks following the end of treatment . This endpoint was determined in 98 patients of the reinforced group and 105 patients of the nonreinforced group . At the end of follow-up , a sustained virological response was observed in 29 of the 98 patients ( 29.6 % ) in the reinforced group vs 16 of the 105 patients ( 15.2 % ) in the nonreinforced group ( P = 0.014 ) . In multivariate analysis , factors associated with a sustained virological response were treated with a reinforced regimen [ odds ratio ( OR ) 2.9 ; P = 0.06 ] and genotype 2 or 3 ( OR 8.8 ; P < 0.0002 ) . A total of 160 patients had paired biopsies before and after treatment . Histological activity improvement was observed in 32 of 80 patients ( 40 % ) and fibrosis worsening in 26 of 80 patients ( 33 % ) in the reinforced group vs 13 of 80 ( 16 % ) and 19 of 80 ( 24 % ) in the nonreinforced group ( P = 0.30 and 0.20 , respectively ) . Hence in nonresponders , a high-dose 48-week regimen of IFN and ribavirin combination was more effective than a regimen with interferon at lower dose and ribavirin for 24 weeks only For chronic hepatitis C virus ( HCV ) infection , interferon-alpha ( IFN-alpha ) treatment has recently been established . However , the complete responding rate is not higher than 20 - 25 % . The aim of our study was to assess  IFN-alpha retreatment in chronic hepatitis C. In summary , during a second cycle of IFN-alpha , 60 % of the patients responded to the retreatment . Indeed , a sustained complete response , together with long-lasting normal alanine aminotransferase values and negative serum HCV-RNA , was observed in about 40 % of the retreated patients . Future prospect i ve and controlled trials must define the optimal retreatment strategy , as well as the response-predicting factors including HCV genotypes and quantitative HCV-RNA levels BACKGROUND / AIMS The aim of this study was to increase virologic response rates by individualized treatment according to the early virologic response . METHODS Serum HCV-RNA was frequently quantified in patients with chronic hepatitis C ( n=270 ) treated with peginterferon alfa-2a ( 180 microg/week ) and ribavirin ( 1000 - 1200 mg/day ) . After 6 weeks patients were classified as rapid ( RVR ) , slow ( SPR ) , flat ( FPR ) , or null responders ( NUR ) and r and omized within each viral kinetic class to continue therapy either with an individualized or st and ard regimen . Individualized therapy comprised peginterferon monotherapy ( 48 weeks ) or shorter combination therapy ( 24 weeks ) for RVR , triple therapy with histamine ( 1 mg/day ) ( 48 weeks ) or prolonged combination therapy ( 72 weeks ) for SPR , triple therapy for FPR , and high-dose peginterferon ( 360 microg/week ) plus ribavirin for NUR patients . RESULTS Patients were categorized as RVR ( n=171 ) , SPR ( n=65 ) , FPR ( n=10 ) , or NUR ( n=22 ) . Overall end-of-treatment and sustained virologic response rates were 77 and 60 % in the individualized and 77 and 66 % in the st and ard treatment arm , respectively . Histamine in addition to peginterferon and ribavirin and high-dose peginterferon plus ribavirin did not improve virologic response rates in patients with FPR and NUR , respectively . CONCLUSIONS An improvement in virologic efficacy was not achieved with the available individualized treatment options BACKGROUND / AIMS Our aim was to assess whether histological response was improved by continuing interferon-alpha ( IFN ) treatment in patients with chronic hepatitis C ( HCV ) with a biochemical response and no viral clearance after a usual IFN treatment . METHODS Fifty-seven patients with normal alanine aminotransferase ( ALAT ) levels and positive HCV RNA at the end of a 1 year IFN treatment were r and omly assigned to either group 1 ( n = 28 ) where IFN was stopped , or group 2 ( n = 29 ) where IFN was continued for 1 more year with gradual reduction of the dose to keep serum ALAT activity below the upper limit of normal . Liver biopsies were obtained before , and then 6 months after the end of treatment . RESULTS Knodell 's index improved between paired biopsies in group 2 ( 8.2+/-2.4 vs. 5.5+/-2.1 ) , but not in group 1 ( 8+/-2.3 vs. 6.5+/-2 ) . In post-treatment biopsies , the METAVIR activity score was significantly lower in group 2 than in group 1 ( 0.7+/-0.2 vs. 1.1+/-0.3 , P < 0.05 ) . In group 2 , an improvement of the METAVIR fibrosis score was observed ( 1.3+/-0.4 vs. 1.1+/-0.2 ) , whereas fibrosis progressed in group 1 ( 1.3+/-0.4 vs. 1.6+/-0.4 ) . CONCLUSIONS Maintenance therapy by the minimal dose of IFN able to maintain biochemical response prevents histological progression in the sub-group of patients without virological response R and omized clinical trials ( RCTs ) provide the most reliable therapeutic information available . Unfortunately , there are no systemic listing of RCTs . We compared a MEDLARS search of 3686 biomedical journals for RCTs with a manual search of the medical literature for the period 1966 - 1982 . For the former search we used subject headings ( 1 ) liver disease or ( 2 ) biliary tract disease and subheadings ( 1 ) drug therapy , ( 2 ) surgery , ( 3 ) radiotherapy , or ( 4 ) therapy , and check tags ( 1 ) comparative study or ( 2 ) clinical research . For the manual search , the contents of 34 arbitrarily selected , gastroenterologic , hepatologic , surgical , or general journals were perused . The MEDLARS search identified 160 RCTs and 29 others were found in the references of the 160 . One hundred fifty-four RCTs were identified by both methods . The manual search identified 208 RCTs and an additional 34 were found in the references of the 208 . The MEDLARS search identified only 107 of 208 RCTs found in the references of the 208 . The MEDLARS search identified only 107 of 208 RCTs found manually in the 36 journals , an efficiency rate of 51 % . We estimate that 330 hepatobiliary RCTs had been published during this 17-year period . Sixty percent of the RCTs found by MEDLARS used the key word " r and omized , " " double blind , " or " controlled " in the title , compared to 36 % in those found by the manual search . In order to retrieve RCTs , it is essential that editors require that RCTs be identified in their titles or key words by specific terms such as " controlled , " " r and omized , " and " double blind , " that papers be so catalogued and indexed , and that search ers be instructed in appropriate search strategies The coadministration of ribavirin with recombinant interferon alfa-2b ( rIFN-alpha 2b ) compared 
    Output:
    
No significant differences were seen with regard to the development of ascites , encephalopathy , hepatocellular carcinoma , or the need for liver transplantation .
Adverse effects tended to be more common in the interferon recipients ; the ones that were significantly more common included hematologic complications , infections , flu-like symptoms , and rash .
In this scenario , retreatment with interferon did not appear to provide significant clinical benefit and , when only the trials at low risk of bias were considered , retreatment for several years may even have increased all-cause mortality .
Such treatment also produced adverse events .
On the other h and , the treatment did result in improvement in some surrogate outcomes , namely sustained viral responses and histologic evidence of inflammation .