***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 
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    Input: 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 A r and om-primed complementary DNA library was constructed from plasma containing the uncharacterized non-A , non-B hepatitis ( NANBH ) agent and screened with serum from a patient diagnosed with NANBH . A complementary DNA clone was isolated that was shown to encode an antigen associated specifically with NANBH infections . This clone is not derived from host DNA but from an RNA molecule present in NANBH infections that consists of at least 10,000 nucleotides and that is positive-str and ed with respect to the encoded NANBH antigen . These data indicate that this clone is derived from the genome of the NANBH agent and are consistent with the agent being similar to the togaviridae or flaviviridae . This molecular approach should be of great value in the isolation and characterization of other unidentified infectious agents The coadministration of ribavirin with recombinant interferon alfa-2b ( rIFN-alpha 2b ) compared with rIFN-alpha 2b alone markedly enhanced sustained virologic response rates in relapsed and treatment-naive chronic hepatitis C patients . The potential for ribavirin to likewise exacerbate the adverse events associated with the alpha interferons is review ed . The overall safety and tolerability of combination rIFN-alpha 2b/ribavirin therapy was evaluated in 2,089 patients treated in phase III clinical studies conducted in the United States and internationally .  Serious adverse events were also evaluated on an interim basis in > 25,000 patients --a majority of whom were treated with combination therapy ( open label)--treated worldwide in investigator-initiated studies . Patients in the phase III studies received 3 million International Units rIFN-alpha 2b three times per week by subcutaneous injection plus either ribavirin or placebo orally in divided daily doses of 1,000 or 1,200 mg for patients weighing < or = 75 or > 75 kg , respectively . Adverse event frequency and severity and dose modifications were recorded throughout the 24-week ( relapse ) or 48-week ( naive ) treatment period and 24-week follow-up period . Clinical ly significant adverse events included anemia and depression . There was no evidence that the adverse effects of alpha interferon ( e.g. , fatigue , depression , neutropenia ) were exacerbated by ribavirin .  Severe adverse events were limited due to strict adherence to dose-modification criteria ; approximately 6 % to 9 % of patients discontinued combination therapy because of an adverse event . Clinical ly serious adverse events , dose reductions and discontinuations , and potential mechanisms of toxicity associated with rIFN-alpha 2b and ribavirin are examined Chronic active hepatitis due to HCV represents a severe progressive disorder of the liver , At present , Interferon seems to be the most efficacious treatment available , however , only 20 - 25 % of the patients treated achieve complete remission . The efficacy has , therefore , been evaluated of Ribavirin , a nucleoside analogue active both on DNA and RNA viruses , in the treatment of non responders to a previous course of interferon . Twenty patients were r and omly assigned to two groups : A ) received the association R ( 800 mg/day for 2 months)+interferon ( 9 Mu/week for 6 months ) ; B ) received IFN ( 9 Mu/week for 6 months ) . All patients completed the study without important side effects . Four patients in group A presented reduced ALT and loss of viraemia during treatment with Ribavirin . Only one patient in group B had reduced indices of cell lysis and was negative for HCV-RNA during the course of the study . However , viremia and an increase of ALT values were observed in all of these subjects once treatment was interrupted . The results emerging from this study indicate that Ribavirin therapy , at the dose and duration of treatment employed , is not sufficient to change the natural course of events of chronic active hepatitis from HCV BACKGROUND More than 70 % of patients with chronic hepatitis C are resistant to interferon therapy . Ribavirin , in association with interferon , has been demonstrated as effective , at a dose of 800 - 1200 mg/day , but the efficacy of a lower dose has not been established . METHODS We assessed the effectiveness of the combination of 600 mg/day of ribavirin plus 3 MU of interferon over a period of 6 months , in a group of patients previously resistant to interferon . Sixty-two patients with chronic hepatitis C with serum and hepatic HCV RNA relapsers or non-responders to interferon , were r and omly divided into two groups : group A received 3 MU of interferon alpha-2b , three times a week for 6 months ; group B was given the same dose plus 600 mg per day of ribavirin for 6 months . Two patients from each group dropped from therapy . One patient from group A and two from group B withdrew from treatment because of adverse effects . RESULTS Mean alanine aminotransferase levels were similar in both groups throughout the study . A sustained response was observed in 7 % and 7.4 % of groups A and B with short-term response in 39 % and 59 % , and no response in 54 % and 34 % from both groups respectively ( non-significant ) . At 12 months , 4 and 7 patients from groups A and B respectively , cleared serum HCV RNA however , only one sustained responder from each group cleared HCV RNA from peripheral blood mononuclear cells . At 18 months , 3 patients remained serum HCV RNA negative . Adverse effects were similar . Only haemoglobin values were lower in group B in the first month of therapy ( p<0.05 ) . CONCLUSION In conclusion , the combination of 3 MU of interferon plus 600 mg of ribavirin is not effective in chronic hepatitis C resistant to interferon Although evidence of virologic elimination , normalization of serum alanine aminotransferase levels , and reduction in liver inflammation are the principal therapeutic outcome goals in chronic hepatitis C patients , improvement in health-related quality of life ( HQL ) is also an important aspect of therapeutic outcome . In a recent report of chronic hepatitis C patients treated for 24 weeks with interferon , sustained virologic response ( 24 weeks post-treatment ) was associated with improvement in HQL compared with nonresponse . We report on the relationship between sustained virologic response and Hepatitis Quality -of-Life Question naire ( HQLQ ) survey results of patients who relapsed after a previous course of interferon alfa who were subsequently treated with recombinant interferon alfa-2b ( rIFN-alpha 2b ) either alone or in combination with ribavirin . The HQLQ was administered at baseline , at treatment Weeks 12 and 24 , and at follow-up Weeks 12 and 24 . All patients received rIFN-alpha 2b 3 million International Units by subcutaneous injection three times weekly plus either oral ribavirin ( 1,000 or 1,200 mg ) or placebo daily for 24 weeks . At baseline , patients scored lower than adjusted population norms in HQL . Relative to patients treated with rIFN-alpha 2b monotherapy , patients receiving combination therapy showed better HQL in 6 of 13 domains . Furthermore , sustained virologic response in either treatment group was associated with improvement in the scores of both generic and hepatitis-specific HQL survey domains . These results indicate that successful therapeutic resolution of hepatitis C infection improves HQL as assessed by generic and hepatitis C-specific measures of functional health and well-being . Furthermore , improvements in HQL outcome measures may predict reduced dem and for health care re sources and greater productivity in the workplace BACKGROUND & AIMS Sustained response to interferon treatment for chronic hepatitis C is unsatisfactory . This study examined whether combining interferon alfa with ribavirin induces a better sustained efficacy than interferon alone in the treatment of chronic hepatitis C. METHODS Sixty noncirrhotic patients with chronic hepatitis C were r and omly assigned to three groups . Group 1 received 1200 mg oral ribavirin daily plus 3 million units of recombinant interferon alfa 2a thrice weekly for 24 weeks , group 2 received the same dose of interferon alfa 2a alone for 24 weeks , and group 3 received no treatment . The patients were then followed up for an additional 96 weeks . RESULTS At the end of treatment , a complete response ( normal serum alanine aminotransferase level and undetectable serum hepatitis C virus RNA ) was achieved in 16 of the 21 patients in group 1 ( 76 % ) , as compared with 6 of 19 in group 2 ( 32 % ) and none in group 3 . At 96 weeks after the end of treatment , patients in group 1 sustained a higher complete response rate than patients in group 2 ( 43 % vs. 6 % ) . CONCLUSIONS Combined treatment with ribavirin and interferon alfa 2a for 24 weeks is more effective than interferon alfa 2a alone for the treatment of chronic hepatitis C. The biochemical and virological responses were sustained in about one half of the treated patients for at least 2 years after cessation of the therapy We evaluated oral ribavirin as therapy for chronic hepatitis C infection in a pilot study including 10 patients . Patients ( 7 men , 3 women ; mean age 40 years , range 23 - 54 ) all had biopsy-proven chronic non-A , non-B hepatitis and were repeatedly positive for antibodies to hepatitis C virus . Treatment was with oral ribavirin 1000 - 1200 mg per day in two divided doses for 12 weeks . The  median serum alanine aminotransferase concentration for all patients at enrollment was 3.15 mu kat/l ( range 1.22 - 7.79 ) and decreased significantly ( p less than 0.005 ) to 1.25 mu kat/l ( 0.78 - 2.04 ) after 12 weeks of treatment . Within 6 weeks of the end of treatment the median serum alanine aminotransferase concentration was not significantly different from that before treatment . Side-effects were mild and fully reversible after cessation of therapy . We conclude that ribavirin is the first drug to offer a potentially effective oral treatment for chronic hepatitis C. It should be further evaluated in controlled trials , possibly in combination with interferon alpha BACKGROUND / AIMS A sustained biochemical and virologic response to st and ard interferon therapy for chronic hepatitis C is seen in no more than 25 % of patients , and the efficacy of re-treatment or of higher doses in non-responders and relapsers has not been established . A more effective therapy for interferon alfa-resistant hepatitis C is needed . METHODS A study of ribavirin plus interferon alfa combination therapy was conducted in 30 patients with chronic hepatitis C resistant to a previous st and ard course of interferon alfa ( 14 interferon non-responders , 16 interferon relapsers ) . Patients were r and omly assigned to receive either ribavirin , 800 mg daily , and interferon alfa , 3 MU thrice weekly ( n = 15 ) , or interferon alfa alone , 3 MU thrice weekly ( n = 15 ) , for 6 months . RESULTS At the end of treatment , normal alanine aminotransferase levels were observed in eight patients in the combination therapy group : one ( 14 % ) interferon non-responder and seven ( 87 % ) interferon relapsers ( p = 0.01 ) . Six months post-ther 
    Output:
    
Results of these trials indicate that combination therapy produces larger sustained response rates than monotherapy .
Thus , ribavirin substantially increases drug costs compared with interferon monotherapy .
This shows it is worth treating all patients with combination therapy as first-line treatment for 6 months , but only worth treating those with one or two response factors for a further 6 months .
Those with three or four factors do well by 6 months , but gain very little from