***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 & AIMS Hemophilic siblings provide a unique population to explore the natural history of chronic hepatitis C. METHODS From 3993 hemophilic patients with hepatitis C , 257 sibling pairs , of which both members had evidence of hepatitis C infection , were studied to evaluate the genetic contribution to spontaneous and treatment-induced clearance of hepatitis C infection and progression of liver disease . Familial aggregation was assessed by comparing observed probabilities of concordance for these disease characteristics within sibling pairs to those expected for r and omly paired hemophilic subjects . Additional measures of familial aggregation , heritability , and sibling relative risk were also calculated . RESULTS Among human immunodeficiency virus-negative subjects , concordance for spontaneous viral clearance was 2-fold higher in siblings compared with r and omly paired subjects ( 8.8 % vs 4.3 % , respectively , P = .04 ) . Similarly , the concordance rate for treatment-related viral clearance was over twice that among sibling pairs than among r and omly paired hemophiliacs ( 31.3 % vs 13.3 % , respectively , P = ns ) . Heritability estimates for spontaneous and treatment-induced viral clearance were 0.24 + /- 0.14 ( P = .04 ) and 0.43 + /- 0.42 ( P = .10 ) , respectively . The sibling relative risks for these respective characteristics were 1.6 and 1.7 . Concordance for advanced liver disease was higher among siblings but did not reach statistical significance ( 4.0 % vs 2.3 % , respectively , P = ns ) . The heritability estimate was 0.29 + /- 0.13 ( P = .02 ) . CONCLUSIONS Concordance rates and heritability estimates for spontaneous and treatment-related viral clearance indicate that genetic factors have a modest influence on the outcome of hepatitis C , although shared environmental factors can not be excluded . Investigations to map c and i date disease-susceptibility genes associated with these characteristics must be approached with caution To investigate differences in the effect of interferon ( IFN ) -alpha and IFN-beta treatment for hepatitis C on hepatocellular carcinoma ( HCC ) development , we prospect ively followed 351 consecutive patients ( median age , 56.6 years ; mean follow-up , 5.7 ± 2.6 years ) with chronic hepatitis C virus ( HCV ) viremia . Of 260 IFN-alpha and 91 IFN-beta treated patients , 17 ( 6.5 % ) and 4 ( 4.4 % ) , respectively , developed HCC . Virological response ( VR ) was defined as persistent HCV RNA disappearance from serum , and biochemical response ( BR ) as persistent alanine aminotransferase ( ALT ) normalization after treatment . No significant between-group differences in HCC development were found between those with and without VR . Although the HCC development rate in patients without BR was significantly higher than that in patients with BR in the IFN-alpha group ( 11.4 % and 0.8 % ; P ≪ 0.05 ) , no significant difference was found in the IFN-beta group ( 6.3 % and 2.3 % ) . Similar rates of HCC development were found in patients with chronic HCV viremia treated with either IFN-alpha or IFN-beta Sustained responses to interferon-alpha occur in 10 % to 25 % of patients with chronic hepatitis C , but the long-term outcome is not well defined . We evaluated the long-term clinical , histological , and virological outcomes of 10 patients with chronic hepatitis C who were treated between 1984 and 1987 with interferon-alpha-2b for 52 + /- 6 weeks ( total doses of 492 + /- 116 MU ) . Before therapy , all 10 had hepatitis C virus ( HCV ) RNA , elevations of serum aminotransferases , and chronic hepatitis with fibrosis on liver biopsy . Clinical follow up was 6 to 13 years , and liver biopsies were done 5 to 11 years after initiation of therapy . HCV RNA was assayed by qualitative and quantitative reverse transcriptase-polymerase chain reaction assays . Among 5 patients who had a 6-month sustained response after therapy , all remained HCV RNA negative , and at last follow-up , 4 had normal and 1 minimally elevated serum aminotransferase levels . Liver biopsy specimens were nonreactive for HCV RNA , and all the patients showed improvements in both inflammation and fibrosis and were either normal or had mild , nonspecific inflammatory changes . Among 5 patients without a sustained response , all continued to have HCV RNA in serum and persistent or intermittent aminotransferase elevations . Liver biopsy specimens showed little or no change in necrosis and inflammation ; all except 1 patient had progression of fibrosis scores or cirrhosis . All 5 patients had symptoms of chronic hepatitis , 1 underwent liver transplantation , and another had progressive hepatic decompensation . In conclusion , patients with a 6-month posttreatment virological response have a favorable long-term clinical and histological outcome BACKGROUND / AIMS Assessment of chronic hepatitis C outcome in sustained responders to interferon requires prolonged observation and close monitoring . We prospect ively studied the impact of sustained response on histology and clinical ly relevant outcomes . METHODS The 47 sustained responders ( ten with cirrhosis ) from two interferon trials involving 235 chronic hepatitis C patients ( 81 with cirrhosis ) were included .  Hepatitis C virus ( HCV ) RNA was assessed every 6 months , liver histological changes from baseline , 6 - 12 and 48 - 72 months after treatment discontinuation . RESULTS The mean follow-up was 102 + /- 19 months . HCV RNA became undetectable in 36/47 responders . Four responders , who had remained viremic , later relapsed . The histology progressively improved in non-viremic and viremic patients , with a more marked improvement in the former ( P = 0.0089 ) , normalizing in 53 vs. 0 % ( P = 0.0220 ) . No patient progressed to cirrhosis . One non-viremic cirrhotic patient developed a hepatocellular carcinoma . Non-responders from the two original trials had worse histological outcomes and those with cirrhosis had a higher rate of clinical ly relevant events compared with cirrhotics showing a sustained biochemical response ( 4.5 vs. 1.2 cases/100 person-years ; CI for the difference , 0.3 - 6.3 ) . CONCLUSIONS Most sustained , virological responders without cirrhosis normalize liver histology in the long-term and are cured of the disease . Sustained responders remaining viremic still show histological improvement , albeit to a lesser extent Objective : Interferon ( IFN ) therapy has been used as antiviral therapy for chronic hepatitis C ( CH-C ) ; however , complete response to the therapy is observed in only about 30 % of patients in Japan . Background factors involved in the responsiveness to IFN therapy , and progression to liver cirrhosis ( LC ) and hepatocellular carcinoma ( HCC ) after IFN therapy have not yet been sufficiently investigated . Methods : One hundred twenty-one patients with CH-C who received IFN therapy at Showa University Hospital between 1984 and 1999 were analyzed . Results : At 6 months after the termination of IFN therapy , 53 patients achieved a complete response , 11 patients incomplete response , and 57 patients no response . During a mean follow-up of 52.7 months , 12 patients progressed to LC , and 10 patients developed HCC . Multivariate analysis showed that significant independent factors involved in progression to LC were platelet count and the efficacy of IFN therapy . The significant independent factor involved in the development of HCC was platelet count . The factor involved in the therapeutic effect at 6 months after the termination of IFN administration was the serum hepatitis C virus ( HCV ) RNA levels before IFN therapy . Conclusion : Patients with high HCV RNA levels and low platelet counts  should be considered to be at high risk of progressing to LC and developing of HCC and should be carefully followed after IFN therapy using ultrasonography , CT scan and MRI BACKGROUND Covalent attachment of a 40-kd branched-chain polyethylene glycol moiety to interferon alfa-2a results in a compound ( peginterferon alfa-2a ) that has sustained absorption , a slower rate of clearance , and a longer half-life than unmodified interferon alfa-2a . We compared the clinical effects of a regimen of peginterferon alfa-2a with those of a regimen of interferon alfa-2a in the initial treatment of patients with chronic hepatitis C. METHODS We r and omly assigned 531 patients with chronic hepatitis C to receive either 180 microg of peginterferon alfa-2a subcutaneously once per week for 48 weeks ( 267 patients ) or 6 million units of interferon alfa-2a subcutaneously three times per week for 12 weeks , followed by 3 million units three times per week for 36 weeks ( 264 patients ) . All the patients were assessed at week 72 for a sustained virologic response , defined as an undetectable level of hepatitis C virus RNA ( < 100 copies per milliliter ) . RESULTS In the peginterferon group , 223 of the 267 patients completed treatment and 206 completed follow-up . In the interferon group , 161 of the 264 patients completed treatment and 154 completed follow-up . In an intention-to-treat analysis in which patients who missed the examination at the end of treatment or follow-up were considered not to have had a response at that point , peginterferon alfa-2a was associated with a higher rate of virologic response than was interferon alfa-2a at week 48 ( 69 percent vs. 28 percent , P=0.001 ) and at week 72 ( 39 percent vs. 19 percent , P=0.001 ) . Sustained normalization of serum alanine aminotransferase concentrations at week 72 was also more common in the peginterferon group than in the interferon group ( 45 percent vs. 25 percent , P=0.001 ) . The two groups were similar with respect to the frequency and severity of adverse events , which were typical of those associated with interferon alfa . CONCLUSIONS In patients with chronic hepatitis C , a regimen of peginterferon alfa-2a given once weekly is more effective than a regimen of interferon alfa-2a given three times weekly BACKGROUND The long-term benefit for chronic hepatitis C ( CHC ) patients treated with interferon (IFN)/ribavirin ( RBV ) combination therapy  remains unclear . We aim ed to evaluate the long-term effects of IFN monotherapy and IFN/RBV combination therapy on reducing hepatocellular carcinoma ( HCC ) and mortality in patients with chronic hepatitis C virus ( HCV ) infection , adjusting for risk factors . METHODS A total of 1,619 patients with biopsy-proven CHC , including 1,057 receiving IFN-based therapy ( 760 on IFN/RBV combination therapy ) and 562 untreated controls from three medical centres and one regional core hospital in Taiwan were enrolled in this retrospective- prospect i ve cohort study . RESULTS The incidence of HCC and survival during a follow-up period of 1.0 - 15.3 ( mean 5.18 ) and 1 - 16 ( mean 5.15 ) years in treated and untreated patients , respectively , was analysed using Cox proportional hazards regression . The cumulative incidence of HCC was 35.2 % and 12.2 % for untreated and treated groups , respectively ( P=0.0013 ) . The cumulative survival rate was 93.1 % and 96.2 % for untreated and treated groups , respectively ( P=0.3928 ) . Significantly lower incidences of HCC and mortality were observed in sustained virological responders ( both for IFN monotherapy and IFN/RBV combination ) but not in nonresponders when compared with untreated patients . HCV genotype 1 patients had significantly higher incidences of HCC than genotype non-1 patients . In multivariate analysis , pre-existing cirrhosis , non-response , HCV genotype-1 and age were associated with HCC ; pre-existing cirrhosis and non-response correlated to mortality . CONCLUSION A sustained virological response secondary to IFN monotherapy or IFN/RBV combination therapy could reduce the risk for HCC and improve survival of CHC patients BACKGROUND / AIM To evaluate long-term outcomes in decompensated HCV-related cirrhotic patients treated with antiviral therapy .  METHODS Of 129 eligible patients , 66 received peginterferon alfa-2b and ribavirin for 24 weeks , and 63 were controls .  Survival and recurrence of liver failure events after therapy were main outcomes . RESULTS Therapy was tolerated by 27 patients , dose reduced in 26 for toxicity , and discontinued in 13 for intolerance . End-of-therapy and sustained v 
    Output:
    
An SVR can lead to regression of fibrosis and cirrhosis , and has been associated with a reduced rate of hepatic decompensation , a reduced risk for hepatocellular carcinoma , and reduced liver-related mortality