***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: A prospect i ve study was performed to establish whether infection with specific hepatitis C virus ( HCV ) genotypes was associated with an increased risk of development of hepatocellular carcinoma ( HCC ) in cirrhosis . A cohort of 163 consecutive hepatitis C virus antibody (anti-HCV)-positive cirrhotic patients was prospect ively evaluated for the development of HCC at 6-month intervals by ultrasound ( US ) scan and alpha-fetoprotein ( AFP ) concentration . HCV genotypes were determined according to Okamoto . Risk factors associated with cancer development were analyzed by univariate and multivariate statistics . At enrollment , 101 patients ( 62 % ) were infected with type 1b , 48 ( 29.5 % ) were infected with type 2a/c , 2 ( 1.2 % ) were infected with type 3a , 1 ( 0.6 % ) was infected with type 1a , 3 ( 1.8 % ) had a mixed-type infection , and , in 8 patients ( 4.9 % ) , genotype could not be assigned . After a 5- to 7-year follow-up ( median , 68 months ) , HCC developed in 22 of the patients , 19 infected with type 1b and 3 with type 2a/c ( P < .005 ) . Moreover , HCC developed more frequently in males ( P < .01 ) , patients with excessive alcohol intake ( P < .01 ) , those over 60 years of age ( P < .02 ) , and in patients who did not receive interferon treatment ( P < .02 ) . Multivariate analysis showed that type 1b was the most important risk factor associated with tumor development ( odds ratio 6.14 , 1.77 - 21.37 95 % confidence interval ) . Other independent risk factors were older age and male sex . Cirrhotic patients infected with HCV type 1b carry a significantly higher risk of developing HCC than patients infected by other HCV types . The latter may require a less intensive clinical surveillance for the early detection of neoplasia 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 AIM To determine the role of interferon ( IFN ) with or without ribavirin in preventing or delaying hepatocellular carcinoma ( HCC ) development in patients with hepatitis C virus ( HCV ) related cirrhosis . Data on the preventive effect of IFN plus ribavirin treatment are lacking . METHODS A total of 101 patients ( 62 males and 39 females , mean age 55.1+/-1.4 years ) with histologically proven HCV related liver cirrhosis plus compatible biochemistry and ultrasonography were enrolled in the study . Biochemistry and ultrasonography were performed every 6 mo . Ultrasound guided liver biopsy was performed on all detected focal lesions . Follow-up lasted for 5 years . Cellular proliferation , evaluated by measuring Ag-NOR proteins in hepatocytes nuclei , was expressed as AgNOR-Proliferative index ( AgNOR-PI ) ( cut-off = 2.5 ) . Forty-one patients ( 27 males , 14 females ) were only followed up after the end of an yearly treatment with IFN-alpha2b ( old treatment control group = OTCG ) . Sixty naive patients were stratified according to sex and AgNOR-PI and then r and omized in two groups : 30 were treated with IFN-alpha2b + ribavirin ( treatment group = TG ) , the remaining were not treated ( control group = CG ) . Nonresponders ( NR ) or relapsers in the TG received further IFN/ribavirin treatments after a 6 mo of withdrawal . RESULTS AgNOR-PI was significantly lowered by IFN ( P<0.001 ) . HCC incidence was higher in patients with AgNOR-PI>2.5 ( 26 % vs 3 % , P<0.01 ) . Two NR in the OTCG , none in the TG and 9 patients in the CG developed HCC during follow-up . The Kaplan-Mayer survival curves showed statistically significant differences both between OTCG and CG ( P<0.004 ) and between TG and CG ( P<0.003 ) . CONCLUSION IFN/ribavirin treatment associated with re-treatment courses of NR seems to produce the best results in terms of HCC prevention . AgNOR-PI is a useful marker of possible HCC development Context Few studies address long-term outcomes of antiviral therapy for patients with chronic hepatitis C and cirrhosis . Contribution This prospect i ve study of adults with chronic hepatitis C and cirrhosis compares outcomes between 74 patients who declined treatment and 271 patients treated with thrice-weekly interferon injections for 26 to 88 weeks . Median follow-up was 6.8 years . Fewer treated patients developed hepatocellular cancer ( 31 % vs. 47 % of untreated patients ) or died ( 17 % vs. 32 % ) . Caution s Because the study was not a r and omized , controlled trial , prognostic factors other than interferon might have contributed to the differences between groups . The Editors Chronic hepatitis C is a common disease that progresses slowly to cirrhosis and eventually may lead to hepatocellular carcinoma ( 1 - 5 ) . The annual incidence of hepatocellular carcinoma and mortality rate were 1.4 % to 3.3 % and 1.9 % to 5.5 % , respectively , in retrospective series of white patients with hepatitis C virus (HCV)related compensated cirrhosis ( 4 - 9 ) ; in Japan , the annual incidence of hepatocellular carcinoma was 5 % to 7 % ( 10 - 12 ) . Risk factors for hepatocellular carcinoma include age older than 50 to 60 years , male sex , advanced fibrosis stage , high histologic activity score , and high alanine aminotransferase ( ALT ) levels ( 4 - 14 ) . Several retrospective studies have shown inhibition of hepatocellular carcinoma development after interferon therapy ( 11 - 14 ) . This inhibitory effect was seen in patients with moderate fibrosis for whom antiviral therapy was effective ( 11 - 14 ) . However , the inhibitory effect in patients with liver cirrhosis was not statistically significant ( 4 , 7 , 8 , 15 ) , possibly because of the low efficacy of interferon therapy in cirrhotic patients ( 15 - 17 ) . Other retrospective ( 6 , 9 ) and prospect i ve ( 18 ) studies that had small patient sample s indicated that interferon therapy reduced the development of hepatocellular carcinoma . Because cirrhosis is a major risk factor for hepatocellular carcinoma , a prospect i ve study is needed to determine whether interferon therapy benefits cirrhotic patients . We previously performed 2 prospect i ve studies on the efficacy of interferon treatment in cirrhotic patients ( 19 , 20 ) . During enrollment , many cirrhotic patients who fulfilled the inclusion criteria were enrolled as controls to clarify the long-term effect of interferon therapy on development of liver tumors . We conducted a 7-year study on the inhibition of hepatocellular carcinoma development in the previous cohorts of our multicenter , prospect i ve study . Methods Study Sample Enrollment of Patients with Compensated Liver Cirrhosis Design s for the 2 protocol s , Interferon alfa-2a prospect i ve trial for cirrhotic patients modification of treatment duration by monitoring HCV RNA in the serum ( 19 ) and Natural interferon trial for cirrhotic patients modification of interferon treatment duration according to pretreatment viral load ( 20 ) were finalized on 18 December 1992 and 20 April 1993 , respectively . While discussing these 2 protocol s , we decided to extend the prospect i ve studies after the initial trial to examine the effect of antiviral therapy on the inhibition of hepatocellular carcinoma development and patient survival as secondary end points . Inclusion Criteria Our previous reports ( 19 , 20 ) describe in more detail the diagnosis of chronic hepatitis C with cirrhosis and the inclusion criteria for the 2 trials ( 19 , 20 ) . The diagnostic criteria were elevated serum ALT levels for more than 6 months , positivity for anti-HCV antibody by the phytohemagglutinin assay ( Dinabbot , Tokyo , Japan ) or enzyme-linked immunosorbent assay ( Ortho Diagnostic Systems , Tokyo , Japan ) , and abnormal histologic findings on liver biopsy specimens . The presence of HCV RNA was tested by reverse transcriptase polymerase chain reaction ( RT-PCR ) ( detection limit , 102 copies/mL ) , and the serum HCV RNA level was measured by competitive RT-PCR according to the method of Kato and colleagues ( 21 ) . The HCV genotype was established by using the method of Okamoto and colleagues ( 22 ) . Liver biopsy was done in all patients within 12 months before enrollment , and specimens were evaluated according to the criteria of Desmet and colleagues ( 23 ) . Inclusion criteria were based on liver histologic characteristics indicating fibrotic stage F4 , positivity for HCV RNA by RT-PCR , platelet count greater than 50 109 cells/L , leukocyte count greater than 3 109 cells/L , and ChildPugh A classification . We excluded patients who had liver cirrhosis caused by hepatitis B , autoimmune hepatitis , primary biliary cirrhosis , or drug-induced liver disease . Before enrollment , patients had abdominal ultrasonography , dynamic computed tomography ( CT ) , or magnetic resonance imaging ( MRI ) ; we excluded patients who were found to have hepatocellular carcinoma .  Antiviral Therapy A total of 157 patients received 9 million units ( MU ) of interferon-2a ( Nippon Roche KK , Tokyo , Japan ) by intramuscular injection 3 times a week for 32 to 88 weeks ; duration of therapy was based on serum HCV RNA status during therapy ( 19 ) . The mean and median duration of therapy were 44 and 48 weeks , respectively , and the mean and median dose of interferon were 1011 and 936 MU ( range , 42 to 2378 MU ) , respectively . A total of 114 patients received 9 or 6 MU of natural interferon- ( Sumitomo Pharmaceutical Co. , Osaka , Japan ) by subcutaneous injection 3 times a week for 6 months ( patients with low viral load ) or 12 months ( patients with high viral load ) ( 20 ) . The mean and median duration of therapy were 33 and 26 weeks , respectively , and the mean and median dose of interferon were 688 MU and 564 MU ( range , 18 to 1404 MU ) , respectively . For the 2 trials combined , the mean duration of treatment was 39 weeks ( range , 1 to 88 weeks ) and the mean dose of interferon was 875 MU ( range , 18 to 2376 MU ) . Eighty-eight percent of the patients took more than 80 % of the drug during 80 % of the scheduled treatment period . Patients negative for HCV 
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The sensitivity analyses showed that the cohort studies found that antiviral therapy reduced the risk of HCC .
Antiviral therapy may reduce the risk of HCC in hepatitis C-related fibrosis and cirrhosis .
The effect may be seen irrespective of the virological response , but is more pronounced among virological responders compared with non-responders