***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: 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 Objective : The purpose of this study was to eluci date the long-term outcome after interferon ( IFN ) therapy in chronic hepatitis C elderly patients . Methods : We studied the incidence of hepatocellular carcinoma ( HCC ) and survival probability after the initiation of IFN therapy in 500 Japanese chronic hepatitis C patients > 60 years . The mean age of initiation of IFN was 63 years and the mean follow-up period was 7.4 years . Cox proportional hazard regression analysis was used to evaluate the long-term outcome after initiation of IFN therapy . Sustained virological response ( SVR ) was defined as negative HCV-RNA by RT-nested PCR 6 months after the completion of long-term IFN therapy . Non-response ( NR ) was applied to patients who did not show SVR . Hepatic fibrosis was defined as the fibrosis score ( score 0–4 ) according to Knodell et al. Results : 140 patients ( 28 % ) had an SVR and 360 patients ( 72 % ) had an NR . 71 of 500 patients developed HCC during follow-up . The cumulative incidence of HCC was 9.6 % at the 5th year , 17.4 % at the 10th year , and 31.3 % at the 15th year . HCC developed with significance when : ( 1 ) HCV was not cleared after IFN therapy ( p < 0.0001 ) , ( 2 ) sex was male ( p < 0.0001 ) , and ( 3 ) staging of liver fibrosis was > 2 ( p = 0.008 ) . 53 of the patients died . The cumulative survival probability was 95.7 % at the 5th year , 86.4 % at the 10th year , and 78 % at the 15th year . Patients achieved a long survival with significance when : ( 1 ) staging of liver fibrosis was 1 ( p < 0.0001 ) , ( 2 ) HCV was cleared after IFN therapy ( p = 0.034 ) , and ( 3 ) sex was female ( p = 0.015 ) . Conclusion : Chronic hepatitis C patients with clearance of HCV after IFN therapy had a significantly reduced risk of HCC appearance and achieved prolonged survival even if they are ≧60 years Background No study has compared the long-term prognoses of hepatitis C patients with hepatitis C virus ( HCV ) antibody-negative individuals and investigated the effects of interferon ( IFN ) treatment . To clarify the long-term prognosis of HCV-positive residents of an isolated Japanese isl and and prospect ively investigate the effects of IFN treatment in comparison with the HCV-negative general population . Methods HCV antibody was positive in 1,343 ( 7.6 % ) of the 17,712 individuals screened . 792 HCV RNA-positive , HBsAg-negative subjects were enrolled . 1,584 HCV antibody-negative , HBsAg-negative general residents were sex- and age-matched to the 792 subjects . A total of 154 < 70-year-old patients without liver cirrhosis ( LC ) or hepatocellular carcinoma ( HCC ) underwent IFN treatment . The survival rate with all-cause death as the endpoint was determined and causes of death were compared . Results The 10- and 20-year survival rates of the hepatitis C and general resident groups were 65.4 % and 87.8 % , and 40.8 % and 62.5 % , respectively ( p < 0.001 ; hazard risk ratio , 0.444 ; 95 % confidence interval ( CI ) : 0.389–0.507 ) . There were 167 liver disease-related deaths and 223 deaths from other causes in the hepatitis C group , and 7 and 451 , respectively , in the general resident group . Liver disease-related death accounted for 43.8 % and 1.5 % of deaths in the hepatitis C and general resident groups ( p < 0.0001 ) . The cumulative survival rate of the hepatitis C patients without IFN ( n = 328 ) was significantly lower than the gender- and age-matched general resident group ( n = 656 ) ( p < 0.0001 ) but there was no significant difference between the IFN-treated ( n = 154 ) and general resident groups ( n = 308 ) . Conclusions In the hepatitis C group , the proportion of liver disease-related death was markedly higher , and the survival rate lower , than the general resident group . Introduction of IFN treatment in < 70-year-old patients with hepatitis C without LC or HCC improved the survival rate to a level comparable to that of the general residents Recent data suggest that interferon therapy ( IFN ) can reduce the risk of progression to hepatocellular carcinoma ( HCC ) in patients with hepatitis C virus (HCV)‐related cirrhosis 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 Hepatocellular carcinoma , a major cause of death in patients with cirrhosis , is one of the most prevalent malignant tumors worldwide , and its incidence is increasing [ 1 - 5 ] . After isolation of hepatitis C virus ( HCV ) , most patients with chronic hepatitis and those with cirrhosis of unknown origin were found to be positive for anti-HCV [ 6 - 8 ] . Evidence suggests that HCV-related chronic liver disease plays a role in the development of hepatocellular carcinoma [ 9 - 13 ] . A high proportion of patients with hepatocellular carcinoma have anti-HCV , although the prevalence varies geographically . The highest rate of anti-HCV is in southern Europe and Japan , where about 70 % of patients with hepatocellular carcinoma are positive for anti-HCV [ 5 ] . Interferon has been widely used to treat chronic HCV infection . A series of clinical trials showed that some patients who received interferon had sustained normalization of serum aminotransferase levels and elimination of serum HCV RNA [ 14 - 17 ] . Histologic improvement was also seen in patients who received interferon [ 14 , 18 - 20 ] . It is important to determine whether interferon treatment also lowers the incidence of hepatocellular carcinoma in patients with chronic hepatitis C , but the recognized benefits of interferon make a r and omized , controlled trial to address this question unethical . We did a retrospective study to compare the incidence of hepatocellular carcinoma in  interferon-treated patients with HCV infection and histologically proven chronic hepatitis or cirrhosis with that in historical controls who did not receive interferon .  We also examined the relation between response to interferon therapy and incidence of hepatocellular carcinoma . Methods Patients The interferon group comprised 419 consecutive patients with chronic hepatitis C who had undergone liver biopsy 1 to 2 weeks before interferon therapy and had started treatment between January 1992 and December 1993 . The control group consisted of 144 consecutive patients with chronic hepatitis or cirrhosis who had undergone liver biopsy between January 1986 and December 1989 . All patients had histologically proven chronic hepatitis or cirrhosis ( Child-Pugh class A ) and were positive for anti-HCV .  Interferon Treatment In the interferon group , 176 patients received human lymphoblastoid interferon  , 149 received recombinant interferon- 2a , and 94 received recombinant interferon- 2b for 6 months . The median total interferon dose was 480 mU ( range , 282 to 800 mU ) . No patient had received interferon therapy before study entry . Contraindications to interferon treatment included pregnancy , presence of hepatitis B surface antigen , other types of liver disease , autoimmune disease , and any other serious illness . Efficacy of interferon therapy was categorized as follows . Patients with persistent normalization of alanine aminotransferase ( ALT ) levels during  interferon  therapy and follow-up were considered to have sustained response . Patients whose  serum ALT level was normal at the end of the treatment but increased to an abnormal level after cessation of treatment were considered to have relapse . All other patients were classified as nonresponders . Follow-up Abdominal ultrasonography or computed tomography was performed every 4 to 8 months , and serum -fetoprotein was measured every 2 to 6 months . The diagnosis of hepatocellular carcinoma was confirmed by needle biopsy , by surgically resected tumor specimens , or by typical radiologic findings on hepatic angiography . The starting date of follow-up for patients in the interferon and control groups was defined as the date of liver biopsy . For both groups , the end of follow-up was the development of hepatocellular carcinoma or December 1991 in the control group and the time of the latest abdominal imaging in the interferon group . To detect hepatocellular carcinoma , follow-up examinations were done in 85.4 % of controls and 90.7 % of patients in the interferon group . The Osaka Cancer Registry was used [ 21 , 22 ] to determine whether hepatocellular carcinoma had occurred in patients lost to follow-up . 
    Output:
    
Conclusions In patients with chronic hepatitis C , antiviral therapy can reduce the development of HCC and mortality , especially when SVR is achieved