***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 A total of 738 volunteer blood donors who were positive for anti-hepatitis C virus ( HCV ) were assessed for risk factors and outcomes for up to 15 years within the study and up to 54 years from the estimated onset of infection . METHODS A third-generation recombinant immunoblot assay ( RIBA ) was performed to distinguish true from false anti-HCV reactivity . Findings of HCV polymerase chain reaction classified subjects as having chronic HCV infection or as having recovered . Liver biopsy specimens were staged by Ishak fibrosis score and grade d by histologic activity index . RESULTS Of 738 anti-HCV-positive subjects , 469 ( 64 % ) had positive RIBA results , 217 ( 29 % ) had negative results , and 52 ( 7 % ) had indeterminate results . Primary independent risk factors were injection drug use ( odds ratio [ OR ] , 35.0 ; P < .0001 ) , blood transfusion ( OR , 9.9 ; P < .0001 ) , and intranasal cocaine use , including 79 " snorters " who repeatedly denied injection drug use or blood transfusion ( OR , 8.5 ; P < .0001 ) . Classification and regression tree and r and om forest analyses confirmed these risk factors . A total of 384 RIBA-positive donors ( 82 % ) were HCV RNA positive ; of these , liver biopsy specimens from 185 ( 48 % ) showed no fibrosis in 33 % , mild fibrosis in 52 % , bridging fibrosis in 12 % , and cirrhosis in 2 % a mean duration of 25 years after infection . Analysis of 63 repeat biopsy specimens showed that 8 % progressed ≥2 Ishak stages over 5 years ( mean progression , 0.06 Ishak stages/year ) . CONCLUSIONS Injection drug use and blood transfusion before 1990 are dominant risk factors for HCV acquisition ; intranasal cocaine use may be a surreptitious route of parenteral spread . After a mean of 25 years of HCV infection , histologic outcomes were relatively mild : 85 % had no or mild fibrosis , and only 2 % had cirrhosis . Nearly one-fifth spontaneously recovered BACKGROUND Liver-related mortality among those infected with hepatitis C virus ( HCV ) has been described , but little is known about non-liver-related mortality . Our objective was to determine HCV-associated all-cause , liver- , and non-liver-related mortality in the general US population . METHODS A prospect i ve cohort study of 9378 nationally representative adults aged 17 - 59 years was performed utilizing the Third National Health and Nutrition Examination Survey ( NHANES III ) Linked Mortality File that was made publicly available in 2010 . HCV status was assessed from 1988 to 1994 , with mortality follow-up of the same individuals through 2006 . RESULTS There were 614 deaths over a median follow-up of 14.8 years . After adjusting for all covariate risk factors , HCV chronic infection had a 2.37 times higher all-cause mortality rate ratio [ MRR ] ( 95 % CI : 1.28 - 4.38 ; P = .008 ) , a 26.46 times higher liver-related MRR ( 95 % CI : 8.00 - 87.48 ; P < .001 ) , and 1.79 times higher non-liver-related MRR ( 95 % CI : .77 - 4.19 ; P = .18 ) , compared with being HCV-negative . This represents an estimated 2.46 million US adults aged 17 - 59 years with chronic HCV infection who had an estimated 31,163 deaths from all causes per year , of which 57.8 % ( 95 % CI : 21.9%-77.2 % ) were attributable to HCV . Among those , there was an estimated 9569 liver-related deaths per year , of which 96.2 % ( 95 % CI : 87.5 - 98.9 % ) were attributable to HCV . Non-liver-related deaths were not significantly associated with HCV status . CONCLUSIONS Chronic HCV all-cause mortality is more than twice that of HCV-negative individuals . This suggests that those with chronic HCV infection are at a higher risk of death even after accounting for liver-related morbidity and should be closely monitored 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 BACKGROUND / AIMS HCV infection recurs almost in all HCV-positive patients receiving liver transplantation and carries a poor prognosis . Aim of this study was to analyze efficacy and effect on survival of antiviral therapy in this clinical setting . METHODS Pegylated-interferon alpha-2b and ribavirin were administered at a dose of 1 microg/kg of bwt weekly and 600 - 800 mg/day . Planned duration of treatment was 24 or 48 weeks according to HCV genotype . Patients who failed to respond at week 24 were considered as non-responders . RESULTS 61 patients were enrolled . According to intention-to-treat analysis , 44 ( 72 % ) patients were considered as treatment failure ( 31 non-responders , 4 relapsers , 9 dropout ) . Sustained virological response was achieved in 17 cases ( 28 % ) . Genotype 2 , higher doses of antivirals and absence of histological cirrhosis were predictors of sustained virological response . In the follow up , patients with sustained virological response had a significantly lower mortality compared to patients with treatment failure ( chi2=6.9 ; P<0.01 ) . CONCLUSIONS Response rate to antiviral therapy in HCV reinfection after liver transplantation is higher if a full dose of antiviral drugs is administered and if treatment starts before histological cirrhosis has developed . Sustained virological response improves patient survival BACKGROUND & AIMS The natural history of HCV-related compensated cirrhosis has been poorly investigated in Latin-American countries . Our study evaluated mortality and clinical outcomes in compensated cirrhotic patients followed for 6 years . METHODS Four hundred and two patients with compensated HCV-related cirrhosis were prospect ively recruited in a tertiary care academic center . At the time of admission , patients were stratified as compensated ( absence [ stage 1 ] or presence [ stage 2 ] of esophageal varices ) as defined by D'Amico et al. Subjects were followed to identify overall mortality or liver transplantation and clinical complication rates . RESULTS Among 402 subjects , 294 were categorized as stage 1 and 108 as stage 2 . Over a median of 176 weeks , 42 deaths occurred ( 10 % ) , of which 30 were considered liver-related ( 7 % ) and 12 non-liver-related ( 3 % ) ; eight individuals ( 2 % ) underwent liver transplantation ; 30 patients ( 7 % ) developed HCC , 67 individuals in stage 1 ( 22 % ) developed varices and any event of clinical decompensation occurred in 80 patients ( 20 % ) . The 6-year cumulative overall mortality or liver transplantation was 15 % and 45 % , for stages 1 and 2 , respectively ( p<0.001 ) . The cumulative 6-year HCC incidence was significantly higher among patients with varices ( 29 % ) than those without varices ( 9 % ) , p<0.001 . Similarly , the cumulative 6-year incidence of any clinical liver-related complication was higher in patients with stage 2 ( 66 % ) as compared to 26 % in those with stage 1 , respectively ( p<0.001 ) . CONCLUSIONS Our results indicate significant morbidity and mortality and clinical outcome rates in compensated cirrhotic patients with varices ( stage 2 ) OBJECTIVES : The identification of prognostic factors associated with mortality is crucial in any clinical setting . METHODS : We enrolled in a prospect i ve study 352 patients with compensated hepatitis C virus (HCV)-induced cirrhosis , consecutively observed between 1989 and 1992 . At entry , patients underwent upper endoscopy to detect esophageal varices , and were then surveilled by serial clinical and ultrasonographic examination . The model for end-stage liver disease ( MELD ) score was calculated with information collected at enrollment . Baseline predictors and intercurrent events associated with mortality were assessed using the Cox regression model . RESULTS : During a median follow-up of 14.4 years , 194 subjects received a single course of interferon monotherapy , 
    Output:
    
Published estimates of fatality are high among certain population s of chronic HCV patients , with liver-specific causes being an important contributor .