***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: Context Hepatocellular carcinoma often follows hepatitis C virus infection . Currently available treatments for hepatocellular carcinoma are unsatisfactory . Percutaneous ethanol injection therapy into tumor nodules shows some promise , but recurrence rates are high . Contribution In a carefully selected group of 74 patients with multicentric hepatocellular carcinoma , mild hepatitis C , and mild cirrhosis , patients r and omly assigned to receive interferon in addition to ethanol injections  showed improved survival at 5 and 7 years , particularly among patients with a sustained virologic response . Caution s Combined treatment of multicentric hepatocellular carcinoma offers the possibility of enhanced survival for carefully selected patients ; this study is small , however , and enrolled only patients with low virus levels and mild cirrhosis . The Editors Chronic hepatitis C virus ( HCV ) infection is a common , frequently asymptomatic disease . Despite the clinical ly quiescent course of HCV infection , it may slowly progress to cirrhosis and , eventually , to hepatocellular carcinoma ( 1 , 2 ) . Cirrhosis is a major risk factor for the development of hepatocellular carcinoma ( 3 , 4 ) , and 70 % to 80 % of patients with hepatocellular carcinoma in Japan have HCV infection ( 5 ) . Current strategies for treating hepatocellular carcinoma include surgical resection , transarterial embolization , percutaneous ethanol injection therapy , radiofrequency wave ablation , and chemotherapy ( 6 - 9 ) . Recent studies have shown that percutaneous ethanol injection therapy is effective for hepatocellular carcinoma when the tumors are small ( <3 to 5 cm in diameter ) and limited in number ; survival rates are similar to those obtained with surgery ( 10 - 12 ) . Five-year survival rates , however , are poor ( 30 % to 60 % for both hepatectomy and percutaneous ethanol injection therapy ) . Poor prognosis may be the result of the high incidence of tumor recurrence ; the cumulative recurrence rate at 5 years is 60 % to 100 % ( 10 - 13 ) . Several studies have evaluated the factors that contribute to the recurrence of hepatocellular carcinoma ( 12 , 13 ) . Occasionally , early recurrence develops adjacent to the treated lesion ( local recurrence , 6 % to 33 % depending on tumor size ) ( 14 ) , but most tumors ( 80 % to 90 % ) recur at different sites ( 15 ) . Because hepatocellular carcinoma recurrence and decompensation of underlying liver disease are major problems after medical or surgical treatment , liver transplantation is another option for treating small , unresectable hepatocellular carcinomas in patients with cirrhosis . Studies report 5-year survival rates as high as 75 % with liver transplantation ( 16 - 18 ) . Interferon therapy has beneficial effects in chronic HCV infection ( 19 , 20 ) . In long-term follow-up studies , sustained virologic responders have remained in remission with normal liver function and improved histologic features of inflammation ; in some of these responders , fibrosis even regresses ( 21 , 22 ) . Recently , the frequency of hepatocellular carcinoma in patients receiving interferon therapy  has substantially decreased , especially in patients with sustained virologic and biochemical responses ( 23 - 25 ) . This decreased frequency has occurred even in patients with cirrhosis ( 25 , 26 ) . Our study evaluated whether complete ablation of neoplastic nodules and administration of antiviral therapy could increase survival rates . Methods Study Design Our prospect i ve study was design ed by an eight-member committee in December 1992 . The Ethics Committee of the University of Tokyo approved the study . We obtained informed consent from each patient in accordance with the Helsinki declaration . Patients with compensated cirrhosis , three or fewer nodules of hepatocellular carcinoma , and low HCV RNA loads were recruited after complete ablation of the lesions . Eligibility Criteria Inclusion Criteria Hepatitis C virus infection was diagnosed on the basis of identification of anti-HCV antibody using the passive hemagglutination test ( Dinabbot , Tokyo , Japan ) or enzyme-linked immunosorbent assay ( ELISA ; Ortho Diagnostic Systems , Tokyo , Japan ) . Hepatitis C virus RNA was identified by reverse transcriptase polymerase chain reaction ( RT-PCR ) . The serum HCV RNA level was measured by competitive reverse transcriptase (CRT)-PCR according to the method of Kato and colleagues ( 27 ) ; HCV genotype was determined by the method of Okamoto and colleagues ( 28 ) . Hepatocellular carcinoma was suspected on the basis of several imaging methods , including abdominal ultrasonography , dynamic computed tomography ( CT ) , magnetic resonance imaging ( MRI ) , and arteriography . We confirmed the diagnosis by histologic examination of tumor biopsy specimens obtained from all patients . Evaluation was based on the criteria of the International Working Party ( 29 ) . In addition , we obtained and evaluated biopsy specimens from non-neoplastic lesions according to the methods of Desmet and colleagues ( 30 ) . Hepatocellular carcinoma was treated with percutaneous ethanol injection therapy ( 7 , 8 , 10 ) . Real-time linear-array scanners were used with 3.5-MHz transducers for the sonographic guidance of needles [ 21-gauge with a 15-cm or 20-cm needle ; Hanako , Tokyo , Japan ] into the tumors . Two to 10 mL of 99.5 % ethanol was injected into each lesion . Ethanol injection was repeated several times at different sessions . Complete destruction of the nodules was confirmed on dynamic CT 1 month after ethanol injection according to the following criteria : 1 ) The destructive area was larger than the area of the tumor nodule shown on pretreatment dynamic CT and 2 ) dynamic CT showed no early-phase contrast enhancement of nodules ( 7 , 8 , 10 ) . Inclusion criteria were as follows : 1 ) hepatocellular carcinoma with three or fewer lesions [ verified by histologic examination ] and dynamic CTconfirmed complete ablation of hepatocellular carcinoma lesions by percutaneous ethanol injection therapy , 2 ) detection of HCV RNA by RT-PCR and an HCV RNA load of 2 106 copies/mL or less by CRT-PCR ( the cutoff value was based on unpublished data indicating that interferon treatment was effective in patients with HCV RNA loads of 105 copies/50 L of serum by CRT-PCR [ 27 ] ] , 3 ) platelet count of 50 109 cells/L , 4 ) leukocyte count of 3 109 cells/L or greater , 5 ) compensated cirrhosis in ChildPugh stage A , 6 ) age younger than 70 years , 7 ) no previous treatment with interferon , and 8) su bmi ssion of informed consent . Exclusion Criteria Exclusion criteria were as follows : 1 ) liver diseases due to other causes , such as hepatitis B or primary biliary cirrhosis ; 2 ) HCV RNA load of 2 106 copies/mL or greater by CRT-PCR ; 3 ) severe comorbid diseases , such as heart disease , lung disease , or diabetes mellitus ; 4 ) decompensated cirrhosis in ChildPugh stage B or C ; and 5 ) failure to obtain informed consent . R and omization Patients who enrolled in the study were r and omly assigned in a 2:1 ratio to the interferon group or the control group by the controller . We assigned patients to the treatment group or control group by using a r and omization list . Interferon Therapy and Follow-up of Patients Interferon Therapy We started interferon therapy with natural interferon- ( Sumitomo Pharmaceuticals , Tokyo , Japan ) 2 to 3 months after tumor ablation was confirmed . Patients received 6 million U of interferon by intramuscular injection three times weekly for 48 weeks as out patients . If patients could not tolerate this dose , the interferon dose was reduced to 3 million U. If HCV RNA in serum was still detected by RT-PCR ( detection limit , 102 copies/mL ) after 24 weeks of interferon therapy and serum alanine aminotransferase ( ALT ) levels were higher than pretreatment ALT levels , therapy was discontinued . Criteria for Interferon Response We defined the efficacy of interferon therapy virologically and biochemically . Patients who were negative for HCV RNA ( as determined by RT-PCR ; detection limit , 102 copies/mL ) more than 6 months after the completion of interferon therapy were classified as showing a sustained virologic response .  Patients with persistently normal ALT levels after the completion of interferon therapy  were classified as showing a sustained biochemical response ; patients with abnormal ALT levels  were classified as showing a nonsustained biochemical response . Follow-up Patients attended a monthly medical consultation at the University of Tokyo Hospital outpatient clinic .  Blood biochemical measures , including -fetoprotein ( AFP ) tumor markers , were measured every 1 to 2 months ; ultrasonography was performed every 2 to 3 months ; and dynamic CT was performed every 6 months . Recurrence of hepatocellular carcinoma was detected by the finding of abnormal nodules with low or high echogenic appearance on abdominal ultrasonography or by the finding of abnormal density on dynamic CT . The diagnosis was confirmed histologically through ultrasonography-guided fine-needle biopsy of the tumor . Recurrent nodules were divided into two categories [ 14 , 15 ] : 1 ) local recurrence , in which the nodule appeared adjacent to the previously treated nodules , suggesting that residual tumor cells had not been completely ablated by percutaneous ethanol injection therapy , or 2 ) new foci developing at a distant site . New foci of hepatocellular carcinoma , as well as local recurrent nodules at tumor , node , metastasis ( TNM ) stage I , II , and III , were mainly treated by a second course of percutaneous ethanol injection therapy ; local recurrent nodules at TNM stage IV were treated with transarterial chemoembolization or chemotherapy .  New development of hepatocellular carcinoma and survival of the patients ( tumor recurrence rate and survival rate ) were analyzed in relation to the time interval after initial treatment . Statistical Analysis When estimating the sample size , we assumed that 5-year survival in the control group would be 40 % according to the data of our previous unpublished study . We predicted that 5-year survival would be increased by 35 % as a result of Lamivudine is widely used to treat patients with hepatitis B. However , the outcomes in patients with hepatocellular carcinoma ( HCC ) treated with lamivudine have not been established . This study was conducted to evaluate the outcomes of lamivudine treatment for patients with HCC using an untreated , matched control group . Thirty patients with controlled HCC orally received lamivudine . As controls , 40 patients with HCC who were not treated with lamivudine and matched for clinical features were selected . The lamivudine-treated and untreated groups were compared with respect to changes in liver function , HCC recurrence , survival , and cause of death . In the lamivudine-treated group , there was significant improvement in the Child-Pugh score at 24 months after starting treatment , while no improvement was observed in the untreated group . There was no significant difference in the cumulative incidence of HCC recurrence and survival between the groups . However , there was a significant difference in the cumulative incidence of death due to liver failure ( P= 0.043 ) . A significant improvement in liver function was achieved by lamivudine treatment , even in patients with HCC . These results suggest that lamivudine treatment for patients with HCC may prevent death due to liver failure . Further prospect i ve r and omized studies using a larger number of patients are required BACKGROUND The effectiveness of antiviral therapy in preventing disease progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis is unknown . METHODS Patients with chronic hepatitis B who had histologically confirmed cirrhosis or advanced fibrosis were r and omly assigned in a 2:1 ratio to receive lamivudine ( 100 mg per day ) or placebo for a maximum of five years . Of 651 patients , 436 were assigned to receive lamivudine and 215 to receive placebo .  The primary end point was time to disease progression , defined by hepatic decompensation , hepatocellular carcinoma , spontaneous bacterial peritonitis , bleeding gastroesophageal varices , or death related to liver disease . An independent data and safety monitoring board monitored the progress of the study and performed interim analyses of the data . RESULTS We r and omly assigned 651 patients ( 98 percent Asian and 85 percent male ) to receive lamivudine or placebo . The study was terminated after a median duration of treatment of 32.4 months ( range , 0 to 42 ) owing to a significant difference between treatment groups in the number of end points reached . End points were reached by 7.8 percent of the patients receiving lamivudine and 17.7 percent of those receiving placebo ( hazard ratio for disease progression , 0.45 ; P=0.001 ) . The Child-Pugh score increased in 3.4 percent of the patients receiving lamivudine and 8.8 percent of those receiving placebo ( hazard ratio , 0.45 ; P=0.02 ) , whereas hepatocellular carcin 
    Output:
    
Conclusion Our study suggested benefits of adjuvant NA therapy following curative treatment of HBV-HCC .