***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: 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 Entecavir is an oral antiviral drug with selective activity against hepatitis B virus ( HBV ) . We conducted a r and omized , placebo-controlled , dose-escalating study in patients with chronic hepatitis B infection in which we evaluated the efficacy and safety of entecavir given for 28 days . Follow-up was 24 weeks . All doses of entecavir ( 0.05 mg , 0.1 mg , 0.5 mg , and 1.0 mg ) showed a pronounced suppression of replication of the HBV with a 2.21 , 2.29 , 2.81 , and 2.55 mean log(10 ) reduction of viral load , respectively . Approximately 25 % of patients on entecavir  showed a decline of HBV DNA below the limit of detection of the Chiron HBV-DNA assay ( < 0.7 MEq/mL ) . In the postdosing follow-up period patients who were treated with 0.5 and 1.0 mg of entecavir showed a considerably slower return in their HBV DNA levels to baseline compared with those patients treated with lower dosages ( P < .05 ) . All doses of entecavir were well tolerated with no significant difference between treated patients and those receiving placebo . No significant changes in alanine transaminase ( ALT ) levels within the dose groups and the placebo group between baseline and the end of treatment were observed . Three patients ( 9 % ) ( 1 each in the 0.05- , 0.1- , and 0.5-mg groups ) experienced asymptomatic hepatitis flares 16 weeks ( 2 patients ) and 24 weeks ( 1 patient ) after withdrawal of entecavir . In conclusion , in this 28-day study of entecavir a pronounced decrease of HBV DNA was observed and there were no significant side effects in entecavir patients in comparison with placebo-treated patients OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials BACKGROUND / AIMS To observe the recurrence and prognosis of patients with hepatocellular carcinoma ( HCC ) coexisting with chronic hepatitis B infection with active virus replication after receiving antivirus therapy using lamivudine and thymosin alpha1 postoperatively .  METHODOLOGY From Jan. 2000 to Dec. 2002 , 33 patients with HCC coexisting chronic hepatitis B infection with active virus replication were prospect ively divided into two groups : control group ( n= 17 ) received hepatectomy only , treatment group ( n= 16 ) received hepatectomy and lamivudine plus thymosin alpha1 therapy postoperatively . The suppression of HBV-DNA , HBeAg seroconverted rate , recurrent tumor rate and the median survival for the two groups were observed and calculated . RESULTS For the treatment group and control group , the one-year HBV-DNA suppression rate was 100 % vs. 6 % ( p=0.0016 ) ; HBeAg seroconverted rate was 62.5 % vs. 5.9 % ( p=0.0157 ) ; The median recurrent time was 7.0 vs. 5.0 months ( p=0.0052 ) ; The median survival period was 10.0 vs. 7.0 months ( p=0.10053 ) , respectively . CONCLUSIONS Antivirus therapy using lamivudine and thymosin alpha1 postoperatively may suppress the HBV reaction , delay the recurrent time and prolong the survival for HCC patients coexisting with chronic HBV infection with active virus replication CONTEXT Serum hepatitis B virus ( HBV ) DNA level is a marker of viral replication and efficacy of antiviral treatment in individuals with chronic hepatitis B. OBJECTIVE To evaluate the relationship between serum HBV DNA level and risk of hepatocellular carcinoma . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study of 3653 participants ( aged 30 - 65 years ) , who were seropositive for the hepatitis B surface antigen and seronegative for antibodies against the hepatitis C virus , recruited to a community-based cancer screening program in Taiwan between 1991 and 1992 . MAIN OUTCOME MEASURE Incidence of hepatocellular carcinoma during follow-up examination and by data linkage with the national cancer registry and the death certification systems . RESULTS There were 164 incident cases of hepatocellular carcinoma and 346 deaths during a mean follow-up of 11.4 years and 41,779 person-years of follow-up . The incidence of hepatocellular carcinoma increased with serum HBV DNA level at study entry in a dose-response relationship ranging from 108 per 100,000 person-years for an HBV DNA level of less than 300 copies/mL to 1152 per 100,000 person-years for an HBV DNA level of 1 million copies/mL or greater . The corresponding cumulative incidence rates of hepatocellular carcinoma were 1.3 % and 14.9 % , respectively . The biological gradient of hepatocellular carcinoma by serum HBV DNA levels remained significant ( P<.001 ) after adjustment for sex , age , cigarette smoking , alcohol consumption , serostatus for the hepatitis B e antigen ( HBeAg ) , serum alanine aminotransferase level , and liver cirrhosis at study entry . The dose-response relationship was most prominent for participants who were seronegative for HBeAg with normal serum alanine aminotransferase levels and no liver cirrhosis at study entry . Participants with persistent elevation of serum HBV DNA level during follow-up had the highest hepatocellular carcinoma risk . CONCLUSION Elevated serum HBV DNA level ( > or = 10,000 copies/mL ) is a strong risk predictor of hepatocellular carcinoma independent of HBeAg , serum alanine aminotransferase level , and liver cirrhosis Reactivation of hepatitis B virus ( HBV ) during chemotherapy is well documented . However , there are limited data on this complication in patients with hepatocellular carcinoma ( HCC ) undergoing transarterial chemotherapy . The aim of this study was to evaluate the efficacy of preemptive lamivudine therapy in reducing hepatitis due to HBV reactivation in patients with HCC undergoing transarterial chemo-lipiodolization ( TACL ) and to seek predictors of this event . A total of 73 consecutive HCC patients undergoing TACL using epirubicin 50 mg/m2 and cisplatin 60 mg/m2 at monthly intervals were prospect ively and r and omly assigned to receive lamivudine 100 mg daily from the start of TACL ( preemptive group ) or not ( control group ) . During the study , 11 ( 29.7 % ) of 37 patients in the control group and 1 ( 2.8 % ) of 36 patients in the preemptive group developed hepatitis due to HBV reactivation ( P = .002 ) . In addition , there were significantly more incidences of overall hepatitis ( P = .021 ) and severe grade of hepatitis ( P = .035 ) in the control group . With multivariate Cox regression model , a baseline HBV DNA level of more than 10(4 ) copies/mL was the only independent predictor of hepatitis due to HBV reactivation during chemo-lipiodolization ( P = .046 ) . In conclusion , preemptive lamivudine therapy demonstrated excellent efficacy in reducing hepatitis due to HBV reactivation and hepatic morbidity during TACL . Preemptive therapy should be considered in HCC patients with an HBV DNA level of more than 10(4 ) copies/mL. Further studies are needed to confirm the value of this approach in patients with low-level viremia Lamivudine is a potent inhibitor of hepatitis B virus ( HBV ) replication , but its long-term use may be associated with HBV tyrosine-methionine-aspartate-aspartate ( YMDD ) motif mutation . To examine the clinical features and course after emergence of YMDD mutants , 55 patients who received lamivudine therapy over 104 weeks at our unit were assayed for YMDD mutation(s ) . Thirty-two of them were found to have the YMDD mutation . They continued lamivudine therapy and were followed up weekly or biweekly if clinical ly indicated . Thirty ( 93.7 % ) of them showed elevation of alanine transaminase ( ALT ) , and 13 ( 40.6 % ) experienced acute exacerbation at 4 to 94 weeks ( median , 24 weeks ) after emergence of the YMDD mutant . The incidence of exacerbation is much higher than 4.3 % in patients without the YMDD mutation ( P = .003 ) . Compared with patients without exacerbation , patients with exacerbation had a significantly higher serum HBV-DNA level after emergence of the YMDD mutant ( P < .005 ) . Before exacerbation , serum HBV-DNA level was rising to its peak , followed by the peaking of ALT ( 247 - 2,010 U/L ) 1 to 4 weeks later . Three patients developed hepatic decompensation , but then in association with hepatitis B e antigen ( HBeAg ) seroconversion , recovered . Of the 12 evaluable patients , 8 ( 75 % ) showed HBeAg seroconversion , and 3 showed mutant clearance within 1 to 5 months after exacerbation . In contrast , none of the patients without exacerbation showed HBeAg seroconversion ( P < .001 ) . These results indicate that acute exacerbations may occur after emergence of the YMDD mutation . The incidence , clinicopathological features , and subsequent course , and possibly the underlying immune mechanisms , are similar to those of wild-type HBV chronic infection . Because severe hepatitis may occur , patients should be followed carefully once the YMDD mutant emerges Background The role of antiviral therapy for patients in the immune-active phase of hepatitis B virus ( HBV ) infection who underwent partial hepatectomy for hepatocellular carcinoma ( HCC ) is unknown . Methods From January 2004 to June 2007 , a nonr and omized comparative study for postoperative antiviral treatment was conducted on patients who underwent curative hepatectomy for advanced HCC . Patients in the treatment group ( n = 43 ) received lamivudine with or without adefovir dipivoxil , while the control group ( n 
    Output:
    
Breakthrough hepatitis was a serious adverse event attributable to lamivudine .