***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 Entecavir is a potent and selective guanosine analogue with significant activity against hepatitis B virus ( HBV ) . METHODS In this phase 3 , double-blind trial , we r and omly assigned 715 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who had not previously received a nucleoside analogue  to receive either 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks . The primary efficacy end point was histologic improvement ( a decrease by at least two points in the Knodell necroinflammatory score , without worsening of fibrosis ) at week 48 . Secondary end points included a reduction in the serum HBV DNA level , HBeAg loss and seroconversion , and normalization of the alanine aminotransferase level . RESULTS Histologic improvement after 48 weeks occurred in 226 of 314 patients in the entecavir group ( 72 percent ) and 195 of 314 patients in the lamivudine group ( 62 percent , P=0.009 ) . More patients in the entecavir group than in the lamivudine group had undetectable serum HBV DNA levels according to a polymerase-chain-reaction assay ( 67 percent vs. 36 percent , P<0.001 ) and normalization of alanine aminotransferase levels ( 68 percent vs. 60 percent , P=0.02 ) . The mean reduction in serum HBV DNA from baseline to week 48 was greater with entecavir than with lamivudine ( 6.9 vs. 5.4 log [ on a base-10 scale ] copies per milliliter , P<0.001 ) . HBeAg seroconversion occurred in 21 percent of entecavir-treated patients and 18 percent of those treated with lamivudine ( P=0.33 ) . No viral resistance to entecavir was detected . Safety was similar in the two groups . CONCLUSIONS Among patients with HBeAg-positive chronic hepatitis B , the rates of histologic , virologic , and biochemical improvement are significantly higher with entecavir than with lamivudine . The safety profile of the two agents is similar , and there is no evidence of viral resistance to entecavir . ( Clinical Trials.gov number , NCT00035633 . ) BACKGROUND Entecavir is a potent and selective antiviral agent that has demonstrated efficacy in phase 2 studies in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. METHODS In this phase 3 , double-blind trial , we r and omly assigned 648 patients with HBeAg-negative chronic hepatitis B who had not previously been treated with a nucleoside analogue to receive 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks . The primary efficacy end point was histologic improvement ( a decrease by at least two points in the Knodell necroinflammatory score , without worsening of fibrosis ) . RESULTS Histologic improvement after 48 weeks of treatment occurred in 208 of 296 patients in the entecavir group who had adequate baseline liver-biopsy specimens that could be evaluated ( 70 percent ) , as compared with 174 of 287 such patients in the lamivudine group ( 61 percent , P=0.01 ) . More patients in the entecavir group than in the lamivudine group had undetectable serum hepatitis B virus ( HBV ) DNA levels according to a polymerase-chain-reaction assay ( 90 percent vs. 72 percent , P<0.001 ) and normalization of alanine aminotransferase levels ( 78 percent vs. 71 percent , P=0.045 ) . The mean reduction in serum HBV DNA levels from baseline to week 48 was greater with entecavir than with lamivudine ( 5.0 vs. 4.5 log [ on a base-10 scale ] copies per milliliter , P<0.001 ) . There was no evidence of resistance to entecavir . Safety and adverse-event profiles were similar in the two groups . CONCLUSIONS Among patients with HBeAg-negative chronic hepatitis B who had not previously been treated with a nucleoside analogue , the rates of histologic improvement , virologic response , and normalization of alanine aminotransferase levels were significantly higher at 48 weeks with entecavir than with lamivudine . The safety profile of the two agents was similar , and there was no evidence of viral resistance to entecavir . ( Clinical Trials.gov number , NCT00035789 . ) 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 BACKGROUND & AIMS Entecavir demonstrated superior benefit to lamivudine at 48 weeks in nucleoside-naive patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B ( CHB ) . We evaluated continued entecavir and lamivudine treatment through 96 weeks . METHODS 709 HBeAg-positive CHB patients were r and omized to entecavir 0.5 mg ( n = 354 ) or lamivudine 100 mg ( n = 355 ) once daily . At week 52 , protocol -defined virologic responders could continue blinded treatment for up to 96 weeks . Patients continuing in year 2 ( entecavir , n = 243 ; lamivudine , n = 164 ) were assessed for serum hepatitis B virus ( HBV ) DNA , alanine aminotransferase ( ALT ) normalization , HBeAg seroconversion , and safety . Cumulative confirmed proportions of all treated patients who achieved these responses were also analyzed . RESULTS Among patients treated in year 2 , 74 % of entecavir-treated versus 37 % of lamivudine-treated patients achieved HBV DNA < 300 copies/mL by polymerase chain reaction ( PCR ) , and 79 % of entecavir-treated versus 68 % of lamivudine-treated patients normalized ALT levels . Similar proportions of entecavir-treated and lamivudine-treated patients achieved HBeAg seroconversion ( 11 % vs 12 % , respectively ) . Higher proportions of entecavir-treated than lamivudine-treated patients achieved cumulative confirmed HBV DNA < 300 copies/mL by PCR ( 80 % vs 39 % ; P < .0001 ) and ALT normalization ( 87 % vs 79 % ; P = .0056 ) through 96 weeks . Cumulative confirmed HBeAg seroconversion occurred in 31 % of entecavir-treated versus 25 % of lamivudine-treated patients ( P = NS ) . Through 96 weeks , no patient experienced virologic breakthrough due to entecavir resistance . The safety profile was comparable in both groups . CONCLUSIONS Entecavir treatment through 96 weeks results in continued benefit for patients with HBeAg-positive CHB Current therapy for chronic hepatitis B is suboptimal as a result of limited durable response rates , cumulative viral resistance , and /or poor tolerability . Telbivudine has potent antiviral activity against hepatitis B virus ( HBV ) in vitro and in the woodchuck model and has a promising pre clinical safety profile . In this first clinical study of telbivudine , safety , antiviral activity , and pharmacokinetics were assessed in 43 adults with hepatitis B e antigen-positive chronic hepatitis B. This placebo-controlled dose-escalation trial investigated 6 telbivudine daily dosing levels ( 25 , 50 , 100 , 200 , 400 , and 800 mg/d ) ; treatment was given for 4 weeks , with 12 weeks ' follow-up .  Serum HBV DNA levels were monitored via quantitative polymerase chain reaction . The results indicate that telbivudine was well tolerated at all dosing levels , with no dose-related or treatment-related clinical or laboratory adverse events . telbivudine plasma pharmacokinetics were dose-proportional within the studied dose range . Marked dose-related antiviral activity was evident , with a maximum at telbivudine doses of 400 mg/d or more . In the 800 mg/d cohort , the mean HBV DNA reduction was 3.75 log10 copies/mL at week 4 , comprising a 99.98 % reduction in serum viral load . Correspondingly , posttreatment return of viral load was slowest in the high-dose groups . Viral dynamic analyses suggested a high degree of efficiency of inhibition of HBV replication by telbivudine and helped refine selection of the optimal dose . In conclusion , these results support exp and ed clinical studies of this new agent for the treatment of hepatitis BACKGROUND / AIMS We aim ed to evaluate nucleoside/nucleotide combination therapy in treatment-naïve HBeAg-positive patients with chronic hepatitis B ( CHB ) . METHODS One hundred and fifteen HBeAg-positive patients received lamivudine 100 mg daily plus placebo ( monotherapy ) or lamivudine 100 mg plus adefovir dipoxil 10 mg daily ( combination therapy ) for 104 weeks in a r and omized double-blind study . RESULTS Time-weighted average change in serum HBV DNA from baseline up to week 16 was -4.20 log(10)copies/mL for both groups ( p=0.936 ) . At week 104 , median serum HBV DNA change from baseline ( log(10)copies/mL ) for monotherapy and combination therapy was -3.41 versus -5.22 , respectively . HBV DNA breakthrough was detected in 44 % of monotherapy and 19 % of combination therapy patients . The M204V/I mutation was detected in 43 % ( 15/35 ) and 15 % ( 6/41 ) of each group , respectively . ALT normalization at week 100 and 104 was 34 % ( 19/56 ) in the monotherapy group and 45 % ( 23/51 ) in the combination therapy group ( p=0.018 ) . By week 104 , HBeAg seroconversion occurred in 20 % of monotherapy and 13 % of combination therapy patients . Both regimens were well tolerated . CONCLUSIONS Lower rates of resistance to lamivudine , lower serum HBV DNA levels and higher rates of ALT normalization were seen in the combination therapy group after two years . However , serological outcomes were similar Adefovir dipivoxil ( bis-POM PMEA ) is an adenine nucleotide analogue with activity against retroviruses and herpesviruses , and in vitro activity against hepatitis B virus ( HBV ) . This study was conducted to evaluate its safety and antiviral activity in patients with chronic HBV infection . Twenty patients ( 13 co-infected with human immunodeficiency virus , HIV ) were r and omized in a phase I/II , double-blind , placebo-controlled study . Patients who had been hepatitis B surface antigen (HBsAg)/hepatitis B e antigen ( HBeAg ) positive for > or = 6 months , with elevated hepatic transaminases and serum HBV DNA > or = 50 pg ml-1 , were r and omized to adefovir dipivoxil 125 mg 
    Output:
    
INTRODUCTION Chronic hepatitis B is one of the most frequent infectious disease in the world and represents a serious problem of public health METHODS A systematic review of r and omized clinical trials was conducted to evaluate the efficacy of the nucleoside/nucleotide analogues ( adefovir , entecavir and telbivudine ) used for the treatment of chronic hepatitis B. The data bases PubMed and LILACS were consulted , among others RESULTS Twenty nine articles published between January/1970 to December/2009 were selected CONCLUSIONS All nucleoside/nucleotide analogues demonstrate upper or similar efficacy to lamivudine .
The entecavir can be appropriate for patients with chronic hepatitis B , HBeAg positive and negative treatment-naive as alternative to lamivudine , considering its low potential of viral resistance .
The addition of adefovir to lamivudine presented good results in lamivudine resistant patients .
The use of entecavir and telbivudine in those patients presents risk of crossed resistance .
Adverse events of nucleoside/nucleotide analogues were similar in characteristics , gravity and incidence when compared to the lamivudina and placebo