***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 AND AIM Entecavir is a potent inhibitor of both wild-type and lamivudine-resistant hepatitis B virus ( HBV ) with proven clinical efficacy . We conducted a r and omized , double-blind , multicenter study in Japan ( ETV-052 ) evaluating the efficacy and safety of two doses of entecavir in adult patients with lamivudine-refractory chronic hepatitis B infection . METHODS Eighty-four patients with chronic hepatitis B who were refractory to lamivudine therapy were switched from lamivudine to daily oral doses of 0.5 mg entecavir ( 41 patients ) or 1 mg entecavir ( 43 patients ) for 52 weeks . RESULTS The proportions of patients achieving the primary end-point ( > or=2 log(10 ) reduction in HBV-DNA from baseline by polymerase chain reaction assay or undetectable HBV-DNA levels [ < 400 copies/mL ] at week 48 ) were 90 % and 93 % for entecavir 0.5 mg and 1 mg , respectively , with 33 % of patients in each dosing group achieving < 400 copies/mL. The mean reduction in HBV-DNA from baseline was 3.58 and 3.75 log(10 ) copies/mL for entecavir 0.5 mg and 1 mg , respectively . High proportions of patients achieved alanine aminotransferase normalization at week 48 ( 0.5 mg 86 % , 1 mg 78 % ) . Histological improvement was observed in most patients ( 0.5 mg 52 % , 1 mg 60 % ) . Virological breakthrough ( increase in HBV-DNA of > or=1 log(10 ) copies/mL from nadir ) was observed in one patient but was not associated with selection of entecavir-associated resistance substitutions . Entecavir was well tolerated , with no patients discontinuing study drug due to adverse events . CONCLUSIONS These findings indicate that entecavir is safe and effective for the treatment of Japanese adults with lamivudine-refractory chronic hepatitis 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 . ) AIM To compare the efficacy of a combination of a-interferon ( IFN-a ) and lamivudine with IFN-a alone in the treatment of patients with HBeAg-positive chronic hepatitis B ( CHB ) . METHODS Sixty-eight treatment-naove patients with HBeAg-positive CHB were r and omized to receive either 9 MU of IFN-a2a three times a week and lamivudine 100 mg daily ( Group 1 ) , or IFN-a2a alone in the same dosage ( Group 2 ) , for 12 months . Serum ALT , HBeAg , anti-HBe and HBV DNA were tested at the end of treatment and 6 months later . Complete response was defined as normal ALT , negative HBeAg and negative HBV DNA , six months after stopping treatment . RESULTS Of the 68 patients , 64 completed the study . In Group 1 ( n=31 ) , mean ( SD ) ALT levels decreased from 124 ( 59 ) IU/L to 39 ( 18 ) IU/L at 12 months ; corresponding values in Group 2 ( n=33 ) were 128 ( 57 ) and 56 ( 11 ) IU/L ( p < 0.05 ) . Absence of HBV DNA at the end of treatment was more common in Group 1 ( 28/31 ) than in Group 2 ( 22/33 ; p < 0.022 ) . The number of patients with seroconversion to anti-HBe ( 4/31 [ 13 % ] vs. 4/33 [ 12 % ] , respectively ; p>0.05 ) , as also those with complete response ( 4/31 [ 13 % ] and 4/33 [ 12 % ] , respectively ; p>0.05 ) six months after completion of treatment was similar in Group 1 and Group 2 . CONCLUSION Combination treatment with IFN-a and lamivudine was better than IFN-a monotherapy in normalization of ALT and clearance of HBV DNA ; however , it did not have a better sustained response rate than IFN-a alone BACKGROUND Pegylated interferon (PEG-IFN)-alpha monotherapy is the current st and ard of care for short-term antiviral treatment of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B ( CHB ) . We aim ed to assess the safety and efficacy of PEG-IFN-alpha plus adefovir dipivoxil ( ADV ) versus PEG-IFN-alpha monotherapy for compensated HBeAg-negative CHB . METHODS A multicentre r and omized controlled trial was performed in eight outpatient hepatology/infectious disease clinics in central Italy . A total of 60 patients ( 67 % male and median age 48 years ) with biopsy-proven HBeAg-negative compensated CHB ( mean alanine aminotranferase [ ALT ] levels 3.3 + /-3x the upper normal limit and serum hepatitis B virus [ HBV ] DNA 5.8 + /-0.9 log(10 ) IU/ml ) were r and omized at baseline to receive PEG-IFN-alpha2a 180 microg/week plus ADV 10 mg/day or PEG-IFN-alpha2a monotherapy for 48 weeks . Post-treatment follow-up was for 24 additional weeks . The primary end point was sustained HBV DNA suppression defined as serum HBV DNA<2,000 IU/ml after 24 weeks of post-treatment follow-up . The secondary end point was ALT normalization at the end of follow-up . RESULTS At week 48 , HBV DNA was undetectable in 20/30 ( 67 % ) in the combination group versus 11/30 ( 37 % ) patients in the monotherapy group ( P=0.02 ) . ALT normalization was achieved in 17/30 ( 57 % ) versus 10/30 ( 30 % ) patients , respectively ( P=0.03 ) . At week 72 , sustained virological response was achieved in 7/30 ( 23.3 % ) in the combination group versus 6/30 ( 20 % ) patients in the monotherapy group ( P=0.75 ) ; 5 ( 16 % ) patients in each group dropped out because of adverse events or non-compliance . CONCLUSIONS In HBeAg-negative CHB , combination PEG-IFN-alpha2a plus ADV for 48 weeks is safe and result ed in greater on-treatment efficacy than PEG-IFN-alpha2a monotherapy . No difference in sustained virological and biochemical response rates were observed between the two treatment regimens 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 = . 
    Output:
    
In the sensitivity analysis , adefovir showed lower cost-utility than telbivudine in some situations .
In this study , tenofovir presented the best cost-utility ratio .