***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 . ) Current therapies for chronic hepatitis B ( CHB ) have a number of limitations , and better treatment options are needed . Peginterferon alpha-2a ( 40 kDa ) is superior to conventional interferon alpha-2a in the treatment of chronic hepatitis C. This is the first report on peginterferon alpha-2a ( 40 kDa ) in the treatment of CHB . In this phase II study , 194 patients with CHB not previously treated with conventional interferon-alpha were r and omized to receive weekly subcutaneous doses of peginterferon alpha-2a ( 40 kDa ) 90 , 180 or 270 microg , or conventional interferon alpha-2a 4.5 MIU three times weekly . Twenty-four weeks of therapy were followed by 24 weeks of treatment-free follow-up . All subjects were assessed for loss of hepatitis B e antigen ( HBeAg ) , presence of hepatitis B antibody ( anti-HBe ) , suppression of hepatitis B virus ( HBV ) DNA , and normalization of serum alanine transaminase ( ALT ) after follow-up . At the end of follow-up , HBeAg was cleared in 37 , 35 and 29 % of patients receiving peginterferon alpha-2a ( 40 kDa ) 90 , 180 and 270 microg , respectively , compared with 25 % of patients on conventional interferon alpha-2a . The combined response ( HBeAg loss , HBV DNA suppression , and ALT normalization ) of all peginterferon alpha-2a ( 40 kDa ) doses combined was twice that achieved with conventional interferon alpha-2a ( 24%vs 12 % ; P = 0.036 ) . All treatment groups were similar with respect to frequency and severity of adverse events . These results indicate that peginterferon alpha-2a ( 40 kDa ) is superior in efficacy to conventional interferon alpha-2a in chronic hepatitis B based on clearance of HBeAg , suppression of HBV DNA , and normalization of ALT 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 . ) 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 carcinoma occurred in 3.9 percent of those in the lamivudine group and 7.4 percent of those in the placebo group ( hazard ratio , 0.49 ; P=0.047 ) . Genotypic resistance YMDD mutations developed in 49 percent of the patients treated with lamivudine , and the Child-Pugh score was more likely to increase in patients with these mutations than in the other patients treated with lamivudine ( 7 percent vs. < 1 percent ) . Overall , 12 percent of the patients in the lamivudine group and 18 percent of the patients in the placebo group reported serious adverse events . CONCLUSIONS Continuous treatment with lamivudine delays clinical progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis by significantly reducing the incidence of hepatic decompensation and the risk of hepatocellular carcinoma OBJECTIVE To determine whether lamivudine or interferon-alpha ( IFN-alpha ) is the more successful treatment for chronic hepatitis B given a fixed drug budget . STUDY DESIGN A decision-tree model of 1 year . PATIENTS AND METHODS Average wholesale prices were used to estimate drug costs . A fixed drug budget of $ 558,910 , sufficient to treat 100 patients with IFN-alpha  , was assumed . Clinical data were taken from r and omized controlled trials . The outcome measures used were hepatitis B " e " antigen ( HBeAg ) seroconversion rates and rates of progression to cirrhosis . RESULTS The analysis showed that given the fixed drug budget , 353 patients could be treated with lamivudine  , result ing in an expected 62 HBeAg seroconversions  , with 6 patients progressing to cirrhosis . Given the same drug budget , 100 patients could be treated with IFN-alpha , leaving 253 patients untreated . This treatment scenario would result in an expected 32 HBeAg seroconversions , with 28 patients progressing to cirrhosis . Compared with no treatment , the costs per additional HBeAg seroconversion obtained were $ 12,703 for lamivudine and $ 39,922 for IFN-alpha . In addition , each case of cirrhosis avoided through lamivudine treatment result ed in significant annual cost savings .  Lamivudine therapy also provided additional clinical benefits ( e.g. , normalization of alanine transaminase levels , reduction in hepatitis B virus DNA levels , improvement in liver histology ) to patients who do not seroconvert . CONCLUSION From the perspective of a third-party payer with a fixed drug budget , lamivudine is more cost-effective therapy than IFN-alpha for the treatment of chronic hepatitis Background : Treatment with interferon‐alpha has been shown to be effective in one‐third of hepatitis B e antigen‐positive chronic hepatitis B patients , but is clinical ly associated with relevant adverse events 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 BACKGROUND AND AIMS : Hepatitis B surface antigen ( HBsAg ) loss is the hallmark of a complete response to antiviral therapy for chronic hepatitis B. In this study , we investigated the frequency of HBsAg loss after treatment with pegylated (Peg)-interferon α-2b . METHODS : In a multicenter r and omized controlled trial , 266 HBeAg 
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Following withdrawal of ADV , levels were similar to those in placebo patients .
In the ADV versus ADV plus LAM trial , there was a statistically significant difference in favour of the combination treatment .
In the PEG-alpha trials , there were statistically significant differences favouring PEG-alpha-2b plus LAM compared with either one of the drugs given as monotherapy .
PEG-alpha-2a was associated with increased treatment costs and gains in quality -adjusted life expectancy .
Both ADV and PEG-alpha are beneficial for patients with CHB in terms of suppressing viral load , reducing liver damage-associated biochemical activity , inducing HBeAg seroconversion , and reducing liver fibrosis and necroinflammation .
The effects of long-term treatment with ADV are generally durable , with relatively low rates of resistance .