***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: 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 Treatment with adefovir dipivoxil for 48 weeks result ed in histologic , virologic , and biochemical improvement in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. We evaluated the effect of continued therapy as compared with cessation of therapy . METHODS One hundred eighty-five HBeAg-negative patients with chronic hepatitis B were assigned to receive 10 mg of adefovir dipivoxil or placebo once daily for 48 weeks ( ratio , 2:1 ) . After week 48 , patients receiving adefovir dipivoxil were again r and omly assigned either to receive an additional 48 weeks of the drug or to switch to placebo . Patients originally assigned to placebo were switched to adefovir dipivoxil . Patients treated with adefovir dipivoxil during weeks 49 through 96 were subsequently offered continued therapy . The primary end points were changes in hepatitis B virus ( HBV ) DNA and alanine aminotransferase levels . RESULTS Treatment with adefovir dipivoxil result ed in a median decrease in serum HBV DNA of 3.47 log copies per milliliter ( on a base-10 scale ) at 96 weeks and 3.63 log copies per milliliter at 144 weeks . HBV DNA levels were less than 1000 copies per milliliter in 71 percent of patients at week 96 and 79 percent at week 144 . In the majority of patients who were switched from adefovir dipivoxil to placebo , the benefit of treatment was lost ( median change in HBV DNA levels from baseline , -1.09 log copies per milliliter ; only 8 percent of patients had levels below 1000 copies per milliliter at week 96 ) . Side effects during weeks 49 through 144 were similar to those during the initial 48 weeks . Resistance mutations rtN236 T and rtA181V were identified in 5.9 percent of patients after 144 weeks . CONCLUSIONS In patients with HBeAg-negative chronic hepatitis B , the benefits achieved from 48 weeks of adefovir dipivoxil were lost when treatment was discontinued . In patients treated for 144 weeks , benefits were maintained , with infrequent emergence of viral resistance To evaluate the effect of interferon and the benefit of prednisolone pretreatment in Oriental patients with chronic active hepatitis B , 120 male Chinese patients were r and omly allocated to receive : 1 ) group A : a 4-week course of prednisolone followed by 2 weeks of no treatment and then a 12-week course of human lymphoblastoid interferon , 4 to 6 MU/m2 intramuscularly ; 2 ) group B : as group A , but with placebo given instead of prednisolone ; 3 ) group C : an 18-week course of placebo .  Clearance of serum hepatitis B virus-DNA and HBeAg ( complete response ) was achieved in 21 % of group A , 5 % of group B and none of group C at the end of therapy ( A vs B : p = 0.054 ; A vs C : p < 0.01 ) . When assessed 12 months after the end of therapy , the complete response rate was 46 % in group A , 24 % in group B and 25 % in group C ( p < 0.05 ) . Those with baseline alanine transaminase < or = 200 U/l showed a better response to interferon  following prednisolone withdrawal ( 48 % ) than with interferon therapy alone ( 20 % , p = 0.056 ) and no treatment ( 9 % , p < 0.01 ) . Those with a baseline serum hepatitis B virus-DNA < or = 1000 pg/ml also showed a higher complete response rate when pretreated with prednisolone ( 59 % ) than when treated with interferon alone ( 29 % , p = 0.084 ) or untreated ( 22 % , p < 0.03 ) . The strongest independent predictor of a response to treatment was prednisolone withdrawal ( p < 0.05 ) . None of the responders lost hepatitis B surface antigen . ( ABSTRACT TRUNCATED AT 250 WORDS To assess the impact of sequential therapy with adefovir dipivoxil ( ADV ) and pegylated interferon alfa-2a ( PEG-IFN ) on virological ( serum HBV-DNA ) and serological ( serum HBsAg ) response in 20 consecutive HBeAg-negative patients . Patients received ADV for 20 weeks , then ADV and PEG-IFN for 4 weeks and lastly PEG-IFN for 44 weeks . Serum HBV-DNA and HBsAg were assessed at baseline , during therapy ( weeks 20 , 44 and 68 ) and follow-up ( weeks 92 and 116 ) . Sustained virological response ( SVR ) was defined as serum HBV-DNA < 10 000 copies/mL ( partial ) or < 70 copies/mL ( complete ) 24 weeks after stopping treatment . A serological response was defined as a serum HBsAg decrease ≥1 log(10 ) IU/mL at the end of treatment . Baseline median serum HBV-DNA and HBsAg levels were 7.6 log(10 ) copies/mL and 3.8 log(10 ) IU/mL , respectively . Ten patients ( 50 % ) achieved SVR , six of them had partial response and four complete response . Four patients ( 20 % ) achieved serological response . Complete SVRs showed a major and steep decline in HBsAg level with a median decrease of 0.5 , 1.6 and 2.0 log(10 ) IU/mL at treatment week 20 , 44 and 68 , respectively . Partial SVRs showed a slight and slow decline in serum HBsAg level ( 0.1 , 0.4 , and 0.6 log IU/mL at weeks 20 , 44 and 68 , respectively ) . On-treatment serum HBsAg decrease had a high accuracy to predict SVR ( AUROC = 0.88 ) . Our results suggest that sequential therapy might be an interesting strategy for HBeAg-negative patients . Serum HBsAg kinetics seem to be an accurate tool to predict SVR . Large clinical trials are needed to explore this strategy with more potent analogues Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objective Treatment with peginterferon α-2a ( PegIFN ) for 48 weeks is the st and ard of care for selected HBeAg-negative patients chronically infected with hepatitis B virus ( HBV ) , but with limited treatment efficacy . A study was undertaken to investigate whether treatment extension to 96 weeks improves the outcome in this patient population . Methods 128 HBeAg-negative patients ( 120 genotype D ) were r and omised to weekly 180 μg PegIFN for 48 weeks ( group A , n=51 ) , 180 μg PegIFN for 48 weeks followed by 135 μg weekly for an additional 48 weeks ( group B , n=52 ) or 180 μg PegIFN plus lamivudine ( 100 mg/day ) for 48 weeks then 135 μg PegIFN for 48 weeks ( group C , n=25 ) . Endpoints were alanine aminotransferase normalisation plus HBV DNA < 3400 IU/ml ( primary ) , HBV DNA < 2000 IU/ml and HBsAg clearance at 48 weeks after treatment . Results Forty-eight weeks after treatment , six patients in group A and 13 in group B achieved alanine aminotransferase normalisation plus HBV DNA < 3400 IU/ml ( 11.8 % vs 25.0 % , p=0.08 ) , 6 vs 15 patients had HBV DNA < 2000 IU/ml ( 11.8 % vs 28.8 % , p=0.03 ) , 0 vs 3 achieved HBsAg clearance ( 0 % vs 5.8 % , p=0.24 ) and 0 vs 5 had HBsAg < 10 IU/ml ( 0 % vs 9.6 % , p=0.06 ) . While extended PegIFN treatment was the strongest independent predictor of response , the combination with lamivudine did not improve responses . Discontinuation rates were similar among the groups ( 19.6 % , 23.1 % , 32.0 % , p=0.81 ) and were mostly due to PegIFN-related adverse events . Conclusions In HBeAg-negative genotype D patients with chronic hepatitis B  , PegIFN treatment for 96 weeks was well tolerated and the post-treatment virological response improved significantly compared with 48 weeks of treatment . Trial registration number http:// Clinical Trials.gov registration number : NCT01095835 The focus of this study was to evaluate the safety and efficacy of sequential peginterferon α-2a ( Pegasys ) therapy for chronic hepatitis B with acute exacerbation [ ALT > 10 × upper limit of normal ( ULN ) , bilirubin < 2.0 mg/dL ] . Four groups of patients categorized by HBeAg status and treatment regimens were studied since May 2007 . Nineteen HBeAg-positive patients ( Group 1 ) had received entecavir pretreatment ( when ALT > 10 × ULN ) plus Pegasys ( 180 μg/kg/week , when ALT was 5–10 × ULN ) for 24 weeks . Thirteen HBeAg-negative patients ( Group 2 ) had the same protocol for 48 weeks . In both groups , entecavir was then discontinued 14 days after the initiation of Pegasys . The results were compared , respectively , to 35 HBeAg-positive patients ( Group 3 ) and 24 HBeAg-negative patients ( Group 4 ) , all with ALT > 5 × ULN , under continual entecavir monotherapy . The ALT levels of patients in Group 1 and 2 who had received entecavir pretreatment for a duration of 19.63 ± 3.34 days were below four times of ULN following 4 weeks of Pegasys treatment . At week 96 , the rates of sustained virological response were 69.2 % ( 9/13 ) and 80 % ( 8/10 ) , and the relapse rates were 23.1 % ( 3/13 ) and 11.2 % ( 1/9 ) for HBeAg-positive and HBeAg-negative patients with two-step Pegasys treatment , respectively . The HBeAg seroconversion rates were 46.2 % in Group 1 , and 42.1 % in Group 3 ; HBsAg loss rates were 15.4 % ( 2/13 ) in Group 1 , and 30 % ( 3/10 ) in Group 2 , whereas none achieved HBsAg loss with entecavir monotherapy ( Group 3 and 4 ) . The two-step Pegasys treatment offers an alternative , other than the nucleos(t)ides , for treating chronic hepatitis B with acute exacerbation and provides a safe , efficacious , short-term and finite strategy B 
    Output:
    
Our analysis revealed that PEG-IFNα + lamivudine combination therapy  produced better virological and biochemical responses  than PEG-IFNα monotherapy in HBeAg-positive and HBeAg-negative patients at the end of treatment .
PEG-IFNα + adefovir dipivoxil achieved better seroconversion rate  than PEG-IFNα in HBeAg-positive patients at the end of treatment .
The present findings demonstrated a beneficial response rate  following PEG-IFNα combination therapy with nucelos(t)ides among HBeAg-positive and HBeAg-negative patients with CHB .