***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 / Aims : The ideal end point of treatment for chronic hepatitis B virus ( HBV ) infection is sustained off-therapy hepatitis B surface antigen ( HBsAg ) loss with or even without seroconversion to anti-HBs . We investigated the role of adding PEGylated interferon ( PEG IFN ) to ongoing tenofovir treatment in chronic HBV patients for achieving HBsAg clearance . Patients and Methods : In this r and omized controlled trial , chronic HBV patients who have been receiving tenofovir for > 6 months with HBV viral load < 2000 IU/ml were r and omized into two groups . One group ( add-on therapy ) was given subcutaneous PEG IFN 180 mcg weekly for 12 months in addition to tenofovir . Patients in the other group received only tenofovir 300 mg orally on a daily basis . Patients in both groups were followed up for a total of two years , and patients in both groups were given tenofovir 300 mg daily indefinitely until they developed HBsAg clearance . Results : Twenty-three patients were allocated to the PEG IFN and tenofovir ( add-on therapy ) group , and another 25 patients were recruited to the tenofovir monotherapy group . Before r and omization , patients had received tenofovir for 1135 mean days ( range203 to 1542 days ) . One patient ( 4.3 % ) in add-on therapy lost HBsAg and seroconverted . Within two years , mean HBsAg decreased significantly with add-on therapy ( from 4753 IU/ml to 2402 ; P= 0.03 ) ; and it decreased from 5957 IU/ml to 4198 ; P= 0.09 in tenofovir monotherapy group . More patients in the add-on group developed serious side effects , with treatment discontinuation , and dose reductions ( P = 0.3 ) . Conclusion : PEG IFN and tenofovir add-on therapy was successful in achieving HBsAg clearance and seroconversion in 4.3 % of the patients . Add-on therapy patients had a significant decrease in HBsAg levels in two years ; and no significant decrease in HBsAg levels with the tenofovir monotherapy . With no significant HBsAg clearance , the utility of this combination regimen is question able BACKGROUND AND AIMS Results of studies using lamivudine and interferon combination in the treatment of chronic hepatitis B are not consistent or conclusive . This study aim ed to evaluate the efficacy of interferon plus lamivudine use versus single lamivudine in anti-HBe-positive chronic hepatitis B. METHODS Eighty patients were treated with either lamivudine or lamivudine plus simultaneously started interferon .  Patients were assigned in groups according to r and om allocation rule . Lamivudine was given 150 mg/day for 96 weeks in each group ; interferon was administered 10 MU three times a week for 24 weeks in the combination therapy group . RESULTS Alanine aminotransferase ( ALT ) normalization was achieved earlier in patients treated with lamivudine alone . At the end of treatment , there was no difference between the groups with respect to HBV DNA negativity , ALT normalization and breakthrough rate . Histological improvement was remarkable in each group , but fibrosis score and necro-inflammatory activity were much lower in lamivudine-treated patients . CONCLUSIONS Addition of interferon to the lamivudine regimen does not increase the effectiveness of the treatment . Considering the side effects of interferon treatment , this combination seems not to be convenient for anti-HBe-positive chronic hepatitis 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 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 Background : The aims of this study were to compare the efficacy and safety of the addition of adefovir dipivoxil ( ADV ) ( started at different time points ) to pegylated interferon alpha-2a ( PEG-INF-&agr;2a ) and PEG-INF-&agr;2a monotherapy . This prospect i ve , r and omized study sought to evaluate the safety and efficacy of the combination of PEG-INF-&agr;2a and ADV at different time points.120 patients were r and omized into groups that received PEG-INF-&agr;2a as monotherapy ( group A ) or in combination with ADV started at week 0 ( group B ) , 12 ( group C ) , or 24 ( group D ) . All patients were followed for 48 weeks . Efficacy and safety analyses were performed . Methods : Patients in group a received 135 & mgr;g of PEG-INF-&agr;2a by subcutaneous injection once weekly for 48 weeks . Patients in the ADV add-on group received 135 & mgr;g of PEG-INF-&agr;2a subcutaneously once weekly and received 10 mg of ADV administered once daily for 48 weeks . HBV DNA , HBsAg , HBeAg , and hepatitis B e antibody levels were determined . Responses were determined at week 12 ( ADV add-on ) , the end of treatment for PEG-INF-&agr;2a ( 48weeks ) and ADV ( EOT ) and at the end of 96 weeks of follow-up ( EOF ) . Results : The rate of HBV DNA loss were higher in the combination groups than group A at the week 12 , week 48 , the EOT and EOF ( P < 0.05 ) . The rates of HBeAg seroconversion and HBsAg loss were similar among the treatment groups ( P>0.05 ) . The alanineaminotransferase ( ALT ) normalization rate was higher in the combination group than group A only at the EOT ( P = 0.007 ) . By the EOF , the patients with ADV added at week 12 achieved higher rates of HBV DNA loss ( 71.9 % ) , HBeAg seroconversion ( 50.0 % ) , HBsAg loss ( 15.6 % ) , and ALT normalization ( 78.1 % ) . Conclusions : PEG-INF-&agr;2a plus ADV combination therapy is safe and superior to PEG-INF-&agr;2amonotherapyfor decreasing serum HBV DNA and normalizing the ALT level but has no significant impact on the rate of HBeAg seroconversion and HBsAg loss . Adding ADV at week 12 may be an optimal combination strategy BACKGROUND & AIMS Durable post-treatment response is uncommon in chronic hepatitis B ( CHB ) patients on nucleos(t)ide analogue therapy .  Response , response predictors and safety were assessed in patients who switched from long-term entecavir ( ETV ) to peginterferon alfa-2a .  METHODS Hepatitis B e antigen (HBeAg)-positive CHB patients who had received ETV for 9 - 36 months , with HBeAg < 100 PEIU/ml and HBV DNA ⩽1000 copies/ml , were r and omised 1:1 to receive peginterferon alfa-2a 180 μg/week or ETV 0.5mg/day for 48 weeks . The primary endpoint was HBeAg seroconversion at week 48 ( Clinical Trials.gov : NCT00940485 ) . RESULTS 200 patients were r and omised ; 197 received ⩾1 study drug dose . Five patients who were anti-HBe-positive at baseline were excluded from the modified intention-to-treat population ( peginterferon alfa-2a , n = 94 ; ETV , n = 98 ) . Patients who switched to peginterferon alfa-2a achieved higher week 48 HBeAg seroconversion rates vs. those who continued ETV ( 14.9 % vs. 6.1 % ; p = 0.0467 ) . Only patients receiving peginterferon alfa-2a achieved HBsAg loss ( 8.5 % ) . Among peginterferon alfa-2a-treated patients with HBeAg loss and HBsAg < 1500 IU/ml at r and omisation , 33.3 % and 22.2 % achieved HBeAg seroconversion and HBsAg loss , respectively . Early on-treatment HBsAg decline predicted response at week 48 ; highest rates were observed in patients with week 12 HBsAg < 200 IU/ml ( HBeAg seroconversion , 66.7 % ; HBsAg loss , 77.8 % ) . Alanine aminotransferase elevations were not associated with viral rebound ( n = 38 ) . Peginterferon alfa-2a was well-tolerated . CONCLUSIONS For patients who achieve viro 
    Output:
    
In conclusion , IFN monotherapy/combination had a small but significant increase in HBsAg loss over NA , associated with st and ard dose of IFN and ≥48weeks of therapy , although this effect faded over time