***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: Tenofovir disoproxil fumarate ( DF ) is highly effective for the suppression of hepatitis B virus ( HBV ) in chronically infected adults . This study evaluated the safety and efficacy of tenofovir DF in adolescents with chronic hepatitis B ( CHB ) . In this double‐blind , placebo‐controlled trial , adolescents 12 to < 18 years of age with CHB were r and omized to tenofovir DF 300 mg ( n = 52 ) or placebo ( n = 54 ) once daily for 72 weeks . The primary endpoint was virologic response ( HBV DNA < 400 copies/mL ) at week 72 . One hundred six patients were enrolled ; 101 patients completed 72 weeks of treatment . At baseline , 91 % of patients were hepatitis B e antigen – positive and 85 % had prior exposure to HBV therapy .  A virologic response was observed in 89 % ( 46/52 ) of patients who received tenofovir DF and 0 % ( 0/54 ) of patients who received placebo ( P < 0.001 ) . Treatment response was not affected by prior HBV treatment . Furthermore , no resistance  to tenofovir DF developed through week 72 . Among patients with an alanine aminotransferase ( ALT ) level greater than the upper limit of normal at baseline , normalization of ALT occurred in 74 % of patients receiving tenofovir DF and 31 % of patients receiving placebo ( P < 0.001 ) . The rate of grade 3/4 adverse events was higher among patients treated with placebo ( 24 % ) than patients treated with tenofovir DF ( 10 % ) . No patients met the safety endpoint of a 6 % decrease in spine bone mineral density at week 72 . Conclusion : Tenofovir DF  therapy in HBV‐infected adolescents was well tolerated and highly effective at suppressing HBV DNA and normalizing ALT values in both treatment‐naïve adolescents and those with prior exposure to HBV therapy . ( HEPATOLOGY 2012;56:2018–2026 Background Chronic HBV infects 350 million people causing cancer and liver failure . We aim ed to assess the safety and efficacy of plasmid DNA ( pSG2.HBs ) vaccine , followed by recombinant modified vaccinia virus Ankara ( MVA.HBs ) , encoding the surface antigen of HBV as therapy for chronic HBV . A secondary goal was to characterize the immune responses . Methods Firstly 32 HBV e antigen negative ( eAg– ) participants were r and omly assigned to one of four groups : to receive vaccines alone , lamivudine ( 3TC ) alone , both , or neither .  Later 16 eAg+ volunteers in two groups received either 3TC alone or both 3TC and vaccines . Finally , 12 eAg– and 12 eAg+ subjects were enrolled into higher-dose treatment groups . Healthy but chronically HBV-infected males between the ages of 15 – 25 who lived in the western part of The Gambia were eligible . Participants in some groups received 1 mg or 2 mg of pSG2.HBs intramuscularly twice followed by 5 × 107 pfu or 1.5 × 108 pfu of MVA.HBs intradermally at 3-weekly intervals with or without concomitant 3TC for 11–14 weeks . Intradermal rabies vaccine was administered to a negative control group . Safety was assessed clinical ly and biochemically . The primary measure of efficacy was a quantitative PCR assay of plasma HBV . Immunity was assessed by IFN-γ ELISpot and intracellular cytokine staining . Results Mild local and systemic adverse events were observed following the vaccines . A small shiny scar was observed in some cases after MVA.HBs . There were no significant changes in AST or ALT . HBeAg was lost in one participant in the higher-dose group . As expected , the 3TC therapy reduced viraemia levels during therapy , but the prime-boost vaccine regimen did not reduce the viraemia . The immune responses were variable . The majority of IFN-γ was made by antigen non-specific CD16 + cells ( both CD3 + and CD3– ) . Conclusions The vaccines were well tolerated but did not control HBV infection . Trial Registration IS RCT N IS RCT This study investigated the efficacy , safety , and pharmacokinetics of adefovir dipivoxil ( ADV ) in children and adolescents with chronic hepatitis B ( CHB ) . A total of 173 treatment‐naive and treatment‐experienced children with hepatitis B e antigen (HBeAg)+ CHB were r and omized to ADV or placebo . R and omization was stratified by age ( 2 to < 7 years ; > 7 to < 12 years ; > 12 to < 18 years ) and prior treatment . Significantly more ADV‐treated subjects aged 12 to < 18 years achieved the primary efficacy endpoint ( serum hepatitis B virus [ HBV ] DNA < 1,000 copies/mL and normal alanine aminotransferase ) compared to placebo‐treated subjects ( 23 % versus 0 % ; P = 0.007 ) . In the younger groups , differences between ADV and placebo at the end of blinded treatment were not statistically significant . More ADV‐treated subjects had HBeAg seroconversion : 18 of 113 ( 15.9 % ) versus three of 57 ( 5.3 % ) ( but P = 0.051 ) , and more met the combined endpoint of HBeAg seroconversion , HBV DNA < 1,000 copies/mL and normal alanine aminotransferase ( 12/113 versus 0/57 ; P = 0.009 ) . No subject developed an ADV‐associated mutation that has been linked to HBV DNA rebound ( that is , mutations rtN236 T or rtA181V ) . ADV plasma concentrations were comparable across groups and within the target range . ADV treatment was well tolerated ; no new safety issues were identified . Treatment‐related adverse events were reported for 12 % of ADV‐treated and 10 % of placebo‐treated subjects . After 48 weeks of ADV  treatment , antiviral efficacy in subjects ages 12 to < 18 years with HBeAg+ CHB was similar to that observed in a study in adult treatment‐naive subjects with HBeAg+ CHB . ADV was not different from placebo in subjects aged 2 to 11 years despite adequate plasma ADV exposure in all three age groups . Conclusion : ADV showed significant antiviral efficacy in subjects aged 12 to 17 years with HBeAg+ CHB , but was not different from placebo in subjects aged 2 to 11 years . ( HEPATOLOGY 2008 . One year of lamivudine treatment results in increased hepatitis B e antigen ( HBeAg ) seroconversion and serum hepatitis B virus ( HBV ) DNA negativity in children with chronic hepatitis B and high serum alanine aminotransferase concentrations . Two hundred seventy-six children who participated in a 1-year r and omized , placebo-controlled study of lamivudine  were enrolled in a 24-month , open-label extension . Patients were stratified into two groups based on HBeAg status at week 48 of the previous study : 213 HBeAg-positive children were entered into a treatment arm , and 63 HBeAg-negative children were entered into an observation arm to evaluate durability of HBeAg loss . In the treatment arm , 28 of 133 ( 21 % ) children previously treated with lamivudine and 23 of 77 ( 30 % ) children who previously received placebo achieved the primary end point : virological response ( VR ) ( HBeAg loss and HBV DNA negativity ) at month 24 . The incidence of YMDD ( tyrosine , methionine , aspartate , aspartate ) mutations at month 24 was 64 % ( 66/103 ) in the children previously treated with lamivudine and 49 % ( 34/70 ) in those previously treated with placebo . The incidence of VR at month 24 was 5 % ( 5/100 ) for patients with YMDD mutant HBV and 54 % ( 39/72 ) for patients without . The durability of response in the observation arm was 89 % ( 48/54 ) at month 24 . In conclusion , further clinical response was seen over the 24-month open-label study period in children who had not initially achieved a VR after 12 months of lamivudine treatment . However , the incidence of YMMD mutations increased over time and result ed in lower response rates . VR was maintained in most patients who had initially responded to lamivudine in the first 12 months BACKGROUND & AIMS Treatment of chronic hepatitis B with interferon alfa is not approved in children . The aim of this study was to evaluate the safety and efficacy of interferon alfa ( IFN-alpha ) in children with chronic hepatitis B and increased transaminase levels . METHODS Children were given either IFN-alpha2b ( 6 megaunits/m2 thrice weekly for 24 weeks ) or no treatment . Clearance of markers of viral replication was evaluated 24 weeks after therapy and after 48 weeks of observation in controls . RESULTS Of 149 children enrolled , 144 were evaluable ( 70 treated and 74 controls ) .  Serum hepatitis B e antigen and viral DNA became negative in 26 % of treated children and 11 % of controls ( P < 0.05 ) . Serum aminotransferase levels normalized and liver histology improved among responders . Hepatitis B surface antigen became undetectable in 10 % of treated patients and 1 % of controls . Female gender and interferon treatment were the only significant predictors of response . Ethnic origin , baseline aminotransferase level , initial DNA levels , and histology did not correlate with response . Most adverse reactions were mild or moderate , and dose was reduced in 24 % of children . CONCLUSIONS In children with chronic hepatitis B , INF-alpha promotes loss of viral replication markers and surface antigen and improves aminotransferases and histology The comparative efficacy of prednisolone followed by interferon alfa ( IFN-alpha ) versus IFN-alpha alone in enhancing the rate of antibody to hepatitis B e antigen ( anti-HBe ) seroconversion has not been evaluated in a large cohort of white children . To determine this , a multicenter-controlled trial was conducted in 95 hepatitis B virus (HBV)-DNA/hepatitis B e antigen (HBeAg)-positive children ( median age , 9 years [ range , 2 - 16 years ] ; 56 boys ; 84 [ 89 percent ] white ) , all having inflammatory changes on liver biopsy . Patients were r and omized to receive either prednisolone followed by IFN-alpha ( n = 34 ) ; placebo followed by IFN-alpha ( n = 30 ) ; or no treatment ( n = 31 ) . The prednisolone/placebo was given on a double-blind basis . Lymphoblastoid IFN-alpha was given at 5 MU/m(2 ) three times a week for 12 weeks . Baseline clinical , biochemical , and histological features were similar for the three groups . The majority ( 85 percent ) had a baseline aspartate aminotransferase ( AST ) level < or = 100 IU/L. On follow-up between 12 and 18 months ( median , 15 months ) after treatment , the loss of HBeAg with anti-HBe seroconversion was more common in patients pretreated with steroids ( 12 of 34 [ 35 percent ] ) or placebo [ 12 of 30 ( 40 percent ) ] as against controls ( 4 of 31 [ 13 percent ] , P < .05 ) . Factors predictive of anti-HBe seroconversion were baseline HBV-DNA concentration of < or = 1,000 pg/mL and a greater degree of portal tract inflammation on pretrial biopsy . Our results show that in white children treatment with IFN-alpha , at the dose and duration used in this study , improves the rate of anti-HBe seroconversion . Steroid priming does not potentiate the effect of IFN-alpha We assessed the efficacy of prolonged interferon-alpha ( IFN ) therapy in children with chronic hepatitis caused by hepatitis delta virus ( HDV ) by treating 26 paediatric cases with IFN-alpha 2b ( 5 MU m-2 , then 3 MU m-2 three times weekly for 12 ( medium-term group MTG ) or 24 months ( long-term group , LTG ) .  Compliance and tolerability were acceptable . At the end of therapy a complete biochemical response [ normalization of alanine aminotransferase ( ALT ) ] occurred in 12 children ( 5/13 in MTG and 7/13 in LTG ) . A relapse occurred after stopping IFN in 10 cases ( five in MTG and five in LTG ) . Two patients from the LTG had normal liver function tests during 12 months of follow-up . Six of the eight hepatitis B e antigen ( HBeAg ) positive children lost HBeAg , while all six hepatitis B virus ( HBV ) DNA positive patients lost HBV DNA 
    Output:
    
Conclusion The results of reported studies confirmed that at least some of the new drugs , with greater efficacy and /or minor side-effects , will be used clinical ly