***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 aim of this study was to evaluate the long-term sustainability of response in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B treated with pegylated interferon ( PEG-IFN ) alpha-2b alone or in combination with lamivudine .  METHODS All 266 patients enrolled in the HBV99 - 01 study were offered participation in a long-term follow-up ( LTFU ) study . Patients were treated with PEG-IFN alpha-2b ( 100 mug/wk ) alone or in combination with lamivudine ( 100 mg/day ) for 52 weeks . Initial response was defined as HBeAg negativity at 26 weeks posttreatment . For the LTFU study , patients had one additional visit after the initial study ( mean interval , 3.0 + /- 0.8 years ) . RESULTS Of 266 patients enrolled in the initial study , 172 ( 65 % ) participated in the LTFU study . At LTFU , HBeAg and hepatitis B surface antigen ( HBsAg ) negativity were observed in 37 % and 11 % of 172 patients , respectively . Sixty-four patients were classified as initial responders and 108 as nonresponders . Among the initial responders , sustained HBeAg negativity and HBsAg loss were observed in 81 % and 30 % , respectively . Significantly higher rates of HBeAg negativity were observed in genotype A-infected initial responders compared with those with genotype non-A ( 96 % vs 76 % ; P = .06 ) as well as HBsAg loss ( 58 % vs 11 % ; P < .001 ) . CONCLUSIONS HBeAg loss after treatment with PEG-IFN alpha-2b alone or in combination with lamivudine is sustained in the majority of patients and is associated with a high likelihood of HBsAg loss , particularly in genotype A-infected patients . Therefore , PEG-IFN alpha-2b remains an important treatment option in this era of nucleos(t)ide analogue therapy 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 Treatment of HBeAg-positive patients with chronic hepatitis B is not effective in most . A combination of immunomodulatory pegylated interferon alfa-2b and antiviral lamivudine might improve the rate of sustained response . METHODS 307 HBeAg-positive patients with chronic hepatitis B were assigned combination therapy ( 100 microg/week pegylated interferon alfa-2b and 100 mg/day lamivudine ) or monotherapy ( 100 microg/week pegylated interferon alfa-2b and placebo ) for 52 weeks . During weeks 32 - 52 the pegylated interferon dose was 50 microg/week in both treatment groups . The analyses were based on the modified intention-to-treat population after exclusion of 24 patients from one centre withdrawn for misconduct , ten who lost HBeAg before the study start , and seven who received no study medication . All included patients were followed up for 26 weeks after treatment . FINDINGS 49 ( 36 % ) of 136 patients assigned monotherapy and 46 ( 35 % ) of 130 assigned combination therapy had lost HBeAg at the end of follow-up ( p=0.91 ) . More of the combination-therapy than of the monotherapy group had cleared HBeAg at the end of treatment ( 57 [ 44 % ] vs 40 [ 29 % ] ; p=0.01 ) but relapsed during follow-up . Patterns were similar when response was assessed by suppression of serum hepatitis B virus ( HBV ) DNA or change in concentrations of alanine aminotransferase . Response rates ( HBeAg loss ) varied by HBV genotype ( p=0.01 ) : A , 42 ( 47 % ) patients ; B , ten ( 44 % ) ; C , 11 ( 28 % ) ; and D , 26 ( 25 % ) . INTERPRETATION Treatment with pegylated interferon alfa-2b is effective for HBeAg-positive chronic hepatitis B. Combination with lamivudine in the regimen used is not superior to monotherapy . HBV genotype is an important predictor of response to treatment This retrospective analysis was conducted to describe the characteristics of  nucleoside-naïve hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B , who achieved hepatitis B surface antigen ( HBsAg ) loss during entecavir or lamivudine therapy . HBeAg-positive adults with chronic hepatitis B , elevated serum alanine aminotransferase , and compensated liver disease were r and omized to double-blind treatment for up to 96 weeks with entecavir 0.5 mg/day or lamivudine 100 mg/day . HBsAg and hepatitis B virus ( HBV ) DNA were measured at regular intervals during and off-treatment follow-up . Through a maximum duration of 96 weeks on-treatment and 24 weeks off-treatment , HBsAg loss was confirmed in 18/354 ( 5.1 % ) patients treated with entecavir and 10/355 ( 2.8 % ) patients treated with lamivudine . Among the 28 patients with confirmed HBsAg loss  , 27 ( 96 % ) achieved HBV DNA < 300 copies/mL , and 27 ( 96 % ) achieved confirmed HBeAg loss . All entecavir recipients with HBsAg loss had HBV DNA < 300 copies/mL. Caucasian patients , and those infected with HBV genotype A or D , were significantly more likely to lose HBsAg . This retrospective analysis of data from a r and omized , global phase three trial shows that confirmed loss of HBsAg occurred in 5 % of nucleoside-naïve HBeAg-positive patients treated with entecavir , and that HBsAg loss is associated with sustained off-treatment suppression of HBV DNA BACKGROUND There is increasing evidence that host immune responses influence antiviral efficacy in chronic hepatitis B ( CHB ) . The aim of this study was to characterize the immunological features responsible for improved treatment responses with pegylated interferon (PEG-IFN)-α2a in  entecavir (ETV)-suppressed patients with CHB . METHODS Peripheral natural killer ( NK ) cells , Toll-like receptors ( TLRs ) , T-cell subsets , regulatory T-cells ( Tregs ) and programmed death 1 ( PD-1 ) were evaluated dynamically in 77 patients undergoing a clinical trial ( OSST trial , NCT00940485 ) by flow cytometry  . Response was defined as hepatitis B e antigen ( HBeAg ) seroconversion , hepatitis B surface antigen ( HBsAg ) loss and HBsAg seroconversion ( either as singular events or in combination at week 48 ) . RESULTS Compared with ETV responders or PEG-IFN-α non-responders , PEG-IFN-α responders exhibited a significant decline in HBsAg during treatment ( P=0.033 and P<0.001 , respectively ) and a significant decline in Treg proportions from week 12 to week 24 ( P=0.036 and P=0.004 , respectively ) . Moreover , PEG-IFN-α responders showed a significantly higher increase in the NKG2C(+ ) NK cell proportions from baseline to week 12 ( P=0.0073 ) and of TLR2(+ ) monocytes at week 12 than PEG-IFN-α non-responders ( P=0.039 ) . CONCLUSIONS Successful response to PEG-IFN-α correlates with an early significant restoration of impaired immune responses . Although antiviral treatment response can be achieved by both IFN and ETV , the underlying immunological features vary which may explain the generally observed difference in off-treatment durability of response between the two treatments , as well as effects on HBsAg Summary Currently available monotherapies of oral nucleoside/nucleotide analogs or interferon are unable to achieve a sustained and effective response in most of patients with chronic hepatitis B ( CHB ) . The objective of the present study was to compare the efficacy and safety of pegylated interferon ( Peg-IFN ) alpha-2b plus adefovir dipivoxil combination therapy versus Peg-IFN alpha-2b alone .  Sixty-one HBeAg-positive chronic hepatitis B patients were r and omized to receive Peg-IFN alpha-2b alone ( 1.5 μg/kg once weekly ) or Peg-IFN alpha-2b plus adefovir ( 10 mg daily ) for up to 52 weeks . Efficacy and safety analyses were performed on all participants who received at least one dose of study medication . The rate of HBeAg seroconversion and undetectable HBV-DNA were evaluated after 52 weeks of therapy . At the end of treatment , 11 of 30 ( 36.7 % ) patients receiving combination therapy achieved HBeAg seroconversion versus 8 of 31 ( 25.8 % ) in the monotherapy group ( P=0.36 ) . In contrast , the percentage of patients with undetectable serum HBV DNA was significantly higher in the combination group than in the monotherapy group ( 76.7 % vs. 29.0 % , P<0.001 ) . Thyroid dysfunction was more frequent in the combination group than in the monotherapy group ( P<0.05 ) . In HBeAg-positive CHB , combination of Peg-IFN alpha-2b and adefovir for 52 weeks result ed , at the end of treatment , in a higher virological response but without significant impact on the rate of HBeAg seroconversion and possibly an adverse effect on thyroid function 
    Output:
    
The combination between PEG-IFNα and LAM or ADV was not superior to monotherapy of PEG-IFNα in terms of HBsAg seroclearance or seroconversion