***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: AIM The endpoint of treatment with nucleoside analogs remains unclear for patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. We report the results of a r and omized trial to determine the optimal duration of additional therapy after response to lamivudine in HBeAg-negative patients . METHODS Twenty-two patients with HBeAg-negative chronic hepatitis B who exhibited biochemical and virological responses to lamivudine were enrolled . When patients responded to treatment , they were r and omly assigned to receive 12 more months of therapy ( Group A , 11 patients ) or 24 more months of therapy ( Group B , 11 patients ) . RESULTS The baseline characteristics of the patients were similar in the two groups . Biochemical and virological responses were obtained in all patients within 6 months . Drug resistance developed in one patient in Group A during month 7 of additional therapy , and in five patients in Group B from months 13 - 23 of additional therapy . Ten patients in Group A and six in Group B completed the protocol and were included in analysis . Eight of the 10 patients in Group A experienced relapse between months 2 and 14 after the discontinuation of therapy , while three of the six patients in Group B experienced relapse between months 2 and 24 . There was no difference in cumulative relapse rate between the groups ( P = 0.275 ) . CONCLUSION Additional therapy with lamivudine for longer than 12 months after biochemical and virological responses in patients with HBeAg-negative chronic hepatitis B could increase the risk of drug resistance , but did not reduce the rate of relapse BACKGROUND Whether long-term suppression of replication of hepatitis B virus ( HBV ) has any beneficial effect on regression of  advanced liver fibrosis associated with chronic HBV infection remains unclear . We aim ed to assess the effects on fibrosis and cirrhosis of at least 5 years ' treatment with tenofovir disoproxil fumarate ( DF ) in chronic HBV infection . METHODS After 48 weeks of r and omised double-blind comparison ( trials NCT00117676 and NCT00116805 ) of tenofovir DF with adefovir dipivoxil , participants ( positive or negative for HBeAg ) were eligible to enter a 7-year study of open-label tenofovir DF treatment , with a pre-specified repeat liver biopsy at week 240 . We assessed histological improvement ( ≥2 point reduction in Knodell necroinflammatory score with no worsening of fibrosis ) and regression of fibrosis ( ≥1 unit decrease by Ishak scoring system ) . FINDINGS Of 641 patients who received r and omised treatment , 585 ( 91 % ) entered the open-label phase , and 489 ( 76 % ) completed 240 weeks . 348 patients ( 54 % ) had biopsy results at both baseline and week 240 . 304 ( 87 % ) of the 348 had histological improvement , and 176 ( 51 % ) had regression of fibrosis at week 240 ( p<0·0001 ) . Of the 96 ( 28 % ) patients with cirrhosis ( Ishak score 5 or 6 ) at baseline , 71 ( 74 % ) no longer had cirrhosis ( ≥1 unit decrease in score ) , whereas three of 252 patients without cirrhosis at baseline progressed to cirrhosis at year 5 ( p<0·0001 ) . Virological breakthrough occurred infrequently and was not due to resistance to tenofovir DF . The safety profile was favourable : 91 ( 16 % ) patients had adverse events but only nine patients had serious events related to the study drug . INTERPRETATION In patients with chronic HBV infection , up to 5 years of treatment with tenofovir DF  was safe and effective . Long-term suppression of HBV can lead to regression of fibrosis and cirrhosis . FUNDING Gilead Sciences Background and objective The off-treatment durability of nucleos(t)ide analogue therapy in Asian hepatitis B e antigen ( HBeAg ) negative chronic hepatitis B ( CHB ) and the role of hepatitis B surface antigen ( HBsAg ) levels in predicting off-treatment durability has not been well investigated . Methods Following Asia-Pacific Association for the Study of the Liver guidelines , entecavir was stopped in Asian HBeAg negative patients treated for ≥2 years with undetectable HBV DNA levels on ≥3 separate occasions 6 months apart before treatment cessation .  HBsAg and HBV DNA levels were prospect ively monitored every 6–12 weeks for 48 weeks . Entecavir was restarted if there was virologic relapse ( defined as HBV DNA > 2000 IU/mL ) . Result 184 patients ( mean age 53.9 years , 67.9 % male ) were recruited . The cumulative rate of virologic relapse at 24 and 48 weeks was 74.2 % and 91.4 % , respectively . The median HBV DNA level at virologic relapse was 11 000 ( range 2115 to > 1.98 × 108 ) IU/mL. 42 ( 25.8 % ) patients had elevated alanine aminotransferase ( median level 97 U/L , range 37–1058 U/L ) during virologic relapse . Mean rate of off-treatment HBsAg decline was 0.018 ( ±0.456 ) log IU/mL/year . No patients cleared HBsAg . There was no correlation between off-treatment serial HBsAg and HBV DNA levels ( r=−0.026 , p=0.541 ) . HBsAg levels at the time of entecavir commencement , entecavir cessation and the subsequent rate of HBsAg reduction were not associated with virologic relapse ( all p>0.05 ) . Conclusions Entecavir cessation in Asian HBeAg negative CHB result ed in high rates of virologic relapse , suggesting nucleos(t)ide analogue therapy should be continued indefinitely until the recognised treatment endpoint of HBsAg seroclearance 
    Output:
    
CONCLUSION Durable VR seems to be feasible in a substantial proportion of patients who discontinue long-term NA therapy ; on-therapy VR > 24 months offers higher chances of off-NA VR in patients with HBeAg-negative chronic hepatitis