You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Optimal duration of additional therapy after biochemical and virological responses to lamivudine in patients with HBeAg-negative chronic hepatitis B: a randomized trial.
Abstract 1:
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


Title 2:
Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study
Abstract 2:
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


Title 3:
Treatment cessation of entecavir in Asian patients with hepatitis B e antigen negative chronic hepatitis B: a multicentre prospective study
Abstract 3:
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
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