***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 Entecavir is a potent and selective guanosine analogue with significant activity against hepatitis B virus ( HBV ) . METHODS In this phase 3 , double-blind trial , we r and omly assigned 715 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who had not previously received a nucleoside analogue  to receive either 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks . The primary efficacy end point was histologic improvement ( a decrease by at least two points in the Knodell necroinflammatory score , without worsening of fibrosis ) at week 48 . Secondary end points included a reduction in the serum HBV DNA level , HBeAg loss and seroconversion , and normalization of the alanine aminotransferase level . RESULTS Histologic improvement after 48 weeks occurred in 226 of 314 patients in the entecavir group ( 72 percent ) and 195 of 314 patients in the lamivudine group ( 62 percent , P=0.009 ) . More patients in the entecavir group than in the lamivudine group had undetectable serum HBV DNA levels according to a polymerase-chain-reaction assay ( 67 percent vs. 36 percent , P<0.001 ) and normalization of alanine aminotransferase levels ( 68 percent vs. 60 percent , P=0.02 ) . The mean reduction in serum HBV DNA from baseline to week 48 was greater with entecavir than with lamivudine ( 6.9 vs. 5.4 log [ on a base-10 scale ] copies per milliliter , P<0.001 ) . HBeAg seroconversion occurred in 21 percent of entecavir-treated patients and 18 percent of those treated with lamivudine ( P=0.33 ) . No viral resistance to entecavir was detected . Safety was similar in the two groups . CONCLUSIONS Among patients with HBeAg-positive chronic hepatitis B , the rates of histologic , virologic , and biochemical improvement are significantly higher with entecavir than with lamivudine . The safety profile of the two agents is similar , and there is no evidence of viral resistance to entecavir . ( Clinical Trials.gov number , NCT00035633 . ) BACKGROUND & AIMS The study objective was to determine the risk of all-cause and cause-specific mortality as well as to examine the predictors of mortality in chronic hepatitis B infection . METHODS We performed a prospect i ve cohort study of 23,820 persons ( age , 30 - 65 y ) recruited between 1991 and 1992 and followed up through 2004 from 7 townships in Taiwan . The main outcomes were all-cause and liver-related mortality rates . Mortality analyses used time-to-events methods , and survival curves were derived by the Kaplan-Meier method . Cox proportional hazard models were used to estimate multivariable-adjusted hazard ratios . RESULTS There were 1814 deaths during a mean follow-up period of 12.5 years ( 282,323.7 person-years of follow-up evaluation ) . Persons positive for hepatitis B surface antigen ( HBsAg ) had significantly ( P < .01 ) higher adjusted hazard ratios for all causes of mortality ( 1.7 ; 95 % confidence interval [ CI ] , 1.5 - 1.9 ) , liver cancer mortality ( 22.4 ; 95 % CI , 15.2 - 32.9 ) , and chronic liver disease and cirrhosis mortality ( 5.4 ; 95 % CI , 3.5 - 8.4 ) . When compared with HBsAg-negative persons , hepatitis B virus (HBV)-infected persons with HBV DNA levels less than 10(4 ) had a high risk of hepatocellular carcinoma mortality ( 4.4 ; 95 % CI , 2.4 - 8.2 ) . In HBsAg-positive persons , the mortality rate increased with cohort entry serum HBV DNA level . Liver cancer mortality ranged from 72.8 per 100,000 person-years for subjects with HBV DNA levels less than 300 copies/mL to 815.6 per 100,000 person-years for those with HBV DNA levels of 1 million copies/mL or greater . Chronic liver disease and cirrhosis deaths ranged from 9.1 to 267.4 per 100,000 person-years . CONCLUSIONS Chronic HBV infection is associated with significant preventable excess mortality risk . This mortality risk is correlated strongly with the level of viral replication among other factors Background Patients with chronic hepatitis B virus ( HBV ) infection are at risk for death from complications of liver disease and development of hepatocellular carcinoma ( HCC ) . To identify the time course and risk factors associated with these events , we conducted a prospect i ve study in chronic hepatitis B patients referred to our clinic . Methods From January 1989 to March 1998 , 400 hepatitis B surface antigen (HBsAg)-positive patients were classified into three categories : inactive carriers ( N=110 ) , chronic hepatitis ( N=151 ) , and cirrhosis ( N=139 ) . These patients were observed at 3- to 6-month intervals with liver tests , alpha-fetoprotein ( AFP ) levels , and ultrasound examinations . The study endpoints were death from liver disease complications and development of HCC . Results The patients were followed for a mean time ( ± SD ) of 83.6 ± 39.6 months . During this period , no liver-related deaths or HCC were noted in inactive carriers . However , 38 of 139 ( 27.3 % ) patients with cirrhosis died from non-HCC-related liver complications . Multivariate analysis demonstrated that male sex ( odds ratio [ OR ] 5.9 ; 95 % confidence interval [ CI ] , 2.0 - 22.6 ; P=.003 ) , decreased initial serum albumin ( OR 69.1 ; 95 % CI , 11.5 - 486.4 ; P=.0009 ) , low platelet count ( OR 8.8 ; 95 % CI , 0.96 - 92.9 ; P=.05 ) , and presence of cirrhosis ( OR 14.2 ; 95 % CI , 3.4 - 111.8 ; P=.0009 ) were independently associated with increased mortality from chronic hepatitis B. During the same time period , nine of 151 ( 6.0 % ) chronic hepatitis patients and 22 of 139 ( 15.8 % ) patients with cirrhosis developed HCC . By multivariate analysis , progression to HCC was associated with advanced age ( OR 19.7 ; 95 % CI , 1.9 - 231.9 ; P=.01 ) and presence of cirrhosis ( OR 3.6 ; 95 % CI , 1.6 - 8.9 ; P=.003 ) . Patients positive for hepatitis B early antigen ( HBeAg ) and HBeAg antibodies experienced liver-related deaths and developed HCC at similar rates . Conclusions This prospect i ve study from the United States confirms previous observations of the high risk of mortality and development of HCC in patients infected with HBV . To decrease the risk of these complications , antiviral therapy should be initiated early in the course of the disease . In addition , surveillance for HCC must be performed at least every 6 months in patients with chronic hepatitis and cirrhosis Thirty male patients ( 27 homosexual ) with biopsy proven chronic active hepatitis B were r and omised to receive lymphoblastoid interferon ( Wellferon ) or no treatment .  All patients were HBeAg positive and had continuing viral replication . Patients receiving treatment were given a single daily intramuscular injection of interferon for 28 days at a starting dose of 2.5 MU/m2 increasing to a maximum of 7.5 MU/m2/day . Transient side effects of malaise and influenza like symptoms occurred in all patients and resolved rapidly after treatment . Hepatitis B viral replication was suppressed during interferon treatment in all patients but the effect was limited to the period of therapy . After one year there was no appreciable difference in viral markers between the two groups of patients and this treatment schedule appears less effective than the thrice weekly , three month regimes recently reported from other centres BACKGROUND Entecavir is a potent and selective antiviral agent that has demonstrated efficacy in phase 2 studies in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. METHODS In this phase 3 , double-blind trial , we r and omly assigned 648 patients with HBeAg-negative chronic hepatitis B who had not previously been treated with a nucleoside analogue to receive 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks . The primary efficacy end point was histologic improvement ( a decrease by at least two points in the Knodell necroinflammatory score , without worsening of fibrosis ) . RESULTS Histologic improvement after 48 weeks of treatment occurred in 208 of 296 patients in the entecavir group who had adequate baseline liver-biopsy specimens that could be evaluated ( 70 percent ) , as compared with 174 of 287 such patients in the lamivudine group ( 61 percent , P=0.01 ) . More patients in the entecavir group than in the lamivudine group had undetectable serum hepatitis B virus ( HBV ) DNA levels according to a polymerase-chain-reaction assay ( 90 percent vs. 72 percent , P<0.001 ) and normalization of alanine aminotransferase levels ( 78 percent vs. 71 percent , P=0.045 ) . The mean reduction in serum HBV DNA levels from baseline to week 48 was greater with entecavir than with lamivudine ( 5.0 vs. 4.5 log [ on a base-10 scale ] copies per milliliter , P<0.001 ) . There was no evidence of resistance to entecavir . Safety and adverse-event profiles were similar in the two groups . CONCLUSIONS Among patients with HBeAg-negative chronic hepatitis B who had not previously been treated with a nucleoside analogue , the rates of histologic improvement , virologic response , and normalization of alanine aminotransferase levels were significantly higher at 48 weeks with entecavir than with lamivudine . The safety profile of the two agents was similar , and there was no evidence of viral resistance to entecavir . ( Clinical Trials.gov number , NCT00035789 . ) BACKGROUND Long-term effects of lamivudine treatment on chronic hepatitis B patients without advanced disease remain unknown . Our aim was to investigate the effects of long-term lamivudine treatment and lamivudine-resistant virus ( YMDD ) on the development of cirrhosis and hepatocellular carcinoma ( HCC ) in asymptomatic patients without advanced disease . METHODS One hundred and forty-two hepatitis B e antigen (HBeAg)-positive patients ( median age : 33.9 years ) on long-term lamivudine ( median treatment duration : 89.9 months ) and 124 HBeAg-positive controls ( median age : 33.4 years ) were prospect ively followed up . Patients were monitored for the development of cirrhosis and HCC , liver biochemistry , hepatitis B virus ( HBV ) DNA levels , HBeAg seroconversion and hepatitis flares . YMDD mutations ( YMDD-MT ) were determined annually . RESULTS Lamivudine-treated patients had a significantly lower cumulative rate of development of cirrhosis and /or HCC compared with controls ( P = 0.005 ) . YMDD-MT occurred in 76.3 % of patients after 8 years of lamivudine treatment . When compared with controls and patients with YMDD-MT , patients without YMDD-MT had the greatest reduction of HBV DNA and bilirubin levels , slowest decline of albumin level , highest rate of HBeAg seroconversion and lowest risk of hepatitis flare . Patients with YMDD-MT still had a lower risk for developing cirrhosis and /or HCC ( P = 0.024 ) and a greater HBV DNA reduction ( P = 0.001 ) in comparison with controls . Patients with YMDD-MT and controls had a similar chance of hepatitis flares and hepatic decompensation . CONCLUSIONS Long-term lamivudine treatment was associated with a reduced chance of developing cirrhosis and HCC in patients without advanced disease . Although YMDD-MT reduced the benefits from lamivudine therapy , the outcome of these patients was still better than untreated patients BACKGROUND The effectiveness of antiviral therapy in preventing disease progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis is unknown . METHODS Patients with chronic hepatitis B who had histologically confirmed cirrhosis or advanced fibrosis were r and omly assigned in a 2:1 ratio to receive lamivudine ( 100 mg per day ) or placebo for a maximum of five years . Of 65 
    Output:
    
Moderate- quality evidence supported the effectiveness of antiviral therapy in patients with immune active chronic HBV infection in reducing the risk of cirrhosis , decompensated liver disease , and hepatocellular carcinoma .
In immune tolerant patients , moderate- quality evidence supports improved intermediate outcomes  with antiviral therapy .
Only very low- quality evidence informed the questions about discontinuing versus continuing antiviral therapy in hepatitis B e antigen-positive patients who seroconverted from hepatitis B e antigen to hepatitis B e antibody and about the safety  of entecavir versus tenofovir .
Noncomparative and indirect evidence was available for questions about stopping versus continuing antiviral therapy  in hepatitis B e antigen-negative patients , monotherapy versus adding a second agent in patients with persistent viremia during treatment , and the effectiveness of antivirals in compensated cirrhosis with low-level viremia .