***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 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 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 651 patients , 436 were assigned to receive lamivudine and 215 to receive placebo .  The primary end point was time to disease progression , defined by hepatic decompensation , hepatocellular carcinoma , spontaneous bacterial peritonitis , bleeding gastroesophageal varices , or death related to liver disease . An independent data and safety monitoring board monitored the progress of the study and performed interim analyses of the data . RESULTS We r and omly assigned 651 patients ( 98 percent Asian and 85 percent male ) to receive lamivudine or placebo . The study was terminated after a median duration of treatment of 32.4 months ( range , 0 to 42 ) owing to a significant difference between treatment groups in the number of end points reached . End points were reached by 7.8 percent of the patients receiving lamivudine and 17.7 percent of those receiving placebo ( hazard ratio for disease progression , 0.45 ; P=0.001 ) . The Child-Pugh score increased in 3.4 percent of the patients receiving lamivudine and 8.8 percent of those receiving placebo ( hazard ratio , 0.45 ; P=0.02 ) , whereas hepatocellular carcinoma occurred in 3.9 percent of those in the lamivudine group and 7.4 percent of those in the placebo group ( hazard ratio , 0.49 ; P=0.047 ) . Genotypic resistance YMDD mutations developed in 49 percent of the patients treated with lamivudine , and the Child-Pugh score was more likely to increase in patients with these mutations than in the other patients treated with lamivudine ( 7 percent vs. < 1 percent ) . Overall , 12 percent of the patients in the lamivudine group and 18 percent of the patients in the placebo group reported serious adverse events . CONCLUSIONS Continuous treatment with lamivudine delays clinical progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis by significantly reducing the incidence of hepatic decompensation and the risk of hepatocellular carcinoma BACKGROUND Antiviral therapy for hepatitis B virus ( HBV ) infection is frequently prescribed for patients with chronic HBV infection during surveillance for hepatocellular carcinoma ( HCC ) . In patients who subsequently develop HCC , the impact of antiviral therapy on the outcome of HCC remains unclear . AIMS We aim ed to study the impact of antiviral therapy on the survival of patients who developed HCC . METHODS From two prospect i ve surveillance cohorts , the use of antiviral therapy for patients with HCC was retrospectively review ed . We compared the overall survival , liver function and tumour characteristics between patients with and without antiviral therapy during surveillance .  Multivariate analysis was conducted to determine the independent prognostication of antiviral therapy . RESULTS During a median follow-up of 10.1 years of 1429 patients , 148 cases of HCC were diagnosed and followed up for a median of 5.7 years . Twenty-nine patients were given antiviral therapy during surveillance and continued treatment after diagnosis of HCC . The median survival of this group of patients was better than the rest of cohorts ( hazard ratio : 0.472 ; 95 % CI : 0.25 - 0.89 ; P = 0.0191 ) . Use of antiviral therapy  remained an independent prognostic factor after adjustment for demographic factors and tumour staging on multivariate analysis . Exploratory analysis revealed that patients who commenced antiviral therapy during surveillance had lower HBV DNA , lower serum alanine transaminase , better hepatic reserves and higher rate of local treatment at diagnosis of HCC . CONCLUSION This study provides evidence that commencement of antiviral therapy during the surveillance period is associated with improvement in overall survival in HBV-related HCC The long-term usefulness of interferon-alpha ( IFN-alpha ) in chronic hepatitis B remains controversial . To investigate the long-term efficacy of IFN-alpha therapy in chronic hepatitis B , 62 Japanese patients , including 27 patients treated with IFN-alpha ( IFN group ) and 35 patients without antiviral therapy matched by age and sex as controls ( control group ) , were followed up for 2 - 14 years . At entry , the  serum alanine aminotransferase ( ALT ) level in the IFN group was significantly higher than that in the control group ( 238.6+/-250.1 vs. 142.3+/-152.1 IU/l , P < 0.05 ) . The prevalence of genotype C was 89 % , with no difference between the two groups ( 93 vs. 86 % ) . There was no significant difference in the presence of the precore mutation or the dual core promoter mutations between the IFN and control groups ( 37 vs. 46 % , 74 vs. 66 % ) . After long-term follow-up , the rate of sustained HBeAg seroconversion was comparable in the two groups ( 33 vs. 31 % ) . Normalization of serum ALT level was seen in 44 % of the IFN group and 51 % of the control group , with no difference . There was also no difference in the percentage of cases with loss of serum HBV-DNA by PCR assay between the two groups ( 33 vs. 29 % ) . During follow-up , two patients of the control group and three patients of the IFN group developed cirrhosis , and one of the IFN- treated patients progressed to hepatocellular carcinoma . The results of this long-term follow-up study showed that no benefit of IFN-alpha treatment was detectable during long-term follow-up in Japanese patients with chronic hepatitis BACKGROUND Data regarding the outcome of hepatitis B virus (HBV)-related cirrhosis after the onset of decompensation is scanty . METHOD From January 1998 to December 2008 , a retrospective- prospect i ve inception cohort study involving HBV-related decompensated cirrhotics was performed . Predictors of death and clinical events after the onset of decompensation were evaluated . Patients with co-infection with hepatitis C virus and /or human immunodeficiency virus , alcohol consumption to any degree and diabetes diagnosed before the detection of liver disease were excluded . RESULT AND ANALYSIS Two hundred and fifty-three patients ( 231 males , 139 e-negative ) , including 102 untreated patients , were analysed . The mean ( + /-SD ) age was 43.0 ( + /-12.0 ) years . The mean ( + /-SD ) follow-up period was 47 ( + /-47 ) months . Decompensation was the first presentation of liver disease in 210 ( 83 % ) patients . Ascites ( 70 % ) and variceal bleed ( 28 % ) were predominant modes of decompensation . Forty-three ( 17 % ) patients died ( 22 vs 14 % in untreated and treated cohort , respectively ; P=0.002 ) . Type 2 hepato-renal syndrome was the commonest cause of death ( 32 % ) . Survival was independent of e-antigen status . In the total cohorts , predictors of death were occurrence of sepsis 
    Output:
    
Conclusions The effect of antiviral therapy on clinical outcomes in HBV remains to be established .