***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 Activation of hepatic stellate cells is the earliest step in fibrogenesis . Alpha-smooth muscle actin ( alpha-SMA ) , expressed by activated hepatic stellate cells , and C-terminal procollagen alpha1(III ) propeptide ( PIIICP ) are early markers of fibrogenesis and should precede fibrosis . AIM Determine if suppression of hepatitis B virus replication with lamivudine would decrease fibrogenesis as measured by immunohistochemical markers . METHODS Paired liver biopsies from patients with hepatitis B before and after therapy with lamivudine ( n=47 ) or placebo ( n=33 ) were studied . alpha-SMA and PIIICP were detected in paraffin-embedded tissue by immunohistochemistry and quantified in a blinded manner by video imaging analysis . RESULTS Liver biopsies from patients treated with lamivudine showed a significant decrease in alpha-SMA expression ( 1.06+/-0.23 vs. 0.58+/-0.11 , pre vs. post , P<0.05 ) . Placebo recipients had increased levels of alpha-SMA ( 0.82+/-0.14 vs. 1.32+/-0.21 , P<0.05 ) . PIIICP was similarly decreased after lamivudine . Among subjects whose Histologic Activity Index fibrosis score was unchanged or worsened , the mean change in alpha-SMA expression was significantly decreased in the lamivudine group compared with placebo . CONCLUSIONS Lamivudine decreased markers of hepatic stellate cell activation and collagen synthesis . Immunohistochemical techniques are sensitive for assessing fibrogenesis and will be useful in trials of antiviral and antifibrotic agents Short-term interferon treatment of serum hepatitis B e antigen (HBeAg)-negative carriers with serum hepatitis B virus ( HBV ) DNA and histological features of chronic hepatitis B has been largely unsuccessful . In a pilot study of long-term treatment , 42 such patients were r and omly assigned to 6 million units of interferon alfa 2b ( IFN-alpha2b ) three times per week for 24 consecutive months ( n = 21 , 4 with cirrhosis ) or to no therapy ( n = 21 , 3 with cirrhosis ) . Five patients ( 24 % ) discontinued therapy because of treatment-related adverse reactions . Serum levels of alanine transaminase ( ALT ) became persistently normal and HBV DNA undetectable by dot-blot assay in 8 patients receiving interferon and in 2 untreated controls ( 38 % vs. 10 % ; P = .03 ) . Hepatitis flare-ups disappeared in 17 patients during therapy compared with 6 controls ( 81 % vs. 29 % ; P < .001 ) . During a median period of 22 months after interferon was stopped , 2 treated patients ( 10 % ) lost serum hepatitis B surface antigen ( HBsAg ) and seroconverted to antibodies to hepatitis B surface antigen ( anti-HBs ) . Serum ALT remained persistently normal and HBV DNA undetectable by dot-blot assay in 6 initial responders and 1 initial nonresponder , compared with none of the 21 untreated controls ( sustained response : 33 % vs. 0 ; P < .001 ) . Comparative analysis of pre- and posttreatment liver biopsies showed that mean Knodell scores dropped in the treated group ( 10.3 to 5.3 ; P = .01 ) , but not in the untreated group ( 9.3 to 9.8 ; not significant ) . In conclusion , a 24-month course of treatment with 6 MU IFN-alpha2b was well tolerated by most patients , led to sustained suppression of HBV in one third , and attenuated hepatitis in 81 % of patients 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 . ) Current therapies for chronic hepatitis B ( CHB ) have a number of limitations , and better treatment options are needed . Peginterferon alpha-2a ( 40 kDa ) is superior to conventional interferon alpha-2a in the treatment of chronic hepatitis C. This is the first report on peginterferon alpha-2a ( 40 kDa ) in the treatment of CHB . In this phase II study , 194 patients with CHB not previously treated with conventional interferon-alpha were r and omized to receive weekly subcutaneous doses of peginterferon alpha-2a ( 40 kDa ) 90 , 180 or 270 microg , or conventional interferon alpha-2a 4.5 MIU three times weekly . Twenty-four weeks of therapy were followed by 24 weeks of treatment-free follow-up . All subjects were assessed for loss of hepatitis B e antigen ( HBeAg ) , presence of hepatitis B antibody ( anti-HBe ) , suppression of hepatitis B virus ( HBV ) DNA , and normalization of serum alanine transaminase ( ALT ) after follow-up . At the end of follow-up , HBeAg was cleared in 37 , 35 and 29 % of patients receiving peginterferon alpha-2a ( 40 kDa ) 90 , 180 and 270 microg , respectively , compared with 25 % of patients on conventional interferon alpha-2a . The combined response ( HBeAg loss , HBV DNA suppression , and ALT normalization ) of all peginterferon alpha-2a ( 40 kDa ) doses combined was twice that achieved with conventional interferon alpha-2a ( 24%vs 12 % ; P = 0.036 ) . All treatment groups were similar with respect to frequency and severity of adverse events . These results indicate that peginterferon alpha-2a ( 40 kDa ) is superior in efficacy to conventional interferon alpha-2a in chronic hepatitis B based on clearance of HBeAg , suppression of HBV DNA , and normalization of ALT UNLABELLED BACKGROUND , AIM , AND METHODS : Alpha interferon is the generally approved therapy for HBe antigen positive patients with chronic hepatitis B , but its efficacy is limited . Lamivudine is a new oral nucleoside analogue which potently inhibits hepatitis B virus ( HBV ) DNA replication . To investigate the possibility of an additive effect of interferon-lamivudine combination therapy compared with interferon or lamivudine monotherapy , we conducted a r and omised controlled trial in 230 predominantly Caucasian patients with hepatitis B e antigen ( HBeAg ) and HBV DNA positive chronic hepatitis B. Previously untreated patients were r and omised to receive : combination therapy of lamivudine 100 mg daily with alpha interferon 10 million units three times weekly for 16 weeks after pretreatment with lamivudine for eight weeks ( n=75 ) ; alpha interferon 10 million units three times weekly for 16 weeks ( n=69 ) ; or lamivudine 100 mg daily for 52 weeks ( n=82 ) . The primary efficacy end point was the HBeAg seroconversion rate at week 52 ( loss of HBeAg , development of antibodies to HBeAg and undetectable HBV DNA ) . RESULTS The HBeAg seroconversion rate at week 52 was 29 % for the combination therapy , 19 % for interferon monotherapy , and 18 % for lamivudine monotherapy ( p=0.12 and p=0.10 , respectively , for comparison of the combination therapy with interferon or lamivudine monotherapy ) . The HBeAg seroconversion rates at week 52 for the combination therapy and lamivudine monotherapy were significantly different in the per protocol analysis ( 36 % ( 20/56 ) v 19 % ( 13/70 ) , respectively ; p=0.02 ) . The effect of combining lamivudine and interferon appeared to be most useful in patients with moderately elevated alanine aminotransferase levels at baseline .  Adverse events with the combination therapy were similar to interferon monotherapy ; patients receiving lamivudine monotherapy had significantly fewer adverse events . CONCLUSIONS HBeAg seroconversion rates at one year were similar for lamivudine monotherapy ( 52 weeks ) and st and ard alpha interferon therapy ( 16 weeks ) . The combination of lamivudine and interferon appeared to increase the HBeAg seroconversion rate , particularly in patients with moderately elevated baseline aminotransferase levels . The potential benefit of combining lamivudine and interferon should be investigated further in studies with different regimens of combination therapy Background : Long‐term effect of YMDD mutations on liver histology in Chinese hepatitis B patients is unknown The aim of the study was to evaluate the safety and effectiveness of interferon alfa-2b , alone and following prednisone withdrawal , in patients with chronic type B hepatitis . Thirty-five patients ( 27 men and eight women ) were r and omly allocated to two treatment groups . Group I ( n = 17 ) received 6 weeks of prednisone followed by interferon alfa-2b ( INTRON A , Schering-Plough Corporation ) 10 million units subcutaneously , three times a week for 16 weeks . Group II ( n = 18 ) was used as an untreated control group for 24 weeks , after which they received 16 weeks of treatment with the same dose of interferon as Group I. Both groups were followed up for 24 weeks after treatment . In Group I , 10/17 patients ( 58.8 % ) eliminated hepatitis B e antigen ; 8/17 ( 47.1 % ) developed antibodies to hepatitis B e antigen ; 9/17 ( 52.9 % ) became hepatitis B virus DNA negative and 1/17 ( 5.9 % ) was hepatitis B surface antigen negative at the end of follow up . In Group II , during the control phase , 1/18 ( 5.5 % ) became hepatitis B e antigen negative . When treated with interferon , 7/15 ( 46.7 % ) eliminated the e antigen , and 6/15 ( 40 % ) developed antibodies to hepatitis B e antigen and were hepatitis B virus DNA negative at the end of follow up . Serum alanine aminotransferase reached normal levels in all seroconverted patients . Liver biopsies showed a marked reduction of inflammation and disappearance of hepatitis B core antigen in liver cell nuclei in almost all cases . ( ABSTRACT TRUNCATED AT 250 WORDS A r and omized controlled trial of recombinant interferon alfa-2b has been initiated in patients with chronic active hepatitis who were negative for serum hepatitis B e antigen but positive for serum hepatitis B virus DNA and hepatitis B core antigen expression in the liver . Twenty-five patients received interferon alfa-2b 3 million units thrice weekly for 14 - 16 weeks and 25 served as untreated controls . Seventeen patients in the treatment and 18 in the control group have already completed a 12-month period of observation . Interferon alfa-2b was well toler 
    Output:
    
RESULTS Despite sustained improvements in selected biomarkers , no one drug regimen improved all intermediate outcomes .
Adverse events were common and more frequent after interferon .