Park, Moon Young Kim, Soon Koo Baik, Yun Soo Kim, Ju Hyun Kim, Jung Il Lee, Jin-Woo Lee, Sun P. Hong, Soon Ho Um INTRODUCTION:Chronic hepatitis B (CHB) infection is a common cause of hepatocellular carcinoma (HCC).Nucleos(t)ide analogues (NA) are effective in suppressing viral replication and decreasing the inflammatory response in the liver,but their effect on progression to HCC is unclear.This study examines the factors affecting development of HCC in patients receiving long-term NA therapy.

METHODS:CHB patients,who received at least 12 months of NA therapy,were enrolled in the study.The patients who diagnosed with HCC before they have completed the first 12 selleck months of treatment were excluded.Clinical and biochemical findings, stage of fibrosis and type of NA treatment were recorded .The patients were screened for HCC at every 6 months by USG and AFP. A drug with a higher genetic barrier against resistance was added or switched,if HBVDNA negativity could not be achieved or genotypic resistance/virological breakthrough developed during treatment. Lamivudine and adefovir were accepted to be low genetic barrier drugs,while entecavir and tenofovir click here were defined

as high genetic barrier drugs. RESULTS:661 patients with genotype D CHB infection (71% male,mean age 50±12 years,71% HBeAg (-) ) were enrolled in the study.66% of patients were pre-cirrhotic, while 34% were cirrhotic.The median duration of NA treatment was 48 months (1 2 – 1 94 months). HCC developed in a total of 57 (8.6%) patients.The cumulative incidence of HCC was significantly higher Tolmetin in patients with cirrhosis than in those without (p<0.001).Also it tended to be higher in patients with decom-pensated cirrhosis compared to those with compensated cirrhosis.Cumulative HCC incidence in cirrhotic and CHB patients were 2.3% vs.0.2% at 1st year, 8.3% vs.0.5

% at 2nd year, 14.8% vs. 1.4% 3rd year and 22.9% vs.2.6% at 5th year, respectively (log-rank,p<0.001 ).The median time for HCC development during NA treatment was 36 months.In univariate Cox regression analyses,factors associated with HCC development were found to be male sex (p=0.002), cirrhosis (p<0.001),alcohol (p=0.02),HBeAg negativity (p=0.001),low genetic barrier drug regimen (p<0.001),resistance/virological breakthrough (p=0.002) and diabetes (p=0.03).In a multivariate analysis,cirrhotic liver (p<0.001), low genetic barrier drug regimens (p=0.02) and resistance-virological breakthrough (p=0.04) were independent factors associated with HCC development.