title: Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients with hepatitis B virus infection.
abstract: Chronic hepatitis B virus (HBV) infection leads to cirrhosis and hepatocellular carcinoma (HCC). Antiviral agents are thought to reduce HCC development, but agents such as lamivudine (LAM) have a high rate of drug resistance. We compared the incidence of HCC in 472 entecavir (ETV)-treated patients and 1,143 nontreated HBV patients (control group). Propensity score matching eliminated the baseline differences, resulting in a sample size of 316 patients per cohort. The drug mutation resistance was 0.8% (4/472) in the ETV group. The cumulative HCC incidence rates at 5 years were 3.7% and 13.7% for the ETV and control groups, respectively (P < 0.001). Cox proportional hazard regression analysis, adjusted for a number of known HCC risk factors, showed that patients in the ETV group were less likely to develop HCC than those in the control group (hazard ratio: 0.37; 95% confidence interval: 0.15-0.91; P = 0.030). Both cohorts were applied in three previously reported risk scales and risk scores were generated based on age, gender, cirrhosis status, levels of alanine aminotransferase, hepatitis B e antigen, baseline HBV DNA, albumin, and bilirubin. The greatest HCC risk reduction occurred in high-risk patients who scored higher on respective risk scales. In sub analyses, we compared treatment effect between nucleos(t)ide analogs, which included matched LAM-treated patients without rescue therapy (n = 182). We found HCC suppression effect greater in ETV-treated (P < 0.001) than nonrescued LAM-treated (P = 0.019) cirrhosis patients when they were compared with the control group.
  
  
  CONCLUSIONS
  Long-term ETV treatment may reduce the incidence of HCC in HBV-infected patients. The treatment effect was greater in patients at higher risk of HCC.
authors.affiliation: Department of Hepatology, Toranomon Hospital, Tokyo, Japan. hosa-p@toranomon.gr.jp
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hosaka
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Suzuki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Yuya
authors.initials: Y
authors.lastname: Seko
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kawamura
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sezaki
authors.forename: Norio
authors.initials: N
authors.lastname: Akuta
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Saitoh
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Arase
authors.forename: Kenji
authors.initials: K
authors.lastname: Ikeda
authors.forename: Mariko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D019259:Lamivudine / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D019259:Lamivudine; C413685:entecavir; D006147:Guanine