title: Effects of long-term entecavir treatment on the incidence of hepatocellular carcinoma in chronic hepatitis B patients.
abstract: OBJECTIVE
  Entecavir is one of the most-used nucleoside analogues for the treatment of patients with chronic hepatitis B virus (HBV) infection. The aim of this study was to clarify the effects of long-term entecavir treatment on the incidence of hepatocellular carcinoma (HCC).
  
  
  METHODS
  The participants were 249 patients with chronic HBV infection who had been treated by entecavir for more than 2 years. Hepatic functional reserve and incidence of HCC were evaluated, and the factors that might contribute to the development of HCC were analyzed.
  
  
  RESULTS
  Prothrombin activity was significantly elevated at 60 months after starting entecavir (from 85.9 ± 17.4 to 97.0 ± 16.9%, p < 0.001). The albumin level was also significantly elevated at 60 months after starting entecavir (from 4.0 ± 0.5 to 4.3 ± 0.3 mg/dL, p < 0.001). The annual incidence of HCC decreased over time, and the incidence of HCC was only 1.8% at 5 years after starting entecavir. On multivariate analysis for HCC incidence, older age and low platelet count were significant, independent contributing factors.
  
  
  CONCLUSIONS
  Long-term treatment with entecavir improved hepatic functional reserve and decreased the incidence of HCC over time after 3 years. To decrease the incidence of HCC, careful induction of long-term entecavir treatment in younger patients with chronic HBV infection and better hepatic functional reserve would be important.
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. t_watanabe0303@yahoo.co.jp.
authors.forename: Takao
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. yotoku@m.ehime-u.ac.jp.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Tokumoto
authors.affiliation: Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Bunkyocho 1, Matsuyama, Ehime, 790-8524, Japan. koujijoko@matsuyama.jrc.or.jp.
authors.forename: Kouji
authors.initials: K
authors.lastname: Joko
authors.affiliation: Department of Gastroenterology, Ehime Prefectural Central Hospital, Kasugamachi 83, Matsuyama, Ehime, 790-0024, Japan. kojiromichitaka@gmail.com.
authors.forename: Kojiro
authors.initials: K
authors.lastname: Michitaka
authors.affiliation: Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Bunkyocho 1, Matsuyama, Ehime, 790-8524, Japan. matoshi@matsuyama.jrc.or.jp.
authors.forename: Toshie
authors.initials: T
authors.lastname: Mashiba
authors.affiliation: Department of Gastroenterology, Ehime Prefectural Central Hospital, Kasugamachi 83, Matsuyama, Ehime, 790-0024, Japan. hirage@gmail.com.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hiraoka
authors.affiliation: Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Bunkyocho 1, Matsuyama, Ehime, 790-8524, Japan. hironori@m.ehime-u.ac.jp.
authors.forename: Hironori
authors.initials: H
authors.lastname: Ochi
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. ykoizumi@m.ehime-u.ac.jp.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Koizumi
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. fuji0227@m.ehime-u.ac.jp.
authors.forename: Fujimasa
authors.initials: F
authors.lastname: Tada
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. masashih@m.ehime-u.ac.jp.
authors.forename: Masashi
authors.initials: M
authors.lastname: Hirooka
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. yoshidao@m.ehime-u.ac.jp.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yoshida
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. yskyskimai@yahoo.co.jp.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Imai
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. masaben@m.ehime-u.ac.jp.
authors.forename: Masanori
authors.initials: M
authors.lastname: Abe
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. hiasa@m.ehime-u.ac.jp.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Hiasa
mesh_terms: D000328:Adult; D000368:Aged; D000418:Albumins / Q000378:metabolism; D000998:Antiviral Agents / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000503:physiopathology / Q000821:virology*; D015331:Cohort Studies; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000453:epidemiology / Q000503:physiopathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011516:Prothrombin / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000418:Albumins; D000998:Antiviral Agents; C413685:entecavir; D006147:Guanine; D011516:Prothrombin
keywords: Age; Entecavir; Long-term; Platelet count