title: Long-term follow-up of patients with hepatitis B e antigen negative chronic hepatitis B.
abstract: OBJECTIVE
  After hepatitis B virus (HBV) e antigen (HBeAg) seroconversion, HBV-DNA continues to replicate, and HBeAg-negative patients still face the risk of liver disease progression. We investigated the predictive factors for alanine aminotransferase (ALT) elevation, antiviral drug use, and hepatocellular carcinoma (HCC) occurrence in HBeAg-negative patients.
  
  
  METHODS
  Age, sex, ALT, platelet counts, HBV-DNA levels, genotype, antidiabetic drug use, body mass index, smoking, and alcohol consumption were analyzed for a total of 244 HBV carriers who were HBeAg-negative.
  
  
  RESULTS
  Of 244 HBeAg-negative patients, 158 (64.8%) showed normal ALT levels at baseline. Multivariate Cox hazard regression analysis identified high HBV-DNA levels and high ALT at baseline as independent risk factors for ALT elevation in the patients with normal ALT at baseline. The threshold ALT and HBV-DNA levels were determined to be 31 IU/L and 5.3 log copies/mL, respectively. Seventeen (7.0%) patients used antiviral drugs. Multivariate Cox hazard regression analysis identified high HBV-DNA levels (threshold, 5.7 log copies/mL), the use of antidiabetic drugs, and daily alcohol consumption at baseline as an independent risk factor for the use of antiviral drugs in HBeAg-negative patients. In 10 patients (4.1%), HCC was detected, and a low platelet count (threshold, 10.0×10(4)/mm(3)) was associated with the occurrence of HCC.
  
  
  CONCLUSIONS
  This study identified predictors of future active liver disease in HBeAg-negative patients, i.e. ALT elevation, unavoidable use of antiviral drugs, and occurrence of HCC.
authors.affiliation: Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Dan
authors.initials: D
authors.lastname: Bekku
authors.forename: Makoto
authors.initials: M
authors.lastname: Arai
authors.forename: Fumio
authors.initials: F
authors.lastname: Imazeki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yonemitsu
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kanda
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Kenichi
authors.initials: K
authors.lastname: Fukai
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sato
authors.forename: Sakae
authors.initials: S
authors.lastname: Itoga
authors.forename: Fumio
authors.initials: F
authors.lastname: Nomura
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D016009:Chi-Square Distribution; D004279:DNA, Viral / Q000097:blood; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000097:blood* / Q000235:genetics; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000821:virology*; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase