title: Precore and core promoter mutations, hepatitis B virus DNA levels and progressive liver injury in chronic hepatitis B.
abstract: OBJECTIVE
  To elucidate the viral factors responsible for progressive liver injury in chronic hepatitis B.
  
  
  METHODS
  We analyzed 179 persistently infected patients (21 asymptomatic carriers, 126 with chronic hepatitis and 32 with cirrhosis) with genotype C hepatitis B virus (HBV). HBeAg/anti-HBe, levels of HBV DNA, mutations in the basic core promoter (BCP) region at nucleotides 1762/1764 and mutation in the precore (preC) region at nucleotide 1896 were determined. Serial samples from 18 patients also were analyzed.
  
  
  RESULTS
  HBeAg/anti-HBe and HBV DNA levels per se were not related to liver fibrosis. The frequency of BCP mutations increased with progression of liver fibrosis. Although the preC mutation was detected more often among the LC group, the role of this mutation in progression of fibrosis seems less than that of the BCP mutations. Sequential analysis showed that (1) rapidly progressing cases were positive continuously for double mutations in the BCP with a wild-type precore sequence, and (2) asymptomatic cases with anti-HBe acquired the preC mutation during their clinical course.
  
  
  CONCLUSIONS
  Double mutations in the BCP region at nucleotide 1762/1764 are closely related to progression of chronic liver disease. Acquisition of mutation in the preC region at nucleotide 1896 may contribute to inactivation of chronic liver disease.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Miyamae-ku, Kawasaki, Japan. hyotsu@marianna-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yotsuyanagi
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Hino
authors.forename: Eiichi
authors.initials: E
authors.lastname: Tomita
authors.forename: Joji
authors.initials: J
authors.lastname: Toyoda
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Yasuda
authors.forename: Shiro
authors.initials: S
authors.lastname: Iino
mesh_terms: D000328:Adult; D004279:DNA, Viral / Q000097:blood; D005260:Female; D005838:Genotype; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000473:pathology* / Q000821:virology*; D006801:Humans; D008103:Liver Cirrhosis / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D004279:DNA, Viral; D006512:Hepatitis B Core Antigens