title: Clinical significance of hepatitis B virus precore and core promoter variants in Korean patients with chronic hepatitis B.
abstract: OBJECTIVE
  We aimed to clarify the clinical significance of precore (preC)/core promoter (CP) variants of hepatitis B virus (HBV) in chronic hepatitis B (CHB) patients.
  
  
  METHODS
  We assessed serum HBeAg, HBV DNA levels, alanine transferase (ALT) levels, and progression of liver fibrosis in 226 Korean CHB patients, presumed to be infected with genotype C HBV, to analyze HBV variants in the preC region (G1896A) and CP regions (A1762T, G1764A).
  
  
  RESULTS
  CP and preC variants were more frequently found in HBeAg-negative patients than in HBeAg-positive patients (P<0.05). HBeAg-positive patients with CP variants had higher ALT levels and more advanced fibrosis scores (all P<0.01) than those without variants; those with preC variant had lower HBV DNA levels (P=0.009), with no significant difference in ALT levels and fibrosis scores. However, no significant correlation was found between HBV variants and clinicopathologic findings in HBeAg-negative patients. Furthermore, multivariate analysis revealed that (1) progression of liver fibrosis (≥F2) was associated with older age in both HBeAg-positive and HBeAg-negative patients (P<0.05) and with CP variants in the HBeAg-positive group (P=0.007), and (2) HBV DNA levels were positively correlated with ALT levels, irrespective of HBeAg (P<0.05), whereas they were negatively correlated with the presence of preC variant in the HBeAg-positive group (P=0.004).
  
  
  CONCLUSIONS
  In HBeAg-positive CHB patients infected with genotype C HBV, preC variant was associated with enhanced host immune response with lower HBV DNA levels, whereas CP variants were associated with severe liver damage and liver fibrosis progression.
authors.affiliation: *Department of Internal Medicine, Division of Gastroenterology and Hepatology, Korea University College of Medicine, Seoul †Department of Internal Medicine, Division of Gastroenterology and Hepatology, Cheju Halla General Hospital, Cheju, Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Yim
authors.forename: Soon Ho
authors.initials: SH
authors.lastname: Um
authors.forename: Jin
authors.initials: J
authors.lastname: Young Jung
authors.forename: Tae Hyung
authors.initials: TH
authors.lastname: Kim
authors.forename: Jin Dong
authors.initials: JD
authors.lastname: Kim
authors.forename: Bora
authors.initials: B
authors.lastname: Keum
authors.forename: Yeon Seok
authors.initials: YS
authors.lastname: Seo
authors.forename: Hyung Joon
authors.initials: HJ
authors.lastname: Yim
authors.forename: Yoon Tae
authors.initials: YT
authors.lastname: Jeen
authors.forename: Hong Sik
authors.initials: HS
authors.lastname: Lee
authors.forename: Hoon Jai
authors.initials: HJ
authors.lastname: Chun
authors.forename: Chang Duck
authors.initials: CD
authors.lastname: Kim
authors.forename: Ho Sang
authors.initials: HS
authors.lastname: Ryu
mesh_terms: D000328:Adult; D000367:Age Factors; D000410:Alanine Transaminase / Q000097:blood; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000473:pathology / Q000821:virology*; D006801:Humans; D008103:Liver Cirrhosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D056910:Republic of Korea; D014758:Viral Core Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D014758:Viral Core Proteins; D000410:Alanine Transaminase