Sequential accumulation of the basal core promoter and the precore mutations in the progression of hepatitis B virus-related chronic liver disease.
OBJECTIVE
Despite the pathogenic role of the basal core promoter (BCP) and the precore mutations in chronic hepatitis B virus (HBV) infection, their role in the progression of liver disease is still controversial. We analyzed whether the accumulation of these mutations might enhance the progression of HBV-related chronic liver disease.


METHODS
Forty consecutive patients at each clinical status were analyzed. Clinical statuses were as follows: HBeAg-positive asymptomatic carrier (HBeAg(+) ASC) (defined as HBeAg(+), anti-HBe(-), HBV-DNA(+) by hybridization, normal ALT); inactive HBsAg carrier; chronic hepatitis B; liver cirrhosis. The genotype and the BCP/precore regions were determined by PCR using genotype specific primers and direct sequencing, respectively.


RESULTS
All patients except one were infected with genotype C. The A to T mutation at nucleotide 1762 and/or G to A mutation at nucleotide 1764 were found in 30% in HBeAg(+) ASC, 65.7% in inactive HBsAg carrier, 95% in chronic hepatitis B, and 90% in liver cirrhosis (p < 0.001). The prevalence of the G to A mutation at nucleotide 1896 was 5% in HBeAg(+) ASC, 22.5% in inactive HBsAg carrier, 32.5% in chronic hepatitis B, and 50% in liver cirrhosis, respectively (p < 0.001). The T to C/A mutation at nucleotide 1753 in the BCP and G to A mutation at nucleotide 1899 in the precore were more frequent in liver cirrhosis than in the other clinical statuses (p < 0.05).


CONCLUSIONS
Sequential accumulation of mutations in the BCP/precore has an important role in the progression of HBV-related liver disease.
Song
Byung-Cheol
BC
Department of Internal Medicine, Cheju National University College of Medicine, Cheju National University Hospital, Jeju, Republic of Korea. drsong@cheju.ac.kr
Cui
Xiu Ji
XJ
Kim
Heung Up
HU
Cho
Yoo-Kyung
YK
D000328:Adult; D002353:Carrier State / Q000276:immunology / Q000473:pathology / Q000821:virology; D018450:Disease Progression; D005260:Female; D006509:Hepatitis B / Q000235:genetics*; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000175:diagnosis* / Q000276:immunology / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D013045:Species Specificity
D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens