Precore and core promoter mutations, hepatitis B virus DNA levels and progressive liver injury in chronic hepatitis B.
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.
Yotsuyanagi
Hiroshi
H
Department of Internal Medicine, Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Miyamae-ku, Kawasaki, Japan. hyotsu@marianna-u.ac.jp
Hino
Kunihiko
K
Tomita
Eiichi
E
Toyoda
Joji
J
Yasuda
Kiyomi
K
Iino
Shiro
S
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
D004279:DNA, Viral; D006512:Hepatitis B Core Antigens