Comparison of sequence changes of precore and core promoter regions in HBeAg-positive chronic hepatitis B patients with and without HBeAg clearance in lamivudine therapy.
OBJECTIVE
The aim of this study was to compare the serial sequence changes of precore and core promoter regions in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients with and without HBeAg clearance in lamivudine treatment.


METHODS
Precore and core promoter genes of the hepatitis B virus (HBV) were sequenced from five serial serum samples of 74 HBeAg-positive CHB patients received lamivudine for 9-12 months (34 complete responders and 40 non-responders).


RESULTS
Before lamivudine therapy, stepwise logistic regression analysis disclosed that ALT level > or =300 U/L, A1896 mutant, and log HBV DNA levels were the major determinants for complete response. In addition, Cox regression showed that age < 35 years and G1752 mutant were independent factors for sustained response. Compared with complete responders, a higher frequency of mutation in nucleotides 1773, 1802, 1803, 1845, 1850, and 1858 was found in the non-responders during therapy. Lamivudine therapy resulted in a further increase in T1762/1764 mutants and a further decrease in A1896 mutant during treatment and after HBeAg clearance in complete responders.


CONCLUSIONS
T1762/A1764 mutation (not A1896) played an important role in lamivudine-induced HBeAg clearance. Moreover, T1773, C1802, G1803, T1846, A1850, and C1858 mutations might have significant correlation with HBeAg nonseroconversion.
Chen
Chien-Hung
CH
Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta Pei Road, Kaohsiung, Taiwan, ROC.
Lee
Chuan-Mo
CM
Lu
Sheng-Nan
SN
Changchien
Chi-Sin
CS
Wang
Jyh-Chwan
JC
Wang
Jing-Houng
JH
Hung
Chao-Hung
CH
Hu
Tsung-Hui
TH
D000293:Adolescent; D000328:Adult; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006510:Hepatitis B Antibodies / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome; D014758:Viral Core Proteins / Q000235:genetics*
D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D014758:Viral Core Proteins; D019259:Lamivudine