Hepatitis B virus basal core promoter mutation and DNA load correlate with expression of hepatitis B core antigen in patients with chronic hepatitis B.
BACKGROUND
Expression of intrahepatic hepatitis B core antigen (HBcAg) is related to the immunopathogenesis of hepatitis B virus (HBV) infection. This study investigated the role that HBV genotype and basal core promoter (BCP) mutation play in the expression of HBcAg.


METHODS
A total of 70 hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis (genotype B in 52 patients and genotype C in 18 patients; BCP mutation T1762/A1764 in 16 patients) were enrolled. Clinical, virologic, and histologic features were compared with regard to localization and expression of intrahepatic HBcAg. The effects that HBV genotype and BCP mutation T1762/A1764 had on expression of HBcAg were further evaluated by in vitro assays.


RESULTS
Cytoplasmic, mixed cytoplasmic/nuclear, and nuclear localization of intrahepatic HBcAg was found in 38 (56.7%), 25 (37.3%), and 4 (6.0%) patients, respectively; HBcAg was not discernible in 3 patients. A total of 58 (82.9%) of these patients expressed a high level of HBcAg. In multivariate analysis, cytoplasmic localization of HBcAg correlated only with a low HBV load in serum (P = .045) and BCP mutation (P = .04). A high expression level of HBcAg also correlated with a high HBV load in serum (P = .015) and with BCP wild-type sequence (P = .037). In vitro assays indicated that the HBV BCP mutant strain had lower subcellular expression of HBcAg than did the BCP wild-type strain.


CONCLUSIONS
HBV BCP mutation and HBV load, but not genotype, contribute to the expression of intrahepatic HBcAg.
Liu
Chun-Jen
CJ
Graduate Institute of Clinical Medicine, Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei.
Jeng
Yung-Ming
YM
Chen
Chi-Lin
CL
Cheng
Huei-Ru
HR
Chen
Pei-Jer
PJ
Chen
Ting-Chi
TC
Liu
Chen-Hua
CH
Lai
Ming-Yang
MY
Chen
Ding-Shinn
DS
Kao
Jia-Horng
JH
D000328:Adult; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D005838:Genotype; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D008103:Liver Cirrhosis / Q000821:virology; D008297:Male; D015999:Multivariate Analysis; D009154:Mutation; D016017:Odds Ratio; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D019562:Viral Load; D055815:Young Adult
D004279:DNA, Viral; D006512:Hepatitis B Core Antigens