Cytoplasmic expression of hepatitis B core antigen in chronic hepatitis B virus infection: role of precore stop mutants.
OBJECTIVE
The cytoplasmic expression of HBcAg is a possible target of immune hepatocytolysis and it is important for the pathogenesis of hepatic injury in chronic hepatitis B virus (HBV) infection. Cytoplasmic HBcAg expression has been suggested to be related to the precore sequence of HBV, HBV DNA level or cell cycle of hepatocytes and the aim of this study was to understand its mechanism.


METHODS
We studied the expression pattern of HBcAg and its relationship to serum HBV DNA levels, cell proliferation activity of hepatocytes and precore mutation using 66 patients' sera and biopsied liver specimens of chronic hepatitis B.


RESULTS
The expression patterns of HBcAg were cytoplasmic predominant (CP) in 17 cases, nuclear and cytoplasmic (NC) in 10 cases and nuclear predominant (NP) in 9 cases and negative in 30 cases. CP expression cases showed a higher grade of hepatitis activity than NP expression cases. Serum HBV DNA levels showed a wide range and there was no significant difference according to the expression pattern of HBcAg. Cell proliferation activity of hepatocytes, measured by Ki-67 (MIB-1) labelling index was higher in CP expression cases than in NP expression cases and it was also significantly higher in cases of high grade than in low grade hepatitis activity. The precore region was evaluated by primer extension assay in 51 cases and there were 16 cases of 1896 precore mutant, 23 cases of wild type, 12 cases of mixed infection of 1896 precore mutant type and wild type. CP expression of HBcAg was significantly more frequent in 1896 precore mutant cases (86%) than in wild type cases (26%).


CONCLUSIONS
CP expression of HBcAg is the major pattern of 1896 precore mutant cases and it might be involved in the severe liver injury of precore mutants. One of the mechanisms regulating CP HBcAg expression is suggested to be precore mutation of HBV as well as cell cycle of hepatocyte.
Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
Y N
YN
Park
K H
KH
Han
K S
KS
Kim
J P
JP
Chung
S
S
Kim
C
C
Park
D000328:Adult; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004279:DNA, Viral / Q000096:biosynthesis / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006512:Hepatitis B Core Antigens / Q000096:biosynthesis* / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D009154:Mutation; D012720:Severity of Illness Index; D014779:Virus Replication / Q000235:genetics
D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D019394:Ki-67 Antigen