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Cytoplasmic expression of hepatitis B core antigen in chronic hepatitis B virus infection: role of precore stop mutants

 Young Nyun Park  ;  Kwang Hyub Han  ;  Kyung Sup Kim  ;  Jun Pyo Chung  ;  Seungtaek Kim  ;  Chanil Park 
 LIVER, Vol.19(3) : 199-205, 1999 
Journal Title
LIVER (Liver)
Issue Date
Adult ; Cell Division ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; DNA, Viral/biosynthesis ; DNA, Viral/blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Hepatitis B Core Antigens/biosynthesis* ; Hepatitis B Core Antigens/genetics* ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/blood ; Hepatitis B, Chronic/metabolism* ; Hepatitis B, Chronic/pathology ; Humans ; Immunohistochemistry ; Ki-67 Antigen/metabolism ; Male ; Mutation ; Severity of Illness Index ; Virus Replication/genetics
AIMS/BACKGROUND: 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.

MATERIAL/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%).

CONCLUSION: 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.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sup(김경섭) ORCID logo https://orcid.org/0000-0001-8483-8537
Kim, Seung Taek(김승택)
Park, Young Nyun(박영년) ORCID logo https://orcid.org/0000-0003-0357-7967
Park, Chan Il(박찬일)
Han, Kwang-Hyub(한광협) ORCID logo https://orcid.org/0000-0003-3960-6539
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