Korean J Hepatol.  1999 Jun;5(2):105-115.

Persistent Negative Anti-Bc in Chronic Hepatitis B Virus Carrier: linical Review, HBcAg and Nucleotide Sequence of It's Epitope in HLA A2 Heterozygotes

• Kim JH
• Kim HC

Abstract

BACKGROUND/AIMS
HBcAg is the most immunogenic HBV component and anti-Bc usually persists irrespective of ongoing liver disease or clearance of the virus in human. Therefore anti-Bc is considered as the most sensitive and occasionally the only marker of the HBV infection. Nevertheless, there are a few HBsAg carrier with persistent negative anti-Bc. The epitope which responds to HBcAg is recently defined in HLA A2 from acute viral hepatitis patient due to HBV. So we studied the clinical and laboratory features and nucleotide sequence of HBcAg corresponding to HLA A2 in the HBsAg carrier with persistent negative anti-Bc.
METHODS
The subject of these study consists of eight HBsAg chronic carriers with persistent negative anti-Bc. We followed up the clinical features and serological markers of HBV infection and determined the amount of humoral immunoglobulin, HBV DNA and HBcAg when we performed the HLA class I typing and sequencing analysis of core of HBV. Control cases were selected from 3 HLA A2 heterozygote cases with chronic HBsAg carriers with anti-Bc.
RESULTS
All subjects had the HBsAg persistently and good health conditions with normal ranges of aminotransferase and humoral immunoglobulin. One of them was converted to anti-Bc-ositive during follow-p period. The level of HBV DNA in serum was higher than 1.2 pg/mL in 7 of 8 chronic HBV carriers. There was a trend of differences between chronic anti-Bc negative carriers and converted one case to anti-Bc positive in the serum of HBcAg and HBV DNA(p=0.06). But strong positive correlation was observed between the amount of HBcAg and HBV DNA in sera. The core portion of HBV was amplified in 4 of 6 HLA A2 heterozygotes by single PCR. When sequenced the PCR products of the above 4 chronic anti-Bc negative HBV carriers and 3 control cases directly, there were no significant difference in the nucleotide and amino acid sequence at the HBcAg epitope which corresopond to class 1 HLA A2.
CONCLUSIONS
Our results show that persistent anti-Bc negative chronic HBV carriers may be caused by large amounts of HBV DNA and HBcAg in their sera and not by variants of HBV. These suggested that active viral replication was going on, but are undetectable by the available commercial tests due to binding with excessive amount of HBcAg in the HBV carriers with persistent negative anti-Bc.

Keyword

HBsAg; HBcAg; HBV DNA; Negative Anti-Bc; Nucleotide

MeSH Terms

Amino Acid Sequence
Base Sequence*
DNA
Hepatitis
Hepatitis B Core Antigens*
Hepatitis B Surface Antigens
Hepatitis B, Chronic*
Hepatitis, Chronic*
Heterozygote*
Humans
Immunoglobulins
Liver Diseases
Polymerase Chain Reaction
Reference Values
DNA
Hepatitis B Core Antigens
Hepatitis B Surface Antigens
Immunoglobulins