Mechanisms of the Undetectability of HBsAg in Patients with Chronic Liver Disease, Type B

Yoon, Jung Hwan; Lee, Hyo Suk; Kim, Chung Yong

Abstract

BACKGROUND AND AIMS: The presence of serum HBV DNA m HBsAg-negative patients with chronic liver disease indicates that the chronic liver disease was caused by HBV in these patients. The precise mechanism of the undetectability of HBsAg in these patients still remains to be investigated, though several possible mechanisms have been theoretically proposed as follows; 1) the concentration of HBsAg in the serum may be too low to be detected by available assay; 2) HBsAg epitope may have been masked by the formation of immune complex with anti-HBs; 3) mutations in the S region of the HBV genome may have resulted in the alteration of antigenicity of HBsAg. Therefore, the present study was performed to clarify the mechanisrn of the negativity of HBsAg in HBsAg-negative patients with chronic liver disease type B.
METHODS
Sixteen HBsAg and anti-HCV-negative patients with chronic liver disease, who were positive for serum HBV DNA by PCR using primers designed to amplify the S region of HHV genome, were enrolled and subsequently analyzed for the quantitation of serum HBU DNA to estimate the concentration of HBsAg, the presence of HBsAg/anti-HBs immune complexes in their sera and the nucleotide sequences in the envelope region of HBV genonie.
RESULTS
The concentration of serum HBV DNA determined by liquid hybridization was less than 1 pg/ml in 12 out of 16 patients with serum HBV DNA detectable by PCR; in the last 4 patients, the concentration was over 1 pg/ml. Following the dissociation of immune complexes in sera by glycine-hydrochloride treatment, HBsAg was detected in one patient with serum HBV DNA more than 1 pg/ml; the HBV was wild-type in this patient. Out of 4 patients with serum HBV DNA over 1 pg/ml, 3 had mutant HBVs with amino acid substitutions in the S region; amino acid changes in the S region, identified only during the HBsAg-negative period, were at codons 114, 118, 123, 127, 134 (Phe-Ser), and 135.
CONCLUSIONS
These results demonstrated that all three independent mechanisms above were involved in the undetectability of HBsAg in HBsAg-negative chronic 1iver disease type B. However, we found that lower concentrations of HBsAg than the detection level of radioimmunoassay for HBsAg was the most cornmon mechanism.