Korean J Lab Med.  2009 Jun;29(3):224-230. 10.3343/kjlm.2009.29.3.224.

Analysis of Clinical Characteristics and S Gene Mutation of Hepatitis B Virus (HBV) in Patients with Hepatitis B Surface Antigen RIA Negative and HBV DNA Positive

• Sohn YH
• Oh HB
• Ko SY
• Lim YS
• Kwon OJ

• KMID: 1096974
• DOI: http://doi.org/10.3343/kjlm.2009.29.3.224

Abstract

BACKGROUND: We investigated hepatitis B virus (HBV) infection cases, who were HBsAg negative by radioimmunoassay (RIA) and HBV DNA positive for their clinical characteristics, the S gene mutation of hepatitis B virus (HBV), and usefulness of other HBsAg immunoassay.
METHODS
Among the patients requested for HBV DNA quantification, 16 patients positive in HBV DNA but negative in HBsAg RIA (BNIBT HBsAg Kit, China) were enrolled. The "a" determinant of HBV S gene was sequenced and clinical characteristics were reviewed. Additional HBsAg assay was performed using Architect HBsAg kit (Abbott laboratories, USA) employing chemiluminescent immunoassay method.
RESULTS
Eleven of the 16 patients showed multiple mutations in the "a" determinant. These patients received liver transplantation several years ago and have been treated with hepatitis B immune globulin (HBIG) and antiviral drugs. G145R mutation was found in 8 patients and G145K, D144G, and D144A were also frequently found. Among 9 of the 11 patients tested for HBsAg by Architect HBsAg kit, 8 showed positive results. Among 4 of the remaining 5 patients, only 2 showed weak positive results (< or =1 IU/mL) in Architect HBsAg kit.
CONCLUSIONS
HBV DNA-positive/HBsAg RIA-negative results were mostly observed in the patients treated with HBIG after liver transplantation, in whom HBIG escape mutations were found. Majority of these cases were positive in Architect HBsAg assay, and it is recommended to use other HBsAg immunoassay methods that are more sensitive than RIA in the detection limit as well as in the detection of escape mutant in hospitals performing liver transplantation.

Keyword

Hepatitis B virus; Occult hepatitis B virus infection; HBIG escape mutation; HBsAg assay

MeSH Terms

Adolescent
Adult
Aged
Amino Acid Sequence
Antiviral Agents/therapeutic use
DNA, Viral/analysis
Female
Hepatitis B/*diagnosis/drug therapy/virology
Hepatitis B Surface Antigens/*analysis/genetics
Hepatitis B virus/*genetics/isolation & purification
Humans
Immunoassay
Immunoglobulins/therapeutic use
Immunologic Factors/therapeutic use
Male
Middle Aged
Molecular Sequence Data
Mutation
Radioimmunoassay

Figure

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  Fig. 1. Amino acid sequences of major hydrophilic region (100-160) including “a” determinant (124-147) in HBV S gene of 16 patients. Lower cases mean that its amino acids are mixed with reference amino acids. “∗” shown in pt 15 indicates that its sequence could not be read due to background noise.

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