B형 간염바이러스(HBV) DNA 양성이나 HBV 표면항원 방사선면역측정 음성인 B형 간염 환자의 임상상 및 S 유전자 변이 분석
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
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배경 : B형 간염바이러스(Hepatitis B virus, HBV) 항원(HBsAg) 방사선면역 측정법 음성이면서 HBV DNA 증폭검사상 양 성인 경우의 임상적 상황, S 유전자 변이와 다른 HBsAg 검사법 의 유용성을 알아보고자 하였다. 방법 : HBV DNA정량검사가 의뢰된 환자 중 결과가 양성이면 서 방사선면역측정법에 의한 HBsAg (BNIBT HBsAg Kit, China) 검사상 음성인 16명을 대상으로 하였다. 각 검체에 대해 S 유전 자“a”결정기의 염기서열을 분석하였고 이들의 임상적 특징을 분석하였다. 또한 화학발광면역측정법 (CLIA) 원리를 이용하는 Architect HBsAg kit (Abbott laboratories, USA)로 HBsAg 추가검사를 시행하였다. 결과 : 대상 16명 중 11명에서“a”결정기에 다수의 변이가 관찰 되었다. 이들 11명은 수년 전에 간이식을 받고 B형 간염바이러스 면역글로블린(Hepatitis B immune glubolin, HBIG)과 항바이 러스제제를 투여 중인 환자이었다. G145R 변이가 8명에서 관 찰되었으며, 그 외 G145K, D144G, D144A 등이 흔히 관찰되었 다. 이들 11명 중 9명에서 Architect HBsAg kit으로 HBsAg을 검사하였는데, 8명에서는 양성(3.0 IU/mL 이상, 중간값 69.0 IU/mL) 결과를 보였다. 변이가 관찰되지 않은 나머지 5명 중 4명에서 Architect HBsAg kit으로 추가검사를 시행한 결과 2명에서만 약양성(1 IU/mL 이하)을 보였다. 결론 : HBV DNA 양성/HBsAg RIA 음성은 간이식 후에 HBIG 를 투여받는 환자군에서 주로 발견되었으며 HBIG 도피 변이가 관찰되었다. 이들 증례의 대부분에서 Architect HBsAg kit에 서 양성을 보인 점을 고려할 때 간이식을 많이 시행하는 병원에 서는 RIA 보다는 변이를 더 잘 검출할 수 있으며 낮은 수준의 HBsAg까지 검출할 수 있는 다른 면역검사법을 사용하여 HBs- Ag을 검사하는 것이 권장된다.
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 HBs-Ag kit, 8 showed positive results. Among 4 of the remaining 5 patients, only 2 showed weak positive results (≤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.
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