대한수혈학회지 : 제 21 권제 3 호, 2010 헌혈혈액선별검사외부신빙도조사결과보고 (2010) 차영주 1 ㆍ김진규 2 = Abstract = 중앙대학교의과대학진단검사의학교실 1, 건국대학교의과대학진단검사의학교실 2 External Quality Assurance Survey for the Blood Donor Screening Tests Performed in 2010 Young Joo Cha 1, Jin Q Kim 2 Department of Laboratory Medicine, College of Medicine, Chung-Ang University 1, Konkuk University 2, Seoul, Korea Background: To prevent blood-borne infections and guarantee safe transfusion, we proposed a quality assurance program for donor screening tests, such as hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus antibody (anti-hcv), by introducing external proficiency testing for the laboratories that perform donor screening tests. Methods: The materials for external proficiency testing (PT) were prepared from the HBsAg Standard Panels and anti-hcv Reference Panels provided by the Korea Food and Drug Administration (KFDA), and the normal Human Serum was provided by the Serum Bank of the Korea National Research Resource Center. The external PT materials were sent to 83 laboratories that performed donor screening tests after evaluating their quality. Results: The results of evaluating the quality of the PT materials were acceptable. All the laboratories receiving the materials answered with a 100% response rate. All the laboratories answered that they obtained positive results for the HBsAg Standard Panel E, H, I and J; however, one laboratory answered in the gray-zone and that lab had negative results for HBsAg Standard Panel C and G. Seventy laboratories (84%) and 42 laboratories (51%) among the total 83 laboratories answered they had positive results for HBsAg Standard Panel B and D, suggesting that many laboratories could not detect a low level of HBsAg. All 83 laboratories answered that they had concordant results for the external PT for anti-hcv. Conclusion: Donor screening laboratories can detect low levels of HBsAg and anti-hcv without any errors and the performance of the laboratories that could not detect low levels of HBsAg remains to be improved. Quality assurance program using external PT with materials that contain various genotypes and mutants should 접수일 :2010년 11월 17일, 수정일 :2010년 12월 15일, 승인일 :2010년 12월 17일책임저자 : 차영주 156-755 서울시동작구흑석동 224-1 중앙대학교병원진단검사의학과 TEL: 02) 6299-2720, FAX: 02) 6298-8630, E-mail: chayoung@cau.ac.kr 이논문은 2010년도질병관리본부위탁연구용역사업지원에의한것임. 이논문에서사용된바이러스표지자가음성인정상인혈청은국가지정연구소재중앙센터인체유래고위험군바이러스소재은행인혈청검체은행으로부터분양받아사용하였음. - 201 -
대한수혈학회지 : 제 21 권제 3 호 be conducted to maintain the quality of donor screening tests. (Korean J Blood Transfus 2010;21:201-9) Key words: Donor screening tests, Quality assurance program, Standard serum panel, HBV variants, External proficiency testing 서론 헌혈혈액선별검사로시행하고있는바이러스검사는고도의정확도가요구되는검사로위양성결과는혈액의효율적인사용을방해하고위음성결과는수혈감염으로이어질수있는바, 헌혈혈액선별검사의위양성및위음성사례를최소화하기위한체계적인품질보증체계가요구된다. 1,2) 혈액의안전을위하여세계각국에서는헌혈혈액선별검사를위한별도의품질보증프로그램 (quality assurance program) 을가지고있는데, 현재국내에는헌혈혈액선별검사종목인 B형간염표면항원 (hepatitis B surface antigen, HBsAg), C형간염바이러스항체 (anti-hcv) 및후천성면역결핍증바이러스항체 (anti-hiv) 등에관하여사단법인대한임상검사정도관리협회및질병관리본부국립보건원에서외부신빙도조사프로그램을운영하고있지만, 이는환자의진단을위한검사에대한품질보증프로그램으로서헌혈혈액선별검사의품질보증및표준화에는한계가있다. 따라서우리나라에는아직별도의헌혈혈액선별검사에대한품질보증프로그램은없는상황이고헌혈혈액선별검사의정확도를확보하기위한체계적인품질보증체계를구축할필요성이대두되고있는실정이다. 1,2) 특히세계적으로저농도양성및변이형바이러스보유헌혈자에의한수혈감염이보고 3,4) 되고있고, 우리나라에서도 HBsAg 변이형항원을가진헌혈자가보고되고있으므로헌혈혈액선별검사에대하여저농도양성혈청및다양한바이러스 표현형을가지는인간혈청을이용한외부신빙도조사가필요하다. 세계보건기구에서는가능하면자국민에대한선별검사에활용할국가표준물질을스스로개발하여품질평가에활용하도록권고하고있고, 영국이나호주에서는국가차원의생물의약품국가표준물질을확립하여자국내검사실에서사용하여일관성있게품질관리를시행할수있는체계를갖추고있으며, 타국에서요청할경우에이품질관리물질을판매하기도하는데, 싱가포르에서는호주의국가표준검사실에서제조ㆍ공급하는품질관리물질을사용하여외부및내부품질관리를실시하고있다. 1,2) 국내에서도체외진단용의약품의검증이나헌혈혈액선별검사에필요한안전하고안정적인국가표준품및품질관리물질의필요성을인식하고식품의약품안전청 ( 식약청 ) 주도로 B형간염바이러스 (HBV) 항원검사표준품을포함하여바이러스검사에대한표준품을확립하거나개발하고있고, 교육과학기술부에서지원하고있는국가지정연구소재중앙센터혈청검체은행에서도고위험군바이러스항원, 항체및핵산을포함하고있는감염된환자의혈액을수집하고분양규정에따라분양하고있어일관성있게품질관리를시행할수있는기반이구축되고있다. 2007년헌혈혈액선별검사국가품질관리체계구축방안개발연구 5) 에서식약청이제공한저농도 HBV 항원국가표준품을활용하여품질관리프로그램을시범적으로실시한결과 HBsAg 작업표준품 (working standard) 중에서 0.02 11.52 IU/mL 이상의농도를보이는표준품에대해서는일관된 - 202 -
헌혈혈액선별검사외부신빙도조사 (2010) 양성을보였으나약양성인표준품검체에대해서는시약과기관에따라상이한결과를보여약양성검체의경우검사환경에따라결과가달라질수있음을확인한바있다. 따라서본연구에서는다양한농도로구성된식약청의 HBsAg 표준품패널과 C형간염바이러스 (HCV) 참조패널및국가지정연구소재중앙센터혈청검체은행에서분양된혈청을사용하여헌혈혈액선별검사에대한외부신빙도조사사업을도입하여혈액의안전성을높이고헌혈혈액선별검사의품질관리를지속적으로수행할수있는체계적인품질보증프로그램을수립하고자하였다. 대상및방법 1. 외부신빙도조사물질제조및품질평가 1) HBsAg 외부신빙도조사물질다양한농도로구성된식약청의 HBsAg 표준품패널을사용하였고, 식약청 HBsAg 표준품패널에대한정보는 Table 1과같다. 2) Anti-HCV 외부신빙도조사물질제조및품질평가식약청의 HCV 참조패널을바이러스표지자가음성인정상인혈청으로희석하여제조한후품질평가를실시하였다. 식약청 HCV 참조패널에대한정보는 Table 2와같고, 바이러스표지자가음성인정상인혈청은국가지정연구소재중앙센터혈청검체은행으로부터분양받아사용하였다. HCV 참조패널 2번은 HCV genotype 2a/2c, 6번과 8번은 HCV genotype 1b로서정상인혈청을이용하여 400배희석하여다양한역가의 anti-hcv 외부신빙도조사물질 (Table 3) 을 Table 4와같은과정을거쳐제조하였다. Anti-HCV 외부신빙도조사물질에대한품질평가는우선원료물질에대한특성화시험을 4종의자동면역검사기용시약과 3종의간이검사용시약을이용하여양성물질과음성물질을각시험당 1회실시하였다. 병내균질성시험은제조된패널한세트를 10회반복시험하여동일한결과를보이는지확인하였고, 병간의균질성시험은제조된패널각 5세트를시험하여동일한결과를보이는지확인하였으며, 단기안정성시험은제조 Table 1. HBs Ag working standards (KFDA08/024) HBV genotype/subtype C2/adr HBV genotype/subtype C1/adw BTRI HBV/WS A B C D E F G H I J HBs Ag (IU/mL) 11.52 2.23 0.38 0.07 0.02 11.46 2.37 0.46 0.09 0.03 Table 2. HCV reference panel used for anti-hcv proficiency testing Panel No. ORTHO HCV 3.0 ELISA Murex anti-hcv 3.0 S/C ratio Genedia HCV ELISA 3.0 RIBA LG HCD 3.0 c100p c33 c22p NS5 SOD Genotype 2 5.924 4.897 8.467 3.860 4+ 4+ 4+ 4+ 2a/2c 6 5.959 4.897 8.206 3.811 4+ 4+ +/ 3+ 1b 8 5.986 4.953 8.258 3.863 3+ 4+ 4+ 4+ 1b - 203 -
대한수혈학회지 : 제 21 권제 3 호 Table 3. Dilution of HCV reference panel with normal human serum for anti-hcv proficiency testing testing No. HCV reference panel No. Volume of HCV reference panel (ml) Volume of normal human serum (ml) S/C ratio Interpretation HCV-10-01 2 1 400 2.5 Positive HCV-10-02 0 400 0.07 Negative HCV-10-03 6 1 400 7.4 Positive HCV-10-04 8 1 400 4.9 Positive HCV-10-05 0 400 0.07 Negative Table 4. Procedures preparing material for anti-hcv proficiency testing Stage Procedure 1 Prepare positive samples after filtering 10 ml of HCV reference panels using 0.22 μm filter 2 Mix filtered HCV reference panels and normal human serum with a defined ratio as shown in Table 3, stirring with magnetic bar in low speed at 4 o C for 18 hours 3 After centrifugation (8,000 rpm, 30 minutes), remove precipitation and keep inactivated at 56 o C for 3 hours 4 Do filtration once using 0.22 μm filter 5 After autoclaving vials and rubber stoppers, dry-heat sterilize 6 Dispense serum to each vial and put a rubber stopper under the clean bench 7 Seal the vials with aluminium cap 8 Pack the vials in a box testing no. HCV-10-01 HCV-10-02 HCV-10-03 HCV-10-04 HCV-10-05 된패널을 4 o C에보관하며 0, 1, 2, 3, 4주간격으로시험하여동일한결과를보이는지확인하였다. 2. 헌혈혈액선별검사에대한외부신빙도조사수행 헌혈혈액선별검사외부신빙도조사는헌혈혈액원을개설하고있는기관중헌혈혈액선별검사를실시하고있는 83기관을대상으로 2항목 (HBsAg과 anti-hcv) 에대하여실시하였다. HBsAg 외부신빙도조사물질은 2010년 5월 3일에, anti- HCV 외부신빙도조사물직은 2010년 9월 2일에각각냉장택배로발송하였다. 결과 1. 외부신빙도조사물질의품질평가결과 Anti-HCV 정도관리물질원료물질특성화시험에서 4종의자동면역검사기용시약과 3종의간이검사용시약을이용하여양성물질과음성물질을각시험당 1회실시한결과제조당시의결과와모두일치된결과를보였다 (Table 5). 제조된패널한세트에서 10회반복시험하여확인한병내균질성시험에서양성및음성검체에대하여모두일치된결과를확인할수있었고, 제조된패널각 5세트를선정하여시험한병간균질성시험에서도양성및음성검체에대하여모두일치된결과 - 204 -
헌혈혈액선별검사외부신빙도조사 (2010) Table 5. Characterization of prepared material for anti-hcv proficiency testing Automated immunoassay Rapid immunochromatography testing No. ADVIA Centaur HCV 1 ARCHITECT Anti-HCV 2 AXSYM HCV 3 Modular Analytics E170 4 ASAN Easy Test HCV 5 SD HCV (Multi) 6 GENEDIA HCV Rapid 7 HCV-10-01 Pos (2.5) Pos (2.6) Pos (2.2) Pos (280) Pos Pos Pos HCV-10-02 Neg (0.07) Neg (0.07) Neg (0.4) Neg (0.14) Neg Neg Neg HCV-10-03 Pos (7.4) Pos (4.6) Pos (5.7) Pos (383) Pos Pos Pos HCV-10-04 Pos (4.9) Pos (3.7) Pos (4.2) Pos (645) Pos Pos Pos HCV-10-05 Neg (0.07) Neg (0.07) Neg (0.4) Neg (0.13) Neg Neg Neg Abbreviations: Pos, positive; Neg, negative. 1 ADVIA Centaur HCV (Bayer Healthcare LLC, Diagnostics Division, NY, USA); 2 ARCHITECT anti-hcv assay (Abbott- Laboratory, Wiesbaden, Germany); 3 AxSYM HCV version 3.0 (Abbott Laboratories, IL, USA); 4 Modular Analytics E170 (Roche Diagnostics, Mannheim, Germany); 5 Asan Easy Test HCV (Asan Pharm Co., Whasung, Korea); 6 SD BIOLINE HCV (Standard diagnostics, Yongin, Korea); 7 GENEDIA HCV Rapid (Green Cross MS, Inc., Yongin, Korea). 를확인할수있었으며, 제조된패널의안전성을알아보기위하여실시한단기안정성시험에서도 4 o C에보관하며 4주간의결과값을평가한결과, 양성및음성검체에서모두결과값에변화가없음을확인할수있었다. 2. HBsAg 외부신빙도조사결과 HBsAg 외부신빙도조사물질을발송한 83기관모두에서결과를회신하여회신율은 100% 였다. 외부신빙도조사결과분석은식약청에서제시하는결과값과참여기관이보고한값을참고하여판정기준을정하여분석하였다 (Table 6). 패널 A와 F는 HBsAg 양성검체를희석하여제조한신빙도조사물질이기때문에대부분의기관에서음성을보고하였다고하여음성으로판정하기는어렵고, 일반적인검사법의민감도이하의 HBsAg을포함하고있어음성결과를보고한기관이많았지만 Axsym (Abbott, Illinois, USA) 과 PRISM (Abbott, Illinois, USA) 을사용하고있는기관에서양성을보고하였다 (Table 7). 패널 B와 D는최근개발된검사법에서제시하는민감도인 0.05 IU/mL 이상이므로양성을보고하여야하는물질임에도불구하고참여한기관의 90% 이상에서일치된결과를보이지않아서이번조사에서는결과판정을보류하였는데, 이결과판정을보류한 2검체에서약양성이상의양성결과를보고한기관은각각 70기관 (84%), 42 기관 (51%) 있었다. 특히패널 D의경우동일한기기를사용함에도불구하고양성결과를내는기관과음성결과를내는기관이있었다 (Table 7). 패널 C, E, G, H, I, J는헌혈혈액선별검사를실시하는검사실의경우반드시양성을보고하여야하는물질이어서약양성또는양성으로보고한기관을정답으로평가하였다. 그러나패널 C 와 G에서는각각 1기관씩이회색지대 (grayzone) 와음성으로결과를보고하여오답으로평가하였고, 정답을보고한기관은 81기관 (98%) 이었다. 나머지패널 E, H, I, J에서는모든기관 (100%) 에서양성으로보고하였다. 반드시양성을보고하여야하는물질임에도불구하고음성으로보고한기관 - 205 -
대한수혈학회지 : 제 21 권제 3 호 Table 6. Results of HBsAg proficiency testing testing No. HBsAg panel IU/mL* Numbers of lab Neg Gray WP Pos Intended result 1 A 0.02 79 1 3 Very low positive 2 F 0.03 79 4 under detection limit 3 D 0.07 33 8 8 34 4 B 0.09 11 2 11 59 5 C 0.38 1 1 8 73 6 G 0.46 1 1 7 74 7 I 2.23 2 81 Positive 8 H 2.37 2 81 9 J 11.46 83 10 E 11.52 83 Abbreviations: Pos, positive; Neg, negative; WP, weakly positive; Gray, grayzone. *Average results were calculated from measuring in duplicate for 3 days in 5 laboratories with abbott architect HBsAg, Laboratory using immunochromatography, Laboratory using chemiluminescence immunoassay. Table 7. Results of HBs Ag proficiency testing according to instruments (except all positive answer instruments) HBs Ag panels A B C D F G Result N G P N G WP P N G WP P N G WP P N P N G WP P instrument ADVIA 9 1 1 3 4 1 1 7 5 21 2 9 1 1 7 CENTAUR 1 ARCHITECT 2 41 3 1 4 33 3 38 17 5 3 16 41 2 39 AXSYM 3 2 1 3 3 2 1 2 1 3 E170 4 22 5 3 14 4 18 7 1 2 12 22 4 18 E601 5 2 1 1 2 1 1 2 2 ELECSYS 2010 6 1 1 1 1 1 1 PRISM 7 1 2 3 3 3 3 3 VITROS ECIQ 8 1 1 1 1 1 1 SD (ICA) 9 1 1 1 1 1 1 Total 79 1 3 11 2 11 59 1 1 8 73 33 8 8 34 79 4 1 1 7 74 Abbreviations: P, positive; N, negative; WP, weakly positive; G, grayzone. 1 ADVIA Centaur (Bayer Healthcare LLC, Diagnostics Division, NY, USA); 2 ARCHITECT (Abbott Laboratory, Wiesbaden, Germany); 3 AxSYM (Abbott Laboratories, IL, USA); 4 Modular Analytics E170 (Roche Diagnostics, Mannheim, Germany); 5 Cobas 6000 e601 modular platform (Roche Diagnostics, Mannheim, Germany); 6 Elecsys 2010 (Roche Diagnostics, Mannheim, Germany); 7 Abbott PRISM (Abbott Diagnostics, Wiesbaden, Germany); 8 Ortho Vitros ECiQ (Ortho Diagnostic Systems, NJ, USA); 9 SD HBsAg and Anti-HBs (Standard Diagnostics, Inc., Yongin, Korea). - 206 -
헌혈혈액선별검사외부신빙도조사 (2010) Table 8. Results of anti-hcv proficiency testing testing No. No. of laboratories Negative Positive Intended result HCV-10-01 0 83 Positive HCV-10-02 83 0 Negative HCV-10-03 0 83 Positive HCV-10-04 0 83 Positive HCV-10-05 83 0 Negative 은면역크로마토그래피법을이용하는기관이었고, grayzone을보고한기관은화학발광면역측정법을사용하는기관이었다 (Table 7). 모두양성으로보고된패널은별도의표를작성하지않았다. 3. Anti-HCV 외부신빙도조사결과 Anti-HCV 외부신빙도조사역시물질을발송한 83기관전기관에서결과를회신하여회신율은 100% 였다. 결과분석은검체의특성을참고하여판정기준을정하여분석하였는데, 식약청참조패널로제조한양성물질인 HCV-10-01, -03, -04에서는전기관이양성을보고하였고, 정상인혈청으로만제조한음성물질인 HCV-10-02, -05에서는전기관이음성을보고하여전기관이일치된결과를보였다 (Table 8). Anti-HCV를헌혈혈액선별검사로실시하는검사실에서사용하고있는기기현황을조사하였다 (Table 9). 고찰 본연구는국내에서는처음으로헌혈혈액선별검사를실시하는헌혈혈액원검사실을대상으로실시한외부신빙도조사로서헌혈혈액선별검사에대한품질관리능력및혈액의안전성을평가하고자하였다. 그결과다양한농도로구성된식약청의 HBsAg 표준품패널에서반드시양성을 Table 9. Instruments used for anti-hcv test in donor screening laboratories Instrument Method CLIA ECL MEIA EIA ICA Total 9 2 ARCHITECT 1 38 38 ADVIA 20 20 CENTAUR 2 991 (DXL) 3 1 1 MODULAR 9 E170 4 COBAS E411 5 2 2 AXSYM 6 4 4 QUADRIGA 2 BEFREE 7 BEP 2000 8 1 1 BEP SERIES 9 1 1 DSX 10 1 1 DYNEX 11 1 1 EVOLIS 12 1 1 Manual 1 1 SD 13 1 1 Total 59 11 4 8 1 83 1 ARCHITECT anti-hcv assay (Abbot Laboratory, Wiesbaden, Germany); 2 ADVIA Centaur HCV (Bayer Healthcare LLC, Diagnostics Division, NY, USA); 3 UniCel Dxl (Beckman Coulter, CA, USA); 4 Modular Analytics E170 (Roche Diagnostics, Mannheim, Germany); 5 Cobas e411 modular platform (Roche Diagnostics, Mannheim, Germany); 6 AxSYM HCV version 3.0 (Abbott Laboratories, IL, USA); 7 Quadriga BeFree anti-hcv (Siemens Healthcare diagnotics, IL, USA); 8,9 BEP 2000, BEP Series (Siemens Healthcare diagnotics, IL, USA); 10,11 Dynex Dsx, BEP II (Dynex Technologies, Chantilly, VA. USA); 12 EVOLIS Twin Plus system, Monolisa Anti-HCV Plus Version 2 (Bio-Rad Laboratories, Inc., Marnes La Coquette, France); 13 SD BIOLINE HCV (Standard diagnostics, Yongin, Korea). 보고하여야하는물질임에도불구하고패널 C 와 G에서각각 1기관씩이 grayzone과음성으로결과를보고하여정답을보고한기관은 81기관 (98%) - 207 -
대한수혈학회지 : 제 21 권제 3 호 으로엄격한정확도가요구되는검사임을감안할때부족함이있다고생각되었다. 또한분석민감도근처에있는물질인패널 B와 D에서는약양성이상의양성결과를보고한기관이각각 70기관 (84%), 42기관 (51%) 으로저농도 HBsAg을검출하지못하는기관은상당히많음을알수있었고, 동일한기기와시약을사용하고있음에도불구하고양성과음성이라는전혀다른결과를보고하고있어사용하고있는검사법의민감도를확인하여적절한결과를산출하고있는지점검하여야할것으로생각되었다. HBsAg의경우매우낮은농도까지예민하게측정하는것이필요한바헌혈혈액선별검사를실시하고있는기관의저농도의 HBsAg 검출및품질관리능력은더욱개선되어야할것으로생각된다. 우리나라검사실에서저농도 HBsAg 검출및품질관리능력이취약함은사단법인대한임상검사정도관리협회면역혈청분과위원회에서 2007년실시한외부신빙도조사에서도보고 6) 된바있는데, 2007년에낮은농도의 HBsAg 양성관리물질로판매되는상품화된품질관리물질 ACCURUN 1 Multi-Marker Positive Control (Boston Biomedica Inc. USA) 4100 (Lot No. 110128) 을이용하여외부신빙도조사를실시한결과, 총 610기관중민감도가우수하다고알려진화학발광면역검사법이나전기화학발광면역검사법을사용하고있는기관도각각 29기관 (17%) 과 25기관 (16%) 에서음성을보고하여낮은농도의 HBsAg 검출에대한품질관리에매우문제가있다고지적된바있다. 이때사용한신빙도조사물질은혈청이아니고상품화된품질관리물질이어서낮은농도이기때문에검출하지못한원인도있지만일부에서는상품화된품질관리물질이혈청이아니기때문에발생하는문제도있을것으로분석하였었는데, 본연구에서사용한물질은혈청이기때문에이와 같은문제점은없다고생각되고전반적으로낮은농도의 HBsAg 검출이취약함을알수있었다. 특히우리나라에서는 HBV 감염이흔하고변이형도자주발견되고있는데, HBV 변이형에감염된환자의경우에도야생형 HBV를낮은농도로가지고있을수있으므로일반적인체외진단용의약품으로 HBV 변이형을검출하지못하여도낮은농도로존재하는야생형 HBV의검출이중요한바, 낮은농도의 HBsAg 검출은매우중요하다. Anti-HCV에대한외부신빙도조사결과본연구에서는모두일치된결과를얻었지만, 사단법인대한임상검사정도관리협회면역혈청분과위원회에서 2007년실시한외부신빙도조사에서는낮은농도의 anti-hcv의경우검출을못하는기관이많은것으로보고 6) 된바있어, 헌혈혈액의안전성을위하여낮은농도의 anti-hcv 검출에주의를기울여야할것이다. 따라서헌혈혈액선별검사의품질관리능력을향상시키고지속적인혈액의안전을위하여서는저농도항원 / 항체까지정확하게검출할수있도록다양한유전자형및변이형을포함하는신뢰도가검증된품질관리물질과상품화된품질관리물질이아닌혈청으로부터제조된표준혈청패널이나저역가패널을포함하는품질관리물질을사용하여체계적인품질보증프로그램을운영하여야할것이다. 이와같은다양한농도, 특성을가지는외부신빙도조사물질을제조하기위하여서는지속적인검체수집이요구되는바, 본연구에서는양성인혈액은식약청의표준품과참조패널을이용하였고, 음성인정상인혈액은국가지정연구소재은행인재단법인연구소재중앙센터의혈청검체은행으로부터분양받아사용하였는데, 지속적으로헌혈혈액선별검사외부신빙도조사사업을실시하기위하여서는고위험군바이러스 - 208 -
헌혈혈액선별검사외부신빙도조사 (2010) 를수집하는혈청검체은행의기능이활성화되어야할것으로생각된다. 요약배경 : 헌혈혈액선별검사에대한외부신빙도조사사업을도입하여헌혈혈액선별검사의위양성및위음성사례를최소화함으로써혈액의안전성을높이고헌혈혈액선별검사의품질관리를지속적으로수행할수있는체계적인품질보증프로그램을수립하고자하였다. 방법 : 식약청의 HBsAg 표준품패널과 HCV 참조패널및국가지정연구소재중앙센터혈청검체은행에서제공된정상혈청을사용하여신빙도조사물질을제조하였다. 품질평가를실시한후헌혈혈액선별검사를실시하고있는헌혈혈액원검사실 83기관을대상으로외부신빙도조사를실시하였다. 결과 : 외부신빙도조사물질의품질평가결과제조당시목표한값과모두일치하는결과를얻었다. HBsAg과 anti-hcv 외부신빙도조사물질을발송한 83기관모두에서결과를회신하여회신율은 100% 였다. HBsAg 외부신빙도조사에서는반드시양성을보고하여야하는물질중패널 E, H, I, J에서는모든기관 (100%) 에서양성으로보고하였지만, 패널 C와 G에서는각각 1기관씩이 grayzone과음성으로결과를보고하였다. 그리고패널 B와 D에서는약양성이상의양성결과를보고한기관이각각 70기관 (84%), 42기관 (51%) 으로, 저농도 HBsAg을검출하지못하는기관은상당히많음을알수있었다. Anti-HCV 외부신빙도조사에서는발송한모든물질에대하여전기관에서일치된결과를보였다. 결론 : 헌혈혈액선별검사를실시하고있는기관들에서저농도의 HBsAg과 anti-hcv를오류없 이검출해내었으며그렇지못했던일부기관의저농도 HBsAg 검출및품질관리능력은더욱개선되어야할것으로생각된다. 지속적인헌혈혈액선별검사의품질관리를위하여서는저농도항원 / 항체까지정확하게검출할수있도록다양한유전자형및변이형을포함하는신뢰도가검증된품질관리물질을사용하여체계적인품질보증프로그램을운영하여야할것이다. 참고문헌 1. Oh DJ, Cho YJ, Kwon SY, Cho NS, Kwon SW, Um TH, et al. A proposal for developing a national quality assurance program for donor bloodassays. Korean J Blood Transfus 2008;19: 197-206 2. Cha YJ. The results of external proficiency tests to prevent transfusion-transmitted virus infection: there is a need for a quality assurance program for donor screening tests to prevent blood-borne virus infections. Korean J Blood Transfus 2010;21:25-35 3. Hou J, Wang Z, Cheng J, Lin Y, Lau GK, Sun J, et al. Prevalence of naturally occurring surface gene variants of hepatitis B virus in nonimmunized surface antigen-negative Chinese carriers. Hepatology 2001;34:1027-34 4. Levicnik-Stezinar S. Hepatitis B surface antigen escape mutant in a first time blood donor potentially missed by a routine screening assay. Clin Lab 2004;50:49-51 5.Korea Center for Disease Control and Prevention, hemovigilance team, A Proposal for Developing a National Quality Assurance Program for Donor Blood assays, Korea center for disease control, 2009;22-6 6. Cha YJ, Kwon SY, Kim TY, Kim JR, Kim HS, Park MH, et al. Annual report on external quality assessment in immunoserology in Korea (2007). J Lab Med Qual Assur J Lab Med Qual Assur 2008;30:49-74 - 209 -