Jpn. J. Infect. Dis., 55, 33‑36, 2002

ReportRe‑Evaluation of HCV Ab Detection Kits Approved fわr Marketing in Japan

Committeefor Evaluation of In Vitro Diagnostic Devices,
National Institute of Infectious Diseases② HCVAb low titerpanel: PIⅣ105 (15 samples) purchased

INTRODUC TION

from BBI.

As of2001, the Japanese Ministry of Health and Welfare③ HCV Ab mixed titer panel: Twenty HCV Ab‑positive

sera kept at NIID.

(Ministry ofHealth, Labour and Welfare at present; MHLW)
has approved approximately 30 diagnostic kits for detection of④ HCV Ab seroconversion panels (genotype lb): PHV‑

antibodies against various epitopes of HCV (Hepatitis C virus)

906 (7 samples) and PHV‑907 (7 samples) purchased fromin clinical settlngS. All orthem are commercially available inBBI. Sample numbers 1 to 7 indicate the order ofbleedings

Japan. In order to provide medical personnel with up‑to‑dateduring the course of infection.

information on each kit's characteristics, such as its sensitivity

The above 68 samples were analyzed independently twiceand specificity, ln Order to enable them to choose approprlate

uslng each test kit, and the results are shown in Table 2. The

HCV Ab (antibody) detection kits, National Institute of
Infectious Diseases (NIID), according to the guidance of theresults of the lst generation kit, the Core‑Ab detection kits

MHLW, has re‑evaluated the diagnostic kits provided byreport as references, although they are not intended formanufacturers/distributors. The present reports are the results

diagnostic purposes. ln the result chart, "generationH and"prlnCiple/procedure" of the kits were indicated so that one(3 kits), and the RIBA3 kit were included in the presentof the re‑evaluation of HCV Ab detection kits.

can compare the results obtained by uslng different kits within
the same category. The results obtained丘.om the RIBA3 kit

METHODS

were also included in the charts, which would be useful for

TTCV Ab detection kits evaluated in this study (Table 1)
In this study, we categorized HCV Ab detection kits into

interpretation of the antlgen SPeCificities detected by eachkit. The RIBA3 results are expressed as intensities orbands

the f0日Owlng four groups according to prlnCiple/procedure(levels 1 to 4) detected on the test strips. …+/‑" represents aused; (A) IRMA (Immunoradiometric assay), (良) Immuno‑visible band with an intensity ofless than level 1. Empty boxes

chroratography, (C) Agglutination/aggregation (including

indicate that no visible band was detected. Interpretation ofPassive Hemagglutination Test, Particle Agglutination Test,Latex Photometric lmmunoassay, and Particle Agglutination

the RIBA3 results is as fわllows: REACTIVE ‑ level 1 orMediated lmmunoassay, designated as PHA, PA, LPIA, andPAMIA, respectively), (D) EIA (Enzyme lmmunoassay), (E)DETERMINATE ‑ Bands of level 1 or greater reactivlty are

greater reactivlty tO any two HCV recombinant antIgens, IN‑

present but the patterndoes not meet the criteria for REACI
TIVE, and NONREACTIVE ‑ No bands of level 1 or greater

CLEIA/CLIA (Chemiluminescent [enzyme] immunoassay),reactivity are present.

(F) EV‑FIA (Evanescent wavefluoro immunoassay), and (G)RIBA (Immunoblot). These kits were also categorized into
four groups according to another criterion, i.e., the HCVRESUIXS AND DISCUSSION

antlgenS utilized f♭r detection of anti‑HCV Ab, namely, Core

Listed in Table 1 are the product names, manufactures/Results of each of the 25 kits, including three core Ab‑
detection kits (Nos. 1, 2, and 3), one lst generation kit (No.
4), and one RIBA3 kit (No. 25), are shown in Table 2. As awhole, there are no noticeable differences in sensitivities as

distributors, and assay objects.

well as specificities between the 2nd and 3rd generation kits.

Ab detection kit, l st generation kit (NS3‑NS4 protein), 2mdgeneration kit (NS3‑NS4 protein + Core Protein), and 3rdgeneration kit (NS3‑NS4 proteh + Core proteln + NS5 prot血).

In other words, we could not obtain any evidence indicatlng

Test Procedurethat the 3rd generation kits are more sensitive than the 2md

Test samples utilized in the present re‑evaluation tests weregeneration kits. These results support the previous suggestionthat the inclusion of the NS5 antlgen in the 3rd generation

as fわllows:① Negative samples‥ Eighteen HCV Ab‑negative s?ra,kits does not improve the specificities/sensitivities of the kits

which have been utilized at NIID for in‑house qualificatlOntests,and one HCV Ab‑negative sample (Acctmn 1 multi‑marker(Vemelen, K. et al. [1994]: Lancet, 343, 853; Goffin, E. et al.
[ 1 994] : Lancet, 343, 853‑854). There are substantial differences

negative control serum) purchased from Boston Biomedica

in the sensitivities among kits within the same generation. Itlnc. ([BBI], West Bridgewater, Mass., USA).

is likely that variation of some HCV antlgenS, Other than theNS5 in the 3rd generation kits,might be responsible for such

* Members of the Committee for Evaluation of In Vitro Diagnostic

differences･ For example, when the seroconversion panel

Devices are listed in the Appendix.

PHV‑906 was tested, the kit No.13 judged all the samples
negative, although the same samples were judged positive by

Corresponding author: Toshiaki Mizuochi, Department or

the kits No･10 and No･1 1, which belong to the same category
as the kit No. 13 (Table 2). On the other hand, when the PHV1907 panel was tested, the kit No. 13 seemed to be moresensitive than the kits No. 10 and No.ll (Table 2). These

Bacterial and Blood Products, National Institute of lnfTectious
Diseases, Toyama 1‑23‑1 , Shinjuku‑ku, Tokyo 162‑8640, Japan.
¶∋1:十81‑3‑5285‑1111 ext. 2324, Fax: +81‑3‑5285‑1150, E‑mail:miz@nih.go.jp

33

Table 1(A) Core‑Ab detection kit

No. 疲
123

ﾖR

Manufacturer/Distributor 磐WF

微'F

d6&Rﾔ

ﾔ疋U5Bт5d6

班Vﾖ&T&ﾅ$ﾔ

FW7B"乃ﾈuE4Vﾇ6S

B

DetectionofHCVAbin

MitsubishiKagakuMedical,Ⅰnc.

滅$ﾔsemm/plasma

MEDICAL&B10LOGICAL LABORATORIESCO.,LTD. 嚢uD'F

d6&Rﾔ

"

FUJⅠREB101NC.

ﾄT

semm/plasma

4ﾄserum/plasma(B) lst generation kit

No,疲

ﾖR

Manufbcturer/Distributor

4 微'Fdﾔ

FW7B

磐WF

B

DetectionofHCVAbin

MitsubishiKagakuMedica1,1nc. 滅$ﾔ

senlm/plasma(C) 2nd generation kit

No. 疲
5ﾖR

Manufacturer/Distributor 磐WF

EDe

$$

6U$

7&襯vV觚&HuD

微'F

ﾔ又5bd8 班Vﾖ%

9$$
粕ﾗED

dTbﾔ

"GDbll

5番&&

GGD

12V6ｲ臙ﾔd3S$ｶ

膝&躔613

妊UDT:*$

14$4DT5B

WF

serum/plasma

FUJⅠREB101NC.

F柳bserum/plasma

4ﾄserum/plasma
semm/plasma

乃serum/plasma

Ⅰnterna.tionalRcagentsCo叩Oration

AZWELLlnc.

乃

DAINABOTC0.,1JD.

serum/plasma

嚢uD

嚢uD

DAINABOTCO"LTD.

ｷW6蹤椿ﾆﾄ5b

ﾄT

DAINABOTCO.,LTD.

DAⅠNABOTCO.,ⅠJD,

b

DetectionofHCVAbin

serum/plasma

EIKENCHEMICALCO.,LTD.

&襯v6觚&&&B

DAINABOTCO.,LTD.

FUJⅠREB101NC.

FW7Fﾆﾄ

B$V霧V

10F柳

乃

senlm/plasma

serum/plasma
ﾄT

4ﾆﾄ

serum/plasma(D) 3rd generation kit

No. 疲ﾖR

Manufacturer/Distributor 磐WF

15ｴ44U$V

16T

17 微'F18窒F19 微'F

$$

21

2223&

廼d

班S

FW7Bd(uE$ﾔ

FW7FﾆﾇB

25E$

DU5E5&T

DU5D2竄蹤綴d$DTﾒ"

ﾔ27G&ﾖVE4fR

DAINAB(ーTCO.,LTD.
ｴ

OAINABOTCO.,LTD.

B

76

着6ﾄb

滅$ﾔ

廼D

senJltt/Plasma

廼D

sen1111/P一asma

廼bﾔgD

ﾄT

serum/plasma

sertlm/plaslTla

RochcDiagnostjcsK.K.

'F

Senlm

serultl/Plasma

OrthOClinicalDiagnosticsK̲K̲ 廼D

NISSUⅠPH∧RMACEUTICAL

ﾆﾖﾗV蔕&ﾆsen】m/plasma

ﾘuD

MitsubishiKagakuMedica1,Tnc.

v友Х諞

dXb

DetectionofHCVAbjll
FMitsubishiKagakuMedjcal,Tnc, 版

Vﾇ6S
ﾆﾆB

免ﾖﾗV踐6SYSMEXCORPORATtON

$ﾅ

EDVﾄ

EE

MIZUHOMEDYd46

$$

24"

ﾖﾆﾄ5fﾈuDU

c2趾TﾇE42(ーd4ﾄsenlm/plasma

senlItl/plaslma

FUJIREBlOINC.

011hoClinicalDiagnosticsK.K.

5

ﾄX自J｢

4ﾄuC

B

GFﾗV蔕&ﾆSerum

senlm/plasma

results may indicate that the kit No.13 is 1110re Sensitive indetectlng anti‑Core Ab but less sensitive in detectlng the NS3/NS4 antlgenS than the kits N0. 10 and No.ll. 1t is suggested

the results obtained by a slngle HCV detection kit. SerologlCal

that kits within the same category differ in their ability for

judgment.

confirmatory tests such as the RIBA3 and/or tests for detec‑tion ofHCV virus RNA should be utilized to obtain the final

detectlng HCV‑related Ab, depending on the qualitative as

well as quantitative differences in their utilization ofHCV
antlgenS aS ePltOPeS. This kind of difference lS qulte apparent
when the seroconversion panel PHV‑906, whose donor did not
elicit the anti‑Core Ab, was tested. The results indicate thatLegellds to nble 2.
Nulnbers 1 through 25 at the top of the charts indicate the scrial nulllbersof the kits tcsted, and coITeSPOnd to the numbers appearlng in Table 1.

there are substantial differences in capabilities of detectlng

Symbols:

the NS reglOn antlgenS among Various kits.

□: Nega.live.

lr: positlVe in duplicate assays.
□‥ positive in one assay and meg?tive in the other.

CONCLUSION

E]: +/‑ in on? assay and negative ln the othcr･
E] : lndetermlnate.

Since the HCV Ab detection kits available in Japan have

区卜Not done.
Princlplc/procedure orthe kits are indicated as alphabets:

in general been developed rather recently, they appear to beindistinguishable斤om each other with respect to their quality,a : IRMA (lmlnunOradiometric assay)

whereas several kits, such as No. 1 5 (imunochromatography),b : 1mmunochromatographyc: Agglutination/aggregation (PIIA / P^ / LPIA / PAMIA)

seem to have room fわr improvement. As already mentioned

d: EIA (Enzyme imlllu110aSSay)e: CLEIA/CLIA (Chenlilumjnescent lenzynle] ilTmlunOaSSay)
r: EV‑FIA (Evanescent wave nuoro illlnlunOaSSay)in the report regarding the re‑evaluation of HBsAg detection
kits, diagnosis ofHCV infection should not rely solely upon34

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910.3r^%4424釘十/̲Toshitada Takemori (Chai叩erSOn), Hiroshi Yoshikura,ACKNOWLEDGMENTS

Takeshi Kurata, Toshio Kishimoto, Ichiro Kurane, Nobuhiko

We are grateful to the manufacturers/distributors of HCVOkabe, Katsutoshi Komuro, Masahiro Sakaguchi, Tetsuro

Ab detection kits for their helpful cooperation; to Drs. K.
Ohnishi, K. Ootake, Y. Takahashi, S.‑I. Hashimoto, and Y.
Yokota (Dept. of Immunology, NIID) for their technicalSuzuki, Masato Tashiro, Shu‑ichi Nakayama, Toshiaki
Mizuochi, Tatsuo Miyamura, Namiko Yoshihara, and Haruo
Watanabe.

support; and to Ms. M. Tsujimoto (Dept. of lmmunology,
This article will appear in Japanese in the official Journal

NIID) for clerical assistance,of Japanese Society of Laboratory Medicine (Rinshobyouri)
and the Japanese Joumal of Medical Technology (Igakukensa)
in order to disseminate this infbmation to the public.

APIIENDIX
The members of the committee are as fわllows:36