Are asymptomatic blood donors with indeterminate results on RIBA 3 really able to transmit HCV infection?

Journal of Hepatology 1995, 23 35%360 Pt mted tn Denrnatk All rzghts reso ved

Copytight © Journalof Hepatology 1995

Journal of Hepatology ISSN 0168-8278

Correspondence

Are asymptomatic blood donors with indeterminate results on RIBA 3 really able to transmit HCV infection? To the Editor

Since the introduction in 1989 (1) of the serological tests to diagnose infection by the hepatitis C virus (HCV), it has become apparent that HCV is the mare cause of most cases of post-transfusion-associated hepatitis Although the introduction of screening tests for anti-HCV is considered as a giant leap In the prevention of HCV infection, they still have some limitations and serious problems concerning diagnosis One of these is the ELISA-reactave samples with an '~indetermlnate" result (reactive only for one HCV antibody) on lmmunoblot tests such as RIBA According to test interpretation criteria, they cannot be considered posltlve but are not necessarily negative With the help of the polymerase chain reaction (PCR), the RNA genome of the HCV can be detected in serum In spite of the limitations of this technique (2), it currently provides the most accurate data about the presence of the Infectious agent in any sample. A significant proportion (1 4%) of our blood donations are repeatedly reactive wlth a third-generation HCV ELISA (Ortho HCV 3 0 ELISA test system) and 15% of them yield indeterminate results in a supplementary immunoblot assay (Chlron RIBA HCV test system 3 0) During a period of at least 2 years, we followed the clinical evolution of 13 such blood donors and tested their serum samples by PCR to evaluate the meaning of single reactwlty to the c22 peptlde or c33c recombinant antigen with RIBA 3 0 The male/female ratio was 8/5 All donors but two had normal levels of alamne aminotransferase (Table 1) Only three of them had received a single blood transfusion 11, 13 and 5 years, respectively, before this study Three were reactive to the C33c antigen and 10 to the c22 peptide One subject reactive to C33c became negative after 28 months, but the ELISA ratio remained > 1. Interestingly, no additional reactivity to other bands appeared in the follow up in any of these subjects HCV RNA was present in samples of two patients (both reactive to the core protein) at least, over 24 months No correlation was evident between vlraemaa and ELISA ratio in serum samples

TABLE 1 Patient data SubJects

Reactivity

Ehsa ratio

Polymerase chain reaction

1 2*# 3 4 5 6 7* 8 9 10# 11 12# 13

c33c c33c c33c c22 c22 c22 c22 c22 c22 c22 c22 c22 c22

>5 >3 >2 >3 >3 >3 >5 >5 >5 >5 >5 >3 >5

Neg Neg Neg Neg Neg Pos Neg Neg Pos Neg Neg Neg Neg

* Elevated alamne amlnotransferase # Received transfusion

The meaning of a single reactivity on RIBA is controversial Negative PCR results but serological evidence of HCV infection represent residual antibodies to remote infection This is true specially when considering core antibodies (3). Some authors suggest that the presence of antibodies to c22 alone might be considered as false-positive results because of the low rate of PCR reactivity observed, the absence of surrogate markers and the lack of appearance of other reactivity over time (4) On the other hand, a large number of individuals with Indeterminate results on RIBA 3 are really infected since the number of PCR positive results observed is as high as 58% (5) In asymptomatlc blood donors, the PCR positlvlty is lower than in other groups of patients (6). In our population, 2 of 13 blood donors with indeterminate results are really infected with HCV and therefore, they can efficiently transmit the infectious agent Although appropriate counselling of donors is very difficult, they must be told about the possibility of being infected. We conclude that an indeterminate result on RIBA in asymptomatlc blood donors requires the investigation of hver disease and the determination of HCV RNA by PCR to differentiate infected Individuals with the potential to transmit the disease from those with remote infection or even those who present cross-reactivity in serological HCV tests. Maria L Mateos and Elena Lasa 1 Departments o f Microbiology and 1Hematology Hospltal Ram6n y Cajal, UmvetsMad de Alcald de Henares, Madrid, Spare

References 1. Kuo G, Choo L, Alter H J, Gltmck GL, Redeker AG, Purcell RH, Miyamura T, Dlenstag JL, Alter M J, Stevens CE, Tegtmeier GE, Bonano E Colombo M, Lee WS, Kuo C, Berger K, Shuster JR, Overby LR, Bradley DW, Houghton M An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis Science 1989, 244 3 6 2 4 2. Zaajer HL, Cuypers HTM, Reesink HW, Wmkel IN, Gerken G, Lehe PN. Rehabfllty of polymerase chain reaction for detection of hepatitis C virus Lancet 1993; 341. 7 2 2 4 3 Manzini P, Calvo PL, Lorena A, Cerchler A, Plantmo P, Vallaun R D'Antlco S, Sympson B, Klarmann R, Schlffer M, Callea E Verme G, Bonmo E Brunetto M Asymptomatlc anti-HCV seroposltlve subjects include patients with chronic active hepatitis and individuals with normal liver, can we distinguish them? J Hepatol 1994, 21 136-7 4 ToNer LH, Busch MP, Wilber J, Danello R, Quan S, Pohto A, Kochesky R, Bahl C, Nelles M, Lee SR Evaluation of indeterminate c22-3 reactivity in blood donors Transfusion 1994; 34. 1304. 5. Lamorll J, Lunel E Laurent Ping R Defer C, Loiseau P, Lefrere J J, Pawlotsky JM, Marcelhn P, Bouchardeau E Bogard M Indeterminate thwd-generatlon recombinant lmmunoblot assay In hepatitis C virus Infection. J Hepatol 1994, 21. 1334 6 Garson JA, Clewley JP, Simmonds R Hepatms C vlraemma in Umted Kingdom blood donors. Vox Sang 1992, 62. 218-23

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