Letters to the Editor the appropriateness of discarding blood units with ALT exceeding the upper limit of normal.
Second-generation anti-HCV tests and surrogate markers in volunteer blood donors
NICOLASBURINDES R O Z I E R S , ~ OLIVIER NASR, MD Cenhe Departmental de Transfusion Sanguine CHRU 5 rue Hoche 3000 Nimes, France
To the Editor: The correlation between the presence of antibodies to hepatitis C virus (anti-HCV) and antibodies to hepatitis B core antigen (anti-KBc) or increased alanine aminotransferase (ALT) level is reported to be low.’*2However, such comparisonswere obtained by using first-generation enzyme-linked immunosorbent assays (ELISAs) and the c-100 antigen. We report our findings (Table 1) in 10,736 unselected consecutive volunteer blood donors screened by the second-generationELISA (Ortho Diagnostic Systems, Raritan, NJ) and a four-antigen recombinant immunoblot assay (4-RIBA) (Chiron, Emeryville, CA). Seventy (0.6%) of 10,736 were repeatedly positive for antiHCV on ELISA. Of those 70 sera, 19 (27%) had a specimen absorbance-to-cutoff ratio less than 4. Seventeen of these 19 sera were negative on the 4-RIBA, 1 was positive (reactive to the c22-3 and c33c bands, ELISA ratio 3.8), and 1 was indeterminate (reactive to the c22-3 band only, ELISA ratio 1.7). Twenty-eight of the 51 samples with ELISA ratio higher than 4 were selected at random and were tested by 4-RIBA. Twentytwo (79%) of the 28 reacted (13 with 3 or 4 antigens, 9 only with Q3c and c22-3 antigens), and 6 (21%) were indeterminate (5 reactive to the c22-3 band, 1 to c33c). ALT levels were measured by spectrophotometry in optimized conditions at 37°C. The upper limit of normal was 39 IU per L. The mean ALT level was only significantly raised in the group with high ELISA ratio (>4): 35.5 f 21.5 IU versus 11.1 IU per L in normal blood donors ( p ~ l o - ~ ) . 16.9 Twenty-two (43.1%) of 51 sera had ALT levels >39 IU per L, compared with 3.5 percent in the normal population. The mean ALT level was also higher in 4-RIBA-positive sera (44.0 f 20.9 IU/L) than in 4-RIBA-indeterminate sera (15.1 f 14.3 IWL). Twelve (52%) of 23 4-RIBA-positive sera had ALT >39 IU per L, versus 1 (14%) of 7 4-RIBA-indeterminatesera (Fischer’s exact test, p = 0.079). Only 5 (9.8%) of 51 anti-HCV ELISA-positiveblood donors with high ELISA ratio had anti-HBc (with raised ALT in 2 out of 5 cases), as compared with 2.1 percent in the normal population (p>0.3). These data suggest a low effectiveness of antiHBc screening for the prevention of non-A,non-B hepatitis in our population. Finally, about 50 percent of 4-RIBA-positive samples (a result that is closely associated with non-A,non-B hepatitis transmission)’ had raised ALT values. Moreover, since ALT screening may detect infective blood units during the delay between infection and seroconversion,* these results confirm
References 1. Janot C, Couroud AM, Maniez M. Antibodies to hepatitis C virus in French blood donors (letter). Lancet 1989;2796-7. 2. Ohto H, Nomura H, Ohmura K, Ishijima A, Okazaki S. Low werlap between anti-HCV and anti-HBc in Japanese (letter). Transfusion 1991;31:88-9. 3. Van der Poel CL,Cuypers HTM, Reesink HW,et al. Confirmation of hepatitis C virus infection by new four-antigen recombinant immunoblot assay. Lancet 1991;337:317-9. 4. Alter HJ, Purcell RH, Shih JW,et al. Detection of antibodies to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A,non-B hepatitis N Engl J Med 1989;321: 1494-SOO.
*
What is a blood group antigen? To the Editor: An antigen is defined either as a molecule that generates an immune response or as a molecule that reacts with antibodies (or primed T cells).’ To quote Roitt,’ “A man cannot be a husband without a wife and a molecule cannot be an antigen without a corresponding antiserum or antibody (or T-cell receptor).” Blood group antigens are determinants in the blood defined by antibodies, although the term is generally restricted to antigens on the red cell surface. A recent article in the Journal of Clinical Investigation2described the gene encoding the DP blood group antigen and the rare allele to that gene. The purpose of this letter is to suggest that blood group terminology be restricted to blood group antigens defined by specific antibodies and that it not be used to name variant glycoproteins defined by DNA sequencing or by restriction fragment length polymorphisms.
Table 1. Results of surrogate markers in blood donors
c0.5
Number tested ALT (mean 2 SD) ALT >39 IUR Anti-HBc-positive
10,577 16.9 2 11.1 372 (3.5%) 218 (2.1%)
Anti-HCV ELISA (optical density:cutoff ratio) 0.5-1 1-4 89 17.1 2 10.9 5 (5.7%) 2 (2.2%)
492
19 16.7 f 7.3 0 (0.0%) 0 (0.0%)
>4 51 35.5 2 21.5 22 (43.1%) 5 (9.8%)
Second-generation anti-HCV tests and surrogate markers in volunteer blood donors
NICOLASBURINDES R O Z I E R S , ~ OLIVIER NASR, MD Cenhe Departmental de Transfusion Sanguine CHRU 5 rue Hoche 3000 Nimes, France
To the Editor: The correlation between the presence of antibodies to hepatitis C virus (anti-HCV) and antibodies to hepatitis B core antigen (anti-KBc) or increased alanine aminotransferase (ALT) level is reported to be low.’*2However, such comparisonswere obtained by using first-generation enzyme-linked immunosorbent assays (ELISAs) and the c-100 antigen. We report our findings (Table 1) in 10,736 unselected consecutive volunteer blood donors screened by the second-generationELISA (Ortho Diagnostic Systems, Raritan, NJ) and a four-antigen recombinant immunoblot assay (4-RIBA) (Chiron, Emeryville, CA). Seventy (0.6%) of 10,736 were repeatedly positive for antiHCV on ELISA. Of those 70 sera, 19 (27%) had a specimen absorbance-to-cutoff ratio less than 4. Seventeen of these 19 sera were negative on the 4-RIBA, 1 was positive (reactive to the c22-3 and c33c bands, ELISA ratio 3.8), and 1 was indeterminate (reactive to the c22-3 band only, ELISA ratio 1.7). Twenty-eight of the 51 samples with ELISA ratio higher than 4 were selected at random and were tested by 4-RIBA. Twentytwo (79%) of the 28 reacted (13 with 3 or 4 antigens, 9 only with Q3c and c22-3 antigens), and 6 (21%) were indeterminate (5 reactive to the c22-3 band, 1 to c33c). ALT levels were measured by spectrophotometry in optimized conditions at 37°C. The upper limit of normal was 39 IU per L. The mean ALT level was only significantly raised in the group with high ELISA ratio (>4): 35.5 f 21.5 IU versus 11.1 IU per L in normal blood donors ( p ~ l o - ~ ) . 16.9 Twenty-two (43.1%) of 51 sera had ALT levels >39 IU per L, compared with 3.5 percent in the normal population. The mean ALT level was also higher in 4-RIBA-positive sera (44.0 f 20.9 IU/L) than in 4-RIBA-indeterminate sera (15.1 f 14.3 IWL). Twelve (52%) of 23 4-RIBA-positive sera had ALT >39 IU per L, versus 1 (14%) of 7 4-RIBA-indeterminatesera (Fischer’s exact test, p = 0.079). Only 5 (9.8%) of 51 anti-HCV ELISA-positiveblood donors with high ELISA ratio had anti-HBc (with raised ALT in 2 out of 5 cases), as compared with 2.1 percent in the normal population (p>0.3). These data suggest a low effectiveness of antiHBc screening for the prevention of non-A,non-B hepatitis in our population. Finally, about 50 percent of 4-RIBA-positive samples (a result that is closely associated with non-A,non-B hepatitis transmission)’ had raised ALT values. Moreover, since ALT screening may detect infective blood units during the delay between infection and seroconversion,* these results confirm
References 1. Janot C, Couroud AM, Maniez M. Antibodies to hepatitis C virus in French blood donors (letter). Lancet 1989;2796-7. 2. Ohto H, Nomura H, Ohmura K, Ishijima A, Okazaki S. Low werlap between anti-HCV and anti-HBc in Japanese (letter). Transfusion 1991;31:88-9. 3. Van der Poel CL,Cuypers HTM, Reesink HW,et al. Confirmation of hepatitis C virus infection by new four-antigen recombinant immunoblot assay. Lancet 1991;337:317-9. 4. Alter HJ, Purcell RH, Shih JW,et al. Detection of antibodies to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A,non-B hepatitis N Engl J Med 1989;321: 1494-SOO.
*
What is a blood group antigen? To the Editor: An antigen is defined either as a molecule that generates an immune response or as a molecule that reacts with antibodies (or primed T cells).’ To quote Roitt,’ “A man cannot be a husband without a wife and a molecule cannot be an antigen without a corresponding antiserum or antibody (or T-cell receptor).” Blood group antigens are determinants in the blood defined by antibodies, although the term is generally restricted to antigens on the red cell surface. A recent article in the Journal of Clinical Investigation2described the gene encoding the DP blood group antigen and the rare allele to that gene. The purpose of this letter is to suggest that blood group terminology be restricted to blood group antigens defined by specific antibodies and that it not be used to name variant glycoproteins defined by DNA sequencing or by restriction fragment length polymorphisms.
Table 1. Results of surrogate markers in blood donors
c0.5
Number tested ALT (mean 2 SD) ALT >39 IUR Anti-HBc-positive
10,577 16.9 2 11.1 372 (3.5%) 218 (2.1%)
Anti-HCV ELISA (optical density:cutoff ratio) 0.5-1 1-4 89 17.1 2 10.9 5 (5.7%) 2 (2.2%)
492
19 16.7 f 7.3 0 (0.0%) 0 (0.0%)
>4 51 35.5 2 21.5 22 (43.1%) 5 (9.8%)
