Experience with a transfusion recipient education program about hepatitis C

Shortly after test kits for antibodies to the hepatitis C virus (HCV) were licensed in May of 1990, our medical community undertook a public education program encouraging previous transfusion recipients to see their physicians about the wisdom of being tested for anti-HCV. In response, 1034 samples were received for testing. All samples repeatably reactive (RR) with anti-HCV enzyme-linked immunoassay (EIA) were tested further with a research recombinant immunoblot assay (RIBA). Overall, 76 of the 1034 (7.4%) recipient samples were RR and 64 of these (84.2%) were reactive with RIBA. Recipients transfused prior to surrogate testing (alanine aminotransferase [ALT] and anti-hepatitis B core [anti-HBc]) in 1986 showed a 8.6 percent reactivity with RIBA and those transfused after surrogate testing showed a 4.8 percent reactivity, a 44 percent reduction. Of the 57 recipient samples reactive with RIBA and suitable for assay, 11 (19.3%) had an elevated ALT. Among 76 randomly selected blood donors with RR EIAs studied for comparison with recipients, 20 (26.3%) were reactive with RIBA, 9 of which had an abnormal surrogate test that would have disqualified them. ALT concentrations were abnormal in 6 (30%) of the donors who were reactive on RIBA. We conclude that an education program that encourages previous transfusion recipients to seek medical advice about anti-HCV testing is practical from the standpoint of the blood center. We believe more widespread implementation of similar programs should be considered.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevalence of hepatitis C virus and genotype distribution in an Australian volunteer blood donor population

BACKGROUND: This study was undertaken to assess the prevalence of hepatitis C virus (HCV) antibody and RNA in first-time blood donors and to examine the HCV genotype distribution. STUDY DESIGN AND METHODS: A third-generation enzyme-linked immunosorbent assay (ELISA) was used to screen 34,725 donors for HCV antibodies. Donors who were repeatably reactive were tested in two immunoblot assays-a second-generation and a third-generation recombinant immunoblot assay-as well as by a polymerase chain reaction (PCR) assay. PCR-positive donors were genotyped. All samples were screened for alanine aminotransferase levels. RESULTS: The ELISA repeat reactivity rate was 0.55 percent. PCR testing showed that 69 (38%) of the 183 ELISA-reactive samples contained HCV RNA. The third-generation recombinant immunoblot assay identified all 69 viremic samples as antibody positive; however, only 63 tested positive on the second-generation immunoblot. The remaining six PCR-positive donors tested antibody-indeterminate to the core peptide. All six of these donors had HCV subtype 3a infections. Genotype distribution among 58 samples showed that 34 were type 1, of which 22 could be further subtyped as 1a (16) and 1b (6); 2 were 2a; 5 were 2b; and 17 were subtyped as 3a. Donors infected with 2b and 3a had reduced antibody reactivity to the NS4 and NS3 peptides only on the second-generation immunoblot. CONCLUSION: The prevalence of confirmed anti-HCV and viral RNA in new donors is 0.29 and 0.2 percent, respectively. The third-generation recombinant immunoblot assay was more sensitive than the second-generation immunoblot assay in detecting 2b and 3a HCV subtypes. The inclusion of the NS5 peptide in the third- generation recombinant immunoblot did not result in positive tests in any additional donors. Rather, the improvement was due to the increased detection of NS3 and, to a lesser extent, NS4 antibodies. Subtypes 1a and 3a were most prevalent in this population.     

Epidemiology of hepatitis C virus: a study of male blood donors in Saudi Arabia

BACKGROUND: Few epidemiologic reports on the prevalence of hepatitis C in Saudi blood donors have been published. STUDY DESIGN AND METHODS: Men (of several nationalities) donating blood at the King Khalid National Guard Hospital (Jeddah, Saudi Arabia) were randomly selected (n = 744) for this study examining the prevalence of hepatitis C virus (HCV) in the local donor population, the relationship of antibody to HCV (anti-HCV) to the surrogate markers alanine aminotransferase (ALT) and antibody to hepatitis B core antigen (anti-HBc), and the effect of the use of these markers on the discard rate. RESULTS: The prevalence of anti-HCV in the group examined was 3.2 percent (24/744), with a significantly high prevalence of 24.5 percent (12/49) in donors who were Egyptian (p < 0.0001). Exclusion of this group would lower the prevalence to 1.7 percent (12/695). Anti-HCV prevalence peaked in the group aged 30 to 39, and a significant relationship was found between anti-HCV and ALT level > 65 U/L (p < 0.0001). There was no significant relationship between anti-HCV and anti-HBc (p = 0.66). The prevalence of anti-HCV in the Saudis studied was 1.7 percent (9/528). The prevalence of anti-HCV in non-Bedouin Saudis was significantly greater than that in Bedouin Saudis (7/165 [4.2%] vs. 2/363 [0.5%]; p < 0.01). The prevalence of anti-HBc was found to be 28.7 percent (214/744). The use of elevated ALT (> 90 U/L) and anti-HBc as surrogate markers would increase the current discard rate (8.3%) by 2.8 and 23.8 percent, respectively. CONCLUSION: These findings demonstrate the practical difficulties of using anti-HBc as a surrogate marker for hepatitis C in areas endemic for hepatitis B virus.     

Infective, chronic carriers of Hepatitis C virus among blood donors with no history of clinical hepatitis

Summary. We investigated the infectivity of three hepatitis C virus antibody (anti-HCV) positive blood donors with either hepatitis B core antibodies (anti-HBc) (Nos 1 and 2) or raised alanine aminotransferase (ALT) (No. 3). The 57 recipients of blood products from these donors during the period 1971–1990 were identified and the living 23 were tested for anti-HCV. Among these, 11 out of 14 (78%) recipients from Nos 1 and 2, and 1 out of 9 (11 %) recipients from No. 3 were anti-HCV positive. The former donors had high titres of anti-C 100-3 and high rating scores in the HCV recombinant immunoblot assay (RIBA). They were evidently infective, chronic carriers of HCV but had no clinical signs or medical history of hepatitis. The latter donor had low titres of anti-C100-3 and a low RIBA rating score. She had clinical signs of chronic hepatitis and persistently elevated ALT, but only one of her recipients was anti-HCV positive.     

The use of a recombinant immunoblot assay in the interpretation of anti- hepatitis C virus reactivity among prospectively followed patients, implicated donors, and random donors

Samples from prospectively followed recipients, their respective donors, and a cohort of random donors were used to evaluate the specificity and efficacy of a recombinant immunoblot assay (RIBA) as an adjunct to anti-hepatitis C virus (HCV) testing by enzyme immunoassay (EIA). RIBA reacted (RIBA+) in 100 percent of patients who developed hepatitis associated with anti-HCV seroconversion documented by EIA and in 100 percent of the EIA-positive (EIA+) donors implicated in these cases. In contrast, RIBA reacted in none of 10 recipients who were EIA+ but did not develop hepatitis, in none of 7 EIA+ patients with hepatitis B or cytomegalovirus infection, in 33 percent of EIA+ donors who were not implicated in hepatitis transmission, and in 37 percent of EIA+ random donors. Hence, the vast majority of EIA+ individuals who have ancillary evidence of HCV infection react on RIBA, whereas the majority of EIA+ individuals in low-risk settings do not react (RIBA-negative, or RIBA-). There was a strong association between RIBA reactivity and the presence of a surrogate marker (elevated alanine aminotransferase [ALT] and/or antibody to hepatitis B core antigen); 43 percent of RIBA+ implicated donors had a surrogate marker as compared to none of 14 EIA+, RIBA- donors. Among EIA+ random donors, 77 percent of those with a surrogate marker were RIBA+, as compared with 29 percent of those without a surrogate marker. In addition, in EIA+ donors, RIBA reactivity correlated with the extent of ALT elevation; 86 percent of those with an ALT greater than 135 IU per L were RIBA+ compared with 18 percent of those with an ALT less than 30 IU per L.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of indeterminate c22-3 reactivity in volunteer blood donors

Background: Approximately 25 percent of blood donor sera that are repeatably reactive for hepatitis C virus (HCV) on second-generation enzyme immunoassay (EIA 2.0) are indeterminate on second-generation recombinant immunoblot assay (RIBA 2.0), and over 76 percent of these results are due to single reactivity to the HCV recombinant antigen c22- 3. Study Design and Methods: Data are presented on 46 volunteer allogeneic blood donors who were reactive on EIA2.0 and c22-3 indeterminate in RIBA 2.0. Index and follow-up samples were evaluated by using a panel of five synthetic peptide EIAs, a prototype strip immunoblot assay that uses synthetic peptides in addition to recombinant protein (RIBA 3.0), and polymerase chain reaction (PCR) for HCV RNA. Results: All 46 donations had normal alanine aminotransferase values; only 2 (4.3%) reacted for antibody to hepatitis B core antigen. With a panel of 12 synthetic peptides spanning the entire sequence of the c22-3 recombinant antigen, 33 plasmas (72%) reacted to one peptide or none, including 19 plasmas with reactivity restricted entirely to the N-terminal peptide (1–15 amino acids) of c22-3. With RIBA 3.0, 28 donations (61%) were nonreactive, including 25 that reacted with one peptide or none in EIA. Of these 25 plasmas, 18 reacted with the N- terminal sequence only. All 46 index donations were tested by PCR; the single PCR-positive unit reacted with four HCV peptides, was positive by RIBA 3.0, and reacted for antibody to hepatitis B core antigen. Twenty-six index donors were successfully recalled 3 to 7 months after their index donation. None seroconverted to positivity in RIBA 2.0, 1 was nonreactive, and 25 remained positive for c22-3 only. The restricted epitope reactivity in peptide EIA and RIBA 3.0 was maintained over time in all cases. All 26 of the follow-up samples tested negative by PCR. Conclusion: On the basis of the restricted peptide reactivity and PCR negativity of index and follow-up samples, it is concluded that the majority of c22-3 RIBA 2.0-indeterminate results are due to nonspecific cross-reactivity to restricted (principally, N-terminal) regions of HCV core antigen.     

Prevalence of anti-HCV in Norwegian blood donors with anti-HBc or increased ALT levels

Testing for hepatitis B core antibodies (anti-HBc) was performed in 12,104 consecutive blood donors, 139 (1.15%) of whom were found to be positive. The first 6036 donors were also screened for ALT; 91 (1.51%) had repeatedly elevated values. ALT screening was of no help in detecting anti-HBc-positive donors. Those with anti-HBc or repeatedly raised ALT levels were further tested for hepatitis C virus antibodies (anti-HCV), and 3 (2.16%) and 1 (1.10%) anti-HCV-positive donors were detected, respectively. This prevalence of anti-HCV (0.5%) is not significantly different from that found in 1000 unselected donors at our blood bank. Testing for ALT and anti-HBc as surrogate markers for hepatitis C is therefore not recommended in Norwegian blood donors and should be replaced by anti-HCV screening.     

Antibody to hepatitis C virus in blood donors found positive for other agents. I. Treponemal infection

Summary. Stored serum samples from 169 blood donors found positive for TPHA were tested for antibodies to hepatitis C virus (anti-HCV) and to hepatitis B core (anti-HBc), as evidence of previous HBV infection, a condition known to be sexually transmissible. Only three donors were positive with a 'first generation' anti-HCV and all three failed to confirm with a recombinant immunoblot assay (RIBA). In contrast, 33 (19·5%) of the TPHA-positive donors were positive for anti-HBc. The results suggest that sexual transmission is not a major factor in the spread of HCV.     

Evaluation of the persistence and characteristics of indeterminate reactivity against hepatitis C virus in blood donors

BACKGROUND: A substantial number of individuals are excluded from blood donation due to indeterminate results in screening tests for hepatitis C virus antibody (anti-HCV). Disclosure of the characteristics of the indeterminate serologic pattern could optimize the testing and the management and care of blood donors.
STUDY DESIGN AND METHODS: Ninety-two former blood donors deferred from blood donation due to consistent reactivity in anti-HCV enzyme immunoassay and indeterminate HCV recombinant immunoblot assay (RIBA) results were retested for anti-HCV to examine the extent of disappearance of reactivity. In addition, they were screened for selected viral, immunologic, and inflammatory variables to detect possible causes of the test reactivity pattern.
RESULTS: After a median observation time of 75 months, 66 of 92 individuals had persistent indeterminate HCV RIBA results. Reactivity against the nonstructural NS5 antigen was the most frequent finding. A significant association was detected both between indeterminate reactivity in HCV RIBA and against the NS5 antigen independently and detectable antibody against adenovirus. Novel indeterminate reactivity showed increased prevalence during autumn and winter months.
CONCLUSION: Indeterminate HCV RIBA reactivity in blood donors persists over years. Increased prevalence during autumn and winter and association to detection of adenovirus antibody indicate that viral infection and cross-reactivity are etiologic factors in indeterminate HCV RIBA reactivity. Further prospective studies are needed to confirm the results.     

High frequency of HCV infection in individuals with isolated antibody to hepatitis B core antigen

Although isolated antibody to hepatitis B core antigen (anti-HBc) is frequently nonspecific or may be the only serological marker of past self-limiting hepatitis B, where antibodies against the surface antigen have disappeared, isolated anti-HBc seropositivity is frequently associated with chronic hepatitis B in HIV- and HCV-infected individuals. Of 5,520 samples that tested positive for anti-HBc (IMx and AxSYM CORE, Abbott, Delkenheim, Germany) at the Institute of Virology, University Clinic Frankfurt during the time interval from January 1994 to February 1996, 643 (11.6%) were isolated anti-HBc-reactive in the IMx and AxSYM CORE assays (inhibition values >90%). There was a statistically significant association between isolated anti-HBc seropositivity and HCV and HIV/HCV coinfection (p < 0.05). A total of 190 samples were available for further testing. Six (3.2%) of 190 isolated anti-HBc-positive samples were considered false-positive since they were only positive in the AxSYM or IMx CORE assay and a linear decrease of the measured signal could not be observed in dilution series. Of 184 serum samples tested with nested PCR using primers of the S genome region, only 6 (3.3%) were HBV DNA-positive. Anti-HBc-IgM antibody could be detected in 3 (1.6 %) of the tested samples using the IMx CORE-M. With the more sensitive VIDAS HBc IgM specific IgM antibody was detected in 15 (8.5%) of 177 samples at concentrations ranging from 10 to >200 Paul Ehrlich Institute U/ml. HIV or HCV coinfection was present in 28.1% and 37.5% of isolated anti-HBc-positive individuals, respectively. We conclude from our observations that only a limited proportion of anti-HBc-isolated individuals are potentially infectious, however anti-HBc-IgM which is detectable in any form of liver disease associated with HBV infection was present in more than 8% of the individuals. Of isolated anti-HBc-positive sera 37% were positive for anti-HCV, suggesting that anti-HCV antibody testing should be performed in isolated anti-HBc-positive individuals.     

Anti-hepatitis C virus (HCV) screening at a Canadian Red Cross center: significance of a positive c100 HCV enzyme-linked immunosorbent assay

The c100 hepatitis C virus (HCV) enzyme-linked immunosorbent assay (ELISA) has been used to screen blood donors to prevent transfusion-associated non-A,non-B hepatitis. This test is not specific, and only about 25 percent of c100 HCV ELISA-positive blood samples appear to transmit hepatitis C. However, the intensity of the ELISA (sample/cutoff ratio [S/C], greater than 2) could identify a subpopulation of donors that are at high risk for transmitting hepatitis. Blood samples from 20,186 volunteer blood donors at a Canadian Red Cross blood transfusion center were screened for antibodies to HCV using the c100 HCV ELISA. Fifty-nine (0.3%) of these donors were repeatably reactive on ELISA. When their samples were tested with the c100 recombinant immunoblot assay (RIBA) and second-generation RIBA (RIBA-2), 26 (44%) and 31 (52%) samples, respectively, were found to be positive. Thirty-three of the 59 ELISA-reactive donors had an S/C greater than 2. Of these 33 donors, 30 (91%) had elevated alanine aminotransferase (ALT), 27 (82%) were RIBA-2 positive, and 22 (67%) had risk factors for hepatitis. In contrast, of the 26 ELISA-reactive donors with S/C less than 2, only 7 (27%) had elevated ALT, and 4 (15%) were RIBA-2 positive and also had high risk factors for hepatitis. Thus, while the HCV ELISA may lack specificity, its intensity can serve to identify a subgroup of donors that are at high risk for transmitting hepatitis.     

Characteristics of hepatitis C-positive blood donors in Victoria, Australia

Data from 3156 voluntary blood donors in Victoria, Australia, who were repeatedly reactive on anti-HCV screening test were analysed. It showed that between 1990 and 1997, 0.97% of routine blood donors were anti-HCV repeat reactive. Sixty-four (64) donors tested positive for HCV RNA. They were more likely to be male, had a mean age of 32.7 +/- 10.9 years and a mean serum ALT level of 70.9 +/- 46.5 i.u.L-1: the latter value being significantly different from donors with biological false reactivity (P < 0.0001). Among HCV antibody-positive donors there was a significantly increased rate of prior injecting drug use (34 vs. 1%), transfusion (25 vs. 10%) and tattooing (31 vs. 7%) than among donors with biological false reactivity (all P < 0.0001). The association of these risk factors is stronger with positivity for both immunoblot and HCV RNA than immunoblot alone. The data suggest that efforts should be made to increase the efficacy of donor questioning about prior drug use.     

Geographic risk factors for viral hepatitis and cytomegalovirus infection among United States Armed Forces blood donors

In an effort to determine whether residence in a foreign country increases the risk of hepatitis B and C and cytomegalovirus (CMV) infection in United States (US) Armed Forces blood donors, 5719 volunteer donors at four US Navy blood banks were evaluated. Most participants were repeat donors (68%) and were young (mean age, 25 years), male (88%), and white (80%), black (10%), or Hispanic (7%). Birth outside of the United States was reported by 6 percent of subjects, and 34 percent had lived in a foreign country for more than 3 months. Twenty (0.3%) subjects had hepatitis B surface antigen (HBsAg), and 100 (1.7%) had antibody to hepatitis B core antigen (anti-HBc). Thirty-four (0.6%) were repeatably reactive in enzyme-linked immunosorbent assay for antibody to hepatitis C virus (anti-HCV); 11 (0.2%) had anti-HCV in immumoblot assay. Of the 3484 donors tested for anti-CMV, 1117 (32.1%) were positive. When demographic characteristics were controlled for both anti-HBc and anti-CMV seropositivies were independently associated in male blood donors with residence in the Philippines. Geographic factors were not associated with HBsAg and anti-HCV positivity. These findings indicate that the prevalence of serologic markers for viral hepatitis is low in military blood donors, but that residence in the Western Pacific is a risk factor for hepatitis B and CMV infection.     

A comparison of two supplemental procedures for confirmation of antibody to hepatitis C virus c100-3 antigen in Louisiana blood donors

In a pilot study designed to evaluate the performance of supplemental hepatitis C virus (HCV) tests, 146 consecutive HCV enzyme immunoassay (EIA)-reactive samples (0.98% of 14,949 donors) were comparatively evaluated with two sets of supplemental tests: HCV antibody neutralization/c100-3 peptide EIA and the first-generation HCV recombinant immunoblot assay (RIBA). Of these samples, 68.5 percent were positive and 17.8 percent were negative on both supplemental assays. Nineteen samples were discordant. Eleven samples were positive on one assay (9 on neutralization/peptide, 2 on RIBA) and negative or indeterminate on the alternate supplemental test, but reacted with two additional HCV antigens outside the c100-3 region in a second-generation dot immunoblot assay. The dot immunoblot assay was used as a reference and reactive samples were considered confirmed. The remaining eight discordant samples were indeterminate or negative on either assay and did not react on the dot immunoblot assay. These data indicate a 0.74-percent prevalence of HCV exposure detected by reactivity with the c100-3 antigen in blood donors in southern Louisiana.     

Antibody to hepatitis C virus in blood donors found positive for other agents. II. Anti-HIV-1

Summary. Stored serum samples from 24 blood donors confirmed positive for anti-HIV-1 were tested for antibody to hepatitis C virus (HCV). Those repeatedly reactive using the anti-HCV ELISA screening test were retested by the HCV recombinant immunoblot (RIBA). Risk-factors for the contraction of HIV infection that had been elicited at formal counselling sessions were evaluated in relation to HCV/HIV modes of infection. The only two donors confirmed to be anti-HCV positive both admitted to intravenous drug use.     

Predictive markers for hepatitis C antibody ELISA specificity in Australian blood donors

The hepatitis C antibody reactivity rate in 91,748 blood donors tested using the ORTHO HCV C-100 ELISA system was 0.51%. Specificity of ELISA positive reactions was measured using a recombinant immunoblot assay (RIBA). The aim of this study was to identify markers in ELISA positive donors which were predictive of a RIBA positive result. Samples from 430 ELISA positive donors were tested by the first generation RIBA, RIBA-1, which incorporates two HCV peptides C-100 and 5-1-1. Fifty-five per cent (236) were positive and 19% (83) indeterminate. Multivariate analysis of gender, age, HCV ELISA OD ratio, alanine aminotransferase (ALT) status and hepatitis B core antibody (anti-HBc) status identified age, magnitude of HCV ELISA OD ratio and anti-HBc status as the only independent predictors of a positive RIBA-1 result. The relative odds of being RIBA-1 positive were 4.6-fold (95% CI 1.3-16.4) higher among donors aged 25-34 years compared with donors less than 25 or greater than 44; 6.1-fold (2.1-17.9) higher if the donor was anti-HBc positive and 273.4-fold (30.9-2417) higher if the HCV ELISA OD ratio was greater than 5.98 compared to those with a ratio less than 1.77. Seventy-eight of the 83 RIBA-1 indeterminates were tested on the second generation RIBA, RIBA-2, which includes two additional HCV peptide, C22 and C33c. Thirty-one per cent (24) were positive and 41% (32) were negative.(ABSTRACT TRUNCATED AT 250 WORDS)     

The prevalence of anti-HCV among Chinese voluntary blood donors in Taiwan

In Taiwan, the prevalence of circulating anti-HCV is 2 percent among first-time voluntary Chinese blood donors, 10 percent among donors with elevated ALT levels (greater than 45 IU/L), and higher among older men. The carrier rate for HBsAg was 18.6 percent and the frequency of positive HBV marker(s) (HBsAg, anti-HBc, anti-HBs) was 86.4 percent among first-time donors. There is no significant correlation between HBV and HCV infections in Taiwan, because there is no significant difference in the frequency of anti-HCV among donors with or without HBV markers. The frequency of anti-HCV among qualified donors in Taiwan (ALT less than 45 IU/L, not tested for anti-HBc) is 1.8 percent, which is not significantly different from the frequency (1.6%) in donors with normal ALT and negative for HBV marker(s) (qualified donors by Western Standards). Therefore, ALT is the most important surrogate marker for HCV infection in Taiwan.     

Donor levels of serum alanine aminotransferase activity and antibody to hepatitis B core antigen associated with recipient hepatitis C and non- B, non-C outcomes

BACKGROUND: Hepatitis virus(es) that are neither hepatitis B (HBV) nor hepatitis C (HCV) (non-B, non-C [NBNC]) may be transmitted by transfusion. The present study assessed donor values for alanine aminotransferase (ALT) and antibody to hepatitis B core antigen (anti- HBc) for their association with HCV and NBNC hepatitis outcomes among allogeneic blood recipients. STUDY DESIGN AND METHODS: Data on blood donors and recipients enrolled in the Transfusion- Transmitted Viruses Study in four United States cities from 1974 through 1980 were supplemented by anti-HBc testing of donors and anti-HCV evaluation of recipients. Two statistical approaches estimated the value of these indirect tests in detecting donors associated with HCV seroconversion and NBNC hepatitis in recipients. RESULTS: For HCV cases, donor ALT alone (at > or = 60 IU/L) had a sensitivity and a specificity of 30 and 96 percent, respectively, and anti-HBc alone (at > or = 60% inhibition) had a sensitivity and specificity of 53 and 86 percent, respectively. The two markers combined had a sensitivity and a specificity of 69 and 83 percent. For NBNC hepatitis cases, each measure had low sensitivity (20%) that was not improved by using both (28%) [corrected]. CONCLUSION: The indirect tests proved to be equal in sensitivity to the first-generation anti-HCV tests. The positive predictive power of these indirect tests in the 1980s was sufficient to affect HCV incidence in studies during that period. Improved anti-HCV assays, however, replaced the need for indirect tests. The sensitivity of indirect tests for NBNC hepatitis contributed little.     

Value and cost-effectiveness of screening blood donors for antibody to hepatitis B core antigen as a way of detecting window-phase human immunodeficiency virus type 1 infections. The HIV Blood Donor Study Group

BACKGROUND: The value of screening donors for antibody to hepatitis B core antigen (anti-HBc) for the prevention of posttransfusion hepatitis has declined markedly. However, anti-HBc screening may still be useful as a surrogate marker for the window period (WP) of human immunodeficiency virus type 1 (HIV-1) infection. STUDY DESIGN AND METHODS: First, the relationship between anti-HBc reactivity and HIV-1 WP infections was examined among 225 donors who had seroconverted to anti-HIV-1 positivity between 1987 and 1990. In addition, data from 1654 HIV-1 seropositive donors were analyzed to characterize the relationship among anti-HBc reactivity, donor demographics, and HIV-1- related risk factors. The yield and cost-effectiveness of anti-HBc for HIV-1 prevention were then projected on the basis of a published decision analysis model. RESULTS: Forty (18%) of 225 HIV-1- seroconverting donors tested anti-HBc-reactive on the donation preceding anti-HIV-1 seroconversion; in contrast, 341 (34%) of 1014 HIV- 1-seropositive donors interviewed tested anti-HBc-reactive (chi-square test; p < 0.001). Anti-HBc reactivity was more common among HIV-1- seropositive donors reporting male-to-male sexual contact (169/360, 47%) and injection drug use (44/83, 53%) than among those with heterosexual contacts known to be HIV-1-positive (31/190, 16%) or transfusion exposure (3/21, 14%) or among females with no identified risk factors (21/124, 17%). The estimates of 18 to 34 percent sensitivity for anti-HBc in detecting HIV-1 WP donations and a current rate of 1 in 676,000 HIV-1 WP donations (after p24 antigen screening) suggest that continued use of anti-HBc screening could result in the transfusion of 5 to 12 fewer HIV-1-infected units per year in the United States, which would add 19 to 48 quality-adjusted years of life for the 3.5 million annual transfusion recipients at a cost of $992,020 to $2,345,000 per quality-adjusted life-year saved. CONCLUSION: The low yield and very poor cost-effectiveness of anti-HBc screening indicate that this test is not an effective screening test for HIV-1 WP donations.     

Declining value of alanine aminotransferase in screening of blood donors to prevent posttransfusion hepatitis B and C virus infection. The Retrovirus Epidemiology Donor Study

BACKGROUND: Since the mid-1980s, blood banks in the United States have screened donors for elevated alanine aminotransferase (ALT) in an effort to prevent posttransfusion hepatitis. The present study was designed to quantitate the residual value of ALT screening following the implementation of hepatitis C virus (HCV) assays. STUDY DESIGN AND METHODS: Two approaches were used. First, a database of 2.3 million donations made by 586,507 volunteer blood donors between 1991 and 1993 was used to compare the incidence of seroconversion to hepatitis B virus (HBV) and HCV marker positivity in donors with elevated ALT values and with normal ALT values. Second, the duration of ALT elevation prior to HBV and HCV seroconversion was determined from 34 well-documented cases of posttransfusion HBV and HCV; elevated-ALT window periods were multiplied by rates of HBV and HCV incidence in donors to project the yield of ALT screening. Predictive value and cost- effectiveness analyses were also performed to compare the value of ALT screening before and after HCV screening was implemented. RESULTS: Both approaches indicate that ALT testing does not detect HBV in the window phase but does currently identify approximately 3 HCV window-phase donations per 1 million donations; this contrasts with ALT detection of approximately 1800 HCV-infectious units per 1 million donations prior to anti-HCV screening. Currently, only 8 in 10,000 donated units with elevated ALT (negative anti-HCV) are infected with HCV. The cost of continued ALT screening was estimated at $7,931,000 per quality- adjusted year of life saved. CONCLUSION: The yield, predictive value, and cost-effectiveness of ALT screening of blood donors have declined dramatically with the implementation of progressively improved anti-HCV assays. ALT screening of volunteer blood donors should be discontinued.