Hepatitis C virus and GB virus C/hepatitis G virus viremia in Swedish blood donors with different alanine aminotransferase levels

BACKGROUND: Hepatitis C virus (HCV) is a known blood-borne hepatotropic virus for which antibody screening of blood donors is universally practiced. The newly identified GB virus C (GBV-C) and its strain variant hepatitis G virus (HGV) are of unknown pathogenic significance, and screening of blood donors for this agent has not yet been implemented. Polymerase chain reaction (PCR) is the most sensitive method for detecting HCV viremia and is the only method presently available for the diagnosis of GBV-C/HGV infection. STUDY DESIGN AND METHODS: RNA extracts of sera from 577 anti-HCV-negative blood donors (393 with elevated alanine aminotransferase [ALT] levels, 184 with normal ALT levels) were tested with nested PCR for HCV and GBV-C/HGV directed at the 5'-noncoding regions of the two viruses. RESULTS: One donor with elevated ALT was HCV PCR positive. This donor was anti-HCV negative when recruited to the study but subsequently developed anti- HCV. Of the 19 donors with GBV-C/HGV viremia in the series as a whole, 16 belonged to the group with elevated ALT levels and 3 to the group with normal ALT levels; the group difference in prevalence was nonsignificant (4.1% [16/393] vs. 1.6% [3/184; p = 0.20]). Phylogenetic analysis showed 16 of the GBV-C/HGV isolates to be classifiable as subtype 2a and three as subtype 2b. At follow-up 3 to 5 years later, 11 of 18 donors were still viremic. CONCLUSION: There was no significant difference in GBV-C/HGV viremia in the group with elevated ALT levels and the group with normal ALT levels. The frequency and subtype distribution in the present series were similar to those in other Western countries.     

Detection of hepatitis C virus infection with recombinant immunoblot assay,synthetic immunoblot assay,and polymerase chain reaction

The newly developed immunoblot assay, RIBA SIA (recombinant and synthetic polypeptide immunoblot assay), Chiron, Calif., was compared with the commercially available second generation recombinant immunoblot assay (RIBA-2) for the detection of antibody to hepatitis C virus (anti-HCV). The two immunoblot tests were also compared with the polymerase chain reaction (PCR) for the detection of HCV RNA. Ninety-one percent of samples reactive by RIBA-2 were positive for anti-HCV by RIBA SIA. A total of 31% of RIBA-2 indeterminate samples became reactive by RIBA SIA, 24% became non-reactive, and 45% remained the same. Samples reactive by RIBA-2 or SIA from different risk groups, were mostly positive (67-100%) by PCR for HCV RNA. All indeterminate samples from hemophiliacs and intravenous drug users were PCR positive. RIBA SIA is more sensitive and specific than RIBA-2 and correlates well with PCR results © 1993 Wiley-Liss, Inc.     

Lack of detection of human immunodeficiency virus type 1 DNA by polymerase chain reaction in the plasma and lymphocytes of seronegative exposed hemophiliacs

Direct detection of human immunodeficiency virus type 1 (HIV-1) DNA in serum or plasma samples has been reported in seronegative as well as seropositive individuals. An alkaline lysis procedure was adapted for polymerase chain reaction (PCR) analysis of plasma specimens. Eighty- five seronegative hemophiliacs, 52 of whom had been exposed to HIV- contaminated blood components, and 19 seronegative at-risk individuals were studied. Each sample was extracted and amplified with SK38/39 gag primers at least three times. Seventy-six samples (72%) were consistently negative for HIV-1 DNA, 24 (22%) were positive only once, and 4 (3%) were positive twice. Genomic DNA from peripheral mononuclear cells was prepared from 12 of 76 negative samples, 18 of 24 samples that were positive once, and 2 of 4 samples that were positive twice and analyzed with both gag and long terminal repeat primers. None (0/32) of these cellular DNAs were positive for HIV-1, which suggests that these seronegative exposed hemophiliacs were not latently infected with HIV-1. In contrast, all (10/10) control cells from seropositive patients were positive with both primer pairs. The detection of HIV-1 DNA in serum or plasma may be prone to a high level of false-positive PCR signals and should be interpreted with caution.     

A search for hepatitis C virus polymerase chain reaction-positive but seronegative subjects among blood donors with elevated alanine aminotransferase

BACKGROUND: Previous studies reported the existence of hepatitis C virus (HCV) polymerase chain reaction (PCR)-positive but seronegative sera. This is not surprising in the case of window-phase specimens, because PCR can detect HCV RNA many weeks before the appearance of antibody. To determine whether such sera can also be found in chronically infected subjects, a high-risk population of blood donors with elevated alanine aminotransferase was studied. STUDY DESIGN AND METHODS: Freshly frozen plasma from 301 donors with alanine aminotransferase > 100 IU per L was tested with PCR assays that were rigidly controlled for specificity and contamination, and with current and newer versions of assays for anti-HCV. Sera were classified as seropositive if positive in two screening assays and one supplemental assay or if positive in two screening assays and PCR. RESULTS: New versions of screening assays detected 100 percent of seropositive samples. A second-generation immunoblot assay detected 98 percent of seropositive sera, a second-generation recombinant immunoblot assay detected 96 percent, and an enzyme immunoassay for antibody to the envelope protein of HCV detected 98 percent. Fifty-one of 54 seropositive sera were PCR positive. None of the 247 seronegative samples was reproducibly positive on PCR. CONCLUSION: No PCR-positive but seronegative donors were found in this high-risk donor population. The possible benefit of PCR screening of blood donors can be determined only by large-scale comparative testing of donor populations and may be limited to the detection of window-phase infections.     

Absence of human immunodeficiency virus (HIV) proviral sequences in seronegative hemophilic men and sexual partners of HIV-seropositive hemophiliacs

To detect latent infection with human immunodeficiency virus (HIV), specimens of peripheral blood leukocytes from HIV-seronegative hemophiliacs and from sexual partners of HIV-seropositive hemophiliacs were examined by polymerase chain reaction (PCR). The primer pair SK 38/39 derived from the gag region and/or the primer pair SK 68/69 corresponding to a conserved region of the env gene were used. Whereas HIV proviral DNA was detected by PCR in samples from 86 (97%) of 89 HIV-seropositive hemophiliacs, no HIV-DNA was found in blood samples of 198 HIV-seronegative hemophiliacs at risk. Of 40 HIV-seronegative sexual partners of HIV-infected hemophiliacs, none was PCR positive. Thus, PCR is proving to be a sensitive method by which to confirm infection in seropositive hemophiliacs, while the negative results in HIV-seronegative hemophiliacs and HIV-seronegative sexual partners of HIV-seropositive hemophiliacs suggest that a prolonged seronegative period of latent HIV infection is the exception.     

Comparative evaluation of Abbott and Murex antibody assays and Roche Amplicor PCR for diagnosis of human hepatitis C

Of 135 serum samples from 135 patients suspected of hepatitis C virus (HCV) infection, 67 were detected by Abbott IMX antibody assay, 89 by Murex anti-HCV (version III), and 47 by Roche Amplicor polymerase chain reaction (PCR). Furthermore, 44 of the 62 positive serum samples by both Abbott and Murex antibody assays, 2 of the 27 positive samples by Murex antibody assay only, none of the 5 positive samples by Abbott antibody assay only, and one of the 43 negative samples by both Abbott and Murex antibody assays had measurable HCV RNA by Roche Amplicor PCR, suggesting active hepatitis C viremia. Whereas Abbott and Murex antibody assays were in agreement with each other in 103 of the 135 serum samples tested, they showed discrepancy with regard to the other 32. Despite generating a small percentage of false positives, Abbott and Murez antibody assays are useful in monitoring serum antibody levels of the past or continuing hepatitis C virus infection. Abbott IMX appears to be more specific than Murex anti-HCV (version III). The use of Roche Amplicor PCR provides a means of revealing active hepatitis C viremia, and helping clarify antibody indeterminate serum samples.     

Prevalence of cytomegalovirus antibody in hemophiliacs and homosexuals infected with human immunodeficiency virus type 1

We determined the prevalence of antibody to cytomegalovirus (CMV) in the sera of non-homosexual hemophilia patients and homosexual men infected with the human immunodeficiency virus type 1 (HIV-1). CMV antibody testing by latex agglutination revealed 33 of 58 HIV-1 infected hemophiliacs (57%) were antibody-positive compared with 54 of 54 HIV-1 infected asymptomatic non-hemophiliac homosexuals (100%) (p less than .001). Nine of 15 hemophiliacs (60%) with symptomatic HIV-1 infection were CMV antibody-positive. We also tested 22 HIV-1 antibody-negative hemophiliacs who had received non-heat treated factor concentrates. 14 of these 22 (64%) were CMV antibody-positive compared with 57% of HIV-1 antibody-positive hemophiliacs. We conclude 1) there is little correlation between transmission of HIV-1 and CMV by factor concentrates, 2) the presence of CMV antibody does not appear to be associated with clinical stage of HIV-1 infection in hemophiliacs, and 3) there may be a significant number of CMV antibody-negative hemophiliacs with HIV-1 infection at risk for primary infection and subsequent disease if CMV seronegative blood products are not provided for future transfusions.     

Serological and histological features of anti-HCV-positive individuals without serum HCV RNA.

Antibody to hepatitis C virus (anti-HCV) in patients who are negative for HCV RNA in serum may indicate a memory of past infection of HCV. However, their clinical features have not been well understood. Fourteen anti-HCV-positive but HCV RNA-negative individuals were examined for serological and histological features. As a result, it was found that they had only antibody to HCV core antigen C22-3 with or without antibody to nonstructural viral antigen C33c on a recombinant immunoblot assay (RIBA), and that an concentration of anti-C22 was low. Liver biopsy showed two having no evidence of an obvious hepatic injury, two having a minimal change, and two having portal fibrosis. HCV RNA was not found in the liver. These results corroborate an idea that the anti-HCV in HCV RNA-negative individuals implies a past infection of HCV. Furthermore, it is suggested that a combination of an appearance pattern of antibody to HCV antigens on RIBA and anti-C22 titer are an useful marker to distinguish anti-HCV-positive individuals without viremia from those with viremia.     

Transmission of parvovirus B19 by coagulation factor concentrates exposed to 100 degrees C heat after lyophilization

BACKGROUND: Double inactivation by solvent/detergent treatment plus heating at 100 degrees C for 30 minutes after lyophilization has been adopted to improve viral safety of factor VIII and factor IX concentrates, particularly with respect to non-lipid-enveloped viruses. The aim of this study was to evaluate the safety of concentrates exposed to these virucidal methods. STUDY DESIGN AND METHODS: Twenty- six previously untreated hemophiliacs, 19 with factor VIII deficiency and 7 with factor IX deficiency, were investigated in a prospective multicenter study over a 12-month follow-up period by the use of serologic and virologic markers for lipid- and non-lipid-enveloped viruses (human immunodeficiency virus types 1 and 2; hepatitis A, B, and C viruses; B19 parvovirus antibodies; and B19 DNA). Overall, 270,000 U of factor VIII and 102,000 U of factor IX concentrate were administered during the study period. RESULTS: None of the 26 patients seroconverted for human immunodeficiency virus or hepatitis C virus. Hepatitis B virus markers remained negative in the 10 unvaccinated hemophiliacs. No hepatitis A virus seroconversion occurred among 17 susceptible patients. B19 seroconversion (IgM) and B19 viremia were observed within 2 weeks of the first concentrate infusion in 8 of 15 susceptible patients, 5 of 11 treated with factor VIII and 3 of 4 with factor IX concentrate. CONCLUSION: This prospective study indicates that very high temperatures applied to lyophilized concentrates appear to prevent the transmission of hepatitis A virus to hemophiliacs. However, B19 parvovirus still contaminates concentrates despite the use of this robust virucidal method.     

Detection of hepatitis C virus RNA by a two-stage polymerase chain reaction with two pairs of primers deduced from the 5'-noncoding region

The 5'-noncoding region of hepatitis C virus (HCV) genomes is highly conserved. A two-stage polymerase chain reaction (PCR), involving two pairs of primers deduced from the 5'-noncoding region of the HCV genome, was developed for a sensitive and specific detection of HCV RNA. The first stage of PCR was performed for 35 cycles with primers capable of multiplying fragments of 221 base pairs. PCR products in samples negative for HCV RNA were subjected to the second stage of PCR for 30 cycles with primers located internal to those employed in the first stage of PCR. The two-stage PCR detected up to 10 chimpanzee infectious doses/ml of HCV, and HCV RNA in 11 (92%) of 12 sera from patients with chronic non-A, non-B hepatitis without detectable antibodies to HCV by a commercial assay kit. Primers from the 5'-noncoding region of the HCV genome would be suitable for detecting HCV RNA by PCR, since the other regions of the HCV genome diverge extensively in sequence because of its nature as an RNA virus.     

High antibody level: an accurate serologic marker of viremia in asymptomatic people with hepatitis C infection

BACKGROUND: The screening and diagnosis of hepatitis C virus (HCV) infection is initiated by testing for antibody to HCV (anti‐HCV). A positive anti‐HCV test in blood donors represents ongoing infection in only a variable proportion of individuals. Because a high anti‐HCV level has been associated with viremia, a study was conducted to determine whether a high antibody level is an accurate serologic marker for viremia in asymptomatic anti‐HCV–positive persons. STUDY DESIGN AND METHODS: In a diagnostic test study, we included 856 anti‐HCV–positive blood donors in a blood bank at Guadalajara, Jalisco, Mexico, between 2002 and 2007. A third‐generation amplified chemiluminescence assay (ChLIA HCV) was used to detect anti‐HCV. A positive result of the qualitative nucleic acid test (HCV RNA) was considered the gold standard for viremia. RESULTS: By receiver operating characteristic analysis, the signal‐to‐cutoff (S/CO) ratio of 20 or more was chosen as optimal to identify viremia and so was defined as high anti‐HCV level. There was a significant difference in the proportion of viremia between subjects with high antibody level and those with lower levels (93.7% vs. 1.8%, respectively; p < 0.001). A high antibody level showed a sensitivity for viremia of 96.6% (95% confidence interval [CI], 93.8%‐98.1%), a specificity of 96.6 % (95% CI, 94.8%‐97.8%), and a likelihood ratio of 28.6 (95% CI, 18.4%‐44.6%). CONCLUSION: A high antibody level (S/CO ratio ≥20 by ChLIA HCV) clearly divides the viremic from the nonviremic blood donors and functions as an accurate serologic marker to guide the use of routine HCV RNA testing to confirm hepatitis C infection.     

Hepatitis C virus RNA in serum of blood donors with or without elevated transaminase levels

The pattern of hepatitis C virus (HCV) viremia in blood donors who are positive for antibody to HCV (anti-HCV) according to the level of transaminase activity is unclear. A polymerase chain reaction-based HCV RNA detection method was used to study two clearly defined groups of anti-HCV-positive blood donors with repeatedly normal (n = 27) and elevated (n = 17) alanine aminotransferase (ALT) levels. HCV RNA was detected in only 4 of 27 blood donors with normal ALT values and 15 of 17 with elevated ALT values. These results indicate that anti-HCV- positive blood donors with normal ALT levels constitute a heterogeneous group, as HCV viremia is detectable in only a small proportion of cases. Polymerase chain reaction should be useful in the surveillance of anti-HCV-positive blood donors with normal ALT levels, by identifying those who might benefit from further investigation and treatment.     

Infection with hepatitis delta and human immunodeficiency viruses among hemophiliacs in Japan

Two hundred two patients with hemophilia, dependent solely on imported coagulation factor concentrates, were tested for markers of hepatitis B virus infection, antibody to hepatitis delta virus (anti-HD), and antibody to human immunodeficiency virus (anti-HIV). Nine carriers of hepatitis B surface antigen (HBsAg) were identified. Six (66.7%) of them were positive for anti-HD, a prevalence much higher than that in HBsAg carriers without hemophilia in Japan (1/113 or 0.9%, p less than 0.001). Anti-HIV was found in 96 (47.5%), in sharp contrast to the low prevalence (0/1205) in apparently healthy blood donors (p less than 0.001). These results implicated imported plasma products in the transmission of both delta and human immunodeficiency viruses to hemophiliacs. An efficient method for the sterilization of plasma products is warranted to prevent exposure of hemophiliacs to the accompanying pathogenic viruses.     

Role of screening for hepatitis C virus in children with malignant disease and who undergo bone marrow transplantation

BACKGROUND: Children with malignant disease who received multiple blood transfusions before the clinical definition of hepatitis C virus (HCV) require evaluation for HCV infection. STUDY DESIGN AND METHODS: The role of HCV infection in 54 children with primary malignant disease was evaluated in terms of the following aspects: prevalence of HCV infection, distribution of HCV subtype, the benefit of screening of blood donors, and the presence of chronic liver disease. The benefit of screening for HCV in a subset of patients who underwent bone marrow transplantation (BMT) was also evaluated. RESULTS: Seventeen patients (31.4%) of 54 tested were seropositive in a second-generation HCV antibody test. Thirteen patients (24.0%) were also positive for circulating HCV RNA. HCV subtype 1b and HCV subtype 2b were found in six and two patients, respectively. Multiple HCV genotypes were present in two patients. One of these two patients had relatively progressive liver disease. Before the introduction of blood screening with a second- generation HCV antibody test, 15 of 35 patients seroconverted, whereas none of 7 patients seroconverted after the screening was used (p = 0.032). For patients who underwent BMT, the screening drastically decreased the seroconversion rate, from 7 of 11 patients to 0 of 6 (p = 0.016). CONCLUSION: A considerable number of children with primary malignant disease who received multiple blood transfusions became infected by HCV before HCV screening was used. Patients who underwent BMT were at high risk for HCV infection. Screening with a second- generation HCV antibody test has proven to be remarkably beneficial in preventing HCV infection in these children.     

Hepatitis C viral markers in patients who received blood that was positive for hepatitis C virus core antibody, with genetic evidence of hepatitis C virus transmission

BACKGROUND: Despite the use of the anti-c100-3 assay for blood donor screening, posttransfusion non-A,non-B hepatitis still occurred. A more sensitive assay should be developed to prevent this. STUDY DESIGN AND METHODS: Stored serum specimens from 2020 healthy blood donors who were negative for c100-3 antibody to hepatitis C virus (HCV) were retrospectively screened for the presence of antibodies against a core protein of HCV using an enzyme-linked immunosorbent assay and Western blot analysis as part of a study on posttransfusion non-A,non-B hepatitis. RESULTS: Eight (0.4%) of the 2020 donors were positive for HCV core antibody. Posttransfusion non-A,non-B hepatitis occurred in 5 of five patients known to have received blood that was positive for HCV core antibody and 1 of 141 patients transfused with blood that was negative for HCV core antibody. The total incidence of posttransfusion non-A,non-B hepatitis was 4.1 percent (6/146). The nucleotide sequence of the nonstructural 5 region of the HCV genome obtained from two donors and corresponding recipients was also analyzed. The HCV genome sequences were identical for one donor-recipient pair, and there was 99.4-percent homology for a second pair. CONCLUSION: Anti-core-positive blood proved to be highly infectious for HCV, and this validated the use of the second-generation anti-HCV assay for blood donor screening.     

Transmission of hepatitis G virus in patients with angioedema treated with steam-heated plasma concentrates of C1 inhibitor

BACKGROUND: Hepatitis G virus (HGV) is a blood-borne flavivirus that may cause acute and chronic transfusion-transmitted infections. Patients with complement component 1 (C1) inhibitor (C1-INH) deficiency may acquire blood-borne infections through infusion of plasma concentrates. STUDY DESIGN AND METHODS: Serum samples from 84 patients with C1-INH deficiency (19 who received unmodified C1-INH concentrates, 23 who received steam-heated concentrates, and 42 untreated patients) were tested for HGV RNA and hepatitis C virus (HCV) RNA by a nested polymerase chain reaction (PCR). The samples were also tested for antibodies to the E2 envelope protein of HGV (anti-HGV) and to HCV with enzyme-linked immunosorbent assays. RESULTS: Nine (11%) patients had serum HGV RNA; that is, 7 (17%) of 42 patients previously treated with C1-INH concentrates and 2 of 42 previously untreated patients. HGV RNA was as common in the 19 patients treated with unmodified concentrates as in the 23 given steam-heated concentrates (16 vs. 17%, p = 0.60). Anti-HGV was more common among the recipients of unmodified concentrates than among those given steam-heated concentrates (26 vs. 0%, p = 0.014). HCV RNA was more frequently detected in treated patients than in untreated patients (33 vs. 7%, p = 0.005) and in the 19 recipients of unmodified concentrates than in the 23 treated with steam-heated concentrates (58 vs. 16%, p = 0.003). Only one HGV RNA- seropositive patient had elevated serum aminotransferase activity, compared to 11 with HCV RNA. CONCLUSION: HGV was transmitted by both unmodified and steam-heated concentrates, but it caused persistent viremia in a minority of the cases and was rarely associated with liver disease.     

Sensitivity of HCV core antigen and HCV RNA detection in the early infection phase

BACKGROUND: Various countries have introduced HCV NAT to exclude infectious donations collected during the preseroconversion window phase (PWP). For the same purpose, an ELISA has also been developed to detect HCV core antigen (cAg). STUDY DESIGN AND METHODS: Using sequential samples from regular plasma donors with very recent HCV infections, a total of 494 samples from 52 anti-HCV-negative donors were collected. These panels were used for direct comparison of the performance of PCR and ELISA in detecting viral markers (RNA and cAg) during the PWP of HCV infection. The panels were genotyped, and each sample was analyzed by qualitative and quantitative HCV PCR and by cAg ELISA. The HCV RNA doubling time was calculated from quantitation of viral RNA in consecutive samples during the earliest outbreak of viremia. RESULTS: Concurrent detection of HCV RNA and cAg in 218 and nondetection in 185 samples yielded 81.6-percent concordance in the results of 494 samples. Unidirectional discrepancy of results (i.e., PCR positive and cAg negative) was seen in 91 of 494 (18.4%) samples, which was consistent with 65 specimens with RNA concentrations ranging between 300 and 100,000 IU per mL and 26 specimens with less than 300 IU per mL (limit of quantitative PCR). Individual genotyped panels had different kinetics and courses of viremia. The mean doubling time in the early PWP at the onset of viremia was derived to be 10.8 (range, 5.8-21.0) hours. CONCLUSION: A majority of HCV RNA-positive samples were also cAg-positive during the PWP. The current cAg detection corresponds to 100,000 IU per mL of HCV RNA. Since low-titer samples would be identified only by single-donation NAT, which is often affordable only in developed countries, the cAg ELISA could offer a practical alternative for some countries. The doubling time for HCV RNA at the onset of viremia corresponds to a calculated mean delay of cAg detection during the virus burst phase of 2 or 5 days, when compared with minipool (5000 IU/mL) or single-donation NAT (50 IU/mL), respectively.     

Seroconversion to human immunodeficiency virus (HIV) in hemophiliacs. Relation to lymphadenopathy

The authors studied the natural history of human immunodeficiency virus (HIV) exposure in 187 hemophiliacs followed for an average of 45 months. Overall, 55 percent developed antibody specific for HIV and 21 percent developed persistent generalized lymphadenopathy. Most patients seroconverted sometime between early 1982 and the end of 1984. Four patients developed acquired immune deficiency syndrome (AIDS) and four seropositive patients developed idiopathic thrombocytopenia (ITP). One of the four patients who developed AIDS and three of the four with ITP had preexisting lymphadenopathy. None of the 10 patients with lymphadenopathy or the 20 asymptomatic patients was seropositive for human T-lymphotropic virus, type I. Although seropositivity and lymphadenopathy have been found in many of the authors' patients, few have developed clinical disease that can be related to HIV infection.     

Correlates of hepatitis C virus (HCV) RNA negativity among HCV-seropositive blood donors

BACKGROUND: Approximately 20 percent of persons infected with hepatitis C virus (HCV) clear viremia. Factors associated with resolution of viremia are not well defined. Implementation of routine nucleic acid testing (NAT) of blood donors has yielded a large data set for analysis of demographic correlates of resolved viremia. STUDY DESIGN AND METHODS: HCV antibody and NAT data, liver enzyme (alanine aminotransferase [ALT]) results, and donor demographic characteristics were compiled for 2,579,290 allogeneic donations given at five large blood centers after NAT implementation in 1999 through December 2001. Donation HCV RNA status was compared between first-time donors categorized by ALT levels, sex, age, race and/or ethnicity, country of birth, level of education, blood center location, and blood group, with chi-square tests and multivariable logistic regression methods. RESULTS: Of 35 confirmed-seropositive repeat donors, 19 (54.3%) tested negative for the presence of HCV RNA; there was no association between RNA status and preseroconversion intervals (p = 0.74). Of 2105 RIBA-positive, first-time donors, 402 (19.1%) tested negative for the presence of HCV RNA by NAT (presumptive resolved infections). There were significant differences in the frequency of RNA negativity among first-time donors categorized by ALT levels and by race and/or ethnicity. ALT levels were more likely to be elevated in RNA-positive, first-time donors (p < 0.0001). Viremia was less likely to resolve in Asian (8.2%) and black non-Hispanic (14.4%) donors than in white non-Hispanic (20.7%), Hispanic (22.1%), and other race and/or ethnicity (22.1%) donors (p = 0.02). No significant associations were found for age, sex, country of origin, level of education, blood type, and donor center location. CONCLUSION: These results confirm that the frequency of HCV RNA negativity among seropositive persons differs by race and/or ethnicity. Follow-up studies of donors with resolved viremia are warranted to further elucidate viral, immunologic, and genetic factors underlying spontaneous viral clearance.