Second generation screening improved detection of Hepatitis C infection
ACP J Club. 1992 May-June;116:87. doi:10.7326/ACPJC-1992-116-3-087
Aach RD, Stevens CE, Hollinger FB, et al. Hepatitis C virus infectionin post-transfusion hepatitis. An analysis with first- and second-generation assays. N Engl J Med. 1991 Nov 7;325:1325-9.
To clarify the role of hepatitis C virus (HCV) in post-transfusion hepatitis.
Cohort study comparing the occurrence of HCV detected by 3 enzyme-linked immunoassays (EIA) in patients with an independent clinical diagnosis of non-A, non-B hepatitis. Patients were followed for ≥ 148 days.
Urban medical centers in the United States between 1976 and 1979.
Hospitalized patients who developed hepatitis were identified from 1247 transfusion recipients and 1235 patients who were typed and cross-matched but did not receive a transfusion (control group). Patients who had serologic evidence of HCV at entry to the study, or who developed hepatitis A or B, or nonviral hepatitis were excluded.
Description of test and diagnostic standard
2 first-generation EIAs that detect antibody to a nonstructural antigen of HCV and a second-generation EIA that, in addition, detects antibodies to core and protease antigens were used to test serum samples collected from hepatitis-infected patients.
Non-A, non-B hepatitis was diagnosed between 11 and 180 days after transfusion or enrollment by an increase in alanine aminotransferase (ALT) of ≥ 45 IU/L in ≥ 2 consecutive blood specimens drawn within a period of 3 to 17 days, with ≥ 1 level ≥ 90 IU/L. Chronic hepatitis was defined as an elevated ALT for ≥ 6 months.
Main outcome measures
Detection of anti-HCV; features associated with seroconversion.
111 transfusion recipients (9%) developed non-A, non-B hepatitis. Seroconversion was detected in 51 of these patients (46%) by the first-generation assays and in an additional 16 (14%) by the second-generation assay for a total of 67 patients (60%). Non-A, non-B hepatitis was diagnosed in 37 control patients (3%), of whom none developed anti-HCV seroconversion by EIAs. Transfusion recipients who seroconverted and those whose peak ALT was ≥ 450 IU/L (64% vs 7%) were at higher risk for developing chronic hepatitis (51% vs 9%) than were transfusion recipients with hepatitis who did not seroconvert. All units of blood for 99 transfusion recipients with non-A, non-B hepatitis were tested. Of the 39 patients who received blood that was anti-HCV negative, 4 (10%) seroconverted. Of the 60 who received blood that was anti-HCV positive, 55 (92%) seroconverted.
Hepatitis C virus caused a large proportion of post-transfusion non-A, non-B hepatitis and an even greater proportion of severe and chronic hepatitis. A second-generation enzyme-linked immunoassay improved detection of hepatitis C compared with first-generation immunoassays.
Source of funding: National Heart, Lung, and Blood Institute.
Address for article reprint: Dr. R.D. Aach, Mount Sinai Medical Center, 1 Mount Sinai Drive, Cleveland, OH 44106, USA.
This well-designed, prospective study found a 5.4% incidence of post-transfusion hepatitis associated with HCV. It provides further evidence that HCV is the predominant cause of non-A, non-B post-transfusion hepatitis.
The study raises 2 important questions. One is related to the use of second-generation EIA for the detection of anti-HCV. Of 67 patients who developed hepatitis C, anti-HCV was detected in the blood of 76% of the patients by testing with both first- and second-generation EIAs. In 24% of these patients, however, anti-HCV could be detected only by the use of second-generation EIA. Based on these data, it appears to be appropriate to use second-generation EIA to routinely screen blood donors for the presence of anti-HCV as well as to diagnose hepatitis C.
The other issue is the screening of blood donors for elevated levels of ALT. The data indicate that among the donors who were anti-HCV positive, the incidence of anti-HCV seroconversions in transfusion recipients was similar whether or not the donor blood contained increased ALT titers. The study also found that 3.6% of non-A, non-B post-transfusion hepatitis was not caused by HCV and that a similar incidence of non-A, non-B, non-C hepatitis (3%) occurred among the controls who did not receive transfusions. In the past, routine screening of donors for ALT titers undoubtedly helped reduce the incidence of post-transfusion hepatitis. But with anti-HCV screening, one wonders whether routine screening for ALT elevations should be continued. In this study 8 patients received anti-HCV negative blood that contained elevated ALT titers, and none of them seroconverted. Although the number of patients is small, the results do suggest that routine screening for ALT titers is relatively unproductive.
Tom D.Y. Chin, MD
University of Kansas Medical CenterKansas City, Kansas, USA
Tom D.Y. Chin, MD
University of Kansas Medical Center
Kansas City, Kansas, USA