Lot-to-lot variation in anti-hepatitis C signal-to-cutoff ratio.

Abstract

Hepatitis C virus (HCV), the most common chronic viral infection in North America, affects an estimated 2.7 million individuals in the US (1). Hepatitis C is more common in certain populations, including injection drug users, prison inmates, the homeless, dialysis patients, and those seeking care in Veterans Affairs medical centers (2)(3)(4)(5). Hepatitis C is the leading cause for end-stage liver complications, including hepatocellular carcinoma and need for liver transplantation; the frequency of these is expected to increase two- to threefold by 2030 (6). Antibodies to HCV (anti-HCV) can indicate one of three possible conditions: current active infection with HCV, past infection with HCV, or a false-positive reaction (7). Although tests are usually interpreted as positive or negative, samples with low-positive anti-HCV results are usually falsely positive, whereas >90% of samples that are high-positive are from patients who test positive for HCV RNA (8)(9). Recently, the CDC revised guidelines for laboratories, recommending confirmatory testing for samples with low signal-to-cutoff (S/C) ratios (10). When enzyme immunoassays (EIAs) are used, they suggested a S/C ratio <3.8 to identify low-positive samples; when chemiluminescence assays (CAs) are used, a S/C ratio <8.0 was recommended (10). No data exist on the reproducibility of S/C ratios between lots. Because calibration of both EIA and CA methods involves a single point (the cutoff value), S/C ratios may vary significantly between lots. I retrospectively reviewed data for S/C ratios and confirmatory test results by lot of reagent for both EIAs and CAs. The Pathology and Laboratory Medicine Service maintains a blinded database of all patients with positive anti-HCV results; details of the screening program and the assays used have been reported previously (8)(9). A total of 13 714 individuals were tested over a 13-month period by a …