Non-A, Non-B Hepatitis and the Anti-HCV Assay

Abstract

The successful cloning of a non-structural antigen from the genome of what is now designated as the ‘hepatitis C virus’ (HCV) has transformed an erstwhile diagnosis of exclusion for non-A, non-B hepatitis (NANBH). The assay has been validated against panels of known infectivity for NANBH and sera from haemophiliac patients treated either with virally inactivated or uninactivated factor VIII. The predictive value of the assay is being assessed clinically in prospective studies of post-transfusion hepatitis and by using laboratory techniques such as polymerase chain reaction. While the assay shows good predictability in high-risk subjects, an appreciable number of false-positive results are likely in blood donor populations. Furthermore, the extent of infectivity of seropositive blood donors is still the subject of active research. The prevalence of anti-HCV in blood donors varies from approximately 0.2 to 1.5% around the world, based on repeat reactivity in the Ortho antiglobulin ELISA assay. These rates may be appreciably reduced following supplementary testing with recombinant immunoblot assay (RIBA). Prevalence data in African sera are as yet unreliable, pending assessment by RIBA, presumably because of high levels of IgG interfering with the assay. Presence of anti-HBc or elevated alanine aminotransferase associates to a greater or lesser extent with seropositivity, especially when both surrogate markers are present, but conversely many (unconfirmed) seropositive subjects lack these surrogate markers. An understanding of the modes of transmission of HVC is of obvious importance to transfusion practice. Intravenous drug use is a striking risk factor, but the contribution made by sexual transmission is not so clear. Results with the highly innovative anti-HCV assay represent the first dramatic ‘ranging shots’ to hit the target of NANBH, albeit at the periphery. Some of the various limitations of this expensive assay and associated supplementary tests are likely to be resolved by the advent of improved tests based on other HCV antigens, including structural ones. Hopefully, they will produce results closer to the centre of the target.

Hepatitis C virus and porphyria cutanea tarda: Evidence of a strong association

“…Almost all positive subjects had antibodies against the structural (c22-3) and nonstructural antigens (c33c), and half had antibodies against the nonstructural 5-1-1 and c100-3 antigens. The homogeneous pattern of antibody response in our PCT patients indicated a similar infection status in these subjects, although the relationship between positivity for a given antigen and infectivity has not yet been defined (30). The finding that no difference existed between HCV prevalence in patients with normal or increased y-globulin levels and the absence of autoantibodies in nearly all patients ruled out the possibility of false-positive cases due to immune factors (31).…”

Prevalence of Anti‐Hepatitis C Virus in the Blood Donor Population of Rio de Janeiro

“…124 Considerable variation in anti-HCV seroprevalence rates in blood donors has been observed in Europe, Japan and the USA. Depending on the country, the rates have ranged from 0.2 to 1.5% [13] based on repeat reactivity in ELISA screening assays. These rates may be considerably reduced after confirmatory testing using immunoblot assays.…”

Completed hepatitis C lookback in Northern Ireland

“…Screening and supplemental tests that are used are serological tests to detect antibody and are not exclusive for HCV. A positive result may indicate past infection or active current infection (Barbara & Contreras, 1991a). The latest generation of tests which make use of synthetic peptides and recombinant proteins from both the core and nonstructural regions of the HCV genome show improved performance.…”

“…Polymerase chain reaction (PCR) confirms viral replication but there are problems due to lack of standardization between reference laboratories (Dow et al, 1993) and false negative results caused by variant strains and high mutation rate of HCV (Garson et al, 1990a;Barbara & Contreras, 1991a, b). While a positive PCR result is thought to indicate an adverse prognosis (Alberti et al, 1992) and greater infectivity (Garson et al, 1990a;Farci et al, 1991), a negative result does not indicate absence of HCV infection (Barbara & Contreras, 1991a). The natural history of post-transfusion HCV infection is far from certain and there is a lack of longitudinal follow-up studies (Wood et al, 1989;Alberti et al, 1992;Seef et al, 1992).…”

“…NIBTS has effectively completed its HCV lookback exercise. Twelve recipients are HCV antibody negative and a further three who are RIBA positive and PCR negative have probably eliminated the virus (Barbara & Contreras, 1991a). Seven recipients are RIBA positive and PCR positive, six of whom have been referred to a hepatologist.…”