F. McOmish

Detection of three types of hepatitis C virus in blood donors : investigation of type-specific differences in serologic reactivity and rate of alanine aminotransferase abnormalities

The serologic reactivity and epidemiology associated with different hepatitis C virus (HCV) variants were investigated in a cohort of 113 anti‐HCV‐positive donors. In Scotland, HCV type 1 accounted for one‐ half of all infections; 40 percent of subjects were infected with HCV type 3, and the remainder were infected with type 2. Reactivity with the NS‐4‐encoded antigens in the first‐generation anti‐c100 assay was absent in 68 percent of donors infected with types 2 and 3, as compared with 10 percent for those infected with type 1. Even when combined with surrogate marker testing, first‐generation tests would have failed to detect 12 percent of HCV‐infected blood donors. The age distribution, incidence of past infection with hepatitis B virus, and reported risk factors were similar in donors infected with types 1 and 3 (mean ages were 31.9 and 29.9; 18 and 17.5% were positive for antibody to hepatitis B core antigen; and 47 and 48% had past intravenous drug abuse). However, the distributions of alanine aminotransferase levels were significantly different in those infected with type 3 (abnormally raised in 83%) and those infected with type 1 (55% abnormal alanine aminotransferase; p < 0.05) or type 2 (60%; p < 0.01) and those who were nonviremic (8%; p < 0.0001). These data suggest that HCV type 1 is the most common HCV infection in blood donors and that infection with HCV type 3 may be associated with more severe liver disease, because of more recent infection or because of a greater inherent pathogenicity of type 3 variants.

Serological responses to infection with three different types of hepatitis C virus

6. Scambler PJ, Carey AH, Wyse RKH, et al. Microdeletions within 22q1 1 associated with sporadic and familial DiGeorge syndrome. Genomics 1991, 10: 201-06 7. Driscoll DA, Budarf M, McDermid H, Emanuel BS. Molecular analysis of DiGeorge syndrome: 22q11 interstitial deletions Am J Hum Genet 1990, 47: A215. 8. Driscoll DA, Budarf ML, Emanuel BS. Mapping the critial region in DiGeorge syndrome. Am J Hum Genet 1991; 49: A86. 9. Kuwano A, Ledbetter SA, Dobyns WB, Emanuel BS, Ledbetter DH Detection of deletions and cryptic translocations in Miller-Dieker syndrome by in situ hybridization Am J Hum Genet 1991; 49: 707-14.

Hepatitis C virus transmission by intravenous immunoglobulin

The polymerase chain reaction was used to detect hepatitis C virus infection in patients who had previously been reported to have developed non-A, non-B hepatitis after intravenous immunoglobulin infusion. Of the 33 patients with intravenous immunoglobulin associated non-A, non-B hepatitis studied, HCV RNA could be detected in 15 out of 17 patients (88%) who were HCV RNA negative prior to the development of non-A, non-B hepatitis after implicated intravenous immunoglobulin batches. Similarly, eight out of nine patients (89%) in whom no sample was available for polymerase chain reaction testing prior to intravenous immunoglobulin therapy, had detectable HCV RNA after intravenous immunoglobulin therapy with intravenous immunoglobulin batches implicated in non-A, non-B hepatitis transmission. Two of the three intravenous immunoglobulin preparations implicated in non-A, non-B hepatitis transmissions that were available for polymerase chain reaction testing also had detectable HCV RNA, confirming that hepatitis C virus is the implicated virus in intravenous immunoglobulin-associated non-A, non-B hepatitis.

Failure of 2nd- and 3rd-generation HCV ELISA and RIBA to detect HCV polymerase chain reaction-positive donations

In the early 1980s, several countries introduced alanine aniinotransferase (ALT) testing of blood donors as a surrogate test for non-A non-B hepatitis. During the period 1980-1984, an ALT study was performed on 10,521 West of Scotland blood donors including 5,057 donors from prisons in West Scotland. A total of 54 donations, 50 from prison donors and 4 from other donors, were found to have ALT values in excess of 2.5 times the upper limit of nonnal criteria used by many to indicate hepatitis. All 54 donations were HBsAg negative by radioimmunoassay (Ausria 2: Abbott Laboratories). Thirty-two of the 54 plasma donations were stored at -20°C and aliquots were tested for the presence of anti-HCV, HCV RNA and anti-HBc in 1993. All 32 were male donors and all but 1 were prisoners, all fiilfilling the 1984 criteria for donors. Anti-HCV screening was performed using 2ndand 3rd-generation Abbott and Ortho Diagnostics HCV ELISAs. Twenty-six of the 32 donations were reactive with all 4 ELISAs whilst the remaining 6 were non-reactive with all 4 ELISAs. In the RIBA-2 assay (Chinon Corp.) 23 of the reactives were positive and 3 were indeterminate (1 c22; 2 c33 only). The 6 ELISA non-reactives were negative. All samples were retested by RIBA-3. The 3 RIBA-2 indeterminates became positive suggesting that all 26 of the donations that were reactive by 2ndand 3rd-generation Failure of 2ndand 3rd-Generation HCV ELSA and RIBA to Detect HCV Polymerase Chain ReactionPositive Donations

Derivation of a rational nomenclature for hepatitis C virus by phylogenetic analysis of the NS-5 region.

Different isolates of hepatitis C virus (HCV) are highly polymorphic throughout the genome. Phylogenetic analysis of nucleotide sequences derived from part of the gene encoding a nonstructural protein (NS-5) has provided evidence for six major genotypes of HCV among a worldwide collection of 76 samples from HCV-infected blood donors and patients with chronic hepatitis. Many of these HCV types comprised a number of more closely related subtypes, leading to a current total of 11 genetically distinct viral populations. Analysis of other regions of the viral genome produced equivalent relationships between published sequences to those found in NS-5, apart from the more highly conserved 5′ noncoding region where only the six major HCV types, but not subtypes, could be differentiated. A new nomenclature for HCV variants is proposed in this communication that reflects the two-tiered nature of sequence differences between different viral isolates.