The role of cytotoxic T lymphocyte responses, restricted by human leukocyte antigen (HLA) class I alleles, is recognized as highly significant in the successful clearance of hepatitis C virus (HCV). The frequency of class I alleles in females inoculated with HCV genotype 1b from a single source was examined for an association with outcome. Class I typing was performed using polymerase chain reaction sequence-specific primers in 227 female subjects: 141 had chronic infection and 86 had viral clearance. Statistical analysis included 2 testing and multiple logistic regression analysis. A*03, B*27, and Cw*01 occurred more frequently in those with viral clearance (39.5%, 14%, and 9.3%, respectively) compared with those with chronic infection (19.1%, 2.1%, and 1.4%, respectively; P < .005). B*08 occurred more often in those with chronic infection compared with viral clearance (39.7% vs. H epatitis C virus (HCV) is a hepatotropic virus with a high rate of chronic infection. It is known that progression to cirrhosis and hepatocellular carcinoma may take up to 20 years in individuals who are chronically infected and thus represents a leading cause of hepatocellular morbidity and mortality. [1][2][3][4] To date, viral factors (e.g., genotype) and host factors (e.g., age of acquisition, male sex, and alcohol consumption) are known to alter both the natural history of the disease and treatment outcomes. 2,4-6 As yet, no in vivo models of infection are available in HCV infection, therefore the pathogenic mechanism of disease remains unclear. 19.8%; P ‫؍‬ .002). In combination with previously reported class II allele associations, overIn HCV infection, recognition and elimination of infected cells by cytotoxic T lymphocytes (CTLs) require the presentation of specific HCV antigens on the membrane of hepatocytes in the context of HLA-A, -B and -C antigens. In acute HCV infection, animal models suggest that viral clearance appears to be dependent on an intrahepatic CTL response directed against multiple HCV antigens restricted by several class I molecules. 7 Human studies on peripheral blood similarly report that viral clearance is associated with a strong initial HCV-specific

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The long-term evolution of the hepatitis C virus hypervariable region (HVR) and flanking regions of the E1 and E2 envelope proteins have been studied in a cohort of women infected from a common source of anti-D immunoglobulin. Whereas virus sequences in the infectious source were relatively homogeneous, distinct HVR variants were observed in each anti-D recipient, indicating that this region can evolve in multiple directions from the same point. Where HVR variants with dissimilar sequences were present in a single individual, the frequency of synonymous substitution in the flanking regions suggested that the lineages diverged more than a decade previously. Even where a single major HVR variant was present in an infected individual, this lineage was usually several years old. Multiple lineages can therefore coexist during long periods of chronic infection without replacement. The characteristics of amino acid substitution in the HVR were not consistent with the random accumulation of mutations and imply that amino acid replacement in the HVR was strongly constrained. Another variable region of E2 centered on codon 60 shows similar constraints, while HVR2 was relatively unconstrained. Several of these features are difficult to explain if a neutralizing immune response against the HVR is the only selective force operating on E2. The impact of PCR artifacts such as nucleotide misincorporation and the shuffling of dissimilar templates is discussed.

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This study confirms that near-miss events occur far more frequently than adverse events causing harm. Collecting near-miss data is an effective means of highlighting human and system failures associated with transfusion that may otherwise go unnoticed. These data can be used to identify areas where resources need to be targeted in order to prevent future harm to patients, improving the overall safety of transfusion.

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