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Searching for unknown transfusion-transmitted hepatitis viruses: a binational cohort study of 1.5 million transfused patients.

ABSTRACT: BACKGROUND:Both hepatitis B and C viruses were transmitted through blood transfusion before implementation of donor screening. The existence of additional, yet unknown transfusion transmittable agents causing liver disease could have important public health implications. METHODS:Analyses were based on the Scandinavian Donations and Transfusions (SCANDAT2) database. Cox regression models were used to estimate the hazard ratio (HR) of developing chronic liver disease in recipients of blood from donors who later developed any chronic liver disease compared to recipients who received blood transfusion from healthy donors. We also studied whether the risk of liver disease was increased in patients who received units from 'high-risk' donors, defined as donors who had a higher than expected occurrence of liver disease amongst their previous recipients. All analyses were stratified before and after 1992 to account for the effect of screening for hepatitis C virus. RESULTS:A total of 1 482 922 transfused patients were included in the analyses. Analyses showed evidence of transfusion transmission of liver diseases before, but not after the implementation of hepatitis C virus screening in 1992, with HRs for any liver disease of 1.38 [95% confidence interval (CI), 1.30-1.46] and 0.99 (95% CI, 0.91-1.07), before and after 1992, respectively. Similarly, blood components from 'high-risk' donors conferred increased risks before, but not after 1992. CONCLUSIONS:Our data provide no evidence for transfusion transmission of agents causing liver disease after the implementation of screening for hepatitis B and C, and suggest that if such transmission does occur, it is rare.

SUBMITTER: Edgren G

PROVIDER: S-EPMC6013371 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Searching for unknown transfusion-transmitted hepatitis viruses: a binational cohort study of 1.5 million transfused patients.

Edgren G G Hjalgrim H H Rostgaard K K Dahl V V Titlestad K K Erikstrup C C Wikman A A Norda R R Majeed A A

Journal of internal medicine 20180425 1

<h4>Background</h4>Both hepatitis B and C viruses were transmitted through blood transfusion before implementation of donor screening. The existence of additional, yet unknown transfusion transmittable agents causing liver disease could have important public health implications.<h4>Methods</h4>Analyses were based on the Scandinavian Donations and Transfusions (SCANDAT2) database. Cox regression models were used to estimate the hazard ratio (HR) of developing chronic liver disease in recipients o ...[more]

PMID: 29624755

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Project description:UnlabelledThe interaction between hepatitis C virus (HCV) and cellular immune responses during very early infection is critical for disease outcome. To date, the impact of antigen-specific cellular immune responses on the evolution of the viral population establishing infection and on potential escape has not been studied. Understanding these early host-virus dynamics is important for the development of a preventative vaccine. Three subjects who were followed longitudinally from the detection of viremia preseroconversion until disease outcome were analyzed. The evolution of transmitted/founder (T/F) viruses was undertaken using deep sequencing. CD8(+) T cell responses were measured via enzyme-linked immunosorbent spot (ELISpot) assay using HLA class I-restricted T/F epitopes. T/F viruses were rapidly extinguished in all subjects associated with either viral clearance (n = 1) or replacement with viral variants leading to establishment of chronic infection (n = 2). CD8(+) T cell responses against 11 T/F epitopes were detectable by 33 to 44 days postinfection, and 5 of these epitopes had not previously been reported. These responses declined rapidly in those who became chronically infected and were maintained in the subject who cleared infection. Higher-magnitude CD8(+) T cell responses were associated with rapid development of immune escape variants at a rate of up to 0.1 per day. Rapid escape from CD8(+) T cell responses has been quantified for the first time in the early phase of primary HCV infection. These rapid escape dynamics were associated with higher-magnitude CD8(+) T cell responses. These findings raise questions regarding optimal selection of immunogens for HCV vaccine development and suggest that detailed analysis of individual epitopes may be required.ImportanceA major limitation in our detailed understanding of the role of immune response in HCV clearance has been the lack of data on very early primary infection when the transmitted viral variants successfully establish the acute infection. This study was made possible through the availability of specimens from a unique cohort of asymptomatic primary infection cases in whom the first available viremic samples were collected approximately 3 weeks postinfection and at regular intervals thereafter. The study included detailed examination of both the evolution of the viral population and the host cellular immune responses against the T/F viruses. The findings here provide the first evidence of host cellular responses targeting T/F variants and imposing a strong selective force toward viral escape. The results of this study provide useful insight on how virus escapes the host response and consequently on future analysis of vaccine-induced immunity.

Dataset Information

Searching for unknown transfusion-transmitted hepatitis viruses: a binational cohort study of 1.5 million transfused patients.

Publications

Searching for unknown transfusion-transmitted hepatitis viruses: a binational cohort study of 1.5 million transfused patients.

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