Phillips, Laura Teresa; (2025) Genomic and phylo-epidemiological surveillance of hepatitis C virus diversity and antiviral resistance in the UK. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Background: Hepatitis C virus (HCV) remains a major public health burden in the UK as the 2030 target for elimination approaches. Progress towards this target will require infection control measures including early identification of transmission networks, monitoring reinfection rates, and identifying cases of people infected with harder to treat endemic and novel HCV subtypes. Methods: Real-world data gathered by the UK Health Security Agency was used to determine and evaluate thresholds for HCV clustering using genomic regions compared to whole genome sequences (WGS) and explore the use of genomic data to identify reinfections by the same subtype. In addition, Bayesian inference phylogenetic methods were used to study the viral migration of HCV infections in an ongoing outbreak in Northern Ireland (NI). Finally, factors associated with, and disparities between treatment outcomes were assessed in people infected with endemic and epidemic HCV subtypes. Results: WGS data enabled the determination of tailored thresholds to define HCV clusters using individual genomic regions and found the E1 region to produce highly concordant clusters to WGS. In contrast, a small Sanger sequenced genomic region was not sufficient to establish a threshold for determining reinfections with the same subtype. Phylogeography analyses showed increased viral migration from people living in outer Belfast towards people in central Belfast within the NI HCV outbreak. Finally, a significant discrepancy in treatment outcomes was observed among people with endemic and epidemic HCV subtypes treated in England, with intrinsic resistance playing a role in treatment failure. Conclusion: Access to centrally collected WGS data facilitated phylo-epidemiological analyses to identify ongoing transmissions, track the spread of viral lineages within an outbreak, and identify endemic HCV subtypes ‘rare’ to the UK with intrinsic antiviral resistance. These methods and outputs contribute to our understanding of, and ability to maintain, progress towards HCV elimination in the UK.

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