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Title: Telaprevir as an effective treatment for genotype 3 hepatitis C
Author: De Silva, Sampath
ISNI:       0000 0004 7971 8065
Awarding Body: Queen Mary University of London
Current Institution: Queen Mary, University of London
Date of Award: 2018
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Genotype 3 hepatitis C accounts for 35% of cases of chronic hepatitis C infection in the United Kingdom. At the time this work was commenced there were limited treatment options for patients with genotype 3 hepatitis C with advanced liver disease who had failed treatment with interferon and ribavirin. Approximately 30% of patients with genotype 3 hepatitis C demonstrated a significant virological response on a clinical trial with two weeks of treatment with telaprevir monotherapy. A novel in vitro capture fusion assay had been developed by our group which enabled assessment of in-vitro hepatitis C virus (HCV) sensitivity to antiviral drugs and indicated that sensitivity to telaprevir could be pre-determined by viral phenotyping. A multi-centre open label clinical trial was undertaken to evaluate whether the addition of twelve weeks of treatment with telaprevir to standard treatment with 24 weeks interferon and ribavirin was of benefit to patients with advanced liver disease who had previously failed treatment with interferon and ribavirin and whether the 'capture fusion' assay could identify patients likely to respond. In addition, we assessed the value of next generation sequencing as a predictor of clinical response. The main findings were that four out of fourteen patients (29%) achieved an SVR. The capture fusion assay identified two of these four patients as having HCV that was sensitive to telaprevir in vitro. No pre-treatment substitutions were identified on next generation sequencing that correlated with the clinical outcome of treatment. Trial recruitment was discontinued when sofosbuvir containing all oral regimens became available for patients eligible to participate in the trial. Although telaprevir may be of benefit to a proportion of patients with genotype 3 hepatitis C, advances in the treatment of hepatitis C have resulted in newer, more potent, direct acting antiviral drugs superseding telaprevir.
Supervisor: Not available Sponsor: Janssen UK
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available