Treatment optimisation for hepatitis C in the era of combination direct-acting antiviral therapy: a systematic review and meta-analysis
File(s)
Author(s)
Jones, Christopher
Flower, Barnaby
Barber, Ella
Simmons, Bryony
Cooke, Graham
Type
Journal Article
Abstract
Background: Prior to direct-acting antiviral (DAA) therapy, personalised medicine played an important role in the treatment of hepatitis C virus (HCV). Whilst simplified treatment strategies are central to treatment scale-up, some patients will benefit from treatment optimisation. This systematic review and meta-analysis explores treatment optimisation strategies in the DAA era. Methods: We systematically searched Medline, Embase, and Web of Science for studies that adopted a stratified or personalised strategy using a licensed combination DAA regimen, alone or with additional agents. We performed a thematic analysis to classify optimisation strategies and a meta-analysis of sustained virologic response rates (SVR), exploring heterogeneity with subgroup analyses and meta-regression. Results: We included 64 studies (9450 participants). Thematic analysis found evidence of three approaches: duration, combination, and/or dose optimisation. We separated strategies into those aiming to maintain SVR in the absence of predictors of failure, and those aiming to improve SVR in the presence of predictors of failure. Shortened duration regimens achieve pooled SVR rates of 94.2% (92.3-95.9%) for 8 weeks, 81.1% (75.1-86.6%) for 6 weeks, and 63.1% (39.9-83.7%) for ≤4 weeks. Personalised strategies (100% vs 87.6%; p<0.001) and therapy shortened according to ≥3 host/viral factors (92.9% vs 81.4% or 87.2% for 1 or 2 host/viral factors, respectively; p=0.008) offer higher SVR rates when shortening therapy. Hard-to-treat HCV genotype 3 patients suffer lower SVR rates despite treatment optimisation (92.6% vs 98.2%; p=0.001). Conclusions: Treatment optimisation for individuals with multiple predictors of treatment failure can offer high SVR rates. More evidence is needed to identify with confidence those individuals in whom SVR can be achieved with shortened duration treatment.
Date Issued
2019-09-06
Date Acceptance
2019-09-01
Citation
Wellcome Open Research, 2019, 4 (132), pp.1-15
ISSN
2398-502X
Publisher
F1000Research
Start Page
1
End Page
15
Journal / Book Title
Wellcome Open Research
Volume
4
Issue
132
Copyright Statement
© 2019 Jones CR et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Identifier
https://wellcomeopenresearch.org/articles/4-132/v1
Publication Status
Published
Date Publish Online
2019-09-06