Therapeutic monitoring of direct-acting antivirals for the treatment of hepatitis C


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(Mémoire de) maîtrise (master)
Therapeutic monitoring of direct-acting antivirals for the treatment of hepatitis C
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Université de Lausanne, Faculté de biologie et médecine
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Background. Chronic hepatitis C virus (HCV) infection affects about 71 million people worldwide. Nowadays, the standard therapy of chronic HCV infection is based on direct-acting antivirals (DAAs). DAAs are significantly more effective than pegylated interferon-alfa and ribavirin. Moreover, these drugs have a good tolerance and allow short treatment durations. It is common practice to monitor treatment efficacy with measurements of blood HCV viral load. However, we do not have clear recommendations for this monitoring, based on a model describing viral kinetics under DAA-based treatment. The additional usefulness of DAA concentration monitoring is uncertain.
The aim of our study was to analyze whether HCV RNA profiles during DAA-based therapies predict the final treatment outcome, to assess the adjunctive predictive value of drug concentration and liver function tests monitoring, and to describe clinical and laboratory characteristics of patients with post-treatment relapse.
Methods. We conducted a retrospective observational study with chronic HCV infected patients. All included patients were ≥ 18 years old, treated with DAAs from 2013 to 2017 at CHUV (Lausanne, Switzerland).
Results. We included in the study 202 patients (71% men, mean age 55 years). A sustained virologic response (SVR) was achieved by 193 (95.5%) patients, while 9 (4.5%) patients had a post-treatment relapse. A previous history of hepatocellular carcinoma, HBV co-infection, and IL28B rs12979860 genotype CT were independent predictors of treatment failure. We did not find a relationship between therapy outcome and either HCV RNA, ALT or AST at baseline, at week 2, week 4, or at the end of treatment. The concentrations of sofosbuvir metabolite GS331007 and daclatasvir tended to be lower in patients with post-treatment relapse compared with patients with SVR, however the limited number of patients precludes any firm conclusion.
Conclusions. Beyond known pre-existing prognostic factors, confirmed in our study, there is no indication that the regular monitoring of HCV RNA, AST, and ALT during DAAs treatment could help to predict the sustained virologic response of HCV chronic infection to novel DAAs. The potential role of DAA concentration monitoring deserves to be evaluated in a larger study.
Hepatitis C virus, direct-acting antivirals, sustained virologic response, HCV RNA, monitoring
Création de la notice
02/09/2019 14:55
Dernière modification de la notice
08/09/2020 7:09
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