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- Title
Comparison of the effect of direct-acting antiviral with and without ribavirin on cyclosporine and tacrolimus clearance values: results from the ANRS CO23 CUPILT cohort.
- Authors
Barrail-Tran, Aurélie; Goldwirt, Lauriane; Gelé, Thibaut; Laforest, Claire; Lavenu, Audrey; Danjou, Hélène; Radenne, Sylvie; Leroy, Vincent; Houssel-Debry, Pauline; Duvoux, Christophe; Kamar, Nassim; De Ledinghen, Victor; Canva, Valérie; Conti, Filomena; Durand, François; D'Alteroche, Louis; Botta-Fridlund, Danielle; Moreno, Christophe; Cagnot, Carole; Samuel, Didier
- Abstract
Purpose: Direct-acting antiviral agents have demonstrated their efficacy in treating HCV recurrence after liver transplantation and particularly the sofosbuvir/daclatasvir combination. Pharmacokinetic data on both calcineurin inhibitors and direct-acting antiviral exposure in liver transplant recipients remain sparse. Methods: Patients were enrolled from the ANRS CO23 CUPILT cohort. All patients treated with sofosbuvir/daclatasvir with or without ribavirin were included in this study when blood samples were available to estimate the clearance of immunosuppressive therapy before direct-acting antiviral initiation and during follow-up. Apparent tacrolimus and cyclosporine clearances were estimated from trough concentrations measured using validated quality control assays. Results: Sixty-seven mainly male patients (79%) were included, with a mean age of 57 years and mean MELD score of 8.2; 50 were on tacrolimus, 17 on cyclosporine. Ribavirin was combined with sofosbuvir/daclatasvir in 52% of patients. Cyclosporine clearance remained unchanged as well as tacrolimus clearance under the ribavirin-free regimen. Tacrolimus clearance increased 4 weeks after direct-acting antivirals and ribavirin initiation versus baseline (geometric mean ratio 1.81; 90% CI 1.30–2.52). Patients under ribavirin had a significantly higher fibrosis stage (> 2) (p = 0.02) and lower haemoglobin during direct-acting antiviral treatment (p = 0.02) which impacted tacrolimus measurements. Direct-acting antiviral exposure was within the expected range. Conclusion: Our study demonstrated that liver transplant patients with a recurrence of hepatitis C who are initiating ribavirin combined with a sofosbuvir-daclatasvir direct-acting antiviral regimen may be at risk of lower tacrolimus concentrations because of probable ribavirin-induced anaemia and higher fibrosis score, although there are no effects on cyclosporine levels. Trial registration: NCT 01944527
- Subjects
RIBAVIRIN; ANTIVIRAL agents; BLOOD collection; CONFIDENCE intervals; CYCLOSPORINE; TACROLIMUS; HEPATITIS C; IMMUNOSUPPRESSION; IMMUNOSUPPRESSIVE agents; LIVER transplantation; LONGITUDINAL method; NUCLEOTIDES; SCIENTIFIC observation; PHARMACOLOGY; TRANSPLANTATION of organs, tissues, etc.
- Publication
European Journal of Clinical Pharmacology, 2019, Vol 75, Issue 11, p1555
- ISSN
0031-6970
- Publication type
Article
- DOI
10.1007/s00228-019-02725-x