Pharmacokinetics, efficacy and safety of daclatasvir plus asunaprevir in dialysis patients with chronic hepatitis C: pilot study

Abstract

The aim of this study was to evaluate the pharmacokinetic profile of daclatasvir (DCV) and asunaprevir (ASV) dual therapy in haemodialysis patients infected with hepatitis C virus (HCV). Eighteen haemodialysis patients and 54 patients with normal renal function were treated with DCV and ASV dual therapy for 24 weeks. We evaluated the pharmacokinetic profiles of DCV and ASV and examined the rate of sustained virological response 12 weeks after the end of treatment (SVR ) and incidence of adverse events during treatment of haemodialysis patients infected with chronic HCV genotype 1 infection. To adjust for potential differences in baseline characteristics between haemodialysis patients and patients with normal renal function, we used propensity scores case-control matching methods. Area under the plasma concentration time curve from 0 to 6 h (AUC ) of DCV was slightly lower in haemodialysis patients than in patients with normal renal function (P > 0.6). AUC of ASV was significantly lower in haemodialysis patients (P = 0.012). SVR rates were 100% (18/18) for haemodialysis and 96.2% (52/54) for patients with normal renal function. Changes in mean log HCV RNA levels and viral response were higher in haemodialysis patients compared to patients with normal renal function. No discontinuations due to adverse events occurred. In conclusion, DCV and ASV dual therapy for HCV infection is effective and safe with similar results in haemodialysis patients compared to patients with normal renal function.

Combination Therapy with Ombitasvir/Paritaprevir/Ritonavir for Dialysis Patients Infected with Hepatitis C Virus: A Prospective Multi-Institutional Study

“…5.1) of the Japan Society of Hepatology (JSH) guideline for the management of HCV infection recommends combination therapy with daclatasvir and asunaprevir (DCV/ASV) as interferon-free direct-acting antiviral agents (DAAs) for dialysis patients with chronic infection of HCV genotype 1b (HCV/1b) in Japan. While the antiviral efficacy of DCV/ASV combination therapy for dialysis patients has been reported in several studies (Miyazaki and Miyagi 2016;Kawakami et al 2016;Sato et al 2016;Toyoda et al 2016;Suda et al 2016), this therapy has several flaws compared to more updated regimens with DAAs such as sofosbuvir and ledipasvir (SOF/LDV) or ombitasvir, paritaprevir, and ritonavir (OBV/PTV/r), as will be discussed later.…”

Novel Treatment of Hepatitis C Virus Infection for Patients with Renal Impairment

“…The C max was 28.6% higher and the AUC was 10.1% lower in dialysis subjects, compared with the controls. Recently, Kawakami et al 68. reported the ASV pharmacokinetics determined in HCV-infected dialysis patients and compared with HCV-infected patients with normal renal function.…”

Improvement of Proteinuria due to Combination Therapy with Daclatasvir and Asunaprevir in Hepatitis C Virus-associated Renal Disease without Cryoglobulinemia

“…Daclatasvir (DCV) and asunaprevir (ASV) are both mainly metabolized in the liver and can be used for patients with chronic renal dysfunction or dialysis (5-13). We herein report a case of HCV-associated renal disease without cryoglobulinemia in a patient who showed a sustained virological response at week 24 (SVR24) and marked amelioration of proteinuria and ascites by combination therapy with DCV/ASV.…”