Predictors of response to daclatasvir in addition to sofosbuvir in hepatitis C virus-infected patients with stage 4 and 5 chronic kidney disease and patients on maintenance hemodialysis

Abstract

Abstract Background The FDA authorized the use of sofosbuvir-based therapy in persons with chronic kidney disease (CKD) stages 4 and 5 and in those on maintenance hemodialysis (HD). It has been known that treatment efficacy might be affected by virus- and host-related parameters. The aim of this study was to identify the response rate of sofosbuvir plus daclatasvir in CKD stage 4/5 and HD patients. The secondary aim was to identify the predictors of treatment failure. Methods This cross-sectional study was conducted on 55 HCV-infected patients recruited from Alexandria University hospitals. The study included patients on maintenance HD or CKD stages 4–5. Baseline characteristics and SNP genotyping of the IFNL4 rs368234815 variant were addressed as possible predictors of response. The participants received sofosbuvir alongside daclatasvir with or without ribavirin for 3–6 months, according to the EASL guidelines. The response was evaluated by testing serum HCV RNA using PCR 12 weeks after treatment. Results Only 29 patients achieved sustained virologic response (SVR) (52.7%). Non-responders had statistically significantly lower hemoglobin, platelets, and albumin, while they had higher INR, liver enzymes, bilirubin, and APRI scores. FIB-4 scores were significantly lower among responders (1.64 ± 0.74 versus 4.81 ± 1.82) ( p < 0.001). Among those with treatment failure, 13 patients (50%) had the TT/G genotype, while only 3 patients (11.5%) of the TT/TT genotype failed to achieve SVR12. Only 13.8% of patients with the G/G genotype achieved SVR12 ( P = 0.001). Multivariate regression revealed that higher FIB-4 was the only predictor of failure to achieve SVR12. FIB-4 at a cutoff level of 2.63 has a sensitivity, specificity, PPV, and NPV for prediction of treatment failure of 88.46%, 93.10%, 92%, and 90%, respectively. Conclusions FIB-4 above 2.63 is a predictor of lower SVR rates among patients with advanced CKD stages.