SP778EFFECTIVENESS AND SAFETY OF SOFOSBUVIR-BASED THERAPY OF CHRONIC HEPATITIS C PATIENTS AFTER KIDNEY TRANSPLANTATION

Abstract

INTRODUCTION AND AIMS: The introduction of direct acting antivirals (DAA) to the therapy of chronic hepatitis C made significant breakthrough in the effectiveness and safety and provided an access to such treatment of also kidney transplant recipients (KTR) who could not be treated with standard interferon based therapy. Till now, there are only a few published observations in this population. THE AIM OF THE STUDY was to assess the effectiveness and safety of new DAA therapy in stable KTR. METHODS: Out of 70 KTR with presence of anti-HCV antibodies, the HCV-RNA was detected in 35 patients (20M/15F, mean time after transplantation: 10.4±7.3 years). Patients were infected with following HCV genotypes: 1β (GT1β) - 26 (79%), 2α (GT2α) - 2 (6%) , 3 (GT3) - 3 (9%) and 4 (GT4) - 2 (6%). GT1- and GT4-infected KTR were treated 12 weeks (first eight patients for 24 weeks) with 400 mg of sofosbuvir (SOF) and 90 mg of ledipasvir (LDV), with initial dose of ribavirin (RBV) 0-800 mg depending on the starting hemoglobin level. Patients infected with GT2 and GT3 were treated for 24 weeks with 400mg SOF with initial dose of RBV 200-800mg. The effectiveness of therapy was analyzed by assessing of rapid virologic response (RVR), endtherapeutic response (ETR) and sustained virologic response (SVR12) defined as an undetectable serum hepatitis C virus (HCV) RNA level at week 4, the end of therapy and after 12 weeks after treatment, respectively. Safety of therapy was monitored by repeated estimation of GFR (eGFR) and measurement of blood haemoglobin (Hb) concentration. RESULTS: The RVR (n=33), ETR (n=26) and SVR12 (n=20) rates were 100%. The therapy did not significantly influence eGFR (56.2±26,2 vs 53.9±25,7ml/min before DAA therapy, p=0,075). The mean initial blood Hb concentration was 13.59±1.93g/dl, range 9.2-19.1 g/dl, and after 4 weeks it decreased to 11.6±1.89 g/dl, range 8.1-16.2 g/ dl (p<0.001). RBV administration was modified according to product characteristics, leading to improvement of Hb level in most of patients. RBV had to be discontinued in 4 patients because of severe anaemia, and in one infected with GT3 with SOF/RBVtreated patient, the therapy was completely interrupted after 6 weeks. Two patients required single blood transfusion and erythropoietin supplementation. Disturbances of blood Hb concentration disappeared one month after the end of treatment. Any other important side effects were observed during therapy. CONCLUSIONS: 1. In KTR, the new anti HCV therapies with SOF6LDV and RBV are characterized by 100 % effectiveness and very good safety profile. 2. The decrease of Hb concentration resulting from RBV administration, however expected, in some cases (11% of patients) was the indication for discontinuation of RBV therapy. 3. In patients treated with RBV and co-therapy within new DAA regimens, close monitoring of blood Hb concentration and early RBV dose reduction is necessary.